Novel Flt3 Antibodies and Antibody-Drug-Conjugates Based Thereon, Therapeutic Methods and Uses Thereof in Combination with Tyrosine Kinase Inhibitors

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This invention discloses a new class of highly specific antibodies targeting the human FLT3 (Fms-like tyrosine kinase 3) receptor, which is commonly overexpressed or mutated in acute myeloid leukemia (AML). These FLT3 antibodies are used to construct antibody-drug conjugates (ADCs), whereby a potent cytotoxic drug is directly linked to the antibody to selectively kill FLT3-positive cancer cells. The approach is particularly effective when combined with tyrosine kinase inhibitors (TKIs), such as midostaurin, which further enhances anti-leukemic efficacy. The patent also covers methods, compositions, and kits for cancer treatment, especially for FLT3-mutated or FLT3-overexpressing AML, using the antibodies, ADCs, and their combinations with TKIs.

Use CasesContent extracted from patent full text and abstract with AI.

• Targeted treatment of acute myeloid leukemia (AML) patients, especially those with FLT3-ITD or FLT3-TKD mutations.
• Use as a new therapeutic option for relapsed or refractory AML.
• Combination therapy with FLT3-specific TKIs (e.g., midostaurin, gilteritinib) for improved efficacy.
• Diagnostic applications to detect FLT3 expression or monitor disease progression in AML.
• Ex vivo use for screening new anti-cancer drugs or assessing drug sensitivity in patient-derived cells.
• Potential extension to other FLT3-expressing or FLT3-mutant hematological malignancies.
• Use in research and development of novel antibody-drug conjugates targeting FLT3.

BenefitsContent extracted from patent full text and abstract with AI.

• Provides highly selective delivery of cytotoxic drugs directly to FLT3-expressing tumor cells, sparing most healthy cells and reducing off-target toxicity.
• Enables potent anti-leukemic activity, including against cells with FLT3 mutations driving treatment resistance.
• Demonstrated synergy with tyrosine kinase inhibitors, supporting more effective combination therapies.
• Minimizes hematological toxicity at therapeutic concentrations due to selectivity for tumor cells.
• Targets a broader population of AML patients, regardless of exact mutation, as FLT3 is overexpressed in most AML blasts.
• Supports durable, potentially curative responses in preclinical models, including complete tumor remission.
• Utilizes advanced conjugation chemistry (P5 technology) for stable and efficient antibody-drug conjugates.

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Patent Abstract

The present invention relates to novel anti-FLT3 antibodies for specifically targeting extracellular domain of FLT3. The present invention further relates to targeting FLT3 by novel antibody-drug- conjugates (ADCs) based on the novel anti-FLT3 antibodies of the present invention, especially in combination with kinase inhibitors, for use in therapy and/or for use in a method of cancer treatment (e.g., acute myeloid leukemia (AML) with or without internal tandem duplication (ITD) mutations in the FLT3 gene (FLT3-ITD)).