KMT2A-MAML2 fusion molecules and uses thereof
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12559800-B2
Publication Date
2026-02-24
Expiration Date
Abstract
The present disclosure provides KMT2A-MAML2 fusion nucleic acid molecules, and KMT2A-MAML2 fusion polypeptides, as well as methods, kits and reagents for detecting such KMT2A-MAML2 fusion nucleic acid molecules and KMT2A-MAML2 fusion polypeptides. The disclosure also provides methods for evaluating, identifying, assessing, and/or treating an individual having a cancer, such an epithelial neoplasm or a thymoma.
Core Innovation
The disclosure concerns recurrent KMT2A-MAML2 fusion nucleic acid molecules and fusion polypeptides in thymomas, including aggressive adult thymomas with B2/B3 histology. Breakpoint configurations join KMT2A exons 7–11 to MAML2 exons 2–4, retaining the KMT2A CXXC DNA-binding domain and MAML2 acidic domains with associated NOTCH and Ras/MAPK signaling. The fusion is detectable across diverse sample types using fusion-detection kits, breakpoint-targeting oligonucleotides, primer sets, probes, baits, arrays, or sequencing assays.
The disclosure further concerns methods of treating thymoma associated with a KMT2A-MAML2 fusion nucleic acid molecule or polypeptide in an individual's sample. The claimed treatments comprise administering an effective amount of anti-cancer therapy that inhibits KMT2A-MAML2 activity or expression, inhibits the NOTCH pathway, or inhibits EGFR activity or expression. These methods apply when the fusion is present, known, or affirmatively acquired, whereas background technical problems remain not explicitly described.
Claims Coverage
The claims include three independent claims covering methods of treating thymoma, setting forth three inventive features that differ in how KMT2A-MAML2 fusion status is established or utilized.
Treatment of thymoma comprising a KMT2A-MAML2 fusion
Treating an individual whose thymoma comprises a KMT2A-MAML2 fusion nucleic acid molecule or fusion polypeptide by administering an effective amount of anti-cancer therapy that inhibits KMT2A-MAML2 activity or expression, inhibits the NOTCH pathway, or inhibits EGFR activity or expression.
Treatment responsive to knowledge of a KMT2A-MAML2 fusion
Treating thymoma by administering an effective amount of anti-cancer therapy responsive to knowledge of a KMT2A-MAML2 fusion nucleic acid molecule or fusion polypeptide in a sample from the individual, wherein the therapy inhibits KMT2A-MAML2 activity or expression, the NOTCH pathway, or EGFR activity or expression.
Treatment following acquisition of fusion knowledge
Treating thymoma by acquiring knowledge of a KMT2A-MAML2 fusion nucleic acid molecule or fusion polypeptide in a sample from the individual and administering an effective amount of anti-cancer therapy that inhibits KMT2A-MAML2 activity or expression, the NOTCH pathway, or EGFR activity or expression.
The three independent claims cover treating thymoma based on KMT2A-MAML2 fusion status, distinguishing whether fusion status is an inherent characteristic, previously known, or affirmatively acquired, with each specifying anti-cancer therapy inhibiting KMT2A-MAML2, the NOTCH pathway, or EGFR.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating thymoma associated with or comprising a KMT2A-MAML2 fusion nucleic acid molecule or polypeptide using anti-cancer therapy directed against KMT2A-MAML2, the NOTCH pathway, or EGFR, including therapy guided by the presence, knowledge, or acquisition of knowledge of the fusion.
Detecting, amplifying, or sequencing KMT2A-MAML2 fusion nucleic acid molecules and polypeptides in thymoma and other cancer samples using fusion-detection kits, breakpoint-targeting oligonucleotides, primer sets, probes, baits, hybridization, or arrays for diagnosis and patient selection.
Interested in licensing this patent?