Nucleic acid molecules that encode human anti-IFN-gamma neutralizing antibodies as selective IFN-gamma 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 nucleic acid that encodes a human IgG antibody that binds to a human interferon gamma, wherein the antibody comprises
(a) a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 34, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a heavy chain CDR3 of comprising the amino acid sequence SEQ ID NO: 36 or SEQ ID NO: 37; and
(b) a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 38, SEQ ID NO: 39, or SEQ ID NO: 40; a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 41 or SEQ ID NO: 42; and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 43 or SEQ ID NO: 44.
2. The nucleic acid of claim 1 , wherein the antibody comprises
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: 37,
the light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 39,
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 nucleic acid of claim 1 , wherein the antibody comprises
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,
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.
4. The nucleic acid of claim 1 , wherein the antibody comprises
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: 37,
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.
5. The nucleic acid of claim 1 , wherein the antibody comprises
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: 37,
the light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 40,
the light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 42, and
the light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 44.
6. A host cell comprising the nucleic acid of claim 1 .
7. A method of making an antibody comprising:
(a) culturing a host cell under conditions such that it expresses the antibody, wherein the host cell comprises a nucleic acid that encodes the antibody, wherein the antibody comprises:
(i) a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO, 34, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 35, and a heavy chain CDR3 of comprising the amino acid sequence SEQ ID NO: 36 or SEQ ID NO: 37 and
(ii) a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 38, SEQ ID NO: 39, or SEQ ID NO: 40, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 41 or SEQ ID NO: 42, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 43 or SEQ ID NO: 44;
and
(b) collecting the antibody from the culture medium or the host cell;
wherein the antibody is a human IgG antibody that binds to a human interferon gamma.
8. A host cell comprising the nucleic acid of claim 3 .
9. The method of claim 7 , wherein the antibody comprises
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,
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.
10. An isolated nucleic acid which encodes a human IgG antibody that binds to a human Interferon gamma, wherein the antibody comprises the amino acid sequence of:
SEQ ID NO: 6 and/or SEQ ID NO: 8;
SEQ ID NO: 10 and/or SEQ ID NO: 12;
SEQ ID NO: 14 and/or SEQ ID NO: 16;
SEQ ID NO: 30 and/or SEQ ID NO: 12; or
SEQ ID NO: 14 and/or SEQ ID NO: 31.
11. The nucleic acid of claim 10 , wherein the antibody comprises the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 12, SEQ ID NO: 16, or SEQ ID NO: 31.
12. The nucleic acid of claim 10 , wherein the antibody comprises the amino acid sequence of SEQ ID NO: 6, SEQ ID NO: 10, SEQ ID NO: 14, or SEQ ID NO: 30.
13. The nucleic acid sequence of claim 12 , wherein the antibody comprises the amino acid sequence of SEQ ID NO: 8, SEQ ID NO: 12, SEQ ID NO: 16, or SEQ ID NO: 31.
14. The nucleic acid of claim 13 , wherein the antibody comprises the amino acid sequences of SEQ ID NO: 6 and SEQ ID NO: 8.
15. A host cell comprising the nucleic acid of claim 10 .
16. A method of making an antibody comprising:
(a) culturing a host cell under conditions such that it expresses the antibody, wherein the host cell comprises a nucleic acid that encodes the antibody, wherein the antibody comprises the amino acid sequence of:
SEQ ID NO: 6 and/or SEQ ID NO: 8;
SEQ ID NO: 10 and/or SEQ ID NO: 12;
SEQ ID NO: 14 and/or SEQ ID NO: 16;
SEQ ID NO: 30 and/or SEQ ID NO: 12; or
SEQ ID NO: 14 and/or SEQ ID NO: 31: and
(b) collecting the antibody from the culture medium or the host cell;
wherein the antibody is a human IgG antibody that binds to a human interferon gamma.
17. A host cell comprising the nucleic acid of claim 12 .
18. The method of claim 16 , wherein the antibody comprises the amino acid sequence of SEQ ID NO: 6, SEQ ID NO: 10, SEQ ID NO: 14, or SEQ ID NO: 30.
19. A host cell comprising the nucleic acid of claim 14 .
20. The method of- claim 18 , wherein the antibody comprises the amino acid sequences of SEQ ID NO: 6 and SEQ ID NO: 8.
21. An isolated nucleic acid that encodes a human antibody that binds to a human interferon gamma, wherein the nucleic acid comprises the nucleotide sequence of:
SEQ ID NO: 5 and/or SEQ ID NO: 7;
SEQ ID NO: 9 and/or SEQ ID NO: 11;
SEQ ID NO: 13 and/or SEQ ID NO: 15;
SEQ ID NO: 56 and/or SEQ ID NO: 11; or
SEQ ID NO: 13 and/or SEQ ID NO: 57.
22. The nucleic acid of claim 21 comprising SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 13, or SEQ ID NO: 56.
23. The nucleic acid of claim 21 comprising SEQ ID NO: 7, SEQ ID NO: 11, SEQ ID NO: 15, or SEQ ID NO: 57.
24. The nucleic acid of claim 21 comprising the nucleotide sequences of SEQ ID NO: 5 and SEQ ID NO: 7.
25. A host cell comprising the nucleic acid of claim 21 .
26. A method of making an antibody comprising:
(a) culturing a host cell under conditions such that it expresses the antibody, wherein the host cell comprises a nucleic acid that encodes the antibody and which comprises the nucleotide sequence of:
SEQ ID NO: 5 and/or SEQ ID NO: 7;
SEQ ID NO: 9 and/or SEQ ID NO: 11;
SEQ ID NO: 13 and/or SEQ ID NO: 15;
SEQ ID NO: 56 and/or SEQ ID NO: 11; or
SEQ ID NO: 13 and/or SEQ ID NO: 57; and
(b) collecting the antibody from the culture medium or the host cell;
wherein the antibody is a human IgG antibody that binds to a human interferon gamma.
27. A host cell comprising the nucleic acid of claim 24 .
28. The method of claim 26 , wherein the nucleic acid comprises the nucleotide sequences of SEQ ID NO: 5 and SEQ ID NO: 7.