US Patent 11,351,166: Olanzapine-Samidorphan Method-of-Use Claims, Exclusivity and Generic Risk
US Patent No. 11,351,166 protects daily treatment of bipolar disorder or schizophrenia with olanzapine combined with 10 mg of samidorphan, calculated on a free-base basis, to mitigate olanzapine-associated weight gain. The patent is directed to clinical use rather than to samidorphan itself, olanzapine itself, or a broad composition-of-matter claim.
The claims track the clinical profile of Lybalvi, Alkermes’ fixed-dose olanzapine and samidorphan product. Lybalvi contains olanzapine and samidorphan hydrochloride in four approved strengths: 5 mg/10 mg, 10 mg/10 mg, 15 mg/10 mg and 20 mg/10 mg [1].
What drug and compound does US Patent 11,351,166 cover?
The unidentified compound in the supplied claims is samidorphan, an orally active opioid receptor antagonist. The commercial product uses samidorphan hydrochloride. The claim language requiring 10 mg "based on the free base weight" therefore covers the amount of samidorphan equivalent to 10 mg of samidorphan free base, regardless of the additional mass attributable to the hydrochloride salt.
| Item |
Patent scope |
| Active antipsychotic |
Olanzapine |
| Weight-mitigation agent |
Samidorphan |
| Claimed daily amount |
10 mg samidorphan, free-base equivalent |
| Salt form |
Free base or pharmaceutically acceptable salt in claim 1; salt required in claims 8, 11 and 13 |
| Patient population |
Bipolar disorder or schizophrenia; narrower claims specify bipolar I and manic or mixed episodes |
| Dosage form |
Any pharmaceutical composition in claim 1; tablet in claims 3 and 9 |
| Excipients |
Any pharmaceutically acceptable excipient; lactose and magnesium stearate are expressly claimed |
| Administration |
Daily; orally administered in claims 8, 10 and 13 |
| Therapeutic result |
Mitigation of weight gain compared with olanzapine alone |
What are the independent claims in US Patent 11,351,166?
The patent has four independent claims with overlapping but materially different infringement theories.
Claim 1: Combination-composition treatment claim
Claim 1 requires:
- A human patient with bipolar disorder or schizophrenia.
- A need for olanzapine treatment and mitigation of olanzapine-associated weight gain.
- Daily administration.
- A pharmaceutical composition containing olanzapine, 10 mg free-base-equivalent samidorphan or a pharmaceutically acceptable salt, and an excipient.
- Weight gain that is mitigated compared with administration of olanzapine alone.
This is the broadest independent claim in the supplied set because it does not expressly require oral administration, a tablet, a specific salt, lactose or magnesium stearate. It covers a fixed-dose product and potentially other pharmaceutical compositions that contain both active ingredients.
Claim 8: Oral salt-combination claim
Claim 8 narrows claim 1 by requiring:
- Oral administration.
- Daily dosing.
- Samidorphan in a pharmaceutically acceptable salt form.
- A composition containing olanzapine and 10 mg free-base-equivalent samidorphan.
Claim 8 most closely tracks the approved Lybalvi product.
Claim 10: Separate administration or coadministration claim
Claim 10 does not require a single fixed-dose composition. It requires:
- A patient with bipolar disorder I or bipolar disorder I with a mixed or manic episode.
- Daily oral administration of 10 mg free-base-equivalent samidorphan.
- Daily administration of olanzapine as the antipsychotic.
- Mitigation of weight gain associated with olanzapine treatment.
This claim reaches a regimen in which samidorphan and olanzapine are supplied separately, provided the claimed dosing and therapeutic conditions are met.
Claim 13: Manic, mixed-episode and schizophrenia claim
Claim 13 covers treatment of:
- A manic or mixed episode associated with bipolar disorder I; or
- Schizophrenia.
It requires oral daily samidorphan, in salt form, and daily olanzapine. Compared with claim 10, it expressly includes schizophrenia and focuses on the manic or mixed-episode and schizophrenia populations.
How do the dependent claims narrow the patent?
| Claim |
Limitation |
| 2 |
Samidorphan is present as a pharmaceutically acceptable salt |
| 3 |
Composition is a tablet |
| 4 |
Composition contains lactose |
| 5 |
Composition contains magnesium stearate |
| 6 |
Composition contains both magnesium stearate and lactose |
| 7 |
Patient has bipolar disorder I with a mixed or manic episode |
| 9 |
Claim 8 composition is a tablet |
| 11 |
Samidorphan is present in a pharmaceutical composition as a pharmaceutically acceptable salt |
| 12 |
Samidorphan and olanzapine are administered concurrently |
| 14 |
Samidorphan is present in the pharmaceutical composition as a pharmaceutically acceptable salt |
The lactose and magnesium stearate limitations are formulation-specific fallbacks. They are relevant to a tablet that uses conventional direct-compression or granulation excipients, but they do not materially expand the core commercial coverage.
What formulations are protected by US Patent 11,351,166?
The strongest commercial read-on is a daily oral tablet containing olanzapine and samidorphan hydrochloride, with samidorphan at 10 mg free-base equivalent. The patent does not require a specific olanzapine strength in the supplied claims.
That distinction matters because Lybalvi is marketed with multiple olanzapine doses while retaining 10 mg samidorphan:
| Lybalvi strength |
Olanzapine |
Samidorphan hydrochloride, free-base equivalent |
| 5 mg/10 mg |
5 mg |
10 mg |
| 10 mg/10 mg |
10 mg |
10 mg |
| 15 mg/10 mg |
15 mg |
10 mg |
| 20 mg/10 mg |
20 mg |
10 mg |
A tablet with lactose or magnesium stearate falls within the narrower dependent claims if the other limitations are satisfied. A capsule, suspension or separately packaged regimen could still implicate the broader independent claims, depending on the administration and composition facts.
Does the patent cover separate olanzapine and samidorphan products?
Yes, claims 10 and 13 are drafted to reach separate administration. They require daily samidorphan and daily olanzapine but do not require that both ingredients be in the same tablet.
Claim 12 narrows claim 10 to concurrent administration. "Concurrent" does not necessarily require a single dosage unit. A patient could take separate olanzapine and samidorphan products at the same time and potentially satisfy the claim, subject to the claim construction adopted in litigation.
This separate-administration coverage increases the patent's relevance to:
- A generic olanzapine product paired with a separately supplied samidorphan product.
- A co-packaged regimen.
- A dual-product treatment protocol.
- A physician-directed combination regimen.
What is the FDA and Orange Book status of Lybalvi?
The FDA approved Lybalvi on May 28, 2021, for adults with schizophrenia and for adults with bipolar I disorder, including acute treatment of manic or mixed episodes and maintenance treatment [1]. The product combines olanzapine with samidorphan to reduce the weight-gain liability associated with olanzapine.
Lybalvi is approved under NDA 214369. Its regulatory protection has two separate components:
| Protection |
Relevance |
| New chemical entity exclusivity |
Samidorphan was a new active ingredient in the approved product |
| Listed patents |
Patent-based barriers to ANDA approval and commercial launch |
| Clinical-use labeling |
Supports method-of-use patent coverage for weight-gain mitigation |
| Pediatric exclusivity |
Any additional six-month period depends on the FDA exclusivity record |
The five-year NCE exclusivity period for the samidorphan-containing product generally runs from the May 28, 2021 approval date, subject to the applicable statutory treatment of the combination and active ingredient. A Paragraph IV ANDA filing could occur during the final year of NCE exclusivity, but FDA approval would remain blocked until the exclusivity period ends unless an exception applies [2].
The Orange Book must be reviewed for the current patent listing, expiration dates and any pediatric-extension adjustment. Patent listing and patent enforceability are separate issues. An Orange Book listing does not establish that every listed claim is valid or infringed.
When does US Patent 11,351,166 lose exclusivity?
The patent term is determined from its relevant nonprovisional filing date, subject to patent-term adjustment, patent-term extension and any terminal disclaimer. The priority chain, USPTO term calculation and Orange Book entry control the operative expiration date.
The patent is a later-issued patent in the Lybalvi estate, but its issue date does not establish the expiration date. A patent issued in 2022 can expire earlier than a later-issued continuation if both claim priority to the same application family.
For commercial planning, three dates must be separated:
- FDA NCE exclusivity expiration.
- The expiration date listed for US 11,351,166.
- The earliest date on which a generic or authorized generic can launch after resolving listed-patent litigation.
The third date may be later because of a 30-month stay, a court injunction, a settlement restriction or a later-expiring patent in the same estate.
How strong is the patent estate for olanzapine-samidorphan?
The estate is stronger as a combination and clinical-use portfolio than as a standalone samidorphan portfolio.
Strengths
- The claims cover the commercially important 10 mg samidorphan dose.
- The claims reach both fixed-dose compositions and separate administration.
- The claims cover the approved schizophrenia and bipolar I populations.
- The claims are tied to the product's principal clinical value proposition: reducing olanzapine-associated weight gain.
- The claims cover multiple formulation configurations, including tablets and common excipients.
Vulnerabilities
- The 10 mg samidorphan dose is highly specific and may be designed around by using a different dose, subject to clinical viability and infringement analysis.
- The weight-mitigation limitation may create proof issues if a challenger disputes whether the accused regimen produces the claimed comparative result.
- The claims are treatment claims, so infringement depends on actual or induced use for the claimed indications.
- The formulation claims using lactose or magnesium stearate are narrow and may not cover every generic formulation.
- Prior-art challenges may focus on earlier olanzapine/opioid-antagonist combination concepts, clinical weight-gain data, obviousness of dose selection and written-description support for the claimed patient populations.
The patent is more difficult to design around while preserving the approved Lybalvi regimen than a conventional excipient claim. A competitor changing only the tablet excipients would remain exposed to the independent claims.
Which companies are likely to challenge the Lybalvi patent estate?
Generic companies may challenge Lybalvi through ANDA filings containing Paragraph IV certifications against Orange Book-listed patents. The commercial targets are likely to include:
- The fixed-dose olanzapine/samidorphan tablet.
- The 10 mg samidorphan component.
- The method of reducing olanzapine-associated weight gain.
- Separate administration of olanzapine and samidorphan.
The supplied information does not establish a specific Paragraph IV filer, litigation docket, settlement agreement or launch date for US 11,351,166. Those events must be tied to individual ANDA filings and district-court records rather than inferred from the patent claims.
What generic launch scenarios exist?
Scenario 1: No successful Paragraph IV challenge
A generic applicant waits until relevant patents and exclusivities expire. Launch timing is determined by the latest enforceable patent or settlement restriction.
Scenario 2: Invalidity or noninfringement judgment
A challenger may launch before the listed patent expiry if the court finds the asserted claims invalid or not infringed and no other barrier remains.
Scenario 3: Section VIII carve-out
A generic applicant may omit a patented indication from its labeling if the remaining label supports approval without the protected use. This route is difficult where the central commercial use is the combination of olanzapine and samidorphan for weight-gain mitigation.
Scenario 4: Settlement with licensed entry
Alkermes and a generic applicant could agree to a later launch date, an authorized-generic arrangement or another commercial resolution. The terms would determine whether the generic can launch before patent expiration.
What litigation issues are most important?
The principal litigation issues are likely to be:
- Whether the accused product contains 10 mg samidorphan on a free-base-equivalent basis.
- Whether samidorphan is present in a qualifying salt form.
- Whether the product is administered daily and orally.
- Whether the patient population falls within bipolar I, manic or mixed episodes, or schizophrenia.
- Whether the accused labeling induces the claimed weight-mitigation use.
- Whether the claimed therapeutic result is a required limitation and how it is measured.
- Whether earlier combination patents or publications render the claims obvious.
- Whether the patent adequately supports the full range of claimed patient populations and formulations.
How does US Patent 11,351,166 compare with composition patents?
A composition patent generally protects the product regardless of the indication. US 11,351,166 is narrower in that it requires a claimed treatment method and clinical context. It is also commercially significant because the claimed method corresponds to the labeled use of Lybalvi.
| Patent type |
Principal protection |
Typical design-around |
| Samidorphan composition-of-matter patent |
Samidorphan molecule or salt |
Difficult; usually strongest protection |
| Olanzapine-samidorphan composition patent |
Fixed-dose product |
Separate products, different ratios or formulations |
| Formulation patent |
Tablet architecture or excipients |
Change excipients, process or dosage form |
| US 11,351,166 |
Daily clinical use for weight-gain mitigation |
Change dose, indication, administration or labeling |
Key Takeaways
- US 11,351,166 covers daily administration of olanzapine with 10 mg free-base-equivalent samidorphan.
- The compound is samidorphan, and the commercial salt is samidorphan hydrochloride.
- Claim 1 is the broadest supplied claim and reaches combination compositions.
- Claims 10 and 13 extend protection to separate daily administration of samidorphan and olanzapine.
- The patent covers schizophrenia and bipolar I treatment, including manic or mixed episodes.
- Tablet, lactose and magnesium stearate limitations provide narrower formulation fallbacks.
- The patent is a method-of-use asset within the broader Lybalvi patent estate.
- FDA exclusivity, Orange Book patent expiry, patent litigation and settlement dates must be analyzed separately.
- Generic risk is highest for a product that duplicates Lybalvi's 10 mg samidorphan dose, approved indications and weight-mitigation labeling.
FAQs
Is US 11,351,166 a patent on samidorphan itself?
No. The supplied claims protect treatment methods using samidorphan with olanzapine. They do not claim samidorphan as a molecule in isolation.
Does a different olanzapine dose avoid the patent?
Not necessarily. The supplied claims specify 10 mg samidorphan but do not specify a particular olanzapine dose. A different olanzapine strength could still fall within the claims.
Does using a capsule instead of a tablet avoid infringement?
It may avoid claims expressly limited to tablets, such as claims 3 and 9. It would not automatically avoid claim 1 or the broader administration claims.
Can a generic omit the weight-gain language from its label?
A label carve-out may reduce method-of-use exposure, but it must satisfy FDA labeling rules and must not otherwise induce the patented use. The feasibility depends on the remaining approved indications and the Orange Book listing.
Is samidorphan hydrochloride dosed at 10 mg or at a higher salt mass?
The claims measure the dose by samidorphan free-base weight. The hydrochloride product therefore contains a greater total mass than 10 mg because the salt includes hydrochloride, while the claimed active moiety remains 10 mg free-base equivalent.
References
- U.S. Food and Drug Administration. (2021). Lybalvi (olanzapine and samidorphan) prescribing information.
- U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
- U.S. Patent and Trademark Office. (2022). U.S. Patent No. 11,351,166, methods for treating patients with olanzapine and samidorphan.
- U.S. Food and Drug Administration. (2021). NDA 214369 approval letter for Lybalvi.
