United States Patent 10,835,527: Scope, Claims, Exclusivity and Contrave Patent Landscape

U.S. Patent No. 10,835,527 protects a narrow method of using the naltrexone-bupropion combination to treat overweight or obesity in patients with elevated cardiovascular risk. The patent does not claim naltrexone, bupropion, or the combination composition itself. Its commercial relevance is concentrated in patient selection, dose titration, treatment duration and cardiovascular-risk outcomes associated with Contrave.

The patent issued on November 17, 2020, from an Orexigen Therapeutics patent family directed to obesity treatment in higher-risk cardiovascular populations. Its earliest priority date is March 30, 2011, producing a nominal patent-term endpoint in 2031 before any applicable patent-term adjustment or terminal disclaimer.

What does U.S. Patent 10,835,527 cover?

The patent covers a treatment method requiring all of the following core elements:

The patient is overweight or obese.
The patient has an increased risk of adverse cardiovascular outcomes.
The patient receives daily naltrexone and bupropion.
The naltrexone dose is 4 to 50 mg per day.
The bupropion dose is 50 to 400 mg per day.
Treatment continues for at least 12 weeks.

The broadest independent claim is claim 1. The patent is therefore a method-of-use patent, not a composition patent or manufacturing patent.

Core claim elements

Element	Claim 1 requirement	Commercial significance
Disease state	Overweight or obesity	Limits the method to weight-management treatment
Patient population	Increased risk of adverse cardiovascular outcomes	Creates the principal narrowing limitation
Naltrexone dose	4-50 mg daily	Encompasses the Contrave maintenance dose
Bupropion dose	50-400 mg daily	Encompasses the Contrave maintenance dose
Duration	At least 12 weeks	Excludes short-term use
Drug form	Compound or pharmaceutically acceptable salt	Covers naltrexone hydrochloride and bupropion hydrochloride
Administration	Daily dosing	Requires a recurring daily regimen

Contrave’s labeled maintenance regimen is two tablets twice daily, with each tablet containing 8 mg of extended-release naltrexone hydrochloride and 90 mg of extended-release bupropion hydrochloride. The total daily maintenance dose is 32 mg of naltrexone hydrochloride and 360 mg of bupropion hydrochloride, subject to the label’s salt-equivalence presentation and formulation details [1].

How do the dependent claims narrow the patent?

The dependent claims divide the patent into several commercially relevant subgroups.

Smoking and diabetes status

Claim 2 covers a current smoker who does not have type 2 diabetes. Claim 9 separately covers a current smoker, while claims 7 and 8 cover patients with type 2 diabetes, including patients diagnosed for less than six years.

This creates overlapping but distinct patient categories:

Patient characteristic	Relevant claims
Current smoker, no type 2 diabetes	Claim 2
Current smoker, generally	Claim 9
Type 2 diabetes	Claim 7
Type 2 diabetes for less than six years	Claim 8
Established cardiovascular disease	Claim 10 and claim 11

The claims do not require that smoking, diabetes or prior cardiovascular disease be the reason for the patient’s increased cardiovascular risk. Those characteristics are additional claim limitations.

Titration regimen

Claims 3 and 5 recite the standard four-week dose-escalation schedule:

Treatment week	Daily naltrexone	Daily bupropion
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 also require that this schedule be followed by continued treatment at the week-four dose. Claims 4 and 6 extend the minimum treatment period from 12 weeks to at least 20 weeks.

These claims are important because they track the commercial Contrave titration schedule rather than merely claiming any naltrexone-bupropion regimen.

Established cardiovascular disease

Claim 10 covers a patient with a history of cardiovascular disease. Claim 11 defines that history through specified clinical events or measurements, including:

Myocardial infarction more than three months before treatment;
Coronary, carotid or peripheral revascularization;
Angina with ischemic changes;
ECG changes during a graded exercise test;
A positive cardiac imaging study;
An ankle-brachial index below 0.9 within two years before treatment; or
More than 50% stenosis in a coronary, carotid or lower-extremity artery within two years before treatment.

Claim 11 is materially narrower than claim 10. It gives a more objective definition of qualifying cardiovascular disease and may be more useful in infringement analysis because it identifies documentary clinical criteria.

What cardiovascular outcomes are covered?

Claims 12 through 20 add an outcome limitation requiring that treatment decrease the patient’s risk of a major adverse cardiovascular outcome.

Claims 16 through 20 define the relevant outcomes as:

Cardiovascular death;
Nonfatal myocardial infarction; and
Nonfatal stroke.

The claims therefore address a composite major adverse cardiovascular event endpoint rather than general cardiovascular health or a reduction in blood pressure.

A key distinction exists between claims 1, 12 and 16:

Claim 1 requires a patient with increased cardiovascular risk.
Claim 12 adds sustained-release naltrexone and sustained-release bupropion and requires a decrease in major adverse cardiovascular-outcome risk.
Claim 16 identifies the specific adverse outcomes.

Claims 13 through 15 apply the risk-reduction limitation to patients with diabetes, patients with diabetes of less than six years’ duration and current smokers. Claims 17 through 20 then define the cardiovascular outcomes for those subgroups.

Which claims are commercially strongest?

Claim 1 is the broadest claim and the principal enforcement claim. It captures a wide range of naltrexone-bupropion products if the patient has increased cardiovascular risk and receives the combination for at least 12 weeks.

Claims 3 and 5 are commercially important because they map closely onto the labeled Contrave titration regimen. They may be easier to prove when prescribing and dispensing records show the standard dose-escalation schedule.

Claims 10 and 11 may be significant in cardiometabolic clinics, where patients have documented cardiovascular disease. Claim 11 is narrower but provides specific medical-record criteria.

Claims 12 through 20 present greater enforcement complexity because they require a cardiovascular-risk reduction result. A claim requiring a therapeutic result can raise proof issues involving physician intent, patient selection, clinical evidence and the meaning of “decreases” in an individual patient.

A practical hierarchy is:

Claim group	Breadth	Likely commercial relevance
Claim 1	Broadest method claim	High
Claims 3 and 5	Standard Contrave titration	High
Claims 4 and 6	At least 20 weeks	Moderate
Claims 7-9	Diabetes and smoking subgroups	Moderate
Claims 10-11	Established cardiovascular disease	High in specialty populations
Claims 12-20	Cardiovascular-risk reduction outcome	High value, higher proof burden

When does U.S. Patent 10,835,527 expire?

The patent’s earliest priority date is March 30, 2011. The base U.S. patent term is therefore expected to run until March 30, 2031, subject to any patent-term adjustment, terminal disclaimer or other USPTO term calculation.

The practical exclusivity date must be determined from the USPTO patent-term data and any Orange Book listing. A patent expiry date is not the same as FDA marketing exclusivity. The patent may block an ANDA applicant through the expiration date if the applicant’s proposed labeling and use fall within an enforceable claim.

Exclusivity timeline

Event	Date or period
Earliest priority	March 30, 2011
Patent issued	November 17, 2020
Nominal 20-year term endpoint	March 30, 2031
FDA approval of Contrave	September 2014
Expected patent-based protection	Through approximately March 2031, subject to USPTO term calculation

The patent issued after Contrave’s approval and functions as a later-expiring method-of-use layer around an already approved combination product.

What is the Orange Book status of Patent 10,835,527?

Contrave is approved under NDA 200063 for chronic weight management in adults with obesity or overweight plus at least one weight-related condition. The product contains extended-release naltrexone hydrochloride and bupropion hydrochloride [1].

Patents claiming an approved method of use can be listed in the FDA Orange Book if they meet the statutory listing requirements. Patent 10,835,527 is directed to the approved drug’s use in an identifiable patient population and is therefore relevant to Orange Book patent-listing analysis.

An Orange Book-listed method patent can trigger a Paragraph IV certification by an ANDA applicant. If the patent holder timely files suit within 45 days after receiving notice, the filing can create a 30-month stay of ANDA approval under the Hatch-Waxman framework [2].

The central regulatory issue is whether an ANDA applicant’s proposed labeling includes the patented cardiovascular-risk population or otherwise induces use within the claims. A section viii “skinny label” may avoid some method claims if the patented use can be carved out without undermining the approved non-patented indication. That strategy is less effective where the patented patient population overlaps materially with the principal approved use.

Are there Paragraph IV challenges to Contrave patents?

Publicly reported generic activity must be evaluated patent-by-patent. A Paragraph IV certification is not itself a finding that a patent is invalid or not infringed. The relevant questions are:

Which Contrave patents are listed for NDA 200063?
Which listed patents have been challenged?
Whether the patent owner filed an infringement action within 45 days;
Whether a 30-month stay was triggered;
Whether litigation ended through judgment, dismissal or settlement; and
Whether the ANDA applicant received tentative or final approval.

For Patent 10,835,527, a generic applicant would likely attack the patent through one or more of the following theories:

The claims are obvious over earlier naltrexone-bupropion obesity regimens.
The cardiovascular-risk population is an inherent or predictable patient subset.
The claim language does not adequately define “increased risk.”
The asserted cardiovascular benefit is not enabled across the full dose range and patient population.
The claims lack written-description support for the full 4-50 mg and 50-400 mg ranges.
A proposed generic label does not encourage the claimed use.
The method claims are not infringed by a carved-out label.

No biosimilar pathway applies. Naltrexone-bupropion is a small-molecule combination product, so generic competition would proceed through an ANDA rather than a biosimilar application under the Public Health Service Act.

What other patents protect Contrave?

The Contrave patent estate is broader than Patent 10,835,527. It can be divided into four categories:

Patent category	Subject matter	Relevance
Composition patents	Naltrexone-bupropion combinations	Protect the active combination
Formulation patents	Extended-release tablets and release profiles	Protect the commercial dosage form
Method-of-use patents	Obesity treatment and patient subgroups	Protect prescribing and treatment
Manufacturing patents	Tablet production, granulation and coating	May create technical barriers

Patent 10,835,527 is principally a cardiovascular-risk method patent. It does not, based on the supplied claims, require a particular tablet architecture, excipient, dissolution profile, particle size, coating, granulation process or manufacturing sequence.

The formulation claims that matter most for generic entry are those covering the extended-release combination tablet. A generic applicant can avoid infringement of a formulation patent only if its product does not practice the claimed formulation or if the patent is invalid or unenforceable. Method-of-use patents can present a separate obstacle even where the generic tablet is chemically and pharmaceutically equivalent.

How strong is the patent estate?

Patent 10,835,527 has meaningful commercial scope but a narrower litigation profile than a core composition or formulation patent.

Strengths

The dose range encompasses the marketed Contrave maintenance regimen.
The titration claims track the approved dosing schedule.
The treatment-duration limitation is clinically realistic.
The cardiovascular-risk population is commercially identifiable.
Claims 10 and 11 provide objective patient-selection criteria.
The patent extends protection beyond the initial approval period.

Vulnerabilities

Naltrexone and bupropion were individually known drugs.
The combination was known before the patent’s priority date.
Obesity treatment with the combination was already established.
“Increased risk of adverse cardiovascular outcomes” may require factual interpretation.
Claims requiring a reduction in cardiovascular risk may present enablement and proof issues.
A generic applicant may limit labeling to non-patented uses.
The claims do not directly protect the physical Contrave tablet.

The patent’s value is highest when the branded product is prescribed to patients with documented cardiovascular risk and the record supports continued use for at least 12 weeks. Its value is lower against a generic label that omits the patented population and cardiovascular-risk language.

What litigation and settlement risks affect generic launch?

A Paragraph IV dispute involving Patent 10,835,527 could produce several outcomes:

Outcome	Effect on generic launch
Patent upheld and infringed	Launch blocked until expiry or settlement date
Patent invalidated	Early launch possible, subject to other listed patents
No infringement	Generic may proceed after regulatory approval
Settlement with delayed entry	Entry date depends on agreement terms
Label carve-out accepted	Generic may launch for non-patented uses
Multiple patents remain	Other formulation or composition patents may continue to block launch

A settlement involving one Contrave patent would not necessarily clear all patent barriers. Generic launch analysis must assess the entire Orange Book portfolio, not Patent 10,835,527 in isolation.

What generic entry scenarios exist?

Scenario 1: Full-label ANDA challenge

The applicant seeks approval for the full approved indication and certifies Paragraph IV against listed patents. This creates the highest litigation risk but preserves the broadest commercial market.

Scenario 2: Section viii carve-out

The applicant removes the patented cardiovascular-risk use from its labeling. This may reduce infringement exposure but can be difficult if the omitted population overlaps with the principal weight-management indication.

Scenario 3: At-risk launch

The applicant launches before final resolution of patent litigation. This creates potential damages, injunction and destruction-of-market-share exposure.

Scenario 4: Post-expiry launch

The applicant waits until the relevant patent and any stronger formulation or composition patents expire. This produces the lowest litigation risk but delays market entry.

What is the revenue exposure?

Patent 10,835,527 matters because it can preserve branded use in a high-risk cardiometabolic segment after earlier combination and formulation patents have expired or weakened.

The affected market includes:

Patients with obesity and established cardiovascular disease;
Current smokers with obesity;
Patients with obesity and type 2 diabetes;
Patients treated for at least 12 to 20 weeks;
Patients receiving the commercial four-week titration schedule.

The patent does not protect all Contrave prescriptions. It protects prescriptions that satisfy the patient-risk, dosing and duration limitations. Revenue exposure therefore depends on the percentage of branded prescriptions directed to covered patients and the ability of a generic sponsor to use a carved-out label.

Public financial reporting has not established a reliable standalone revenue figure attributable specifically to the claims of Patent 10,835,527. The correct commercial approach is to model exposure by covered patient segment rather than assign the entire Contrave market to this patent.

Key Takeaways

Patent 10,835,527 is a method-of-use patent for naltrexone-bupropion obesity treatment in patients at elevated cardiovascular risk.
Claim 1 covers daily naltrexone doses of 4-50 mg and bupropion doses of 50-400 mg for at least 12 weeks.
Claims 3 and 5 closely track Contrave’s commercial four-week titration schedule.
Claims 7-11 target diabetes, smoking and established cardiovascular-disease subgroups.
Claims 12-20 add a cardiovascular-risk reduction limitation and define major adverse cardiovascular outcomes.
The patent does not claim the chemical combination, tablet composition or manufacturing process.
The nominal patent-term endpoint is approximately March 30, 2031, subject to USPTO term adjustments and any terminal disclaimer.
Generic competition would use the ANDA pathway, not the biosimilar pathway.
Paragraph IV litigation would likely focus on obviousness, enablement, claim construction, induced infringement and label carve-outs.
The patent’s commercial value is strongest for branded prescriptions involving documented cardiovascular risk and long-term use.

FAQs About U.S. Patent 10,835,527

Does Patent 10,835,527 cover all Contrave prescriptions?

No. It covers prescriptions meeting the claimed cardiovascular-risk, dose and treatment-duration limitations. It does not cover every use of Contrave for obesity.

Does the patent cover bupropion or naltrexone by themselves?

No. The claims require administration of both naltrexone and bupropion in the claimed daily dose ranges.

Can a generic omit the cardiovascular-risk indication?

Potentially. A generic applicant may pursue a section viii labeling carve-out, but the feasibility depends on the scope of the listed patents, FDA labeling requirements and whether the remaining label still induces the claimed use.

Does the patent require extended-release tablets?

Only claim 12 expressly requires sustained-release naltrexone and sustained-release bupropion. Claim 1 does not expressly include a sustained-release limitation.

Is Patent 10,835,527 a biosimilar barrier?

No. Contrave is a small-molecule drug product. Competition would arise through an ANDA, with patent certifications under the Hatch-Waxman Act.

Does a cardiovascular benefit have to be proven in every patient?

The claims that require a decrease in cardiovascular-outcome risk create a distinct claim limitation. In litigation, the legal effect would depend on claim construction, the evidence of therapeutic effect and the conduct of the prescribing parties.

References

U.S. Food and Drug Administration. (2014). Contrave (naltrexone hydrochloride and bupropion hydrochloride) extended-release tablets: Prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/200063s000lbl.pdf
U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
U.S. Patent and Trademark Office. (2020). U.S. Patent No. 10,835,527: Methods of treating overweight or obesity in subjects at increased risk of adverse cardiovascular outcomes. https://patents.google.com/patent/US10835527B2/en
U.S. Food and Drug Administration. (2024). Abbreviated new drug application submissions and patent certifications under the Hatch-Waxman Act. https://www.fda.gov/drugs/cder-small-business-industry-assistance-sbia/abbreviated-new-drug-application-anda-submissions-patent-certifications-and-30-month-stays

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	⤷ 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
Canada	2932127	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,835,527

Which drugs does patent 10,835,527 protect, and when does it expire?

Summary for Patent: 10,835,527