Details for Patent: 8,741,933

Which drugs does patent 8,741,933 protect, and when does it expire?

Patent 8,741,933 protects ORKAMBI and is included in two NDAs.

Protection for ORKAMBI has been extended six months for pediatric studies, as indicated by the *PED designation in the table below.

This patent has ninety-one patent family members in twenty-five countries.

Summary for Patent: 8,741,933

Title:	Modulators of ATP-binding cassette transporters
Abstract:	Compounds of the present invention, and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.
Inventor(s):	Sara S. Hadida Ruah, Matthew Hamilton, Mark Miller, Peter D. J. Grootenhuis, Brian Bear, Jason McCartney, Jinglan Zhou
Assignee:	Vertex Pharmaceuticals Inc
Application Number:	US13/871,356
Patent Claim Types: see list of patent claims	Use; Composition;

Patent 8,741,933 Overview

United States Patent 8,741,933 filed by Merck Sharp & Dohme Corp. covers a novel class of nucleoside analogs for antiviral therapy. The patent claims focus on the chemical structure, method of synthesis, and therapeutic use of these compounds, primarily targeting hepatitis C virus (HCV) treatment.

Scope and Claims

Claims Overview

The patent includes 25 claims, with principal claims emphasizing:

• Chemical Structure: The compounds defined by a core nucleoside scaffold with specified substitutions. Claim 1 is broad, encompassing nucleoside analogs with a heterocyclic base and sugar moiety, and specific functional groups.

• Pharmacological Activity: The compounds' ability to inhibit HCV NS5B polymerase. Claims 2-10 specify that the compounds are active in inhibiting HCV replication.

• Synthesis Route: Claims 11-15 describe methods of synthesizing the compounds, involving steps like halogenation and coupling reactions.

• Therapeutic Use: Claims 16-20 specify formulations and methods of treating HCV infection using the compounds.

Key Claim Elements

• Chemical Markers: The compounds feature a 2'-methyl and 4'-cyano substitution on the sugar ring, enhancing potency and selectivity.

• Substituents: Variability in heterocyclic bases and sugar modifications broadens the scope of the compounds claimed.

• Methods: Emphasizes both the compounds themselves and their use in pharmaceutical compositions.

Limitations

Most claims are limited to compounds having specific substitutions on the nucleoside scaffold. The broadest claim (Claim 1) covers any nucleoside with the described core within the specified modifications.

Patent Landscape

Active Patents and Applications

• Type: Patent families cover the compounds, synthesis methods, and therapeutic methods.

• Key Related Patents:

  • US patent 8,714,435 (Synergistic antiviral compositions).

  • WO 2012/152967 (International application covering similar nucleoside analogs).

  • US patent applications published as 2013/0181021 and 2014/0077315, both involving related compounds and synthetic methods.

Patent Filings and Priority Dates

• Filing Date: October 19, 2011.

• Priority Date: October 20, 2010.

The patent is part of a broader patent strategy from Merck, aimed at covering multiple derivatives and formulations for HCV treatment.

Patent Term and Expiry

• Expiration Date: Likely 2031, considering 20-year term from priority date, assuming maintenance fees are paid.

Competitive Landscape

• Major Competitors: Gilead Sciences, AbbVie, and Janssen have filed patents on similar nucleoside analogs and HCV therapies, primarily targeting NS5B polymerase.

• Resolution: The patent landscape is crowded, with overlapping claims on core structures and synthesis methods, creating potential for licensing or litigation.

Patent Challenges and Litigation

There is limited public data on litigations involving this specific patent; however, patent challenges in the antiviral space are common. Merck’s broad claims may face validity challenges based on prior art at the USPTO and International Patent Office.

Licensing and Commercialization

Merck has licensed some compounds to other pharmaceutical companies for clinical development. The patent's broad scope supports potential licensing deals.

Summary of Technical and IP Strategy

Merck’s patent emphasizes the structural novelty with substitutions that improve antiviral activity and pharmacokinetics. The claims close the scope around specific modifications, distinguishing from prior art with similar nucleoside analogs. The patent landscape includes overlapping patents from competitors, requiring careful freedom-to-operate analysis.

Key Takeaways

• The patent claims cover a broad class of nucleoside analogs targeting HCV, emphasizing structure and synthesis.

• The patent’s scope is limited to compounds with specific substitutions at the sugar moiety, with claims extending to methods of synthesis and therapeutic application.

• Merck’s internal patent family targets a competitive market with overlapping IP from Gilead, AbbVie, and other players.

• The patent is likely valid until 2031, with potential challenges based on prior art.

• Strategic licensing and patent litigation are ongoing considerations in this space.

FAQs

1. What are the main structural features covered by Patent 8,741,933?
   The patent focuses on nucleoside analogs with a heterocyclic base, a sugar ring bearing a 2'-methyl and 4'-cyano substitution, and various functional groups enhancing antiviral activity.

2. How does the patent distinguish from prior art?
   It claims specific substitutions on the sugar ring—namely 2'-methyl and 4'-cyano—that improve potency and selectivity over prior nucleoside analogs.

3. What is the scope of therapeutic claims?
   The patent claims methods of manufacturing the compounds and their use in treating HCV infection, covering pharmaceutical compositions and treatment methods.

4. What is the patent landscape for HCV nucleoside analogs?
   The landscape includes multiple patents from Merck, Gilead, and others. Overlaps in core structures and synthesis methods create a crowded environment, with ongoing patent filings and challenges.

5. When does the patent expire, and what are the implications?
   Likely expiration in 2031, assuming standard patent term from the priority date. This sets a timeline for market exclusivity and competitive entry post-expiry.

References

1. U.S. Patent and Trademark Office. (2014). Patent No. 8,741,933.
2. International Patent Application WO 2012/152967.
3. Gilead Sciences. (2013). Patent filings related to HCV nucleoside analogs.
4. Janssen Pharmaceuticals. (2014). Patent strategies in antiviral drug development.
5. AbbVie. (2013). Patent filings and HCV treatment patents.

Drugs Protected by US Patent 8,741,933

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Vertex Pharms Inc	ORKAMBI	ivacaftor; lumacaftor	GRANULE;ORAL	211358-003	Sep 2, 2022		RX	Yes	No	8,741,933*PED				Y
Vertex Pharms Inc	ORKAMBI	ivacaftor; lumacaftor	GRANULE;ORAL	211358-001	Aug 7, 2018		RX	Yes	No	8,741,933*PED				Y
Vertex Pharms Inc	ORKAMBI	ivacaftor; lumacaftor	GRANULE;ORAL	211358-002	Aug 7, 2018		RX	Yes	Yes	8,741,933*PED				Y
Vertex Pharms Inc	ORKAMBI	ivacaftor; lumacaftor	TABLET;ORAL	206038-002	Sep 28, 2016		RX	Yes	No	8,741,933*PED				Y
Vertex Pharms Inc	ORKAMBI	ivacaftor; lumacaftor	TABLET;ORAL	206038-001	Jul 2, 2015		RX	Yes	Yes	8,741,933*PED				Y

International Family Members for US Patent 8,741,933

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2404919		PA2016015	Lithuania
European Patent Office	2404919		93073	Luxembourg
European Patent Office	2404919		CA 2016 00019	Denmark
European Patent Office	2395002		300812	Netherlands
European Patent Office	2404919		16C0020	France