Structure-based selection and affinity maturation of antibody library
US7117096B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | May 20, 2002 |
| Grant date | Oct 3, 2006 |
| Priority date | — |
| Expiry date | May 16, 2023 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07K2319/00
- WIPO fieldBiotechnology
- WIPO sectorChemistry
Abstract
The present invention provides a structure-based methodology for efficiently generating and screening protein libraries for optimized proteins with desirable biological functions, such as antibodies with high binding affinity and low immunogenicity in humans. In one embodiment, a method is provided for constructing a library of antibody sequences based on a three dimensional structure of a lead antibody. The method comprises: providing an amino acid sequence of the variable region of the heavy chain (VH) or light chain (VL) of a lead antibody, the lead antibody having a known three dimensional structure which is defined as a lead structural template; identifying the amino acid sequences in the CDRs of the lead antibody; selecting one of the CDRs in the VH or VL region of the lead antibody; providing an amino acid sequence that comprises at least 3 consecutive amino acid residues in the selected CDR, the selected amino acid sequence being a lead sequence; comparing the lead sequence profile with a plurality of tester protein sequences; selecting from the plurality of tester protein sequences at least two peptide segments that have at least 10% sequence identity with lead sequence, t…
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