Anti-mesothelin antibodies
Inventors
MUNOZ-OLAYA, JOSE • FERTIN, REMI • WOLLERTON, FRANCISCA • Tuna, Mihriban • Brewis, Neil
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12325742-B2
Publication Date
2025-06-10
Expiration Date
Abstract
The present application relates to antibody molecules that bind mesothelin (MSLN). The antibody molecules find application in the treatment and diagnosis of diseases and disorders, such as cancer.
Core Innovation
The disclosed invention relates to an antibody molecule that binds mesothelin (MSLN), where the antigen-binding site comprises the VH domain CDR1, CDR2 and CDR3 together with the VL domain CDR1, CDR2 and CDR3 of specified FS28 antibody variants. The CDR sequences are defined according to the ImMunoGeneTics (IMGT) numbering scheme and/or the Kabat numbering scheme, with specific SEQ ID NO mappings for the listed variants and sequence listings for heavy and light chains and variable domains.
The disclosure addresses preferential targeting of membrane-bound MSLN over soluble shed MSLN to avoid sink effects and supports selection of antibodies with higher avidity or affinity for immobilised, cell-surface-like MSLN than for soluble shed MSLN. It also distinguishes epitope subsets by reference to MUC16 blocking versus non-blocking subsets.
Further embodiments include conditional immune activation in multispecific formats in which a second antigen-binding site is located in constant domains and binds a second antigen associated with TNFRSF members. Functional and clinical-use embodiments include immune activation, cancer detection and diagnosis, ADCC, bispecific TNFRSF agonism without Fc crosslinking, ADC and conjugate formats, and diagnostic and therapeutic methods and kits.
Claims Coverage
The provided independent claim content covers two inventive features: a mesothelin-binding antibody defined by specified VH and VL CDR sequence sets using IMGT and/or Kabat numbering schemes, and exclusion of a CD137 antigen-binding site located in a CH3 domain.
Msln-binding antibody with specified VH and VL CDR sequence sets
An antibody molecule that binds mesothelin (MSLN) wherein the antigen-binding site comprises the VH domain CDR1, CDR2 and CDR3 and the VL domain CDR1, CDR2 and CDR3 of the listed FS28 variants, with CDR sequences defined according to the ImMunoGeneTics (IMGT) numbering scheme and/or the Kabat numbering scheme via the listed SEQ ID NO mappings.
Cd137 ch3-domain antigen-binding site exclusion
The antibody molecule does not comprise a CD137 antigen-binding site located in a CH3 domain of the antibody molecule, said CD137 antigen-binding site comprising a first sequence as set forth in SEQ ID NO: 198 located in the AB structural loop of the CH3 domain and a second sequence as set forth in SEQ ID NO: 199 located in the EF structural loop of the CH3 domain.
Coverage centers on a specific set of MSLN-binding antibodies defined by enumerated FS28 VH and VL CDR sequence sets under IMGT and/or Kabat numbering schemes, while excluding CD137 antigen-binding sites positioned in a CH3 domain using the specified AB and EF structural loop sequences.
Stated Advantages
Preferential targeting of membrane-bound MSLN over soluble shed MSLN to avoid sink effects.
Higher avidity or affinity for immobilised, cell-surface-like MSLN than for soluble shed MSLN.
ADCC activity abrogated by Fc engineering, including LALA.
Documented Applications
Cancer treatment and diagnosis using anti-mesothelin antibodies, including methods and kits for detection and diagnosis of cancer in an individual.
Immune activation associated with MSLN binding as part of therapeutic embodiments.
Diagnostic and therapeutic use cases including ADCC and multispecific TNFRSF agonism, including bispecific formats and ADC or conjugate formats.
In vivo tumor growth and survival for bispecifics involving CD137 and MSLN.
Interested in licensing this patent?