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Publication Number
US-11753478-B2
Publication Date
2023-09-12
Expiration Date
Abstract
The present invention provides anti-CD115 monoclonal antibodies and related compositions, which may be used in any of a variety of therapeutic and diagnostic methods for the treatment of cancer, autoimmune, and other diseases.
Core Innovation
The invention relates to isolated anti-CD115 (CSF1R/M-CSFR) antibodies, or antigen-binding fragments thereof, defined by heavy chain and light chain variable regions comprising specified HCDR1, HCDR2, and HCDR3 sequences and specified LCDR1, LCDR2, and LCDR3 sequences mapped to SEQ ID NOs. The described antibody sets include explicit CDR sequence identifier combinations and further examples of defined variable-region content.
The disclosed anti-CD115 antibodies include chimeric and fully human antibody forms, including variants derived from a mouse monoclonal antibody (CCK423A) converted into fully human IgG1/IgG2/IgG4 variants while maintaining binding and neutralization potency as described. The disclosure further covers multiple antibody formats including whole antibodies, scFv, bispecific and multi-specific antibodies, Fab, and F(ab’)2, as well as recombinant polynucleotides and expression constructs for generating the antibodies.
Functionally, the antibodies are described as antagonists/neutralizers of CSF-1 and IL-34 binding and as inhibiting CD115 signaling, including ligand-induced phosphorylation and downstream phosphorylation readouts. The disclosure also describes properties such as epitope binning, internalization, and binding kinetics, and provides exemplary measurements of binding and IL-34 blocking/neutralization outcomes in the context of anti-CD115 activity.
Claims Coverage
The disclosed independent claim covers an isolated anti-CD115 antibody or antigen-binding fragment defined by specific heavy-chain and light-chain variable regions with alternative sets of explicitly enumerated CDR SEQ ID NO combinations. Inventive features are expressed as defined CDR sequence constraints, with dependent claims refining format and composition context, including human antibodies and pharmaceutical compositions.
Cd115 antibody with specified HCDR and LCDR sequence identifiers
An isolated anti-CD115 antibody, or an antigen-binding fragment thereof, comprising a heavy chain variable region (VH) with HCDR1, HCDR2, and HCDR3 comprising SEQ ID NOs 445, 877, and 1309, and a light chain variable region (VL) with LCDR1, LCDR2, and LCDR3 comprising SEQ ID NOs 661, 1093, and 1525.
Cd115 antibody with alternative specified HCDR and LCDR sequence identifiers
An isolated anti-CD115 antibody, or an antigen-binding fragment thereof, comprising a heavy chain variable region with VHCDR1, VHCDR2, and VHCDR3 comprising SEQ ID NOs 481, 913, and 1345, and a light chain variable region comprising VLCDR1, VLCDR2, and VLCDR3 comprising SEQ ID NOs 697, 1129, and 1561.
Cd115 antibody with further alternative specified HCDR and LCDR sequence identifiers
An isolated anti-CD115 antibody, or an antigen-binding fragment thereof, comprising a heavy chain variable region with VHCDR1, VHCDR2, and VHCDR3 comprising SEQ ID NOs 533, 965, and 1397, and a light chain variable region comprising VLCDR1, VLCDR2, and VLCDR3 comprising SEQ ID NOs 749, 1181, and 1613.
Antibody format restriction to selected structural categories
The antibody, or an antigen-binding fragment thereof, is selected from antibody formats including a single-variable domain antibody, a single chain antibody (scFv), bispecific and multi-specific antibodies, and fragment types Fab and F(ab’)2.
Human anti-CD115 antibody
The isolated anti-CD115 antibody, or an antigen-binding fragment thereof, is a human antibody.
Pharmaceutical composition with physiologically acceptable carrier
A pharmaceutical composition comprising the antibody, or an antigen-binding fragment thereof, together with a physiologically acceptable carrier.
Overall, the claim coverage is centered on an isolated anti-CD115 antibody defined by enumerated CDR SEQ ID NOs in the VH and VL, with dependent claim refinements that restrict the antibody to selected structural formats, specify a human antibody, and define a pharmaceutical composition including a physiologically acceptable carrier.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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