Details for Patent: 10,058,518

« Back to Dashboard

Which drugs does patent 10,058,518 protect, and when does it expire?

Patent 10,058,518 protects AUVELITY and is included in one NDA.

This patent has two hundred and thirty-four patent family members in thirty-three countries.

Summary for Patent: 10,058,518

Title:	Bupropion as a modulator of drug activity
Abstract:	Dosage forms, drug delivery systems, and methods related to sustained release of dextromethorphan or improved therapeutic effects are disclosed. Typically, bupropion or a related compound is orally administered to a human being to be treated with, or being treated with, dextromethorphan.
Inventor(s):	Herriot Tabuteau
Assignee:	Antecip Bioventures II LLC
Application Number:	US15/688,660
Patent Claim Types: see list of patent claims	Use; Dosage form;

US Patent 10,058,518: Scope, Claim Construction, Expiration, and Dextromethorphan-Bupropion Patent Landscape

US Patent No. 10,058,518 protects a pharmacokinetic treatment method using dextromethorphan with bupropion. Its core limitation is not simply co-administration of the two active ingredients. The claimed method requires a defined dose range, repeated dosing, treatment of an extensive metabolizer, and measured eighth-day dextromethorphan exposure showing both an absolute trough concentration and a substantial increase over dextromethorphan administered without bupropion.

The patent is closely aligned with the pharmacology and dosing regimen of Auvelity, Axsome Therapeutics' dextromethorphan hydrobromide and bupropion hydrochloride product. The commercially relevant regimen is 45 mg of dextromethorphan and 105 mg of bupropion per tablet, administered twice daily, for total daily doses of 90 mg and 210 mg, respectively.[1]

What does US Patent 10,058,518 protect?

The patent protects a method of reducing the dextromethorphan trough effect in an extensive metabolizer by administering bupropion and dextromethorphan for at least eight consecutive days.

The independent claim requires all of the following:

Claim element	Requirement
Active ingredients	Bupropion plus dextromethorphan
Administration frequency	Once or twice daily
Treatment duration	At least eight consecutive days
Patient population	Human being who is an extensive metabolizer of dextromethorphan
Dextromethorphan dose	About 40 mg to about 140 mg per day
Eighth-day trough	Dextromethorphan Cmin of at least about 20 ng/mL
Comparative exposure	Eighth-day Cmin at least about 20 times the Cmin produced by the same dextromethorphan dose without bupropion

The claim is therefore a pharmacokinetic method-of-use claim. It is narrower than a general claim covering any combination of dextromethorphan and bupropion.

The phrase "reducing a dextromethorphan trough effect" describes the therapeutic objective, but the enforceable boundaries are supplied by the dose, patient-metabolizer, duration, and pharmacokinetic limitations.

How broad is independent claim 1?

Claim 1 has moderate commercial breadth but substantial proof requirements.

It covers:

• Immediate-release or modified-release products, unless another claim limitation narrows the dosage form.
• A single daily dose or divided twice-daily dosing.
• Total daily dextromethorphan doses from approximately 40 mg to 140 mg.
• Bupropion generally, without a required bupropion dose in the independent claim.
• Treatment lasting eight days or longer.
• Patients classified as extensive metabolizers.
• Regimens producing the specified eighth-day Cmin result.

The claim does not expressly require:

• A particular salt of either active ingredient.
• A particular tablet design.
• A fixed dextromethorphan-to-bupropion ratio.
• A specific indication such as major depressive disorder.
• A particular release profile.
• A particular excipient.
• A specific brand-name product.

The claim does require the pharmacokinetic result. A product may contain the same ingredients and doses but fall outside the claim if the relevant patient population or measured Cmin relationship is not established.

What are the key limitations for infringement?

The most important limitations are the extensive-metabolizer requirement and the eighth-day pharmacokinetic thresholds.

Extensive metabolizer limitation

The patient must be an extensive metabolizer of dextromethorphan. This limitation relates primarily to CYP2D6 metabolism. Dextromethorphan is substantially metabolized through CYP2D6, while bupropion and its metabolites inhibit CYP2D6 activity.[2]

A generic manufacturer could face infringement risk if its labeling directs treatment to the same patient population or if clinical evidence shows that the labeled regimen produces the claimed pharmacokinetic profile in extensive metabolizers.

The limitation also creates a proof issue. In a patent case, the patentee may need to establish:

1. The relevant patient is an extensive metabolizer.
2. The patient received the claimed regimen.
3. The patient continued treatment through the relevant measurement day.
4. The measured Cmin met the absolute and comparative thresholds.

A product label does not need to use the exact phrase "extensive metabolizer" for induced infringement risk to exist. Instructions that direct ordinary use of the regimen can be relevant if practicing the labeled method necessarily or predictably satisfies the claim.

Comparative Cmin limitation

The claim requires Cmin of at least about 20 ng/mL and at least about 20 times the reference Cmin produced by dextromethorphan without bupropion.

This creates two separate requirements:

• An absolute threshold: at least approximately 20 ng/mL.
• A relative threshold: at least approximately 20-fold over the no-bupropion reference.

The comparator must use the same amount of dextromethorphan administered for eight consecutive days without bupropion. The comparison is therefore regimen-specific rather than a comparison to a population-wide historical average.

The relative limitation may be powerful against a conventional dextromethorphan-only product because dextromethorphan monotherapy would ordinarily produce substantially lower exposure in an extensive metabolizer. It may be less effective against alternative CYP2D6 inhibitors or formulations if those products produce materially different exposure profiles.

How do the dependent claims expand the patent’s coverage?

The dependent claims divide into dose, pharmacokinetic, formulation, duration, and patient-population groups.

Dose and bupropion claims

Claims 2 through 4 focus on the commercial dosing range:

Claim	Added limitation
2	About 90 mg dextromethorphan per day
3	About 44 mg to about 46 mg per single dextromethorphan dose
4	About 200 mg to about 250 mg bupropion per day when dextromethorphan is about 90 mg per day

The commercial Auvelity regimen falls within these limitations: two tablets per day provide 90 mg of dextromethorphan and 210 mg of bupropion.[1]

Claim 3 is particularly relevant because a 45 mg single dose falls directly within its range. Claim 4 similarly captures the 210 mg daily bupropion dose used by the approved product.

Cmax claims

Claims 5 through 12 add eighth-day peak-concentration thresholds:

• At least approximately 45 ng/mL.
• At least approximately 55 ng/mL.
• At least approximately 75 ng/mL.
• At least approximately 30 times the no-bupropion Cmax.
• Corresponding versions tied to the 200 mg to 250 mg daily bupropion range.

These claims are narrower than claim 1 because they require specific Cmax results in addition to the Cmin requirements. They may be useful where clinical pharmacokinetic data demonstrate the claimed exposure but may be harder to enforce without access to product-development or postmarketing data.

Deuterium-modified compounds

Claims 13 and 14 cover deuterium-modified bupropion or deuterium-modified dextromethorphan in specified claim contexts.

These claims are not necessary to cover the standard Auvelity formulation, which uses conventional bupropion and dextromethorphan compounds. They create a separate species of protection for isotope-modified alternatives.

Single oral dosage form and excipients

Claims 15 through 20 cover administration as a single oral dosage form and then narrow to solid forms, including tablets, troches, pills, or capsules.

Claims 17 through 19 identify:

• Magnesium stearate.
• Hydroxypropyl methylcellulose.
• Microcrystalline cellulose.

These excipient claims are formulation-specific. A solid combination product that includes the active ingredients but uses a materially different excipient system may avoid these dependent claims while remaining potentially exposed to claim 1 or other formulation patents.

Long-duration treatment

Claims 21 and 22 extend the method to at least 30 or 60 consecutive days. These claims are commercially important because major depressive disorder treatment is chronic rather than limited to an eight-day pharmacokinetic assessment period.

The eight-day limitation in claim 1 is a threshold for establishing the claimed exposure. Claims 21 and 22 cover continued practice of the regimen for longer periods.

AUC and disease-exclusion claims

Claims 23 through 26 add eighth-day AUC0-12 requirements ranging from at least 400 ng·hr/mL to specified ranges up to 1,100 ng·hr/mL.

Claim 27 excludes patients suffering from neuropathic pain. This limitation may distinguish the claimed method from certain earlier dextromethorphan-bupropion development programs directed to pain treatment.

What formulation patents are relevant to dextromethorphan-bupropion products?

US Patent 10,058,518 includes formulation-related dependent claims, but its central protection is pharmacokinetic and method-based.

The broader patent landscape for a dextromethorphan-bupropion product generally separates into four categories:

Patent category	Typical subject matter	Commercial relevance
Combination composition	Dextromethorphan with bupropion in defined ratios	Protects the product composition
Method of treatment	Depression, CNS disease, pseudobulbar affect, or other indications	Creates use-based barriers
Pharmacokinetic method	Cmin, Cmax, AUC, exposure ratios, or metabolizer status	Targets the clinical regimen and biological result
Formulation and manufacturing	Tablets, release profiles, salts, granulation, coatings, and excipients	Raises design-around and manufacturing barriers

The patent at issue is strongest against products that replicate the approved dose and administration schedule while producing the claimed eighth-day exposure. It is less comprehensive as a standalone barrier against every formulation of the two active ingredients.

A competitor could attempt to design around the patent by changing one or more of the following:

• Dextromethorphan daily dose.
• Bupropion dose.
• Dosing frequency.
• Release mechanism.
• Patient population.
• CYP2D6 inhibition strategy.
• Active-ingredient salt or formulation.
• Treatment indication.

A design-around must account for the other patents in the family and related Orange Book-listed patents. Avoiding US 10,058,518 alone would not necessarily eliminate infringement risk.

What is the FDA and Orange Book status of the product protected by this patent?

The relevant commercial product is Auvelity, approved by the FDA in August 2022 for the treatment of major depressive disorder in adults.[1]

Auvelity contains:

• 45 mg dextromethorphan hydrobromide.
• 105 mg bupropion hydrochloride.
• A recommended starting regimen of one tablet daily for three days, followed by one tablet twice daily.
• A maintenance total of 90 mg dextromethorphan and 210 mg bupropion per day.

The approved product is an extended-release tablet. Its commercial regimen maps closely to claims 2, 3, 4, 15, 16, and 20, subject to the pharmacokinetic limitations in those claims.

FDA Orange Book listing status must be evaluated by reference to the current electronic Orange Book and the applicable NDA patent certifications. Patent listing, expiration, pediatric exclusivity, patent-term adjustment, and any later-issued patents are separate questions.[3]

A listed patent can require an ANDA applicant to make a Paragraph IV certification if the applicant seeks approval before the listed patent expires. A Paragraph IV certification asserts that the patent is invalid, unenforceable, or will not be infringed. The NDA holder may then file a patent-infringement action, triggering a potential 30-month stay under the Hatch-Waxman framework.[4]

When does US Patent 10,058,518 expire?

The patent has a nominal term extending into 2034 based on its underlying application and priority structure. The operative expiration date must be confirmed from the USPTO patent record because patent-term adjustment, terminal disclaimers, and any applicable patent-term extension can affect the enforceable end date.[5]

For commercial planning, the patent should be treated as part of a broader Auvelity exclusivity period extending into the mid-2030s, subject to:

• Other issued or pending patents.
• Orange Book listing decisions.
• Paragraph IV litigation.
• Settlement terms.
• Patent-term adjustment.
• FDA regulatory exclusivity.
• Potential pediatric exclusivity.

The expiration of US 10,058,518 alone would not establish an unrestricted generic-launch date.

Which companies are challenging the Auvelity patent estate?

The supplied claim record does not establish a current Paragraph IV filer, ANDA applicant, litigation docket, or settlement agreement. Those matters require separate review of FDA Orange Book records, district-court dockets, and company disclosures.

The most relevant potential challengers are generic manufacturers seeking approval for a dextromethorphan-bupropion combination tablet. Their exposure would likely involve:

1. The composition patents covering the combination.
2. The pharmacokinetic method claims in US 10,058,518.
3. Formulation and release-profile patents.
4. Method-of-use patents covering major depressive disorder.
5. Later-issued patents listed against the Auvelity NDA.

A Paragraph IV challenge could attack validity based on obviousness, written description, enablement, indefiniteness, or lack of anticipation. The pharmacokinetic limitations may create validity defenses centered on predictability, inherency, experimental variability, and whether the claimed exposure thresholds distinguish over prior dextromethorphan-bupropion use.

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

US 10,058,518 has meaningful product relevance because its dependent claims track the approved Auvelity dose and tablet regimen. Its principal strengths are:

• Direct alignment with the 90 mg daily dextromethorphan dose.
• Direct alignment with the 210 mg daily bupropion dose.
• Coverage of 45 mg single-dose administration.
• Coverage of once-daily and twice-daily dosing.
• Coverage of prolonged treatment.
• Pharmacokinetic limitations that can be evaluated in clinical studies.
• Potential induced-infringement relevance through an approved label.

Its weaknesses or litigation pressure points are:

• The need to establish extensive-metabolizer status.
• The need to prove both absolute and comparative Cmin results.
• Potential disputes over the meaning of "about."
• Dependence on patient-level or population-level pharmacokinetic evidence.
• The possibility of alternative dosing and formulation strategies.
• Potential obviousness challenges based on known CYP2D6 inhibition by bupropion.

The patent is strongest as part of a layered estate. It is less likely to function as a complete standalone barrier against every generic or follow-on product.

What generic launch scenarios exist?

Three launch scenarios are commercially relevant.

Early launch after Paragraph IV litigation

A generic applicant could file an ANDA with a Paragraph IV certification and prevail in litigation, secure a settlement permitting an agreed launch date, or launch at risk after the statutory stay and before patent expiration.

Launch after patent expiration

A generic could wait for the relevant listed patents to expire and avoid litigation risk, although later-issued patents or pediatric exclusivity could alter the date.

Design-around launch

A competitor could pursue a formulation or dosing strategy that avoids the asserted claims. This route may require a different dose, release profile, active-ingredient ratio, indication, or exposure profile. It may also reduce clinical or regulatory substitutability with Auvelity.

For an AB-rated generic, the most practical route is usually to match the reference listed drug closely. That strategy increases regulatory substitutability but can increase exposure to formulation, composition, method, and pharmacokinetic patents.

What is the geographic coverage of US Patent 10,058,518?

US Patent 10,058,518 provides rights only in the United States. Its claims do not directly control foreign manufacture, sale, or use unless another legal theory applies, such as infringement based on importation or a related foreign patent.

International risk depends on corresponding patents in jurisdictions such as:

• European Union member states.
• Canada.
• Japan.
• Australia.
• China.
• South Korea.

Foreign counterparts may differ materially in claim scope, validity, prosecution history, and expiration date. A US freedom-to-operate conclusion cannot be applied automatically to foreign markets.

What manufacturing and intellectual-property barriers remain after this patent expires?

Even after expiration of US 10,058,518, a follow-on manufacturer may face:

• Active-ingredient sourcing requirements.
• Controlled manufacturing and quality systems.
• Extended-release tablet development.
• Bioequivalence requirements.
• Stability and dissolution specifications.
• Other composition or formulation patents.
• Method-of-use patents.
• Regulatory exclusivity.
• Trade-secret manufacturing processes.
• Supply agreements and commercial scale-up constraints.

The patent’s excipient claims are comparatively narrow, but formulation development can still create technical barriers. A generic manufacturer that uses a different excipient system may avoid claims 17 through 19 while retaining the need to demonstrate bioequivalence and address the broader Auvelity patent estate.

Key Takeaways

• US Patent 10,058,518 is a pharmacokinetic method-of-treatment patent covering dextromethorphan plus bupropion.
• Claim 1 requires at least eight consecutive days of treatment, an extensive-metabolizer patient, dextromethorphan dosing of approximately 40 mg to 140 mg daily, and defined eighth-day Cmin exposure.
• Claims 2 through 4 closely track the Auvelity regimen of 90 mg dextromethorphan and 210 mg bupropion per day.
• Claims 5 through 12 add Cmax requirements, while claims 23 through 26 add AUC0-12 thresholds.
• Claims 15 through 20 cover single oral dosage forms and specified solid formulations.
• The patent’s nominal term extends into 2034, subject to the official USPTO term calculation and any adjustment.
• The patent creates meaningful generic risk but must be assessed with the broader composition, formulation, method-of-use, and later-issued patent estate.
• A Paragraph IV challenge, litigation status, settlement date, and final generic-entry date are not established by the claim text alone.
• The patent has US-only territorial effect; foreign launch risk requires separate counterpart analysis.

FAQs About US Patent 10,058,518

Does US Patent 10,058,518 cover Auvelity?

Its dependent dosing and dosage-form claims closely correspond to Auvelity's 45 mg dextromethorphan and 105 mg bupropion tablet administered twice daily. Infringement also depends on satisfying the claimed pharmacokinetic results and patient-population limitations.

Can a generic avoid this patent by using a different bupropion dose?

Potentially, but only if the alternative regimen avoids the limitations of this patent and all relevant claims in related patents. Claim 1 does not specify a bupropion dose, so changing bupropion dosage may not by itself avoid the independent claim.

Why does the patent require an extensive metabolizer?

The limitation reflects the role of CYP2D6 in dextromethorphan metabolism. Bupropion-mediated CYP2D6 inhibition can increase dextromethorphan exposure, particularly in patients who otherwise metabolize dextromethorphan extensively.

Are the pharmacokinetic claims difficult to enforce?

They can be. Enforcement may require clinical, pharmacokinetic, labeling, or population-level evidence showing the Cmin, Cmax, AUC, and comparative exposure limitations. The evidentiary burden is higher than for a claim requiring only the presence of two active ingredients.

Does expiration of US Patent 10,058,518 permit immediate generic launch?

No. Launch timing also depends on other Orange Book-listed patents, regulatory exclusivity, patent-term adjustment, litigation outcomes, settlements, and any later-issued patents covering the reference product.

References

1. U.S. Food and Drug Administration. (2022). Auvelity (dextromethorphan hydrobromide and bupropion hydrochloride) prescribing information.
2. U.S. Food and Drug Administration. (2022). Clinical pharmacology review: Auvelity NDA 212278.
3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
4. U.S. Code, 21 U.S.C. § 355(j).
5. United States Patent and Trademark Office. (2018). U.S. Patent No. 10,058,518, Methods of reducing a dextromethorphan trough effect.

Drugs Protected by US Patent 10,058,518

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	10,058,518					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	10,058,518					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	10,058,518					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 10,058,518

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