Details for Patent: 7,635,704

Which drugs does patent 7,635,704 protect, and when does it expire?

Patent 7,635,704 protects GENVOYA, STRIBILD, and VITEKTA, and is included in three NDAs.

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

This patent has forty-six patent family members in twenty-eight countries.

Summary for Patent: 7,635,704

Title:	Stable crystal of 4-oxoquinoline compound
Abstract:	Provision of a stabilized crystal of 6-(3-chloro-2-fluorobenzyl)-1-[(S)-1-hydroxymethyl-2-methylpropyl]-7-methoxy-4-oxo-1, 4-dihydroquinoline-3-carboxylic acid (compound A). A crystal of compound A, which shows a particular X-ray powder diffraction pattern of a characteristic diffraction peaks at diffraction angles 2θ(°) as measured by X-ray powder diffractmetry.
Inventor(s):	Motohide Satoh, Takahisa Motomura, Takashi Matsuda, Kentaro Kondo, Koji Ando, Koji Matsuda, Shuji Miyake, Hideto Uehara
Assignee:	Japan Tobacco Inc
Application Number:	US11/133,471
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,635,704
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

US Patent 7,635,704: Elvitegravir Crystal Forms, Claim Scope, Expiration and Generic-Entry Risk

US Patent 7,635,704 protects specified crystalline forms of elvitegravir, the integrase inhibitor used in Vitekta, Stribild and Genvoya. Its principal commercial value is the protection of solid-state elvitegravir used in tablets and other non-liquid dosage forms. The claims do not broadly cover every elvitegravir formulation or every method of treating HIV. They focus on two XRPD-defined crystal forms, a thermally defined crystal, non-liquid pharmaceutical compositions, and HIV-treatment methods using the claimed crystal.

The patent is assigned to Japan Tobacco Inc. and is associated with the elvitegravir program licensed to Gilead Sciences. The patent term is generally reported to extend into 2027, subject to the applicable patent-term-adjustment calculation and any Orange Book listing applicable to the relevant product.[1]

What compound does US Patent 7,635,704 protect?

The claimed compound is elvitegravir, also known as GS-9137 and JTK-303. The chemical name in the claims is:

6-(3-chloro-2-fluorobenzyl)-1-[(S)-1-hydroxymethyl-2-methylpropyl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid.

Elvitegravir is an HIV-1 integrase strand-transfer inhibitor. It prevents integration of viral DNA into the host-cell genome. In commercial products, elvitegravir is administered with cobicistat or another pharmacokinetic enhancer because CYP3A-mediated metabolism reduces unboosted exposure.[2-4]

Commercial products containing elvitegravir

Product	FDA status	Elvitegravir role	Commercial relevance
Vitekta	Approved September 2014; later discontinued in the U.S.	Single-agent elvitegravir tablet	Direct single-agent product
Stribild	Approved August 2012	Elvitegravir plus cobicistat, emtricitabine and tenofovir disoproxil fumarate	Earlier fixed-dose combination
Genvoya	Approved November 2015	Elvitegravir plus cobicistat, emtricitabine and tenofovir alafenamide	Main continuing commercial product

The crystal claims are relevant because the marketed products contain elvitegravir as a solid pharmaceutical ingredient. A product may infringe even if the applicant does not identify the crystal form in its public labeling, depending on the form actually manufactured and supplied.

What are the independent claims in US Patent 7,635,704?

Claims 1, 2, 3, 4, 7, 8, 9, 10 and 11 are the principal claim groups. Claims 5, 6 and 12-15 narrow those claims.

Claim group	Subject matter	Main limitation
Claims 1-2	Elvitegravir crystals	Specific XRPD diffraction peaks
Claim 3	Elvitegravir crystal	Extrapolated onset temperature of 162.1 ± 5.0°C
Claims 4-6	Pharmaceutical compositions	Claimed crystal plus non-liquid carrier; tablet, pill, powder or granule
Claims 7-9	Therapeutic methods	Integrase inhibition, antiviral treatment or HIV treatment
Claims 10-11	Combination therapy	Claimed crystal plus one or more other anti-HIV agents
Claims 12-15	Human treatment	Narrows mammal claims to humans

The word "comprising" in the composition and combination-treatment claims generally leaves those claims open to additional ingredients, excipients and active agents unless another limitation excludes them.

What crystal forms are protected by claims 1 and 2?

Claims 1 and 2 use powder X-ray diffraction, or XRPD, as the defining product characteristic.

Claim 1 crystal

Claim 1 requires characteristic peaks at:

2θ angle

6.56°

13.20°

19.86°

20.84°

21.22°

25.22°

Claim 2 crystal

Claim 2 requires characteristic peaks at:

2θ angle

8.54°

14.02°

15.68°

17.06°

17.24°

24.16°

25.74°

These are product-by-process-independent crystal claims. The accused product does not avoid the claims merely because it is made by a different crystallization process. The key question is whether the final elvitegravir solid has the claimed diffraction characteristics.

The claims do not expressly specify peak intensity, relative intensity, peak-width limits, sample-preparation conditions or a numerical tolerance for the diffraction angles. Those details can become important in infringement and validity disputes because XRPD results vary with instrument calibration, sample orientation, crystallite size, impurities and analytical conditions.

Infringement testing

A practical infringement protocol would include:

1. Sampling the finished active pharmaceutical ingredient and, where necessary, the finished dosage form.
2. Recording XRPD under calibrated conditions.
3. Comparing the observed peaks against the claimed angles.
4. Testing multiple batches to address polymorph conversion and batch variability.
5. Using DSC or thermogravimetric analysis where claim 3 is asserted.
6. Examining whether tablet manufacture changes the polymorphic state.

A failure to observe one listed peak may be material, but it is not automatically dispositive. Peak visibility depends on relative intensity and sample quality. Expert evidence would normally address whether a missing peak reflects a different crystal form or an analytical artifact.

How does claim 3 protect elvitegravir?

Claim 3 covers an elvitegravir crystal having an extrapolated onset temperature of 162.1 ± 5.0°C. The literal temperature range is:

157.1°C to 167.1°C.

This claim uses a thermal property rather than a diffraction pattern. It may capture a crystal that falls within the specified thermal range even if the asserted XRPD pattern is not identical to the pattern in claims 1 or 2.

The claim raises measurement questions. "Extrapolated onset temperature" ordinarily refers to a differential scanning calorimetry measurement, but the claim excerpt does not state the heating rate, sample mass, atmosphere, pan type, instrument or baseline method. Those variables can affect the reported onset temperature. A party assessing risk should therefore test the material under the patent specification's analytical conditions, not rely only on a routine DSC result.

What formulations are protected by US Patent 7,635,704?

Claims 4-6 protect compositions containing one of the claimed elvitegravir crystals and a pharmaceutically acceptable carrier, provided the carrier is not a liquid carrier.

The covered dosage forms expressly include:

• Tablets
• Pills
• Powders
• Granules

Claim 6 narrows the composition to a tablet.

Formulation scope

The formulation claims can cover conventional excipients, including diluents, binders, disintegrants, lubricants and coatings, provided the composition contains the claimed crystal and the carrier is not a liquid carrier.

The express exclusion of a liquid carrier is important. A liquid solution, suspension or other formulation relying on a liquid carrier is outside the literal scope of claim 4 unless another component independently satisfies the claim language or infringement is established under a different theory. The claims are better suited to solid oral products, which corresponds to the commercial tablet presentations of elvitegravir-containing products.

The patent does not, on the quoted claims, require cobicistat, emtricitabine, tenofovir, a particular dissolution profile, a particular particle size, a specific excipient, a fixed dose or a particular release mechanism.

What method-of-use claims does the patent contain?

Claims 7-15 cover therapeutic use of the claimed crystal.

The method categories are:

Claims	Use
7, 12	Inhibiting integrase
8, 13	Treating a viral infection
9, 14	Treating HIV infection
10	Anti-HIV composition with other anti-HIV active substances
11, 15	Treating HIV with the crystal and other anti-HIV active substances

The independent therapeutic claims use broad "mammal" language. The dependent claims narrow the subject to humans. Claim 11 is particularly relevant to fixed-dose combinations because it covers treatment with the claimed crystal together with one or more other anti-HIV active substances.

These claims are narrower in practical enforcement than the composition claims when the accused product is a marketed tablet. A generic applicant's labeling, proposed indication and dosing instructions can determine whether a method-of-use claim is implicated. For an ANDA product, the section viii carve-out mechanism may remove a patented indication from the proposed labeling, but it does not necessarily eliminate risk under product or composition claims.

When does US Patent 7,635,704 lose exclusivity?

The patent's ordinary 20-year term is tied to the relevant U.S. filing or international filing date, not to the date of FDA approval. Public patent records associate US 7,635,704 with a 2007 U.S. filing and a 2006 priority claim. The nominal term therefore reaches approximately 2027, before considering patent-term adjustment.[1]

Event	Date or period
Priority basis	2006
U.S. filing period	2007
Patent issued	December 22, 2009
Nominal expiration period	2027
Commercial products affected	Vitekta, Stribild and Genvoya, depending on listing and claim applicability

Patent expiration and FDA exclusivity are separate. FDA regulatory exclusivity for an approved product can end before the patent expires. Conversely, a patent may continue after regulatory exclusivity ends. The relevant commercial entry date depends on all listed patents, pediatric exclusivity, settlement terms and the applicant's litigation strategy.

What is the Orange Book status of the patent?

FDA Orange Book listings identify patents submitted by sponsors for approved drug products. Elvitegravir-related listings must be evaluated separately for Vitekta, Stribild and Genvoya because each product has a different NDA and may have different listed patents.[5]

US 7,635,704 is commercially significant because it is directed to the elvitegravir crystal used in oral solid dosage forms. The listing analysis should distinguish:

• Patents covering elvitegravir itself or its crystal form.
• Patents covering cobicistat.
• Patents covering tenofovir alafenamide or tenofovir disoproxil fumarate.
• Patents covering fixed-dose combinations.
• Patents covering specific methods of treatment.
• Patents listed for one NDA but not necessarily another.

An Orange Book listing does not establish validity or infringement. It gives the reference product sponsor a basis to invoke the ANDA patent-certification framework. An applicant challenging a listed patent may file a Paragraph IV certification. The sponsor can then bring an infringement action under Hatch-Waxman, generally triggering a 30-month stay unless the litigation is resolved earlier or the stay is modified.

Which companies are challenging elvitegravir products?

The competitive challenge is directed primarily at fixed-dose products rather than at elvitegravir as an independent commercial franchise. Potential ANDA applicants include major generic manufacturers that have filed or may file applications for combinations containing elvitegravir, cobicistat and tenofovir.

The principal barriers are:

1. The elvitegravir crystal patent.
2. Cobicistat composition and formulation patents.
3. Tenofovir alafenamide or tenofovir disoproxil fumarate patents.
4. Fixed-dose-combination patents.
5. Bioequivalence requirements for a four-drug product.
6. Manufacturing controls needed to preserve the target polymorph.
7. Labeling restrictions for patented indications.

A Paragraph IV challenge to US 7,635,704 would likely attack one or more of the following:

• Whether the XRPD peaks distinguish a patentable crystal from prior art.
• Whether the claimed crystal is enabled across the full claim scope.
• Whether the peak language is sufficiently definite.
• Whether the accused material has the claimed crystal form.
• Whether the thermal onset limitation is reproducible.
• Whether the claims are obvious in view of known elvitegravir solid forms and crystallization techniques.

No conclusion about a specific company's current Paragraph IV position should be inferred solely from the patent claims. The definitive record is the applicable FDA Orange Book entry, the ANDA certification, and any filed district-court complaint.

How strong is the patent estate for elvitegravir?

US 7,635,704 is a focused but commercially meaningful patent.

Strengths

• It claims the active pharmaceutical ingredient in defined crystalline forms.
• It covers solid oral compositions, including tablets.
• It does not depend on a specific manufacturing route.
• It reaches combination treatment with other anti-HIV agents.
• Solid-state form claims can block a generic using the same polymorph even when the generic avoids a process patent.

Weaknesses and attack points

• The claims identify XRPD peaks without the tolerances and intensities shown in the excerpt.
• Claim 3 depends on a thermal measurement that may vary by method.
• The composition claims exclude liquid carriers.
• The method claims may be avoidable through labeling strategies if product claims do not apply.
• A generic may attempt to develop a different polymorph, amorphous material or salt, although it must still meet pharmaceutical and bioequivalence requirements.
• The patent does not, by itself, cover cobicistat or the entire Stribild or Genvoya combination.

The estate is therefore stronger against a conventional generic tablet using the same elvitegravir polymorph than against a deliberately engineered alternative solid form.

What generic launch scenarios exist?

Scenario	Commercial result
Patent upheld and no settlement	Entry delayed until patent expiration or authorized launch
Paragraph IV challenge succeeds	Earlier ANDA launch possible, subject to remaining patents
Generic uses a non-infringing polymorph	Potential launch, subject to quality and bioequivalence approval
Settlement grants a future entry date	Entry occurs on the agreed date, often with licensing conditions
Crystal patent expires but combination patents remain	Elvitegravir entry may still be blocked for Stribild or Genvoya
Only a method-of-use patent remains	A section viii carve-out may reduce the practical barrier

For Genvoya, the commercial issue is not limited to elvitegravir. A generic must address all relevant active ingredients and the combination's formulation, bioequivalence and patent position. Genvoya's tenofovir alafenamide and cobicistat components may create separate barriers even if US 7,635,704 is invalidated or expires.

What licensing deals affect the patent?

Japan Tobacco developed elvitegravir and licensed the compound to Gilead. Gilead obtained rights to develop and commercialize elvitegravir for HIV treatment, while Japan Tobacco retained rights in certain territories and indications under the parties' broader collaboration arrangements.[6]

The license matters because the patent owner, listed drug sponsor and commercial product company may be different entities. Patent enforcement, Orange Book listing and settlement authority must be reviewed against the specific agreement and product. The existence of a license does not itself establish that every Gilead product patent is owned by Gilead.

What geographic coverage does the patent provide?

US 7,635,704 provides protection only in the United States. International counterparts must be analyzed separately. The principal geographic issues are:

• Whether a corresponding patent issued in Europe, Japan or other major markets.
• Whether each jurisdiction granted claims to the same crystal forms.
• Whether national patents have expired, lapsed or been opposed.
• Whether local products use the same polymorph.
• Whether patent-term extensions or supplementary protection certificates apply.

The U.S. patent does not prevent manufacture or sale outside the United States. Conversely, a foreign polymorph patent does not create U.S. infringement risk without a U.S. claim.

Key Takeaways

• US 7,635,704 is an elvitegravir solid-state patent.
• Claims 1 and 2 cover two XRPD-defined crystal forms.
• Claim 3 covers a crystal with an extrapolated onset temperature of 162.1 ± 5.0°C.
• Claims 4-6 cover non-liquid solid compositions, including tablets.
• Claims 7-15 cover integrase inhibition, antiviral treatment, HIV treatment and combination therapy.
• The patent is commercially relevant to Vitekta, Stribild and Genvoya, but it does not alone cover every component of those products.
• The patent's ordinary expiration period is approximately 2027.
• Generic risk depends on the crystal form actually used, Orange Book listings, Paragraph IV certifications, combination-product patents and any settlement agreements.
• A different polymorph may reduce infringement risk but creates separate development, manufacturing and regulatory obligations.

FAQs

Does US Patent 7,635,704 cover all forms of elvitegravir?

No. The claims focus on specified crystalline forms identified by XRPD peaks or thermal onset temperature. They do not expressly cover every amorphous form, salt, solvate or polymorph of elvitegravir.

Can a generic avoid the patent by using a different manufacturing process?

Not necessarily. Claims 1-3 are product claims. A different process will not avoid infringement if the resulting elvitegravir crystal has the claimed characteristics.

Does the patent cover Genvoya as a complete product?

No. It may cover the elvitegravir component or a composition containing the claimed crystal, but separate patents may cover cobicistat, tenofovir alafenamide, the fixed-dose combination or specific uses.

Can an ANDA applicant use a Paragraph IV certification against this patent?

Yes, if the patent is listed for the relevant reference product and the applicant asserts that the patent is invalid, unenforceable or not infringed. The sponsor may respond with a Hatch-Waxman infringement action.

What evidence is most important in a crystal-form dispute?

The key evidence is batch-specific XRPD, DSC data, solid-state characterization, analytical-method validation, manufacturing records and the applicant's proposed product composition. The patent specification's measurement conditions are central to interpreting both the diffraction and thermal limitations.

References

1. U.S. Patent No. 7,635,704. (2009). Crystal of 6-(3-chloro-2-fluorobenzyl)-1-[(S)-1-hydroxymethyl-2-methylpropyl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid. United States Patent and Trademark Office.

2. U.S. Food and Drug Administration. (2012). Stribild prescribing information. FDA.

3. U.S. Food and Drug Administration. (2015). Genvoya prescribing information. FDA.

4. U.S. Food and Drug Administration. (2014). Vitekta prescribing information. FDA.

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

6. Gilead Sciences, Inc. (2012). Annual report. Gilead Sciences.

Drugs Protected by US Patent 7,635,704

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	GENVOYA	cobicistat; elvitegravir; emtricitabine; tenofovir alafenamide fumarate	TABLET;ORAL	207561-001	Nov 5, 2015		RX	Yes	Yes	7,635,704*PED				Y
Gilead Sciences Inc	STRIBILD	cobicistat; elvitegravir; emtricitabine; tenofovir disoproxil fumarate	TABLET;ORAL	203100-001	Aug 27, 2012		RX	Yes	Yes	7,635,704*PED				Y
Gilead Sciences Inc	VITEKTA	elvitegravir	TABLET;ORAL	203093-001	Sep 24, 2014		DISCN	Yes	No	7,635,704*PED				Y

Foreign Priority and PCT Information for Patent: 7,635,704

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	2004-150979	May 20, 2004

International Family Members for US Patent 7,635,704

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	3281939		122023000055	Germany
Argentina	049280
Argentina	096100