US Patent 8,227,471: Flibanserin HSDD Claims, Expiration, Orange Book Status, and Generic Risk

US Patent 8,227,471 protects methods of treating hypoactive sexual desire disorder, or HSDD, with flibanserin or specified pharmaceutically acceptable acid-addition salts. Its broadest claim covers administration of a therapeutically effective amount to a patient with HSDD. Dependent claims narrow the protection by patient sex, daily dose, dosage-unit strength, and salt form.

The patent is a method-of-use patent, not a composition-of-matter patent. It does not independently control manufacture of flibanserin, possession of the active ingredient, or every formulation containing flibanserin. The principal commercial relevance is its potential use against an ANDA applicant seeking approval for a flibanserin product labeled for HSDD.

What does US Patent 8,227,471 protect?

US Patent 8,227,471 protects administration of flibanserin to treat HSDD. The patent's independent claim is broad:

A method of treating a patient having HSDD by administering a therapeutically effective amount of flibanserin or a pharmaceutically acceptable acid-addition salt.

The claim does not limit the patient to women. Claim 2 expressly covers male patients, while claim 1 is drafted broadly enough to encompass a patient of either sex.

The patent covers:

Claim category	Claims	Scope
Core therapeutic method	1	Flibanserin treatment of HSDD
Male patient	2	Treatment of HSDD in a male patient
Daily dose ranges	3-5	0.1-400 mg, 1-300 mg, and 2-200 mg per day
Dosage-unit ranges	6-7	0.01-100 mg and 0.1-50 mg per unit
Specific dosage units	8-11	150 mg, 100 mg, 80 mg, and 50 mg
Acid-addition salts	12	Listed salt classes
Individual salts	13-24	Succinic, hydrobromic, acetic, fumaric, maleic, methanesulfonic, lactic, phosphoric, hydrochloric, sulfuric, tartaric, and citric acid salts

The central commercial claim is claim 1. If claim 1 is valid and enforceable, a narrower dependent claim is not required for infringement when a competing product is administered under a label that directs treatment of HSDD with flibanserin.

How should claim 1 be interpreted?

Claim 1 has four principal elements:

A patient must have HSDD.
The accused activity must involve treatment of that condition.
Flibanserin or a pharmaceutically acceptable acid-addition salt must be administered.
The amount administered must be therapeutically effective.

The claim does not require:

A particular sex, unless claim 2 is asserted.
A specific daily dose.
A particular dosage form.
A particular salt.
Administration at bedtime.
Treatment of premenopausal women.
A specific duration of treatment.
A named brand such as Addyi.

The phrase "therapeutically effective amount" is the principal functional limitation. An infringement analysis would likely focus on the product label, prescribing information, clinical instructions, and the intended use communicated by the ANDA applicant or commercial manufacturer.

A generic applicant could attempt to avoid infringement by pursuing a label that omits HSDD treatment. That strategy would be commercially difficult for a product whose approved use and market identity are tied to HSDD. Under the Hatch-Waxman framework, the relevant issue would be whether the proposed labeling directs, recommends, or encourages the patented use.

What are the dose and dosage-unit limitations?

Claims 3 through 11 create overlapping dose coverage.

Claim	Dose limitation
3	0.1-400 mg per day
4	1-300 mg per day
5	2-200 mg per day
6	0.01-100 mg per dosage unit
7	0.1-50 mg per dosage unit
8	150 mg per dosage unit
9	100 mg per dosage unit
10	80 mg per dosage unit
11	50 mg per dosage unit

The approved Addyi regimen is 100 mg taken orally at bedtime. That regimen falls within claim 3, claim 4, and claim 5, and the 100 mg tablet corresponds directly to claim 9. The approved dose therefore maps onto both broad daily-dose claims and the specific 100 mg dosage-unit claim [2].

The dose claims are not mutually exclusive. A 100 mg tablet administered once daily may satisfy:

Claim 1;
Claim 3;
Claim 4;
Claim 5;
Claim 6;
Claim 7; and
Claim 9.

The precise infringement analysis would depend on how "amount administered" and "dosage unit" are construed and on the facts of the accused product's labeling and use.

What salt forms are protected by US Patent 8,227,471?

Claim 12 lists 12 acid classes. Claims 13 through 24 separately claim each salt category.

The claimed salts are:

Claim	Salt
13	Succinic acid
14	Hydrobromic acid
15	Acetic acid
16	Fumaric acid
17	Maleic acid
18	Methanesulfonic acid
19	Lactic acid
20	Phosphoric acid
21	Hydrochloric acid
22	Sulfuric acid
23	Tartaric acid
24	Citric acid

The salt claims broaden the patent beyond a specific marketed solid form. A competing product using a different salt may avoid claims 12 through 24, but it would not necessarily avoid claim 1. Claim 1 covers flibanserin itself and any pharmaceutically acceptable acid-addition salt.

The salt claims do not appear to be composition claims that independently protect the isolated salt as a chemical product. They are limitations within a therapeutic-use method. The commercial consequence is that a salt-selection strategy does not automatically remove method-of-use risk.

When does US Patent 8,227,471 expire?

The patent claims priority to a 2006 filing and issued in 2012. Its ordinary US patent term is generally measured from the earliest effective nonprovisional filing date, subject to patent-term adjustment and any applicable regulatory extension.

Public patent records identify an expected expiration in September 2027, subject to the official USPTO term calculation and any applicable adjustment. The relevant commercial date is therefore approximately September 2027, rather than the 20th anniversary of the 2012 issue date [1].

Event	Date or period
Earliest identified priority	September 8, 2006
US patent application	Filed before issuance
Patent issued	June 24, 2012
Expected ordinary expiration	Approximately September 8, 2027
Product regulatory exclusivity	Separate from patent term
Commercial relevance	Potential HSDD method-of-use barrier through 2027

Patent expiration must be distinguished from FDA regulatory exclusivity. FDA exclusivity may expire before or after a patent, and expiration of regulatory exclusivity does not invalidate an unexpired patent.

What is the FDA and Orange Book status of flibanserin?

The FDA approved Addyi, containing flibanserin, in August 2015 for the treatment of acquired, generalized HSDD in premenopausal women [3]. The approval was granted under NDA 022526.

The approved labeling specifies:

100 mg orally once daily at bedtime.
Discontinuation after eight weeks if there is no improvement.
Use for acquired, generalized HSDD.
No indication for enhancing sexual performance.
Contraindications and warnings involving hepatic impairment and certain CYP3A4 inhibitors.
Clinically important interaction considerations involving alcohol and other central nervous system depressants, as addressed in the applicable labeling.

The FDA indication is narrower than claim 1 in several respects. The patent covers a patient with HSDD without limiting the patient to premenopausal women. The FDA label, by contrast, limits the approved indication to premenopausal women.

The Orange Book is the key source for NDA-linked patent and exclusivity listings. A current Orange Book review should distinguish:

Patents listed against NDA 022526;
Their use codes;
Any expiration dates;
Any pediatric exclusivity appended to the listed patent term; and
Approved ANDAs and their labeling restrictions [4].

US Patent 8,227,471 is the principal patent relevant to the claims supplied here. The patent's method-of-use character means that an ANDA applicant's Paragraph IV certification and proposed labeling are central to the risk analysis.

What Paragraph IV risks exist for a flibanserin generic?

An ANDA applicant seeking approval before the patent expiration date would generally need to address each Orange Book-listed patent through one of the statutory certifications. For a listed method-of-use patent, the applicant could pursue:

A Paragraph III certification, accepting approval only after patent expiration;
A Paragraph IV certification, asserting that the patent is invalid, unenforceable, or not infringed; or
A section viii statement carving out the patented use, if the remaining approved uses can be marketed without the protected indication.

For flibanserin, a section viii strategy would have limited value if the applicant seeks approval for the same HSDD indication covered by the Addyi label. The patent's claim 1 tracks the approved therapeutic use closely. A carve-out that removes HSDD treatment would materially reduce the commercial value of a flibanserin product.

A Paragraph IV challenge would likely focus on:

Lack of novelty based on earlier flibanserin use disclosures;
Obviousness based on prior pharmacology and sexual-dysfunction treatment references;
Written-description or enablement issues relating to HSDD treatment;
Indefiniteness of "therapeutically effective amount";
Claim construction concerning the scope of HSDD; and
Noninfringement based on labeling, patient population, dose, or salt form.

Because the patent claims a therapeutic use rather than a new chemical entity, validity risk is generally more concentrated in obviousness and written-description analysis than in chemical identity.

What patent litigation affects flibanserin?

The supplied patent was issued to protect the HSDD use of flibanserin. The most important litigation trigger would be a Paragraph IV notice from an ANDA applicant targeting NDA 022526.

A complete current litigation assessment requires matching:

The current Orange Book patent listing;
Any Paragraph IV notice;
The NDA holder's complaint under 21 U.S.C. § 271(e)(2);
The filing date of the complaint;
Any 30-month stay;
Claim-construction rulings;
Settlement terms; and
Final judgment or dismissal.

The core statutory litigation risk is clear. If the patent is listed for the HSDD use and an ANDA applicant seeks approval for that use before expiration, the NDA holder could assert induced infringement or infringement based on the proposed labeling under the Hatch-Waxman framework [5].

No conclusion about a current settlement, court judgment, or active Paragraph IV case should be drawn solely from the issued patent. Patent ownership, NDA sponsorship, and litigation control may have changed since issuance.

How strong is the patent estate for flibanserin?

The estate represented by US Patent 8,227,471 is commercially meaningful but structurally narrower than a composition-of-matter estate.

Strengths

Claim 1 directly covers the approved therapeutic concept.
The approved 100 mg dose falls within multiple dependent claims.
The patent covers both flibanserin and pharmaceutically acceptable acid-addition salts.
The method claim does not depend on a particular branded formulation.
The claim set includes both broad and narrow fallback positions.

Limitations

The patent does not broadly claim flibanserin as a chemical compound.
It does not necessarily block all manufacture or sale of flibanserin outside the patented use.
The male-patient claim is commercially disconnected from the current FDA indication.
Dose and salt claims are subordinate to claim 1 and may not provide meaningful protection if claim 1 is invalid.
A carefully drafted label carve-out could reduce infringement exposure if a non-HSDD use were independently approvable.
The patent has a finite remaining term ending approximately in 2027.

The estate is strongest against a generic seeking the same indication, same 100 mg dosage, and same HSDD labeling. It is weaker against off-label supply, non-HSDD indications, alternative labeled uses, or products marketed after patent expiration.

What generic launch scenarios exist?

Scenario	Likely timing	Commercial effect
Paragraph III certification	After patent expiration	Delayed but lower litigation risk
Paragraph IV certification, no successful challenge	After settlement or patent expiry	Potential early entry subject to terms
Paragraph IV litigation victory for generic	Before expiration	Earlier launch possible
Section viii carve-out	Before expiration if legally viable	Approval may be limited and commercially weak
At-risk launch	Before final resolution	Exposure to damages and injunctive relief
Post-expiration launch	After approximately September 2027	Method-of-use patent no longer blocks the claimed use

The most credible generic strategy is a Paragraph IV challenge directed at claim validity or a negotiated entry date. A section viii carve-out is less attractive because HSDD is the principal approved use.

What manufacturing and formulation barriers remain?

US Patent 8,227,471 does not appear, from the supplied claims, to claim:

A specific tablet-excipient combination;
A particular dissolution profile;
A controlled-release system;
A manufacturing process;
A polymorph;
A crystalline form;
A particle-size distribution;
A packaging configuration; or
A specific impurity-control process.

Those barriers would have to be assessed through separate patents and regulatory records. The supplied claims reach the therapeutic method, not the complete product-development and manufacturing platform.

A generic could therefore avoid the salt-dependent claims by using a different pharmaceutical form, but it would still face claim 1 if its labeling directs flibanserin treatment for HSDD.

How does this patent compare with a composition patent?

Issue	US Patent 8,227,471	Composition-of-matter patent
Protected subject matter	HSDD treatment method	Chemical compound or defined composition
Label importance	Very high	Relevant but not always decisive
Manufacture outside indication	May be possible	Usually blocked during term
Salt substitution	May avoid narrower salt claims	Depends on claim drafting
Generic design-around	Label, indication, dose, or use	Usually more difficult
Commercial leverage	Strongest for approved indication	Broadest across uses and products
Expiration impact	Directly affects branded indication	Directly affects product supply

The patent provides use-based protection rather than full molecule exclusivity. Its practical value depends on whether a competitor must market flibanserin for HSDD to achieve meaningful commercial penetration.

Does the patent cover male HSDD treatment?

Yes. Claim 2 specifically covers treatment of HSDD in a male patient. Claim 1 is broader and is not expressly limited by sex.

The FDA approval for Addyi is for premenopausal women, not men. Therefore, claim 2 has limited current label-based commercial relevance unless a product is approved or marketed for male HSDD. Its presence may still matter in an off-label use or future-indication analysis.

Key Takeaways

US Patent 8,227,471 is a method-of-use patent covering flibanserin treatment of HSDD.
Claim 1 is the commercially dominant claim.
The patent covers patients generally, while claim 2 specifically covers male patients.
Claims 3 through 11 cover broad dose ranges and specific dosage units, including 100 mg.
Claims 12 through 24 cover flibanserin acid-addition salts, including hydrochloride, hydrobromide, succinate, fumarate, and citrate forms.
The FDA-approved Addyi regimen of 100 mg at bedtime maps directly onto multiple claims.
The patent's expected expiration is approximately September 2027, subject to the official patent-term calculation.
The patent does not itself provide broad composition, formulation, polymorph, or manufacturing protection.
A generic seeking the HSDD indication would face the greatest Paragraph IV and induced-infringement risk.
A section viii carve-out may be commercially unattractive because HSDD is the principal approved use.
The strength of the estate is concentrated in the overlap between the patent's broad method claim and the FDA-approved Addyi label.

FAQs About US Patent 8,227,471 and Flibanserin Exclusivity

Is US Patent 8,227,471 a formulation patent?

No. The claims are directed to methods of treating HSDD with flibanserin. The claims recite doses, dosage units, and salts, but they do not claim a specific tablet formulation or excipient system.

Does US Patent 8,227,471 cover Addyi?

It potentially covers use of Addyi for the patented HSDD indication. The patent does not claim the Addyi trademark or every physical tablet as such. Its relevance arises from administering flibanserin to treat HSDD.

Can a generic sell flibanserin before patent expiration?

Potentially, but the launch strategy would depend on the Orange Book listing, certification, labeling, litigation outcome, and any settlement. A generic seeking the same HSDD indication would face the highest risk.

Does changing the flibanserin salt avoid the patent?

Not necessarily. Claims 1 and 12 are drafted broadly enough to cover flibanserin and pharmaceutically acceptable acid-addition salts. A different salt may avoid a specific dependent salt claim while remaining within claim 1.

Is male HSDD an FDA-approved use of Addyi?

No. Addyi was approved for acquired, generalized HSDD in premenopausal women. The patent's male-patient claim is broader than the current FDA-approved indication.

Sources

United States Patent and Trademark Office. (2012). US Patent No. 8,227,471 B2: Use of flibanserin for treating hypoactive sexual desire disorder.
U.S. Food and Drug Administration. (2023). Addyi (flibanserin) prescribing information. Sprout Pharmaceuticals, Inc.
U.S. Food and Drug Administration. (2015, August 18). FDA approves Addyi to treat acquired, generalized hypoactive sexual desire disorder in premenopausal women.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Congress. (1984). Drug Price Competition and Patent Term Restoration Act, Pub. L. No. 98-417, codified in relevant part at 21 U.S.C. § 355 and 35 U.S.C. § 271(e).

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
	01125020	Oct 20, 2001

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	037109	⤷ Start Trial
Argentina	077480	⤷ Start Trial
Austria	327757	⤷ Start Trial
Australia	2002333894	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 8,227,471

Summary for Patent: 8,227,471