Chapter   2400  Biotechnology
---SECTION---2401 Introduction

This chapter provides guidance on the practices and procedures for
implementation of the deposit rules (37 CFR 1.801 - 1.809) and the
sequence rules (37 CFR 1.821 - 1.825). The final rule for deposits of
biological materials for patent purposes was published in the Federal
Register, 54 FR 34864 (August 22, 1989) and in the Official Gazette,
1106 O.G. 37 (September 12, 1989).  The deposit rules went into effect
on January 1, 1990. The final rule for the requirements for patent
applications containing nucleotide sequence and/or amino acid sequence
disclosures   was published in the Federal Register, 55 FR 18230 (May 1,
1990) and in the Official Gazette, 1114 O.G. 29 (May 15, 1990) and went
into effect on October  1, 1990.  Revised sequence rules were published
in the Federal Register at 63 FR 29620 (June 1, 1998) and in the
Official Gazette at 1121 O.G. 82 (June 23, 1998) and went into effect on
July 1, 1998.

Additional information regarding the development of the deposit rules
can be obtained in the text of the draft policy statement, published in
BNA's Patent, Trademark and Copyright Journal, 32 PTCJ 781 at 76, 90
(May 22, 1986), the advanced notice of proposed rulemaking, published in
the Federal Register, 52 FR 34080 (September 9, 1987), and in the
Official Gazette, 1082 O.G. 47 (September 29, 1987) and in the notice of
proposed rulemaking, published in the Federal Register, 53 FR 39420
(October 6, 1988), and in the Official Gazette, 1095 O.G. 47 (October
25, 1988).  Additional information regarding the development of the
sequence rules can be obtained in the text of the notice of proposed
rulemaking, published in the   Federal Register, 54 FR 18671 (May 2,
1989) and in the Official Gazette, 1102 O.G. 34 (May 16, 1989).

See MPEP Section  803.04 and Section  1850 for restriction and unity of
invention practice respectively in patent applications claiming
independent and distinct nucleotide sequences.  See also MPEP Section 
2434.

---SECTION---2402 The Deposit Rules

Every patent must contain a written description of the invention
sufficient to enable a person skilled in the art to which the invention
pertains to make and use the invention.  Where the invention involves a
biological material and words alone cannot sufficiently describe how to
make and use the invention in a reproducible manner, access to the
biological material may be necessary for the satisfaction of the
statutory requirements for patentability under  35 U.S.C. 112.  Courts
have recognized the necessity and desirability of permitting an
applicant for a patent to supplement the written disclosure in an
application with a deposit of biological material which is essential to
meet some requirement of the statute with respect to the claimed
invention. Merck and Co., Inc. v. Chase Chemical Co., 273 F. Supp. 68,
155 USPQ 139 (D. N.J. 1967);   In re Argoudelis, 434 F.2d 666, 168 USPQ
99 (CCPA 1970).  To facilitate the recognition of deposited biological
material in patent applications throughout the world, the Budapest
Treaty on the International Recognition of the Deposit of Microorganisms
for the Purposes of Patent Procedure was established in 1977, and became
operational in 1981.  The Treaty requires signatory countries, like the
United States, to recognize a deposit with any depository which has been
approved by the World Intellectual Property Organization (WIPO).

The deposit rules (37 CFR 1.801 - 1.809) set forth examining procedures
and conditions of deposit which must be satisfied in the event a deposit
is required.  The rules do not address the substantive issue of whether
a deposit is required under any particular set of facts.

The rules are effective for all applications filed on or after January
1, 1990, and for all reexamination proceedings in which the request for
reexamination was filed on or after January 1, 1990, except that
deposits made prior to the effective date which were acceptable under
the then current practice will be acceptable in such applications and
proceedings.  Since most of the provisions of the rules reflect policy
and practice existing prior to January 1, 1990, little change in
practice or burden on applicants for patent and patent owners relying on
the deposit of biological material has occurred.  Applicants and patent
owners are encouraged to comply with these rules even if their
applications and reexamination proceedings were filed prior to January
1, 1990.

---SECTION---2403 Deposit of Biological Material

37 CFR 1.801 Biological material.

For the purposes of these regulations pertaining to the deposit of
biological material for purposes of patents for inventions under  35
U.S.C. 101, the term biological material shall include material that is
capable of self-replication either directly or indirectly. 
Representative examples include bacteria, fungi including yeast, algae,
protozoa, eukaryotic cells, cell lines, hybridomas, plasmids, viruses,
plant tissue cells, lichens and seeds.  Viruses, vectors, cell
organelles and other non-living material existing in and reproducible
from a living cell may be deposited by deposit of the host cell capable
of reproducing the non-living material.

37 CFR 1.801 indicates that the rules pertaining to deposits for
purposes of patents for inventions under  35 U.S.C. 101 are intended to
relate to biological material.  For the purposes of these rules, the
term "biological material" is defined in terms of a non-exhaustive list
of representative materials which can be deposited in accordance with
the procedures defined in these rules.  These rules are intended to
address procedural matters in the deposit of biological material for
patent purposes.  They are not designed to decide substantive issues
such as whether a deposit of a particular organism or material would be
recognized or necessary for the purposes of satisfying the statutory
requirements for patentability under  35 U.S.C. 112. Although the issue
of the need to make a deposit of biological material typically arises
under the enablement requirement of the first paragraph of  35 U.S.C.
112, the issue could also arise under the description requirement (35
U.S.C. 112, first paragraph), best mode requirement (35 U.S.C. 112,
first paragraph) or the requirements of the second paragraph of  35
U.S.C. 112 with respect to the claims.

37 CFR 1.801 does not attempt to identify what biological material
either needs to be or may be deposited to comply with the requirements
of  35 U.S.C. 112.  For the most part, this issue must be addressed on a
case-by-case basis.  Thus, while the Office does not currently
contemplate that there would be any situations where a material that is
not capable of self-replication either directly or indirectly would be
acceptable as a deposit, an applicant is clearly not precluded by these
rules from attempting to show in any given application why the deposit
of such a material should be acceptable to satisfy the requirements of 
35 U.S.C. 112.

---SECTION---2403.01 Material Capable of Self-Replication

Biological material includes material that is capable of
self-replication either directly or indirectly.  Direct self-replication
includes those situations where the biological material reproduces by
itself.  Representative examples of materials capable of
self-replication are defined in the rule.  Indirect self-replication is
meant to include those situations where the biological material is only
capable of replication when another self-replicating biological material
is present.  Self-replication after insertion in a host is one example
of indirect self-replication.  Examples of indirect replicating
biological materials include viruses, phages, plasmids, symbionts, and
replication defective cells.  The list of representative examples of
each type of replicating material includes viruses to demonstrate that
the two lists in the rule are not intended to be mutually exclusive.

---SECTION---2403.02 Plant Material

Although plant material is included within the scope of the definition
of biological material for purposes of patents for plant inventions
under  35 U.S.C. 101, the rules on deposits are not applicable to
applications filed under the Plant Patent Act (35 U.S.C. 161-164).  The
Office is of the view that a deposit is not required under the present
provisions of  35 U.S.C. 162. Thus, a deposit is not necessary for the
grant of a plant patent under the provisions of  35 U.S.C. 161-164.  As
with other biological material deposited for purposes of patents for
inventions under  35 U.S.C. 101, the deposit of plant material together
with the written specification must enable those skilled in the art to
make and use the claimed invention, in accordance with the requirements
of  35 U.S.C. 112.

As with some types of reproducible biological material, seeds can be
reproduced only after a growing season which may be relatively long.
Although the rules do not specify a specific number of seeds to be
deposited to meet the requirements of these rules, the Office will
consider 2500 to be a minimum number in the normal case, but will give
an applicant the opportunity to provide justification why a lesser
number would be suitable under the circumstances of a particular case. 
The Department of Agriculture requires a deposit of 2500 seeds for the
grant of a Plant Variety Protection Certificate under the Plant Variety
Protection Act (7 U.S.C. 2321 et seq.). As the reproduction of seeds
will often take a substantial period of time, the Office will require,
at a minimum for the grant of a patent, a number of seeds that is likely
to satisfy demand for samples once the patent is granted.  In one
instance, the Office accepted a deposit of 600 seeds coupled with an
undertaking to deposit 1900 more seeds with due diligence. The
particular situation involved a  "seedless" vegetable with very few
seeds per "fruit;" about two growing seasons were required to provide
the additional 1900 seeds.

---SECTION---2404 Need or Opportunity to Make a Deposit

37 CFR 1.802 Need or opportunity to make a deposit.

(a) Where an invention is, or relies on, a biological material, the
disclosure may include reference to a deposit of such biological
material.

(b) Biological material need not be deposited unless access to such
material is necessary for the satisfaction of the statutory requirements
for patentability under  35 U.S.C. 112.  If a deposit is necessary, it
shall be acceptable if made in accordance with these regulations. 
Biological material need not be deposited, inter alia, if it is known
and readily available to the public or can be made or isolated without
undue experimentation.  Once deposited in a depository complying with
these regulations, a biological material will be considered to be
readily available even though some requirement of law or regulation of
the United States or of the country in which the depository institution
is located permits access to the material only under conditions imposed
for safety, public health or similar reasons.

(c) The reference to a biological material in a specification disclosure
or the actual deposit of such material by an applicant or patent owner
does not create any presumption that such material is necessary to
satisfy  35 U.S.C. 112 or that deposit in accordance with these
regulations is or was required.

37 CFR 1.802(a) permits a deposit of a biological material to be
referenced in a patent application where an invention is, or relies on,
a biological material.  The invention may rely on a biological material
for the purposes of making or using the invention, either as a preferred
mode or an alternative mode of operation. A reference to a deposit may
be included in a specification even though the deposit is not required
to satisfy the requirements of  35 U.S.C. 112.

There is no necessary implication or presumption that can or should be
made about the need for a deposit simply because reference to a deposit
is made in an application disclosure, as noted in paragraph (c).  As
noted in paragraph (b), biological material need not be deposited unless
access to such material is necessary for the satisfaction of the
statutory requirements for patentability under  35 U.S.C. 112 and that
access is not otherwise available in the absence of a deposit.  Where a
deposit is required to provide the necessary access, a deposit is
acceptable for patent purposes only where it is made in accordance with
these regulations. Even where access to biological material is required
to satisfy these statutory requirements, a deposit may not be necessary
if access sufficient to satisfy these requirements is otherwise
available.

---SECTION---2404.01 Biological Material That Is Known and Readily
Available to the Public

In an application where the invention required access to specific
biological material, an applicant could show that the biological
material is accessible because it is known and readily available to the
public.  The concepts of "known and readily available" are considered to
reflect a level of public accessibility to a necessary component of an
invention disclosure that is consistent with an ability to make and use
the invention.  To avoid the need for a deposit on this basis, the
biological material must be both known and readily available - neither
concept alone is sufficient.  A material may be known in the sense that
its existence has been published, but is not available to those who wish
to obtain that particular known biological material. Likewise, a
biological material may be available in the sense that those having
possession of it would make it available upon request, but no one has
been informed of its existence.

The Board of Patent Appeals and Interferences has held that a
description of the precise geographic location of marine tunicates, as a
biological material, used in a claimed invention was adequate to satisfy
the enablement requirement of  35 U.S.C. 112. Ex Parte Rinehart, 10
USPQ2d 1719 (Bd Pat. App. & Int. 1985).  The term "readily" used in the
phrase "known and readily available" is considered appropriate to define
that degree of availability which would be reasonable under the
circumstances.  If the biological material and its natural location can
be adequately described so that one skilled in the art could obtain it
using ordinary skill in the art, the disclosure would appear to be
sufficient to meet the enablement requirement of  35 U.S.C. 112 without
a deposit so long as its degree of availability is reasonable under the
circumstances.

By showing that a biological material is known and readily available or
by making a deposit in accordance with these rules, applicant does not
guarantee that such biological material will be available forever. 
Public access during the term of the patent may affect the
enforceability of the patent.  Although there is a public interest in
the availability of a deposited biological material during and after the
period of enforceability of the patent, there should not be any undue
concern about continued access to the public.  Unless there is a
reasonable basis to believe that the biological material will cease to
be available during the enforceable life of the patent, current
availability would satisfy the requirement. The incentives provided by
the patent system should not be constrained by the mere possibility that
a disclosure that was once enabling would become non-enabling over a
period of time through no fault of the patentee. In re Metcalfe, 410
F.2d 1378, 161 USPQ 789 (CCPA 1969).

If an applicant has adequately established that a biological material is
known and readily available, the Office will accept that showing.  In
those instances, however, the applicant takes the risk that the material
may cease to be known and readily available.  Such a defect cannot be
cured by reissue after the grant of a patent.

On the other hand, Ex parte Humphreys, 24 USPQ2d 1255 (Bd Pat. App. &
Int. 1992), held that the only manner in which applicants could satisfy
their burden of assuring public access to the needed biological
material, and, thereby, compliance with the enablement requirement of 
35 U.S.C. 112, was by making an appropriate deposit.  The fact that
applicants and other members of the public were able to obtain the
material in question from a given depository prior to and after the
filing date of the application in issue did not establish that upon
issuance of a patent on the application that such material would
continue to be accessible to the public. The applicants did not make of
record any of the facts and circumstances surrounding their access to
the material in issue from the depository, nor was there any evidence as
to the depository's policy regarding the material if a patent would have
been granted.  Further, there was no assurance that the depository would
have allowed unlimited access to the material if the application had
matured into a patent.

There are many factors that may be used as indicia that a biological
material is known and readily available to the public.  Relevant factors
include commercial availability, references to the biological material
in printed publications, declarations of accessibility by those working
in the field, evidence of predictable isolation techniques, or an
existing deposit made in accordance with these rules.  Each factor alone
may or may not be sufficient to demonstrate that the biological material
is known and readily available. Those applicants that rely on evidence
of accessibility other than a deposit take the risk that the patent may
no longer be enforceable if the biological material necessary to satisfy
the requirements of  35 U.S.C. 112 ceases to be accessible.

The Office will accept commercial availability as evidence that a
biological material is known and readily available only when the
evidence is clear and convincing that the public has access to the
material.  A product could be commercially available but only at a price
that effectively eliminates accessibility to those desiring to obtain a
sample. The relationship between the applicant relying on a biological
material and the commercial supplier is one factor that would be
considered in determining whether the biological material was known and
readily available. However, the mere fact that the biological material
is commercially available only through the patent holder or the patent
holder's agents or assigns shall not, by itself, justify a finding that
the necessary material is not readily available, absent reason to
believe that access to the biological material would later be improperly
restricted.

The mere reference to a deposit or the biological material itself in any
document or publication does not necessarily mean that the deposited
biological material is readily available. Even a deposit made under the
Budapest Treaty and referenced in a United States or foreign patent
document would not necessarily meet the test for known and readily
available unless the deposit was made under conditions that are
consistent with those specified in these rules, including the provision
that requires, with one possible exception, that all restrictions on the
accessibility be irrevocably removed by the applicant upon the granting
of the patent. Ex parte Hildebrand, 15 USPQ2d 1662 (Bd Pat. App. & Int.
1990).

A Budapest Treaty deposit cited in a U.S. patent need not be made
available if it was not required to satisfy  35 U.S.C. 112.  Thus, a
reference to a deposit will not be certified available unless either (1)
the deposit was necessary to overcome a rejection under  35 U.S.C. 112,
or (2) there is, in the record, a statement by the examiner that a
rejection under  35 U.S.C. 112 would have been made "but for" the
deposit (assumes deposit information in record, as filed).  Otherwise,
public access cannot be certified and the deposit cannot be relied upon
for other purposes, e.g., the deposit cannot be relied upon by a third
party to establish "known" and "readily available" in another
application. See  37 CFR 1.808 and MPEP Section  2410 and Section 
2410.02.

Once a deposit is made in a depository complying with these rules, and
under conditions complying with these rules, a biological material will
be considered to be readily available even though some requirement of
law or regulation in the United States or in the country where the
depository institution is located permits access to the material only
under conditions imposed for health, safety or similar reasons. This
provision is consistent with the Budapest Treaty (Article 5) and is
designed to permit the patenting of inventions involving materials
having restricted distribution, where the restrictions are imposed for
the public, as opposed to the private, welfare.

---SECTION---2404.02 Biological Material That Can Be Made or Isolated
Without Undue Experimentation

Applicant may show that a deposit is not necessary even though specific
biological materials are required to practice the invention if those
biological materials can be made or isolated without undue
experimentation. Deposits may be required to support the claims if an
isolation procedure requires undue experimentation to obtain the desired
biological material. Ex Parte Jackson, 217 USPQ 804 (Bd App. 1982).  No
deposit is required, however, where the required biological materials
can be obtained from publicly available material with only routine
experimentation and a reliable screening test. Tabuchi v. Nubel, 559
F.2d 1183, 194 USPQ 521 (CCPA 1977); Ex Parte Hata, 6 USPQ2d 1652 (Bd
Pat. App. & Int. 1987).

---SECTION---2404.03 Reference to a Deposit in the Specification

37 CFR 1.802(c) specifically provides that the mere reference to a
biological material in the specification disclosure or the actual
deposit of such material does not create any presumption that such
referenced or deposited material is necessary to satisfy  35 U.S.C. 112,
or that a deposit in accordance with these regulations is or was
required.  It should be noted, however, that a reference to a biological
material, present in an application upon filing, may form the basis for
making a deposit, where required, after the filing date of a given
application but that the reference to the biological material, itself,
cannot be added after filing without risking the prohibited introduction
of new matter (35 U.S.C. 132).  See the discussion of the Lundak
application in MPEP Section  2406.01.

---SECTION---2405 Acceptable Depository

37 CFR 1.803 Acceptable depository.

(a) A deposit shall be recognized for the purposes of these regulations
if made in

(1) any International Depositary Authority (IDA) as established under
the Budapest Treaty on the International Recognition of the Deposit of
Microorganisms for the Purposes of Patent Procedure, or

(2) any other depository recognized to be suitable by the Office. 
Suitability will be determined by the Commissioner on the basis of the
administrative and technical competence, and agreement of the depository
to comply with the terms and conditions applicable to deposits for
patent purposes.  The Commissioner may seek the advice of impartial
consultants on the suitability of a depository.  The depository must:

(i) Have a continuous existence;

(ii) Exist independent of the control of the depositor;

(iii) Possess the staff and facilities sufficient to examine the
viability of a deposit and store the deposit in a manner which ensures
that it is kept viable and uncontaminated;

(iv) Provide for sufficient safety measures to minimize the risk of
losing biological material deposited with it;

(v) Be impartial and objective;

(vi) Furnish samples of the deposited material in an expeditious and
proper manner; and

(vii) Promptly notify depositors of its inability to furnish samples,
and the reasons why.

(b) A depository seeking status under paragraph (a)(2) of this section
must direct a communication to the Commissioner which shall:

(1) Indicate the name and address of the depository to which the
communication relates;

(2) Contain detailed information as to the capacity of the depository to
comply with the requirements of paragraph  (a) (2) of this section,
including information on its legal status,  scientific standing, staff
and facilities;

(3) Indicate that the depository intends to be available,  for the
purposes of deposit, to any depositor under these same conditions;

(4) Where the depository intends to accept for deposit only certain
kinds of biological material, specify such kinds;

(5) Indicate the amount of any fees that the depository will, upon
acquiring the status of suitable depository under paragraph (a) (2) of
this section, charge for storage, viability statements and furnishings
of samples of the deposit.

(c) A depository having status under paragraph (a)(2) of this section
limited to certain kinds of biological material may extend such status
to additional kinds of biological material by directing a communication
to the Commissioner in accordance with paragraph (b) of this section. 
If a previous communication under paragraph (b) of this section is of
record, items in common with the previous communication may be
incorporated by reference.

(d) Once a depository is recognized to be suitable by the Commissioner
or has defaulted or discontinued its performance under this section,
notice thereof will be published in the Official Gazette of the Patent
and Trademark Office.

37 CFR 1.803 indicates that a depository will be recognized as
acceptable for the purposes of these regulations if it is either an
International Depository Authority (IDA) established under the Budapest
Treaty, or if it is a depository recognized as suitable by the
Commissioner.  After the effective date of these regulations, a deposit
of biological material which is made in a depository which is not
recognized as acceptable under this regulation will not be considered as
satisfying the requirements of  35 U.S.C. 112.  See Ex parte Humphreys,
24 USPQ2d 1255 (Bd Pat. App. & Int. 1992).  On the other hand, if a
deposit is not required to satisfy the requirements of  35 U.S.C. 112,
it is permissible to make reference to such a deposit even though it may
not be in a depository or made under the conditions which are acceptable
under these regulations. As new depositories are recognized as suitable
by the Commissioner, their identity will be announced in the Official
Gazette.

An organization may be recognized as suitable by the Office if the
procedure and conditions specified in  37 CFR 1.803(a)(2) and  37 CFR
1.803(b) are followed.  Generally, it is not the intention of the Office
to recognize as suitable any organization where the need for a suitable
depository for patent purposes is being met by depositories recognized
as IDAs under the Budapest Treaty. Suitability will be judged by the
Commissioner, based on need and the information supplied by the
organization seeking status, and information obtained from other sources
that may be consulted.

While there is a desire to provide flexibility to a patent applicant in
selecting an appropriate depository, these rules are not intended to
permit each patent applicant to become its own depository since both the
patent owner and the public have an interest in the continued
availability and accessibility of the deposit during the enforceable
life of the patent, and the public has a continuing interest in its
availability when the patent is no longer enforceable.  The concept of a
depository independent of the control of the depositor or an IDA as an
acceptable depository is based on the need and desire to ensure the safe
and reliable storage of a deposited biological material under
circumstances that are substantially free of the opportunity for
intentional mishandling or negligent handling of the deposited material. 
The use of an independent depository or internationally recognized
depository will tend to preserve the integrity of the deposit process
against those that may accidentally alter the deposited material, may
wish to tamper with the deposited material or may wish to resume control
of its availability when the patent is no longer enforceable, and will
tend to preserve the interest of the public in the access to the
biological material once the term of the patent expires.

When a depository having status under  37 CFR 1.803(a)(2) seeks to
change the kinds of biological materials that it will accept and
maintain for the purposes of these rules, a communication requesting
such a change should be directed to the Commissioner containing the
information requested in  37 CFR 1.803(b).  When such a change is
requested, the requesting depository should provide a complete list of
the kinds of biological materials it will accept.

37 CFR 1.803(d) indicates that once a depository is recognized as
suitable for the purposes of this rule, or has defaulted or discontinued
its performance under this section, notice thereof will be published in
the Official Gazette of the Patent and Trademark Office. A current list
(as of January, 1998) of IDAs recognized under the Budapest Treaty, with
addresses, is included below.  The mere fact that a deposit has been
made in one of these depositories does not mean that the terms of the
deposit meet either the requirements of the Budapest Treaty or the
deposit regulations.  Many of the depositories recognized under the
Budapest Treaty have many different arrangements under which biological
material may be stored.

The World Intellectual Property Organization (WIPO) publishes a Guide to
the Deposit of Micro-organisms under the Budapest Treaty (WIPO
Publication No. 661 (E)) on the procedures and requirements concerning
the deposit of biological material, including procedures for obtaining a
sample of deposited material, in each of the international depository
authorities.

CURRENT IDAs

The following constitutes the list of IDAs recognized under the Budapest
Treaty. The list is current as of January, 1998.

Advanced Biotechnology Center (ABC)

Interlab Cell Line Collection

(Biotechnology Dept.)

Largo Rossana Benzi, 10

16132 Genova

Italy

Agricultural Research Service

Culture Collection (NRRL)

1815 North University Street

Peoria, Illinois  61604

USA

All-Russian Scientific Center of Antibiotics (VNIIA)

Nagatinskaya Street 3-a

Moscow 113105

Russian Federation

American Type Culture Collection (ATCC)

10801 University Blvd.

Manassas, Virginia 20110-2209

USA

Australian Government Analytical

Laboratories (AGAL)

The New South Wales Regional Laboratory

1, Suakin Street

Pymble, NSW  2073

Australia

Belgian Coordinated Collections of

Microorganisms (BCCM)

Prime Minister's Services

Federal Office for Scientific, Technical and

Cultural Affairs (OSTC)

Rue de la Science 8

B-1000 Brussells

Belgium

Centraalbureau Voor Schimmelcultures (CBS)

Oosterstraat 1

Postbus 273

NL-3740 AG Baarn

Netherlands

China Center for Type Culture Collection (CCTCC)

Wuhan University

Wuhan 430072

China

China General Microbiological Culture Collection

Center (CGMCC)

China Committee for Culture Collection of

Microorganisms

P.O. Box 2714

Beijing 100080

China

Coleci&oacute;n Espa&ntilde;ola de Cultivos Tipo (CECT)

Universidad de Valencia

Edificio de Investigaci&oacute;n

Campus de Burjasot

46100 Burjasot (Valencia)

Spain

Collection Nationale De Cultures

De Microorganismes (CNCM) 

Institut Pasteur

28, rue du Dr Roux

75724 Paris C&eacute;dex 15

France

Collection of Industrial Yeasts (DBVPG)

Applied Microbiology Section

Department of Plant Biology

Faculty of Agriculture

University of Perugia

Borgo 20 Giugno, 74

06122 Perugia

Italy

Culture Collection of Algae and Protozoa (CCAP)

Institute of Freshwater Ecology

Windermere Laboratory

Ambleside, Cumbria LA22 0LP

United Kingdom and Dunstaffnage Marine Laboratory

P.O. Box 3

Oban, Argyll PA34 4AD

United Kingdom

Culture Collection of Yeasts (CCY)

Institute of Chemistry

Slovak Academy of Sciences

D&uacute;bravsk&aacute; cesta 9

842 38 Bratislava,

Slovakia

Czech Collection of Microorganisms (CCM)

Masaryc University

ul. Tvrd&eacute;ho &ccaron;. 14

602 00 Brno

Czech Republic

DSMZ-Deutsche Sammlung Von Mikroorganismen

und Zellkulturen GmbH (DSMZ)

Mascheroder Weg 1b

D-38124 Braunschweig

Germany

European Collection of Cell Cultures (ECACC)

Vaccine Research and Production Laboratory

Public Health Laboratory Service

Centre for Applied Microbiology and Research

Porton Down

Salisbury, Wiltshire SP4 0JG

United Kingdom

International Mycological Institute (IMI)

Bakeham Lane

Englefield Green

Egham, Surrey TW20 9TY

United Kingdom

Korea Research Institute of Bioscience and

Biotechnology (KRIBB)

52, Oun-Dong

Yusong-Ku

Taejon 305-333

Republic of Korea

Korean Cell Line Research Foundation (KCLRF)

Cancer Research Institute

Seoul National University College of Medicine

28 Yungon-dong, Chongno-gu

Seoul 110-799

Republic of Korea

Korean Culture Center of Microorganisms (KCCM)

College of Engineering

Yonsei University

Sodaemun gu

Seoul 120-749

Republic of Korea

Microbial Strain Collection of Latvia (MSCL)

University of Latvia

Faculty of Biology

Blvd. Kronvalda 4

LV-1586 Riga

Latvia

National Bank for Industrial Microorganisms and

Cell Cultures (NBIMCC)

125, Tsarigradskochausse Blvd.

Block 2

1113 Sofia

Bulgaria

National Collection of Agricultural and Industrial

Microorganisms (NCAIM)

Department of Microbiology and Biotechnology

University of Horticulture and the Food Industry

Soml&oacute;i &ucirc;t 14-16

H-1118 Budapest

Hungary

National Collection of Type Cultures (NCTC)

Central Public Health Laboratory

61 Colindale Avenue

London, NW9 5HT

United Kingdom

National Collection of Yeast Cultures (NCYC)

AFRC Institute of Food Research

Norwich Laboratory

Colney Lane

Norwich NR4 7UA

United Kingdom

National Collections of Industrial and

Marine Bacteria Limited (NCIMB)

23 St. Machar Drive

Aberdeen AB2 1RY

Scotland, United Kingdom

National Institute of Bioscience and

Human-Technology (NIBH)

Agency of Industrial Science and Technology

Ministry of International Trade and Industry

1-3, Higashi 1-chome

Tsukuba-shi

Ibaraki-ken 305

Japan

Russian Collection of Microorganisms (VKM)

Prospekt Naouki, 5

142292 Puschino (Moscow Region)

Russian Federation

Russian National Collection of Industrial

Microorganisms (VKPM)

GNII Genetika

Dorozhny proezd. 1

Moscow 113545

Russian Federation

---SECTION---2406 Time of Making an Original Deposit

37 CFR 1.804 Time of making an original deposit.

(a) Whenever a biological material is specifically identified in an
application for patent as filed, an original deposit thereof may be made
at any time before filing the application for patent or, subject to
Section  1.809, during pendency of the application for patent.

(b) When the original deposit is made after the effective filing date of
an application for patent, the applicant must promptly submit a
statement from a person in a position to corroborate the fact, stating
that the biological material which is deposited is a biological material
specifically identified in the application as filed.

37 CFR 1.804 specifies the time for making an original deposit to
fulfill the requirements of  35 U.S.C. 112. For the reasons discussed
throughout this section, it is recommended that a deposit be made before
the filing date of the application.  However, for the purposes of
complying with the requirements of  35 U.S.C. 112, a deposit of a
biological material may be made at any time before filing the
application for patent or during the pendency of the application subject
to the conditions of  37 CFR 1.809.  Where a deposit is needed to
satisfy the requirements of  35 U.S.C. 112 and it is made during the
pendency of the application, it must be made no later than the time
period set by the examiner at the time the Notice of Allowance and Issue
Fee Due is mailed. A necessary deposit need not be made by an applicant
until the application is in condition for allowance so long as the
applicant provides a written assurance that an acceptable deposit will
be made on or before the payment of the issue fee. This written
assurance must provide sufficiently detailed information to convince the
examiner that there is no outstanding issue regarding deposits that
needs to be resolved.

These rules are equally applicable in the cases of international and
national stage applications filed under the Patent Cooperation Treaty.
Insofar as the rules do not permit post-issuance original deposits, the
failure to make an original deposit in an application cannot be cured by
filing a reissue application or instituting a reexamination proceeding.
However, if an amendment of claims in a reexamination proceeding raises
the need for a deposit, an original deposit may be made during the
reexamination proceeding.

---SECTION---2406.01 Description in Application Specification

37 CFR 1.804(a) specifies not only a permissible time frame for making
an original deposit, but also specifies that the biological material
deposited must be specifically identified in the application for patent
as filed. The requirement for a specific identification is consistent
with the description requirement of the first paragraph of  35 U.S.C.
112 and provides an antecedent basis for the biological material which
either has been or will be deposited before the patent is granted.

The description in the Lundak application as filed (now patent
4,594,325) provides a suitable illustration of the specific
identification and description which are required in an application as
filed. In that application, an immortal B-cell line was disclosed and
claimed. The cell line was referred to in the application, as filed, as
WI-L2-729 HF2.  The methods of obtaining and using this cell line were
also described in the application as filed.  A deposit of the cell line
was made with the American Type Culture Collection (ATCC) about a week
after the application was filed in the United States. The United States
Court of Appeals for the Federal Circuit held that the requirements of
access by the Office to a sample of the cell line during pendency, and
public access after grant, were met by Lundak's procedures. The Court
further held that the addition of information designating the
depository, accession number, and deposit date of the deposited cell
line in ATCC after the filing date did not violate the prohibition
against new matter in  35 U.S.C. 132. In re Lundak, 773 F.2d 1216, 227
USPQ 90 (Fed. Cir. 1985).  However, it must be clear from the
application as filed that the invention claimed and described in the
specification "was fully capable of being reduced to practice (i.e., no
technological problems, the resolution of which would require more than
ordinary skill and reasonable time, remained in order to obtain an
operative, useful process)." Feldman v. Aunstrup, 517 F.2d 1351, 1355,
186 USPQ 108, 113 (CCPA 1975), cert. denied, 424 U.S. 912 (1976).

---SECTION---2406.02 Deposit After Filing Date - Corroboration

When the original deposit is made after the effective filing date of an
application for patent, an applicant is required to promptly submit a
statement from a person in a position to corroborate that the biological
material which is deposited is a biological material specifically
identified in the application (the filing date of which is relied upon)
as filed. The nature of this corroboration will depend on the
circumstances in the particular application under consideration,
including the length of time between the application filing date and the
date of deposit. While few, if any, situations can be imagined where the
description requirement of  35 U.S.C. 112 can be satisfied where the
biological material was not in existence at the time of filing, the
rules will not preclude such a situation as there is no requirement in
the patent law that an actual reduction to practice occur as a condition
precedent to filing a patent application.

---SECTION---2406.03 Possible Loss of U.S. Filing Date in Other
Countries

Those applicants intending to file patent applications in a country
foreign to the United States relying upon biological material that must
be deposited to satisfy the requirements of  35 U.S.C. 112 when the
application is filed in the United States are cautioned that in many
countries the deposit must be made before the filing date of the
priority application in order to obtain foreign priority rights.  Thus,
while the deposit of a biological material subsequent to the effective
filing date of a United States application is sufficient to comply with 
35 U.S.C. 112, an applicant may not be able to rely on the filing date
of such a U.S. application if a patent is sought in certain countries
foreign to the United States.

---SECTION---2407 Replacement or Supplement of Deposit

37 CFR 1.805 Replacement or supplement of deposit.

(a) A depositor, after receiving notice during the pendency of an
application for patent, application for reissue patent or reexamination
proceeding, that the depository possessing a deposit either cannot
furnish samples thereof or can furnish samples thereof but the deposit
has become contaminated or has lost its capability to function as
described in the specification, shall notify the Office in writing, in
each application for patent or patent affected.  In such a case, or
where the Office otherwise learns, during the pendency of an application
for patent, application for reissue patent or reexamination proceeding,
that the depository possessing a deposit either cannot furnish samples
thereof or can furnish samples thereof but the deposit has become
contaminated or has lost its capability to function as described in the
specification, the need for making a replacement or supplemental deposit
will be governed by the same considerations governing the need for
making an original deposit under the provisions set forth in Section 
1.802(b).  A replacement or supplemental deposit made during the
pendency of an application for patent shall not be accepted unless it
meets the requirements for making an original deposit under these
regulations, including the requirement set forth under Section 
1.804(b).  A replacement or supplemental deposit made in connection with
a patent, whether or not made during the pendency of an application for
reissue patent or a reexamination proceeding or both, shall not be
accepted unless a certificate of correction under Section  1.323 is
requested by the patent owner which meets the terms of paragraphs  (b) 
and  (c)  of this section.

(b) A request for certificate of correction under this section shall not
be granted unless the certificate identifies:

(1) The accession number for the replacement or supplemental deposit;

(2) The date of the deposit; and

(3) The name and address of the depository.

(c) A request for a certificate of correction under this section shall
not be granted unless the request is made promptly after the replacement
or supplemental deposit has been made and the request:

(1) Includes a statement of the reason for making the replacement or
supplemental deposit;

(2) Includes a statement from a person in a position to corroborate the
fact, and stating that the replacement or supplemental deposit is of a
biological material which is identical to that originally deposited;

(3) Includes a showing that the patent owner acted dili gently --

(i) In the case of a replacement deposit, in making the deposit after
receiving notice that samples could no longer be furnished from an
earlier deposit; or

(ii) In the case of a supplemental deposit, in making the deposit after
receiving notice that the earlier deposit had become contaminated or had
lost its capability to function as described in the specification;

(4) Includes a statement that the term of the replacement or
supplemental deposit expires no earlier than the term of the deposit
being replaced or supplemented; and

(5) Otherwise establishes compliance with these regulations.

(d) A depositor s failure to replace a deposit, or in the case of a
patent, to diligently replace a deposit and promptly thereafter request
a certificate of correction which meets the terms of paragraphs (b) and
(c) of this section, after being notified that the depository possessing
the deposit cannot furnish samples thereof, shall cause the application
or patent involved to be treated in any Office proceeding as if no
deposit were made.

(e) In the event a deposit is replaced according to these regulations,
the Office will apply a rebuttable presumption of identity between the
original and the replacement deposit where a patent making reference to
the deposit is relied upon during any Office proceeding.

(f) A replacement or supplemental deposit made during the pendency of an
application for patent may be made for any reason.

(g) In no case is a replacement or supplemental deposit of a biological
material necessary where the biological material, in accordance with
Section  1.802(b), need not be deposited.

(h) No replacement deposit of a biological material is necessary where a
depository can furnish samples thereof but the depository for national
security, health or environmental safety reasons is unable to provide
samples to requesters outside of the jurisdiction where the depository
is located.

(i) The Office will not recognize in any Office proceeding a replacement
deposit of a biological material made by a patent owner where the
depository could furnish samples of the deposit being replaced.

37 CFR 1.805 relates to the deposit of a biological material to replace
or supplement a previous deposit. The term "replacement" is directed to
those situations where one deposit is being substituted for another. An
applicant may have greater latitude in replacing a deposit during the
pendency of an application than after the patent is granted. Replacement
will typically take place where the earlier deposit is no longer viable. 
The term "supplement" is directed to those situations where the earlier
deposit is still viable in the sense that it is alive and capable of
replication either directly or indirectly, but has lost a quality (e.g.,
purity, functionality) it allegedly possessed at the time the
application was filed. The procedures in these rules contemplate that
only the original depositor would have a right to replace or supplement
the original deposit.

---SECTION---2407.01 In a Pending Application

37 CFR 1.805(a) relates to the procedure for replacing or supplementing
a deposit with respect to a pending application or a patent.  An
applicant or patent owner is required to notify the Office when it
obtains information that the depository possessing a deposit cannot
furnish samples of the deposit to satisfy the requirements of  35 U.S.C.
112.  When the Office is so informed or otherwise becomes aware that
samples of the deposited material cannot be furnished by the depository,
the examiner will treat the application or reexamination proceeding,
whichever is applicable, as if no deposit existed. A replacement or
supplemental deposit will be accepted if it meets all the requirements
for making an original deposit.

It should be noted that in a pending application, an applicant need not
replace the identical material previously deposited, but may make an
original deposit of a biological material which is specifically
identified and described in the application as filed. Whether this
alternative deposit will meet the requirements of  35 U.S.C. 112 with
respect to the claimed subject matter must be resolved by the examiner
on a case-by-case basis. The conditions in  37 CFR 1.802(b) and  37 CFR
1.804 (b) must be satisfied.

---SECTION---2407.02 After a Patent Has Issued

A replacement deposit made in connection with an application for reissue
patent or a reexamination proceeding or both shall not be accepted
unless a certificate of correction is requested which meets the terms of 
37 CFR 1.805(b) and  37 CFR 1.805 (c)  for replacement deposits. Any
correction made to the original patent will be automatically
incorporated into the reissued or reexamined patent unless changes are
made during examination of the reissue application or reexamination
proceeding.

37 CFR 1.805(b) and  37 CFR 1.805(c) specify the procedures that a
patent owner may follow to ensure that a patent contains the appropriate
information about a deposited biological material in the event that a 
replacement or supplemental deposit is made after the patent is granted.
37 CFR 1.805(b) describes the information which must be contained in the
certificate of correction, whereas  37 CFR 1.805(c) describes the
information which must be provided in the request to make the
correction.

---SECTION---2407.03 Failure to Replace

37 CFR 1.805(d) sets forth the Office position that the failure to make
a replacement deposit in a case pending before the Office, for example a
reissue or reexamination proceeding, where a deposit is considered to be
necessary to satisfy the requirements of  35 U.S.C. 112, shall cause the
application or patent involved to be treated in any Office proceeding as
if no deposit were made.  The provisions of  37 CFR 1.805(g) indicate
that a replacement need not be made where, at the point in time when
replacement would otherwise be necessary, access to the necessary
biological material was otherwise available.  For example, a replacement
deposit would not be required under the circumstances where access to
the necessary biological material was established through commercial
suppliers.

---SECTION---2407.04 Treatment of Replacement

37 CFR 1.805(e) indicates that the Office will apply a rebuttable
presumption of identity between the replacement deposit and an original
deposit where a patent making reference to the deposit is relied on
during any Office proceeding. This means that where a replacement
deposit is permitted and made, the examiner will assume that the same
material as described in the patent is accessible from the identified
depository unless evidence to the contrary comes to the attention of the
Office.

An applicant for patent may make a replacement deposit during the
pendency of the application for any reason.  The provisions of  37 CFR
1.805(f) recognize that since an original deposit may be made during the
pendency of the application subject to the conditions of  37 CFR 1.809,
a replacement deposit logically cannot be held to any higher standard or
any further requirements.

---SECTION---2407.05 Exemption From Replacement

The provisions of  37 CFR 1.805(h) indicate that a replacement deposit
is not required even though the depository cannot furnish samples, under
certain conditions, to those requesting a sample outside of the
jurisdiction where the depository is located.  The conditions are
specified in this paragraph as being limited to national security,
health or environmental safety reasons.

---SECTION---2407.06 Replacement May Not Be Recognized

Finally,  37 CFR 1.805(i) indicates that the Office will not recognize
in any Office proceeding a replacement deposit made by the patent owner
where the depository could furnish samples of the original deposit being
replaced. The best evidence of what was originally deposited should not
be lost through destruction or replacement if made in association with
an existing patent. A supplemental deposit may be accepted in an Office
proceeding, however, depending on the circumstances in each case.

---SECTION---2408 Term of Deposit

37 CFR 1.806 Term of deposit.

A deposit made before or during pendency of an application for patent
shall be made for a term of at least thirty (30) years and at least five
(5) years after the most recent request for the furnishing of a sample
of the deposit was received by the depository.  In any case, samples
must be stored under agreements that would make them available beyond
the enforceable life of the patent for which the deposit was made.

The term of deposit must satisfy the requirements of the Budapest Treaty
which sets a term of at least 30 years from the date of deposit and at
least 5 years after the most recent request for the furnishing of a
sample of the deposit was received by the depository. In the event that
the 30-year term covers the 17-year term or 20-year term of the patent
plus 6 years to include the Statute of Limitations, no further
requirement is necessary.  Unless applicant indicates that the deposit
has been made under the Budapest Treaty, applicant must indicate the
term for which the deposit has been made.  The mere possibility of
patent term extension or extended litigation involving the patent should
not be considered in this analysis.

In the event that the 30-year term of deposit measured from the date of
deposit would necessarily terminate within the period of enforceability
of the patent (the normal 17-year term or 20-year term plus 6 years to
include the Statute of Limitations), samples must be stored under
agreements that would make them available beyond the enforceable life of
the patent (i.e., until 23 years after issuance or 26 years after
application filing) for which the deposit was made. No requirement
should be made as to any particular period of time beyond the
enforceable life of the patent.  The purpose of the requirement is to
insure that a deposited biological material necessary for the practice
of a patented invention would be available to the public after
expiration of the patent for which the deposit was made.  The term of
the deposit must comply with the requirements of each sentence of  37
CFR 1.806 whether or not the deposit is made under the Budapest Treaty.
A specific statement that the deposit complies with the second sentence
of this section is required only where the 30-year term would terminate
within the enforceable life of the patent.

---SECTION---2409 Viability of Deposit

37 CFR 1.807 Viability of deposit.

(a) A deposit of biological material that is capable of self-replication
either directly or indirectly must be viable at the time of deposit and
during the term of deposit.  Viability may be tested by the depository.
The test must conclude only that the deposited material is capable of
reproduction.  No evidence is necessarily required regarding the ability
of the deposited material to perform any function described in the
patent application.

(b) A viability statement for each deposit of a biological material
defined in paragraph (a) of this section not made under the Budapest
Treaty on the International Recognition of the Deposit of Microorganisms
for the Purposes of Patent Procedure must be filed in the application
and must contain:

(1) The name and address of the depository;

(2) The name and address of the depositor;

(3) The date of deposit;

(4) The identity of the deposit and the accession number given by the
depository;

(5) The date of the viability test;

(6) The procedures used to obtain a sample if the test is not done by
the depository; and

(7) A statement that the deposit is capable of reproduction.

(c) If a viability test indicates that the deposit is not viable upon
receipt, or the examiner cannot, for scientific or other valid reasons,
accept the statement of viability received from the applicant, the
examiner shall proceed as if no deposit has been made.  The examiner
will accept the conclusion set forth in a viability statement issued by
a depository recognized under Section  1.803(a).

37 CFR 1.807 requires that the deposit of biological material that is
capable of self-replication either directly or indirectly must be viable
at the time of deposit and during the term of deposit. This requirement
for viability is essentially a requirement that the deposited material
is capable of reproduction.  For the purpose of making a deposit under
these rules, there is no requirement that evidence be provided that the
deposited material is capable or has the ability to perform any function
described in the patent application. However, as with any other issue of
description or enablement, if the examiner has evidence or reason to
question the objective statements made in the patent application,
applicants may be required to demonstrate that the deposited biological
material will perform in the manner described.

Under the Budapest Treaty, there is a requirement that the deposit be
tested for viability before it is accepted.  Thus, a mere statement by
an applicant, an authorized representative of applicant or the assignee
that the deposit has been accepted under the Budapest Treaty would
satisfy  37 CFR 1.807.

For each deposit which is not made under the Budapest Treaty, a
viability statement must be filed in the patent application and contain
the information listed in paragraph (b) of this section. Under  37 CFR
1.807(c), the examiner will accept the conclusion set forth in a
viability statement which is issued by a depository recognized under  37
CFR 1.803(a). If the viability test indicates that the deposit is not
viable upon receipt, or the examiner cannot, for scientific or other
valid reasons, accept the statement of viability received from the
applicant, the examiner shall so notify the applicant stating the
reasons for not accepting the statement and proceed with the examination
process as if no deposit had been made.

---SECTION---2410 Furnishing of Samples

37 CFR 1.808 Furnishing of samples.

(a) A deposit must be made under conditions that assure that:

(1) Access to the deposit will be available during pendency of the
patent application making reference to the deposit to one determined by
the Commissioner to be entitled thereto under Section  1.14 and  35
U.S.C. 122, and

(2) Subject to paragraph (b) of this section, all restrictions imposed
by the depositor on the availability to the public of the deposited
material will be irrevocably removed upon the granting of the patent.

(b) The depositor may contract with the depository to require that
samples of a deposited biological material shall be furnished only if a
request for a sample, during the term of the patent:

(1) Is in writing or other tangible form and dated;

(2) Contains the name and address of the requesting party and the
accession number of the deposit; and

(3) Is communicated in writing by the depository to the depositor along
with the date on which the sample was furnished and the name and address
of the party to whom the sample was furnished.

(c) Upon request made to the Office, the Office will certify whether a
deposit has been stated to have been made under conditions which make it
available to the public as of the issue date of the patent grant
provided the request contains:

(1) The name and address of the depository;

(2) The accession number given to the deposit;

(3) The patent number and issue date of the patent referring to the
deposit; and

(4) The name and address of the requesting party.

---SECTION---2410.01 Conditions of Deposit

37 CFR 1.808 requires that the deposit of biological material be made
under two conditions:

(A) access to the deposit will be available during pendency of the
patent application making reference to the deposit to one determined by
the Commissioner to be entitled thereto under  37 CFR 1.14 and  35
U.S.C. 122, and

(B) with one exception, that all restrictions imposed by the depositor
on the availability to the public of the deposited biological material
be irrevocably removed upon the granting of the patent.

The one exception that is permitted is specified in  37 CFR
1.808(b)which permits the depositor to contract with the depository to
require that samples of a deposited biological material shall be
furnished only if a request for a sample, during the term of the patent, 
meets any one or all of the three conditions specified in this
paragraph.  These conditions are:

(A) the request is in writing or other tangible form and dated; and/or

(B) the request contains the name and address of the requesting party
and the accession number of the deposit; and/or

(C) the request is communicated in writing by the depository to the
depositor along with the date on which the sample was furnished and the
name and address of the party to whom the sample was furnished.

It should be noted that this exception to the general rule that all
restrictions will be removed must be strictly followed and that no
variations of this explicit exception will be accepted as meeting the
conditions of this section.  Although this exception is consistent with
the provisions in the Budapest Treaty and its implementing regulations
(Rule 11.4), other conditions on accessibility are permitted under the
Budapest Treaty as prescribed by national law. Consequently, the mere
indication that a deposit has been made under conditions prescribed by
the Budapest Treaty would satisfy all conditions of these regulations
except the requirement that all restrictions on access be removed on
grant of the patent.   Ex parte Hildebrand, 15 USPQ2d 1662 (Bd Pat. App.
& Int. 1990).

---SECTION---2410.02 Certification of Accessibility of Deposit

Since the mere description of a deposit or identity of a deposit in a
patent specification is not necessarily an indication that a requirement
for deposit was made or that a deposit which complies with these rules
has been made, accessibility to a deposited material referenced in a
patent may depend on the satisfaction of conditions not apparent on the
face of the patent. For these reasons, and upon request made to the
Patent and Trademark Office, the Office will certify whether a deposit
has been stated to have been made under conditions which would make it
available to the public as of the issue date of the patent grant
provided the request is made to the Director of Patent Examining Group
1640 or 1650, and contains the following information:

(A) the name and address of the depository;

(B) the accession number given to the deposit;

(C) the patent number and issue date of the patent referring to the
deposit; and

(D) the name and address of the requesting party.

For those deposits made pursuant to the Budapest Treaty, the World
Intellectual Property Organization provides a form (Form BP-12) for
requesting a certification of the availability of samples of deposited
microorganisms pursuant to Rule 11.3(a) of the Regulations under the
Budapest Treaty. Copies of this form are available from the Director of
Patent Examining Group 1640 or 1650.

---SECTION---2411 Examination Procedures

37 CFR 1.809 Examination procedures.

(a) The examiner shall determine pursuant to Section  1.104 in each
application for patent, application for reissue patent or reexamination
proceeding if a deposit is needed, and if needed, if a deposit actually
made is acceptable for patent purposes.  If a deposit is needed and has
not been made or replaced or supplemented in accordance with these
regulations, the examiner, where appropriate, shall reject the affected
claims under the appropriate provision of  35 U.S.C. 112, explaining why
a deposit is needed and/or why a deposit actually made cannot be
accepted.

(b) The applicant for patent or patent owner shall respond to a
rejection under paragraph (a) of this section by- 

(1) In the case of an applicant for patent, making an acceptable
original or replacement or supplemental deposit or assuring the Office
in writing that an acceptable deposit will be made on or before the date
of payment of the issue fee, or, in the case of a patent owner,
requesting a certificate of correction of the patent which meets the
terms of paragraphs (b) and (c) of Section  1.805, or

(2) Arguing why a deposit is not needed under the circumstances of the
application or patent considered and/or why a deposit actually made
should be accepted.  Other replies to the examiner s action shall be
considered non-responsive.  The rejection will be repeated until either
paragraph (b) (1) of this section is satisfied or the examiner is
convinced that a deposit is not needed.

(c) If an application for patent is otherwise in condition for allowance
except for a needed deposit and the Office has received a written
assurance that an acceptable deposit will be made on or before payment
of the issue fee, the Office will mail to the applicant a Notice of
Allowance and Issue Fee Due together with a requirement that the needed
deposit be made within three months.  The period for satisfying this
requirement is extendible under Section  1.136.  Failure to make the
needed deposit in accordance with this requirement will result in
abandonment of the application for failure to prosecute.

(d) For each deposit made pursuant to these regulations, the
specification shall contain:

(1) The accession number for the deposit;

(2) The date of the deposit;

(3) A description of the deposited biological material sufficient to
specifically identify it and to permit examination; and

(4) The name and address of the depository.

37 CFR 1.809 sets forth procedures that will be used by the examiner to
address a deposit issue.  The burden is initially on the Office to
establish that access to a biological material is necessary for the
satisfaction of the statutory requirements for patentability under  35
U.S.C. 112.  Once the Office has met this burden, the burden shifts to
the applicant or patent owner to demonstrate that access to such
biological material either is not necessary, or is already available, or
that a deposit of such material will be made in accordance with these
regulations.

---SECTION---2411.01 Rejections Based on Deposit Issue

Under  37 CFR 1.809(a), once the examiner has determined that access to
a biological material is necessary, and there is no information that
would support the conclusion that access is currently available in
accordance with these regulations, the examiner should make an
appropriate rejection under  35 U.S.C. 112 until such time as a deposit
in accordance with these regulations is actually made or a written
assurance is received in the patent application that such a deposit will
be made upon an indication of allowability of the application. The
examiner should clearly indicate the statutory basis for the rejection
and the reasons that are relied upon by the examiner to conclude that
the application does not comply with some requirement of  35 U.S.C. 112.
Although not exhaustive, the following grounds of rejection may be
applicable in appropriate circumstances:

(A) 35 U.S.C. 112, first paragraph - lack of an enabling disclosure
without access to a specific biological material. This ground of
rejection should be accompanied by evidence of scientific reasoning to
support the conclusion that a person skilled in the art could not make
or use the invention defined in and commensurate with the claims without
access to the specific biological material.

(B) 35 U.S.C. 112, first paragraph - description requirement.  This
ground of rejection typically arises in the context that the application
as filed does not contain a description to support an amendment to the
specification or claims. An amendment to the claims that is not
described in the application as filed would justify a rejection of the
affected claims under  35 U.S.C. 112, first paragraph.  If an amendment
is made to the application, other than the claims, that is not described
in the application as filed, this would justify an objection under  35
U.S.C. 112, first paragraph and/or  35 U.S.C. 132 (prohibition against
the introduction of new matter) and a requirement that the amendment be
canceled.

(C) 35 U.S.C. 112, first paragraph - best mode requirement.  This ground
of rejection will be rare in the ex parte examination process because it
requires (1) a finding by the examiner that, at the time the application
was filed, the inventor(s) knew of a specific material that was
considered by the inventor(s) to be better than any other, and (2) if a
best mode was contemplated at that time, that the inventor(s) concealed
the best mode (accidentally or intentionally) by failing to adequately
describe that best mode.  See Chemcast Corp. v. Arco Industries Corp.,
913 F.2d 923, 16 USPQ2d 1033 (Fed. Cir. 1990).  The Court of Appeals for
the Federal Circuit has at least twice resolved a best mode issue
arising in the context of a biotechnology invention in favor of the
patentee.  See Scripps Clinic and Research Foundation v. Genentech Inc.,
927 F.2d 1565, 18 USPQ2d 1001 (Fed. Cir. 1991) with respect to
monoclonal antibodies, and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd.,
927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991) with respect to mammalian
host cells.

(D) 35 U.S.C. 112, second paragraph - indefiniteness. This ground of
rejection, as applied to a deposit issue, requires the examiner to
provide reasons why the terms in the claims and/or scope of the
invention are unclear because of an incomplete or inaccurate description
or the absence of a reference to a biological material.

(E) 35 U.S.C. 112, second paragraph - claims do not set forth what
applicants regard as their invention.  This ground of rejection requires
the citation of some evidence, not contained in the application as
filed, that the claims do not set forth what applicants regard as their
invention. In re Prater, 415 F.2d 1393, 162 USPQ 541 (CCPA 1969).  Any
disagreement between the content of the application disclosure and the
scope of the claims should be addressed under  35 U.S.C. 112, first
paragraph.  See In re Ehrreich, 590 F.2d 902, 200 USPQ 504 (CCPA 1979). 

Where a deposit is required to satisfy  35 U.S.C. 112, a deposit must be
made in accordance with these regulations.  A deposit accepted in any
IDA under the Budapest Treaty shall be accepted for patent purposes if
made under conditions which comply with  37 CFR 1.806 and  37 CFR
1.808(a) concerning term of deposit and permissible conditions on access
once the patent is granted.

---SECTION---2411.02 Replies to Rejections Based on Deposit Issue

Once a rejection under  35 U.S.C. 112 has been made by the examiner
directed to the absence of access to a biological material, applicant
may reply, pursuant to  37 CFR 1.809 (b)(1), by either making an
acceptable original or replacement deposit in accordance with these
regulations, or assuring the Office in writing that an acceptable
deposit will be made on or before the date of payment of the issue fee,
or by submitting an argument of why a deposit is not required under the
circumstances of the application being considered.  Other replies to
such a rejection by the examiner shall be considered nonresponsive and
may result in abandonment of the application.  The rejection will be
repeated and made final until the requirements of  37 CFR 1.809(b)(1)
are satisfied or the examiner is convinced that a deposit is not
required for the claimed subject matter. Once the rejection is made
final, the requirements of  37 CFR 1.116 apply to further submissions.
The written assurance will be accepted by the Office if it clearly
states that an acceptable deposit will be made within the required time
and under conditions which satisfy these rules. In the case that an
acceptable written assurance has been made by the applicant, the
rejection under 35 U.S.C 112 directed to the absence of access to the
biological material should be removed. 

---SECTION---2411.03 Application in Condition for Allowance Except for
Deposit

As set forth in  37 CFR 1.809(c), in the event that an application for
patent is otherwise in condition for allowance except for a required
deposit and the Office has received a written assurance that an
acceptable deposit will be made, the Office will mail to the applicant a
requirement that the required deposit be made within 3 months together
with the Notice of Allowance and Issue Fee Due. Although the period for
paying the issue fee cannot be extended under the provisions of  37 CFR
1.136, the period for satisfying the requirement to make an acceptable
deposit may be extended under the provisions of that section.  Failure
to make the needed deposit in accordance with this requirement may be
considered a failure to prosecute the application under  35 U.S.C. 133
and result in abandonment of the application. Once the deposit has been
made, information regarding the deposit, such as the name of the
depository, the accession number and the date of the deposit, that is to
be added to the specification must be added by means of filing an
amendment under the provisions of  37 CFR 1.312. A petition and fee are
required if the  37 CFR 1.312 amendment is filed after the issue fee has
been paid.

---SECTION---2411.04 After a Patent Has Been Granted

In a proceeding involving a patent, it may not be possible to request a
certificate of correction of the patent which meets the terms of  37 CFR
1.805(b) and  37 CFR 1.805(c). For example, if the patent owner is on
notice that samples of an original deposit can no longer be furnished by
the depository, failure to diligently make a replacement deposit will
preclude grant of a certificate of correction. A replacement deposit
subsequently made will not be recognized by the Office nor will a
request for certificate of correction, even if made promptly thereafter,
be granted.  It would also not be possible to request a certificate of
correction of the patent which meets the terms of  37 CFR 1.805(b) and 
37 CFR 1.805(c) where no original deposit was made before or during the
pendency of the application which matured into the patent.

A patent defective because of lack of a necessary deposit is necessarily
fatally defective for failure to comply with the first paragraph of  35
U.S.C. 112. Reissue is not available in such cases. See In re Hay, 534
F.2d 917, 189 USPQ 790 (CCPA 1976). Whether reissue is available where a
biological material necessary for compliance with  35 U.S.C. 112 was
known and readily available at the time of issuance of the patent and
subsequently ceased to be readily available is problematic. 
Nevertheless, the rules do not provide for post-issuance original
deposits.

Where an applicant for patent has any doubt as to whether access to a
biological material specifically identified in the specification is
necessary to satisfy  35 U.S.C. 112 or whether such a material, while
currently freely available, may become unavailable in the future, the
applicant would be well-advised to make a deposit thereof before any
patent issues.  Similarly, where a patent owner has any doubt whether a
deposit referred to in the specification is a biological material
necessary to satisfy  35 U.S.C. 112 and, if the material is necessary,
whether it is otherwise known and readily available, the patent owner
would be well-advised to follow the procedures set forth in  37 CFR
1.805(b) and  37 CFR 1.805(c) after receiving the notice specified in
those paragraphs.

---SECTION---2411.05 Content of Application with Respect to Deposited
Material

37 CFR 1.809(d) sets forth the requirements for the content of the
specification with respect to a deposited biological material. 
Specifically, the specification shall contain the accession number for
the deposit, the date of the deposit, the name and address of the
depository, and a description of the deposited biological material
sufficient to specifically identify it and to permit examination. The
description also must be sufficient to permit verification that the
deposited biological material is in fact that disclosed.  Once the
patent issues, the description must be sufficient to aid in the
resolution of questions of infringement.  As a general rule, the more
information that is provided about a particular deposited biological
material, the better the examiner will be able to compare the identity
and characteristics of the deposited biological material with the prior
art.

---SECTION---2420 The Requirements for Patent Applications Containing
Nucleotide Sequence and/or Amino Acid Sequence Disclosures - the
Sequence Rules

Prior to the effective date (October 1, 1990) and implementation of the
sequence rules (37 CFR 1.821 through 1.825), applications for patents
that included nucleotide or amino acid sequence information posed
special problems for the Office.  While not related to the disclosure
requirements of an invention, problems existed in the presentation,
examination and printing of nucleotide and amino acid sequence data that
appeared in patent applications because of the lack of uniformity in
submission of sequence data to the Office and the impracticality of
properly searching and examining sequences submitted in paper form.  In
summary, the diversity and complexity of nucleotide and amino acid
sequence data resulted in searching and analysis difficulties both
within the Office and outside the Office, decreased accuracy of search
and reproduction and increased costs. These difficulties made the
development and implementation of the sequence rules a critical
necessity for the Office. As such, the Office amended its regulations to
establish a standardized format for descriptions of nucleotide and amino
acid sequence data submitted as a part of patent applications, in
conjunction with the required submission of that data in computer
readable form.  The final rules were published in the Federal Register
at 55 FR 18230 (May 1, 1990) and in the Official Gazette at 1114 O.G. 29
(May 15, 1990). The sequence rules went into effect on October 1, 1990.
The sequence rules were subsequently revised effective July 1, 1998. See
63 FR 29634 (June 1, 1998) and 1121 O.G. 82 (June 23, 1998)

---SECTION---2421 Overview of the Sequence Rules

---SECTION---2421.01 Applications Affected

The sequence rules require the use of standard symbols and a standard
format for sequence data in most sequence-type patent applications. They
further require the submission of that data in computer readable form. 
Compliance is required for most disclosures of sequence data in new
applications filed on or after October 1, 1990. The revised sequence
rules apply to most new applications filed on or after July 1, 1998. See
the final rule publications as cited in MPEP Section  2420 for more
detailed applicability information.

The Office encourages voluntary compliance for applications not subject
to the rules, but all aspects of the rules must be complied with before
data will be entered into the database. This includes submission of all
statements required by the rules. In exceptional circumstances, it
should be noted that the Office may waive the rules via a  37 CFR 1.183
petition.

---SECTION---2421.02 Summary of the Requirements of the Sequence Rules

Basically, the sequence rules define a set of symbols and procedures
that are both mandatory and the only way that an applicant is permitted
to describe information about a sequence that falls within the
definitions used in the rules.  Thus,  37 CFR 1.821 defines a sequence
for the purpose of the rules, the requirements for specific symbols,
formats, paper and computer readable copies of the sequence, and the
deadlines for complying with the requirements.  37 CFR 1.822 to  37 CFR
1.824 set forth detailed descriptions of the requirements that are
mandatory for the presentation of sequence data, and  37 CFR 1.825 sets
forth procedures that are available to an applicant in the event that
amendments to the sequence information or replacement of the computer
readable copy become necessary. 

The sequence rules embrace all unbranched nucleotide sequences with ten
or more bases and all unbranched, non-D amino acid sequences with four
or more amino acids. The rules apply to all sequences in a given
application, whether claimed or not. All such sequences are relevant for
the purposes of building a comprehensive database and properly assessing
prior art. It is therefore essential that all sequences, whether only
disclosed or also claimed, be included in the database.

---SECTION---2421.03 Notification of a Failure to Comply

With respect to the Office's determination of compliance with the
sequence rules and the opportunities afforded applicants to satisfy the
requirements of the rules, applicants will be notified of easily
detectable deficiencies early in the application process. Deficiencies
of a more sophisticated nature will likely only be detected by the
examiner to whom the application is assigned.  Applicants whose computer
readable forms are damaged in the mail, are not readable, or are missing
mandatory elements will be notified shortly after receipt of the
application by the Office. Other errors or inconsistencies will be noted
by the examiner early in the examination process. Upon detection of
damage or a deficiency, a notice will be sent to the applicant detailing
the damage or deficiency and setting at least a 30-day period for reply.
The period for reply will usually be 1 month.  However, if the notice is
sent out with an Office communication having a longer period for reply,
the period for reply may be longer than 1 month, e.g., where the notice
is sent with an Office action on the merits setting a 3-month period for
reply. Extensions of time in which to reply will be available pursuant
to  37 CFR 1.136.  When an action by the applicant, such as a reply to a
Notice to Comply from the Office, is determined to be a bona fide
attempt to comply with the rules and it is apparent that compliance with
some requirement has inadvertently been omitted, the applicant may be
given a new time period to correct the omission. See  37 CFR 1.135(c). 
The relevant form paragraphs and a copy of the Notice to Comply to be
used in applications subject to the sequence rules are included in MPEP
Section  2427 through Section  2427.02.

A notification of a failure to comply with the sequence rules will
usually be accompanied by an analysis of a submitted computer readable
form. Any inquiries regarding a specific computer readable form that has
been processed by the Office should be directed to the Systems Branch of
the Chemical/Biotechnology Division of the Scientific and Technical
Information Center.

---SECTION---2421.04 Future Changes to the Sequence Rules

With general regard to the symbols and format to be used for nucleotide
and/or amino acid sequence data set forth in  37 CFR 1.822 and the form
and format for sequence submissions in computer readable form set forth
in  37 CFR 1.824, the Office intends to accommodate progress in the
areas of both standardization and computerization as they relate to
sequence data by subsequently amending the rules to take into account
any such progress.  This progress will probably be reflected in the
refinement of or liberalization of the rules.  For example, progress in
the area of the standardization of sequence data will likely result in a
more comprehensive rule.  For example, the D-amino acids and branched
sequences that are currently excluded from the rule may, in the future,
be brought within the scope of the rule once the necessary
standardization technology becomes available. As a further example, the
computer readable form is currently limited to certain forms of
electronic media, but it can readily be seen that progress in the
technology for developing databases of the type the Office has
envisioned will likely permit a broadening of the permissible types of
computer readable forms that may be submitted. The same can be said for
the computer/operating-system configurations that are currently
permitted by the rules.  As the Office becomes able to provide greater
refinement and liberality in these areas, the Office will do so by the
publication of notices in the Official Gazette or formal rulemaking
proposals, as appropriate.

---SECTION---2422 Nucleotide and/or Amino Acid Sequence Disclosures in
Patent Applications

37 CFR 1.821 Nucleotide and/or amino acid sequence disclosures in patent
applications.

(a) Nucleotide and/or amino acid sequences as used in Section Section 
1.821 through 1.825 are interpreted to mean an unbranched sequence of
four or more amino acids or an unbranched sequence of ten or more
nucleotides. Branched sequences are specifically excluded from this
definition. Sequences with fewer than four specifically defined
nucleotides or amino acids are specifically excluded from this section.
"Specifically defined" means those amino acids other than "Xaa" and
those nucleotide bases other than "n" defined in accordance with the
World Intellectual Property Organization (WIPO) Handbook on Industrial
Property Information and Documentation, Standard ST.25: Standard for the
Presentation of Nucleotide and Amino Acid Sequence Listings in Patent
Applications (1998), including Tables 1 through 6 in Appendix 2, herein
incorporated by reference. (Hereinafter "WIPO Standard ST.25 (1998)'').
This incorporation by reference was approved by the Director of the
Federal Register in accordance with  5 U.S.C. 552(a) and 1 CFR part 51.
Copies of WIPO Standard ST.25 (1998) may be obtained from the World
Intellectual Property Organization; 34 chemin des Colombettes; 1211
Geneva 20 Switzerland. Copies of ST.25 may be inspected at the Patent
Search Room; Crystal Plaza 3, Lobby Level; 2021 South Clark Place;
Arlington, VA 22202. Copies may also be inspected at the Office of the
Federal Register, 800 North Capitol Street, NW, Suite 700, Washington,
DC. Nucleotides and amino acids are further defined as follows:

(1) Nucleotides: Nucleotides are intended to embrace only those
nucleotides that can be represented using the symbols set forth in WIPO
Standard ST.25 (1998), Appendix 2, Table 1. Modifications, e.g.,
methylated bases, may be described as set forth in WIPO Standard ST.25
(1998), Appendix 2, Table 2, but shall not be shown explicitly in the
nucleotide sequence.

(2) Amino acids: Amino acids are those L-amino acids commonly found in
naturally occurring proteins and are listed in WIPO Standard ST.25
(1998), Appendix 2, Table 3. Those amino acid sequences containing
D-amino acids are not intended to be embraced by this definition. Any
amino acid sequence that contains post-translationally modified amino
acids may be described as the amino acid sequence that is initially
translated using the symbols shown in WIPO Standard ST.25 (1998),
Appendix 2, Table 3 with the modified positions; e.g., hydroxylations or
glycosylations, being described as set forth in WIPO Standard ST.25
(1998), Appendix 2, Table 4, but these modifications shall not be shown
explicitly in the amino acid sequence. Any peptide or protein that can
be expressed as a sequence using the symbols in WIPO Standard ST.25
(1998), Appendix 2, Table 3 in conjunction with a description in the
Feature section to describe, for example, modified linkages, cross links
and end caps, non-peptidyl bonds, etc., is embraced by this definition.

(b) Patent applications which contain disclosures of nucleotide and/or
amino acid sequences, in accordance with the definition in paragraph (a)
of this section, shall, with regard to the manner in which the
nucleotide and/or amino acid sequences are presented and described,
conform exclusively to the requirements of Section Section  1.821
through 1.825.

(c) Patent applications which contain disclosures of nucleotide and/or
amino acid sequences must contain, as a separate part of the disclosure,
a paper copy disclosing the nucleotide and/or amino acid sequences and
associated information using the symbols and format in accordance with
the requirements of Section Section  1.822 and 1.823. This paper copy is
hereinafter referred to as the "Sequence Listing." Each sequence
disclosed must appear separately in the "Sequence Listing." Each
sequence set forth in the "Sequence Listing" shall be assigned a
separate sequence identifier. The sequence identifiers shall begin with
1 and increase sequentially by integers. If no sequence is present for a
sequence identifier, the code "000" shall be used in place of the
sequence. The response for the numeric identifier &lt;160&gt; shall
include the total number of SEQ ID NOs, whether followed by a sequence
or by the code "000."

(d) Where the description or claims of a patent application discuss a
sequence that is set forth in the "Sequence Listing" in accordance with
paragraph (c) of this section, reference must be made to the sequence by
use of the sequence identifier, preceded by "SEQ ID NO:" in the text of
the description or claims, even if the sequence is also embedded in the
text of the description or claims of the patent application.

(e) A copy of the "Sequence Listing" referred to in paragraph (c) of
this section must also be submitted in computer readable form in
accordance with the requirements of Section  1.824. The computer
readable form is a copy of the "Sequence Listing" and will not
necessarily be retained as a part of the patent application file. If the
computer readable form of a new application is to be identical with the
computer readable form of another application of the applicant on file
in the Patent and Trademark Office, reference may be made to the other
application and computer readable form in lieu of filing a duplicate
computer readable form in the new application if the computer readable
form in the other application was compliant with all of the requirements
of these rules. The new application shall be accompanied by a letter
making such reference to the other application and computer readable
form, both of which shall be completely identified. In the new
application, applicant must also request the use of the compliant
computer readable "Sequence Listing" that is already on file for the
other application and must state that the paper copy of the "Sequence
Listing" in the new application is identical to the computer readable
copy filed for the other application.

(f) In addition to the paper copy required by paragraph (c) of this
section and the computer readable form required by paragraph (e) of this
section, a statement that the content of the paper and computer readable
copies are the same must be submitted with the computer readable form,
e.g., a statement that "the information recorded in computer readable
form is identical to the written sequence listing."

(g) If any of the requirements of paragraphs (b) through (f) of this
section are not satisfied at the time of filing under  35 U.S.C. 111(a)
or at the time of entering the national stage under  35 U.S.C. 371,
applicant will be notified and given a period of time within which to
comply with such requirements in order to prevent abandonment of the
application. Any submission in reply to a requirement under this
paragraph must be accompanied by a statement that the submission
includes no new matter.

(h) If any of the requirements of paragraphs (b) through (f) of this
section are not satisfied at the time of filing an international
application under the Patent Cooperation Treaty (PCT), which application
is to be searched by the United States International Searching Authority
or examined by the United States International Preliminary Examining
Authority, applicant will be sent a notice necessitating compliance with
the requirements within a prescribed time period. Any submission in
reply to a requirement under this paragraph must be accompanied by a
statement that the submission does not include matter which goes beyond
the disclosure in the international application as filed. If applicant
fails to timely provide the required computer readable form, the United
States International Searching Authority shall search only to the extent
that a meaningful search can be performed without the computer readable
form and the United States International Preliminary Examining Authority
shall examine only to the extent that a meaningful examination can be
performed without the computer readable form.

37 CFR 1.821 incorporates by reference the World Intellectual Property
Organization (WIPO) Handbook on Industrial Property Information and
Documentation, Standard ST.25 (1998), including Tables 1 through 6 of
Appendix 2. Copies may be obtained from the World Intellection Property
Organization; 34 chemin des Colombettes; 1211 Geneva 20 Switzerland.
Copies may be inspected at the Patent Search Room; Crystal Plaza 3,
Lobby Level; 2021 South Clark Place; Arlington, VA 22202. Copies may
also be inspected at the Office of the Federal Register, 800 North
Capitol Street, NW, Suite 700, Washington, DC 20408. These tables are
reproduced below.

WIPO Standard ST.25 (1998), Appendix 2, Table 1, provides that the bases
of a nucleotide sequence should be represented using the following
one-letter code for nucleotide sequence characters:

Table 1: List of Nucleotides

Symbol	Meaning	Origin of designation

 a	a	adenine

 g	g	guanine

 c	c	cytosine

 t	t	thymine

 u	u	uracil

 r	g or a	purine

 y	t/u or c	pyrimidine

 m	a or c	amino

 k	g or t/u	keto

 s	g or c	strong interactions 3H-bonds

 w	a or t/u	weak interactions 2H-bonds

 b	g or c or t/u	not a

 d	a or g or t/u	not c

 h	a or c or t/u	not g

 v	a or g or c	not t, not u

 n	a or g or c or t/u, unknown, or other	any

WIPO Standard ST.25 (1998), Appendix 2, Table 2, provides that modified
bases may be represented as the corresponding unmodified bases in the
sequence itself, if the modified base is one of those listed below and
the modification is further described in the Feature section of the
Sequence Listing. The codes from the list below may be used in the
description (i.e., the specification and drawing, or in the Sequence
Listing) but these codes may not be used in the sequence itself.

Table 2:  List of Modified Nucleotides

Symbol	Meaning

 ac4c	4-acetylcytidine

 chm5u	5-(carboxyhydroxymethyl)uridine

 cm	2'-O-methylcytidine

 cmnm5s2u	5-carboxymethylaminomethyl-2-thiouridine

 cmnm5u	5-carboxymethylaminomethyluridine

 d	dihydrouridine

 fm	2'-O-methylpseudouridine

 gal q	beta, D-galactosylqueuosine

 gm	2'-O-methylguanosine

 i	inosine

 i6a	N6-isopentenyladenosine

 m1a	1-methyladenosine

 m1f	1-methylpseudouridine

 m1g	1-methylguanosine

 m1i	1-methylinosine

 m22g	2,2-dimethylguanosine

 m2a	2-methyladenosine

 m2g	2-methylguanosine

 m3c	3-methylcytidine

 m5c	5-methylcytidine

 m6a	N6-methyladenosine

 m7g	7-methylguanosine

 mam5u	5-methylaminomethyluridine

 mam5s2u	5-methoxyaminomethyl-2-thiouridine

 man q	beta, D-mannosylqueuosine

 mcm5s2u	5-methoxycarbonylmethyl-2-thiouridine

 mcm5u	5-methoxycarbonylmethyluridine

 mo5u	5-methoxyuridine

 ms2i6a	2-methylthio-N6-isopentenyladenosine

 ms2t6a	
N-((9-beta-D-ribofuranosyl-2-methylthiopurine-6-yl)carbamoyl)threonine

 mt6a	N-((9-beta-D-ribofuranosylpurine-6-yl)N-methylcarbamoyl)threonine

 mv	uridine-5-oxyacetic acid-methylester

 o5u	uridine-5-oxyacetic acid

 osyw	wybutoxosine

 p	pseudouridine

 q	queuosine

 s2t	5-methyl-2-thiouridine

 s2c	2-thiocytidine

 s2t	5-methyl-2-thiouridine

 s2u	2-thiouridine

 s4u	4-thiouridine

 t	5-methyluridine

 t6a	N-((9-beta-D-ribofuranosylpurine-6-yl)-carbamoyl)threonine

 tm	2'-O-methyl-5-methyluridine

 um	2'-O-methyluridine

 yw	wybutosine

 x	3-(3-amino-3-carboxy-propyl)uridine, (acp3)u

WIPO Standard ST.25 (1998), Appendix 2, Table 3, provides that the amino
acids should be represented using the following three-letter code with
the first letter as a capital.

Table 3:  List of Amino Acids

Symbol	Meaning

Ala	Alanine

Cys	Cysteine

Asp	Aspartic Acid

Glu	Glutamic Acid

Phe	Phenylalanine

Gly	Glycine

His	Histidine

Ile	Isoleucine

Lys	Lysine

Leu	Leucine

Met	Methionine

Asn	Asparagine

Pro	Proline

Gln	Glutamine

Arg	Arginine

Ser	Serine

Thr	Threonine

Val	Valine

Trp	Tryptophan

Tyr	Tyrosine

Asx	Asp or Asn

Glx	Glu or Gln

Xaa	unknown or other

WIPO Standard ST.25 (1998), Appendix 2, Table 4, provides that modified
and unusual amino acids may be represented as the corresponding
unmodified amino acids in the sequence itself if the modified or unusual
amino acid is one of those listed below and the modification is further
described in the Feature section of the Sequence Listing. The codes from
the list below may be used in the description (i.e., the specification
and drawings, or in Sequence Listing) but these codes may not be used in
the sequence itself.

Table 4:  List of Modified and Unusual Amino Acids

Symbol	Meaning

Aad	2-Aminoadipic acid

 bAad	3-Aminoadipic acid

 bAla 	beta-Alanine, beta-Aminopropionic acid

Abu	2-Aminobutyric acid

 4Abu	4-Aminobutyric acid, piperidinic acid

Acp	6-Aminocaproic acid

Ahe	2-Aminoheptanoic acid

Aib	2-Aminoisobutyric acid

 bAib	3-Aminoisobutyric acid

Apm	2-Aminopimelic acid

Dbu	2,4-Diaminobutyric acid

Des	Desmosine

Dpm	2,2' -Diaminopimelic acid

Dpr	2,3-Diaminopropionic acid

EtGly	N-Ethylglycine

EtAsn	N-Ethylasparagine

Hyl	Hydroxylysine

 aHyl	allo-Hydroxylysine

 3Hyp	3-Hydroxyproline

 4Hyp	4-Hydroxyproline

Ide	Isodesmosine

 aIle	allo-Isoleucine

MeGly	N-Methylglycine, sarcosine

MeIle	N-Methylisoleucine

MeLys	6-N-Methyllysine

MeVal	N-Methylvaline

Nva	Norvaline

Nle	Norleucine

Orn	Ornithine

WIPO Standard ST.25 (1998), Appendix 2, Table 5, provides for feature
keys related to DNA sequences.

Table 5:  List of Feature Keys Related to Nucleotide Sequences

Key	Description

 allele	a related individual or strain contains stable, alternative
forms of the same gene which differs from the presented sequence at this
location (and perhaps others)

 attenuator	(1)  region of DNA at which regulation of termination of
transcription occurs, which controls the expression of some bacterial
operons; (2)  sequence segment located between the promoter and the
first structural gene that causes partial termination of transcription

C_region	constant region of immunoglobulin light and heavy chains, and
T-cell receptor alpha, beta, and gamma chains; includes one or more
exons depending on the particular chain

CAAT_signal	CAAT box; part of a conserved sequence located about 75 bp
up-stream of the start point of eukaryotic transcription units which may
be involved in RNA polymerase binding; consensus=GG (C or T) CAATCT

CDS	coding sequence; sequence of nucleotides that corresponds with the
sequence of amino acids in a protein (location includes stop codon);
feature includes amino acid conceptual translation

 conflict	independent determinations of the "same" sequence differ at
this site or region

D-loop	displacement loop; a region within mitochondrial DNA in which a
short stretch of RNA is paired with one strand of DNA, displacing the
original partner DNA strand in this region; also used to describe the
displacement of a region of one strand of duplex DNA by a single
stranded invader in the reaction catalyzed by RecA protein

D-segment	diversity segment of immunoglobulin heavy chain, and T-cell
receptor beta chain

 enhancer	a cis-acting sequence that increases the utilization of (some)
eukaryotic promoters, and can function in either orientation and in any
location (upstream or downstream) relative to the promoter

 exon	region of genome that codes for portion of spliced mRNA; may
contain 5'UTR, all CDSs, and 3'UTR

GC_signal	GC box; a conserved GC-rich region located upstream of the
start point of eukaryotic transcription units which may occur in
multiple copies or in either orientation; consensus=GGGCGG

 gene	region of biological interest identified as a gene and for which a
name has been assigned

 iDNA	intervening DNA; DNA which is eliminated through any of several
kinds of recombination

 intron	a segment of DNA that is transcribed, but removed from within
the transcript by splicing together the sequences (exons) on either side
of it

J_segment	joining segment of immunoglobulin light and heavy chains, and
T-cell receptor alpha, beta, and gamma chains

LTR	long terminal repeat, a sequence directly repeated at both ends of a
defined sequence, of the sort typically found in retroviruses

 mat_peptide	mature peptide or protein coding sequence; coding sequence
for the mature or final peptide or protein product following
post-translational modification; the location does not include the stop
codon (unlike the corresponding CDS)

 misc_binding	site in nucleic acid which covalently or non-covalently
binds another moiety that cannot be described by any other Binding key
(primer_bind or protein_bind)

 misc_difference	feature sequence is different from that presented in
the entry and cannot be described by any other Difference key (conflict,
unsure, old_sequence, mutation, variation, allele, or modified_base)

 misc_feature	region of biological interest which cannot be described by
any other feature key; a new or rare feature

 misc_recomb	site of any generalized, site-specific or replicative
recombination event where there is a breakage and reunion of duplex DNA
that cannot be described by other recombination keys (iDNA and virion)
or qualifiers of source key (/insertion_seq, /transposon, /proviral)

 misc_RNA	any transcript or RNA product that cannot be defined by other
RNA keys (prim_transcript, precursor_RNA, mRNA, 5'clip, 3'clip, 5'UTR,
3'UTR, exon, CDS, sig_peptide, transit_peptide, mat_peptide, intron,
polyA_site, rRNA, tRNA, scRNA, and snRNA)

 misc_signal	any region containing a signal controlling or altering gene
function or expression that cannot be described by other Signal keys
(promoter, CAAT_signal, TATA_signal, -35_signal, -10_signal, GC_signal,
RBS, polyA_signal, enhancer, attenuator, terminator, and rep_origin)

 misc_structure	any secondary or tertiary structure or conformation that
cannot be described by other Structure keys (stem_loop and D-loop)

 modified_base	the indicated nucleotide is a modified nucleotide and
should be substituted for by the indicated molecule (given in the
mod_base qualifier value)

 mRNA	messenger RNA; includes 5' untranslated region (5'UTR), coding
sequences (CDS, exon) and 3' untranslated region (3'UTR)

 mutation	a related strain has an abrupt, inheritable change in the
sequence at this location

N_region	extra nucleotides inserted between rearranged immunoglobulin
segments

 old_sequence	the presented sequence revises a previous version of the
sequence at this location

 polyA_signal	recognition region necessary for endonuclease cleavage of
an RNA transcript that is followed by polyadenylation; consensus=AATAAA

 polyA_site	site on an RNA transcript to which will be added adenine
residues by post-transcriptional polyadenylation

 precursor_RNA	any RNA species that is not yet the mature RNA product;
may include 5' clipped region (5'clip), 5' untranslated region (5'UTR),
coding sequences (CDS, exon), intervening sequences (intron), 3'
untranslated region (3'UTR), and 3' clipped region (3'clip)

 prim_transcript	primary (initial, unprocessed) transcript; includes 5'
clipped region (5'clip), 5' untranslated region (5'UTR), coding
sequences (CDS, exon), intervening sequences (intron), 3' untranslated
region (3'UTR), and 3' clipped region (3'clip)

 primer_bind	non-covalent primer binding site for initiation of
replication, transcription, or reverse transcription; includes site(s)
for synthetic, for example, PCR primer elements

 promoter	region on a DNA molecule involved in RNA polymerase binding to
initiate transcription

 protein_bind	non-covalent protein binding site on nucleic acid

RBS	ribosome binding site

 repeat_region	region of genome containing repeating units

 repeat_unit	single repeat element

 rep_origin	origin of replication; starting site for duplication of
nucleic acid to give two identical copies

 rRNA	mature ribosomal RNA; the RNA component of the ribonucleoprotein
particle (ribosome) which assembles amino acids into proteins

S_region	switch region of immunoglobulin heavy chains; involved in the
rearrangement of heavy chain DNA leading to the expression of a
different immunoglobulin class from the same B-cell

 satellite	many tandem repeats (identical or related) of a short basic
repeating unit; many have a base composition or other property different
from the genome average that allows them to be separated from the bulk
(main band) genomic DNA

 scRNA	small cytoplasmic RNA; any one of several small cytoplasmic RNA
molecules present in the cytoplasm and (sometimes) nucleus of a
eukaryote

 sig_peptide	signal peptide coding sequence; coding sequence for an
N-terminal domain of a secreted protein; this domain is involved in
attaching nascent polypeptide to the membrane; leader sequence

 snRNA	small nuclear RNA; any one of many small RNA species confined to
the nucleus; several of the snRNAs are involved in splicing or other RNA
processing reactions

 source	identifies the biological source of the specified span of the
sequence; this key is mandatory; every entry will have, as a minimum, a
single source key spanning the entire sequence; more than one source key
per sequence is permissable

 stem_loop	hairpin; a double-helical region formed by base-pairing
between adjacent (inverted) complementary sequences in a single strand
of RNA or DNA

STS	Sequence Tagged Site; short, single-copy DNA sequence that
characterizes a mapping landmark on the genome and can be detected by
PCR; a region of the genome can be mapped by determining the order of a
series of STSs

TATA_signal	TATA box; Goldberg-Hogness box; a conserved AT-rich septamer
found about 25 bp before the start point of each eukaryotic RNA
polymerase II transcript unit which may be involved in positioning the
enzyme for correct initiation; consensus=TATA(A or T)A(A or T)

 terminator	sequence of DNA located either at the end of the transcript
or adjacent to a promoter region that causes RNA polymerase to terminate
transcription; may also be site of binding of repressor protein

 transit_peptide	transit peptide coding sequence; coding sequence for an
N-terminal domain of a nuclear-encoded organellar protein; this domain
is involved in post-translational import of the protein into the
organelle

 tRNA	mature transfer RNA, a small RNA molecule (75-85 bases long) that
mediates the translation of a nucleic acid sequence into an amino acid
sequence

 unsure	author is unsure of exact sequence in this region

V_region	variable region of immunoglobulin light and heavy chains, and
T-cell receptor alpha, beta, and gamma chains; codes for the variable
amino terminal portion; can be made up from V_segments, D_segments,
N_regions, and J_segments

V_segment	variable segment of immunoglobulin light and heavy chains, and
T-cell receptor alpha, beta, and gamma chains; codes for most of the
variable region (V_region) and the last few amino acids of the leader
peptide

 variation	a related strain contains stable mutations from the same gene
(for example, RFLPs, polymorphisms, etc.) which differ from the
presented sequence at this location (and possibly others)

 3'clip	3'-most region of a precursor transcript that is clipped off
during processing

 3'UTR	region at the 3' end of a mature transcript (following the stop
codon) that is not translated into a protein

 5'clip	5'-most region of a precursor transcript that is clipped off
during processing

 5'UTR	region at the 5' end of a mature transcript (preceding the
initiation codon) that is not translated into a protein

 -10_signal	pribnow box; a conserved region about 10 bp upstream of the
start point of bacterial transcription units which may be involved in
binding RNA polymerase; consensus=TAtAaT

 -35_signal	a conserved hexamer about 35 bp upstream of the start point
of bacterial transcription units; consensus=TTGACa [  ] or TGTTGACA [  ]

	WIPO Standard ST.25 (1998), Appendix 2, Table 6 provides for feature
keys related to protein sequences.

Table 6: List of Feature Keys Related to Protein Sequences

Key	Description

CONFLICT	different papers report differing sequences

VARIANT	authors report that sequence variants exist

VARSPLIC	description of sequence variants produced by alternative
splicing

MUTAGEN	site which has been experimentally altered

MOD_RES	post-translational modification of a residue

     ACETYLATION	N-terminal or other

     AMIDATION	generally at the C-terminal of a mature active peptide

     BLOCKED	undetermined N- or C-terminal blocking group

     FORMYLATION	of the N-terminal methionine

     GAMMA-CARBOXYGLUTAMIC ACID HYDROXYLATION	of asparagine, aspartic
acid, proline or lysine

     METHYLATION	generally of lysine or arginine

     PHOSPHORYLATION	of serine, threonine, tyrosine, aspartic acid or
histidine

     PYRROLIDONE CARBOXYLIC      ACID	N-terminal glutamate which has
formed an internal cyclic lactam

      SULFATATION	generally of tyrosine

LIPID	covalent binding of a lipidic moiety

      MYRISTATE	myristate group attached through an amide bond to the
N-terminal glycine residue of the mature form of a protein or to an
internal lysine residue

      PALMITATE	palmitate group attached through a thioether bond to a
cysteine residue or through an ester bond to a serine or threonine
residue

      FARNESYL	farnesyl group attached through a thioether bond to a
cysteine residue

      GERANYL-GERANYL	geranyl-geranyl group attached through a thioether
bond to a cysteine residue

      GPI-ANCHOR	glycosyl-phosphatidylinositol (GPI) group linked to the
alpha-carboxyl group of the C-terminal residue of the mature form of a
protein

      N-ACYL DIGLYCERIDE	N-terminal cysteine of the mature form of a
prokaryotic lipoprotein with an amide-linked fatty acid and a glyceryl
group to which two fatty acids are linked by ester linkages

DISULFID	disulfide bond; the "FROM" and "TO" endpoints represent the two
residues which are linked by an intra-chain disulfide bond; if the
"FROM" and "TO" endpoints are identical, the disulfide bond is an
interchain one and the description field indicates the nature of the
cross-link

THIOLEST	thiolester bond; the "FROM" and "TO" endpoints represent the
two residues which are linked by the thiolester bond

THIOETH	thioether bond;  the "FROM" and "TO" endpoints represent the two
residues which are linked by the thioether bond

CARBOHYD	glycosylation site;  the nature of the carbohydrate (if known)
is given in the description field

METAL	binding site for a metal ion; the description field indicates the
nature of the metal

BINDING	binding site for any chemical group (co-enzyme, prosthetic
group, etc.); the chemical nature of the group is given in the
description field

SIGNAL	extent of a signal sequence (prepeptide)

TRANSIT	extent of a transit peptide (mitochondrial, chloroplastic, or
for a microbody)

PROPEP	extent of a propeptide

CHAIN	extent of a polypeptide chain in the mature protein

PEPTIDE	extent of a released active peptide

DOMAIN	extent of a domain of interest on the sequence; the nature of
that domain is given in the description field

CA_BIND	extent of a calcium-binding region

DNA_BIND	extent of a DNA-binding region

NP_BIND	extent of a nucleotide phosphate binding region; the nature of
the nucleotide phosphate is indicated in the description field

TRANSMEM	extent of a transmembrane region

ZN_FING	extent of a zinc finger region

SIMILAR	extent of a similarity with another protein sequence; precise
information, relative to that sequence is given in the description field

REPEAT	extent of an internal sequence repetition

HELIX	secondary structure:  Helices, for example, Alpha-helix, 3(10)
helix, or Pi-helix

STRAND	secondary structure:  Beta-strand, for example, Hydrogen bonded
beta-strand, or Residue in an isolated beta-bridge

TURN	secondary structure:  Turns, for example, H-bonded turn (3-turn,
4-turn, or 5-turn)

ACT_SITE	amino acid(s) involved in the activity of an enzyme

SITE	any other interesting site on the sequence

INIT_MET	the sequence is known to start with an initiator methionine

NON_TER	the residue at an extremity of the sequence is not the terminal
residue;  if applied to position 1, this signifies that the first
position is not the N-terminus of the complete molecule; if applied to
the last position, it signifies that this position is not the C-terminus
of the complete molecule; there is no description field for this key

NON_CONS	non consecutive residues; indicates that two residues in a
sequence are not consecutive and that there are a number of unsequenced
residues between them

UNSURE	uncertainties in the sequence; used to describe region(s) of a
sequence for which the authors are unsure about the sequence assignment

FILING INTERNATIONALLY

The revisions to  37 CFR 1.821 through 1.825 are the result of an effort
to harmonize the PTO, PCT, EPO and JPO Sequence Listing requirements to
the extent possible.  The requirements of WIPO Standard ST.25 are
substantially identical to the requirements of  37 CFR 1.821 through
1.825.  PatentIn   Version 2.0 software, now available (see MPEP Section 
2430), meets all of the requirements of WIPO Standard ST.25 (1998).  The
requirements of  37 CFR 1.821 through 1.825, however, are less stringent
than the requirements of WIPO Standard ST.25 (1998).  Thus, applicants
who wish to file in countries which adhere to WIPO Standard ST.25 (1998)
should consider the following when not using PatentIn Version 2.0:

(A) The WIPO Standard ST.25 (1998) does not permit submissions using a
Macintosh computer;

(B) The WIPO Standard ST.25 (1998) does not accept the range of media
permitted by  37 CFR 1.821 through 1.825;

(C) The answers in fields &lt;221&gt; and &lt;222&gt; must use
selections from Tables 5 and 6 of WIPO Standard ST.25 (1998) to comply
with that standard.  The terms from these Tables are considered language
neutral vocabulary;

(D) Any free text in numeric identifier &lt;223&gt; of a Sequence
Listing will not be translated and thus must also appear in the
specification of applications filed under WIPO Standard ST.25 (1998) for
compliance;

(E) A CRF filed after the filing of an application under the PCT does
not form part of the disclosure and will not be published in the
pamphlet;

(F) Paragraph 39 of WIPO Standard ST.25 (1998) requires the specific
wording "the information recorded on the form is identical to the
written sequence listing"; and

(G) WIPO Standard ST.25 (1998), paragraph 24, requires spaces between
specified numeric identifiers in the Sequence Listing.

---SECTION---2422.01 Definitions of Nucleotide and/or Amino Acids for
Purpose of Sequence Rules

37 CFR 1.821(a) presents a definition for "nucleotide and/or amino acid
sequences." This definition sets forth limits, in terms of numbers of
amino acids and/or numbers of nucleotides, at or above which compliance
with the sequence rules is required. Nucleotide and/or amino acid
sequences as used in  37 CFR 1.821 through 1.825 are interpreted to mean
an unbranched sequence of four or more amino acids or an unbranched
sequence of ten or more nucleotides.  Branched sequences are
specifically excluded from this definition.  Sequences with fewer than
four specifically defined nucleotides or amino acids are specifically
excluded from this section. "Specifically defined"  means those amino
acids other than  "Xaa"  and those nucleotide bases other than  "n" 
defined in accordance with the World Intellectual Property Organization
(WIPO) Handbook on Industrial Property Information and Documentation,
Standard ST.25: Standard for the Presentation of Nucleotide and Amino
Acid Sequence Listings in Patent Applications (1998), including Tables 1
through 6 in Appendix 2 (see MPEP Section  2422).

The limit of four or more amino acids was established for consistency
with limits in place for industry database collections whereas the limit
of ten or more nucleotides, while lower than certain industry database
limits, was established to encompass those nucleotide sequences to which
the smallest probe will bind in a stable manner.  The limits for amino
acids and nucleotides are also consistent with those established for
sequence data exchange with the Japanese Patent Office and the European
Patent Office.

37 CFR  1.821(a)(1) and  37 CFR 1.821(a)(2) present further definitions
for those nucleotide and amino acid sequences that are intended to be
embraced by the sequence rules.  Situations in which the applicability
of the rules are in issue will be resolved on a case-by-case basis. 

Nucleotide sequences are further limited to those that can be
represented by the symbols set forth in  37 CFR 1.822(b), which
incorporates by reference WIPO Standard ST.25 (1998), Appendix 2, Table
1 (see MPEP Section  2422).  The presence of other than typical 5' to 3'
phosphodiester linkages in a nucleotide sequence does not render the
rules inapplicable. The Office does not want to exclude linkages of the
type commonly found in naturally occurring nucleotides, e.g., eukaryotic
end capped sequences. 

Amino acid sequences are further limited to those listed in  37 CFR
1.822(b), which incorporates by reference WIPO Standard ST.25 (1998),
Appendix 2, Table 3 (see MPEP Section  2422), and those L-amino acids
that are commonly found in naturally occurring proteins.  The limitation
to L-amino acids is based upon the fact that there currently exists no
widely accepted standard nomenclature for representing the scope of
amino acids encompassed by non-L-amino acids, and, as such, the process
of meaningfully encoding these other amino acids for computerized
searching and printing is not currently feasible. The presence of one or
more D-amino acids in a sequence will exclude that sequence from the
scope of the rules. (Voluntary compliance is, however, encouraged in
these situations; the symbol "Xaa" can be used to represent D-amino
acids.)  The sequence rules embrace "[a]ny peptide or protein that can
be expressed as a sequence using the symbols in WIPO Standard ST.25
(1998), Appendix 2, Table 3 in conjunction with a description in the
Feature section to describe, for example, modified linkages, cross links
and end caps, non-peptidyl bonds, etc."  37 CFR 1.821(a)(2).

With regard to amino acid sequences, the use of the terms "peptide or
protein" implies, however, that the amino acids in a given sequence are
linked by at least three consecutive peptide bonds. Accordingly, an
amino acid sequence is not excluded from the scope of the rules merely
due to the presence of a single non-peptidyl bond.  If an amino acid
sequence can be represented by a string of amino acid abbreviations,
with reference, where necessary, to a features table to explain
modifications in the sequence, the sequence comes within the scope of
the rules.  However, the rules are not intended to encompass the subject
matter that is generally referred to as synthetic resins.

---SECTION---2422.02 The Requirement for Exclusive Conformance;
Sequences Presented in Drawing Figures

37 CFR 1.821(b) requires exclusive conformance, with regard to the
manner in which the nucleotide and/or amino acid sequences are presented
and described, with the sequence rules for all applications that include
nucleotide and amino acid sequences that fall within the definitions.
This requirement is necessary to minimize any confusion that could
result if more than one format for representing sequence data was
employed in a given application. It is also expected that the required
standard format will be more readily and widely accepted and adopted if
its use is exclusive, as well as mandatory.

In view of the fact that many significant sequence characteristics may
only be demonstrated by a figure, the exclusive conformance requirement
of this section may be relaxed for drawing figures. This is especially
true in view of the fact that the representation of double stranded
nucleotides is not permitted in the "Sequence Listing" and many
significant nucleotide features, such as "sticky ends" and the like,
will only be shown effectively by reference to a drawing figure. 
Further, the similarity or homology between/among sequences can only be
depicted in an effective manner in a drawing figure.  Similarly, drawing
figures are recommended for use with amino acid sequences to depict
structural features of the corresponding protein, such as finger regions
and Kringle regions.  The situations discussed herein are given by way
of example only and there may be many other reasons for relaxing the
requirements of this section for the drawing figures. It should be
noted, though, that when a sequence is presented in a drawing,
regardless of the format or the manner of presentation of that sequence
in the drawing,  the sequence must still be included in the Sequence
Listing and the sequence identifier ("SEQ ID NO:X") must be used, either
in the drawing or in the Brief Description of the Drawings.

---SECTION---2422.03 The Requirements for a Sequence Listing and
Sequence Identifiers; Sequences Embedded in Application Text; Variants
of a Presented Sequence

37 CFR 1.821(c) requires that applications containing nucleotide and/or
amino acid sequences that fall within the above definitions, contain, as
a separate part of the disclosure on paper copy, a disclosure of the
nucleotide and/or amino acid sequences, and associated information,
using the format and symbols that are set forth in  37 CFR 1.822 and  37
CFR 1.823.  This separate part of the disclosure, beginning on a new
page within the specification, is referred to as the "Sequence Listing,"
and requires that each sequence disclosed in the application appear
separately in the "Sequence Listing," with each sequence further being
assigned a sequence identification number, referred to as "SEQ ID NO." 
A plurality of sequences may, if feasible, be presented on a single
page, and this may be extended to the separate presentation of both
nucleotide and amino acid sequences on the same page. The requirement
for sequence identification numbers, at a minimum, requires that each
sequence be assigned a different number for purposes of identification. 
However, where practical and for ease of reference, sequences should be
presented in the separate part of the application in numerical order and
in the order in which they are discussed in the application.

The requirement for compliance in  37 CFR 1.821(c) is directed to " 
disclosures of nucleotide and/or amino acid sequences."  (Emphasis
added.) All sequence information, whether claimed or not, that meets the
length thresholds in  37 CFR 1.821(a) is subject to the rules.  The goal
of the Office is to build a comprehensive database that can be used for,
inter alia, the purpose of assessing the prior art.  It is therefore
essential that all sequence information, whether only disclosed or also
claimed, be included in the database. In those instances in which prior
art sequences are only referred to in a given application by name and a
publication or accession reference, they need not be included as part of
the "Sequence Listing," unless an examiner considers the referred- to
sequence to be "essential material," per MPEP Section  608.01(p).
However, if the applicant presents the sequence as a string of
particular bases or amino acids, it is necessary to include the sequence
in the "Sequence Listing," regardless of whether the applicant considers
the sequence to be prior art. In general, any sequence that is disclosed
and/or claimed as a sequence, i.e., as a string of particular bases or
amino acids, and that otherwise meets the criteria of  37 CFR 1.821(a),
must be set forth in the "Sequence Listing." 

It is generally acceptable to present a single, general sequence in
accordance with the sequence rules and to discuss and/or claim variants
of that general sequence without presenting each variant as a separate
sequence in the "Sequence Listing."  By way of example only, the
following types of sequence disclosures would be treated as noted herein
by the Office.  With respect to "conservatively modified variants
thereof" of a sequence,  the sequences may be described as SEQ ID NO:X
and "conservatively modified variants thereof," if desired. With respect
to a sequence that "may be deleted at the C-terminus by 1, 2, 3, 4, or 5
residues," all of the implied variations do not need to be included in
the "Sequence Listing."  If such a situation were encompassed by the
rules, it would introduce far too much complexity into the "Sequence
Listing" and the Office's database.  The possible mathematical
variations that could result from this type of language could reasonably
require a "Sequence Listing" that would be thousands of pages in length. 
In this latter example, only the undeleted sequence needs to be included
in the "Sequence Listing," and the sequences may be described as SEQ ID
NO:X from which deletions have been made at the C-terminus by 1, 2, 3,
4, or 5 residues.  The Office's database will only contain the undeleted
sequence.

37 CFR 1.821(d) requires the use of the assigned sequence identifier in
all instances where the description or claims of a patent application
discuss sequences regardless of whether a given sequence is also
embedded in the text of the description or claims of an application. 
This requirement is also intended to permit references, in both the
description and claims, to sequences set forth in the "Sequence Listing"
by the use of assigned sequence identifiers without repeating the
sequence in the text of the description or claims.  Sequence identifiers
can also be used to discuss and/or claim parts or fragments of a
properly presented sequence. For example, language such as "residues 14
to 243 of SEQ ID NO:23" is permissible and the fragment need not be
separately presented in the "Sequence Listing."  Where a sequence is
embedded in the text of an application, it must be presented in a manner
that complies with the requirements of the sequence rules.

The rules do not alter, in any way, the requirements of  35 U.S.C. 112. 
The implementation of the rules has had no effect on disclosure and/or
claiming requirements.  The rules, in general, or the use of sequence
identifiers throughout the specification and claims, specifically,
should not raise any issues under  35 U.S.C. 112, first or second
paragraphs. The use of sequence identification numbers (SEQ ID NO:X)
only provides a shorthand way for applicants to discuss and claim their
inventions.  These identification numbers do not in any way restrict the
manner in which an invention can be claimed.

---SECTION---2422.04 The Requirement for a Computer Readable Copy of the
Official Paper Copy of the Sequence Listing

37 CFR 1.821(e) requires the submission of a copy of the  "Sequence
Listing"  in computer readable form.  The information on the computer
readable form will be entered into the Office's database for searching
and printing nucleotide and amino acid sequences. This electronic
database will also enable the Office to exchange patented sequence data,
in electronic form, with the Japanese Patent Office and the European
Patent Office.  It should be noted that the Office's database complies
with the confidentiality requirement imposed by  35 U.S.C. 122. Pending
application sequences are maintained in the database separately from
published or patented sequences. That is, the Office will not exchange
or make public any information on any sequence until the patent
application containing that information is published or matures into a
patent, or as otherwise allowed by  35 U.S.C. 122.

The second sentence of  37 CFR 1.821(e) indicates that, as between the
paper copy of the "Sequence Listing" and the computer readable copy
thereof, the paper copy serves as the official copy.  However, the
Office may permit correction of the paper copy, at the least, during the
pendency of a given application by reference to the computer readable
copy thereof if both the paper and computer readable forms were
submitted at the time of filing of the application and the totality of
the circumstances otherwise substantiate the proposed correction. A mere
discrepancy between the paper copy and the computer readable form may
not, in and of itself, be sufficient to justify a proposed correction. 
In this regard, the Office will assume that the computer readable form
has been incorporated by reference into the application when the paper
and computer readable forms were submitted at the time of filing of the
application.  The Office will attempt to accommodate or address all
correction issues, but it must be kept in mind that the real burden
rests with the applicant to ensure that any discrepancies between the
paper copy and the computer readable form are eliminated or minimized.
Applicants should be aware that there will be instances where the
applicant may have to suffer the consequences of any discrepancies
between the two. The paper copy also serves as the official copy for
priority purposes. The Office does not desire to be bound by a
requirement to permanently preserve computer readable forms for support,
priority or correction purposes. For example, the Office will make
corrections, where appropriate, by reference to the computer readable
form as long as the computer readable form is still available to the
Office. However, once use of the computer readable form by the Office
for processing has ended, i.e., once the Office has entered the data
contained on the computer readable form into the appropriate database,
the Office does not intend to further preserve the computer readable
form submitted by the applicant.

---SECTION---2422.05 Reference to Previously Filed Identical Computer
Readable Form; Continuing or Derivative Applications; Request for
Transfer of Computer Readable Form

The last three sentences of  37 CFR 1.821(e) set forth the procedure to
be followed when a computer readable form of a given application is
identical with a computer readable form of another application.  In that
situation, an applicant may make reference to the other application and
computer readable form therein in lieu of filing a duplicate computer
readable form in the given application. That is, additional computer
readable forms will not be required in derivative or continuing
applications if the sequence information is exactly the same, i.e., with
no additions or deletions, as that in a parent or previously filed
application in which a complying computer readable form had been filed.
If sequence information is deleted from or added to that submitted in a
previously filed application, the procedure in this paragraph is not
available and a new computer readable form is required.  To take
advantage of the procedure outlined in this section, applicants must
request that the previously submitted sequence information be used in
the given application in much the same manner as applicants must now
request the transfer of drawings in derivative or continuing
applications. A letter must be submitted in the given application
requesting use of the previously filed sequence information. The letter
must completely identify the other application, by application number,
and the computer readable form, by indicating whether it was the only
computer readable form filed in that application or whether it was the
second, or subsequent, computer readable form filed.

A sample letter requesting transfer of the previously filed sequence
information is set forth below:

The paper copy of the Sequence Listing in this application [application
number], is identical to the computer readable copy of the Sequence
Listing filed in application [application number], filed [date]. In
accordance with  37 CFR 1.821(e), please use the [first-filed,
last-filed or only, whichever is applicable] computer readable form
filed in that application as the computer readable form for the instant
application. It is understood that the Patent and Trademark Office will
make the necessary change in application number and filing date for the
instant application. A paper copy of the Sequence Listing is [included
in the originally-filed specification of the instant application,
included in a separately filed preliminary amendment for incorporation
into the specification, whichever is applicable].

---SECTION---2422.06 Requirement for Statement Regarding Content of
Paper and Computer Readable Copies of Sequence Listing

37 CFR 1.821(f) requires that the paper and computer readable copies of
the "Sequence Listing" be accompanied by a statement that the content of
the paper and computer readable copies are the same, at the time when
the computer readable form is submitted.  Such a statement may be made
by the applicant. See MPEP Section  2428 for further information and
Sample Statements.

---SECTION---2422.07 Requirements for Compliance, Statements Regarding
New Matter, and Sanctions for Failure to Comply

37 CFR 1.821(g) requires compliance with the requirements of  37 CFR
1.821(b) through (f), as discussed above, if they are not satisfied at
the time of filing under  35 U.S.C. 111(a) or at the time of entering
the national stage of an international application under  35 U.S.C. 371,
within the period of time set in a notice requiring compliance.  Failure
to comply will result in the abandonment of the application. Submissions
in reply to requirements under this paragraph must be accompanied by a
statement that the submission includes no new matter. Such a statement
may be made by the applicant.  Extensions of time in which to reply to a
requirement under this paragraph are available pursuant to  37 CFR
1.136. When an action by the applicant is a bona fide attempt to comply
with these rules and it is apparent that compliance with some
requirement has inadvertently been omitted, the applicant may be given a
new time period to correct the omission.  See  37 CFR 1.135(c).

Applications filed under  35 U.S.C.  111(b)  need not comply with  37
CFR 1.821 through 1.825,  however,  applicants are encouraged to file a 
Sequence Listing as defined in 37 CFR 1.821(c) for ease of
identification of the sequence information contained in the provisional
application.

37 CFR 1.821(h) requires compliance with the requirements of  37 CFR
1.821(b) through (f), as discussed above, within the time period
prescribed in a notice requiring compliance in an international
application filed in the United States Receiving Office under the Patent
Cooperation Treaty (PCT), if the above noted requirements are not
satisfied at the time of filing.  Submissions in reply to requirements
under this paragraph must be accompanied by a statement that the
submission does not include matter which goes beyond the disclosure in
the international application as filed. Such a statement may be made by
an applicant. International applications that fail to comply with any of
the requirements of  37 CFR 1.821(b)-(f) will be searched to the extent
possible without the benefit of the information in computer readable
form.

The requirement to submit a statement that a submission in reply to the
requirements of this section does not include new matter or matter which
goes beyond the disclosure in the application as filed is not the first
instance in which the applicant has been required to ensure that there
is not new matter upon amendment.  The requirement is analogous to that
found in  37 CFR 1.125 regarding substitute specifications.  When a
substitute specification is required because the number or nature of
amendments would make it difficult to examine the application, the
applicant must include a statement that the substitute specification
includes no new matter. The necessity of requiring a substitute
"Sequence Listing," or pages thereof, is similar to the necessity of
requiring a substitute specification and, likewise, the burden is on the
applicant to ensure that no new matter is added. Applicants have a duty
to comply with the statutory prohibition (35 U.S.C. 132 and  35 U.S.C.
251) against the introduction of new matter.

It should be noted that the treatment accorded errors in sequencing or
any other errors prior to the implementation date of the sequence rules
will be no different for those applications filed on or after the
implementation date of these rules. The correction of errors in
sequencing or any other errors that are made in describing an invention
are, as they have always been, subject to the statutory prohibition (35
U.S.C. 132 and  35 U.S.C. 251) against the introduction of new matter.

---SECTION---2422.08 Presumptions Regarding Compliance

Neither the presence nor absence of information which is not required
under the sequence rules will create a presumption that such information
is necessary to satisfy any of the requirements of  35 U.S.C. 112. 
Further, the grant of a patent on an application that is subject to  37
CFR 1.821 through  37 CFR 1.825 constitutes a conclusive presumption
that the granted patent complies with the requirements of these rules.

---SECTION---2422.09 Box Sequence; Hand Delivery of Sequence Listings
and Computer Readable Forms

To facilitate administrative processing of all papers associated with
sequence rule compliance, all computer readable forms, fees, and papers
accompanying them filed in the Office should be marked "Box SEQUENCE." 

Correspondence relating to the sequence rules may also be hand-delivered
to the Group.  In cases of hand delivery to the Customer Service Window
or to the Group, the floppy disk or tape should be placed in a
protective mailer labeled with at least the application number, if
available. The labeling requirements of  37 CFR 1.824(a)(6) must also be
complied with.  The use of staples and clips, if any, should be confined
to carefully attaching the mailer to the submitted papers without
contact or compression of the magnetic media which may cause the disk or
tape to be unreadable. In no situations should additional or
complimentary copies of diskettes or tapes be delivered to examiners or
other Office personnel.

---SECTION---2423 Symbols and Format To Be Used for Nucleotide and/or
Amino Acid Sequence Data

37 CFR 1.822 Symbols and format to be used for nucleotide and/or amino
acid sequence data.

(a) The symbols and format to be used for nucleotide and/or amino acid
sequence data shall conform to the requirements of paragraphs (b)
through (e) of this section.

(b) The code for representing the nucleotide and/or amino acid sequence
characters shall conform to the code set forth in the tables in WIPO
Standard ST.25 (1998), Appendix 2, Tables 1 and 3. This incorporation by
reference was approved by the Director of the Federal Register in
accordance with  5 U.S.C. 552(a) and 1 CFR part 51. Copies of ST.25 may
be obtained from the World Intellectual Property Organization; 34 chemin
des Colombettes; 1211 Geneva 20 Switzerland. Copies of ST.25 may be
inspected at the Patent Search Room; Crystal Plaza 3, Lobby Level; 2021
South Clark Place; Arlington, VA 22202. Copies may also be inspected at
the Office of the Federal Register, 800 North Capitol Street, NW, Suite
700, Washington, DC. No code other than that specified in these sections
shall be used in nucleotide and amino acid sequences. A modified base or
modified or unusual amino acid may be presented in a given sequence as
the corresponding unmodified base or amino acid if the modified base or
modified or unusual amino acid is one of those listed in WIPO Standard
ST.25 (1998), Appendix 2, Tables 2 and 4, and the modification is also
set forth in the Feature section. Otherwise, each occurrence of a base
or amino acid not appearing in WIPO Standard ST.25 (1998), Appendix 2,
Tables 1 and 3, shall be listed in a given sequence as "n" or "Xaa,"
respectively, with further information, as appropriate, given in the
Feature section, preferably by including one or more feature keys listed
in WIPO Standard ST.25 (1998), Appendix 2, Tables 5 and 6.

(c) Format representation of nucleotides. (1) A nucleotide sequence
shall be listed using the lower-case letter for representing the
one-letter code for the nucleotide bases set forth in WIPO Standard
ST.25 (1998), Appendix 2, Table 1.

(2) The bases in a nucleotide sequence (including introns) shall be
listed in groups of 10 bases except in the coding parts of the sequence.
Leftover bases, fewer than 10 in number, at the end of noncoding parts
of a sequence shall be grouped together and separated from adjacent
groups of 10 or 3 bases by a space.

(3) The bases in the coding parts of a nucleotide sequence shall be
listed as triplets (codons). The amino acids corresponding to the codons
in the coding parts of a nucleotide sequence shall be typed immediately
below the corresponding codons. Where a codon spans an intron, the amino
acid symbol shall be typed below the portion of the codon containing two
nucleotides.

(4) A nucleotide sequence shall be listed with a maximum of 16 codons or
60 bases per line, with a space provided between each codon or group of
10 bases.

(5) A nucleotide sequence shall be presented, only by a single strand,
in the 5 to 3 direction, from left to right.

(6) The enumeration of nucleotide bases shall start at the first base of
the sequence with number 1. The enumeration shall be continuous through
the whole sequence in the direction 5 to 3. The enumeration shall be
marked in the right margin, next to the line containing the one-letter
codes for the bases, and giving the number of the last base of that
line.

(7) For those nucleotide sequences that are circular in configuration,
the enumeration method set forth in paragraph (c)(6) of this section
remains applicable with the exception that the designation of the first
base of the nucleotide sequence may be made at the option of the
applicant.

(d) Representation of amino acids. (1) The amino acids in a protein or
peptide sequence shall be listed using the three-letter abbreviation
with the first letter as an upper case character, as in WIPO Standard
ST.25 (1998), Appendix 2, Table 3.

(2) A protein or peptide sequence shall be listed with a maximum of 16
amino acids per line, with a space provided between each amino acid.

(3) An amino acid sequence shall be presented in the amino to carboxy
direction, from left to right, and the amino and carboxy groups shall
not be presented in the sequence.

(4) The enumeration of amino acids may start at the first amino acid of
the first mature protein, with the number 1. When presented, the amino
acids preceding the mature protein, e.g., pre-sequences, pro-sequences,
pre-pro-sequences and signal sequences, shall have negative numbers,
counting backwards starting with the amino acid next to number 1.
Otherwise, the enumeration of amino acids shall start at the first amino
acid at the amino terminal as number 1. It shall be marked below the
sequence every 5 amino acids. The enumeration method for amino acid
sequences that is set forth in this section remains applicable for amino
acid sequences that are circular in configuration, with the exception
that the designation of the first amino acid of the sequence may be made
at the option of the applicant.

(5) An amino acid sequence that contains internal terminator symbols
(e.g., "Ter", "*", or ".", etc.) may not be represented as a single
amino acid sequence, but shall be presented as separate amino acid
sequences.

(e) A sequence with a gap or gaps shall be presented as a plurality of
separate sequences, with separate sequence identifiers, with the number
of separate sequences being equal in number to the number of continuous
strings of sequence data. A sequence that is made up of one or more
noncontiguous segments of a larger sequence or segments from different
sequences shall be presented as a separate sequence.

Tables 1-6 of WIPO Standard ST.25 (1998), Appendix 2, are reproduced in
MPEP Section  2422.

---SECTION---2423.01 Format and Symbols To Be Used in Sequence Listings

37 CFR 1.822 sets forth the format and symbols to be used for listing
nucleotide and/or amino acid sequence data. The codes for representing
the nucleotide and/or amino acid characters in the sequences are set
forth in the tables of WIPO Standard ST.25 (1998), Appendix 2, Tables 1
and 3. See MPEP Section  2422.  No other symbols shall be used in
nucleotide and amino acid sequences.  The "modified base" and "modified
and unusual amino acid" codes appearing in WIPO Standard ST.25 (1998),
Appendix 2, Tables 2 and 4 (see  37 CFR 1.822 and MPEP Section  2422)
are not to be used in setting forth the sequences, but, they may be used
in the description and/or the "Sequence Listing" corresponding to, but
not including, the sequence itself.  A modified base or amino acid may
be presented in a given sequence as the corresponding unmodified base or
amino acid if the modified base or amino acid is one of those listed in
WIPO Standard ST.25 (1998), Appendix 2, Table 2 or 4 and the
modification is also set forth in the features section of the Sequence
Listing.  Otherwise, all bases or amino acids not appearing in WIPO
Standard ST.25 (1998), Appendix 2, Table 1 or 3 must be listed in a
given sequence as "n" or "Xaa,"  respectively, with further information
given in the features section of the "Sequence Listing."  See  37 CFR
1.823(b).

In  37 CFR 1.822(b) and  37 CFR 1.822(d), the use of three-letter codes
for amino acids is required. The use of the three-letter codes for amino
acids is preferred over the one-letter codes from the perspective of
facilitating the examiner's review of the application papers, including
the "Sequence Listing", and the public's, as well as the examiner's, use
of the printed patents. The three-letter codes must be presented using
the upper case for the first character and lower case for the remaining
two characters.

37 CFR 1.822(c) through (e) set forth the format for presenting sequence
data. These paragraphs set forth the manner in which the characters in
sequences are to be grouped, spaced, presented and numbered.

---SECTION---2423.02 Depiction of Coding Regions

If applicant chooses to depict coding regions,  37 CFR 1.822 (c)(3)
requires the amino acids corresponding to the codons in the coding parts
of a nucleotide sequence to be typed immediately below the corresponding
codons. Further, in  37 CFR 1.822 (c)(3), the situation in which a codon
spans an intron has been addressed. In those situations, the "amino acid
symbol shall be typed below the portion of the codon containing two
nucleotides."  This requirement clarifies the representation of an amino
acid that corresponds to a codon that spans an intron.

It should be noted that the sequence rules do not, in any way, require
the depiction of coding regions or the amino acids corresponding to the
codons in those coding regions. 37 CFR 1.822 (d)  only requires that
where amino acids corresponding to the codons in the coding parts of a
nucleotide sequence are depicted, they must be depicted below the
corresponding codons. There is absolutely no requirement in the rules to
depict coding regions. Nor is there a requirement to separately list the
amino acids corresponding to the codons in the coding parts of a
nucleotide sequence unless the applicant desires to discuss the amino
acids as a separate sequence.  That is, when the coding parts of a
nucleotide sequence and their corresponding amino acids have been
identified, if applicant desires to discuss those amino acids in the
coding parts of the nucleotide as a separate sequence, those amino acids
must also be set forth as a separate sequence. The separate submission
of the amino acid sequence that corresponds to the coding parts of a
nucleotide sequence is, however, recommended and encouraged because the
amino acid sequence may not be captured in the sequence database if it
is only presented in the "Sequence Listing" as a mixed nucleotide and
amino acid sequence.

---SECTION---2423.03 Presentation and Enumeration of Sequences

37 CFR 1.822(c)(5) provides that nucleotide sequences shall only be
represented by a single strand, in the 5&prime; to 3&prime; direction,
from left to right. That is, double stranded nucleotides shall not be
represented in the "Sequence Listing." A double stranded nucleotide may
be represented as two single stranded nucleotides, and any relationship
between the two may be shown in the drawings.

The procedures for presenting and numbering amino acid sequences are set
forth in  37 CFR 1.822(d). Two alternatives are presented for numbering
amino acid sequences. Amino acid sequences may be numbered with respect
to the identification of the first amino acid of the first mature
protein or with respect to the first amino acid appearing at the amino
terminal. The enumeration procedure for nucleotides is set forth in  37
CFR 1.822(c)(6).  Sequences that are circular in configuration are
intended to be encompassed by these rules, and numbering procedures for
them are provided in  37 CFR 1.822(c)(7) and (d)(4).  The numbering
procedures set forth in  37 CFR 1.822(c) and (d) are not necessarily
intended to be consistent with all currently employed numbering
procedures. The objective here is to establish a reasonable numbering
procedure that can readily be followed and adhered to. These formatting
procedures also reflect those that have been agreed to for electronic
data exchange with the JPO and the EPO.

In  37 CFR 1.822(e) the procedures for presenting and numbering hybrid
and gapped sequences are set forth.  A sequence that is made up of one
or more noncontiguous segments of a larger sequence or segments from
different sequences, i.e., a hybrid sequence, shall be presented as a
separate sequence. A "gap" for the purpose of this section is not
intended to embrace a gap or gaps that is/are introduced into the
presentation of otherwise continuous sequence information in, e.g., a
drawing figure, to show alignments or similarities with other sequences. 
The "gaps" referred to in this section are gaps representing unknown or
undisclosed regions in a sequence between regions that are known or
disclosed.  In the situation where a contiguous fragment of a sequence
that has already been properly set forth in a "Sequence Listing" is
discussed and/or claimed, the fragment does not need to be separately
included in the "Sequence Listing." It may be referred to in the
specification, claims or drawings as, e.g., "residues 2 through 33 of
SEQ ID NO:12," assuming that SEQ ID NO:12 has been properly included in
the "Sequence Listing." 

---SECTION---2424 Requirements for Nucleotide and/or Amino Acid
Sequences as Part of the Application Papers

37 CFR 1.823 Requirements for nucleotide and/or amino acid sequences as
part of the application papers.

(a) The "Sequence Listing" required by Section  1.821(c), setting forth
the nucleotide and/or amino acid sequences and associated information in
accordance with paragraph (b) of this section, must begin on a new page
and must be titled "Sequence Listing". The "Sequence Listing" preferably
should be numbered independently of the numbering of the remainder of
the application. Each page of the "Sequence Listing" should contain no
more than 66 lines and each line should contain no more than 72
characters. A fixed-width font should be used exclusively throughout the
"Sequence Listing."

(b) The "Sequence Listing" shall, except as otherwise indicated, include
the actual nucleotide and/or amino acid sequence, the numeric
identifiers and their accompanying information as shown in the following
table. The numeric identifier shall be used only in the "Sequence
Listing." The order and presentation of the items of information in the
"Sequence Listing" shall conform to the arrangement given below. Each
item of information shall begin on a new line and shall begin with the
numeric identifier enclosed in angle brackets as shown. The submission
of those items of information designated with an "M" is mandatory. The
submission of those items of information designated with an "O" is
optional. Numeric identifiers &lt;110&gt; through &lt;170&gt; shall only
be set forth at the beginning of the "Sequence Listing." The following
table illustrates the numeric identifiers.



Numeric Identifier	Definition	Comments and format	Mandatory (M) or
Optional (O)

 &lt;110&gt; ......	Applicant.........................	Preferably max.
of 10 names; one name per line; preferable format: Surname,  Other Names
and/or Initials. 	M.

 &lt;120&gt; ......	Title of Invention.............	
................................................................	M.

 &lt;130&gt; ......	File Reference..................	Personal file
reference............................	M when filed prior to assignment
or appl. number

 &lt;140&gt; ......	Current Application Number.	Specify as: US
07/999,999 or PCT/US96/99999.	M, if available.

 &lt;141&gt; ......	Current Filing Date..........	Specify as:
yyyy-mm-dd.........................	M, if available.

 &lt;150&gt; ......	Prior Application Number. 	Specify as: US 07/999,999
or PCT/US96/99999. 	M, if applicable include priority documents under 
35 USC 119 and 120

 &lt;151&gt; ......	Prior Application Filing Date.	 Specify as:
yyyy-mm-dd  ...................... 	M, if applicable

 &lt;160&gt; ......	Number of SEQ ID NOs.	Count includes total number of
SEQ ID NOs......................................................... 	M.

 &lt;170&gt; ......	Software.............................	Name of
software used to create the Sequence Listing. 	O.

 &lt;210&gt; ......	SEQ ID NO:#:..................	Response shall be an
integer representing the SEQ ID NO shown. 	M.

 &lt;211&gt; ......	Length..............................	Respond with an
integer expressing the number of bases or amino acid residues. 	M.

 &lt;212&gt; ......	Type.................................	Whether
presented sequence molecule is DNA, RNA, or PRT (protein). If a
nucleotide sequence contains both DNA and RNA fragments, the type shall
be "DNA." In addition, the combined DNA/  RNA molecule shall be further
described in the  &lt;220&gt; to &lt;223&gt; feature section.  	M.

 &lt;213&gt; ......	Organism.........................	Scientific name,
i.e. Genus/ species, Unknown or Artificial Sequence. In addition, the
"Unknown" or "Artificial Sequence" organisms shall be further described
in the &lt;220&gt; to &lt;223&gt; feature section. 	M.

 &lt;220&gt; ......	Feature.............................	Leave blank
after &lt;220&gt;. &lt;221-223&gt; provide for a description of points
of biological significance in the sequence..	M, under the following
conditions: if "n,'' "Xaa,'' or a modified or unusual L-amino acid or
modified base was used in a sequence; if ORGANISM is "Artificial
Sequence" or "Unknown"; if molecule is combined DNA/RNA''

 &lt;221&gt; ......	Name/Key........................	Provide appropriate
identifier for feature, preferably from WIPO Standard ST.25 (1998),
Appendix 2, Tables 5 and 6. 	 M, under the following conditions: if "n,"
"Xaa," or a modified or unusual L-amino acid or modified base was used
in a sequence.

 &lt;222&gt; ......	Location...........................	Specify location
within sequence; where appropriate state number of first and last
bases/amino acids in feature.	M, under the following conditions: if "n,"
"Xaa," or a modified or unusual L-amino acid or modified base was used
in a sequence.

 &lt;223&gt; ......	Other Information............	Other relevant
information; four lines
maximum................................................	M, under the
following conditions: if "n," "Xaa," or a modified or unusual L-amino
acid or modified base was used in a sequence; if ORGANISM is "Artificial
Sequence" or "Unknown"; if molecule is combined DNA/RNA.

 &lt;300&gt;....	Publication Information... 	Leave blank after
&lt;300&gt;	O.

 &lt;301&gt;	Authors............................ 	Preferably max of ten
named authors of publication; specify one name per line; preferable
format: Surname, Other Names and/or Initials.	O.

 &lt;302&gt;	Title.................................. 	
................................................................	O.

 &lt;303&gt;	Journal.............................  	
................................................................	O.

 &lt;304&gt;	Volume ........................... 	
................................................................	O.

 &lt;305&gt;	Issue ................................	
................................................................	O.

 &lt;306&gt;	Pages ...............................	
................................................................	O.

 &lt;307&gt;	Date..............	Journal date on which data published;
specify as yyyy- mm-dd, MMM-yyyy or Season- yyyy.	O.

 &lt;308&gt;	Database Accession Number.	Accession number assigned by
database including database name.	O.

 &lt;309&gt;	Database Entry Date........ 	Date of entry in database;
specify as yyyy-mm-dd or MMM-yyyy.	O.

 &lt;310&gt;	Patent Document Number.	Document number; for patent- type
citations only. Specify as, for example, US 07/ 999,999.	O.

 &lt;311&gt;	Patent Filing Date..............	 Document filing date, for
patent-type citations only; specify as yyyy-mm-dd.	O.

 &lt;312&gt;	Publication Date................	Document publication date,
for patent-type citations only; specify as yyyy-mm-dd.	O.

 &lt;313&gt;	Relevant Residues............ 	FROM (position) TO
(position)................. 	O.

 &lt;400&gt;	Sequence..........................	SEQ ID NO should follow
the numeric identifier and should appear on the line preceding the
actual sequence.	M.

---SECTION---2424.01 Informational Requirements for the Sequence Listing

37 CFR 1.823 sets forth the informational requirements for inclusion in
the separate part of the disclosure on paper copy (the "Sequence
Listing") that must be submitted in accordance with  37 CFR 1.821(c). 
This section lists the items of information that are to be included in
the "Sequence Listing," which constitutes the separate part of the
disclosure on paper copy.  The items of information are to be presented
in the "Sequence Listing" in the order in which those items are listed
in  37 CFR 1.823. Page and line length requirements are set forth. The
requirement to use a fixed width font to present sequence data is also
set forth. This latter requirement is made to ensure that the desired
sequence character spacing and numbering is maintained upon printing.
The numeric identifier for each item of information shall not include
the explanatory information included in  37 CFR 1.823.

---SECTION---2424.02 Sequence Listing Numeric Identifiers

37 CFR 1.823(b) sets forth the order and presentation of the items of
information in the Sequence Listing.  Each item of information in the
Sequence Listing must include the appropriate numeric identifier and its
accompanying information as shown in the table below.  Each item of
information must begin on a new line with the numeric identifier
enclosed in angle brackets.  The submission of those items of
information designated with an  "M"  is mandatory.  The submission of
those items of information designated with an  "O"  is optional. 
Numeric identifiers &lt;110&gt; through &lt;170&gt; must be set forth at
the beginning of the Sequence Listing. 

The following table illustrates the numeric identifiers.  See MPEP
Section  2431 for a sample Sequence Listing.



Numeric Identifier	Definition	Comments and format	Mandatory (M) or
Optional (O)

 &lt;110&gt; ...	Applicant......................	Preferably max. of 10
names; one name per line; preferable format: Surname,  Other Names
and/or Initials. 	M.

 &lt;120&gt; ...	Title of Invention..........	
.............................................................	M.

 &lt;130&gt; ...	File Reference...............	Personal file
reference.........................	M when filed prior to assignment or
appl. number

 &lt;140&gt; ...	Current Application Number.	Specify as: US 07/999,999
or PCT/US96/99999.	M, if available.

 &lt;141&gt; ...	Current Filing Date.......	Specify as:
yyyy-mm-dd......................	M, if available.

 &lt;150&gt; ...	Prior Application Number. 	Specify as: US 07/999,999 or
PCT/US96/99999. 	M, if applicable include priority documents under  35
USC 119 and 120

 &lt;151&gt; ...	Prior Application Filing Date.	 Specify as: yyyy-mm-dd 
................... 	M, if applicable

 &lt;160&gt; ...	Number of SEQ ID NOs.	Count includes total number of
SEQ ID NOs. ...............................................	M.

 &lt;170&gt; ...	Software.......................	Name of software used
to create the Sequence Listing. 	O.

 &lt;210&gt; ...	SEQ ID NO:#:..............	Response shall be an integer
representing the SEQ ID NO shown. 	M.

 &lt;211&gt; ...	Length...........................	Respond with an
integer expressing the number of bases or amino acid residues. 	M.

 &lt;212&gt; ...	Type..............................	Whether presented
sequence molecule is DNA, RNA, or PRT (protein). If a nucleotide
sequence contains both DNA and RNA fragments, the type shall be "DNA."
In addition, the combined DNA/  RNA molecule shall be further described
in the  &lt;220&gt; to &lt;223&gt; feature section. 	M.

 &lt;213&gt; ...	Organism......................	Scientific name, i.e.
Genus/species, Unknown or Artificial Sequence. In addition, the
"Unknown" or "Artificial Sequence" organisms shall be further described
in the &lt;220&gt; to &lt;223&gt; feature section. 	M.

 &lt;220&gt; ...	Feature..........................	Leave blank after
&lt;220&gt;. &lt;221-223&gt; provide for a description of points of
biological significance in the sequence.	M, under the following
conditions: if "n," "Xaa," or a modified or unusual L-amino acid or
modified base was used in a sequence; if ORGANISM is "Artificial
Sequence" or "Unknown"; if molecule is combined DNA/RNA"

 &lt;221&gt; ...	Name/Key.....................	Provide appropriate
identifier for feature, preferably from WIPO Standard ST.25 (1998),
Appendix 2, Tables 5 and 6. 	 M, under the following conditions: if "n,"
"Xaa," or a modified or unusual L-amino acid or modified base was used
in a sequence.

 &lt;222&gt; ...	Location........................	Specify location
within sequence; where appropriate state number of first and last
bases/amino acids in feature.	M, under the following conditions: if "n,"
"Xaa," or a modified or unusual L-amino acid or modified base was used
in a sequence.

 &lt;223&gt; ...	Other Information.........	Other relevant information;
four lines maximum.............................................	M, under
the following conditions: if "n," "Xaa," or a modified or unusual
L-amino acid or modified base was used in a sequence; if ORGANISM is
"Artificial Sequence" or "Unknown"; if molecule is combined DNA/RNA.

 &lt;300&gt;....	Publication Information.... 	Leave blank after
&lt;300&gt;	O.

 &lt;301&gt;	Authors......................... 	Preferably max of ten
named authors of publication; specify one name per line; preferable
format: Surname, Other Names and/or Initials.	O.

 &lt;302&gt;	Title.............................. 	
.............................................................	O.

 &lt;303&gt;	Journal..........................  	
.............................................................	O.

 &lt;304&gt;	Volume ........................ 	
.............................................................	O.

 &lt;305&gt;	Issue .............................	
.............................................................	O.

 &lt;306&gt;	Pages ............................	
.............................................................	O.

 &lt;307&gt;	Date..............	Journal date on which data published;
specify as yyyy- mm-dd, MMM-yyyy or Season- yyyy.	O.

 &lt;308&gt;	Database Accession Number.	Accession number assigned by
database including database name.	O.

 &lt;309&gt;	Database Entry Date..... 	Date of entry in database;
specify as yyyy-mm-dd or MMM-yyyy.	O.

 &lt;310&gt;	Patent Document Number.	Document number; for patent- type
citations only. Specify as, for example, US 07/ 999,999.	O.

 &lt;311&gt;	Patent Filing Date.........	 Document filing date, for
patent-type citations only; specify as yyyy-mm-dd.	O.

 &lt;312&gt;	Publication Date...........	Document publication date, for
patent-type citations only; specify as yyyy-mm-dd.	O.

 &lt;313&gt;	Relevant Residues........ 	FROM (position) TO (position)
..........	O.

 &lt;400&gt;	Sequence.......................	SEQ ID NO should follow the
numeric identifier and should appear on the line preceding the actual
sequence.	M.

---SECTION---2424.03 Additional Miscellaneous Requirements

Throughout  37 CFR 1.823(b), the items of information relating to patent
applications and patent publications should be provided keeping in mind
the appropriate standards that have been established by the World
Intellectual Property Organization (WIPO).  In general, an application
should be identified by a country code, a number and a filing date,
while a published patent document should be identified by a country
code, a number and kind code.  Proper citation of priority patent
applications is covered in MPEP Section  201.14(d).  For published
patent documents, the country code, number and kind code will appear on
the front page of the document. Unpublished PCT applications are
identified by the letters PCT, the country code of the Receiving Office,
the last two digits of the year of filing and a number, e.g.,
PCT/AT81/00033, PCT/FR88/00100.  A published PCT application is
identified by the letters WO, the last two digits of the year of
publication, a number and a kind code, e.g., WO82/02827A, WO88/06811A.
Country codes from WIPO Standard ST.3 Annex A and kind codes from WIPO
Standard ST.16 are reproduced in MPEP Section  1851.  Questions on
proper citation of patent documents should be directed to the Search and
Information Resources Administration, International Liaison Staff.

In  37 CFR 1.823(b), numeric identifier &lt;110&gt;, the item of
information relating to "APPLICANT" should be limited to a maximum of
the first ten named applicants in the application.  Similarly, in
numeric identifier &lt;301&gt;, the item of information relating to
"AUTHORS" should be limited to to a maximum of the first ten named
authors in the publication.

In  37 CFR 1.823(b) "yyyy-mm-dd" is the format for the presentation of
patent related date information in the "Sequence Listing."  Other date
information may also be presented as MMM-yyyy or Season-yyyy. The lower
case letters designate numeric responses and the upper case letters
designate alphabetical responses.  As such, March 2, 1988, would be
presented as 1988-03-02 or MAR 1988.

In numeric identifiers &lt;220&gt; - &lt;223&gt;, relating to "Features"
or the description of the points of biological significance in a given
sequence, it is recommended, but not required, that the information that
is provided by the applicant conform to the controlled vocabulary that
is set forth in GenBank's "Feature Representation in Nucleotide Sequence
Data Libraries," Release 57.0, as may be amended.  Further, the feature
"LOCATION" should be specified using the syntax of the DDBJ/EMBL/GenBank
Feature Table Definition. See MPEP Section  2422 when filing in
countries which adhere to WIPO Standard ST.25.

In numeric identifiers &lt;300&gt; - &lt;312&gt;, publication
information for a given sequence is collected. The publication
information encompasses both patent-type publications and non-patent
literature publications. Numeric identifier &lt;313&gt;, Relevant
Residues, is intended to collect information relating to the
correspondence between a sequence set forth in the "Sequence Listing"
and published sequence information. The starting (FROM) and end (TO)
positions in the listed sequence that correspond to the published
sequence information should be set forth.

---SECTION---2425 Form and Format for Nucleotide and/or Amino Acid
Sequence Submissions in Computer Readable Form

37 CFR 1.824 Form and format for nucleotide and/or amino acid sequence
submissions in computer readable form.

(a) The computer readable form required by Section  1.821(e) shall meet
the following specifications:

(1) The computer readable form shall contain a single "Sequence Listing"
as either a diskette, series of diskettes, or other permissible media
outlined in paragraph (c) of this section.

(2) The "Sequence Listing" in paragraph (a) (l) of this section shall be
submitted in American Standard Code for Information Interchange (ASCII)
text. No other formats shall be allowed.

(3) The computer readable form may be created by any means, such as word
processors, nucleotide/amino acid sequence editors or other custom
computer programs; however, it shall conform to all specifications
detailed in this section.

(4) File compression is acceptable when using diskette media, so long as
the compressed file is in a self-extracting format that will decompress
on one of the systems described in paragraph (b) of this section.

(5) Page numbering shall not appear within the computer readable form
version of the "Sequence Listing" file.

(6) All computer readable forms shall have a label permanently affixed
thereto on which has been hand-printed or typed: the name of the
applicant, the title of the invention, the date on which the data were
recorded on the computer readable form, the operating system used, a
reference number, and an application serial number and filing date, if
known.

(b) Computer readable form submissions must meet these format
requirements:

(1) Computer: IBM PC/XT/AT, or compatibles, or Apple Macintosh;

(2) Operating System: MS-DOS, Unix or Macintosh;

(3) Line Terminator: ASCII Carriage Return plus ASCII Line Feed;

(4) Pagination: Continuous file (no "hard page break" codes permitted);

(c) Computer readable form files submitted may be in any of the
following media:

(1) Diskette: 3.50 inch, 1.44 Mb storage; 3.50 inch, 720 Kb storage;
5.25 inch, 1.2 Mb storage; 5.25 inch, 360 Kb storage.

(2) Magnetic tape: 0.5 inch, up to 24000 feet; Density: 1600 or 6250
bits per inch, 9 track; Format: Unix tar command; specify blocking
factor (not "block size"); Line Terminator: ASCII Carriage Return plus
ASCII Line Feed.

(3) 8mm Data Cartridge: Format: Unix tar command; specify blocking
factor (not "block size"); Line Terminator: ASCII Carriage Return plus
ASCII Line Feed.

(4) CD-ROM: Format: ISO 9660 or High Sierra Format

(5) Magneto Optical Disk: Size/Storage Specifications: 5.25 inch, 640
Mb.

(d) Computer readable forms that are submitted to the Office will not be
returned to the applicant.

37 CFR 1.824 sets forth the requirements for sequence submissions in
computer readable form.  Any computer operating system may be utilized
to produce a sequence submission, provided that the system is capable of
producing a file having the characteristics specified in  37 CFR  1.824,
and is capable of writing the properly formatted file to one of the
acceptable electronic media. If a given sequence and its associated
information cannot practically or possibly fit on the electronic media
required in  37 CFR 1.824(c), an exception via a non-fee petition to
waive this provision will normally be granted.  As set forth in  37 CFR 
1.824(d), the computer readable forms that are submitted in accordance
with these rules will not be returned to the applicant. 37 CFR 
1.824(a)(6) requires the labeling, with appropriate identifying
information, of the computer readable forms that are submitted in
accordance with these rules.

---SECTION---2426 Amendments to or Replacement of Sequence Listing and
Computer Readable Copy Thereof

37 CFR 1.825 Amendments to or replacement of sequence listing and
computer readable copy thereof.

(a) Any amendment to the paper copy of the "Sequence Listing" (Section 
1.821(c)) must be made by the submission of substitute sheets.
Amendments must be accompanied by a statement that indicates support for
the amendment in the application, as filed, and a statement that the
substitute sheets include no new matter.

(b) Any amendment to the paper copy of the "Sequence Listing," in
accordance with paragraph (a) of this section, must be accompanied by a
substitute copy of the computer readable form (Section  1.821(e))
including all previously submitted data with the amendment incorporated
therein, accompanied by a statement that the copy in computer readable
form is the same as the substitute copy of the "Sequence Listing."

(c) Any appropriate amendments to the "Sequence Listing'' in a patent;
e.g., by reason of reissue or certificate of correction, must comply
with the requirements of paragraphs (a) and (b) of this section.

(d) If, upon receipt, the computer readable form is found to be damaged
or unreadable, applicant must provide, within such time as set by the
Commissioner, a substitute copy of the data in computer readable form
accompanied by a statement that the substitute data is identical to that
originally filed.

37 CFR 1.825 sets forth the procedures for amending the  "Sequence
Listing" and the computer readable copy thereof.  The procedures that
have been defined in  37 CFR 1.825 involve the submission of either
substitute sheets of the "Sequence Listing" or substitute copies of the
computer readable form, in conjunction with statements that indicate
support for the amendment in the application, as filed, and that the
substitute sheets or copies include no new matter.  (See MPEP Section 
2428 for further information and Sample Statements.) The requirement for
statements regarding the absence of new matter follows current practice
relating to the submission of substitute specifications, as set forth in 
37 CFR 1.125.  37 CFR 1.825 (c) addresses the situation where amendments
to the  "Sequence Listing" are made after a patent has been granted,
e.g., by a certificate of correction, reissue or reexamination. 37 CFR
1.825 (d) addresses the possibility and presents a remedy for the
situation where the computer readable form may be found by the Office to
be damaged or unreadable.

---SECTION---2427 Form Paragraphs and Notice to Comply

---SECTION---2427.01 Form Paragraphs

In order to minimize the extension of pendency due to the implementation
of the sequence rules, all compliance issues should be addressed in a
single communication with the applicant. That communication should set a
1-month (not less than 30 days) period for reply that may be extended in
accordance with the provisions of  37 CFR 1.136.  However, depending
upon the nature of applicant's reply, a follow-up communication
regarding the sequence rules may be necessary. The form paragraphs that
follow are to be used in these communications. The form paragraphs
should be used as follows:

7.200 - This form paragraph should be used for the first mailing of a
Notice to Comply.

7.201 - This form paragraph should be used for the first mailing of a
CRF Diskette Problem Report.

7.202 - This form paragraph should be used when an applicant has made a
bona fide attempt to comply but the reply generates an error listing
from the Scientific and Technical Information Center (STIC). This should
be used for a second mailing to applicant unless it is evident that
there has been a deliberate omission; this form paragraph may also be
used to extend the period for reply for the initially mailed notice.

7.203 - This form paragraph should be used when there has been a
deliberate omission in the reply or where the reason the reply is
incomplete cannot be characterized as an apparent oversight or instance
of inadvertence.

7.200 Cover Letter for Use With Notice To Comply With Sequence Rules

This application contains sequence disclosures that are encompassed by
the definitions for nucleotide and/or amino acid sequences set forth in 
37 CFR 1.821(a)(1) and (a)(2).  However, this application fails to
comply with the requirements of  37 CFR 1.821 through 1.825 for the
reason(s) set forth on the attached Notice To Comply With Requirements
For Patent Applications Containing Nucleotide Sequence And/Or Amino Acid
Sequence Disclosures.

Applicant is given ONE MONTH, or THIRTY DAYS, whichever is longer, from
the mailing date of this letter within which to comply with the sequence
rules,  37 CFR 1.821 - 1.825.  Failure to comply with these requirements
will result in ABANDONMENT of the application under  37 CFR 1.821(g). 
Extensions of time may be obtained by filing a petition accompanied by
the extension fee under the provisions of  37 CFR 1.136(a).  In no case
may an applicant extend the period for reply beyond the SIX MONTH
statutory period.  Direct the reply to the undersigned.  Applicant is
requested to return a copy of the attached Notice to Comply with the
reply.

Examiner Note:

1. Use this form paragraph only for the initial communication to the
applicant.  Use either 7.203 or 7.203 for subsequent communications.

2. Conclude action with appropriate form paragraph(s) 7.100-7.102.

3. Print this paragraph on a PTOL-90 and attach a Notice To Comply With
Requirements for Patent Applications Containing Nucleotide And/Or Amino
Acid Sequence Disclosures, along with a marked-up copy of the Raw
Sequence Listing, if any.

7.201 Cover Letter for Use with CRF Diskette Problem Report

This application contains sequence disclosures that are encompassed by
the definitions for nucleotide and/or amino acid sequences set forth in 
37 CFR 1.821(a)(1) and (a)(2).  A computer readable form (CRF) of the
sequence listing was submitted.  However, the CRF could not be processed
by the Scientific and Technical Information Center (STIC) for the
reason(s) set forth on the attached CRF Diskette Problem Report.

Applicant is given ONE MONTH, or THIRTY DAYS, whichever is longer, from
the mailing date of this letter within which to comply with the sequence
rules,  37 CFR 1.821 - 1.825.  Failure to comply with these requirements
will result in ABANDONMENT of the application under  37 CFR 1.821(g). 
Extensions of time may be obtained by filing a petition accompanied by
the extension fee under the provisions of  37 CFR 1.136(a).  In no case
may an applicant extend the period for reply beyond the SIX MONTH
statutory period.  Direct the reply to the undersigned.  Applicant is
requested to return a copy of the attached CRF Diskette Problem Report
with the reply.

Examiner Note:

1. Use this form paragraph only for the initial communication to the
applicant.  Use either 7.203 or 7.203 for subsequent communications.

2. Conclude action with appropriate form paragraph(s) 7.100-7.102.

3. Print this paragraph on a PTOL-90 and attach the CRF Diskette Problem
Report.

7.202 CRF Submission Is Not Fully Responsive, Bona Fide Attempt

The reply filed [1] is not fully responsive to the Office communication
mailed [2] for the reason(s) set forth on the attached Notice To Comply
With The Sequence Rules or CRF Diskette Problem Report.

Since the above-mentioned reply appears to be bona fide, applicant is
given a TIME PERIOD of ONE (1) MONTH or THIRTY (30) DAYS from the
mailing date of this notice, whichever is longer, within which to supply
the omission or correction in order to avoid abandonment.  EXTENSIONS OF
THIS TIME PERIOD MAY BE GRANTED UNDER  37 CFR 1.136(a).

Examiner Note:

1. This form paragraph may be used whether or not the six-month period
for reply has expired.  It is intended for use whenever a bona fide
reply has been submitted.  This practice does not apply where there has
been a deliberate omission of some necessary part of a complete reply or
where the reason the reply is incomplete cannot be characterized as an
apparent oversight or apparent inadvertence.  Under such cases the
examiner has no authority to grant an extension if the six-month period
for reply has expired.  Use form paragraph 7.203 under such
circumstances.

2. In bracket 1, insert the date of the reply and in bracket 2, insert
the mail date of the communication requiring compliance.

3. Print this paragraph on a PTOL-90 and attach a Notice To Comply With
Requirements For Patent Applications Containing Nucleotide Sequence
And/Or Amino Acid Sequence Disclosures, along with a marked-up copy of
the Raw Sequence Listing, or CRF Diskette Problem Report.

4. See  37 CFR 1.135(c), 1.821(g);  MPEP Section Section  710.02(c), 
711.02(a),  714.02 and  714.03.

7.203 CRF Submission Is Not Fully Responsive

The communication filed [1] is not fully responsive to the communication
mailed [2] for the reason(s) set forth on the attached Notice To Comply
With The Sequence Rules or CRF Diskette Problem Report.

If a complete reply has not been submitted by the time the shortened
statutory period set in the communication mailed [3] has expired, this
application will become abandoned unless applicant corrects the
deficiency and obtains an extension of time under  37 CFR 1.136(a).  In
no case may an applicant extend the period for reply beyond the SIX
MONTH statutory period.

Examiner Note:

1. This form paragraph may not be used when the six month period for
reply has expired.  Use this form paragraph in the situation where, in
the reply (within the six-months), there has been a deliberate omission
of some necessary part of a complete reply.  When the reply appears to
be bona fide, but through an apparent oversight or inadvertence failed
to provide a complete reply, use form paragraph 7.202.

2. In bracket 1, insert the date of the reply and in brackets 2 and 3,
insert the mail date of the communication requiring compliance.

3. Print this paragraph on a PTOL-90 and attach a Notice To Comply With
Requirements For Patent Applications Containing Nucleotide Sequence
And/Or Amino Acid Sequence Disclosures, along with a marked-up copy of
the Raw Sequence Listing, or CRF Diskette Problem Report.

---SECTION---2427.02 Notice To Comply

The text of the Notice to Comply With Requirements For Patent
Applications Containing Nucleotide Sequence and for Amino Acid Sequence
Disclosures, Form PTO-1661, follows. The appropriate box on the notice
should be checked depending upon the particular deficiencies that have
been identified.  A copy of the "Raw Sequence Listing," where available,
should also be sent to the applicant. The "Raw Sequence Listing" should
also be entered into the application file upon receipt from STIC.

Form PTO-1661. Notice to Comply with Requirements for Patent
Applications Containing Nucleotide Sequence and/or Amino Acid Sequence
Disclosures[GRAPHIC]

---SECTION---2428 Sample Statements

Sample language for the statements required to support sequence rule
submissions is provided below. These statements are given by way of
example only; other language may, of course, be used. For the statements
that relate to the assertion that the content of the paper and computer
readable copies are the "same," it is acknowledged that there may be
some nonsubstantive differences between the two, e.g., page numbers and
page breaks may be present in the paper copy but not in the computer
readable copy thereof. This requirement for sameness relates to the
informational content of the paper and computer readable copies relevant
to the requirements of the sequence rules.

37 CFR 1.821(f) -  I hereby state that the information recorded in
computer readable form is identical to the written sequence listing.

   37 CFR 1.821(g) [or (h)] - I hereby state that the submission, filed
in accordance with  37 CFR 1.821(g) [or (h)], herein does not include
new matter [or matter which goes beyond the disclosure in the
international application].

   37 CFR 1.825(a) - I hereby state that the amendments, made in
accordance with  37 CFR 1.825(a), included in the substitute sheet(s) of
the Sequence Listing are supported in the application, as filed, at
_____________.  I hereby state that the substitute sheet(s) of the
Sequence Listing does (do) not include new matter.

   37 CFR 1.825(b) - I hereby state that the substitute copy of the
computer readable form, submitted in accordance with  37 CFR 1.825(b),
is the same as the amended Sequence Listing.

   37 CFR 1.825(d)   - I hereby state that the substitute copy of the
computer readable form, submitted in accordance with  37 CFR 1.825(d),
is identical to that originally filed.

---SECTION---2429 Helpful Hints for Compliance

The Office has now had a good deal of experience in the implementation
of the sequence rules. The following list sets forth helpful hints, for
both examiners and applicants, for compliance.  For the most part, the
list is a compilation of frequently asked questions.

-Compliance is not a filing date issue.

-Compliance is not a  35 U.S.C. 112 issue.

-Compliance is not a  35 U.S.C. 119/120 issue.

-Compliance is not a new matter issue. The standard for resolution of
inconsistencies between the paper and the electronic copies and/or
errors in the paper copy of sequence information is based on the new
matter standard.

-Compliance can be achieved via amendment.

-The paper copy of Sequence Listing is an integral part of the
application. The Sequence Listing must begin on a new page, should
appear at the end of the application, and preferably should be numbered
independently of the numbering of the remainder of the application. The
new page that begins the "Sequence Listing" should be entitled "Sequence
Listing." If not submitted as such at filing, the Sequence Listing must
be inserted into the application via amendment, e.g., by preliminary
amendment.

-Substitute pages must be used for changes to the Sequence Listing.

-Angle brackets and numeric identifiers listed in  37 CFR 1.823 are very
important for our database. Extra punctuation should not be used in
Sequence Listings.

-The computer readable form cannot contain page numbers.  Page numbers
should only be placed on the paper copy of the Sequence Listing.

-The PatentIn computer program is not the only means by which to comply
with the rules. Any word processing program can be used to generate a
Sequence Listing if it has the capability to convert a file into ASCII
text.

-If a word processing program is used to generate a  "Sequence Listing,"
hard page break controls should not be used and margins should be
adjusted to the smallest setting.

-Word processing files should not be submitted to the Office; the
Sequence Listing generated by a word processing file should be saved as
an ASCII text file for submission. Most word processing programs provide
this feature.

-Statements in accordance with  37 CFR 1.821(f), (g), (h) and  37 CFR
1.825 and proper labeling in accordance with  37 CFR 1.824(a)(6) should
be noted.  Sample statements to support filings and submissions in
accordance with  37 CFR 1.821 through 1.825 are provided in MPEP Section 
2428 Sample Statements.

-Use Box Sequence.

-Three and a half inch disks are less fragile than five and a quarter
inch disks.

-On nucleotide sequences, since only single strands may be depicted in
the "Sequence Listing," show strands in 5&prime; to 3&prime; direction.

-The single stranded nucleotide depicted in the "Sequence Listing" may
represent a strand of a nucleotide sequence that may be single or double
stranded which may be, further, linear or circular.  An amino acid
sequence or peptide may be linear or circular.  In some instances, a
sequence may be both single stranded and double stranded and/or both
linear and circular. The response "not relevant" is also an acceptable
response for both "Strandedness" and "Topology."

-Numeric identifiers "&lt;140&gt;, Current Application Number,"
"&lt;141&gt;, Current Filing Date," "&lt;150&gt;, Prior Application
Number," and "&lt;151&gt;, Prior Application Filing Date," should appear
in the "Sequence Listing" in all cases.  If the information about the
current application is not known or is unavailable at the time of
completing the Sequence Listing, then the lines following numeric
identifiers &lt;140&gt; and &lt;141&gt; should be left blank. This would
normally be the case when the "Sequence Listing" is included in a newly
filed application. Similarly, if information regarding prior
applications is inapplicable, or not known at the time of completing the
"Sequence Listing" but will be later filed, then the numeric identifiers
&lt;150&gt; and &lt;151&gt; should appear with the line following the
numeric identifiers left blank.

-If you receive a Notice to Comply that should not have been sent to
you, send a letter in the form of a request for reconsideration of the
notice to the organization sending the notice.

-There are a limited number of mandatory items of information. They are
identifed in MPEP Section  2424.02 Sequence Listing Numeric Identifiers.

-Figures can be used to convey information not readily conveyed by the
Sequence Listing.  The exclusive conformance requirement of  37 CFR
1.821(b) will be relaxed for drawing figures. However, the sequence
information so conveyed must still be included in a "Sequence Listing"
and the sequence identifier ("SEQ ID NO:X") must be used, either in the
drawing or in the "Brief Description of the Drawings."

-Extra copies of computer readable forms should not be sent to
examiners.

 -Inosine may be represented by the use of "I" in the features section,
otherwise use "n."

 -Stop codons, represented by an asterisk, are not permitted in amino
acid sequences.

 -Punctuation should not be used in a sequence to indicate unknown
nucleotide bases or amino acid residues nor should punctuation be used
to delimit active or functional regions of a sequence.  These regions
should be noted as Features of the sequence per  37 CFR 1.823(b) (see
numeric identifiers &lt;220&gt; - &lt;223&gt;.

-The presence of an unnatural amino acid in a sequence does not have the
same effect as the presence of a D-amino acid.  The sequence may still
be subject to the rules even though one or more of the amino acids is
not naturally occurring.

-Cyclic and branched peptides are causing some confusion in the
application of the rules. Specific questions should be directed to Group
1650 personnel.

-A cyclic peptide with a tail is regarded as a branched sequence, and
thereby exempt from the rules, if all bonds adjacent to the amino acid
from which the tail emanates are normal peptide bonds.

-Sequences that have variable-length regions depicted as, for example,
Ala Ala Leu Leu (Xaa Xaa)n Ile Pro where n=0-234 or
agccttgggaca(nnnnn)mgtcatt where m=0-354 or Ser Met Ala Xaa Ser where
Xaa could be 1, 2, 3, 4 and/or  5 amino acids must still comply with the
Sequence Rules.  The method to use is to repeat the variable-length
region as many times as the maximum length and specify in the Features
section that the amino acid (or nucleotide) at a specified position is
either absent or present.  The variables Xaa and n may stand for only
one residue, hence the need to repeat the variable.  The correct way to
submit the third example is Ser Met Ala Xaa Xaa Xaa Xaa Xaa Ser combined
with an explanation in the Features section of the listing that any one
or all of amino acids 4-8 can either be present or absent.

-Single letter amino acid abbreviations are not acceptable within the
Sequence Listing but may appear elsewhere in the application.

-Zero (0) is not used when the numbering of amino acids uses negative
numbers to distinguish the mature protein.

-Subscripts or superscripts are not permitted in a Sequence Listing.

-If a "Sequence Listing" is amended, an entirely new computer readable
form is required regardless of the triviality of the amendment.
Amendments to the paper copy of the "Sequence Listing" must be made by
substitute sheets. 

-Note field length limitations. For specific in stances, they may be
waived, but compliance is encouraged.

-The exclusive conformance requirement of  37 CFR 1.821(b) requires that
any amendment of the sequence information in a "Sequence Listing" be
accompanied by an amendment to the corresponding information, if any,
embedded in the text of the specification or presented in a drawing
figure.

-Any inquiries regarding a specific computer readable form that has been
processed by the Office should be directed to the Systems Branch of the
Chemical/Biotechnology Division of the Scientific and Technical
Information Center.

---SECTION---2430 PatentIn Information; Utilities Programs; Training

In those areas of biotechnology in which nucleotide and/or amino acid
sequence information is significant, many patent applicants are
accustomed to, or familiar with, the submission of such sequence
information, in electronic form, to various sequence databases, such as
GenBank, which is produced by the National Institutes of Health. In
order to facilitate such submissions, or merely for the purpose of
researching and developing sequence information, many eventual patent
applicants also generate or encode sequence information in computer
readable form. In order to further facilitate compliance with the
sequence rules, the Office has made available to the public an input
program that is based on the AuthorIn program produced by GenBank. This
input program, called PatentIn version 1.3, was specifically tailored to
the requirements of the sequence rules which were in effect prior to
July 1, 1998.

The Office has completed an updated version of the PatentIn program,
called PatentIn version 2.0.  This new version is compliant with
Microsoft Windows 3.1x, 95, and NT.  This new version also incorporates
changes in the required format for the Sequence Listing to ensure
compliance with the new World Intellectual Property Office (WIPO)
Standard ST.25 which became effective July 1, 1998 and with revisions to
the U.S. sequence rules which became effective July 1, 1998.  This new
WIPO Standard simplifies the Sequence Listing requirements, and
harmonizes the format among all Trilateral Patent Offices and many other
patent offices around the world. By using PatentIn version 2.0,
customers will be able to generate a Sequence Listing once and use that
same listing to file at multiple patent offices worldwide. Applications
filed in the U.S. after July 1, 1998 containing Sequence Listings
prepared using PatentIn version 1.3 will not be in compliance with the
U.S. sequence rules. Applications filed in the member countries of WIPO
after July 1, 1998 containing Sequence Listings prepared using PatentIn
version 1.3 will not be in compliance with ST.25. 

The new PatentIn version 2.0, and the companion User Manual, are
available on the Office world wide web site (www.uspto.gov) for free
downloading.  Copies of both the program and the user manual are also
available on 3 1/2 inch floppy diskette at a cost of $25.00 for each
item.  PatentIn version 2.0 has similar space, memory, and system
requirements as those for PatentIn version 1.3, except that to function
properly PatentIn 2.0 requires a Microsoft Windows operating system. See
MPEP Section  1730 for additional information regarding ordering and
using PatentIn.

While use of the PatentIn program is not required for compliance with
the sequence rules, its use is highly recommended as Office experience
has shown that submissions developed with PatentIn are far less likely
to include errors than those developed without the program. The many
automatic features of the PatentIn program also greatly ease the
generation of Sequence Listings when compared to generating them by hand
in a word processing environment. This is especially true for Sequence
Listings that include many sequences and/or sequences having great
lengths.

The Office provides hands-on training in the use of the PatentIn and
associated utilities programs. The classes are held in Washington D.C.
as demand warrants.  In addition, on site training may be arranged at
locations outside Washington, D.C. To express interest in such classes,
please contact the Search and Information Resources Administration.

---SECTION---2431 Sample Sequence Listing

A sample "Sequence Listing" is included below. 

[GRAPHIC]

[GRAPHIC]

---SECTION---2434 Examination of Patent Applications Claiming Large
Numbers of Nucleotide Sequences

The Patent and Trademark Office recently published its policy for the
examination of patent applications that claim large numbers of
nucleotide sequences in the   Official Gazette, 1192 O.G. 68 (November
19, 1996). Nucleotide sequences encoding different proteins are
structurally distinct chemical compounds and are unrelated to one
another. These sequences are thus deemed to normally constitute
independent and distinct inventions within the meaning of  35 U.S.C.
121. Absent evidence to the contrary, each such nucleotide is presumed
to represent an independent and distinct invention, subject to a
restriction requirement pursuant to  35 U.S.C. 121 and  37 CFR 1.141. In
establishing the new policy, the Commissioner has partially waived the
requirements of  37 CFR 1.141 and will permit a reasonable number of
such nucleotide sequences to be claimed in a single application. Under
this policy, in most cases, up to 10 independent and distinct nucleotide
sequences will be examined in a single application without restriction.
Those sequences which are patentably indistinct from the sequences
selected by the applicant will also be examined. Nucleotide sequences
encoding the same protein are not considered to be independent and
distinct and will continue to be examined together. In some exceptional
cases, the complex nature of the claimed material may necessitate that
the reasonable number of sequences to be selected be less than 10. In
other cases, applicants may petition pursuant to  37 CFR 1.181 for
examination of additional nucleotide sequences by providing evidence
that the different nucleotide sequences do not cover independent and
distinct inventions. For examples of typical nucleotide sequence claims
and additional information on the search and examination procedures, see
the above cited O.G. Notice.  See also MPEP Section  803.04.

