Peptide therapeutics – from GLP-1 agonists to peptide hormones, antimicrobial peptides and cyclic peptide scaffolds – sit at an awkward intersection of patent practice: they’re chemical compounds, but they’re also defined by an amino acid sequence, which brings in a whole layer of formatting rules that small-molecule patents never have to deal with. Getting a peptide patent application right means handling two distinct problems well: the mandatory sequence listing (a formatting and compliance exercise) and the claim strategy around a sequence-based invention (a substantive, high-stakes drafting exercise). Getting either one wrong can cost an applicant priority, scope, or the application entirely.
Part 1: The Sequence Listing
When a Sequence Listing Is Required
Under 37 CFR § 1.821(a), any patent application that discloses a nucleotide or amino acid sequence “by enumeration of its residues” – which covers essentially any peptide claimed or described by its actual sequence – must include a formal Sequence Listing as a separate part of the specification. For peptides, this threshold is easy to trigger: even disclosing a short signal peptide, a linker, or a single preferred embodiment sequence in the specification can require a compliant listing, not just the sequences that appear in the claims.
ST.25 vs. ST.26: Know Which Standard Applies
This is the single most consequential formatting issue in peptide patent drafting today, because the two standards are not interchangeable and there was no transition period:
- Applications filed on or before June 30, 2022 must continue to use the older WIPO ST.25 format (37 CFR §§ 1.821–1.825) for the life of that application – including in continuations and divisionals that carry the same effective filing date. A listing that was compliant under ST.25 cannot simply be converted to ST.26 partway through prosecution.
- Applications filed on or after July 1, 2022 must comply with WIPO ST.26 (37 CFR §§ 1.831–1.835), which requires the sequence listing to be submitted as a single XML file rather than the plain-text (.txt) format used under ST.25. For PCT national phase applications, it’s the international filing date – not the U.S. national phase entry date – that determines which standard governs.
Practical implications for peptide applicants:
- Amino acid representation changed. ST.26 narrows how ambiguous or non-standard residues can be represented; for example, symbols that were used more loosely under ST.25 are now tied strictly to the 22 naturally occurring amino acids, which means legacy sequences drafted under old conventions may need careful review – not a mechanical find-and-replace – when preparing a new ST.26-era application that references them.
- File format and filing channel. ST.26 listings must be filed electronically in XML through the USPTO’s Patent Center; paper or plain-text submissions are not acceptable for post-July-2022 filings.
- Priority chains spanning the transition date. If your peptide program has a priority application filed before July 1, 2022 and you’re now filing continuations, PCT applications, or foreign counterparts after that date, you need to track which format each new filing requires – and confirm the sequences carried forward remain fully consistent with what was originally disclosed, since a listing that inadvertently narrows or alters a sequence during reformatting can create a written description or priority problem.
Common Sequence Listing Pitfalls
- Sequences described only in prose, not enumerated as a formal sequence. If your specification describes a peptide’s sequence in running text (e.g., in a table or paragraph) but doesn’t also present it as part of a compliant Sequence Listing, you risk a formality objection – and worse, if the listing is added later, a possible new matter problem.
- Inconsistency between the listing and the claims. The sequence recited in a claim must exactly match the corresponding entry in the Sequence Listing, including any indicated modifications (D-amino acids, non-natural residues, cyclization, N- or C-terminal modifications). Discrepancies are a common source of formal USPTO objections and can create ambiguity about claim scope.
- Failing to capture modified/non-standard residues correctly. Many therapeutic peptides include non-natural amino acids, PEGylation sites, stapled or cyclic backbones, or D-isomers. These need to be captured using the correct feature annotations in the listing (particularly critical under ST.26’s stricter XML schema) – generic “linear peptide” treatment of a cyclic or heavily modified peptide risks an inaccurate disclosure.
- Late-filed or missing listings. A missing sequence listing at filing is a defect that must be corrected and correcting it after the fact – if it introduces sequence information not clearly present in the original disclosure – can trigger new matter objections. Prepare the listing in parallel with the specification, not as a last step before filing.
Part 2: Claim Drafting Strategy for Therapeutic Peptides
Decide What You’re Actually Claiming
Peptide claims commonly take several forms and most robust applications combine more than one:
- Composition-of-matter claims reciting the exact sequence (e.g., “a peptide comprising the amino acid sequence of SEQ ID NO: 1”) – the narrowest but most defensible claim type.
- Sequence identity / homology claims (e.g., “a peptide having at least 90% sequence identity to SEQ ID NO: 1 and retaining [specified activity]”) – broader, capturing variants and analogs, but exposed to enablement and written description challenges (see below).
- Functionally defined claims (e.g., “a peptide that binds receptor X with an affinity of Y and elicits Z activity”) – broadest in scope, but the highest-risk claim type post-Amgen v. Sanofi.
- Structural feature claims – cyclic backbone, specific linker chemistry, PEGylation pattern, or stapled helix architecture, which can be valuable independent of a specific sequence and may survive even if a sequence-based claim is designed around.
- Method-of-treatment and formulation claims – dosing regimens, routes of administration, or specific pharmaceutical formulations, which can extend commercially meaningful protection well beyond the core composition claim and are often less vulnerable to sequence-based design-arounds.
- Salt, prodrug and conjugate claims – pharmaceutically acceptable salts, PEG-conjugates, or Fc-fusion versions of the core peptide, which are frequently the actual marketed form of the drug.
Enablement and Written Description: The Post-Amgen Reality
The Supreme Court’s 2023 decision in Amgen v. Sanofi significantly raised the bar for broad functional claims across biologics generally and its logic applies squarely to peptides: a claim that covers a broad genus defined largely by function (e.g., “any peptide that binds and activates receptor X”) must be enabled across the full scope of the claim, not just for the specific embodiments actually made and tested. Practical drafting responses:
- Anchor broad claims with a meaningful number of working examples spanning the structural diversity you want to claim and where possible, show a structure-function rationale (e.g., a defined pharmacophore or conserved binding motif) rather than relying on a single lead sequence plus an open-ended functional limitation.
- Use tiered claim sets. Pair a narrow, unquestionably enabled composition claim (the exact clinical candidate sequence) with progressively broader dependent or related claims (percent identity ranges, defined substitution positions, functional limitations) so that if the broadest claims are challenged, the narrower claims remain a fallback.
- Support percent-identity claims with actual variant data. A “90% identical” claim is much stronger if the specification includes data (or at least a clear, art-recognized rationale) showing that variants across that range retain the claimed activity – not just the single exemplified sequence.
- Be deliberate about which positions can vary. Where you know certain residues are conserved for activity (e.g., a receptor-binding motif) and others are tolerant of substitution, claim language that specifies conserved positions explicitly while allowing defined substitutions elsewhere is both more defensible and often more commercially useful than a blanket percent-identity claim.
Subject Matter Eligibility for Natural and Near-Natural Peptides
Many therapeutic peptides are analogs of naturally occurring hormones or signaling peptides (insulin analogs, GLP-1 analogs, calcitonin analogs). Under the Myriad/Mayo framework, claims to an unmodified naturally occurring sequence can face Section 101 eligibility objections as a product of nature. Drafting responses:
- Claim the synthetic or modified analog with structural differences from the wild-type sequence (substitutions, non-natural residues, truncations, or conjugation) that are clearly stated in the claim, rather than the natural sequence itself.
- Where the invention includes an isolated or purified form with markedly different characteristics from the natural counterpart (a different formulation, stability profile, or pharmacokinetic property), make those differences explicit in the specification so they can support an eligibility argument if raised in examination.
Obviousness and Obviousness-Type Double Patenting
Peptide analog programs frequently generate large families of related sequences and applications, which raises two recurring issues:
- Obviousness over close natural or prior art analogs. Where a claimed peptide differs from a known peptide by only a few conservative substitutions, expect an obviousness rejection; be prepared to show unexpected results (improved potency, half-life, selectivity, or reduced immunogenicity) tied specifically to the claimed modifications.
- Obviousness-type double patenting (ODP) across a peptide family. Filing multiple applications directed to closely related analogs, salts, or formulations of the same core peptide invites ODP rejections between family members. Terminal disclaimers are the standard fix, but should be planned deliberately as part of a portfolio strategy – particularly important post-In re Cellect, which affects how patent term adjustment interacts with ODP and terminal disclaimers across a family with different expiration dates.
Practical Drafting Checklist
- Confirm which sequence listing standard (ST.25 or ST.26) governs based on the actual effective filing date and prepare the listing in the correct format and file type from the outset.
- Cross-check every sequence recited in the claims against the Sequence Listing for exact consistency, including modified residues, before filing.
- Draft a tiered claim set: exact-sequence composition claims, supported percent-identity or defined-substitution claims, structural feature claims and method/formulation claims.
- Build the specification’s working examples and data to support the full scope of any functional or percent-identity claim language – don’t rely on a single lead compound to carry a broad genus claim.
- Explicitly recite structural or functional differences from any naturally occurring counterpart to preempt Section 101 product-of-nature objections.
- Anticipate obviousness rejections against close analogs by developing comparative data on potency, stability, selectivity, or immunogenicity.
- Map out the family’s terminal disclaimer and ODP strategy across related applications before they’re filed, not after a rejection arrives.