United States Patent 12,138,250: Scope, Claim Structure, and RET-fusion Competitive Landscape
What does US 12,138,250 claim, at the highest level?
US 12,138,250 claims methods of treating patients with RET-fusion positive solid tumors by administering a compound of Formula (I), or specific pharmaceutical forms of it (including salts and solid forms), to patients in need. The scope is anchored on three pillars:
- Indication class: “RET-fusion positive solid tumors” and “RET-associated cancers” that are enumerated in the claims.
- Treatment modality: administering a therapeutically effective amount of a “Formula (I)” compound (or pharmaceutically acceptable salt/amorphous/polymorph).
- Sub-populations and use conditions: thyroid and lung sub-types, and clinical settings such as advanced/metastatic and refractory or intolerant disease with prior platinum/PD-1/PD-L1 exposure.
The independent method claims are written as use-method claims (method of treatment), not composition claims. This framing drives how competitors can design around: they can avoid infringement by changing the target biology definition, the delivered active, or the claimed treatment context.
What is the core claim scope in claim 1?
Claim 1 is the broadest independent method claim you provided. It requires all elements below:
- Patient population: “patients having RET-fusion positive solid tumors”
- Tumor biology definition: the RET-fusion positive tumors are “RET-associated cancers”
- Therapy: administer a therapeutically effective amount of:
- a compound of Formula (I), or
- a pharmaceutically acceptable salt, or
- an amorphous form or polymorph form thereof
- Cancer list: the RET-associated cancers are selected from:
- thyroid cancer
- lung cancer
- pancreatic cancer
- pancreatic ductal carcinoma
- breast cancer
- colon cancer
- colorectal cancer
- prostate cancer
- renal cell carcinoma
- head and neck tumors
- neuroblastoma
- melanoma
Scope implications
- The claim is set-enumerated, not open-ended. In practice, the cancer list is the primary boundary for whether a method falls within the claim.
- The claim does not require metastatic/refractory status in claim 1; that narrowing appears in dependent claims.
How do claims 2, 3 narrow the molecule definition?
Claim 2: tosylate salt
- “The pharmaceutically acceptable salt is the tosylate salt.”
This narrows the salt definition to a single identified salt form. If a competitor uses a different acceptable salt, infringement depends on whether the competitor’s salt falls outside the “tosylate” limitation for the specific dependent claim. Under standard claim hierarchy, the narrowing applies to that dependent claim only; the independent claim 1 remains broader if it does not require tosylate.
Claim 3: thyroid and lung subtype sub-selection
- Thyroid cancer is selected from:
- papillary thyroid carcinoma
- medullary thyroid carcinoma
- Lung cancer is selected from:
- lung adenocarcinoma
- small-cell lung carcinoma
This is a subcategory narrowing that matters for later landscape mapping, because it affects whether a clinician protocol targeting other thyroid or lung histologies would still land inside dependent claim coverage.
What is the independent claim 4 and what changes vs claim 1?
Claim 4 is another independent method claim with essentially the same structure as claim 1, but it uses alternative phrasing:
- Treat patients with RET-associated solid tumors
- Administer Formula (I) compound or acceptable salt/amorphous/polymorph forms
- RET-associated cancers are selected from the same enumerated cancer set as claim 1
Key delta
- Claim 1 starts with “RET-fusion positive solid tumors” and then says those are “RET-associated cancers.”
- Claim 4 starts with “RET-associated solid tumors” and then sets the cancer list.
In infringement analysis, this can create arguments about whether “RET-associated” and “RET-fusion positive” are coextensive in the patent’s technical context. Still, both claims are bound to the same enumerated cancer set and the same Formula (I)-based administration.
How do claims 6 to 7 narrow the clinical context?
Claim 6: advanced solid tumors
- “The solid tumors are advanced solid tumors.”
This adds a clinical stage limiter. It does not define “advanced” in the text you provided, so the practical scope will track how “advanced” is used in the patent specification and prosecution record, but the dependent claim clearly intends narrower coverage than claim 1/4.
Claim 7: thyroid and lung subtype narrowing again
This repeats the thyroid and lung subtype limitations from claim 3 for the claim 4 path:
- papillary or medullary thyroid carcinoma
- lung adenocarcinoma or small-cell lung carcinoma
So claim 7 functions as a narrower “histology within RET-associated cancers” dependent layer.
What does claim 8 add that claim 1 does not?
Claim 8 adds both patient status and disease extent:
- “human patients having advanced or metastatic RET-fusion positive solid tumors”
- administer Formula (I) compound or acceptable salt/amorphous/polymorph forms
This is a narrower independent method claim than claim 1 because it imposes advanced or metastatic disease status.
How do claims 9 to 13 constrain the use case (salt form, refractoriness, and prior therapy)?
Claim 9: tosylate
- Compound of Formula (I) is the tosylate salt.
Claims 10-12: treatment line limitations
Each depends on claim 9 and requires refractory/intolerant or absence of standard therapy:
- Claim 10: tumor is “refractory or intolerant to standard therapy”
- Claim 11: tumor is “refractory or intolerant to prior therapy”
- Claim 12: tumor “has no standard therapy”
These capture the typical oncology legal framing for late-line use.
Claim 13: prior exposure to specific therapy classes
- Patient has undergone prior therapy with:
- platinum-based chemotherapy
- PD-1/PDL1 immunotherapy
- or both
This is a further narrowing on prior treatment history and is often used to cover post-late-line real-world protocols.
Practical claim-set map (what is covered vs what is not)
Covered by the claim set (based strictly on your text)
- Biology: RET-fusion positive solid tumors / RET-associated solid tumors, tied to the enumerated cancer set.
- Active: “compound of Formula (I)” and specified pharmaceutical forms:
- pharmaceutically acceptable salt(s) (with tosylate singled out in dependent claims)
- amorphous form
- polymorph form
- Dosing concept: “therapeutically effective amount” (no regimen limits stated in the claim text you provided).
- Clinical stage: advanced, or advanced or metastatic (claims 6 and 8).
- Late-line framing: refractory or intolerant; no standard therapy (claims 10-12).
- Prior treatment classes: platinum chemo and PD-1/PD-L1 immunotherapy (claim 13).
Not stated in the provided claims (design-out opportunities)
- No explicit required comparator therapy.
- No explicit dosing schedule (cycle length, dose, route).
- No explicit biomarker assay or threshold beyond “RET-fusion positive.”
- No explicit tumor-site restrictions beyond the cancer list and histology narrowing in dependent claims.
The absence of regimen parameters generally means the claim could read across dosing schedules so long as the administration achieves a therapeutically effective amount.
How does this claim construction affect design-around strategy?
From a patent landscape standpoint, infringement exposure tracks what you can’t change:
1) Avoiding the target definition
If a competitor’s program is used for RET-driven tumors that are not RET-fusion positive (for example, RET mutations without fusions), they may avoid “RET-fusion positive” coverage, but claim 4 also uses “RET-associated” language. Either way, the claims you provided still require falling within the listed cancers and satisfying the dependent claim elements for specific coverage.
2) Avoiding the cancer list
A design-around can target indications outside the enumerated list. The provided list includes many solid tumors but it is not identical to “all RET cancers.”
3) Avoiding the active coverage
Because the molecule is described as “compound of Formula (I),” the decisive variable is whether the competitor’s active is literally within Formula (I) as defined by the patent’s full chemical structure. Your excerpt doesn’t include the Formula (I) definition itself, so the landscape assessment for chemical equivalence cannot be completed from the text supplied.
4) Avoiding salt and solid-form dependent claims
Even if a compound is covered by Formula (I), the dependent claims add:
- tosylate salt (claims 2, 5, 9)
This can create practical infringement differences between using tosylate vs other salt forms, but only for those dependent claims.
5) Avoiding late-line/protocol dependent claims
Claims 10-13 require refractory/intolerant/no standard therapy and/or prior platinum and PD-1/PD-L1. A competitor’s intended label for earlier-line use or different treatment history can reduce exposure to those dependent claims while leaving the broader independent claims still relevant.
United States patent landscape: where this patent sits relative to the RET-fusion standard of care
This patent is method-of-use IP aimed at RET-fusion driven solid tumors. The current RET-fusion clinical space is dominated by selective RET inhibitors and multi-target kinase inhibitors used across lines of therapy. In the U.S., generic or “design-around” claims typically focus on:
- new chemical entities that fall outside the specific Formula (I),
- new salt/solid forms where the claims do not compel them,
- and new indications that sit outside the claim’s cancer list and disease status definitions.
However, because your excerpt does not include the identity of “compound of Formula (I),” the landscape cannot be mapped to specific molecules without the Formula (I) structure or the patent’s title/assignee.
So the only complete landscape statements possible from your provided text are claim-based rather than asset-based (i.e., which infringement paths are open or closed, independent of the identity of Formula (I)).
Scope stress points for investors and competitors
The claim’s strongest coverage features
- Multiple cancer types in one independent claim (broad indication set).
- No required metastatic status in claim 1 and 4.
- No required prior therapy in claim 1 and 4.
- Broad formulation coverage (salt, amorphous, polymorph, as permitted by the independent claims).
The claim’s narrowing features (where challenges are most likely)
- Dependent claims limit to tosylate.
- Dependent claims limit to:
- advanced or advanced/metastatic
- refractory or intolerant or no standard therapy
- prior platinum and/or PD-1/PD-L1
- Dependent claims narrow to specific histologies within thyroid and lung cancers.
For business planning, these narrowing features matter because infringement risk can be tiered:
- “Any use” risk under claim 1/4 is broader.
- “Late-line with tosylate and prior platinum/PD-(L)1” risk maps to claims 9-13.
Key Takeaways
- US 12,138,250 is a method-of-treatment patent that covers administering a Formula (I) compound (and specified forms) to treat RET-fusion positive / RET-associated solid tumors within an enumerated cancer list.
- Independent claim coverage (claims 1 and 4) is broad on disease stage and line of therapy; dependent claims add tosylate, advanced/metastatic status, and late-line/refractory/prior therapy constraints.
- The main infringement levers are: RET-fusion status definition, whether the tumor fits the enumerated cancer list, and whether the administered active falls within Formula (I) (plus whether the use fits dependent claim conditions like tosylate and prior platinum/PD-1/PD-L1).
FAQs
1) Does this patent require metastatic disease?
Not in claim 1 or claim 4. Claims 6 and 8 add “advanced” and “advanced or metastatic” respectively.
2) Is tosylate required for all coverage?
No. Tosylate is required only in dependent claims (for example claim 2, claim 5, claim 9), not in claim 1/4 as written in your excerpt.
3) Are all RET-driven cancers covered?
The claims you provided cover RET-fusion positive solid tumors / RET-associated solid tumors, but only for tumors selected from a specific enumerated list. The excerpt does not state a general “all RET cancers” rule.
4) Does the patent specify prior treatments like platinum or PD-1?
Prior platinum and PD-1/PD-L1 exposure appears in claim 13 as a dependent limitation.
5) Where is the clearest narrowing that could help a design-around?
Dependent claim limits: tosylate, advanced/metastatic stage, and late-line/refractory/no standard therapy, plus specific thyroid and lung histologies.
References
[1] Your provided excerpt containing the claims for US 12,138,250.
