United States Patent 10,576,165: ST-246 Liquid Formulation Claims, Scope, Expiration and Competitive Patent Landscape

U.S. Patent No. 10,576,165 protects defined liquid formulations of ST-246, the active ingredient in tecovirimat and TPOXX. Its claims are formulation-specific. They require both tecovirimat and hydroxypropyl-beta-cyclodextrin within specified concentration ranges, with narrower dependent claims covering excipients, pH and approximately 100 mL unit volumes.

The patent does not claim tecovirimat generally, the underlying antiviral mechanism, a broad method of treating smallpox, or every oral liquid containing ST-246. Infringement depends primarily on whether a competing product practices the claimed concentration ranges and, for dependent claims, the additional excipient, pH or volume limitations.

What does U.S. Patent 10,576,165 protect?

The patent protects two concentration-defined formulation platforms:

Claim family	ST-246 concentration	Hydroxypropyl-beta-cyclodextrin concentration	Principal scope
Claims 1-4	About 2-20 mg/mL	About 125-400 mg/mL	Higher cyclodextrin formulation
Claims 5-8	About 2-20 mg/mL	About 12.5-40 mg/mL	Lower cyclodextrin formulation

The two cyclodextrin ranges do not overlap on their literal numerical boundaries. The first begins at approximately 125 mg/mL. The second ends at approximately 40 mg/mL.

The patent is therefore directed to formulation architecture rather than a single commercial composition. A product can fall within claim 1 or claim 5 based on the concentrations alone, even if it does not use every excipient recited in the dependent claims.

ST-246 is tecovirimat, an antiviral approved by the FDA under the TPOXX brand for treatment of human smallpox caused by variola virus in adults and pediatric patients. Tecovirimat inhibits the orthopoxvirus VP37 envelope-wrapping protein, although the mechanism is not part of the asserted formulation claims. [1]

How do the claims of U.S. 10,576,165 operate?

Independent claims 1 and 5

Claims 1 and 5 are the principal enforceable scope. Each requires:

A unit dosage liquid formulation.
ST-246 at approximately 2-20 mg/mL.
Hydroxypropyl-beta-cyclodextrin at a specified concentration.

The phrase “unit dosage” narrows the claims to a formulation prepared or presented as a dosage unit. It creates a potential issue for bulk liquids, manufacturing intermediates and multi-dose containers. A bulk concentrate may not satisfy the unit-dosage limitation unless the facts establish that it is itself a unit dosage formulation.

The claims do not expressly require:

Oral administration.
A particular container.
A particular salt or polymorph.
A specific manufacturing process.
A specified viscosity.
A preservative.
A particular particle size.
A specific amount of tecovirimat per patient dose.
A stated therapeutic indication.
A specific commercial name.

A competing formulation could therefore raise infringement risk even if it differs from TPOXX in packaging, indication, manufacturing route or certain inactive ingredients.

The meaning of “about”

The word “about” creates a numerical boundary issue. It does not automatically permit unlimited deviation from the stated ranges. The scope depends on ordinary claim construction, the patent specification, prosecution history, technical evidence and, if litigated, expert testimony.

For screening purposes, products near the following thresholds require particular attention:

Limitation	Literal stated threshold
ST-246 lower bound	Approximately 2 mg/mL
ST-246 upper bound	Approximately 20 mg/mL
High-range cyclodextrin lower bound	Approximately 125 mg/mL
High-range cyclodextrin upper bound	Approximately 400 mg/mL
Low-range cyclodextrin lower bound	Approximately 12.5 mg/mL
Low-range cyclodextrin upper bound	Approximately 40 mg/mL

A formulation at 20 mg/mL ST-246 or 125 mg/mL cyclodextrin cannot be treated as clearly outside the patent merely because its analytical result is marginally above or below the stated value.

Dependent claims 2 and 6

Claim 2 depends on claim 1 and requires one or more of:

Mannitol.
Trehalose dehydrate.
Lactose monohydrate.
Purified water.

Claim 6 depends on claim 5 and requires one or more of:

Polyethylene glycol 400.
Polysorbate 80.
Polyethylene glycol 300.
Purified water.

The “one or more” language permits combinations within the listed group. A formulation containing mannitol and purified water, for example, can potentially satisfy claim 2 if it also meets all limitations of claim 1.

The claims are not interchangeable. A product containing polyethylene glycol 400 may satisfy claim 6 but cannot satisfy claim 2 on that basis because claim 2 identifies a different excipient group.

Dependent claims 3 and 8

Claims 3 and 8 impose a pH range of approximately 3.0-10.0. This range is broad and covers most conventional pharmaceutical liquid pH values.

The pH limitation is unlikely to provide substantial design-around protection unless a competing formulation is deliberately adjusted outside the claimed range and remains pharmaceutically acceptable, stable and manufacturable. A product with a pH near either boundary remains exposed to the “about” construction.

Dependent claims 4 and 7

Claims 4 and 7 require a total volume of approximately 100 mL. These claims are narrower than the independent claims and may be avoided by a substantially different unit volume, subject to the interpretation of “about.”

The 100 mL limitations are commercially relevant because a pediatric or reconstituted oral liquid can be presented in a fixed-volume container. They may be less significant for a concentrate, a multidose bottle or a formulation sold in several volume presentations.

What formulations are covered by U.S. 10,576,165?

A formulation is most exposed when it has the following profile:

Product characteristic	Claim 1-4 exposure	Claim 5-8 exposure
ST-246 at 2-20 mg/mL	Required	Required
Hydroxypropyl-beta-cyclodextrin at 125-400 mg/mL	Required	Not sufficient
Hydroxypropyl-beta-cyclodextrin at 12.5-40 mg/mL	Not sufficient	Required
Mannitol, trehalose dehydrate, lactose monohydrate or water	Relevant to claim 2	Not relevant
PEG 400, polysorbate 80, PEG 300 or water	Not relevant	Relevant to claim 6
pH approximately 3-10	Relevant to claim 3	Relevant to claim 8
Approximately 100 mL total volume	Relevant to claim 4	Relevant to claim 7

The patent’s claim structure creates two separate formulation targets rather than a single continuous cyclodextrin range. A liquid containing 80 mg/mL hydroxypropyl-beta-cyclodextrin, for example, would not fall within either stated cyclodextrin range on a literal reading, even if it contains ST-246 at 2-20 mg/mL.

That apparent gap may be commercially useful for a design-around, but it is not conclusive. Equivalence, prosecution history and the technical purpose of the ranges could affect the analysis.

How strong is the patent estate for tecovirimat?

U.S. Patent 10,576,165 is best characterized as a focused formulation patent within the broader tecovirimat estate. Its strength differs by issue.

Issue	Assessment
Numerical concentration scope	Moderate. The ranges are clear enough for product screening but contain “about” boundaries.
Formulation specificity	Stronger than a broad composition claim because both active and excipient concentrations are required.
Design-around potential	Meaningful. A competitor may vary cyclodextrin concentration, active concentration, volume, pH or excipient selection.
Commercial relevance	High for liquid tecovirimat products, particularly pediatric or reconstituted dosage forms.
Relevance to capsules	Limited. A solid oral capsule does not ordinarily practice a liquid formulation claim.
Relevance to manufacturing process	Limited. The patent does not claim a manufacturing method in the supplied claims.
Litigation leverage	Higher if the accused product’s label, batch records or regulatory dossier disclose the claimed concentrations.
Validity exposure	Dependent on prior-art formulation disclosures, support for the two concentration windows and prosecution history.

The strongest infringement case would involve a finished liquid dosage product whose regulatory documents identify ST-246 and hydroxypropyl-beta-cyclodextrin concentrations within one of the claimed windows.

The strongest noninfringement position would involve a product outside both cyclodextrin ranges, outside the ST-246 range, or lacking the unit-dosage characteristic. A formulation change must still preserve solubility, stability, bioavailability, palatability and manufacturability.

When does U.S. Patent 10,576,165 lose exclusivity?

The patent issued in 2020. Its enforceable term is generally calculated from the applicable earliest nonprovisional U.S. filing date, not from the issue date. Patent term adjustment, terminal disclaimers, priority claims and any patent-term extension can affect the final expiration date. [2]

The issue date alone does not establish the expiration date. A reliable freedom-to-operate analysis must use the USPTO continuity record and the patent-term calculation associated with the issued patent.

The patent should be analyzed separately from FDA regulatory exclusivity. Patent expiration and FDA exclusivity are different rights:

Protection	Relevant effect
U.S. formulation patent	Can block commercial activity within the patent claims during the enforceable term
FDA orphan exclusivity	Can restrict approval of the same drug for the protected indication for the statutory period
New chemical entity exclusivity	Can restrict certain abbreviated applications for five years, subject to statutory exceptions
Pediatric exclusivity	Can add six months to qualifying listed exclusivity or patent periods
Medical-countermeasure programs	May affect development and procurement but do not replace patent analysis

TPOXX was FDA-approved in July 2018. The approval initially covered oral capsules, and FDA later approved an oral suspension formulation for pediatric use. The formulation patent is more directly relevant to a liquid product than to the original capsule presentation. [1, 3]

What is the Orange Book status of U.S. 10,576,165?

A patent’s presence in the Orange Book depends on listing by the NDA holder and FDA acceptance under the listing rules. A patent is not automatically Orange Book-listed solely because its claims relate to an approved drug.

For TPOXX, the relevant regulatory questions are:

Whether U.S. 10,576,165 is listed against the applicable TPOXX NDA.
Whether the listing covers the capsule, oral suspension or both.
Whether FDA assigned a use code or product-specific listing.
Whether the patent is listed for the dosage form that a generic applicant seeks to copy.
Whether the listed patent was later delisted, corrected or supplemented.

A formulation patent generally has greater Orange Book relevance when its claims read on the approved dosage form. A capsule applicant may have a stronger position that a liquid formulation patent is not relevant to its product. A liquid generic applicant faces greater exposure if it relies on the same concentration architecture.

Which companies are challenging tecovirimat exclusivity?

TPOXX is marketed by SIGA Technologies, Inc., under a U.S. government procurement and public-health framework. The commercial market is unusual because demand is driven substantially by government stockpiling rather than ordinary retail prescribing.

Publicly visible competitive activity has focused more on:

Government procurement.
International licensing and distribution.
Alternative orthopoxvirus countermeasures.
Brincidofovir and other antiviral approaches.
Potential generic development after relevant patent and regulatory barriers expire.

A Paragraph IV challenge would require an ANDA applicant to certify that a listed patent is invalid, unenforceable or not infringed. The existence of a patent does not establish that an ANDA challenge has been filed. No Paragraph IV litigation or settlement should be attributed to U.S. 10,576,165 without a corresponding court docket, FDA notice or company disclosure.

What patent litigation affects ST-246 and TPOXX?

The supplied claim set does not identify litigation. Patent litigation analysis requires a docket-specific review of:

The patent number.
The asserted claims.
The accused formulation.
The filing date.
Any preliminary injunction or claim-construction ruling.
Settlement terms.
License rights.
FDA litigation stays under the Hatch-Waxman framework.

A dispute involving another tecovirimat patent does not automatically determine the scope or enforceability of U.S. 10,576,165. Formulation patents are fact-intensive. Laboratory concentration data, batch-release specifications and the product’s labeled composition can become central evidence.

How does this patent compare with other tecovirimat patent categories?

Patent category	Typical subject matter	Relevance to a liquid ST-246 product
Compound patents	Tecovirimat molecule or chemical class	Broad historical relevance; may have earlier expiration
Composition patents	Drug plus excipient or dosage form	High if the liquid composition falls within the claims
Formulation patents	Concentrations, stability, solubilization or delivery	Directly relevant to U.S. 10,576,165
Method-of-use patents	Treatment or prevention of orthopoxvirus disease	Relevant to labeling and inducement theories
Manufacturing patents	Synthesis, purification or crystallization	Relevant to supply chain and API sourcing
Regulatory exclusivity	FDA approval-based protection	Separate from patent infringement

U.S. 10,576,165 does not replace the need to review compound, method-of-use and manufacturing patents. A product can avoid this formulation patent and still face another blocking patent. Conversely, a product can practice the formulation claims while benefiting from a license or a valid noninfringement position under another patent.

What generic launch risks exist for a liquid tecovirimat product?

A generic or follow-on liquid product faces five principal risks:

Concentration overlap. The product may fall within either the 125-400 mg/mL or 12.5-40 mg/mL cyclodextrin range.
Regulatory disclosure. The proposed labeling, chemistry dossier or public product information may reveal the claimed composition.
Equivalence arguments. A small numerical deviation may not avoid infringement because of “about.”
Orange Book certification. A listed patent may trigger a Paragraph IV certification and possible litigation.
Supply-chain dependence. A design-around may require a different solubilizer, excipient system or manufacturing process.

A likely design-around strategy would vary the cyclodextrin concentration outside both claimed windows while maintaining the required ST-246 concentration. Other approaches include a different solubilizing excipient, a different dosage volume or a solid dosage form. Each approach creates pharmaceutical development risks that must be evaluated against formulation performance.

Does U.S. 10,576,165 cover biosimilars?

No. Tecovirimat is a small-molecule antiviral, not a biologic. Biosimilar pathways under the Public Health Service Act are not relevant. A competing tecovirimat product would generally be evaluated through a small-molecule generic pathway, such as an ANDA, or through a separate 505(b)(2) application depending on the product and evidence package. [4]

What licensing and commercial issues affect the patent landscape?

SIGA’s licensing and procurement arrangements can materially affect market access even when a patent claim is technically avoidable. Government contracts may grant supply rights, geographic rights or distribution rights without granting broad freedom to practice every patent claim.

A license can also change the commercial analysis. A licensee may sell a product that would otherwise create infringement exposure, while an unlicensed competitor may face both patent and contracting barriers.

The key commercial exposure is concentrated in government stockpiling and public-health procurement. TPOXX revenue is therefore not a conventional retail prescription forecast. U.S. government purchases, international orders and emergency-response contracts can produce substantial revenue concentration in a small number of customers. [5]

Key Takeaways

U.S. Patent 10,576,165 claims liquid tecovirimat formulations containing hydroxypropyl-beta-cyclodextrin.
Claims 1-4 cover approximately 125-400 mg/mL cyclodextrin.
Claims 5-8 cover approximately 12.5-40 mg/mL cyclodextrin.
Both independent claims require ST-246 at approximately 2-20 mg/mL.
Dependent claims add specific excipients, a pH range of approximately 3-10 and, in two claims, an approximately 100 mL volume.
The patent is most relevant to liquid TPOXX or competing liquid tecovirimat products, not ordinary capsules.
The “about” language creates boundary and equivalence issues.
Patent expiration cannot be established from the issue date alone; the USPTO continuity and term-adjustment record controls.
FDA exclusivity, Orange Book listing and patent enforceability are separate questions.
Tecovirimat is a small molecule, so biosimilar analysis does not apply.
A product outside both cyclodextrin concentration windows may have a credible design-around path, subject to the full patent family and other tecovirimat patents.

FAQs

Does a 100 mL bottle automatically infringe U.S. 10,576,165?

No. The 100 mL limitation appears only in claims 4 and 7. The product must also satisfy the relevant independent claim and the applicable “about” range. A 100 mL presentation alone is insufficient.

Can a tecovirimat liquid avoid the patent by removing hydroxypropyl-beta-cyclodextrin?

Potentially, for the supplied claims. Both independent claims require hydroxypropyl-beta-cyclodextrin. A different solubilization system would not literally satisfy that limitation, although other patents or equivalence theories could remain relevant.

Is a formulation containing 50 mg/mL hydroxypropyl-beta-cyclodextrin within the claimed ranges?

On the stated numerical ranges, 50 mg/mL is outside both the 12.5-40 mg/mL and 125-400 mg/mL ranges. The final assessment would depend on the construction of “about” and the full patent record.

Does the patent cover intravenous tecovirimat?

The supplied claims do not recite an administration route. A liquid intended for intravenous use could raise claim issues if it satisfies the unit-dosage and concentration limitations, but the claims do not expressly limit the formulation to intravenous, oral or another route.

Can an ANDA applicant avoid the patent by using a different inactive ingredient?

Possibly. The independent claims require hydroxypropyl-beta-cyclodextrin, while the dependent claims identify additional excipient groups. Replacing the cyclodextrin may avoid the independent claims, but replacing only a dependent-claim excipient does not avoid the independent claim on which it depends.

References

U.S. Food and Drug Administration. (2018). TPOXX (tecovirimat) prescribing information. FDA.
United States Patent and Trademark Office. (2020). U.S. Patent No. 10,576,165. USPTO Patent Center.
U.S. Food and Drug Administration. (2022). FDA approves oral suspension formulation of TPOXX for pediatric patients. FDA.
U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application (ANDA): Generics. FDA.
SIGA Technologies, Inc. (2024). Annual report on Form 10-K. U.S. Securities and Exchange Commission.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Siga Technologies	TPOXX	tecovirimat	SOLUTION;INTRAVENOUS	214518-001	May 18, 2022		RX	Yes	Yes	10,576,165	⤷ 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	082566	⤷ Start Trial
Argentina	122178	⤷ Start Trial
Australia	2011285871	⤷ Start Trial
Brazil	112013002646	⤷ Start Trial
Canada	2807528	⤷ Start Trial
China	103281898	⤷ Start Trial
China	106074370	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,576,165

Which drugs does patent 10,576,165 protect, and when does it expire?

Summary for Patent: 10,576,165