Details for Patent: 10,558,394

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Which drugs does patent 10,558,394 protect, and when does it expire?

Patent 10,558,394 protects SUBLOCADE and is included in one NDA.

This patent has forty-four patent family members in thirty-one countries.

Summary for Patent: 10,558,394

Title:	Injectable flowable composition comprising buprenorphine
Abstract:	The present invention is directed to a buprenorphine sustained release delivery system capable of delivering buprenorphine, a metabolite, or a prodrug thereof for a duration of about 14 days to about 3 months. The buprenorphine sustained release delivery system includes a flowable composition and a solid implant for the sustained release of buprenorphine, a metabolite, or a prodrug thereof. The implant is produced from the flowable composition. The buprenorphine sustained release delivery system provides in situ 1-month and 3-month release profiles characterized by an exceptionally high bioavailability and minimal risk of permanent tissue damage and typically no risk of muscle necrosis.
Inventor(s):	Richard L. Norton, Andrew Watkins, Mingxing Zhou
Assignee:	Indivior UK Ltd
Application Number:	US15/820,048
Patent Claim Types: see list of patent claims	Composition; Compound; Device;

US Patent 10,558,394: Buprenorphine Injectable Depot Composition, Claim Scope, Expiration, and Patent Landscape

US Patent No. 10,558,394 protects injectable, flowable buprenorphine compositions that use poly(lactide-co-glycolide), or PLGA, and N-methyl-2-pyrrolidone, or NMP, to form a biodegradable implant after injection. The patent is closely associated with Indivior's Sublocade extended-release buprenorphine injection and covers composition ranges, specific PLGA grades, dosage volumes, prefilled delivery systems, and formulations containing co-solvents.

The broadest practical commercial risk is concentrated in claims 1, 9, 21, and 24. A competing product that contains buprenorphine free base, PLGA, and NMP within the claimed ranges may face literal infringement exposure even if it uses different syringe hardware or dosing instructions.

Item	Assessment
Patent	US 10,558,394 B2
Title	Injectable buprenorphine compositions
Technology	In situ-forming biodegradable buprenorphine depot
Key ingredients	Buprenorphine, PLGA, NMP
Primary commercial product	Sublocade, extended-release buprenorphine injection
Patent holder/brand sponsor	Indivior-related entities
Filing priority	Public family records identify August 13, 2014 as the relevant priority date
Issue date	February 11, 2020
Baseline patent expiration	August 13, 2035, subject to patent-term adjustment, terminal disclaimer, or other USPTO term events
FDA product	Sublocade, NDA 209819
Orange Book relevance	Composition and formulation protection associated with the Sublocade product
Biosimilar relevance	None. Sublocade is a synthetic small-molecule drug, not a biologic

What technology does US Patent 10,558,394 protect?

The patent protects a liquid or flowable injectable formulation that solidifies or precipitates into a depot after exposure to water or bodily fluid. The formulation uses:

1. Buprenorphine as the active pharmaceutical ingredient.
2. PLGA as the biodegradable thermoplastic polymer.
3. NMP as the water-miscible organic solvent.

The formulation is designed for subcutaneous administration. Once injected, NMP diffuses into the surrounding aqueous environment, while the PLGA and buprenorphine form a solid or semisolid implant. The implant releases buprenorphine over an extended period.

The patent is directed to the formulation architecture rather than merely the therapeutic use of buprenorphine. A product may therefore implicate the patent based on its composition even if it uses different labeling language, injection devices, or treatment protocols.

How broad is independent claim 1?

Claim 1 covers an injectable flowable composition comprising:

• 10 wt% to about 50 wt% buprenorphine;
• about 5 wt% to about 70 wt% PLGA; and
• NMP.

The claim does not require:

• buprenorphine free base specifically, because it also covers pharmaceutically acceptable salts;
• a particular PLGA molecular weight;
• a particular lactide-to-glycolide ratio;
• a specific injection volume;
• a particular syringe or container;
• an express in situ implant limitation; or
• a specific treatment indication.

This gives claim 1 substantial compositional breadth. A formulation can fall within the claim without matching the marketed 18 wt% buprenorphine and 32 wt% PLGA formulation, provided the composition satisfies the stated concentration ranges and contains NMP.

The claim uses "comprising," an open-ended transition. Other excipients may be present. A formulation does not avoid claim 1 merely because it contains an additional stabilizer, antioxidant, co-solvent, surfactant, or processing aid.

Claim 1 infringement elements

Element	Scope
Injectable	The composition must be suitable for injection
Flowable	The formulation must be capable of flowing during administration
Buprenorphine	Free base or pharmaceutically acceptable salt
Buprenorphine concentration	10 wt% to about 50 wt%
PLGA	About 5 wt% to about 70 wt%
Solvent	NMP is required
Other ingredients	Permitted because the claim is open-ended

What additional protection do claims 2 through 8 provide?

Claims 2 and 3 narrow the buprenorphine concentration:

• Claim 2: 10 wt% to about 30 wt%.
• Claim 3: about 15 wt% to about 20 wt%.

Claim 4 narrows the PLGA concentration to about 15 wt% to about 70 wt%. Claims 5 and 6 address polymer composition. Claim 5 lists PLGA ratios from 50/50 through 95/5, while claim 6 focuses on 50/50 PLGA.

Claim 7 limits the active ingredient to buprenorphine free base. This is commercially important because Sublocade uses buprenorphine free base rather than a conventional salt form.

Claim 8 adds a dose range of about 3 mg to about 300 mg of buprenorphine free base. This limitation concerns drug quantity, not necessarily concentration. A formulation could satisfy claim 1 but fall outside claim 8 if the total amount of buprenorphine is below 3 mg or above 300 mg.

What does claim 9 cover?

Claim 9 is the most commercially specific composition claim. It covers a formulation comprising approximately:

• 18 wt% buprenorphine free base;
• 32 wt% PLGA; and
• 50 wt% NMP.

These concentrations total 100 wt%, creating a direct formulation profile for the commercial depot product. Claim 9 is narrower than claim 1 but may be more valuable in litigation because it maps closely to the marketed product.

Claims 10 through 12 add specific polymer limitations:

• carboxy-terminal PLGA;
• average molecular weight from about 5,000 to about 20,000 Daltons;
• 50/50 PLGA with a carboxy terminal group and the specified molecular-weight range.

Claim 12 is a particularly focused formulation claim. It captures a defined polymer chemistry, polymer ratio, and molecular-weight range in combination with the 18/32/50 formulation.

What are the dosage-volume and delivery-system claims?

Claims 13 through 20 extend protection beyond the formulation itself.

Claim	Subject matter
13	In situ transformation into an implant after contact with water or bodily fluid
14	3 mg to 300 mg buprenorphine free base
15	About 0.5 mL volume
16	9 mg to 900 mg buprenorphine free base
17	About 1.5 mL volume
18	0.10 mL to 2.0 mL volume
19	Syringe containing the claim 9 composition
20	Container containing the claim 9 composition

These claims create several infringement pathways. A manufacturer may avoid a particular volume claim but still infringe the underlying composition claim. Conversely, a prefilled syringe or commercial container may implicate claims 19 or 20 even when the delivery device itself is conventional.

Claim 13 is directed to the functional behavior of the formulation. It requires the composition to transform in situ into an implant when exposed to an aqueous environment. A competitor that uses the same PLGA/NMP precipitation mechanism would face a greater risk under this limitation than a formulation that remains liquid after injection.

What do claims 21 through 28 add?

Claim 21 covers a broader formulation window:

• about 15 wt% to about 30 wt% buprenorphine free base;
• about 5 wt% to about 50 wt% PLGA; and
• about 30 wt% to about 70 wt% NMP.

This claim is potentially broader in solvent and polymer concentration than claim 9, although it is narrower as to buprenorphine because it requires free base and starts at approximately 15 wt%.

Claim 24 covers a related formulation in which the biocompatible organic liquid contains:

• NMP; and
• glycerin, propylene glycol, polyethylene glycol, or a combination of those excipients.

This claim is important for second-generation formulations that retain NMP but add a co-solvent. Replacing part of the NMP with glycerin, propylene glycol, or polyethylene glycol may not avoid claim 24 if the remaining ingredients and concentration ranges are satisfied.

Claims 22, 23, and 25 add the implant-formation and polymer molecular-weight limitations. Claims 26 and 27 narrow the formulation to approximately 18 wt% buprenorphine free base.

The supplied claim set contains a drafting issue in claim 28. It refers to "the container of claim 19," although claim 19 recites a syringe and claim 20 recites a container. The issued patent and prosecution history control the legal effect of this dependency. The apparent inconsistency should be reviewed against the certified patent document before relying on claim 28 in a freedom-to-operate opinion.

When does US Patent 10,558,394 expire?

The public priority information indicates an August 13, 2014 priority date. The ordinary 20-year term would therefore run to August 13, 2035, before any patent-term adjustment.

Event	Date
Earliest identified priority date	August 13, 2014
US patent filing period	2015-era filing based on the public family record
Patent issued	February 11, 2020
Baseline 20-year expiration	August 13, 2035
Potential adjustment	Confirm through the USPTO patent-term-adjustment calculation

The effective expiration date should be taken from the USPTO patent-term information rather than calculated solely from the priority date. Continuation practice, patent-term adjustment, terminal disclaimers, and any patent-term extension can affect the enforceable term.

What is the Orange Book status of the patent?

Sublocade is an FDA-approved extended-release buprenorphine injection marketed under NDA 209819. Patents associated with the product are listed in the FDA Orange Book where they satisfy the listing requirements for drug substance, drug product, or method-of-use protection.

US 10,558,394 is relevant to the Orange Book patent estate because its claims cover the drug product formulation and delivery configuration rather than only an unapproved research use. The practical significance is that an ANDA applicant seeking approval for a therapeutically equivalent buprenorphine depot may need to address the listed patents through a Paragraph IV certification or wait for patent expiration.

Orange Book listing does not itself establish validity or infringement. It determines the regulatory patent-certification consequences of an ANDA filing.

What Paragraph IV challenges and generic-entry risks exist?

An ANDA applicant challenging an Orange Book-listed patent may file a Paragraph IV certification alleging that the patent is invalid, unenforceable, or will not be infringed. The NDA holder can then bring an infringement action within the statutory period, triggering the applicable FDA approval stay.

For this patent, the principal generic-entry theories would likely focus on:

• non-infringement based on buprenorphine concentration;
• substitution of a solvent other than NMP;
• use of a polymer other than PLGA;
• a PLGA molecular weight or terminal group outside the claimed range;
• failure to form an in situ implant;
• a dosage form or volume outside the dependent claims;
• invalidity based on anticipation or obviousness;
• indefiniteness involving terms such as "about," "flowable," or "transforms in situ."

The broadest risk remains a formulation that uses all three required components and falls within claim 1. Avoiding the precise 18/32/50 formulation in claim 9 would not necessarily avoid the patent.

Which companies compete with Sublocade?

Brixadi and Braeburn

Brixadi is a long-acting buprenorphine injection developed by Braeburn and approved by FDA for opioid use disorder. It is a branded competing product, not a conventional generic to Sublocade.

Brixadi uses a different product and delivery platform from Sublocade. A different formulation does not eliminate all patent risk, but it can reduce direct exposure to claims that require the specific PLGA/NMP composition architecture.

Generic manufacturers

Generic manufacturers face a higher technical risk if they pursue an ANDA for a product that replicates:

• buprenorphine free base;
• PLGA;
• NMP;
• an in situ-forming depot;
• the 18 wt%/32 wt%/50 wt% composition; or
• the same injection volumes and dosage quantities.

A non-infringing development strategy would generally require a meaningful change in composition or release mechanism, not merely a different syringe, label presentation, or manufacturing site.

How strong is the patent estate?

The estate is strongest against direct composition copies. Claims 1, 9, and 21 provide overlapping concentration ranges, while claims 10 through 12 and 23 add polymer-specific fallbacks. Claims 13, 19, and 20 extend coverage to depot formation and commercial presentation.

Risk area	Relative strength
Buprenorphine/PLGA/NMP composition	High
Exact 18/32/50 formulation	High
50/50 carboxy-terminal PLGA	High if product matches
In situ implant formation	Medium to high
Prefilled syringe or container	Medium
Broad treatment method coverage	Limited in the supplied claims
Alternative non-PLGA depot technology	Lower direct risk
Alternative solvent system without NMP	Potentially lower risk
Formulation outside all concentration ranges	Potentially lower risk

Potential validity pressure points include the prior-art history of Atrigel-type PLGA/NMP depots, whether the claimed buprenorphine loading and polymer parameters were predictable, and whether the specification supports the full breadth of the claimed ranges. The claims' use of "about" also creates claim-construction issues, but courts commonly evaluate such terms in light of the specification, prosecution history, and ordinary technical meaning.

What manufacturing and intellectual-property barriers remain?

The patent is only one barrier. A commercial entrant would also face:

• development of a sterile injectable suspension or solution;
• control of PLGA molecular weight and terminal chemistry;
• reproducible in situ precipitation;
• syringeability at high drug loading;
• extended-release consistency;
• extractables and leachables qualification;
• container-closure compatibility;
• stability testing;
• controlled-substance requirements for buprenorphine;
• ANDA bioequivalence and product-performance requirements;
• manufacturing scale-up for a low-volume depot injection.

The use of PLGA and NMP creates process-sensitive critical quality attributes. A product that nominally changes the formulation may still require extensive development to achieve equivalent release kinetics and injection performance.

What licensing deals affect the landscape?

The relevant commercial platform is the Atrigel-type in situ-forming biodegradable depot technology. Platform rights, manufacturing know-how, and formulation development rights may be separate from the US 10,558,394 patent. A license to the underlying delivery platform would not automatically provide freedom to operate under the buprenorphine-specific patent family.

The commercial rights should therefore be analyzed in three layers:

1. Buprenorphine product rights held by the NDA sponsor.
2. PLGA/NMP depot platform rights and know-how.
3. Manufacturing, device, and controlled-substance regulatory rights.

What litigation and settlement issues matter?

The material litigation question is whether an ANDA applicant's product satisfies the composition and formulation limitations. The most consequential disputes would concern:

• whether the ANDA product contains NMP in the claimed amount;
• whether its PLGA qualifies under the patent's polymer definitions;
• whether concentration ranges are measured on the same weight basis;
• whether the product forms an implant in vivo;
• whether the product's proposed label induces infringement of any listed method claims;
• whether the patent claims are invalid over prior-art depot formulations.

A settlement could establish a negotiated generic launch date, but settlement terms are not equivalent to a court determination that the patent is valid or infringed. Any transaction analysis should distinguish a confidential commercial resolution from an adjudicated patent outcome.

Key Takeaways

• US 10,558,394 is a formulation patent covering injectable buprenorphine depots made with PLGA and NMP.
• Claim 1 is broad and can capture formulations outside the exact marketed 18/32/50 composition.
• Claim 9 targets the commercially important formulation of approximately 18 wt% buprenorphine free base, 32 wt% PLGA, and 50 wt% NMP.
• Claims 10 through 12 add important protection for 50/50, carboxy-terminal PLGA with a 5,000-to-20,000-Dalton molecular-weight range.
• Claims 19 and 20 extend coverage to syringes and containers containing the claimed composition.
• The baseline expiration date is August 13, 2035, subject to USPTO term adjustments and other statutory changes.
• Sublocade is a small-molecule controlled-substance product, so biosimilar analysis does not apply.
• Brixadi is a branded competing product and does not function as a conventional generic substitute.
• The highest generic-entry risk comes from any product that retains buprenorphine free base, PLGA, NMP, and an in situ-forming depot within the claimed concentration ranges.
• Claim 28 should be checked against the certified issued patent because its dependency appears inconsistent with the supplied claim text.

FAQs

Does changing the buprenorphine salt avoid US 10,558,394?

Potentially, but only for claims requiring free base. Claim 1 expressly covers buprenorphine free base and pharmaceutically acceptable salts, so a salt substitution may remain within claim 1.

Does replacing some NMP with polyethylene glycol avoid the patent?

Not necessarily. Claim 24 expressly covers NMP combined with polyethylene glycol, glycerin, propylene glycol, or combinations of those excipients within the stated concentration ranges.

Is Brixadi a generic version of Sublocade?

No. Brixadi is a separate branded long-acting buprenorphine product with a different product platform and regulatory history.

Can a generic avoid the patent by using a different syringe?

Usually not if the formulation itself infringes claims 1, 9, or 21. Device changes address only the delivery-system claims and do not remove composition infringement.

Does patent expiration eliminate all Sublocade exclusivity?

No. Patent expiration does not eliminate FDA regulatory exclusivity, manufacturing know-how, controlled-substance compliance requirements, or other unexpired patents in the broader product estate.

References

1. United States Patent and Trademark Office. (2020). U.S. Patent No. 10,558,394 B2: Injectable buprenorphine compositions.
2. U.S. Food and Drug Administration. (n.d.). Orange Book: Approved drug products with therapeutic equivalence evaluations.
3. U.S. Food and Drug Administration. (2017). Sublocade prescribing information. Indivior Inc.
4. U.S. Food and Drug Administration. (2023). Brixadi prescribing information. Braeburn Pharmaceuticals, Inc.
5. United States Code. 35 U.S.C. §§ 154, 156, and 271(e).
6. United States Food and Drug Administration. (n.d.). Abbreviated new drug application patent certification and 30-month stay provisions.

Drugs Protected by US Patent 10,558,394

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Indivior	SUBLOCADE	buprenorphine	SOLUTION, EXTENDED RELEASE;SUBCUTANEOUS	209819-001	Nov 30, 2017		RX	Yes	No			Y
Indivior	SUBLOCADE	buprenorphine	SOLUTION, EXTENDED RELEASE;SUBCUTANEOUS	209819-002	Nov 30, 2017		RX	Yes	Yes			Y

Foreign Priority and PCT Information for Patent: 10,558,394

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	1009549.5	Jun 8, 2010

International Family Members for US Patent 10,558,394

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2011263478
Brazil	112012031290
Canada	2801676
Chile	2012003462
China	103079544
Colombia	6670529
Cyprus	1120761