Human anti-IFN-γ neutralizing antibodies as selective IFN-γ pathway inhibitors
View Patent ↗This invention provides antibodies that interact with or bind to human interferon-gamma (IFN-γ) and methods for treating IFN-γ mediated diseases by administering a pharmaceutically effective amount of antibodies to IFN-γ. Methods of detecting the amount of IFN-γ in a sample using antibodies to IFN-γ are also provided.
1. An isolated antibody comprising a light chain CDR1, a light chain CDR2, a light chain CDR3, a heavy chain CDR1, a heavy chain CDR2, and a heavy chain CDR3, wherein
the heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO:34;
the heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO:35;
the heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO:36 or SEQ ID NO:37;
the light chain CDR1 comprising the amino acid sequence of SEQ ID NO:38, SEQ ID NO:39, or SEQ ID NO:40;
the light chain CDR2 comprising the amino acid sequence of SEQ ID NO:41 or SEQ ID NO:42;
the light chain CDR3 comprising the amino acid sequence of SEQ ID NO:43 or SEQ ID NO:44; and
the antibody specifically binds to IFN-γ.
2. The antibody of claim 1 , wherein
the heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO:36,
the light chain CDR1 comprising the amino acid sequence of SEQ ID NO:38,
the light chain CDR2 comprising the amino acid sequence of SEQ ID NO:41, and
the light chain CDR3 comprising the amino acid sequence of SEQ ID NO:43.
3. The antibody of claim 1 , wherein the antibody is a humanized antibody or a fully human antibody.
4. The antibody of claim 1 comprising a heavy chain and a light chain,
wherein the heavy chain comprising the amino acid sequence of SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, or SEQ ID NO:32 and
the light chain comprising the amino acid sequence of SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, or SEQ ID NO:33.
5. The antibody of claim 1 comprising a heavy chain variable region and a light chain variable region,
wherein the heavy chain variable region comprising the amino acid sequence of SEQ ID NO:6, SEQ ID NO:10, SEQ ID NO:14, or SEQ ID NO:30 and
the light chain variable region comprising the amino acid sequence of SEQ ID NO:8, SEQ ID NO:12, SEQ ID NO:16, or SEQ ID NO:31.
6. A method of treating a human patient comprising administering to the patient a therapeutically effective amount of the IFN-γ antibody of claim 1 , wherein the patient has systemic lupus erythematosus (SLE) or lupus nephritis.
7. A composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the antibody of claim 1 .
8. The antibody of claim 4 comprising SEQ ID NO:17 and SEQ ID NO:18.
9. The antibody of claim 4 comprising SEQ ID NO:19 and SEQ ID NO:20.
10. The antibody of claim 4 comprising SEQ ID NO:21 and SEQ ID NO:22.
11. The antibody of claim 4 comprising SEQ ID NO:21 and SEQ ID NO:33.
12. The antibody of claim 4 comprising SEQ ID NO:32 and SEQ ID NO:20.
13. The antibody of claim 5 comprising SEQ ID NO:6 and SEQ ID NO:8.
14. The antibody of claim 5 comprising SEQ ID NO:10 and SEQ ID NO:12.
15. The antibody of claim 5 comprising SEQ ID NO:14 and SEQ ID NO:16.
16. The antibody of claim 5 comprising SEQ ID NO:14 and SEQ ID NO:31.
17. The antibody of claim 5 comprising SEQ ID NO:30 and SEQ ID NO:12.