Anti-CTLA4 antibodies, antibody fragments, their immunoconjugates and uses thereof
Inventors
Short, Jay M. • Frey, Gerhard • Chang, Hwai Wen
Assignees
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Publication Number
US-12649793-B2
Publication Date
2026-06-09
Expiration Date
Abstract
A polypeptide having a heavy chain variable region and/or light chain variable region that specifically binds to CTLA4 protein as well as antibodies and antibody fragments containing the heavy chain variable region and/or the light chain variable region that bind to CTLA4 protein. Pharmaceutical compositions and kits comprising the polypeptide or antibodies and antibody fragments containing the polypeptide are also provided.
Core Innovation
An anti-CTLA4 antibody or antigen-binding antibody fragment is provided with a heavy chain variable region including complementarity determining regions H1, H2, and H3 having defined sequences, and a light chain variable region including complementarity determining regions L1, L2, and L3 having defined sequences. The antibody is characterized as having CTLA4 binding behavior that is dependent on pH, with stronger binding at tumor-microenvironment pH than at physiological pH.
The document describes conditionally active anti-CTLA4 antibody binding and affinity, including characterization of antibodies BA-087-05-19 and BA-087-08-32. It reports functional activity associated with the pH-dependent CTLA4 binding, including potentiation of IL-2 secretion and CTLA4 ligand-blocking, with reduced activity at higher pH.
The disclosure also describes anti-CTLA4 immunoconjugate architectures and chemical linkers, including self-immolative spacers and dendritic linkers, together with linker and drug moiety connectivity. It further discusses protease-cleavable versus acid-labile linker contexts, drug loading parameters, and immunogenicity prediction.
Claims Coverage
The provided claim content centers on one independent claim defining an anti-CTLA4 antibody or antibody fragment for treatment of multiple specified cancers. The claim requires three heavy-chain CDRs and three light-chain CDRs with defined sequences.
Anti-CTLA4 antibody cdr-defined heavy and light chain variable regions
An anti-CTLA4 antibody or antibody fragment for use in a method for treating specified cancers, wherein the antibody comprises a heavy chain variable region including three complementarity determining regions H1, H2, and H3 having defined H1, H2, and H3 sequences, and a light chain variable region including three complementarity determining regions L1, L2, and L3 having defined L1, L2, and L3 sequences.
The claim coverage is centered on an anti-CTLA4 antibody or antibody fragment defined by specific heavy-chain and light-chain CDR sequences for treating the listed cancers.
Stated Advantages
pH-dependent CTLA4 binding with stronger binding at tumor-microenvironment pH than at physiological pH.
Functional activity associated with CTLA4 binding, including potentiation of IL-2 secretion and CTLA4 ligand-blocking, with reduced activity at higher pH.
Reducing normal-tissue side effects while maintaining efficacy.
Documented Applications
Method for the treatment of small cell lung cancer, non-small cell lung cancer, renal cancer, liver cancer, melanoma, bladder cancer, cervical cancer, hepatic cancer, gastric cancer or kidney cancer in a patient using an anti-CTLA4 antibody or antibody fragment.
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