US Patent 10,265,311: Scope, Claims, Expiration, Orange Book Status, and Cobenfy Patent Landscape

US Patent 10,265,311 protects oral combination treatment with xanomeline and trospium chloride for specified central nervous system disorders. Its broadest claim covers daily xanomeline doses from 75 mg to 300 mg combined with 20 mg to 200 mg of trospium chloride. The patent directly overlaps the approved Cobenfy treatment regimen for schizophrenia and is a core patent risk for any generic or follow-on product containing both active ingredients.

The patent was granted to Karuna Therapeutics, now part of Bristol Myers Squibb, on April 23, 2019. Its expected expiration date is August 30, 2033, subject to any applicable patent-term adjustment or extension reflected in official records. Cobenfy received FDA approval on September 26, 2024, for adults with schizophrenia. FDA-listed regulatory exclusivity extends beyond the patent’s grant date and creates a separate market-entry barrier through at least 2029.

What does US Patent 10,265,311 protect?

The patent protects a method of treating a CNS disorder by orally administering xanomeline and trospium chloride within specified daily dose ranges.

Claim element	Scope under claim 1
Administration route	Oral
Xanomeline dose	75 mg to 300 mg during 24 hours
Trospium chloride dose	20 mg to 200 mg during 24 hours
Covered disorders	Schizophrenia, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, or Lewy body dementia
Combination purpose	Trospium must alleviate a side effect associated with xanomeline
Product relationship	Both agents may be administered in the same or different dosage vehicles

The claim is a method-of-treatment claim rather than a claim limited to a particular capsule composition, excipient system, salt form, manufacturing process, or commercial product configuration.

The central inventive concept is the use of peripheral muscarinic antagonism from trospium chloride to reduce adverse effects associated with xanomeline while retaining xanomeline’s central muscarinic activity. Trospium’s poor central nervous system penetration is relevant to the claimed therapeutic strategy because it is intended to reduce peripheral cholinergic adverse effects without materially blocking xanomeline’s central activity.

How broad is claim 1 of US 10,265,311?

Claim 1 is broad in three respects.

First, it covers five distinct CNS disorders. The claim does not require schizophrenia. It reaches Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and Lewy body dementia as well.

Second, the dose ranges are broad. The xanomeline range extends from 75 mg to 300 mg per 24 hours. The trospium range extends from 20 mg to 200 mg per 24 hours. A product or regimen can fall within the claim even if its exact dose differs from the approved commercial regimen, provided the total daily amounts remain within the claimed ranges.

Third, the claim permits separate dosage vehicles. A single fixed-dose combination is not required. Separate xanomeline and trospium products administered during the same 24-hour period can potentially satisfy the claim.

The key limiting language is the requirement that trospium chloride alleviate a side effect associated with xanomeline. A claimant would generally need to establish that the administered trospium is used for that functional purpose. For a product expressly labeled as a xanomeline-trospium combination intended to reduce xanomeline-related adverse effects, this limitation presents a lower practical barrier than it would for an unrelated coadministration regimen.

What do claims 2 through 15 add?

The dependent claims create narrower positions around the disorders, doses, administration schedules, and dosage vehicles.

Claims	Added limitation	Commercial significance
2	Schizophrenia	Directly aligned with the FDA-approved Cobenfy indication
3	Alzheimer’s disease	Covers a non-approved disease use within the patent
4	Huntington’s disease	Covers a non-approved disease use
5	Parkinson’s disease	Covers a non-approved disease use
6	Lewy body dementia	Covers a non-approved disease use
7	225 mg xanomeline and 20-60 mg trospium daily	Narrow dose position
8	Same dosage vehicle	Supports a fixed-dose combination theory
9	Different dosage vehicles	Covers coadministration of separate products
10	Xanomeline administered three times daily	Regimen-specific protection
11	Trospium administered twice daily	Regimen-specific protection
12	20-60 mg trospium daily	Lower trospium dose band
13	60-200 mg trospium daily	Higher trospium dose band
14	75-225 mg xanomeline and 20-60 mg trospium daily	Narrower combined dose range
15	300 mg xanomeline and 60-200 mg trospium daily	High-dose regimen

Claims 8 and 9 are alternative positions. Claim 8 covers administration in one dosage vehicle, while claim 9 covers separate dosage vehicles. This drafting reduces the ability of a potential entrant to avoid the patent solely by changing the physical presentation of the two active ingredients.

Claims 12 and 13 divide the trospium range into lower and higher dose bands, with an overlap at 60 mg. Claims 7 and 14 focus on dose combinations that are narrower than claim 1. Claim 15 protects the upper end of the xanomeline range.

Does US 10,265,311 cover Cobenfy?

Yes. The patent’s claim structure overlaps the approved Cobenfy regimen.

Cobenfy contains xanomeline and trospium chloride and is administered orally. FDA labeling provides twice-daily dosing with titration across capsule strengths. The labeled maintenance regimen of 125 mg xanomeline and 30 mg trospium chloride per dose produces a total daily dose of 250 mg xanomeline and 60 mg trospium chloride. That falls within claim 1’s daily ranges and within several narrower claim positions.

Cobenfy characteristic	Relationship to US 10,265,311
Oral administration	Meets the route limitation
Xanomeline-trospium combination	Meets the combination requirement
Daily xanomeline amount	Within the 75-300 mg range under labeled dosing
Daily trospium amount	Within the 20-200 mg range
Schizophrenia treatment	Expressly covered by claim 2
Twice-daily administration	Consistent with claim 11 for trospium
Peripheral side-effect management	Corresponds to the claimed purpose of trospium

The commercial product therefore provides a practical infringement reference point for claims 1, 2, 7, 8 or 9, 11, 12, and 14, depending on the precise dosage form and formulation.

What is the expiration date of US Patent 10,265,311?

US Patent 10,265,311 has an expected expiration date of August 30, 2033, based on its underlying priority and filing chronology. The patent was granted on April 23, 2019. The relevant term is measured from the applicable nonprovisional or international filing date, not from the grant date. The USPTO patent record and FDA Orange Book should control for any patent-term adjustment, terminal disclaimer, or later correction.[1][2]

The patent’s effective commercial value is also affected by:

FDA regulatory exclusivity for Cobenfy;
other Orange Book-listed patents;
pending continuation applications;
formulation or dosage-form patents;
method-of-use patents;
potential pediatric exclusivity;
the timing and content of any ANDA Paragraph IV certification.

Patent expiry in 2033 does not necessarily represent the earliest possible generic entry date. A generic applicant could challenge the patent before expiration, while a settlement could establish an earlier licensed-entry date.

What is the Orange Book status of US 10,265,311?

US 10,265,311 is associated with the Cobenfy product and is listed as a relevant patent for the xanomeline and trospium chloride combination. The listing gives the patent practical importance under the Hatch-Waxman framework because an ANDA applicant seeking approval for a product referencing Cobenfy must address listed patents through the applicable certification pathway.[2][3]

The relevant certification options include:

Certification	Effect
Paragraph I	No patent information has been submitted
Paragraph II	Patent has expired
Paragraph III	Applicant will wait until patent expiration
Paragraph IV	Patent is invalid, unenforceable, or will not be infringed
Section viii statement	Applicant seeks approval for a use not covered by a listed method-of-use patent

For a full-combination generic containing both xanomeline and trospium chloride, a Paragraph III certification would defer approval until patent expiry unless the applicant successfully challenges the patent or reaches a settlement. A Paragraph IV certification would create litigation risk and could trigger a 30-month stay if the patent owner files an infringement action within the statutory period.[3]

When does Cobenfy lose FDA exclusivity?

Cobenfy was approved on September 26, 2024, for the treatment of schizophrenia in adults.[4] Because xanomeline had not previously received FDA approval as an active moiety, the product received new chemical entity exclusivity. The five-year NCE period is generally expected to run through September 26, 2029, subject to FDA’s official exclusivity coding and any pediatric extension.

Protection	Expected timing
FDA approval	September 26, 2024
Five-year NCE exclusivity	Approximately through September 26, 2029
US Patent 10,265,311	Approximately through August 30, 2033
Potential generic entry under ordinary patent expiry	After applicable patent expiry and regulatory requirements
Earlier entry	Possible through successful challenge or settlement

NCE exclusivity does not prevent a competitor from filing an ANDA or submitting a patent challenge during the exclusivity period. It restricts FDA approval of certain abbreviated applications during the statutory exclusivity window.

What generic entry risks exist for Cobenfy?

The highest-risk generic scenario is a product that reproduces the full xanomeline-trospium combination, uses oral administration, and targets schizophrenia. Such a product would likely fall within claim 1 and claim 2 if its daily doses remain in the claimed ranges.

A generic applicant could pursue several strategies:

Challenge the validity of the patent under anticipation, obviousness, written description, enablement, or subject-matter eligibility theories.
Argue that the proposed regimen does not satisfy the side-effect-alleviation limitation.
Design a dose outside the claimed ranges, although this may conflict with the FDA-approved regimen.
Seek a section viii carveout for unclaimed or non-patented uses where legally available.
Develop a non-combination product, such as xanomeline alone, if clinically and commercially viable.
Negotiate a settlement providing a specified launch date before patent expiry.

The dose-design option is commercially weak for a direct Cobenfy substitute because the approved product’s dosing falls squarely within the principal claim ranges. Avoiding the patent by changing the vehicle is also difficult because claim 1 is not limited to a single dosage vehicle, and claims 8 and 9 cover both same-vehicle and separate-vehicle administration.

Which companies are challenging the Cobenfy patent estate?

No publicly established Paragraph IV litigation or settlement involving US 10,265,311 is identified in the patent and FDA materials cited here. The absence of a reported case does not eliminate future challenge risk. The principal potential challengers are generic pharmaceutical companies with experience in complex oral combinations and CNS products.

A generic applicant would face a more substantial development burden than an ordinary single-active-ingredient ANDA applicant because it would need to demonstrate bioequivalence for a combination containing xanomeline and trospium chloride and address the relevant patent listings.

No biosimilar pathway applies. Cobenfy is a small-molecule drug, so any follow-on product would proceed through an ANDA, a 505(b)(2) application, or a full NDA rather than the biologics license application pathway.

How strong is the patent estate for xanomeline and trospium?

US 10,265,311 is commercially strong against the approved combination because the claim captures the product’s route, active ingredients, therapeutic indication, and daily dose range. Its main vulnerabilities are legal rather than design-based.

Strengths

The broad claim covers the FDA-approved schizophrenia use.
The claimed dose ranges encompass the marketed regimen.
Separate or combined dosage vehicles are covered.
The claim identifies a specific therapeutic rationale for trospium.
Dependent claims create multiple narrower positions.
The patent has a long remaining term after Cobenfy approval.

Potential weaknesses

The active ingredients and their pharmacology may create prior-art issues.
The functional limitation concerning side-effect alleviation may require factual proof.
Method claims can face divided-infringement issues if prescribing, dispensing, and administration are performed by different actors.
Claims covering multiple disorders may face written-description or enablement challenges if the specification does not adequately support every claimed disease.
The patent does not itself establish protection for every formulation, manufacturing process, or chemical form of the commercial product.

The patent should therefore be evaluated as one layer of a broader portfolio rather than as the entire Cobenfy exclusivity position.

What formulation and manufacturing patents may protect Cobenfy?

The 10,265,311 patent is principally a therapeutic-use patent. It does not, based on the supplied claims, require:

a particular excipient;
a specific capsule shell;
a defined dissolution profile;
a particular particle-size distribution;
a specific manufacturing process;
a salt or polymorph beyond the stated trospium chloride;
a particular xanomeline-to-trospium release profile.

Separate patent families may protect these technical features. Such patents can create additional barriers even if a challenger avoids the method claims. The most commercially relevant adjacent rights would cover fixed-dose capsules, stability, impurity control, immediate-release delivery, combination packaging, and manufacturing processes for xanomeline-containing dosage forms.

A freedom-to-operate review must therefore compare the proposed product against the complete USPTO and Orange Book portfolio, not only US 10,265,311.

What litigation and settlement issues affect generic entry?

A Paragraph IV notice concerning US 10,265,311 could lead to district-court litigation by the patent owner. The principal legal issues would likely include:

obviousness of combining xanomeline with trospium;
whether the prior art disclosed the claimed dose ranges;
whether the prior art taught the claimed side-effect reduction;
written-description support for all five CNS disorders;
enablement across the broad dose and disease ranges;
infringement under a proposed generic label;
whether the proposed product’s prescribing information induces use of the patented method.

A settlement could specify a launch date before August 30, 2033. It could also include a license, supply arrangement, authorized-generic commitment, or restrictions tied to particular indications. No publicly reported settlement specific to this patent is identified in the cited records.

How does US 10,265,311 compare with ordinary CNS drug patents?

US 10,265,311 has a broader therapeutic-use profile than a patent limited to one indication, but it is narrower than a composition-of-matter patent covering xanomeline or a proprietary fixed-dose formulation.

Patent type	Relevance to Cobenfy
Composition of matter	Usually the strongest protection, but not represented by the supplied claims
Combination composition	Could protect the physical product
Method of treatment	US 10,265,311 falls in this category
Formulation	Could protect capsule technology or release characteristics
Manufacturing process	Could restrict production routes
Method of use	Can protect schizophrenia or other disease-specific uses
Regulatory exclusivity	Separately delays approval of certain applications

The patent’s commercial value comes from its alignment with the approved product, not from control over xanomeline as a chemical entity in every use.

Key Takeaways

US Patent 10,265,311 covers oral xanomeline plus trospium chloride for five CNS disorders.
Claim 1 covers 75-300 mg of xanomeline and 20-200 mg of trospium chloride per 24 hours.
The claims cover both fixed-dose and separately administered products.
The approved Cobenfy schizophrenia regimen falls within the principal claim ranges.
The patent was granted on April 23, 2019, and is expected to expire on August 30, 2033.
Cobenfy was FDA-approved on September 26, 2024, with expected five-year NCE exclusivity through approximately September 26, 2029.
The patent creates substantial risk for a full-combination generic using the approved oral dosing regimen.
No biosimilar pathway applies because Cobenfy is a small-molecule product.
Additional formulation, manufacturing, and continuation patents may materially extend or strengthen the overall exclusivity position.
No publicly reported Paragraph IV litigation or settlement specific to US 10,265,311 is identified in the cited materials.

FAQs

Can a generic avoid US 10,265,311 by selling xanomeline and trospium in separate packages?

Not necessarily. Claim 9 expressly covers administration in different dosage vehicles. Separate packaging alone would not avoid infringement if the proposed use otherwise satisfies the claim elements.

Does US 10,265,311 cover xanomeline monotherapy?

No. The supplied claims require administration of both xanomeline and trospium chloride. A xanomeline-only product would not literally satisfy the combination limitation, although other patents or regulatory theories could remain relevant.

Does the patent cover treatment of dementia with Lewy bodies?

Yes. Claim 6 specifically narrows claim 1 to Lewy body dementia. The FDA-approved Cobenfy indication, however, is schizophrenia, not Lewy body dementia.

Can an ANDA applicant file a Paragraph IV certification before 2033?

Yes. A Paragraph IV certification can challenge a listed patent before expiration. The patent owner may then file infringement litigation, potentially triggering the statutory 30-month stay under the Hatch-Waxman Act.

Is trospium chloride itself protected by this patent?

The supplied claims do not claim trospium chloride as a standalone chemical entity. They claim its use together with xanomeline in specified treatment methods and dose ranges.

References

United States Patent and Trademark Office. (2019). U.S. Patent No. 10,265,311, Methods of treating central nervous system disorders.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
Drug Price Competition and Patent Term Restoration Act of 1984, 21 U.S.C. § 355(j).
U.S. Food and Drug Administration. (2024, September 26). FDA approves drug with novel mechanism for treating schizophrenia.
Bristol Myers Squibb. (2023). Bristol Myers Squibb to acquire Karuna Therapeutics.

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	⤷ Start Trial	⤷ Start Trial				TREATMENT OF SCHIZOPHRENIA IN ADULTS	⤷ Start Trial
Bristol-myers	COBENFY	trospium chloride; xanomeline tartrate	CAPSULE;ORAL	216158-002	Sep 26, 2024		RX	Yes	No	⤷ Start Trial	⤷ Start Trial				TREATMENT OF SCHIZOPHRENIA IN ADULTS	⤷ Start Trial
Bristol-myers	COBENFY	trospium chloride; xanomeline tartrate	CAPSULE;ORAL	216158-003	Sep 26, 2024		RX	Yes	No	⤷ Start Trial	⤷ Start Trial				TREATMENT OF SCHIZOPHRENIA IN ADULTS	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

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

Details for Patent: 10,265,311

Which drugs does patent 10,265,311 protect, and when does it expire?

Summary for Patent: 10,265,311