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METHOD FOR THE HUMANIZATION OF ANTIBODIES AND HUMANIZED ANTIBODIES THEREBY OBTAINED
METHOD FOR THE HUMANIZATION OF ANTIBODIES AND HUMANIZED ANTIBODIES THEREBY OBTAINED
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机译:获得抗体的人源化方法和由此获得的人源化抗体
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摘要
Method for the humanization of the VH and VL variable regions of an animal antibody of known sequence, comprising the steps of (a) if not available, obtaining the crystallographic structure of the VH and VL regions of the animal antibody; (b) pre-selecting a series of 0 to n possible frameworks acceptors of human origin or humanized antibodies, whose structure was determined experimentally with a resolution no greater than 2.5 A, based on the highest level of homology and identity with the primary sequence of the framework of the animal antibody; (c) conducting a structural comparison between the VH and VL variable regions of the animal antibody and the regions VH and VL obtained in b), respectively and calculating for each comparison the root mean square deviation (RMS), to identify the region VH and the region VL of human origin with the smaller RMS; (d) inserting in appropriate position the sequences of the CDR regions of the animal antibody in the human sequences identified in c); (e) if necessary, retromutate one or more amino acid residues of the human VH and VL regions identified in c).
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