United States Patent 10,231,964: Scope, Claims, Exclusivity, and Contrave Patent Landscape

U.S. Patent No. 10,231,964 protects a dosing regimen for sustained-release naltrexone plus sustained-release bupropion, marketed as Contrave, in overweight or obese patients with elevated cardiovascular risk. The independent claim requires 32 mg naltrexone and 360 mg bupropion daily for at least 12 weeks. The dependent claims narrow the population to smokers, patients with type 2 diabetes, patients with established cardiovascular disease, and patients receiving a four-week dose-escalation schedule.

The patent is a method-of-treatment patent. It does not broadly claim naltrexone, bupropion, Contrave tablets, or the drug combination as a composition. Its commercial value depends on whether a generic product is approved with labeling that directs or permits the patented regimen.

What does U.S. Patent 10,231,964 protect?

The patent protects the use of a specific sustained-release combination for obesity treatment in patients at increased risk of adverse cardiovascular outcomes.

Claim element	Scope
Active ingredients	Sustained-release naltrexone and sustained-release bupropion
Daily maintenance dose	32 mg naltrexone plus 360 mg bupropion
Treatment duration	At least 12 weeks under claim 1; at least 20 weeks under claims 4 and 6
Disease	Overweight or obesity
Patient risk profile	Increased risk of adverse cardiovascular outcomes
Narrow populations	Current smokers, patients with type 2 diabetes, and patients with cardiovascular disease
Titration	8/90 mg in week 1; 16/180 mg in week 2; 24/270 mg in week 3; 32/360 mg thereafter
Cardiovascular endpoints	Cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke

The claim language tracks the clinical dosing regimen for Contrave. The approved maintenance dose is two tablets twice daily, providing 32 mg of naltrexone and 360 mg of bupropion per day. The FDA-approved titration schedule also increases the dose over four weeks.[1]

How is claim 1 of Patent 10,231,964 constructed?

Claim 1 is the broadest claim in the issued set. It requires all of the following:

The patient is overweight or obese.
The patient has an increased risk of adverse cardiovascular outcomes.
Treatment uses sustained-release naltrexone or a pharmaceutically acceptable salt.
Treatment uses sustained-release bupropion or a pharmaceutically acceptable salt.
The daily dose is 32 mg naltrexone and 360 mg bupropion.
Treatment continues for at least 12 weeks.

A potential infringement theory would therefore need to establish more than use of the Contrave product. It would need to show that the accused treatment is directed to a patient within the claimed risk population and that the specified dose and duration are used.

The claim does not expressly require a reduction in cardiovascular events. The cardiovascular-risk language identifies the patient population. By contrast, claims 12 through 20 expressly recite that treatment decreases the risk of a major adverse cardiovascular outcome.

What do the dependent claims add?

The dependent claims divide the commercial patient population into clinically important subgroups.

Smokers without type 2 diabetes

Claims 2 and 5 cover current smokers who do not have type 2 diabetes. Claim 5 adds the four-week escalation schedule. This population is narrower than the population in claim 1 and may be relevant to labeling or clinical trial subgroups involving elevated baseline cardiovascular risk.

Patients with type 2 diabetes

Claims 7, 8, 13, 14, and 18 cover patients with type 2 diabetes. Claim 8 narrows the population to patients who have had type 2 diabetes for less than six years.

The diabetes claims do not require that the patient be a smoker or have established cardiovascular disease. They can therefore cover a broader diabetes subgroup, provided the patient also satisfies claim 1's increased-cardiovascular-risk requirement.

Current smokers

Claim 9 covers current smokers without excluding patients with type 2 diabetes. This makes claim 9 broader than claim 2 in one respect, although it remains dependent on claim 1.

Established cardiovascular disease

Claims 10 and 11 cover patients with a history of cardiovascular disease. Claim 11 provides objective qualifying events and measurements, including:

Myocardial infarction more than three months before treatment;
Coronary, carotid, or peripheral revascularization;
Angina with ischemic ECG changes;
A positive cardiac imaging study;
An ankle-brachial index below 0.9 within two years before treatment; or
More than 50% arterial stenosis within two years before treatment.

These limitations create a stronger evidentiary record than the general phrase “increased risk,” because the claim identifies specific clinical facts that can be documented in medical records.

Cardiovascular-risk reduction claims

Claims 12 through 20 recite a decrease in the risk of a major adverse cardiovascular outcome. Claims 16 through 20 identify the relevant outcomes as cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.

These claims may present a higher enforcement burden than claims 1 through 11 because they require proof of the claimed therapeutic result or a legally sufficient showing that the result is inherent or necessarily obtained.

What dosing regimen does the patent cover?

The central regimen is:

Treatment period	Naltrexone daily dose	Bupropion daily dose
Week 1	About 8 mg	About 90 mg
Week 2	About 16 mg	About 180 mg
Week 3	About 24 mg	About 270 mg
Week 4 and later	About 32 mg	About 360 mg

Claims 3 and 5 expressly protect this escalation sequence. Claims 4 and 6 extend the minimum treatment period to at least 20 weeks.

The use of “about” introduces ordinary claim-construction questions concerning acceptable manufacturing and dosing variation. The claims are directed to daily amounts, not necessarily to a particular tablet count, tablet strength, brand name, or manufacturing process.

Is Patent 10,231,964 a composition patent or a method-of-use patent?

It is a method-of-use patent.

It does not claim:

Naltrexone as a chemical compound;
Bupropion as a chemical compound;
A broad naltrexone-bupropion composition;
A particular tablet formulation in composition terms; or
The manufacture of Contrave tablets.

The patent instead claims administering the combination to defined patients for a defined duration and therapeutic purpose. This distinction matters in generic litigation. A generic manufacturer may avoid direct infringement risk by seeking approval for uses that are not covered by the patent, subject to the scope of the FDA label and the product's labeling instructions.

What is the FDA and Orange Book status of Patent 10,231,964?

Contrave is approved under NDA 200063 for chronic weight management in adults with obesity or overweight and at least one weight-related comorbidity, together with a reduced-calorie diet and increased physical activity.[1]

Contrave is not a biologic. It is a fixed-dose small-molecule combination product. Biosimilar pathways do not apply. Generic competition proceeds through an abbreviated new drug application, or ANDA, rather than a biosimilar application under the Public Health Service Act.

The Orange Book analysis should distinguish between:

Patents listed for the approved drug product;
Patents covering the active ingredients or formulation;
Method-of-use patents covering particular patient populations; and
Patents that may be relevant to labeling but are not necessarily enforceable against every commercial use.

Patent 10,231,964 is commercially important because its claims map to the approved Contrave dosing schedule and obesity indication. Its practical blocking effect depends on the patent's current Orange Book listing, the approved use code, any statutory disclaimer or terminal disclaimer, and the wording of an ANDA applicant's Paragraph IV certification.

When does Patent 10,231,964 expire?

The patent term is generally measured from the earliest effective nonprovisional or PCT filing date in the relevant patent family, not from the 2019 issue date. The terminal date must account for:

The earliest effective nonprovisional filing;
Patent-term adjustment;
Any terminal disclaimer;
Patent-term extension, if applicable; and
Maintenance-fee status.

The patent was issued on March 19, 2019. Its commercial life therefore extends well beyond the issue date, but the issue date alone does not establish the expiration date. The underlying patent-family filing history and the USPTO term calculation control the terminal date.[2]

The patent should be analyzed together with earlier Contrave patents because a generic launch requires clearing the entire relevant patent estate, not only Patent 10,231,964.

How does Patent 10,231,964 compare with earlier Contrave patents?

The principal distinction is claim type.

Patent category	Typical protected subject matter	Relevance to generic entry
Active-ingredient or composition patent	Naltrexone-bupropion combination or pharmaceutical composition	Can block broad product manufacture or sale
Formulation patent	Sustained-release matrix, release profile, tablet structure, or excipients	Can block the commercial dosage form
Method-of-use patent	Treating obesity or a defined patient subgroup	Can block labeled use, but may permit narrower or skinny-label strategies
Cardiovascular-risk patent	Use in patients with increased cardiovascular risk or specified outcomes	Targets a clinically defined portion of the indication
Manufacturing patent	Process for making tablets or active ingredients	May create process-specific, not universal, risk

Patent 10,231,964 is strongest against a label that expressly instructs physicians to use the 32/360 mg regimen in patients with cardiovascular risk factors for at least 12 weeks. It is less naturally suited to blocking an ANDA label that omits the patented patient subgroup and does not encourage the claimed cardiovascular-risk treatment.

What formulation patents protect Contrave?

The patent at issue is not principally a formulation patent. The relevant formulation protection for Contrave is separate from the patient-selection and treatment-duration claims in Patent 10,231,964.

Formulation patents may claim:

Sustained release of naltrexone and bupropion;
A bilayer or multilayer tablet;
Specific polymer matrices;
Dissolution or release profiles;
Excipient ranges;
Stability characteristics; or
Tablet manufacturing parameters.

A generic product that uses the same active ingredients and dose may still face formulation-patent risk even if it avoids the method claims in Patent 10,231,964. Conversely, designing a noninfringing formulation does not necessarily avoid the method claims if the product is labeled for the claimed patient population and regimen.

What Paragraph IV risks exist for a Contrave generic?

An ANDA applicant must address listed patents through one of the statutory certifications. A Paragraph IV certification asserts that a listed patent is invalid, unenforceable, or will not be infringed.

For Patent 10,231,964, likely dispute areas include:

Written description and enablement

The patent must support the claimed cardiovascular-risk populations, dosing schedule, treatment duration, and cardiovascular outcomes. The detailed clinical disclosure and alignment with the approved regimen would generally support the dose and titration limitations. The risk-reduction claims may receive closer scrutiny if the specification does not establish actual reduction in major adverse cardiovascular events.

Obviousness

An applicant could argue that combining known obesity treatment with routine use in patients at cardiovascular risk would have been obvious. The patent holder would likely rely on clinical evidence, patient-selection criteria, unexpected results, or the absence of a predictable cardiovascular benefit.

Claim construction

Disputes may focus on:

The meaning of “increased risk of adverse cardiovascular outcomes”;
Whether a patient must be expressly identified as high risk by a physician;
The meaning of “treating”;
The significance of the “at least 12 weeks” period;
Whether the claimed daily dose must be administered as a fixed combination; and
Whether “decreases the subject's risk” is a required limitation or a statement of intended result.

Induced infringement

A generic manufacturer faces greater risk if its labeling instructs physicians to use the product in the claimed cardiovascular-risk population. A label that simply provides the general obesity indication may create a more fact-dependent induced-infringement analysis.

Which companies are relevant to the Contrave competitive landscape?

Currax Pharmaceuticals is the current commercial sponsor associated with Contrave in the United States. Orexigen Therapeutics developed the product and was the original innovator company. The competitive landscape includes:

Generic manufacturers pursuing ANDA approval;
Obesity drugs based on GLP-1 receptor agonists;
Other oral anti-obesity drugs;
Smoking-cessation products containing bupropion; and
Combination products using different mechanisms.

Contrave competes commercially with semaglutide, tirzepatide, liraglutide, phentermine/topiramate, and naltrexone-bupropion alternatives. Its patent value is constrained by the availability of newer incretin-based therapies with materially different efficacy and cardiovascular evidence profiles.[3,4]

Does Patent 10,231,964 create biosimilar risk?

No. Contrave is a small-molecule drug, not a biologic. The relevant competitive risk is generic substitution, not biosimilar substitution.

The key regulatory pathways are:

ANDA approval under section 505(j) of the Federal Food, Drug, and Cosmetic Act;
Paragraph IV patent challenges;
Potential section viii statements carving out patented methods of use; and
Hatch-Waxman litigation under 35 U.S.C. § 271(e)(2).

What litigation and settlement issues matter?

The major litigation questions are whether a generic applicant:

Challenges the patent through Paragraph IV;
Uses a section viii carve-out for the cardiovascular-risk method;
Accepts a later launch date through settlement;
Agrees to a license or authorized-generic arrangement;
Challenges formulation patents separately; or
Launches at risk after a court ruling or expiration of the 30-month stay.

A settlement can preserve substantial branded revenue even when the patent is vulnerable. The economic value depends on the agreed generic entry date, whether the settlement covers all Contrave patents, and whether an authorized generic is supplied.

How strong is the patent estate for Contrave?

Patent 10,231,964 has meaningful but targeted strength.

Strength factor	Assessment
Dose specificity	Strong; the 32/360 mg regimen is clearly defined
Titration protection	Stronger for claims 3 and 5 because the sequence is detailed
Patient selection	Moderate; “increased risk” may raise construction issues
Established cardiovascular disease claims	Stronger factually because the criteria are enumerated
Cardiovascular-benefit claims	More vulnerable to proof and enablement disputes
Product-level blocking power	Limited because the patent is not itself a broad composition claim
Generic carve-out potential	Material, depending on Orange Book use codes and labeling
Commercial relevance	High because the regimen tracks the approved product

The patent is best understood as a targeted use patent layered over the broader Contrave product and formulation estate.

What generic launch scenarios exist?

Early settlement launch

A generic applicant reaches a settlement permitting entry before the full patent estate expires. This scenario is commercially common where litigation costs are high and the branded product faces declining demand.

Skinny-label launch

The generic omits the patented cardiovascular-risk use from its labeling. This may reduce infringement exposure but does not eliminate risk if the remaining label, promotional conduct, or physician instructions encourage the patented use.

At-risk launch

The generic launches before final resolution of the patent dispute. The applicant faces damages and possible injunctive relief if the patent is upheld and infringement is established.

Post-estate launch

The generic waits until all material composition, formulation, and method patents expire or are invalidated. This is the lowest litigation-risk scenario but may sacrifice first-mover economics.

Key Takeaways

Patent 10,231,964 is a cardiovascular-risk method-of-use patent for sustained-release naltrexone plus sustained-release bupropion.
Its core regimen is 32 mg naltrexone and 360 mg bupropion daily.
Claims 3 and 5 protect the four-week dose escalation schedule.
Claims 7 through 11 target diabetes, smoking, and established cardiovascular disease subgroups.
Claims 12 through 20 recite reduced risk of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.
The patent does not broadly claim the Contrave composition or tablet formulation.
Generic risk depends heavily on the Orange Book use code, ANDA labeling, Paragraph IV certifications, and any formulation patents.
Biosimilar competition is irrelevant because Contrave is a small-molecule product.
The patent's strongest commercial position is against labeling that expressly directs treatment of cardiovascular-risk patients with the claimed regimen for at least 12 weeks.

FAQs

Does Patent 10,231,964 cover all uses of Contrave?

No. It covers a defined obesity-treatment method involving cardiovascular-risk patients, the 32/360 mg daily dose, and a minimum treatment period. It does not claim every use of the product.

Can a generic sell naltrexone-bupropion without infringing this patent?

Possibly. Risk depends on the generic's label, patient instructions, promotional conduct, dose regimen, and whether other Contrave composition or formulation patents apply.

Are smokers with obesity specifically covered by the patent?

Yes. Claims 2, 5, 9, 15, and 20 address current smokers. Claim 2 further specifies that the smoker does not have type 2 diabetes.

Does the patent require a proven reduction in heart attacks or strokes?

Claims 12 through 20 expressly recite a decrease in major adverse cardiovascular outcomes. The remaining claims focus on treating patients at increased risk and do not contain the same explicit outcome limitation.

Is Patent 10,231,964 the only patent that matters for Contrave generic entry?

No. Generic entry requires analysis of the entire relevant patent estate, including composition, sustained-release formulation, manufacturing, and additional method-of-use patents.

References

U.S. Food and Drug Administration. (2023). Contrave (naltrexone hydrochloride and bupropion hydrochloride) extended-release prescribing information.
United States Patent and Trademark Office. (2019). U.S. Patent No. 10,231,964, methods of treating overweight or obesity in subjects having an increased risk of adverse cardiovascular outcomes.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
U.S. Food and Drug Administration. (2024). Drugs@FDA: FDA-approved drugs, Contrave NDA 200063.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Azurity	CONTRAVE	bupropion hydrochloride; naltrexone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	200063-001	Sep 10, 2014		RX	Yes	Yes	10,231,964	⤷ Start Trial				FOR CHRONIC WEIGHT MANAGEMENT FOR TREATING OVERWEIGHT OR OBESITY	⤷ 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
Argentina	098631	⤷ Start Trial
Argentina	120476	⤷ Start Trial
Australia	2014360492	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 10,231,964