Details for Patent: 10,039,718

Which drugs does patent 10,039,718 protect, and when does it expire?

Patent 10,039,718 protects EVOTAZ, PREZCOBIX, SYMTUZA, GENVOYA, STRIBILD, and TYBOST, and is included in six 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 ninety patent family members in thirty-three countries.

Summary for Patent: 10,039,718

Title:	Use of solid carrier particles to improve the processability of a pharmaceutical agent
Abstract:	The invention provides a composition comprising, a compound of formula (I): or a pharmaceutically acceptable salt thereof and a plurality of solid carrier particles, as well as methods for using the composition to inhibit the activity of cytochrome P-450.
Inventor(s):	Joanna M. Koziara, Mark M. Menning, Robert G. Strickley, Richard Yu, Brian P. Kearney, Anita A. Mathias
Assignee:	Gilead Sciences Inc
Application Number:	US12/434,513
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,039,718
Patent Claim Types: see list of patent claims	Use; Composition;

US Patent 10,039,718: Scope, Expiration, Orange Book Position and Patent Landscape

US Patent 10,039,718 protects solid pharmaceutical compositions in which elvitegravir is deposited in the pores or on the surface of hydrophilic fumed silicon dioxide particles. The claims also cover the preparation process, particle-size and surface-area specifications, reduced hygroscopicity, stereochemical enrichment, a 150 mg elvitegravir presentation, and a four-drug combination containing elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate.

The patent is formulation-focused. It does not broadly claim elvitegravir as a chemical entity, HIV treatment generally, or every formulation of the Stribild combination. Infringement risk is highest for products that reproduce the claimed silica carrier system and its measurable physical properties.

What does US Patent 10,039,718 cover?

The patent has three independent claim groups:

Claim group	Independent claim	Protected subject matter
Composition	1	Elvitegravir associated with hydrophilic fumed silicon dioxide
Manufacturing method	5	Combining elvitegravir, solvent and hydrophilic fumed silicon dioxide
Pharmaceutical combination	10	Elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate with the silica carrier

The patent is directed to a solid-state formulation approach. Elvitegravir is placed “in the pores or on the surface” of the silicon dioxide particles. The claimed arrangement is materially narrower than simply mixing elvitegravir with a conventional excipient.

What compound is formula (I)?

Based on the supplied claims, formula (I) is elvitegravir. Claim 17 specifies approximately 150 mg of formula (Ia), and claim 10 identifies the accompanying ingredients as tenofovir disoproxil fumarate, emtricitabine and elvitegravir. That ingredient profile corresponds to the active pharmaceutical combination used in Stribild.

Claim 4 requires an enriched concentration of approximately 99% ±1% of the specified elvitegravir stereoisomer. The stereochemical limitation is important because it narrows the claim to a substantially single stereoisomer rather than a racemic or materially mixed product.

How broad is independent claim 1?

Claim 1 requires all of the following:

1. A composition.
2. A plurality of hydrophilic fumed silicon dioxide particles.
3. A compound of formula (I), interpreted here as elvitegravir.
4. Elvitegravir located in the pores or on the surface of the silica particles.

The claim does not require a particular tablet, capsule, dosage strength, solvent, particle size, surface area or additional active ingredient. Those limitations appear in dependent claims.

The principal infringement questions would be:

• Whether the accused silica is “hydrophilic fumed silicon dioxide.”
• Whether the accused product contains a plurality of particles rather than a different silica form or a molecularly dispersed excipient.
• Whether elvitegravir is actually located in the pores or on the surface of the particles.
• Whether the accused material is the claimed formula (I), including relevant stereochemistry.
• Whether the product is a composition within the meaning of the claim rather than a manufacturing intermediate outside the claim scope.

A formulation that contains elvitegravir and colloidal silicon dioxide may still avoid literal infringement if the silica is not fumed, is not hydrophilic, or does not contain elvitegravir in the claimed physical location. Those issues would generally require particle characterization, surface analysis, manufacturing records and potentially expert evidence.

What formulation parameters are protected?

Claims 2, 3 and 18 add physical specifications for the silica carrier.

Parameter	Narrow limitation	Broader dependent limitation
Mean grain or particle diameter	20-40 microns	About 10-120 microns
BET surface area	At least 150 m²/g	About 40-400 m²/g
Elvitegravir-to-silica weight ratio	Not specified in claims 2-3	1.0 ± 0.5

The broader range in claim 18 is significant. A product outside the 20-40 micron range may still fall within claim 18 if its mean particle diameter is approximately 10-120 microns and its BET surface area is approximately 40-400 m²/g.

The claims use both “mean grain diameter” and “mean particle diameter.” A defendant would likely examine whether those terms have distinct technical meanings in the specification and whether the selected measurement method changes the result.

What does the BET limitation add?

BET surface area is a measure of accessible surface area, usually determined by gas adsorption. The limitation is directed to a high-surface-area silica carrier capable of holding elvitegravir in pores or on particle surfaces.

The claim structure creates several infringement pathways:

• A product with surface area of at least 150 m²/g may satisfy claim 3.
• A product with surface area below 150 m²/g but within approximately 40-400 m²/g may fall within claim 18.
• A product outside both ranges may still be evaluated against claim 1, because claim 1 has no numerical surface-area requirement.

What does the hygroscopicity limitation protect?

Claims 20, 23 and 26 require that:

• the silica and elvitegravir, when considered separately, have higher hygroscopicity; and
• the combined silica-elvitegravir system has lower hygroscopicity.

This is a functional limitation directed to moisture management. It is potentially valuable commercially because elvitegravir-containing products must maintain chemical and physical stability during storage.

The limitation also presents enforcement issues. The patent owner would need a reproducible test showing:

1. the hygroscopicity of silica alone;
2. the hygroscopicity of elvitegravir alone; and
3. the hygroscopicity of the combined composition.

The claims do not state the measurement protocol in the supplied text. The specification, examples and prosecution history would therefore be important in determining the applicable test conditions, humidity exposure, temperature and endpoint.

What manufacturing process does claim 5 protect?

Claim 5 covers a method of preparing the composition by combining:

• elvitegravir;
• a suitable solvent; and
• hydrophilic fumed silicon dioxide particles,

to produce a mixture in which elvitegravir is located in the pores or on the surface of the silica.

Claims 8 and 9 narrow the solvent to a C1-C6 alcohol and specifically to ethanol. Claims 21-23 add particle, BET, ratio and hygroscopicity limitations.

The method claims create risk even where the final product is difficult to characterize. A process using ethanol to load elvitegravir onto high-surface-area hydrophilic fumed silica would be closely aligned with the asserted method claims.

A process may face infringement exposure even if the manufacturer later compresses, granulates, coats or encapsulates the loaded silica. The relevant issue is whether the claimed composition is made during the process, not only whether the commercial dosage form retains an identifiable intermediate.

Does the patent cover Stribild?

What is the claimed Stribild-type combination?

Claim 10 recites:

• elvitegravir;
• cobicistat;
• emtricitabine;
• tenofovir disoproxil fumarate; and
• hydrophilic fumed silicon dioxide carrying elvitegravir.

That combination tracks the active ingredients in Stribild, marketed by Gilead Sciences. Stribild was approved by the FDA in 2012 for treatment of HIV-1 infection in specified patient populations.[2]

Claims 11-13 add the silica particle and stereochemical limitations. Claims 24-26 add the broader particle-size, surface-area, ratio and hygroscopicity requirements.

A product containing the same four active ingredients but using a different excipient system may avoid claim 10 if it does not include the required silica-elvitegravir arrangement. Conversely, a product with a different brand name remains exposed if it uses the claimed formulation architecture.

Does the patent cover Genvoya?

Genvoya contains elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide, not tenofovir disoproxil fumarate. Because claim 10 expressly recites tenofovir disoproxil fumarate, Genvoya is not literally within claim 10 based solely on the supplied claim language.

Claims 1-9 and 14-26 may require separate analysis. Those claims can cover elvitegravir compositions without requiring the specific Stribild combination, particularly claims 1, 5 and 14-19.

How does US 10,039,718 compare with other elvitegravir patent rights?

Elvitegravir products typically involve several patent layers:

Patent layer	Subject matter	Relevance to US 10,039,718
Compound patents	Elvitegravir chemical structure and stereochemistry	Separate from the silica formulation claims
Process patents	Synthesis, purification and stereochemical control	May block manufacture independently
Combination patents	Elvitegravir with cobicistat, emtricitabine and tenofovir products	Overlap may exist with claim 10
Formulation patents	Particle loading, excipients, moisture control and dosage forms	Directly relevant
Method-of-use patents	HIV treatment and dosing	Separate from the composition claims
Regulatory exclusivity	New chemical entity, combination or clinical exclusivity	Does not expand the patent claims

The ’718 patent is strongest as a formulation patent. Its value depends on whether a generic or follow-on manufacturer must use the same silica-loading technology to achieve acceptable content uniformity, stability, dissolution or tablet performance.

When does US Patent 10,039,718 expire?

The patent issued on July 31, 2018, under US Patent No. 10,039,718.[1] A US utility patent generally receives a term measured from the earliest effective nonprovisional filing date in the applicable priority chain, subject to patent-term adjustment, terminal disclaimers and other statutory modifications.[3]

The patent’s precise expiration date cannot be established from the supplied claims. The controlling date is the USPTO patent-term calculation associated with the full patent record, not the issue date. A diligence review should treat the patent as potentially extending into the late 2020s or early 2030s depending on its priority and continuity history.

Patent expiration does not necessarily equal market-entry date. FDA exclusivity, other Orange Book patents, pediatric extensions, litigation stays and settlement agreements can affect launch timing.

What is the Orange Book status of US 10,039,718?

The patent claims are directed to a formulation used in an FDA-approved HIV product, making Orange Book relevance commercially important. The patent number itself, however, does not establish that FDA listed it for a particular NDA.

Orange Book listing is product-specific. The relevant questions are:

• whether the patent is listed against Stribild or another NDA;
• which claims are identified as covering the approved product;
• whether FDA lists a use code;
• whether the patent is active or delisted;
• whether an ANDA applicant must make a Paragraph IV certification.

The formulation claims are more naturally associated with a product patent listing than a method-of-use listing. If listed against Stribild, claims 10-13 and 24-26 would be the most direct product-relevance provisions. Claims 1-9 and 14-23 could also support a listing if they are considered to read on the approved product under FDA’s patent-listing standards.[4]

Are Paragraph IV challenges likely?

A generic applicant seeking approval before expiration of a listed formulation patent could submit a Paragraph IV certification asserting that the patent is invalid, unenforceable or not infringed.[5]

For this patent, likely challenge theories would include:

• the silica is not hydrophilic fumed silicon dioxide;
• elvitegravir is not in the pores or on the surface;
• the accused product does not meet the particle-size or BET limitations;
• the hygroscopicity limitation is not satisfied;
• the claim is anticipated by an earlier silica-loading formulation;
• the claimed combination would have been obvious;
• the specification does not adequately support or enable the full claim scope;
• the patent is unenforceable because of prosecution misconduct, if supported by the record.

A Paragraph IV case would likely require substantial technical discovery. Standard product testing may not establish the location of elvitegravir on or within silica particles without specialized analytical methods.

No conclusion about a specific Paragraph IV notice or litigation outcome follows from the claim text alone.

What generic entry risks exist?

Stribild-type generic risk

A generic Stribild product faces two separate commercial pathways:

1. replicate the silica-based formulation and confront the ’718 patent; or
2. design around the silica carrier and accept possible differences in stability, dissolution, manufacturing yield or bioequivalence risk.

The second pathway may reduce patent exposure but increase development cost. A formulation that substitutes a non-fumed silica, a hydrophobic silica, a different porous carrier or a conventional blend requires comparative pharmaceutical development.

Design-around options

Potential design-around directions include:

• using a non-silica carrier;
• using hydrophobic rather than hydrophilic silica;
• incorporating elvitegravir into a polymeric dispersion;
• using a spray-dried or hot-melt-dispersed system;
• avoiding the claimed elvitegravir-to-silica ratio;
• using particle and BET specifications outside the dependent claims;
• introducing elvitegravir through a process that does not combine it with silica in the claimed manner.

These approaches do not automatically avoid claim 1 or claim 5. The broad independent claims lack numerical particle and surface-area limitations.

What litigation affects the patent?

The supplied information identifies no litigation docket, Paragraph IV notice, settlement agreement or final validity decision for US 10,039,718. The patent should not be treated as cleared merely because a particular generic product uses a different brand or dosage form.

The relevant litigation record would include:

• district-court actions under the Hatch-Waxman Act;
• Federal Circuit appeals;
• inter partes review petitions;
• post-grant proceedings;
• covenant-not-to-sue agreements;
• confidential or public ANDA settlements;
• FDA tentative-approval and final-approval dates.

A formulation patent can remain commercially significant without a reported trial if applicants choose a design-around or settle before judgment.

Is there biosimilar risk?

There is no biosimilar pathway for Stribild or elvitegravir because these are small-molecule products. The relevant competitors are ANDA applicants, not biosimilar applicants under the Biologics Price Competition and Innovation Act.

The applicable regulatory routes are:

• an ANDA under section 505(j) for a conventional generic;
• a 505(b)(2) application for a product relying partly on existing safety and efficacy information but differing in formulation, dosage form or other characteristics.

A 505(b)(2) applicant could face the same patent claims if its product contains the claimed silica-elvitegravir composition.

How strong is the patent estate?

The ’718 patent has moderate-to-strong value against exact or near-exact replication of the claimed formulation, but weaker value against materially different carrier technologies.

Strength factor	Assessment
Direct coverage of silica-loaded elvitegravir	Strong
Coverage of Stribild-like four-drug formulation	Strong if the approved product uses the claimed carrier
Coverage of all elvitegravir formulations	Weak
Dependence on difficult analytical proof	Moderate enforcement burden
Design-around flexibility	Moderate to substantial
Biosimilar relevance	None
ANDA relevance	High
Manufacturing-process relevance	High where ethanol or alcohol loading is used
Value after compound-patent expiry	Potentially significant for delayed generic entry

The strongest claims are claims 1, 5 and 10 because they establish the core composition, manufacturing and combination categories. Claims 2-4, 6-9 and 11-13 provide narrower fallback positions. Claims 18-26 broaden some numerical ranges but also add ratio and hygroscopicity requirements.

Key Takeaways

• US 10,039,718 is a formulation and manufacturing patent centered on elvitegravir loaded onto hydrophilic fumed silicon dioxide.
• Claim 1 is broad within the silica-carrier concept but does not cover every elvitegravir formulation.
• Claim 5 creates process risk for alcohol-based or ethanol-based silica-loading operations.
• Claim 10 directly targets a Stribild-type combination containing elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate.
• The patent does not literally cover Genvoya’s tenofovir alafenamide combination under claim 10.
• Particle diameter, BET surface area, elvitegravir-to-silica ratio and hygroscopicity are central infringement and design-around variables.
• There is no biosimilar pathway; generic exposure proceeds through ANDA or, in some cases, 505(b)(2) applications.
• The exact patent expiration date and Orange Book status must be determined from the USPTO continuity and FDA listing records rather than from the claim language.
• A non-silica or materially different elvitegravir delivery system may reduce infringement risk but could create separate formulation and bioequivalence challenges.

FAQs About US Patent 10,039,718

Does US 10,039,718 claim elvitegravir itself?

No. The supplied claims require elvitegravir in association with hydrophilic fumed silicon dioxide. The patent is not a broad composition-of-matter patent for unformulated elvitegravir.

Does the patent cover a tablet containing elvitegravir and colloidal silicon dioxide?

Potentially. Literal infringement depends on whether the colloidal silicon dioxide is hydrophilic and fumed, and whether elvitegravir is located in the pores or on the particle surface.

Can a generic avoid the patent by changing the silica particle size?

Not necessarily. Claims 1 and 5 do not contain numerical particle-size limitations. Changing particle size may avoid claims 2, 6, 11, 18, 21 or 24 while leaving the independent claims in issue.

Does an ethanol-based process create particular risk?

Yes. Claims 8 and 9 specifically identify C1-C6 alcohols and ethanol. An ethanol-loading process closely resembles the narrower method claims.

Is US 10,039,718 a patent on HIV treatment?

No. The supplied claims are directed to compositions and preparation methods. They do not broadly claim treating HIV with elvitegravir.

References

1. United States Patent and Trademark Office. (2018). US Patent No. 10,039,718.
2. U.S. Food and Drug Administration. (2012). Stribild prescribing information.
3. United States Code, 35 U.S.C. §§ 154, 156.
4. U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations: Orange Book.
5. United States Code, 21 U.S.C. § 355(j)(2)(A)(vii)(IV).

Drugs Protected by US Patent 10,039,718

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	EVOTAZ	atazanavir sulfate; cobicistat	TABLET;ORAL	206353-001	Jan 29, 2015		RX	Yes	Yes	10,039,718		Y
Janssen Prods	PREZCOBIX	cobicistat; darunavir ethanolate	TABLET;ORAL	205395-002	Mar 21, 2025		RX	Yes	Yes	10,039,718		Y
Janssen Prods	PREZCOBIX	cobicistat; darunavir ethanolate	TABLET;ORAL	205395-001	Jan 29, 2015		RX	Yes	Yes	10,039,718		Y
Janssen Prods	SYMTUZA	cobicistat; darunavir; emtricitabine; tenofovir alafenamide fumarate	TABLET;ORAL	210455-001	Jul 17, 2018		RX	Yes	Yes	10,039,718		Y

International Family Members for US Patent 10,039,718

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	3089
African Regional IP Organization (ARIPO)	3250
Argentina	075369
Australia	2009242451