Department of Commerce
                          Patent and Trademark Office

                                 37 CFR Part 1
                        [Docket No: 960828235-6235-01]
                                RIN: 0651-AA88


                    Changes Implementing Nucleotide and/or
                         Amino Acid Sequence Listings

Agency: Patent and Trademark Office, Commerce.
Action: Notice of Proposed Rulemaking and Request for Comments.
Summary: The Patent and Trademark Office (PTO) is proposing to amend the
rules for submitting nucleic acid or amino acid sequences in computer
readable form (CRF) for patent applications to simplify the requirements
of the rules, to rearrange portions of the rules for better
understanding and to establish consistent rules to permit a single
internationally acceptable computer readable form. The Sequence Listing
will be presented in an international, language neutral format using
numeric identifiers rather than the current subject headings and the
paper Sequence Listing will be a separately numbered section of the
patent application. Sequences which contain fewer than four (4)
specifically identified nucleotides or amino acids will no longer be
required to be submitted in computer readable form.
Date: Written comments must be received by December 3, 1996.
Addresses: Address written comments to: Box Comments - Patents,
Assistant Commissioner for Patents, Washington, DC 20231, Attention:
Esther M. Kepplinger or by Fax to (703) 305-3601 to her attention.
Comments may be sent by mail message over the Internet addressed to
seqrule@uspto.gov. The written comments will be available for public
inspection in Suite 520, Crystal Park One, 2011 Crystal Drive,
Arlington, Virginia.
For Further Information Contact: Esther M. Kepplinger, by telephone at
(703) 308-2339 or by mail addressed to: Box Comments - Patents,
Assistant Commissioner for Patents, Washington, DC 20231 marked to her
attention or by Fax to (703) 305-3601 or by electronic mail at
ekepplin@uspto.gov.
Supplemental Information: The existing sequence rules (37 CFR
1.821-1.825) provide a standardized format for the description of
nucleotide and amino acid sequence data in patent applications and
require the submission of such sequences in computer readable form
(CRF). The existing sequence rules have provided the following benefits
to the PTO: (1) improved search capabilities; (2) improved interference
detection; (3) more efficient examination; (4) cost savings for the
input of the sequence data; (5) more efficient and accurate printing of
sequences in patents; (6) exchange of the sequence data with other
patent offices electronically and (7) improved public access to the
sequences electronically.
   In an effort to streamline and reduce the procedural requirements of
the existing rules and to respond to the needs of our customers while
establishing an internationally acceptable standard, the PTO proposes to
modify the current rules requiring the submission of computer readable
forms for nucleotide and amino acid sequences.
   To decrease the burden on applicants who file applications containing
nucleotide and amino acid sequence information under the Patent
Cooperation Treaty (PCT), the PTO entered into discussions at the PCT
Meeting of International Authorities (MIA) in November 1994 on changing
the applicable rules for submission and transfer of Sequence Listings.
Under the current PCT rules, each International Searching Authority and
national Office may set the standard for submission of the paper and
electronic Sequence Listing information. This may impose a burden on
applicants of providing several different formats of Sequence Listings
in different languages during the international and national phases of
the PCT procedure.
   Under the current PCT practice, the applicant serves as the data
repository for requests during each stage of the PCT practice for new
electronic copies of the Sequence Listings.
   Under national practice, a Sequence Listing may be required to be
translated into the national language at considerable cost and posing
the danger that the data could be inadvertently altered.
   At the November 1994 MIA to address these problems, rule changes were
proposed to require a language neutral Sequence Listing submission which
would suffice for PCT and national stage sequence information
processing. Initial Trilateral meetings and correspondence suggest that
such a sequence submission would be acceptable under European Patent
Office (EPO) and Japanese Patent Office (JPO) procedures, thus further
lessening the burden on applicants.
   These sequence rules are proposed to be revised in concert with World
Intellectual Property Organization (WIPO) International Standards ST.23
and ST.24 for the paper and electronic submission of sequence
information in patent applications, as well as PCT requirements. This
should result in an applicant having to produce a single Sequence
Listing that would satisfy the filing requirements in all countries, as
well as permitting an applicant to submit only a single electronic
Sequence Listing in PCT applications.
   In an effort to profit from the experiences of the nucleotide
database information providers which pioneered the electronic submission
of sequence information, the PTO discussed with them the possible
simplification of the PTO sequence submission rules. In response to
their advice (which confirmed the PTO experience), the number of
mandatory data elements is proposed to be reduced.
   Thus, the proposed rule changes include:
   (1) use of numeric identifiers to replace the language subject
headings within the submission;
   (2) elimination of unnecessary and confusing data elements;
   (3) movement of the paper Sequence Listing to the end of the
application as a section with separately numbered pages;
   (4) modification of 37 CFR    1.77 to include the paper Sequence
Listing as a part of the specification and to provide a place for the
paper Sequence Listing in the printed patent;
   (5) elimination of the requirement to provide a submission for
sequences with fewer than four specifically defined nucleotides or amino
acids;
   (6) use of lower-case one-letter codes for nucleotide bases;
   (7) rearrangement of portions of the rules to improve their context;
and
   (8) clarification and simplification of the rules to aid in
understanding of the requirements that they set forth.

Request For Comments:

   The PTO is particularly interested in receiving comments on three
queries. Currently sequences containing D-amino acids need not be
provided in the "Sequence Listing", but the PTO has accepted voluntary
submissions of sequences containing D-amino acids.
   The commercially available sequence searching software used to search
prior art databases is not capable of discerning D-amino acids since
they do not have distinct designators. It is for this reason that the
rules do not require a computer readable form for the disclosure of
sequences which contain D-amino acids.
   Those seeking to volunteer the information in accordance with these
rules might be seeking assurance that a machine search of the closest
prior art will be conducted by the PTO or they consider the information
useful and wish it to be in the database. If the PTO does not accept
voluntary submissions, that would exclude information from the databases
that at least some applicants believe to be valuable information.
   The potential conflict created by accepting these D-amino
acid-containing sequences is that the published database will contain
sequences with D-amino acids and those using the published database may
be operating on the assumption that it does not, given the indication in
   1.821(a)(2) that D-amino acid-containing sequences are not intended
to be included. For this reason, there may be an advantage to having the
D-amino acids indicated by Xaa to alert the user that the Feature
section must be consulted. A disadvantage of voluntary submissions is
that they will result in the generation of a database which is
incomplete and cannot be relied upon to provide a complete search of the
U.S. patent literature including sequences containing D-amino acids.
   The PTO seeks comments on the following query:

   (1) Should the PTO accept voluntary submissions of computer readable
forms and Sequence Listings where a D-amino acid is contained in the
sequence? If such voluntary submissions are accepted, should there be a
restriction on the choice of identifying a D-amino acid by an Xaa or by
its L-amino acid counterpart abbreviation?

   Section 1.821(c) will continue to require that all sequence information
contained in a disclosure, including in the specification, drawings or
claims, be presented in the Sequence Listing in accordance with
1.821 - 1.825. This provision does not discriminate between prior art
sequences and "new" sequences. The PTO has received comments in the past
and is seeking additional comments on this issue. The suggestion has
been made that sequences which are prior art, and/or are contained in a
database at the time of filing, need not be provided to the PTO in
computer readable form since the sequence information is obtainable by
other means. Responsive to these public comments, the PTO is considering
amending the rules to permit omission of some sequences from the
Sequence Listing if these sequences are admitted prior art to applicant
and are in a publicly available, electronic, sequence database and the
database accession number is supplied.
   The suggestion to exclude prior art sequences was made when
1.821 - 1.825 were originally adopted. 55 FR 18230, 18237 (1990). The
final rules, however, required the submission of all sequence
information in computer readable form. The reasons for that decision
include: 1) the assessment of whether a particular sequence falls within
the requirements of the current rules is simple; 2) the general public
is assured that all patents which contain any sequence information
contain all of the sequence information in the Sequence Listing and all
sequences are available in a computer accessible form; 3) as a
publication, the contextual association of new and old information is
potentially unique to the patent and very valuable to anyone assessing
the state of the art at the time of a patented invention, and thus are
desirable to be present in electronic form in association with that
patent; and 4) these rules do not require any information to be
disclosed in the form of a sequence, but rather require a particular
format whenever information is presented in the form of a sequence.
These reasons continue to be relevant.
   The PTO is concerned about how such a provision would be drafted
without creating difficult questions. A provision which excludes
sequences whenever a sequence is prior art and has previously been
included in a publicly available, electronic, sequence database appears
to be straightforward; however, many technical and legal issues would
result. What constitutes a publicly available, electronic, sequence
database? Would the USPTO and the other patent offices which have
similar rules be required to produce a list of internationally accepted
databases? What would be the criteria for such acceptance? An additional
issue would exist involving electronic records maintenance: is there any
assurance that once information is contained in a database that it will
be retained and available indefinitely without alteration? Changes to
the information in nucleic acid sequence databases resulting from the
discovery of sequencing errors are well-known. Does the mere existence
of the sequence information in such a record constitute reasonable means
of retrieval? Would not one need some text basis or other identifier to
retrieve the information?
   Concerns have been voiced that the redundancy of including old
sequences in the PTO database creates electronic searching problems,
such as increased cost and reduced speed. Upon investigation, it has
been found that requiring all disclosed sequences to be included in the
Sequence Listing does not cause search processing problems at the PTO or
incur increased costs.
   The PTO seeks comments on the following query:

   (2) Should the provisions of 37 CFR 1.821(c) be altered to exclude some
prior art sequences from inclusion in the Sequence Listing even though
they are presented in a patent application disclosure as sequences?
Should the reference to an accession number of an admitted prior art
sequence in a publicly available, electronic, sequence database suffice
and exclude that sequence from the requirements of the sequence rules?

   At the November 1994 MIA, it was proposed that the Sequence Listings
submitted in an international application filed under the PCT would no
longer be published on paper. It was suggested that the Sequence
Listings be published electronically and be available in the electronic
form from several sequence repositories throughout the world. These
repositories would have the Sequence Listings available in electronic
form at the time of publication of the PCT pamphlet.
   The PTO seeks comments on the following query:

  (3) Should Sequence Listings filed in an international application filed
under the PCT be published only electronically and made available for
retrieval electronically by an accession number from several sequence
repositories?

   Written comments will be available for public inspection and will be
available on the Internet (address: www.uspto.gov). Commentators should
note that since their comments will be made publicly available,
information that is not desired to be made public, such as the address
and phone number of the commentator, should not be included in the
comments. A public hearing will not be conducted.

Discussion of Specific Rules

   Section 1.77 is proposed to be amended by revising paragraph (g),
which would provide for a reference to a Sequence Listing Annex, if any
exists. In the application as filed, on a separate page immediately
before the claims, reference would be made to a Sequence Listing Annex
and the Sequence Listing would be provided as a separately numbered
section or Annex to the application. In a printed patent the Sequence
Listing would appear immediately before the claims.
   Section 1.77 is proposed to be amended to redesignate existing
paragraphs (g) - (j) as paragraphs (h) - (k) and add an additional
paragraph (l) Sequence Listing Annex. In the application as filed, the
Sequence Listing would be provided by applicants as a separately
numbered section or Annex of the application. The pages of the Sequence
Listing Annex should be numbered independently from the specification
using sequential integers preceded by "A" to identify them as a part of
the Annex and to prevent any confusion which might arise from using
numbers already used in the specification. In a printed patent the
Sequence Listing would be printed immediately before the claims. In
cases where the Sequence Listing is voluminous, the files are difficult
to handle. This change would permit easier storage of very large
Sequence Listings apart from the main part of the application during
pendency. The presentation of the Sequence Listing as a separate Annex
would also facilitate compliance with PCT requirements and other
national patent office rules.
   Sections 1.821(a)(1) and (2) are proposed to be amended by referring
to sections in World Intellectual Property Organization (WIPO) Handbook
on Industrial Property Information and Documentation, Standard ST.23,
paragraphs 8 through 12, April 1994, herein incorporated by reference,
rather than to paragraphs in    1.822. The WIPO Standard ST. 23 (April
1994) is consistent with    1.822 except for certain corrections which
are noted herein and the requirement of the use of the lower case for
the one-letter code for nucleotide bases. The proposed rule states that
the incorporation has been approved. This language is required by the
Federal Register. This incorporation by reference will be reviewed by
the Director of the Federal Register in accordance with 5 U.S.C. 552(a)
and 1 CFR part 51 before any Final Rule is adopted. Copies may be
obtained from the World Intellectual 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; or at the Office of the Federal Register,
800 North Capitol Street, NW, Suite 700, Washington, DC 20408.
   Section 1.821(a) is proposed to be amended so that sequences with
fewer than four specifically defined amino acids or nucleotides would be
expressly excluded from this rule. "Specifically defined" means those
amino acids other than "Xaa" and those nucleotide bases other than "N"
defined in accordance with WIPO Standard ST.23.
   This change is being proposed to reduce the burden on applicants for
those sequences that contain only a minimal amount of sequence
information. For example, if an amino acid sequence is disclosed as
being entirely "Xaa" residues, the 1990 version of the sequence rules
would require this sequence to be submitted in computer readable form.
However, this sequence has no value as sequence information because each
of the positions is represented as a "wild card." Such low-information
sequences are not very useful in any sequence matching and alignment
algorithm. In order to minimize the inclusion of such
low-information-value sequence data in the database and to relieve the
burden on applicants to submit low-information-value sequences, the
Office proposes this change to the sequence rules. If applicants should
wish to voluntarily submit a CRF for such sequences, they would be
accepted and entered in the PTO's database.
   It is not necessary that any of the non-N or non-Xaa residues be
adjacent to any other non-N or non-Xaa residue in order for a sequence
to be subject to    1.821(a).
   Sections 1.821(a)(2) and 1.822(b) are proposed to be amended by
changing "elsewhere in the `Sequence Listing'" to "in the Feature
section." The purpose of this change is to enhance clarity of the rule.
The only place in the "Sequence Listing" where additional information is
permitted is in the Feature section. The current language implies that
there are other acceptable portions of the "Sequence Listing"
appropriate for additional information and thus is ambiguous and
misleading.
   Section 1.821(a)(2) will continue to indicate that sequences
containing D-amino acids need not comply with the provisions of
1.822 - 1.825. To date, the PTO has accepted voluntary submissions of
sequences which contain D-amino acids. The sequence information has
either indicated an Xaa at each occurrence of a D-amino acid or has
indicated the amino acid (or imino acid) by abbreviation as if it were
an L-amino acid (or imino acid) and explained the existence of the
D-amino acid in the Feature section associated with that sequence.
   Section 1.821(c) is proposed to be amended by clarifying and
establishing a language neutral format sequence listing. Specifically,
the use of integer identifiers is proposed for identifying sequences.
Where a sequence integer identifier is intentionally omitted, it must be
noted by applicant to avoid confusion in the published document.
   Section 1.821(d) is proposed to be amended by changing "assigned
identifier" to "integer identifier" to be consistent with the term used
in    1.821(c).
   Section 1.821(d) is proposed to be amended by adding the phrase,
"preceded by `SEQ ID NO:' ". This change is necessitated by the change
to    1.821(c). Since the integer identifier in the "Sequence Listing"
would be defined now as a numeral only, it is necessary that any
reference to a particular sequence in the specification and claims be
preceded by "SEQ ID NO:". It is not acceptable to use only a numeric
identifier, such as "<200>" or "<400>"- see infra Sequence Listing
table, in the description or the claims because one reading a patent may
not reasonably be presumed to be familiar with the meanings of numeric
identifiers.
   Section 1.821(e) is proposed to be amended by setting forth the
procedure for transferring an accepted computer readable Sequence
Listing from one application to a subsequently filed application. The
existing rules did not adequately describe the process of transferring a
computer readable Sequence Listing into a new application if an
identical CRF was previously accepted by the PTO for another
application. A further description of the intended procedures has been
added for purposes of clarity. This section is intended to describe that
if a computer readable Sequence Listing is identical to one that is
error-free and already on file at the PTO, an applicant has two options.
A new diskette may be submitted, or an applicant may submit a statement
clearly directing the PTO to use the previously submitted CRF since they
are identical, and that the paper copy of the Sequence Listing in the
new application is identical to the disk in the previous application.
   Section 1.821(g) is proposed to be amended by correcting the
reference to 35 U.S.C. 111(a) applications. Section 1.821(h) is proposed
to be amended by clarifying that this rule applies to all international
applications searched and examined by the PTO. In addition to
international applications filed in the United States Receiving Office,
the United States is a competent International Searching Authority (ISA)
for applications filed in receiving Offices of, or acting for, Brazil,
Israel, Mexico, and Trinidad and Tobago. The United States is also a
competent ISA for applications filed in the International Bureau where
at least one of the applicants is a resident or national of the United
States or a resident or national of Barbados. In addition, the United
States acts as an International Preliminary Examining Authority for
certain applications searched in the EPO. The language change regarding
the time limit for compliance and statement accompanying the submission
are necessary to conform with the language found in PCT Rule 13ter.1.
   Section 1.822 is proposed to be revised for clarity and better
organization and to accommodate an international request for the use of
lower case one-letter codes for nucleotide bases.
   Section 1.822 (b) is proposed to be amended to refer to WIPO Standard
ST.23 (April 1994) and incorporate the information therein. The
reorganization groups all nucleotide and all amino acid formats together.
   Section 1.822 (c)(1) is proposed to be amended by requiring the use
of lower case one-letter code for the nucleotide bases. This change
would put the PTO requirements in conformance with most large databases.
Additionally, the use of lower case letters in a sequence makes the
confusion of "g" for "c" and vice versa less likely.
   Current paragraph (d) is proposed to be redesignated as a part of
paragraph (c)(3) and current paragraph (e) is proposed to be deleted
with the substance of the paragraph being incorporated into (d)(1).
Current paragraph (f) is proposed to be redesignated as paragraph
(c)(2); current paragraph (g) is proposed to be redesignated as
paragraph (c)(3) and amended to incorporate current paragraph (d).
Current paragraph (h) is proposed to be redesignated as paragraph
(d)(2). Current paragraphs (i) and (j) are proposed to be redesignated
as (c)(4) and (c)(5). Current paragraph (k) is proposed to be
redesignated as (d)(3). Current paragraph (l) is proposed to be
redesignated as (c)(6) and current paragraph (m) is proposed to be
redesignated as (d)(4). Current paragraph (n) is proposed to be
redesignated as (c)(7) and amended to delete a sentence, the substance
of which is incorporated into (d)(4).
   Paragraph (d)(1) is proposed to be added to include a reference to
WIPO Standard ST.23 (April 1994). Paragraphs (d)(2-4) incorporate the
material from current paragraphs (h), (k), (m) and a sentence of (n).
Paragraph (d)(5) is proposed to be added to clarify that the use of
terminator symbols is not acceptable in amino acid sequences either as
"internal" terminator symbols or following the carboxy terminal amino
acid of a peptide or polypeptide.
   Current paragraph (o) is proposed to be redesignated as paragraph (e)
and amended to recite integer identifier to be consistent with    1.821
(c) and to permit the language neutral submission.
   Current paragraph (p) is proposed to be deleted.
   The lists of nucleic acid and amino acid abbreviations and the lists
of modified base controlled vocabulary and the modified and unusual
amino acids would be replaced by reference to WIPO Standard ST.23
RECOMMENDATION FOR THE PRESENTATION OF NUCLEOTIDE AND AMINO ACID
SEQUENCE LISTINGS IN PATENT APPLICATIONS AND IN PUBLISHED PATENT
DOCUMENTS (April 1994) to simplify and shorten the rules. This
information will also appear in an appropriate section of the Manual of
Patent Examining Procedure to assist applicants in preparing Sequence
Listings. For purposes of facilitating review of these proposed rule
changes, appropriate corrected excerpts of paragraphs 8, 9, 11 and 12 of
WIPO Standard ST.23 are provided below.
   WIPO Standard ST.23, paragraph 8, provides that the bases of a
nucleotide sequence should be represented using the following one-letter
code for nucleotide sequence characters.

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) or
                        (unknown or other)      aNy

    WIPO Standard ST.23, paragraph 9, provides: 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 elsewhere in the Sequence Listing. The codes from
the list below may be used in the description or the Sequence Listing
but not in the sequence itself.

Symbol                          Meaning

ac4c                            4-acetylcytidine
chm5u                           5-(carboxyhydroxylmethyl)uridine
cm                              2'-O-methylcytidine
cmnm5s2u                        5-carboxymethylaminomethyl-2-
                                thiouridine
cmnm5u                          5-carboxymethylaminomethyluridine
d                               dihydrouridine
fm                              2'-O-methylpseudouridine
gal q                           *beta, D-galactosylqueosine
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-mannosylqueosine
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 (v)
osyw                            wybutoxosine
p                               pseudouridine
q                               *queosine
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

* Indicates a correction of minor typographical errors.

   WIPO Standard ST.23, paragraph 11, provides that the amino acids should
be represented using the following three-letter code with the first
letter as a capital.

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.23, paragraph 12, provides: Modified and unusual
amino acids may be represented as the corresponding unmodified amino
acids in the sequence itself if the modified amino acid is one of those
listed below and the modification is further described elsewhere in the
Sequence Listing. The codes from the list below may be used in the
description or the Sequence Listing but not in the sequence itself.

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

* Indicates a correction of a minor typographical error.

  Section 1.823(a) is proposed to be amended to provide for a reference to
a Sequence Listing Annex in the application immediately before the
claims and to provide the paper Sequence Listing as an Annex, which is a
separately numbered section of the application. This is an
internationally desired change and also would facilitate easier storage
of very large Sequence Listings separate from the main part of the file
during pendency of the application.
   Section 1.823(b) is proposed to be amended to insert a table to
depict items of information (data elements) which are to be included in
the Sequence Listing and to indicate whether they are mandatory or
optional. The proposed revisions reflect the change to a language
neutral submission. The English language data elements headings would be
replaced by numeric identifiers. The numeric identifiers are similar to
INID codes ("Internationally agreed Numbers for the Identification of
Data" as per WIPO Standard ST.9, December 1990) already utilized
internationally in patent documents. This change would facilitate a
single international standard which would eliminate the need for
translations into non-English languages. Large portions of Section
1.823(b) are proposed to be deleted to lessen the burden on applicants
and to eliminate collections of material which is of limited use to the
Office. The following items are typical of material which would be
deleted:

(1)(vi)(C) CLASSIFICATION;
(2)(i)(C) STRANDEDNESS;
(2)(ii) MOLECULE TYPE through (2)(vii)(C) UNITS; and
(2)(ix)(C) IDENTIFICATION METHOD.

   In order to clarify the rule, the proposed change would identify
specifically those items which can be enumerated once in a Sequence
Listing.
   It is proposed that the recommended designation be eliminated,
leaving only mandatory and optional elements. Accordingly, it is
proposed to change element <140> Correspondence Address and elements
<150> through <154> from mandatory to optional. Elements <100> General
Information,<200> Information for SEQ ID NO, and <400> Sequence
Description: SEQ ID NO have been clarified as mandatory. In element
<193>, it is proposed to change TELEX to Electronic mail address to be
current with technology.
   It is proposed to eliminate Strandedness because the information is
of limited use to the Office. It is proposed to limit the response for
Topology to linear or circular because any other response does not
permit an adequate search. Because it is essential to the search to know
whether the sequence is circular, providing one of these two responses
to this data element is mandatory in the Sequence Listing. Consistent
with the international desire for eliminating language in the Sequence
Listing, Topology would be identified as L (linear) or C (circular), and
sequence Type would be N (nucleotide) or A (amino acid).
   It is proposed to change Feature from a recommended to a mandatory
element if the sequence contains "N", "Xaa", a modified or unusual
L-amino acid or a modified base. This change would highlight the
presence of an unusual residue in the sequence which is important to
anyone using Sequence Listing information.
   Section 1.824 is proposed to be amended by revising the current
paragraphs (a) through (h) into paragraphs (a) through (c).

   Specifically, the following changes are proposed for    1.824:

   Current    1.824, paragraph (a), is proposed to be redesignated as
paragraph (a)(1). In addition, the term "series of diskettes" would be
added to indicate the acceptability of receiving numerous disks for
large submissions. Current paragraph (b) is proposed to be redesignated
as paragraph (a)(2). Current paragraph (c) is proposed to be
redesignated as paragraph (a)(3). Current paragraph (d) is proposed to
be deleted because it is incorporated into paragraph (a)(1). Current
paragraph (e) is proposed to be deleted since the PTO has not found it
to be necessary and feels it should not be a requirement placed on the
applicant, although the applicant may optionally continue the practice
of using write-protection if desired. In proposed paragraph (a)(4), a
"compressed file" format would be introduced as an acceptable means to
submit a large sequence listing, and in proposed paragraph (a)(5),
directions on suppressing page numbering on the computer readable form
version would be added for clarity.
   The text of current paragraph (f) is proposed to be deleted, but the
list of computer readable files is proposed to be redesignated as
paragraphs under new (b) and (c). In proposed paragraph (b), the
explanation for "pagination" is proposed to be revised to reflect the
correct format required. Proposed paragraph (b)(1) is proposed to be
revised by deleting diskettes from PS/2 operating system as an accepted
format. In proposed paragraph (c), the diskette requirements are
proposed to be rearranged so that the most common diskette size used for
submissions is at the top of the list. Also in proposed paragraph
(c)(2), "format" is proposed to be amended to accommodate the current
PTO equipment, and in proposed new paragraphs (c)(3), (4), and (5),
additional items would be added to the list of acceptable media types
due to the changes in available equipment at the PTO.
   Current paragraph (g) is proposed to be redesignated as paragraph (d).
   Current paragraph (h) is proposed to be deleted because the text is
proposed to be incorporated into paragraph (a)(6). The label
requirements would be rewritten more concisely than with the previous
rules. In addition, fewer items would be required to be placed on the
label under this proposed paragraph because the other items are no
longer deemed necessary by the PTO.
   Current Appendix A is proposed to be rewritten to reflect the correct
format of a Sequence Listing. The proposed Appendix A is presented to
provide a sample listing in the correct format as described in the Table
of amended    1.823(b). This sample includes the use of numeric
identifiers which reflect the change to a language neutral submission.
Current Appendix B is proposed to be deleted as the information it
presents is no longer valid under changes in this proposed rule.

Review Under the Paperwork Reduction Act of 1995

   This proposed rule change contains information collection requirements
which are subject to review by the Office of Management and Budget (OMB)
under the Paperwork Reduction Act of 1995, 44 U.S.C. 3501, et seq. The
title, description and respondent description of the information
collection is shown below with an estimate of the annual reporting
burdens. Included in the estimate is the time for reviewing
instructions, gathering and maintaining the data needed, and completing
and reviewing the collection of information.
   With respect to the following collection of information, the PTO
invites comments on: (1) whether the proposed collection of information
is necessary for the proper performance of the PTO's functions,
including whether the information will have practical utility; (2) the
accuracy of the PTO's estimate of the burden of the proposed collection
of information, including the validity of the methodology and
assumptions used; (3) ways to enhance the quality, utility, and clarity
of the information to be collected; and (4) ways to minimize the burden
of the collection of information on respondents, including through the
use of automated collection techniques, when appropriate, and other
forms of information technology.
   Notwithstanding any other provision of law, no person is required to
respond to nor shall a person be subject to a penalty for failure to
comply with a collection of information subject to the requirements of
the Paperwork Reduction Act unless that collection of information
displays a currently valid OMB control number.

   OMB Number: 0651-0024
   Title: Requirements for Patent Applications Containing Nucleotide
    Sequence and/or Amino Acid Sequence Disclosures
   Form Numbers: None
   Type of Review: Revision of currently approved collection
   Affected Public: Individuals or households, business or other
    for-profit institutions, not-for-profit institutions, and Federal
    Government
   Estimated Number of Respondents: 4,600
   Estimated Time Per Response: 80 minutes
   Estimated Total Annual Burden Hours: 6,133

   Needs and Uses: The PTO requires biotechnology patent applicants to
submit sequence information to enable the PTO to properly examine and
process their applications.
   As required by the Paperwork Reduction Act of 1995, 44 U.S.C.
3507(d), the PTO has submitted a copy of this proposed rulemaking to OMB
for its review of this information collection. Interested persons are
requested to send comments regarding these information collections,
including suggestions for reducing this burden, to the Office of
Information and Regulatory Affairs of OMB, New Executive Office Bldg.,
725 17th Street, N.W., Room 10235, Washington, D.C. 20503, Attn: Desk
Officer for the Patent and Trademark Office.
   OMB is required to make a decision concerning the collection of
information in these proposed regulations between 30 and 60 days after
the publication of this document in the Federal Register. Therefore, a
comment to OMB is best assured of having its full effect if OMB receives
it within 30 days of publication. This does not affect the deadline for
the public to comment to the PTO on the proposed regulations.

Other Considerations

   This proposed rule change is in conformity with the requirements of the
Regulatory Flexibility Act (5 U.S.C. 601 et seq.), Executive Order
12612, and the Paperwork Reduction Act of 1995, 44 U.S.C. 3501 et seq.
It has been determined that this proposed rule is not significant for
the purposes of Executive Order 12866.
   The Assistant General Counsel for Legislation and Regulation of the
Department of Commerce has certified to the Chief Counsel for Advocacy,
Small Business Administration, that this proposed rule change would not
have a significant economic impact on a substantial number of small
entities (Regulatory Flexibility Act, 5 U.S.C. 601 et seq.). The
principal effect of this rule change is to simplify and clarify the
rules governing the submission of Sequence Listings for patent
applications containing nucleic acid and/or amino acid sequences.
   The PTO has also determined that this proposed rule change has no
Federalism implications affecting the relationship between the National
Government and the States as outlined in Executive Order 12612.

List of Subjects in 37 CFR Part 1

Administrative practice and procedure, Courts, Freedom of Information,
Inventions and patents, Reporting and record-keeping requirements, Small
businesses.

   For the reasons set forth in the preamble and under the authority
granted to the Commissioner of Patents and Trademarks by 35 U.S.C. 6,
the PTO proposes to amend 37 CFR Part 1 as set forth below. Removals are
indicated by brackets ([]) and additions indicated by arrows (><).

Part 1 - Rules of Practice in Patent Cases

1. The authority citation for 37 CFR Part 1 would continue to read as
follows:

Authority: 35 U.S.C. 6 unless otherwise noted.

2. Section 1.77 is proposed to be amended by redesignating current
paragraphs (g) through (j) as paragraphs (h) through (k) and by adding
new paragraphs (g) and (l) to read as follows:

   1.77 Arrangement of application elements.

* * * * *

   >(g) Reference to Sequence Listing Annex.<
   [(g)]>(h)< Claim or claims.
   [(h)]>(i)< Abstract of the disclosure.
   [(i)]>(j)< Signed oath or declaration.
   [(j)]>(k)< Drawings.
   >(l) Sequence Listing Annex.<

3. Section 1.821 is proposed to be amended by revising paragraphs (a)
and (c)-(h) to read as follows:

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

  (a) Nucleotide and/or amino acid sequences as used in      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 rule. "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.23: Recommendation for the Presentation
of Nucleotide and Amino Acid Sequence Listings in Patent Applications
and in Published Patent Documents, paragraphs 8 through 12, April 1994,
herein incorporated by reference. (Hereinafter "WIPO Standard ST.23
(April, 1994)"). 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.23 may be obtained from the World
Intellectual Property Organization; 34 chemin des Colombettes; 1211
Geneva 20 Switzerland. Copies of ST.23 may be inspected at the Patent
Search Room; Crystal Plaza 3, Lobby Level; 2021 South Clark Place;
Arlington, VA 22202; or at the Office of the Federal Register, 800 North
Capitol Street, NW, Suite 700, Washington, D.C. < Nucleotides and amino
acids are further defined as follows:
   (1) Nucleotides are intended to embrace only those nucleotides that
can be represented using the symbols set forth in [   1.822(b)(1)] >WIPO
Standard ST.23 (April 1994), paragraph 8<. Modifications, e.g.,
methylated bases, may be described as set forth in [   1.822(b)] >WIPO
Standard ST.23 (April 1994), paragraph 9< , but shall not be shown
explicitly in the nucleotide sequence.
   (2) Amino acids are those L-amino acids commonly found in naturally
occurring proteins and are listed in [   1.822(b)(2)] >WIPO Standard
ST.23 (April 1994), paragraph 11<. 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 [   1.822(b)(2)] >WIPO Standard
ST.23 (April 1994), paragraph 11< with the modified positions; e.g.,
hydroxylations or glycosylations, being described as set forth in [
1.822(b)] >WIPO Standard ST.23 (April 1994), paragraph 12<, 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 [   1.822(b)(2)] >WIPO Standard ST.23 (April 1994), paragraph
11< in conjunction with a description [elsewhere in the "Sequence
Listing"] >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) * * *
   (c) Patent applications which contain disclosures of nucleotide
and/or amino acid sequences must contain, as a separate part of the
disclosure on paper copy, hereinafter referred to as the "Sequence
Listing," a disclosure of the nucleotide and/or amino acid sequences and
associated information using the symbols and format in accordance with
the requirements of      1.822 and 1.823. Each sequence disclosed must
appear separately in the "Sequence Listing." Each sequence set forth in
the "Sequence Listing" shall be assigned a separate >integer< identifier
[written as SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, etc]. >The integer
identifiers shall begin with 1 and increase sequentially by integers. If
no sequence is present for an integer identifier, the words "This
sequence omitted" shall appear following the integer identifier.<
   (d) Where the description or claims of a patent application discuss a
sequence listing 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 [assigned] >integer< 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    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 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.
Such a statement must be a verified statement if made by a person not
registered to practice before the Office.
   (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 has one month from the date of a notice which will be sent
requiring compliance with the requirements in order to prevent
abandonment of the application. Any submission in response to a
requirement under this paragraph must be accompanied by a statement that
the submission includes no new matter. Such a statement must be a
verified statement if made by a person not registered to practice before
the Office.
   (h) If any of the requirements of paragraphs (b) through (f) of this
section are not satisfied at the time of filing [,in the United States
Receiving Office,] an international application under the Patent
Cooperation Treaty (PCT) [applicant has one month from the date of a
notice which] >, 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< requiring compliance with the requirements [,or such
other time as may be set by the Commissioner, in which to comply]
>within a prescribed time period<. Any submission in response to a
requirement under this paragraph must be accompanied by a statement that
the submission does not include [new] matter [or go] >which goes< beyond
the disclosure in the international application as filed. Such a
statement must be a verified statement if made by a person not
registered to practice before the Office. 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 >and the United States International
Preliminary Examining Authority shall examine only to the extent that a
meaningful examination can be performed<.

* * * * *

4. Section 1.822 is proposed to be revised to read as follows:

   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 [(p)] >(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
[paragraphs (b)(1) and (b)(2) of this section] >WIPO Standard ST.23
(April 1994), paragraphs 8 and 11. 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.23 may be obtained from
the World Intellectual Property Organization; 34 chemin des Colombettes;
1211 Geneva 20 Switzerland. Copies of ST.23 may be inspected at the
Patent Search Room; Crystal Plaza 3, Lobby Level; 2021 South Clark
Place; Arlington, VA 22202; or at the Office of the Federal Register,
800 North Capitol Street, NW, Suite 700, Washington, DC <. No code other
than that specified in [this section] >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 [paragraphs
(p)(1) or (p)(2) of this section] >WIPO Standard ST.23 (April 1994),
paragraphs 9 and 12< and the modification is also set forth [elsewhere
in the Sequence Listing (for example, FEATURES    1.823(b)(2)(ix))] >in
the Feature section<. Otherwise, all bases or amino acids not appearing
in paragraphs [(b)(1) or (b)(2) of this section] >8 and 11 of the WIPO
Standard ST.23 (April 1994)< shall be listed in a given sequence as "N"
or "Xaa," respectively, with further information, as appropriate, given
[elsewhere in the Sequence Listing] >in the Feature section<.
[ (1) Base codes:

Symbol                          Meaning

A                               A; adenine
C                               C; cytosine
G                               G; guanine
T                               T; thymine
U                               U; uracil
M                               A or C
R                               A or G
W                               A or T/U
S                               C or G
Y                               C or T/U
K                               G or T/U
V                               A or C or G; not T/U
H                               A or C or T/U; not G
D                               A or G or T/U; not C
B                               C or G or T/U; not A
N                               (A or C or G or T/U) or (unknown or other)

(2) Amino acid three-letter abbreviations:

Abbreviation                    Amino acid name

Ala                             Alanine
Arg                             Arginine
Asn                             Asparagine
Asp                             Aspartic Acid
Asx                             Aspartic Acid or Asparagine
Cys                             Cysteine
Glu                             Glutamic Acid
Gln                             Glutamine
Glx                             Glutamine or Glutamic Acid
Gly                             Glycine
His                             Histidine
Ile                             Isoleucine
Leu                             Leucine
Lys                             Lysine
Met                             Methionine
Phe                             Phenylalanine
Pro                             Proline
Ser                             Serine
Thr                             Threonine
Trp                             Tryptophan
Tyr                             Tyrosine
Val                             Valine
Xaa                             Unknown or other ]

   (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[,
as] >set forth< in [paragraph (b)(1) of this section] >WIPO Standard
ST.23 (April 1994), paragraph 8<.
   [(d) 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.
   (e) 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 paragraph (b)(2) of this section.]
   [(f)] >(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.
   [(g)] >(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.<
   [(h) 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.]
   [(i)] >(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.
   [(j)] >(5)< A nucleotide sequence shall be presented, only by a
single strand, in the 5' to 3' direction, from left to right.
   [(k) 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.]
   [(l)] >(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.
   [(m) The enumeration of amino acids may start at the first amino acid
of the first mature protein, with the number 1. The amino acids
preceding the mature protein, e.g., pre-sequences, pro-sequences,
pre-pro-sequences and signal sequences, when presented, 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.]
   [(n)] >(7)< For those nucleotide sequences that are circular in
configuration, the enumeration method set forth in paragraph [(l)]
>(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. [The enumeration method for amino acid
sequences that is set forth in paragraph (m) of this section remains
applicable for amino acid sequences that are circular in configuration.]
   >(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.23 (April 1994), paragraph 11.
   (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. The amino acids
preceding the mature protein, e.g., pre-sequences, pro-sequences,
pre-pro-sequences and signal sequences, when presented, 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.
   (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)< [(o)] A sequence with a gap or gaps shall be presented as a
plurality of separate sequences, with separate [sequence] >integer<
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.
   [(p) The code for representing modified nucleotide bases and modified
or unusual amino acids shall conform to the code set forth in the tables
in paragraphs (p)(1) and (p)(2) of this section. The modified base
controlled vocabulary in paragraph (p)(1) of this section and the
modified and unusual amino acids in paragraph (p)(2) of this section
shall not be used in the nucleotide and/or amino acid sequences; but may
be used in the description and/or the "Sequence Listing" corresponding
to, but not including, the nucleotide and/or amino acid sequence.
   (1) Modified base controlled vocabulary:

Abbreviation                    Modified base description

ac4c                            4-acetylcytidine.
chm5u                           5-(carboxyhydroxylmethyl)uridine.
cm                              2'-O-methylcytidine.
cmnm5s2u                        5-carboxymethylaminomethyl-2-
                                thioridine.
cmnm5u                          5-carboxymethylaminomethyluridine.
d                               dihydrouridine.
fm                              2'-O-methylpseudouridine.
galq                            beta,D-galactosylqueosine.
gm                              2'-O-methylguanosine.
i                               inosine.
i6a                             N6-isopentenyladenosine.
m1a                             1-methyladenosine.
m1f                             1-methylpseudouridine.
m1g                             1-methylguanosine.
ml1                             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.
manq                            beta,D-mannosylqueosine.
mcm5s2u                         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 (v).
osyw                            wybutoxosine.
p                               pseudouridine.
q                               queosine.
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-carboxypropyl)uridine,
                                (acp3)u.

(2) Modified and unusual amino acids:

Abbreviation                    Modified and unusual amino acid

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                           N-Methylvaline.
Nva                             Norvaline.
Nle                             Norleucine.
Orn                             Ornithine. ]

5. Section 1.823 is proposed to be revised to read as follows:

   1.823 Requirements for nucleotide and/or amino acid sequences as
partof the application papers.

   (a) The "Sequence Listing" required by    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 be titled "Sequence Listing" [and appear] >. On a separate page of
the application specification,< immediately prior to the claims [.]>,
there shall be a reference to the presence of the "Sequence Listing" in
a "Sequence Listing Annex." The "Sequence Listing" shall appear in the
"Sequence Listing Annex," which is numbered independently of the
numbering of the remainder of the application and shall be placed in the
application file. Upon printing the application as a patent, the
"Sequence Listing Annex" containing the paper "Sequence Listing" shall
be printed immediately before the patented claims.< Each page of the
"Sequence Listing" shall contain no more than 66 lines and each line
shall contain no more than 72 characters. A fixed-width font shall be
used exclusively throughout the "Sequence Listing."
   (b) The "Sequence Listing" shall, except as otherwise indicated,
include, in addition to and immediately preceding the actual nucleotide
and/or amino acid sequence, the [following items of information.] >
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 [,except that parenthetical explanatory information
following the headings (identifiers) is to be omitted]. Each item of
information shall begin on a new line [, enumerated with the
number/numeral/letter in parentheses as shown below, with the heading
(identifier) in upper case characters, followed by a colon, and then
followed by the information provided] > beginning with the numeric
identifier enclosed in angle brackets as shown<. Except as allowed
below, no item of information shall occupy more than one line. [Those
items of information that are applicable for all sequences shall only be
set forth once in the "Sequence Listing."] The submission of those items
of information designated with an "M" is mandatory. [The submission of
those items of information designated with an "R" is recommended, but
not required.] The submission of those items of information designated
with an "O" is optional. >Numeric identifiers <100> through <193> shall
only be set forth at the beginning of the "Sequence Listing."< Those
items designated with "rep" may have multiple responses and, as such,
the item may be repeated in the "Sequence Listing."
   [(1) GENERAL INFORMATION (Application, diskette/tape and publication
information):

(i) APPLICANT (maximum of first ten named applicants; specify one name
per line: SURNAME comma OTHER NAMES and/or INITIALS - M/rep):
(ii) TITLE OF INVENTION (title of the invention, as elsewhere in
application, four lines maximum - M):
(iii) NUMBER OF SEQUENCES (number of sequences in the "Sequence Listing"
(M):
(iv) CORRESPONDENCE ADDRESS (M):

(A) ADDRESSEE (name of applicant, firm, company or institution, as may
be appropriate):
(B) STREET (correspondence street address, as elsewhere in application,
four lines maximum):
(C) CITY (correspondence city address, as elsewhere in application):
(D) STATE (correspondence state, as elsewhere in application):
(E) COUNTRY (correspondence country, as elsewhere in application):
(F) ZIP (correspondence zip or postal code, as elsewhere in application):

(v) COMPUTER READABLE FORM (M):

(A) MEDIUM TYPE (type of diskette/tape submitted):
(B) COMPUTER (type of computer used with diskette/tape submitted):
(C) OPERATING SYSTEM (type of operating system used):
(D) SOFTWARE (type of software used to create computer readable form):

(vi) CURRENT APPLICATION DATA (M, if available):

(A) APPLICATION NUMBER (U.S application number, including a series code,
a slash and a serial number, or U.S. PCT application number, including
the letters PCT, a slash, a two-letter code indicating the U.S. as the
Receiving Office, a two-digit indication of the year, a slash and a
five-digit number, if available):
(B) FILING DATE (U.S. or PCT application filing date, if available;
specify as dd-MMM-yyyy):
(C) CLASSIFICATION (IPC/US classification or F-term designation, where
F-terms have been developed, if assigned, specify each designation, left
justified, within an eighteen-position alpha numeric field - rep, to a
maximum of ten classification designations):

(vii) PRIOR APPLICATION DATA (prior domestic, foreign priority or
international application data, if applicable - M/rep):

(A) APPLICATION NUMBER (application number; specify as two-letter
country code and an eight-digit application number; or if a PCT
application, specify as the letters PCT, a slash, a two-letter code
indicating the Receiving Office, a two-digit indication of the year, a
slash and a five-digit number):
(B) FILING DATE (document filing date, specify as dd-MMM-yyyy):

(viii) ATTORNEY/AGENT INFORMATION (O):

(A) NAME (attorney/agent name; SURNAME comma OTHER NAMES and/or
INITIALS):
(B) REGISTRATION NUMBER (attorney/agent registration number):
(C) REFERENCE/DOCKET NUMBER (attorney/agent reference or docket number):

(ix) TELECOMMUNICATION INFORMATION (O):

(A) TELEPHONE (telephone number of applicant or attorney/agent):
(B) TELEFAX (telefax number of applicant or attorney/agent):
(C) TELEX (telex number of applicant or attorney/agent):
   (2) INFORMATION FOR SEQ ID NO: X (rep):

(i) SEQUENCE CHARACTERISTICS (M):

(A) LENGTH (sequence length, expressed as number of base pairs or amino
acid residues):
(B) TYPE (sequence type, i.e., whether nucleic acid or amino acid):
(C) STRANDEDNESS (if nucleic acid, number of strands of source organism
molecule, i.e., whether single-stranded, double-stranded, both or
unknown to applicant):
(D) TOPOLOGY (whether source organism molecule is circular, linear, both
or unknown to applicant):

(ii) MOLECULE TYPE (type of molecule sequenced in SEQ ID NO:X (at least
one of the following should be included with subheadings, if any, in
Sequence Listing - R)):
   - Genomic RNA;
   - Genomic DNA;
   - mRNA
   - tRNA;
   - rRNA;
   - snRNA;
   - scRNA;
   - preRNA;
   - cDNA to genomic RNA;
   - cDNA to mRNA;
   - cDNA to tRNA;
   - cDNA to rRNA;
   - cDNA to snRNA;
   - cDNA to scRNA;
   - Other nucleic acid;

(A) DESCRIPTION (four lines maximum):
   - protein and
   - peptide.

(iii) HYPOTHETICAL (yes/no - R):

(iv) ANTI-SENSE (yes/no - R):

(v) FRAGMENT TYPE (for proteins and peptides only, at least one of the
following should be included in the Sequence Listing - R):
   - N-terminal fragment;
   - C-terminal fragment and
   - internal fragment.

(vi) ORIGINAL SOURCE (original source of molecule sequenced in SEQ
IDNO:X - R):

(A) ORGANISM (scientific name of source organism):
(B) STRAIN:
(C) INDIVIDUAL ISOLATE (name/number of individual/isolate):
(D) DEVELOPMENTAL STAGE (give developmental stage of source organism and
indicate whether derived from germ-line or rearranged developmental
pattern):
(E) HAPLOTYPE:
(F) TISSUE TYPE:
(G) CELL TYPE:
(H) CELL LINE:
(I) ORGANELLE:

(vii) IMMEDIATE SOURCE (immediate experimental source of the sequence in
SEQ ID NO:X - R):

(A) LIBRARY (library -type, name):
(B) CLONE (clone(s)):

(viii) POSITION IN GENOME (position of sequence in SEQ ID NO:X in genome
- R):

(A) CHROMOSOME/SEGMENT (chromosome/segment - name/number):
(B) MAP POSITION:
(C) UNITS (units for map position, i.e., whether units are genome
percent, nucleotide number or other/specify):

(ix) FEATURE (description of points of biological significance in the
sequence in SEQ ID NO:X -R/rep):

(A) NAME/KEY (provide appropriate identifier for feature - four lines
maximum):
(B) LOCATION (specify location according to syntax of DDBJ/EMBL/GenBank
Feature Tables Definition, including whether feature is on complement of
presented sequence; where appropriate state number of first and last
bases/amino acids in feature - four lines maximum):
(C) IDENTIFICATION METHOD (method by which the feature was identified,
i.e., by experiment, by similarity with known sequence or to an
established consensus sequence, or by similarity to some other pattern -
four lines maximum):
(D) OTHER INFORMATION (include information on phenotype conferred,
biological activity of sequence or its product, macromolecules which
bind to sequence or its product, or other relevant information - four
lines maximum):

(x) PUBLICATION INFORMATION (Repeat section for each relevant
publication - O/rep):

(A) AUTHORS (maximum of first ten named authors of publication; specify
one name per line: SURNAME comma OTHER NAMES and/or INITIALS - rep):
(B) TITLE (title of publication):
(C) JOURNAL (journal name in which data published):
(D) VOLUME (journal volume in which data published):
(E) ISSUE (journal issue number in which data published):
(F) PAGES (journal page numbers in which data published):
(G) DATE (journal date in which data published; specify as dd-MMM-yyyy,
MMM-yyyy or Season-yyyy):
(H) DOCUMENT NUMBER (document number, for patent type citations only;
specify as two-letter country code, eight-digit document number (right
justified), one letter and as appropriate, one number or a space as a
document type code; or if a PCT application specify as the letters PCT,
a slash, a two-letter code indicating the Receiving Office, a two-digit
indication of the year, a slash and a five-digit number; or if a PCT
publication, specify as the two letters WO, a two-digit indication of
the year, a slash and a five-digit publication number):
(I) FILING DATE (document filing date, for patent-type citations only;
specify as dd-MMM-yyyy):
(J) PUBLICATION DATE (document publication date; for patent-type
citations only, specify as dd-MMM-yyyy):
(K) RELEVANT RESIDUES In SEQ ID NO:X (rep): FROM (position) TO (position)

(xi) SEQUENCE DESCRIPTION: SEQ ID NO:X:]
>

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

<100>           General         Leave blank after       M
                Information     <100>

<110>           Applicant       Max. of 10              M
                                names; one name per
                                line; use format:
                                Surname, Other Names
                                and/or Initials; rep

<120>           Title of        Four lines maximum      M
                Invention

<130>           Number of       Use an integer as a     M
                Sequences       response

<140>           Correspondence  <140> must be present   O
                Address         if subheadings <141>-
                                <146> are used

<141>           Addressee                               O

<142>           Street          Four lines maximum      O

<143>           City                                    O

<144>           State or                                O
                Province

<145>           Country                                 O

<146>           Zip or Postal                           O
                Code

<150>           Computer        Leave blank after       O
                Readable Form   <150>

<151>           Medium Type     Type of                 O
                                diskette/tape
                                submitted

<152>           Computer        Type of computer        O
                                used to create
                                diskette/tape

<153>           Operating       Type of operating       O
                System          system on computer

<154>           Software        Type of software used   O
                                to create computer
                                readable form

<160>           Current         Leave blank after<160>; M, if available
                Application     <160> must be present
                Data            if subheadings <161>
                                &<162> are used

<161>           Application     Specify as: US          M, if available
                Number          07/999,999
                                or PCT/US96/99999

<162>           Filing Date     Specify as:             M, if available
                                dd-MMM-yyyy

<170>           Prior           Insert heading/         M, if applicable
                Application     subheadings
                Data            only if applicable;
                                leave blank after<170>;
                                <170> must be present if
                                subheadings <171> &
                                <172> are used; rep.

<171>           Application     Specify as: US          M, if applicable
                Number          07/999,999 or
                                PCT/US96/99999

<172>           Filing Date     Specify as:             M, if applicable
                                dd-MMM-yyyy

<180>           Attorney/Agent  Leave blank after       O
                Information     <180>

<181>           Name            Use format: Surname,    O
                                Other Names and/or
                                Initials

<182>           Registration                            O
                Number

<183>           File Reference                          O
                /Docket Number

<190>           Telecommunica-  Leave blank after       O
                tion Informa-   <190>
                tion

<191>           Telephone                               O

<192>           Telefax                                 O

<193>           Electronic                              O
                mail address

<200>           Information     Response shall be an    M
                for SEQ ID      integer representing
                NO:#:           the SEQ ID NO shown;
                                rep.

<210>           Sequence        Leave blank after       M
                Character-      <210>
                istics

<211>           Length          Respond with an         M
                                integer expressing
                                the number of bases
                                or amino acid
                                residues

<212>           Type            Whether presented       M
                                sequence molecule is
                                nucleotide or amino
                                acid, indicated by
                                N or A

<214>           Topology        Whether presented       M
                                sequence molecule is
                                linear or circular,
                                indicated as L or C

<290>           Feature         Description of points   M, if "N", "Xaa",
                                of biological           or a modified or
                                significance in the     unusual L-amino
                                sequence; leave blank   acid or modified
                                after <290>; rep.       base was used in
                                                        the sequence

<291>           Name/Key        Provide appropriate     M, if "N", "Xaa",
                                identifier for feature; or a modified or
                                four lines maximum      unusual L-amino
                                                        acid or modified
                                                        base was used in
                                                        the sequence

<292>           Location        Specify location        M, if "N", "Xaa",
                                within sequence;        or a modified or
                                where appropriate       unusual L-amino
                                state number of         acid or modified
                                first and last bases    base was used in
                                /amino acids in         the sequence
                                feature; four lines
                                maximum

<294>           Other           Other relevant          M, if "N", "Xaa",
                Information     information; four       or a modified or
                                lines maximum           unusual L-amino
                                                        acid or modified
                                                        base was used in
                                                        the sequence

<300>           Publication     Leave blank after       O
                Information     <300>; rep.

<301>           Authors         Maximum of ten          O
                                named authors of
                                publication; specify
                                one name per line;
                                use format:
                                Surname, Other Names
                                and/or Initials

<302>           Title                                   O

<303>           Journal                                 O

<304>           Volume                                  O

<305>           Issue                                   O

<306>           Pages                                   O

<307>           Date            Journal date in         O
                                which data published;
                                specify as dd-MMM-yyyy,
                                MMM-yyyy or Season-yyyy

<308>           Patent          Document number; for    O
                Document        patent-type citations
                Number          only

<309>           Filing Date     Document filing date,   O
                                for patent-type
                                citations only;
                                specify as dd-MMM-
                                yyyy

<310>           Publication     Document publication    O
                Date            date, for patent-type
                                citations only;
                                specify as
                                dd-MMM-yyy

<311>           Relevant        FROM (position)         O
                Residues        TO (position)

<400>           Sequence        Response shall be       M
                Description:    an integer
                SEQ ID NO:#:    representing
                                the SEQ ID NO
                                shown; rep.

<

6. Section 1.824 is proposed to be revised to read as follows:

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

   (a) The computer readable form required by    1.821(e) shall [contain a
printable copy of the "Sequence Listing," as defined in      1.821(c),
1.822 and 1.823, recorded as] >meet the following specifications:
   (1) The computer readable form shall contain< a single [file on]
>"Sequence  Listing" as< either a diskette, [or a magnetic tape] >series
of diskettes, or other permissible media outlined in    1.824(c)<. [The
computer readable form shall be encoded and formatted such that a
printed copy of the "Sequence Listing" may be recreated using the print
commands of the computer/operating-system configurations specified in
paragraph (f) of this section.]
   [(b)] >(2)< The [file] >"Sequence Listing"< in paragraph (a) >(l)< of
this section shall be [encoded in a subset of the] >submitted in<
American Standard Code for Information Interchange (ASCII) >text<. [This
subset shall consist of all printable ASCII characters including the
ASCII space character plus line-termination, pagination and end-of-file
characters associated with the computer/operating-system configurations
specified in paragraph (f) of this section.] No other [characters]
>formats< shall be allowed.
   [(c)] >(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 [be readable by one of the
computer/operating-systemconfigurations specified in paragraph (f) of
this section, and shall] conform to [the] >all< specifications [in
paragraphs (a) and (b) of] >detailed in< this section.
   [(d) The entire printable copy of the "Sequence Listing shall be
contained within one file on a single diskette or magnetic tape unless
it is shown to the satisfaction of the Commissioner that it is not
practical or possible to submit the entire printable copy of the
"Sequence Listing" within one file on a single diskette or magnetic tape.
   (e) The submitted diskette or tape shall be write-protected such as
by covering or uncovering diskette holes, removing diskette write tabs
or removing tape write rings.
   (f) As set forth in paragraph (c), above, any means may be used to
create the computer readable form, as long as the following conditions
are satisfied. A submitted diskette shall be readable on one of the
computer/operating-system configurations described in paragraphs (1)
through (3), below. A submitted tape shall satisfy the format
specifications described in paragraph (4), below.]
   >(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 name and type of computer and
operating system used, and application serial number and filing date, if
known.
   (b) Computer readable form files submitted must meet these format
requirements:<
   (1) Computer: IBM PC/XT/AT, >or compatibles< [ IBM PS/2 or
compatibles]>,or Apple Macintosh<;
   [(i)]>(2)<operating System: [PC-DOS or] MS-DOS [(Versions 2.1 or
above)]>, Unix or Macintosh<;
   [(ii)]>(3)< Line terminator: ascii carriage Return plus ASCII Line
Feed;
   [(iii)]>(4)< Pagination: [ASCII Form Feed or Series of Line
Terminators] >Continuous file (no "hard page break" codes permitted)<;
   [(iv) End-of-File:ASCII SUB (Ctrl-Z);
   (v)Media:]
   >(c) Computer readable form files submitted may be in any of the
following media:<
   [(A) Diskette - 5.25 inch, 360 Kb storage;
   (B) Diskette - 5.25 inch, 1.2 Mb storage;
   (C) Diskette - 3.50 inch, 720 Kb storage;
   (D) Diskette - 3.5 inch, 1.44 Mb storage;]
   >(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;

   [(vi) Print Command: PRINT filename.extension;
   (2) Computer: IBM PC/XT/AT, IBM PS/2 or compatibles;
   (i) Operating system:  Xenix;
   (ii) Line Terminator: ASCII Carriage Return;
   (iii) Pagination: ASCII Form Feed or Series of Line Terminators;
   (iv) End-of-File: None;
   (v) Media:
   (A) Diskette - 5.25 inch, 360 Kb storage;
   (B) Diskette - 5.25 inch, 1.2 Mb storage;
   (C) Diskette - 3.50 inch, 720 Kb storage;
   (D) Diskette - 3.5 inch, 1.44 Mb storage;
   (vi) Print Command: Ipr filename;
   (3) Computer: Apple Macintosh;
   (i) Operating System: Macintosh;
   (ii) Macintosh File Type: text with line termination
   (iii) Line Terminator: Pre-defined by text type file;
   (iv) Pagination: Pre-defined by text type file;
   (v) End-of-File: Pre-defined by text type file;
   (vi) Media:
   (A) Diskette - 3.50 inch, 400 Kb storage;
   (B) Diskette - 3.50 inch, 800 Kb storage;
   (C) Diskette - 3.50 inch, 1.4 Mb storage;
   (vii) Print Command: Use PRINT command from any Macintosh Application
that processes text files, such as Mac-Write or TeachText;
   (4) Magnetic tape: 0.5 inch, up to 2400 feet;
   (i) Density: 1600 or 6250 bits per inch, 9 track;
   (ii) Format:raw, unblocked;
   (iii) Line Terminator: ASCII Carriage Return plus optional ASCII Line
Feed;
   (iv) Pagination: ASCII Form Feed or Series of Line Terminators;
   (v) Print Command (Unix shell version given here as sample response
-mt/dev/rmt0; 1pr/dev/rmt0):]
   >(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<

   [(g)]>(d)< computer readable forms that are submitted to the Office
will not be returned to the applicant.
   [(h) All computer readable forms shall have a label permanently
affixed thereto on which has been hand-printed or typed, a description
of the format of the computer readable form as well as the name of the
applicant, the title of the invention, the date on which the data were
recorded on the computer readable form and the name and type of computer
and operating system which generated the files on the computer readable
form. If all this information cannot be printed on a label affixed to
the computer readable form, by reason of size or otherwise, the label
shall include the name of the applicant and the title of the invention
and a reference number, and the additional information may be provided
on a container for the computer readable form with the name of the
applicant, the title of the invention, the reference number and the
additional information affixed to the container. If the computer
readable form is submitted after the date of filing under 35 U.S.C. 111,
after the date of entry in the national stage under 35 U.S.C. 371 or
after the time of filing, in the United States Receiving Office, an
international application under the PCT, the labels mentioned herein
must also include the date of the application number, including series
code and serial number.]

7. Section 1.825 is proposed to be amended by revising paragraphs (a),
(b) and (d ) to read as follows:

   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" (
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. Such a statement must be
averified statement if made by a person not registered to practice
before the Office.
   (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 (   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." Such a
statement must be a verified statement if made by a person not
registered to practice before the Office.

   (c) * * *

   (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. Such a statement must be a verified statement if
made by a person not registered to practice before the Office.

8. Appendix A to Subpart G is proposed to be revised to read as follows:

Appendix A To Subpart G Of Part 1 - Sample Sequence Listing
[(1) GENERAL INFORMATION:
   (i) APPLICANT: Doe, Joan X, Doe, John Q
   (ii) TITLE OF INVENTION: Isolation and Characterization of a Gene
Encoding a Protease from Paramecium sp.
   (iii) NUMBER OF SEQUENCES: 2
   (iv) CORRESPONDENCE ADDRESS:

(A) ADDRESSEE: Smith and Jones
(B) STREET: 123 Main Street
(C) CITY: Smalltown
(D) STATE: Anystate
(E) COUNTRY: USA
(F) ZIP: 12345

   (v) COMPUTER READABLE FORM:

(A) MEDIUM TYPE: Diskette, 3.50 inch, 800 Kb storage
(B) COMPUTER: Apple Macintosh
(C) OPERATING SYSTEM: Macintosh 5.0
(D) SOFTWARE: MacWrite

   (vi) CURRENT APPLICATION DATA:

(A) APPLICATION NUMBER: 09/999,999
(B) FILING DATE: 28-FEB-1989
(C) CLASSIFICATION: 999/99

   (vii) PRIOR APPLICATION DATA:

(A) APPLICATION NUMBER: PCT/US88/99999
(B) FILING DATE: 01-MAR-1988

   (viii) ATTORNEY/AGENT INFORMATION:

(A) NAME: Smith, John A
(B) REGISTRATION NUMBER: 00001
(C) REFERENCE/DOCKET NUMBER: 01-0001

   (ix) TELECOMMUNICATIONS INFORMATION:

(A) TELEPHONE: (909) 999-001
(B) TELEFAX: (909) 999-0002
(2) INFORMATION FOR SEQ ID NO: 1:

   (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 954 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
   (ii) MOLECULE TYPE: genomic DNA
   (iii) HYPOTHETICAL: yes
   (iv) ANTI-SENSE: no
   (vi) ORIGINAL SOURCE:

(A) ORGANISM: Paramecium sp
(C) INDIVIDUAL/ISOLATE: XYZ2
(G) CELL TYPE: unicellular organism

   (vii) IMMEDIATE SOURCE:

(A) LIBRARY: genomic
(B) CLONE: Para-XYZ2/36

   (x) PUBLICATION INFORMATION:

(A) AUTHORS: Doe, Joan X, Doe, John Q
(B) TITLE: Isolation and Characterization of a Gene Encoding a Protease
from Paramecium sp.
(C) JOURNAL: Fictional Genes
(D) VOLUME: I
(E) ISSUE: 1
(F) PAGES: 1-20
(G) DATE: 02-MAR-1988
(K) RELEVANT RESIDUES IN SEQ ID NO: 1: FROM 1 TO 954

   (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 1:

ATCGGGATAG  TACTGGTCAA  GACCGGTGGA  CACCGGTTAA  CCCCGGTTAA  GTACCGGTTA  60

TAGGCCATTT  CAGGCCAAAT  GTGCCCAACT  ACGCCAATTG  TTTTGCCAAC  GGCCAACGTT 120

ACGTTCGTAC  GCACGTATGT  ACCTAGGTAC  TTACGGACGT  GACTACGGAC  ACTTCCGTAC 180

GTACGTACGT  TTACGTACCC  ATCCCAACGT  AACCACAGTG  TGGTCGCAGT  GTCCCAGTGT 240

ACACAGACTG  CCAGACATTC  TTCACAGACA  CCCC ATG ACA CCA CCT GAA CGT CTC   295
                                         Met Thr Pro Pro Glu Arg Leu
                                                                 -30

TTC CTC CCA  AGG GTG TGT  GGC ACC ACC  CTA CAC CTC  CTC CTT CTG GGG    343
Phe Leu Pro  Arg Val Cys  Gly Thr Thr  Leu His Leu  Leu Leu Leu Gly
        -25                   -20                   -15

CTG CTG CTG  GTT CTG CTG  CCT GGG GCC  CAT    GTGAGGCAGC AGGAGAATGG    393
Leu Leu Leu  Val Leu Leu  Pro Gly Ala  His
    -10                   -5

GGTGGCTCAG  CCAAACCTTG  AGCCCTAGAG  CCCCCCTCAA CTCTGTTCTC CTAG GGG Gly 450

CTC ATG CAT  CTT GCC CAC  AGC AAC CTC  AAA CCT GCT  GCT CAC CTC  ATT   498
Leu Met His  Leu Ala His  Ser Asn Leu  Lys Pro Ala  Ala His Leu  Ile
  1              5                     10                   15

GTAAACATCC  ACCTGACCTC  CCAGACATGT  CCCCACCAGC TCTCCTCCTA CCCCTGCCTC  558

AGGAACCCAA  GCATCCACCC  CTCTCCCCCA  ACTTCCCCCA CGCTAAAAAA AACAGAGGGA  618

GCCCACTCCT  ATGCCTCCCC  CTGCCATCCC  CCAGGAACTC AGTTGTTCAG TGCCCACTTC  678

TAC CCC AGC AAG CAG AAC TCA CTG CTC TGG AGA GCA AAC ACG GAC CGT       726
Tyr Pro Ser Lys  Gln Asn Ser Leu Leu Trp Arg Ala Asn Thr Asp Arg
            20                   25                  30

GCC TTC CTC CAG GAT GGT TTC TCC TTG AGC AAC AAT TCT CTC CTG GTC       774
Ala Phe Leu Gln Asp Gly Phe Ser Leu Ser Asn Asn Ser Leu Leu Val
        35                  40                  45

TAGAAAAAAT  AATTGATTTC  AAGACCTTCT  CCCCATTCTG  CCTCCATTCT GACCATTTCA 834

GGGGTCGTCA  CCACCTCTCC  TTTGGCCATT  CCAACAGCTC  AAGTCTTCCC TGATCAAGTC 894

ACCGGAGCTT  TCAAAGAAGG  AATTCTAGGC  ATCCCAGGGG  ACCCACACCT CCCTGAACCA 954

(2) INFORMATION FOR SEQ ID NO: 2:
   (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH: 82 amino acids
(B) TYPE: amino acid
(C) TOPOLOGY: linear

   (ii) MOLECULE TYPE: protein
   (ix) FEATURE:

(A) NAME/KEY: signal sequence
(B) LOCATION: -34 to -1
(C) IDENTIFICATION METHOD: similarity to other signal sequences,
hydrophobic
(D) OTHER INFORMATION: expresses protease

   (x) PUBLICATION INFORMATION:

(A) AUTHORS: Doe, Joan X, Doe, John Q
(B) TITLE: Isolation and Characterization of a Gene Encoding a Protease
from Paramecium sp.
(C) JOURNAL: Fictional Genes
(D) VOLUME: I
(E) ISSUE: 1
(F) PAGES: 1-20
(G) DATE: 02-MAR-1988
(H) RELEVANT RESIDUES IN SEQ ID NO:2: FROM -34 TO 48
   (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 2:

Met Thr Pro Pro Glu Arg Leu Phe Leu Pro Arg Val Cys Gly Thr Thr
                -30                 -25                 -20
Leu His Leu Leu Leu Leu Gly Leu Leu Leu Val Leu Leu Pro Gly Ala
            -15             -10                      -5
His Gly Leu Met His Leu Ala His Ser Asn Leu Lys Pro Ala Ala His
        1               5                   10
Leu Ile Tyr Pro Ser Lys Gln Asn Ser Leu Leu Trp Arg Ala Asn Thr
15                  20              25                      30
Asp Arg Ala Phe Leu Gln Asp Gly Phe Ser Leu Ser Asn Asn Ser Leu
                35                  40                  45

Leu Val ]

>

<100>
   <110> Doe, Joan X, Doe, John Q
   <120> Isolation and Characterization of a Gene Encoding a Protease
from Paramecium sp.
   <130> 2
   <140>
   <141> Smith and Jones
   <142> 123 Main Street
   <143> Smalltown
   <144> Anystate
   <145> USA
   <146> 12345
   <150>
   <151> Floppy disk
   <152> IBM PC compatible
   <153> PC-DOS/MS-DOS
   <154> PatentIn Release #2.00
   <160>
   <161> 09/999,999
   <162> 28-FEB-1989
   <170>
   <171> PCT/US/88/99999
   <172> 01-MAR-1988
   <180>
   <181> Smith, John A
   <182> REGISTRATION NUMBER: 00001
   <183> 01-0001
   <190>
   <191> (909) 999-0001
   <192> (909) 999-0002
   <200> 1
   <210>
   <211> 954 base pairs
   <212> N
   <214> L
   <290>
   <291> CDS
   <292> join(275..373, 448..498, 679..774)
   <290>
   <291> mat_peptide
   <292> join(451..498, 679..774)
   <300>
   <301> Doe , Joan X, Doe, John Q
   <302> Isolation and Characterization of a Gene Encoding a Protease
from Paramecium sp.
   <303> Fictional Genes
   <304> 1
   <305> 1
   <306> 1-20
   <307> 02-MAR-1988
   <308> FROM 1 TO 957
   <400> 1

atcgggatag tactggtcaa  gaccggtgga  caccggttaa  ccccggttaa  gtaccggtta   60

taggccattt caggccaaat  gtgcccaact  acgccaattg  ttttgccaac  ggccaacgtt  120

acgttcgtac gcacgtatgt  acctaggtac  ttacggacgt  gactacggac  acttccgtac  180

gtacgtacgt ttacgtaccc  atcccaacgt  aaccacagtg  tggtcgcagt  gtcccagtgt  240

acacagactg ccagacattc  ttcacagaca  cccc atg    aca cca cct gaa cgt     292
                                        Met    Thr Pro Pro Glu Arg
                                                           -30

ctc ttc ctc  cca agg gtg  tgt ggc acc  acc cta cac  ctc ctc ctt  ctg   340
Leu Phe Leu  Pro Arg Val  Cys Gly Thr  Thr Leu His  Leu Leu Leu  Leu
             -25                  -20                   -15

ggg ctg ctg  ctg gtt ctg  ctg cct ggg  gcc cat  gtgaggcagc  aggagaatgg 393
Gly Leu Leu  Leu Val Leu  Leu Pro Gly  Ala His
        -10                   -5

ggtggctcag  ccaaaccttg  agccctagag  cccccctcaa  ctctgttctc  ctag ggg   450
                                                            Gly

ctc atg cat  ctt gcc cac  agc aac ctc  aaa cct gct  gct cac ctc   att  498
Leu Met His  Leu Ala His  Ser Asn Leu  Lys Pro Ala  Ala His Leu   Ile
1                5                     10                    15

gtaaacatcc acctgacctc ccagacatgt ccccaccagc tctcctccta cccctgcctc      558

aggaacccaa gcatccaccc ctctccccca acttccccca cgctaaaaaa aacagaggga      618

gcccactcct atgcctcccc ctgccatccc ccaggaactc agttgttcag tgcccacttc      678

tac ccc agc  aag cag aac  tca ctg ctc  tgg aga gca  aac acg gac  cgt   726
Tyr Pro Ser  Lys Gln Asn  Ser Leu Leu  Trp Arg Ala  Asn Thr Asp  Arg
             20                   25                    30

gcc ttc ctc  cag gat ggt  ttc tcc ttg  agc aac aat  tct ctc ctg  gtc   774
Ala Phe Leu  Gln Asp Gly  Phe Ser Leu  Ser Asn Asn  Ser Leu Leu  Val
         35                   40                    45

tagaaaaaat  aattgatttc  aagaccttct  ccccattctg  cctccattct gaccatttca  834

ggggtcgtca  ccacctctcc  tttggccatt  ccaacagctc  aagtcttccc tgatcaagtc  894

accggagctt  tcaaagaagg  aattctaggc  atcccagggg  acccacacct ccctgaacca  954

   <200> 2
   <210>
   <211> 82 amino acids
   <212> A
   <214> L
   <400> 2

Met Thr Pro  Pro Glu Arg  Leu Phe Leu  Pro Arg Val  Cys Gly Thr   Thr
                 -30                   -25                  -20

Leu His Leu  Leu Leu Leu  Gly Leu Leu  Leu Val Leu  Leu Pro Gly   Ala
             -15                  -10                   -5

His Gly Leu  Met His Leu  Ala His Ser  Asn Leu Lys  Pro Ala Ala   His
         1                 5                   10

Leu Ile Tyr  Pro Ser Lys  Gln Asn Ser  Leu Leu Trp  Arg Ala Asn   Thr
15                    20                   25                     30

Asp Arg Ala  Phe Leu Gln  Asp Gly Phe  Ser Leu Ser  Asn Asn Ser   Leu
                 35                40                       45

Leu Val <

9. Appendix B to Subpart G is proposed to be removed.
   [Appendix B To Subpart G of Part 1- Headings For Information Items In
   1.823
(1) GENERAL INFORMATION:
   (i) APPLICANT:
   (ii) TITLE OF INVENTION:
   (iii) NUMBER OF SEQUENCES:
   (iv) CORRESPONDENCE ADDRESS:

(A) ADDRESSEE:
(B) STREET:
(C) CITY:
(D) STATE:
(E) COUNTRY:
(F) ZIP:

   (v) COMPUTER READABLE FORM:

(A) MEDIUM TYPE:
(B) COMPUTER:
(C) OPERATING SYSTEM:
(D) SOFTWARE

   (vi) CURRENT APPLICATION DATA:

(A) APPLICATION NUMBER:
(B) FILING DATE:
(C) CLASSIFICATION:

   (vii) PRIOR APPLICATION DATA:

(A) APPLICATION NUMBER:
(B) FILING DATE:

   (viii) ATTORNEY/AGENT INFORMATION:

(A) NAME:
(B) REGISTRATION NUMBER:
(C) REFERENCE/DOCKET NUMBER:

   (ix) TELECOMMUNICATIONS INFORMATION:

(A) TELEPHONE:
(B) TELEFAX:
(C) TELEX:

(2) INFORMATION FOR SEQ ID NO: X:
   (i) SEQUENCE CHARACTERISTICS:

(A) LENGTH:
(B) TYPE:
(C) STRANDEDNESSS:
(D) TOPOLOGY:
   (ii) MOLECULE TYPE:
   - Genomic RNA;
   - Genomic DNA;
   - mRNA;
   - tRNA;
   - rRNA;
   - snRNA;
   - scRNA;
   -preRNA;
   - cDNA to genomic RNA;
   - cDNA to mRNA;
   - cDNA to tRNA; - cDNA to rRNA;
   - cDNA to snRNA;
   - cDNA to scRNA;
   - Other nucleic acid;
   (A) DESCRIPTION:
   - protein and
   - peptide.
   (iii) HYPOTHETICAL:
   (iv) ANTI-SENSE:
   (v) FRAGMENT TYPE:
   (vi) ORIGINAL SOURCE:

(A) ORGANISM:
(B) STRAIN:
(C) INDIVIDUAL ISOLATE:
(D) DEVELOPMENTAL STAGE:
(E) HAPLOTYPE:
(F) TISSUE TYPE:
(G) CELL TYPE:
(H) CELL LINE:
(I) ORGANELLE:

   (vii) IMMEDIATE SOURCE:

(A) LIBRARY:
(B) CLONE:

   (viii) POSITION IN GENOME:

(A) CHROMOSOME/SEGMENT:
(B) MAP POSITION:
(C) UNITS:

   (ix) FEATURE:

(A) NAME/KEY:
(B) LOCATION:
(C) IDENTIFICATION METHOD:
(D) OTHER INFORMATION:

   (x) PUBLICATION INFORMATION:

(A) AUTHORS:
(B) TITLE:
(C) JOURNAL:
(D) VOLUME:
(E) ISSUE:
(F) PAGES:
(G) DATE:
(H) DOCUMENT NUMBER:
(I) FILING DATE:
(J) PUBLICATION DATE:
(K) RELEVANT RESIDUES:

   (xi) SEQUENCE DESCRIPTION: SEQ ID NO:X: ]

September 23, 1996                                      BRUCE A. LEHMAN
                                    Assistant Secretary of Commerce and
                                 Commissioner of Patents and Trademarks