MPEP § 2412 — MPEP § 2412
Current through: 2022-07-01

2412-The Requirements for Patent Applications Containing Nucleotide Sequence and/or Amino Acid Sequence Disclosures to Include
 a Sequence Listing in XML file format
 
 
 

 
 
 
 
 
 
 
 

 

 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 

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 Chapter 2400 

 Section 2412 
 

 
 
 
 
 
 2412 The Requirements for Patent Applications Containing
 Nucleotide Sequence and/or Amino Acid Sequence Disclosures to Include a Sequence Listing in
 XML file format [R-01.2024]
 

 [Editor Note: This section is applicable to all applications with a filing date,
 or, for national phase applications, an international filing date, on or after July 1,
 2022, having disclosure of one or more nucleotide and/or amino acid sequences as defined
 in 37 CFR
 1.831(b) .] 

 Patent applications that disclose a nucleotide and/or amino
 acid sequence(s) by enumeration of its residues, as defined in 37 CFR
 1.831(b) , must present each sequence and associated sequence data in
 a standardized electronic eXtensible Markup Language (XML) format, (a “Sequence Listing
 XML”) as a separate part of the specification. This standardized format is set forth in the
 World Intellectual Property Organization (WIPO) Standard ST.26, and applies to sequence
 listings in international applications filed under the Patent Cooperation Treaty (PCT) and
 in national and regional applications filed in the intellectual property offices (IPOs) of
 WIPO member states. As a result, a single sequence listing in compliance with WIPO Standard
 ST.26 can be prepared for use in all IPOs of WIPO member states. The regulatory provisions
 found at 37 CFR
 1.831 - 1.835 implement WIPO Standard ST.26 in
 the USPTO and set forth requirements for presenting sequence data in patent applications
 filed on or after July 1, 2022, that disclose nucleotide sequences and/or amino acid
 sequences. 
 

 WIPO Standard ST.26 is incorporated by reference into the
 USPTO regulations by including new regulatory text at 37 CFR
 1.839 :
 

 
 37 CFR 1.839 Incorporation by reference. 

 
 (a) Certain material is incorporated by reference into
 this subpart with the approval of the Director of the Federal Register under 5
 U.S.C. 552(a) and 1 CFR part 51. All approved incorporation by reference (IBR)
 material is available for inspection at the USPTO and at the National Archives and
 Records Administration (NARA). Contact the USPTO’s Office of Patent Legal
 Administration at 571–272–7701. For information on the availability of this
 material at NARA, email fr.inspection@nara.gov or go to www.archives.gov/federal-register/cfr/ibr-locations.html . The
 material may be obtained from the source(s) in paragraph (b) of this section. 
 

 (b) World Intellectual Property Organization (WIPO), 34
 chemin des Colombettes, 1211 Geneva 20 Switzerland, www.wipo.int. 
 
 (1) WIPO Standard ST.26. WIPO Handbook on
 Intellectual Property Information and Documentation, Standard ST.26:
 Recommended Standard for the Presentation of Nucleotide and Amino Acid
 Sequence Listings Using XML (eXtensible Markup Language) including Annexes
 I–VII, version 1.6, approved November 25, 2022; IBR approved for §§
 1.831 through
 1.834 . 
 

 (2) [Reserved]

 
 

 
 

 For ease of access, WIPO Standard ST.26 can be found at:
 www.wipo.int/export/sites/www/standards /en/pdf/03-26-01.pdf 

 A link to WIPO Standard ST.26 is also found on the USPTO’s
 Sequence Listing Resource Center:
 

 www.uspto.gov/patents/apply/sequence- listing-resource-center 

 
 2412.01 Overview of the Sequence Rules [R-01.2024]

 [Editor Note: This section is applicable to all applications with a filing
 date, or, for national phase applications, an international filing date, on or after
 July 1, 2022, having disclosure of one or more nucleotide and/or amino acid sequences
 as defined in 37 CFR 1.831(b) .] 

 Under the sequence listing rules, 37 CFR
 1.831 - 1.834 , an application having a
 filing date on or after July 1, 2022, that discloses one or more nucleotide and/or amino
 acid sequences by enumeration of its residues, as defined in 37 CFR 1.831(a), must
 contain, as a part of the description, a sequence listing in eXtensible Markup Language
 (XML) format, where the XML file of the sequence information conforms to the
 requirements of 37 CFR 1.831 - 1.834 ,
 which specify requirements of particular paragraphs of WIPO Standard ST.26. For U.S.
 applications, the sequence rules do not require that all sequences and associated
 sequence information contained in the required sequence listing part of the description
 be disclosed elsewhere in the application; the content of a sequence listing is
 considered part of the disclosure of the invention. However, for international
 applications, all sequences and associated sequence information contained in the
 required sequence listing part of the description is considered an application part if
 present on the filing date without an incorporation by reference.
 

 

 
 2412.02 Definition of “Sequence Listing XML” [R-01.2024]

 [Editor Note: This section is applicable to all applications with a filing
 date, or, for national phase applications, an international filing date, on or after
 July 1, 2022, having disclosure of one or more nucleotide and/or amino acid sequences
 as defined in 37 CFR 1.831(b) .] 

 
 37 CFR 1.831 Requirements for patent applications filed on
 or after July 1, 2022, having nucleotide and/or amino acid sequence disclosures. 

 
 (a) Patent applications disclosing a nucleotide
 and/or amino acid sequences by enumeration of its residues, as defined in
 paragraph (b) of this section, must contain, as a separate part of the
 disclosure, a computer readable Sequence Listing in XML format (a “Sequence
 Listing XML”). Disclosed nucleotide or amino acid sequences that do not meet
 the definition in paragraph (b) of this section must not be included in the
 “Sequence Listing XML.” The “Sequence Listing XML” contains the information of
 the nucleotide and/or amino acid sequence(s) disclosed in the patent
 application using the symbols and format in accordance with the requirements of
 §§ 1.832 through 1.834 .
 

 
 *****

 

 
 

 For 35 U.S.C. 111 applications and
 international applications filed on or after July 1, 2022, that disclose one or more
 nucleotide and/or amino acid sequences as enumerated by its residues, each nucleotide
 and/or amino acid sequence and associated sequence data must be presented as a separate
 part of the disclosure that comprises the sequences in computer readable XML format in
 accordance with WIPO Standard ST.26 as implemented by 37 CFR
 1.831 - 1.834 . This sequence listing is
 referred to as a “Sequence Listing XML” in order to distinguish it from a “Sequence
 Listing” submitted in an application having a filing date BEFORE July 1, 2022. For
 35 U.S.C.
 111 applications and international applications having a filing
 date before July 1, 2022, that disclose of nucleotide and/or amino acid sequences, see
 37 CFR
 1.821(c) and 1.821(e)(1) . See also
 MPEP §§ 2421.01 and
 2421.02 .
 

 
 2412.02(a) “Enumeration of its residues” [R-01.2024]

 [Editor Note: This section is applicable to all applications with a filing
 date, or, for national phase applications, an international filing date, on or
 after July 1, 2022, having disclosure of one or more nucleotide and/or amino acid
 sequences as defined in 37 CFR
 1.831(b) .] 

 
 37 CFR 1.831 Requirements for patent applications filed
 on or after July 1, 2022, having nucleotide and/or amino acid sequence
 disclosures. 

 
 
 *****

 

 (d) “Enumeration of its residues” means
 disclosure of a nucleotide or amino acid sequence in a patent application by
 listing, in order, each residue of the sequence, where the residues are
 represented in the manner as defined in paragraph 3(c)(i) or (ii) of WIPO
 Standard ST.26 (incorporated by reference, see §
 1.839 ).
 

 
 *****

 

 
 

 WIPO Standard ST.26 specifies that “enumeration of
 its residues” means “disclosure of a sequence in a patent application by listing, in
 order, each residue of the sequence, wherein either (i) the residue is represented by
 a name, abbreviation, symbol, or structure (e.g., HHHHHHQ or HisHisHisHisHisHisGln);
 or (ii) multiple residues are represented by a shorthand formula (e.g., His6Gln)
 (WIPO Standard ST.26, paragraph 3(c)). See also the Guidance portion of the Standard,
 Annex VI, page 3.26.vi.2 for a discussion of “enumeration of its residues” and page
 3.26.vi.18-19, 51, 53 for examples.
 

 

 

 
 2412.03 Nucleotides and Amino Acids Included and
 Excluded From a “Sequence Listing XML” [R-01.2024]
 

 [Editor Note: This section is applicable to all applications with a filing
 date, or, for national phase applications, an international filing date, on or after
 July 1, 2022, having disclosure of one or more nucleotide and/or amino acid sequences
 as defined in 37 CFR 1.831(b) .] 

 
 37 CFR 1.831 Requirements for patent applications filed
 on or after July 1, 2022, having nucleotide and/or amino acid sequence
 disclosures. 

 
 
 *****

 

 (b) Nucleotide and/or amino acid sequences, as used
 in this section and §§ 1.832 through
 1.835 , encompass: 
 
 (1) An unbranched sequence or linear region
 of a branched sequence containing 4 or more specifically defined amino
 acids, wherein the amino acids form a single peptide backbone; or 
 

 (2) An unbranched sequence or linear region
 of a branched sequence of 10 or more specifically defined nucleotides,
 wherein adjacent nucleotides are joined by: 
 
 (i) A 3' to 5' (or 5' to 3')
 phosphodiester linkage; or 
 

 (ii) Any chemical bond that results in
 an arrangement of adjacent nucleobases that mimics the arrangement
 of nucleobases in naturally occurring nucleic acids
 ( i.e., nucleotide analogs). 
 

 
 

 
 

 
 *****

 

 (j) A “Sequence listing XML” must not include any
 sequences having fewer than 10 specifically defined nucleotides, or fewer than
 4 specifically defined amino acids.
 

 
 

 Generally, nucleotide sequences that are an unbranched
 sequence or constitute a linear portion of a branched sequence of 10 or more
 specifically defined nucleotides are required to be listed in a “Sequence Listing XML.”
 See MPEP §§
 2412.03(d) and (e) for definitions of
 nucleotide and modified nucleotide, respectively. See MPEP § 2412.03(a) for definition of
 “specifically defined.” 
 

 Similarly, amino acid sequences that are an unbranched
 sequence or constitute a linear portion of a branched sequence of 4 or more specifically
 defined amino acids are required to be listed in a “Sequence Listing XML.” See
 MPEP §§
 2412.03(b) and (c) for definitions of amino
 acid and modified amino acid, respectively. See MPEP § 2412.03(a) for definition of
 “specifically defined.”
 

 37 CFR 1.831(b) sets forth the
 nucleotide and amino acid sequences which must be included in a “Sequence Listing XML”.
 37 CFR
 1.831(j) specifies that any sequence having fewer than 10
 specifically defined nucleotides, or fewer than 4 specifically defined amino acids must
 be excluded from any “Sequence listing XML.”
 

 
 2412.03(a) “Specifically Defined” [R-01.2024]

 [Editor Note: This section is applicable to all applications with a filing
 date, or, for national phase applications, an international filing date, on or
 after July 1, 2022, having disclosure of one or more nucleotide and/or amino acid
 sequences as defined in 37 CFR
 1.831(b) .] 

 
 37 CFR 1.831 Requirements for patent applications
 filed on or after July 1, 2022, having nucleotide and/or amino acid sequence
 disclosures. 

 
 
 *****

 

 (e) “Specifically defined” means any amino acid
 or nucleotide as defined in paragraph 3(k) of WIPO Standard ST.26.
 

 
 *****

 

 
 

 WIPO Standard ST.26, paragraph 3(k), provides that
 “specifically defined” means any nucleotide other than those represented by the
 symbol “n” and any amino acid other than those represented by the symbol “X,”,
 wherein “n” and “X” are used in a conventional manner as shown below in Table 1 for
 nucleotide symbols and Table 3 for amino acids symbols.
 

 
 Table 1: List of Nucleotides
 Symbols
 
 
 
 Symbol 
 Definition 
 

 
 
 
 a 
 adenine 
 

 
 c 
 cytosine 
 

 
 g 
 guanine 
 

 
 t 
 thymine in
 DNA/uracil in RNA (t/u)
 
 

 
 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; “unknown” or “other”
 
 

 
 
 Reproduced from WIPO Standard ST.26, Annex I, Section
 1.
 

 
 Table 3: List of Amino Acids
 Symbols
 
 
 
 Symbol 
 Definition 
 

 
 
 
 A 
 Alanine 
 

 
 R 
 Arginine 
 

 
 N 
 Asparagine 
 

 
 D 
 Aspartic acid
 (Aspartate)
 
 

 
 C 
 Cysteine 
 

 
 Q 
 Glutamine 
 

 
 E 
 Glutamic acid
 (Glutamate)
 
 

 
 G 
 Glycine 
 

 
 H 
 Histidine 
 

 
 I 
 Isoleucine 
 

 
 L 
 Leucine 
 

 
 K 
 Lysine 
 

 
 M 
 Methionine 
 

 
 F 
 Phenylalanine 
 

 
 P 
 Proline 
 

 
 O 
 Pyrrolysine 
 

 
 S 
 Serine 
 

 
 U 
 Selenocysteine 
 

 
 T 
 Threonine 
 

 
 W 
 Tryptophan 
 

 
 Y 
 Tyrosine 
 

 
 V 
 Valine 
 

 
 B 
 Aspartic acid or
 Asparagine
 
 

 
 Z 
 Glutamine or
 Glutamic acid
 
 

 
 J 
 Leucine or
 Isoleucine
 
 

 
 X 
 A or R or N or D
 or C or Q or E or G or H or I or L or K or M or F or P or O or S or U or
 T or W or Y or V; “unknown” or “other”
 
 

 
 
 Reproduced from WIPO Standard ST.26, Annex I, Section
 3.
 

 

 
 2412.03(b) “Amino Acid” [R-01.2024]

 [Editor Note: This section is applicable to
 all applications with a filing date, or, for national phase applications, an
 international filing date, on or after July 1, 2022, having disclosure of one or
 more nucleotide and/or amino acid sequences as defined in 37 CFR
 1.831(b) . ] 

 
 37 CFR 1.831 Requirements for patent applications
 filed on or after July 1, 2022, having nucleotide and/or amino acid sequence
 disclosures. 

 
 
 *****

 

 (f) “Amino acid” includes any D- or L-amino acid
 or modified amino acid as defined in paragraph 3(a) of WIPO Standard
 ST.26.
 

 
 *****

 

 
 

 WIPO Standard ST.26, paragraph 3(a), defines “amino
 acid” to mean any amino acid that can be represented using any of the symbols shown
 in Annex I, Table 3: List of Amino Acids Symbols of WIPO Standard ST.26 (reproduced
 in MPEP
 § 2412.03(a) ). Such amino acids include, inter
 alia, D-amino acids and amino acids containing modified or synthetic
 side chains. Amino acids will be construed as unmodified L-amino acids unless further
 described in a “feature table”. See MPEP §
 2413.01(g) , subsection I, for discussion of a “feature
 table”. A peptide nucleic acid (PNA) residue is not considered an amino acid, but is
 considered a nucleotide.
 

 

 

 
 2412.03(c) “Modified Amino Acid” [R-01.2024]

 [Editor Note: This section is applicable to
 all applications with a filing date, or, for national phase applications, an
 international filing date, on or after July 1, 2022, having disclosure of one or
 more nucleotide and/or amino acid sequences as defined in 37 CFR
 1.831(b) . Formatting representations of XML (eXtensible
 Markup Language) elements in this section appear different than shown in Standard
 ST.26, which may be accessed at: www.wipo.int /export/sites/www/
 standards/en/pdf/03-26-01.pdf .] 

 
 37 CFR 1.831 Requirements for patent applications
 filed on or after July 1, 2022, having nucleotide and/or amino acid sequence
 disclosures. 

 
 
 *****

 

 (g) “Modified amino acid” includes any amino
 acid as described in paragraph 3(e) of WIPO Standard ST.26.
 

 
 *****

 

 
 

 WIPO Standard ST.26, paragraph 3(e), defines
 “modified amino acid” to mean any amino acid as described in the definition of “amino
 acid”, other than L-alanine, L-arginine, L-asparagine, L-aspartic acid, L-cysteine,
 L-glutamine, L-glutamic acid, L-glycine, L-histidine, L-isoleucine, L-leucine,
 L-lysine, L-methionine, L-phenylalanine, L-proline, L-pyrrolysine, L-serine,
 L-selenocysteine, L-threonine, L-tryptophan, L-tyrosine, or L-valine. See
 MPEP
 § 2412.03(b) .
 

 Modified amino acids, including D-amino acids, should
 be represented in the sequence as the corresponding unmodified amino acids whenever
 possible. Any modified amino acid in a sequence that cannot otherwise be represented
 by a symbol set forth in Table 3 must be represented by “X”, i.e., an “other” amino
 acid.
 

 A modified amino acid must be further described in a
 feature table. See MPEP § 2413.01(g), subsection I, for discussion of a “feature
 table”. Where applicable, the feature keys “CARBOHYD” or “LIPID” should be used
 together with the qualifier “note”. The feature key “MOD_RES” should be used for
 other post-translationally modified amino acids together with the qualifier “note”.
 The feature key “SITE” together with the qualifier “note” should be used when the
 modified amino acid is not a post-translationally modified amino acid. See
 MPEP §
 2413.01(g) , subsections II and III, for discussion of a
 “feature key”. The value for the qualifier “note” must either be an abbreviation set
 forth in Table 4 below or the complete, unabbreviated name of the modified amino
 acid. The abbreviations set forth in Table 4 or the complete, unabbreviated names
 must not be used in the sequence itself.
 

 

 
 Table 4: List of Modified Amino
 Acids
 
 
 
 Abbreviation 
 Modified 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 
 

 
 alle 
 allo-Isoleucine 
 

 
 MeGly 
 N-Methylglycine,
 sarcosine
 
 

 
 Melle 
 N-Methylisoleucine 
 

 
 MeLys 
 6-N-Methyllysine 
 

 
 MeVal 
 N-Methylvaline 
 

 
 Nva 
 Norvaline 
 

 
 Nle 
 Norleucine 
 

 
 Orn 
 Ornithine 
 

 
 
 Reproduced from WIPO Standard ST.26, Annex I, Section
 4.
 

 

 
 2412.03(d) “Nucleotide” [R-01.2024]

 [Editor Note: This section is applicable to
 all applications with a filing date, or, for national phase applications, an
 international filing date, on or after July 1, 2022, having disclosure of one or
 more nucleotide and/or amino acid sequences as defined in 37 CFR
 1.831(b) . Formatting representations of XML (eXtensible
 Markup Language) elements in this section appear different than shown in Standard
 ST.26, which may be accessed at: www.wipo.int /export/sites/www/
 standards/en/pdf/03-26-01.pdf .] 

 
 37 CFR 1.831 Requirements for patent applications
 filed on or after July 1, 2022, having nucleotide and/or amino acid sequence
 disclosures. 

 
 
 *****

 

 (h) “Nucleotide” includes any nucleotide,
 nucleotide analog, or modified nucleotide as defined in paragraphs 3(f) and
 3(g) of WIPO Standard ST.26.
 

 
 *****

 

 
 

 WIPO Standard ST.26, paragraphs 3(f) and (g), identify
 a “nucleotide” to encompass any nucleotide or nucleotide analogue or “modified
 nucleotide” (see MPEP § 2412.03(e) ) that can
 be represented using any of the symbols set forth in Table 1: List of Nucleotides
 Symbols (see MPEP § 2412.03(a) ), wherein the
 nucleotide, or nucleotide analogue, or modified nucleotide contains:
 

 
 (i) a backbone moiety selected from:
 
 (1) 2’ deoxyribose 5’ monophosphate (the
 backbone moiety of a deoxyribonucleotide) or ribose 5’ monophosphate (the
 backbone moiety of a ribonucleotide); or
 

 (2) an analogue of a 2’ deoxyribose 5’
 monophosphate or ribose 5’ monophosphate, which when forming the backbone
 of a nucleic acid analogue, results in an arrangement of nucleobases that
 mimics the arrangement of nucleobases in nucleic acids containing a 2’
 deoxyribose 5’ monophosphate or ribose 5’ monophosphate backbone, wherein
 the nucleic acid analogue is capable of base pairing with a complementary
 nucleic acid; examples of backbone moieties include amino acids as in
 peptide nucleic acids, glycol molecules as in glycol nucleic acids,
 threofuranosyl sugar molecules as in threose nucleic acids, morpholine
 rings and phosphorodiamidate groups as in morpholinos, and cyclohexenyl
 molecules as in cyclohexenyl nucleic acids; and
 

 
 

 (ii) the backbone moiety is either:
 
 (1) joined to a nucleobase, including a
 modified or synthetic purine or pyrimidine nucleobase; or
 

 (2) lacking a purine or pyrimidine nucleobase
 when the nucleotide is part of a nucleotide sequence, referred to as an
 “AP site” or an “abasic site”.
 

 
 

 
 

 
 2412.03(e) “Modified Nucleotide” [R-01.2024]

 [Editor Note: This section is applicable to
 all applications with a filing date, or, for national phase applications, an
 international filing date, on or after July 1, 2022, having disclosure of one or
 more nucleotide and/or amino acid sequences as defined in 37 CFR
 1.831(b) . Formatting representations of XML (eXtensible
 Markup Language) elements in this section appear different than shown in Standard
 ST.26, which may be accessed at: www.wipo.int /export/sites/www/
 standards/en/pdf/03-26-01.pdf .] 

 
 37 CFR 1.831 Requirements for patent applications
 filed on or after July 1, 2022, having nucleotide and/or amino acid sequence
 disclosures. 

 
 
 *****

 

 (i) “Modified nucleotide” includes any
 nucleotide as described in paragraph 3(f) of WIPO Standard ST.26.
 

 
 *****

 

 
 

 WIPO Standard ST.26, paragraph 3(f), provides that a
 “modified nucleotide” means any “nucleotide” as explained in MPEP §
 2412.03(d) other than deoxyadenosine 3’-monophosphate,
 deoxyguanosine 3’-monophosphate, deoxycytidine 3’-monophosphate, deoxythymidine
 3’-monophosphate, adenosine 3’-monophosphate, guanosine 3’-monophosphate, cytidine
 3’-monophosphate, or uridine 3’-monophosphate.
 

 

 

 
 2412.04 Use of Sequence Identifiers to Denote Sequences
 Disclosed in the Description, Drawings or Claims [R-01.2024]
 

 [Editor Note: This section is applicable to all applications with a filing
 date, or, for national phase applications, an international filing date, on or after
 July 1, 2022, having disclosure of one or more nucleotide and/or amino acid sequences
 as defined in 37 CFR 1.831(b) . Formatting
 representations of XML (eXtensible Markup Language) elements in this section appear
 different than shown in Standard ST.26, which may be accessed at: www.wipo.int /export/sites/www/
 standards/en/pdf/03-26-01.pdf .] 

 
 37 CFR 1.831 Requirements for patent applications filed
 on or after July 1, 2022, having nucleotide and/or amino acid sequence disclosures. 

 
 
 *****

 

 (c) Where the description or claims of a patent
 application discuss a sequence that is set forth in the “Sequence Listing XML”
 in accordance with paragraph (a) of this section, reference must be made to the
 sequence by use of the sequence identifier, preceded by “SEQ ID NO:” or the
 like 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.
 Where a sequence is presented in a drawing, reference must be made to the
 sequence by use of the sequence identifier (§ 1.832(a) ), either in the drawing or in the Brief
 Description of the Drawings, where the correlation between multiple sequences
 in the drawing and their sequence identifiers (§ 1.832(a) ) in the Brief Description is clear.
 *****

 

 
 

 37 CFR 1.831(c) requires that each
 nucleotide and/or amino acid sequence set forth in a “Sequence Listing XML” in
 accordance with 37 CFR § 1.831(a) must be referenced
 by a sequence identifier as defined in 37 CFR 1.832(a) (see MPEP §
 2412.05(a) ), preceded by the notation “SEQ ID NO:” or the
 like, when the sequence appears in the description or claims. Additionally, where a
 sequence set forth in a “Sequence Listing XML” is presented in a drawing, reference must
 be made using the sequence identifier preceded by the notation “SEQ ID NO:” or the like,
 either in the drawing or in the Brief Description of the Drawings. The sequence
 identifiers in the disclosure must correspond to sequence identifiers set forth in the
 “Sequence Listing XML” as defined in 37
 CFR 1.832(a) .
 

 37 CFR 1.831(c) is also intended to
 permit references in the application (e.g., specification, claims, or drawings) to
 sequences set forth in the “Sequence Listing XML” by the use of assigned sequence
 identifiers without enumerating the sequence. Sequence identifiers can also be used to
 discuss and/or claim parts or fragments of a properly presented sequence. For example,
 language such as “residues 14 to 243 of SEQ ID NO:23” is permissible and the fragment
 need not be separately presented in the “Sequence Listing XML.” 
 

 37 CFR 1.831(c) does not alter, in
 any way, the requirements of 35 U.S.C. 112 . The implementation of this
 rule has had no effect on disclosure and/or claiming requirements. 37 CFR
 1.831 - 1.835 , in general, or the use of
 sequence identifiers throughout the specification and claims, specifically, should not
 raise any issues under 35 U.S.C. 112(a) or 35 U.S.C.
 112(b) because the of sequence identifiers (preceded by “SEQ ID
 NO: or the like”) only provides a shorthand way for applicants to discuss and claim
 their inventions. These identifiers do not in any way restrict the manner in which an
 invention can be claimed.
 

 

 
 2412.05 Representation and Symbols for Nucleotide
 and/or Amino Acid Sequences [R-01.2024]
 

 [Editor Note: This section is applicable to all applications with a filing
 date, or, for national phase applications, an international filing date, on or after
 July 1, 2022, having disclosure of one or more nucleotide and/or amino acid sequences
 as defined in 37 CFR 1.831(b) .] 

 WIPO Standard ST.26 sets forth specific symbols for
 representing nucleotide and/or amino acid residues in a sequence. The USPTO rules
 incorporate those specific symbols and XML formatting representations.
 

 
 2412.05(a) Use of Sequentially Numbered Sequence
 Identifiers in the “Sequence Listing XML” [R-01.2024]
 

 [Editor Note: This section is applicable to all applications with a filing
 date, or, for national phase applications, an international filing date, on or
 after July 1, 2022, having disclosure of one or more nucleotide and/or amino acid
 sequences as defined in 37 CFR 1.831(b) . Formatting
 representations of XML (eXtensible Markup Language) elements in this section
 appear different than shown in Standard ST.26, which may be accessed at:
 
 www.wipo.int
 /export/sites/www/standards/en/pdf/03-26-01.pdf .] 

 
 37 CFR 1.832 Representation of nucleotide and/or amino
 acid sequence data in the “Sequence Listing XML” part of a patent application
 filed on or after July 1, 2022. 

 
 (a) Each disclosed nucleotide or amino acid
 sequence that meets the requirements of § 1.831(b) must appear separately in the “Sequence
 Listing XML.” Each sequence set forth in the “Sequence Listing XML” must be
 assigned a separate sequence identifier. The sequence identifiers must begin
 with 1 and increase sequentially by integers as defined in paragraph 10 of
 WIPO Standard ST.26 (incorporated by reference, see §
 1.839 ).
 

 
 *****

 

 
 

 In accordance with 37 CFR
 1.832(a) , the sequence identifiers in the “Sequence Listing
 XML” must begin with 1 and increase sequentially by integers. The requirement for
 sequence identifiers, at a minimum, requires that each sequence be assigned a
 different number for purposes of identification. However, where practical and for
 ease of reference, sequences should be presented in the “Sequence Listing XML” in
 numerical order and in the order in which they are discussed in the application. 
 

 Each nucleotide and/or amino acid sequence that meets
 the definition in 37 CFR 1.831(b) and is enumerated
 by its residues must be assigned a separate sequence identifier, including a sequence
 which is identical to a region of a longer sequence. See MPEP §
 2412.02 for further description of a “sequence”.
 

 Where no sequence is present for a sequence
 identifier, i.e. an intentionally skipped sequence, “000” must be used in place of a
 sequence in a “Sequence Listing XML”. The total number of sequences indicated in the
 “Sequence Listing XML” must equal the total number of sequence identifiers, whether
 followed by a sequence or by “000”. 
 

 WIPO Standard ST.26 paragraphs 58 and 59 require that
 an intentionally skipped sequences in a “Sequence Listing XML” must be represented as
 follows: 
 

 
 (a) the value of the element SequenceData and its
 attribute sequenceIDNumber, is the sequence identifier of the skipped
 sequence;
 

 (b) no value is provided for the elements INSDSeq
 _length, INSDSeq _moltype, and INSDSeq _division; 
 

 (c) the element INSDSeq _feature-table is not
 included; and 
 

 (d) the value of the element INSDSeq _sequence is
 the string “000”.
 

 
 

 
 2412.05(b) Representation and Symbols of Nucleotide
 Sequence Data [R-01.2024]
 

 [Editor Note: This section is applicable to
 all applications with a filing date, or, for national phase applications, an
 international filing date, on or after July 1, 2022, having disclosure of one or
 more nucleotide and/or amino acid sequences as defined in 37 CFR
 1.831(b) . Formatting representations of XML (eXtensible
 Markup Language) elements in this section appear different than shown in Standard
 ST.26, which may be accessed at: 
 www.wipo.int
 /export/sites/www/standards/en/pdf/03-26-01.pdf .] 

 
 37 CFR 1.832 Representation of nucleotide and/or amino
 acid sequence data in the “Sequence Listing XML” part of a patent application
 filed on or after July 1, 2022. 

 
 
 *****

 

 (b) The representation and symbols for nucleotide
 sequence data shall conform to the requirements of paragraphs (b)(1) through
 (4) of this section.
 
 (1) A nucleotide sequence must be
 represented in the manner described in paragraphs 11–12 of WIPO
 Standard ST.26.
 

 (2) All nucleotides, including nucleotide
 analogs, modified nucleotides, and “unknown” nucleotides, within a
 nucleotide sequence must be represented using the symbols set forth in
 paragraphs 13–16, 19, and 21 of WIPO Standard ST.26. 
 

 (3) Modified nucleotides within a
 nucleotide sequence must be described in the manner discussed in
 paragraphs 17, 18, and 19 of WIPO Standard ST.26.
 

 (4) A region containing a known number of
 contiguous “a,” “c,” “g,” “t,” or “n” residues for which the same
 description applies may be jointly described in the manner described
 in paragraph 22 of WIPO Standard ST.26.
 

 
 

 
 *****

 

 
 
 I. REPRESENTATION OF NUCLEOTIDE
 SEQUENCE WIPO Standard ST.26, paragraph 11, provides that a
 nucleotide sequence must be represented only by a single strand, in the 5’ to 3’
 direction from left to right, or in the direction from left to right that mimics
 the 5’ to 3’ direction. The designations 5’ and 3’ or any other similar
 designations must not be included in the sequence. A double-stranded nucleotide
 sequence disclosed by enumeration of the residues of both strands must be
 represented as: 
 

 
 (a) a single sequence or as two separate
 sequences, each assigned its own sequence identifier, where the two separate
 strands are fully complementary to each other, or
 

 (b) two separate sequences, each assigned its
 own sequence identifier, where the two strands are not fully complementary
 to each other.
 

 
 WIPO Standard ST.26, paragraph 12, provides that
 the first nucleotide presented in the sequence is residue position number 1. When
 nucleotide sequences are circular in configuration, applicant must choose the
 nucleotide in residue position number 1. Numbering is continuous throughout the
 entire sequence in the 5’ to 3’ direction, or in the direction that mimics the 5’
 to 3’ direction. The last residue position number must equal the number of
 nucleotides in the sequence.
 

 II. SYMBOLS FOR A NUCLEOTIDE
 SEQUENCE WIPO Standard ST.26, paragraph 13, provides that
 all nucleotides in a sequence must be represented using the symbols as listed in
 Table 1: List of Nucleotides Symbols (see MPEP §
 2412.03(a) ). Only lower-case letters must be used. Any
 symbol used to represent a nucleotide is the equivalent of only one residue. 
 

 WIPO Standard ST.26, paragraph 14, sets forth that
 the symbol “t” will be construed as thymine in deoxyribonucleic acid (DNA) and
 uracil in ribonucleic acid (RNA). Uracil in DNA or thymine in RNA is considered a
 modified nucleotide and must be further described in a feature table. See
 MPEP § 2413.01(g) , subsection I for more detail
 regarding a “feature table.” 
 

 WIPO Standard ST.26, paragraph 15, provides that
 where an ambiguity symbol (representing two or more alternative nucleotides) is
 appropriate, the most restrictive symbol should be used, as listed in Table 1:
 List of Nucleotides Symbols (see MPEP §
 2412.03(a) ). For example, if a nucleotide in a given
 position could be “a” or “g”, then “r” should be used, rather than “n”. The symbol
 “n” will be construed as any one of “a”, “c”, “g”, or “t/u” except where it is
 used with a further description in a feature table. The symbol “n” must not be
 used to represent anything other than a nucleotide. A single modified or “unknown”
 nucleotide may be represented by the symbol “n”, together with a further
 description in a feature table. See MPEP §
 2413.01(g) , subsection I, for more detail regarding a
 “feature table.” For representation of sequence variants, i.e., alternatives,
 deletions, insertions or substitutions relative to a primary sequence, see
 MPEP § 2412.05(c) ; and also MPEP §
 2413.01(g) , subsection XII for information on
 variants.
 

 WIPO Standard ST.26, paragraph 16, sets forth that
 modified nucleotides should be represented in the sequence as the corresponding
 unmodified nucleotides, i.e., “a”, “c”, “g” or “t” whenever possible. Any modified
 nucleotide in a sequence that cannot otherwise be represented by any other symbol
 in Table 1: List of Nucleotides Symbols (see MPEP §
 2412.03(a) ), i.e., an “other” nucleotide, such as a
 non-naturally occurring nucleotide, must be represented by the symbol “n”. The
 symbol “n” is the equivalent of only one residue.
 

 WIPO Standard ST.26, paragraph 19, specifies that
 uracil in DNA or thymine in RNA are considered modified nucleotides and must be
 represented in the sequence as “t” and be further described in a feature table
 using the feature key “modified_base”, the qualifier “mod_base” with “OTHER” as
 the qualifier value and the qualifier “note” with “uracil” or “thymine”,
 respectively, as the qualifier value. See MPEP §
 2413.01(g) , subsection I for more detail regarding a
 “feature table.” 
 

 WIPO Standard ST.26, paragraph 21, provides that
 any “unknown” nucleotide must be represented by the symbol “n” in the sequence. An
 “unknown” nucleotide should be further described in a feature table using the
 feature key “unsure”. The symbol “n” is the equivalent of only one residue. See
 MPEP § 2413.01(g) , subsection I, for more detail
 regarding a “feature table.”
 

 III. DESCRIPTION OF MODIFIED
 NUCLEOTIDES WITHIN A NUCLEOTIDE SEQUENCE WIPO Standard ST.26, paragraph 17, specifies that a
 modified nucleotide must be further described in a feature table (see
 MPEP § 2413.01(g) , subsection I, for more detail
 regarding a “feature table”) using the feature key “modified_base” and the
 mandatory qualifier “mod_base” in conjunction with a single abbreviation from
 Table 2: List of Modified Nucleotides, below, as the qualifier value. See
 MPEP § 2413.01(g) subsections II and III, for more
 information regarding use of a feature key; and MPEP §
 2413.01(g) subsections V and VI, for more information
 regarding use of a qualifier. If the abbreviation is “OTHER”, the complete
 unabbreviated name of the modified nucleotide must be provided as the value in a
 “note” qualifier. For a listing of alternative modified nucleotides, the qualifier
 value “OTHER” may be used in conjunction with a further “note” qualifier. The
 abbreviations (or full names) provided in Table 2 must not be used in the sequence
 itself.
 

 WIPO Standard ST.26, paragraph 18, describes that
 a nucleotide sequence including one or more regions of consecutive modified
 nucleotides that share the same backbone moiety must be further described in a
 feature table as required for a modified nucleotide. See MPEP §
 2413.01(g) , subsection I, for information regarding a
 feature table and MPEP § 2412.03(e) regarding
 modified nucleotides. The modified nucleotides of each such region may be jointly
 described in a single INSDFeature element of a “feature table” as described below.
 See MPEP § 2413.01(g) , subsection I, for information
 regarding INSDFeature elements of a feature table. The most restrictive
 unabbreviated chemical name that encompasses all of the modified nucleotides in
 the range or a list of the chemical names of all the nucleotides in the range must
 be provided as the value in the “note” qualifier. For example, a glycol nucleic
 acid sequence containing “a”, “c”, “g”, or “t” nucleobases may be described in the
 “note” qualifier as “2,3-dihydroxypropyl nucleosides.” Alternatively, the same
 sequence may be described in the “note” qualifier as “2,3-dihydroxypropyladenine,
 2,3-dihydroxypropylthymine, 2,3-dihydroxypropylguanine, or
 2,3-dihydroxypropylcytosine.” Where an individual modified nucleotide in the
 region includes an additional modification, then the modified nucleotide must also
 be further described in the feature table as required for a modified nucleotide. 
 

 WIPO Standard ST.26, paragraph 19, provides that
 uracil in DNA or thymine in RNA are considered modified nucleotides and must be
 represented in the sequence as “t” and be further described in a feature table
 using the feature key “modified_base”, the qualifier “mod_base” with “OTHER” as
 the qualifier value and the qualifier “note” with “uracil” or “thymine”,
 respectively, as the qualifier value.See MPEP §
 2413.01(g) , subsections II and III, for more information
 regarding use of a feature key; and MPEP §
 2413.01(g) , subsections V and VI, for more information
 regarding use of a qualifier.
 

 
 Table 2: List of Modified
 Nucleotides
 
 
 
 Abbreviation 
 Definition 
 

 
 
 
 ac4c 
 4-acetylcytidine 
 

 
 chm5u 
 5-(carboxyhydroxymethyl)uridine 
 

 
 cm 
 2'-O-methylcytidine 
 

 
 cmnm5s2u 
 5-carboxymethylaminomethyl-2- thiouridine 
 

 
 cmnm5u 
 5-carboxymethylaminomethyluridine 
 

 
 dhu 
 dihydrouridine 
 

 
 fm 
 2'-O-methylpseudouridine 
 

 
 gal q 
 beta,
 D-galactosylqueuosine
 
 

 
 gm 
 2'-O-methylguanosine 
 

 
 i 
 inosine 
 

 
 i6a 
 N6-isopentenyladenosine 
 

 
 m1a 
 1-methyladenosine 
 

 
 m1f 
 1-methylpseudouridine 
 

 
 m1g 
 1-methylguanosine 
 

 
 m1i 
 1-methylinosine 
 

 
 m22g 
 2,2-dimethylguanosine 
 

 
 m2a 
 2-methyladenosine 
 

 
 m2g 
 2-methylguanosine 
 

 
 m3c 
 3-methylcytidine 
 

 
 m4c 
 N4-methylcytosine 
 

 
 m5c 
 5-methylcytidine 
 

 
 m6a 
 N6-methyladenosine 
 

 
 m7g 
 7-methylguanosine 
 

 
 mam5u 
 5-methylaminomethyluridine 
 

 
 mam5s2u 
 5-methoxyaminomethyl-2-thiouridine 
 

 
 man q 
 beta,
 D-mannosylqueuosine
 
 

 
 mcm5s2u 
 5-methoxycarbonylmethyl-2- thiouridine 
 

 
 mcm5u 
 5-methoxycarbonylmethyluridine 
 

 
 mo5u 
 5-methoxyuridine 
 

 
 ms2i6a 
 2-methylthio-N6- isopentenyladenosine 
 

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

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

 
 mv 
 uridine-5-oxyacetic acid-methylester 
 

 
 o5u 
 uridine-5-oxyacetic acid 
 

 
 osyw 
 wybutoxosine 
 

 
 p 
 pseudouridine 
 

 
 q 
 queuosine 
 

 
 s2c 
 2-thiocytidine 
 

 
 s2t 
 5-methyl-2-thiouridine 
 

 
 s2u 
 2-thiouridine 
 

 
 s4u 
 4-thiouridine 
 

 
 m5u 
 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 
 

 
 OTHER 
 (requires
 note qualifier)
 
 

 
 
 Reproduced from WIPO Standard ST. 26, Annex I,
 Section 2.
 

 IV. JOINTLY DESCRIBING A REGION OF A
 NUCLEOTIDE SEQUENCE WIPO Standard ST.26, paragraph 22, specifies that a
 region containing a known number of contiguous “a”, “c”, “g”, “t”, or “n” residues
 for which the same description applies may be jointly described using a single
 INSDFeature element with the syntax “x..y” as the location descriptor in the
 element INSDFeature_location. See MPEP §
 2413.01(g) subsection IV, for information regarding
 INSDFeature_location. For representation of sequence variants, i.e., alternatives,
 deletions, insertions or substitutions, see MPEP §
 2412.05(c) and MPEP §
 2413.01(g) , subsection XI.
 

 

 
 2412.05(c) Representation and Inclusion of
 Variants [R-01.2024]
 

 [Editor Note: This section is applicable to
 all applications with a filing date, or, for national phase applications, an
 international filing date, on or after July 1, 2022, having disclosure of one or
 more nucleotide and/or amino acid sequences as defined in 37 CFR
 1.831(b) . Formatting representations of XML (eXtensible
 Markup Language) elements in this section appear different than shown in Standard
 ST.26, which may be accessed at: 
 www.wipo.int
 /export/sites/www/standards/en/pdf/03-26-01.pdf .] 

 A primary sequence and any variant of that sequence,
 each disclosed by enumeration of its residues and meeting the definition in
 37
 CFR 1.831(a) and 1.831(b) , must each be included
 in the “Sequence Listing XML” and assigned its own sequence identifier. Where a
 variant sequence is disclosed as a single sequence with enumerated alternative
 residues at one or more positions, it must be included in the “Sequence Listing XML”
 and should be represented by a single sequence, wherein the enumerated alternative
 residues are represented by the most restrictive ambiguity symbol. Any variant
 sequence, disclosed only by reference to deletion(s), insertion(s), or
 substitution(s) in a primary sequence, should be included in the “Sequence Listing
 XML”. The table below indicates the proper use of feature keys and qualifiers for
 nucleic acid and amino acid sequence variants: 
 

 
 List of Feature Keys and
 Qualifiers
 
 
 
 Type of
 sequence
 
 Feature
 Key
 
 Qualifier 
 Use 
 

 
 
 
 Nucleic
 acid
 
 variation 
 replace or
 note
 
 Naturally
 occurring mutations and polymorphisms, e.g., alleles, RFLPs.
 
 

 
 Nucleic
 acid
 
 misc_difference 
 replace or
 note
 
 Variability
 introduced artificially, e.g., by genetic manipulation or by chemical
 synthesis.
 
 

 
 Amino
 acid
 
 VAR_SEQ 
 note 
 Variant produced
 by alternative splicing, alternative promoter usage, alternative
 initiation and ribosomal frameshifting.
 
 

 
 Amino
 acid
 
 VARIANT 
 note 
 Any type of
 variant for which VAR_SEQ is not applicable.
 
 

 
 
 Reproduced from paragraph 96 of WIPO Standard
 ST.26.
 

 For additional information about feature keys and
 qualifiers, see MPEP § 2413.01(g) , subsections II,
 III and V. 
 

 For additional information about the representation
 of sequence variants in a “Sequence Listing XML,” see MPEP §
 2413.01(g) , subsection XI.
 

 

 
 2412.05(d) Representation and Symbols of Amino Acid
 Sequence Data [R-01.2024]
 

 [Editor Note: This section is applicable to
 all applications with a filing date, or, for national phase applications, an
 international filing date, on or after July 1, 2022, having disclosure of one or
 more nucleotide and/or amino acid sequences as defined in 37 CFR
 1.831(b) . Formatting representations of XML (eXtensible
 Markup Language) elements in this section appear different than shown in Standard
 ST.26, which may be accessed at: 
 www.wipo.int
 /export/sites/www/standards/en/pdf/03-26-01.pdf .] 

 
 37 CFR 1.832 Representation of nucleotide and/or amino
 acid sequence data in the “Sequence Listing XML” part of a patent application
 filed on or after July 1, 2022. 

 
 
 *****

 

 (c) The representation and symbols for amino acid
 sequence data shall conform to the requirements of paragraphs (c)(1) through
 (4) of this section. 
 
 (1) The amino acids in an amino acid
 sequence must be represented in the manner described in paragraphs 24
 and 25 of WIPO Standard ST.26. 
 

 (2) All amino acids, including modified
 amino acids and “unknown” amino acids, within an amino acid sequence
 must be represented using the symbols set forth in paragraphs 26–29
 and 32 of WIPO Standard ST.26
 

 (3) Modified amino acids within an amino
 acid sequence must be described in the manner discussed in paragraphs
 29 and 30 of WIPO Standard ST.26.
 

 (4) A region containing a known number of
 contiguous “X” residues for which the same description applies may be
 jointly described in the manner described in paragraph 34 of WIPO
 Standard ST.26.
 

 
 

 
 *****

 

 
 
 I. REPRESENTATION OF AN AMINO ACID
 SEQUENCE WIPO Standard ST.26, paragraph 24, specifies that
 the amino acids in an amino acid sequence must be represented in the amino to
 carboxy direction from left to right. The amino and carboxy groups must not be
 represented in the sequence. 
 

 WIPO Standard ST.26, paragraph 25, indicates that
 the first amino acid in the sequence is residue position number 1, including amino
 acids preceding the mature protein, for example, pre-sequences, pro-sequences,
 pre-pro-sequences and signal sequences. When an amino acid sequence is circular in
 configuration and the ring consists solely of amino acid residues linked by
 peptide bonds, i.e., the sequence has no amino and carboxy termini, applicant must
 choose the amino acid in residue position number 1. Numbering is continuous
 through the entire sequence in the amino to carboxy direction. 
 

 II. SYMBOLS FOR AN AMINO ACID
 SEQUENCE WIPO Standard ST.26, paragraph 26, specifies that
 all amino acids in a sequence must be represented using the symbols set forth in
 Table 3: List of Amino Acids Symbols, in MPEP §
 2412.03(a) above. Only uppercase letters must be used.
 Any symbol used to represent an amino acid is the equivalent of only one
 residue.
 

 WIPO Standard ST.26, paragraph 27, indicates that
 where an ambiguity symbol (representing two or more amino acids in the
 alternative) is appropriate, the most restrictive symbol should be used, as listed
 in Table 3: List of Amino Acids Symbols ( MPEP §
 2412.03(a) ). For example, if an amino acid in a given
 position could be aspartic acid or asparagine, the symbol “B” should be used,
 rather than “X”. The symbol “X” will be construed as any one of “A”, “R”, “N”,
 “D”, “C”, “Q”, “E”, “G”, “H”, “I”, “L”, “K”, “M”, “F”, “P”, “O”, “S”, “U”, “T”,
 “W”, “Y”, or “V”, except where it is used with a further description in the
 feature table. The symbol “X” must not be used to represent anything other than an
 amino acid. A single modified or “unknown” amino acid may be represented by the
 symbol “X”, together with a further description in a feature table (see
 MPEP § 2413.01(g) , subsection I or MPEP § 2412.03(c),
 for more detail regarding a “feature table”). For representation and inclusion of
 sequence variants, see MPEP § 2412.05(c) . For details of
 how to represent variants in a “Sequence Listing XML,” see MPEP §
 2413.01(g) , subsection XI.
 

 WIPO Standard ST.26, paragraph 28, specifies that
 disclosed amino acid sequences separated by internal terminator symbols,
 represented for example by “Ter” or asterisk “*” or period “.” or a blank space,
 must be included as separate sequences for each enumerated amino acid sequence
 that contains at least four specifically defined amino acids and is encompassed by
 the description of sequences found in MPEP §
 2412.03 . Each such separate sequence must be assigned
 its own sequence identifier (see MPEP §
 2412.05(a) ). Terminator symbols and spaces must not be
 included in a sequence contained in a “Sequence Listing XML”. 
 

 Any “unknown” amino acid must be represented by
 the symbol “X” in the sequence. An “unknown” amino acid designated as “X” must be
 further described in a feature table (see MPEP §
 2413.01(g) , subsection I, for more detail regarding a
 “feature table” ) using the feature key “UNSURE” and optionally the qualifier
 “note.” The symbol “X” is the equivalent of only one residue (WIPO Standard ST.26,
 paragraph 32).
 

 III. DESCRIPTION OF MODIFIED AMINO
 ACIDS WITHIN AN AMINO ACID SEQUENCE WIPO Standard ST.26, paragraph 29, specifies that
 modified amino acids, including D-amino acids, should be represented in the
 sequence as the corresponding unmodified amino acids whenever possible. Any
 modified amino acid in a sequence that cannot otherwise be represented by any
 other symbol in Table 3: List of Amino Acids Symbols (see MPEP §
 2412.03(a) ), i.e., an “other” amino acid, must be
 represented by “X”. The symbol “X” is the equivalent of only one residue.
 

 WIPO Standard ST.26, paragraph 30, provides that a
 modified amino acid must be further described in a feature table (see
 MPEP § 2413.01(g) , subsection I, for more detail
 regarding a “feature table”). Where applicable, the feature keys “CARBOHYD” or
 “LIPID” should be used together with the qualifier “note”. The feature key
 “MOD_RES” should be used for other post-translationally modified amino acids
 together with the qualifier “note”. The feature key “SITE” together with the
 qualifier “note” should be used when the modified amino acid is not a
 post-translationally modified amino acid. The value for the qualifier “note” must
 either be an abbreviation set forth in Table 4: List of Modified Amino Acids (see
 MPEP § 2412.03(c) ), above, or the complete,
 unabbreviated name of the modified amino acid. The abbreviations set forth in
 Table 4, or the complete, unabbreviated names must not be used in the sequence
 itself.
 

 IV. JOINTLY DESCRIBING A REGION OF AN
 AMINO ACID SEQUENCE WIPO Standard ST.26, paragraph 34, provides that a
 region containing a known number of contiguous “X” residues for which the same
 description applies may be jointly described in one feature key using the syntax
 “x..y” as the location descriptor in the element INSDFeature_location (see
 MPEP § 2413.01(g) subsections II-III for information
 regarding “feature keys” and subsection IV, for information regarding
 INSDFeature_location). For representation and inclusion of sequence variants, see
 MPEP § 2412.05(c) . For details of how to represent
 variants in a “Sequence Listing XML,” see MPEP §
 2413.01(g) , subsection XII.
 

 

 
 2412.05(e) Presentation of Special
 Situations [R-01.2024]
 

 [Editor Note: This section is applicable to
 all applications with a filing date, or, for national phase applications, an
 international filing date, on or after July 1, 2022, having disclosure of one or
 more nucleotide and/or amino acid sequences as defined in 37 CFR
 1.831(b) ]. 

 
 37 CFR 1.832 Representation of nucleotide and/or amino
 acid sequence data in the “Sequence Listing XML” part of a patent application
 filed on or after July 1, 2022. 

 
 
 *****

 

 (d) A nucleotide and/or amino acid sequence that
 is constructed as a single continuous sequence derived from one or more
 non-contiguous segments of a larger sequence or of segments from different
 sequences must be listed in the “Sequence Listing XML” in the manner
 described in paragraph 35 of WIPO Standard ST.26.
 

 (e) A nucleotide and/or amino acid sequence that
 contains regions of specifically defined residues separated by one or more
 regions of contiguous “n” or “X” residues, wherein the exact number of “n”
 or “X” residues in each region is disclosed, must be listed in the “Sequence
 Listing XML” in the manner described in paragraph 36 of WIPO Standard
 ST.26.
 

 (f) A nucleotide and/or amino acid sequence that
 contains regions of specifically defined residues separated by one or more
 gaps of an unknown or undisclosed number of residues must be listed in the
 “Sequence Listing XML” in the manner described in paragraph 37 of WIPO
 Standard ST.26.
 

 
 

 WIPO Standard ST.26, paragraph 35, describes that a
 sequence disclosed by enumeration of its residues that is constructed as a single
 continuous sequence from one or more non-contiguous segments of a larger sequence or
 of segments from different sequences must be included in the “Sequence Listing XML”
 and assigned its own sequence identifier, as defined in 37 CFR
 1.832(a) . See MPEP §
 2412.05(a) .
 

 WIPO Standard ST.26, paragraph 36, describes that a
 sequence that contains regions of specifically defined residues separated by one or
 more regions of contiguous “n” or “X” residues, wherein the exact number of “n” or
 “X” residues in each region is disclosed, must be included in the “Sequence Listing
 XML” as one sequence and assigned its own sequence identifier.
 

 WIPO Standard ST.26, paragraph 37, describes that a
 sequence that contains regions of specifically defined residues separated by one or
 more gaps of an unknown or undisclosed number of residues must not be represented in
 the “Sequence Listing XML” as a single sequence. Each region of specifically defined
 residues (as encompassed by the definition in 37 CFR 1.831(a) ) must be included
 in the “Sequence Listing XML” as a separate sequence and assigned its own sequence
 identifier.
 

 

 

 
 2412.06 The Requirement for Exclusive Conformance;
 Sequences Presented in Drawing Figures [R-01.2024]
 

 [Editor Note: This section is applicable to all applications with a filing
 date, or, for national phase applications, an international filing date, on or after
 July 1, 2022, having disclosure of one or more nucleotide and/or amino acid sequences
 as defined in 37 CFR 1.831(b) .] 

 For all applications that disclose a nucleotide sequence
 and/or amino acid sequence(s) by enumeration of its residues, as defined in
 37 CFR
 1.831(b) , 37 CFR 1.831(a) requires conformance
 to the requirements of 37 CFR 1.832 through
 37 CFR
 1.834 with regard to the manner in which the disclosed nucleotide
 and/or amino acid sequences are presented and described in the “Sequence Listing XML.”
 This requirement is necessary to minimize any confusion that could result if more than
 one format for representing sequence data was employed in a given application.
 

 Pursuant to 37 CFR 1.83(a) , sequences that are
 included in the “Sequence Listing XML” should not be duplicated in the drawings. With
 the use of feature keys and qualifiers in a “Sequence Listing XML” to represent and
 describe features of a nucleotide or amino acid sequence, the need to re-present a
 sequence in a drawing is less critical. However, in certain instances, a significant
 sequence characteristic may not be readily conveyed by the sequence-associated data of
 the “Sequence Listing XML” and may need to be depicted in a figure. For example, in view
 of the fact that the representation of double stranded nucleic acids is not permitted in
 the “Sequence Listing XML,” many significant nucleic acid features, such as “sticky
 ends” and the like, may only be shown effectively by reference to a drawing figure.
 Further, the similarity or homology between/among sequences may only be depicted in an
 effective manner in a drawing figure. Similarly, drawing figures are recommended for use
 with amino acid sequences to depict structural features of the corresponding protein,
 such as epitopes and interaction domains. The situations discussed herein are given by
 way of example only and there may be many other reasons for including a sequence in a
 drawing. However, when an enumerated sequence is presented in a drawing, the sequence
 must still be included in the “Sequence Listing XML” if the sequence falls within the
 definition set forth in 37 CFR 1.831(b) , and a sequence
 identifier (preceded by “SEQ ID NO:X” or the like) must be used, either in the drawing
 itself or in the Brief Description of the Drawings.
 

 

 
 2412.07 Examination of Patent Applications Claiming
 Large Numbers of Nucleotide Sequences [R-07.2022]
 

 Content regarding the examination of patent applications claiming large numbers of
 nucleotide sequences is located in MPEP § 2434 .
 

 

 [top] 

 

 

 
 

 
 

 

 

 

 
 
 
 2401-Introduction 

 2402-The Deposit Rules 

 2403-Deposit of Biological Material 
 2403.01-Material Capable of Self- Replication 

 2403.02-Plant Material 

 
 

 2404-Need or Opportunity to Make a Deposit 
 2404.01-Biological Material That Is Known and Readily Available to the Public 

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

 2404.03-Reference to a Deposit in the Specification 

 
 

 2405-Acceptable Depository 

 2406-Time of Making an Original Deposit 
 2406.01-Description in Application Specification 

 2406.02-Deposit After Filing Date - Corroboration 

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

 
 

 2407-Replacement or Supplement of Deposit 
 2407.01-In a Pending Application 

 2407.02-After a Patent Has Issued 

 2407.03-Failure to Replace 

 2407.04-Treatment of Replacement 

 2407.05-Exemption From Replacement 

 2407.06-Replacement May Not Be Recognized 

 
 

 2408-Term of Deposit 

 2409-Viability of Deposit 

 2410-Furnishing of Samples 
 2410.01-Conditions of Deposit 

 2410.02-Certification of Statement of Availability of Deposit 

 
 

 2411-Examination Procedures 
 2411.01-Rejections Based on Deposit Issue 

 2411.02-Replies to Rejections Based on Deposit Issue 

 2411.03-Application in Condition for Allowance Except for Deposit 

 2411.04-[Reserved] 

 2411.05-Content of Application with Respect to Deposited Material 

 
 

 2412-The Requirements for Patent Applications Containing Nucleotide Sequence and/or Amino Acid Sequence Disclosures to Include
 a Sequence Listing in XML file format 
 2412.01-Overview of the Sequence Rules 

 2412.02-Definition of “Sequence Listing XML” 
 2412.02(a)-“Enumeration of its residues” 

 
 

 2412.03-Nucleotides and Amino Acids Included and Excluded From a “Sequence Listing XML” 
 2412.03(a)-“Specifically Defined” 

 2412.03(b)-“Amino Acid” 

 2412.03(c)-“Modified Amino Acid” 

 2412.03(d)-“Nucleotide” 

 2412.03(e)-“Modified Nucleotide” 

 
 

 2412.04-Use of Sequence Identifiers to Denote Sequences Disclosed in the Description, Drawings or Claims 

 2412.05-Representation and Symbols for Nucleotide and/or Amino Acid Sequences 
 2412.05(a)-Use of Sequentially Numbered Sequence Identifiers in the “Sequence Listing XML” 

 2412.05(b)-Representation and Symbols of Nucleotide Sequence Data 

 2412.05(c)-Representation and Inclusion of Variants 

 2412.05(d)-Representation and Symbols of Amino Acid Sequence Data 

 2412.05(e)-Presentation of Special Situations 

 
 

 2412.06-The Requirement for Exclusive Conformance; Sequences Presented in Drawing Figures 

 2412.07-Examination of Patent Applications Claiming Large Numbers of Nucleotide Sequences 

 
 

 2413-Content of a “Sequence Listing XML” and Form and Format of the “Sequence Listing XML” File 
 2413.01-Parts of the “Sequence Listing XML” 
 2413.01(a)-The “Sequence Listing XML” is a Single File Encoded Using Unicode UTF-8 

 2413.01(b)-The “Sequence Listing XML” Must Be Valid According To the DTD 

 2413.01(c)-The “Sequence Listing XML” Must Contain an XML Declaration 

 2413.01(d)-The “Sequence Listing XML” Must Contain a DOCTYPE Declaration 

 2413.01(e)-The “Sequence Listing XML” Must Contain a Root Element 

 2413.01(f)-The “Sequence Listing XML” Must Contain a General Information Part 

 2413.01(g)-The “Sequence Listing XML” Must Contain a Sequence Data Part 

 2413.01(h)-Language Dependent Free Text Qualifier Values in the English Language 

 2413.01(i)-Title Element in “Sequence Listing XML” 

 
 

 2413.02-Form and Format of the XML file containing the “Sequence Listing XML” 

 2413.03-How to Submit the “Sequence Listing XML” 

 2413.04-Requirements Regarding Incorporation By Reference of the “Sequence Listing XML” 

 2413.05-Presumptions Regarding Compliance 

 
 

 2414-Notification of a Failure to Comply with Sequence Listing Requirements and Amendments Relating to “Sequence Listing XML” Files
 Under 37 CFR 1.835 
 2414.01-Issuance of a Notice Relating to the Requirements For Patent Applications Containing Nucleotide and/or Amino Acid Sequence
 Disclosures 

 2414.02-Amendment to Add an Initial “Sequence Listing XML” under 37 CFR 1.835(a) 

 2414.03-Amendment Adding to, Deleting from, or Replacing Sequence Information in a “Sequence Listing XML” under 37 CFR 1.835(b) 

 2414.04-Translation of “Sequence Listing XML” is Not an Amended “Sequence Listing XML” under 37 CFR 1.835(b) 

 2414.05-Notifications for Failure to Submit a “Sequence Listing XML” in an International Application under the PCT to be Searched
 by the United States International Searching Authority or Examined by International Preliminary Examination Authority 

 2414.06-Amendment of a “Sequence Listing XML” in a Patent 

 
 

 2415-Applicability date of “Sequence Listing XML” Requirements to Applications Based on Filing Date of Application and Procedures
 for Failure to Submit Correct Format of Sequence Listing 
 2415.01-Determining if a “Sequence Listing XML” Must be Submitted 

 2415.02-Provisional Applications Containing Disclosures of Nucleotides and/or Amino Acids, Compliance with 37 CFR 1.831-1.834 

 2415.03-Improper Submissions of “Sequence Listing” under 1.821(c) When a “Sequence Listing XML” was Required 

 
 

 2416-Form Paragraphs 

 2417-Helpful Hints for Sequence Rules Compliance under WIPO Standard ST.26 

 2418-WIPO Sequence Tool 

 2419-Publishing of Patent Grants and Patent Application Publications with a “Sequence Listing XML” 
 2419.01-Patent Grants and Patent Application Publications Containing a Non-Lengthy “Sequence Listing XML” 

 2419.02-Patent Grants and Patent Application Publications Containing a Lengthy “Sequence Listing XML” 

 2419.03-Patent Grants and Patent Application Publications Containing a “Sequence Listing XML” of 1GB or Larger 

 
 

 2420-The Requirements for Patent Applications Containing Nucleotide Sequence and/or Amino Acid Sequence Disclosures under World
 Intellectual Property Office Standard ST.25 (WIPO ST.25) - the Sequence Rules 

 2421-Overview of the Sequence Rules under WIPO ST.25 
 2421.01-Definition of “Sequence Listing” and Computer Readable Form (CRF) 

 2421.02-Summary of the Requirements of the Sequence Rules 

 2421.03-Notification of a Failure to Comply 

 2421.04-[Reserved] 

 
 

 2422-Nucleotide and/or Amino Acid Sequence Disclosures in Patent Applications Subject to WIPO ST.25 
 2422.01-Nucleotide and/or Amino Acids Disclosures Requiring a “Sequence Listing” 

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

 2422.03-Sequence Listing Submission 

 2422.03(a)-“Sequence Listing” Submitted as ASCII Plain Text Files 

 2422.04-The Requirement for a Computer Readable Copy of the “Sequence Listing” 

 2422.05-[Reserved] 

 2422.06-Requirement for Statement Regarding Information Contained in the “Sequence Listing” and Separate Computer Readable Form 

 2422.07-Requirements for Compliance and Consequences of Non-Compliance 

 2422.08-Presumptions Regarding Compliance 

 2422.09-[Reserved] 

 
 

 2423-Symbols and Format To Be Used for Nucleotide and/or Amino Acid Sequence Data for WIPO ST.25 
 2423.01-Format and Symbols To Be Used in a “Sequence Listing” 

 2423.02-Depiction of Coding Regions 

 2423.03-Presentation and Numbering of Sequences 

 
 

 2424-Requirements for Content of a “Sequence Listing” Part of the Specification under WIPO ST.25. 
 2424.01-Informational Requirements for the “Sequence Listing” 

 2424.02-“Sequence Listing” Numeric Identifiers 

 2424.03-Additional Miscellaneous Requirements 

 
 

 2425-Form and Format for a Nucleotide and/or Amino Acid Sequence Submission as an ASCII Plain Text File under WIPO ST.25 

 2426-Amendments to Add or Replace a “Sequence Listing” and CRF Copy Thereof Subject to WIPO ST. 25 

 2427-Form Paragraphs for Applications Subject to WIPO ST.25 

 2428-Sample Statements under WIPO ST.25 

 2429-Helpful Hints for Sequence Rules Compliance under WIPO ST.25 

 2430-PatentIn Information 

 2431-Sample “Sequence Listing” under WIPO ST.25 

 2432-[Reserved] 

 2433-Box Sequence; Hand Delivery of a “Sequence Listing” and Computer Readable Forms 

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

 2435-Publishing of Patents and Patent Application Publications with a Lengthy “Sequence Listing” 

 

 

 
 

 
 
 

 
 

 

 
 
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