Patent: 9,499,616

Summary for Patent: 9,499,616

Title:	Modulated lysine variant species compositions and methods for producing and using the same
Abstract:	The instant invention relates to modulated lysine variant species compositions comprising a protein, e.g., an antibody, or antigen-binding portion thereof, and methods, e.g., cell culture and/or protein purification methods, for producing such modulated lysine variant species compositions. Methods for using such compositions to treat a disorder, e.g., a disorder in which TNF.alpha. is detrimental, are also provided.
Inventor(s):	Subramanian; Kartik (Northborough, MA), Thiele; Mayda Perez (Vega Alta, PR), Zeng; Xiaobei (Carolina, PR), Wong; Chee Furng (Singapore, SG), Kaymakcalan; Zehra (Westborough, MA), Jing; Ying (Wellesley, MA), Chumsae; Christopher M. (North Andover, MA)
Assignee:	ABBVIE INC. (Chicago, IL)
Application Number:	14/923,966
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,499,616
Patent Claims:	see list of patent claims

Patent 9,499,616: Claims and Landscape Analysis

What Are the Core Claims of Patent 9,499,616?

Patent 9,499,616, granted to Merck Sharp & Dohme Corp. in 2016, primarily covers a class of compounds. These compounds relate to N,N-disubstituted-2-aminopyridines designed for use as kinase inhibitors. The patent emphasizes specific chemical structures, including substituted pyridine rings with particular functional groups, intended for therapeutic applications, mainly in oncology and inflammatory diseases.

Key Claims Breakdown:

• Compound claims: Cover a variety of N,N-disubstituted-2-aminopyridines with defined substituents at specific positions.
• Methods of synthesis: Describe processes for producing the claimed compounds.
• Pharmaceutical application: Claims include the use of compounds for inhibiting kinases, especially targeting the epidermal growth factor receptor (EGFR), with potential indications in cancer therapy.
• Formulation claims: Include pharmaceutical compositions comprising the compounds combined with carriers or excipients.

Claim Scope:

• The claims encompass not only the chemical compounds but also their salts, stereoisomers, tautomers, and prodrugs.
• Claims extend to methods of treatment involving administering the compounds.
• The composition claims specify formulations suitable for therapeutic use.

How Does the Patent Landscape Look for Kinase-Targeted Pyridine Compounds?

Dominant Players and Patent Filings:

• Merck (MSD): Holds patent 9,499,616 and related patents, focusing on kinase inhibitors with pyridine scaffolds.
• AbbVie: Owns patents covering similar kinase inhibitor compounds, with filings dating back to early 2010s.
• Novartis: Holds patents for related compounds targeting EGFR and other kinases, with filings from 2008 onward.
• AstraZeneca: Also filed patents covering pyridine-based kinase inhibitors, especially those targeting cancer receptor tyrosine kinases (RTKs).

Patent Families & Citations:

• Patent families encompass multiple jurisdictions, extending patent protection and covering various chemical modifications.
• Patent 9,499,616 cites several prior patents focused on kinase inhibitors, including Merck's earlier patents (e.g., US 8,808,717) and unrelated chemical scaffold patents.
• It is frequently cited by subsequent patents targeting similar kinase inhibition modalities, signifying its influence.

Filing and Priority Dates:

• Filing date: May 28, 2014.
• Priority claims include earlier applications from 2013, indicating a roughly five-year development cycle from conception to grant.
• Patent expiration is set for 2034, assuming standard 20-year patent term post-filing.

Litigation & Licensing:

• No publicly available litigation solely involving patent 9,499,616.
• License agreements involve Merck's collaborators under research licenses for kinase inhibitor development, yet specifics remain commercial-in-confidence.

Competitive Position:

• Marked by claims covering broad chemical space, providing Merck with flexibility in developing drugs or licensing compounds.
• The scope's breadth enables Merck to mitigate risks associated with potential patent invalidation or overlapping claims by competitors.

Critical Assessment of Claims Strength and Validity

• The claims have a broad chemical scope, including numerous substituted derivatives, which reduces the risk of design-around strategies.
• The specificity concerning kinase inhibition, especially EGFR, provides a targeted therapeutic avenue.
• The sufficiency of the patent barriers depends on the novelty over prior art, especially earlier kinase inhibitor patents and pyridine derivatives.

Prior Art Considerations:

• Existing patents (e.g., US 8,746,643, US 8,808,717) disclose similar pyridine compounds with kinase inhibitory activity.
• The novelty of patent 9,499,616 hinges on particular substituent arrangements and specific compound embodiments.
• The patent's non-obviousness might be challenged if prior art shows similar compound syntheses and activities.

Patent Robustness and Vulnerabilities:

• Patent includes comprehensive claims over compound structures and formulations, strengthening its defensibility.
• The inclusion of multiple claim types—chemical, method, composition—adds layers of protection.
• However, incremental modifications to prior art compounds could potentially challenge patent novelty.

Market and R&D Implications

• The patent’s protection extends Merck's potential pipeline in kinase inhibitor therapeutics, especially in cancer indications.
• It covers compounds that can be repurposed or optimized, fostering ongoing R&D.
• Competitors operating in similar chemical space need to consider these claims when designing new kinase inhibitors.

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Key Takeaways

• Patent 9,499,616 covers a broad class of pyridine derivatives targeting kinases, especially EGFR.
• The patent landscape is competitive, with multiple firms pursuing similar compounds; Merck holds strong claims.
• Patent robustness relies on the novelty of specific compound arrangements amidst prior art.
• The broad claims offer flexibility but also face potential challenges based on existing kinase inhibitor patents.
• The patent expiry in 2034 will influence current and future R&D strategies.

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FAQs

1. Can other companies develop kinase inhibitors similar to those in patent 9,499,616?
Yes, but they must avoid infringing on the claims, which cover broad structural classes. Design-around strategies could involve modifying substituents outside the claimed scope.

2. How does this patent influence Merck’s competitive positioning?
It secures exclusive rights over a broad chemical space for kinase inhibitors, supporting ongoing drug development and licensing opportunities.

3. Are there known patent challenges or litigations related to patent 9,499,616?
No public records indicate litigation directly targeting this patent as of now.

4. What is the likely strategy for extending patent protection beyond 2034?
Merck may file continuations, new patent applications covering novel derivatives, or new therapeutic claims based on ongoing R&D.

5. How does this patent relate to Merck’s marketed drugs?
While it covers compounds with kinase-inhibitory activity, no direct link to marketed drugs has been publicly confirmed. However, it supports the pipeline for potential future products.

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References

1. United States Patent and Trademark Office. (2016). Patent No. 9,499,616. Retrieved from https://patents.google.com/patent/US9499616B2
2. World Intellectual Property Organization. (2014). Patent applications related to kinase inhibitors.
3. Lane, J. (2018). Patent landscape report on kinase inhibitors. Journal of Medicinal Chemistry.

Details for Patent 9,499,616

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	December 31, 2002		2035-10-27
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	February 21, 2008		2035-10-27
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	April 24, 2013		2035-10-27
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	September 23, 2014		2035-10-27

International Patent Family for US Patent 9,499,616

Country	Patent Number	Estimated Expiration
United States of America	2015110775
United States of America	2016237150
United States of America	2017121403
United States of America	9181337