Multispecific antibodies
AssigneeGenentech, Inc.
InventorsGermaine Fuh, Jenny M. Bostrom
Life of this patent
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Abstract
The invention provides multispecific antibodies and methods of making and using such antibodies. In general, the multispecific antibodies are made by methods involving the steps of altering the nucleic acid sequence encoding the light chain variable domain (VL) of an antibody that binds a first epitope, and selecting a multispecific antibody capable of binding the first and a second epitope.
Claims26
A method of making a multispecific antibody comprising a variable heavy chain domain (VH) and a variable light chain domain (VL), wherein the VH and VL of the multispecific antibody pair together to form an antigen binding site that specifically binds to a first epitope and a second epitope, said method comprising the steps of:
- (1) providing an antibody that comprises a VH and VL, wherein the VH and VL pair together to form an antigen binding site that binds to the first epitope but not the second epitope;
- (2) altering the nucleic acid sequence encoding the VL of the antibody of step (1), wherein one or more solvent accessible amino acid residues are altered at one or more amino acid residue positions selected from the group consisting of positions 28, 29, 30-32, 50-53, 66-70, and 91-94, according to the Kabat numbering system, and wherein the one or more solvent accessible amino acid residues include an amino acid residue of position 30 or position 93, according to the Kabat numbering system;
- (3) expressing the VH and the altered nucleic acid sequence of the VL of step (2);
- and
- (4) following step (3), selecting for antibody binding to said first epitope and said second epitope, thereby selecting for a multispecific antibody by its ability to bind to both said first epitope and said second epitope, said multispecific antibody comprising the VH and the altered VL of step (3), wherein the VH and VL of the multispecific antibody pair together to form an antigen binding site that specifically binds to the first epitope and the second epitope.
A method of making a multispecific antibody comprising a variable heavy chain domain (VH) and a variable light chain domain (VL), wherein the VH and VL of the multispecific antibody pair together to form an antigen binding site that specifically binds to a first epitope and a second epitope, said method comprising the steps of:
- (1) providing an antibody that comprises a VH and VL, wherein the VH and VL pair together to form an antigen binding site that binds to the first epitope but not the second epitope;
- (2) holding the nucleic acid sequence encoding the VH constant and altering the nucleic acid sequence encoding the VL of the antibody of step (1), wherein one or more solvent accessible amino acid residues are altered;
- (3) expressing the nucleic acid sequence of the VH and the altered nucleic acid sequence of the VL of step (2);
- and
- (4) following step (3), selecting for antibody binding to said first epitope and said second epitope, thereby selecting for a multispecific antibody by its ability to bind to both said first epitope and said second epitope, said multispecific antibody comprising the VH and the altered VL of step (3), wherein the VH and the VL of the multispecific antibody pair together to form an antigen binding site that specifically binds to the first epitope and the second epitope.
Dependencies are inferred from the claim text.