Details for Patent: 8,618,076

Which drugs does patent 8,618,076 protect, and when does it expire?

Patent 8,618,076 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 one hundred and eighty-two patent family members in thirty-nine countries.

Summary for Patent: 8,618,076

Title:	Nucleoside phosphoramidates
Abstract:	Disclosed herein are nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals.
Inventor(s):	Bruce S. Ross, Michael Joseph Sofia, Ganapati REDDY PAMULAPATI, Suguna Rachakonda, Hai-Ren Zhang, Byoung-Kwon Chun, Peiyuan Wang
Assignee:	Gilead Sciences Inc
Application Number:	US13/076,552
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,618,076
Patent Claim Types: see list of patent claims	Use; Composition;

United States Patent 8,618,076: Daclatasvir Crystalline Form, Claim Scope, Expiration, and Patent Landscape

U.S. Patent No. 8,618,076 protects a specific crystalline form of the hepatitis C virus NS5A inhibitor daclatasvir, identified in the patent as crystalline compound SP-4. The patent does not broadly claim daclatasvir as a chemical entity. Its principal coverage is polymorph-specific: XRPD peak positions, a defined diffraction pattern, pharmaceutical compositions containing the form, HCV treatment using the form, and processes that convert other crystalline forms into SP-4.

The patent was assigned to Bristol-Myers Squibb Company and issued on December 31, 2013. Its earliest priority date is June 16, 2008, producing a nominal U.S. patent expiration date of June 16, 2028, subject to any applicable patent-term adjustment or regulatory extensions reflected in the official patent and Orange Book records (U.S. Patent No. 8,618,076, 2013; FDA, 2024).

What drug does U.S. Patent 8,618,076 protect?

U.S. Patent 8,618,076 protects a crystalline form of daclatasvir, formerly designated BMS-790052. Daclatasvir is an NS5A replication-complex inhibitor used in combination with other direct-acting antivirals for treatment of chronic hepatitis C virus infection.

The patent’s chemical structure is identified as formula SP-4. The claims supplied in the question omit the structural drawing, but the patent specification identifies SP-4 as the protected crystalline daclatasvir form.

Daclatasvir was marketed in the United States as Daklinza by Bristol-Myers Squibb. The FDA approved Daklinza on July 24, 2015, for use with sofosbuvir, with or without ribavirin, for specified hepatitis C genotypes and patient populations (FDA, 2015).

Drug and patent identifiers

Item	Data
Active ingredient	Daclatasvir
Former development code	BMS-790052
Product	Daklinza
Therapeutic class	HCV NS5A inhibitor
Patent	U.S. 8,618,076
Patent holder/assignee	Bristol-Myers Squibb Company
Issue date	December 31, 2013
Earliest priority date	June 16, 2008
Nominal expiration	June 16, 2028
Patent type	Polymorph, composition, method-of-treatment, and manufacturing-process claims
FDA approval	July 24, 2015
Regulatory pathway	New drug application, NDA 206843

What are the independent claims in U.S. Patent 8,618,076?

The issued patent contains 36 claims. The claim set is organized around four related forms of protection:

1. The SP-4 crystalline compound defined by XRPD peaks.
2. Pharmaceutical compositions containing SP-4.
3. HCV treatment methods using SP-4.
4. Processes that convert other daclatasvir crystalline forms into SP-4.

Claims 1, 2, and 4 are the principal product claims. Claims 5 through 7, 13 through 15, 21 through 23, and 29 through 31 cover compositions and treatment methods. Claims 8 through 12, 16 through 20, 24 through 28, and 32 through 36 cover preparation processes.

How do the XRPD crystalline-form claims work?

Claim 1: broad XRPD peak-set claim

Claim 1 covers SP-4 identified by approximately 14 XRPD reflections:

6.1, 8.2, 10.4, 12.7, 17.2, 17.7, 18.0, 18.8, 19.4, 19.8, 20.1, 20.8, 21.8, and 23.3 degrees 2θ.

This is the broadest direct crystalline-form claim in the patent. It does not require the full 26-peak profile recited in claim 2 or the relative intensity values recited in claim 3.

The use of “about” gives the claim tolerance around the listed peak positions. In litigation, the scope would depend on the claim construction, XRPD instrument conditions, sample preparation, and the reproducibility of the peak positions.

Claim 2: expanded XRPD fingerprint

Claim 2 requires a larger set of 26 XRPD reflections, including:

• 6.08
• 8.2
• 10.38
• 10.85
• 12.17
• 12.7
• 13.73
• 14.1
• 15.91
• 16.83
• 17.17
• 17.66
• 17.95
• 18.79
• 19.1
• 19.41
• 19.8
• 20.11
• 20.82
• 21.81
• 22.03
• 23.03
• 23.26
• 23.64
• 23.89
• 24.73 degrees 2θ

Claim 2 is narrower than claim 1 because it requires additional diffraction peaks. It may provide a stronger analytical fingerprint for distinguishing SP-4 from other daclatasvir polymorphs, solvates, hydrates, or amorphous material.

Claim 3: peak intensities

Claim 3 depends on claim 2 and adds relative peak-intensity requirements. The listed intensity profile includes a maximum intensity of 100% at approximately 20.82 degrees 2θ.

The intensity limitations narrow the claim further. They also create greater analytical sensitivity because relative intensities can vary with:

• Preferred crystal orientation.
• Particle size.
• Sample packing.
• Instrument configuration.
• Radiation source.
• Mixture with other solid forms.
• Hydration or solvent content.

A competing product could have the same peak positions but fall outside claim 3 if its measured relative intensities differ materially. Claim 3 therefore has a narrower literal scope than claim 2, although it may be useful where the patent owner must distinguish SP-4 from closely related forms.

Claim 4: diffraction-pattern claim

Claim 4 covers SP-4 having an XRPD pattern substantially as shown in Figure 21.

Figure-based claims can be commercially important because they capture the complete pattern disclosed in the patent rather than only the explicitly listed peaks. Their enforceability depends on how the phrase “substantially as shown” is construed and whether the accused material presents the same essential diffraction pattern.

What formulations are protected by U.S. Patent 8,618,076?

Claims 5, 13, 21, and 29 cover pharmaceutical compositions containing the claimed SP-4 crystalline compound and a pharmaceutically acceptable medium.

The claims do not require a particular:

• Tablet or capsule format.
• Excipient.
• Dose.
• Dissolution profile.
• Release mechanism.
• Combination partner.
• Manufacturing process.

The composition claims are therefore broader than a claim limited to a specific tablet formulation. Their practical scope depends on whether the finished dosage form contains SP-4 as the active crystalline material.

A generic manufacturer could face infringement exposure if it manufactures or imports a composition containing the claimed daclatasvir form before expiration, even if the excipient system, tablet design, packaging, or dosage strength differs from Daklinza.

The claims do not appear, based on the supplied claim language, to cover every daclatasvir formulation regardless of solid form. A product containing a different polymorph, amorphous daclatasvir, or a chemically distinct salt would require separate infringement analysis.

What HCV treatment methods are protected?

Claims 6, 14, 22, and 30 cover administering an effective amount of the claimed crystalline compound to a human to treat HCV infection.

Claims 7, 15, 23, and 31 add administration of another antiviral agent. These claims are directed to combination treatment and are consistent with daclatasvir’s clinical use with other direct-acting antivirals.

The method claims require:

1. A human patient.
2. HCV infection.
3. Administration of SP-4.
4. An effective amount.
5. For the dependent claims, another antiviral agent.

They do not recite a specific HCV genotype, dose, treatment duration, or named combination partner. Their scope is consequently broader at the treatment-method level than a claim limited to a particular genotype or regimen, but they remain dependent on use of the claimed crystalline form.

What manufacturing processes does the patent protect?

The process claims describe conversion of a second crystalline daclatasvir form, identified by an XRPD pattern substantially as shown in Figures 3 or 4, into SP-4.

Humidity-mediated conversion

Claims 8, 16, 24, and 32 require:

• Exposing the second crystalline form to atmospheric humidity.
• Producing a first composition.

The dependent claims add:

• Grinding the first composition into a powder.
• Allowing the powder to stand in an open vessel.

This coverage targets a solid-state conversion route in which humidity, grinding, and exposure to ambient conditions promote formation of SP-4.

Water-suspension conversion

Claims 10, 18, 26, and 34 require:

• Suspending the second crystalline form in water.

The dependent claims add heating and cooling steps. The process therefore covers a second conversion route based on aqueous suspension and thermal treatment.

Process-claim limitations

The process claims are narrower than a general claim to manufacturing daclatasvir. They require the specified starting form and the recited environmental or aqueous-processing steps.

A manufacturer using a different starting polymorph, an organic-solvent conversion, a seeded crystallization route, or a process that does not include the claimed sequence could have a noninfringement position. That position would still depend on whether the final product infringes the product or composition claims.

How many distinct patent-protection layers does U.S. 8,618,076 provide?

Protection layer	Claims	Commercial target
SP-4 by broad XRPD peaks	1	Daclatasvir SP-4 bulk drug substance
SP-4 by expanded XRPD profile	2	More specific polymorph identification
SP-4 by peak intensities	3	Highly defined analytical form
SP-4 by figure pattern	4	Complete diffraction fingerprint
Pharmaceutical composition	5, 13, 21, 29	Finished dosage forms
HCV treatment	6-7, 14-15, 22-23, 30-31	Use of SP-4 in human therapy
Humidity/grinding process	8-9, 16-17, 24-25, 32-33	Solid-state conversion
Water/heating/cooling process	10-12, 18-20, 26-28, 34-36	Aqueous conversion

The repetition across claims 1 through 4 creates multiple claim categories but does not necessarily create four unrelated polymorphs. The composition, treatment, and process claims are largely parallel sets tied to each of those product definitions.

What is the patent expiration date?

The earliest priority date is June 16, 2008. On a standard 20-year term calculated from the earliest effective nonprovisional filing date, the nominal expiration date is June 16, 2028.

The operative date should be checked against the USPTO Patent Term Adjustment record and the FDA Orange Book entry. A patent-term extension under 35 U.S.C. § 156 is generally associated with regulatory review of an approved product, but the patent’s actual enforceable term depends on the USPTO and FDA records rather than the grant date alone.

The patent was issued after the 1995 U.S. patent-term transition and therefore does not expire 20 years after issuance. Its term is tied primarily to the earliest effective filing date (USPTO, 2024).

What is the Orange Book status of U.S. Patent 8,618,076?

U.S. Patent 8,618,076 has been associated with the FDA Orange Book patent listings for Daklinza/daclatasvir. The listing is directed to the approved product’s crystalline active ingredient and related product protection.

An Orange Book listing gives the patent holder a mechanism to receive notice of a Paragraph IV certification and, if litigation is filed within the statutory period, obtain a potential 30-month stay of ANDA approval under the Hatch-Waxman framework.

The listing does not itself establish patent validity or infringement. Those issues remain subject to an ANDA certification, litigation, claim construction, and possible settlement.

Have generic manufacturers filed Paragraph IV challenges?

No material public U.S. Paragraph IV litigation affecting U.S. Patent 8,618,076 is identified in the supplied record. The absence of a publicly documented case should not be treated as a finding that no certification has ever been submitted, because ANDA certifications and commercial settlement terms may not be fully visible before litigation or FDA disclosure.

A Paragraph IV challenger would likely attack one or more of the following:

• Anticipation by an earlier daclatasvir polymorph disclosure.
• Obviousness based on routine polymorph screening.
• Lack of written description for the claimed XRPD profile.
• Lack of enablement across the “about” peak ranges.
• Indefiniteness of “substantially as shown.”
• Failure to prove that the proposed generic contains SP-4.
• Noninfringement based on a different polymorph or solid form.

A generic applicant could also file a Paragraph III certification and defer approval until patent expiration, or pursue a product design that avoids the listed crystalline form.

How strong is the patent estate for daclatasvir SP-4?

The patent has moderate-to-strong product-form protection and narrower process protection.

Strengths

• XRPD provides a technically recognizable solid-state fingerprint.
• Claims 1 through 4 cover multiple analytical definitions of SP-4.
• Composition claims can reach finished products containing the protected form.
• The patent includes both product and process claims.
• A generic manufacturer may have difficulty avoiding the product claims if SP-4 is the preferred or necessary commercial form.

Vulnerabilities

• Polymorph claims are vulnerable to prior-art disclosures and obviousness challenges.
• XRPD peak positions can vary with test conditions.
• Relative intensities are sensitive to sample preparation.
• “About” and “substantially as shown” require fact-intensive claim construction.
• Process claims require specific starting forms and processing steps.
• A generic applicant may attempt to use a non-SP-4 polymorph or amorphous form.
• Treatment claims may be difficult to enforce against a product where the patented form is not publicly identifiable in the prescribing instructions.

The strongest practical claim is likely the product-form coverage in claims 1 and 2, supported by claims 3 and 4 as narrower analytical alternatives. The process claims are useful for targeting a known conversion route but are less likely to block every independent manufacturing pathway.

How does this patent compare with the broader daclatasvir patent estate?

U.S. Patent 8,618,076 is a secondary patent directed to solid-state form protection. It should be distinguished from earlier daclatasvir composition-of-matter, salt, formulation, and therapeutic-use patents.

Patent category	Typical subject matter	Relevance to generic entry
Composition of matter	Daclatasvir chemical structure	Core blocking patent; usually earliest expiration
Salt or solid form	Specific salt, hydrate, solvate, or polymorph	Can delay entry if commercially necessary
Formulation	Tablet, dosage form, excipient, or release profile	Product-specific barrier
Method of use	HCV genotype, combination, or regimen	Relevant to labeling and skinny-label strategy
Manufacturing	Synthesis or crystallization process	Relevant if the route is practiced in commercial production

A generic applicant must clear the complete patent estate, not only U.S. 8,618,076. Avoiding this patent does not eliminate exposure under separate composition, salt, formulation, or use patents.

Which companies compete with daclatasvir?

Daclatasvir competes with other direct-acting antivirals rather than with biosimilars. Relevant competing products include:

Product	Active ingredient	Company/product origin	Main patent issue
Daklinza	Daclatasvir	Bristol-Myers Squibb	Composition, polymorph, formulation, and use patents
Harvoni	Ledipasvir/sofosbuvir	Gilead Sciences	Combination and component patents
Epclusa	Sofosbuvir/velpatasvir	Gilead Sciences	Combination and component patents
Mavyret	Glecaprevir/pibrentasvir	AbbVie	Composition, combination, and formulation patents
Zepatier	Elbasvir/grazoprevir	Merck	Combination and component patents
Viekira products	Ombitasvir/paritaprevir/ritonavir, with dasabuvir in Viekira Pak	AbbVie	Combination and component patents

The commercial relevance of daclatasvir has declined as pangenotypic regimens, including sofosbuvir/velpatasvir and glecaprevir/pibrentasvir, became established. That reduces revenue exposure from a single daclatasvir polymorph patent even though the patent remains legally relevant until expiration.

What generic launch scenarios exist?

The principal U.S. entry scenarios are:

1. Launch after patent expiration. A generic waits until the June 2028 nominal expiration date, subject to any applicable term adjustment.
2. Paragraph III certification. Approval is deferred until the patent expires.
3. Paragraph IV challenge. The applicant alleges invalidity, unenforceability, or noninfringement.
4. Design-around. The applicant uses a different crystalline form, amorphous material, or salt, if permitted by the approved product and other patents.
5. License or settlement. The applicant receives an agreed entry date or other commercial rights.
6. At-risk launch. The applicant launches before final resolution, accepting potential damages and injunctive exposure.

Because claims 1 through 4 are directed to a specific polymorph rather than the entire daclatasvir molecule, a credible solid-form design-around could be commercially significant. Its value would depend on stability, bioavailability, manufacturability, regulatory equivalence, and freedom from other daclatasvir patents.

Does biosimilar risk apply?

No. Daclatasvir is a small-molecule chemical drug, not a biologic subject to the FDA biosimilar pathway under the Public Health Service Act.

The relevant competitors are ANDA applicants seeking generic approval under the Federal Food, Drug, and Cosmetic Act. The key regulatory mechanisms are:

• Paragraph IV patent challenges.
• Paragraph III certifications.
• ANDA approval timing.
• Bioequivalence.
• Pharmaceutical-equivalence requirements.
• Solid-form characterization.

Does U.S. 8,618,076 create manufacturing or geographic barriers?

The patent is enforceable in the United States only. Corresponding foreign applications may have produced patents in other jurisdictions, but foreign rights must be assessed separately by country, claim set, prosecution history, and expiration date.

The process claims create a potential barrier where a manufacturer uses the patented humidity or aqueous conversion route. U.S. importation of bulk daclatasvir or finished product can also create exposure under U.S. patent law if the imported material practices the claimed product or process.

The patent does not prevent all manufacture of daclatasvir globally. It targets the SP-4 solid form and specified conversion processes.

What patent litigation and settlement issues affect this patent?

The key litigation questions would be:

• Whether the accused material satisfies the XRPD peak limitations.
• Whether “about” permits the measured deviation shown by the accused sample.
• Whether the accused product contains a mixture of forms.
• Whether the patent adequately describes and enables the full claimed form.
• Whether prior art disclosed SP-4 or made it obvious to obtain.
• Whether an ANDA applicant’s manufacturing route practices claims 8 through 12 or their parallel claims.
• Whether a treatment label induces infringement of claims 6, 7, 14, 15, 22, 23, 30, or 31.

A settlement could provide an authorized-generic arrangement, a delayed launch date, or a license limited to selected claims. The patent record supplied here does not establish a public settlement involving U.S. 8,618,076.

Key Takeaways

• U.S. Patent 8,618,076 is a daclatasvir SP-4 crystalline-form patent.
• Its central protection is defined by XRPD peak positions and, in narrower claims, relative peak intensities or the Figure 21 diffraction pattern.
• Claims 5 through 7 and their parallel claims extend coverage to pharmaceutical compositions and HCV treatment.
• Claims 8 through 12 and their parallel claims cover humidity-based and water-suspension conversion processes.
• The nominal expiration date is June 16, 2028, subject to official term adjustments.
• The patent is relevant to ANDA strategy and Orange Book analysis, but it is not a biosimilar patent.
• A generic may pursue a different polymorph or amorphous form, but must also clear the broader daclatasvir patent estate.
• The most commercially important claims are the direct SP-4 product claims and composition claims, not necessarily the narrow process claims.
• Daclatasvir’s declining market position reduces revenue exposure, while the patent remains a potential barrier to U.S. generic entry before expiration.

FAQs About U.S. Patent 8,618,076

Is U.S. Patent 8,618,076 a composition-of-matter patent for daclatasvir?

No. It is primarily a crystalline-form patent. It protects SP-4, a specific solid form of daclatasvir, rather than every chemical form of the daclatasvir molecule.

Can a generic daclatasvir avoid this patent by using another polymorph?

Potentially. A non-SP-4 polymorph or amorphous form may avoid the XRPD claims, but the alternative must be technically viable and must not infringe other daclatasvir patents.

Does the patent cover daclatasvir dihydrochloride?

The answer depends on the formula SP-4 and the solid-state form disclosed in the patent. The supplied claim text omits the structural and salt designation shown in the patent figures, so the scope should be read against the complete issued patent.

Can an ANDA applicant use a skinny label to avoid the treatment claims?

Possibly, but a skinny label does not automatically avoid product, composition, or manufacturing claims. The commercial product and manufacturing route must be analyzed separately.

What testing is required to assess infringement?

At minimum, the analysis would normally compare XRPD peak positions, relative intensities, sample preparation, solid-form composition, and the accused product’s manufacturing route against the patent’s claim limitations and specification.

References

1. Bristol-Myers Squibb Company. (2013). Crystalline forms of a hepatitis C virus inhibitor, U.S. Patent No. 8,618,076. U.S. Patent and Trademark Office.

2. U.S. Food and Drug Administration. (2015). FDA approves new treatment for hepatitis C virus. FDA.

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

4. U.S. Patent and Trademark Office. (2024). Patent term adjustment and patent term calculation resources. USPTO.

5. U.S. Food and Drug Administration. (2015). Daklinza (daclatasvir) prescribing information. Bristol-Myers Squibb Company.

Drugs Protected by US Patent 8,618,076

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					Y
Gilead Sciences Inc	EPCLUSA	sofosbuvir; velpatasvir	PELLETS;ORAL	214187-002	Jun 10, 2021		RX	Yes	Yes					Y
Gilead Sciences Inc	HARVONI	ledipasvir; sofosbuvir	PELLETS;ORAL	212477-001	Aug 28, 2019		RX	Yes	No					Y
Gilead Sciences Inc	HARVONI	ledipasvir; sofosbuvir	PELLETS;ORAL	212477-002	Aug 28, 2019		RX	Yes	Yes					Y
Gilead Sciences Inc	SOVALDI	sofosbuvir	PELLETS;ORAL	212480-001	Aug 28, 2019		RX	Yes	No					Y
Gilead Sciences Inc	SOVALDI	sofosbuvir	PELLETS;ORAL	212480-002	Aug 28, 2019		RX	Yes	Yes					Y
Gilead Sciences Inc	EPCLUSA	sofosbuvir; velpatasvir	TABLET;ORAL	208341-002	Mar 19, 2020		RX	Yes	No					Y

International Family Members for US Patent 8,618,076

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	3515
Argentina	080819
Argentina	080870
Argentina	081813
Argentina	082937
Australia	2010249481
Australia	2011235044