Granted Patent
B2
US 12,240,917 · App. 17/548,135 · Granted Mar 4, 2025
Anti-complement C1s antibodies and uses thereof
Inventors:
Peter Van Vlasselaer (Portola Valley, CA); Graham Parry (Burlington, MA); Nancy E. Stagliano (South San Francisco, CA); Sandip Panicker (South San Francisco, CA)
Assignee:
Bioverativ USA Inc.
C07K16/40A01N1/021A61K49/00A61K49/16A61K51/10C07K16/18C12Y304/21042G01N33/6893A61K2039/505A61K2039/54A61K2039/545C07K2317/21C07K2317/24C07K2317/33C07K2317/34C07K2317/35C07K2317/54C07K2317/55C07K2317/56C07K2317/565C07K2317/76C07K2317/92C07K2319/00G01N2800/52
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Abstract
The present disclosure provides antibodies that bind complement C1s protein; and nucleic acid molecules that encode such antibodies. The present disclosure also provides compositions comprising such antibodies, and methods to produce and use such antibodies, nucleic acid molecules, and compositions.
Claims (24)
1. A humanized antibody that binds complement C1s protein and comprises:
a light chain variable region that comprises a CDR-L1 amino acid sequence set forth as SEQ ID NO: 32, a CDR-L2 amino acid sequence set forth as SEQ ID NO: 33, and a CDR-L3 amino acid sequence set forth as SEQ ID NO: 3;
a heavy chain variable region that comprises a CDR-H1 amino acid sequence set forth as SEQ ID NO: 34, a CDR-H2 amino acid sequence set forth as SEQ ID NO: 35, and a CDR-H3 amino acid sequence set forth as SEQ ID NO: 36; and
a human IgG4 constant region, wherein the human IgG4 constant region comprises a S241P substitution (by Kabat numbering) and an L235 E substitution (by EU numbering).
2. A pharmaceutical composition comprising the humanized antibody of claim 1 and a pharmaceutically-acceptable excipient.
3. A method comprising administering to an individual a humanized antibody that binds complement C1s protein and comprises:
a light chain variable region that comprises a CDR-L1 amino acid sequence set forth as SEQ ID NO: 32, a CDR-L2 amino acid sequence set forth as SEQ ID NO: 33, and a CDR-L3 amino acid sequence set forth as SEQ ID NO: 3;
a heavy chain variable region that comprises a CDR-H1 amino acid sequence set forth as SEQ ID NO: 34, a CDR-H2 amino acid sequence set forth as SEQ ID NO: 35, and a CDR-H3 amino acid sequence set forth as SEQ ID NO: 36; and
a human IgG4 constant region, wherein the human IgG4 constant region comprises a S241P substitution (by Kabat numbering) and an L235 E substitution (by EU numbering),
wherein the individual has a complement-mediated disease.
4. The method of claim 3 , wherein the complement-mediated disease is cold-agglutinin disease.
5. A method of treating a complement-mediated disease in an individual, the method comprising administering to the individual a humanized antibody in an amount effective to treat the complement-mediated disease, wherein the humanized antibody binds complement C1s protein and comprises:
a light chain variable region that comprises a CDR-L1 amino acid sequence set forth as SEQ ID NO: 32, a CDR-L2 amino acid sequence set forth as SEQ ID NO: 33, and a CDR-L3 amino acid sequence set forth as SEQ ID NO: 3;
a heavy chain variable region that comprises a CDR-H1 amino acid sequence set forth as SEQ ID NO: 34, a CDR-H2 amino acid sequence set forth as SEQ ID NO: 35, and a CDR-H3 amino acid sequence set forth as SEQ ID NO: 36; and
a human IgG4 constant region, wherein the human IgG4 constant region comprises a S241P substitution (by Kabat numbering) and an L235 E substitution (by EU numbering).
6. The method of claim 5 , wherein the complement-mediated disease is cold-agglutinin disease.
7. A nucleic acid encoding the light chain variable region of the humanized antibody of claim 1 .
8. An expression vector comprising the nucleic acid of claim 7 .
9. A nucleic acid encoding the heavy chain variable region of the humanized antibody of claim 1 or the heavy chain variable region and the human IgG4 constant region of the humanized antibody of claim 1 .
10. An expression vector comprising the nucleic acid of claim 9 .
11. A composition comprising nucleic acids encoding the light chain variable region, the heavy chain variable region, and the human IgG4 constant region of claim 1 .
12. A host cell comprising:
a nucleic acid encoding the light chain variable region and a nucleic acid encoding the heavy chain variable region of the humanized antibody of claim 1 .
13. A method comprising culturing the host cell of claim 12 .
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Mar 11, 2022
From: VAN VLASSELAER, PETER; PARRY, GRAHAM; STAGLIANO, NANCY E.; PANICKER, SANDIP
To: TRUE NORTH THERAPEUTICS, INC.
Reel/Frame 059237/0487 →
CHANGE OF NAME
Recorded Mar 11, 2022
From: TRUE NORTH THERAPEUTICS, INC.
To: BIOVERATIV USA INC.
Reel/Frame 059362/0400 →
Continuity (11)
Provisional Application
61846402
· Jul 15, 2013
Provisional Application
61779180
· Mar 13, 2013
Provisional Application
61754123
· Jan 18, 2013
Provisional Application
61721916
· Nov 2, 2012
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