United States Patent 8,841,310: Rilpivirine, Tenofovir and Emtricitabine Patent Scope and Landscape

U.S. Patent No. 8,841,310 protects once-daily HIV treatment combinations containing rilpivirine, tenofovir or tenofovir disoproxil fumarate, and emtricitabine. The patent is directed primarily to the fixed-dose combination marketed as Complera in the United States and Eviplera in Europe. Its strongest commercial claims cover a tablet containing rilpivirine hydrochloride, tenofovir disoproxil fumarate, and emtricitabine.

The patent does not claim rilpivirine alone, tenofovir alone, emtricitabine alone, or a general HIV treatment regimen containing any three antiretrovirals. Its core requirement is the specific combination of the three named active ingredients, administered at therapeutically effective, once-daily doses.

What drug does U.S. Patent 8,841,310 protect?

The compound identified by its chemical name in the claims is rilpivirine, a non-nucleoside reverse transcriptase inhibitor, or NNRTI. The commercially relevant form is E-rilpivirine hydrochloride.

Claimed component	Pharmaceutical identity	Drug class
E-4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile	Rilpivirine	NNRTI
Tenofovir	Tenofovir	Nucleotide reverse transcriptase inhibitor
Tenofovir disoproxil fumarate	TDF	Tenofovir prodrug
Emtricitabine	FTC	Nucleoside reverse transcriptase inhibitor

The commercial fixed-dose product corresponding to the principal claim scope is Complera, also known as Eviplera outside the United States. Complera contains rilpivirine hydrochloride, emtricitabine, and tenofovir disoproxil fumarate in a once-daily tablet. The FDA-approved strength is 25 mg rilpivirine, 200 mg emtricitabine, and 300 mg tenofovir disoproxil fumarate.[2]

What are the independent claims in U.S. Patent 8,841,310?

The patent has five practical independent claim groups:

Claim 1: The active-ingredient combination.
Claim 17: A once-daily HIV treatment method using the combination.
Claim 21: A pharmaceutical formulation containing the combination and a carrier.
Claim 31: A kit containing the combination and instructions for use.
Related formulation and method claims: Claims 24, 26, 28, 29, and 30 narrow the formulation to specific rilpivirine forms or TDF-containing embodiments.

The central claim is claim 1:

rilpivirine or a stereoisomeric form;
a pharmaceutically acceptable salt;
tenofovir or tenofovir disoproxil fumarate;
emtricitabine; and
therapeutic activity as HIV inhibitors at a once-daily dose.

The claims therefore operate as combination claims rather than single-compound claims.

How broad is claim 1?

Claim 1 is broader than the commercial Complera formulation in several respects.

It covers:

rilpivirine in a stereoisomeric form;
rilpivirine free base;
pharmaceutically acceptable rilpivirine salts;
tenofovir itself;
tenofovir disoproxil fumarate;
the three ingredients administered together or in a regimen capable of once-daily administration.

Claim 1 does not expressly require:

a tablet;
a fixed-dose formulation;
a particular strength;
a particular excipient;
a particular order of administration;
simultaneous administration;
the marketed 25/200/300 mg strength.

Those limitations appear in dependent claims or in the product label, not in the broadest combination claim.

The once-daily requirement remains important. A regimen using the same three active ingredients but requiring twice-daily dosing would have a stronger noninfringement position against claim 1, subject to the construction of “at a dose that can be administered once daily” and the factual dosing evidence.

What forms of rilpivirine are protected?

Claims 2 through 4 identify specific rilpivirine forms.

Claim	Rilpivirine form
1	Rilpivirine, stereoisomer, or pharmaceutically acceptable salt
2	E-rilpivirine
3	E-rilpivirine hydrochloride
4	Rilpivirine hydrochloride, without the same express E limitation
6	E-rilpivirine hydrochloride with TDF and emtricitabine

Claim 3 is commercially significant because the marketed product uses rilpivirine hydrochloride. Claims 6, 15, and 16 narrow the combination further by specifying TDF and a unitary formulation, ultimately reaching the tablet embodiment.

A product using the same active moiety but a different pharmaceutically acceptable salt could remain within claim 1, although it would not necessarily fall within every narrower salt-specific claim. A product using E-rilpivirine hydrochloride is the clearest target of claims 3, 6, 13, 14, 15, and 16.

What formulations are protected by the patent?

Claims 10 through 16, 21 through 27, and 31 through 33 extend protection beyond the active-ingredient combination.

The formulation claims cover:

unitary formulations;
tablets;
capsules;
parenteral compositions;
injectable solutions;
injectable suspensions;
a pharmaceutically acceptable carrier;
kits packaged with instructions.

The commercial center of gravity is the tablet claims. Claims 12, 14, 16, 23, 25, and 27 expressly cover tablets. The injectable and parenteral language is broader from a claim-drafting perspective but has limited commercial relevance for Complera because the approved product is an oral tablet.

A separate tablet containing the three active ingredients can implicate claims 10, 12, 13, 14, 15, or 16 depending on the rilpivirine form and whether the formulation uses TDF.

Does the patent cover a fixed-dose combination?

Yes. The patent covers fixed-dose formulations through claims requiring the three active ingredients to be “together in a unitary pharmaceutically acceptable formulation.”

A unitary tablet containing:

25 mg rilpivirine hydrochloride;
300 mg tenofovir disoproxil fumarate; and
200 mg emtricitabine

falls within the commercial profile of the narrower tablet claims, assuming the remaining claim elements are met.

The patent also has broader regimen claims that do not require a single tablet. A co-packaged or separately administered regimen may still raise claim 1 or the method claims, depending on how the product is supplied and administered.

What are the dosage limitations?

Claims 7 through 9 address rilpivirine dosage.

Claim	Rilpivirine amount
7	10 mg to 500 mg
8	10 mg to 300 mg
9	About 25 mg

Claim 9 most closely tracks the FDA-approved Complera dose. The “about 25 mg” language may encompass ordinary manufacturing and measurement variation, although its precise scope would depend on claim construction and relevant prosecution history.

The dosage limitations do not independently claim the FDA-approved 200 mg emtricitabine and 300 mg TDF amounts. Claims 7 through 9 focus on the rilpivirine amount, while the combination requirement supplies the other active ingredients.

What HIV treatment methods are protected?

Claims 17 through 20 and 28 through 30 cover methods of treating HIV infection by administering the combination once daily.

The method claims are narrower in practical application than the product claims because they require:

a patient;
HIV infection;
administration of the claimed combination; and
once-daily use.

Claims 18 through 20 are directed to unitary formulations, including the specific tablet embodiments. Claims 28 through 30 depend on the pharmaceutical formulation claims and therefore incorporate the carrier and dosage-form limitations.

A generic applicant seeking approval for the same fixed-dose tablet could face both product-by-process-independent formulation claims and method-of-use claims. The FDA labeling strategy would be relevant to the method claims, particularly if the approved label includes once-daily HIV treatment instructions.

When does U.S. Patent 8,841,310 expire?

The reported statutory expiration date is August 29, 2027, based on the patent’s priority and filing chain.[1] The patent was issued on September 23, 2014.

Event	Date
Earliest reported priority date	August 29, 2006
U.S. patent issuance	September 23, 2014
Reported statutory expiration	August 29, 2027
FDA small-molecule exclusivity	Expired before the patent term
Earliest ordinary patent-based entry date	After expiration, absent invalidation, license, or settlement

Patent expiration does not itself establish regulatory approval timing. A generic applicant must also satisfy the abbreviated new drug application requirements and address any listed patents through Paragraph IV certification, a section viii statement, or another applicable pathway.

What is the Orange Book status?

The patent is associated with the patent estate for rilpivirine, emtricitabine, and tenofovir disoproxil fumarate combination products, including Complera. The FDA Orange Book is the controlling source for current listed-patent status and use codes.[3]

The relevant Orange Book analysis has four separate questions:

Whether U.S. Patent 8,841,310 is currently listed for the relevant NDA.
Whether the listing applies to the product, an approved method of use, or both.
Whether the listed expiration date includes any patent-term adjustment.
Whether the NDA holder has removed, corrected, or amended the listing.

A patent listing does not establish validity or enforceability. It creates a regulatory certification issue for an ANDA applicant. The applicant may certify that the patent has expired, will expire on a stated date, is not infringed, or is invalid. The patent holder may then bring an infringement action within the statutory 45-day period following notice of a Paragraph IV certification, which can trigger a 30-month approval stay under the Hatch-Waxman framework.[4]

Are there Paragraph IV challenges?

The claim text does not identify a Paragraph IV filing, and a patent number alone does not establish whether an ANDA applicant has issued a certification notice.

For this patent, a Paragraph IV challenge would likely focus on one or more of the following issues:

obviousness of combining rilpivirine with tenofovir and emtricitabine;
lack of adequate written description for the broad stereoisomer and salt language;
enablement of all claimed once-daily combinations;
indefiniteness of “about 25 mg” or “can be administered once daily”;
anticipation by earlier HIV combination therapy disclosures;
noninfringement based on separate dosage forms or a different rilpivirine salt;
noninfringement based on a dosing regimen outside the claimed once-daily scope.

The strongest invalidity target is likely the combination concept if prior art disclosed each component, the same therapeutic class, and once-daily HIV treatment. The patent holder’s counterargument would rely on the specific selection of rilpivirine with TDF and FTC, the claimed pharmacologic compatibility, and the claimed dosing profile.

How strong is the patent estate?

U.S. Patent 8,841,310 has meaningful product coverage but a narrower strategic position than a basic compound patent.

Estate characteristic	Assessment
Core compound protection	Limited; the patent does not claim rilpivirine alone
Combination protection	Strong for rilpivirine plus tenofovir/FTC
Fixed-dose tablet coverage	Strong, particularly for rilpivirine hydrochloride plus TDF and FTC
Method-of-use coverage	Moderate to strong for once-daily HIV treatment
Formulation coverage	Moderate; claims cover dosage forms but do not recite detailed excipient architecture
Manufacturing protection	Weak under this patent; no manufacturing-process claims are identified
Salt and stereochemical coverage	Broad in claim 1, narrower in dependent claims
Generic blocking potential	Material through 2027 if listed and enforceable
Biosimilar relevance	None; the products are chemically synthesized small molecules

The patent is not a manufacturing barrier for rilpivirine or TDF. It does not appear to claim a particular synthetic route, polymorph, impurity profile, particle-size distribution, or tablet manufacturing process. A competitor that avoids the claimed combination could potentially design around this patent while still confronting separate patents covering the individual active ingredients, formulations, or other products.

How does the patent compare with competing HIV combination products?

The patent is specific to the rilpivirine/TDF/FTC architecture.

Product	NNRTI or anchor agent	Tenofovir form	Emtricitabine	Relevance to U.S. 8,841,310
Complera	Rilpivirine	TDF	Yes	Direct commercial embodiment
Eviplera	Rilpivirine	TDF	Yes	Same core combination outside the U.S.
Odefsey	Rilpivirine	TAF	Yes	Not the claimed TDF combination
Atripla	Efavirenz	TDF	Yes	No rilpivirine
Biktarvy	Bictegravir	TAF	Yes	No rilpivirine and no TDF
Genvoya	Elvitegravir/cobicistat	TAF	Yes	Outside the patent’s core combination

Odefsey is commercially related but not a direct embodiment of the TDF limitation in claims 5, 6, and 15. Its use of tenofovir alafenamide creates a meaningful claim-distinction point. Claim 1, however, recites tenofovir or TDF rather than TAF, so TAF substitution is relevant to both infringement analysis and design-around strategy.

What generic launch scenarios exist?

Three principal launch scenarios exist:

Launch after patent expiration

A generic applicant can target entry after the reported August 29, 2027 expiration date, subject to other listed patents, regulatory requirements, and any applicable pediatric exclusivity or patent-term adjustment.

Paragraph IV launch

An applicant may seek earlier entry by alleging that the patent is invalid, unenforceable, or not infringed. Litigation risk would center on the product’s exact composition, dosage, dosage form, labeling, and salt form.

Design-around launch

A competitor could explore:

replacing TDF with TAF;
separating the active ingredients into distinct dosage forms;
using a regimen that does not meet the once-daily limitation;
using a product not containing emtricitabine;
using a non-covered formulation or administration protocol.

Design-around value is constrained because a commercial HIV regimen must also satisfy FDA efficacy, safety, bioequivalence, and labeling requirements. Avoiding one combination patent may create new development and regulatory burdens.

What litigation and licensing issues affect the patent?

The patent’s practical value depends on more than its claim language. Key commercial questions include:

whether the patent was listed for the relevant NDA;
whether a generic applicant filed a Paragraph IV certification;
whether the patent holder sued within 45 days;
whether a settlement permits licensed entry before expiration;
whether the settlement includes an authorized generic or supply arrangement;
whether any court decision narrowed, invalidated, or upheld the claims.

The patent itself does not disclose licensing terms or settlement rights. Janssen/Tibotec and Gilead have had commercial relationships involving rilpivirine and fixed-dose HIV products, but a commercial collaboration does not establish a license to practice every claim of the patent. Patent ownership, NDA ownership, product marketing rights, and supply rights must be analyzed separately.

What is the revenue exposure?

The patent’s direct revenue exposure is tied primarily to Complera or Eviplera-type products, not to all rilpivirine sales.

The exposure is narrower than the total rilpivirine franchise because:

Edurant contains rilpivirine without the TDF/FTC combination;
Odefsey uses rilpivirine with FTC and TAF rather than TDF;
the patent does not claim rilpivirine monotherapy;
the patent does not claim every rilpivirine formulation or indication.

Revenue risk would increase if a generic entrant obtained approval for a directly substitutable TDF/FTC/rilpivirine tablet. It would be lower for products using TAF or a different anchor agent.

Key Takeaways

U.S. Patent 8,841,310 is a combination patent centered on rilpivirine, tenofovir or TDF, and emtricitabine.
The commercial target is the Complera/Eviplera fixed-dose tablet.
Claims 3, 6, 15, and 16 most closely track rilpivirine hydrochloride plus TDF and emtricitabine in a tablet.
Claims 17 through 20 and 28 through 30 cover once-daily HIV treatment methods.
Claims 31 through 33 cover kits with instructions for use.
The reported patent expiration date is August 29, 2027.
The patent does not claim rilpivirine alone, TAF combinations, manufacturing processes, or biologic products.
A Paragraph IV challenge would likely focus on obviousness, enablement, written description, claim construction, and design-around arguments.
Biosimilar analysis is not applicable because rilpivirine, TDF, and emtricitabine are small-molecule active ingredients.
The main generic opportunity is a directly substitutable rilpivirine/TDF/FTC tablet after patent expiry or through a successful Paragraph IV strategy.

FAQs

Does U.S. Patent 8,841,310 cover Odefsey?

Not directly. Odefsey contains rilpivirine, emtricitabine, and tenofovir alafenamide. The patent claims tenofovir or tenofovir disoproxil fumarate, not tenofovir alafenamide.

Does the patent cover rilpivirine hydrochloride by itself?

No. The claims require rilpivirine together with tenofovir or TDF and emtricitabine. Rilpivirine-only products require analysis of separate compound, formulation, or method patents.

Can a generic sell emtricitabine and TDF without infringing this patent?

Generally, a product containing only emtricitabine and TDF would not satisfy the required rilpivirine limitation. Other patents and regulatory exclusivities may still apply.

Is a two-bottle regimen outside the patent?

Not automatically. The broad combination and method claims do not uniformly require a single tablet. A two-product regimen could still raise infringement issues if it contains the claimed ingredients and is administered once daily as required.

Does patent expiration automatically permit generic Complera approval?

No. The applicant must still address all Orange Book-listed patents and meet FDA approval requirements. Other patents, pediatric exclusivity, regulatory stays, or settlement terms can affect the actual launch date.

References

United States Patent and Trademark Office. (2014). U.S. Patent No. 8,841,310, pharmaceutical combinations comprising rilpivirine.
U.S. Food and Drug Administration. (2021). Complera prescribing information. Gilead Sciences, Inc.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
Drug Price Competition and Patent Term Restoration Act, 21 U.S.C. § 355(j).
U.S. Food and Drug Administration. (2019). Approved drug products with therapeutic equivalence evaluations, patent and exclusivity information.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
	03103275	Sep 3, 2003
	03103319	Sep 8, 2003
	03103335	Sep 10, 2003
	03103668	Oct 2, 2003

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1419152	⤷ Start Trial	C300529	Netherlands	⤷ Start Trial
European Patent Office	1419152	⤷ Start Trial	C300532	Netherlands	⤷ Start Trial
European Patent Office	1419152	⤷ Start Trial	PA2012008	Lithuania	⤷ Start Trial
European Patent Office	1419152	⤷ Start Trial	PA2012009	Lithuania	⤷ Start Trial
European Patent Office	1419152	⤷ Start Trial	CA 2012 00021	Denmark	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 8,841,310

Summary for Patent: 8,841,310