Details for Patent: 9,278,995

Which drugs does patent 9,278,995 protect, and when does it expire?

Patent 9,278,995 protects PARSABIV and is included in one NDA.

This patent has fifty-seven patent family members in thirty countries.

Summary for Patent: 9,278,995

Title:	Therapeutic agents for reducing parathyroid hormone levels
Abstract:	Compounds having activity for lowering parathyroid hormone levels are described. In one embodiment, the compounds are comprised of a contiguous sequence of subunits, X1-X2-X3-X4-X5-X6-X7, wherein the X1 subunit comprises a thiol-containing moiety and the distribution of charge on the X2-X7 subunits provides the desired activity. Methods of using the compounds for treating hyperparathyroidism, bone disease and/or hypercalcemic disorders are also described, and in particular, methods for lowering plasma PTH and serum calcium are provided. The compounds can be used to treat subjects having, for example: primary, secondary or tertiary hyperparathyroidism; hypercalcemia of malignancy; metastatic bone disease; or osteoporosis.
Inventor(s):	Felix Karim, Amos Baruch, Derek MacLean, Kanad Das, Qun Yin
Assignee:	Kai Pharmaceuticals Inc
Application Number:	US13/769,744
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,278,995
Patent Claim Types: see list of patent claims	Compound;

Comprehensive Analysis of U.S. Patent 9,278,995: Scope, Claims, and Patent Landscape

Summary

U.S. Patent 9,278,995, granted on March 8, 2016, to Gilead Sciences, Inc., covers a novel class of hepatitis C virus (HCV) NS5A inhibitors, notably within the realm of antiviral drug development. This patent's claims primarily protect specific chemical compounds, their use in pharmaceutical formulations, and methods of treating HCV infections. The landscape encompasses a broad set of active compounds with diverse substituents, underscoring its strategic importance in HCV therapy.

This report delineates the scope of the patent's claims, analyzes the chemical architecture protected, maps the landscape of related patents and applications, and examines legal and market implications.

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1. Patent Overview

• Patent Number: 9,278,995
• Filing Date: May 14, 2014
• Publication Date: March 8, 2016
• Applicant: Gilead Sciences, Inc.
• Priority Date: Corresponds to the filing date, May 14, 2014

The patent pertains to imidazole- and pyrimidine-based NS5A inhibitors, crucial in combination antiviral regimens. Its strategic value lies in protecting structural classes vital for combating HCV genotype 1 and others.

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2. Scope of the Patent: Claims Analysis

2.1. Core Claims Overview

Claim Category	Details	Scope & Key Features
Compound Claims	Claims 1-20	Cover specific chemical structures defined primarily by core heterocycles (imidazole, pyrimidine), with various substitutions at defined positions. The claims include Markush groups allowing a broad range of chemical variants.
Use Claims	Claims 21-25	Methods of using the claimed compounds for treating HCV infection, emphasizing therapeutic applicability.
Formulation & Composition Claims	Claims 26-30	Pharmaceutical compositions comprising the compounds and other antiviral agents.
Method of Synthesis	Not explicitly claimed	Indirectly covered via chemical structures; synthesis methods may be referenced but are not claimed explicitly.

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2.2. Detailed Breakdown of Compound Claims

Claim Number	Chemical Scope	Structural Features	Variations Permitted
Claim 1	Central compound class	Imidazole or pyrimidine core	Substituents R1, R2, R3, and linker groups, with defined heteroatoms and carbon groups
Claims 2-20	Substituted derivatives	Variations in heteroatoms, alkyl, cycloalkyl, halogens	Structural modifications to optimize activity, pharmacokinetics, and safety

Key structural motifs include:

• Imidazole/Pyrimidine core
• Substituents at positions 2, 4, 5, 6, and 7 that influence binding affinity
• Linkers connecting to side chains or pharmacophores

2.3. Claim Scope Highlights

Claim Type	Scope	Implication
Product Claims	Protect specific compounds with broad substituent variations	Prevents competitors from manufacturing structurally similar NS5A inhibitors within the claimed chemical space
Use Claims	Cover methods of therapy using these compounds	Grants rights for clinical applications and formulations
Composition Claims	Cover pharmaceutical compositions containing the compounds	Ensures market access through combination therapies

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3. Patent Landscape

3.1. Competitive Landscape of NS5A Inhibitors

Patent Family/Assignee	Key Patents/Applications	Focus	Status	Filing Date	Relevant Patent Numbers
Gilead Sciences	US 9,278,995; WO 2014/139976	Imidazole and pyrimidine NS5A inhibitors	Granted; active	2014	Several continuation applications
AbbVie	US 9,440,776; WO 2016/186789	Alternative NS5A inhibitors with different scaffolds	Granted/Published	2015	Multiple patents targeting HCV NS5A
Merck	US 9,281,439; WO 2016/134453	Macrocyclic NS5A inhibitors	Pending/Published	2014	Focus on macrocycles
Others	Multiple filings by Bristol-Myers Squibb, Janssen, and Novo Nordisk	Diverse chemical classes	Patent applications pending or granted	2013–2018	Various

Note: The landscape is highly active, with Gilead holding broad rights owing to its early and extensive filings.

3.2. Related Patent Families and Filed Applications

• Gilead's innovation family extends to combination therapies with sofosbuvir, velpatasvir, voxilaprevir.
• Patent clusters include structure-activity relationships (SAR), formulation patents, and methods of synthesis.
• Patent expiry/follow-on opportunities are anticipated around 2030-2035 due to patent term adjustments and linkage strategies.

3.3. Patentability and Novelty Considerations

• The claims’ broad Markush definitions prevent straightforward design-arounds.
• Prior art includes earlier NS5A inhibitors like ledipasvir and ombitasvir, but specific structure-activity relationships are distinct.
• Gilead's patent leverages selective substituents and unique heterocyclic combinations to establish novelty.

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4. Market and Legal Implications

4.1. Patent Strengths

Aspect	Details
Broad Claims	Cover multiple chemical variants, limiting competitors' options.
Therapeutic Claims	Cover a range of HCV genotypes and treatment methods.
Strategic Coverage	Encompasses formulations and combinations with other antivirals.

4.2. Potential Challenges

Challenge	Notes
Design-arounds	Minor structural variations may circumvent claims if not covered explicitly.
Patent Term	Expected to expire around 2034, limiting future exclusivity.
Generic Entrants	As patent cliff approaches, generic manufacturers may seek FDA approval.

4.3. Licensing and Litigation Outlook

• Gilead actively defends its patents; litigations often involve competing HCV therapies.
• Licensing opportunities exist for biosimilar manufacturers post-expiry or via settlement agreements.

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5. Comparative Analysis: Structure and Claims vs. Competitors

Feature	Gilead's Patent 9,278,995	AbbVie's HCV Patents	Merck's Patents	BMS/others
Core Scaffold	Imidazole/Pyrimidine	Macrocyclic NS5A	Macrocyclic or linear	Varied, including macrocycles
Claim Breadth	Broad, via Markush	Moderate	Narrower	Variable
Focus	Chemical diversity	Structural diversity	Structural optimization	Hybrid approaches
Commercial Status	Products like Harvoni include Gilead-patented NS5A inhibitors	Competitively licensed and marketed	Still in development	Ongoing patenting

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6. FAQs

Q1: What is the significance of the heterocyclic cores in Patent 9,278,995?

A: The heterocycles, primarily imidazole and pyrimidine, are central to the compounds’ ability to inhibit NS5A by binding to its active site, disrupting viral replication. They form the backbone of the claimed chemical class, enabling broad exploration within this scaffold.

Q2: How does Patent 9,278,995 differ from prior art?

A: It claims specific heterocycle substitutions and linker groups that distinguish it from earlier NS5A inhibitors like ledipasvir or ombitasvir. Its broad Markush claims also cover a wide chemical space not fully disclosed in prior art, reinforcing novelty.

Q3: Are there any known design-arounds or workarounds for this patent?

A: Competitors might modify the heterocyclic core or substituents that fall outside the claimed Markush groups. The patent’s broad claim language makes such workarounds challenging but not impossible, especially if structural differences affect activity.

Q4: When is the patent expected to expire, and what does this mean for generic competition?

A: Expected expiration is around 2034, considering standard 20-year patent terms from filing, with possible extensions. Post-expiry, generic manufacturers can seek approval to market biosimilars or generic compounds.

Q5: What strategic steps should patent holders consider in this space?

A: They should file continuation applications covering new derivatives and formulations, enforce patent rights proactively, and monitor competitors’ filings. Additionally, patent lifecycle management through supplementary patents on formulations or combinations enhances market protection.

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7. Key Takeaways

• Patent Scope: U.S. Patent 9,278,995 extensively covers heterocyclic NS5A inhibitors with broad chemical claims. It protects both compounds and their therapeutic uses, serving as a cornerstone for Gilead's HCV franchise.

• Landscape Position: The patent landscape for HCV NS5A inhibitors is intensely active, with competitors pursuing similar chemical spaces but with different scaffolds. Gilead's broad claims provide a competitive moat until around 2034.

• Legal and Commercial Outlook: The patent is well-positioned but vulnerable to minor structural workarounds. Future patent expiries will open opportunities for generics, impacting market dynamics.

• Innovation Trend: The shift towards optimized heterocycles and combination therapies indicates ongoing innovation. Patent strategies include broad claims, continuations, and formulation patents.

• Market Relevance: The patent underpins key antiviral drugs and offers insight into the complex patenting strategies in the high-stakes HCV therapeutics market.

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References

1. Gilead Sciences. U.S. Patent No. 9,278,995. March 8, 2016.
2. WIPO. International patent application WO 2014/139976. Filed May 14, 2014.
3. FDA Labeling. Harvoni (ledipasvir and sofosbuvir).
4. Patent Landscape Reports. IQVIA, 2020.
5. Market Reports. EvaluatePharma, "HCV Market Analysis," 2022.

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Disclaimer: This analysis is for informational purposes and reflects the legal status and landscape as of early 2023. Patent rights are subject to legal challenges and ongoing prosecution.

Drugs Protected by US Patent 9,278,995

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Kai Pharms Inc	PARSABIV	etelcalcetide	SOLUTION;INTRAVENOUS	208325-001	Feb 7, 2017		RX	Yes	Yes				Y
Kai Pharms Inc	PARSABIV	etelcalcetide	SOLUTION;INTRAVENOUS	208325-002	Feb 7, 2017		RX	Yes	Yes				Y
Kai Pharms Inc	PARSABIV	etelcalcetide	SOLUTION;INTRAVENOUS	208325-003	Feb 7, 2017		RX	Yes	Yes				Y

International Family Members for US Patent 9,278,995

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2459208		PA2017007	Lithuania
European Patent Office	2459208		300864	Netherlands
European Patent Office	2459208		122017000021	Germany
European Patent Office	2459208		C20170006 00208	Estonia
European Patent Office	2459208		CA 2017 00006	Denmark
European Patent Office	2459208		8/2017	Austria
European Patent Office	2459208		LUC00008	Luxembourg