Details for Patent: 10,238,643

Which drugs does patent 10,238,643 protect, and when does it expire?

Patent 10,238,643 protects COBENFY and is included in one NDA.

This patent has nineteen patent family members in nine countries.

Summary for Patent: 10,238,643

Title:	Methods and compositions for treatment of disorders ameliorated by muscarinic receptor activation
Abstract:	Methods for the treatment of CNS disorders using combinations of muscarinic activators and inhibitors, and medicaments comprising muscarinic activators and inhibitors.
Inventor(s):	Eric Elenko, Philip E. Murray, III, Andrew C. Miller
Assignee:	Puretech Health LLC , Puretech Management Inc
Application Number:	US15/400,108
Patent Claim Types: see list of patent claims	Composition; Formulation; Compound; Dosage form;

United States Patent 10,238,643: Xanomeline-Trospium Claim Scope, Cobenfy Coverage, and Patent Landscape

US Patent No. 10,238,643 is a core composition patent covering oral products that combine xanomeline, or a xanomeline salt, with trospium chloride to reduce a xanomeline-associated side effect. Its broadest claim covers daily xanomeline doses from 25 mg to 700 mg and trospium chloride doses from 5 mg to 200 mg. The patent also claims immediate-release and controlled-release presentations, combined and separate release profiles, specific dosage ranges, single-capsule products, and selected xanomeline/trospium strength combinations.

The patent is directly relevant to Karuna Therapeutics’ Cobenfy, the FDA-approved xanomeline and trospium chloride product for schizophrenia in adults. The FDA-approved Cobenfy regimen falls within the quantitative ranges of several claims, particularly claims 1, 5, 15, and 16. The patent is listed in the FDA Orange Book with an expiration date reported as March 30, 2035. [1, 2]

What does US Patent 10,238,643 cover?

The patent covers an oral medicament containing two active pharmaceutical ingredients:

Component	Claimed range
Xanomeline or xanomeline salt	25 mg to 700 mg during 24 hours
Trospium chloride	5 mg to 200 mg during 24 hours
Pharmaceutical carrier	Required
Therapeutic rationale	Trospium alleviates a side effect associated with xanomeline

Claim 1 is the principal independent composition claim. It is drafted broadly enough to encompass a range of dosage strengths, release technologies, and pharmaceutical carriers. The claim does not require a particular disease indication, patient population, administration frequency, capsule size, excipient system, or manufacturing process.

The central technical concept is the combination of a centrally acting muscarinic agonist, xanomeline, with trospium chloride, a peripherally restricted antimuscarinic agent. The combination is intended to preserve xanomeline’s therapeutic activity while reducing peripheral cholinergic adverse effects such as gastrointestinal and urinary effects.

How broad is claim 1 of US 10,238,643?

Claim 1 has four material limitations:

1. An oral medicament.
2. Xanomeline or a xanomeline salt in the stated 24-hour amount.
3. Trospium chloride in the stated 24-hour amount.
4. A pharmaceutically acceptable carrier, with trospium used to alleviate a xanomeline-associated side effect.

The claim uses “comprising,” which generally permits the presence of additional ingredients. A product containing xanomeline, trospium chloride, and additional active or inactive ingredients could therefore fall within the claim if the required elements are present.

The dose limitation is expressed over a 24-hour period rather than solely as the amount per capsule or tablet. A twice-daily product may therefore satisfy the claim based on the aggregate daily dose, even if each individual capsule contains only part of the claimed quantity.

The side-effect limitation is important. A challenger could argue over whether a particular product or use satisfies the requirement that trospium “alleviates a side effect associated with use of the xanomeline.” The patent holder would likely rely on product labeling, clinical data, formulation rationale, and the known pharmacology of the combination to establish that limitation.

Which dependent claims cover formulations and release profiles?

Claims 2 through 4 address release characteristics.

Claim	Scope
2	Immediate-release formulation
3	Controlled-release formulation
4	Controlled-release xanomeline with immediate-release trospium chloride

Claim 4 is commercially significant because it addresses a differentiated release strategy. It requires xanomeline and trospium to have different release profiles, rather than merely requiring that the finished product be classified as immediate release or controlled release.

A product could face different infringement arguments depending on whether the two active ingredients are released from the same matrix, separate layers, separate particles, multiparticulates, or different dosage units administered together. The claim language supplied does not require a specific manufacturing architecture.

What dosage strengths are specifically protected?

Claims 5 through 16 narrow the broad ranges and create overlapping species claims.

Claims	Claimed xanomeline	Claimed trospium chloride	Dosage-form limitation
5	25 mg to 225 mg	5 mg to 60 mg	Single dosage form per 24 hours
6	25 mg	Within claim 5	Not separately specified
7	75 mg	Within claim 5	Not separately specified
8	Within claim 5	6.5 mg	Not separately specified
9	Within claim 5	20 mg	Not separately specified
10	25 mg	5 mg	Single capsule; “consisting essentially of”
11	75 mg	20 mg	Single capsule; “consisting essentially of”
12	25 mg	20 mg	Single capsule; “consisting essentially of”
13	75 mg	5 mg	Single capsule; “consisting essentially of”
14	Within claim 1	Within claim 1	Cellulose and lactose carrier
15	25 mg to 300 mg	5 mg to 200 mg	Single dosage form per 24 hours
16	25 mg to 225 mg	5 mg to 60 mg	Single dosage form per 24 hours

Claims 5 and 16 appear substantially overlapping in the supplied text. Claim 16 may have been included as a separate claim during prosecution for procedural or fallback purposes, but its practical scope is materially similar to claim 5.

The “consisting essentially of” language in claims 10 through 13 is narrower than “comprising.” It generally permits ingredients that do not materially affect the basic and novel characteristics of the claimed combination. The exact scope depends on the specification and prosecution history, particularly how the patent defines the basic and novel characteristics of the xanomeline-trospium combination.

Does US 10,238,643 cover Cobenfy?

Yes, the patent’s dosage ranges encompass the FDA-approved Cobenfy regimen.

Cobenfy is supplied as capsules containing xanomeline and trospium chloride. The FDA-approved dosing schedule begins at 50 mg xanomeline and 20 mg trospium chloride twice daily, with possible increases to 100 mg/20 mg twice daily and 125 mg/30 mg twice daily. [1]

Cobenfy strength per dose	Approximate 24-hour amount	Relevant claim ranges
50 mg xanomeline / 20 mg trospium chloride twice daily	100 mg / 40 mg	Claims 1, 5, 15, 16
100 mg / 20 mg twice daily	200 mg / 40 mg	Claims 1, 5, 15, 16
125 mg / 30 mg twice daily	250 mg / 60 mg	Claims 1, 15

The highest approved daily xanomeline amount, 250 mg, exceeds the 225 mg xanomeline ceiling in claims 5 and 16 but remains within claim 15’s 25 mg-to-300 mg range and claim 1’s 25 mg-to-700 mg range. The 60 mg daily trospium amount at the highest approved dose remains within the narrower claim 5 and claim 16 trospium range.

The approved commercial strengths are not identical to the single-capsule strengths recited in claims 10 through 13. Those claims specifically identify 25 mg/5 mg, 75 mg/20 mg, 25 mg/20 mg, and 75 mg/5 mg capsules. A Cobenfy product may therefore fall within broader claims without necessarily matching every narrow single-capsule claim.

What is the FDA regulatory status of the covered product?

The FDA approved Cobenfy, formerly known as KarXT, on September 26, 2024, for the treatment of schizophrenia in adults. The product combines xanomeline and trospium chloride and is administered orally. [1]

Cobenfy is a small-molecule drug product, not a biologic. Biosimilar provisions under the Public Health Service Act therefore do not apply. Competitive entry would proceed through an abbreviated new drug application, or ANDA, rather than a biosimilar application.

The relevant regulatory protection consists of:

• New drug application approval for Cobenfy.
• Orange Book-listed patents.
• Any applicable statutory exclusivity associated with the approved NDA.
• Patent and regulatory protections covering the active combination, formulations, uses, and manufacturing technology.

The Orange Book identifies patent protection associated with Cobenfy, including US 10,238,643. The listed expiration date for US 10,238,643 is March 30, 2035. [2]

When does US Patent 10,238,643 lose exclusivity?

The reported patent expiration date is March 30, 2035. [2]

The effective commercial entry date could differ from the nominal expiration date because of:

• Patent-term adjustment.
• Patent-term extension.
• A court judgment affecting validity or enforceability.
• A settlement agreement permitting earlier entry.
• Regulatory exclusivity that expires before or after the patent.
• An ANDA applicant’s Paragraph IV certification and litigation outcome.

The Orange Book expiration date is the primary commercial reference point for generic planning. It does not, by itself, establish that every claim remains valid and enforceable through that date.

What patent landscape surrounds Cobenfy and xanomeline-trospium?

The Cobenfy patent estate is broader than US 10,238,643. The relevant protection can be divided into four categories.

Combination composition patents

These patents cover products containing xanomeline and trospium chloride. US 10,238,643 is a principal example. Combination claims can create a direct barrier to an ANDA that uses the same active ingredients within the claimed dose ranges.

Method-of-use patents

Separate patents may cover treating schizophrenia or other central nervous system disorders with the xanomeline-trospium combination. Method-of-use patents can be important where a generic applicant seeks approval for a use that is carved out of the label or where the branded label contains patented indications.

The strength of a method-of-use patent depends on the exact indication, dosing regimen, patient population, and whether the proposed generic label includes the patented use.

Formulation and release-profile patents

Claims directed to immediate-release, controlled-release, or differential-release formulations may restrict design-around options. Claim 4 of US 10,238,643 is particularly relevant to a product that uses controlled-release xanomeline and immediate-release trospium.

Formulation patents can create separate technical barriers even if a competitor avoids a broad composition claim. The commercial risk depends on whether the competitor uses the same release mechanism, excipient system, dosage form, and pharmacokinetic profile.

Manufacturing and process patents

Manufacturing patents may cover granulation, particle engineering, coating, encapsulation, blending, stability control, or the production of xanomeline-trospium dosage units. These rights can be difficult to evaluate from the final product alone because process details may not be publicly apparent.

A generic manufacturer could avoid a process patent while still infringing a composition or formulation claim. Conversely, a non-infringing active-ingredient source does not eliminate risk from product-level claims.

How strong is the patent estate for xanomeline-trospium?

US 10,238,643 has meaningful commercial breadth for four reasons:

1. Claim 1 covers a wide dose range for both active ingredients.
2. The claims encompass immediate-release and controlled-release products.
3. The patent reaches single-dosage-form products, including capsule presentations.
4. The claim structure overlaps the approved Cobenfy dosing range.

The main potential limitations are equally important. The patent is not a pure xanomeline composition patent. It requires trospium chloride and a pharmaceutical carrier. A competitor that develops xanomeline monotherapy, a different peripheral antimuscarinic, or a substantially different therapeutic combination would not satisfy the literal combination requirement.

The side-effect limitation may also create claim-construction and proof issues. A product containing both drugs could dispute whether trospium is used to alleviate a xanomeline-associated side effect or is included for another therapeutic purpose. The commercial relevance of that argument would depend on the proposed labeling, clinical development program, and prosecution history.

Which companies are challenging Cobenfy patents?

No publicly reported Paragraph IV litigation involving an ANDA challenging US 10,238,643 is identified in the cited FDA and patent records through the available public record reviewed for this analysis. [2, 3]

That does not eliminate future challenge risk. A generic applicant could file an ANDA with a Paragraph IV certification, triggering the Hatch-Waxman notice and litigation framework. The patent holder could then file suit within the statutory period, potentially obtaining a 30-month stay of FDA approval, subject to statutory exceptions and court developments. [4]

No biosimilar challenge is relevant because Cobenfy is a small-molecule product.

What generic launch scenarios exist?

Launch after patent expiry

The lowest-risk scenario for an ANDA applicant is launch after March 30, 2035, assuming no later-expiring Orange Book patent, regulatory exclusivity, injunction, or settlement restriction applies.

Paragraph IV challenge

An ANDA applicant could challenge validity, enforceability, or infringement before expiry. Possible grounds could include lack of written description, enablement, anticipation, obviousness, indefiniteness, or non-infringement. The commercial value of a challenge depends on the remaining market size and the number of surviving patents.

Design-around product

A competitor could attempt to avoid the claims by changing:

• The trospium dose.
• The xanomeline dose.
• The release profile.
• The dosage form.
• The active combination.
• The indication or label.
• The carrier or manufacturing process.

Design-around options are constrained by the breadth of claim 1 and claim 15, which cover wide dose ranges. A product with xanomeline and trospium in a materially different dosage regimen could still face infringement arguments if the aggregate 24-hour amounts fall within the claimed ranges.

How does US 10,238,643 compare with a conventional xanomeline patent?

Issue	US 10,238,643	Conventional xanomeline-only patent
Active ingredients	Requires xanomeline plus trospium chloride	May require xanomeline alone
Primary protection	Combination product	Active ingredient, use, or formulation
Dose focus	Both active ingredients over 24 hours	Xanomeline dose or exposure
Cobenfy relevance	Direct	Depends on claim language
Biosimilar pathway	Not applicable	Not applicable
Main design-around	Change trospium, dose, release profile, or combination	Change formulation, dose, or use

The patent is strategically more relevant to Cobenfy than a xanomeline-only patent because it targets the product’s defining combination.

Key Takeaways

• US 10,238,643 claims oral xanomeline-trospium medicaments across broad daily dose ranges.
• Claim 1 covers 25 mg to 700 mg xanomeline and 5 mg to 200 mg trospium chloride during 24 hours.
• Claims 2 through 4 address immediate-release, controlled-release, and differential-release formulations.
• Claims 5 through 16 add narrower ranges, specific strengths, single-capsule products, and cellulose/lactose carriers.
• Cobenfy’s approved dosing regimen falls within several claims, including claims 1, 5, 15, and 16.
• The reported Orange Book expiration date is March 30, 2035.
• Cobenfy is a small-molecule product, so biosimilar litigation is not applicable.
• No publicly reported Paragraph IV challenge to US 10,238,643 is identified in the cited records.
• Generic risk will depend on the full Orange Book estate, later-expiring formulation or use patents, prosecution history, and any Hatch-Waxman settlement.

FAQs About US Patent 10,238,643 and Cobenfy

Does US 10,238,643 claim Cobenfy by brand name?

No. The patent claims compositions defined by xanomeline, trospium chloride, dose ranges, formulation characteristics, and pharmaceutical carriers. It does not need to identify Cobenfy by brand name to cover a product meeting the claim limitations.

Is a xanomeline-only product covered by US 10,238,643?

Generally, no. The claims supplied require trospium chloride. A xanomeline-only product would not satisfy the combination limitation of claim 1.

Does changing from a capsule to a tablet avoid the patent?

Not necessarily. Claim 1 broadly covers an oral medicament and does not require a capsule. A tablet could remain within the patent if it contains the required ingredients and dose amounts.

Can a generic use a different trospium dose?

Possibly, but the dose must be assessed against every asserted claim. Claim 1 covers 5 mg to 200 mg trospium chloride per 24 hours, while narrower claims cover smaller ranges. A dose outside one claim may remain within another claim or a separate patent in the Cobenfy estate.

Is the March 30, 2035 date the final possible Cobenfy launch date?

Not necessarily. It is the reported expiration date for US 10,238,643. Later-expiring Orange Book patents, regulatory exclusivity, litigation outcomes, or settlement terms could affect the actual launch date.

References

1. U.S. Food and Drug Administration. (2024, September 26). FDA approves drug with new mechanism of action for treatment of schizophrenia. https://www.fda.gov/news-events/press-announcements/fda-approves-drug-new-mechanism-action-treatment-schizophrenia

2. U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations: Cobenfy, xanomeline and trospium chloride. Orange Book database. https://www.accessdata.fda.gov/scripts/cder/ob/

3. United States Patent and Trademark Office. (2019). U.S. Patent No. 10,238,643: Xanomeline-trospium compositions and methods of use. https://patents.google.com/patent/US10238643B2/en

4. U.S. Food and Drug Administration. (2024). ANDA submissions: Amendments and requirements related to Paragraph IV certifications. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/anda-submissions-questions-and-answers-supplements-and-other-questions-and-answers-anda-submissions

Drugs Protected by US Patent 10,238,643

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-myers	COBENFY	trospium chloride; xanomeline tartrate	CAPSULE;ORAL	216158-001	Sep 26, 2024		RX	Yes	Yes			Y
Bristol-myers	COBENFY	trospium chloride; xanomeline tartrate	CAPSULE;ORAL	216158-002	Sep 26, 2024		RX	Yes	No			Y
Bristol-myers	COBENFY	trospium chloride; xanomeline tartrate	CAPSULE;ORAL	216158-003	Sep 26, 2024		RX	Yes	No			Y

International Family Members for US Patent 10,238,643

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	2804215
Denmark	3061821
European Patent Office	2456868
European Patent Office	3061821
European Patent Office	3646870
Spain	2742728
Hungary	E044653