Details for Patent: 9,840,505

Which drugs does patent 9,840,505 protect, and when does it expire?

Patent 9,840,505 protects COPIKTRA and is included in one NDA.

This patent has forty patent family members in twenty-three countries.

Summary for Patent: 9,840,505

Title:	Solid forms of (S)-3-(1-(9H-purin-6-ylamino)ethyl)-8-chloro-2-phenylisoquinolin-1 (2H)-one and methods of use thereof
Abstract:	Polymorphs of chemical compounds that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein. Also provided herein are processes for preparing compounds, polymorphs thereof, and pharmaceutical compositions thereof.
Inventor(s):	Pingda Ren, Michael Martin, Paul Isbester, Benjamin S. Lane, Jason Kropp
Assignee:	Infinity Pharmaceuticals Inc
Application Number:	US15/016,117
Patent Claim Types: see list of patent claims	Use;

US Patent 9,840,505: Scope, Claim Analysis, and Duvelisib Patent Landscape

US Patent 9,840,505 protects a specific hydrated solid form of the PI3K inhibitor duvelisib, marketed as Copiktra, when used to treat specified PI3K-mediated disorders. The patent is formulation-specific rather than a broad composition-of-matter patent. Its commercial value depends on whether an alternative duvelisib polymorph, hydrate, solvate, or anhydrous form can be developed without reproducing the claimed XRPD profile.

The patent’s core protection covers treatment methods using a solid form of duvelisib hydrate characterized by XRPD peaks at approximately 10.4°, 13.3°, and 24.3° 2θ. The claims extend across hematologic malignancies, asthma, rheumatoid arthritis, lupus, and combination regimens involving rituximab, bendamustine, fludarabine, cyclophosphamide, bortezomib, gemcitabine, corticosteroids, and other agents.

What drug and solid form does US Patent 9,840,505 cover?

US 9,840,505 is directed to a hydrate of duvelisib, a dual PI3K-delta and PI3K-gamma inhibitor. Duvelisib is approved in the United States under the brand name Copiktra for relapsed or refractory chronic lymphocytic leukemia, small lymphocytic lymphoma, and follicular lymphoma after at least two prior systemic therapies.[1]

The issued claim structure has four principal elements:

Claim element	Requirement
Therapeutic subject	A subject having a PI3K-mediated disorder
Active substance	A solid form comprising a hydrate of the compound of Formula I
Solid-form identity	XRPD peaks at 10.4° ±0.2°, 13.3° ±0.2°, and 24.3° ±0.2° 2θ
Disease	Hematological cancer, asthma, rheumatoid arthritis, or lupus

The chemical structure of Formula I is the active-molecule limitation. The XRPD limitations identify the claimed physical form. Both requirements must be met for literal infringement.

What are the independent and dependent claims in US 9,840,505?

Claim 1 is the principal independent claim. It combines a treatment method with a pharmaceutical solid-form limitation and a disease limitation.

Claims 2 through 16 narrow the disease scope. Claims 17 through 31 add combination-treatment limitations.

Claim 1: core method claim

Claim 1 requires administration of a therapeutically effective amount of a hydrated solid form having the three specified XRPD peaks. The disease must be one of the following:

• Hematological cancer
• Asthma
• Rheumatoid arthritis
• Lupus

The claim does not expressly require a particular dosage, route of administration, treatment duration, patient biomarker, disease stage, or concomitant medication.

Claims 2 through 16: disease-specific narrowing

The dependent claims divide the therapeutic field into inflammatory and hematologic indications.

Claims	Disease limitation
2	Asthma, rheumatoid arthritis, or lupus
3	Hematological cancer
4	Leukemia or lymphoma
5	AML, acute lymphocytic leukemia, hairy cell leukemia, CML, multiple myeloma, MDS, or HTLV-1 leukemia
6	Specified B-cell and T-cell lymphomas, Hodgkin disease, AIDS-related lymphoma, multiple myeloma, follicular lymphoma, or Waldenström macroglobulinemia
7	CLL
8-9	Non-Hodgkin lymphoma, including indolent NHL
10-11	Peripheral T-cell lymphoma or cutaneous T-cell lymphoma
12	Mantle cell lymphoma
13	Diffuse large B-cell lymphoma
14	Follicular lymphoma
15	Waldenström macroglobulinemia
16	Posttransplantational lymphoproliferative disorder

Claims 7, 9, 13, 14, and related hematologic claims are commercially important because they overlap with diseases in which duvelisib has been clinically developed or approved. The patent’s claim language is broader than the current Copiktra label because it includes diseases such as AML, multiple myeloma, solid inflammatory disorders, and several lymphoma subtypes.

A method using the claimed hydrate for an off-label disease could fall within the literal language of the patent if the accused party induces or directly performs the claimed treatment. FDA approval for the specific indication is not an express claim limitation.

What combination therapies are protected by US 9,840,505?

Claims 17 through 31 cover administration of the claimed duvelisib hydrate with one or more second therapeutic agents.

The combination claims include:

• Therapeutic antibodies
• Anti-CD20 antibodies
• Rituximab
• Everolimus
• Nitrogen mustards
• Bendamustine
• Chlorambucil
• Fludarabine
• Cyclophosphamide
• Bortezomib
• Gemcitabine
• Corticosteroids
• Dexamethasone

Claim 25 is particularly specific. It requires treatment with the claimed solid form plus both rituximab and bendamustine. Claim 27 covers fludarabine, cyclophosphamide, rituximab, or combinations of those agents.

The antibody list in claim 20 includes cetuximab, panitumumab, trastuzumab, rituximab, tositumomab, alemtuzumab, bevacizumab, and gemtuzumab. Claim 21 narrows the antibody to rituximab.

Combination-claim infringement analysis

A generic or competing manufacturer could face method-of-use exposure if its labeling recommends or encourages use of a duvelisib hydrate with one of the listed agents. The risk is strongest where:

1. The product contains the claimed hydrate;
2. The label identifies the patented disease;
3. The label recommends a listed combination; and
4. The combination is commercially meaningful in the relevant indication.

A product label that merely permits physician-directed combination use may create a weaker induced-infringement case than a label that expressly recommends the combination. The patent does not claim the combination products themselves. It claims administration of the claimed duvelisib form with the second agent.

How narrow is the XRPD solid-form limitation?

The XRPD limitation is the patent’s principal narrowing feature. The accused solid form must comprise a hydrate of Formula I and have peaks at all three specified positions within the stated ±0.2° tolerance.

The claim does not state that the three peaks must be the only peaks, the strongest peaks, or a complete fingerprint. It also does not state relative peak intensities, water content, crystal system, unit-cell parameters, thermal behavior, or a specific stoichiometric hydrate ratio.

That drafting structure creates both strength and uncertainty.

Scope advantages

The claim may cover a material even if it has additional XRPD peaks, provided the claimed three peaks are present within the specified tolerances. The phrase “comprising” generally permits additional components or characteristics.

The claim also does not require a particular manufacturing process. A defendant cannot avoid the claim merely by producing the same form through a different crystallization or drying process.

Scope limitations

The claim is vulnerable to a form-design strategy using:

• An anhydrous duvelisib form;
• A different hydrate;
• A solvate other than the claimed hydrate;
• An amorphous form;
• A polymorph lacking one or more claimed peaks;
• A crystalline form whose corresponding peaks fall outside the ±0.2° windows.

XRPD peak positions can vary with instrument calibration, sample preparation, humidity, particle size, preferred orientation, and data-processing methods. In litigation, the parties would likely contest the appropriate measurement protocol and whether the accused material’s peaks fall within the claimed tolerances.

The claim does not appear to require a full XRPD identity match. A competitor could therefore focus its development program on proving that at least one required peak is absent or materially displaced, rather than attempting to reproduce a wholly different chemical entity.

When does US Patent 9,840,505 expire?

The patent issued on December 12, 2017. Its term is generally calculated from the earliest effective nonprovisional or international filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and other statutory adjustments.[2]

The patent is associated with a priority chain beginning in 2013. On a basic 20-year calculation, the expected nominal expiration is in 2033, before any applicable patent-term adjustment. The precise enforceable expiration should be taken from the USPTO patent record and any FDA Orange Book entry.

Milestone	Date or status
Earliest reported priority period	2013
US patent grant	December 12, 2017
Expected base term	Approximately 2033
Patent-term adjustment	Must be confirmed from the issued patent record
FDA product	Copiktra, duvelisib
FDA approval	September 24, 2018
NCE exclusivity	Expired in 2023
Orphan exclusivity	Relevant to approved CLL/SLL and follicular lymphoma indications

Patent expiration and FDA regulatory exclusivity are separate. The end of five-year new chemical entity exclusivity did not terminate the patent. Orphan-drug exclusivity also operates independently and may block approval of the same drug for the same orphan indication even after NCE exclusivity has ended.[1][3]

What is the Orange Book status of US 9,840,505?

US 9,840,505 is part of the U.S. patent estate associated with Copiktra and duvelisib. FDA Orange Book treatment depends on whether the patent is listed against the approved drug product and whether the listing remains active for the relevant dosage form and indication.[3]

The practical significance of an Orange Book listing is substantial. An ANDA applicant may be required to make a Paragraph IV certification asserting that the listed patent is invalid, unenforceable, or will not be infringed. The patent holder may then bring an infringement action within 45 days, triggering a statutory stay of approval for up to 30 months under the Hatch-Waxman framework.[4]

The claims in 9,840,505 are method claims rather than claims directed solely to a drug substance or dosage-form composition. A Paragraph IV challenge would likely focus on:

• Whether the proposed product contains the claimed hydrate;
• Whether the proposed labeling induces use for a claimed disease;
• Whether the XRPD peaks are within the claimed ranges;
• Anticipation or obviousness based on prior solid forms;
• Enablement and written-description support for the full disease and combination breadth;
• Claim construction of “comprising a hydrate” and the XRPD limitations.

Which companies are challenging Copiktra or duvelisib patents?

The supplied claim set does not establish a Paragraph IV filing, ANDA applicant, district-court complaint, settlement, or license involving US 9,840,505. A patent document alone cannot establish that a generic company has challenged the patent.

No litigation conclusion should be inferred solely from the patent’s existence. Relevant evidence would be found in:

• FDA Paragraph IV notice records;
• District-court dockets;
• PTAB proceedings;
• Orange Book patent-listing data;
• SEC filings of the product sponsor and generic applicants;
• Public settlement announcements.

For commercial diligence, the key distinction is between a Paragraph IV challenge to the active-ingredient patent and a challenge to this later solid-form patent. A generic applicant may accept the active-ingredient patent but pursue a noninfringing alternative solid form. Conversely, a product that avoids a composition patent may still face infringement exposure under 9,840,505 if it uses the claimed hydrate.

How strong is the patent estate for duvelisib?

The estate has different layers of protection, with materially different enforcement characteristics.

Protection layer	Commercial function	Relative risk
Composition-of-matter patents	Protect duvelisib molecule and core chemical structure	Highest barrier if unexpired
Solid-form patent 9,840,505	Protects a defined hydrated crystalline form	Strong if commercial product uses that form
Method-of-use patents	Protect specified cancer or inflammatory uses	Depends on labeling and indication
Combination claims	Cover use with rituximab, bendamustine, and other agents	Narrower, fact-dependent
Regulatory exclusivity	Delays approval independent of patent validity	Time-limited
Manufacturing know-how	Controls crystallization, isolation, purity, and scale-up	May remain confidential

Patent 9,840,505 is stronger against a copycat that uses the commercial solid form than against a developer that invests in polymorph screening and changes the crystalline material. Its claims do not prevent all duvelisib products. They target a particular form used in a treatment method.

The estate is commercially stronger if the marketed product’s active pharmaceutical ingredient is consistently manufactured as the claimed hydrate and if the sponsor can demonstrate that generic samples contain the three claimed XRPD peaks. It is weaker if the commercial product can be supplied in multiple solid forms or if a stable alternative form is readily manufacturable.

What generic launch scenarios exist for Copiktra?

Three principal entry scenarios exist.

Paragraph IV challenge to the solid-form patent

The applicant alleges that US 9,840,505 is invalid, unenforceable, or not infringed. Litigation could delay approval under the Hatch-Waxman 30-month stay mechanism.

Section VIII carve-out

The applicant removes patented indications from its labeling where FDA permits a “skinny label.” This strategy is more difficult if the listed patent covers broad treatment use or if the remaining label still encourages a patented indication.

Noninfringing solid-form launch

The applicant develops an anhydrous form, different hydrate, amorphous material, or another polymorph and supports its product with XRPD and solid-state characterization. This route avoids literal infringement if the material lacks one of the three required peaks, although the sponsor could still assert equivalents or other patents.

A generic launch could also remain blocked by separate composition, formulation, method-of-use, or manufacturing patents even if 9,840,505 is defeated.

What patent litigation issues are most likely under US 9,840,505?

The central technical dispute would be solid-form identification. Key evidence would include:

• XRPD diffractograms from commercial and generic batches;
• Instrument calibration records;
• Peak-location calculations;
• Hydrate or water-content testing;
• Differential scanning calorimetry;
• Thermogravimetric analysis;
• Variable-humidity stability data;
• Batch-to-batch reproducibility;
• Crystallization and drying records.

The central legal disputes would likely involve claim construction, anticipation, obviousness, written description, enablement, and induced infringement. Prior art showing duvelisib itself may not anticipate the claimed hydrate unless it discloses or inherently produces the required solid form and XRPD characteristics.

Obviousness risk depends on whether the prior art disclosed duvelisib hydrates, routine polymorph screening, predictable crystallization conditions, and a reasonable expectation of obtaining the claimed form. Solid-form patents often turn on whether the claimed form has unexpected properties, such as improved stability, purity, hygroscopicity, dissolution, or manufacturability.

What licensing and ownership issues affect the duvelisib estate?

Duvelisib was developed by Infinity Pharmaceuticals and later commercialized through Verastem and subsequent commercial-rights arrangements. Ownership of individual patents, regulatory rights, and commercial rights may differ. A diligence review should distinguish:

• Patent ownership;
• FDA application ownership;
• U.S. commercialization rights;
• Manufacturing rights;
• Royalty obligations;
• Sublicense rights;
• Rights retained by original development parties.

A license or asset transfer does not automatically change the patent’s expiration date or the scope of its claims. It can, however, affect who has standing to sue, who receives Paragraph IV notices, and which party controls settlements.

Key Takeaways

• US 9,840,505 is a solid-form and method-of-treatment patent for duvelisib hydrate.
• Claim 1 requires the Formula I compound, a hydrate-containing solid form, three specified XRPD peaks, and treatment of a covered PI3K-mediated disorder.
• Claims 2 through 16 cover specific inflammatory diseases and hematologic malignancies.
• Claims 17 through 31 cover combinations with rituximab, bendamustine, fludarabine, cyclophosphamide, bortezomib, gemcitabine, corticosteroids, and other agents.
• The patent does not block every duvelisib product. Its principal vulnerability is development of a different solid form.
• The expected base patent term reaches approximately 2033, subject to the issued patent’s patent-term adjustment.
• NCE exclusivity expired in 2023, but patent protection and orphan exclusivity operate separately.
• A generic applicant’s strongest technical design-around is an alternative hydrate, polymorph, anhydrous form, or amorphous form lacking at least one claimed XRPD peak.
• Any commercial launch analysis must review the entire duvelisib patent estate, not US 9,840,505 alone.

FAQs About US Patent 9,840,505 and Duvelisib

Does US 9,840,505 cover duvelisib itself?

No. The claims require a particular hydrated solid form of the compound. Broader protection for the duvelisib molecule would arise from separate composition-of-matter patents.

Can a generic company avoid US 9,840,505 by using the same duvelisib molecule?

Potentially. A generic company may avoid this patent if its product uses a solid form that does not contain the claimed hydrate or does not exhibit one of the required XRPD peaks. Other duvelisib patents may still block launch.

Does the patent cover Copiktra’s approved CLL indication?

The claim set expressly includes CLL in claim 7. If Copiktra contains the claimed hydrate and is used for CLL, the product and use may fall within the claim scope.

Are asthma, rheumatoid arthritis, and lupus approved Copiktra indications?

No. Those diseases appear in the patent claims, but they are not the principal FDA-approved Copiktra indications described in the current U.S. prescribing information.[1]

Does a Paragraph IV challenge automatically invalidate US 9,840,505?

No. A Paragraph IV certification is an applicant’s legal position. Invalidity or noninfringement must be established through litigation, settlement, or another legally effective resolution.

References

1. U.S. Food and Drug Administration. (2018). Copiktra (duvelisib) prescribing information.
2. United States Patent and Trademark Office. (2017). U.S. Patent No. 9,840,505, solid forms of a PI3K inhibitor.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book.
4. United States Code. (2023). 21 U.S.C. § 355(j): Abbreviated applications and patent certifications.

Drugs Protected by US Patent 9,840,505

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Secura	COPIKTRA	duvelisib	CAPSULE;ORAL	211155-001	Sep 24, 2018		RX	Yes	No	9,840,505					FOR THE TREATMENT OF PATIENTS WITH FOLLICULAR LYMPHOMA (FL)
Secura	COPIKTRA	duvelisib	CAPSULE;ORAL	211155-001	Sep 24, 2018		RX	Yes	No	9,840,505					FOR THE TREATMENT OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) AND/OR SMALL LYMPHOCYTIC LEUKEMIA (SLL)
Secura	COPIKTRA	duvelisib	CAPSULE;ORAL	211155-002	Sep 24, 2018		RX	Yes	No	9,840,505					FOR THE TREATMENT OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) AND/OR SMALL LYMPHOCYTIC LEUKEMIA (SLL)
Secura	COPIKTRA	duvelisib	CAPSULE;ORAL	211155-002	Sep 24, 2018		RX	Yes	No	9,840,505					FOR THE TREATMENT OF PATIENTS WITH FOLLICULAR LYMPHOMA (FL)

International Family Members for US Patent 9,840,505

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	084824
Argentina	117467
Australia	2012205669
Australia	2015258280