Details for Patent: 7,964,580

Which drugs does patent 7,964,580 protect, and when does it expire?

Patent 7,964,580 protects EPCLUSA, HARVONI, SOVALDI, and VOSEVI, and is included in seven NDAs.

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

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

Summary for Patent: 7,964,580

Title:	Nucleoside phosphoramidate prodrugs
Abstract:	Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.
Inventor(s):	Michael Joseph Sofia, Jinfa Du, Peiyuan Wang
Assignee:	Gilead Sciences Inc
Application Number:	US12/053,015
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,964,580
Patent Claim Types: see list of patent claims	Use; Composition;

U.S. Patent 7,964,580 Scope and Claims Analysis for (S)-Isopropyl Phenoxy-Phosphorylamino Propionate Nucleoside Conjugate (HCV-Directed)

U.S. Patent 7,964,580 claims a specific stereodefined prodrug-like nucleoside conjugate defined by a (S)-isopropyl phosphoramidate/phenoxy-phosphoryl-amino propionate connected to a substituted tetrahydrofuran nucleoside moiety and coupled via a phenoxy-phosphoryl linkage to a pyrimidinone base. The patent scope centers on (i) the compound and its stereoisomers, (ii) pharmaceutical compositions, (iii) treatment methods broadly covering multiple viruses but with an explicit hepatitis C virus (HCV) treatment claim set, and (iv) a manufacturing route using a coupling reaction between a “compound 4″” and a “nucleoside analog 5′” with a leaving group.

Patent claims overview (as provided)

Claim	Category	What is claimed (high-level)	Practical infringement focus
1	Product (Markush)	(S)-2-{[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid isopropyl ester or stereoisomers	Making or selling the specific compound (including stereochemical variants)
2	Composition	Claim 1 compound + pharmaceutically acceptable medium	Formulation and sale for HCV-related use
3	HCV composition	Effective amount for treating HCV	Product intended for HCV use (labeling, marketing, submission claims)
4	Method (broad virus panel)	Administering claim 1 compound to treat virus selected from listed panel	Off-label or labeled use across any of the listed viruses
5	Method (HCV-specific)	Administering claim 1 compound for HCV infection	Straight method-use claim for HCV
6	Process	React “compound 4″” with “nucleoside analog 5′” where X′ is a leaving group	Manufacturing route (chemical steps and intermediates)
7	Process product	Product obtained by the process of claim 6	Products made by the claimed process (process-by-product)
8	Product (single stereochemical variant)	Specific fully specified stereochemical compound (different naming formatting than claim 1 but same core)	Compound embodiment with tighter stereochemical recitation
9	Composition	Claim 8 compound + pharmaceutically acceptable medium	Formulation and sale
10	HCV composition	Effective amount for treating HCV	Labeling/indication-driven exposure
11	Method (broad virus panel)	Administering claim 8 compound to treat listed viruses	Same panel infringement pathway as claim 4
12	Method (HCV-specific)	Administering claim 8 compound for HCV infection	HCV use pathway
13	Process	React “compound 4″” with “nucleoside analog 5′” where X′ is leaving group	Manufacturing route exposure tied to named intermediates
14	Process product	Product obtained by the process of claim 13	Process-by-product route limitation

What is the practical scope of claim 1 and claim 8 (compound coverage, stereochemistry, and “stereoisomer” risk)?

Core structure: stereodefined nucleoside conjugate + (S)-isopropyl ester

Both claim 1 and claim 8 cover a single defined chemical scaffold with:

• A nucleoside-like tetrahydrofuran stereocenter set: (2R,3R,4R,5R)
• A 2,4-dioxo-pyrimidinyl group attached to position 1 of the tetrahydrofuran ring system
• A fluoro substituent at the 4-position and a hydroxy at the 3-position
• A methyl at the 4-position (“4-methyl-tetrahydro-furan” plus “3-hydroxy” language)
• A methoxy linkage to a phenoxy-phosphoryl-amino propionate segment
• A prodrug-like stereochemical constraint: (S)-isopropyl ester on the propionic acid moiety
• A defined phenoxy-phosphorylamino linkage (phosphoryl-amino propionic acid isopropyl ester)

“Or a stereoisomer thereof” expands beyond the explicit stereochemical drawing

Claim 1 is not limited solely to the one stereoisomer written in the claim body. It explicitly includes “or a stereoisomer thereof,” which functionally broadens coverage to additional stereoisomers that are “stereoisomer(s) thereof” of the compound. For enforcement and risk analysis, the question becomes whether a competitor’s compound is:

• the exact stereochemical embodiment described, or
• another stereoisomer that falls within “stereoisomer thereof” interpretation under claim construction.

Claim 8 tightens into a fully specified named stereochemical form (the claim text is a second embodiment with full stereochemical specification). For validity and infringement analysis, claim 8 generally acts as a narrower “anchor” embodiment within the broader claim 1 Markush-style stereoisomer coverage.

Included subject matter types

The patent is structured around three layers:

1. Chemical entity (compound and stereoisomers)
2. Composition/formulation (compound + acceptable medium)
3. Methods of treatment (HCV-specific and multi-virus panel)

That structure is relevant to litigation because a generic or alternative-synthesis entrant can attack the entity claims and still face composition or method-use exposure if their product is deemed the same compound embodiment.

What do the method claims cover (HCV-only vs. multi-virus panel selection language)?

HCV-specific method claims (claims 3, 5, 10, 12)

• Claim 3: HCV composition (effective amount + medium)
• Claim 5: administering claim 1 compound for treating HCV infection
• Claim 10: HCV composition for claim 8 compound
• Claim 12: administering claim 8 compound for HCV infection

These claims align with standard enforcement triggers for product makers and label-based pathways. In the U.S., method claims typically require showing direct infringement by prescribing/dispensing/using the patented method depending on the court’s and statute’s interpretation, but commercially they are usually paired with labeling and intended use.

Broad virus panel method claims (claims 4 and 11)

Claims 4 and 11 cover administering to treat a virus selected from:

• hepatitis C virus
• West Nile virus
• yellow fever virus
• dengue virus
• rhinovirus
• polio virus
• hepatitis A virus
• bovine viral diarrhea virus
• Japanese encephalitis virus

This panel selection language is important in two ways:

1. Scope breadth: It is not limited to HCV, so the method claims could be asserted even if the challenger argues the product is “developed for HCV,” as long as the accused use falls under one of the enumerated viruses.
2. Labeling and evidence: Practical infringement evidence often hinges on clinical development programs, promotional materials, and prescription intent. Even if marketing is HCV-focused, off-label use or broader intended-use statements can create method exposure.

What formulations are claimed (composition claims 2, 9 and HCV compositions 3, 10)?

Claims 2 and 9 are broad “compound + pharmaceutically acceptable medium” composition claims. They do not specify dosage form (tablet, capsule, solution, lyophilisate), release profile (immediate vs. extended), or excipient identities. That generally makes them resistant to narrow design-around based solely on changing excipients.

Claims 3 and 10 add an HCV treatment intent framing: they claim a composition “for treating a hepatitis C virus” with an effective amount. That tends to track indication-based use and can be implicated by:

• product labeling
• FDA indication (if any)
• clinical trial inclusion and communication

What manufacturing scope is claimed (process claims 6 and 13, and process-by-product claims 7 and 14)?

Process claims 6 and 13: coupling via “compound 4″” + “nucleoside analog 5′ where X′ is leaving group”

Claims 6 and 13 define a preparation route using language tied to intermediate numbering (“compound 4″” and “nucleoside analog 5′”), and a leaving group parameter (X′ is a leaving group). This is a classic “chemical step + intermediate class” approach.

Key scope implications:

• The claims are limited to the defined coupling between those intermediate categories, not a general multi-step synthesis.
• The leaving group parameter suggests the nucleoside analog can vary in the identity of X′ as long as it is a leaving group.

Process-by-product claims 7 and 14: product “obtained by” the process

Claims 7 and 14 claim the product obtained by the process of claims 6 and 13. These are often used to capture entities made through the claimed route even if structural equivalence is debated.

In infringement posture, process-by-product claims can matter if:

• accused manufacturing is hard to “read out” by direct comparison of intermediates; and
• the resulting product is alleged to be the same as the patented compound.

How does claim breadth compare between claim 1/8 (entity) and claims 2-5/9-12 (composition and methods)?

Hierarchy of risk to competitors

• Highest risk: direct making, selling, and importing of the exact compound of claim 1 or claim 8 (product claims).
• Medium risk: selling formulations containing that compound (composition claims).
• Medium-to-high risk: prescribing/using/dispensing for HCV or other listed viruses (method claims), especially where marketing or clinical evidence supports the specific intended use.

Design-around pressure

Because composition claims are broad on “pharmaceutically acceptable medium,” and the entity claims include stereoisomer language, practical design-around generally requires:

• changing the chemical entity beyond “stereoisomer” coverage, or
• using a materially different scaffold, or
• pursuing a non-infringing synthesis route that avoids making the claimed product (though product claims may still catch the final entity regardless of route).

Patent landscape for U.S. Patent 7,964,580: what other patents likely matter and how to map them by claim type (entity, formulation, method, process)

A complete, accurate U.S. patent landscape (including exact citations, related family members, assignees, prosecution history events, and Orange Book listings) cannot be produced from the information provided. The patent number alone does not establish the full bibliographic record, the assignee, the foreign family, continuation/divisional status, or whether any reference listed drug (RLD) uses the claimed compound. Under the operating constraint, producing a detailed landscape with named related patents or litigation outcomes without complete source-backed data would risk inaccuracy.

What can be stated precisely from your claim set:

• The patent’s internal claim portfolio spans compound, composition, HCV and multi-virus treatment methods, and specific coupling-process manufacturing, including process-by-product coverage.
• Any landscape analysis that materially affects freedom-to-operate would need to examine, in the same patent family and in other intersecting families:
  • earlier priority compounds or intermediate synthesis claims,
  • later improvements (e.g., specific prodrugs/esters, stereochemical single-isomer selections, solid forms, and specific excipient systems),
  • regulatory-exclusivity linkages (Orange Book) and method-of-use coverage tied to FDA-labeled indications,
  • any second-generation compounds with altered prodrug ester groups, linker substitutions, or nucleoside base modifications,
  • any manufacturing patents that either (i) broaden beyond the “compound 4″ + nucleoside analog 5′ with X′ leaving group” step or (ii) provide alternative coupling chemistry that avoids making the claimed product-by-process.

Key claim construction levers that drive infringement and invalidity risk

(Structured for litigation and design-around.)

1. Stereochemical boundaries

   • Claim 1 includes “stereoisomer thereof,” which can widen coverage beyond the explicitly written stereochemical configuration.
   • Claim 8 is a fully specified embodiment. If a challenger attacks the broader claim, claim 8 can still anchor infringement.

2. “Pharmaceutically acceptable medium” breadth

   • Composition claims are not constrained by dosage form or excipient selection.
   • This pushes differentiation toward changing the active ingredient or the chemical scaffold.

3. Virus panel selection in method claims

   • Claims 4 and 11 cover multiple viruses; the operative issue becomes evidence of “administering… wherein the virus is selected from among…” the listed set.

4. Intermediate-numbered process claims

   • Claims 6/13 depend on the definitions of “compound 4″” and “nucleoside analog 5′” in the specification.
   • If competitors define different intermediates, they may attempt to argue non-coverage, but the leaving-group parameter and reaction description typically require careful technical claim construction.

5. Process-by-product claims

   • Claims 7/14 can be asserted even when manufacturing steps differ, depending on how the “product obtained by” element is proven.

Key Takeaways

• U.S. Patent 7,964,580 protects a specific stereodefined nucleoside-conjugate compound (S)-isopropyl ester form and also “stereoisomers thereof” under claim 1, with a tighter single embodiment under claim 8.
• The claim set is layered: compound (1, 8), compositions (2, 3, 9, 10), and methods (4, 5, 11, 12) including explicit HCV treatment and a multi-virus panel.
• Manufacturing is covered through a specific coupling process between a numbered intermediate (“compound 4″”) and a nucleoside analog (“5′”) with a leaving group (X′), plus process-by-product claims (7, 14).
• A complete external patent landscape for 7,964,580, including related family members, Orange Book status, and litigation risk, cannot be reliably enumerated from the provided data alone.

FAQs

1. Does U.S. Patent 7,964,580 cover only hepatitis C virus or multiple viruses?
   It covers HCV explicitly (claims 3, 5, 10, 12) and also includes method claims for a selected panel of viruses including West Nile, yellow fever, dengue, rhinovirus, polio, hepatitis A, bovine viral diarrhea, and Japanese encephalitis (claims 4 and 11).

2. Are stereoisomer variants covered in addition to the named compound?
   Yes. Claim 1 covers the named (S)-isopropyl ester compound “or a stereoisomer thereof,” while claim 8 provides a specific stereochemical embodiment.

3. Do the composition claims specify dosage form or excipients?
   No. Claims 2 and 9 are broadly “compound + pharmaceutically acceptable medium,” and claims 3 and 10 are framed for HCV treatment with an effective amount.

4. What manufacturing route is claimed?
   Claims 6 and 13 recite reacting a numbered “compound 4″” with a nucleoside analog “5′” where X′ is a leaving group.

5. How do process-by-product claims expand protection?
   Claims 7 and 14 cover the product “obtained by” the process of claims 6 and 13, supporting infringement arguments tied to the end product made via the patented route.

References

1. U.S. Patent 7,964,580 (claim set provided by user).

Drugs Protected by US Patent 7,964,580

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Gilead Sciences Inc	EPCLUSA	sofosbuvir; velpatasvir	PELLETS;ORAL	214187-001	Jun 10, 2021		RX	Yes	No	7,964,580*PED				Y
Gilead Sciences Inc	EPCLUSA	sofosbuvir; velpatasvir	PELLETS;ORAL	214187-002	Jun 10, 2021		RX	Yes	Yes	7,964,580*PED				Y
Gilead Sciences Inc	HARVONI	ledipasvir; sofosbuvir	PELLETS;ORAL	212477-001	Aug 28, 2019		RX	Yes	No	7,964,580*PED				Y
Gilead Sciences Inc	HARVONI	ledipasvir; sofosbuvir	PELLETS;ORAL	212477-002	Aug 28, 2019		RX	Yes	Yes	7,964,580*PED				Y

International Family Members for US Patent 7,964,580

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2203462		214 5029-2014	Slovakia
European Patent Office	2203462		C300704	Netherlands
European Patent Office	2203462		PA2014040	Lithuania
European Patent Office	2203462		CA 2014 00061	Denmark