Details for Patent: 12,011,506

Which drugs does patent 12,011,506 protect, and when does it expire?

Patent 12,011,506 protects JULUCA and is included in one NDA.

This patent has twenty-one patent family members in fifteen countries.

Summary for Patent: 12,011,506

Title:	Combination and uses and treatments thereof
Abstract:	Methods are provided for treating or preventing human immunodeficiency virus-1 (HIV-1) or human immunodeficiency virus-2 (HIV-2) in a virologically suppressed patient in need thereof comprising switching the patient from an antiretroviral treatment regimen comprising at least three antiretroviral agents to a treatment regimen comprising only two antiretroviral agents. In one aspect the two treatment regimen consists of dolutegravir, rilpivirine and at least one pharmaceutically acceptable excipient, diluent or carrier. In another aspect of the invention, there is provided a multilayer tablet comprising dolutegravir or a pharmaceutically acceptable salt thereof and rilpivirine or a pharmaceutically acceptable salt thereof.
Inventor(s):	Kenneth Churchill Campbell, Urbain Alfons C. Delaet, James M. GOODRICH, Juliette Segolène GUAQUIÈRE, Thomas LAUGHERY, Dominique J. LIMET, John C. POTTAGE, Ludovic Sylvain Marc RENOU, Trevor R. SCOTT, Christian Seiler, Mary WOODWARD
Assignee:	Janssen Pharmaceutica NV , GlaxoSmithKline Services ULC , ViiV Healthcare UK Ltd , GlaxoSmithKline Research and Development Ltd , Janssen Sciences Ireland ULC , ViiV Healthcare Co
Application Number:	US16/621,309
Patent Claim Types: see list of patent claims	Compound; Dosage form;

United States Patent 12,011,506: Dolutegravir-Rilpivirine Bilayer Tablet Patent Scope and Landscape

United States Patent 12,011,506 protects a specific bilayer tablet combining dolutegravir sodium and rilpivirine hydrochloride at the strengths used in Juluca, 50 mg dolutegravir and 25 mg rilpivirine. The independent claim is formulation-specific and requires direct contact between two distinct layers. It also uses closed “consists of” language for the layer compositions, creating design-around opportunities based on excipient substitution, quantity changes, layer architecture, or separate dosage units.

The patent’s strongest protection is directed to the disclosed 500 mg uncoated tablet core:

Component	Approximate quantity
Dolutegravir sodium	52.62 mg
Rilpivirine hydrochloride	27.50 mg
First-layer dry mass	300 mg
Second-layer dry mass	200 mg
Total tablet-core mass	500 mg
Target active content	50 mg dolutegravir and 25 mg rilpivirine

Claims 2 through 8 extend protection to a film-coated version, with the narrowest coating limitation requiring approximately 3% w/w coating or approximately 15 mg of coating.

What does United States Patent 12,011,506 protect?

Claim 1 protects a bilayer tablet with five central limitations:

1. A first layer containing dolutegravir sodium.
2. A second layer containing rilpivirine hydrochloride.
3. Direct physical contact between the two layers.
4. A first layer consisting of the specified dolutegravir formulation.
5. A second layer consisting of the specified rilpivirine formulation.

The claim is narrower than a general fixed-dose combination claim. It does not cover every tablet containing dolutegravir and rilpivirine. It requires the specific bilayer arrangement and the listed excipient systems.

What is the active pharmaceutical ingredient scope?

The claimed drug substances are:

• Dolutegravir sodium in the first layer.
• Rilpivirine hydrochloride in the second layer.

The claimed salt forms matter. A formulation using a different dolutegravir salt, free dolutegravir, or a different rilpivirine form could avoid literal infringement if the alternative is legally and technically distinct. Regulatory requirements may limit the commercial practicality of such substitutions because the reference product uses the listed active forms.

The quantities correspond to the marketed strengths of Juluca. Dolutegravir sodium has a molecular-weight adjustment relative to dolutegravir free acid. The claimed 52.62 mg of dolutegravir sodium is approximately equivalent to 50 mg dolutegravir. The 27.50 mg of rilpivirine hydrochloride corresponds approximately to 25 mg rilpivirine.

How do the “comprising” and “consists of” terms affect infringement?

The tablet-level transition “comprising” is open-ended. A tablet may contain additional elements, such as a coating, printing, tooling marks, or other tablet-level features, without necessarily falling outside claim 1.

The two layer definitions use “consists of,” which is materially narrower. Literal infringement generally requires the relevant layer to contain only the listed formulation components, apart from matters inherent in pharmaceutical processing and the interpretation of residual water.

This creates a significant distinction:

Claim language	Practical effect
“Comprising” tablet	Additional tablet features may be permitted
“First layer consists of”	Unlisted first-layer ingredients may create a non-infringement position
“Second layer consists of”	Unlisted second-layer ingredients may create a non-infringement position
“Direct contact”	No intermediate barrier, adhesive layer, or separated tablet units
Exact ingredient masses	Quantity changes may be relevant to claim scope

A generic manufacturer could therefore consider changing one or more excipients, moving an excipient between layers, using different quantities, or adding a non-listed functional excipient. The strength of that strategy would depend on the patent’s full specification, prosecution history, doctrine-of-equivalents analysis, and whether the changed formulation remains bioequivalent to Juluca.

What formulations are protected by the first-layer limitation?

The first layer is a direct-compression or granulation-based dolutegravir formulation containing the following dry components:

First-layer ingredient	Claimed mass
Dolutegravir sodium	52.62 mg
D-mannitol	145.38 mg
Microcrystalline cellulose	60.00 mg
Povidone K29/32	15.00 mg
Sodium starch glycolate, intragranular	15.00 mg
Sodium starch glycolate, extragranular	6.00 mg
Sodium stearyl fumarate	6.00 mg
Purified water	q.s. for processing

The first layer has a nominal dry mass of 300 mg. Its principal formulation functions are apparent from the composition:

• D-mannitol and microcrystalline cellulose provide bulk and compression properties.
• Povidone K29/32 acts as a binder.
• Sodium starch glycolate is divided between intragranular and extragranular portions, supporting disintegration.
• Sodium stearyl fumarate functions as a lubricant.

The split between intragranular and extragranular sodium starch glycolate is a notable limitation. A formulation using the same total amount but placing all sodium starch glycolate in one processing stage could present a claim-construction issue.

What formulations are protected by the second-layer limitation?

The rilpivirine layer has a nominal dry mass of 200 mg:

Second-layer ingredient	Claimed mass
Rilpivirine hydrochloride	27.50 mg
Lactose monohydrate	55.145 mg
Croscarmellose sodium	1.10 mg
Povidone K30	3.25 mg
Polysorbate 20	0.35 mg
D-mannitol	57.755 mg
Silicified microcrystalline cellulose	40.00 mg
Sodium starch glycolate	12.90 mg
Magnesium stearate	2.00 mg
Purified water	q.s. for processing

Polysorbate 20 is a particularly specific limitation. It may support wetting or dispersion of the poorly water-soluble rilpivirine hydrochloride. The combination of lactose monohydrate, D-mannitol, silicified microcrystalline cellulose, croscarmellose sodium, and sodium starch glycolate creates a distinct excipient fingerprint.

Potential design-around variables include:

• Replacing polysorbate 20 with another surfactant.
• Replacing lactose monohydrate or D-mannitol.
• Using ordinary microcrystalline cellulose instead of silicified microcrystalline cellulose.
• Changing the lubricant from magnesium stearate.
• Removing or relocating croscarmellose sodium.
• Using a different binder grade or polymer.
• Changing the relative intragranular and extragranular composition.

What do claims 2 through 8 cover?

Claims 2 through 8 protect coated versions of the bilayer tablet.

Claim	Limitation
2	Bilayer tablet further comprises a coating
3	Coating includes polyvinyl alcohol, titanium dioxide, macrogol/PEG, talc, yellow iron oxide, and red iron oxide
4	About 1 mg to about 30 mg coating
5	About 0.2% to about 6% w/w coating
6	About 2% to about 4% w/w coating
7	About 3% w/w coating
8	About 15 mg film coating

Claim 2 is broader than claims 3 through 8 because it does not expressly require the listed colorants, pigment, plasticizer, or anti-tacking materials. Claim 3 narrows the coating composition. Claims 4 through 8 narrow the coating amount.

The claimed 15 mg coating corresponds closely to 3% of the 500 mg tablet core:

• 15 mg / 500 mg core = 3.0% w/w relative to the core.
• 15 mg / 515 mg finished tablet = approximately 2.91% w/w relative to the finished tablet.

This distinction matters. “3% w/w” can be calculated against the tablet core or total coated tablet depending on the specification and claim construction. Claim 8 provides an absolute mass limitation and may be easier to apply than a percentage limitation.

How strong is the patent estate for the claimed bilayer tablet?

The claim set is technically narrow but potentially commercially relevant. Its strength depends less on broad active-ingredient coverage and more on whether a generic applicant must use the same formulation architecture to obtain approval.

Strengths

The patent has several characteristics that can complicate literal design-around:

• It claims both active ingredients in separate layers.
• It requires direct contact between the layers.
• It specifies the salt forms.
• It identifies detailed excipient systems.
• It claims intragranular and extragranular excipient placement.
• It covers both uncoated and coated versions.
• It identifies a commercially realistic 500 mg tablet core and 15 mg coating.

The direct-contact limitation may be important for manufacturing processes using conventional bilayer compression. A manufacturer using the same layer order and the same detailed excipient system would face a stronger infringement position than one using a substantially different formulation.

Weaknesses

The claim is vulnerable to structured formulation changes:

• A monolithic single-layer tablet is outside the express bilayer limitation.
• Separate dolutegravir and rilpivirine tablets are outside the single-tablet limitation.
• A trilayer tablet with a barrier layer may avoid the direct-contact requirement.
• Replacing one listed excipient may challenge the “consists of” limitation.
• Substantially changing the layer mass or ingredient distribution may avoid literal infringement.
• A coating outside the claimed composition or weight ranges may avoid claims 3 through 8, while claim 2 may remain relevant.

The doctrine of equivalents could limit some design-arounds, particularly if the substituted excipient performs the same function in substantially the same way with substantially the same result. Prosecution-history estoppel could restrict that argument if the applicant narrowed the claims to obtain allowance.

What is the relationship to Juluca?

Juluca is the marketed fixed-dose combination of dolutegravir and rilpivirine. Each tablet contains 50 mg dolutegravir and 25 mg rilpivirine. FDA approved Juluca in November 2017 for adults with HIV-1 infection who are virologically suppressed on a stable antiretroviral regimen and have no history of treatment failure or known resistance to either component [2].

The patent claims correspond to Juluca’s active strengths but do not, based on the supplied claims alone, establish that the patent covers every Juluca tablet or every dolutegravir-rilpivirine combination. The patent appears directed to a particular manufacturing formulation rather than to the active combination as such.

Product or regimen	Active ingredients	Relevance
Juluca	Dolutegravir/rilpivirine	Direct reference-product comparison
Dovato	Dolutegravir/lamivudine	Competing two-drug HIV regimen
Triumeq	Dolutegravir/abacavir/lamivudine	Competing dolutegravir-based regimen
Cabenuva	Cabotegravir/rilpivirine injectable	Competing long-acting regimen
Generic dolutegravir/rilpivirine	Same actives	Potential ANDA target if approval and patent conditions permit

Dovato and Triumeq do not practice the claimed rilpivirine-containing bilayer formulation. Cabenuva uses injectable dosage forms and is outside the tablet claims.

When does Juluca lose regulatory exclusivity?

Juluca received FDA approval in 2017. Its regulatory exclusivity period is separate from patent protection and should not be treated as the same legal barrier.

For a combination product containing previously approved active ingredients, the relevant FDA exclusivity may depend on the new clinical investigations supporting the approved combination and the specific statutory basis recorded by FDA. The five-year new chemical entity period applicable to an entirely new active ingredient does not automatically attach to a fixed-dose combination of previously approved drugs.

The practical market-entry analysis therefore requires separate review of:

• FDA-listed exclusivity for NDA 210495.
• Orange Book patent listings for Juluca.
• Any pediatric exclusivity.
• Approved ANDA or 505(b)(2) pathways.
• Patent certifications and litigation under Hatch-Waxman.

The claim text of Patent 12,011,506 does not establish the FDA exclusivity end date or whether the patent is listed in the Orange Book.

What is the Orange Book status of Patent 12,011,506?

A patent number alone does not establish Orange Book listing. FDA listing depends on the NDA holder’s submission and whether the patent claims the drug substance, drug product, or an approved method of use under applicable Orange Book standards [3].

For a formulation patent of this type, possible listing questions include:

• Whether the patent claims the approved drug product.
• Whether the claimed bilayer formulation corresponds to the FDA-approved Juluca formulation.
• Whether the patent owner is the NDA holder or has assigned listing rights.
• Whether the patent was submitted within the applicable FDA listing framework.
• Whether the listing appears under Juluca’s NDA rather than under a separate product.

If listed, an ANDA applicant could be required to submit a Paragraph IV certification asserting that the patent is invalid, unenforceable, or not infringed. If the NDA holder or patent owner timely files suit, the Hatch-Waxman litigation framework can impose a 30-month stay, subject to statutory exceptions and court action [4].

Which companies are challenging Patent 12,011,506?

The supplied claim information does not identify an ANDA filer, Paragraph IV notice, district-court complaint, inter partes review, post-grant review, or settlement agreement involving Patent 12,011,506.

No challenger, litigation date, settlement term, or authorized generic arrangement can be established from the claim text. A company seeking approval of a dolutegravir-rilpivirine product would likely evaluate the patent through one of three routes:

1. Paragraph III certification and delayed launch until patent expiry.
2. Paragraph IV certification with potential litigation.
3. A non-infringing formulation supported by an ANDA or other FDA pathway.

What generic entry risks exist?

The most credible entry scenarios are:

Same-formulation ANDA

A generic applicant copies the bilayer structure and listed excipient system. This creates the highest direct-infringement exposure, especially if the patent is listed and the reference product uses the claimed formulation.

Modified bilayer formulation

A generic applicant keeps the bilayer architecture but changes one excipient, quantity, layer mass, or processing location. This may reduce literal infringement risk but creates formulation-development and bioequivalence risk.

Single-layer formulation

A one-layer tablet could avoid the express bilayer limitation. The applicant would need to demonstrate equivalent exposure, dissolution, stability, content uniformity, and manufacturability.

Separated dosage units

Two tablets, a tablet-plus-capsule product, or another multi-unit presentation would not satisfy the claimed single bilayer tablet. That approach may fail to qualify as a substitutable generic for Juluca unless FDA accepts the dosage-form difference.

Barrier-layer or multilayer design

A three-layer tablet with a non-active barrier between dolutegravir and rilpivirine could challenge the “direct contact” limitation. Claims 2 through 8 refer to a bilayer tablet and do not expressly broaden the claim to all multilayer architectures.

What manufacturing and intellectual-property barriers matter?

The technical barrier is not the active combination alone. It is the controlled manufacture of two separate layers with different granulation and lubrication systems.

Key manufacturing issues include:

• Maintaining layer weight and content uniformity.
• Preventing cross-contamination between active layers.
• Controlling interface strength between directly contacting layers.
• Managing compression forces so the bilayer does not delaminate.
• Preserving rilpivirine dissolution performance.
• Controlling residual moisture from aqueous granulation.
• Achieving coating uniformity over a two-layer core.
• Demonstrating stability of both active ingredients in the combined tablet.

The claim’s ingredient-specific structure may provide evidence of formulation optimization, but commercial enforceability will depend on the specification’s examples, analytical methods, dissolution data, prosecution amendments, and any terminal disclaimer or related-family patents.

How does this patent compare with broader HIV patent estates?

Patent 12,011,506 is narrower than a foundational compound patent covering dolutegravir or rilpivirine. Compound patents can block use across multiple dosage forms and formulations. This patent is more vulnerable to formulation substitution but may remain important because it targets the exact fixed-dose tablet configuration needed for a conventional Juluca generic.

Patent category	Typical scope	Relevance to this patent
Compound patent	Active molecule or salt	Broader, potentially formulation-independent
Combination patent	Dolutegravir plus rilpivirine use or composition	Broader than the claimed tablet if valid
Method-of-use patent	HIV treatment regimen	May affect labeling and skinny-label strategy
Formulation patent	Specific excipients, dosage form, process	Primary category for Patent 12,011,506
Manufacturing patent	Granulation, compression, coating, or process controls	May create separate technical barriers
Device or delivery patent	Injectable or implantable delivery	Generally outside this tablet claim

Key Takeaways

• Patent 12,011,506 claims a specific dolutegravir-rilpivirine bilayer tablet, not every combination product.
• Claim 1 requires direct contact between a dolutegravir sodium layer and a rilpivirine hydrochloride layer.
• The two layer compositions use “consists of” language, making excipient substitution and ingredient relocation important design-around strategies.
• The claimed core has a nominal 300 mg dolutegravir layer and 200 mg rilpivirine layer.
• Claims 2 through 8 protect coated versions, including a coating of approximately 15 mg or approximately 3% w/w.
• The patent aligns with the 50 mg/25 mg active strengths of Juluca.
• The claim text does not establish Orange Book listing, FDA exclusivity, Paragraph IV challenges, litigation, or settlements.
• Generic risk is highest for a manufacturer using the same two-layer architecture and excipient system.
• Single-layer, separated-unit, barrier-layer, or excipient-substituted products offer potential non-infringement routes but require independent FDA and bioequivalence analysis.
• The patent is a formulation barrier within the Juluca landscape, not a substitute for compound, method-of-use, Orange Book, and regulatory-exclusivity analysis.

FAQs About United States Patent 12,011,506

Does Patent 12,011,506 cover Dovato?

No. Dovato contains dolutegravir and lamivudine, not rilpivirine hydrochloride. It does not meet the active-ingredient limitations of claim 1.

Does a coated Juluca-style tablet automatically infringe claim 8?

No. Claim 8 requires the claimed bilayer tablet and approximately 15 mg of film coating. A coating amount alone is insufficient without the underlying claim 1 elements.

Can a generic use the same active ingredients with different excipients?

Potentially. Different excipients may avoid literal infringement of the “consists of” layer limitations, but the result would require analysis of exact claim construction, equivalents, prosecution history, and FDA bioequivalence.

Would a three-layer tablet avoid the patent?

It may avoid the direct-contact bilayer limitation if a third layer separates dolutegravir and rilpivirine. The specification and prosecution history could affect that conclusion.

Is Patent 12,011,506 necessarily listed in the Orange Book?

No. Patent issuance does not itself establish Orange Book listing. Listing depends on FDA submission and the relationship between the patent claims and the approved Juluca product.

References

1. United States Patent and Trademark Office. (2024). United States Patent No. 12,011,506. Google Patents. https://patents.google.com/patent/US12011506B2/en
2. U.S. Food and Drug Administration. (2017). Juluca prescribing information. https://www.accessdata.fda.gov
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-data-files
4. U.S. Food and Drug Administration. (2018). Approved drug product and therapeutic equivalence evaluations, 21 C.F.R. § 314.94. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D/part-314

Drugs Protected by US Patent 12,011,506

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Viiv Hlthcare	JULUCA	dolutegravir sodium; rilpivirine hydrochloride	TABLET;ORAL	210192-001	Nov 21, 2017		RX	Yes	Yes	12,011,506		Y

International Family Members for US Patent 12,011,506

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	112213
Australia	2018291076
Brazil	112019027915