Treatment of HER3-mutated cancer by administration of anti-HER3 antibody-drug conjugate
Inventors
Koyama, Kumiko • Shiose, Yoshinobu • UENO, Suguru
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12527979-B2
Publication Date
2026-01-20
Expiration Date
Abstract
A therapeutic agent for HER3-mutated cancer containing an anti-HER3 antibody-drug conjugate as an active ingredient and/or a method of treatment for cancer, the method including administering an anti-HER3 antibody-drug conjugate to a subject determined to have HER3-mutated cancer.
Core Innovation
The disclosure provides a method of treatment for cancer by administering an anti-HER3 antibody-drug conjugate to a subject determined to have HER3-mutated cancer. The HER3 mutation includes at least one of D297Y, G325R, and T355I, and the anti-HER3 antibody-drug conjugate comprises a drug-linker conjugated to the anti-HER3 antibody via a thioether bond.
The anti-HER3 antibody is defined by heavy-chain and light-chain complementarity determining regions. The heavy chain comprises CDRH1, CDRH2, and CDRH3 represented by SEQ ID NOs 1, 2, and 3, and the light chain comprises CDRL1, CDRL2, and CDRL3 represented by SEQ ID NOs 4, 5, and 6.
The disclosure further identifies exemplary anti-HER3 antibodies including patritumab/U3-1287, U1-59, AV-203, LJM-716, duligotumab, and related antibodies and variants. Additional embodiments include an average number of drug-linker conjugated units per antibody molecule in defined ranges, including 7 to 8, 7.5 to 8, and 2 to 8, and an option where the antibody lacks a terminal heavy-chain lysine.
Therapeutic use is described for HER3-mutated cancers, and representative cancer types include multiple epithelial cancers as well as glioblastoma multiforme and melanoma. The disclosure also refers to assessment of antitumor effects using in vitro and imaging/clinical response metrics, and evaluation of ADC activity in wild-type and mutant HER3 contexts, including sensitivity/insensitivity relationships in the presence of HER2 overexpression.
Claims Coverage
The independent claim set covers a treatment method that administers a thioether-linked anti-HER3 antibody-drug conjugate to subjects with HER3-mutated cancer carrying at least one of D297Y, G325R, or T355I, and it constrains the anti-HER3 antibody by specified CDR amino acid sequences (SEQ ID NOs 1 to 6). Dependent claims further refine the treatment population and conjugate or antibody structural parameters.
Treatment of HER3-mutated cancer with a thioether-linked anti-HER3 ADC
Administering an anti-HER3 antibody-drug conjugate to a subject determined to have HER3-mutated cancer having a HER3 mutation of at least one of D297Y, G325R, and T355I, wherein the anti-HER3 antibody-drug conjugate comprises a drug-linker conjugated to the anti-HER3 antibody via a thioether bond.
Anti-HER3 antibody defined by specific CDRH and CDRL sequences
Employing an anti-HER3 antibody represented by a specified formula, where the anti-HER3 antibody comprises a heavy chain having CDRH1, CDRH2, and CDRH3 amino acid sequences represented by SEQ ID NOs 1, 2, and 3, respectively, and a light chain having CDRL1, CDRL2, and CDRL3 amino acid sequences represented by SEQ ID NOs 4, 5, and 6, respectively.
Average drug-linker conjugation number constrained to a defined range
The anti-HER3 antibody-drug conjugate has an average number of drug-linker conjugated units per antibody molecule in a defined range, including 7 to 8, 7.5 to 8, and 2 to 8.
Anti-HER3 antibody lacking a terminal heavy-chain lysine
The anti-HER3 antibody lacks a lysine residue at the carboxyl terminus of the heavy chain.
Treatment in selected cancer types
The method of treatment is for cancers selected from a specified group including multiple epithelial cancers, glioblastoma multiforme, and melanoma.
Overall, the claim coverage is directed to administering a thioether-bond anti-HER3 antibody-drug conjugate for HER3-mutated cancer, defined by D297Y, G325R, or T355I and by CDR sequence SEQ ID NOs 1 to 6, with further limitations on drug-linker load, terminal heavy-chain lysine, and selected cancer types.
Stated Advantages
Provides a method of treatment for HER3-mutated cancer using an anti-HER3 antibody-drug conjugate having thioether-linked drug-linker conjugation.
Documented Applications
Treatment method for cancer in subjects determined to have HER3-mutated cancer with HER3 mutation of at least one of D297Y, G325R, and T355I.
Interested in licensing this patent?