US9487525 Patent Analysis: Brepocitinib Crystalline Form B, Tablet Claims, and U.S. Patent Landscape

US Patent 9,487,525 protects crystalline Form B of brepocitinib, also known as PF-06700841, together with pharmaceutical compositions and tablets containing that polymorph. The patent does not claim the underlying brepocitinib molecule, a therapeutic method, or a manufacturing process. Its commercial importance depends on whether a competing product uses Form B or a formulation that falls within the claimed excipient and dose ranges.

The patent was granted on November 8, 2016, and is assigned to Pfizer. Based on the 20-year patent term from the relevant nonprovisional filing date, the expected U.S. expiration is February 21, 2034, subject to any patent-term adjustment or terminal disclaimer recorded in the USPTO file. The patent is not an Orange Book-listed product patent because brepocitinib was not FDA-approved as of the latest publicly available regulatory records reviewed.[1-3]

What drug and compound does US9487525 protect?

The claimed compound is brepocitinib, an oral small-molecule inhibitor of TYK2 and JAK1. Its chemical name in the patent is:

(S)-4-Amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide.

The patent claims a specific solid-state form of this active pharmaceutical ingredient, designated crystalline Form B. Form B is identified primarily through powder X-ray diffraction, or PXRD, peak patterns.

Item	Patent-relevant information
Active ingredient	Brepocitinib, PF-06700841
Chemical class	Pyrrolopyrimidine piperidine carboxamide
Target profile	TYK2 and JAK1 inhibition
Claimed solid form	Crystalline Form B
Patent	U.S. Patent No. 9,487,525
Patent holder	Pfizer
Grant date	November 8, 2016
U.S. filing-date basis	February 21, 2014
Expected base-term expiration	February 21, 2034
Regulatory status	Investigational; no FDA-approved brepocitinib product identified in the Orange Book
Claim categories	Polymorph, pharmaceutical composition, tablet formulation

What are the independent claims in US9487525?

Claims 1, 2, and 3 independently claim crystalline Form B using alternative PXRD peak sets. Claims 4 through 6 claim compositions containing the polymorph. Claims 7 through 9 narrow those compositions by adding four named excipients. Claims 10 through 12 claim tablets with specified quantitative formulation limits.

Claims 1 through 3: crystalline Form B

The first three claims cover Form B by PXRD characterization.

Claim	PXRD limitation
1	Peaks at approximately 10.0°, 12.3°, 15.0°, 17.1°, 19.2°, and 24.4° 2-theta
2	At least ten peaks, including 15.0°, 19.2°, 12.3°, 10.0°, 17.1°, 24.4°, 16.4°, 26.0°, 15.5°, and 23.9°
3	At least ten peaks, including 10.0°, 5.0°, 15.0°, 19.2°, 17.1°, 12.3°, 24.4°, 30.2°, 32.3°, and 23.3°

Claim 1 is the broadest of the three polymorph claims because it requires only six identified peaks. Claims 2 and 3 require at least ten peaks and therefore impose more detailed diffraction limitations.

The claims use “about” before the diffraction angles. That language generally allows analytical variation caused by instrument calibration, sample preparation, crystallinity, radiation source, and measurement conditions. It does not eliminate the need for the accused material to correspond materially to Form B.

Claims 4 through 6: compositions containing Form B

Claims 4, 5, and 6 each cover a pharmaceutical composition containing Form B and a pharmaceutically acceptable diluent or carrier.

These claims are broader than claims 7 through 9 because they do not require a specific excipient set. A composition can potentially fall within claims 4 through 6 even if it uses a carrier system different from the formulation described in claims 7 through 9.

Claims 7 through 9: named excipient combinations

Claims 7, 8, and 9 require the composition to contain:

Microcrystalline cellulose
Mannitol
Croscarmellose sodium
Magnesium stearate

These claims depend on claims 4, 5, and 6, respectively. They therefore require both the Form B polymorph and the specified excipient combination.

Claims 10 through 12: quantitative tablet claims

Claims 10, 11, and 12 are the narrowest and most commercially specific claims. Each requires:

Component	Claimed range
Magnesium stearate	0.5% to 2% by weight
Croscarmellose sodium	2% to 5% by weight
Crystalline Form B	15% to 60% by weight
Microcrystalline cellulose to mannitol ratio	3:1 to 1:1
Form B amount per tablet	50 mg to 500 mg

The claims also require the tablet to include microcrystalline cellulose and mannitol. A tablet outside any one of these quantitative limits may avoid literal infringement of claims 10 through 12, although claims 4 through 9 could remain relevant if the tablet still contains Form B and the specified excipients.

How broad is the patent scope?

The patent has a layered scope rather than a single broad monopoly.

Core protection: Form B itself

Claims 1 through 3 are the central commercial claims. They potentially cover Form B regardless of whether the material is sold as a pure active ingredient, placed in a capsule, compressed into a tablet, or used in another pharmaceutical dosage form.

A competitor using Form B would face the greatest exposure under these claims. Changing the tablet excipients would not necessarily avoid infringement if the active ingredient remains Form B.

Intermediate protection: Form B compositions

Claims 4 through 9 extend protection into pharmaceutical products. Claims 4 through 6 are composition claims with a relatively broad carrier limitation. Claims 7 through 9 focus on the named excipient package.

Narrow product protection: specific tablets

Claims 10 through 12 are limited by percentages, excipient identity, excipient ratio, and Form B dose. They may be difficult to enforce against products that use a different formulation design, even where the active ingredient is Form B.

The commercial hierarchy is therefore:

Form B claims: broadest practical product coverage.
General composition claims: broad formulation coverage.
Named excipient claims: narrower formulation coverage.
Quantitative tablet claims: narrowest but most product-specific coverage.

What is the patent expiration date for US9487525?

The patent issued on November 8, 2016. Its relevant U.S. nonprovisional filing date is February 21, 2014. On that basis, the nominal 20-year term would end on February 21, 2034.

Milestone	Date
Priority or earliest relevant filing period	February 2013
U.S. nonprovisional filing	February 21, 2014
U.S. publication	2015
Patent grant	November 8, 2016
Nominal patent-term endpoint	February 21, 2034

The grant date does not determine expiration. The relevant term generally runs from the earliest effective nonprovisional or international application date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and maintenance-fee status.[4]

Because brepocitinib is not an FDA-approved product, there is no apparent Hatch-Waxman patent-term extension tied to an approved NDA. Any actual adjustment should be confirmed against the USPTO patent record.

What is the FDA and Orange Book status of brepocitinib?

Brepocitinib does not appear to have an FDA-approved product listed in the Orange Book. It has been developed for immune-mediated diseases, including dermatomyositis, noninfectious uveitis, alopecia areata, and other inflammatory conditions.

The regulatory consequences are material:

No approved brepocitinib NDA means no Orange Book listing for U.S. generic-drug certification.
A conventional Abbreviated New Drug Application pathway is not currently available for an unapproved reference product.
A future generic applicant would need an approved reference product or another viable FDA pathway.
A competitor could still challenge the patent through inter partes review, post-grant review where available, declaratory litigation, or an infringement action arising from commercial activity.
If brepocitinib later receives approval, Pfizer or another NDA sponsor could seek Orange Book listing of relevant patents, subject to FDA listing rules.

The absence of an Orange Book listing does not make US9487525 irrelevant. It means that the familiar Paragraph IV framework is not presently the principal route for challenging this patent.

Are there Paragraph IV challenges to US9487525?

No publicly established Paragraph IV challenge is identified for US9487525 in the absence of an approved brepocitinib reference product and corresponding Orange Book listing.

Paragraph IV certification applies to an ANDA applicant challenging a patent listed for an FDA-approved reference product. Because brepocitinib has not been identified as an approved Orange Book reference drug, a generic applicant would not ordinarily file a Paragraph IV certification against this patent today.

If brepocitinib is approved in the future and US9487525 is listed, potential ANDA certifications could include:

Paragraph III certification, accepting expiry before launch.
Paragraph IV certification, alleging invalidity, unenforceability, or noninfringement.
A section viii statement, if the patent claims only an unapproved method of use and not the product or formulation.

US9487525 principally claims the polymorph and dosage-form composition. If listed, it would be more likely to create product or formulation certification issues than a pure method-of-use issue.

What infringement theories apply to Form B?

The principal infringement question is whether a competing product contains the claimed Form B material.

Literal infringement

Literal infringement may be established through:

PXRD comparison against the claimed peak sets.
Solid-state characterization of the active ingredient.
Batch records identifying Form B.
Manufacturing specifications.
Pharmaceutical development reports.
Regulatory chemistry, manufacturing, and controls records.

The six-peak pattern in claim 1 may present the broadest literal-infringement risk. Claims 2 and 3 provide alternative ten-peak definitions that may capture the same polymorph under different analytical descriptions.

Product-by-process considerations

The claims are product claims characterized by PXRD, not process claims. A competitor cannot necessarily avoid them by manufacturing Form B through a different crystallization process. If the resulting material has the claimed Form B characteristics, the production route may not matter.

Mixtures and polymorph conversion

A product containing a mixture of Form B and another solid form presents a fact-intensive issue. The risk depends on whether the accused material contains Form B in a manner covered by the claim and whether the claim requires a substantially pure crystalline form or merely the identified material.

A competitor may seek to use:

An amorphous form.
A different crystalline polymorph.
A hydrate or solvate.
A salt or co-crystal, if chemically distinct.
A formulation in which Form B converts before final dosage-form manufacture.

These approaches require solid-state and pharmaceutical-performance validation. Physical conversion during processing may create infringement and stability risks.

What patent landscape surrounds brepocitinib?

The relevant landscape has several layers.

Patent layer	Typical subject matter	Relationship to US9487525
Core compound patents	Brepocitinib structure and related JAK/TYK2 inhibitors	Earlier and potentially broader chemical protection
Polymorph patents	Form B and other crystalline forms	US9487525 is in this category
Formulation patents	Tablets, excipients, dissolution, stability, dosage strengths	Claims 7 through 12 provide formulation protection
Method-of-use patents	Dermatomyositis, uveitis, alopecia areata, and other indications	Separate from the asserted claims
Manufacturing patents	Crystallization, purification, intermediate preparation	May create independent process barriers
Regulatory exclusivity	New chemical entity, orphan, pediatric, or clinical exclusivity	Depends on FDA approval and designation

US9487525 does not by itself establish exclusivity over every use of brepocitinib. A competitor could potentially avoid this patent by using a non-Form-B solid form, but it may still encounter core compound, method-of-use, manufacturing, or other formulation patents.

Core compound protection

The core compound family is likely more important for early market-entry analysis than the Form B patent. If a core compound patent remains enforceable, changing the polymorph would not provide a complete freedom-to-operate position.

Method-of-use protection

Brepocitinib development programs have involved multiple inflammatory and autoimmune indications. Method-of-use patents may protect particular dosing regimens, patient populations, combinations, or disease indications. Those patents could affect launch strategy even if a competitor avoids Form B.

Manufacturing protection

Manufacturing patents may cover:

Key intermediates.
Enantioselective synthesis.
Coupling of the pyrrolopyrimidine and piperidine fragments.
Resolution or chiral enrichment.
Crystallization of Form B.
Impurity control and purification.

A Form B design-around may therefore shift risk from solid-state IP to process IP.

How strong is the patent estate for Form B?

US9487525 is technically focused but commercially meaningful.

Strengths

Claims the active pharmaceutical ingredient in a defined crystalline form.
Includes multiple PXRD definitions.
Covers compositions broadly through claims 4 through 6.
Includes a specific tablet formulation aligned with conventional oral dosage forms.
The claims do not depend on a particular therapeutic indication.
A different manufacturing process may still produce infringing Form B.

Limitations

The patent does not claim the underlying brepocitinib molecule.
It does not claim every polymorph, hydrate, solvate, or amorphous form.
Tablet claims have narrow quantitative limitations.
PXRD claims can create litigation over peak tolerance, sample preparation, crystallinity, and mixed forms.
No current Orange Book listing creates no immediate ANDA-based litigation pathway.
The patent’s commercial value depends on whether Form B is the development or commercial form.

The strongest position is against a competitor that uses Form B in an oral tablet. The weakest position is against a product using a genuinely distinct solid form and a formulation outside the claimed excipient and quantitative limitations.

What generic or competing launch scenarios exist?

Scenario 1: Form B tablet launch

A competitor uses Form B in a tablet containing the claimed excipients and dose range. This creates the highest direct infringement risk under claims 1 through 12.

Scenario 2: Form B with a different formulation

A competitor uses Form B but substitutes excipients or changes the dose. Claims 1 through 6 may remain relevant even if claims 7 through 12 are avoided.

Scenario 3: Different polymorph

A competitor develops another crystalline form. This may avoid the literal scope of claims 1 through 3, but core compound, manufacturing, formulation, and method-of-use patents remain potential barriers.

Scenario 4: Amorphous material

An amorphous product may avoid a crystalline Form B claim. Development risks include hygroscopicity, physical instability, recrystallization, dissolution variability, and scale-up reproducibility.

Scenario 5: Different salt, solvate, or co-crystal

A chemically distinct solid form may avoid Form B claims, but the approach requires regulatory, bioequivalence, and formulation work. It may also encounter separate solid-form patents.

What licensing and commercial issues affect the patent?

Brepocitinib development has involved Pfizer-originated rights and collaborations connected to Priovant Therapeutics and other development partners. The precise allocation of patent ownership, prosecution control, sublicensing rights, and enforcement authority depends on the relevant transaction documents.

For US9487525, the key diligence questions are:

Whether Pfizer retained ownership or granted exclusive field rights.
Whether a license covers all therapeutic indications or only specified diseases.
Whether the license includes patent enforcement rights.
Whether sublicenses extend to regional development partners.
Whether royalties or milestone obligations apply to commercial sales.
Whether prosecution decisions require partner consent.

Because the patent is not tied to an approved product, present revenue exposure is development-value exposure rather than established product revenue. The economic value increases substantially if brepocitinib receives approval and Form B becomes the commercial solid form.

What geographic coverage does the patent provide?

US9487525 provides U.S. protection only. Foreign protection must be assessed through the corresponding international and national-phase patent family.

The likely relevant jurisdictions for a commercial launch include:

European Patent Office member states.
United Kingdom.
Japan.
China.
Canada.
Australia.
South Korea.
Switzerland.

Foreign claims may differ from the U.S. claims because of prosecution amendments, added matter restrictions, unity objections, national-phase practice, and local standards for polymorph claims. A U.S. freedom-to-operate conclusion cannot be extended automatically to Europe, Japan, or China.

Key Takeaways

US9487525 protects brepocitinib crystalline Form B, not the underlying molecule in all forms.
Claims 1 through 3 are PXRD-defined polymorph claims and provide the primary product protection.
Claims 4 through 9 cover compositions containing Form B, with claims 7 through 9 requiring microcrystalline cellulose, mannitol, croscarmellose sodium, and magnesium stearate.
Claims 10 through 12 cover narrow tablet formulations with defined excipient percentages, a microcrystalline-cellulose-to-mannitol ratio, and 50 mg to 500 mg of Form B.
The expected nominal U.S. expiration date is February 21, 2034, subject to USPTO-recorded term adjustments.
Brepocitinib has not been identified as an FDA-approved Orange Book product, so no current Paragraph IV pathway is apparent.
A different polymorph may avoid US9487525 but could remain exposed to core compound, process, method-of-use, or other formulation patents.
The patent presents the greatest launch risk when Form B is used in an oral tablet resembling the claimed excipient system.

FAQs

Does US9487525 cover all brepocitinib tablets?

No. It covers tablets containing crystalline Form B, and the narrower tablet claims require specified excipients, percentages, dose amounts, and an excipient ratio. Tablets using another solid form may avoid the patent’s literal polymorph claims.

Can a competitor avoid US9487525 by changing the crystallization process?

Not necessarily. The claims are directed to the resulting crystalline Form B and are characterized by PXRD. A different manufacturing process may still produce the claimed polymorph.

Is brepocitinib eligible for an ANDA Paragraph IV challenge?

Not based on the current absence of an FDA-approved Orange Book reference product. A Paragraph IV certification would become relevant if brepocitinib receives approval and the patent is properly listed.

Does an amorphous brepocitinib product infringe Form B claims?

An exclusively amorphous product would generally present a stronger noninfringement position than a product containing Form B. Recrystallization, residual Form B, or mixed solid-state material could alter that analysis.

Does US9487525 protect brepocitinib treatment for dermatomyositis or uveitis?

No. The supplied claims do not recite a disease, patient population, dosing regimen, or therapeutic method. Separate method-of-use patents may protect those indications.

References

Pfizer Inc. (2016). U.S. Patent No. 9,487,525: Crystalline forms of (S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide. U.S. Patent and Trademark Office.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA.
U.S. Food and Drug Administration. (n.d.). Drugs@FDA: FDA-approved drugs database. FDA.
United States Code. (2023). 35 U.S.C. §§ 154, 156: Patent term and patent term extension. U.S. Government Publishing Office.
U.S. Patent and Trademark Office. (n.d.). Patent Center. USPTO.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Astrazeneca	TRUQAP	capivasertib	TABLET;ORAL	218197-001	Nov 16, 2023		RX	Yes	No	⤷ Start Trial	⤷ Start Trial	Y	Y			⤷ Start Trial
Astrazeneca	TRUQAP	capivasertib	TABLET;ORAL	218197-002	Nov 16, 2023		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y	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
Australia	2013204533	⤷ Start Trial
Brazil	112014025586	⤷ Start Trial
Canada	2869936	⤷ Start Trial
China	104203953	⤷ Start Trial
European Patent Office	2847194	⤷ Start Trial
Spain	2650797	⤷ Start Trial
Hong Kong	1206337	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 9,487,525