IP Library › Patent Application 16340991

Patent Application

App. No. 16/340,991

ANTI-C1S ANTIBODIES AND METHODS OF USE THEREOF

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Patent No.: US None
App. No.: 16/340,991

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Abstract

The present disclosure provides antibodies that specifically bind complement pathway component C1s. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the anti-C1s antibodies; and host cells comprising the nucleic acids. The present disclosure provides compositions comprising the anti-C1s antibodies. The present disclosure provides methods of use of the anti-C1s antibodies.

Claims (53)

1 . An antibody, comprising a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable (VH) region and a heavy chain constant region, and the light chain comprises a light chain variable (VL) region;

wherein the VL region comprises a VL complementary determining region (CDR) 1, a VL CDR2, and a VL CDR3, and wherein the VH region comprises a VH CDR1, a VH CDR2, and a VH CDR3;

wherein the VL CDR1 comprises SEQ ID NO: 1;

wherein the VL CDR2 comprises SEQ ID NO: 2;

wherein the VL CDR3 comprises SEQ ID NO: 3;

wherein the VH CDR1 comprises SEQ ID NO: 4;

wherein the VH CDR2 comprises SEQ ID NO: 5;

wherein the VH CDR3 comprises SEQ ID NO: 6;

wherein the heavy chain constant region comprises an IgG4 constant region, wherein amino acid residue 308 of the heavy chain constant region corresponding to SEQ ID NO: 28 is Leu, and amino acid residue 314 of the heavy chain constant region corresponding to SEQ ID NO: 28 is Ser;

and wherein the antibody specifically binds activated C1s.

2 . The antibody of claim 1 , wherein amino acid residue 108 of the heavy chain constant region corresponding to SEQ ID NO: 28 is Pro.

3 . The antibody of claim 1 or 2 , wherein amino acid residue 115 of the heavy chain constant region corresponding to SEQ ID NO: 28 is Glu.

4 . An antibody, comprising a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable (VH) region and a heavy chain constant region, and the light chain comprises a light chain variable (VL) region;

wherein the VL region comprises a VL complementary determining region (CDR) 1, a VL CDR2, and a VL CDR3, and wherein the VH region comprises a VH CDR1, a VH CDR2, and a VH CDR3;

wherein the VL CDR1 comprises SEQ ID NO: 1;

wherein the VL CDR2 comprises SEQ ID NO: 2;

wherein the VL CDR3 comprises SEQ ID NO: 3;

wherein the VH CDR1 comprises SEQ ID NO: 4;

wherein the VH CDR2 comprises SEQ ID NO: 5;

wherein the VH CDR3 comprises SEQ ID NO: 6;

wherein the heavy chain constant region comprises SEQ ID NO: 28;

and wherein the antibody specifically binds activated C1s.

5 . The antibody of any one of claims 1 to 4 , wherein the VL region comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 20, 22, and 24.

6 . The antibody of any one of claims 1 to 5 , wherein the VH region comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 10, 12, 14, 16, and 18.

7 . The antibody of any one of claims 1 to 6 , wherein:

(a) the VH region comprises SEQ ID NO:10, and the VL region comprises SEQ ID NO:20;

(b) the VH region comprises SEQ ID NO:10, and the VL region comprises SEQ ID NO:22;

(d) the VH region comprises SEQ ID NO:12, and the VL region comprises SEQ ID NO:20;

(e) the VH region comprises SEQ ID NO:12, and the VL region comprises SEQ ID NO:22;

(f) the VH region comprises SEQ ID NO:12, and the VL region comprises SEQ ID NO:24;

(g) the VH region comprises SEQ ID NO:14, and the VL region comprises SEQ ID NO:20;

(h) the VH region comprises SEQ ID NO:14, and the VL region comprises SEQ ID NO:22;

(i) the VH region comprises SEQ ID NO:14, and the VL region comprises SEQ ID NO:24;

(j) the VH region comprises SEQ ID NO:16, and the VL region comprises SEQ ID NO:20;

(j) the VH region comprises SEQ ID NO:16, and the VL region comprises SEQ ID NO:22;

(k) the VH region comprises SEQ ID NO:16, and the VL region comprises SEQ ID NO:24;

(l) the VH region comprises SEQ ID NO:18, and the VL region comprises SEQ ID NO:20;

(m) the VH region comprises SEQ ID NO:18, and the VL region comprises SEQ ID NO:22; or

(n) the VH region comprises SEQ ID NO:18, and the VL region comprises SEQ ID NO:24.

8 . The antibody of any one of claims 1 to 7 , wherein the VH region comprises SEQ ID NO:14, and the VL region comprises SEQ ID NO:22.

9 . The antibody of any one of claims 1 to 8 , wherein the light chain further comprises a light chain constant region.

10 . The antibody of claim 9 , wherein the light chain constant region comprises SEQ ID NO: 45.

11 . The antibody of any one of claims 1 to 10 , where the heavy chain comprises SEQ ID NO: 29.

12 . The antibody of any one of claims 1 to 11 , wherein the light chain comprises SEQ ID NO: 30.

13 . The antibody of any one of claims 1 to 12 , which is a bispecific antibody or a multispecific antibody.

14 . An immunoconjugate comprising the antibody of any one of claims 1 to 13 .

15 . A nucleotide of a set of nucleotides encoding the antibody of any one of claims 1 to 13 .

16 . A vector or a set of vectors comprising the nucleotide of the set of nucleotides of claim 15 .

17 . A host cell comprising the nucleotide of the set of nucleotides of claim 15 or the vector or the set of vectors of claim 16 .

18 . A pharmaceutical composition comprising the antibody of any one of claims 1 to 13 , the immunoconjugate of claim 14 , the nucleotide or the set of nucleotides of claim 15 , the vector or the set of vectors of claim 16 , or the host cell of claim 17 , and a pharmaceutically acceptable excipient.

19 . A method of inhibiting a complement pathway in a subject in need thereof, comprising administering to the subject a pharmaceutically effective amount of the antibody of any one of claims 1 to 13 , the immunoconjugate of claim 14 , the nucleotide or the set of nucleotides of claim 15 , the vector or the set of vectors of claim 16 , or the host cell of claim 17 , or the pharmaceutical composition of claim 18 .

20 . A method of treating a complement-mediated disease or disorder in a subject in need thereof, comprising administering to the subject a pharmaceutically effective amount of the antibody of any one of claims 1 to 13 , the immunoconjugate of claim 14 , the nucleotide or the set of nucleotides of claim 15 , the vector or the set of vectors of claim 16 , or the host cell of claim 17 , or the pharmaceutical composition of claim 18 .