US Patent 10,912,814: Scope, Claim Construction, Expiration and Vosevi Patent Landscape

US Patent 10,912,814 protects a specific fixed-dose tablet combining 400 mg of crystalline sofosbuvir with 100 mg each of substantially amorphous velpatasvir and voxilaprevir, where both latter ingredients are contained in copovidone-based solid dispersions. The claims are formulation-specific, not broad claims to the three active ingredients alone. A competing product would face the greatest literal-infringement risk if it uses the Vosevi strength, copovidone matrices, and the claimed solid-state characteristics.

What does US Patent 10,912,814 claim?

The patent claims a pharmaceutical dosage form and a tablet containing three hepatitis C direct-acting antivirals:

Active ingredient	Claimed amount	Claimed physical form	Delivery structure
Sofosbuvir	About 400 mg	Substantially crystalline	Present as the active ingredient, not required to be in a solid dispersion
Velpatasvir	About 100 mg	Substantially amorphous	About 200 mg solid dispersion in copovidone
Voxilaprevir	About 100 mg	Substantially amorphous	About 200 mg solid dispersion in copovidone

Claim 1 covers a “pharmaceutical dosage form.” Claim 2 covers a tablet. Both claims require the same active ingredients, approximately the same quantities, the same solid-state distinctions, and copovidone as the polymer for both velpatasvir and voxilaprevir dispersions. Claim 2 is narrower because it expressly limits the dosage form to a tablet.

The patent therefore targets the formulation architecture associated with Vosevi, rather than the individual active compounds.

How should the independent claims be construed?

“About 400 mg,” “about 200 mg,” and “about 100 mg”

The term “about” creates numerical flexibility, but it does not eliminate the requirement for the claimed dosage design. The construction would normally depend on the specification, examples, analytical tolerances, manufacturing standards, and prosecution history.

A product containing 400 mg of sofosbuvir and 100 mg each of velpatasvir and voxilaprevir presents the clearest literal-infringement scenario. A materially different strength, such as a pediatric or reduced-dose product, would require a separate analysis of the scope of “about.”

“Substantially crystalline” sofosbuvir

The sofosbuvir limitation requires a predominantly crystalline form or a crystal structure meeting the patent’s specification-based standard. A formulation using fully amorphous sofosbuvir would not satisfy this limitation literally.

The term does not necessarily require every sofosbuvir molecule to be crystalline. The relevant question is the degree and characterization of crystallinity under the patent’s disclosure and analytical methods.

“Substantially amorphous” velpatasvir and voxilaprevir

The claims require both velpatasvir and voxilaprevir to be substantially amorphous. This limitation is important because the patent does not merely claim the presence of the two active ingredients. It claims their physical-state control within polymer matrices.

A formulation in which either active is predominantly crystalline, or in which the solid-state profile falls outside the patent’s disclosed standard, could avoid literal infringement. The commercial importance of this limitation is high because amorphous dispersions are commonly used to improve dissolution and bioavailability for poorly water-soluble compounds.

“Solid dispersion”

Each 100 mg dose of velpatasvir and voxilaprevir must be present in a separate approximately 200 mg solid dispersion. The claim language indicates that the active is dispersed in a polymer matrix, rather than simply blended with a polymer as an excipient.

A formulation in which the active is molecularly dissolved, separately granulated, or physically mixed without the claimed dispersion structure would create a non-infringement position. The result would depend on the actual manufacturing process and final dosage-form characterization.

Copovidone as polymer A and polymer B

The claims expressly require polymer A and polymer B to be copovidone. Copovidone is also known as vinylpyrrolidone-vinyl acetate copolymer and is used as a solid-dispersion carrier.

The wording does not require polymer A and polymer B to be different materials. Because both are required to be copovidone, a single copovidone grade used for both dispersions can satisfy the limitation. A formulation using hypromellose acetate succinate, hydroxypropyl cellulose, povidone, or another polymer would present a stronger design-around position, subject to equivalents analysis.

What is the relationship between Claims 1 and 2?

Claim 1 is broader in dosage-form category. It covers a pharmaceutical dosage form, which could potentially include a tablet, capsule, sachet, granule, or another oral form if the remaining limitations are met.

Claim 2 is narrower because it requires a tablet. The claims otherwise track each other closely:

Limitation	Claim 1	Claim 2
400 mg sofosbuvir	Yes	Yes
Crystalline sofosbuvir	Yes	Yes
100 mg velpatasvir	Yes	Yes
Amorphous velpatasvir	Yes	Yes
Velpatasvir solid dispersion	Yes	Yes
100 mg voxilaprevir	Yes	Yes
Amorphous voxilaprevir	Yes	Yes
Voxilaprevir solid dispersion	Yes	Yes
Copovidone for both matrices	Yes	Yes
Tablet requirement	No	Yes

The practical result is that a Vosevi-type tablet would be analyzed under both claims, while a non-tablet dosage form could fall within Claim 1 but outside Claim 2.

What patent protects Vosevi’s formulation?

US 10,912,814 is directed to the combination and physical-form arrangement corresponding to Vosevi, the fixed-dose combination of sofosbuvir, velpatasvir, and voxilaprevir marketed by Gilead Sciences.

Vosevi contains:

400 mg sofosbuvir;
100 mg velpatasvir; and
100 mg voxilaprevir.

The FDA-approved product is an oral tablet. The patent claims align closely with that strength and dosage form, including the use of amorphous solid dispersions for velpatasvir and voxilaprevir and crystalline sofosbuvir.[1][2]

The claims do not cover every formulation containing these three compounds. They require the specific combination of dose, solid-state form, dispersion structure, and polymer identity.

When does US Patent 10,912,814 expire?

The patent issued on February 9, 2021. Its effective term is generally calculated from the earliest relevant nonprovisional or international filing date, subject to patent-term adjustment, terminal disclaimers, and any applicable regulatory extension.[3]

The patent family is associated with a 2016 priority period, placing the ordinary 20-year patent-term endpoint in approximately January 2036, before any patent-term adjustment. The controlling expiration date should be taken from the USPTO Patent Center record and the Orange Book listing because the enforceable date may differ from a simple 20-year calculation.[3][4]

Event	Date or period
Earliest reported priority period	2016
Patent issued	February 9, 2021
Ordinary 20-year endpoint	Approximately January 2036
Potential adjustment	Depends on USPTO patent-term adjustment
Potential extension	Depends on any granted patent-term extension

A patent-term extension under 35 U.S.C. § 156 would require a qualifying regulatory product and a granted extension. The patent’s commercial relevance is therefore expected to extend into the mid-2030s unless invalidated, disclaimed, or narrowed.

What is the FDA and Orange Book status of Vosevi?

FDA approved Vosevi on July 18, 2017, for treatment of chronic hepatitis C virus infection in adults and certain adolescents, subject to the product labeling and genotype indications in effect at the time.[1]

Because sofosbuvir, velpatasvir, and voxilaprevir had already been separately developed or approved in related products, Vosevi’s regulatory exclusivity position differs from that of a conventional new chemical entity. The principal commercial barrier is the patent estate rather than a fresh five-year NCE exclusivity period for each ingredient.

The FDA Orange Book is the controlling source for listed patents, expiration dates, use codes, and approved drug-product information. Orange Book listings can change through patent-listing updates, delistings, corrections, pediatric extensions, or regulatory amendments.[4]

Orange Book significance

For a listed Vosevi patent, an ANDA applicant seeking approval before the relevant patent expiration would generally need to certify under Paragraph IV that the patent is invalid, unenforceable, or will not be infringed. The patent listing does not itself establish validity or infringement.

A Paragraph IV certification can trigger patent litigation under the Hatch-Waxman Act. A timely infringement action can impose a statutory 30-month stay of FDA approval, subject to statutory exceptions and court developments.[5]

Are there Paragraph IV challenges to US 10,912,814?

A patent-specific Paragraph IV conclusion requires the FDA’s current Orange Book listing data and public ANDA litigation records. The patent itself does not identify an ANDA challenger, settlement, or court decision.

The relevant challenge pathways are:

An ANDA applicant may certify that US 10,912,814 is invalid or not infringed.
The patent owner may sue within the Hatch-Waxman statutory period.
The applicant may pursue a formulation design-around that excludes at least one required limitation.
A later-filed applicant may wait for the listed patent to expire and avoid Paragraph IV litigation.

A challenge directed only to the active ingredients would not fully address this patent. The challenger would need to attack the combination of:

dose amounts;
crystalline sofosbuvir;
amorphous velpatasvir;
amorphous voxilaprevir;
separate solid dispersions; and
copovidone matrices.

The formulation limitations create several potential validity and non-infringement arguments. The main validity questions would concern written description, enablement, anticipation, obviousness, claim construction, and whether the claimed combination was predictable from earlier sofosbuvir, velpatasvir, voxilaprevir, and solid-dispersion disclosures.

How strong is the patent estate?

US 10,912,814 has meaningful commercial strength against a product that copies the Vosevi formulation closely. Its strongest characteristics are the detailed alignment between the claims and the marketed dosage strength and the requirement for a defined solid-dispersion architecture.

Its scope is narrower against alternative formulations.

Risk factor	Assessment
Direct coverage of Vosevi-strength tablet	High
Coverage of the individual active ingredients	None under these claims
Coverage of all SOF/VEL/VOX dosage forms	No
Dependence on solid-state testing	High
Dependence on copovidone use	High
Ease of polymer-based design-around	Potentially significant
Biosimilar relevance	None
Small-molecule generic relevance	High
Litigation value	Highest for a copycat tablet

A generic manufacturer could seek to avoid the patent by changing the polymer, using a different solid-dispersion process, altering the physical form of one active ingredient, changing the dosage form, or selecting a different strength. Each route creates technical and regulatory tradeoffs.

What formulation patents and related patent layers matter?

The patent should be evaluated within several overlapping patent layers.

Sofosbuvir patents

Sofosbuvir patents may cover the active compound, stereochemistry, prodrug structure, polymorphs, formulations, and methods of treating HCV. Earlier compound patents may expire before the combination-formulation patent.

Velpatasvir patents

Velpatasvir patents may cover the NS5A inhibitor, crystalline or amorphous forms, salts, processes, and HCV treatment methods. These patents can create separate barriers even if a manufacturer avoids US 10,912,814.

Voxilaprevir patents

Voxilaprevir patents may cover the NS3/4A protease inhibitor, compounds related to the inhibitor class, pharmaceutical compositions, and treatment regimens. Because voxilaprevir is the newest component of the combination, its underlying compound and use patents can have different expiration dates.

Combination patents

Combination patents cover the co-administration or fixed-dose use of the three agents. US 10,912,814 is narrower than a broad combination claim because it requires specific physical forms and solid dispersions.

Manufacturing patents

Manufacturing patents can cover spray drying, solvent systems, granulation, particle engineering, crystallization, blending, compression, and coating. These rights may create practical manufacturing barriers even where the final-product claims are avoided.

Are biosimilars a risk to Vosevi?

No. Vosevi is a small-molecule drug product, not a biologic. The relevant competitive pathway is an ANDA for a generic drug, not a biosimilar application under the Public Health Service Act.

A generic applicant must establish pharmaceutical equivalence and bioequivalence or otherwise satisfy FDA approval requirements. The applicant may also need to address Orange Book patents through Paragraph III or Paragraph IV certifications.[4][5]

Which companies compete with Vosevi?

Vosevi competes primarily with other direct-acting antiviral regimens rather than with products that duplicate all three active ingredients.

Product	Sponsor	Principal actives	Relationship to Vosevi
Vosevi	Gilead Sciences	Sofosbuvir/velpatasvir/voxilaprevir	Three-drug salvage or retreatment regimen
Epclusa	Gilead Sciences	Sofosbuvir/velpatasvir	Broad HCV treatment competitor
Mavyret	AbbVie	Glecaprevir/pibrentasvir	Major pangenotypic competitor
Zepatier	Merck	Elbasvir/grazoprevir	Earlier HCV competitor
Sovaldi-based regimens	Gilead Sciences	Sofosbuvir combinations	Earlier treatment platform

Market substitution depends on genotype, prior treatment, resistance, cirrhosis, payer policy, treatment duration, and physician preference. A generic version of Vosevi would compete against branded HCV therapies and any generic components or alternative fixed-dose combinations.

What generic launch scenarios exist?

Early Paragraph IV launch

A generic applicant could file an ANDA with a Paragraph IV certification and challenge the listed patent. The principal arguments would likely focus on obviousness, claim construction, and failure to prove infringement of the amorphous or copovidone limitations.

Paragraph III launch

A manufacturer could certify that it will wait until patent expiration. This reduces litigation risk but delays market entry until the relevant patent barriers end.

Formulation design-around

A manufacturer could use a polymer other than copovidone or alter the physical form of velpatasvir or voxilaprevir. This may avoid literal infringement but could affect dissolution, stability, bioequivalence, and manufacturing cost.

Non-tablet dosage form

A capsule or multiparticulate product could potentially avoid Claim 2, but it would remain exposed to Claim 1 if all other limitations are met.

What geographic coverage does the patent provide?

US 10,912,814 provides protection only in the United States. Corresponding international applications or national-phase patents must be assessed separately. Foreign patent rights can differ in:

claim scope;
validity;
prosecution amendments;
expiration dates;
supplementary protection certificates;
patent-term adjustments or extensions; and
regulatory linkage rules.

A US design-around does not establish freedom to operate in Europe, Canada, Japan, China, Australia, or other markets.

Key Takeaways

US 10,912,814 is a formulation patent directed to a Vosevi-type fixed-dose tablet.
The claimed product contains 400 mg crystalline sofosbuvir and 100 mg each of substantially amorphous velpatasvir and voxilaprevir.
Velpatasvir and voxilaprevir must be in approximately 200 mg copovidone-based solid dispersions.
Claim 1 covers a pharmaceutical dosage form; Claim 2 is narrower and requires a tablet.
The patent does not broadly claim sofosbuvir, velpatasvir, voxilaprevir, or their combination without the specified formulation limitations.
The ordinary patent-term endpoint is approximately January 2036, subject to USPTO patent-term adjustment and any applicable extension.
The main generic risks are Paragraph IV litigation and technical design-around failure.
Biosimilar competition is irrelevant because Vosevi is a small-molecule product.
The patent’s commercial strength is high against a close copy and materially lower against a formulation using a different polymer or solid-state design.

FAQs

Does US 10,912,814 cover Epclusa?

No. Epclusa contains sofosbuvir and velpatasvir but does not contain voxilaprevir. It therefore does not satisfy the claimed three-active-ingredient combination.

Can a generic use povidone instead of copovidone?

Possibly. Povidone and copovidone are different polymers. A product using povidone instead of copovidone would require analysis under literal infringement and the doctrine of equivalents.

Does the patent cover a capsule containing the same three drugs?

Claim 1 could potentially cover a capsule if every claimed dose, solid-state, dispersion, and polymer limitation is satisfied. Claim 2 requires a tablet and would not literally cover a capsule.

Can a company challenge the patent through inter partes review?

Yes. A party meeting the statutory requirements may petition the Patent Trial and Appeal Board for inter partes review based on patents or printed publications. IPR does not replace an ANDA Paragraph IV certification and does not itself authorize generic marketing.

Does FDA approval of Vosevi prove that the patent claims are valid?

No. FDA approval addresses safety, efficacy, quality, and regulatory requirements. Patent validity is determined under US patent law by the USPTO, federal courts, or the Patent Trial and Appeal Board.

References

U.S. Food and Drug Administration. (2017). Vosevi (sofosbuvir/velpatasvir/voxilaprevir) prescribing information.
Gilead Sciences, Inc. (2017). Vosevi product labeling and pharmaceutical composition information.
United States Patent and Trademark Office. (2021). U.S. Patent No. 10,912,814, pharmaceutical composition comprising sofosbuvir, velpatasvir, and voxilaprevir.
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 of 1984, 21 U.S.C. § 355(j); 35 U.S.C. §§ 271(e), 156.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Gilead Sciences Inc	VOSEVI	sofosbuvir; velpatasvir; voxilaprevir	TABLET;ORAL	209195-001	Jul 18, 2017		RX	Yes	Yes	10,912,814	⤷ Start Trial	Y				⤷ 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
Argentina	108616	⤷ Start Trial
Australia	2017273851	⤷ Start Trial
Brazil	102017011025	⤷ Start Trial
Canada	3025380	⤷ Start Trial
China	109310678	⤷ Start Trial
Eurasian Patent Organization	201892376	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 10,912,814