Patent ID: 6897044
Filing Date: 2005-05-24
Classification: A61K,A61P,C07K

Abstract:
1. A method for producing an antibody heterodimer comprising an anti-CD20 antibody and an anti-CD23 antibody, comprising: (i) obtaining or constructing a DNA molecule that encodes an antibody molecule heavy chain that has binding specificity to a CD20 or CD23 antigen when said heavy chain is paired with a corresponding light chain, and introducing at least one cysteine codon into said antibody molecule heavy chain via recombinant DNA mutagenesis; (ii) expressing said DNA molecule in a suitable host cell, or expression system, together with a DNA molecule that encodes an antibody molecule light chain having the same specificity as the heavy chain, to produce a first anti-CD20 or anti-CD23 antibody molecule containing said introduced cysteine residue; (iii) purifying said first antibody molecule from said host cell or expression system; (iv) contacting said purified antibody molecule with an amount of a suitable reducing agent sufficient to partially reduce the intra or inter molecular disulfide bonds of said antibody molecule and thereby enhance dimerization of said first antibody molecule with a second antibody molecule; and (v) contacting said purified first antibody molecule with a second antibody molecule that has a binding specificity to CD20 when said first antibody is an anti-CD23 antibody, or to CD23 when said first antibody is an anti-CD20 antibody, and allowing sufficient time for dimerization to proceed to thereby to produce a tetravalent antibody heterodimer comprising both an anti-CD20 antibody and an anti-CD23 antibody, wherein following dimerization, the anti-CD20 antibody of the heterodimer has binding specificity to CD20 and the anti-CD23 antibody of the heterodimer has binding specificity to CD23.