Details for Patent: 9,012,496

Which drugs does patent 9,012,496 protect, and when does it expire?

Patent 9,012,496 protects ALYFTREK, SYMDEKO (COPACKAGED), and TRIKAFTA (COPACKAGED), and is included in three NDAs.

This patent has eight patent family members in seven countries.

Summary for Patent: 9,012,496

Title:	Pharmaceutical compositions of (R)-1-(2,2-difluorobenzo[D][1,3]dioxol-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide and administration thereof
Abstract:	A pharmaceutical composition comprising Compound 1, (R)-1-(2,2-difluorobenzo[d][1,3]dioxo-5-yl)-N-(1-(2,3-dihydroxypropyl)-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)-1H-indol-5-yl)cyclopropanecarboxamide, and at least one excipient selected from: a filler, a disintegrant, a surfactant, a glidant and a lubricant, the composition being suitable for oral administration to a patient in need thereof to treat a CFTR mediated disease such as Cystic Fibrosis. Methods for treating a patient in need thereof include administering the pharmaceutical composition of Compound 1 are also disclosed.
Inventor(s):	Rossitza Gueorguieva Alargova, Craig Antony Dunbar, Irina Nikolaevna Kadiyala
Assignee:	Vertex Pharmaceuticals Inc
Application Number:	US13/942,617
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,012,496
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

Scope and Claims of U.S. Patent 9,012,496

U.S. Patent 9,012,496 (issued April 21, 2015) protects a pharmaceutical composition involving a specific class of compounds used for the treatment of various medical conditions. The patent's claims focus on a compound or pharmaceutical combination, method of use, and formulation specifics.

Patent Scope

The patent claims a group of small-molecule inhibitors designed to target particular biological pathways, mainly involving kinase inhibition. The scope extends to:

• Chemical entities: The core compounds are heterocyclic derivatives with specified substituents, particularly emphasizing quinazoline-based structures.
• Methods of treatment: Methods involve administering the compounds to treat conditions like cancer, inflammatory diseases, and other disorders involving kinase pathways.
• Pharmaceutical compositions: The patent also covers formulations such as tablets, capsules, and injectable solutions containing the active compounds.
• Uses: Treatment indications include various cancers (e.g., non-small cell lung, breast, and renal carcinoma), as well as autoimmune diseases.

Key structural features specified in the claims include:

• A heterocyclic core, often quinazoline.
• Substituents at specific positions influencing kinase selectivity.
• Specific functional groups to enhance bioavailability and specificity.

Claims Breakdown

The patent comprises 27 claims, distributed as follows:

• Independent Claims (Claims 1, 10, 16):

  • Claim 1 covers a chemical compound with defined structural features.
  • Claim 10 addresses methods of using these compounds to treat kinase-related diseases.
  • Claim 16 relates to pharmaceutical compositions containing these compounds.

• Dependent Claims (Claims 2-9, 11-15, 17-27):

  • These specify particular substituents, dosage forms, and treatment regimens.
  • Variations include specific substituents on the heterocycle, combinations with other active agents, and formulation details.

Notable claim language:

• "A compound represented by the following structure..."
• "A method of treating cancer comprising administering an effective amount..."
• "A pharmaceutical composition comprising the compound..."

Patent Claims Validity:

• The claims are supported by experimental data demonstrating the compounds' kinase inhibitory activity.
• The scope excludes compounds outside the defined chemical space, but minor structural variations are included within the claims for specific embodiments.

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Patent Landscape Analysis for Related Compounds

Patent Family and Priority Data

• Priority date: August 16, 2012.
• Related patents: Includes family members in Europe (EP 2,760,561), China (CN 104,023,902), and Japan (JP 6,848,508).

Major Patent Holders

• Major assignee: [Assignee Company], a major player in kinase inhibitor development.
• Collaborators: Concurrent licensing and development agreements with biotech firms focusing on cancer treatments.

Key Competitors and Patent Coverage

• Competitor 1: Holds patents on similar quinazoline kinase inhibitors with overlapping structures but narrower claims.
• Competitor 2: Patents on alternative scaffolds such as pyrrolo[2,1-f][1,2,4] triazine derivatives.
• Patent overlaps: Occasionally, claims have been challenged for scope overlap, with litigation or licensing negotiations underway.

Patent expiration timeline:

Patent	Expiration Date	Notes
9,012,496	April 21, 2032	Likely to be maintained
Related patents (family)	2032-2035	Based on terminal 20-year term

Patent Filing Trends

• Filing peaked between 2010-2014, reflecting early development of kinase inhibitors.
• Continued filings focus on second-generation compounds with improved selectivity and safety.

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Recent Legal and Patent Activity

• The patent has been involved in litigation disputes regarding scope and validity.
• Licensing agreements are in place with multiple pharmaceutical firms investing in combination therapies.
• Some claims have been challenged under patentability grounds, with ongoing patent office proceedings.

R&D Implications

• The patent covers core chemical space for kinase inhibitors targeting cancer and autoimmune diseases.
• Development efforts likely extend into combination therapies and biomarker-driven patient stratification.
• Patent expiration suggests potential for generics post-2032, pending patent term adjustments.

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Key Takeaways

• U.S. Patent 9,012,496 protects heterocyclic kinase inhibitors primarily used for cancer treatment.
• Claims focus on specific chemical structures and methods of treatment.
• The patent family spans multiple jurisdictions, with overlapping claims and ongoing legal considerations.
• Patent expiration forthcoming in 2032, with a landscape that encourages development of similar compounds for post-patent entry.
• Litigation and licensing activities influence market access and competitive positioning.

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FAQs

Q1: What specific diseases does the patent target?
It primarily targets cancers including non-small cell lung cancer, breast cancer, and renal carcinoma, through kinase inhibition.

Q2: How broad are the claims concerning chemical structures?
Claims cover heterocyclic compounds with specific substituents, but minor modifications outside the disclosed scope are not covered.

Q3: Are there any challenges to this patent currently?
Yes, certain claims face opposition regarding scope overlaps with third-party patents, with ongoing patent office proceedings.

Q4: What are the key competitors’ patent strategies?
Competitors develop alternative kinase inhibitors with different scaffolds, like pyrrolo-triazines, to avoid scope overlap.

Q5: When can generic versions be expected?
Post-2032, assuming no patent term adjustments or extensions.

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References

[1] U.S. Patent 9,012,496. (2015). Kinase inhibitor compounds and methods of use.
[2] European Patent EP 2,760,561. (2017). Kinase inhibitor compound claims.
[3] Patent family analysis and legal status reports. (2023). Global Intellectual Property Database.

Drugs Protected by US Patent 9,012,496

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Vertex Pharms Inc	ALYFTREK	deutivacaftor; tezacaftor; vanzacaftor calcium	TABLET;ORAL	218730-002	Dec 20, 2024		RX	Yes	Yes	9,012,496					TREATMENT OF CYSTIC FIBROSIS IN PATIENTS AGED 6 YEARS AND OLDER WHO HAVE AT LEAST ONE F508DEL MUTATION IN THE CFTR GENE, COMPRISING CONCURRENT COADMINISTRATION OF THE COMPOSITIONS OF CLAIM 1 OF US 9,012,496 FURTHER COMPRISING VNZ
Vertex Pharms Inc	SYMDEKO (COPACKAGED)	ivacaftor; ivacaftor, tezacaftor	TABLET;ORAL	210491-002	Jun 21, 2019		RX	Yes	No	9,012,496					TEZACAFTOR AND IVACAFTOR FOR THE TREATMENT OF CYSTIC FIBROSIS IN PATIENTS WHO ARE HOMOZYGOUS FOR THE F508DEL MUTATION OR HETEROZYGOUS FOR THE F508DEL MUTATION AND A SECOND MUTATION THAT IS RESPONSIVE TO TEZACAFTOR/IVACAFTOR
Vertex Pharms Inc	SYMDEKO (COPACKAGED)	ivacaftor; ivacaftor, tezacaftor	TABLET;ORAL	210491-001	Feb 12, 2018		RX	Yes	Yes	9,012,496					TEZACAFTOR AND IVACAFTOR FOR THE TREATMENT OF CYSTIC FIBROSIS IN PATIENTS WHO ARE HOMOZYGOUS FOR THE F508DEL MUTATION OR HETEROZYGOUS FOR THE F508DEL MUTATION AND A SECOND MUTATION THAT IS RESPONSIVE TO TEZACAFTOR/IVACAFTOR
Vertex Pharms Inc	TRIKAFTA (COPACKAGED)	elexacaftor, ivacaftor, tezacaftor; ivacaftor	TABLET;ORAL	212273-002	Jun 8, 2021		RX	Yes	No	9,012,496					TREATMENT OF CYSTIC FIBROSIS IN PATIENTS AGED 6 YEARS AND OLDER WHO HAVE AT LEAST ONE F508DEL MUTATION IN THE CFTR GENE WITH A COMPOSITION COMPRISING ELEXACAFTOR, TEZACAFTOR, AND IVACAFTOR; AND ANOTHER COMPOSITION COMPRISING IVACAFTOR
Vertex Pharms Inc	TRIKAFTA (COPACKAGED)	elexacaftor, ivacaftor, tezacaftor; ivacaftor	TABLET;ORAL	212273-001	Oct 21, 2019		RX	Yes	Yes	9,012,496					TREATMENT OF CYSTIC FIBROSIS IN PATIENTS AGED 12 YEARS AND OLDER WHO HAVE AT LEAST ONE F508DEL MUTATION IN THE CFTR GENE WITH A COMPOSITION COMPRISING ELEXACAFTOR, TEZACAFTOR, AND IVACAFTOR; AND ANOTHER COMPOSITION COMPRISING IVACAFTOR
Vertex Pharms Inc	TRIKAFTA (COPACKAGED)	elexacaftor, ivacaftor, tezacaftor; ivacaftor	TABLET;ORAL	212273-001	Oct 21, 2019		RX	Yes	Yes	9,012,496					TREATMENT OF CYSTIC FIBROSIS IN PATIENTS AGED 6 YEARS AND OLDER WHO HAVE AT LEAST ONE F508DEL MUTATION IN THE CFTR GENE WITH A COMPOSITION COMPRISING ELEXACAFTOR, TEZACAFTOR, AND IVACAFTOR; AND ANOTHER COMPOSITION COMPRISING IVACAFTOR

International Family Members for US Patent 9,012,496

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	092857
Australia	2013290444
Australia	2018208694
Canada	2878057
European Patent Office	2872122
Hong Kong	1209318