MPEP § 2423.03 — Presentation and Numbering of Sequences (Annotated Rules)

§2423.03 Presentation and Numbering of Sequences

USPTO MPEP version: BlueIron's Update: 2025-12-31

This page consolidates and annotates all enforceable requirements under MPEP § 2423.03, including statutory authority, regulatory rules, examiner guidance, and practice notes. It is provided as guidance, with links to the ground truth sources. This is information only, it is not legal advice.

Presentation and Numbering of Sequences

This section addresses Presentation and Numbering of Sequences. Primary authority: 37 CFR 1.822(c)(5), 37 CFR 1.822(d), and 37 CFR 1.822(c)(6). Contains: 4 requirements, 1 prohibition, 4 permissions, and 5 other statements.

Key Rules

Topic

Sequence Listing Content

10 rules
StatutoryInformativeAlways
[mpep-2423-03-d640dc990ba2d4b63cc63904]
Not Applicable to Nucleotide and Amino Acid Sequences After July 1, 2022
Note:
This rule does not apply to applications filed on or after July 1, 2022 that disclose nucleotide and/or amino acid sequences.

[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 1.77 · 37 CFR 1.831(b)Sequence Listing ContentSequence Listing Requirements
StatutoryRequiredAlways
[mpep-2423-03-ba9e2a0ffa3e1ee1132c8e4f]
Nucleotide Sequences Must Be Represented Unidirectionally
Note:
Nucleotide sequences in the Sequence Listing must be shown as a single strand from 5′ to 3′, not double-stranded.

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

Jump to MPEP Source · 37 CFR 1.822(c)(5)Sequence Listing ContentSequence Listing RequirementsSequence Listing Format
StatutoryPermittedAlways
[mpep-2423-03-8f3e068b4a92a0b7510c8ac5]
Double Stranded Nucleotides Must Be Represented as Two Single Strands
Note:
Nucleotide sequences in the Sequence Listing must be shown as two single strands, with any relationship depicted in drawings.

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

Jump to MPEP Source · 37 CFR 1.822(c)(5)Sequence Listing ContentSequence Listing RequirementsSequence Listing Format
StatutoryInformativeAlways
[mpep-2423-03-b12c729004cbb930c1e8d856]
Procedures for Presenting and Numbering Amino Acid Sequences
Note:
The rule outlines the methods for presenting and numbering amino acid sequences in sequence listings.

The procedures for presenting and numbering amino acid sequences are set forth in 37 CFR 1.822(d). Two alternatives are presented for numbering amino acid sequences. Amino acid sequences may be numbered with respect to the identification of the first amino acid of the first mature protein or with respect to the first amino acid appearing at the amino terminal. The numbering procedure for nucleotides is set forth in 37 CFR 1.822(c)(6). Sequences that are circular in configuration are intended to be encompassed by these rules, and the numbering procedures described above remain applicable with the exception that the designation of the first nucleotide base or amino acid of the sequence may be made at the option of the applicant. See 37 CFR 1.822(c)(7) and (d)(4).

Jump to MPEP Source · 37 CFR 1.822(d)Sequence Listing ContentSequence Listing RequirementsSequence Listing Format
StatutoryInformativeAlways
[mpep-2423-03-2fdaaae523298735305f0e7d]
Two Alternatives for Numbering Amino Acid Sequences
Note:
The rule provides two methods for numbering amino acid sequences, either starting from the first mature protein or from the amino terminal.

The procedures for presenting and numbering amino acid sequences are set forth in 37 CFR 1.822(d). Two alternatives are presented for numbering amino acid sequences. Amino acid sequences may be numbered with respect to the identification of the first amino acid of the first mature protein or with respect to the first amino acid appearing at the amino terminal. The numbering procedure for nucleotides is set forth in 37 CFR 1.822(c)(6). Sequences that are circular in configuration are intended to be encompassed by these rules, and the numbering procedures described above remain applicable with the exception that the designation of the first nucleotide base or amino acid of the sequence may be made at the option of the applicant. See 37 CFR 1.822(c)(7) and (d)(4).

Jump to MPEP Source · 37 CFR 1.822(d)Sequence Listing ContentSequence Listing RequirementsSequence Listing Format
StatutoryPermittedAlways
[mpep-2423-03-5ceb301dd2396090fcf5b10e]
Amino Acid Sequence Numbering Alternatives
Note:
The rule allows numbering amino acid sequences either from the first mature protein's initial amino acid or from the amino terminal.

The procedures for presenting and numbering amino acid sequences are set forth in 37 CFR 1.822(d). Two alternatives are presented for numbering amino acid sequences. Amino acid sequences may be numbered with respect to the identification of the first amino acid of the first mature protein or with respect to the first amino acid appearing at the amino terminal. The numbering procedure for nucleotides is set forth in 37 CFR 1.822(c)(6). Sequences that are circular in configuration are intended to be encompassed by these rules, and the numbering procedures described above remain applicable with the exception that the designation of the first nucleotide base or amino acid of the sequence may be made at the option of the applicant. See 37 CFR 1.822(c)(7) and (d)(4).

Jump to MPEP Source · 37 CFR 1.822(d)Sequence Listing ContentSequence Listing RequirementsSequence Listing Format
StatutoryInformativeAlways
[mpep-2423-03-14aa7fafc3b274b75e429af1]
Numbering Procedure for Nucleotides
Note:
The rule outlines the method for numbering nucleotide sequences in sequence listings.

The procedures for presenting and numbering amino acid sequences are set forth in 37 CFR 1.822(d). Two alternatives are presented for numbering amino acid sequences. Amino acid sequences may be numbered with respect to the identification of the first amino acid of the first mature protein or with respect to the first amino acid appearing at the amino terminal. The numbering procedure for nucleotides is set forth in 37 CFR 1.822(c)(6). Sequences that are circular in configuration are intended to be encompassed by these rules, and the numbering procedures described above remain applicable with the exception that the designation of the first nucleotide base or amino acid of the sequence may be made at the option of the applicant. See 37 CFR 1.822(c)(7) and (d)(4).

Jump to MPEP Source · 37 CFR 1.822(d)Sequence Listing ContentSequence Listing FormatSequence Listing Requirements
StatutoryPermittedAlways
[mpep-2423-03-850f5d8db65e484acaffd679]
Option for First Nucleotide or Amino Acid Designation
Note:
Applicants may choose the first nucleotide base or amino acid of circular sequences, as no specific numbering is mandated by these rules.

The procedures for presenting and numbering amino acid sequences are set forth in 37 CFR 1.822(d). Two alternatives are presented for numbering amino acid sequences. Amino acid sequences may be numbered with respect to the identification of the first amino acid of the first mature protein or with respect to the first amino acid appearing at the amino terminal. The numbering procedure for nucleotides is set forth in 37 CFR 1.822(c)(6). Sequences that are circular in configuration are intended to be encompassed by these rules, and the numbering procedures described above remain applicable with the exception that the designation of the first nucleotide base or amino acid of the sequence may be made at the option of the applicant. See 37 CFR 1.822(c)(7) and (d)(4).

Jump to MPEP Source · 37 CFR 1.822(d)Sequence Listing ContentSequence Listing FormatSequence Listing Requirements
StatutoryRequiredAlways
[mpep-2423-03-908eb4425eea252ec6afafc7]
Regions of Contiguous n or Xaa Residues Must Be Single Sequence
Note:
A sequence containing regions of contiguous 'n' or 'Xaa' residues, with exact counts disclosed, must be listed as a single sequence in the Sequence Listing.

In 37 CFR 1.822(e) the procedures for presenting and numbering hybrid and gapped sequences are set forth. A sequence with a gap or gaps shall be presented as a plurality of separate sequences, each having separate sequence identifiers, with the number of separate sequences being equal in number to the number of continuous strings of sequence data. The term “gap” is not intended to embrace a gap or gaps that is/are introduced into the presentation of otherwise continuous sequence information in, e.g., a drawing figure, to show alignments or similarities with other sequences. The “gaps” referred to in this section are gaps representing unknown or undisclosed regions in a sequence between regions that are known or disclosed. On the other hand, a sequence that contains one or more regions of contiguous “n” or “Xaa” residues, wherein the exact number of “n” or “Xaa” residues in each region is disclosed, must be included in the “Sequence Listing” as a single sequence with a single sequence identifier. A sequence disclosed by enumeration of its residues that is constructed as a single continuous sequence from one or more non-contiguous segments of a larger sequence or segments from different sequences must be included in the “Sequence Listing” as a single sequence with a single sequence identifier. A fragment of a larger sequence need not be enumerated by its residues, and may be referred to in the specification, claims or drawings as, e.g., “residues 2 through 33 of SEQ ID NO:12,” assuming that SEQ ID NO:12 has been properly included in the “Sequence Listing”.

Jump to MPEP Source · 37 CFR 1.822(e)Sequence Listing ContentSequence Listing FormatSequence Listing Requirements
StatutoryRequiredAlways
[mpep-2423-03-36aa0d463b510013b82d2d83]
Continuous Sequence Must Be One Identifier
Note:
A sequence constructed from non-contiguous segments must be included in the Sequence Listing as a single sequence with one identifier.

In 37 CFR 1.822(e) the procedures for presenting and numbering hybrid and gapped sequences are set forth. A sequence with a gap or gaps shall be presented as a plurality of separate sequences, each having separate sequence identifiers, with the number of separate sequences being equal in number to the number of continuous strings of sequence data. The term “gap” is not intended to embrace a gap or gaps that is/are introduced into the presentation of otherwise continuous sequence information in, e.g., a drawing figure, to show alignments or similarities with other sequences. The “gaps” referred to in this section are gaps representing unknown or undisclosed regions in a sequence between regions that are known or disclosed. On the other hand, a sequence that contains one or more regions of contiguous “n” or “Xaa” residues, wherein the exact number of “n” or “Xaa” residues in each region is disclosed, must be included in the “Sequence Listing” as a single sequence with a single sequence identifier. A sequence disclosed by enumeration of its residues that is constructed as a single continuous sequence from one or more non-contiguous segments of a larger sequence or segments from different sequences must be included in the “Sequence Listing” as a single sequence with a single sequence identifier. A fragment of a larger sequence need not be enumerated by its residues, and may be referred to in the specification, claims or drawings as, e.g., “residues 2 through 33 of SEQ ID NO:12,” assuming that SEQ ID NO:12 has been properly included in the “Sequence Listing”.

Jump to MPEP Source · 37 CFR 1.822(e)Sequence Listing ContentSequence Listing FormatSequence Listing Requirements
Topic

Sequence Listing Format

4 rules
StatutoryProhibitedAlways
[mpep-2423-03-a48314d380f0340e2926e1eb]
Single Strand Required for Nucleotide Sequences
Note:
Nucleotide sequences must be represented by a single strand, not double stranded, in the Sequence Listing.

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

Jump to MPEP Source · 37 CFR 1.822(c)(5)Sequence Listing FormatSequence Listing RequirementsSequence Listing Content
StatutoryRequiredAlways
[mpep-2423-03-dfed0afac8a91287c7366a36]
Gaps Must Be Separated Into Separate Sequences
Note:
Sequences with gaps must be split into separate sequences, each with its own identifier, to accurately represent known and unknown regions.

In 37 CFR 1.822(e) the procedures for presenting and numbering hybrid and gapped sequences are set forth. A sequence with a gap or gaps shall be presented as a plurality of separate sequences, each having separate sequence identifiers, with the number of separate sequences being equal in number to the number of continuous strings of sequence data. The term “gap” is not intended to embrace a gap or gaps that is/are introduced into the presentation of otherwise continuous sequence information in, e.g., a drawing figure, to show alignments or similarities with other sequences. The “gaps” referred to in this section are gaps representing unknown or undisclosed regions in a sequence between regions that are known or disclosed. On the other hand, a sequence that contains one or more regions of contiguous “n” or “Xaa” residues, wherein the exact number of “n” or “Xaa” residues in each region is disclosed, must be included in the “Sequence Listing” as a single sequence with a single sequence identifier. A sequence disclosed by enumeration of its residues that is constructed as a single continuous sequence from one or more non-contiguous segments of a larger sequence or segments from different sequences must be included in the “Sequence Listing” as a single sequence with a single sequence identifier. A fragment of a larger sequence need not be enumerated by its residues, and may be referred to in the specification, claims or drawings as, e.g., “residues 2 through 33 of SEQ ID NO:12,” assuming that SEQ ID NO:12 has been properly included in the “Sequence Listing”.

Jump to MPEP Source · 37 CFR 1.822(e)Sequence Listing FormatSequence Listing RequirementsFigure Requirements
StatutoryInformativeAlways
[mpep-2423-03-0ff716f76cb818e0026d587f]
Gaps Represent Unknown Regions in Sequence
Note:
Sequences with gaps representing unknown regions must be presented as separate sequences, not including introduced gaps for alignments.

In 37 CFR 1.822(e) the procedures for presenting and numbering hybrid and gapped sequences are set forth. A sequence with a gap or gaps shall be presented as a plurality of separate sequences, each having separate sequence identifiers, with the number of separate sequences being equal in number to the number of continuous strings of sequence data. The term “gap” is not intended to embrace a gap or gaps that is/are introduced into the presentation of otherwise continuous sequence information in, e.g., a drawing figure, to show alignments or similarities with other sequences. The “gaps” referred to in this section are gaps representing unknown or undisclosed regions in a sequence between regions that are known or disclosed. On the other hand, a sequence that contains one or more regions of contiguous “n” or “Xaa” residues, wherein the exact number of “n” or “Xaa” residues in each region is disclosed, must be included in the “Sequence Listing” as a single sequence with a single sequence identifier. A sequence disclosed by enumeration of its residues that is constructed as a single continuous sequence from one or more non-contiguous segments of a larger sequence or segments from different sequences must be included in the “Sequence Listing” as a single sequence with a single sequence identifier. A fragment of a larger sequence need not be enumerated by its residues, and may be referred to in the specification, claims or drawings as, e.g., “residues 2 through 33 of SEQ ID NO:12,” assuming that SEQ ID NO:12 has been properly included in the “Sequence Listing”.

Jump to MPEP Source · 37 CFR 1.822(e)Sequence Listing FormatSequence Listing RequirementsFigure Requirements
StatutoryPermittedAlways
[mpep-2423-03-4a447d2354514278c52713f5]
Fragments May Be Referenced By Identifier
Note:
A fragment of a larger sequence can be referred to by its identifier without enumerating all residues, as long as the full sequence is included in the Sequence Listing.

In 37 CFR 1.822(e) the procedures for presenting and numbering hybrid and gapped sequences are set forth. A sequence with a gap or gaps shall be presented as a plurality of separate sequences, each having separate sequence identifiers, with the number of separate sequences being equal in number to the number of continuous strings of sequence data. The term “gap” is not intended to embrace a gap or gaps that is/are introduced into the presentation of otherwise continuous sequence information in, e.g., a drawing figure, to show alignments or similarities with other sequences. The “gaps” referred to in this section are gaps representing unknown or undisclosed regions in a sequence between regions that are known or disclosed. On the other hand, a sequence that contains one or more regions of contiguous “n” or “Xaa” residues, wherein the exact number of “n” or “Xaa” residues in each region is disclosed, must be included in the “Sequence Listing” as a single sequence with a single sequence identifier. A sequence disclosed by enumeration of its residues that is constructed as a single continuous sequence from one or more non-contiguous segments of a larger sequence or segments from different sequences must be included in the “Sequence Listing” as a single sequence with a single sequence identifier. A fragment of a larger sequence need not be enumerated by its residues, and may be referred to in the specification, claims or drawings as, e.g., “residues 2 through 33 of SEQ ID NO:12,” assuming that SEQ ID NO:12 has been properly included in the “Sequence Listing”.

Jump to MPEP Source · 37 CFR 1.822(e)Sequence Listing FormatPatent Application ContentSequence Listing Requirements
Topic

Figure Requirements

2 rules
StatutoryInformativeAlways
[mpep-2423-03-7f2db907100c1122ce31e53d]
Presentation and Numbering of Hybrid and Gapped Sequences
Note:
The rule outlines how to present and number sequences with gaps or hybrid segments in a patent application.

In 37 CFR 1.822(e) the procedures for presenting and numbering hybrid and gapped sequences are set forth. A sequence with a gap or gaps shall be presented as a plurality of separate sequences, each having separate sequence identifiers, with the number of separate sequences being equal in number to the number of continuous strings of sequence data. The term “gap” is not intended to embrace a gap or gaps that is/are introduced into the presentation of otherwise continuous sequence information in, e.g., a drawing figure, to show alignments or similarities with other sequences. The “gaps” referred to in this section are gaps representing unknown or undisclosed regions in a sequence between regions that are known or disclosed. On the other hand, a sequence that contains one or more regions of contiguous “n” or “Xaa” residues, wherein the exact number of “n” or “Xaa” residues in each region is disclosed, must be included in the “Sequence Listing” as a single sequence with a single sequence identifier. A sequence disclosed by enumeration of its residues that is constructed as a single continuous sequence from one or more non-contiguous segments of a larger sequence or segments from different sequences must be included in the “Sequence Listing” as a single sequence with a single sequence identifier. A fragment of a larger sequence need not be enumerated by its residues, and may be referred to in the specification, claims or drawings as, e.g., “residues 2 through 33 of SEQ ID NO:12,” assuming that SEQ ID NO:12 has been properly included in the “Sequence Listing”.

Jump to MPEP Source · 37 CFR 1.822(e)Figure RequirementsSequence Listing Content
StatutoryInformativeAlways
[mpep-2423-03-757b4f0871106ee4c0fc3d14]
Gaps Must Not Show Alignments
Note:
Gaps in sequences should not be used to show alignments with other sequences but must represent unknown regions between known segments.

In 37 CFR 1.822(e) the procedures for presenting and numbering hybrid and gapped sequences are set forth. A sequence with a gap or gaps shall be presented as a plurality of separate sequences, each having separate sequence identifiers, with the number of separate sequences being equal in number to the number of continuous strings of sequence data. The term “gap” is not intended to embrace a gap or gaps that is/are introduced into the presentation of otherwise continuous sequence information in, e.g., a drawing figure, to show alignments or similarities with other sequences. The “gaps” referred to in this section are gaps representing unknown or undisclosed regions in a sequence between regions that are known or disclosed. On the other hand, a sequence that contains one or more regions of contiguous “n” or “Xaa” residues, wherein the exact number of “n” or “Xaa” residues in each region is disclosed, must be included in the “Sequence Listing” as a single sequence with a single sequence identifier. A sequence disclosed by enumeration of its residues that is constructed as a single continuous sequence from one or more non-contiguous segments of a larger sequence or segments from different sequences must be included in the “Sequence Listing” as a single sequence with a single sequence identifier. A fragment of a larger sequence need not be enumerated by its residues, and may be referred to in the specification, claims or drawings as, e.g., “residues 2 through 33 of SEQ ID NO:12,” assuming that SEQ ID NO:12 has been properly included in the “Sequence Listing”.

Jump to MPEP Source · 37 CFR 1.822(e)Figure RequirementsSequence Listing Format

Citations

Primary topicCitation
Sequence Listing Content
Sequence Listing Format
37 CFR § 1.822(c)(5)
Sequence Listing Content37 CFR § 1.822(c)(6)
Sequence Listing Content37 CFR § 1.822(c)(7)
Sequence Listing Content37 CFR § 1.822(d)
Figure Requirements
Sequence Listing Content
Sequence Listing Format
37 CFR § 1.822(e)
Sequence Listing Content37 CFR § 1.831(b)
Sequence Listing ContentMPEP § 2412

Source Text from USPTO’s MPEP

This is an exact copy of the MPEP from the USPTO. It is here for your reference to see the section in context.

BlueIron Last Updated: 2025-12-31