US Patent 9,352,013: Bremelanotide Formulation, Scope, Expiration, and Patent Landscape

US Patent No. 9,352,013 protects clinical use of subcutaneously administered bremelanotide formulations designed to limit systemic exposure and reduce adverse effects, particularly nausea, flushing, headache, vomiting, hypertension, and cardiovascular changes. The strongest commercial overlap is with Vyleesi, the 1.75 mg subcutaneous bremelanotide product approved by the FDA for acquired, generalized hypoactive sexual desire disorder in premenopausal women.

The patent is primarily a method-of-treatment patent. It does not broadly claim bremelanotide as a molecule, and it does not create product-only infringement from manufacture or possession alone. Infringement generally requires use of the claimed composition in the claimed patient population, by the claimed route, with pharmacokinetic results meeting the specified limits.

What does US Patent 9,352,013 cover?

US 9,352,013 covers methods of treating female sexual dysfunction by subcutaneous administration of bremelanotide in a formulation containing glycerin, with the dose selected to produce a peak plasma concentration within 60 minutes of no more than 120 ng/mL, or no more than 100 ng/mL under dependent claims.[1]

The patent has two principal independent claims:

Claim	Core formulation requirement	Core pharmacokinetic requirement	Principal limitation
1	Bremelanotide acetate, 6%-12% w/w acetic acid, and 2.5% w/v glycerin in aqueous solution	Cmax within 60 minutes no more than 120 ng/mL	Treat female sexual dysfunction and reduce side effects
13	Bremelanotide or a pharmaceutically acceptable salt and 2.5% w/v glycerin	Cmax within 60 minutes no more than 120 ng/mL	Composition need not expressly include acetic acid in the independent claim

Claim 13 is materially broader in formulation terms than claim 1. It does not require the acetate salt, excess acetic acid, or an aqueous solution in the independent claim. It does require 2.5% glycerin and the same subcutaneous administration, therapeutic purpose, patient context, and pharmacokinetic result.

What are the required elements of claim 1?

A party practicing claim 1 would need to satisfy each of the following elements:

The patient is female.
The patient has been diagnosed with female sexual dysfunction.
The patient anticipates sexual activity.
Bremelanotide is administered by subcutaneous injection.
The formulation is an aqueous solution.
Bremelanotide is present as the acetate salt.
The solution contains 6%-12% w/w acetic acid.
The solution contains 2.5% w/v glycerin.
The dose produces a bremelanotide peak plasma concentration of no more than 120 ng/mL within 60 minutes.
The treatment reduces undesirable side effects associated with bremelanotide.

Dependent claims add narrower limitations involving:

A Cmax of no more than 100 ng/mL.
A net bremelanotide dose of 1.25-1.75 mg.
Specified adverse effects.
A formulation consisting essentially of bremelanotide acetate, excess acetic acid, water, glycerin, and optional pH-adjusting agents.
pH 5.0.
Hydrochloric acid or sodium hydroxide as pH-adjusting agents.
Premenopausal patients.
Less than 30% coefficient of variation for peak plasma concentration.
Lower pharmacokinetic variability than intranasal administration.

How broad is independent claim 13?

Claim 13 creates the principal infringement risk because it removes several express formulation restrictions found in claim 1.

It requires:

Subcutaneous injection.
A composition comprising bremelanotide or a pharmaceutically acceptable salt.
2.5% w/v glycerin.
Administration to a female patient diagnosed with female sexual dysfunction and anticipating sexual activity.
A dose producing a Cmax no higher than 120 ng/mL within 60 minutes.
Treatment of the dysfunction while reducing undesirable side effects.

The word "comprising" generally permits additional formulation ingredients. A competing formulation could therefore contain buffers, preservatives, stabilizers, surfactants, or other excipients and still fall within claim 13 if it retains bremelanotide, 2.5% glycerin, and the claimed clinical pharmacokinetic result.

Claim 13 is less dependent on the exact Vyleesi formulation than claim 1. A non-acetate salt could potentially fall within claim 13, provided it is a pharmaceutically acceptable salt and the other claim limitations are met.

What formulations are protected by US 9,352,013?

The patent protects two formulation categories.

Acetate formulation claims

Claims 1 and 5-8 target an aqueous bremelanotide acetate formulation containing:

6%-12% w/w acetic acid;
2.5% w/v glycerin;
water;
optional pH-adjusting agents; and
in narrower claims, pH 5.0.

The use of excess acetic acid is technically important. It distinguishes the claimed formulation from a simple aqueous solution of bremelanotide acetate and may support solubility, stability, or delivery characteristics.

Broader glycerin-containing compositions

Claims 13-24 cover compositions containing bremelanotide or a pharmaceutically acceptable salt with 2.5% w/v glycerin. The dependent claims restore some of the limitations associated with claim 1, including acetic acid concentration, pH, and acetate salt.

The specification and claims link the formulation to a controlled exposure profile rather than merely to chemical composition. That creates a potential dispute over whether a formulation falls within the claims based on actual patient pharmacokinetic data, population averages, or expected product performance.

How does the patent protect Vyleesi?

Vyleesi contains bremelanotide acetate and is administered subcutaneously through a prefilled autoinjector. The FDA-approved dose is 1.75 mg administered at least 45 minutes before anticipated sexual activity. The product is limited to one dose in a 24-hour period and no more than eight doses per month.[2]

The approved product has the principal characteristics recited in the asserted claims:

Vyleesi characteristic	Relevance to US 9,352,013
Bremelanotide acetate	Directly relevant to claim 1 and dependent claims
Subcutaneous administration	Required by claims 1 and 13
1.75 mg dose	Within the 1.25-1.75 mg range in claims 4 and 15
Glycerin-containing formulation	Directly relevant to claim 13 and dependent claims
Premenopausal patient population	Recited in claims 9 and 21
Administration before anticipated sexual activity	Expressly recited in claims 1 and 13
Reduced exposure and adverse-effect objective	Central functional limitation

The FDA indication is narrower than the broad phrase "female sexual dysfunction." Vyleesi is approved for acquired, generalized hypoactive sexual desire disorder in premenopausal women, not for every form of female sexual dysfunction.[2] That distinction affects induced-infringement analysis, labeling strategy, and the scope of any generic carve-out.

What is the patent expiration date for US 9,352,013?

The patent issued on May 31, 2016, from an application claiming priority to a 2012 filing. Its nominal patent expiration is November 1, 2033, based on the earliest applicable nonprovisional priority date and the 20-year patent term.[1]

Event	Date
Earliest priority date	November 1, 2012
US patent grant	May 31, 2016
Nominal expiration	November 1, 2033
FDA approval of Vyleesi	June 21, 2019

The practical exclusivity date may be affected by patent-term adjustment, patent-term extension, terminal disclaimers, or later Orange Book treatment. The patent's commercial significance is driven less by the basic peptide molecule and more by the formulation, delivery route, patient population, and exposure-control limitations.

What is the Orange Book status of US 9,352,013?

US 9,352,013 has been associated with the Vyleesi regulatory patent estate and is relevant to FDA-listed patent protection for the approved product.[2] The Orange Book question is separate from the patent's validity and enforceability:

Orange Book listing identifies patents submitted by the NDA holder.
Listing does not establish that every claim is valid.
A listed method-of-use patent may be addressed through a Paragraph IV certification or a section viii statement, depending on the generic labeling strategy.
A formulation or drug-product patent generally creates a more direct ANDA certification issue than a narrowly drafted method-of-use patent.

The commercial impact depends on whether the FDA's approved labeling requires the generic applicant to practice the patented method. If the patented method covers the entire labeled use, a full label carve-out may be difficult. If the generic applicant can omit the patented use while retaining an unpatented use, a section viii route may be available.

When does Vyleesi lose exclusivity?

FDA regulatory exclusivity and patent exclusivity have different timelines.

FDA exclusivity

Vyleesi received approval in 2019. The product's principal New Chemical Entity exclusivity period ended in 2024, subject to the exact FDA exclusivity record. Regulatory exclusivity does not determine the expiration of US 9,352,013.

Patent exclusivity

The principal patent term associated with US 9,352,013 runs nominally to November 2033. Other patents may expire earlier or later depending on their priority dates, patent-term adjustment, and claim subject matter.

The commercial entry date for an ANDA applicant could occur before November 2033 if:

the applicant defeats the patent;
the patent is found invalid or unenforceable;
the applicant obtains a non-infringing label;
the listed patent is not enforceable against the proposed product or use; or
the patent owner settles on an earlier entry date.

What Paragraph IV challenges affect bremelanotide?

The claims create several potential Paragraph IV attack points.

Anticipation

An accused prior-art reference would need to disclose all elements of the asserted claim, including the combination of:

subcutaneous bremelanotide;
glycerin at 2.5% w/v;
the relevant salt or acetic acid concentration;
female sexual dysfunction treatment;
administration before anticipated sexual activity; and
the specified Cmax within 60 minutes.

Earlier bremelanotide development programs involving intranasal delivery, other injection formulations, or different exposure levels may disclose individual elements without anticipating the full combination.

Obviousness

Obviousness is the more substantial validity issue. A challenger could combine prior art relating to:

bremelanotide for female sexual dysfunction;
subcutaneous delivery;
glycerin as a formulation excipient;
acetic acid and acetate salt formulations;
dose-ranging studies;
nausea and blood-pressure adverse effects; and
pharmacokinetic exposure reduction.

The patent's best defense would be evidence that the claimed formulation and exposure ceiling produced an unexpected reduction in adverse effects while preserving efficacy. The claims are most vulnerable if the Cmax limitation is treated as an inherent or routine result of selecting a known dose and route.

Indefiniteness and written description

The terms "reducing side effects," "undesirable side effects," and "in an amount sufficient to result in" may generate indefiniteness and written-description disputes. The claim does not specify a required percentage reduction in adverse effects. It also does not define one universal pharmacokinetic sampling protocol for determining Cmax within 60 minutes.

The patent owner can argue that the specification and clinical data provide objective boundaries. A challenger can argue that infringement depends on variable patient results and that the claims fail to identify a reproducible threshold for side-effect reduction.

How strong is the patent estate for bremelanotide?

US 9,352,013 is strongest against a product that closely follows the Vyleesi formulation and labeled use. Its protection is weaker against materially different products or uses.

Risk factor	Assessment
Product overlap with Vyleesi	High
Protection of the bremelanotide molecule itself	Low
Protection of subcutaneous use	High within the claimed patient and PK context
Protection of glycerin-containing formulations	Moderate to high
Dependence on clinical pharmacokinetics	High
Risk from alternative salts	Lower under claim 1; remains under claim 13
Risk from non-glycerin formulations	Lower
Risk from different therapeutic indications	Potentially lower
Biosimilar relevance	Not applicable

The patent is commercially important because it aligns formulation, route, dose, patient population, and administration timing with the approved product. Its main weakness is that several claims depend on measured clinical outcomes rather than only on structural formulation features.

What patent litigation and licensing issues affect Vyleesi?

Palatin Technologies developed bremelanotide and entered into a North American commercialization arrangement with AMAG Pharmaceuticals. AMAG later became part of Covis Pharma, and Vyleesi commercialization rights subsequently moved through the product's commercial ownership chain.[3][4]

The principal legal issues for a generic entrant would likely involve:

validity of the pharmacokinetic limitations;
whether 2.5% w/v glycerin is present in the proposed formulation;
whether a proposed salt falls within claim 13;
whether the generic label induces use for the claimed female sexual dysfunction population;
whether a section viii carve-out can remove the patented use;
whether the ANDA product's actual Cmax meets the claimed threshold; and
whether the claims are enforceable against physician-prescribed use.

The claim record supplied does not identify a specific Paragraph IV complaint, settlement agreement, or final infringement judgment involving US 9,352,013. The patent itself does not establish that a generic challenge has been filed or resolved.

What generic launch scenarios exist?

Scenario 1: Full-label ANDA launch after patent expiry

A generic applicant includes the Vyleesi indication and certifies to the listed patents. This route creates the clearest litigation exposure but preserves the commercial value of the approved indication.

Scenario 2: Paragraph IV challenge

The applicant argues that the claims are invalid, unenforceable, or not infringed. The strongest arguments would focus on obviousness, the clinical-result limitations, and the lack of objective boundaries for "reducing undesirable side effects."

Scenario 3: Section viii carve-out

The applicant removes the patented use from labeling while retaining an indication that does not require practice of the claimed method. This strategy may be difficult if the only commercially meaningful use is the Vyleesi indication.

Scenario 4: Formulation design-around

A competitor could alter one or more of the following:

glycerin concentration;
acetic acid concentration;
salt form;
pH;
route of administration;
dose;
delivery device; or
patient or indication language.

A design-around must still avoid claim 13, which has broader formulation language than claim 1.

Is there biosimilar risk for bremelanotide?

Biosimilar risk is not the relevant pathway. Bremelanotide is a synthetic peptide drug, not an FDA-approved biologic subject to the standard 351(k) biosimilar framework. A competing manufacturer would generally pursue an abbreviated or full drug application pathway applicable to the product's regulatory classification, rather than a biosimilar application.

The relevant competitive threats are therefore generic or follow-on peptide products, alternative bremelanotide formulations, and competing therapies for hypoactive sexual desire disorder.

How does US 9,352,013 compare with earlier bremelanotide patents?

Earlier bremelanotide patents generally addressed the peptide, melanocortin receptor agonism, or broad therapeutic uses. Those rights are less commercially important as they approach or pass expiration.

US 9,352,013 is later-generation protection. It focuses on:

a particular administration route;
a defined excipient concentration;
exposure control;
reduced adverse effects;
pharmacokinetic variability;
premenopausal patients; and
use before anticipated sexual activity.

This structure shifts the patent risk from molecule ownership to product-use implementation. A competitor may avoid older composition-of-matter rights but still face US 9,352,013 if it uses a formulation and label materially aligned with Vyleesi.

Key Takeaways

US 9,352,013 is a method-of-treatment patent, not a broad composition-of-matter patent.
Claim 1 is narrow and requires bremelanotide acetate, 6%-12% acetic acid, 2.5% glycerin, an aqueous solution, and a Cmax no higher than 120 ng/mL within 60 minutes.
Claim 13 is broader because it covers bremelanotide or a pharmaceutically acceptable salt with 2.5% glycerin and does not expressly require acetic acid in the independent claim.
The patent closely maps to Vyleesi's 1.75 mg subcutaneous product and approved use in premenopausal women.
The nominal expiration date is November 1, 2033.
The main validity risks are obviousness, indefiniteness, written description, and the evidentiary basis for the pharmacokinetic and side-effect limitations.
A generic applicant's principal options are Paragraph IV litigation, a section viii label carve-out, or a formulation and labeling design-around.
Biosimilar analysis is not applicable; the relevant competitors are generic or follow-on bremelanotide products.
The patent's commercial strength is high for a Vyleesi-like product and lower for materially different salts, excipient systems, routes, doses, or indications.

FAQs About US Patent 9,352,013

Does US 9,352,013 cover bremelanotide itself?

No. The patent covers specified methods of using bremelanotide formulations. It does not broadly claim the bremelanotide molecule independent of formulation, route, patient, and treatment limitations.

Can a non-acetate bremelanotide salt avoid the patent?

It may avoid claim 1, which requires the acetate salt, but claim 13 covers bremelanotide or a pharmaceutically acceptable salt. A non-acetate salt must be analyzed against the full set of claim 13 limitations.

Does a product infringe merely because it contains 2.5% glycerin?

No. The claims require additional elements, including subcutaneous administration, treatment of the specified condition, the patient and sexual-activity context, and the claimed pharmacokinetic result.

Can a generic omit the female sexual dysfunction indication?

Potentially, depending on the remaining label and actual use. Removing the patented indication may support a section viii strategy, but the analysis depends on whether the remaining labeling or marketing still encourages use covered by the patent.

Is the 2033 date the guaranteed generic entry date?

No. It is the nominal expiration date for US 9,352,013. Earlier entry could result from invalidity, noninfringement, a successful label carve-out, settlement, or another legal resolution.

References

United States Patent No. 9,352,013. (2016). Methods and compositions for treating female sexual dysfunction. U.S. Patent and Trademark Office.
U.S. Food and Drug Administration. (2019). Vyleesi (bremelanotide) injection prescribing information. FDA.
Palatin Technologies, Inc. (2017). Palatin announces North American license agreement with AMAG Pharmaceuticals for bremelanotide. Company press release.
AMAG Pharmaceuticals, Inc. (2020). Corporate transaction and product portfolio announcements concerning Vyleesi. Company disclosures.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Cosette	VYLEESI (AUTOINJECTOR)	bremelanotide acetate	SOLUTION;SUBCUTANEOUS	210557-001	Jun 21, 2019		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial				TREATMENT OF HYPOACTIVE SEXUAL DESIRE DISORDER (HSDD)	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2013337341	⤷ Start Trial
Brazil	112015009936	⤷ Start Trial
Canada	2890081	⤷ Start Trial
China	104755094	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,352,013

Which drugs does patent 9,352,013 protect, and when does it expire?

Summary for Patent: 9,352,013