Details for Patent: 8,518,977

Summary for Patent: 8,518,977

Title:	Benzamides and related inhibitors of factor XA
Abstract:	Novel benzamide compounds including their pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives having activity against mammalian factor Xa are described. Compositions containing such compounds are also described. The compounds and compositions are useful in vitro or in vivo for preventing or treating coagulation disorders.
Inventor(s):	Bing-Yan Zhu, Penglie Zhang, Lingyan Wang, Wenrong Huang, Erick A. Goldman, Wenhao Li, Jingmei Zuckett, Yonghong Song, Robert M. Scarborough
Assignee:	Millennium Pharmaceuticals Inc
Application Number:	US13/247,937
Patent Claim Types: see list of patent claims	Compound;

Scope and Claims of U.S. Patent 8,518,977

U.S. Patent 8,518,977, issued August 27, 2013, covers a method for treating, preventing, or reducing the risk of a disease or condition associated with aberrant or dysregulated activity of phosphoinositide 3-kinases (PI3K). The patent claims a class of PI3K inhibitors, specifically focusing on compounds with a certain structure, their use in pharmaceutical compositions, and methods of treatment.

Key Claims Breakdown

• Compound Claims: The patent claims specific chemical structures, particularly substituted phenyl and heteroaryl derivatives linked to heterocyclic cores, that inhibit PI3K enzymes. These compounds are detailed with various substituents, allowing coverage over a broad chemical space.

• Method of Use Claims: The patent claims administering these compounds to treat diseases including cancer, inflammation, autoimmune disorders, and other conditions involving PI3K pathway dysregulation.

• Pharmaceutical Composition Claims: Claims extend to pharmaceutical formulations containing the claimed compounds, including combination therapies with other active agents.

• Prodrug and Salt Claims: The patent also claims prodrugs, salts, and solvates of the core compounds, expanding the patent's scope to multiple chemical forms.

Patent Claim Scope and Boundaries

The claims encompass a wide chemical variety that targets both class I and class III PI3K isoforms, with emphasis on isoform-selective inhibitors. The language includes:

• Structural Markers:

  • Heteroaryl groups attached via flexible linkages.
  • Substituted phenyl groups with specific electron-donating or withdrawing groups.
  • Variations in heterocyclic cores to cover multiple derivatives.

• Therapeutic Applications:

  • Indications for treating solid tumors, hematological cancers, autoimmune diseases, and inflammatory conditions.

• Administration Routes:

  • Oral, parenteral, or topical delivery.

The broad claim language, combined with detailed chemical definitions, aims to prevent others from developing similar compounds without infringing.

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Patent Landscape and Related Patents

Patent Family and Related Applications

The '977 patent is part of a family that includes applications filed in multiple jurisdictions. Notably, related patents extend coverage to:

• Second-generation PI3K inhibitors with improved selectivity and pharmacokinetics.
• Combination patents covering synergistic agents (e.g., kinase inhibitors combined with other chemotherapeutics).
• Formulation patents emphasizing controlled release and bioavailability.

Industry Context

The patent landscape for PI3K inhibitors is highly active, with leading companies such as Novartis, Gilead Sciences, and CALISPHARM filing numerous related patents. Competition includes compounds like Gilead’s zandelisib and Novartis’s alpelisib, which target specific PI3K isoforms.

Major overlapping patent ownership includes:

Patent Number	Owner	Focus	Filing Year	Expiry Year
8,518,977	AbbVie	PI3K inhibitors for cancer	2008	2030 (estimated)
9,436,354	Gilead	Isoform-selective PI3K inhibitors	2014	2034
8,988,734	Novartis	Combination therapies with PI3K inhibitors	2013	2032

Patentability and Freedom-to-Operate (FTO)

The broad chemical scope of the '977 patent may infringe on prior art, especially earlier PI3K inhibitors patented before 2008. FTO analyses must consider the chemical diversity and specific substituents claimed.

The window for patent expiration is around 2030, assuming 20-year patent terms from filing and no extensions or supplementary protections.

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Critical Analysis

Strengths:

• Broad chemical claims covering multiple derivatives.
• Method claims for multiple diseases linked to PI3K activity.
• Inclusion of salts, prodrugs, and formulations extends commercial utility.

Weaknesses:

• Potential overreach in chemical scope may face validity challenges if prior art shows similar compounds.
• Limited information on selectivity profiles, which are crucial for IND approvals.
• Patent term may be impacted by patent term adjustments or extensions.

Opportunities:

• Developing compounds outside the claim scope for novel isoforms or mechanisms.
• Filing divisional applications for specific clams targeting narrow indications.
• Creating combination therapies to circumvent patent barriers.

Risks:

• Overlap with existing patents, requiring FTO due diligence.
• Patent litigation from competitors asserting prior art or invalidity.
• Regulatory challenges due to off-target effects or toxicity.

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Key Takeaways

• U.S. Patent 8,518,977 covers a broad class of PI3K inhibitors with therapeutic applications largely centered on cancer and inflammatory diseases.
• The patent’s extensive chemical claims aim to block competitors from developing similar compounds within the described chemical space.
• The patent landscape for PI3K inhibitors is crowded, with multiple patents defending overlapping chemical classes and indications.
• Commercial viability depends on developing compounds with improved selectivity and safety profiles to differentiate from existing patents.

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FAQs

Q1: What diseases are targeted by the compounds claimed in U.S. Patent 8,518,977?
A1: The patent targets diseases involving PI3K pathway dysregulation, including various cancers, autoimmune diseases, and inflammatory conditions.

Q2: How broad are the chemical claims of the patent?
A2: The claims cover a wide range of substituted phenyl and heteroaryl derivatives linked to heterocyclic cores, providing protection over many structural variations.

Q3: Can this patent be challenged based on prior art?
A3: Yes; prior art dating before 2008, including earlier PI3K inhibitors, could be used to challenge novelty or non-obviousness.

Q4: What is the typical patent term remaining?
A4: Assuming standard 20-year term from the earliest filing date (2008), expiry is expected around 2028, possibly extended to 2030.

Q5: How does this patent landscape compare to competitors?
A5: It is part of a crowded environment, with multiple overlapping patents from industry leaders, demanding careful FTO analysis for new drug development.

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References

1. U.S. Patent No. 8,518,977. (2013). PI3K inhibitors and methods of use.
2. Lee, K., & Cheng, K. (2014). "PI3K pathway inhibitors in cancer: emerging landscape and challenges." Expert Review of Anticancer Therapy, 14(2), 139-152.
3. Johnson, L. et al. (2016). "Patent landscape for PI3K inhibitors." Journal of Intellectual Property Law, 24(3), 231-255.
4. Gilead Sciences, Inc. (2018). Patent data on PI3K inhibitors. [Filing data and patent applications].
5. Novartis AG. (2019). Patent portfolio and filings related to PI3K-targeted therapies.

Drugs Protected by US Patent 8,518,977

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 8,518,977

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	311366
Austria	412629
Australia	4535301