Antibody library containing common light chain, and preparation method therefor and use thereof

A bispecific antibody, comprising a first antigen-binding portion and a second antigen-binding portion, wherein the first antigen-binding portion and the second antigen-binding portion comprise a common light chain, and the common light chain is encoded by an IGKV3 or IGKV1 light chain germline gene;

• preferably, encoded by an IGKV3-20, IGKV3-11, IGKV1-39, IGKV1-5, or IGKV1-33 light chain germline gene;
• more preferably, encoded by an IGKV3-20 or IGKV1-39 light chain germline gene;
• For example, the common light chain in the bispecific antibody comprises CDRs selected from:
• (a) LCDR1 shown in SEQ ID NO:
• 1 or a variant having no more than 2 amino acid changes from LCDR1 shown in SEQ ID NO:
• 1, LCDR2 shown in SEQ ID NO:
• 2 or a variant having no more than 2 amino acid changes from LCDR2 shown in SEQ ID NO:
• 2, and LCDR3 shown in SEQ ID NO:
• 3 or a variant having no more than 2 amino acid changes from LCDR3 shown in SEQ ID NO:
• 3;
• (b) LCDR1 shown in SEQ ID NO:
• 4 or a variant having no more than 2 amino acid changes from LCDR1 shown in SEQ ID NO:
• 4, LCDR2 shown in SEQ ID NO:
• 5 or a variant having no more than 2 amino acid changes from LCDR2 shown in SEQ ID NO:
• 5, and LCDR3 shown in SEQ ID NO:
• 6 or a variant having no more than 2 amino acid changes from LCDR3 shown in SEQ ID NO:
• 6;
• (c) LCDR1 shown in SEQ ID NO:
• 7 or a variant having no more than 2 amino acid changes from LCDR1 shown in SEQ ID NO:
• 7, LCDR2 shown in SEQ ID NO:
• 8 or a variant having no more than 2 amino acid changes from LCDR2 shown in SEQ ID NO:
• 8, and LCDR3 shown in SEQ ID NO:
• 9 or a variant having no more than 2 amino acid changes from LCDR3 shown in SEQ ID NO:
• 9;
• (d) LCDR1 shown in SEQ ID NO:
• 10 or a variant having no more than 2 amino acid changes from LCDR1 shown in SEQ ID NO:
• 10, LCDR2 shown in SEQ ID NO:
• 11 or a variant having no more than 2 amino acid changes from LCDR2 shown in SEQ ID NO:
• 11, and LCDR3 shown in SEQ ID NO:
• 12 or a variant having no more than 2 amino acid changes from LCDR3 shown in SEQ ID NO:
• 12;
• (e) LCDR1 shown in SEQ ID NO:
• 13 or a variant having no more than 2 amino acid changes from LCDR1 shown in SEQ ID NO:
• 13, LCDR2 shown in SEQ ID NO:
• 14 or a variant having no more than 2 amino acid changes from LCDR2 shown in SEQ ID NO:
• 14, and LCDR3 shown in SEQ ID NO:
• 15 or a variant having no more than 2 amino acid changes from LCDR3 shown in SEQ ID NO:
• 15;
• (f) LCDR1 shown in SEQ ID NO:
• 16 or a variant having no more than 2 amino acid changes from LCDR1 shown in SEQ ID NO:
• 16, LCDR2 shown in SEQ ID NO:
• 17 or a variant having no more than 2 amino acid changes from LCDR2 shown in SEQ ID NO:
• 17, and LCDR3 shown in SEQ ID NO:
• 18 or a variant having no more than 2 amino acid changes from LCDR3 shown in SEQ ID NO:
• 18;
• (g) LCDR1 shown in SEQ ID NO:
• 19 or a variant having no more than 2 amino acid changes from LCDR1 shown in SEQ ID NO:
• 19, LCDR2 shown in SEQ ID NO:
• 20 or a variant having no more than 2 amino acid changes from LCDR2 shown in SEQ ID NO:
• 20, and LCDR3 shown in SEQ ID NO:
• 21 or a variant having no more than 2 amino acid changes from LCDR3 shown in SEQ ID NO:
• 21;
• (h) LCDR1 shown in SEQ ID NO:
• 22 or a variant having no more than 2 amino acid changes from LCDR1 shown in SEQ ID NO:
• 22, LCDR2 shown in SEQ ID NO:
• 23 or a variant having no more than 2 amino acid changes from LCDR2 shown in SEQ ID NO:
• 23, and LCDR3 shown in SEQ ID NO:
• 24 or a variant having no more than 2 amino acid changes from LCDR3 shown in SEQ ID NO:
• 24;
• (i) LCDR1 shown in SEQ ID NO:
• 25 or a variant having no more than 2 amino acid changes from LCDR1 shown in SEQ ID NO:
• 25, LCDR2 shown in SEQ ID NO:
• 26 or a variant having no more than 2 amino acid changes from LCDR2 shown in SEQ ID NO:
• 26, and LCDR3 shown in SEQ ID NO:
• 27 or a variant having no more than 2 amino acid changes from LCDR3 shown in SEQ ID NO:
• 27;
• (j) LCDR1 shown in SEQ ID NO:
• 28 or a variant having no more than 2 amino acid changes from LCDR1 shown in SEQ ID NO:
• 28, LCDR2 shown in SEQ ID NO:
• 29 or a variant having no more than 2 amino acid changes from LCDR2 shown in SEQ ID NO:
• 29, and LCDR3 shown in SEQ ID NO:
• 30 or a variant having no more than 2 amino acid changes from LCDR3 shown in SEQ ID NO:
• 30;
• (k) LCDR1 shown in SEQ ID NO:
• 31 or a variant having no more than 2 amino acid changes from LCDR1 shown in SEQ ID NO:
• 31, LCDR2 shown in SEQ ID NO:
• 32 or a variant having no more than 2 amino acid changes from LCDR2 shown in SEQ ID NO:
• 32, and LCDR3 shown in SEQ ID NO:
• 33 or a variant having no more than 2 amino acid changes from LCDR3 shown in SEQ ID NO:
• 33;
• (l) LCDR1 shown in SEQ ID NO:
• 34 or a variant having no more than 2 amino acid changes from LCDR1 shown in SEQ ID NO:
• 34, LCDR2 shown in SEQ ID NO:
• 35 or a variant having no more than 2 amino acid changes from LCDR2 shown in SEQ ID NO:
• 35, and LCDR3 shown in SEQ ID NO:
• 36 or a variant having no more than 2 amino acid changes from LCDR3 shown in SEQ ID NO:
• 36;
• (m) LCDR1 shown in SEQ ID NO:
• 37 or a variant having no more than 2 amino acid changes from LCDR1 shown in SEQ ID NO:
• 37, LCDR2 shown in SEQ ID NO:
• 38 or a variant having no more than 2 amino acid changes from LCDR2 shown in SEQ ID NO:
• 38, and LCDR3 shown in SEQ ID NO:
• 39 or a variant having no more than 2 amino acid changes from LCDR3 shown in SEQ ID NO:
• 39;
• (n) LCDR1 shown in SEQ ID NO:
• 40 or a variant having no more than 2 amino acid changes from LCDR1 shown in SEQ ID NO:
• 40, LCDR2 shown in SEQ ID NO:
• 41 or a variant having no more than 2 amino acid changes from LCDR2 shown in SEQ ID NO:
• 41, and LCDR3 shown in SEQ ID NO:
• 42 or a variant having no more than 2 amino acid changes from LCDR3 shown in SEQ ID NO:
• 42;
• (o) LCDR1 shown in SEQ ID NO:
• 43 or a variant having no more than 2 amino acid changes from LCDR1 shown in SEQ ID NO:
• 43, LCDR2 shown in SEQ ID NO:
• 44 or a variant having no more than 2 amino acid changes from LCDR2 shown in SEQ ID NO:
• 44, and LCDR3 shown in SEQ ID NO:
• 45 or a variant having no more than 2 amino acid changes from LCDR3 shown in SEQ ID NO:
• 45;
• (p) LCDR1 shown in SEQ ID NO:
• 46 or a variant having no more than 2 amino acid changes from LCDR1 shown in SEQ ID NO:
• 46, LCDR2 shown in SEQ ID NO:
• 47 or a variant having no more than 2 amino acid changes from LCDR2 shown in SEQ ID NO:
• 47, and LCDR3 shown in SEQ ID NO:
• 48 or a variant having no more than 2 amino acid changes from LCDR3 shown in SEQ ID NO:
• 48;
• (q) LCDR1 shown in SEQ ID NO:
• 49 or a variant having no more than 2 amino acid changes from LCDR1 shown in SEQ ID NO:
• 49, LCDR2 shown in SEQ ID NO:
• 50 or a variant having no more than 2 amino acid changes from LCDR2 shown in SEQ ID NO:
• 50, and LCDR3 shown in SEQ ID NO:
• 51 or a variant having no more than 2 amino acid changes from LCDR3 shown in SEQ ID NO:
• 51;
• (r) LCDR1 shown in SEQ ID NO:
• 49 or a variant having no more than 2 amino acid changes from LCDR1 shown in SEQ ID NO:
• 49, LCDR2 shown in SEQ ID NO:
• 52 or a variant having no more than 2 amino acid changes from LCDR2 shown in SEQ ID NO:
• 52, and LCDR3 shown in SEQ ID NO:
• 53 or a variant having no more than 2 amino acid changes from LCDR3 shown in SEQ ID NO:
• 53;
• or
• (s) LCDR1 shown in SEQ ID NO:
• 54 or a variant having no more than 2 amino acid changes from LCDR1 shown in SEQ ID NO:
• 54, LCDR2 shown in SEQ ID NO:
• 35 or a variant having no more than 2 amino acid changes from LCDR2 shown in SEQ ID NO:
• 35, and LCDR3 shown in SEQ ID NO:
• 55 or a variant having no more than 2 amino acid changes from LCDR3 shown in SEQ ID NO:
• 55;
• Preferably, the common light chain in the bispecific antibody comprises any of the light chain variable region sequences shown in SEQ ID NOs:
• 56-74, or a sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more sequence identity with the light chain variable region sequence.