MPEP § 2422 — MPEP § 2422
Current through: 2022-07-01

2422-Nucleotide and/or Amino Acid Sequence Disclosures in Patent Applications Subject to WIPO ST.25 
 
 

 
 
 
 
 
 
 
 

 

 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 

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 Chapter 2400 

 Section 2422 
 

 
 
 
 
 
 2422 Nucleotide and/or Amino Acid Sequence Disclosures in Patent
 Applications Subject to WIPO ST.25 [R-07.2022]
 

 [Editor Note: This section is not applicable to applications filed on or after
 July 1, 2022, having disclosures of nucleotide and/or amino acid sequences as defined in
 37 CFR
 1.831(b) . See MPEP §§
 2412 - 2419 for guidance on WIPO ST.26
 requirements for applications filed on or after July 1, 2022.] 

 
 37 CFR 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 4 or more amino acids or an
 unbranched sequence of 10 or more nucleotides. Branched sequences are specifically
 excluded from this definition. Sequences with fewer than four specifically defined
 nucleotides or amino acids are specifically excluded from this section.
 “Specifically defined” means those amino acids other than “Xaa” and those
 nucleotide bases other than “n,” defined in accordance with Appendices A through F
 to this subpart. Nucleotides and amino acids are further defined as follows:
 
 (1) Nucleotides: Nucleotides are intended to embrace only
 those nucleotides that can be represented using the symbols set forth in
 Appendix A to this subpart. Modifications ( e.g., 
 methylated bases) may be described as set forth in Appendix B to this
 subpart but shall not be shown explicitly in the nucleotide sequence. 
 

 (2) Amino acids: Amino acids are those L-amino acids commonly
 found in naturally occurring proteins and are listed in appendix C to this
 subpart. 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
 appendix C to this subpart, with the modified positions
 ( e.g., hydroxylations or glycosylations) being
 described as set forth in appendix D to this subpart, 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
 appendix C to this subpart, in conjunction with a description in the Feature
 section, to describe, for example, modified linkages, cross links and end
 caps, non-peptidyl bonds, etc., is embraced by this definition.
 

 
 

 Note 1 to paragraph (a): Appendices A
 through F to this subpart contain Tables 1– 6 of the World Intellectual Property
 Organization (WIPO) Handbook on Industrial Property Information and Documentation,
 Standard ST.25: Standard for the Presentation of Nucleotide and Amino Acid
 Sequence Listings in Patent Applications (2009).
 

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

 (c) Patent applications that contain disclosures of nucleotide and/or
 amino acid sequences, as defined in paragraph (a) of this section, must contain a
 “Sequence Listing,” which is a separate part of the specification containing each
 of those 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 . The “Sequence Listing” must be submitted as follows,
 except for a national stage entry under § 1.495(b)(1) , where the “Sequence Listing” has been
 previously communicated by the International Bureau or originally filed in the
 United States Patent and Trademark Office and complies with Patent Cooperation
 Treaty (PCT) Rule 5.2 :
 
 (1) As an ASCII plain text file, in compliance
 with § 1.824 , submitted via the USPTO patent electronic
 filing system or on a read-only optical disc under § 1.52(e) , accompanied by an incorporation by reference
 statement of the ASCII plain text file, in a separate paragraph of the
 specification, in accordance with § 1.77(b)(5) ; 
 

 (2) As a PDF file via the USPTO patent
 electronic filing system; or 
 

 (3) On physical sheets of paper.

 
 

 (d) Where the description or claims of a patent application discuss a
 sequence that is set forth in the “Sequence Listing,” in accordance with paragraph
 (c) of this section, reference must be made to the sequence by use of the sequence
 identifier (§ 1.823(a)(5) ), 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 (§ 1.823(a)(5) ), 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 (§ 1.823(a)(5) ) in the Brief Description is clear.
 

 (e)
 
 (1) If the “Sequence Listing” under paragraph
 (c) of this section is submitted in an application filed under
 35 U.S.C. 111(a) as a PDF file (§ 1.821(c)(2) ) via the USPTO patent electronic filing
 system or on physical sheets of paper (§ 1.821(c)(3) ), then the following must be submitted: 
 
 (i) A CRF of the “Sequence Listing,” in
 accordance with the requirements of § 1.824 ; and 
 

 (ii) A statement that the sequence
 information contained in the CRF submitted under paragraph (e)(1)(i)
 of this section is identical to the sequence information contained in
 the “Sequence Listing” under paragraph (c) of this section.
 

 
 

 (2) If the “Sequence Listing” under paragraph (c)
 of this section in an application submitted under 35 U.S.C.
 371 is a PDF file (paragraph (c)(2) of this section)
 or on physical sheets of paper (paragraph (c)(3) of this section), and not
 also as an ASCII plain text file, in compliance with § 1.824 
 (paragraph (c)(1) of this section), then the following must be
 submitted:
 
 (i) A CRF of the “Sequence Listing,” in
 accordance with the requirements of § 1.824 ; and
 

 (ii) A statement that the sequence
 information contained in the CRF submitted under paragraph (e)(2)(i)
 of this section is identical to the sequence information contained in
 the “Sequence Listing” under paragraph (c)(2) or (3) of this
 section.
 

 
 

 (3) If a “Sequence Listing” in ASCII plain text
 format, in compliance with § 1.824 , has not been submitted for an
 international application under the PCT, and that application contains
 disclosures of nucleotide and/or amino acid sequences, as defined in
 paragraph (a) of this section, and is to be searched by the United States
 International Searching Authority or examined by the United States
 International Preliminary Examining Authority, then the following must be
 submitted:
 
 (i) A CRF of the “Sequence Listing,” in
 accordance with the requirements of § 1.824 ; 
 

 (ii) The late furnishing fee for providing a
 “Sequence Listing” in response to an invitation, as set forth in §
 1.445(a)(5) ;
 and
 

 (iii) A statement that the sequence
 information contained in the CRF, submitted under paragraph (e)(3)(i)
 of this section, does not go beyond the disclosure in the
 international application as filed, or a statement that the
 information recorded in the ASCII plain text file, submitted under
 paragraph (e)(3)(i) of this section, is identical to the sequence
 listing contained in the international application as filed, as
 applicable. 
 

 
 

 (4) The CRF may not be retained as a part of the
 patent application file.
 

 
 

 (f) [reserved]

 (g) If any of the requirements of paragraphs (b) through (e) 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 , the applicant will be notified and given a period of
 time within which to comply with such requirements in order to prevent abandonment
 of the application. Any amendment to add or replace a “Sequence Listing” and CRF
 copy thereof in reply to a requirement under this paragraph must be submitted in
 accordance with the requirements of § 1.825 .
 

 (h) If any of the requirements of paragraph (e)(3) of this section
 are not satisfied at the time of filing an international application under the
 PCT, and the application is to be searched by the United States International
 Searching Authority or examined by the United States International Preliminary
 Examining Authority, the applicant may be sent a notice necessitating compliance
 with the requirements within a prescribed time period. Where a “Sequence Listing”
 under PCT Rule
 13ter is provided in reply to a requirement under this paragraph, it
 must be accompanied by a statement that the information recorded in the ASCII
 plain text file under paragraph (e)(3)(i) of this section is identical to the
 sequence listing contained in the international application as filed, or does not
 go beyond the disclosure in the international application as filed, as applicable.
 It must also be accompanied by the late furnishing fee, as set forth in §
 1.445(a)(5) . If the applicant fails to timely provide the
 required CRF, the United States International Searching Authority shall search
 only to the extent that a meaningful search can be performed without the CRF, and
 the United States International Preliminary Examining Authority shall examine only
 to the extent that a meaningful examination can be performed without the CRF.
 

 
 
 I. APPENDICES A-F REFERENCED IN 37 CFR 1.821 AND 1.822 37 CFR
 1.821 and 37 CFR 1.822 reference Appendices
 A-F, which contain Tables 1–6 of the World Intellectual Property Organization (WIPO)
 Handbook on Industrial Property Information and Documentation, Standard ST.25: Standard
 for Nucleotide and Amino Acid Sequence Listings in Patent Applications (2009)
 (hereinafter WIPO Standard ST.25 (2009)). Appendices A-F are reproduced below. The
 current version of WIPO Standard ST.25 is available online at www.wipo.int /export/sites/ www/standards/en/pdf/03-25-01.pdf .
 

 Appendix A provides that the bases of a nucleotide sequence should be
 represented using the following one-letter symbol for nucleotide sequence characters: 
 

 

 
 Appendix A to Subpart G of Part 1 -
 List of Nucleotides 
 
 
 Symbol 
 Meaning 
 Origin of
 designation 
 

 
 
 
 a 
 a 
 a denine.
 
 

 
 g 
 g 
 g uanine.
 
 

 
 c 
 c 
 c ytosine.
 
 

 
 t 
 t 
 thymine. 
 

 
 u 
 u 
 u racil.
 
 

 
 r 
 g or a 
 purine. 
 

 
 y 
 t/u or c 
 p y rimidine.
 
 

 
 m 
 a or c 
 a m ino.
 
 

 
 k 
 g or t/u 
 k eto.
 
 

 
 s 
 g or c 
 strong interactions 3H-bonds. 
 

 
 w 
 a or t/u 
 w eak interactions 2H-bonds.
 
 

 
 b 
 g or c or t/u 
 not a. 
 

 
 d 
 a or g or t/u 
 not c. 
 

 
 h 
 a or c or t/u 
 not g. 
 

 
 v 
 a or g or c 
 not t, not u. 
 

 
 n 
 a or g or c or t/u, unknown, or other 
 a n y.
 
 

 
 
 Appendix B provides that modified bases may be
 represented as the corresponding unmodified bases in the sequence itself, if the
 modification is further described in numeric identifier <223> of the Feature
 section of the “Sequence Listing”. The symbols from the list below may be used in the
 description (i.e., the specification and drawing, or in the Feature section of the
 “Sequence Listing”) but these symbols may not be used in the sequence itself.
 Modifications not listed in Appendix B may also be represented as the corresponding
 unmodified base in the sequence itself, and the modification should be described using
 its full chemical name in the Feature section of the “Sequence Listing”.
 

 

 
 Appendix B to Subpart G of Part 1 - List of
 Modified Nucleotides
 
 
 
 Symbol 
 Meaning 
 

 
 
 
 ac4c 
 4-acetylcytidine. 
 

 
 chm5u 
 5-(carboxyhydroxymethyl)uridine. 
 

 
 cm 
 2'-O-methylcytidine. 
 

 
 cmnm5s2u 
 5-carboxymethylaminomethyl-2- thiouridine. 
 

 
 cmnm5u 
 5-carboxymethylaminomethyluridine. 
 

 
 d 
 dihydrouridine. 
 

 
 fm 
 2'-O-methylpseudouridine. 
 

 
 gal q 
 beta, D-galactosylqueuosine. 
 

 
 gm 
 2'-O-methylguanosine. 
 

 
 i 
 inosine. 
 

 
 i6a 
 N6-isopentenyladenosine. 
 

 
 m1a 
 1-methyladenosine. 
 

 
 m1f 
 1-methylpseudouridine. 
 

 
 m1g 
 1-methylguanosine. 
 

 
 m1i 
 1-methylinosine. 
 

 
 m22g 
 2,2-dimethylguanosine. 
 

 
 m2a 
 2-methyladenosine. 
 

 
 m2g 
 2-methylguanosine. 
 

 
 m3c 
 3-methylcytidine. 
 

 
 m5c 
 5-methylcytidine. 
 

 
 m6a 
 N6-methyladenosine. 
 

 
 m7g 
 7-methylguanosine. 
 

 
 mam5u 
 5-methylaminomethyluridine. 
 

 
 mam5s2u 
 5-methoxyaminomethyl-2-thiouridine. 
 

 
 man q 
 beta, D-mannosylqueuosine. 
 

 
 mcm5s2u 
 5-methoxycarbonylmethyl-2- thiouridine. 
 

 
 mcm5u 
 5-methoxycarbonylmethyluridine. 
 

 
 mo5u 
 5-methoxyuridine. 
 

 
 ms2i6a 
 2-methylthio-N6- isopentenyladenosine. 
 

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

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

 
 mv 
 uridine-5-oxyacetic acid-methylester. 
 

 
 o5u 
 uridine-5-oxyacetic acid. 
 

 
 osyw 
 wybutoxosine. 
 

 
 p 
 pseudouridine. 
 

 
 q 
 queuosine. 
 

 
 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. 
 

 
 
 Appendix C provides that the amino acids should be represented using
 the following three-letter symbols with the first letter as a capital. 
 

 
 Appendix C to Subpart G of Part 1 - List of
 Amino Acids
 
 
 
 Symbol 
 Meaning 
 

 
 
 
 Ala 
 Alanine. 
 

 
 Cys 
 Cysteine. 
 

 
 Asp 
 Aspartic Acid. 
 

 
 Glu 
 Glutamic Acid. 
 

 
 Phe 
 Phenylalanine. 
 

 
 Gly 
 Glycine. 
 

 
 His 
 Histidine. 
 

 
 Ile 
 Isoleucine. 
 

 
 Lys 
 Lysine. 
 

 
 Leu 
 Leucine. 
 

 
 Met 
 Methionine. 
 

 
 Asn 
 Asparagine. 
 

 
 Pro 
 Proline. 
 

 
 Gln 
 Glutamine. 
 

 
 Arg 
 Arginine. 
 

 
 Ser 
 Serine. 
 

 
 Thr 
 Threonine. 
 

 
 Val 
 Valine. 
 

 
 Trp 
 Tryptophan. 
 

 
 Tyr 
 Tyrosine. 
 

 
 Asx 
 Asp or Asn. 
 

 
 Glx 
 Glu or Gln. 
 

 
 Xaa 
 unknown or
 other.
 
 

 
 
 Appendix D provides that modified and unusual amino acids may be
 represented as the corresponding unmodified amino acids in the sequence itself if the
 modification is further described in numeric identifier <223> of the Feature
 section of the “Sequence Listing”. The symbols from the list below may be used in the
 description (i.e., the specification and drawings, or in the Feature section of the
 “Sequence Listing”) but these symbols may not be used in the sequence itself.
 Modifications not listed in Appendix D may also be represented as the corresponding
 unmodified amino acid in the sequence itself, and the modification should be described
 using its full chemical name in the Feature section of the “Sequence Listing”.
 

 
 Appendix D to Subpart G of Part 1 - List of
 Modified and Unusual Amino Acids
 
 
 
 Symbol 
 Meaning 
 

 
 
 
 Aad 
 2-Aminoadipic acid. 
 

 
 bAad 
 3-Aminoadipic acid. 
 

 
 bAla 
 beta-Alanine, beta-Aminopropionic acid. 
 

 
 Abu 
 2-Aminobutyric acid. 
 

 
 4Abu 
 4-Aminobutyric acid, piperidinic acid. 
 

 
 Acp 
 6-Aminocaproic acid. 
 

 
 Ahe 
 2-Aminoheptanoic acid. 
 

 
 Aib 
 2-Aminoisobutyric acid. 
 

 
 bAib 
 3-Aminoisobutyric acid. 
 

 
 Apm 
 2-Aminopimelic acid. 
 

 
 Dbu 
 2,4 Diaminobutyric acid. 
 

 
 Des 
 Desmosine. 
 

 
 Dpm 
 2,2'-Diaminopimelic acid. 
 

 
 Dpr 
 2,3-Diaminopropionic acid. 
 

 
 EtGly 
 N-Ethylglycine. 
 

 
 EtAsn 
 N-Ethylasparagine. 
 

 
 Hyl 
 Hydroxylysine. 
 

 
 aHyl 
 allo-Hydroxylysine. 
 

 
 3Hyp 
 3-Hydroxyproline. 
 

 
 4Hyp 
 4-Hydroxyproline. 
 

 
 Ide 
 Isodesmosine. 
 

 
 aIle 
 allo-Isoleucine. 
 

 
 MeGly 
 N-Methylglycine, sarcosine. 
 

 
 MeIle 
 N-Methylisoleucine. 
 

 
 MeLys 
 6-N-Methyllysine. 
 

 
 MeVal 
 N-Methylvaline. 
 

 
 Nva 
 Norvaline. 
 

 
 Nle 
 Norleucine. 
 

 
 Orn 
 Ornithine. 
 

 
 
 Appendix E provides for feature keys related to nucleotide sequences. 

 
 Appendix E to Subpart G of Part 1 - List of
 Feature Keys Related to Nucleotide Sequences
 
 
 
 Key 
 Description 
 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

 
 N_region 
 extra nucleotides inserted between rearranged immunoglobulin segments.
 
 
 

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

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

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

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

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

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

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

 
 protein_bind 
 non-covalent protein binding site on nucleic acid. 
 

 
 RBS 
 ribosome binding site. 
 

 
 repeat_region 
 region of genome containing repeating units. 
 

 
 repeat_unit 
 single repeat element.
 
 
 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

 
 unsure 
 author is unsure of exact sequence in this region. 
 

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

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

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

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

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

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

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

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

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

 
 
 Appendix F provides for feature keys related to protein sequences.

 
 Appendix F to Subpart G of Part 1-List of
 Feature Keys Related to Protein Sequences
 
 
 
 Key 
 Description 
 

 
 
 
 CONFLICT 
 different papers report differing sequences. 
 

 
 VARIANT 
 authors report that sequence variants exist. 
 

 
 VARSPLIC 
 description of sequence variants produced by alternative
 splicing. 
 
 

 
 MUTAGEN 
 site which has been experimentally altered. 
 

 
 MOD_RES 
 post-translational modification of a residue. 
 

 
 ACETYLATION 
 N-terminal or other. 
 

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

 
 BLOCKED 
 undetermined N- or C-terminal blocking group. 
 

 
 FORMYLATION 
 of the N-terminal methionine. 
 

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

 
 METHYLATION 
 generally of lysine or arginine. 
 

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

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

 
 SULFATATION 
 generally of tyrosine. 
 

 
 LIPID 
 covalent binding of a lipidic moiety. 
 

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

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

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

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

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

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

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

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

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

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

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

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

 
 SIGNAL 
 extent of a signal sequence (prepeptide). 
 

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

 
 PROPEP 
 extent of a propeptide. 
 

 
 CHAIN 
 extent of a polypeptide chain in the mature protein.
 
 
 

 
 PEPTIDE 
 extent of a released active peptide. 
 

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

 
 CA_BIND 
 extent of a calcium-binding region. 
 

 
 DNA_BIND 
 extent of a DNA-binding region. 
 

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

 
 TRANSMEM 
 extent of a transmembrane region. 
 

 
 ZN_FING 
 extent of a zinc finger region. 
 

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

 
 REPEAT 
 extent of an internal sequence repetition. 
 

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

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

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

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

 
 SITE 
 any other interesting site on the sequence. 
 

 
 INIT_MET 
 the sequence is known to start with an initiator methionine.
 
 
 

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

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

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

 
 II. INTERNATIONAL AND FOREIGN APPLICATIONS The requirements of 37 CFR 1.821 through
 37 CFR
 1.825 are the result of an effort to harmonize the USPTO
 requirements with international sequence listing requirements to the extent possible.
 The requirements of 37
 CFR 1.821 through 37 CFR 1.825 substantially
 correspond to the requirements of WIPO Standard ST.25 (2009). However, the requirements
 of 37 CFR
 1.821 through 37 CFR 1.825 are less stringent than
 the requirements of WIPO Standard ST.25 (2009). Thus, applicants who have filed or wish
 to file international applications or applications in countries that adhere to WIPO
 Standard ST.25 (2009) should be aware of the following requirements: 
 

 
 (A) The data in numeric identifier <221> must use selections
 from Tables 5 and 6 of WIPO Standard ST.25 (2009) to comply with that standard.
 The terms from these Tables are considered language neutral vocabulary;
 

 (B) WIPO Standard ST.25 (2009), paragraph 24, requires a blank line
 between numeric identifiers in the sequence listing when the digit in the first or
 second position of the numeric identifier changes; 
 

 (C) Where the sequence listing forming part of the description of the
 international application contains free text, e.g., free text in numeric
 identifier <223>, any such free text shall be repeated in the main part of the
 description in the language thereof ( PCT Rule 5.2(b) ). It is
 recommended that the free text in the language of the main part of the description
 be put in a specific section of the description called “Sequence Listing Free
 Text”;
 

 (D) A sequence listing filed after the international filing date is
 generally not considered to be part of the disclosure and usually will not be
 published as part of the international application publication (see
 PCT Article
 34 and PCT Rules 26 and
 91 for exceptions); and
 

 (E) Paragraph 4(v) of WIPO Standard ST.25 (2009) requires an
 accompanying statement with the specific wording “the information recorded in
 electronic form furnished under PCT Rule 13ter is identical to
 the sequence listing as contained in the international application ”.
 
 

 
 With further regard to requirements (A) and (B), is noted
 that PatentIn Version 3.5.1 software (see MPEP § 2430 ) generates sequence
 listings that meet all of the requirements of WIPO Standard ST.25 (2009). Applicants
 should similarly be aware that filing requirements for sequence listings may differ
 between a national US application, a foreign application and an international
 application during international phase. For example, where an international application
 is filed in paper, the sequence listing part of the international application must
 similarly be provided in paper. In addition, a copy of the sequence listing in ASCII
 plain text, to be used for the purpose of the international search ( PCT Rule 13ter )
 must be filed on read-only optical disc or via the USPTO electronic filing system.
 Furthermore, in contrast to US national applications, a sequence listing filed with
 RO/US in ASCII plain text that is 300 MB or more in size is not subject to a size fee
 during the international phase of an international application. 
 

 
 2422.01 Nucleotide and/or Amino Acids Disclosures Requiring a “Sequence
 Listing” [R-07.2022]
 

 [Editor Note: This section is not applicable to applications filed on or after
 July 1, 2022, having disclosures of nucleotide and/or amino acid sequences as defined
 in 37
 CFR 1.831(b) . See MPEP §§
 2412 - 2419 for guidance on WIPO ST.26
 requirements for applications filed on or after July 1, 2022.] 

 I. LENGTH THRESHOLDS 37 CFR
 1.821(a) presents a definition for “nucleotide and/or amino
 acid sequences.” This definition sets forth limits, in terms of numbers of amino
 acids and/or numbers of nucleotides, at or above which compliance with the sequence
 rules is required. Nucleotide and/or amino acid sequences as used in
 37 CFR
 1.821 through 37 CFR 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 ten specifically defined nucleotides or four
 specifically defined amino acids are specifically excluded from 37 CFR 1.821 .
 “Specifically defined” means those amino acids other than “Xaa” and those nucleotide
 bases other than “n” defined in Appendices A-F to 37 CFR part 1, Subpart G (see
 MPEP §
 2422(I) ).
 

 The limit of four or more amino acids was established for
 consistency with limits in place for industry database collections whereas the limit
 of ten or more nucleotides, while lower than certain industry database limits, was
 established to encompass those nucleotide sequences to which the smallest probe will
 bind in a stable manner. 
 

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

 Nucleotide sequences are further limited to those that can be
 represented by the symbols set forth in 37 CFR 1.822(b) and Appendices A
 and B to 37 CFR part 1, Subpart G (see MPEP § 2422(I) ). The presence of
 other than typical 5' to 3' phosphodiester linkages in a nucleotide sequence does not
 render the rules inapplicable. For example, the Office does not want to exclude
 linkages of the type commonly found in naturally occurring nucleotides, e.g.,
 eukaryotic end capped sequences. 
 

 Amino acid sequences are further limited to those in
 37 CFR
 1.822(b) and Appendices C and D to 37 CFR part 1, Subpart G
 (see MPEP §
 2422(I) ) and those L-amino acids that are commonly found in
 naturally occurring proteins. The presence of one or more D-amino acids in a sequence
 will exclude that sequence from the scope of the rules. Voluntary compliance is,
 however, encouraged in these situations; the symbol “Xaa” can be used to represent
 D-amino acids. The sequence rules embrace “[a]ny peptide or protein that can be
 expressed as a sequence using the symbols in Appendix C to 37 CFR part 1, Subpart G
 (see MPEP §
 2422(I) ) in conjunction with a description in the Feature
 section to describe, for example, modified linkages, cross links and end caps,
 non-peptidyl bonds, etc.” 37 CFR 1.821(a)(2) . 
 

 With regard to amino acid sequences, the use of the terms “peptide
 or protein” implies that the amino acids in a given sequence are linked by at least
 three consecutive peptide bonds. Accordingly, an amino acid sequence is not excluded
 from the scope of the rules merely due to the presence of a single non-peptidyl bond.
 If an amino acid sequence can be represented by a string of amino acid abbreviations,
 modifications in the sequence, if any, set forth in the Features section, the
 sequence comes within the scope of the rules. However, the rules are not intended to
 encompass the subject matter that is generally referred to as synthetic resins. 
 

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

 IV. VARIANTS OF A PRESENTED SEQUENCE It is generally acceptable to present a single,
 primary sequence in the specification and “Sequence Listing” by enumeration of its
 residues in accordance with the sequence rules (“primary sequence”) and to discuss
 and/or claim variants of that primary sequence without presenting each variant as a
 separate sequence in the “Sequence Listing”. Where the variant sequence meets the
 length thresholds of 37 CFR 1.821(a) and is disclosed
 by enumeration of its residues anywhere in an application, it must be presented in a
 “Sequence Listing” in a manner that complies with the requirements of the sequence
 rules. However, the primary sequence should be annotated in the “Sequence Listing” to
 reflect such variants. By way of example only, the following types of sequence
 disclosures would be treated as noted herein by the Office. With respect to a primary
 sequence and “conservatively modified variants thereof,” the sequences may be
 described as SEQ ID NO:X (the primary sequence) and “conservatively modified variants
 thereof,” if desired. With respect to a sequence that “may be deleted at the
 C-terminus by 1, 2, 3, 4, or 5 residues,” all of the implied variations do not need
 to be included in the “Sequence Listing”. In this latter example, only the sequence
 without deletions needs to be included in the “Sequence Listing”, though applicant is
 encouraged to annotate the sequence to indicate that deletions have been made at the
 C-terminus by 1, 2, 3, 4, or 5 residues.
 

 The Office's database will only contain the unmodified
 sequence. It is strongly recommended that any sequences appearing in the claims, or
 sequences that are considered essential to understanding the invention, be included
 in the “Sequence Listing” as a separate sequence.
 

 V. SEQUENCE IDENTIFIER 37 CFR
 1.821(d) and 37 CFR 1.823(a)(5) require that
 each disclosed nucleic acid and/or amino acid sequence in the application appear
 separately in the “Sequence Listing”, with each sequence further being assigned a
 sequence identifier, referred to as “SEQ ID NO.” or the like. The use of “SEQ ID NO:”
 is preferred, but including “or the like” is intended to ensure that a formalities
 notice is not sent when an application uses, for example, “SEQ NO.” or “Seq. Id. No.”
 or any similar identification for an amino acid or nucleotide sequence in the
 specification or claims where it is clear that a sequence from the “Sequence Listing”
 is shown in the description or claims. The sequence identifiers 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” in numerical order and in the order in which
 they are discussed in the application.
 

 37 CFR
 1.821(d) further requires that where the description or claims
 of a patent application discuss a sequence that is set forth in the “Sequence
 Listing”, a reference to the sequence identifier of that sequence is required at all
 occurrences, even if in the text of the description or claims where the sequence is
 set forth by enumeration of its residues. This requirement is also intended to permit
 references elsewhere in the application (e.g., specification, claims, or drawings) to
 sequences set forth in the “Sequence Listing” by the use of assigned sequence
 identifiers without repeating 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”. Where a sequence
 that meets the length thresholds of 37 CFR 1.821(a) is disclosed by
 enumeration of its residues anywhere in an application, it must be presented in a
 “Sequence Listing” in a manner that complies with the requirements of the sequence
 rules.
 

 The rules do not alter, in any way, the requirements
 of 35 U.S.C.
 112 . The implementation of the rules has had no effect on
 disclosure and/or claiming requirements. The rules, in general, or the use of
 sequence identifiers throughout the specification and claims, specifically, should
 not raise any issues under 35 U.S.C. 112(a) or
 35
 U.S.C. 112(b) . The use of sequence identifiers (SEQ ID NO:X 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.
 

 

 
 2422.02 The Requirement for Exclusive Conformance; Sequences Presented
 in Drawing Figures [R-07.2022]
 

 [Editor Note: This section is not applicable to applications filed on or after
 July 1, 2022, having disclosures of nucleotide and/or amino acid sequences as defined
 in 37
 CFR 1.831(b) . See MPEP §§
 2412 - 2419 for guidance on WIPO ST.26
 requirements for applications filed on or after July 1, 2022.] 

 For all applications that disclose nucleic acid and/or amino acid
 sequences that fall within the definition set forth in 37 CFR 1.821(a) ,
 37 CFR
 1.821(b) requires exclusive conformance to the requirements of
 37 CFR
 1.821 through 37 CFR 1.825 with regard to the
 manner in which the disclosed nucleotide and/or amino acid sequences are presented and
 described. 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 sequence listings should not be duplicated in the drawings. However many
 significant sequence characteristics may only be demonstrated by a figure. This is
 especially true in view of the fact that the representation of double stranded
 nucleotides is not permitted in the “Sequence Listing” and many significant nucleotide
 features, such as “sticky ends” and the like, 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 a sequence is presented in a
 drawing, the sequence must still be included in the “Sequence Listing” if the sequence
 falls within the definition set forth in 37 CFR 1.821(a) , and a sequence
 identifier (“SEQ ID NO:X” or the like) must be used, either in the drawing itself or in
 the Brief Description of the Drawings. 
 

 

 
 2422.03 Sequence Listing Submission [R-07.2022]

 [Editor Note: This section is not applicable to applications filed on or after
 July 1, 2022, having disclosures of nucleotide and/or amino acid sequences as defined
 in 37
 CFR 1.831(b) . See MPEP §§
 2412 - 2419 for guidance on WIPO ST.26
 requirements for applications filed on or after July 1, 2022.] 

 37 CFR
 1.821(c) requires that applications containing disclosures of
 nucleotide and/or amino acid sequences that fall within the definitions of
 37 CFR
 1.821(a) contain, as a separate part of the specification, a
 disclosure of each of the nucleotide and/or amino acid sequences, and associated
 information, using the format and symbols that are set forth in 37 CFR 1.822 and
 37 CFR
 1.823 . This separate part of the specification is referred to as
 the “Sequence Listing”. Except for submission of a national phase application under
 35 U.S.C.
 371 of an international application (PCT) that is compliant with
 PCT Rule
 5.2(a) , the “Sequence Listing” required pursuant to
 37 CFR
 1.821(c) must be submitted (1) as an ASCII plain text file via the
 USPTO patent electronic filing system or on a read-only optical disc under
 37 CFR
 1.52(e) , accompanied by an incorporation by reference statement of
 the ASCII plain text file, in a separate paragraph of the specification, in accordance
 with 37 CFR
 1.77(b)(5) (see 37 CFR 1.821(c)(1) ); (2) as a PDF
 image file submitted via the USPTO patent electronic filing system (see
 37 CFR
 1.821(c)(2) ); or (3) on physical sheets of paper (see
 37 CFR
 1.821(c)(3) ). If the “Sequence Listing” required by
 37 CFR
 1.821(c) is submitted on physical sheets of paper or as a PDF
 image file, the “Sequence Listing” is a separate part of the specification which must
 begin on a new page within the specification. Also, in an application filed under
 35 U.S.C.
 111(a) in which sequence information is submitted in an ASCII
 plain text file in compliance with 37 CFR 1.824 and as a PDF image file
 or on physical sheets of paper, the PDF image file or the physical sheets of paper will
 comply with the listing requirement under 37 CFR 1.821(c) and the ASCII plain
 text file will comply with the CRF requirement under 37 CFR
 1.821(e)(1)(i) .
 

 When the “Sequence Listing” is submitted as a PDF image
 file under 37 CFR 1.821(c)(2) via USPTO patent electronic filing system or
 on physical sheets of paper under 37 CFR 1.821(c)(3) ,
 37 CFR
 1.821(e)(1) requires that the copy of the 1.821(c) “Sequence
 Listing” must also be submitted in a separate computer readable form (CRF) in accordance
 with the requirements of 37 CFR 1.824 . Similarly, in the case
 of a national stage application submitted under 35 U.S.C. 371 , when the “Sequence
 Listing” is submitted as a PDF image file via the USPTO patent electronic filing system
 under 37
 CFR 1.821(c)(2) or on physical sheets of paper under
 37 CFR
 1.821(c)(3) , 37 CFR 1.821(e)(2) requires that the
 copy of the “Sequence Listing” referred to in 37 CFR 1.821(c) must also be
 submitted in a separate CRF in accordance with the requirements of 37 CFR 1.824 .
 37 CFR
 1.821(e)(3) requires that, in text format in an international
 application under the PCT that is to be searched by the United States International
 Searching Authority or examined by the United States International Preliminary Examining
 Authority, a CRF in accordance with the requirements of 37 CFR 1.824 must
 be submitted if a “Sequence Listing” in ASCII plain text format in compliance with
 37 CFR
 1.824 has not been submitted and the application contains
 disclosures of nucleotide and/or amino acid sequences, as defined in 37 CFR 1.821(a) . 
 

 At entry into the national stage under 35 U.S.C. 371 , an
 international application compliant with PCT Rule 5.2 that contains a
 “Sequence Listing” in ASCII plain text format as part of the description satisfies the
 requirements of 37 CFR
 1.821(c) and 37 CFR 1.821(e) . If the
 international application was previously communicated by the International Bureau under
 PCT Article
 20 and/or was originally filed in the United States Patent and
 Trademark Office, then no further submission of a “Sequence Listing” or incorporation by
 reference into the specification is required. Alternatively, if applicant must provide a
 copy of the international application as required by 37 CFR
 1.495(b)(1) , the copy of the international application must
 include the “Sequence Listing” part of the application, and no incorporation by
 reference into the specification is required. See also 37 CFR
 1.823(b)(2) and 1.825(c) .
 

 Whether submitted via the USPTO patent electronic
 filing system or on read-only optical disc(s), the ASCII plain text file must contain a
 copy of a single “Sequence Listing” in a single file. One hundred (100) megabytes is the
 size limit for “Sequence Listing” and CRF text files submitted via the USPTO patent
 electronic filing system, and “Sequence Listing” and CRF text files cannot be compressed
 when submitted via the USPTO patent electronic filing system. If a user wishes to submit
 an electronic copy of a “Sequence Listing” or CRF text file that exceeds 100 megabytes,
 the “Sequence Listing” or CRF must be filed on read-only optical disc(s). 
 

 I. ASCII PLAIN TEXT FILE SUBMITTED VIA
 USPTO PATENT ELECTRONIC FILING SYSTEM The Office strongly suggests filing the “Sequence Listing” required
 by 37 CFR
 1.821(c) as an ASCII plain text file via the USPTO patent
 electronic filing system. See 37 CFR 1.821(c)(1) . If sequence
 information is submitted in an application filed under 35 U.S.C.
 111(a) as an ASCII plain text file or as a national stage
 application submitted under 35 U.S.C. 371 as an ASCII plain
 text file in compliance with 37 CFR 1.824 via the USPTO patent
 electronic filing system and applicant has not filed a “Sequence Listing” as a PDF
 image file or on physical sheets of paper, the ASCII plain text file will serve as
 both the “Sequence Listing” under 37 CFR 1.821(c) and the CRF of
 the “Sequence Listing” under 37 CFR 1.821(e) . See
 37
 CFR 1.821(e)(1) . See 37 CFR
 1.821(e)(2) . Note that for applications filed under
 35 U.S.C.
 111(a) , the specification must contain a statement in a
 separate paragraph (see 37 CFR 1.77(b)(5) ) that
 incorporates by reference the material in the “Sequence Listing” ASCII plain text
 file identifying the name of the ASCII plain text file, the date of creation, and the
 size of the ASCII plain text file in bytes (see 37 CFR
 1.823(b)(1) ). However, an incorporation by reference statement
 is not required in an international application and is not required in an application
 file under 35
 U.S.C. 371 where the “Sequence Listing” has been previously
 communicated to the International Bureau or originally filed in the USPTO and
 complies with Patent Cooperation Treaty Rule 5.2 . See 37 CFR
 1.821(c) , 1.823(b)(2) , and
 1.825(c) . See also MPEP §
 2422.03(a) for additional information pertaining to USPTO
 patent electronic filing system submissions of a “Sequence Listing”.
 

 II. ASCII PLAIN TEXT FILE ON READ-ONLY
 OPTICAL DISC If the “Sequence Listing” as required by 37 CFR 1.821(c) 
 is submitted on read-only optical disc(s) in accordance with 37 CFR 1.52(e) ,
 the specification must contain an incorporation by reference of the material on the
 read-only optical disc in a separate paragraph (see 37 CFR
 1.77(b)(5) ) identifying the name of the file, the date of
 creation, and the size of the file in bytes ( 37 CFR
 1.823(b)(1) ). However, an incorporation by reference statement
 is not required in an international application and is not required in an application
 file under 35
 U.S.C. 371 where the “Sequence Listing” has been previously
 communicated to the International Bureau or originally filed in the USPTO and
 complies with Patent Cooperation Treaty Rule 5.2 . See 37 CFR
 1.821(c) , 1.823(b)(2) , and
 1.825(c) . It is noted that a “Sequence Listing” may be
 compressed using WinZip®, 7-Zip, or Unix®/Linux® Zip ( 37 CFR
 1.824(b)(2)(ii) ). If a compressed ASCII plain text file does
 not fit on a single read-only optical disc due to storage limitations of the
 read-only optical disc, the compressed ASCII plain text file may be split into
 multiple file parts and placed on multiple read-only optical discs which are labeled
 in compliance with 37 CFR 1.52(e)(5)(vi) and
 ( 37
 CFR 1.824(b)(2)(iv) ).
 

 The read-only optical disc used to submit the
 “Sequence Listing” may also contain “Large Tables” if the table has more than 50
 pages of text. See 1.52(e)(1)(iii) and 37 CFR 1.58(c) , (f) 
 and (i) . The read-only optical disc and duplicate copy must be
 labeled “Copy 1” and “Copy 2,” respectively, and a statement stating that the copies
 are identical must be included. If the two read-only optical discs are not identical,
 the Office will use the disc labeled “Copy 1” for further processing
 ( 37
 CFR 1.58(i) ). See also MPEP § 608.05 . 
 

 If the “Sequence Listing” is submitted in an application filed under
 35 U.S.C.
 111(a) as an ASCII plain text file in compliance with
 37 CFR
 1.824 on read-only optical disc(s) in accordance with
 37 CFR
 1.52(e) and applicant has not filed a “Sequence Listing” as a
 PDF image file or on physical sheets of paper, the ASCII plain text file will serve
 as both the “Sequence Listing” under 37 CFR 1.821(c) and the CRF of
 the “Sequence Listing” under 37 CFR 1.821(e) . See
 37
 CFR 1.821(e)(1) . Similarly, if the “Sequence Listing” is filed
 in a national stage application submitted under 35 U.S.C. 371 as an ASCII plain
 text file in compliance with 37 CFR 1.824 on read-only optical
 disc(s) in accordance with 37 CFR 1.52(e) and applicant has
 not filed a “Sequence Listing” as a PDF image file or on physical sheets of paper,
 the ASCII plain text file will serve as both the “Sequence Listing” under
 37 CFR
 1.821(c) and the CRF of the “Sequence Listing” under
 37 CFR
 1.821(e) .
 

 A. ASCII Plain Text Files Up
 to 300 MB When the “Sequence Listing” or CRF is submitted
 via read-only optical disc(s), the text file may either be compressed or not
 compressed. If the ASCII plain text file is not compressed, the ASCII plain text
 file must be contained on a single read-only optical disc. However, if the file
 does not fit on a single read-only optical disc even after compression, a
 compressed ASCII plain text file may be split into multiple file parts, in
 accordance with the target read-only optical disc size, and labeled in compliance
 with 37 CFR 1.52(e)(5)(vi) . See 37 CFR
 1.824(b) . 
 

 B. ASCII Plain Text Files 300
 MB or Over Any “Sequence Listing” ASCII plain text file of
 300 MB or more is subject to a fee under 37 CFR 1.21(o) to manage
 handling of the oversized submission ( 37 CFR
 1.52(f)(3) ). Pricing for this fee is divided into two tiers
 with Tier 1 for file sizes 300 MB to 800 MB and Tier 2 for file sizes greater than
 800 MB. The level of effort associated with the handling of mega-“Sequence
 Listing” is significant, because the Office’s systems require extra storage and
 special handling for files beyond 300 MB. The fee should encourage applicants to
 draft their specifications such that sequence data that is not essential material
 is not required to be included in a “Sequence Listing”. A reduced number of
 mega-“Sequence Listings” will benefit the Office and the public by reducing the
 strain on Office resources, thus facilitating the effective administration of the
 patent system.
 

 The fee under 37 CFR 1.21(o) is due upon the
 first submission of a “Sequence Listing” that exceeds 800 MB, or the first
 submission of a “Sequence Listing” of at least 300MB, whichever applicable fee is
 higher. As an example, if an application was filed prior to January 16, 2018 (with
 or without a text file “Sequence Listing”), and thereafter a mega-“Sequence
 Listing” that is between 300 and 800 MB is filed, the fee under 37 CFR
 1.21(o)(1) is due. If an applicant thereafter files a
 corrected “Sequence Listing” that is also between 300 and 800 MB, no additional
 fee is due. If a further corrected “Sequence Listing” is filed and the file size
 exceeds 800 MB, then the total fee owed under 37 CFR 1.21(o) is the fee set
 forth in 37 CFR 1.21(o)(2) . The fee,
 which is difference between the current fee and the prior paid fee, is due upon
 submission of the mega-“Sequence Listing”. Subsequent deletion or reduction in
 size of a “Sequence Listing” does not change the requirement to pay the
 mega-“Sequence Listing” submission fee. 
 

 The fee under 37 CFR 1.21(o) does not apply
 to international applications in the international stage, but does apply to the
 submission of mega-“Sequence Listings” received in national stage applications
 under 35 U.S.C.
 371 , including mega-"Sequence Listings" received by the
 Office pursuant to PCT Article 20 . See
 MPEP § 2422.03(a) , subsection IV, for additional
 information. 
 

 

 
 2422.03(a) “Sequence Listing” Submitted as ASCII Plain Text
 Files [R-01.2024]
 

 [Editor Note: This section is not applicable to applications filed on or after
 July 1, 2022, having disclosures of nucleotide and/or amino acid sequences as defined
 in 37
 CFR 1.831(b) . See MPEP §§
 2412 - 2419 for guidance on WIPO ST.26
 requirements for applications filed on or after July 1, 2022.] 

 The Legal Framework for Patent Electronic System
 ( www.uspto.gov/PatentLegalFramework ) and MPEP § 502.05 provide
 detailed information pertaining to filing applications and other documents via the USPTO
 patent electronic filing system. The information below is specific to “Sequence Listing”
 submissions via the USPTO patent electronic filing system.
 

 Pursuant to the Legal Framework for Patent Electronic
 System, applicants may submit a “Sequence Listing” under 37 CFR 1.821 as an
 ASCII plain text file via the USPTO patent electronic filing system or on read-only
 optical disc(s), provided the specification contains a statement in a separate paragraph
 (preferably on the first page) that incorporates by reference the material in the ASCII
 plain text file identifying the name of the ASCII plain text file, the date of creation,
 and the size of the ASCII plain text file in bytes. See 37 CFR 1.77(b)(5) 
 and 1.823(b)(1) . An exception is that an incorporation by reference
 statement is not required in an international application and is not required in an
 application file under 35 U.S.C. 371 where the “Sequence Listing” has been previously
 communicated to the International Bureau or originally filed in the USPTO and complies
 with Patent Cooperation Treaty Rule 5.2 . See 37 CFR 1.821(c) ,
 1.823(b)(2) , and 1.825(c) . The requirements of
 37 CFR
 1.52(e) for documents submitted on read-only optical disc(s) are
 not applicable to a “Sequence Listing” submitted as ASCII plain text files via the USPTO
 patent electronic filing system. However, each text file must be an ASCII plain text
 file and have a file name with a “.txt” extension. See 37 CFR 1.824 .
 

 I. ASCII PLAIN TEXT FILES SERVE AS BOTH THE “SEQUENCE LISTING” AND THE CRF It is recommended that a “Sequence Listing” be
 submitted as an ASCII plain text file via the USPTO patent electronic filing system
 rather than as a PDF image file. See subsection IV, below, for information regarding
 filing an international application (PCT) with a sequence listing ASCII plain text
 file via the USPTO patent electronic filing system.
 

 If the “Sequence Listing” is submitted in an
 application filed under 35 U.S.C. 111(a) as an ASCII
 plain text file in compliance with 37 CFR 1.824 via the USPTO patent
 electronic filing system and applicant has not filed a “Sequence Listing” as a PDF
 image file or on physical sheets of paper, the ASCII plain text file will serve as
 both the “Sequence Listing” under 37 CFR 1.821(c) and the CRF of
 the “Sequence Listing” under 37 CFR 1.821(e) . See
 37
 CFR 1.821(e)(1) . Similarly, if the “Sequence Listing” is filed
 in a national stage application submitted under 35 U.S.C. 371 as an ASCII plain
 text file in compliance with 37 CFR 1.824 via the USPTO patent
 electronic filing system, the ASCII plain text file will serve as both the “Sequence
 Listing” under 37
 CFR 1.821(c) and the CRF of the “Sequence Listing” under
 37 CFR
 1.821(e) . Thus, the following are not required and should not
 be submitted: (1) a second copy of the “Sequence Listing” as a PDF image file or on
 physical sheets of paper; and (2) a statement under 37 CFR
 1.821(e)(1)(ii) or (2)(ii) (indicating that the sequence information contained in
 the “Sequence Listing” under 37 CFR 1.821(c) and CRF copy of
 the “Sequence Listing” under 37 CFR 1.821(e)(1)(ii) or
 (2)(ii) are identical). Also, the practice of CRF transfers
 has been eliminated. Checker software that may be used to check a “Sequence Listing”
 for compliance with the requirements of 37 CFR 1.824 is available on the
 USPTO website at www.uspto.gov/Checker4 . The User Notes on the Checker website
 should be consulted for an explanation of the scope of errors and content that is
 able to be verified by the Checker software.
 

 If a user adds a “Sequence Listing” (under
 PCT Rule
 13ter ) as an ASCII plain text file via the USPTO patent
 electronic filing system in response to a requirement under 37 CFR
 1.821(h) , the “Sequence Listing” ASCII plain text file must be
 accompanied by a statement that the ASCII plain text file does not go beyond the
 disclosure in the international application as filed and the late furnishing fee as
 set forth in 37 CFR 1.445(a)(5) . However, if a
 user submits an amendment to add or replace a “Sequence Listing” (under
 37 CFR
 1.821(c) ) as an ASCII plain text file via the USPTO patent
 electronic filing system in response to a requirement under 37 CFR
 1.821(g) , the submission must comply with 37 CFR 1.825 .
 See MPEP §
 2426 .
 

 In applications filed under 35 U.S.C.
 111(a) and 371 , submission of the “Sequence
 Listing” as a PDF image file or on physical sheets of paper is not recommended. Where
 the “Sequence Listing” is submitted as a PDF image or on physical sheets of paper,
 applicant must provide the CRF required by 37 CFR
 1.821(e)(1)(i) . Note that the “Sequence Listing” in the PDF
 image file or on physical sheets of paper will not be excluded when determining the
 application size fee. The USPTO prefers the submission of sequence information in an
 ASCII plain text file via the USPTO patent electronic filing system because as stated
 above, if in an application filed under 35 U.S.C. 111(a) or
 35 U.S.C.
 371 applicant has not filed a second copy of the “Sequence
 Listing” as a PDF image file or on physical sheets of paper (see 37 CFR
 1.821(e)(1) ), the ASCII plain text file will serve as both the
 “Sequence Listing” required by 37 CFR 1.821(c) and the CRF
 required by 37 CFR
 1.821(e) . 
 

 II. APPLICATION SIZE FEE Any “Sequence Listing” or CRF of a “Sequence Listing”
 submitted as an ASCII plain text file via the USPTO patent electronic filing system
 that is in compliance with 37 CFR 1.821(c) or
 (e) will be excluded when determining the application size fee
 required by 37 CFR 1.16(s) or
 1.492(j) as per 37 CFR 1.52(f)(2) . A “Sequence
 Listing” submitted as a PDF image file via the USPTO patent electronic filing system
 or on read-only optical disc will not be excluded when determining the application
 size fee.
 

 See subsection IV, below, for additional information
 regarding application size fees in an international application (PCT).
 

 III. SIZE RESTRICTIONS FOR ASCII PLAIN TEXT FILES One hundred (100) megabytes is the size limit for
 “Sequence Listing” ASCII plain text files submitted via the USPTO patent electronic
 filing system, and compression is not allowed for a “Sequence Listing” submitted via
 the USPTO patent electronic filing system. If a user wishes to submit a “Sequence
 Listing” ASCII plain text file that exceeds 100 megabytes, it is recommended that the
 user file the application without the “Sequence Listing” using the USPTO patent
 electronic filing system to obtain the application number and confirmation number,
 and then file the “Sequence Listing” on read-only optical disc(s) in accordance with
 37 CFR
 1.52(e) and 1.824 on the same day by using
 Priority Mail Express® from the USPS in accordance with 37 CFR 1.10 , or
 hand delivery, in order to secure the same filing date for all parts of the
 application. Note: a submission of a “Sequence Listing” in electronic form of 300 MB
 or more in size is subject to an oversized submission fee set forth in
 37 CFR
 1.21(o) . See 37 CFR 1.52(f)(3) . Alternatively,
 a user may submit the application on physical sheets of paper and include the
 “Sequence Listing” ASCII plain text file on read-only optical disc(s) in accordance
 with 37 CFR
 1.52(e) . “Sequence Listing” ASCII plain text files may not be
 divided into multiple files so as to not exceed the 100 MB size limit for filing via
 the USPTO patent electronic filing system, and any “Sequence Listing” greater than
 100 MB must be submitted on read-only optical disc(s). If the “Sequence Listing” is
 filed on a read-only optical disc, the ”Sequence Listing” must be a single file, and
 any not compressed file must be contained on a single read-only optical disc.
 However, a compressed file that does not fit on a single read-only optical disc may
 be split into multiple file parts, in accordance with the target read-only optical
 disc size, and must have a label permanently affixed thereto on which the following
 information has been hand-printed or typed: (i) First-named inventor (if known); (ii)
 Title of the invention; (iii) Attorney docket or file reference number (if
 applicable); (iv) Application number and filing date (if known); (v) Date on which
 the data were recorded on the read-only optical disc; and (vi) Disc order (e.g., “1
 of X”), if multiple read-only optical discs are submitted. See 37 CFR
 1.52(e)(5) and 1.824(b) . 
 

 See subsection IV.B, below, for information regarding
 submission of a sequence listing text file that exceeds 100 megabytes in an
 international application (PCT) filed via the USPTO patent electronic filing
 system.
 

 The current size limit on the USPTO patent electronic
 filing system for ASCII plain text file submissions of “Large Tables” and a “Computer
 Program Listing Appendix” is 25 megabytes per submission, and compression is not
 allowed for “Large Tables” and a “Computer Program Listing Appendix” submitted as
 ASCII plain text files via the USPTO patent electronic filing system. Files above the
 25 MB limit for “Large Tables” and a “Computer Program Listing Appendix” may be
 either (1) broken up into multiple files that are no larger than 25 MB each and those
 smaller files may be submitted via the USPTO patent electronic filing system or (2)
 submitted on read-only optical disc(s) (see 37 CFR 1.52(e) ). If the user
 chooses to break up a “Large Table” or “Computer Program Listing Appendix” file so
 that it may be submitted via the USPTO patent electronic filing system, the file
 names must indicate their order (e.g., “1 of X”, “2 of X”). If a user wishes to file
 an application with a “Large Table” or “Computer Program Listing Appendix” ASCII
 plain text file that is larger than 25 megabytes, it is recommended that the user
 file the application without the “Large Table” or “Computer Program Listing Appendix”
 using the USPTO patent electronic filing system to obtain the application number and
 confirmation number, and then file the “Large Table” or “Computer Program Listing
 Appendix” on read-only optical disc(s) in accordance with 37 CFR 1.52(e) 
 and 1.58(c) or 1.96(c) on the same day by using
 Priority Mail Express® from the USPS in accordance with 37 CFR 1.10 , or
 hand delivery, in order to secure the same filing date for all parts of the
 application. Alternatively, a user may submit the application on physical sheets of
 paper and include the “Large Table” or “Computer Program Listing Appendix” ASCII
 plain text file on read-only optical disc(s) in accordance with 37 CFR 1.52(e) 
 in order to secure the same filing date for all parts of the application. See
 37
 CFR 1.58(f) and 37 CFR 1.96(c)(4) . 
 

 IV. FILING A SEQUENCE LISTING IN INTERNATIONAL APPLICATIONS (PCT) VIA THE USPTO
 PATENT ELECTRONIC FILING SYSTEM 
 

 A. Sequence Listing Must Be Presented as a Separate Part of the
 Description Under PCT Rule 5.2(a) , “where the
 international application contains disclosure of one or more nucleotide and/or
 amino acid sequences, the description shall contain a sequence listing complying
 with the standard provided for in the Administrative Instructions and presented as
 a separate part of the description in accordance with that standard”. The standard
 is set forth in the PCT Administrative Instructions Annex C, entitled Standard for
 the Presentation of Nucleotide and Amino Acid Sequence Listings in International
 Patent Applications Under the PCT. When filing an international application (PCT)
 using the USPTO patent electronic filing system, it is highly recommended to
 submit a sequence listing as a single ASCII plain text file with a “.txt”
 extension on the international filing date. Note that 100 megabytes is the size
 limit for submitting a sequence listing ASCII plain text file via the USPTO patent
 electronic filing system. See subsection IV.B, below. Although it is not
 recommended, applicant can also submit the sequence listing in a PCT application
 as a PDF image file as part of the application on the international filing
 date.
 

 If the sequence listing is submitted as an ASCII
 plain text file when filing a new international application (PCT), applicant need
 not and should not submit any additional copies, including PDF image files. The
 single ASCII plain text file is preferred because the ASCII plain text file will
 serve both as the sequence listing part of the description required under
 PCT Rule
 5.2 and the electronic form under PCT Rule
 13ter.1(a) in the absence of a PDF
 sequence listing file. The check list (Box No. IX) of the PCT Request (form
 PCT/RO/101) provided via the USPTO patent electronic filing system together with
 the international application (PCT) must indicate that the sequence listing
 submitted as an ASCII plain text file forms part of the international application.
 Furthermore, the statement as set forth in paragraph 4(v) of the AI Annex C 
 (Administrative Instructions under the PCT, Annex C), that “the information
 recorded in electronic form furnished under PCT Rule 13ter is identical to the sequence listing as contained in the
 international application,” is not necessary.
 

 Submission of the sequence listing part of the
 description as a PDF image file in a new international application (PCT) is not
 recommended because, where the application does not contain a sequence listing as
 an ASCII plain text file, the International Searching Authority or the
 International Preliminary Authority may invite applicant to furnish a copy of the
 sequence listing in ASCII plain text format for the purposes of international
 search and/or preliminary examination. Any sequence listing submitted in response
 to this invitation will not form part of the application. 
 

 When a sequence listing is filed via the USPTO
 patent electronic filing system in a new PCT international application as both a
 PDF image file and an ASCII plain text file, but the Request form Box No. IX does
 not indicate which one forms part of the international application, the PDF image
 copy of the sequence listing will be considered to form part of the application
 and the ASCII plain text file will be considered to be an accompanying item for
 search purposes under PCT Rule 13ter.1(a) only.
 

 The international filing fee for an international
 application (PCT) that includes a sequence listing, filed via the USPTO patent
 electronic filing system, is calculated based on the type of sequence listing file
 that is part of the description of the international application (PCT). A sequence
 listing filed as an ASCII plain text file will not be included in the sheet count
 of the international application (PCT). A sequence listing filed as a PDF image
 file will be included in the sheet count of the international application (PCT),
 when it is part of the description. When a new PCT international application is
 filed via the USPTO patent electronic filing system and contains the sequence
 listing part of the description as a PDF image file and a sequence listing ASCII
 plain text to be used only for search purposes under PCT Rule
 13ter.1(a) , the sheets of the PDF image file will count
 towards excess sheet fees, if any.
 

 B. File Size and Quantity Limits One hundred (100) megabytes is the size limit for
 sequence listing ASCII plain text files submitted via the USPTO patent electronic
 filing system. See 37 CFR 1.824(b)(1) . Sequence
 listing ASCII plain text files must not be partitioned into multiple files for
 filing via the USPTO patent electronic filing system. The sequence listing must be
 in a single ASCII plain text file. 
 

 Applicant may use the USPTO patent electronic
 filing system to file part of the international application (PCT) and to obtain
 the international application (PCT) number and the confirmation number, and then
 file the remainder of the international application (PCT) on the same day as one
 or more follow-on submissions using the USPTO patent electronic filing system, in
 order to secure the same filing date for all parts of the international
 application (PCT). However, applicant is not permitted to file part of the
 international application (PCT) electronically via the USPTO patent electronic
 filing system, and then file the remainder of the international application (PCT)
 on paper to secure a filing date of all parts of the international application
 (PCT).
 

 In the situation where applicant needs to file a
 sequence listing that is over one hundred (100) megabytes, applicant may use the
 USPTO patent electronic filing system to file the international application (PCT)
 without the sequence listing to obtain the international application (PCT) number
 and the confirmation number, and then file the sequence listing on read-only
 optical discs on the same day by using Priority Mail Express® from the USPS in
 accordance with 37 CFR 1.10 , or by hand delivery, in order to secure the
 same filing date for all parts of the international application (PCT). However,
 the read-only optical discs must not contain PDF image files and must fully comply
 with the guidelines for filing a sequence listing on electronic media. The check
 list of the PCT Request provided via the USPTO patent electronic filing system
 together with the international application (PCT) must indicate that the sequence
 listing will be filed separately on physical data carrier(s), on the same day and
 in the form of an Annex C/ST.25 text file. The sequence listing must be a single
 file, but the file may be split for submission on multiple physical media using
 software designed to divide a file into multiple files for subsequent
 concatenation. If the user breaks up a sequence listing for submission on multiple
 read-only optical discs, the read-only optical discs must be labeled to indicate
 their order (e.g., “1 of X”, “2 of X”).
 

 Submissions of very lengthy sequence listings (300
 MB or over a.k.a. mega-sequence listings) in international applications are not
 subject to the mega-sequence listing submission fees set forth in
 37 CFR
 1.21(o) . However, for mega-sequence listing submissions on
 or after January 16, 2018, the fee under 37 CFR 1.21(o) does apply to
 the submission of mega-sequence listings received in national stage applications
 under 35 U.S.C.
 371 , including mega-sequence listings received by the Office
 pursuant to PCT
 Article 20 . Similarly, if an international application is
 filed at RO/US with a mega-sequence listing, and thereafter a bypass continuing
 application is filed under 35 U.S.C. 111(a) , the fee
 under 37 CFR
 1.21(o) will be due in the continuing application for
 mega-sequence listing submissions on or after January 16, 2018. See
 37
 CFR 1.52(f)(3) .
 

 

 
 2422.04 The Requirement for a Computer Readable Copy of the “Sequence
 Listing” [R-07.2022]
 

 [Editor Note: This section is not applicable to applications filed on or after
 July 1, 2022, having disclosures of nucleotide and/or amino acid sequences as defined
 in 37
 CFR 1.831(b) . See MPEP §§
 2412 - 2419 for guidance on WIPO ST.26
 requirements for applications filed on or after July 1, 2022.] 

 37
 CFR 1.821(e) requires the submission of a copy of the “Sequence
 Listing” in computer readable form (CRF) in an application filed under 35 U.S.C.
 111(a) or in a national stage application submitted under
 35 U.S.C.
 371 . A separate computer readable form must be submitted via the
 USPTO patent electronic filing system or on read-only optical disc(s), as permitted by
 37 CFR
 1.824(b) , when the “Sequence Listing” required by
 37 CFR
 1.821(c) is submitted as a PDF image file or on physical sheets of
 paper in a U.S. application filed under 35 U.S.C. 111(a) (see
 37 CFR
 1.821(e)(1) ) or when the “Sequence Listing” required by
 37 CFR
 1.821(c) is submitted as a PDF image file or on physical sheets of
 paper and not also submitted as an ASCII plain text file in a national stage application
 (see 37
 CFR 1.821(e)(2) ). However, the Office prefers submission of
 sequence information as an ASCII plain text file via the USPTO patent electronic filing
 system or on read-only optical disc(s) without a copy of the “Sequence Listing” as a PDF
 image file or on physical sheets of paper in all applications because such an ASCII
 submission will serve as both the “Sequence Listing” required by 37 CFR 1.821(c) 
 and the CRF of the “Sequence Listing” required by 37 CFR 1.821(e) and the “Sequence
 Listing” submitted as an ASCII plain text file will not be included in the application
 size fee determination under 37 CFR 1.52(f)(1) or
 (2) . See MPEP § 2422.03(a)(I) .
 

 The information on the computer readable form will be
 entered into the Office’s database for searching and printing nucleotide and amino acid
 sequences. This electronic database will also enable the Office to provide published
 sequence data, in electronic form, to the National Center for Biotechnology Information
 (NCBI) for publication in GenBank, and enable NCBI to exchange data with the DNA Data
 Bank of Japan (DDBJ) and the European Bioinformatics Institute (EBI). It should be noted
 that the Office’s database complies with the confidentiality requirement imposed by
 35 U.S.C.
 122 . Unpublished pending application sequences are maintained in
 the database separately from published or patented sequences. That is, the Office will
 not exchange or make public any information on any sequence until the patent application
 containing that information is published or matures into a patent, or as otherwise
 allowed by 35 U.S.C.
 122 . 
 

 The Office may permit correction of the “Sequence Listing” submitted
 pursuant to 37 CFR
 1.821(c) , whether on physical sheets of paper or as a PDF image
 file, at the least, during the pendency of a given application by reference to the
 computer readable form thereof submitted pursuant to 37 CFR 1.821(e) if both the
 “Sequence Listing” and computer readable form were submitted at the time of filing of
 the application and the totality of the circumstances otherwise substantiate the
 proposed correction. A mere discrepancy between the “Sequence Listing” and the computer
 readable form may not, in and of itself, be sufficient to justify a proposed correction.
 In this regard, the Office will assume that the computer readable form has been
 incorporated by reference into the application when the “Sequence Listing” and computer
 readable form were submitted at the time of filing of the application. The Office will
 attempt to accommodate or address all correction issues, but it must be kept in mind
 that the real burden rests with the applicant to ensure that any discrepancies between
 the “Sequence Listing” and the CRF copy are eliminated or minimized. Applicants should
 be aware that there will be instances where the applicant may have to suffer the
 consequences of any discrepancies between the two. It is noted that in an application
 filed under 35
 U.S.C. 111(a) in which applicant has not filed a second copy of
 the “Sequence Listing” as a PDF image file or on physical sheets of paper (see
 37 CFR
 1.821(e)(1) ), an ASCII plain text file will serve as both the
 “Sequence Listing” required by 37 CFR 1.821(c) and the CRF required
 by 37 CFR
 1.821(e) , eliminating any chance for discrepancies. Filing the
 “Sequence Listing” as an ASCII plain text file submitted via the USPTO patent electronic
 filing system that complies with both 37 CFR 1.821(c) and
 (e) is the Office’s preferred method of receiving a “Sequence
 Listing”. 
 

 The Office does not desire to be bound by a requirement to permanently
 preserve computer readable forms submitted on read-only optical disc(s) for support,
 priority or correction purposes. Thus, once use of the CRF by the Office for processing
 has ended, i.e., once the Office has entered the data contained on the computer readable
 form into the appropriate database, the Office does not intend to further preserve the
 CRF submitted by the applicant, and applicant should not expect to have the read-only
 optical disc(s) returned. See 37 CFR 1.52(e)(6) . 
 

 

 
 2422.05 [Reserved]

 

 
 2422.06 Requirement for Statement Regarding Information Contained in
 the “Sequence Listing” and Separate Computer Readable Form [R-07.2022]
 

 [Editor Note: This section is not applicable to applications filed on or after
 July 1, 2022, having disclosures of nucleotide and/or amino acid sequences as defined
 in 37
 CFR 1.831(b) . See MPEP §§
 2412 - 2419 for guidance on WIPO ST.26
 requirements for applications filed on or after July 1, 2022.] 

 When a separate computer readable form (CRF) of a “Sequence Listing”
 is submitted in an application filed under 35 U.S.C. 111(a) because the
 “Sequence Listing” is filed as a PDF image file ( 37 CFR
 1.821(c)(2) ) or on physical sheets of paper ( 37 CFR
 1.821(c)(3) ) (see 37 CFR 1.821(e)(1)(i) ) or filed in a
 national stage application submitted under 35 U.S.C. 371 because the “Sequence
 Listing” is filed as a PDF image file ( 37 CFR 1.821(c)(2) ) or on physical
 sheets of paper ( 37 CFR 1.821(c)(3) ) and not also as
 an ASCII plain text file in compliance with 37 CFR 1.824 (see 37 CFR
 1.821(e)(2)(i) ), 37 CFR 1.821(e)(1)(ii) and
 (2)(ii) require, a statement that the information contained in
 the “Sequence Listing” and the separate CRF are identical. When a CRF is submitted in
 the international stage of an international application under the PCT in response to an
 notice requesting a ASCII plain text formatted sequence listing by the United States
 International Searching Authority or by the United States International Preliminary
 Examining Authority because a sequence listing in ASCII plain text format in compliance
 with 37 CFR
 1.824 has not been filed (see 37 CFR
 1.821(e)(3)(i) ), 37 CFR 1.821(e)(3)(iii) requires a
 statement that the information contained in the CRF does not go beyond the disclosure in
 the international application as filed or a statement that the information recorded in
 the ASCII plain text file of the CRF is identical to the sequence listing contained in
 the international application as filed, as applicable. Such a statement may be made by a
 registered practitioner, the applicant, an inventor, or the person who actually compares
 the sequence data on behalf of the aforementioned. See MPEP § 2428 for
 further information and Sample Statements.
 

 Note that, in an application filed under
 35 U.S.C.
 111(a) , if a “Sequence Listing” is filed as an ASCII plain text
 file via the USPTO patent electronic filing system or on a read-only optical disc under
 37 CFR
 1.52(e) , and applicant has not filed a “Sequence Listing” as a PDF
 image file or on physical sheets of paper, the ASCII plain text file will serve as both
 the “Sequence Listing” required by 37 CFR 1.821(c) and the computer
 readable form (CRF) required by 37 CFR 1.821(e) ( 37 CFR
 1.821(e)(1) ). Also, in a national stage application submitted
 under 35 U.S.C.
 371 , if a “Sequence Listing” is filed as an ASCII plain text file
 via the USPTO patent electronic filing system or on a read-only optical disc under
 37 CFR
 1.52(e) , the ASCII plain text file will serve as both the
 “Sequence Listing” required by 37 CFR 1.821(c) and the computer
 readable form (CRF) required by 37 CFR 1.821(e) . See
 MPEP §
 2422.03(a) , subsection I, for additional information. See also
 MPEP §
 2422.03(a) subsection IV, for additional information regarding
 international stage applications. Thus, for applications filed under 35 U.S.C.
 111(a) and 35 U.S.C. 371 , the following are not
 required and should not be submitted: (1) a second copy of the “Sequence Listing” as a
 PDF image file or on physical sheets of paper; and (2) a statement under
 37 CFR
 1.821(e)(1)(ii) or (2)(ii) (indicating that the
 sequence information contained in the “Sequence Listing” under 37 CFR 1.821(c) 
 and CRF copy of the “Sequence Listing” under 37 CFR
 1.821(e)(1)(ii) or (2)(ii) are identical).
 

 

 
 2422.07 Requirements for Compliance and Consequences of
 Non-Compliance [R-07.2022]
 

 [Editor Note: This section is not applicable to applications filed on or after
 July 1, 2022, having disclosures of nucleotide and/or amino acid sequences as defined
 in 37
 CFR 1.831(b) . See MPEP §§
 2412 - 2419 for guidance on WIPO ST.26
 requirements for applications filed on or after July 1, 2022.] 

 37 CFR
 1.821(g) requires compliance with the requirements of
 37 CFR
 1.821(b) through (e) , as discussed above, if they are
 not satisfied at the time of filing under 35 U.S.C. 111(a) or at the time of
 entering the national stage of an international application under 35 U.S.C. 371 ,
 within the period of time set in a notice requiring compliance. When applicant files an
 amendment to comply with the requirements of 37 CFR 1.821(g) and that amendment
 adds or replaces a “Sequence Listing” and CRF copy thereof, the amendment must be
 submitted in accordance with the requirements of 37 CFR 1.825 . Failure to provide a
 proper reply in compliance with 37 CFR 1.825 will result in the
 abandonment of the application. See MPEP § 2426 . Extensions of time in
 which to reply to a requirement under this paragraph are available pursuant to
 37 CFR
 1.136 . Note, however, that patent applications filed under
 35 U.S.C.
 111 on or after December 18, 2013, and international patent
 applications in which the national stage commenced under 35 U.S.C. 371 on
 or after December 18, 2013, may be subject to reductions in patent terms adjustment
 pursuant to 37 CFR 1.704(c)(13) if they are not in condition for examination
 within eight months from the filing date or date of commencement, respectively. “In
 condition for examination” includes compliance with 37 CFR 1.821 through
 1.825 (see 37 CFR 1.704(f) ).
 

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

 If any of the requirements of 37 CFR
 1.821(e)(3) are not satisfied at the time of filing an
 international application under the Patent Cooperation Treaty (PCT), and the application
 is to be searched by the United States International Searching Authority or examined by
 the United States International Preliminary Examining Authority, the applicant may be
 sent a notice necessitating compliance with the requirements within a prescribed time
 period. Where a sequence listing under PCT Rule 13ter is provided in reply
 to a under 37 CFR
 1.821(h) , the sequence listing must be accompanied by a statement
 that the information recorded in the ASCII plain text file under 37 CFR
 1.821(e)(3)(i) is identical to the sequence listing contained in
 the international application as filed, or does not go beyond the disclosure in the
 international application as filed, as applicable. Such a statement may be made by a
 registered practitioner, the applicant, an inventor, or the person who actually compares
 the sequence data on behalf of the aforementioned. Also, the ASCII plain text file under
 37 CFR
 1.821(e)(3)(i) must be accompanied by the late furnishing fee, as
 set forth in 37 CFR 1.445(a)(5) . International
 applications that fail to comply with any of the requirements of 37 CFR
 1.821(e)(3) will be searched and/or examined only to the extent
 possible without the benefit of the information in computer readable form. See
 PCT Administrative
 Instructions Section 513(c) . 
 

 The requirement to submit a statement that a submission in reply to the
 requirement under 37
 CFR 1.821(h) does not go beyond the disclosure in the application
 as filed or that the information recorded in the ASCII plain text file under
 37 CFR
 1.821(e)(3)(i) is identical to the sequence listing contained in
 the international application as filed is not the first instance in which the applicant
 has been required to ensure that there is not new matter upon amendment. The requirement
 is analogous to that found in 37 CFR 1.125 regarding substitute
 specifications. When a substitute specification is required because the number or nature
 of amendments would make it difficult to examine the application, the applicant must
 include a statement that the substitute specification includes no new matter. The
 necessity of requiring sequence information as an ASCII plain text file is similar to
 the necessity of requiring a substitute specification and, likewise, the burden is on
 the applicant to ensure that no new matter is added. Applicants have a duty to comply
 with the statutory prohibition ( 35 U.S.C. 132 and 35 U.S.C. 251 )
 against the introduction of new matter.
 

 The correction of errors in sequencing or any other errors that are
 made in describing an invention are subject to the statutory prohibition
 ( 35 U.S.C.
 132 and 35 U.S.C. 251 ) against the
 introduction of new matter.
 

 

 
 2422.08 Presumptions Regarding Compliance [R-07.2022]

 [Editor Note: This section is not applicable to applications filed on or after
 July 1, 2022, having disclosures of nucleotide and/or amino acid sequences as defined
 in 37
 CFR 1.831(b) . See MPEP §§
 2412 - 2419 for guidance on WIPO ST.26
 requirements for applications filed on or after July 1, 2022.] 

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

 

 
 2422.09 [Reserved]

 

 [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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 Last Modified: 
 
 03/09/2026 20:49:36