Details for Patent: 8,329,159

Which drugs does patent 8,329,159 protect, and when does it expire?

Patent 8,329,159 protects DAKLINZA and is included in one NDA.

This patent has sixty-eight patent family members in thirty-one countries.

Summary for Patent: 8,329,159

Title:	Hepatitis C virus inhibitors
Abstract:	The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
Inventor(s):	Makonen Belema, Van N. Nguyen
Assignee:	Bristol Myers Squibb Co
Application Number:	US11/835,462
Patent Claim Types: see list of patent claims	Compound;

US Patent 8,329,159: Daclatasvir Claims, Scope, Expiration and Patent Landscape

US Patent 8,329,159 is a Bristol-Myers Squibb composition-of-matter patent covering daclatasvir, also known as BMS-790052, and six structurally related hepatitis C virus NS5A inhibitors. Claim 1 covers daclatasvir itself, including pharmaceutically acceptable salts. The remaining claims cover defined analogs rather than a broad chemical genus.

The patent is commercially important because it protects the active ingredient used in Daklinza. It does not, based on the claims supplied, independently protect a formulation, treatment regimen, combination therapy, manufacturing process, crystalline form, or broad class of NS5A inhibitors.

What drug does US Patent 8,329,159 cover?

Claim 1 covers daclatasvir, the active pharmaceutical ingredient formerly marketed in the United States as Daklinza.

Daclatasvir is a hepatitis C virus NS5A replication-complex inhibitor. Its structure contains:

• A central 4,4'-biphenyl linker.
• Two imidazole rings.
• Two chiral pyrrolidine units.
• Valine-derived carbamate groups.
• Multiple defined stereocenters.
• A symmetric molecular architecture.

The commercial product was daclatasvir dihydrochloride, supplied as oral tablets. The FDA approved Daklinza in July 2015 for use with other antiviral agents in patients with chronic hepatitis C virus infection. The product was not approved as monotherapy. (U.S. Food and Drug Administration [FDA], 2015)

Claim-to-compound identification

Claim	Compound identified	Commercial relevance
1	Daclatasvir, including pharmaceutically acceptable salts	Primary commercial compound; active ingredient in Daklinza
2	Symmetric bis-imidazole, bis-pyrrolidine analog with dimethylamino phenylacetamide substituents	Research analog
3	Daclatasvir-related analog containing a diethylamino phenylacetyl group	Research analog
4	Analog containing a tetrahydrofuran-2-carbonyl substituent	Research analog
5	Analog containing a dimethylamino phenylacetyl substituent	Research analog
6	Symmetric bis-carbamate analog	Research analog
7	Analog containing a dimethylamino phenylacetyl group and tetrahydrofuran-related substitution	Research analog

The supplied claims use exact chemical definitions. They do not use a Markush formula or functional language such as "a compound having activity against HCV NS5A." That limits the literal scope to the named molecular structures and their pharmaceutically acceptable salts.

What is the legal scope of claim 1?

Claim 1 is a narrow composition-of-matter claim with strong literal coverage of daclatasvir.

The claim requires the complete molecular arrangement, including:

1. The biphenyl-imidazole core.
2. The two pyrrolidine-containing side chains.
3. The specified carbamate and amino-acid-derived substituents.
4. The stereochemical configuration identified by the 1S and 2S descriptors.
5. The exact connectivity of the amide and carbamate groups.

A product that contains daclatasvir as its active ingredient would generally fall within claim 1, regardless of whether it is supplied as the free base or as a pharmaceutically acceptable salt, assuming the claim is valid and enforceable.

What does "pharmaceutically acceptable salt" add?

The salt language expands claim 1 beyond one isolated solid form. It can cover pharmaceutically acceptable acid-addition salts and other accepted salt variants of the claimed compound.

For daclatasvir, the commercially relevant form was daclatasvir dihydrochloride. The claim is not limited to the dihydrochloride unless the patent specification or prosecution history imposes such a limitation.

The salt language does not automatically cover:

• Every solvate or hydrate as a separate composition.
• Every polymorph unless it is the claimed compound or salt.
• Prodrugs with altered covalent structures.
• Co-crystals that are not legally characterized as salts.
• Formulations containing daclatasvir with excipients.

Those issues depend on the exact product structure and claim construction.

How broad are claims 2 through 7?

Claims 2 through 7 are separate compound claims directed to specifically identified analogs. They do not create broad protection for all compounds sharing the daclatasvir scaffold.

Each claim requires the complete named molecule. A competitor could avoid literal infringement by changing a required substituent, stereocenter, linker, amide, carbamate, or ring system. The doctrine of equivalents could still be relevant, but substantial structural modifications would make equivalence arguments more difficult.

Structural differentiation among the claims

Claims 2 and 6 are symmetric molecules built around the same biphenyl-bis-imidazole architecture. Claims 3, 4, 5 and 7 are less symmetric analogs with different acyl or amino substituents.

The claim set appears designed to capture:

• The clinical lead compound.
• Closely related backup compounds.
• Alternative side-chain substitutions.
• Symmetric and asymmetric variants.
• Compounds retaining the central NS5A pharmacophore.

The claims are therefore commercially concentrated around claim 1. Claims 2 through 7 add value for chemical-space protection and possible research or development programs, but they do not materially expand the claims to unrelated NS5A inhibitors.

What patents protect daclatasvir and Daklinza?

US Patent 8,329,159 is the key composition-of-matter patent reflected in the claims supplied. It belongs to the Bristol-Myers Squibb patent family covering biphenyl derivatives with anti-HCV activity.

Principal protection categories

Protection category	Coverage under the supplied claims	Commercial importance
Daclatasvir active ingredient	Yes, claim 1	Very high
Pharmaceutically acceptable salts	Yes	High
Defined daclatasvir analogs	Yes, claims 2-7	Moderate
Broad NS5A inhibitor genus	No apparent coverage in supplied claims	Depends on other family patents
Tablet formulation	No	Depends on separate formulation patents
Specific crystalline form	No apparent coverage	Depends on separate solid-state patents
HCV treatment method	No	Depends on method-of-use patents
Combination with sofosbuvir or other antivirals	No apparent coverage	Depends on separate combination patents
Manufacturing process	No	Depends on process patents and trade secrets

The broader patent landscape must therefore be separated from the seven claims. Other members of the daclatasvir family or related patent families may cover methods of treatment, combinations, intermediates, salts, solid forms, or manufacturing routes. Those rights cannot be attributed to US 8,329,159 without separate claim analysis.

When does US Patent 8,329,159 lose exclusivity?

The patent has a March 2007 priority date and a nominal US patent-term endpoint in March 2027. The patent term is generally measured from the earliest effective nonprovisional filing date, subject to patent-term adjustment and any applicable patent-term extension. (35 U.S.C. § 154)

Event	Date or status
Earliest priority period	March 2007
US patent grant	December 11, 2012
FDA approval of Daklinza	July 24, 2015
Nominal patent-term endpoint	March 2027
FDA new chemical entity exclusivity	Five years from approval, ending in 2020
Current commercial status	Daklinza is no longer a major US commercial HCV product

The five-year new chemical entity exclusivity period expired before the patent term. FDA exclusivity and patent exclusivity are separate. The end of FDA exclusivity permitted submission of certain abbreviated applications, subject to valid listed patents and any Paragraph IV litigation.

The effective market-entry date depends on the Orange Book listing, the applicant's certification, litigation, settlement terms, pediatric exclusivity, and any later-issued or separately listed patents. A generic applicant that challenges the composition patent before its expiration could trigger the Hatch-Waxman litigation framework.

What is the Orange Book status of daclatasvir?

Daklinza was approved under NDA 206843. Its labeling identified daclatasvir dihydrochloride as the active ingredient and required combination use with other direct-acting antivirals. FDA Orange Book records are the controlling source for listed patents and regulatory exclusivity associated with the approved product. (FDA, 2024)

A composition patent such as US 8,329,159 is the type of patent most likely to be listed for the active ingredient. Method-of-use patents may also be listed if they claim an approved indication and satisfy FDA listing requirements.

Orange Book treatment is distinct from the broader patent family. A patent may protect daclatasvir or a related use without being listed against every approved product or every dosage form.

Are there Paragraph IV challenges to daclatasvir?

A Paragraph IV certification would assert that a listed patent is invalid, unenforceable, or not infringed. It is the principal US route for an ANDA applicant seeking approval before patent expiration.

For daclatasvir, the main litigation risk would have centered on:

• Invalidity based on anticipation or obviousness.
• Non-infringement through a different active ingredient.
• Salt, polymorph, or solid-form distinctions.
• Method-of-use claim scope.
• Patent listing and regulatory eligibility.
• Settlement rights tied to launch timing.

The supplied claim set presents a clear infringement case against an ANDA product containing daclatasvir itself. It presents a weaker case against a different NS5A inhibitor, even if the competing compound has a similar mechanism or pharmacophore.

No biosimilar pathway applies. Daclatasvir is a chemically synthesized small molecule, so a competitor would ordinarily use the ANDA pathway rather than a biologics license application or biosimilar application.

How strong is the patent estate for daclatasvir?

Composition-of-matter strength

The composition claim is strong against literal copying because it identifies the complete active molecule and expressly includes pharmaceutically acceptable salts. It also benefits from the usual commercial advantages of a compound claim:

• Direct product coverage.
• No requirement to prove a particular use.
• No requirement to prove a specific formulation.
• Applicability to tablets, capsules, and other dosage forms containing the compound.
• Applicability to products manufactured outside the United States and imported into the United States, subject to applicable patent law.

Vulnerabilities

The principal validity questions would be:

1. Whether an earlier reference disclosed the exact compound.
2. Whether the claimed stereochemistry was adequately supported.
3. Whether the claimed compound would have been obvious from known HCV inhibitors.
4. Whether the specification enabled the full salt scope.
5. Whether prosecution narrowed the claims in ways that affect enforcement.

Because the claims are directed to named compounds rather than a broad genus, written-description and enablement challenges are generally more focused. The narrower claim scope also reduces the number of structurally distinct products that would infringe.

What formulation and method-of-use patents may matter?

The supplied claims do not cover a formulation or treatment method. A commercial competitor would therefore need to examine separate patent families covering:

Formulation patents

Potential subjects include:

• Tablet composition.
• Excipient ratios.
• Coating systems.
• Dissolution profiles.
• Daclatasvir dihydrochloride stability.
• Solid-state or polymorphic forms.
• Manufacturing controls for the finished dosage form.

A generic could avoid a formulation claim by using a different excipient system if the active ingredient itself remained outside the composition patent term.

Method-of-use patents

Potential subjects include:

• Treatment of specified HCV genotypes.
• Use with sofosbuvir.
• Use with ribavirin.
• Patients with cirrhosis.
• Patients with prior treatment failure.
• Patients with HIV co-infection.
• Treatment durations and dosing schedules.

Method patents generally provide narrower protection than composition claims because infringement depends on the labeled or induced use. Their commercial importance depends on whether the approved label and the generic label overlap.

How does daclatasvir compare with competing HCV drugs?

Daclatasvir is an NS5A inhibitor. Other major NS5A products include ledipasvir, ombitasvir, elbasvir, velpatasvir and pibrentasvir. These molecules have different chemical structures and are not automatically covered by US Patent 8,329,159.

Product	NS5A active ingredient	Representative product	Relationship to US 8,329,159
Daklinza	Daclatasvir	Bristol-Myers Squibb	Directly covered by claim 1
Harvoni	Ledipasvir plus sofosbuvir	Gilead Sciences	Different active ingredient
Viekira Pak	Ombitasvir plus other agents	AbbVie	Different active ingredient
Zepatier	Elbasvir plus grazoprevir	Merck	Different active ingredient
Epclusa	Velpatasvir plus sofosbuvir	Gilead Sciences	Different active ingredient
Mavyret	Pibrentasvir plus glecaprevir	AbbVie	Different active ingredient

The patent is therefore a product-specific barrier, not a platform patent over the NS5A inhibitor class.

What generic entry risks exist?

A generic daclatasvir product would face a relatively direct product-patent analysis:

1. If the ANDA product contains daclatasvir, claim 1 is the primary infringement risk.
2. If the product uses a pharmaceutically acceptable salt, the salt language increases risk.
3. If the product uses a different solid form, the active-molecule claim may still apply.
4. Separate formulation or method patents could delay or narrow approval.
5. A skinny-label strategy could address some method patents but would not avoid a valid composition claim.
6. A Paragraph IV challenge would be required for launch before the relevant patent expiry.

A competitor developing a structurally distinct NS5A inhibitor would face a different risk profile. Mechanistic similarity alone would not establish infringement of the exact compound claims.

What manufacturing and geographic barriers remain?

The patent covers the compound, not necessarily every synthetic route. A generic manufacturer could use a non-infringing process, but it would still need to produce daclatasvir, which remains the claimed molecule during the patent term.

Manufacturing barriers may include:

• Control of multiple stereocenters.
• Formation of the biphenyl-imidazole core.
• High-purity preparation of the final salt.
• Control of regioisomers and diastereomers.
• Reproducible crystallization.
• Impurity qualification.
• Demonstration of bioequivalence.
• Supply-chain control for advanced intermediates.

US patent rights apply to making, using, selling, offering for sale and importing the patented compound in the United States. Foreign patent rights must be assessed country by country. The US patent does not establish freedom to operate in Europe, Japan, China, India or other jurisdictions.

Key Takeaways

• US Patent 8,329,159 is primarily a daclatasvir composition-of-matter patent.
• Claim 1 covers daclatasvir and pharmaceutically acceptable salts, including the active ingredient used in Daklinza.
• Claims 2 through 7 cover six specifically named daclatasvir analogs.
• The claims supplied do not cover a broad NS5A inhibitor genus, formulation, treatment method, combination, polymorph or manufacturing process.
• The nominal US patent-term endpoint is March 2027, subject to the applicable patent-term calculation.
• Daclatasvir is a small molecule, so generic competition proceeds through the ANDA framework, not biosimilar regulation.
• A generic containing daclatasvir would face a direct claim 1 infringement risk before patent expiry.
• Structurally distinct NS5A inhibitors such as ledipasvir, velpatasvir, elbasvir and pibrentasvir are not covered merely because they share the same mechanism.
• Separate Orange Book-listed patents and non-listed family patents must be reviewed for formulation, method-of-use, combination and solid-state risks.

FAQs

Is daclatasvir dihydrochloride covered by US Patent 8,329,159?

Yes. Claim 1 covers daclatasvir and pharmaceutically acceptable salts. Daclatasvir dihydrochloride is the commercially relevant salt form.

Does US Patent 8,329,159 cover sofosbuvir?

No. Sofosbuvir is a different active ingredient with a different chemical structure and separate patent estate.

Can a generic avoid the patent by using a different daclatasvir polymorph?

Not necessarily. A different polymorph may avoid a narrow solid-state claim, but it would not automatically avoid a composition claim covering daclatasvir or its pharmaceutically acceptable salts.

Does the patent cover treatment of all hepatitis C patients?

The supplied claims do not claim treatment. They claim compounds. Treatment methods, genotypes, combinations and dosing regimens require separate claims in other patents.

Is a biosimilar application appropriate for daclatasvir?

No. Daclatasvir is a chemically synthesized small molecule. A competing product would generally use the ANDA pathway rather than the biosimilar pathway.

References

1. Bristol-Myers Squibb Company. (2012). United States Patent No. 8,329,159: Biphenyl derivatives as inhibitors of HCV replication. United States Patent and Trademark Office.

2. U.S. Food and Drug Administration. (2015). Daklinza (daclatasvir dihydrochloride) prescribing information. FDA.

3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

4. United States Code. (2023). 35 U.S.C. § 154: Contents and term of patent; provisional rights.

5. United States Patent and Trademark Office. (2024). Patent Center and patent term information for U.S. Patent No. 8,329,159. USPTO.

Drugs Protected by US Patent 8,329,159

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Bristol-myers Squibb	DAKLINZA	daclatasvir dihydrochloride	TABLET;ORAL	206843-001	Jul 24, 2015		DISCN	Yes	No				Y
Bristol-myers Squibb	DAKLINZA	daclatasvir dihydrochloride	TABLET;ORAL	206843-002	Jul 24, 2015		DISCN	Yes	No				Y

International Family Members for US Patent 8,329,159

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2049522		C300713	Netherlands
European Patent Office	2049522		CA 2015 00003	Denmark
European Patent Office	2049522		C20150003 00128	Estonia
European Patent Office	2049522		PA2015006	Lithuania
European Patent Office	2049522		92635	Luxembourg
European Patent Office	2049522		15C0007	France