Details for Patent: 10,369,144

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Which drugs does patent 10,369,144 protect, and when does it expire?

Patent 10,369,144 protects COBENFY and is included in one NDA.

This patent has twenty-eight patent family members in fourteen countries.

Summary for Patent: 10,369,144

Title:	Methods and compositions for treatment of disorders ameliorated by muscarinic receptor activation
Abstract:	The present disclosure provides a method of treating a central nervous system disorder in a patient in need thereof. The method comprises orally administering between 75 mg and 300 mg xanomeline and between 20 mg and 200 mg trospium chloride to the patient during a 24-hour period. The central nervous system disorder is selected from schizophrenia, Alzheimer's disease, Huntington's disease, Parkinson's disease, and Lewy Body dementia, wherein use of the trospium chloride alleviates a side effect associated with use of the xanomeline.
Inventor(s):	Eric Elenko, Philip E. Murray, III, Andrew C. Miller
Assignee:	Puretech Health LLC , Puretech Management Inc
Application Number:	US16/289,165
Patent Claim Types: see list of patent claims	Use; Formulation; Dosage form;

US Patent 10,369,144: Claim Scope, Exclusivity, Orange Book Status and Cobenfy Patent Landscape

US Patent 10,369,144 protects a single oral capsule combining xanomeline, or a xanomeline salt, with trospium chloride. The core invention addresses xanomeline-associated cholinergic adverse effects through co-formulation with trospium. The broadest claim requires a single capsule, oral administration, a xanomeline amount capable of causing specified adverse effects, and a trospium amount effective to reduce those effects. Dependent claims add immediate-release and controlled-release formats, dose ranges, a 20-mg trospium dose, twice-daily schizophrenia treatment, and central nervous system indications.

The patent is commercially important to Bristol Myers Squibb's Cobenfy, formerly KarXT, which combines xanomeline and trospium for schizophrenia. It is a small-molecule patent, not a biologic patent, so biosimilar rules do not apply. Generic risk will focus on ANDA certification, formulation design, claim construction, obviousness, enablement, and whether a proposed product uses a single capsule containing both active ingredients.

What does US Patent 10,369,144 protect?

US 10,369,144 protects pharmaceutical compositions and treatment methods using xanomeline and trospium chloride in a single oral capsule. Claim 1 is the independent composition claim. Claim 12 is the independent treatment-method claim.

Claim group	Subject matter	Commercial significance
Claim 1	Single oral capsule containing xanomeline or a salt and trospium chloride	Core combination-product protection
Claims 2-4	Immediate-release, controlled-release, and mixed-release formats	Covers release-profile alternatives
Claims 5-8	Xanomeline dose ranges from 1 mg to 1 gram	Broad and progressively narrower xanomeline ranges
Claims 9-11	Trospium chloride ranges, including 20 mg	Claim 11 tracks the commercial 20-mg dose
Claims 12-14	Twice-daily treatment of schizophrenia	Method-of-use protection for the principal approved indication
Claim 15	Tartaric-acid salt of xanomeline	Salt-specific composition protection
Claim 16	CNS disorders, including Alzheimer's, Huntington's, Parkinson's and Lewy body dementia	Research and potential future-indication coverage

The patent does not merely cover the simultaneous use of xanomeline and trospium. Its strongest commercial limitation is the requirement that the two agents be present in a single capsule. A regimen using two separate capsules may avoid literal infringement of claim 1, although other patent claims, doctrine-of-equivalents arguments, or regulatory-substitution issues could remain relevant.

How broad is independent claim 1?

Claim 1 has four principal limitations:

1. A single capsule formulation.
2. Oral administration.
3. Xanomeline or a xanomeline salt in an amount capable of causing nausea, vomiting, diarrhea, sweating, or excess salivation.
4. Trospium chloride in an amount effective to reduce the xanomeline-associated side effect.

The claim does not specify a particular excipient, capsule shell, manufacturing process, particle size, dissolution profile, xanomeline-to-trospium ratio, or pharmacokinetic parameter. That gives the claim potentially broad formulation coverage.

The claim is also functionally drafted. The xanomeline amount is defined partly by the adverse-effect result it can produce, while the trospium amount is defined by its effect on reducing that adverse effect. A generic challenger would likely examine whether those functional phrases impose measurable limitations and whether the patent specification adequately teaches the full claimed range.

What does “single capsule” mean?

The ordinary commercial reading is one capsule containing both xanomeline, or a salt of xanomeline, and trospium chloride. A blister pack containing two separate capsules would not naturally satisfy the single-capsule limitation.

The limitation may cover:

• A capsule with both active ingredients in one immediate-release matrix.
• A capsule with separate internal pellets or beads.
• A capsule containing a controlled-release xanomeline component and an immediate-release trospium component.
• A capsule containing separate compartments or multiparticulate systems, provided both agents are delivered within one capsule.

The claim does not require the ingredients to be physically mixed. A capsule containing separate drug layers, pellets, or mini-tablets could fall within the language if both active ingredients are part of the same capsule formulation.

What formulations are protected by US 10,369,144?

Claims 2 through 4 create a release-profile framework.

Immediate-release formulation

Claim 2 covers a formulation described as immediate release. It may cover a capsule in which both active ingredients release promptly after oral administration.

Controlled-release formulation

Claim 3 covers a controlled-release formulation. The claim language supplied does not limit controlled release to a particular polymer, coating, dissolution target, or release duration.

Controlled-release xanomeline with immediate-release trospium

Claim 4 is commercially significant because it reflects a pharmacological design in which xanomeline exposure is controlled while trospium is available promptly to reduce peripheral cholinergic effects. A product using this architecture could face a direct claim issue even if its excipients, pellet structure, or manufacturing process differ from the commercial formulation.

The patent therefore reaches beyond a simple powder blend. It can cover differentiated release components within a single capsule.

What dose ranges are covered?

The claims create nested xanomeline and trospium ranges.

Claims	Active ingredient	Range or dose
Claim 5	Xanomeline or salt	1 mg to 1,000 mg
Claim 6	Xanomeline or salt	5 mg to 700 mg
Claim 7	Xanomeline or salt	5 mg to 500 mg
Claim 8	Xanomeline or salt	25 mg to 300 mg
Claim 9	Trospium chloride	1 mg to 400 mg
Claim 10	Trospium chloride	6.5 mg to 200 mg
Claim 11	Trospium chloride	20 mg
Claim 13	Trospium chloride	20 mg in the schizophrenia method
Claim 14	Xanomeline or salt	25 mg to 300 mg in the schizophrenia method

The 20-mg trospium limitation is particularly important because the approved Cobenfy dosing regimen uses 20 mg of trospium chloride in each capsule, with titration through different xanomeline strengths. The broad range claims may capture alternative commercial strengths, while claim 11 provides a narrow, dose-specific fallback position.

Does the patent cover Cobenfy?

Cobenfy contains xanomeline and trospium chloride and is administered orally for schizophrenia. The FDA-approved product is therefore aligned with the principal elements of claims 1, 11, and 12-14, subject to the precise formulation and claim interpretation.

Cobenfy's approved dosage is administered twice daily. The product is supplied in strength combinations containing xanomeline and trospium chloride, including 50 mg/20 mg and 100 mg/20 mg capsules, with titration from lower xanomeline strengths in the approved regimen. The FDA-approved indication is schizophrenia in adults.[2]

The patent claims are broader in some respects than the approved label. Claim 1 reaches specified side-effect-reducing combinations without being limited to schizophrenia. Claim 16 extends to multiple CNS disorders that are not the current approved indication. The patent consequently has both a marketed-use component and a pipeline-use component.

What is the Orange Book status of US 10,369,144?

US 10,369,144 is associated with the Cobenfy regulatory patent estate and is relevant to FDA-listed patent protection for the product. The Orange Book listing determines whether an ANDA applicant must make a patent certification and whether a timely infringement action can trigger the statutory 30-month stay.[3]

For a generic applicant, the relevant certifications are:

• Paragraph I: no patent information has been submitted.
• Paragraph II: the patent has expired.
• Paragraph III: the applicant will market after patent expiration.
• Paragraph IV: the patent is invalid, unenforceable, or will not be infringed.

A Paragraph IV certification concerning a listed Cobenfy patent can create litigation exposure if the patent owner or NDA holder files suit within 45 days. The filing of a timely suit generally imposes a 30-month stay on final FDA approval, subject to statutory exceptions and court action.[4]

The patent itself does not create a separate biologic exclusivity period. Cobenfy is regulated as a small-molecule drug under an NDA, and an ANDA, rather than a biosimilar application, is the expected abbreviated pathway for a generic xanomeline-trospium product.

When does US 10,369,144 lose exclusivity?

The earliest claimed priority date for the patent family is in December 2014. On that basis, the ordinary 20-year patent term would run into December 2035, before any patent-term adjustment or patent-term extension.

Exclusivity component	Approximate endpoint or status
US 10,369,144 ordinary patent term	December 2035, subject to USPTO term calculation
FDA new chemical entity exclusivity for Cobenfy	September 2029, based on the September 2024 approval
Potential ANDA filing restriction during NCE period	Generally through September 2029
Paragraph IV launch timing	Dependent on litigation, patent validity, and final FDA approval
Biosimilar exclusivity	Not applicable

FDA five-year new chemical entity exclusivity generally prevents submission of an ANDA for four years and prevents approval for five years, subject to the Paragraph IV exception.[3] That regulatory protection expires well before the expected ordinary patent term.

The patent term should be confirmed against the USPTO Patent Term Adjustment calculation and the Orange Book expiration entry. A continuation patent or later-issued formulation patent may provide separate protection beyond the term of US 10,369,144.

What method-of-use protection does the patent provide?

Claim 12 requires:

• A patient in need of treatment.
• Schizophrenia.
• Oral administration.
• The single-capsule formulation of claim 1.
• Twice-daily administration.

Claims 13 and 14 narrow the method to 20 mg of trospium chloride and 25 mg to 300 mg of xanomeline or a xanomeline salt.

This structure matters in an ANDA case. A generic applicant may attempt to avoid an indicated method-of-use claim through labeling designed to omit the patented use. That strategy is more difficult where the patented indication is the principal or only commercially meaningful use of the drug combination. Section viii labeling strategies are generally more practical when an unpatented use can be carved out without promoting or directing the patented use.

Claim 16 is broader therapeutically but may present different enforcement issues. It covers treatment of Alzheimer's disease, Huntington's disease, Parkinson's disease, and Lewy body dementia. Those indications were not the initial FDA-approved use of Cobenfy. The claim could become commercially important if clinical development supports additional indications.

What patentability and validity issues affect the estate?

The principal validity issues are likely to center on obviousness, written description, enablement, and claim construction.

Obviousness

A challenger could combine prior art showing:

• Xanomeline's activity at muscarinic receptors.
• Xanomeline's gastrointestinal and other cholinergic adverse effects.
• Trospium's peripheral antimuscarinic activity.
• The limited central nervous system penetration of trospium.
• Known use of anticholinergic agents to manage peripheral adverse effects.
• Pharmaceutical co-formulation and modified-release techniques.

The patent holder's response would likely focus on the specific combination, the separation of central and peripheral pharmacology, the selection of trospium chloride, the single-capsule architecture, and clinical evidence showing tolerability or treatment persistence.

Written description and enablement

Claim 1 covers broad xanomeline and trospium amounts and multiple adverse effects. A challenger could argue that the specification does not support every concentration, release architecture, salt, and side-effect relationship across the full claim scope.

The patent holder would rely on working examples, disclosed dose ranges, pharmacology, and the predictable nature of pharmaceutical formulation development. Claims 5 through 11 provide narrower positions if a court limits the broad functional language.

Functional limitations

The phrases “in an amount to cause a side effect” and “in an amount effective to reduce the side effect” may become central to litigation. The parties could dispute:

• Whether the adverse effect must occur in the treated patient.
• Whether the effect must be statistically demonstrated.
• Whether reduction means complete prevention, a measurable decrease, or clinical improvement.
• Whether the relevant comparison is xanomeline alone versus the combination.
• Whether the functional terms are limitations of the product itself or statements of intended use.

A narrow interpretation may reduce infringement risk. A broad interpretation may strengthen coverage but increase validity pressure.

How strong is the patent estate for Cobenfy?

US 10,369,144 is commercially strong against a product that reproduces the central design: a single capsule containing xanomeline and 20 mg trospium chloride, administered twice daily for schizophrenia.

Its strongest features are:

• Direct alignment with the commercial combination.
• A single-capsule limitation that maps to the marketed dosage form.
• Narrow fallback claims directed to 20 mg trospium.
• Separate formulation claims for immediate and controlled release.
• A method claim tied to the approved schizophrenia regimen.
• Multiple nested dose ranges.

Its limitations are equally clear:

• The patent does not necessarily block separate-capsule coadministration.
• Functional adverse-effect language may create claim-construction and proof issues.
• Broad dose and disease claims may face written-description or enablement challenges.
• A generic could develop a different release architecture or pursue a noninfringing label.
• The patent does not independently protect every manufacturing process, excipient system, salt, or crystalline form.

The commercial estate must therefore be evaluated as a portfolio, not through US 10,369,144 alone. Later formulation, dosage, process, and method patents may provide additional barriers.

Which companies are challenging Cobenfy patents?

Publicly established generic challenges should be evaluated through FDA Paragraph IV notices, district-court dockets, and Orange Book records. A company should not be treated as a confirmed challenger solely because it has filed an ANDA or is developing an antipsychotic product.

The most relevant future challengers are generic manufacturers with:

• An ANDA strategy for a fixed-dose xanomeline-trospium capsule.
• A formulation capable of matching the FDA-required dissolution profile.
• A Paragraph IV position against the listed patent estate.
• Sufficient commercial incentive to challenge a product with patent protection extending beyond NCE exclusivity.

The absence of an identified public Paragraph IV case does not eliminate risk. ANDA litigation may become visible only after the NDA holder receives a notice letter and files an action.

What licensing deals affect the patent rights?

Karuna obtained rights relating to xanomeline from Eli Lilly before developing the xanomeline-trospium program. Bristol Myers Squibb acquired Karuna in a transaction completed in March 2024. BMS therefore became the commercial owner of Cobenfy and the principal entity managing the associated regulatory and patent strategy.[5]

The acquisition is more important to control and enforcement than to claim scope. Ownership changes do not expand the claims of US 10,369,144. Any license restrictions, field-of-use provisions, prosecution obligations, or royalty interests must be reviewed in the underlying assignment and license documents.

What generic launch scenarios exist?

Scenario 1: No Paragraph IV challenge

A generic applicant waits for the patent and regulatory barriers to expire. Commercial entry would likely occur after the relevant patent term and FDA approval timing.

Scenario 2: Paragraph IV challenge with settlement

The applicant challenges validity or infringement, the patent holder files suit, and the parties settle for a licensed entry date. The settlement would be subject to antitrust review and applicable FDA reporting requirements.

Scenario 3: Noninfringing separate-capsule product

A company markets xanomeline and trospium as separate capsules or tablets, if it can obtain approval and establish acceptable clinical and labeling support. This approach could avoid the “single capsule” limitation but would face formulation, regulatory, substitution, and other patent barriers.

Scenario 4: Formulation redesign

A challenger may use a different release mechanism, salt, capsule configuration, or dose. Design-around value depends on whether the revised product still satisfies the broad functional limitations and any later portfolio patents.

Scenario 5: Invalidity victory

A successful obviousness, enablement, written-description, or indefiniteness challenge could remove the principal single-capsule barrier. The commercial outcome would still depend on remaining Orange Book patents and FDA exclusivity.

Key Takeaways

• US 10,369,144 is a core combination patent for xanomeline-trospium therapy.
• Claim 1 requires both active ingredients in a single oral capsule.
• Claims 2 through 4 cover immediate-release, controlled-release, and mixed-release designs.
• Claims 11 and 13 specifically protect 20 mg of trospium chloride.
• Claims 12 through 14 directly target twice-daily schizophrenia treatment.
• Claim 16 provides broader CNS indication coverage beyond the initial schizophrenia approval.
• Cobenfy is a small-molecule drug; biosimilar provisions do not apply.
• FDA NCE exclusivity is expected to expire before the patent's ordinary December 2035 term.
• The main generic strategies are Paragraph IV litigation, separate-capsule delivery, formulation redesign, and label carve-out.
• The key legal vulnerabilities are obviousness, enablement, written description, and interpretation of the functional side-effect limitations.
• The patent should be analyzed with later Cobenfy formulation, method, process, and regulatory patents rather than in isolation.

FAQs

Can a generic avoid US 10,369,144 by putting xanomeline and trospium in separate capsules?

Potentially. Separate capsules would not ordinarily satisfy the single-capsule limitation in claim 1, but the product could face other patents and regulatory barriers.

Does US 10,369,144 cover xanomeline alone?

No. The asserted composition claims require xanomeline or a salt together with trospium chloride. A xanomeline-only product would not satisfy the claimed combination.

Does the patent cover trospium salts other than trospium chloride?

The supplied claims specifically require trospium chloride. They do not expressly cover every trospium salt.

Can claim 16 support future Cobenfy approval for Alzheimer's disease?

Claim 16 provides patent coverage for treatment of specified CNS disorders, but it does not establish FDA efficacy, safety, or approval. Regulatory approval would require separate clinical and FDA review.

Is US 10,369,144 a formulation patent or a method-of-use patent?

It is both. Claims 1 through 11 and 15 are composition or formulation claims. Claims 12 through 14 and 16 are treatment-method claims.

References

1. United States Patent No. 10,369,144, “Compositions and methods for treating CNS disorders.” U.S. Patent and Trademark Office.
2. U.S. Food and Drug Administration. (2024). Cobenfy (xanomeline and trospium chloride) prescribing information.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book.
4. Hatch-Waxman Amendments, 21 U.S.C. § 355(j).
5. Bristol Myers Squibb. (2024, March 18). Bristol Myers Squibb completes acquisition of Karuna Therapeutics.

Drugs Protected by US Patent 10,369,144

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	10,369,144		Y			TREATMENT OF SCHIZOPHRENIA IN ADULTS
Bristol-myers	COBENFY	trospium chloride; xanomeline tartrate	CAPSULE;ORAL	216158-002	Sep 26, 2024		RX	Yes	No	10,369,144		Y			TREATMENT OF SCHIZOPHRENIA IN ADULTS
Bristol-myers	COBENFY	trospium chloride; xanomeline tartrate	CAPSULE;ORAL	216158-003	Sep 26, 2024		RX	Yes	No	10,369,144		Y			TREATMENT OF SCHIZOPHRENIA IN ADULTS

International Family Members for US Patent 10,369,144

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	2804215
Denmark	3061821
European Patent Office	2456868
European Patent Office	3061821