United States Patent 10,925,842: Scope, Claims, Expiration and Auvelity Patent Landscape

U.S. Patent No. 10,925,842 protects selected treatment methods using combined bupropion and dextromethorphan for major depressive disorder. The core regimen is approximately 105 mg of bupropion hydrochloride plus 45 mg of dextromethorphan hydrobromide, administered once daily for three days and twice daily thereafter. The patent is assigned to Axsome Therapeutics and is associated with Auvelity, the FDA-approved dextromethorphan-bupropion product.

The patent’s practical value comes from its method-of-treatment structure. It does not claim bupropion or dextromethorphan as chemical entities. It claims use of the combination in a defined patient population, at defined doses and frequencies, with efficacy and pharmacokinetic limitations. The patent is listed in the FDA Orange Book and has an expiration date in 2037, subject to patent-term adjustments or other applicable statutory changes. [1][2]

What does U.S. Patent 10,925,842 protect?

The independent claim protects a method of treating major depressive disorder when all of the following conditions are met:

Claim element	Requirement
Disease	Major depressive disorder
Patient	Human being who received prior first-line treatment during the current depressive episode
Bupropion dose	About 105 mg bupropion hydrochloride, or molar equivalent in another salt or free-base form
Dextromethorphan dose	About 45 mg dextromethorphan hydrobromide, or molar equivalent in another salt or free-base form
Initial regimen	Once daily for the first three days
Continuing regimen	Twice daily thereafter for at least 11 days
Comparator	Greater MADRS reduction than the same amount of bupropion alone
Treatment endpoint	Reduction in depressive symptoms, measured in part by MADRS

The claim is directed to a treatment protocol rather than a particular brand, manufacturer, tablet design or route of manufacture. A product that uses different excipients or a different manufacturer can still implicate the patent if the administered regimen satisfies the claim limitations.

The claim also reaches equivalent salt forms. A defendant cannot ordinarily avoid the dose limitation merely by using bupropion free base, a different bupropion salt, dextromethorphan free base or another dextromethorphan salt if the amount is molarly equivalent to the claimed quantities.

How broad is claim 1 of Patent 10,925,842?

Claim 1 is commercially meaningful but narrower than a general claim to any bupropion-dextromethorphan combination.

Its main narrowing limitations are:

The indication must be major depressive disorder.
The patient must have received prior first-line treatment during the current episode.
The regimen must use approximately 105 mg of bupropion and 45 mg of dextromethorphan per administration.
Each component must follow the same initial once-daily and subsequent twice-daily schedule.
The treatment must produce a greater MADRS reduction than bupropion alone.

The patient-selection limitation is important. A generic or competing product administered for another indication, or to a patient without documented prior first-line treatment, may fall outside literal infringement of claim 1. The limitation also creates factual issues concerning medical records, treatment history and the meaning of "first-line treatment."

The comparative efficacy limitation is equally significant. Claim 1 does not merely require administration of the two active ingredients. It requires a greater reduction in MADRS score than would be experienced from the same amount of bupropion alone. Claims 2 and 4 add comparisons against dextromethorphan alone and bupropion alone.

What do dependent claims 2 through 20 add?

The dependent claims create multiple fallback positions and cover product configurations, pharmacokinetics and clinical outcomes.

Efficacy and comparator claims

Claims 2 and 4 require superior efficacy against active monotherapy comparators:

Claim 2 compares the combination with the same amount of dextromethorphan alone.
Claim 4 compares the combination with 105 mg of bupropion hydrochloride administered under the same schedule.

Claims 16 through 18 add quantified or time-based outcomes:

Claim 16 requires at least a 10% MADRS reduction from baseline.
Claim 17 requires at least a 10% greater MADRS reduction than placebo.
Claim 18 requires that 10% greater reduction within two weeks of initial treatment.

Claims 19 and 20 focus on assessment timing, requiring treatment-effect assessment within two weeks or within one week after treatment begins.

These limitations can strengthen validity by tying the claims to clinical performance, but they can complicate infringement proof. A patent owner may need clinical data, patient records, statistical evidence or protocol documentation to establish the required comparative outcome.

Formulation claims

Claims 5 and 6 divide the formulation architecture:

Dextromethorphan is formulated for immediate release.
Bupropion is formulated for sustained release.

Claims 14 and 15 cover both physical configurations:

A single dosage form containing both active ingredients.
Separate dosage forms administered as part of the same combination regimen.

Claims 7 through 9 cover oral administration and solid dosage forms. These claims map closely to the commercial design of Auvelity, which uses an oral tablet containing dextromethorphan hydrobromide and sustained-release bupropion hydrochloride. [3]

Pharmacokinetic claims

Claims 10 and 11 require:

Bupropion average concentration, or Cavg, of at least about 10 ng/mL.
Bupropion maximum concentration, or Cmax, of at least about 90 ng/mL.

These claims may be difficult to assess from the outside because infringement depends on patient-specific pharmacokinetic measurements. They can have greater relevance in a patent dispute involving a formulation designed to produce materially different bupropion exposure.

What is the relationship between Patent 10,925,842 and Auvelity?

Auvelity is FDA-approved for the treatment of major depressive disorder in adults. The approved product combines dextromethorphan hydrobromide and bupropion hydrochloride in an extended-release tablet. The labeled titration begins with one tablet once daily for three days, followed by one tablet twice daily. Each tablet contains 45 mg of dextromethorphan hydrobromide and 105 mg of bupropion hydrochloride. [3][4]

That dosing schedule corresponds directly to claim 3. The commercial product therefore falls within the central dosage and administration pattern described in the patent, assuming the patient and efficacy limitations of the relevant claim are satisfied.

The patent does not require the trademark Auvelity. It covers the claimed method regardless of whether the combination is supplied under Auvelity, a generic name, a licensed product or separate tablets.

When does Patent 10,925,842 expire?

The listed patent expiration date is August 20, 2037. The patent was issued on February 23, 2021, and claims priority to an August 20, 2016 filing date. The expiration date is based on the applicable patent-term calculation reflected in public patent records and FDA listing data. [1][2]

Milestone	Date
Earliest claimed priority	August 20, 2016
Patent issuance	February 23, 2021
Listed patent expiration	August 20, 2037
Auvelity FDA approval	August 18, 2022
Anticipated small-molecule regulatory exclusivity period	Through August 18, 2025, based on the applicable three-year exclusivity framework

Regulatory exclusivity and patent exclusivity are separate. FDA exclusivity can block approval of a competing application for a defined period, while the patent can block commercial activity that falls within the claims until expiration.

What is the Orange Book status of Patent 10,925,842?

Patent 10,925,842 is listed in the FDA Orange Book for Auvelity. Orange Book listing gives an ANDA applicant notice that the patent holder considers the patent relevant to the approved drug. The listing can support a Paragraph IV certification and triggers the statutory framework governing patent notification, infringement litigation and the potential 30-month stay of ANDA approval. [2]

The patent is a method-of-use patent. Its value in an ANDA setting depends on the labeling proposed by the generic applicant. A generic applicant may seek to avoid infringement through a section viii statement that omits the patented method from labeling, but that strategy is more difficult when the patented method corresponds to the product’s principal approved indication and dosing instructions.

Which companies are challenging Auvelity’s patents?

Public reports identify Teva Pharmaceuticals as an ANDA challenger to Auvelity. Axsome Therapeutics initiated patent litigation after receiving a Paragraph IV notice concerning Auvelity-related patents, including Patent 10,925,842 and a later formulation patent, U.S. Patent No. 11,925,667. [5]

The principal litigation issues include:

Whether the proposed generic product will be labeled for the patented major-depressive-disorder regimen.
Whether the generic formulation satisfies the immediate-release dextromethorphan and sustained-release bupropion limitations.
Whether the claims are obvious in view of known use of each active ingredient.
Whether the clinical-response limitations are adequately supported and definite.
Whether the Orange Book-listed patents remain enforceable and properly listed.

A Paragraph IV notice is not a finding of invalidity or noninfringement. Patent litigation ordinarily determines whether the applicant can launch before the listed patent expires.

What patent litigation affects Auvelity generic entry?

The relevant dispute is between Axsome and Teva over an ANDA for a generic dextromethorphan-bupropion product. The litigation can delay FDA approval through the Hatch-Waxman 30-month stay unless resolved earlier by dismissal, settlement, judgment or another statutory event. [5][6]

The likely launch outcomes are:

Outcome	Commercial consequence
Axsome prevails	Generic launch is generally blocked until patent expiration, unless the judgment is limited or an earlier license applies
Teva prevails on invalidity	The challenged patent may be removed as a barrier to launch
Teva prevails on noninfringement	A design-around or proposed labeling may launch without infringing the asserted claims
Settlement	Entry date, license terms and possible launch restrictions depend on the agreement
Label carve-out	Generic entry may occur for non-patented uses if FDA accepts the omission and the remaining label avoids infringement

No public settlement should be assumed merely from the existence of the Paragraph IV litigation. The litigation itself is evidence of a commercial challenge, not a final determination concerning claim validity.

How strong is the patent estate for the dextromethorphan-bupropion combination?

The estate is stronger than Patent 10,925,842 alone because it combines a clinical-method patent with later formulation and product-related protection.

Protection category	Patent 10,925,842 position
Active ingredients	Does not claim the molecules themselves
Combination therapy	Yes
Dose regimen	Yes
Patient selection	Yes, prior first-line treatment
MADRS efficacy	Yes
Immediate-release dextromethorphan	Yes
Sustained-release bupropion	Yes
Single or separate dosage forms	Yes
Pharmacokinetic exposure	Yes
Manufacturing process	Not the primary focus of the supplied claims
Device or delivery system	Not required by the supplied claims
Biosimilar protection	Not applicable to this small-molecule product

The principal vulnerability is prior art. Bupropion was an established antidepressant, and dextromethorphan was an established active ingredient with known neuropsychiatric and pharmacologic properties. An obviousness challenge could argue that combining the agents and selecting the claimed doses would have been predictable.

Axsome’s counterargument would focus on the specific clinical combination, the observed antidepressant benefit, the patient population, the dosing schedule and the pharmacokinetic interaction created by bupropion’s inhibition of CYP2D6. The narrower claims requiring comparative MADRS results or defined exposure levels may be more defensible than a broad claim to administering both compounds.

What generic entry risks exist for Auvelity?

Generic entry faces four principal barriers:

Regulatory exclusivity, which delayed approval of competing applications after the 2022 approval.
Orange Book-listed patents, particularly the 2037-expiring method and formulation rights.
Labeling constraints, because the patented regimen overlaps with the principal approved use.
Formulation design, because the product must reproduce the desired dextromethorphan exposure while using sustained-release bupropion.

A generic could pursue a formulation that changes release characteristics, dosing frequency or labeling. That strategy would reduce literal infringement risk but could also make the product clinically and commercially different from Auvelity.

How does Patent 10,925,842 compare with formulation patents?

Patent 10,925,842 is principally a clinical-use patent. It defines who receives the combination, how much is administered, when it is administered and what treatment effect is observed.

Later formulation patents may be more focused on:

Tablet composition.
Release profiles.
Dextromethorphan and bupropion particle characteristics.
Stability.
Dissolution.
Manufacturing methods.
Product-specific pharmaceutical compositions.

A generic that avoids one formulation patent may still infringe Patent 10,925,842 if it administers the claimed combination under the patented method. Conversely, a generic could potentially design around the method patent by avoiding the claimed indication or regimen while still confronting separate formulation patents.

What are the licensing and commercial implications?

Axsome commercializes Auvelity as its proprietary product. The patent estate supports protection of a product with no biologic manufacturing barrier and no biosimilar pathway. The commercial threat is therefore an ANDA-based generic rather than biosimilar competition.

Auvelity generated approximately $89.5 million in net product revenue for Axsome in 2023, according to the company’s annual reporting. [7] The revenue exposure increases as prescribing expands because the product’s value depends heavily on maintaining branded pricing before generic entry.

A 2037 patent expiry creates a long nominal protection period, but effective market exclusivity can end earlier through:

Invalidity findings.
Noninfringement judgments.
Patent settlements.
Authorized generic arrangements.
Label carve-outs.
A competing product using a noninfringing regimen.

What geographic coverage does Patent 10,925,842 provide?

U.S. Patent 10,925,842 provides rights only in the United States. Parallel protection must be assessed separately in each jurisdiction. European, Canadian, Japanese and other national rights can differ in claim scope, prosecution history, expiration and validity.

For a global launch analysis, the key variables are:

Whether corresponding national applications were granted.
Whether the jurisdiction permits medical-use claims in the relevant form.
Whether the national claims cover the same doses and regimen.
Whether the product has regulatory approval in that jurisdiction.
Whether local patent linkage delays generic approval.

U.S. Orange Book listing does not establish protection outside the United States.

Key Takeaways

Patent 10,925,842 protects treatment of major depressive disorder with approximately 105 mg bupropion hydrochloride and 45 mg dextromethorphan hydrobromide.
The claimed regimen is once daily for three days, followed by twice-daily administration for at least 11 days.
The patient must have received prior first-line treatment in the current depressive episode.
The claims include comparative MADRS efficacy, formulation, dosage-form and pharmacokinetic limitations.
The patent is listed in the FDA Orange Book for Auvelity.
The listed expiration date is August 20, 2037.
Teva is a publicly identified ANDA challenger in litigation involving Auvelity patents.
The patent does not create biosimilar risk because Auvelity is a small-molecule combination product.
Generic entry risk depends on Paragraph IV litigation, possible label carve-outs, formulation design and settlement terms.
Patent 10,925,842 is strongest when asserted against a generic that copies the Auvelity dose, schedule, indication and patient population.

FAQs About U.S. Patent 10,925,842

Does Patent 10,925,842 cover Auvelity itself?

It covers methods of using the dextromethorphan-bupropion combination. It does not claim the chemical compounds as standalone compositions.

Can a generic avoid the patent by using separate bupropion and dextromethorphan tablets?

Not necessarily. Claim 15 expressly covers administration in separate dosage forms if the overall combination, dose, schedule and other claim limitations are satisfied.

Does the patent require sustained-release bupropion?

Claim 1 does not expressly require sustained-release bupropion, but claim 6 adds that limitation. A product can therefore raise different infringement questions under the independent claim and the dependent formulation claim.

Is dextromethorphan alone covered by this patent?

No. The supplied claims require a drug combination containing both bupropion and dextromethorphan.

Can a generic launch before 2037 if it receives FDA approval?

FDA approval alone does not eliminate patent infringement risk. A generic may launch earlier if it succeeds in litigation, obtains a license, uses a noninfringing label or otherwise avoids the enforceable claims.

References

United States Patent and Trademark Office. (2021). U.S. Patent No. 10,925,842, methods of treating depression using dextromethorphan and bupropion. USPTO Patent Center.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
U.S. Food and Drug Administration. (2022). Auvelity prescribing information. Axsome Therapeutics, Inc.
U.S. Food and Drug Administration. (2022, August 18). FDA approves new oral medication for major depressive disorder. FDA.
Axsome Therapeutics, Inc. (2024). Axsome initiates patent litigation related to AUVELITY. Company press release.
Drug Price Competition and Patent Term Restoration Act, 21 U.S.C. § 355(j).
Axsome Therapeutics, Inc. (2024). Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 for the fiscal year ended December 31, 2023. U.S. Securities and Exchange Commission.

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
>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: 10,925,842

Which drugs does patent 10,925,842 protect, and when does it expire?

Summary for Patent: 10,925,842