Cd20 binding molecules and uses thereof
AssigneeIGM Biosciences, Inc.
InventorsBruce Keyt, Omar Duramad, Beatrice Tien-Yi Wang, Ramesh Baliga, Fen Zhang
Life of this patent
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Abstract
This disclosure provides pentameric and hexameric CD20 binding molecules and methods of using such molecules to direct complement-mediated, T-cell-mediated, or both complement-mediated and T-cell-mediated killing of CD20-expressing cells.
Claims52
A multimeric binding molecule comprising at least two bivalent binding units, wherein each binding unit comprises at least two heavy chain constant regions or fragments thereof, each associated with an antigen-binding domain, wherein at least three antigen binding domains of the binding molecule are identical CD20 antigen binding domains comprising (a) six immunoglobulin complementarity determining regions HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO:
- 39 or SEQ ID NO:
- 39 with one or two single amino acid substitutions;
- the HCDR2 comprises the amino acid sequence of SEQ ID NO:
- 40 or SEQ ID NO:
- 40 with one or two single amino acid substitutions;
- the HCDR3 comprises the amino acid sequence of SEQ ID NO:
- 41, SEQ ID NO:
- 41 with one or two single amino acid substitutions;
- the LCDR1 comprises the amino acid sequence of SEQ ID NO:
- 43, or SEQ ID NO:
- 43 with one or two single amino acid substitutions;
- the LCDR2 comprises the amino acid sequence of SEQ ID NO:
- 44 or SEQ ID NO:
- 44 with one or two single amino acid substitutions;
- and the LCDR3 comprises the amino acid sequence of SEQ ID NO:
- 45 or SEQ ID NO:
- 45 with one or two single amino acid substitutions;
- or (b) an antibody heavy chain variable region (VH) and an antibody light chain variable region (VL), wherein the VH comprises an amino acid sequence at least at least 90% identical to SEQ ID NO:
- 38, and the VL comprises an amino acid sequence at least 90% identical to SEQ ID NO:
- 42.
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A method for directing complement-mediated, T-cell-mediated, or both complement-mediated and T-cell-mediated killing of a CD20-expressing cell comprising contacting a CD20-expressing cell with a dimeric, pentameric, or hexameric binding molecule comprising two, five, or six bivalent binding units, respectively, wherein each binding unit comprises two IgA or IgM heavy chain constant regions or fragments thereof and two antigen binding domains, wherein at least one antigen binding domain of the binding molecule is a CD20 antigen binding domain, and wherein the binding molecule can direct complement-mediated killing of a CD-20-expressing cell at higher potency than an equivalent amount of a monospecific, bivalent IgG1 antibody or fragment thereof that specifically binds to the same CD20 epitope as the CD20 antigen binding domain.
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Dependencies are inferred from the claim text.