Method for making multispecific antibodies having heteromultimeric and common components
First Claim
1. A multispecific antibody comprising four polypeptides, wherein a first and a second of said polypeptides each comprise a heavy chain constant domain and a heavy chain variable domain, and a third and a fourth of said polypeptides are each common light chains that are identical to each other, wherein said first polypeptide and said third polypeptide form a binding domain that binds a first antigen, and wherein said second polypeptide and said fourth polypeptide form a binding domain that binds a different antigen, and wherein said first polypeptide and said second polypeptide dimerize to form a multispecific antibody, wherein the multispecific antibody is an IgG, IgE or IgD antibody.
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Abstract
The invention relates to a method of preparing heteromultimeric polypeptides such as bispecific antibodies, bispecific immunoadhesins and antibody-immunoadhesin chimeras. The invention also relates to the heteromultimers prepared using the method. Generally, the method provides a multispecific antibody having a common light chain associated with each heteromeric polypeptide having an antibody binding domain. Additionally the method further involves introducing into the multispecific antibody a specific and complementary interaction at the interface of a first polypeptide and the interface of a second polypeptide, so as to promote heteromultimer formation and hinder homomultimer formation; and/or a free thiol-containing residue at the interface of a first polypeptide and a corresponding free thiol-containing residue in the interface of a second polypeptide, such that a non-naturally occurring disulfide bond is formed between the first and second polypeptide. The method allows for the enhanced formation of the desired heteromultimer relative to undesired heteromultimers and homomultimers.
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Citations
12 Claims
- 1. A multispecific antibody comprising four polypeptides, wherein a first and a second of said polypeptides each comprise a heavy chain constant domain and a heavy chain variable domain, and a third and a fourth of said polypeptides are each common light chains that are identical to each other, wherein said first polypeptide and said third polypeptide form a binding domain that binds a first antigen, and wherein said second polypeptide and said fourth polypeptide form a binding domain that binds a different antigen, and wherein said first polypeptide and said second polypeptide dimerize to form a multispecific antibody, wherein the multispecific antibody is an IgG, IgE or IgD antibody.
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7. A multispecific antibody comprising two heteromeric polypeptides and two light chains wherein:
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(a) the first heteromeric polypeptide comprises a first heavy chain variable domain and a first multimerization domain; and (b) the second heteromeric polypeptide comprises a second heavy chain variable domain and a second multimerization domain; and
wherein the two light chains have an amino acid sequence identity of 100%, and the first and second heteromeric polypeptides dimerize by interaction of the first and second multimerization domains to form a multispecific antibody, wherein the multispecific antibody is an IgG, IgE or IgD antibody. - View Dependent Claims (8, 9, 10, 11, 12)
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Specification