Details for Patent: 10,195,138

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Which drugs does patent 10,195,138 protect, and when does it expire?

Patent 10,195,138 protects RISVAN and is included in one NDA.

This patent has one hundred and ninety-seven patent family members in thirty-six countries.

Summary for Patent: 10,195,138

Title:	Methods for the preparation of injectable depot compositions
Abstract:	Injectable depot compositions, comprising a biocompatible polymer which is a polymer or copolymer based on lactic acid and/or lactic acid plus glycolic acid having a monomer ratio of lactic to glycolic acid in the range from 48:52 to 100:0, a water-miscible solvent having a dipole moment of about 3.7-4.5 D and a dielectric constant of between 30 and 50, and a drug, were found suitable for forming in-situ biodegradable implants which can evoke therapeutic drug plasma levels from the first day and for at least 14 days.
Inventor(s):	Ibon GUTIERRO ADURIZ, Maria Teresa Gomez Ochoa
Assignee:	Laboratorios Farmaceuticos Rovi SA
Application Number:	US16/032,270
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Device;

US Patent 10,195,138: Scope, Claims, Expiration Risk and Risperidone Depot Patent Landscape

US Patent 10,195,138 protects a narrowly defined risperidone in-situ depot system rather than risperidone use generally. Its independent claim requires a specific combination of drug loading, particle-size distribution, DMSO-to-risperidone ratio, PLGA composition, polymer viscosity, dissolved-drug limit and therapeutic administration. The claim is most relevant to long-acting injectable risperidone products using DMSO-dissolved, end-capped 50:50 PLGA.

The patent does not cover every injectable risperidone formulation, every PLGA depot, or every product administered at four-week or longer intervals. A competing product would generally need to satisfy every limitation of claim 1, either literally or under the doctrine of equivalents, before the dependent pharmacokinetic, manufacturing, sterilization, packaging or dosing limitations become relevant.

The principal commercial products in the adjacent landscape are Teva’s Uzedy, Indivior’s Perseris and Janssen’s Risperdal Consta. Uzedy is the closest product conceptually because it uses a subcutaneous in-situ depot approach. Perseris is also a close formulation comparator, while Risperdal Consta uses a different microsphere technology.

What does US Patent 10,195,138 cover?

The patent covers a method of treating schizophrenia or bipolar disorder by administering a specified injectable depot composition that forms an implant in the patient.

Independent claim 1

Claim 1 is a combination claim with multiple mandatory limitations:

Claim element	Required limitation
Therapeutic use	Treatment of schizophrenia or bipolar disorder
Active ingredient	Risperidone
Dosage form	Injectable depot composition forming an implant in the subject
Polymer system	Polymeric solution of DMSO and PLGA copolymer
Drug loading	13 wt%, with a stated ±10% range
Drug particle size	One of three specified particle-distribution alternatives
DMSO ratio	DMSO:risperidone mass ratio of 4.66:1 ±10%
Polymer-solution ratio	Polymeric solution:risperidone mass ratio of approximately 6.66:1 ±10%
PLGA chemistry	End-capped 50:50 lactide:glycolide copolymer ±10%
Polymer viscosity	Approximately 0.20 to 0.50 dl/g inherent viscosity, ±10%
Formulation viscosity	Approximately 0.5 to 3.0 Pa·s, ±10%
Dissolved drug	No more than 20 wt% of risperidone dissolved in the composition

The claim therefore combines formulation composition, particle engineering, polymer characterization and clinical use. A formulation that contains risperidone and PLGA but uses a different solvent, different PLGA ratio, different particle distribution or materially different ratios may avoid literal infringement.

Why the “consists of” language matters

Claim 1 states that the injectable depot composition “consists of” risperidone and a polymeric solution of DMSO and PLGA copolymer. “Consists of” is generally a closed transitional phrase. It excludes additional ingredients that materially alter the claimed composition, subject to claim construction and the doctrine of equivalents.

The claim is therefore narrower than a claim using “comprising.” Potentially relevant formulation differences include:

• A solvent other than DMSO.
• A co-solvent, surfactant, buffer or stabilizer that is treated as an additional composition component.
• A polymer other than the claimed end-capped 50:50 PLGA.
• Risperidone present predominantly as dissolved drug rather than suspended particles.
• A drug loading outside the claimed range.
• A composition whose particle distribution falls outside all three alternatives.

The commercial significance depends on how a court construes the closed composition language and whether an added excipient is viewed as immaterial or claim-defeating.

How broad are the particle-size limitations?

The particle-size limitations are central technical restrictions, not incidental specifications.

Claim 1 provides three alternative particle-size definitions:

1. Less than 10% of particle volume below 10 microns, less than 10% above 225 microns, and d0.5 between 10 and 200 microns.
2. Less than 10% below a 1 to 10 micron lower boundary, less than 10% above a 225 to 400 micron upper boundary, and d0.5 of approximately 40 to 200 microns.
3. d0.9 of approximately 150 to 400 microns, d0.5 of approximately 40 to 200 microns and d0.1 of approximately 10 to 60 microns.

The alternatives overlap but are not identical. The patent uses volume-based distribution language in several places. Particle-size results measured by laser diffraction, microscopy or another analytical method may produce different values. Testing protocol, dispersion medium, agglomeration control and reporting basis can affect whether a product falls within the claim.

A design-around strategy could focus on:

• Shifting d0.5 outside the 40 to 200 micron range.
• Increasing the fine-particle fraction above the stated threshold.
• Increasing the coarse-particle fraction above the stated threshold.
• Using a different particle morphology or measurement basis.
• Using a substantially dissolved formulation.

Those changes may also affect syringeability, burst release, depot formation and pharmacokinetics. A technically effective design-around may therefore impose development costs.

What do claims 2 through 11 protect?

Claims 2 through 11 add pharmacokinetic and release-profile limitations.

Claims	Additional subject matter
2	Therapeutic risperidone or metabolite levels beginning within one day and continuing for at least four weeks
3	Total risperidone plus 9-hydroxyrisperidone plasma levels of approximately 5 to 80 ng/mL for specified doses
4	Cmin, Cavg and Cmax ranges during at least 14 days
5	Intramuscular, intraperitoneal, intrathecal, intravaginal, subcutaneous, intracranial or intracerebral administration
6	Release of approximately 0.5% to no more than 12% within 24 hours
7	Plasma profile within ±15% of the average over at least 14 days
8	Plasma profile within ±10% of the average over at least 14 days
9	Plasma profile within ±20% of the average over at least 28 days
10	Release of approximately 0.5% to no more than 12% within 24 hours
11	Release of approximately 0.5% to no more than 8% within 24 hours

Claims 6 and 10 are substantially overlapping release limitations. Claims 7 through 9 are difficult-to-prove performance claims because infringement may require validated clinical or in vivo pharmacokinetic data rather than a simple product assay.

Claim 4 is particularly broad numerically. Its Cmin, Cavg and Cmax ranges overlap many sustained-release risperidone profiles. The claim still depends on all limitations of claim 1, so the pharmacokinetic breadth does not eliminate the composition restrictions.

What manufacturing and packaging processes are protected?

Claims 12 through 26 extend protection into manufacturing, sterilization and administration.

Sterilization and irradiation

Claims 12 through 15 cover:

• A sterilized injectable composition.
• PLGA sterilized before incorporation into the formulation.
• PLGA sterilized before addition of DMSO.
• Beta irradiation in the range of 5 to 25 kGy.
• Irradiation sufficient to reduce PLGA molecular weight and intrinsic viscosity.

These claims may be important because PLGA molecular weight and viscosity influence injection force, depot formation and release kinetics. However, they require the accused product to satisfy the underlying limitations of claim 1 as well.

Kit and point-of-care mixing

Claims 17 through 22 cover kits containing:

• PLGA in a first container.
• DMSO in a second container.
• Risperidone in one of those containers or a third container.
• A syringe, vial or cartridge.
• Solid risperidone or PLGA before mixing.
• Risperidone and PLGA in the same container before DMSO is added.
• Mixing before administration.

These claims create potential exposure for dual-chamber or multi-container presentations. A fully manufactured, ready-to-inject formulation may avoid the kit claims while remaining exposed to the formulation and method claims.

Dosing interval, temperature and filtration

Claims 23 through 26 cover:

• Administration intervals from four weeks to six months.
• Warming or cooling before administration.
• Filtration through a nominal 0.22-micron or smaller medium.
• Multiple injection sites or multiple subcutaneous deposition points from one needle entry.

Claim 23 is commercially relevant to monthly and extended-interval products, but it does not independently claim a four-week dosing regimen. The composition must still meet claim 1.

How does the patent compare with competing risperidone products?

Product	Sponsor	Administration	Depot technology	Relationship to US 10,195,138
Uzedy	Teva Pharmaceuticals	Subcutaneous; monthly or every two months	In-situ extended-release depot	Closest commercial technology profile
Perseris	Indivior	Subcutaneous; monthly	ATRIGEL-based in-situ depot	Close dosage-form comparator; formulation details must be compared limitation by limitation
Risperdal Consta	Janssen Pharmaceuticals	Intramuscular; every two weeks	PLGA microspheres	Different delivery architecture and dosing schedule
Generic oral risperidone	Multiple manufacturers	Oral	Immediate or conventional oral dosage form	Generally outside the patent’s injectable-depot scope

Uzedy received FDA approval in 2023 for the treatment of schizophrenia in adults. Its monthly and every-two-month administration schedules overlap the interval language in claim 23, but dosing interval alone does not establish infringement. The relevant analysis is whether the product’s composition, particle distribution, polymer, solvent ratio, viscosity and release characteristics satisfy claim 1 and its dependents.[1]

Perseris received FDA approval in 2018 for the treatment of schizophrenia in adults. It is an in-situ subcutaneous depot using a polymer-based delivery platform. The presence of a subcutaneous depot does not itself establish that Perseris falls within US 10,195,138. The product’s exact PLGA grade, DMSO ratio, risperidone loading, particle distribution and composition structure control the analysis.[2]

Risperdal Consta uses risperidone-loaded microspheres administered intramuscularly. It does not appear to use the same DMSO-based in-situ implant architecture. Its primary patent and regulatory position is therefore distinct from the composition claimed in US 10,195,138.[3]

What is the FDA and Orange Book relevance?

US 10,195,138 is relevant to FDA-approved risperidone depot products only if the patent is listed for the applicable approved drug product and remains listed for the relevant NDA.

The Orange Book distinguishes between:

• Drug substance patents.
• Drug product or formulation patents.
• Method-of-use patents.
• Patents subject to a statutory certification by an ANDA applicant.

A method-of-use patent may be listed only for an approved use corresponding to the labeling and FDA listing requirements. A claim directed to schizophrenia or bipolar disorder does not automatically create an Orange Book barrier for every risperidone product.

For an ANDA applicant, a listed patent may trigger:

• Paragraph I certification if the patent information is not yet available.
• Paragraph II certification if the patent has expired.
• Paragraph III certification accepting delayed approval until expiration.
• Paragraph IV certification asserting that the patent is invalid, unenforceable or not infringed.[4]

The FDA does not decide whether a Paragraph IV certification is substantively correct. The NDA holder may bring an action under 21 U.S.C. § 355(j)(5)(B)(iii). A timely infringement action can create a statutory stay of approval, subject to the applicable statutory conditions.[5]

When does US Patent 10,195,138 lose exclusivity?

The patent’s enforceable term is determined by its earliest effective nonprovisional filing date, applicable patent-term adjustment, terminal disclaimers and any patent-term extension. The issue date, January 29, 2019, does not determine expiration.

The critical exclusivity points are:

Exclusivity issue	Relevance
Patent term	Normally 20 years from the earliest effective nonprovisional filing date
Patent-term adjustment	May extend the term for qualifying USPTO delays
Terminal disclaimer	May limit the term if the patent is tied to an earlier patent
Patent-term extension	May apply only if statutory regulatory requirements are satisfied
Regulatory exclusivity	Separate from patent term and depends on the NDA and approval pathway
Orange Book status	Determines whether an ANDA applicant must address the patent through certification

A reliable expiration date requires the current USPTO patent record, including the term-adjustment calculation and any terminal disclaimer. The claim text supplied does not contain those data. The nominal patent term should therefore not be treated as the commercial launch date for a generic or competing depot product.

For Uzedy and Perseris, any later-issued formulation, method-of-use or manufacturing patents may extend practical market protection beyond the expiration of US 10,195,138. Such later patents do not extend the term of this patent itself. They may, however, create separate Paragraph IV litigation risk.

Which companies are most likely to challenge the patent?

The immediate challenge population is smaller than for oral risperidone because an ANDA applicant would need to develop a technically comparable injectable depot and demonstrate bioequivalence or another FDA-accepted pathway.

Potential challengers include:

• Generic injectable manufacturers with PLGA depot capabilities.
• Contract development and manufacturing organizations with long-acting injectable platforms.
• Sponsors developing subcutaneous risperidone depots.
• Companies licensing alternative in-situ forming implant technologies.
• Sponsors using a 505(b)(2) application rather than an ANDA.

A conventional oral-risperidone manufacturer has little direct incentive to challenge this patent because an oral product does not practice the claimed injectable composition. A biosimilar challenge is also inapplicable. Risperidone is a small molecule, not a biologic, so the Purple Book biosimilar framework does not govern the product.[6]

What generic launch scenarios exist?

Scenario 1: Non-infringing alternative depot

A developer could pursue a depot using:

• A different solvent system.
• A different polymer ratio or end-group chemistry.
• Microspheres rather than an in-situ implant.
• A different drug particle-size profile.
• A substantially dissolved risperidone formulation.
• A different drug-to-polymer or DMSO-to-drug ratio.

This route reduces direct claim exposure but may require new clinical and CMC work.

Scenario 2: Paragraph IV challenge

An ANDA or 505(b)(2) applicant could assert that the patent is:

• Not infringed because one or more claim limitations are absent.
• Invalid for anticipation.
• Invalid for obviousness.
• Indefinite because a parameter lacks objective boundaries or reproducible measurement.
• Unenforceable if supported by litigation-specific evidence.

The strongest invalidity issues would likely concern the combination of known PLGA/DMSO depot technology with known risperidone treatment, particle-size control and pharmacokinetic targets. The patent holder would argue that the precise formulation window and controlled release profile produce an unexpected technical result.

Scenario 3: Post-expiration entry

A competitor could wait for patent expiration and pursue an abbreviated regulatory pathway. This reduces litigation risk but may leave later-issued patents, regulatory exclusivity and product-specific manufacturing patents in force.

How strong is the patent estate?

US 10,195,138 is strongest against a product that deliberately copies the claimed formulation architecture. Its strongest claim features are:

• The combination of DMSO and end-capped 50:50 PLGA.
• The specified risperidone loading.
• The DMSO-to-risperidone and polymer-solution-to-risperidone ratios.
• The particle-size distribution.
• The viscosity and intrinsic-viscosity limitations.
• The in-situ implant method of treatment.

Its weaknesses are claim density and parameter sensitivity. A competitor may avoid literal infringement by changing one material limitation. The patent also depends on technical measurements that can generate disputes concerning:

• Whether viscosity is measured on the same formulation or polymer solution.
• Whether particle size is reported by volume or mass.
• Which analytical method controls d0.1, d0.5 and d0.9.
• Whether ±10% modifies each adjacent numerical limitation.
• Whether additional excipients are permitted under “consists of.”
• Whether a measured plasma profile satisfies the claimed statistical band.

The estate should therefore be assessed as a high-value blocking patent for a narrow technology class, not as a broad monopoly over long-acting risperidone.

What patent litigation and settlement risks should be monitored?

The relevant litigation indicators are:

1. Paragraph IV notices involving the NDA covering a risperidone depot.
2. District-court complaints under the Hatch-Waxman statute.
3. Patent Trial and Appeal Board petitions challenging validity.
4. Terminal disclaimers and continuation applications.
5. Orange Book additions or delistings.
6. Confidential settlement agreements that include launch dates, licenses or authorized-generic provisions.
7. Later patents covering dose strength, injection device, manufacturing process or extended dosing interval.

A settlement may permit an earlier launch without invalidating the patent. Publicly available settlement terms may disclose a licensed entry date but often do not reveal royalty rates, manufacturing restrictions or supply obligations.

What is the commercial exposure?

The patent’s commercial exposure is concentrated in long-acting risperidone rather than the broader antipsychotic market.

The relevant revenue pools include:

• Monthly and every-two-month subcutaneous risperidone products.
• Monthly in-situ depot products.
• Intramuscular microsphere products.
• Follow-on long-acting injectable antipsychotics.

Uzedy and Perseris are the closest commercial comparators. Their sales exposure depends on market share, dosing frequency, payer coverage, persistence and the ability to replace oral risperidone. The patent’s value increases if the claimed DMSO/PLGA architecture is difficult to redesign without losing injection performance or pharmacokinetic control.

Key Takeaways

• US 10,195,138 is a narrow, multi-parameter patent covering a risperidone DMSO/PLGA in-situ depot method.
• Claim 1 requires every listed formulation, particle-size, viscosity, ratio and treatment limitation.
• Claims 2 through 11 add pharmacokinetic and release-profile protection.
• Claims 12 through 26 cover sterilization, irradiation, kits, mixing, dosing intervals, temperature handling, filtration and injection-site methods.
• Uzedy is the closest commercial comparator because it is a subcutaneous extended-release risperidone depot.
• Perseris is a relevant formulation comparator, while Risperdal Consta uses a different microsphere platform.
• The patent does not create biosimilar risk because risperidone is a small molecule.
• Paragraph IV exposure depends on the patent’s Orange Book listing for the relevant NDA and on whether a challenger develops a technically comparable depot.
• Exact patent expiration requires review of the USPTO term-adjustment and terminal-disclaimer records. The supplied claim text alone does not establish the enforceable expiration date.
• The patent is commercially significant as a blocking patent for a specific depot architecture, but it is not a broad patent on risperidone or long-acting antipsychotic treatment.

FAQs

Does US 10,195,138 cover oral risperidone?

No. The claims require an injectable depot composition that forms an implant in the subject.

Does the patent cover every subcutaneous risperidone injection?

No. A subcutaneous product must also satisfy the claimed DMSO, PLGA, particle-size, loading, viscosity and ratio limitations.

Can a competitor avoid the patent by using microspheres?

Potentially. A microsphere product may avoid the claimed in-situ polymeric solution architecture, but the complete formulation and method must be compared against every claim limitation.

Does a four-week dosing schedule alone infringe claim 23?

No. The dosing interval is only one dependent limitation. The composition must first satisfy claim 1.

Is a 505(b)(2) application a realistic pathway for a competing depot?

Yes. A 505(b)(2) pathway may be more suitable than an ANDA where the product has a materially different delivery system, formulation or clinical profile. Patent certification and litigation exposure would still require separate analysis.

References

1. U.S. Food and Drug Administration. (2023). Uzedy (risperidone) extended-release injectable suspension prescribing information. FDA.

2. U.S. Food and Drug Administration. (2018). Perseris (risperidone) extended-release injectable suspension prescribing information. FDA.

3. U.S. Food and Drug Administration. (2024). Risperdal Consta (risperidone) long-acting injection prescribing information. FDA.

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

5. 21 U.S.C. § 355(j)(5)(B)(iii).

6. U.S. Food and Drug Administration. (2024). Purple Book: Database of licensed biological products. FDA.

7. United States Patent No. 10,195,138. (2019). Injectable depot compositions and methods of use thereof. United States Patent and Trademark Office.

Drugs Protected by US Patent 10,195,138

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Labs Farms Rovi Sa	RISVAN	risperidone	FOR SUSPENSION, EXTENDED RELEASE;INTRAMUSCULAR	214835-001	Mar 29, 2024		DISCN	Yes	No	10,195,138					TREATMENT OF SCHIZOPHRENIA IN ADULTS BY ADMINISTRATION OF EXTENDED RELEASE INJECTABLE COMPOSITION
Labs Farms Rovi Sa	RISVAN	risperidone	FOR SUSPENSION, EXTENDED RELEASE;INTRAMUSCULAR	214835-002	Mar 29, 2024		DISCN	Yes	No	10,195,138					TREATMENT OF SCHIZOPHRENIA IN ADULTS BY ADMINISTRATION OF EXTENDED RELEASE INJECTABLE COMPOSITION

International Family Members for US Patent 10,195,138

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	3524
Australia	2011260318
Australia	2013269546
Australia	2013269547
Australia	2013298705
Brazil	112012030686
Brazil	112012030707