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Antibody variants

a technology of antibodies and variants, applied in the field of antibodies variants, can solve the problem of uneven distribution of variable domains of antibodies, and achieve the effect of reducing the number of antibodies

Inactive Publication Date: 2007-12-06
CHEN YVONNE M +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0021] The invention further provides a method for treating a mammal compris

Problems solved by technology

However, the variability is not evenly distributed through the variable domains of antibodies.

Method used

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Examples

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example 1

[0237] In this example, antibody variants containing randomized peptide inserts within the antibody CDRs are prepared by phage display which substantially improve the affinity of a humanized Fab for VEGF. Crystallography suggests that these changes result in an increased contact area with antigen.

[0238] VEGF:Fab X-ray Co-Crystal Structure: A crystal structure of the complex between the VEGF antigen and anti-VEGF parent antibody was prepared as described in Muller et al., Structure 6(9):1153-1167 (1998). The conclusion that the three VH CDRs are the main determinants of Fab binding to VEGF is supported by the high-resolution crystal structure of the VEGF:Fab (v36) complex. In addition, the major energetic determinants largely coincide with the principal contacting residues of the Fab in the complex.

[0239] Several randomized libraries were designed with a peptide insertion placed in the antigen-contacting CDRs which, from the crystal structure, were expected to increase the potentia...

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Abstract

Antibody variants of parent antibodies are disclosed which have one or more amino acids inserted in a hypervariable region of the parent antibody and a binding affinity for a target antigen which is at least about two fold stronger than the binding affinity of the parent antibody for the antigen.

Description

[0001] This is a continuation application claiming priority to U.S. application Ser. No. 10 / 624,153, filed Jul. 21, 2003, which is a continuation application of U.S. application Ser. No. 09 / 440,781, issued Oct. 14, 2003 as U.S. Pat. No. 6,632,926, which is a non-provisional application filed under 37 CFR 1.53(b) claiming priority to provisional application 60 / 108,945 filed Nov. 18, 1998, the contents of which are incorporated herein by reference.BACKGROUND OF THE INVENTION [0002] 1. Field of the Invention [0003] This invention relates generally to antibody variants. In particular, antibody variants of parent antibodies are disclosed which have one or more amino acids inserted in a hypervariable region of the parent antibody and a binding affinity for a target antigen which is at least about two fold stronger than the binding affinity of the parent antibody for the antigen. [0004] 2. Description of Related Art [0005] Antibodies are proteins, which exhibit binding specificity to a spe...

Claims

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Application Information

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IPC IPC(8): A61K39/395C07K16/18C12N15/13C12N15/81C12N15/85C12N5/10C12P21/00G01N33/53A61K38/00A61P5/14A61P9/00A61P9/10A61P11/00A61P17/06A61P27/02A61P27/06A61P29/00A61P35/00C07K16/00C07K16/22C07K16/24C12N1/15C12N1/19C12N1/21C12N15/09C12P21/08
CPCA61K38/00B65H2801/87C07K16/00C07K16/22C07K16/24C07K2317/92C07K2316/96C07K2317/24C07K2317/55C07K2317/565C07K2317/73C07K2299/00C07K2317/76A61P11/00A61P17/06A61P27/02A61P27/06A61P29/00A61P35/00A61P43/00A61P5/14A61P9/00A61P9/10C07K16/005C07K2317/14C07K2317/56
Inventor CHEN, YVONNE M.LOWMAN, HENRY B.MULLER, YVES
Owner CHEN YVONNE M
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