United States Patent 11,944,627 (Menin Inhibitors) Patent Landscape: Claim Scope, Coverage, and Generic/Challenge Risk for AML/ALL with Elevated MEIS1
US Drug Patent 11,944,627 claims a biomarker-stratified method of treating acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) using a subset of menin inhibitors defined by a broad Formula (I-B-1) chemical Markush structure, with dependent claims tightening target gene mechanism (including MEIS1, plus gene-expression reduction) and patient genotype (NUP98 fusions, NPM1, DNMT3A, FLT3, IDH1/2, MLL alterations).
The scope is built to capture:
- any menin inhibitor falling within the I-B-1 Markush,
- used in subjects with elevated MEIS1 expression, and
- further narrowed by dependent claims to specific gene-expression reduction and fusion/mutation-defined patient populations.
What claims does US Patent 11,944,627 cover for AML/ALL using menin inhibitors and elevated MEIS1?
Core independent claim (Claim 1) is a method-of-treatment claim that combines three essential elements:
- Indication: “acute myeloid leukemia or acute lymphoblastic leukemia” in a subject.
- Biomarker condition: the subject has elevated myeloid ecotropic viral integration site 1 (MEIS1) expression levels.
- Drug identity (chemical scope): the menin inhibitor must be a compound of Formula (I-B-1) (or a pharmaceutically acceptable salt).
Featured-snippet style answer
Claim 1 covers administering a Formula (I-B-1) menin inhibitor to AML/ALL patients whose tumors show elevated MEIS1 expression.
Practical implication
A competitor cannot avoid infringement by targeting AML/ALL generally; the claim requires the subject to have the MEIS1-high phenotype. In litigation, infringement typically turns on how MEIS1 expression is measured and whether it was elevated in the treated subject (and whether the treated protocol or clinical documentation ties dosing to that biomarker.
How broad is the chemical Markush scope in Claim 1 (Formula I-B-1) for menin inhibitors?
Claim 1’s drug identity is not a single molecule. It is a Markush-style genus defined by a multi-part scaffold:
- C: selected from C3-12 carbocycle and 3- to 12-membered heterocycle
- L2: a bond or various carbonyl/phosphoryl/amido/heteroatom-containing linkers, alkylene/alkenylene/alkynylene variants, and heteroalkylene variants, each optionally substituted with R50.
- L3: alkylene/alkenylene/alkynylene substituted with R56 and optionally substituted with R50.
- Substitution parameters: m, n integers with broad ranges (m,p: 0 to 6; n: 0 to 5).
- R1 and R3: H or R50
- R2: R50
- RA, RB, RC: each occurrence independently from R50, with special rules allowing bridging or ring formation.
- R50, R51, R52, R53/R54, R56, R59: each recursively defined with wide substituent lists (including halo, nitro, cyano, OR, SR, sulfonyl patterns, carbonyl and heteroatom-containing moieties, and ring/alkyl classes).
What this means for coverage
The claim is designed to be chemistry-flexible. Instead of protecting one menin inhibitor, it protects a family of menin inhibitor structures that share the same functional logic and core topology but permit extensive substitution variation across ring/linker positions.
Attack surface for design-arounds
The most likely infringement-control strategy is to change the scaffold so that at least one structural element no longer fits C, L2, L3, R50/R51/R52/R56/R59 parameter constraints. But because the substituent sets are broad and recursive, avoiding coverage may require a qualitative scaffold shift rather than minor substitutions.
What patient-stratification requirements are built into the method claims?
MEIS1 expression requirement
- Claim 1 requires the subject has elevated MEIS1 expression levels.
- Claim 2 narrows further to cases where administering reduces expression of a target gene.
- Claim 3 specifies the target gene as Meis1.
This combination creates a two-layer proof structure:
- patient selection (MEIS1-high), and
- biological effect (gene expression reduction, at least Meis1).
Genotype and fusion/mutation add-ons (Claims 4–13)
Claim 4 adds a broad set of possible AML/ALL-associated genetic features:
- NUP98 gene fusion
- NPM1 mutation
- DNMT3A mutation
- FLT3 mutation
- IDH1 mutation
- IDH2 mutation
- MLL gene amplification
Claims 5–7 then add alternative and more specific MLL alteration categories:
- MLL rearrangement
- partial tandem duplication of MLL
- MLL rearrangement (repetition as separate dependent claim)
Claims 8–13 add stand-alone versions:
- NPM1 mutation (Claim 8)
- NUP98 gene fusion (Claim 9)
- IDH1 mutation (Claim 10)
- IDH2 mutation (Claim 11)
- DNMT3A mutation (Claim 12)
- FLT3 mutation (Claim 13)
Practical implication
If a clinical protocol enrolls AML/ALL based on any of these genetic categories, the sponsor’s compliance with MEIS1-high testing and documentation becomes important. The patent landscape encourages tying dosing decisions to MEIS1 expression rather than genotype alone.
How do dependent claims narrow mechanism-of-action: target gene expression reduction?
- Claim 2: administering reduces expression of a target gene.
- Claim 3: the target gene is Meis1.
This narrows the therapeutic effect requirement. It could be relevant in:
- infringement arguments where the patentee frames the method around a gene-expression endpoint, and
- validity challenges if the claim reads beyond supported experimental results.
How do dependent claims narrow the chemical genus (R-group and structural constraints)?
Several dependent claims operationalize subsets of the Markush parameters:
- Claim 14: narrows R2 and R3 choices (specific lists including halogen, OR52, N(R52)2, CN, small alkyl, and limited alkene/alkyne sizes; and R3 includes H plus halogen/OH/N(R52)2/CN/carbonyl-OR52 and small alkyl/haloalkyl).
- Claim 15: narrows R1 to C1-3 haloalkyl.
- Claim 16: narrows m = 0 and n = 1 to 3.
- Claim 17: narrows L2 to C1-4 alkylene and L3 to C1-4 alkylene.
- Claim 18: ties the compound of I-B-1 to specific additional enumerated formulae (I-B-6 and I-B-8), providing a cross-reference bridge within the same family.
- Claims 19–20: provide specific compound listings for the genus boundaries:
- Claim 19 recites the compound of I-B-1 in drawn form (your text shows the embedded structure placeholder “or a pharmaceutically acceptable salt thereof”).
- Claim 20 recites a second independent method claim using “a compound that is:” with the same elevated MEIS1 expression condition, and the chemical shown as a specific embedded structure placeholder.
Infringement impact
Dependent claims matter for:
- claim construction (what the patentee interprets as belonging to the genus vs. the narrower subsets),
- fallback positions if Claim 1 is narrowed or invalidated,
- settlement leverage (the narrower dependent set can still be asserted even if broad genus coverage is disputed).
When does US 11,944,627 lose exclusivity: what expiration dates should matter for enforcement?
No expiration, filing, priority, or PTA values were provided in the prompt. Without those, a complete and accurate exclusivity timeline cannot be produced.
What patent litigation and Paragraph IV risk exists for a menin inhibitor method claim like this?
The prompt does not include:
- the assignee/inventors,
- the related Orange Book drug product (if any),
- the identity of the specific marketed menin inhibitor covered by the claims,
- any known ANDA/BLA Paragraph IV filings or IPR/IV litigation history.
Without those case identifiers, a complete and accurate litigation-and-risk mapping cannot be produced.
How does this method-of-treatment claim compare with competing menin inhibitor patent estates?
No competing patent numbers, assignee families, or parallel claim sets were provided in the prompt. A credible landscape comparison (coverage overlap, exclusivity stacking, or non-overlap in chemical genus vs. biomarker logic) cannot be done from the information supplied.
What is the regulatory status and Orange Book status of the underlying menin inhibitors?
No NDC/product identifier, FDA approval references, or Orange Book listing details are included in the prompt. A complete Orange Book status and regulatory exclusivity analysis cannot be produced.
What generic entry risks exist for AML/ALL menin inhibitor therapies targeting MEIS1-high patients?
This depends on:
- whether the covered compounds are already marketed under an ANDA-eligible small molecule (unlikely if the current standard is still branded, depending on the specific menin inhibitor),
- whether the method claims are enforced via product labeling or via off-label practice,
- whether there are enforceable composition claims in the same family that would block generic entry regardless of labeling.
Because the prompt includes only the method claim text and not product/regulatory identifiers, a complete “generic entry risk” assessment cannot be produced.
Scope summary: claim elements that must be satisfied for infringement
Independence and fallback structure
- Claim 1 is the anchor: AML/ALL + elevated MEIS1 expression + Formula (I-B-1) menin inhibitor.
- Claims 2–3 add gene expression reduction with Meis1 specified.
- Claims 4–13 add genotype/fusion subsets (NUP98 fusions, NPM1, DNMT3A, FLT3, IDH1/2, MLL amplification, and MLL rearrangement/PTD).
- Claims 14–17 narrow the chemistry parameters.
- Claims 18–20 provide additional cross-references or narrower chemical recitals and a second independent method format.
Infringement “must-haves” checklist for Claim 1
- patient diagnosed with AML or ALL,
- subject has elevated MEIS1 expression,
- dosing uses a menin inhibitor within Formula (I-B-1) (or salt).
Tables: claim scope mapping by element
Table 1: Claim 1 element map
| Claim element |
Requirement in US 11,944,627 |
Practical infringement trigger |
| Indication |
AML or ALL |
Diagnosis coding and clinical trial enrollment criteria |
| Biomarker |
Elevated MEIS1 expression levels |
MEIS1 testing method, threshold, and patient records |
| Drug identity |
Menin inhibitor is Formula (I-B-1) or salt |
Chemical identity and salt form of administered compound |
Table 2: Dependent claims by narrowing type
| Dependent claims |
Type of narrowing |
What it adds |
| 2–3 |
Mechanism/effect |
Reduced expression of target gene, specifically Meis1 |
| 4, 5–7, 8–13 |
Genotype/fusion |
NUP98 fusions; NPM1; DNMT3A; FLT3; IDH1/2; MLL amplification; MLL rearrangement/PTD |
| 14–17 |
Chemical parameter constraints |
Specific allowed choices for R2/R3/R1 and integer constraints for m/n and linker sizes (L2/L3) |
| 18–20 |
Chemical cross-reference and narrowed recitals |
Maps I-B-1 to I-B-6/I-B-8 and recites specific structural embodiments |
Key Takeaways
- US 11,944,627 protects a biomarker-defined AML/ALL treatment method using menin inhibitors that fall within a broad Formula (I-B-1) chemical genus.
- MEIS1-high status is the critical patient-selection limiter; Claims 2–3 add an expression-reduction requirement tied to Meis1.
- The patent’s fallback positions include gene/fusion-defined subpopulations (NUP98 fusions, NPM1, DNMT3A, FLT3, IDH1/2, MLL alterations) and chemistry subsets via parameter narrowing in dependent claims.
- Without filing/priority and regulatory product identifiers, a complete timeline of exclusivity loss, litigation status, Orange Book status, and generic entry risk cannot be accurately established from the information provided.
FAQs
- Does elevated MEIS1 expression need to be causally linked or merely present in the subject for infringement of Claim 1?
- How do NUP98 fusion or FLT3 mutation dependent claims change enforcement compared with the broader Claim 1 MEIS1-high requirement?
- Can design-around work by changing substituents (R50/R56/R59) rather than altering the scaffold core?
- If a clinical protocol enrolls only AML/ALL based on genotype (e.g., MLL PTD) but not MEIS1-high testing, does Claim 1 become harder to enforce?
- What is the strategic value of dependent chemical-parameter claims (Claims 14–17) in settlement if the broad Markush is contested?
References (APA)
No external sources were provided in the prompt; no citations can be generated.
