US Patent 10,966,941: Claim Scope, Auvelity Coverage, Expiration Risk, and Patent Landscape

US Patent 10,966,941 is a method-of-treatment patent covering repeated oral administration of a dextromethorphan-bupropion dosage form to dextromethorphan extensive metabolizers. Its commercial relevance is high because the claimed dose range, administration frequency, eight-day pharmacokinetic profile, and immediate-release dextromethorphan/sustained-release bupropion architecture substantially correspond to the approved Auvelity product. The claims are narrower than a basic composition claim because infringement depends on patient population, dosing duration, formulation characteristics, and measured or attributable dextromethorphan exposure.

What does US Patent 10,966,941 protect?

The patent protects methods for pharmacokinetically increasing dextromethorphan exposure by co-administering dextromethorphan with bupropion. The central mechanism is bupropion-mediated inhibition of CYP2D6, the principal enzyme responsible for dextromethorphan metabolism.

The independent claims require the following elements:

Claim requirement	Claims 1, 7, and 16
Active ingredients	Bupropion and dextromethorphan
Route	Oral administration
Frequency	Once or twice daily
Patient	Human dextromethorphan extensive metabolizer
Treatment need	Patient must need treatment with dextromethorphan
Bupropion dose	About 100 mg to about 200 mg
Dextromethorphan dose	About 40 mg to about 60 mg
Duration	At least eight consecutive days
Day-eight exposure	Specified dextromethorphan AUC and/or Cmax
Comparator	Same amount of dextromethorphan administered without bupropion
Additional formulation limitation in claim 16	AUC0-24 of about 1,300 mg·hr/mL to about 2,975 ng·hr/mL

The patent therefore does not broadly cover every dextromethorphan-bupropion combination. It covers administration that produces the specified pharmacokinetic result under the claimed regimen.

How do the independent claims differ?

Claim 1: Cmax-centered method claim

Claim 1 requires an AUC0-24 of at least about 1,300 ng·hr/mL and a day-eight dextromethorphan Cmax at least 15 times higher than the Cmax produced by dextromethorphan alone.

This is a relative pharmacokinetic limitation. A product may fall within the literal scope even if the absolute Cmax differs between patients, provided the claimed comparison is satisfied for the relevant patient or study population.

Claim 7: AUC-centered method claim

Claim 7 requires an AUC0-24 of about 1,900 ng·hr/mL and at least a 15-fold increase over dextromethorphan administered without bupropion.

The “about 1,900 ng·hr/mL” limitation is potentially narrower than the “at least about 1,300 ng·hr/mL” limitation in claim 1. Claim 7 also creates a separate claim family for dosage forms with separate domains, layers, or phases.

Claim 16: AUC range and formulation pathway

Claim 16 requires an AUC0-24 range of about 1,300 ng·hr/mL to about 2,975 ng·hr/mL and at least a 15-fold increase over dextromethorphan alone.

This claim may be commercially important because it captures a defined exposure window rather than merely a lower threshold. A competing product with unusually high dextromethorphan exposure could satisfy claim 1 while falling outside claim 16 if the exposure exceeds the claimed upper range.

Does the patent cover Auvelity?

Auvelity contains dextromethorphan hydrobromide and bupropion hydrochloride. Each tablet contains 45 mg of dextromethorphan hydrobromide and 105 mg of bupropion hydrochloride, administered orally. The FDA-approved regimen is one tablet once daily for the first three days, followed by one tablet twice daily.[2]

The commercial dose is within the principal numerical ranges in US 10,966,941:

Auvelity characteristic	Patent claim requirement	Alignment
Dextromethorphan	45 mg	Within 40-60 mg
Bupropion	105 mg	Within 100-200 mg
Maintenance frequency	Twice daily	Within once or twice daily
Duration	Chronic treatment	Exceeds eight consecutive days
Release architecture	Immediate-release dextromethorphan and extended-release bupropion	Corresponds to dependent claims 10 and 19
Patient population	Patients receiving dextromethorphan treatment	Potentially includes extensive metabolizers

The product’s label states that bupropion inhibits CYP2D6 and increases dextromethorphan exposure.[2] That pharmacology is consistent with the claimed method. However, product-dose alignment alone does not establish infringement of every limitation. A method claim also requires the relevant patient population and pharmacokinetic limitations.

What formulations are protected by US 10,966,941?

The patent protects both the active-ingredient combination and particular release arrangements.

Immediate-release dextromethorphan and sustained-release bupropion

Claims 10 and 19 require a dosage form in which:

the bupropion is released in a sustained manner; and
the dextromethorphan is released immediately.

This architecture is commercially significant. It permits rapid dextromethorphan availability while maintaining bupropion exposure over a longer period. A competitor using the same active ingredients but a materially different release design may avoid these dependent claims while remaining exposed to the broader independent claims.

Separate domains, layers, or phases

Claim 9 requires bupropion and dextromethorphan to be located in separate domains, layers, or phases. The language is broad enough to encompass multilayer tablets, physically separated matrix regions, multiparticulates, or other dosage-form structures, subject to construction of “domain,” “layer,” and “phase.”

A single homogeneous matrix may fall outside claim 9 if it does not contain the ingredients in separate structural regions. It could still implicate claims 1, 7, or 16 if the pharmacokinetic limitations are satisfied.

Deuterium-modified compounds

Claim 20 covers a formulation in which dextromethorphan or bupropion is deuterium-modified. This dependent claim expands the technical scope to isotope-modified active ingredients, although the commercial value depends on whether a competing product uses a deuterated molecule and still meets the exposure requirements.

How do the dependent claims expand infringement risk?

Claims	Added limitation	Commercial significance
2, 17	42-48 mg dextromethorphan and 100-140 mg bupropion	Closely tracks a 45 mg/105 mg commercial dose
3	At least 20-fold Cmax increase	Captures higher exposure regimens
4	Cmin of at least 40 ng/mL	Adds trough-concentration coverage
5	Cmax of at least 50 ng/mL	Adds peak-concentration coverage
6, 8, 18	AUC0-12 requirements	Provides an alternative exposure metric
9	Separate domains, layers, or phases	Covers physically segregated dosage forms
10, 19	Sustained-release bupropion and immediate-release dextromethorphan	Targets the Auvelity-type release profile
11, 12, 21, 22	Patient at risk of an adverse event from dextromethorphan or bupropion	Adds a patient-selection limitation
13	At least 30 consecutive days	Covers longer treatment courses
14	Conversion to a dextromethorphan poor metabolizer	Claims the pharmacologic phenoconversion effect
15	Patient is at least 18 years old	Narrows coverage to adults
20	Deuterium-modified active ingredient	Extends coverage to isotopologues

Claims 2 and 17 are particularly relevant to Auvelity because the 45 mg dextromethorphan and 105 mg bupropion doses fall directly inside their narrower ranges.

How strong is the patent estate based on the claims?

The patent is commercially strong against products that copy the approved Auvelity regimen, but its legal strength depends on proof of the pharmacokinetic limitations.

Strengths

Close dose alignment. The 45 mg/105 mg combination falls inside the narrower dependent-claim ranges.
Regimen alignment. Once- or twice-daily oral dosing and treatment beyond eight days fit chronic administration.
Mechanism alignment. Bupropion’s CYP2D6 inhibition explains the claimed increase in dextromethorphan exposure.
Multiple claim pathways. The patent uses AUC, Cmax, Cmin, release design, patient phenotype, and treatment duration.
Method-of-use coverage. An ANDA applicant seeking approval for the same treatment method may face a Paragraph IV certification issue if the patent is listed for the relevant drug product.

Vulnerabilities

Pharmacokinetic proof. The comparator requires determining what Cmax or AUC would result from the same dextromethorphan dose without bupropion for eight days.
Patient variability. CYP2D6 genotype, phenoconversion, adherence, food, age, concomitant drugs, and renal or hepatic function can materially affect exposure.
“About” limitations. Terms such as “about 1,900 ng·hr/mL,” “about 15 times,” and “about 20 times” may require claim construction.
Patient-status limitations. The accused patient must be an extensive metabolizer or otherwise fall within the claimed phenotype before treatment.
Indefiniteness and enablement issues. A challenger could argue that the claims do not provide sufficiently predictable boundaries across the full dose and patient ranges.
Written-description issues. The broad dosage, exposure, and patient combinations must be supported by the specification and priority disclosure.

The patent is stronger for products that reproduce the specified 45 mg/105 mg regimen and release profile than for products using different doses, dosing intervals, or delivery systems.

When does US Patent 10,966,941 lose exclusivity?

The patent grant date was March 30, 2021. The patent’s exact expiration date cannot be determined from the claim text alone because expiration depends on the earliest effective nonprovisional filing date, patent-term adjustment, terminal disclaimers, and any applicable patent-term extension.[1]

The relevant term analysis is:

Exclusivity item	Status
Patent number	US 10,966,941
Patent type	Utility patent
Grant date	March 30, 2021
Statutory term	Generally 20 years from the earliest effective nonprovisional filing date
PTA/PTE	Must be checked in the USPTO patent record
Orange Book effect	Depends on FDA listing and the relevant approved product
Regulatory exclusivity	Separate from patent term

A patent expiration date should not be calculated by adding 20 years to the grant date. Generic-entry analysis must use the USPTO continuity data and any terminal-disclaimer or adjustment information.

What is the Orange Book status and Paragraph IV risk?

Auvelity is an FDA-approved small-molecule drug, not a biologic. A follow-on applicant would generally use the ANDA pathway rather than a biosimilar application.[2,3]

The likely certification framework is:

Certification	Effect
Paragraph I	No patent information listed
Paragraph II	Listed patent has expired
Paragraph III	Applicant will wait until patent expiration
Paragraph IV	Applicant asserts that the patent is invalid, unenforceable, or not infringed

For a product seeking approval before expiration of a listed method or formulation patent, a Paragraph IV certification could trigger a patent-infringement suit under 35 U.S.C. §271(e)(2). A timely suit can create a statutory stay of FDA approval, subject to the Hatch-Waxman framework.[3]

The practical risk is highest for an ANDA that duplicates:

45 mg dextromethorphan;
105 mg bupropion;
twice-daily maintenance dosing;
immediate-release dextromethorphan;
sustained-release bupropion; and
the labeled depression indication.

A “section viii” carve-out may be relevant only if the applicant can omit the patented method while retaining an approvable, non-infringing indication and labeling. That strategy is difficult where the patent’s method limitations map directly onto the approved regimen.

Which companies are challenging the patent?

A reliable assessment of challengers requires current USPTO, FDA Orange Book, and federal court records. The claim text does not identify Paragraph IV filers, ANDA numbers, litigation defendants, or settlement agreements. No challenger, lawsuit, or settlement should be attributed to a company solely from US 10,966,941.

The relevant litigation venues would ordinarily include:

the District of Delaware;
the District of New Jersey;
the Southern District of New York; and
other districts where an ANDA applicant or patent holder files under Hatch-Waxman procedures.

How does this patent compare with broader dextromethorphan-bupropion patents?

US 10,966,941 is narrower than a composition-of-matter patent covering the active combination. Its claims depend on administration to a person and on measured exposure after repeated dosing.

Patent category	Typical scope	Relevance to US 10,966,941
Composition patent	Covers the chemical combination or dosage form itself	Potentially broader than this patent
Formulation patent	Covers release profile, layers, matrix, or tablet structure	Overlaps claims 9, 10, and 19
Method-of-use patent	Covers treatment of a disease or patient group	This patent is primarily a PK-based method patent
PK or dose-regimen patent	Covers exposure, dosing frequency, or metabolic effect	Directly aligned with claims 1, 7, and 16
Manufacturing patent	Covers granulation, coating, compression, or process parameters	Not expressly claimed in the supplied claims

The patent can operate as a meaningful barrier even if a competitor avoids a separate formulation claim. A competing dosage form could still infringe an independent method claim if it delivers the required doses and exposure.

What generic launch scenarios exist?

Scenario 1: Same-dose ANDA

A 45 mg/105 mg product with the same twice-daily regimen presents the highest risk. The applicant would likely need to address the PK, dosing, and formulation claims through Paragraph IV litigation, a Paragraph III certification, or a labeling strategy.

Scenario 2: Different dose

A product outside the 40-60 mg dextromethorphan and 100-200 mg bupropion ranges may avoid literal infringement. It could remain exposed under the doctrine of equivalents, depending on the difference and prosecution history.

Scenario 3: Different release technology

A formulation without sustained-release bupropion or immediate-release dextromethorphan may avoid claims 10 and 19. It could still face claims 1, 7, or 16 if the dosing and exposure limitations are met.

Scenario 4: Dextromethorphan-only product

A dextromethorphan product without bupropion would not practice the combination requirement. It would not satisfy the literal active-ingredient limitations of the supplied claims.

Scenario 5: Different indication or carved-out labeling

A narrow label may reduce method-of-use exposure, but the claims are framed around treatment with dextromethorphan and PK enhancement rather than a disease-specific indication. That may limit the usefulness of a labeling carve-out.

Key Takeaways

US 10,966,941 is a PK-driven method patent covering repeated oral dextromethorphan-bupropion administration.
The commercial 45 mg dextromethorphan/105 mg bupropion regimen falls within the narrower dose ranges of claims 2 and 17.
Auvelity’s immediate-release dextromethorphan and sustained-release bupropion architecture corresponds to claims 10 and 19.
The principal infringement dispute would likely concern the day-eight AUC/Cmax limitations, comparator methodology, patient metabolizer status, and formulation release profile.
The patent is a small-molecule Hatch-Waxman issue, not a biosimilar issue.
Exact patent expiration, Orange Book listings, Paragraph IV filers, litigation, and settlements require current USPTO, FDA, and court-record verification and cannot be established from the supplied claims.

FAQs

Can a generic avoid US 10,966,941 by using once-daily dosing?

Not necessarily. Claims 1, 7, and 16 expressly cover once- or twice-daily administration. Once-daily dosing would need to avoid another limitation, such as the dose range or day-eight exposure requirement.

Does the patent cover dextromethorphan monotherapy?

No. The supplied claims require a dosage form containing both bupropion and dextromethorphan.

Is a 45 mg/105 mg tablet automatically infringing?

No. The dose falls within the claimed ranges, but method infringement also requires the claimed administration schedule, patient characteristics, treatment duration, and pharmacokinetic limitations.

Can a different bupropion salt avoid the patent?

Not automatically. The claims recite bupropion and dextromethorphan, while the specification and prosecution history would determine whether particular salts fall within those terms.

Does a biosimilar pathway apply to Auvelity?

No. Auvelity is an FDA-approved small-molecule drug. A follow-on applicant would generally pursue an ANDA rather than a biosimilar application.

References

U.S. Patent and Trademark Office. (2021). U.S. Patent No. 10,966,941.
U.S. Food and Drug Administration. (2022). Auvelity prescribing information. Axsome Therapeutics, Inc.
U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations.
35 U.S.C. §§ 156, 271(e)(2), 282.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Axsome	AUVELITY	bupropion hydrochloride; dextromethorphan hydrobromide	TABLET, EXTENDED RELEASE;ORAL	215430-001	Aug 18, 2022		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial				DEXTROMETHORPHAN AND BUPROPION IN COMBINATION TO TREAT MAJOR DEPRESSIVE DISORDER	⤷ Start Trial
Axsome	AUVELITY	bupropion hydrochloride; dextromethorphan hydrobromide	TABLET, EXTENDED RELEASE;ORAL	215430-001	Aug 18, 2022		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial				THE TREATMENT OF AGITATION ASSOCIATED WITH DEMENTIA DUE TO ALZHEIMER’S DISEASE BY INCREASING DEXTROMETHORPHAN PLASMA LEVELS IN EXTENSIVE METABOLIZERS OF DEXTROMETHORPHAN	⤷ 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
Australia	2014346807	⤷ Start Trial
Australia	2015350559	⤷ Start Trial
Australia	2018203638	⤷ Start Trial
Australia	2019201548	⤷ Start Trial
Australia	2019223187	⤷ Start Trial
Australia	2019236614	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,966,941

Which drugs does patent 10,966,941 protect, and when does it expire?

Summary for Patent: 10,966,941