Anti-interferon gamma antibodies and methods of use thereof
The invention relates to fully human antibodies, and fragments thereof, that bind to human interferon gamma (hIFNγ), thereby modulating the interaction between IFNγ and its receptor, IFNγ-R, and/or modulating the biological activities of IFNγ. The invention also relates to the use of such anti-IFNγ antibodies in the prevention or treatment of immune-related disorders and in the amelioration of a symptom associated with an immune-related disorder.
1. An isolated fully human monoclonal anti-IFNγ antibody or fragment thereof, wherein said antibody comprises:
(a) a V H CDR1 region comprising the amino acid sequence SYAMS (SEQ ID NO:3) or SNAMS (SEQ ID NO:43);
(b) a V H CDR2 region comprising the amino acid sequence AISGSGGSTYYADSVKG (SEQ ID NO:4) or TLTGSGGTAYYADSVEG (SEQ ID NO:44),
(c) a V H CDR3 region comprising an amino acid sequence selected from the group consisting of DGSSGWYVPHWFDP (SEQ ID NO:5); DHSSGWYVISGMDV (SEQ ID NO:13); DLTVGGPWYYFDY (SEQ ID NO:21); DGWNALGWLES (SEQ ID NO:29); GTELVGGGLDN (SEQ ID NO:45); RSFDSGGSFEY (SEQ ID NO:64); VGSWYLEDFDI (SEQ ID NO:69); GGNYGDYFDYFDY (SEQ ID NO:76); and DFWVITSGNDY (SEQ ID NO:89),
(d) a V L CDR1 region comprising an amino acid sequence selected from the group consisting of TRSSGSIASNYVQ (SEQ ID NO:8); TRSSGSIASNYVQ (SEQ ID NO:16); TRSGGSIGSYYVQ (SEQ ID NO:32); TRSSGTIASNYVQ (SEQ ID NO:39); TGSGGSIATNYVQ (SEQ ID NO:48); TGSSGSIASNYVQ (SEQ ID NO:55); TRSSGSIASNYVH (SEQ ID NO:72); TGRNGNIASNYVQ (SEQ ID NO:84); AGSSGSIASNYVQ (SEQ ID NO:97) and TRSSGSIVSNYVQ (SEQ ID NO:106);
(e) a V L CDR2 region comprising an amino acid sequence selected from the group consisting of EDNQRPS (SEQ ID NO:9); EDNQRPS (SEQ ID NO:17); DDDQRPS (SEQ ID NO:25); DDKKRPS (SEQ ID NO:33); EDTQRPS (SEQ ID NO:85) and EDNRRPS (SEQ ID NO:107); and
(f) a V L CDR3 region comprising an amino acid sequence selected from the group consisting of QSYDGSNRWM (SEQ ID NO:10); QSNDSDNVV (SEQ ID NO:18); QSYDSSNVV (SEQ ID NO:26); QSYDSNNLVV (SEQ ID NO:34); QSYDNSNHWV (SEQ ID NO:40); QSYDSDNHHVV (SEQ ID NO:49); QSYDSSNQEVV (SEQ ID NO:56); QSYDSNNFWV (SEQ ID NO:61); QSSDTTYHGGVV (SEQ ID NO:73); QSYEGF (SEQ ID NO:79); QSSDSNRVL (SEQ ID NO:86); QSFDSTNLVV (SEQ ID NO:92); and QSYSYNNQVV (SEQ ID NO:98),
wherein said antibody binds IFNγ.
2. The antibody of claim 1 , wherein said antibody is an IgG isotype.
3. An isolated fully human monoclonal antibody, wherein said antibody comprises a heavy chain variable amino acid sequence selected from the group consisting of SEQ ID NOS: 2, 12, 20, 28, 36, 42, 51, 58, 63, 68, 75, 81, 88, 94 or 103 and a light chain variable amino acid sequence selected from the group consisting of SEQ ID NOS: 7, 15, 23, 31, 38, 47, 54, 60, 66, 71, 78, 83, 91, 96 or 105, wherein said antibody binds IFNγ.
4. A pharmaceutical composition comprising an antibody of claim 1 and a carrier.
5. A pharmaceutical composition comprising an antibody of claim 3 and a carrier.
6. A method of alleviating a symptom of an autoimmune disease or inflammatory disorder, the method comprising administering an antibody of claim 1 to a subject in need thereof in an amount sufficient to alleviate the symptom of the autoimmune disease or inflammatory disorder in the subject, wherein the autoimmune disease or inflammatory disorder is selected from the group consisting of Crohn's Disease, psoriasis, rheumatoid arthritis, and secondary progressive multiple sclerosis.
7. The method of claim 6 , wherein said subject is a human.
8. The method of claim 6 , wherein said antibody comprises a V H CDR1 region comprising the amino acid sequence SYAMS (SEQ ID NO:3); a V H CDR2 region comprising the amino acid sequence AISGSGGSTYYADSVKG (SEQ ID NO:4), a V H CDR3 region comprising the amino acid sequence DGSSGWYVPHWFDP (SEQ ID NO:5); a V L CDR1 region comprising the amino acid sequence TRSSGSIASNYVQ (SEQ ID NO:8); a V L CDR2 region comprising the amino acid sequence EDNQRPS (SEQ ID NO:9); and a V L CDR3 region comprising an amino acid sequence QSYDGSNRWM (SEQ ID NO:10).
9. The method of claim 6 , wherein said antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 2 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 7.
10. The method of claim 6 , wherein said antibody is administered intravenously.