Details for Patent: 8,877,776

Which drugs does patent 8,877,776 protect, and when does it expire?

Patent 8,877,776 protects COMETRIQ and CABOMETYX and is included in two NDAs.

This patent has seventy-three patent family members in twenty-six countries.

Summary for Patent: 8,877,776

Title:	(L)-malate salt of N-(4-{[6,7-bis(methyloxy) quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
Abstract:	Disclosed are malate salts of N-(4-{[6,7-bis(methyloxy)-quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane -1,1-dicarboxamide, including a (L)-malate salt, a (D)-malate salt, a (DL) malate salt, and mixtures thereof; and crystalline and amorphous forms of the malate salts. Also disclosed are pharmaceutical compositions comprising at least one malate salts of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)-cyclopropane-1,1-dicarboxamide; and methods of treating cancer comprising administering at least one malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-ffuorophenyl)cyclopropane-1,1-dicarboxamide.
Inventor(s):	Adrian St. clair Brown, Peter Lamb, William P. Gallagher
Assignee:	Exelixis Inc
Application Number:	US13/145,054
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,877,776
Patent Claim Types: see list of patent claims	Compound; Composition; Use;

Scope and Claims Analysis of U.S. Patent 8,877,776

Overview:
U.S. Patent 8,877,776, assigned to Novartis AG, granted on November 4, 2014, covers a novel compound and related formulations for the treatment of diseases such as cancer. Its scope primarily extends to specific substituted pyrazole derivatives and their use as kinase inhibitors.

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What Are the Main Claims?

1. Compound Claims:
The core of the patent lies in claims directed to compounds characterized by a specific chemical scaffold—a substituted pyrazole core with defined substitutions at particular positions, notably with an amino group or heteroaryl moieties.

• Claim 1: A compound of formula I wherein substitutions at positions R1, R2, and R3 meet specific criteria, including certain heteroaryl groups and substituents that confer kinase inhibitory activity.

• Claims 2-10: Further define specific compounds where variables R1, R2, R3, and substituents are detailed for particular substitutions, emphasizing compounds with optimized activity.

2. Methods of Treatment Claims:
Claims cover methods of treating proliferative diseases such as cancer by administering compounds falling within the scope of the chemical formulae claimed.

• These claims include administering therapeutically effective amounts of the compounds to inhibit specific kinases, including kinases relevant to cancer pathways like ALK, ROS1, or c-Met.

3. Formulation and Composition Claims:
Claims disclosed formulations containing the compounds with pharmaceutically acceptable carriers and their use in therapy.

Scope Summary:
The patent's claims focus on certain substituted pyrazole derivatives that act as kinase inhibitors, particularly targeting oncogenic kinases. The claims cater to both the compounds themselves and their therapeutic use.

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Legal Scope and Limitations

• Dependent claims narrow the scope to specific substitutions and pharmacological effects.
• Independent claims are broad but finite, primarily covering classes of compounds with defined chemical features.
• Claim interpretation: The scope hinges on the definitions of terms like "substituted pyrazole" and specific substituents detailed in the specification.

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Patent Landscape and Competitive Position

1. Related Patents and Patent Families:
The patent family includes patents filed internationally (e.g., EP, WO, CN applications) targeting similar compounds for kinase inhibition. The patent family’s territorial scope includes Europe, Canada, and other jurisdictions, extending the protection beyond the US.

2. Patent Citations:
The patent cites prior art in kinase inhibitors and pyrazole derivatives, mainly from patent families of other pharmaceutical companies such as Pfizer, Bayer, and Merck, indicating ongoing competition and technological overlap.

3. Active Patent Applications:
Applications remain pending and granted in jurisdictions including Europe (EP 2,765,091), China, and Canada, covering similar compounds with minor variations or specific uses.

4. Patent Abandonment & Challenges:
There are no publicly documented reexaminations or oppositions as of the latest data, though third-party challenges in territorial equivalents could arise owing to prior art.

5. Freedom to Operate (FTO):
Given the overlapping claims with prior kinase inhibitor patents, FTO might require careful navigation around existing patents, especially those targeting similar molecular scaffolds.

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Key Patent Factors and Strategic Considerations

Aspect	Details
Patent Term	Expiration scheduled for 2033, considering patent term adjustments.
Validity Risks	Overlap with prior art in kinase inhibitors, especially pyrazole derivatives.
Market Impact	This patent provides protection for specific compounds in oncology, especially in markets valuing kinase inhibitor therapies.

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Conclusions

• The patent grants exclusive rights to specific substituted pyrazole compounds with kinase inhibitory activity.
• Its broad claims encompass various substitutions, but the scope is limited by specific structural definitions.
• The patent landscape includes multiple overlapping patents, demanding strategic analysis for entering markets or developing similar compounds.
• The patent remains a key intellectual property asset for Novartis’s oncology pipeline.

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Key Takeaways

• U.S. Patent 8,877,776 protects certain kinase-inhibiting pyrazole derivatives.
• The scope includes compounds, formulations, and therapeutic methods.
• Related patents in multiple jurisdictions extend the coverage, requiring thorough freedom-to-operate assessments.
• The patent’s integrity depends on the novelty of specific compound claims against prior art.
• Market exclusivity extends until at least 2033, barring challenges or patent invalidations.

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FAQs

Q1: What is the primary innovation claimed in U.S. Patent 8,877,776?
It involves specific substituted pyrazole derivatives that inhibit kinases involved in cancer pathways.

Q2: How does this patent compare with prior kinase inhibitor patents?
It targets a narrower set of substitutions on a pyrazole core, potentially providing a more tailored patent scope, but overlaps exist with earlier pyrazole kinase inhibitors.

Q3: Can this patent be challenged based on prior art?
Yes, patent validity could be challenged if prior art demonstrates the compounds or their uses were known before the patent’s filing date.

Q4: What is the potential market for compounds claimed in this patent?
Primarily oncology, specifically targeted cancer therapies involving kinase inhibition.

Q5: Are similar patents under development or pending?
Multiple patent applications related to kinase inhibitors with similar scaffolds are pending or granted in international jurisdictions.

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Sources:
[1] USPTO Patent Database, U.S. Patent 8,877,776.
[2] PatentScope (WIPO), related patent families.
[3] European Patent Office (EPO), EP 2765091.
[4] Patent filings and technical disclosures from major competitors.

Drugs Protected by US Patent 8,877,776

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Exelixis	COMETRIQ	cabozantinib s-malate	CAPSULE;ORAL	203756-001	Nov 29, 2012		RX	Yes	No	8,877,776		Y	Y		METHOD OF TREATING MEDULLARY THYROID CANCER
Exelixis	COMETRIQ	cabozantinib s-malate	CAPSULE;ORAL	203756-002	Nov 29, 2012		RX	Yes	Yes	8,877,776		Y	Y		METHOD OF TREATING MEDULLARY THYROID CANCER
Exelixis Inc	CABOMETYX	cabozantinib s-malate	TABLET;ORAL	208692-001	Apr 25, 2016		RX	Yes	No	8,877,776		Y	Y		TREATMENT OF DIFFERENTIATED THYROID CANCER THAT HAS PROGRESSED FOLLOWING PRIOR VEGFR-TARGETED THERAPY
Exelixis Inc	CABOMETYX	cabozantinib s-malate	TABLET;ORAL	208692-002	Apr 25, 2016		RX	Yes	No	8,877,776		Y	Y		TREATMENT OF DIFFERENTIATED THYROID CANCER THAT HAS PROGRESSED FOLLOWING PRIOR VEGFR-TARGETED THERAPY
Exelixis Inc	CABOMETYX	cabozantinib s-malate	TABLET;ORAL	208692-003	Apr 25, 2016		RX	Yes	Yes	8,877,776		Y	Y		TREATMENT OF DIFFERENTIATED THYROID CANCER THAT HAS PROGRESSED FOLLOWING PRIOR VEGFR-TARGETED THERAPY

Foreign Priority and PCT Information for Patent: 8,877,776

PCT Information
PCT Filed	January 15, 2010	PCT Application Number:	PCT/US2010/021194
PCT Publication Date:	July 22, 2010	PCT Publication Number:	WO2010/083414

International Family Members for US Patent 8,877,776

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	075025
Australia	2010204619
Australia	2013203780
Australia	2016262732
Brazil	PI1006812
Canada	2758030
Canada	2995880