Nucleic acids encoding interferon alpha antibodies
View Patent ↗The present invention provides isolated anti-interferon alpha monoclonal antibodies, particularly human monoclonal antibodies, that inhibit the biological activity of multiple interferon (IFN) alpha subtypes but do not substantially inhibit the biological activity of IFN alpha 21 or the biological activity of either IFN beta or IFN omega. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for inhibiting the biological activity of IFN alpha using the antibodies of the invention, as well as methods of treating disease or disorders mediated by IFN alpha, such as autoimmune diseases, transplant rejection and graft versus host disease, by administering the antibodies of the invention.
1. An isolated nucleic acid encoding a heavy chain variable region and a light chain variable region of an anti-interferon alpha antibody, or antigen-binding portion thereof, said variable regions comprising:
(a) a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:19; and a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:22;
(b) a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:20; and a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:23;
(c) a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:21; and a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:24; or
(d) a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO: 34, 35, 36 or 37; and a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:22.
2. An isolated nucleic acid encoding:
a) a heavy chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof, comprising amino acids having the sequence of: SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36 or SEQ ID NO:37; or
b) a light chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof, comprising amino acids having the sequence of: SEQ ID NO:22, SEQ ID NO:23, or SEQ ID NO:24.
3. An isolated nucleic acid encoding:
a) a heavy chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof, said nucleic acid comprising nucleotides having the sequence of: SEQ ID NO:25, SEQ ID NO:26, or SEQ ID NO:27; or
b) a light chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof, said nucleic acid comprising nucleotides having the sequence of: SEQ ID NO:28, SEQ ID NO:29, or SEQ ID NO:30.
4. An expression vector comprising the nucleic acid of claim 2 .
5. A host cell expressing a polypeptide encoded by the nucleic acid of claim 2 .
6. The nucleic acid of claim 2 , wherein the anti-interferon alpha antibody, or antigen-binding portion thereof comprises: (a) a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:19; and (b) a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:22.
7. The nucleic acid of claim 2 , wherein the anti-interferon alpha antibody, or antigen-binding portion thereof comprises: (a) a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:20; and (b) a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:23.
8. The nucleic acid of claim 2 , wherein the anti-interferon alpha antibody, or antigen-binding portion thereof comprises: (a) a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:21; and (b) a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:24.
9. The nucleic acid of claim 2 , wherein the anti-interferon alpha antibody, or antigen-binding portion thereof comprises: (a) a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO: 34, 35, 36 or 37; and (b) a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:22.
10. The nucleic acid of claim 3 , which encodes a heavy chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof, comprising amino acids having the sequence of: SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36 or SEQ ID NO:37.
11. The nucleic acid of claim 3 , which encodes a light chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof, comprising amino acids having the sequence of: SEQ ID NO:22, SEQ ID NO:23, or SEQ ID NO:24.
12. The nucleic acid of claim 3 , which encodes (a) a heavy chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof comprising amino acids having the sequence set forth in SEQ ID NO:19; or (b) a light chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof comprising amino acids having the sequence set forth in SEQ ID NO:22.
13. The nucleic acid of claim 3 , which encodes (a) a heavy chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof comprising amino acids having the sequence set forth in SEQ ID NO:20; or (b) a light chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof comprising amino acids having the sequence set forth in SEQ ID NO:23.
14. The nucleic acid of claim 3 , which encodes (a) a heavy chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof comprising amino acids having the sequence set forth in SEQ ID NO:21; or (b) a light chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof comprising amino acids having the sequence set forth in SEQ ID NO:24.
15. The nucleic acid of claim 3 , which encodes (a) a heavy chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof comprising amino acids having the sequence set forth in SEQ ID NO: 34, 35, 36 or 37; or (b) a light chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof comprising amino acids having the sequence set forth in SEQ ID NO:22.
16. The nucleic acid of claim 4 , which encodes a heavy chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof, said nucleic acid comprising nucleotides having the sequence of: SEQ ID NO:25, SEQ ID NO:26, or SEQ ID NO:27.
17. The nucleic acid of claim 4 , which encodes a light chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof, said nucleic acid comprising nucleotides having the sequence of: SEQ ID NO:28, SEQ ID NO:29, or SEQ ID NO:30.
18. The nucleic acid of claim 4 , which encodes (a) a heavy chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof, said nucleic acid comprising nucleotides having the sequence set forth in SEQ ID NO:25, or (b) a light chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof, said nucleic acid comprising nucleotides having the sequence set forth in SEQ ID NO:28.
19. The nucleic acid of claim 4 , which encodes (a) a heavy chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof, said nucleic acid comprising nucleotides having the sequence set forth in SEQ ID NO:26, or (b) a light chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof, said nucleic acid comprising nucleotides having the sequence set forth in SEQ ID NO:29.
20. The nucleic acid of claim 4 , which encodes (a) a heavy chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof, said nucleic acid comprising nucleotides having the sequence set forth in SEQ ID NO:27, or (b) a light chain variable region of an anti-interferon alpha monoclonal antibody, or antigen-binding portion thereof, said nucleic acid comprising nucleotides having the sequence set forth in SEQ ID NO:30.