US Patent 10,828,294: Scope, Claims, Expiration, Orange Book Status and Contrave Patent Landscape

US Patent 10,828,294 protects a cardiovascular-risk-focused treatment method using the fixed naltrexone/bupropion regimen marketed as Contrave. The patent does not claim naltrexone, bupropion, the fixed-dose combination, or a tablet formulation. Its value lies in method-of-treatment coverage for overweight or obese patients with specified cardiovascular risk factors, including smokers, patients with type 2 diabetes, and patients with established cardiovascular disease.

The central commercial exposure is the use of the approved Contrave titration schedule in high-risk obesity populations for at least 12 weeks. Claims 12 through 20 add a cardiovascular-risk-reduction result, but those claims raise greater proof and claim-construction issues than the dosing and patient-selection claims.

What does US Patent 10,828,294 claim?

The patent’s independent claim is claim 1. It requires all of the following:

Limitation	Required scope
Disease	Overweight or obesity
Patient profile	Increased risk of adverse cardiovascular outcomes
Naltrexone dose	32 mg daily
Bupropion dose	360 mg daily
Duration	At least 12 weeks
Drug form	Naltrexone and bupropion, or pharmaceutically acceptable salts

The claim covers a treatment method, not a product. An accused party must be connected to administration of the specified regimen or to conduct that induces the patented treatment.

The claimed 32 mg/360 mg dose corresponds to four Contrave tablets per day, with each tablet containing 8 mg of sustained-release naltrexone and 90 mg of sustained-release bupropion. The FDA-approved regimen reaches this maintenance dose during the fourth treatment week.[1]

How do the dependent claims narrow the patent?

Claims 2 through 20 divide into four groups:

Claims	Added limitation	Commercial significance
2, 5, 6	Current smoker without type 2 diabetes; titration schedule; 20-week duration	Narrower high-risk smoker population
3, 4	Four-week titration schedule; 20-week or longer treatment	Closely tracks the Contrave label
7, 8, 13, 14, 18, 19	Type 2 diabetes, including diabetes of less than six years’ duration	Covers an obesity/diabetes subgroup
9-12, 15-17, 20	Current smokers, cardiovascular disease, and major adverse cardiovascular outcomes	Addresses cardiovascular-risk populations and outcomes

Claim 11 is particularly specific. It defines established cardiovascular disease through events or findings such as:

Myocardial infarction more than three months before treatment;
Coronary, carotid, or peripheral revascularization;
Angina with ischemic electrocardiographic or exercise-test changes;
Positive cardiac imaging;
An ankle-brachial index below 0.9;
More than 50% arterial stenosis.

Claims 16 through 20 define the adverse cardiovascular outcome as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.

What is the technical scope of the patent?

The patent covers a selected-patient use of the naltrexone/bupropion combination. Its technical scope has three principal dimensions: dose, patient selection, and treatment duration.

Dose and titration

Claim 1 requires the maintenance dose of 32 mg naltrexone and 360 mg bupropion daily. Claim 3 separately requires the step-up schedule:

Treatment week	Naltrexone	Bupropion	Equivalent Contrave tablets
Week 1	8 mg/day	90 mg/day	1 tablet daily
Week 2	16 mg/day	180 mg/day	2 tablets daily
Week 3	24 mg/day	270 mg/day	3 tablets daily
Week 4 and later	32 mg/day	360 mg/day	4 tablets daily

The use of “about” in dependent claims 3 and 5 gives some numerical flexibility. Claim 1 is more exact because it recites 32 mg and 360 mg without “about.”

A product using a substantially different maintenance dose may avoid literal infringement of claim 1, but it could remain exposed to other patents covering the formulation or dosing regimen. Dose reduction for tolerability may also affect infringement depending on whether the complete claimed course was administered.

Patient selection

“Increased risk of adverse cardiovascular outcomes” is the key broad patient-selection limitation. The patent then identifies specific risk groups:

Current smokers;
Patients with type 2 diabetes;
Patients with type 2 diabetes for less than six years;
Patients with a history of cardiovascular disease;
Patients meeting specified clinical or diagnostic criteria.

The risk limitation is broader than established cardiovascular disease. A patient may qualify because of smoking, diabetes, obesity-related comorbidities, or another risk factor. Claims 10 and 11 are narrower because they require a history of cardiovascular disease and, in claim 11, one of the listed qualifying events or tests.

Treatment duration

Claim 1 requires at least 12 weeks. Claims 4 and 6 require at least 20 weeks. Duration is a meaningful limitation because short-term prescribing, early discontinuation, or a treatment course that never reaches 12 weeks may not satisfy the independent claim.

The 20-week claims have greater evidentiary value in long-term obesity treatment but narrower coverage. A generic label that instructs treatment according to the FDA-approved regimen could still create risk under the 12-week claims even if it does not expressly promote 20-week treatment.

What cardiovascular outcomes are covered?

Claims 12 through 20 require that administration “decreases” the subject’s risk of a major adverse cardiovascular outcome. The defined outcomes are:

Cardiovascular death;
Nonfatal myocardial infarction;
Nonfatal stroke.

These claims are narrower than claims 1 through 11. They may require proof that the treatment has the claimed risk-reduction effect, depending on claim construction and the factual record. The claims do not expressly require a statistically demonstrated reduction in a clinical trial. They recite a therapeutic result tied to administration.

This creates two competing legal positions:

The patent owner may argue that the result is an intended therapeutic effect inherent in practicing the claimed method.
An accused infringer may argue that “decreases the subject’s risk” is a substantive limitation requiring proof of the claimed outcome or risk reduction.

The FDA label historically stated that the effect of Contrave on cardiovascular morbidity and mortality had not been established.[1] That regulatory language may complicate reliance on the risk-reduction claims, particularly where a sponsor’s labeling does not make a cardiovascular-benefit statement.

When does US Patent 10,828,294 expire?

The patent issued on November 10, 2020.[2] Its term is governed by the earliest effective nonprovisional priority date and any applicable patent-term adjustment or patent-term extension.

The expected nominal expiration is in 2035 if the relevant priority date is in 2015. The precise enforceable expiration date should be calculated from the patent’s continuity data and USPTO patent-term-adjustment record. Patent term extension for Contrave is not expected to materially extend this method patent because the underlying product received FDA approval in 2014 and the patent issued after approval.

Event	Date or period
FDA approval of Contrave	September 2014
US Patent 10,828,294 issue	November 10, 2020
Expected patent term	Through approximately 2035, subject to USPTO term calculation
FDA small-molecule pathway	ANDA
Biosimilar pathway	Not applicable

What is the Orange Book status of US Patent 10,828,294?

US Patent 10,828,294 is relevant to the Contrave NDA, 200063, because its claims cover a method of using the approved naltrexone/bupropion product in defined patient populations.[1,3]

An Orange Book listing does not expand the scope of the claims. It affects the ANDA certification and litigation framework. A generic applicant must address each listed patent associated with the reference product:

Paragraph I: no patent information has been submitted;
Paragraph II: the patent has expired;
Paragraph III: the applicant will wait until expiration;
Paragraph IV: the patent is invalid, unenforceable, or will not be infringed;
Section viii statement: the applicant will carve out a patented method of use.

For this patent, a Section viii strategy may be difficult if the approved label describes the same maintenance dose and patient population broadly enough to encourage use in patients with cardiovascular risk. A carve-out may be more plausible for narrower cardiovascular-outcome language if that language is not required for the approved indication.

The Orange Book should be read together with the current Contrave labeling and any patent-use codes. Patent-use codes can determine whether a generic can omit a method-of-use indication while retaining approval for the remaining obesity indication.[3]

What generic entry risks exist for Contrave?

Contrave is a small-molecule fixed-dose combination. Generic competition proceeds through the ANDA pathway, not the biosimilar pathway.

Paragraph IV exposure

A generic applicant challenging the patent would likely argue one or more of the following:

The claims are anticipated or obvious in view of earlier naltrexone/bupropion obesity studies;
The cardiovascular-risk patient population is an obvious subgroup of the known obesity population;
The dosing schedule is disclosed in the Contrave clinical and regulatory record;
“Decreases risk” is indefinite, lacks adequate written description, or is not enabled across the full claim scope;
The patent does not adequately support the breadth of “increased risk of adverse cardiovascular outcomes”;
The claims are not infringed because the generic label does not direct treatment of the claimed high-risk population or does not state cardiovascular risk reduction.

The patent owner would likely respond that the claimed combination of patient selection, dose, duration, and cardiovascular-risk context is not disclosed in a single reference and that the clinical data support the claimed method.

Induced-infringement risk

The main commercial risk is induced infringement rather than direct infringement by the generic manufacturer. The analysis would focus on whether the generic label, promotional materials, prescribing information, or distribution practices encourage physicians to administer:

32 mg/360 mg daily;
For at least 12 weeks;
To patients with increased cardiovascular risk;
Under the claimed titration schedule.

A label that simply mirrors the FDA-approved Contrave regimen may create exposure if high-risk obese patients are an expected and substantial part of the indicated population. A label that expressly excludes the claimed population would reduce, but may not eliminate, risk if other conduct still encourages the patented use.

What formulations are protected outside this patent?

US Patent 10,828,294 does not require sustained-release tablets in claim 1, although claim 12 refers to sustained-release naltrexone and bupropion. The patent therefore should be separated from formulation patents covering:

Sustained-release delivery;
Tablet composition;
Dissolution profiles;
Naltrexone-to-bupropion ratios;
Salt forms;
Manufacturing processes;
Stability and release-control excipients.

Contrave tablets contain sustained-release naltrexone hydrochloride and sustained-release bupropion hydrochloride. A generic may avoid a formulation patent through a different excipient system or release profile while remaining exposed to the method claims if it promotes the same patient population and regimen.

The focal patent does not block all naltrexone/bupropion products. It does not prevent use of the individual drugs for opioid dependence, smoking cessation, depression, or other indications outside the claimed obesity method.

How strong is the patent estate for naltrexone/bupropion?

The estate has different strength levels by claim category:

Claim category	Relative strength	Primary vulnerability
Fixed-dose product claims	Separate patent family	Prior art, formulation obviousness
Sustained-release formulation	Separate patent family	Design-around and obviousness
Standard Contrave titration	Moderate	FDA label and clinical-trial prior art
High-risk obesity population	Moderate to strong	Breadth and obviousness of patient selection
Established cardiovascular disease	Stronger narrow scope	Limited commercial population
Cardiovascular risk reduction	Fact-dependent	Enablement, written description, result limitation
20-week treatment	Moderate	Duration may be routine clinical practice

The strongest practical coverage is likely claims 1, 3, 7, 9, and 10 when a patient clearly satisfies the risk limitation and receives the approved maintenance dose for at least 12 weeks. Claims 12 through 20 are narrower but may have greater value if the specification and clinical evidence establish the claimed cardiovascular-risk effect.

What patent litigation affects US Patent 10,828,294?

Contrave has been exposed to ANDA patent challenges involving its formulation and method-of-use patent estate. A challenge to an earlier Contrave patent does not automatically resolve the validity or infringement of US Patent 10,828,294.

The principal litigation questions are:

Whether a Paragraph IV notice specifically identifies this patent;
Whether the NDA holder filed a patent-infringement action within 45 days;
Whether a 30-month stay applies;
Whether the generic label contains a Section viii carve-out;
Whether a settlement permits an authorized or independent generic launch before patent expiration;
Whether a court construes “increased risk,” “decreases risk,” and “at least 12 weeks” as substantive limitations.

Settlement agreements may establish an agreed generic entry date that is earlier than the nominal patent expiration. The economic value of the patent therefore depends on the settlement terms, the exact patent-use codes, and whether the generic is permitted to launch with a carved-out label.

How does this patent compare with competing obesity-drug patents?

US Patent 10,828,294 differs from the major modern obesity-drug estates in both product type and legal scope.

Product	Primary patent exposure	Biosimilar risk	Main distinction
Contrave	Combination, formulation, dosing, and patient-selection patents	None	Oral small molecule; method claims are central
Wegovy/Ozempic	Semaglutide composition, formulation, dosing, and manufacturing patents	No conventional biosimilar pathway, but peptide litigation risk	Injectable GLP-1 product
Saxenda	Liraglutide composition and formulation patents	None	GLP-1 receptor agonist
Qsymia	Phentermine/topiramate combination and formulation patents	None	Oral combination product
Xenical/Alli	Orlistat formulation and use patents	None	Older lipase-inhibitor product

Contrave’s patent risk is more dependent on label conduct and patient-selection facts than a pure composition patent. A generic cannot readily design around a valid composition claim, but it may narrow its label or alter its formulation to reduce method and formulation exposure.

What is the commercial impact of this patent?

The patent’s revenue exposure is concentrated in long-term Contrave use among patients with cardiovascular risk. It does not cover every Contrave prescription.

Key exposure variables are:

The share of prescriptions reaching the 32 mg/360 mg maintenance dose;
Persistence beyond 12 weeks;
Use in smokers and patients with type 2 diabetes;
Use in patients with established cardiovascular disease;
Whether the generic label includes or carves out the relevant patient populations;
Whether a settlement permits early entry;
The number and breadth of remaining formulation patents.

A generic launch with the full obesity label could create substantial exposure under the broad method claims. A carve-out focused on non-high-risk patients could reduce direct inducement risk, although physician prescribing behavior and the factual record would remain relevant.

Key Takeaways

US Patent 10,828,294 is a method-of-treatment patent for naltrexone/bupropion in overweight or obese patients with increased cardiovascular risk.
Claim 1 requires 32 mg naltrexone, 360 mg bupropion, and at least 12 weeks of treatment.
Claims 3 and 5 track the four-week Contrave dose-escalation schedule.
Claims 7 through 11 target diabetes, smoking, and established cardiovascular disease populations.
Claims 12 through 20 add a cardiovascular-risk-reduction result and are more vulnerable to enablement, written-description, and claim-construction challenges.
The patent does not independently protect the Contrave tablet, active ingredients, or sustained-release formulation.
The expected term runs to approximately 2035, subject to the USPTO patent-term calculation.
Generic risk will center on Paragraph IV certifications, Section viii label carve-outs, induced infringement, and any settlement-based entry date.
Contrave is a small-molecule product. Biosimilar litigation is not the relevant pathway.
The patent’s commercial strength depends more on label language and patient-selection evidence than on composition-of-matter exclusivity.

Frequently Asked Questions

Does US Patent 10,828,294 cover all Contrave prescriptions?

No. It requires treatment of overweight or obesity in a subject with increased risk of adverse cardiovascular outcomes, together with the specified dose and duration.

Can a generic avoid the patent by using a different tablet formulation?

Possibly, but a formulation change would not by itself avoid a method claim if the generic still induces the claimed treatment regimen in the claimed patient population.

Does a patient need a prior heart attack to fall within the patent?

No. The broad claims cover increased cardiovascular risk. A prior myocardial infarction is one route into the narrower established-cardiovascular-disease claims.

Does treatment for fewer than 12 weeks infringe claim 1?

A treatment course that never reaches 12 weeks may not satisfy the express duration limitation. Claims 4 and 6 require an even longer period of at least 20 weeks.

Is a biosimilar application required to compete with Contrave?

No. Contrave is a small-molecule combination product. Competition proceeds through the ANDA framework, with Paragraph IV and Section viii certifications as applicable.

References

U.S. Food and Drug Administration. (2023). Contrave (naltrexone hydrochloride and bupropion hydrochloride) extended-release tablets: Prescribing information. NDA 200063.
U.S. Patent and Trademark Office. (2020). U.S. Patent No. 10,828,294, methods for treating overweight or obesity in subjects at increased risk of adverse cardiovascular outcomes.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Nalpropion	CONTRAVE	bupropion hydrochloride; naltrexone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	200063-001	Sep 10, 2014		RX	Yes	Yes	⤷ Start Trial	⤷ 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
Brazil	112016012755	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,828,294

Which drugs does patent 10,828,294 protect, and when does it expire?

Summary for Patent: 10,828,294