Details for Patent: 9,861,638

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Which drugs does patent 9,861,638 protect, and when does it expire?

Patent 9,861,638 protects RUBRACA and is included in one NDA.

This patent has sixty-three patent family members in thirty countries.

Summary for Patent: 9,861,638

Title:	Salts and polymorphs of 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one
Abstract:	The present invention relates to novel polymorphic forms of 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one, and to processes for their preparation. Such polymorphic forms may be a component of a pharmaceutical composition and may be used to treat a mammalian disease condition mediated by poly(ADP-ribose) polymerase activity including the disease condition such as cancer.
Inventor(s):	Patricia Ann Basford, Anthony Michael Campeta, Adam Gillmore, Matthew Cameron Jones, Eleftherios Kougoulos, Suman Luthra, Robert Walton
Assignee:	Pfizer Corp SRL
Application Number:	US14/698,463
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

US Patent 9,861,638: Rucaparib Salt, Polymorph, and BRCA-Mutated Ovarian Cancer Claims

US Patent 9,861,638 protects selected pharmaceutical salts and crystalline forms of rucaparib when used to inhibit PARP or treat ovarian cancer in patients with BRCA1 and/or BRCA2 mutations. Its strongest commercial relevance is to Rubraca, the rucaparib camsylate product marketed by Clovis Oncology.

The patent is narrower than a basic compound patent. It does not broadly claim every rucaparib product, every PARP inhibitor, or every cancer indication. Its independent claims require both a specified rucaparib salt and a patient with ovarian cancer carrying a BRCA1 and/or BRCA2 mutation.

What drug and product are covered by US 9,861,638?

The claimed active pharmaceutical ingredient is rucaparib, identified in the patent by its chemical name:

8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one.

The patent covers only two salt categories:

Claimed salt	Commercial relevance
Rucaparib camsylate	Principal relevance to Rubraca
Rucaparib maleate	Covered by the patent but not the principal approved Rubraca form

Rubraca is an oral PARP inhibitor containing rucaparib camsylate. The FDA approved Rubraca tablets for specified ovarian, fallopian-tube and primary peritoneal cancer indications, including treatment settings involving deleterious or suspected deleterious BRCA mutation status.[1]

The patent claims are directed to methods of use rather than a standalone composition of matter. This distinction matters because a product containing rucaparib may implicate other patent families even if a particular use does not satisfy the BRCA-mutated ovarian cancer limitations of US 9,861,638.

What are the independent claims of US 9,861,638?

Claims 1 and 10 are the two independent claims.

Claim	Legal category	Required disease	Required biomarker	Required product
1	Method of inhibiting PARP activity	Ovarian cancer	BRCA1 and/or BRCA2 mutation	Rucaparib camsylate or rucaparib maleate
10	Method of treating cancer	Ovarian cancer	BRCA1 and/or BRCA2 mutation	Rucaparib camsylate or rucaparib maleate

Both claims require administration of a therapeutically effective amount of a pharmaceutical composition containing the specified salt and a pharmaceutically acceptable carrier.

Claim 1 is framed around PARP inhibition. Claim 10 is framed around cancer treatment. In practice, the two claims substantially overlap because administration of rucaparib for treatment of BRCA-mutated ovarian cancer ordinarily produces the claimed PARP-inhibition effect.

The claims do not require:

• A particular line of therapy.
• Platinum sensitivity or platinum resistance.
• A particular BRCA mutation sequence.
• A specified dose within the broad independent claims.
• A particular tablet strength.
• Combination treatment.
• A particular level of PARP inhibition.
• A specific ovarian cancer histology.

How broad is the BRCA and ovarian cancer limitation?

The disease and biomarker limitations materially narrow the patent.

The patient must have ovarian cancer and a BRCA1 and/or BRCA2 mutation. The wording does not expressly limit the claims to germline mutations. On its face, the language can encompass germline and somatic BRCA mutations, provided the patient has the claimed mutation and the other limitations are satisfied.

The claims also do not expressly require that the ovarian cancer be caused by the BRCA mutation. The operative limitation is that the mammal has ovarian cancer and a BRCA1 and/or BRCA2 mutation.

The word "and/or" extends the biomarker limitation to:

1. BRCA1 mutation only;
2. BRCA2 mutation only; or
3. Both BRCA1 and BRCA2 mutations.

A patient with a broader homologous recombination deficiency profile but no BRCA1 or BRCA2 mutation would not satisfy the literal biomarker limitation.

A patient with ovarian cancer but an alteration only in RAD51C, RAD51D, PALB2 or another homologous recombination gene would also fall outside the express BRCA limitation unless another infringement theory applied.

What salts and polymorphs are protected?

Rucaparib camsylate

Claim 4 narrows the camsylate embodiment to S-camsylate polymorph Form A. The claimed powder X-ray diffraction pattern must contain one or more of the following peaks:

Polymorph	Claimed PXRD peaks, 2θ
S-camsylate Form A	12.2° ± 0.2°
	14.8° ± 0.2°
	22.5° ± 0.2°

The claim allows one, two or three of these peaks. It therefore does not require the presence of all three listed peaks under the literal wording.

The PXRD measurement is specified to use copper K-alpha1 radiation at a wavelength of 1.5406 angstroms. That analytical limitation is important. A polymorph assessment would ordinarily compare the accused material against the claimed diffraction characteristics using a controlled powder X-ray diffraction method.

Rucaparib maleate

Claim 5 covers two maleate polymorphs:

Polymorph	Required PXRD peaks, 2θ
Maleate Form A	6.0° ± 0.2°
	20.3° ± 0.2°
	21.7° ± 0.2°
Maleate Form B	7.5° ± 0.2°
	11.3° ± 0.2°
	24.3° ± 0.2°

Unlike claim 4, claim 5 states that each listed form has peaks at the identified angles. The maleate claims therefore provide a more specific solid-state definition.

A rucaparib salt with a different counterion, such as hydrochloride, sulfate, phosphate or a different sulfonate, would not satisfy the express camsylate-or-maleate limitation.

What formulation claims are included?

Claims 6 and 7, and their counterparts claims 15 and 16, cover solid dosage forms.

The listed forms are:

• Tablets;
• Powders;
• Pellets;
• Troches; and
• Lozenges.

The dosage-form limitations apply to the method claims. They do not independently claim a tablet or a formulation in the absence of the required patient, disease, mutation, rucaparib salt and administration limitations.

The most commercially important embodiment is the tablet. Rubraca is marketed as an oral tablet, making the solid-dose claims relevant to the approved product presentation.[1]

The formulation claims are not conventional excipient claims. They do not identify a specific binder, disintegrant, coating, dissolution profile or release mechanism. A generic tablet could therefore implicate the patent based on the active salt and method of administration even if its excipient system differs.

What dose ranges are protected?

Claims 8 and 9, and claims 17 and 18, specify dose ranges based on the amount of salt administered per kilogram of mammal body weight.

Claims	Dose range
8 and 17	About 0.001 to about 1,000 mg/kg
9 and 18	About 0.001 to about 50 mg/kg

The narrower 0.001 to 50 mg/kg range is nested within the broader range.

The use of "about" creates a boundary issue that would depend on claim construction, technical context and the accused dosing regimen. The commercial Rubraca dosing schedule is ordinarily expressed as a fixed tablet dose rather than a body-weight-based dose. Whether an approved regimen falls within a claim range would require conversion of the administered amount to mg/kg for the relevant patient.

Claims 1 and 10 do not require either dose limitation. A method may therefore infringe the independent claim without satisfying claims 8, 9, 17 or 18.

What combination-treatment claims does the patent cover?

Claims 2 and 11 cover administration with another therapeutic agent. The categories include:

• Anti-tumor agents;
• Anti-angiogenesis agents;
• Signal-transduction inhibitors;
• Anti-proliferative agents;
• Mitotic inhibitors;
• Alkylating agents;
• Antimetabolites;
• Intercalating antibiotics;
• Growth-factor inhibitors;
• Cell-cycle inhibitors;
• Enzymes;
• Topoisomerase inhibitors;
• Biological-response modifiers;
• Antibodies;
• Cytotoxic agents;
• Anti-hormones; and
• Anti-androgens.

Claims 3 and 12 identify five specific anti-tumor agents:

1. Temozolomide;
2. Irinotecan;
3. Topotecan;
4. Cisplatin; and
5. Doxorubicin hydrochloride.

These claims require combination administration. They do not merely cover a product that could theoretically be combined with another cancer drug. Evidence would ordinarily be needed that the rucaparib salt and the second agent are administered as part of the claimed treatment method.

How are the claims structured?

The claims are highly repetitive. Claims 1 through 9 cover the PARP-inhibition method, while claims 10 through 18 repeat the same hierarchy for cancer treatment.

Claim group	Scope
1 and 10	Independent treatment/use claims
2 and 11	Combination with broad classes of anti-cancer agents
3 and 12	Combination with five named agents
4 and 13	S-camsylate Form A
5 and 14	Maleate Forms A and B
6 and 15	Solid dosage form
7 and 16	Tablet, powder, pellet, troche or lozenge
8 and 17	Broad dose range
9 and 18	Narrower dose range

The repeated claim structure increases the number of potential infringement combinations but does not materially expand the independent active-ingredient scope.

What patent estate surrounds rucaparib and Rubraca?

US 9,861,638 is one part of the rucaparib patent estate. A commercial freedom-to-operate review should separate the estate into five groups.

Compound and core PARP-inhibitor patents

Earlier patent families may cover the rucaparib molecule, related chemical genus, intermediates or methods for making the active compound. These patents can create exposure independent of the salt and polymorph claims in US 9,861,638.

Salt and solid-state patents

US 9,861,638 is principally important in this category. It covers camsylate and maleate salts, with narrower claims to selected crystalline forms.

Solid-state patents can be difficult to design around when the marketed product uses the claimed form. A generic manufacturer may need to demonstrate that its process produces a different salt, amorphous material or unclaimed polymorph, while also addressing whether another patent covers that alternative.

Method-of-use patents

US 9,861,638 is also a method-of-use patent. Its core method claims combine:

• Rucaparib salt;
• Ovarian cancer;
• BRCA1 and/or BRCA2 mutation; and
• Therapeutic administration.

Other rucaparib method patents may cover different lines of therapy, biomarker populations, maintenance treatment, platinum sensitivity, or broader cancer indications.

Formulation patents

Claims 6, 7, 15 and 16 are dosage-form limitations within treatment claims. They are narrower than a standalone formulation patent because they still require the BRCA-mutated ovarian cancer treatment context.

Manufacturing and process patents

Manufacturing patents may cover preparation of rucaparib, salt formation, crystallization, polymorph control, particle-size management or tablet production. These patents can create a separate barrier even where a finished-product formulation avoids a particular use patent.

What is the Orange Book status of US 9,861,638?

The FDA Orange Book is the principal U.S. source for patents submitted by an approved drug sponsor for listed drug products.[2] The relevant analysis for Rubraca requires checking the current Orange Book patent listing for the applicable rucaparib product and dosage form.

A patent’s presence in the Orange Book does not itself prove validity or infringement. It does, however, affect the abbreviated new drug application process because a generic applicant must address listed patents through a Paragraph IV certification, a Section VIII statement where appropriate, or another statutory certification pathway.

The commercial significance of US 9,861,638 depends on:

1. Whether it is listed against the relevant Rubraca product;
2. Its listed expiration date;
3. Whether pediatric exclusivity or patent-term adjustment applies;
4. Whether a generic applicant makes a Paragraph IV certification;
5. Whether the sponsor brings suit within the statutory period; and
6. Whether a settlement agreement restricts the generic entry date.

The patent number alone is not a reliable substitute for the current Orange Book listing. Patent expiration may differ from the nominal 20-year term because of patent-term adjustment, terminal disclaimers, patent-term extension or other USPTO and FDA records.

When does US 9,861,638 lose exclusivity?

US 9,861,638 loses enforceability when its adjusted expiration date is reached, subject to any applicable statutory adjustment or earlier invalidation.

The governing starting point is generally the earliest effective U.S. nonprovisional filing date in the relevant family, not necessarily the issue date. The issue date of January 9, 2018 does not establish the expiration date.

For business planning, the relevant date should be taken from:

• USPTO Patent Center;
• The patent face and continuity data;
• The Orange Book listing;
• Any terminal disclaimer;
• Any patent-term adjustment calculation; and
• Any applicable pediatric exclusivity.

A generic launch before the expiration date could still occur if the patent is invalidated, not infringed, licensed, disclaimed or otherwise removed from the relevant regulatory barrier.

What Paragraph IV risks exist for a rucaparib generic?

A rucaparib generic applicant could challenge US 9,861,638 through a Paragraph IV certification if the patent is listed against the reference product and the applicant asserts that the patent is invalid, unenforceable or will not be infringed.[3]

The principal challenge theories would likely focus on:

Lack of infringement

A proposed product could avoid literal infringement by using:

• A non-camsylate, non-maleate salt;
• An unclaimed polymorph;
• An amorphous form;
• A formulation not covered by a narrower dependent claim; or
• A label that excludes the claimed BRCA-mutated ovarian cancer use, subject to inducement risk.

A different salt may create separate pharmaceutical and regulatory issues, including whether it is the same active ingredient for abbreviated approval purposes and whether it has comparable pharmaceutical properties.

Invalidity based on anticipation or obviousness

Potential prior-art issues include earlier disclosures of:

• Rucaparib;
• Rucaparib camsylate;
• Rucaparib maleate;
• The claimed polymorphs;
• PARP inhibition in BRCA-mutated ovarian cancer; or
• Combination treatment with the named anti-cancer agents.

The polymorph claims would turn heavily on whether the prior art disclosed the claimed crystalline form and the specified diffraction peaks. The treatment claims would face separate questions concerning the predictability of treating BRCA-mutated ovarian cancer with a PARP inhibitor.

Written description and enablement

The claims cover a broad patient population and multiple salt and treatment embodiments. A challenger could argue that the specification does not adequately support the full scope, particularly if the disclosure is narrower than the issued claims. The strength of that argument depends on the patent specification, examples and prosecution history rather than the claim text alone.

Which companies are most exposed to this patent?

Clovis Oncology has the direct commercial exposure because Rubraca is its branded rucaparib product. Generic manufacturers would face the greatest risk if they seek approval for a rucaparib product that uses rucaparib camsylate and carries a label for BRCA-mutated ovarian cancer.

Potentially exposed parties include:

• The generic applicant;
• Its active-ingredient or salt manufacturer;
• Contract manufacturers producing the claimed form;
• Distributors involved in a product launch; and
• Health-care providers or institutions where a patented use is actively induced.

A generic product with a carved-out label may reduce use-patent exposure, but a skinny label does not eliminate risk if marketing, product information, promotional activity or prescribing patterns support induced infringement.

How strong is the patent estate?

US 9,861,638 has meaningful commercial value because its core claim maps onto the approved rucaparib camsylate product and a clinically important biomarker-defined ovarian cancer population.

Its strength is reduced by the cumulative limitations:

• The claims require ovarian cancer;
• The patient must have a BRCA1 and/or BRCA2 mutation;
• The product must contain camsylate or maleate;
• Some dependent claims require specific solid forms;
• The claims are method claims rather than broad compound claims; and
• The patent does not expressly cover all rucaparib indications.

The strongest practical claims are likely claims 1 and 10 when the marketed product is administered for the claimed BRCA-mutated ovarian cancer population. Claims 4, 5, 13 and 14 provide additional solid-state protection but require analytical proof of the claimed form. Claims 6 through 9 and 15 through 18 add narrower formulation and dose limitations without being necessary to establish infringement of the independent claims.

How does US 9,861,638 compare with competing PARP inhibitor patents?

Product	Active ingredient	Typical patent focus	Relationship to US 9,861,638
Rubraca	Rucaparib camsylate	Rucaparib compound, salts, polymorphs and methods	Directly relevant
Lynparza	Olaparib	Compound, formulation and use patents	Separate estate
Zejula	Niraparib tosylate	Compound, salts, formulations and use patents	Separate estate
Talzenna	Talazoparib tosylate	Compound, formulation and use patents	Separate estate
Elahere	Mirvetuximab soravtansine	Antibody-drug conjugate patents	Not a direct PARP comparison

US 9,861,638 is narrower than a foundational rucaparib compound patent but more product-specific than a broad PARP inhibitor genus patent. Its commercial leverage comes from alignment with the salt form used in the marketed product.

What generic launch scenarios exist?

Three principal launch scenarios exist.

Launch after patent expiry

This is the lowest-risk scenario if all relevant Orange Book patents and regulatory exclusivities have expired or been resolved.

Launch following a successful Paragraph IV challenge

A generic applicant could launch before the listed expiration date if it prevails in litigation, obtains a favorable settlement, or establishes that the patent is not infringed.

Label carve-out or alternative product

A generic may attempt to omit the patented BRCA-mutated ovarian cancer use or use a different salt or solid form. This strategy may reduce exposure to US 9,861,638 but cannot be assessed in isolation from other rucaparib patents and induced-infringement risks.

What geographic coverage does the patent provide?

US 9,861,638 provides rights in the United States only. It does not directly block manufacture, sale or use in Europe, Japan, China, Canada or other jurisdictions.

A global freedom-to-operate review must examine corresponding national patents and applications in each market. The claims, expiration dates, prosecution outcomes and litigation positions can differ substantially by jurisdiction.

Manufacturing in another country may still create U.S. exposure if the patented product is imported into the United States or if the patented method is practiced domestically. U.S. law also contains separate provisions relevant to products made by patented processes and activities undertaken for regulatory submission.

Key Takeaways

• US 9,861,638 covers methods of using rucaparib camsylate or maleate in BRCA1- and/or BRCA2-mutated ovarian cancer.
• Claims 1 and 10 are the principal independent claims.
• The patent does not broadly claim every rucaparib product or every PARP-inhibitor use.
• Claim 4 covers S-camsylate polymorph Form A through specified PXRD peaks.
• Claim 5 covers maleate Forms A and B through separate PXRD peak sets.
• Claims 6, 7, 15 and 16 cover solid dosage-form administration within the claimed treatment methods.
• Claims 8, 9, 17 and 18 add dose-range limitations but are not required for infringement of claims 1 and 10.
• The patent is commercially relevant to Rubraca because the marketed product uses rucaparib camsylate.
• Paragraph IV exposure depends on the current Orange Book listing, expiration data, claim construction, product form and proposed generic labeling.
• Patent-term analysis must use the adjusted expiration date, not the 2018 issue date.

FAQs

Does US 9,861,638 cover rucaparib for prostate cancer?

Not expressly. The independent claims require that the mammal have ovarian cancer. Rucaparib use in prostate cancer would need to be evaluated against other patents and regulatory claims.

Does the patent cover rucaparib free base?

The claims identify camsylate and maleate salts. Rucaparib free base does not literally satisfy those salt limitations, although other patents may cover the molecule or its use.

Can a generic use a different rucaparib polymorph?

A different polymorph may avoid claims directed specifically to S-camsylate Form A or maleate Forms A and B. It would still require analysis of the broader salt claims, other patent families and potential equivalents arguments.

Does BRCA-negative ovarian cancer fall within the claims?

No. The independent claims require a mammal having a BRCA1 and/or BRCA2 mutation. A BRCA-negative patient would not satisfy that express limitation.

Is the patent a composition-of-matter patent?

No. The issued claims provided here are method claims. They require administration of specified rucaparib salts in a defined ovarian cancer and BRCA-mutated patient population.

References

1. U.S. Food and Drug Administration. (2023). Rubraca (rucaparib camsylate) prescribing information.
2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
3. U.S. Food and Drug Administration. (2024). ANDA submissions: Amendments and requests for final approval to tentatively approved ANDAs.
4. United States Patent and Trademark Office. (2018). U.S. Patent No. 9,861,638: Salts of a PARP inhibitor.
5. United States Code, 35 U.S.C. §§ 271, 271(e), 154.

Drugs Protected by US Patent 9,861,638

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Pharmaand	RUBRACA	rucaparib camsylate	TABLET;ORAL	209115-001	Dec 19, 2016		RX	Yes	No						A METHOD FOR TREATING OVARIAN CANCER BY ADMINISTERING RUCAPARIB, WHEREIN THE CANCER IS ASSOCIATED WITH A DELETERIOUS BRCA MUTATION
Pharmaand	RUBRACA	rucaparib camsylate	TABLET;ORAL	209115-001	Dec 19, 2016		RX	Yes	No						A METHOD FOR TREATING EPITHELIAL OVARIAN, FALLOPIAN TUBE, OR PRIMARY PERITONEAL CANCER, WHEREIN THE CANCER IS ASSOCIATED WITH A DELETERIOUS BRCA MUTATION
Pharmaand	RUBRACA	rucaparib camsylate	TABLET;ORAL	209115-003	May 1, 2017		RX	Yes	No						A METHOD FOR TREATING EPITHELIAL OVARIAN, FALLOPIAN TUBE, OR PRIMARY PERITONEAL CANCER, WHEREIN THE CANCER IS ASSOCIATED WITH A DELETERIOUS BRCA MUTATION
Pharmaand	RUBRACA	rucaparib camsylate	TABLET;ORAL	209115-003	May 1, 2017		RX	Yes	No						A METHOD FOR TREATING OVARIAN CANCER BY ADMINISTERING RUCAPARIB, WHEREIN THE CANCER IS ASSOCIATED WITH A DELETERIOUS BRCA MUTATION

International Family Members for US Patent 9,861,638

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2534153		300958	Netherlands
European Patent Office	2534153		CA 2018 00041	Denmark
European Patent Office	2534153		122018000131	Germany
European Patent Office	2534153		PA2018517	Lithuania