Antibodies that bind to AXL proteins
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10787516-B2
Publication Date
2020-09-29
Expiration Date
Abstract
Antibodies that bind to AXL protein and variants thereof are described herein. AXL exhibits a distinct and limited expression pattern in normal adult tissue(s), and is aberrantly expressed in the cancers listed in Table I. Consequently, the MAbs of the invention provide a diagnostic composition for the treatment and management of cancer.
Core Innovation
The invention relates to AXL receptor tyrosine kinase (AXL)-targeting antibodies and antigen-binding fragments comprising defined heavy chain and light chain complementarity determining regions. In particular, the antibody or fragment binds to AXL and comprises a heavy chain variable region with CDR-H1, CDR-H2, and CDR-H3 of the amino acid sequence set forth in SEQ ID NO: 8, and a light chain variable region with CDR-L1, CDR-L2, and CDR-L3 of the amino acid sequence set forth in SEQ ID NO: 10.
The described antibody includes fully human antibodies and antigen-binding fragments, including a specified antibody example V77-2a37.1, with defined CDR sequences. The disclosed work evaluates AXL expression using AXL antibody staining and AXL-related detection workflows including IHC and RNA ISH, and reports AXL expression across multiple tumor types.
The invention also includes characterization showing specificity through epitope mapping/competition, including distinct epitopes between V77-2a37.1 and another AXL antibody (M77-297b81.1.1) and minimal overlap with a commercial comparator (C89E7). The document further describes diagnostic/prognostic and companion diagnostic (CDx) use for detecting AXL expression in tumor specimens, and therapeutic strategies involving AXL antibodies and AXL ADCs for AXL-expressing cancers.
Claims Coverage
The independent claim clm-00001 covers an AXL-binding antibody or antigen-binding fragment defined by specific heavy- and light-chain CDR sequences (SEQ ID NO: 8 and SEQ ID NO: 10). The provided claim set indicates four inventive features in the supplied coverage, with dependent limitations addressing fragment format, fully human status, companion diagnostic use, and patient-selection context.
Axl-binding antibody or antigen-binding fragment defined by specific cdr sequences
An antibody or antigen binding fragment thereof which binds to AXL receptor tyrosine kinase (AXL), wherein the antibody or fragment comprises a heavy chain variable region comprising CDR-H1, CDR-H2, and CDR-H3 of the amino acid sequence set forth in SEQ ID NO: 8 and a light chain variable region comprising CDR-L1, CDR-L2, and CDR-L3 of the amino acid sequence set forth in SEQ ID NO: 10.
Specific antibody fragment formats for the antigen binding fragment
The antigen binding fragment of the claimed antibody is specified to be an antigen binding fragment (Fab), F(ab')2, a variable fragment (Fv), or a single-chain variable fragment (scFv).
Fully human antibody limitation
The antibody is specified to be a fully human antibody.
Companion diagnostic use
The antibody or antigen binding fragment is used as a companion diagnostic (CDx) to screen patients for cancer treatment and management.
Overall, the claims coverage centers on an AXL-binding antibody or antigen-binding fragment defined by specified CDR sequences, with dependent limitations covering fragment format and fully human antibody status, and application of the binding reagent to companion diagnostic screening.
Stated Advantages
Enables detection of AXL expression in tumor specimens for diagnostic/prognostic and companion diagnostic (CDx) use.
Provides specificity for AXL targeting, demonstrated by positive staining in AXL-expressing patient samples and limited/non-specific staining in AXL-negative specimens versus a commercial comparator.
Supports epitope distinction for the disclosed antibody (distinct epitopes between V77-2a37.1 and M77-297b81.1.1 and minimal overlap with C89E7).
Documented Applications
Cancer diagnostics/prognostics using AXL antibody staining and AXL-related detection workflows, including IHC and RNA ISH, for detecting AXL expression in tumor specimens.
Companion diagnostic (CDx) screening to identify patients for cancer treatment and management based on AXL expression positivity.
Therapeutic strategies for AXL-expressing cancers using AXL antibodies and AXL ADCs, including adjunctive therapy with chemotherapy/radiation.
Interested in licensing this patent?