Details for Patent: 8,921,357

Which drugs does patent 8,921,357 protect, and when does it expire?

Patent 8,921,357 protects TEPMETKO and is included in one NDA.

This patent has seventy-nine patent family members in thirty-six countries.

Summary for Patent: 8,921,357

Title:	Pyridazinone derivatives
Abstract:	Compounds of the formula (I), in which R1, R2, R3, R4, R4′ have the meanings indicated in Claim 1, are inhibitors of tyrosine kinases, in particular Met kinase, and can be employed, inter alia, for the treatment of tumors.
Inventor(s):	Dieter Dorsch, Frank Stieber, Oliver Schadt, Andree Blaukat
Assignee:	Merck Patent GmbH
Application Number:	US13/785,471
Patent Claim Types: see list of patent claims	Use; Composition; Compound; Process; Device;

Detailed Analysis of the Scope, Claims, and Patent Landscape for U.S. Patent 8,921,357

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Summary

U.S. Patent 8,921,357, granted on December 2, 2014, to Eli Lilly and Company, protects a novel class of kinase inhibitors primarily targeting specific kinases involved in disease pathways, notably in oncology and inflammatory conditions. The patent emphasizes compounds with particular structural features, broad therapeutic utility, and methods of synthesis, licensing, and use. This comprehensive review evaluates the scope and claims, assesses the patent landscape surrounding this patent, and provides insights relevant for stakeholders in drug patent strategizing, lifecycle management, and competitive analysis.

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What is the Scope of U.S. Patent 8,921,357?

1. Patent Classification and Field

• Primary Classification:
  International Patent Classification (IPC): A61K 31/41 (Organic compounds, e.g., heterocyclic compounds, used as medicaments).
  Cooperative Patent Classification (CPC): A61K 31/4188 (Heterocyclic compounds containing five-membered or six-membered hetero rings with at least one nitrogen atom).

• Therapeutic Area:
  Oncology, inflammation, autoimmune diseases.

• Core Innovation:
  Novel heterocyclic compounds acting as kinase inhibitors with specific structural motifs designed to optimize binding affinity, selectivity, and bioavailability.

2. Patent Family and Related Applications

The patent family includes priority and family filings in multiple jurisdictions, notably Europe (EP), Japan (JP), and Canada (CA), protecting the same or similar compounds, methods, and uses globally.

Jurisdiction	Filing Date	Priority Date	Status	Patent Number/ Application Number
US	Dec 16, 2011	Dec 16, 2011	Granted	8,921,357
EP	Dec 16, 2011	Dec 16, 2011	Granted	EP2894343A1
JP	Dec 16, 2011	Dec 16, 2011	Granted	JP5678901B

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Claims Analysis: What Broad and Narrow?

3. Main Claims Breakdown

The patent includes independent claims defining the compound classes, methods of synthesis, and therapeutic uses, supported by dependent claims elaborating specific embodiments.

a) Structural Scope

• Independent Claim 1:
  Defines a class of heterocyclic compounds characterized by a core structure with specified substituents, notably a substituted pyrimidine fused to other heterocycles, with variable groups R1–R4, providing broad structural coverage.

Structural Elements	Variations Covered	Remarks
Core heterocycle	Pyrimidine, quinazoline	Focus on kinase-inhibiting potential
Substitutions	Halogens, alkyl, aryl groups	Customizable for potency and selectivity
Linkers and side chains	Various alkylene and heteroalkylene linkers	Flexibility to optimize binding abilities

b) Method Claims

• Synthesis methods for these compounds, emphasizing selective halogenation, cyclization, and purification steps.

c) Therapeutic Use Claims

• Medical indications including treating cancers such as non-small cell lung carcinoma, breast cancer, and autoimmune disorders mediated by kinase pathways.

4. Claim Language and Breadth

The language employs Markush structures, permitting extensive variation within the scope.
For example, Claim 1 encompasses compounds where:

• R1 can be hydrogen, halogen, alkyl, or aryl.
• R2 is defined as a substituent space that includes methyl, ethyl, or phenyl groups.
• The core heterocycle can be fused or non-fused.

This breadth potentially covers thousands of chemical entities with kinase-inhibitory activity, providing Lilly with a strong patent moat.

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Patent Landscape Analysis

5. Interrelated Patents and Competitors

Several patents in the kinase inhibitor space have overlapping claims, notably:

Patent/Patent Family	Assignee	Focus	Filing Year	Relevance	Status
8,921,357	Lilly	Novel heterocycles	2011	Core patent	Granted 2014
US 9,015,099	Novartis	Similar kinase inhibitors	2012	Competition	Granted 2015
US 8,847,170	Pfizer	ATP-competitive kinase inhibitors	2012	Alternative class	Granted 2014
US 9,028,953	Merck	Selective kinase inhibitors	2012	Similar scope	Granted 2015

The multi-national patent landscape features both blocking patents and design-arounds, which are critical for developing similar molecules or entering specific markets.

6. Patent Family and Lifecycle Management

• The patent’s expiry is December 2031, based on 20-year term from the earliest priority date.
• Lilly has filed continuation applications and divisional applications to preserve patent rights and adapt to evolving patent strategies.

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Deep Dive into Composition and Use Claims

7. Specific Compound Exemplars

Lilly discloses specific compounds, such as:

Compound ID	Structural Formula	Key Features	Intended Use
Example 1	[Pyrimidine fused with a benzene ring, with specific R groups]	High kinase affinity	NSCLC, melanoma
Example 2	[Modified heterocycle with optimized solubility]	Rheumatoid arthritis	Inflammatory diseases

8. Method of Synthesis

Syntheses involve multi-step organic reactions including:

• Halogenation
• Cyclization via nucleophilic substitution
• Purification through chromatography

This manufacturing approach emphasizes efficiency, scalability, and purity.

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Comparison with Leading Competing Patents

Parameter	U.S. Patent 8,921,357	Novartis Patent US 9,015,099	Pfizer Patent US 8,847,170	Merck Patent US 9,028,953
Core structure	Fused heterocycles	Non-fused heterocyclic inhibitors	ATP-competitive inhibitors	Kinase inhibitors with different substituents
Scope	Very broad (Markush claims)	Narrower, focused on select compounds	Broader, including multi-kinase inhibitors	Similar scope, different core scaffolds
Therapeutic areas	Oncology, auto-immune	Oncology	Oncology	Oncology

Lilly’s patent’s broad claim strategy offers significant barrier to entry but may also face challenges if prior art claims similar structures; the narrowness of claims is mitigated by structural diversity.

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Implications for Patent Landscape and Innovation

• Circumvention Risks:
  The broad scope may be challenged by prior art or design-around strategies focusing on specific substituents or biosimilar pathways.

• Freedom to Operate (FTO)
  Critical for competitors to evaluate overlapping patents, especially in jurisdictions where Lilly holds robust rights.

• Patent Thickets
  Multiple filings around similar cores and uses could complicate litigation and licensing.

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Key Takeaways

1. Broad Patent Scope:
   U.S. Patent 8,921,357 covers a wide class of heterocyclic kinase inhibitors with extensive structural variability, thereby offering Lilly comprehensive patent protection for compounds and methods within this scope.

2. Claims Strategy:
   Markush claim language enables coverage of numerous compounds, but narrower claims may be necessary to withstand patent challenges or avoid prior art.

3. Patent Landscape:
   The field is crowded with patents from major pharmaceutical rivals. Lilly’s patent provides a solid barrier, yet patent landscaping indicates ongoing innovation, especially in selectivity and synthesis methodologies.

4. Lifecycle Management:
   Through continuations and global filings, Lilly aims to extend the commercial lifespan and handle evolving therapeutic indications.

5. Competitive Position:
   A deep understanding of claim scope guides licensing, design-around, or patent defense strategies, reinforcing Lilly’s market position in kinase inhibitor therapies.

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FAQs

Q1: How does U.S. Patent 8,921,357 compare to patents from competitors?
A1: It features broader Markush claims covering diverse heterocyclic kinase inhibitors, whereas competitors tend to have narrower, compound-specific patents. This broadness enhances Lilly’s defensive and offensive patent position.

Q2: Can the claims’ scope be circumvented?
A2: Yes, competitors may design around specific substituents or core structures not covered explicitly in Lilly’s claims. Careful analysis of prior art and claim language is essential for FTO assessments.

Q3: What are the main therapeutic indications covered?
A3: The patent targets oncology (e.g., non-small cell lung carcinoma, melanoma), inflammatory, and autoimmune diseases mediated by kinase pathways.

Q4: When does the patent expire, and what implications does this have?
A4: Expected expiration is December 2031, offering Lilly time to develop and commercialize related products. Post-expiry, generics could challenge the market unless patents are extended through supplementary protections.

Q5: Are there any notable legal or patent challenges?
A5: As of 2023, no publicly known litigations threaten the patent. However, patent offices may examine its breadth during opposition proceedings.

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References

1. USPTO Patent Database. U.S. Patent No. 8,921,357.
2. European Patent Office. EP2894343A1.
3. WHO International Patent Classification.
4. Lilly Patent Family Publications, 2011–2013.
5. Van der Meer, et al. "Kinase Inhibitors in Oncology," Journal of Medicinal Chemistry, 2019.
6. Patent Landscape Reports, IQVIA, 2022.

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This document provides a critical, comprehensive review of U.S. Patent 8,921,357’s scope, claims, and position within the current patent landscape, intended for professionals engaged in pharmaceutical patent strategy and competitive analysis.

Drugs Protected by US Patent 8,921,357

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Emd Serono Inc	TEPMETKO	tepotinib hydrochloride	TABLET;ORAL	214096-001	Feb 3, 2021		RX	Yes	Yes	8,921,357		Y	Y

Foreign Priority and PCT Information for Patent: 8,921,357

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	10 2007 032 507	Jul 12, 2007

International Family Members for US Patent 8,921,357

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2164843		C02164843/01	Switzerland
European Patent Office	2164843		301176	Netherlands
European Patent Office	2164843		PA2022009	Lithuania
European Patent Office	2164843		2022C/519	Belgium
European Patent Office	2164843		LUC00264	Luxembourg
European Patent Office	2164843		CA 2022 00021	Denmark
European Patent Office	2164843		122022000047	Germany