IP Library › Patent Application 18989593

Patent Application

App. No. 18/989,593

ANTI-COMPLEMENT C1S ANTIBODIES AND USES THEREOF

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Patent No.: US None
App. No.: 18/989,593

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Abstract

The present disclosure provides antibodies that bind complement C1s protein; and nucleic acid molecules that encode such antibodies. In some embodiments, such anti-complement C1s antibodies inhibit proteolytic activity of C1s. The present disclosure also provides compositions comprising such antibodies, and methods to produce and use such antibodies, nucleic acid molecules, and compositions.

Claims (112)

1 .- 82 . (canceled)

83 . One or more nucleic acids encoding an antibody that binds to complement C1s protein, wherein the antibody comprises:

(i) a light chain complementarity-determining region 1 (CDR-L1) sequence, a light chain complementarity-determining region 2 (CDR-L2) sequence, and a light chain complementarity-determining region 3 (CDR-L3) sequence of an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 7; and a heavy chain complementarity-determining region 1 (CDR-H1) sequence, a heavy chain complementarity-determining region 2 (CDR-H2) sequence, and a heavy chain complementarity-determining region 3 (CDR-H3) sequence of an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 8;

(ii) a CDR-L1 sequence, a CDR-L2 sequence, and a CDR-L3 sequence of an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 23; and a CDR-H1 sequence, a CDR-H2 sequence, and a CDR-H3 sequence of an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 24;

(iii) a CDR-L1 sequence, a CDR-L2 sequence, and a CDR-L3 sequence of an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 31; and a CDR-H1 sequence, a CDR-H2 sequence, and a CDR-H3 sequence of an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 32;

(iv) a CDR-L1 sequence, a CDR-L2 sequence, and a CDR-L3 sequence of an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 39; and a CDR-H1 sequence, a CDR-H2 sequence, and a CDR-H3 sequence of an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 40;

(v) a CDR-L1 sequence, a CDR-L2 sequence, and a CDR-L3 sequence of an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 47; and a CDR-H1 sequence, a CDR-H2 sequence, and a CDR-H3 sequence of an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 48;

(vi) a CDR-L1 sequence, a CDR-L2 sequence, and a CDR-L3 sequence of an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 55; and a CDR-H1 sequence, a CDR-H2 sequence, and a CDR-H3 sequence of an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 56;

(vii) a CDR-L1 sequence, a CDR-L2 sequence, and a CDR-L3 sequence of an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 63; and a CDR-H1 sequence, a CDR-H2 sequence, and a CDR-H3 sequence of an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 64;

(viii) a CDR-L1 sequence, a CDR-L2 sequence, and a CDR-L3 sequence of an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 71; and a CDR-H1 sequence, a CDR-H2 sequence, and a CDR-H3 sequence of an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 72;

(ix) a CDR-L1 sequence, a CDR-L2 sequence, and a CDR-L3 sequence of an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 79; and a CDR-H1 sequence, a CDR-H2 sequence, and a CDR-H3 sequence of an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 80;

(x) a CDR-L1 sequence, a CDR-L2 sequence, and a CDR-L3 sequence of an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 87; and a CDR-H1 sequence, a CDR-H2 sequence, and a CDR-H3 sequence of an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 88;

(xi) a CDR-L1 sequence, a CDR-L2 sequence, and a CDR-L3 sequence of an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 95; and a CDR-H1 sequence, a CDR-H2 sequence, and a CDR-H3 sequence of an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 96;

(xii) a CDR-L1 sequence, a CDR-L2 sequence, and a CDR-L3 sequence of an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 103; and a CDR-H1 sequence, a CDR-H2 sequence, and a CDR-H3 sequence of an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 104; or

(xiii) a CDR-L1 sequence, a CDR-L2 sequence, and a CDR-L3 sequence of an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 111; and a CDR-H1 sequence, a CDR-H2 sequence, and a CDR-H3 sequence of an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 112.

84 . The one or more nucleic acids of claim 83 , wherein the antibody comprises:

(i) a light chain variable region that comprises a CDR-L1 amino acid sequence set forth in SEQ ID NO: 1, a CDR-L2 amino acid sequence set forth in SEQ ID NO: 2, and a CDR-L3 amino acid sequence set forth in SEQ ID NO: 3; and a heavy chain variable region that comprises a CDR-H1 amino acid sequence set forth in SEQ ID NO: 4, a CDR-H2 amino acid sequence set forth in SEQ ID NO: 5, and a CDR-H3 amino acid sequence set forth in SEQ ID NO: 6;

(ii) a light chain variable region that comprises a CDR-L1 amino acid sequence set forth in SEQ ID NO: 17, a CDR-L2 amino acid sequence set forth in SEQ ID NO: 18, and a CDR-L3 amino acid sequence set forth in SEQ ID NO: 19; and a heavy chain variable region that comprises a CDR-H1 amino acid sequence set forth in SEQ ID NO: 20, a CDR-H2 amino acid sequence set forth in SEQ ID NO: 21, and a CDR-H3 amino acid sequence set forth in SEQ ID NO: 22;

(iii) a light chain variable region that comprises a CDR-L1 amino acid sequence set forth in SEQ ID NO: 25, a CDR-L2 amino acid sequence set forth in SEQ ID NO: 26, and a CDR-L3 amino acid sequence set forth in SEQ ID NO: 27; and a heavy chain variable region that comprises a CDR-H1 amino acid sequence set forth in SEQ ID NO: 28, a CDR-H2 amino acid sequence set forth in SEQ ID NO: 29, and a CDR-H3 amino acid sequence set forth in SEQ ID NO: 30;

(iv) a light chain variable region that comprises a CDR-L1 amino acid sequence set forth in SEQ ID NO: 33, a CDR-L2 amino acid sequence set forth in SEQ ID NO: 34, and a CDR-L3 amino acid sequence set forth in SEQ ID NO: 35; and a heavy chain variable region that comprises a CDR-H1 amino acid sequence set forth in SEQ ID NO: 36, a CDR-H2 amino acid sequence set forth in SEQ ID NO: 37, and a CDR-H3 amino acid sequence set forth in SEQ ID NO: 38;

(v) a light chain variable region that comprises a CDR-L1 amino acid sequence set forth in SEQ ID NO: 41, a CDR-L2 amino acid sequence set forth in SEQ ID NO: 42, and a CDR-L3 amino acid sequence set forth in SEQ ID NO: 43; and a heavy chain variable region that comprises a CDR-H1 amino acid sequence set forth in SEQ ID NO: 44, a CDR-H2 amino acid sequence set forth in SEQ ID NO: 45, and a CDR-H3 amino acid sequence set forth in SEQ ID NO: 46;

(vi) a light chain variable region that comprises a CDR-L1 amino acid sequence set forth in SEQ ID NO: 49, a CDR-L2 amino acid sequence set forth in SEQ ID NO: 50, and a CDR-L3 amino acid sequence set forth in SEQ ID NO: 51; and a heavy chain variable region that comprises a CDR-H1 amino acid sequence set forth in SEQ ID NO: 52, a CDR-H2 amino acid sequence set forth in SEQ ID NO: 53, and a CDR-H3 amino acid sequence set forth in SEQ ID NO: 54;

(vii) a light chain variable region that comprises a CDR-L1 amino acid sequence set forth in SEQ ID NO: 57, a CDR-L2 amino acid sequence set forth in SEQ ID NO: 58, and a CDR-L3 amino acid sequence set forth in SEQ ID NO: 59; and a heavy chain variable region that comprises a CDR-H1 amino acid sequence set forth in SEQ ID NO: 60, a CDR-H2 amino acid sequence set forth in SEQ ID NO: 61, and a CDR-H3 amino acid sequence set forth in SEQ ID NO: 62;

(viii) a light chain variable region that comprises a CDR-L1 amino acid sequence set forth in SEQ ID NO: 65, a CDR-L2 amino acid sequence set forth in SEQ ID NO: 66, and a CDR-L3 amino acid sequence set forth in SEQ ID NO: 67; and a heavy chain variable region that comprises a CDR-H1 amino acid sequence set forth in SEQ ID NO: 68, a CDR-H2 amino acid sequence set forth in SEQ ID NO: 69, and a CDR-H3 amino acid sequence set forth in SEQ ID NO: 70;

(ix) a light chain variable region that comprises a CDR-L1 amino acid sequence set forth in SEQ ID NO: 73, a CDR-L2 amino acid sequence set forth in SEQ ID NO: 74, and a CDR-L3 amino acid sequence set forth in SEQ ID NO: 75; and a heavy chain variable region that comprises a CDR-H1 amino acid sequence set forth in SEQ ID NO: 76, a CDR-H2 amino acid sequence set forth in SEQ ID NO: 77, and a CDR-H3 amino acid sequence set forth in SEQ ID NO: 78;

(x) a light chain variable region that comprises a CDR-L1 amino acid sequence set forth in SEQ ID NO: 81, a CDR-L2 amino acid sequence set forth in SEQ ID NO: 82, and a CDR-L3 amino acid sequence set forth in SEQ ID NO: 83; and a heavy chain variable region that comprises a CDR-H1 amino acid sequence set forth in SEQ ID NO: 84, a CDR-H2 amino acid sequence set forth in SEQ ID NO: 85, and a CDR-H3 amino acid sequence set forth in SEQ ID NO: 86;

(xi) a light chain variable region that comprises a CDR-L1 amino acid sequence set forth in SEQ ID NO: 89, a CDR-L2 amino acid sequence set forth in SEQ ID NO: 90, and a CDR-L3 amino acid sequence set forth in SEQ ID NO: 91; and a heavy chain variable region that comprises a CDR-H1 amino acid sequence set forth in SEQ ID NO: 92, a CDR-H2 amino acid sequence set forth in SEQ ID NO: 93, and a CDR-H3 amino acid sequence set forth in SEQ ID NO: 94;

(xii) a light chain variable region that comprises a CDR-L1 amino acid sequence set forth in SEQ ID NO: 97, a CDR-L2 amino acid sequence set forth in SEQ ID NO: 98, and a CDR-L3 amino acid sequence set forth in SEQ ID NO: 99; and a heavy chain variable region that comprises a CDR-H1 amino acid sequence set forth in SEQ ID NO: 100, a CDR-H2 amino acid sequence set forth in SEQ ID NO: 101, and a CDR-H3 amino acid sequence set forth in SEQ ID NO: 102; or

(xiii) a light chain variable region that comprises a CDR-L1 amino acid sequence set forth in SEQ ID NO: 105, a CDR-L2 amino acid sequence set forth in SEQ ID NO: 106, and a CDR-L3 amino acid sequence set forth in SEQ ID NO: 107; and a heavy chain variable region that comprises a CDR-H1 amino acid sequence set forth in SEQ ID NO: 108, a CDR-H2 amino acid sequence set forth in SEQ ID NO: 109, and a CDR-H3 amino acid sequence set forth in SEQ ID NO: 110.

85 . The one or more nucleic acids of claim 83 , wherein the antibody comprises:

(i) an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 7; and an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 8;

(ii) an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 23; and an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 24;

(iii) an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 31; and an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 32;

(iv) an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 39; and an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 40;

(v) an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 47; and an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 48;

(vi) an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 55; and an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 56;

(vii) an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 63; and an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 64;

(viii) an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 71; and an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 72;

(ix) an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 79; and an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 80;

(x) an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 87; and an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 88;

(xi) an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 95; and an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 96;

(xii) an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 103; and an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 104; or

(xiii) an antibody light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 111; and an antibody heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 112.

86 . The one or more nucleic acids of claim 83 , wherein the antibody is a humanized antibody.

87 . The one or more nucleic acids of claim 83 , wherein the antibody is a Fab fragment, a F(ab′) 2 fragment, a scFv, or a Fv.

88 . The one or more nucleic acids of claim 83 , wherein the antibody further comprises a an IgG1 constant region, an IgG2 constant region, an IgG3 constant region, or an IgG4 constant region.

89 . The one or more nucleic acids of claim 88 , wherein the antibody further comprises an IgG4 constant region.

90 . The one or more nucleic acids of claim 89 , wherein the IgG4 constant region comprises an S241P substitution and an L236E substitution.

91 . One or more vectors comprising the one or more nucleic acids of claim 83 .

92 . The one or more vectors of claim 91 , wherein the one of more nucleic acids encode an antibody comprising:

93 . The one or more vectors of claim 91 , wherein the one or more nucleic acids encode an antibody comprising:

94 . An isolated host cell comprising the one or more vectors of claim 91 .

95 . The isolated host cell of claim 94 , wherein the host cell is a mammalian cell, an insect cell, a yeast cell, or a prokaryotic cell.

96 . The isolated host cell of claim 95 , wherein the host cell is a mammalian cell.

97 . The isolated host cell of claim 96 , wherein the mammalian cell is selected from HeLa cells, CHO cells, 293 cells, Vero cells, NIH 3T3 cells, Huh-7 cells, BHK cells, PC12 cells, COS cells, COS-7 cells, RAT1 cells, mouse L cells, HEK cells, and HLHepG2 cells.

98 . The isolated host cell of claim 97 , wherein the mammalian cell is a CHO cell.

99 . A method of producing an antibody that binds to a complement C1s protein, the method comprising culturing a cell comprising the one or more nucleic acids of claim 83 .

100 . The method of claim 99 , wherein the antibody comprises:

101 . The method of claim 99 , wherein the antibody comprises:

102 . The method of claim 99 , wherein the antibody further comprises an IgG4 constant region comprising an S241P substitution and an L236E substitution.

Assignments (2)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 20, 2025

From: VAN VLASSELAER, PETER; PERRY, GRAHAM; STAGLIANO, NANCY E.; PANICKER, SANDIP

To: TRUE NORTH THERAPEUTICS, INC.

Reel/Frame 070571/0494 →

CHANGE OF NAME Recorded Mar 20, 2025

From: TRUE NORTH THERAPEUTICS, INC.

To: BIOVERATIV USA INC.

Reel/Frame 071725/0038 →