Interferon receptor 1 antibodies and their uses
The present invention provides isolated human monoclonal antibodies that bind to IFNAR-1 and that are capable of inhibiting the biological activity of Type I interferons. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for inhibiting Type I interferon-mediated disorders using the antibodies of the invention, including methods for treating autoimmune disorders, transplant rejection or Graft Versus Host Disease using the antibodies of the invention.
1. A bispecific molecule comprising an antibody or antigen-binding portion thereof that specifically binds to human interferon alpha receptor 1 (IFNAR-1) comprising:
(a) a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 4; a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 8; a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 12; a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 16; a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 20; and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 24;
(b) a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 1; a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 5; a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 9; a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 13; a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 17; and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 21; or
(c) a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 2; a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 6; a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 10; a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 14; a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 18; and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 22,
linked to a second functional moiety having a different binding specificity than said antibody or antigen-binding portion thereof.
2. A composition comprising the bispecific molecule of claim 1 .
3. The bispecific molecule of claim 1 , wherein the antibody or antigen-binding portion thereof comprises a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 4; a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 8; a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 12; a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 16; a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 20; and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 24.
4. A composition comprising the bispecific molecule of claim 3 .
5. The bispecific molecule of claim 1 , wherein the antibody or antigen-binding portion thereof comprises a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 1; a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 5; a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 9; a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 13; a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 17; and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 21.
6. A composition comprising the bispecific molecule of claim 5 .
7. The bispecific molecule of claim 1 , wherein the antibody or antigen-binding portion thereof comprises a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 2; a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 6; a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 10; a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO: 14; a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO: 18; and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO: 22.
8. A composition comprising the bispecific molecule of claim 7 .
9. A bispecific molecule comprising an antibody or antigen-binding portion thereof that specifically binds to human interferon alpha receptor 1 (IFNAR-1) comprising:
(a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 28 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 32;
(b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 25 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 29; or
(c) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 26 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30,
linked to a second functional moiety having a different binding specificity than said antibody or antigen-binding portion thereof.
10. A composition comprising the bispecific molecule of claim 9 .
11. The bispecific molecule of claim 9 , wherein the antibody or antigen-binding portion thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 28 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 32.
12. A composition comprising the bispecific molecule of claim 11 .
13. The bispecific molecule of claim 9 , wherein the antibody or antigen-binding portion thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 25 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 29.
14. A composition comprising the bispecific molecule of claim 13 .
15. The bispecific molecule of claim 9 , wherein the antibody or antigen-binding portion thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 26 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 30.
16. A composition comprising the bispecific molecule of claim 15 .