US Patent 6,794,489: Bremelanotide Claims, Scope, Expiration, and Patent Landscape

US Patent 6,794,489 protects pharmaceutical compositions, purified peptide forms, sexual-response treatment methods, nasal formulations, and nasal-delivery kits containing the cyclic melanocortin peptide now known as bremelanotide, or PT-141. The patent is directed to the peptide Ac-Nle-cyclo(Asp-His-D-Phe-Arg-Trp-Lys)-OH, a cyclic heptapeptide analog of alpha-melanocyte-stimulating hormone.

The patent’s original commercial importance was substantial because it covered the active molecule and multiple administration routes. Its current blocking value is limited because the US patent term has expired. Vyleesi, the FDA-approved bremelanotide product, is now protected primarily by later formulation, manufacturing, delivery, and regulatory exclusivity rights rather than by US Patent 6,794,489 itself.

What drug and peptide does US Patent 6,794,489 cover?

US 6,794,489 covers bremelanotide, also identified as PT-141. The claimed peptide is:

Ac-Nle-cyclo(Asp-His-D-Phe-Arg-Trp-Lys)-OH

The molecule contains:

An N-terminal acetyl group, “Ac”
Norleucine, “Nle”
Histidine
D-phenylalanine
Arginine
Tryptophan
Lysine
A side-chain lactam bridge between Asp and Lys
A free carboxylic acid or pharmaceutically acceptable salt

The Asp-Lys bridge creates the cyclic structure. No separate linker or additional molecular unit is introduced into the ring.

Bremelanotide is a melanocortin receptor agonist. The FDA approved Vyleesi for the treatment of acquired, generalized hypoactive sexual desire disorder in premenopausal women. The approved product is a subcutaneous autoinjector, not a nasal spray. [1]

What are the main claim categories in US 6,794,489?

The claims fall into five functional groups.

Claim group	Claims	Protected subject matter
Composition claims	1-4	Peptide in an aqueous pharmaceutical carrier; cyclic peptide; acetylated peptide; specifically defined bremelanotide
Method-of-use claims	5-12	Stimulating sexual response in mammals, including males and females
Peptide product claims	13-14	Purified or isolated Ac-Nle-cyclo(Asp-His-D-Phe-Arg-Trp-Lys)-OH
Nasal kit claims	15-17	Peptide composition in a nasal device, including a metered 100 µL spray
Salt claims	18	Acetate salt of the peptide

The strongest claims, viewed from a patent-enforcement perspective, are the composition and peptide claims. They do not depend on a particular therapeutic indication or delivery device. Claims 13 and 14 are especially direct because they recite the isolated peptide itself.

What is the scope of independent claim 1?

Claim 1 covers:

A pharmaceutical composition;
Containing the specified cyclic peptide;
In a pharmaceutically acceptable aqueous carrier;
Where the peptide is present as the free acid or a pharmaceutically acceptable salt.

The claim is composition-based. It does not require nasal administration, sexual dysfunction treatment, a particular dosage, a specific concentration, or a specific device.

A product could fall within claim 1 if it contained bremelanotide in an aqueous injectable, nasal, buccal, or other pharmaceutically acceptable formulation, provided the formulation satisfied the claim’s aqueous-carrier limitation.

The claim does not necessarily cover every formulation of bremelanotide. A nonaqueous formulation would present a claim-scope issue. The patent also does not automatically cover every product that merely acts at a melanocortin receptor. The claimed molecule is structurally specific.

Is there a sequence inconsistency in claim 1?

Yes. The supplied version of claim 1 recites:

“Nle-cyclo(-Arg-His-D-Phe-Arg-Trp-Lys)-OH”

Claims 2 and 4 instead identify cyclization through Asp and Lys and recite:

“Ac-Nle-cyclo(-Asp-His-D-Phe-Arg-Trp-Lys)-OH”

Claims 5, 13, and 14 also identify the Asp-containing bremelanotide structure.

The Asp residue is chemically necessary for the stated Asp-Lys side-chain cyclization. The Arg-containing sequence in the supplied claim 1 text is therefore inconsistent with the dependent claims and with the recognized bremelanotide structure. A legal analysis must use the issued patent and its official claim text, including any certificate of correction, rather than an OCR, transcription, or database rendering. The inconsistency should be treated as a claim-construction and validity issue, not silently corrected in an infringement analysis.

What do claims 2 through 4 protect?

Claim 2: side-chain lactam cyclization

Claim 2 requires cyclization through the side chains of Asp and Lys without an additional molecular unit. This narrows the composition to the cyclic lactam structure used in bremelanotide.

The limitation excludes analogs that use:

A separate chemical linker
A disulfide bridge
A polyethylene glycol or other spacer
A ring formed through a different pair of residues
A linear peptide

Claim 3: N-terminal acetylation

Claim 3 requires an acetylated amino terminus. This excludes the corresponding free N-terminal amine unless the doctrine of equivalents could apply.

Claim 4: specific bremelanotide composition

Claim 4 recites the complete acetylated cyclic peptide. It is the principal molecule-specific composition claim in the set.

A generic or follow-on product containing the identical active ingredient would have been exposed to this claim during the patent term, regardless of whether it used a different excipient system or delivery device.

What do claims 5 through 12 protect?

Claims 5 through 12 are method-of-use claims directed to stimulating sexual response.

Claim 5 covers administration of the specified acetylated cyclic peptide in an amount and under conditions effective to stimulate a sexual response. Claims 6 and 7 specify male and female mammals. Claim 8 requires a dose that does not induce emesis or other deleterious side effects.

Claim 10 lists broad routes:

Injection
Mucosal administration
Buccal administration
Oral administration
Dermal administration
Inhalation
Nasal administration

Claims 11 and 12 narrow the nasal route to a metered aqueous-buffer formulation using saline or citrate buffer.

The method claims are broader in route than the later FDA-approved Vyleesi label. They encompass treatment concepts directed to both male and female mammals, while the approved indication is narrower and limited to premenopausal women with acquired, generalized HSDD. [1]

The “without emesis” limitation in claim 8 may create proof issues. In litigation, infringement would require establishing that the administered dose did not induce emesis or other deleterious side effects in the relevant treatment context. The limitation also relates to tolerability and dosing rather than to a structural characteristic of the product.

What do claims 13 and 14 protect?

Claims 13 and 14 cover purified or isolated bremelanotide and its pharmaceutically acceptable salts.

These claims are significant because they are not limited to:

A pharmaceutical carrier
A nasal formulation
A particular dose
A sexual-response indication
A particular patient population
A device

A manufacturer producing the claimed peptide as an active pharmaceutical ingredient could have faced direct product-claim exposure during the patent term. The distinction between “purified” and “isolated” may have affected claim construction, but both claims target the defined molecular entity.

What do claims 15 through 18 protect?

Claims 15 through 17 protect a pharmaceutical kit containing the composition in a nasal-delivery device. Claim 17 narrows the device to a metered spray volume of approximately 100 µL.

Claim 18 covers the acetate salt.

The nasal-kit claims are narrower than claims 1, 4, 13, and 14. They require a device relationship and, for claim 17, a specified approximate spray volume. A nasal product using a different volume could avoid claim 17 while remaining within broader composition or peptide claims, assuming those claims were otherwise valid and enforceable.

The nasal claims are historically important because early bremelanotide development involved intranasal delivery. Vyleesi was ultimately developed and approved as a subcutaneous autoinjector, reducing the commercial relevance of the 100 µL nasal-device limitations to the approved product. [1]

When did US Patent 6,794,489 lose exclusivity?

US 6,794,489 is expired. Its enforceable US patent term ended before the FDA approved Vyleesi in 2019.

The patent issued on September 21, 2004. Under the modern patent-term framework, the relevant term is generally 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment and any applicable patent-term extension. The USPTO patent record and FDA Orange Book records should control the final term calculation. [2, 3]

The patent no longer provides an active US exclusion against generic manufacture, sale, offer for sale, or importation of bremelanotide. A later patent cannot revive the expired claims of US 6,794,489, although later patents can create separate infringement risks.

What is the Orange Book status of bremelanotide?

Vyleesi, manufactured by AMAG Pharmaceuticals at the time of approval and later associated with Palatin Technologies, was approved under NDA 210557. The product contains bremelanotide acetate and is supplied in single-dose autoinjectors for subcutaneous administration. [1]

The Orange Book evaluates listed patents associated with an approved drug application. A listed patent does not establish that every claim is valid or infringed. It identifies patents that the sponsor represented as covering the drug, a method of using the drug, or an approved product characteristic. The status of each listed patent must be checked against the current FDA Orange Book patent listing and patent-term records. [3]

For bremelanotide, the commercially relevant patent estate shifted from the original molecule patent to later patents covering formulations, dosing, delivery systems, and related product configurations.

Which companies have commercial or patent interests in bremelanotide?

Company	Role
Palatin Technologies	Developer and principal owner of the bremelanotide intellectual-property program
AMAG Pharmaceuticals	Commercialization partner for Vyleesi in the United States
Cosette Pharmaceuticals	Acquired AMAG and assumed commercial rights to Vyleesi
Generic manufacturers	Potential ANDA applicants after expiration of the core composition patent and applicable later patents

Palatin and AMAG entered into a commercialization arrangement under which AMAG obtained US commercial rights to Vyleesi. The agreement included milestone and royalty economics reported in company filings. [4, 5]

The commercial structure means that revenue exposure was concentrated in Vyleesi sales rather than in a broad portfolio of approved bremelanotide products. Palatin retained strategic value in the molecule and related intellectual property, while the commercial partner carried launch and distribution responsibilities.

How strong is the patent estate for bremelanotide?

Core molecule protection

The original patent was strong during its enforceable term because claims 4, 13, and 14 directly identified the active peptide. A competing product using the same active ingredient could not readily design around those claims through excipient or device changes.

That strength is now historical because the patent has expired.

Formulation protection

Later patent families may protect:

Aqueous bremelanotide formulations
Concentration ranges
pH and buffering systems
Stabilizers and excipients
Injection-device configurations
Dosing schedules
Reduced adverse-effect regimens

These claims generally provide narrower protection than a molecule claim. Their strength depends on claim construction, written-description support, enablement, anticipation, obviousness, and the exact product configuration.

Method-of-use protection

Method claims directed to HSDD, sexual dysfunction, dosing frequency, or reduction of nausea and vomiting may remain relevant after the core molecule patent expires. Their practical value depends on whether a generic label includes the patented indication or whether induced-infringement evidence can be established.

A generic applicant may seek a “skinny label” excluding patented uses. That strategy does not eliminate all litigation risk where the product is promoted for, or materially used for, the patented indication.

What generic entry risks exist for Vyleesi?

The main generic-entry risks are:

Direct active-ingredient competition. An ANDA applicant can seek approval for bremelanotide acetate after expiration of applicable listed patents and regulatory exclusivities.
Formulation overlap. A generic injectable may use a different formulation and still encounter later composition or concentration patents.
Device overlap. Vyleesi is supplied through a prefilled autoinjector. Device or combination-product claims can create separate risks.
Method-of-use overlap. A label directed to HSDD could implicate method patents even if the active ingredient is no longer protected by the 2004 patent.
Paragraph IV litigation. An ANDA applicant may certify that listed patents are invalid, unenforceable, or not infringed. A Paragraph IV notice can trigger a 30-month FDA approval stay under the Hatch-Waxman framework if the NDA holder files suit within the statutory period. [6]

The expired status of US 6,794,489 removes the principal historical barrier to generic bremelanotide. It does not establish that every later patent has expired or that a proposed product is free of infringement risk.

What patent litigation or settlement issues affect bremelanotide?

US 6,794,489 no longer supports a new Paragraph IV enforcement action because it has expired. Any historical litigation involving that patent would have had to arise during its enforceable term.

Current or future disputes would more likely concern:

Later Orange Book-listed patents
ANDA certifications
Formulation and device patents
Induced infringement of method claims
Patent-term calculations
Patent validity under obviousness or written-description standards
Settlement provisions governing generic launch dates

No settlement concerning an expired patent can extend the patent’s statutory term. A settlement may, however, regulate commercial conduct for a period if supported by separate contractual consideration, subject to antitrust scrutiny.

How does US 6,794,489 compare with later bremelanotide patents?

Issue	US 6,794,489	Later bremelanotide patents
Primary focus	Core peptide, compositions, sexual-response methods, nasal kits	Formulations, injectable delivery, dosing, devices, approved-use methods
Claim breadth	Broad molecule and composition claims plus route-specific methods	Usually narrower, configuration-dependent claims
Approved-product relevance	Covers the active molecule historically; nasal claims do not match Vyleesi’s approved route	More likely to correspond to the marketed injectable product
Current status	Expired	Must be assessed individually by family and jurisdiction
Design-around potential	Low during term for identical peptide	Higher, depending on formulation, device, and dosing limitations
Generic risk	No current blocking effect	Potentially material if later claims remain unexpired

Does US 6,794,489 create biosimilar risk?

No. Bremelanotide is a chemically synthesized peptide drug, not a biologic approved under the Public Health Service Act’s biosimilar pathway.

A competing manufacturer would generally pursue an abbreviated new drug application or another small-molecule drug pathway, depending on the product’s regulatory classification and formulation. Biosimilar concepts such as interchangeability, reference-product exclusivity under the Biologics Price Competition and Innovation Act, and a 351(k) application do not govern ordinary bremelanotide competition. [7]

What is the geographic coverage of US 6,794,489?

The patent provides US rights only. Corresponding international applications may have generated foreign national patents, but each jurisdiction requires separate analysis of:

National-phase filing
Grant status
Patent-term adjustment
Supplementary protection certificate or equivalent extension
Opposition or revocation proceedings
Local claim scope
Local regulatory linkage

Expiration of the US patent does not establish expiration of corresponding European, Canadian, Japanese, or other foreign patents.

Key Takeaways

US 6,794,489 is a foundational bremelanotide patent.
Its central subject matter is Ac-Nle-cyclo(Asp-His-D-Phe-Arg-Trp-Lys)-OH, the peptide known as PT-141 or bremelanotide.
Claims 4, 13, and 14 provide the most direct molecule-level protection.
Claims 5 through 12 cover sexual-response treatment methods, including male and female mammals and multiple administration routes.
Claims 15 through 17 cover nasal-delivery kits, including an approximately 100 µL metered spray.
The supplied version of claim 1 contains a sequence inconsistency involving Arg versus Asp. The issued patent and any certificate of correction control.
The patent is expired and does not currently block US generic manufacture or sale.
Vyleesi’s remaining exclusivity analysis depends on later patents, regulatory exclusivity, formulation claims, device claims, and method-of-use rights.
Bremelanotide is not subject to the biosimilar pathway.
Paragraph IV risk now centers on later Orange Book-listed patents rather than US 6,794,489.

FAQs About US Patent 6,794,489 and Bremelanotide

What is the chemical name of the peptide in US 6,794,489?

The peptide is Ac-Nle-cyclo(Asp-His-D-Phe-Arg-Trp-Lys)-OH, commonly called bremelanotide or PT-141.

Does US 6,794,489 cover Vyleesi’s autoinjector?

The patent’s claims primarily cover the peptide, pharmaceutical compositions, treatment methods, and nasal-delivery kits. Vyleesi’s subcutaneous autoinjector is more directly relevant to later formulation and device patents.

Can a generic sell bremelanotide after US 6,794,489 expired?

Expiration of US 6,794,489 removes that patent as a blocking right. A generic must still address any unexpired listed patents, regulatory exclusivity, product-specific formulation claims, and applicable device or method patents.

Are bremelanotide acetate and bremelanotide free acid both covered?

The claims cover the free acid and pharmaceutically acceptable salts. Claim 18 specifically identifies the acetate salt.

Does the nasal formulation claim cover all nasal bremelanotide products?

No. Claims 11 and 12 require specified features, including a metered aqueous-buffer formulation and saline or citrate buffer. Broader composition or peptide claims could raise separate issues, but claim 17’s approximately 100 µL limitation does not cover every nasal spray volume.

What FDA exclusivity applies to Vyleesi?

Vyleesi received FDA approval under NDA 210557. Its regulatory protection must be analyzed separately from patent protection, including the approval date, any orphan-drug or other exclusivity designation, and the current FDA regulatory record. [1, 3]

References

U.S. Food and Drug Administration. (2019). Vyleesi (bremelanotide injection) prescribing information. FDA.
United States Patent and Trademark Office. (2004). U.S. Patent No. 6,794,489, pharmaceutical compositions and methods involving cyclic melanocortin peptides. USPTO Patent Center.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
Palatin Technologies, Inc. (2017). Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934. U.S. Securities and Exchange Commission.
AMAG Pharmaceuticals, Inc. (2019). Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934. U.S. Securities and Exchange Commission.
Drug Price Competition and Patent Term Restoration Act of 1984, 21 U.S.C. § 355(j).
Biologics Price Competition and Innovation Act of 2009, 42 U.S.C. § 262(k).

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	293453	⤷ Start Trial
Australia	2002322466	⤷ Start Trial
Australia	2005249474	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,794,489

Summary for Patent: 6,794,489