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AssigneeGenetech, Inc.
InventorsW. Robert Arathoon, Paul J. Carter, Anne M. Merchant, Leonard G. Presta
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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.
A method of preparing a multispecific antibody comprising culturing a host cell expressing a multispecific antibody, and recovering the multispecific antibody from the culture, wherein said multispecific antibody comprises 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.
A method of preparing a multispecific antibody comprising culturing a host cell expressing a multispecific antibody, and recovering said multispecific antibody from the culture, wherein said multispecific antibody comprises two heteromeric polypeptides and two light chains, wherein:
A vector comprising nucleic acid sequences capable of encoding a first heteromeric polypeptide, a second heteromeric polypeptide and a common light chain polypeptide that form a multispecific antibody, wherein:
An isolated host cell comprising one or more vectors, wherein said one or more vectors comprise nucleic acid sequences capable of encoding a first heteromeric polypeptide, a second heteromeric polypeptide and a common light chain polypeptide that form a multispecific antibody, wherein:
Dependencies are inferred from the claim text.