| 主权项 |
1. A library comprising synthetic polynucleotides that encode an antibody heavy chain or alternative scaffold containing at least about 104 unique antibody CDRH3 amino acid sequences, wherein each of the polynucleotides encoding the at least about 104 unique antibody CDRH3 amino acid sequences has an antibody CDRH3 amino acid sequence represented by the following formula:
[TN1]-[DH]-[N2]- [H3-JH], wherein: TN1 is a polypeptide corresponding to any of the TN1 polypeptides of Tables 10 and 18-26, or a polypeptide produced by translation of any of the TN1 polynucleotides of Tables 25-26; DH is a polypeptide corresponding to any of the DH polypeptides of Tables 11, 17-25 and 28, or a polypeptide produced by translation of any of the DH-encoding polynucleotides of Tables 16, 25 and 27; N2 is a polypeptide corresponding to any of the N2 polypeptides of Tables 12, 18-25 and 30, or a polypeptide produced by translation of any of the N2-encoding polynucleotides of Tables 25 and 29; H3-JH is a polypeptide corresponding to any of the H3-JH polypeptides of Tables 13, 15, 18-25 and 32, or a polypeptide produced by translation of any of the H3-JH-encoding polynucleotides of Tables 14, 25 and 31; wherein the diversity of the polynucleotides encoding the at least about 104 unique antibody CDRH3 amino acid sequences is created by each of the polynucleotides having a CDRH3 sequence that is different from the CDRH3 sequence of every other polynucleotide; wherein the antibody heavy chain is a variable domain with framework (FRM) and complementary determining regions (CDR) comprising FRMH1-CDRH1-FRMH2-CDRH2-FRMH3-CDRH3-FRMH4; and wherein the alternative scaffold is selected from the group consisting of fibronectin, the β-sandwich, lipocalin, EETI-IFAGRP, BPTIFLAC1-D1/IT1-D2, thioredoxin, protein A, ankyrin repeats, γB-crystallin/ubiquitin, CTLD3 and (LDLR-A module)3. |
