United States Patent 10,251,894: Scope, Claims, Expiration and Brexanolone Patent Landscape

U.S. Patent No. 10,251,894 protects intravenous treatment of postpartum depression using a composition containing allopregnanolone and sulfobutylether-beta-cyclodextrin salt. The patent is method-of-use focused, not a broad compound patent. Its nominal expiration date is April 8, 2036, subject to any applicable patent-term adjustment or terminal-disclaimer limitations. The claims are directed to the clinical use of the intravenous formulation marketed as Zulresso, rather than to every formulation or use of allopregnanolone.

What does U.S. Patent 10,251,894 cover?

Patent 10,251,894 covers a method of treating postpartum depression by intravenous administration of a composition containing two required components:

Allopregnanolone.
Sulfobutylether-beta-cyclodextrin salt.

Claim 1 is the principal claim. Claims 2 and 3 narrow the method by specifying a human subject and the presence of a buffer.

Claim	Scope
1	Treating postpartum depression by administering an effective amount of an allopregnanolone and sulfobutylether-beta-cyclodextrin salt composition intravenously
2	Claim 1 limited to a human subject
3	Claim 1 limited to a composition that also contains a buffer

The patent does not require a particular dosage, infusion rate, treatment duration, concentration, pH, buffer identity or manufacturing process in the issued claims provided. Those limitations may appear in the specification, prosecution history or related patents, but they are not express limitations of the three claims supplied.

How broad is claim 1 of Patent 10,251,894?

Claim 1 has meaningful therapeutic breadth but limited structural breadth.

The claim uses the transitional term "comprising." That term generally permits the composition to contain additional ingredients beyond allopregnanolone and sulfobutylether-beta-cyclodextrin salt. A formulation with water, a buffer, tonicity agents, pH adjusters or other excipients could fall within the claim if it satisfies the remaining limitations.

The claim also uses "an effective amount," which is a functional treatment limitation. The composition need not be defined by a fixed dose in the claim. The relevant question is whether the amount administered is effective to treat postpartum depression under the applicable claim-construction and infringement standards.

The principal restrictions are:

The indication must be postpartum depression.
The composition must contain allopregnanolone.
The composition must contain sulfobutylether-beta-cyclodextrin salt.
Administration must be intravenous.
The treatment must involve a subject in need thereof.

A product containing allopregnanolone but administered orally, intranasally, subcutaneously or intramuscularly would not literally satisfy the intravenous limitation. A composition using a different solubilizer instead of sulfobutylether-beta-cyclodextrin salt would present a stronger non-infringement position, subject to equivalents analysis.

What formulation does Patent 10,251,894 protect?

The claims protect an intravenous allopregnanolone formulation that uses sulfobutylether-beta-cyclodextrin salt as a formulation component. This excipient is commonly used to improve the aqueous solubility and delivery of poorly water-soluble active ingredients.

The patent does not, based on the claims provided, require:

A specific allopregnanolone concentration.
A defined allopregnanolone-to-cyclodextrin ratio.
A particular buffer.
A particular pH.
A particular infusion period.
A specific commercial container or administration set.
A particular manufacturing process.
A specific brand or trade name.

Claim 3 adds a buffer but does not identify its chemical composition. Because claim 3 depends from claim 1, it requires all limitations of claim 1 plus the buffer limitation.

The formulation language creates a potential design-around path. A competing intravenous product that uses allopregnanolone with a non-cyclodextrin solubilizer may avoid literal infringement. The commercial and regulatory feasibility of that approach would depend on achieving adequate solubility, stability, compatibility and clinical performance.

Does Patent 10,251,894 cover Zulresso?

Yes. The claim set is directed to the core therapeutic use of intravenous brexanolone, the active ingredient in Zulresso. Brexanolone is the pharmaceutical formulation of allopregnanolone used for postpartum depression. The FDA approved Zulresso on March 19, 2019, as an intravenous treatment for postpartum depression in adults.[1]

The approved product is administered as a continuous intravenous infusion over 60 hours. The labeled treatment is weight-based and is delivered in a certified healthcare setting because of risks including excessive sedation and sudden loss of consciousness.[2]

The patent does not protect the Zulresso trademark. It protects a method of treatment that may be practiced using the product.

When does U.S. Patent 10,251,894 expire?

The patent’s nominal twenty-year term is calculated from the relevant nonprovisional filing date of April 8, 2016. On that basis, the projected expiration date is April 8, 2036.

Event	Date
Earliest claimed priority	April 9, 2015
U.S. filing date	April 8, 2016
Patent grant	April 9, 2019
Nominal patent expiration	April 8, 2036
FDA approval of Zulresso	March 19, 2019
Five-year NCE exclusivity	March 19, 2024
Seven-year orphan-drug exclusivity	March 19, 2026

The priority date does not ordinarily determine the twenty-year patent term. The term generally runs from the earliest effective U.S. nonprovisional filing date, subject to statutory adjustments under 35 U.S.C. §§ 154 and 156. Patent-term extension under § 156 is potentially important for an FDA-regulated product, although the available term must be confirmed from the USPTO and FDA records before relying on a final date.[3]

What is the FDA exclusivity status of Zulresso?

Zulresso received new chemical entity exclusivity and orphan-drug exclusivity.

Exclusivity	Status and effect
New chemical entity exclusivity	Five years from March 19, 2019, ending March 19, 2024
Orphan-drug exclusivity	Seven years from March 19, 2019, generally ending March 19, 2026
Patent protection under 10,251,894	Nominally through April 8, 2036

NCE exclusivity blocked submission of an ANDA or 505(b)(2) application for the same active moiety for five years, subject to the statutory Paragraph IV exception. Orphan exclusivity separately restricts FDA approval of the same drug for the same orphan indication during the seven-year period, subject to statutory exceptions.[4]

The expiration of NCE exclusivity does not eliminate patent protection. A generic applicant could file an ANDA after the relevant statutory period, but approval could remain blocked by an unexpired listed patent or by orphan exclusivity.

What is the Orange Book status of Patent 10,251,894?

Zulresso is an FDA-approved small-molecule drug, so its relevant patent listings are evaluated under the FDA Orange Book system rather than the Purple Book biologics system. Patent 10,251,894 is associated with the Zulresso patent estate and is directed to the approved postpartum-depression use.[5]

An Orange Book listing does not establish that every claim is valid or infringed. It gives the patent regulatory significance because an ANDA applicant must address the listed patent through one of the statutory certification mechanisms.

The relevant certifications are:

Paragraph I: no patent information has been submitted.
Paragraph II: the patent has expired.
Paragraph III: the applicant will wait until patent expiration.
Paragraph IV: the patent is invalid, unenforceable or will not be infringed.

For a listed method-of-use patent, an ANDA applicant may seek a section viii statement and carve out the patented indication if the remaining label supports a lawful non-infringing use. That strategy is difficult where the branded product’s principal or only approved use is the patented indication.

Have companies filed Paragraph IV challenges against Zulresso?

No publicly established, high-profile Paragraph IV litigation involving Patent 10,251,894 is identified in the supplied record. A definitive litigation conclusion requires current review of FDA Paragraph IV notices, Orange Book updates and federal court dockets.

The absence of known litigation does not mean the patent is immune from challenge. A generic applicant could challenge the patent by asserting that:

The claims are obvious over prior allopregnanolone formulations and postpartum-depression treatment data.
The claims lack adequate written description or enablement.
The composition does not contain the claimed cyclodextrin salt.
The proposed product is not administered intravenously.
The proposed label excludes postpartum depression.
The patent is unenforceable because of prosecution or disclosure conduct.

The strongest infringement issue for an ANDA applicant would likely be the combination of the active ingredient, excipient and intravenous route. A product that reproduces the Zulresso formulation and indication would face a more direct infringement risk than a formulation using a different solubilization system or a label that lawfully omits postpartum depression.

What other patents cover brexanolone and Zulresso?

Patent 10,251,894 is one component of the broader Zulresso estate. The landscape can be divided into four categories.

Method-of-use patents

These cover treatment of postpartum depression using allopregnanolone or brexanolone. Patent 10,251,894 is the key example in the supplied claim set.

Method patents may differ by:

Patient population.
Treatment severity.
Administration route.
Dose or infusion schedule.
Treatment duration.
Clinical response criteria.
Use in women with or without psychotic features.

Formulation patents

Formulation patents may claim:

Allopregnanolone with sulfobutylether-beta-cyclodextrin.
Specific concentrations.
Buffer systems.
pH ranges.
Stability profiles.
Infusion-ready compositions.
Container or packaging configurations.

These patents can create additional barriers even if a competitor avoids the claims of Patent 10,251,894.

Manufacturing patents

Manufacturing claims may cover:

Synthesis of allopregnanolone.
Purification and impurity control.
Sterile filtration.
Aseptic filling.
Preparation of the cyclodextrin complex.
Control of degradation products.

Manufacturing patents are particularly relevant where the active ingredient is difficult to produce at commercial pharmaceutical quality or where the formulation requires narrow stability controls.

Compound and intermediate patents

Earlier patents may claim allopregnanolone itself, steroid intermediates, neuroactive steroid analogues or processes for making the active ingredient. A basic compound patent would ordinarily expire earlier than the later method and formulation patents.

How strong is the patent estate for brexanolone?

The estate is strongest against a competitor that copies the approved Zulresso product and seeks approval for the same postpartum-depression indication. Patent 10,251,894 reaches the combination of the active ingredient, the specified cyclodextrin salt and intravenous administration.

Its principal weaknesses are structural:

It is not a composition claim standing alone.
It does not cover all allopregnanolone products.
It does not cover every route of administration.
It requires the specified therapeutic indication.
It does not expressly recite a fixed dose or concentration.
It may be vulnerable to an alternative-solubilizer formulation.

The practical strength of a method claim also depends on who performs the claimed steps. Intravenous administration ordinarily occurs through coordinated conduct by the healthcare provider and patient. A generic applicant could face induced-infringement allegations if its product labeling encourages the patented use.

Is there biosimilar risk for Zulresso?

No. Zulresso is a small-molecule drug, not a biologic. A competitor would not file a biosimilar application under section 351(k) or rely on the Purple Book pathway.

The principal regulatory routes are:

Section 505(j) ANDA for a therapeutically equivalent generic.
Section 505(b)(2) application for a product relying partly on existing FDA findings but differing in formulation, route, dosage or other characteristics.
A full NDA for a materially different product.

Because Zulresso is an injectable product with a specialized administration protocol, a competing product may face chemistry, manufacturing and controls requirements that exceed those for a conventional oral generic. The formulation must demonstrate appropriate sterility, stability, compatibility and delivery performance.

What generic launch scenarios exist?

Scenario 1: Same formulation and same indication

This is the highest-risk scenario for a generic applicant. The applicant would likely need a Paragraph IV strategy against the listed patents and could face patent litigation and a thirty-month stay if suit is timely filed.

Scenario 2: Same active ingredient, different excipient system

A non-cyclodextrin formulation could avoid literal infringement of Patent 10,251,894. The applicant would still need to demonstrate equivalent or clinically acceptable performance and avoid other formulation patents.

Scenario 3: Intravenous allopregnanolone with a carved-out label

A label excluding postpartum depression could reduce method-of-use exposure. The strategy would be commercially difficult if postpartum depression is the principal viable market for the product.

Scenario 4: Alternative route or dosage form

An oral, intranasal or other route would likely avoid the express intravenous limitation. It would not be a direct generic substitute for Zulresso and would require a different clinical and regulatory development program.

Scenario 5: 505(b)(2) product

A 505(b)(2) applicant could pursue a modified formulation or administration regimen. Patent risk would remain, but the applicant could potentially develop a product outside the literal scope of the issued claims.

How does Zulresso compare with zuranolone?

Zulresso and Zurzuvae have different active ingredients, routes and commercial patent profiles.

Attribute	Zulresso	Zurzuvae
Active ingredient	Brexanolone, an allopregnanolone formulation	Zuranolone
Route	Intravenous infusion	Oral capsule
FDA indication	Postpartum depression	Postpartum depression
Administration	Continuous 60-hour infusion	Short oral treatment course
Sponsor history	Sage Therapeutics, later acquired by Biogen	Sage Therapeutics and Biogen
Biosimilar pathway	Not applicable	Not applicable
Primary competitive issue	Complex infusion and formulation	Oral convenience and newer patent estate

Zuranolone reduces the commercial value of an intravenous-only method patent because it provides an alternative neuroactive-steroid treatment without the 60-hour infusion requirement. It does not, however, eliminate Patent 10,251,894’s legal relevance to a competing intravenous brexanolone product.

What licensing and ownership issues affect the patent estate?

Sage Therapeutics developed brexanolone and Zulresso and was acquired by Biogen in 2023. The acquisition transferred Sage’s commercial and intellectual-property interests to Biogen, subject to transaction terms and any pre-existing licenses or encumbrances.[6]

Ownership analysis should distinguish:

Patent title shown in USPTO assignment records.
NDA holder status.
Commercial marketing rights.
Inventor or university-originated technology licenses.
Security interests and collateral assignments.
Any field-of-use restrictions.

A change in corporate ownership does not itself alter patent scope or expiration. It can affect enforcement authority, licensing strategy and the likelihood of settlement with a generic challenger.

Key Takeaways

Patent 10,251,894 is a method-of-treatment patent for intravenous allopregnanolone in postpartum depression.
The claimed composition must contain allopregnanolone and sulfobutylether-beta-cyclodextrin salt.
Claim 3 adds a buffer; claim 2 limits the subject to a human.
The claims do not expressly require a specific dose, concentration, pH, buffer or infusion duration.
The nominal expiration date is April 8, 2036, subject to patent-term adjustments and other statutory considerations.
Zulresso received FDA approval on March 19, 2019, with five-year NCE exclusivity and seven-year orphan-drug exclusivity.
Zulresso is not a biologic and has no biosimilar pathway.
The highest generic risk would come from a product copying the intravenous formulation and postpartum-depression indication.
A different solubilizer, alternative route or lawful indication carve-out could reduce literal infringement risk.
Zuranolone creates commercial competition but does not directly invalidate or avoid the patent.

FAQs

Can a generic use allopregnanolone without infringing Patent 10,251,894?

Yes, potentially. The patent does not claim all uses of allopregnanolone. Infringement risk depends on the formulation, route, excipient and indication.

Does the patent cover oral allopregnanolone?

No, not literally under the supplied claims. Claim 1 expressly requires intravenous administration.

Does the patent cover a formulation using hydroxypropyl-beta-cyclodextrin instead of sulfobutylether-beta-cyclodextrin salt?

Likely not literally, because the claimed composition requires sulfobutylether-beta-cyclodextrin salt. Equivalents arguments could still be asserted depending on the facts and prosecution history.

Can a company market an intravenous allopregnanolone product for another indication?

Potentially, but the product could face other patents, regulatory restrictions and induced-infringement allegations if its labeling or promotional conduct encourages postpartum-depression treatment.

Is Patent 10,251,894 enough by itself to block a generic launch?

Not necessarily. Launch risk depends on all Orange Book-listed patents, FDA exclusivity, the proposed label, formulation composition, patent-term status and the outcome of any Paragraph IV litigation.

References

U.S. Food and Drug Administration. (2019). FDA approves first treatment for postpartum depression. https://www.fda.gov
U.S. Food and Drug Administration. (2023). Zulresso (brexanolone) prescribing information.
United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term extension provisions. https://www.uspto.gov
U.S. Food and Drug Administration. (n.d.). Orange Book: Approved drug products with therapeutic equivalence evaluations. https://www.accessdata.fda.gov/scripts/cder/ob/
United States Patent and Trademark Office. (2019). U.S. Patent No. 10,251,894.
Biogen Inc. (2023). Biogen completes acquisition of Sage Therapeutics. https://investors.biogen.com

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Sage Therap Supernus	ZULRESSO	brexanolone	SOLUTION;INTRAVENOUS	211371-001	Jun 17, 2019		DISCN	Yes	No	10,251,894	⤷ Start Trial				METHOD OF TREATING POSTPARTUM DEPRESSION	⤷ 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	2013352141	⤷ Start Trial
Australia	2018204865	⤷ Start Trial
Australia	2020201919	⤷ Start Trial
Australia	2022202943	⤷ Start Trial
Canada	2892811	⤷ Start Trial
Denmark	2925327	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,251,894

Which drugs does patent 10,251,894 protect, and when does it expire?

Summary for Patent: 10,251,894