United States Drug Patent 6,133,418: Claim Scope, Exclusivity, Litigation Risk, and Patent Landscape

U.S. Patent No. 6,133,418 claims a defined 36-amino-acid peptide sequence, selected N- and C-terminal modifications, and a pharmaceutical composition containing the acetylated, amidated form. The broadest protection is claim 1. Claim 2 narrows the invention to Ac-YTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWF-NH2. Claim 3 protects compositions containing that specific peptide.

The patent’s commercial value depends on whether the claimed peptide has been developed as a drug, whether the sequence has therapeutic activity that cannot be designed around, and whether related continuation, formulation, manufacturing, or method-of-use patents exist. The three claims supplied do not establish those additional rights.

What does U.S. Patent 6,133,418 claim?

The patent claims a peptide with the following fixed core sequence:

YTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWF

The sequence contains 36 amino acids. The patent uses the single-letter amino-acid code.

Claim	Claimed subject matter	Scope
Claim 1	The 36-residue peptide with defined N- and C-terminal groups	Broadest peptide claim
Claim 2	The same peptide with an acetyl N-terminus and amidated C-terminus	Narrow product claim
Claim 3	Pharmaceutical composition containing the claim 2 peptide	Composition claim

Claim 1 covers the peptide when:

X is an amino group;
X is an acetyl group;
X is a 9-fluorenylmethoxycarbonyl, or Fmoc, group;
X is a hydrophobic group;
Z is a carboxyl group;
Z is an amido group; or
Z is a hydrophobic group.

Claim 2 is limited to the following terminal structure:

Ac-YTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWF-NH2

That form has an acetylated N-terminus and an amidated C-terminus.

How broad is claim 1 of U.S. Patent 6,133,418?

Claim 1 is a sequence-defined genus claim with limited terminal-group variation. Its central limitation is the exact 36-residue peptide sequence. The claim does not cover arbitrary analogs, fragments, substitutions, deletions, insertions, salts, conjugates, or structurally unrelated peptides unless those products fall within the stated X and Z definitions.

The claim has three principal layers:

An exact amino-acid sequence.
Permitted N-terminal modifications.
Permitted C-terminal modifications.

The sequence itself is fixed. The terminal groups are variable, but the wording does not create a broad Markush claim over changes within the 36-residue chain.

N-terminal coverage

The claim expressly covers:

a free amino group;
an acetyl group;
an Fmoc group; and
a hydrophobic group.

The acetylated form is separately recited in claim 2. The Fmoc option is relevant to synthetic intermediates and protected peptide forms. Whether a particular hydrophobic group falls within claim 1 depends on claim construction and the specification’s disclosure of that term.

A peptide with a different N-terminal protecting group, such as Boc, is not literally within the expressly listed alternatives unless the patent’s specification or prosecution history supports a broader construction of “hydrophobic group.” That issue would be fact-dependent.

C-terminal coverage

The claim expressly covers:

a free carboxyl group;
an amido group; and
a hydrophobic group.

The amidated C-terminus is the commercial form specifically selected by claim 2. A peptide ending in a methyl ester, glycolyl group, or other non-amido modification would require separate infringement analysis. It would not automatically fall within the claim.

What does claim 2 protect?

Claim 2 protects one specific terminally modified peptide:

N-acetyl-YTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWF-amide

This is the most commercially important product claim in the supplied set. A product would generally need to contain:

the identical 36-amino-acid sequence;
an acetylated N-terminus; and
an amidated C-terminus.

Claim 2 does not expressly cover sequence variants. A one-amino-acid substitution, deletion, addition, or truncation would create a nonliteral-infringement position, although the doctrine of equivalents could become relevant if the modified product performs substantially the same function in substantially the same way with substantially the same result. The doctrine of equivalents is limited by prosecution history, claim vitiation, and prior-art estoppel. See 35 U.S.C. §§ 271 and 282.

What does claim 3 protect?

Claim 3 covers a pharmaceutical composition comprising:

an effective amount of the claim 2 peptide; and
a pharmaceutically acceptable carrier or excipient.

The claim is not limited to a named dosage form, route of administration, concentration, container, release profile, or excipient. On its face, it can reach solutions, suspensions, lyophilized products, injectable preparations, and other pharmaceutical presentations if they contain the claim 2 peptide and a pharmaceutically acceptable carrier or excipient.

The claim does not independently cover:

the peptide in a nonpharmaceutical research reagent;
a composition containing only a sequence variant;
a composition containing the peptide but no pharmaceutically acceptable carrier or excipient;
a method of treating a disease; or
a manufacturing process.

Those activities could still implicate other claims or other patents not included in the supplied claim set.

How do the claims differ in infringement strength?

Claim 1 is the broadest claim but has the greatest construction exposure because the terms “hydrophobic group” may require interpretation. Claim 2 is narrower but easier to test analytically because the terminal groups are expressly specified. Claim 3 adds a pharmaceutical-composition limitation and therefore may be less useful against an active pharmaceutical ingredient supplier whose product is sold in bulk rather than as a finished dosage form.

Risk category	Claim 1	Claim 2	Claim 3
Exact sequence risk	High	High	High
Terminal-modification coverage	Broad but variable	Narrow and clear	Narrow and clear
Risk from sequence substitution	Generally low absent equivalents	Generally low absent equivalents	Generally low absent equivalents
Risk against active ingredient supplier	High if product form is covered	High for exact acetyl/amidated form	Lower unless supplier sells finished composition
Risk against finished drug product	High	High	High
Formulation specificity	None stated	None stated	Broad, subject to pharmaceutical-composition limitation
Method-of-use coverage	None stated	None stated	None stated

What formulations are protected by U.S. Patent 6,133,418?

Claim 3 is a broad composition claim rather than a detailed formulation claim. It requires a pharmaceutically acceptable carrier or excipient but does not identify a particular formulation technology.

The supplied claims do not expressly protect:

sustained-release formulations;
liposomal delivery;
nanoparticle delivery;
depot injections;
transdermal delivery;
intranasal delivery;
enteric coating;
specific buffers;
stabilizers;
preservatives;
particle sizes;
concentrations; or
device components.

A formulation containing the exact claim 2 peptide could fall within claim 3 even if the formulation uses a carrier not specifically named in the claim. Separate formulation patents could provide stronger protection for a commercial product by claiming a particular concentration, excipient combination, delivery system, stability profile, or dosage regimen.

Does the patent claim a method of use?

No method-of-use claim appears in the supplied claims. The claims do not recite:

treatment of a particular disease;
administration to a patient;
a dosage amount;
a dosing frequency;
a biomarker-defined population;
a therapeutic mechanism; or
a clinical endpoint.

As a result, the supplied claim set does not independently protect clinical use of the peptide. A competitor could face product claims even if it uses the peptide for a different indication, but the patent claims provided do not create a separate use-patent barrier.

Does the patent protect manufacturing methods?

No manufacturing claim appears in the supplied claims. There is no express protection for:

solid-phase peptide synthesis;
recombinant production;
cleavage and deprotection;
terminal acetylation;
C-terminal amidation;
purification;
crystallization;
lyophilization; or
impurity-control procedures.

The Fmoc option in claim 1 identifies one permitted terminal group, but it does not by itself claim an Fmoc synthesis process. A manufacturer could therefore require freedom-to-operate analysis against separate peptide-synthesis, purification, or process patents.

When does U.S. Patent 6,133,418 lose exclusivity?

U.S. Patent No. 6,133,418 issued in 2000. Under the modern U.S. patent-term framework, a utility patent generally expires 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and other statutory adjustments. See 35 U.S.C. § 154.

The issue date alone does not establish the precise expiration date. The enforceable term must be confirmed from the patent’s filing and priority chain, Patent Center records, any terminal disclaimer, and any patent-term adjustment or extension. A patent issued in 2000 would ordinarily have reached the end of its standard term many years ago unless an unusual term adjustment or related right applies.

Any current commercial exclusivity would therefore more likely depend on:

a continuation or divisional patent;
a later formulation patent;
a method-of-use patent;
a manufacturing patent;
regulatory exclusivity; or
trade-secret protection.

What is the Orange Book status of the peptide?

The supplied information does not establish an FDA-approved drug product, NDA number, active ingredient name, sponsor, dosage form, or Orange Book listing. The claims themselves are not evidence of FDA approval or Orange Book status.

If the peptide was never approved under an NDA, the patent would not have an Orange Book listing. If it was approved, only patents that satisfy FDA listing requirements would generally be eligible for listing. Composition, formulation, and method-of-use patents can be relevant, while manufacturing patents ordinarily have different listing treatment. See U.S. Food and Drug Administration, Approved Drug Products with Therapeutic Equivalence Evaluations.

Without an identified approved product, no reliable conclusion can be drawn about:

Orange Book patent listing;
five-year new chemical entity exclusivity;
three-year clinical-investigation exclusivity;
pediatric exclusivity;
reference-listed-drug status; or
a potential Paragraph IV certification.

What Paragraph IV challenges and generic-entry risks exist?

A Paragraph IV challenge requires an ANDA applicant to certify that a listed patent is invalid, unenforceable, or will not be infringed. The supplied claims do not establish an Orange Book-listed drug or an ANDA pathway.

If the peptide were marketed as an approved small-molecule or peptide drug, the main generic-entry strategies would be:

Noninfringement: use a sequence variant, different terminal chemistry, or a product that does not contain the claim 2 form.
Invalidity: challenge anticipation, obviousness, written description, enablement, indefiniteness, or lack of patentable subject matter where applicable.
Regulatory differentiation: pursue a pathway that does not rely on the same listed product or does not require certification against the patent.
Timing challenge: establish that the patent has expired or is unenforceable.

The exact-sequence limitation creates a potentially strong literal-infringement position against an exact-copy peptide. It also creates design-around opportunities because changes anywhere in the 36-residue sequence may avoid literal infringement.

How strong is the patent estate?

The three supplied claims indicate a concentrated product estate rather than a layered pharmaceutical estate.

Strengths

Claim 1 covers multiple terminal forms.
Claim 2 targets a defined acetylated and amidated peptide.
Claim 3 reaches pharmaceutical compositions containing the claim 2 product.
Exact-sequence product claims can be comparatively easy to test through analytical characterization.
The composition claim is not confined to one named excipient or dosage form.

Weaknesses

No method-of-use protection appears.
No manufacturing-process protection appears.
No formulation-specific protection appears.
Sequence substitutions may provide design-around opportunities.
The broad “hydrophobic group” language may generate claim-construction disputes.
The commercial value is highly dependent on the patent’s remaining term and any related family patents.
A single patent family may not protect the full product lifecycle.

On the supplied record, the estate is strongest against an exact-copy peptide product and weaker against modified sequences, alternative terminal chemistry, and products relying on separate delivery technologies.

Which companies are challenging the patent?

No challenger, Paragraph IV notice, district-court action, Federal Circuit appeal, or settlement agreement is identified in the supplied claims. The patent number and claim text alone do not establish active litigation, licensing, or generic challenges.

A complete litigation assessment would require checking:

PACER and district-court dockets;
Federal Circuit decisions;
PTAB proceedings;
FDA Paragraph IV litigation notices;
USPTO Patent Center prosecution records; and
assignment and licensing records.

No litigation or settlement conclusion should be inferred from the existence of the patent.

What geographic coverage does the patent provide?

A U.S. patent provides enforceable rights only in the United States. The claim set does not establish corresponding protection in:

Europe;
Japan;
China;
Canada;
Australia;
South Korea;
India; or
other jurisdictions.

International coverage must be assessed through the patent family. Foreign counterparts may have different claim scope, prosecution history, expiration dates, opposition outcomes, or abandonment status. A U.S. sequence claim does not create global exclusivity.

How does this patent compare with a typical peptide-drug patent estate?

Estate component	U.S. 6,133,418 claims supplied	Typical mature peptide-drug estate
Exact active peptide	Yes	Yes
Terminal chemistry	Yes	Often
Sequence variants	Not apparent	Often claimed separately
Pharmaceutical composition	Yes	Yes
Specific formulation	Not apparent	Often
Method of treatment	Not apparent	Usually
Dosing regimen	Not apparent	Sometimes
Manufacturing process	Not apparent	Often
Device or delivery system	Not apparent	Sometimes
Salt, solvate, or conjugate	Not apparent	Often
Continuation and divisional coverage	Not established	Frequently

The supplied patent is narrower than a fully developed lifecycle estate. Its principal value is the exact peptide and certain terminal forms, not a broad platform covering therapeutic use, formulation, manufacturing, and next-generation analogs.

Key Takeaways

Claim 1 covers the exact 36-amino-acid sequence with specified N- and C-terminal alternatives.
Claim 2 is limited to the acetylated, amidated peptide.
Claim 3 covers pharmaceutical compositions containing an effective amount of the claim 2 peptide.
No method-of-use, formulation-specific, or manufacturing claims appear in the supplied claim set.
Exact-copy products face the highest infringement risk.
Sequence substitutions and alternative terminal groups may create design-around positions.
The patent’s current enforceability depends on its priority chain, term adjustments, and related family rights.
The supplied information does not establish FDA approval, Orange Book listing, Paragraph IV litigation, licensing, settlement, or active commercial exclusivity.
International protection requires separate patent-family analysis.

FAQs About U.S. Patent 6,133,418

Does claim 1 cover a peptide with one substituted amino acid?

Not literally, based on the supplied wording. Claim 1 recites the identified 36-residue sequence. A substituted sequence would require a doctrine-of-equivalents analysis or coverage under a separate claim.

Does claim 3 cover a vial containing the peptide?

It may, if the vial contains the claim 2 peptide in a pharmaceutical composition with a pharmaceutically acceptable carrier or excipient. The vial itself is not separately claimed.

Does an Fmoc-protected peptide fall within claim 2?

No. Claim 2 requires an acetyl group at X and an amido group at Z. An Fmoc-protected form falls within claim 1 only if it otherwise satisfies the sequence and C-terminal limitations.

Can a competitor sell the peptide for research use?

Claim 1 is a product claim and does not depend on therapeutic use. Noncommercial research exemptions are narrow under U.S. law. Commercial manufacture, sale, or use requires a separate infringement analysis under 35 U.S.C. § 271.

Does the patent block a different peptide with the same therapeutic mechanism?

No, not on the supplied claims. The claims are directed to a specific peptide sequence and specified terminal forms, not to a biological mechanism or therapeutic target generally.

Are biosimilars relevant to this patent?

Usually not in the conventional sense. A biosimilar pathway applies to biological reference products under the Public Health Service Act. A synthetic peptide may instead implicate an abbreviated application or another FDA pathway, depending on its regulatory classification, molecular structure, and reference product.

References

U.S. Patent No. 6,133,418. (2000). United States Patent and Trademark Office.
35 U.S.C. § 154. Patent term.
35 U.S.C. § 271. Infringement of patent.
35 U.S.C. § 282. Presumption of validity; defenses.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
Leahy-Smith America Invents Act, Pub. L. No. 112-29, 125 Stat. 284 (2011).

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0774971	⤷ Start Trial	SPC/GB05/026	United Kingdom	⤷ Start Trial
European Patent Office	0774971	⤷ Start Trial	91166	Luxembourg	⤷ Start Trial
European Patent Office	0774971	⤷ Start Trial	300192	Netherlands	⤷ Start Trial
European Patent Office	0774971	⤷ Start Trial	CA 2005 00042	Denmark	⤷ Start Trial
European Patent Office	0774971	⤷ Start Trial	C00774971/01	Switzerland	⤷ Start Trial
European Patent Office	0774971	⤷ Start Trial	SPC014/2005	Ireland	⤷ Start Trial
European Patent Office	0774971	⤷ Start Trial	05C0018	France	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,133,418

Summary for Patent: 6,133,418