Anti-AXL antibodies, antibody fragments and their immunoconjugates and uses thereof
Inventors
Short, Jay M. • Chang, Hwai Wen • Frey, Gerhard
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11897959-B2
Publication Date
2024-02-13
Expiration Date
Abstract
An antibody or antibody fragment having a heavy chain variable region and/or light chain variable region that specifically binds to Axl protein. Immuoconjugages, pharmaceutical compositions and kits comprising the antibodies and antibody fragments are also provided. Also disclosed are methods of treating Axl-expressing cancers using the antibodies, antibody fragments, immunoconjugates and pharmaceutical compositions of the present invention.
Core Innovation
The invention relates to an antibody or antibody fragment that specifically binds to Axl protein and comprises a heavy chain variable region with three complementarity determining regions having H1, H2, and H3 sequences, and a light chain variable region with three complementarity determining regions having L1, L2, and L3 sequences, with permitted residue constraints and associated SEQ ID NOs.
The antibody or antibody fragment has higher binding affinity to human Axl protein in a tumor microenvironment of pH 5.8 to 7.0 compared with a non-tumor microenvironment of pH 7.2 to 7.8. The ratio of binding affinity in the tumor microenvironment to binding affinity in the non-tumor microenvironment is at least 1.5:1.
The disclosure further extends the Axl-binding antibodies into immunoconjugates and pharmaceutical compositions, including embodiments in which at least one selected agent is included and optionally covalently bonded to a linker molecule. It also includes diagnostic/detection concepts using labeled anti-Axl antibodies and treatment contexts for Axl-associated cancers and Axl-expressing cancer.
Claims Coverage
The independent claim coverage centers on one Axl-binding antibody or antibody fragment with defined heavy- and light-chain CDR sequences and pH-dependent selectivity, quantified by a tumor versus non-tumor binding-affinity ratio. The merged dependent coverage includes immunoconjugates, pharmaceutical compositions, diagnostic/detection concepts, and cancer treatment methods.
Axl-binding antibody with defined heavy- and light-chain CDR sequences
An antibody or antibody fragment specifically binds to Axl protein and comprises a heavy chain variable region with three complementarity determining regions having H1, H2, and H3 sequences, and a light chain variable region with three complementarity determining regions having L1, L2, and L3 sequences, with permitted residue constraints and associated SEQ ID NOs.
Tumor microenvironment pH-selective higher human Axl binding affinity
The isolated antibody or antibody fragment has a higher binding affinity to human Axl protein in a tumor microenvironment of pH 5.8 to 7.0 compared with a non-tumor microenvironment of pH 7.2 to 7.8.
Tumor/non-tumor binding-affinity ratio threshold of at least 1.5:1
The antibody or antibody fragment has a ratio of binding affinity to the human Axl protein in the tumor microenvironment to a binding affinity to the human Axl protein in the non-tumor microenvironment of at least 1.5:1.
Immunoconjugate with selected agent categories
An immunoconjugate includes at least one selected agent from chemotherapeutic, radioactive, cytostatic, and cytotoxic agents.
Covalent bonding via a linker in an immunoconjugate
The immunoconjugate covalently bonds the antibody or antibody fragment and at least one agent to a linker molecule.
Pharmaceutical composition with pharmaceutically acceptable carrier
A pharmaceutical composition includes the antibody or antibody fragment together with a pharmaceutically acceptable carrier.
Diagnostic or detection use of labeled anti-Axl antibodies
Diagnostic/detection concepts use labeled anti-Axl antibodies, including imaging concepts with labeled antibodies and radiolabel isotopes.
Method of treating cancer by administering composition to patient with Axl-expressing cancer
A method for treating cancer administers the pharmaceutical composition to a patient who has Axl-expressing cancer.
Overall, the claims are directed to an Axl-specific antibody or antibody fragment defined by heavy- and light-chain CDR sequence constraints and pH-dependent tumor-versus-non-tumor binding selectivity. The additional scope covers immunoconjugates, linker connection, pharmaceutical compositions, diagnostic/detection concepts, and cancer treatment for Axl-expressing cancers.
Stated Advantages
Higher binding affinity to human Axl protein in a tumor microenvironment (pH 5.8 to 7.0) than in a non-tumor microenvironment (pH 7.2 to 7.8).
A tumor microenvironment-to-non-tumor microenvironment binding-affinity ratio of at least 1.5:1.
Documented Applications
Diagnostic/detection using labeled anti-Axl antibodies, including imaging concepts with labeled antibodies and radiolabel isotopes.
Therapeutic treatment of cancer by administering a pharmaceutical composition to a patient who has Axl-expressing cancer.
Immunoconjugate/ADC use cases associated with Axl activity, including anti-Axl antibodies with ADC activity and conditionally active pH-dependent anti-Axl antibodies.
Interested in licensing this patent?