Details for Patent: 10,799,505

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Which drugs does patent 10,799,505 protect, and when does it expire?

Patent 10,799,505 protects VITRAKVI and is included in two NDAs.

This patent has forty-six patent family members in thirty-three countries.

Summary for Patent: 10,799,505

Title:	Crystalline form of (S)-N-(5-((R)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)-pyrazolo[1,5-A]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate
Abstract:	A novel crystalline form of (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutical compositions containing said crystalline form and the use of said crystalline form in the treatment of pain, cancer, inflammation, neurodegenerative disease or Trypanosoma cruzi infection are disclosed. In some embodiments, the novel crystalline form comprises a stable polymorph of (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate. The present invention is further directed to a process for the preparation of the novel crystalline form.
Inventor(s):	Alisha B. Arrigo, Derrick Juengst, Khalid Shah
Assignee:	Array Biopharma Inc
Application Number:	US14/943,014
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,799,505
Patent Claim Types: see list of patent claims	Composition; Compound; Process;

US Patent 10,799,505: Deucravacitinib Crystal Form I-HS Patent Scope and Competitive Landscape

US Patent 10,799,505 protects crystalline form I-HS of deucravacitinib hydrogen sulfate, the active pharmaceutical ingredient used in Bristol Myers Squibb’s Sotyktu. The patent is a solid-form patent, not a broad composition-of-matter patent. Its core protection depends on the claimed crystal being substantially free of amorphous material and meeting specified XRPD, DSC, hygroscopicity, or process limitations. The strongest practical risk for a competing product is manufacture or use of the same I-HS crystal form, even if the competitor uses a different tablet formulation or crystallization process.

The patent does not, based on the supplied claims, cover every crystalline form, amorphous form, free-base form, salt form, or formulation containing deucravacitinib. Its commercial value depends on whether Sotyktu’s approved drug substance uses form I-HS and whether the patent is listed for the product in the FDA Orange Book.

What drug and molecular form does US 10,799,505 protect?

The claimed compound is deucravacitinib hydrogen sulfate, also known as BMS-986165 hydrogen sulfate. Deucravacitinib is a selective TYK2 inhibitor approved by the FDA as Sotyktu for moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.[2]

The chemical identity in the claims is:

(S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate.

The patent claims a specific crystalline salt form designated I-HS. “HS” indicates the hydrogen sulfate salt. The claimed form is distinguished from amorphous material and potentially from other polymorphs, solvates, hydrates, salts, or stereochemical variants.

What is the commercial product associated with the patent?

Item	Relevant information
Active ingredient	Deucravacitinib
Brand	Sotyktu
Developer and sponsor	Bristol Myers Squibb
Product type	Oral small-molecule tablet
FDA approval	September 9, 2022
Initial indication	Moderate-to-severe plaque psoriasis in adults
Dosage form	Immediate-release film-coated tablet
Typical dose	6 mg once daily
Patent subject	Crystalline deucravacitinib hydrogen sulfate, form I-HS

The FDA label identifies Sotyktu as containing deucravacitinib, but the label does not by itself establish the complete solid-form patent position. The relevant question for infringement and generic-entry analysis is whether the commercial drug substance is manufactured and supplied as the patented I-HS crystal.

How many claims does US 10,799,505 contain?

The supplied claims include 15 claims. Claim 1 is the independent product claim. Claims 2 through 10 narrow the crystal by analytical or physical characteristics. Claims 11 and 12 cover pharmaceutical compositions. Claims 13 through 15 claim preparation processes and process substeps.

Claim group	Claims	Subject matter	Scope
Core crystal	1	Crystalline form I-HS substantially free of amorphous form	Broadest product claim
XRPD-defined forms	2-6	Selected diffraction peaks or pattern of Figure 29	Analytical fingerprint limitations
Thermal properties	7-9	DSC onset, heat-flow value, and thermogram	Physical-property limitations
Physical behavior	10	Non-hygroscopic crystalline form	Additional property limitation
Composition	11-12	Pharmaceutical composition containing form I-HS	Product-by-use and mixing claims
Manufacture	13-15	Solvent treatment, heating, filtration, acidification, seeding	Process claims

Claim 1 is the principal claim. The dependent claims provide fallback positions if a court finds claim 1 indefinite, overly broad, or unsupported.

What does claim 1 of US 10,799,505 cover?

Claim 1 covers crystalline form I-HS of the identified deucravacitinib hydrogen sulfate compound when the crystal is substantially free of amorphous material.

The claim has three important limitations:

1. The product must be the specified stereochemical compound.
2. The compound must be in crystalline form I-HS.
3. The crystalline form must be substantially free of amorphous form.

The claim does not expressly require any particular XRPD peak set, DSC result, manufacturing solvent, particle size, tablet formulation, dosage strength, or therapeutic indication. Those limitations appear in dependent claims.

What does “substantially free of the amorphous form” mean?

The phrase is a quality and composition limitation. It distinguishes form I-HS from a material containing a meaningful amount of amorphous deucravacitinib hydrogen sulfate.

The claim text does not specify a numerical maximum for amorphous content. That creates a potential construction and enforcement issue. The patent specification, analytical examples, prosecution history, and industry testing methods would likely determine whether the limitation is interpreted through XRPD, DSC, solid-state NMR, microscopy, or quantitative phase analysis.

For an accused product, the relevant evidence would include:

• XRPD pattern;
• DSC thermogram;
• solid-state form controls;
• polymorph screening data;
• batch release specifications;
• seeding records;
• drying and milling conditions;
• regulatory chemistry, manufacturing, and controls documents.

What XRPD features are protected?

Claims 2 through 6 define form I-HS by characteristic X-ray powder diffraction peaks measured in degrees 2θ.

Claim	Required XRPD peaks
2	18.4, 20.7, 23.1, and 24.0 ± 0.2°
3	10.7, 18.4, 20.7, 23.1, and 24.0 ± 0.2°
4	10.7, 18.4, 19.2, 20.2, 20.7, 21.5, 23.1, and 24.0 ± 0.2°
5	20 listed peaks, including 10.7, 15.3, 16.5, 18.4, 19.2, 19.9, 20.2, 20.7, 21.5, 22.1, 23.1, 24.0, 24.4, 25.6, 26.5, 27.6, 28.2, 28.7, 30.8, and 38.5 ± 0.2°
6	XRPD pattern substantially as shown in Figure 29

The peak tolerances are relatively narrow. A product can avoid literal infringement of a peak-based claim if its measured peaks fall outside the stated ranges, but that does not automatically avoid claim 1. Claim 1 is not expressly limited to the listed peaks.

A competing manufacturer would therefore need to assess the solid form against both the broad crystal claim and the narrower analytical claims. Designing around claims 2 through 6 may have limited value if the product remains form I-HS under claim 1.

What do the DSC and hygroscopicity claims add?

Claims 7 through 10 provide additional analytical definitions:

• Claim 7 requires an onset-to-maximum DSC event of approximately 193°C to 205°C.
• Claim 8 recites a heat-flow value of about 2.415 mW.
• Claim 9 requires a DSC thermogram substantially as shown in Figure 26.
• Claim 10 requires a non-hygroscopic crystalline form.

These claims may be useful as evidentiary alternatives because different laboratories can obtain variable XRPD results from preferred orientation, instrument configuration, sample preparation, or crystallite size.

Claim 8 has a technical drafting issue. “Heat of melting” is ordinarily expressed as energy per unit mass, such as J/g, while mW is a heat-flow unit. The claim may be interpreted in light of the specification and Figure 26 as referring to a DSC peak or heat-flow measurement rather than enthalpy. That issue could affect clarity or enforcement, but it does not necessarily affect claim 1 or the other dependent claims.

Do claims 11 and 12 cover Sotyktu tablets?

Claims 11 and 12 cover pharmaceutical compositions containing form I-HS and a pharmaceutically acceptable carrier.

Claim 11 recites a composition comprising:

• a pharmaceutically acceptable carrier; and
• the claimed crystalline form.

Claim 12 covers a composition made by mixing the crystal with the carrier.

These claims can reach tablets, capsules, powders, granules, or other dosage forms if they contain the patented crystal. They are not limited to Sotyktu’s exact excipient system, tablet shape, coating, strength, or commercial packaging.

The composition claims may be important in a generic case because an ANDA applicant’s proposed product would ordinarily identify its drug substance and formulation. If the proposed drug substance is form I-HS, the applicant could face product or composition claim exposure even if it uses different excipients.

What manufacturing processes are protected?

Claims 13 through 15 protect a particular crystallization and purification route.

Claim 13 process

The process includes:

1. Mixing ethanol-contaminated deucravacitinib hydrogen sulfate with a 5:95 weight/weight water/2-butanone solution.
2. Heating at approximately 65°C to 70°C with stirring until ethanol is about 0.5 weight percent.
3. Forming a slurry.
4. Isolating crystalline form I-HS by filtration.

The claim is directed to a solvent-mediated conversion or purification step designed to remove residual ethanol and produce the target crystalline form.

Claim 14 upstream salt-formation process

Claim 14 adds a process in which:

1. Concentrated sulfuric acid is added to a solution of the free compound in ethanol.
2. Heptane is added to form a slurry.
3. The hydrogen sulfate salt is isolated by filtration.

Claim 15 seeding process

Claim 15 adds seeding at room temperature with deucravacitinib hydrogen sulfate and stirring until a slurry forms.

These process claims are narrower than the product claims. A generic manufacturer may avoid literal infringement of claims 13 through 15 by using a different solvent system, temperature profile, acid addition method, seeding protocol, or isolation technique. That design-around would not avoid infringement if the resulting product is still form I-HS under claim 1.

The process claims may also create manufacturing-disclosure risk. Regulatory filings, inspection materials, supplier records, or discovery in litigation can reveal whether the accused manufacturer uses the claimed solvent and seeding sequence.

When does US Patent 10,799,505 expire?

The patent term must be determined from the issued patent, its earliest effective nonprovisional filing date, terminal disclaimers, patent-term adjustment, and any patent-term extension. The grant number alone does not establish the final enforceable expiration date.

For commercial planning, the relevant expiration date should be taken from the current USPTO patent record and the FDA Orange Book patent listing rather than calculated solely from the issue date. The patent is directed to a later-developed crystalline form and is therefore expected to expire after the basic compound patent, subject to the patent’s recorded term adjustments.

The FDA’s five-year new chemical entity exclusivity for Sotyktu began with approval on September 9, 2022 and generally prevents approval of an ANDA relying on the product’s safety and efficacy data until September 9, 2027, subject to FDA implementation and any applicable exclusivity provisions.[2] NCE exclusivity is regulatory exclusivity, not patent protection.

What is the Orange Book status of the patent?

Orange Book listing is decisive for ANDA litigation timing. A listed patent can require a Paragraph IV certification and support an infringement action under 35 U.S.C. § 271(e)(2). A patent that is not listed may still be enforceable, but it generally does not create the same ANDA litigation trigger.

The supplied claim text does not establish whether US 10,799,505 is currently listed for Sotyktu, whether it is listed against all strengths, or whether any delisting, correction, or patent-term entry has occurred. Those facts must be confirmed against the current FDA Orange Book patent-and-exclusivity data and the patent’s USPTO record.

Are there Paragraph IV challenges to Sotyktu?

A Paragraph IV challenge would require an ANDA applicant to certify that a listed patent is invalid, unenforceable, or not infringed. The applicant must also provide notice to the NDA holder and patent owner. The notice can trigger a 30-month stay of FDA approval if the patent owner files suit within the statutory period.[3]

For US 10,799,505, the key Paragraph IV theories would likely include:

Potential theory	Relevance
Non-infringement	Proposed product is not form I-HS or lacks the required crystal characteristics
Invalidity for anticipation	Earlier reference discloses the same crystal form and required analytical properties
Obviousness	Prior art makes the claimed form and process predictable or routine
Indefiniteness	Terms such as “substantially free,” “about,” and “substantially as shown” lack objective boundaries
Written description or enablement	Specification does not adequately support the full breadth of claim 1
Process design-around	Generic uses different solvents, temperatures, seeding, or isolation conditions

No settlement or Paragraph IV outcome should be inferred from the claim text alone. A current litigation docket and FDA Orange Book record are required to establish whether an ANDA challenge has been filed.

How strong is the patent estate for deucravacitinib?

US 10,799,505 is potentially strong against a product using form I-HS but narrower than a compound patent.

Strength factor	Assessment
Product-form coverage	Strong if the commercial drug substance is confirmed as I-HS
Analytical identification	Strong because XRPD and DSC can provide objective evidence
Amorphous-material limitation	Potentially vulnerable because “substantially free” lacks a numerical threshold in the claim
Composition coverage	Useful against tablets containing I-HS
Manufacturing coverage	Narrower and easier to design around
Dependence on product identity	High; a different polymorph may avoid the claims
Regulatory leverage	High only if the patent is Orange Book-listed
Biosimilar relevance	None; deucravacitinib is a small molecule, not a biologic
Generic-entry relevance	High after NCE exclusivity and listed-patent barriers expire

The patent is most valuable as part of a layered estate that includes the active compound, salts, formulations, methods of treatment, and manufacturing processes. A solid-form patent alone typically does not prevent every form of competition, but it can delay a generic if the approved drug substance must use the claimed form for regulatory or manufacturing reasons.

How does the patent compare with generic and biosimilar risks?

Sotyktu faces generic risk, not biosimilar risk. Deucravacitinib is a chemically synthesized small molecule, so competitors would file ANDAs rather than abbreviated biologics license applications.

Generic risk has several stages:

1. Before September 2027, NCE exclusivity limits reliance on Sotyktu’s clinical data.
2. After NCE exclusivity, an ANDA applicant can pursue approval subject to listed patents.
3. A Paragraph IV certification can create patent litigation and a potential 30-month stay.
4. A generic may attempt to use a different polymorph, amorphous form, salt, or manufacturing process.
5. FDA approval does not resolve patent infringement; patent disputes can continue after approval.

A different solid form could avoid US 10,799,505 while remaining subject to other patents or regulatory requirements. Conversely, a generic that uses a different manufacturing process may still infringe the product or composition claims if its drug substance is form I-HS.

What geographic coverage does the patent provide?

US 10,799,505 provides US patent protection only. Related international applications may protect corresponding crystalline forms or processes in Europe, Japan, China, Canada, and other markets, but foreign rights must be assessed separately.

Geographic analysis should distinguish:

• US patent grant and continuation rights;
• European Patent Office validation and national litigation;
• patent term and supplementary protection certificates in Europe;
• national phase status in China, Japan, Canada, and Australia;
• local Orange Book or equivalent linkage systems;
• manufacturing performed outside the US for import into the US.

A foreign process performed entirely outside the US may raise different infringement questions than importing a product that itself falls within a US product claim. The supplied information does not establish the status of any corresponding foreign family member.

What patent litigation and licensing deals affect this patent?

The supplied material does not identify a lawsuit, Paragraph IV notice, settlement agreement, license, assignment, or royalty arrangement involving US 10,799,505. Patent ownership, enforcement, and licensing should be checked against USPTO assignment records, PACER, district-court dockets, and SEC filings by Bristol Myers Squibb.

No biosimilar licensing issue applies to this asset. Any commercial license would likely concern the compound, TYK2 program, formulation, or geographic commercialization rights rather than the crystal patent alone.

Key Takeaways

• US 10,799,505 is a solid-form patent covering crystalline deucravacitinib hydrogen sulfate form I-HS.
• Claim 1 is the broadest claim and does not expressly require the listed XRPD peaks.
• Claims 2 through 6 define the crystal through XRPD peaks and a reference pattern.
• Claims 7 through 10 add DSC and non-hygroscopicity limitations.
• Claims 11 and 12 can reach tablets and other pharmaceutical compositions containing form I-HS.
• Claims 13 through 15 cover a specific water/2-butanone, ethanol-removal, heptane, and seeding process.
• The patent is relevant to generic ANDA strategy only if it is listed for Sotyktu or otherwise creates a meaningful infringement risk.
• Deucravacitinib creates generic, not biosimilar, competition.
• A manufacturer using another polymorph or amorphous form may avoid this patent but could encounter separate compound, formulation, method-of-use, or process patents.
• The final expiration date, Orange Book status, Paragraph IV activity, litigation posture, and foreign-family coverage require verification in current USPTO, FDA, and court records.

FAQs

Can a generic company avoid US 10,799,505 by using amorphous deucravacitinib?

Potentially. The claims are directed to crystalline form I-HS and compositions containing that form. An amorphous product may avoid literal infringement, but it could face separate patents, stability problems, or regulatory questions.

Does a different XRPD pattern automatically avoid infringement?

No. A different pattern may avoid claims 2 through 6, but claim 1 does not expressly recite the listed peaks. The full solid-state identity of the product would need to be assessed.

Does using a different solvent avoid the patent?

It may avoid process claims 13 through 15 if the process does not use their limitations. It does not avoid product claims if the resulting drug substance is crystalline form I-HS.

Is the patent relevant to all Sotyktu tablet strengths?

Potentially, if each strength contains the same form I-HS drug substance. Orange Book listing details and the product’s approved chemistry, manufacturing, and controls information determine the practical scope.

Can FDA approve a generic while the patent remains in force?

Yes, depending on the certification, litigation status, statutory stay, expiration, and any settlement or court order. FDA approval and patent infringement are separate legal issues.

References

1. United States Patent and Trademark Office. (2020). U.S. Patent No. 10,799,505, crystalline form I-HS of deucravacitinib hydrogen sulfate.
2. U.S. Food and Drug Administration. (2022). Sotyktu (deucravacitinib) prescribing information. Bristol Myers Squibb.
3. U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations: Orange Book.
4. Hatch-Waxman Amendments, 21 U.S.C. § 355(j).
5. Patent Act, 35 U.S.C. § 271(e)(2).

Drugs Protected by US Patent 10,799,505

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Bayer Hlthcare	VITRAKVI	larotrectinib sulfate	CAPSULE;ORAL	210861-001	Nov 26, 2018		RX	Yes	No			Y	Y
Bayer Hlthcare	VITRAKVI	larotrectinib sulfate	CAPSULE;ORAL	210861-002	Nov 26, 2018		RX	Yes	Yes			Y	Y
Bayer Healthcare	VITRAKVI	larotrectinib sulfate	SOLUTION;ORAL	211710-001	Nov 26, 2018		RX	Yes	Yes				Y

International Family Members for US Patent 10,799,505

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2015346046
Brazil	112017010141
Canada	2967951
Chile	2017001249
China	107428760