Details for Patent: 9,707,191

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Which drugs does patent 9,707,191 protect, and when does it expire?

Patent 9,707,191 protects AUVELITY and is included in one NDA.

This patent has one hundred and sixty-two patent family members in thirty-one countries.

Summary for Patent: 9,707,191

Title:	Compositions and methods for increasing the metabolic lifetime of dextromethorphan and related pharmacodynamic effects
Abstract:	This disclosure relates to methods administering various compounds in conjunction with dextromethorphan to a human being. Dosage forms, drug delivery systems, and methods related to dextromethorphan or dextrorphan and bupropion, hydroxybupropion, erythrohydroxybupropion, threohydroxybupropion, or a metabolite or prodrug of any of these compounds are also disclosed.
Inventor(s):	Herriot Tabuteau
Assignee:	Antecip Bioventures II LLC
Application Number:	US15/280,938
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

United States Drug Patent 9,707,191: Claim Scope, Exclusivity, Litigation Risk and Patent Landscape

U.S. Patent No. 9,707,191 protects a pharmacokinetic method for administering dextromethorphan with bupropion or specified bupropion metabolites to an extensive metabolizer. The central limitation is a measured trough concentration of at least about 20 ng/mL after nine days, with the combination producing a dextromethorphan Cmin at least 20 times higher than dextromethorphan administered alone.

The patent is commercially relevant to Auvelity, Axsome Therapeutics’ extended-release dextromethorphan hydrobromide/bupropion hydrochloride product approved for major depressive disorder. The claims are method-of-treatment claims rather than composition-of-matter claims. Their practical value depends on whether a competing product or treatment protocol satisfies the dose, patient-metabolism, duration, dosage-form and pharmacokinetic limitations.

What does U.S. Patent 9,707,191 protect?

The patent protects co-administration of dextromethorphan with bupropion or one of three bupropion metabolites:

• Hydroxybupropion
• Threohydroxybupropion
• Erythrohydroxybupropion
• Bupropion itself

The claimed method applies to a human subject who is an extensive metabolizer of dextromethorphan and needs treatment with dextromethorphan. The claimed regimen must be administered once or twice daily for at least nine consecutive days.

The independent claim requires all of the following:

Limitation	Requirement
Patient	Human subject who is an extensive metabolizer of dextromethorphan
Therapeutic need	Subject is in need of treatment with dextromethorphan
Combination	Dextromethorphan plus bupropion or a specified bupropion metabolite
Frequency	Once daily or twice daily
Duration	At least nine consecutive days
Dextromethorphan dose	About 40 mg to about 350 mg per day
Pharmacokinetic result	First dextromethorphan Cmin is at least about 20 ng/mL on day nine
Comparative PK result	First Cmin is at least about 20 times the Cmin from dextromethorphan alone

The claim is therefore narrower than a general claim to a dextromethorphan-bupropion combination. It requires a patient population, dosing schedule, duration and pharmacokinetic outcome.

How does claim 1 define the core patent monopoly?

Claim 1 is a result-limited method claim. The accused conduct must produce the specified Cmin relationship, not merely involve the same active ingredients.

The claim compares two treatment conditions:

1. The combination of dextromethorphan with bupropion or a bupropion metabolite.
2. The same daily dextromethorphan dose administered without the bupropion component for nine days.

The claimed combination must produce:

• A first Cmin of at least approximately 20 ng/mL; and
• A first Cmin at least approximately 20 times the second Cmin.

This comparative structure creates both strength and enforcement complexity. It gives the patent a pharmacological anchor tied to CYP2D6 inhibition, but it also creates factual questions concerning the comparator regimen, patient metabolism, assay method, treatment duration and whether the claimed result is inherent in the accused product.

The claim does not require a particular disease. It is not limited expressly to major depressive disorder, treatment-resistant depression, agitation, pseudobulbar affect or another named indication. A treatment protocol for another condition could potentially fall within the claim if the other limitations are met.

What dependent claims add to U.S. Patent 9,707,191?

The dependent claims create narrower positions around dose, exposure, formulation, duration and molecular structure.

Dose limitations

Claims 2 through 6 narrow the daily or single dextromethorphan dose:

Claims	Limitation
2	Daily dextromethorphan dose of about 42 mg to about 190 mg
3	Daily dose of about 46 mg to about 100 mg
4	Single dose of about 42 mg to about 44 mg
5	Single dose of about 44 mg to about 46 mg
6	Single dose of about 46 mg to about 48 mg

These ranges are commercially significant because an approximately 45 mg dextromethorphan daily dose is associated with the Auvelity product regimen. Auvelity is administered as one tablet once daily for three days, followed by one tablet twice daily, with each tablet containing 45 mg of dextromethorphan hydrobromide and 105 mg of bupropion hydrochloride. The label’s maintenance regimen therefore corresponds closely to the claimed single-dose and bupropion-dose ranges, although the patent claims must be assessed against the complete limitation set. [2]

Pharmacokinetic limitations

Claims 7 through 15 increase or specify the Cmin result:

• At least about 30 times the comparator Cmin
• At least about 40 times the comparator Cmin
• At least about 50 times the comparator Cmin
• First Cmin of about 20 to 30 ng/mL
• About 55 to 70 ng/mL
• About 70 to 90 ng/mL
• About 115 to 120 ng/mL
• About 170 to 200 ng/mL
• About 20 to 10,000 ng/mL

These limitations are valuable as fallback positions. If a court rejects or narrows the broad 20-fold limitation, the narrower claims may remain relevant where clinical or pharmacokinetic data support the claimed concentration bands.

Bupropion dose limitations

Claims 16 through 19 require:

• Daily bupropion dose of about 40 mg to about 300 mg
• Daily bupropion dose of about 70 mg to about 220 mg
• Single bupropion dose of about 70 mg to about 105 mg
• Single bupropion dose of about 105 mg to about 150 mg

The 105 mg single-dose limitation in claims 18 and 19 maps directly to the bupropion amount in an Auvelity tablet.

Deuterium and stereochemistry

Claims 20 and 21 cover deuterium-modified versions of the active ingredients, including deuterium-modified dextromethorphan. Claim 30 covers bupropion having an enantiomeric excess of R-bupropion or S-bupropion.

These claims broaden the technology beyond the conventional racemic active ingredients. They may create blocking positions against deuterated follow-on products or stereochemically enriched bupropion formulations, subject to written-description, enablement and infringement analysis.

Dosage-form limitations

Claims 22 through 27 cover co-administration in a single oral dosage form, including:

• Solid dosage forms
• Tablets
• Troches
• Pills
• Capsules
• Liquid dosage forms
• Liquid or solid-phase dispersions
• Formulations containing binders, disintegrants or lubricants

The dosage-form claims are important because they reach fixed-dose combination products rather than only separately administered tablets or capsules.

Longer treatment periods

Claims 28 and 29 extend the administration period to:

• At least 30 consecutive days; or
• At least 60 consecutive days

These claims are directed to chronic treatment and may be relevant to products labeled for continuing daily treatment after initiation.

When does U.S. Patent 9,707,191 lose exclusivity?

The patent issued on July 18, 2017. Public patent records identify the patent as part of the Axsome dextromethorphan/bupropion patent family. The commonly reported expiration date is in 2030, subject to the applicable statutory term, terminal disclaimers, patent-term adjustment and any regulatory exclusivity that operates separately from the patent term. [1]

Event	Date or status
Patent issued	July 18, 2017
Patent number	U.S. 9,707,191
Product associated with claims	Dextromethorphan/bupropion, including Auvelity
Expected patent-term endpoint	August 2030 range, based on the family’s reported term
Regulatory product	FDA-approved Auvelity
NDA	214378
Approval	August 18, 2022

The patent does not provide composition-of-matter exclusivity over dextromethorphan or bupropion. Those active ingredients are long-established and their basic compound patents expired years ago. The commercial exclusion instead arises from the combination method, pharmacokinetic profile, formulation and related patent-family claims.

What is the Orange Book status of U.S. Patent 9,707,191?

FDA-approved Auvelity is listed in the Orange Book under NDA 214378. The Orange Book is the principal public source for patents submitted by an NDA sponsor as covering an approved drug, its formulation or an approved method of use. [3]

U.S. Patent 9,707,191 has been associated publicly with the Auvelity patent estate. An Orange Book listing does not establish validity or infringement. It permits the NDA holder to invoke the statutory patent-certification framework against an ANDA applicant that seeks approval before the listed patent expires.

The relevant regulatory distinction is:

• A patent listing concerns a patent submitted as covering the approved product or use.
• FDA does not determine patent validity.
• FDA generally does not resolve claim construction or infringement.
• A Paragraph IV certification can trigger patent litigation and an FDA approval stay of up to 30 months if the NDA holder files suit within the statutory period.

Which companies are challenging the Auvelity patent estate?

Publicly available sources do not establish a final generic market-entry event for the claims of U.S. Patent 9,707,191. The principal commercial risk would arise from an ANDA applicant filing a Paragraph IV certification against one or more Orange Book-listed Auvelity patents.

A complete Paragraph IV challenge would normally address:

• Invalidity for obviousness
• Lack of written description
• Lack of enablement
• Indefiniteness of terms such as “about,” “trough effect” and “extensive metabolizer”
• Non-infringement based on dose, schedule or pharmacokinetic results
• Failure to satisfy the comparative Cmin limitation
• Lack of infringement by a product that uses separate dosage forms or a different dosing schedule

The absence of a confirmed public Paragraph IV litigation record for this specific patent should not be treated as evidence that the patent is unchallenged. ANDA certifications may become public through litigation filings, FDA disclosure processes or sponsor announcements at different times.

What patent litigation affects U.S. Patent 9,707,191?

The patent’s litigation risk is linked to the Auvelity product and the broader Axsome patent portfolio. A case involving a related patent may affect market timing without directly adjudicating every claim of U.S. 9,707,191.

The most likely litigation issues are technical rather than chemical:

1. Whether the accused regimen produces a Cmin of at least 20 ng/mL.
2. Whether the 20-fold comparison must be established in the same patient, the same study or a population-level analysis.
3. Whether “extensive metabolizer” is determined by genotype, phenotype, observed clearance or another method.
4. Whether the accused product is administered once or twice daily for the required duration.
5. Whether a product using a different bupropion salt or metabolite falls within the claims.
6. Whether the pharmacokinetic outcome is inherent in the product and therefore sufficient for infringement.
7. Whether a prescriber, manufacturer or distributor can be liable when the claimed method requires treatment behavior by a third party.

Method claims can be harder to enforce than product claims because infringement depends on the actual administration of the claimed regimen. A fixed-dose product with a label that directs the claimed dosing schedule presents a stronger induced-infringement case than a product whose label omits or discourages the claimed use.

How strong is the patent estate for Auvelity?

The estate is stronger than U.S. 9,707,191 alone because it combines several exclusionary layers:

Layer	Commercial function
Pharmacokinetic method claims	Protect the exposure effect from CYP2D6 inhibition
Dose claims	Cover commercially practical dextromethorphan and bupropion amounts
Fixed-dose formulation claims	Target a combined oral product
Duration claims	Cover chronic treatment
Method-of-use claims	Protect approved depression treatment
Later-family patents	Potentially extend protection beyond the 2030 patent

The principal weakness of U.S. 9,707,191 is claim complexity. Each additional limitation narrows the infringement target. The requirement for a 20-fold Cmin comparison is especially important. A generic applicant may attempt to avoid infringement by using a different dose, administration frequency, formulation, patient population or label.

The main validity risk is obviousness. Dextromethorphan is metabolized by CYP2D6, and bupropion is a known CYP2D6 inhibitor. An opponent could argue that combining the agents to increase dextromethorphan exposure was predictable. The patent owner’s counterargument would rely on the claimed magnitude of exposure improvement, trough-effect reduction, dose selection and clinical utility.

How does U.S. Patent 9,707,191 compare with composition and formulation patents?

U.S. 9,707,191 is not a classic composition-of-matter patent. It does not prevent all use or sale of dextromethorphan, bupropion or their salts. Its coverage is behavioral and pharmacokinetic.

Method patents

Method claims can cover use of old compounds for a new therapeutic or pharmacokinetic purpose. They generally require proof that the accused party’s conduct meets the claimed treatment steps.

Formulation patents

Formulation claims may provide more direct protection against a fixed-dose combination tablet. They can target release characteristics, excipient systems, particle properties, dosage-form architecture or stability. A formulation patent may be infringed by making or selling the product itself, while a method patent may require proof of administration.

Composition patents

A new chemical entity or novel salt composition patent generally provides the broadest product exclusion. That protection is not the basis of U.S. 9,707,191. The commercial patent strategy instead relies on repurposing known drugs through dose selection, pharmacokinetic modulation and fixed-dose delivery.

What generic entry risks exist for Auvelity?

Generic entry before the reported 2030 patent endpoint would most likely require one of four paths:

1. A successful Paragraph IV invalidity or non-infringement challenge.
2. A settlement permitting an earlier launch.
3. A product design that avoids the listed claims.
4. An alternative regulatory route not blocked by the patent claims.

A non-infringing design could attempt to avoid:

• The 40 mg to 350 mg daily dextromethorphan range.
• The once-daily or twice-daily schedule.
• The nine-day duration.
• The extensive-metabolizer population.
• The 20-fold Cmin comparison.
• The single oral dosage-form limitations.
• The claimed bupropion dose ranges.

Those strategies may reduce commercial equivalence to Auvelity. A product that avoids the method claims but does not replicate the pharmacokinetic profile may require separate clinical development and labeling.

What revenue exposure is associated with the patent?

Auvelity is Axsome’s principal commercial product and its patent estate has direct revenue significance. Axsome reported approximately $130 million in Auvelity net product revenue for 2023. [4] Revenue exposure increases as prescribing expands because generic competition would affect the product’s price, formulary position and market-share retention.

The most material risk is not limited to loss of sales after patent expiration. A successful Paragraph IV challenge could accelerate price erosion before the expected 2030 endpoint. A settlement could produce a defined launch date, while a failed challenge could preserve branded pricing until patent expiry or settlement-defined entry.

What are the geographic coverage and manufacturing barriers?

U.S. Patent 9,707,191 has territorial effect only in the United States. Parallel foreign patents must be analyzed separately for:

• European jurisdictions
• Canada
• Japan
• Australia
• Other markets where Axsome or its licensors pursued protection

Manufacturing barriers are comparatively limited at the active-ingredient level because dextromethorphan and bupropion are established pharmaceutical compounds. The more meaningful barriers are:

• Development of a bioequivalent fixed-dose combination
• Control of dose uniformity
• Release and stability specifications
• Demonstration of comparable pharmacokinetics
• Regulatory labeling that avoids patented method limitations
• Potential patents covering formulation or manufacturing processes

The patent does not by itself block manufacture of dextromethorphan or bupropion for unrelated uses.

Key Takeaways

• U.S. Patent 9,707,191 protects a dextromethorphan-plus-bupropion pharmacokinetic treatment method.
• Claim 1 requires an extensive metabolizer, once- or twice-daily dosing, at least nine days of treatment, a dextromethorphan dose of about 40 mg to 350 mg per day, and a Cmin at least 20 times the comparator.
• Claims 2 through 30 narrow protection around dose, Cmin, formulation, duration, deuteration and bupropion stereochemistry.
• The patent is associated with the Auvelity product and has a reported expiration in the August 2030 range.
• The patent is a method patent, not a basic compound patent.
• The strongest infringement case would involve a fixed-dose product labeled for the claimed Auvelity-like regimen.
• The principal attack points are obviousness, indefiniteness, enablement, the extensive-metabolizer limitation and the comparative Cmin requirement.
• Generic entry risk depends on Paragraph IV activity, related Orange Book patents, settlement terms and the ability to design around the pharmacokinetic limitations.

FAQs

Does U.S. Patent 9,707,191 cover dextromethorphan by itself?

No. The claims require co-administration with bupropion or a specified bupropion metabolite and impose additional patient, dose, duration and pharmacokinetic conditions.

Does the patent cover Auvelity’s active ingredients?

It covers specified treatment methods using the active ingredients in the claimed combination. It does not create basic compound exclusivity over dextromethorphan hydrobromide or bupropion hydrochloride.

Can a generic avoid the patent by using separate tablets?

Potentially, but separation alone does not avoid the independent method claim. The generic regimen could still infringe if it satisfies the combination, dose, schedule, patient and Cmin limitations. Separate dosage forms are more relevant to avoiding claims 22 through 27.

Is a 20-fold Cmin increase required for every claim?

The 20-fold comparison is required by claim 1 and claims depending directly on it unless a narrower dependent claim adds limitations without removing the parent limitation. Claims 7 through 9 require even higher fold increases.

Does FDA determine whether U.S. Patent 9,707,191 is valid?

No. FDA administers the drug-approval and patent-certification framework but does not finally decide patent validity, claim construction or infringement. Those issues are resolved through federal court litigation or settlement.

Sources

1. U.S. Patent and Trademark Office. (2017). U.S. Patent No. 9,707,191, Methods of treating a subject with dextromethorphan and bupropion.
2. U.S. Food and Drug Administration. (2022). Auvelity prescribing information. Axsome Therapeutics, Inc.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book, NDA 214378.
4. 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.

Drugs Protected by US Patent 9,707,191

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	215430-002	Apr 30, 2026		RX	Yes	No						THE TREATMENT OF AGITATION ASSOCIATED WITH DEMENTIA DUE TO ALZHEIMER’S DISEASE BY REDUCING A TROUGH EFFECT OF DEXTROMETHORPHAN IN EXTENSIVE METABOLIZERS OF DEXTROMETHORPHAN
Axsome	AUVELITY	bupropion hydrochloride; dextromethorphan hydrobromide	TABLET, EXTENDED RELEASE;ORAL	215430-001	Aug 18, 2022		RX	Yes	Yes						DEXTROMETHORPHAN AND BUPROPION IN COMBINATION TO TREAT MAJOR DEPRESSIVE DISORDER
Axsome	AUVELITY	bupropion hydrochloride; dextromethorphan hydrobromide	TABLET, EXTENDED RELEASE;ORAL	215430-001	Aug 18, 2022		RX	Yes	Yes						THE TREATMENT OF AGITATION ASSOCIATED WITH DEMENTIA DUE TO ALZHEIMER’S DISEASE BY REDUCING A TROUGH EFFECT OF DEXTROMETHORPHAN IN EXTENSIVE METABOLIZERS OF DEXTROMETHORPHAN

International Family Members for US Patent 9,707,191

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2014346807
Australia	2015350559
Australia	2018203638
Australia	2019201548
Australia	2019223187
Australia	2019236614