| 主权项 |
1. A method of producing a population of nucleic acids encoding at least one protein comprising at least one immunoglobulin variable domain having a complementarity determining region 3 (CDR3) of a non-human species embedded in essentially human framework sequences, wherein the method comprises the following steps:
(a) providing at least one nucleic acid comprising a non-human CDR3 encoding sequence, (b) providing a library of scaffold-encoding nucleic acids, wherein a first scaffold-encoding nucleic acid comprises:
(i) the essentially human framework sequences; and(ii) a complementarity determining region 1 (CDR1) encoding sequence and a complementarity determining region 2 (CDR2) encoding sequence,wherein at least one of the CDR1 encoding sequence or CDR2 encoding sequence is different from that of a second scaffold-encoding nucleic acid in the population of scaffold-encoding nucleic acids, andwherein at least one of the CDR1 encoding sequence or CDR2 encoding sequence encodes at least one amino acid present in a respective position of a CDR1 or CDR2 amino acid sequence of the non-human species, respectively, and encodes at least one amino acid present in a respective position of a human CDR1 or human CDR2, respectively; and (c) generating a population of nucleic acids encoding at least one protein comprising at least one immunoglobulin variable domain having the CDR3 embedded in the scaffold protein. |
