US 12,227,580 B2
Antigen binding molecules that bind LIGHT
Steve Holmes, Altrincham (GB)
Assigned to CENTESSA PHARMACEUTICALS (UK) LIMITED, Altrincham (GB)
Filed by CENTESSA PHARMACEUTICALS (UK) LIMITED, Altrincham (GB)
Filed on Apr. 22, 2022, as Appl. No. 17/660,382.
Application 17/660,382 is a division of application No. 16/256,688, filed on Jan. 24, 2019, granted, now 11,312,781.
Claims priority of provisional application 62/621,346, filed on Jan. 24, 2018.
Prior Publication US 2023/0035798 A1, Feb. 2, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/28 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/2875 (2013.01) [A61K 39/001136 (2018.08); A61K 2039/505 (2013.01); C07K 2317/51 (2013.01); C07K 2317/55 (2013.01); C07K 2317/565 (2013.01); C07K 2317/76 (2013.01); C07K 2317/92 (2013.01)] 24 Claims
 
1. A pharmaceutical composition for treatment of a LIGHT-mediated disease or disorder, the pharmaceutical composition comprising:
an anti-LIGHT antigen binding molecule, wherein the antigen binding molecule specifically binds to membrane-bound human LIGHT and has a higher affinity for membrane-bound human LIGHT compared to soluble human LIGHT, wherein the anti-LIGHT antigen binding molecule is selected from the group consisting of:
(a) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYEMH (SEQ ID NO: 38), a VHCDR2 comprising the amino acid sequence EIDPETGDTAYAQKFQG (SEQ ID NO: 147) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 40); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence RASENIYGALN (SEQ ID NO: 34), a VLCDR2 comprising the amino acid sequence GATNLAE (SEQ ID NO: 35) and a VLCDR3 comprising the amino acid sequence QNVLTTPWT (SEQ ID NO: 36);
(b) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYEMH (SEQ ID NO: 6), a VHCDR2 comprising the amino acid sequence EIDPETGDTAYSQKFKG (SEQ ID NO: 7), a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 8); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 2), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 3) and a VLCDR3 comprising the amino acid sequence QNVLTTPWT (SEQ ID NO: 4);
(c) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYEMH (SEQ ID NO: 14), a VHCDR2 comprising the amino acid sequence EIDPETGDTAYSQKFKG (SEQ ID NO: 15) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 16); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 10), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 11) and a VLCDR3 comprising the amino acid sequence QNVLTTPWT (SEQ ID NO: 12);
(d) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYEMH (SEQ ID NO: 22), a VHCDR2 comprising the amino acid sequence EIDPETGDTAYSQKFQG (SEQ ID NO: 23) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 24); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 10), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 11) and a VLCDR3 comprising the amino acid sequence QNVLTTPWT (SEQ ID NO: 12);
(e) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYEMH (SEQ ID NO: 30), a VHCDR2 comprising the amino acid sequence EIDPETGDTAYAQKFQG (SEQ ID NO: 146) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 32); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 10), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 11) and a VLCDR3 comprising the amino acid sequence QNVLTTPWT (SEQ ID NO: 12);
(f) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYEMH (SEQ ID NO: 38), a VHCDR2 comprising the amino acid sequence EIDPETGDTAYAQKFQG (SEQ ID NO: 147) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 40); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 10), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 11) and a VLCDR3 comprising the amino acid sequence QNVLTTPWT (SEQ ID NO: 12);
(g) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYEMH (SEQ ID NO: 14), a VHCDR2 comprising the amino acid sequence EIDPETGDTAYSQKFKG (SEQ ID NO: 15) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 16); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 18), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 19) and a VLCDR3 comprising the amino acid sequence QNVLTTPWT (SEQ ID NO: 20);
(h) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYEMH (SEQ ID NO: 22), a VHCDR2 comprising the amino acid sequence EIDPETGDTAYSQKFQG (SEQ ID NO: 23) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 24); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 18), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 19) and a VLCDR3 comprising the amino acid sequence QNVLTTPWT (SEQ ID NO: 20);
(i) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYEMH (SEQ ID NO: 30), a VHCDR2 comprising the amino acid sequence EIDPETGDTAYAQKFQG (SEQ ID NO: 146) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 32); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 18), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 19) and a VLCDR3 comprising the amino acid sequence QNVLTTPWT (SEQ ID NO: 20);
(j) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYEMH (SEQ ID NO: 38), a VHCDR2 comprising the amino acid sequence EIDPETGDTAYAQKFQG (SEQ ID NO: 147) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 40); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 18), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 19) and a VLCDR3 comprising the amino acid sequence QNVLTTPWT (SEQ ID NO: 20);
(k) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYEMH (SEQ ID NO: 14), a VHCDR2 comprising the amino acid sequence EIDPETGDTAYSQKFKG (SEQ ID NO: 15) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 16); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 26), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 27) and a VLCDR3 comprising the amino acid sequence QNVLTTPWT (SEQ ID NO: 28);
(l) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYEMH (SEQ ID NO: 22), a VHCDR2 comprising the amino acid sequence EIDPETGDTAYSQKFQG (SEQ ID NO: 23) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 24); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 26), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 27) and a VLCDR3 comprising the amino acid sequence QNVLTTPWT (SEQ ID NO: 28);
(m) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYEMH (SEQ ID NO: 30), a VHCDR2 comprising the amino acid sequence EIDPETGDTAYAQKFQG (SEQ ID NO: 146) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 32); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 26), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 27) and a VLCDR3 comprising the amino acid sequence QNVLTTPWT (SEQ ID NO: 28);
(n) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYEMH (SEQ ID NO: 38), a VHCDR2 comprising the amino acid sequence EIDPETGDTAYAQKFQG (SEQ ID NO: 147) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 40); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 26), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 27) and a VLCDR3 comprising the amino acid sequence QNVLTTPWT (SEQ ID NO: 28);
(o) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYEMH (SEQ ID NO: 14), a VHCDR2 comprising the amino acid sequence EIDPETGDTAYSQKFKG (SEQ ID NO: 15) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 16); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence RASENIYGALN (SEQ ID NO: 34), a VLCDR2 comprising the amino acid sequence GATNLAE (SEQ ID NO: 35) and a VLCDR3 comprising the amino acid sequence QNVLTTPWT (SEQ ID NO: 36);
(p) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYEMH (SEQ ID NO: 22), a VHCDR2 comprising the amino acid sequence EIDPETGDTAYSQKFQG (SEQ ID NO: 23) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 24); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence RASENIYGALN (SEQ ID NO: 34), a VLCDR2 comprising the amino acid sequence GATNLAE (SEQ ID NO: 35) and a VLCDR3 comprising the amino acid sequence QNVLTTPWT (SEQ ID NO: 36);
(q) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DYEMH (SEQ ID NO: 30), a VHCDR2 comprising the amino acid sequence EIDPETGDTAYAQKFQG (SEQ ID NO: 146) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 32); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence RASENIYGALN (SEQ ID NO: 34), a VLCDR2 comprising the amino acid sequence GATNLAE (SEQ ID NO: 35) and a VLCDR3 comprising the amino acid sequence QNVLTTPWT (SEQ ID NO: 36);
(r) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DSEIH (SEQ ID NO: 46), a VHCDR2 comprising the amino acid sequence EIDPETGGTAYNQKFKG (SEQ ID NO: 47), a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 48); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 42), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 43) and a VLCDR3 comprising the amino acid sequence QNVLSTPWT (SEQ ID NO: 44);
(s) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DSEIH (SEQ ID NO: 54), a VHCDR2 comprising the amino acid sequence EIDPETGGTAYNQKFKG (SEQ ID NO: 55) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 56); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 50), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 51) and a VLCDR3 comprising the amino acid sequence QNVLSTPWT (SEQ ID NO: 52);
(t) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DSEIH (SEQ ID NO: 62), a VHCDR2 comprising the amino acid sequence EIDPETGGTAYNQKFQG (SEQ ID NO: 63) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 64); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 50), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 51) and a VLCDR3 comprising the amino acid sequence QNVLSTPWT (SEQ ID NO: 52);
(u) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DSEIH (SEQ ID NO: 70), a VHCDR2 comprising the amino acid sequence EIDPETGGTAYAQKFQG (SEQ ID NO: 71) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 72); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 50), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 51) and a VLCDR3 comprising the amino acid sequence QNVLSTPWT (SEQ ID NO: 52);
(v) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DSEMH (SEQ ID NO: 78), a VHCDR2 comprising the amino acid sequence EIDPETGGTAYAQKFQG (SEQ ID NO: 79) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 80); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 50), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 51) and a VLCDR3 comprising the amino acid sequence QNVLSTPWT (SEQ ID NO: 52);
(w) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DSEIH (SEQ ID NO: 54), a VHCDR2 comprising the amino acid sequence EIDPETGGTAYNQKFKG (SEQ ID NO: 55) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 56); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 58), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 59) and a VLCDR3 comprising the amino acid sequence QNVLSTPWT (SEQ ID NO: 60);
(x) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DSEIH (SEQ ID NO: 62), a VHCDR2 comprising the amino acid sequence EIDPETGGTAYNQKFQG (SEQ ID NO: 63) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 64); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 58), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 59) and a VLCDR3 comprising the amino acid sequence QNVLSTPWT (SEQ ID NO: 60);
(y) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DSEIH (SEQ ID NO: 70), a VHCDR2 comprising the amino acid sequence EIDPETGGTAYAQKFQG (SEQ ID NO: 71) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 72); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 58), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 59) and a VLCDR3 comprising the amino acid sequence QNVLSTPWT (SEQ ID NO: 60);
(z) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DSEMH (SEQ ID NO: 78), a VHCDR2 comprising the amino acid sequence EIDPETGGTAYAQKFQG (SEQ ID NO: 79) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 80); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 58), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 59) and a VLCDR3 comprising the amino acid sequence QNVLSTPWT (SEQ ID NO: 60);
(aa) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DSEIH (SEQ ID NO: 54), a VHCDR2 comprising the amino acid sequence EIDPETGGTAYNQKFKG (SEQ ID NO: 55) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 56); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 66), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 67) and a VLCDR3 comprising the amino acid sequence QNVLSTPWT (SEQ ID NO: 68);
(ab) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DSEIH (SEQ ID NO: 62), a VHCDR2 comprising the amino acid sequence EIDPETGGTAYNQKFQG (SEQ ID NO: 63) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 64); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 66), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 67) and a VLCDR3 comprising the amino acid sequence QNVLSTPWT (SEQ ID NO: 68);
(ac) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DSEIH (SEQ ID NO: 70), a VHCDR2 comprising the amino acid sequence EIDPETGGTAYAQKFQG (SEQ ID NO: 71) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 72); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 66), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 67) and a VLCDR3 comprising the amino acid sequence QNVLSTPWT (SEQ ID NO: 68);
(ad) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DSEMH (SEQ ID NO: 78), a VHCDR2 comprising the amino acid sequence EIDPETGGTAYAQKFQG (SEQ ID NO: 79) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 80); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence GASENIYGALN (SEQ ID NO: 66), a VLCDR2 comprising the amino acid sequence GATNLAD (SEQ ID NO: 67) and a VLCDR3 comprising the amino acid sequence QNVLSTPWT (SEQ ID NO: 68);
(ae) an anti-LIGHT antigen binding molecule comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DSEIH (SEQ ID NO: 54), a VHCDR2 comprising the amino acid sequence EIDPETGGTAYNQKFKG (SEQ ID NO: 55) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 56); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence RASENIYGALN (SEQ ID NO: 74), a VLCDR2 comprising the amino acid sequence GATNLAE (SEQ ID NO: 75) and a VLCDR3 comprising the amino acid sequence QNVLSTPWT (SEQ ID NO: 76);
(af) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DSEIH (SEQ ID NO: 62), a VHCDR2 comprising the amino acid sequence EIDPETGGTAYNQKFQG (SEQ ID NO: 63) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 64); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence RASENIYGALN (SEQ ID NO: 74), a VLCDR2 comprising the amino acid sequence GATNLAE (SEQ ID NO: 75) and a VLCDR3 comprising the amino acid sequence QNVLSTPWT (SEQ ID NO: 76);
(ag) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DSEIH (SEQ ID NO: 70), a VHCDR2 comprising the amino acid sequence EIDPETGGTAYAQKFQG (SEQ ID NO: 71) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 72); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence RASENIYGALN (SEQ ID NO: 74), a VLCDR2 comprising the amino acid sequence GATNLAE (SEQ ID NO: 75) and a VLCDR3 comprising the amino acid sequence QNVLSTPWT (SEQ ID NO: 76); and
(ah) an antibody comprising a heavy chain variable region comprising a VHCDR1 comprising the amino acid sequence DSEMH (SEQ ID NO: 78), a VHCDR2 comprising the amino acid sequence EIDPETGGTAYAQKFQG (SEQ ID NO: 79) and a VHCDR3 comprising the amino acid sequence ETDYFFDY (SEQ ID NO: 80); and a light chain variable region comprising a VLCDR1 comprising the amino acid sequence RASENIYGALN (SEQ ID NO: 74), a VLCDR2 comprising the amino acid sequence GATNLAE (SEQ ID NO: 75) and a VLCDR3 comprising the amino acid sequence QNVLSTPWT (SEQ ID NO: 76).