United States Patent 10,786,489: Scope, Claims, Expiration, and Selpercatinib Patent Landscape
U.S. Patent No. 10,786,489 protects pharmaceutical formulations containing selpercatinib, the active ingredient in Eli Lilly’s Retevmo product. Its principal coverage is directed to solid oral dosage forms containing approximately 15% to 35% selpercatinib, 65% to 85% diluent or filler, and 0.1% to 5% glidant. The patent also covers liquid formulations containing selpercatinib and an aqueous sweetener, plus treatment of specified cancers and pediatric patients.
The patent was granted on September 22, 2020. Its 20-year patent term is expected to run from the relevant nonprovisional or international filing date to approximately May 2037, subject to terminal disclaimers, patent-term adjustment, patent-term extension, and any applicable regulatory exclusivity. The patent is associated with the Retevmo formulation estate and is distinct from earlier patents covering the selpercatinib molecule itself.
What drug does U.S. Patent 10,786,489 cover?
Formula I in the patent is selpercatinib, also known as LOXO-292. Selpercatinib is a selective RET kinase inhibitor developed by Loxo Oncology and commercialized by Eli Lilly under the Retevmo brand.
The patent covers selpercatinib in several physical and pharmaceutical forms:
| Covered form |
Expressly covered by the claims |
| Selpercatinib free compound |
Yes |
| Pharmaceutically acceptable salt |
Yes |
| Amorphous form |
Yes |
| Polymorph form |
Yes |
| Solid oral formulation |
Yes |
| Liquid formulation |
Yes |
| 40 mg dosage form |
Yes |
| 80 mg dosage form |
Yes |
| Pediatric administration |
Yes, through claim 18 |
| Specific cancer treatment methods |
Yes |
The claims do not depend on a particular salt, amorphous form, or polymorph for the core solid-formulation coverage. Claim 1 expressly reaches the compound, acceptable salts, amorphous forms, and polymorphs.
What are the principal limitations of claim 1?
Claim 1 requires a solid formulation containing three categories of ingredients within specified weight ranges:
| Component |
Claimed range |
| Selpercatinib or covered form |
About 15 wt% to about 35 wt% |
| Diluent or filler |
About 65 wt% to about 85 wt% |
| Glidant |
About 0.1 wt% to about 5 wt% |
The claim is formulation-specific. It does not cover every selpercatinib product. An accused product would need to satisfy the claimed solid dosage form and the relevant compositional limitations, either literally or under the doctrine of equivalents.
The ranges are broad enough to cover the disclosed commercial-style composition in claim 7:
- Approximately 30 wt% selpercatinib
- Approximately 69 wt% diluent or filler
- Approximately 1 wt% glidant
Because the listed percentages total 100%, claim 7 describes a highly concentrated three-component composition. The claim language does not necessarily exclude minor additional ingredients, such as lubricants, disintegrants, binders, coating materials, coloring agents, or capsule-shell components, unless the patent’s specification or claim construction gives the percentages an exclusive meaning.
How do claims 2 through 7 narrow the solid formulation?
Claims 2 through 7 create progressively narrower formulation positions.
Microcrystalline cellulose limitation
Claim 2 requires the diluent or filler to be microcrystalline cellulose. This is a commercially common pharmaceutical excipient and likely corresponds to the preferred filler used in the patent’s development work.
Claim 2 is narrower than claim 1 but may be more commercially important because a generic product using microcrystalline cellulose would fall within the express dependent claim if all other limitations are met.
Fumed silica or silicon dioxide limitation
Claim 3 requires the glidant to be fumed silica or silicon dioxide. Silicon dioxide is commonly used to improve powder flow and manufacturing performance.
The claim does not appear to require a particular particle size, surface treatment, grade, or supplier. A generic formulation using colloidal silicon dioxide may therefore present a higher literal-infringement risk than a formulation using a chemically distinct flow aid.
Dosage-form limitation
Claim 4 extends coverage to multiple solid dosage forms:
- Tablets
- Capsules
- Sachets
- Powders
- Granules
- Coated particles
- Coated tablets
- Enteric-coated tablets
- Enteric-coated capsules
- Melting strips
- Melting films
This language is unusually broad at the dosage-form level. It is designed to preserve coverage across conventional oral dosage forms and alternative delivery formats.
Claim 5 specifically covers powder formulations encapsulated in hard gelatin capsules. This limitation is relevant to a generic company that avoids a conventional compressed tablet but uses a powder-filled capsule.
Polymorph limitation
Claim 6 requires preparation from a polymorph of selpercatinib or an acceptable salt. A polymorph-specific product may infringe claim 6 even if the manufacturer disputes infringement of the broader product-by-composition claims.
Defined composition and 40 mg or 80 mg dosage
Claim 7 narrows the composition to approximately 30:69:1 by weight. Claim 13 requires the formulation to provide approximately a 40 mg or 80 mg selpercatinib dosage.
The 40 mg and 80 mg limitations align with the approved Retevmo capsule strengths identified in the FDA-approved labeling. [2]
What liquid formulations are protected?
Claims 8 through 12 cover liquid selpercatinib formulations containing an aqueous sweetener.
The sweetener limitations include:
- Sucrose
- Glycerin
- Sorbitol
- Sodium saccharin
- Xanthan gum
- Mannitol
- Dextrose
- Acesulfame
- Aspartame
- Fructose
- Maltitol
- Sucralose
Claim 11 specifically covers a formulation containing glycerin, sorbitol, sodium saccharin, xanthan gum, or a combination thereof, where sucrose is absent.
The liquid claims are not limited to a particular concentration, pH, preservative system, viscosity, flavoring system, or container. They also do not require a particular pediatric dose. The principal structural limitation is the combination of selpercatinib and an aqueous sweetener.
The liquid-formulation claims may be important for pediatric development because solid capsules can present swallowing and dose-flexibility problems. Claim 18 specifically addresses treatment of pediatric patients with the claimed liquid formulation.
What cancer treatment methods are covered?
Claims 14 through 18 cover administration of the claimed formulation to treat a defined set of cancers and related conditions.
| Disease or condition listed in the claims |
| Lung cancer |
| Papillary thyroid cancer |
| Medullary thyroid cancer |
| Differentiated thyroid cancer |
| Recurrent thyroid cancer |
| Refractory differentiated thyroid cancer |
| MEN2A |
| MEN2B |
| Pheochromocytoma |
| Parathyroid hyperplasia |
| Breast cancer |
| Colorectal cancer |
| Papillary renal cell carcinoma |
| Ganglioneuromatosis of the gastroenteric mucosa |
| Cervical cancer |
Claim 15 narrows the method to lung cancer. Claim 16 narrows it to medullary thyroid cancer. Claim 18 narrows the liquid-formulation method to a pediatric patient.
The treatment claims require administration of either the claimed solid formulation or the claimed liquid formulation. They are not simply claims to selpercatinib treatment without a formulation requirement. That distinction is material in litigation because a defendant may attempt to separate the product claim from the method-of-treatment claim by using a formulation outside the claimed composition.
What is the FDA and Orange Book status of the patent?
Retevmo received FDA accelerated approval in May 2020 for RET fusion-positive non-small cell lung cancer, RET-mutant medullary thyroid cancer, and RET fusion-positive thyroid cancer requiring systemic therapy and radioactive iodine-refractory status where appropriate. [3]
The product is approved in 40 mg and 80 mg capsules. The FDA-approved labeling identifies selpercatinib as the active ingredient and provides dosing instructions based on body weight and indication. [2]
U.S. Patent 10,786,489 has been associated with the Retevmo patent estate and is relevant to Orange Book-based generic certification analysis. An Orange Book listing does not itself establish that every claim is infringed by every generic product. It gives an innovator a statutory basis to invoke the Hatch-Waxman litigation mechanism after a Paragraph IV notice.
Because Orange Book listings and patent-status entries can change through corrections, delistings, continuations, terminal disclaimers, and court decisions, the legally operative status is the current FDA Orange Book record and the applicable USPTO and court dockets. [1]
When does selpercatinib lose exclusivity?
Retevmo’s exclusivity has multiple components:
| Exclusivity or protection |
Relevance |
| New chemical entity exclusivity |
Bars certain ANDA submissions for four years after approval |
| Orphan-drug exclusivity |
Can block approval of the same drug for the same orphan indication for seven years |
| Formulation patents |
May delay or complicate generic approval and launch |
| Active-ingredient patents |
May protect the molecule independently of formulation patents |
| Method-of-use patents |
May create indication-specific barriers |
| Pediatric exclusivity |
May add six months if granted for completed FDA-requested studies |
The practical generic-entry date is not determined by the patent expiration date alone. An ANDA applicant can file a Paragraph IV certification before patent expiration. Entry may occur after settlement, after a successful invalidity or noninfringement decision, after a statutory stay expires, or after the patent expires.
The formulation patent is expected to remain relevant through approximately 2037, subject to the patent-term variables stated above. The FDA regulatory exclusivity periods for the original approvals are shorter than the expected patent term and therefore are unlikely to be the primary long-term barrier if the listed formulation patents remain enforceable.
What other patents protect selpercatinib?
The selpercatinib estate is broader than U.S. Patent 10,786,489. It generally includes four patent categories.
Active pharmaceutical ingredient patents
Earlier patent families cover substituted heterocyclic kinase inhibitors, including selpercatinib and related compounds. These patents may contain composition-of-matter claims, pharmaceutical-composition claims, and therapeutic-use claims.
Composition-of-matter patents normally have the strongest exclusionary position because they do not depend on a particular excipient system. If an active-ingredient patent remains enforceable, a generic cannot avoid infringement merely by changing from a capsule to a tablet or by replacing microcrystalline cellulose.
Solid-state and polymorph patents
Separate patent families may address crystalline forms, amorphous material, salts, solvates, particle characteristics, or manufacturing processes. These patents can be relevant when an applicant uses the same solid form as the reference product or relies on a protected form for bioequivalence.
Claim 6 of Patent 10,786,489 creates some polymorph-related coverage, but a complete freedom-to-operate review would require comparison against all identified solid-state families.
Formulation patents
Patent 10,786,489 is principally a formulation patent. Its commercial value comes from the combination of:
- Selpercatinib concentration,
- filler or diluent range,
- glidant range,
- specified excipients,
- dosage-form coverage, and
- method-of-treatment claims.
A generic manufacturer may try to design around this coverage by using different concentration ranges, a different filler, a different glidant, or a liquid vehicle without the claimed sweetener. Each design-around must be evaluated against the independent claim and the doctrine of equivalents.
Method-of-use patents
The treatment claims cover multiple RET-driven malignancies and related syndromes. Method-of-use claims may be asserted against a product label that expressly instructs physicians to use selpercatinib for a claimed indication.
A skinny-label strategy can reduce, but not always eliminate, induced-infringement risk. The analysis depends on the approved label, promotional conduct, prescribing patterns, the scope of the patent claims, and the relevant Federal Circuit precedent.
Which companies are likely to challenge the patent?
Potential challengers include ANDA applicants seeking approval for selpercatinib capsules or alternative oral dosage forms. The identity of a challenger is not reliably established solely from the patent claims. A complete litigation assessment must distinguish:
- Paragraph IV notices,
- ANDA filing activity,
- district-court complaints,
- inter partes review petitions,
- declaratory-judgment actions,
- settlements, and
- authorized generic or license arrangements.
No specific Paragraph IV challenger, settlement, or final invalidity judgment should be attributed to Patent 10,786,489 without a current review of FDA, PACER, PTAB, USPTO, and company disclosures.
How strong is the patent estate?
Strengths
The patent has several commercially useful features:
- Claim 1 covers a broad solid-formulation composition.
- Claims 2 and 3 capture common excipients used in oral dosage forms.
- Claim 4 reaches multiple dosage forms.
- Claim 7 maps to a defined 30:69:1 composition.
- Claim 13 aligns with the marketed 40 mg and 80 mg strengths.
- Claims 14 through 18 add formulation-linked treatment claims.
- The expected expiration is materially later than the original FDA exclusivity periods.
Vulnerabilities
The main vulnerability is claim specificity. A challenger could attack:
- Written description support for the breadth of the excipient and dosage-form lists;
- Enablement of the full composition ranges;
- Obviousness over conventional capsule and tablet formulations;
- Obviousness based on known glidants and fillers;
- Indefiniteness of terms such as "about";
- Lack of novelty for liquid formulations containing an active compound and common aqueous sweeteners;
- Noninfringement based on excipient percentages outside the claimed ranges.
The claims may be stronger against a product that closely reproduces the disclosed composition than against a deliberately redesigned formulation.
What generic launch scenarios exist?
| Scenario |
Commercial effect |
| Generic copies the 40 mg and 80 mg capsule composition |
High formulation-patent risk |
| Generic uses microcrystalline cellulose and silicon dioxide |
Increased risk under claims 2 and 3 |
| Generic changes filler but retains claim 1 ranges |
Claim 1 risk remains |
| Generic changes concentration outside 15% to 35% |
May avoid literal claim 1 infringement |
| Generic uses a liquid formulation with sorbitol or glycerin |
Claims 8 through 12 may apply |
| Generic uses a liquid without an aqueous sweetener |
May avoid the liquid claims, subject to other patents |
| Generic launches after patent expiry |
Lower formulation-patent risk, subject to other rights |
| Generic launches under settlement or license |
Depends on the negotiated entry date and restrictions |
Does the patent create biosimilar risk?
No. Selpercatinib is a small-molecule drug, not a biologic. The relevant pathway is an abbreviated new drug application under Hatch-Waxman, not a biosimilar application under the Public Health Service Act.
The commercial risk is therefore generic substitution, not biosimilar substitution. The principal legal tools are Paragraph I, II, III, and IV certifications, the 30-month stay, patent litigation, and settlement agreements.
What licensing and settlement issues matter?
Loxo Oncology was acquired by Eli Lilly in 2019, before Retevmo’s FDA approval. Lilly is the principal commercial sponsor and patent-estate owner or controller for the Retevmo program. [4]
Licensing and settlement analysis should distinguish between:
- Rights to the selpercatinib molecule;
- Rights to formulation patents;
- Rights to specific indications;
- Authorized-generic arrangements;
- Pediatric formulation rights;
- Territory-specific licenses; and
- Paragraph IV settlement agreements.
No settlement should be treated as established for this patent without a reported agreement, court filing, SEC disclosure, or FDA-recognized entry arrangement.
Key Takeaways
- U.S. Patent 10,786,489 is a selpercatinib formulation patent tied to Retevmo.
- Its core solid claim requires approximately 15% to 35% selpercatinib, 65% to 85% filler, and 0.1% to 5% glidant.
- Microcrystalline cellulose and silicon dioxide are expressly covered through dependent claims.
- The patent reaches tablets, capsules, powders, granules, coated forms, enteric forms, melting strips, and melting films.
- Liquid formulations containing selpercatinib and an aqueous sweetener are separately claimed.
- The patent covers treatment of multiple RET-associated cancers and pediatric treatment using the claimed liquid formulation.
- The 40 mg and 80 mg dosage forms correspond to the approved Retevmo capsule strengths.
- The expected patent term extends to approximately 2037, subject to patent-term adjustments and other statutory modifications.
- Generic risk depends on the full patent estate, not this patent alone.
- A generic formulation that copies the marketed composition is exposed under both the independent and dependent claims.
FAQs About U.S. Patent 10,786,489
Does U.S. Patent 10,786,489 cover selpercatinib itself?
No. Its principal claims cover selpercatinib in specified solid and liquid formulations. Separate composition-of-matter patents may protect selpercatinib as an active pharmaceutical ingredient.
Does using a tablet instead of a capsule avoid this patent?
Not necessarily. Claim 4 expressly includes tablets and capsules, and claim 1 is directed to the composition rather than only one marketed dosage form.
Can a generic avoid the patent by removing microcrystalline cellulose?
Potentially, but removing microcrystalline cellulose would not necessarily avoid claim 1. Claims 2 and 3 are narrower, while claim 1 covers a broader diluent-or-filler category.
Does the patent cover a selpercatinib oral solution for children?
It can cover a liquid formulation containing selpercatinib and an aqueous sweetener. Claim 18 specifically addresses pediatric treatment with the claimed liquid formulation.
Is a Paragraph IV certification required for a generic selpercatinib product?
If a relevant patent is listed in the Orange Book and the applicant seeks approval before patent expiration, the applicant must select the applicable patent certification. A Paragraph IV certification is used when the applicant asserts that the listed patent is invalid, unenforceable, or will not be infringed.
References
- U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
- U.S. Food and Drug Administration. (2024). Retevmo (selpercatinib) prescribing information. Eli Lilly and Company.
- U.S. Food and Drug Administration. (2020). FDA grants accelerated approval to selpercatinib for metastatic RET fusion-positive non-small cell lung cancer. FDA.
- Eli Lilly and Company. (2019). Lilly completes acquisition of Loxo Oncology. Lilly investor relations.
- United States Patent and Trademark Office. (2020). U.S. Patent No. 10,786,489, pharmaceutical compositions comprising selpercatinib. USPTO.
