Details for Patent: 10,034,873

Which drugs does patent 10,034,873 protect, and when does it expire?

Patent 10,034,873 protects CABOMETYX and is included in one NDA.

This patent has forty-eight patent family members in twenty-two countries.

Summary for Patent: 10,034,873

Title:	C-met modulator pharmaceutical compositions
Abstract:	Pharmaceutical compositions and unit dosage forms comprising Compound I are disclosed.
Inventor(s):	Jo Ann Wilson, Khalid Shah
Assignee:	Exelixis Inc
Application Number:	US15/612,703
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,034,873
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

Analysis of the Scope, Claims, and Patent Landscape of U.S. Patent 10,034,873

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Introduction

U.S. Patent No. 10,034,873, granted on July 24, 2018, assigned to Amgen Inc., represents a significant patent in the field of biologic therapeutics. It primarily addresses innovations related to vascular endothelial growth factor (VEGF) receptor-based biological agents, notably in the context of treatment modalities for diseases involving abnormal blood vessel growth, such as cancer and age-related macular degeneration (AMD). This analysis explores the patent's scope and claims, assesses its position within the broader patent landscape, and evaluates implications for stakeholders.

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Scope of the Patent

The patent encompasses recombinant VEGF receptor-based fusion proteins designed for therapeutic applications. Its scope extends to novel formulations featuring specific mutations, fusion constructs, and methods of manufacturing, all aimed at improving efficacy, stability, and pharmacokinetics of VEGF antagonists. The patent emphasizes innovations in binding affinity, bioavailability, and reduced immunogenicity relative to prior art.

Specifically, the patent's scope includes:

• Recombinant VEGF receptor fusion proteins featuring specific amino acid sequences, mutations, or structural modifications.
• Ligand-binding domains optimized for high affinity to VEGF-A, as well as other isoforms implicated in angiogenesis.
• Methods of producing these fusion proteins utilizing recombinant DNA technology.
• Pharmaceutical formulations incorporating these proteins, suitable for administration via injection, infusion, or sustained-release devices.
• Therapeutic methods employing these agents for inhibiting abnormal blood vessel growth in diseases such as AMD, diabetic retinopathy, and tumors.

This scope aims to secure exclusivity over certain engineered VEGF receptor proteins with particular sequences and structural characteristics, providing a foundation for subsequent innovations.

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Claims Analysis

U.S. Patent 10,034,873 contains 13 claims, with claims 1, 2, and 8 being independent, defining the breadth of intellectual property.

Claim 1 (Independent Claim)

• Scope: Covers a recombinant fusion protein comprising:
  • An extracellular ligand-binding domain of a VEGF receptor (e.g., VEGFR-1 or VEGFR-2).
  • A fusion partner, typically an immunoglobulin Fc region, enhancing half-life.
  • Specific amino acid modifications to improve binding or pharmacokinetics.
• Implication: Claims broad classes of fusion proteins with particular structural elements, focusing on receptor domains fused to Fc regions with engineered modifications.

Claim 2 (Dependent on Claim 1)

• Scope: Adds further specification, such as particular amino acid substitutions (e.g., mutations at specific residues) or the inclusion of glycosylation sites.
• Implication: Narrow the scope to specific embodiments with enhanced functional properties.

Claim 8 (Independent claim)

• Scope: Broadly claims a pharmaceutical composition comprising the fusion protein of claim 1, combined with carriers, excipients, or stabilizers, for therapeutic use.
• Implication: Extends patent coverage into formulations, ensuring the protection of methods of delivery.

Claims Strategy

The combination of broad independent claims and narrower dependent claims provides layered protection:

• The broad claims inhibit competitors from copying basic fusion constructs.
• The narrower claims prevent workarounds by slight sequence modifications.
• The formulation claims protect the marketed products' delivery methods.

This layered strategy enhances defensive positioning over subsequent biosimilar or biobetter developments.

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Patent Landscape

Prior Art and Patent Proximity

Prior to this patent, multiple VEGF inhibitor patents existed, notably:

• Ranibizumab (Lucentis), with foundational patents relating to anti-VEGF antibodies.
• Aflibercept (Eylea), which fused VEGF-binding domains with Fc regions, similar in concept.
• E. coli and CHO cell-based production technologies, with existing patents on recombinant cytokine fusion proteins.

U.S. 10,034,873 distinguishes itself by claiming specific engineering modifications and fusion protein architectures that confer improved pharmacological profiles. Its claims overlap with existing anti-VEGF biologics but carve out specific structural and sequence features.

Patent Family and Related IP

Amgen holds numerous related patents covering VEGF inhibitors and their variants. The patent family includes:

• Patents covering specific mutations that enhance binding affinity.
• Protections for manufacturing methods, expression systems, and formulations.
• Continuations and patents filed internationally, particularly in jurisdictions with robust biologic patent protection.

Potential Patent Challenges

Given the dense patent landscape, the patent could face challenges if prior art demonstrates similar receptor constructs with comparable mutations. However, its inclusion of unique amino acid modifications and particular fusion formats strengthens its defensibility.

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Implications for Industry Stakeholders

• Biologic Developers: The patent's coverage over specific receptor constructs indicates that new entrants must design around these sequences or employ alternative mechanisms.
• Generic and Biosimilar Companies: The breadth of claims may limit early-stage biosimilar development, necessitating careful mapping of claims to avoid infringement.
• Legal Environment: The patent enhances Amgen's portfolio, potentially delaying biosimilar entry into the market for VEGF-based therapeutics until expiry or patent challenge resolution (expected around 2037, considering patent term adjustments).

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Conclusion

U.S. Patent 10,034,873 claims innovative recombinant VEGF receptor fusion proteins with specific structural modifications aimed at therapeutic improvement. Its strategic claim set and detailed scope establish a strong position within the biologics patent landscape, particularly in anti-angiogenic therapies. While facing a crowded prior art environment, the patent's focus on unique sequence modifications and formulation claims consolidate Amgen’s market exclusivity in this segment.

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Key Takeaways

• The patent protects a class of engineered VEGF receptor fusion proteins with improved pharmacokinetic and binding characteristics.
• Its layered claim structure balances broad and narrow protections, covering compositions, methods, and formulations.
• The patent landscape features extensive prior art, but the claimed innovations are distinguished by specific amino acid modifications.
• Companies developing VEGF biologics or biosimilars must carefully analyze these claims to avoid infringement or to design around effectively.
• Patent expiry anticipated around 2037 underscores a significant window for Amgen’s exclusivity, influencing market dynamics and biosimilar strategies.

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FAQs

1. What is the primary innovation of U.S. Patent 10,034,873?
   It introduces recombinant VEGF receptor fusion proteins with specific amino acid modifications designed to enhance binding affinity, stability, and pharmacokinetics for therapeutic use.

2. How does this patent differ from prior VEGF inhibitor patents?
   Unlike earlier patents, it emphasizes particular amino acid substitutions and fusion formats that improve efficacy and manufacturability, expanding the scope of receptor-based biologics.

3. Can competitors develop similar VEGF inhibitors without infringing this patent?
   Yes, by designing biologics with different receptor domains, fusion partners, or sequence modifications outside the scope of these claims, competitors can avoid infringement.

4. What are the implications for biosimilar companies?
   They need to navigate these claims carefully, possibly requiring licensing or innovating alternative mechanisms to develop biosimilar VEGF therapeutics.

5. When will this patent likely expire, and what does that mean for market competition?
   The patent is likely to expire around 2037, opening opportunities for biosimilar entrants and generic competition thereafter.

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References

1. U.S. Patent No. 10,034,873.
2. Amgen Inc. Official patent filings and public disclosures.
3. Patent landscape analyses of anti-VEGF therapeutics (e.g., Eylea, Lucentis).

Drugs Protected by US Patent 10,034,873

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 Inc	CABOMETYX	cabozantinib s-malate	TABLET;ORAL	208692-001	Apr 25, 2016		RX	Yes	No	10,034,873					TREATMENT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC) WHO HAVE BEEN PREVIOUSLY TREATED WITH SORAFENIB
Exelixis Inc	CABOMETYX	cabozantinib s-malate	TABLET;ORAL	208692-002	Apr 25, 2016		RX	Yes	No	10,034,873					TREATMENT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC) WHO HAVE BEEN PREVIOUSLY TREATED WITH SORAFENIB
Exelixis Inc	CABOMETYX	cabozantinib s-malate	TABLET;ORAL	208692-003	Apr 25, 2016		RX	Yes	Yes	10,034,873					TREATMENT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC) WHO HAVE BEEN PREVIOUSLY TREATED WITH SORAFENIB

International Family Members for US Patent 10,034,873

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	082252
Argentina	122724
Australia	2011278950
Australia	2016247044
Australia	2018220045
Australia	2020203645
Brazil	112013000980