ANTI-C1s ANTIBODY

Patent metadata

Field	Value
Publication number	US-2024287163-A1
Application number	US-202218286471-A
Country	US
Kind code	A1
Filing date	Apr 14, 2022
Priority date	Apr 15, 2021
Publication date	Aug 29, 2024
Grant date	—

Abstract

The present invention provides antibodies that comprises an antigen-binding region and an antibody constant region and binds to C1s in a pH-dependent manner. The present invention provides pharmaceutical compositions comprising any one of the antibodies, and methods of treating an individual having a complement-mediated disease or disorder, or preventing an individual potentially having a complement-mediated disease or disorder, the method comprising administering any one of the antibodies to the individual.

First claim

1 . An isolated antibody that binds to C1s, comprising
a combination of HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 selected from the group consisting of 1) to 6) below: 1) HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 that comprise the amino acid sequences consisting of SEQ ID NOs: 25, 26, 27, 60, 61, and 62, respectively; 2) HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 that comprise the amino acid sequences consisting of SEQ ID NOs: 37, 38, 39, 56, 57, and 58, respectively; 3) HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 that comprise the amino acid sequences consisting of SEQ ID NOs: 25, 26, 27, 56, 57, and 58, respectively; 4) HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 that comprise the amino acid sequences consisting of SEQ ID NOs: 25, 26, 27, 48, 49, and 50, respectively; 5) HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 that comprise the amino acid sequences consisting of SEQ ID NOs: 29, 30, 31, 52, 53, and 54, respectively; and 6) HVR-H1, HVR-H2, HVR-H3, HVR-L1, HVR-L2, and HVR-L3 that comprise the amino acid sequences consisting of SEQ ID NOs: 33, 34, 35, 56, 57, and 58, respectively.

2 . The antibody of claim 1 , wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL) selected from the group consisting of 1) to 6) below:
1) a VH and VL that comprise the amino acid sequences consisting of SEQ ID NOs: 24 and 59, respectively; 2) a VH and VL that comprise the amino acid sequences consisting of SEQ ID NOs: 36 and 55, respectively; 3) a VH and VL that comprise the amino acid sequences consisting of SEQ ID NOs: 24 and 55, respectively; 4) a VH and VL that comprise the amino acid sequences consisting of SEQ ID NOs: 24 and 47, respectively; 5) a VH and VL that comprise the amino acid sequences consisting of SEQ ID NOs: 28 and 51, respectively; and 6) a VH and VL that comprise the amino acid sequences consisting of SEQ ID NOs: 32 and 55, respectively.

3 . The antibody of claim 1 , wherein the ratio of the KD value at pH6.0 to the KD value at pH7.4 of the antibody is 107 or more.

4 . The antibody of claim 1 , wherein the antibody specifically binds to a CUB1-EGF-CUB2 domain of human C1s.

5 . The antibody of claim 1 , wherein the antibody comprises a mutant constant region comprising at least one amino acid alteration that decreases Fc7 receptor-binding activity.

6 . The antibody of claim 5 , wherein the mutant constant region comprises an amino acid alteration in at least one of positions 235 and 236 according to EU numbering.

7 . The antibody of claim 1 , wherein the antibody comprises a mutant constant region comprising at least one amino acid alteration, and wherein the amino acid alteration decreases isoelectric point (pI) of the mutant constant region as compared to that of a parent constant region that does not contain the at least one amino acid alteration.

8 . The antibody of claim 7 , wherein the mutant constant region comprises an amino acid alteration in at least one of positions 137, 268, 274, 355, and 419 according to EU numbering.

9 . The antibody of claim 1 , wherein pI of the antibody is 7.8 or less.

10 . The antibody of claim 1 , wherein the antibody comprises a heavy chain constant region comprising the amino acid sequence consisting of SEQ ID NO: 45 and a light chain constant region comprising the amino acid sequence consisting of SEQ ID NO: 23.

11 . (canceled)

12 . (canceled)

13 . (canceled)

14 . An antibody comprising a heavy chain (H chain) and a light chain (L chain) selected from the group consisting of 1) to 6) below:
1) an H chain and L chain that comprise the amino acid sequences consisting of SEQ ID NOs: 66 and 67, respectively; 2) an H chain and L chain that comprise the amino acid sequences consisting of SEQ ID NOs: 68 and 69, respectively; 3) an H chain and L chain that comprise the amino acid sequences consisting of SEQ ID NOs: 70 and 71, respectively; 4) an H chain and L chain that comprise the amino acid sequences consisting of SEQ ID NOs: 72 and 73, respectively; 5) an H chain and L chain that comprise the amino acid sequences consisting of SEQ ID NOs: 74 and 75, respectively; and 6) an H chain and L chain that comprise the amino acid sequences consisting of SEQ ID NOs: 76 and 77, respectively.

15 . The antibody of claim 1 , wherein the antibody promotes dissociation of C1q from C1qrs complex and/or inhibits binding of C1q to C1r2s2.

16 . An isolated nucleic acid or nucleic acids encoding the antibody of claim 1 .

17 . A host cell comprising the nucleic acid of claim 16 .

18 . A method of producing an antibody comprising culturing the host cell of claim 17 so that the antibody is produced.

19 . A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.

20 . A method of treating an individual having a complement-mediated disease or disorder, the method comprising administering to the individual an effective amount of the antibody of claim 1 .

21 . An isolated nucleic acid or nucleic acids encoding the antibody of claim 14 .

22 . A host cell comprising the nucleic acid of claim 21 .

23 . A method of producing an antibody comprising culturing the host cell of claim 22 so that the antibody is produced.

24 . A pharmaceutical composition comprising the antibody of claim 14 and a pharmaceutically acceptable carrier.

25 . A method of treating an individual having a complement-mediated disease or disorder, the method comprising administering to the individual an effective amount of the antibody of claim 14 .

Assignees

• Chugai Pharmaceutical Co Ltd

Inventors

• Koga Hikaru

Classifications

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title

• C07K2317/90

  characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/71

  Decreased effector function due to an Fc-modification · CPC title

• C07K2317/526

  CH3 domain · CPC title