CD127 binding proteins
Antigen binding proteins which bind to human IL-7 receptor (CD127) are provided. The antigen binding proteins are typically antibodies, and are useful in the treatment of diseases or disorders in humans, particularly autoimmune diseases such as multiple sclerosis.
1. An isolated antigen-binding protein comprising a heavy chain variable region with a sequence selected from the group consisting of SEQ ID NO:11, 12, 13, 14, 15, 16, 17, 121, 123, 125, 127, 129 and 131 and a light chain variable region comprising the following complementarity determining regions:
(i) CDRL1 as set out in SEQ ID NO:5,
(ii) CDRL2 as set out in SEQ ID NO:6, and
(iii) CDRL3 as set out in SEQ ID NO:7.
2. The isolated antigen-binding protein of claim 1 , which comprises a heavy chain variable region of SEQ ID NO:13.
3. The isolated antigen-binding protein of claim 1 , comprising a heavy chain amino acid sequence selected from the group consisting of: SEQ ID NO:114 and SEQ ID NO:118.
4. The isolated antigen-binding protein of claim 1 , which comprises a heavy chain variable region amino acid sequence selected from the group consisting of: SEQ ID NO:121 and SEQ ID NO:123.
5. The isolated antigen-binding protein of claim 1 , comprising a light chain variable region of SEQ ID NO:22.
6. The isolated antigen-binding protein of claim 1 , comprising a light chain of SEQ ID NO:115.
7. An isolated nucleic acid molecule encoding an isolated antigen-binding protein according to claim 1 .
8. An expression vector comprising a nucleic acid molecule according to claim 7 .
9. An isolated host cell comprising an expression vector according to claim 8 .
10. An isolated antigen-binding protein expressed by a host cell according to claim 9 .
11. A method for the production of an isolated antigen-binding protein, comprising the step of culturing a host cell according to claim 9 in a medium to produce the isolated antigen-binding protein, and isolating or purifying the isolated antigen-binding protein therefrom.
12. A method according to claim 9 , wherein said culturing step is performed in conditions conducive for expression of the isolated antigen-binding protein from the host cell, and secretion of the isolated antigen-binding protein from the cell.
13. A pharmaceutical composition comprising an isolated antigen-binding protein according to claim 1 and a pharmaceutically acceptable carrier or excipient.
14. A method of treating a human subject afflicted with an autoimmune or inflammatory disease, comprising the step of administering to the subject an isolated antigen-binding protein according to claim 1 .
15. A method according to claim 14 , wherein the autoimmune or inflammatory disease is multiple sclerosis.
16. An isolated antigen-binding protein comprising the following complementarity determining regions:
(i) CDRH1 as set out in SEQ ID NO:2,
(ii) CDRH2 as set out in SEQ ID NO:3,
(iii) CDRH3 as set out in any one of SEQ ID NO:132-137,
(iv) CDRL1 as set out in SEQ ID NO:5,
(v) CDRL2 as set out in SEQ ID NO:6, and
(vi) CDRL3 as set out in SEQ ID NO:7.
17. The isolated antigen-binding protein of claim 16 , which comprises a light chain variable region of SEQ ID NO:22.
18. The isolated antigen-binding protein of claim 16 , which comprises a heavy chain variable region of SEQ ID NO:13, with at least one substitution in the heavy chain, said substitution selected from the group consisting of: N98D, N98E, F100bE, F100bH, F100bI and F100bV.
19. The isolated antigen-binding protein according to claim 16 , which comprises a heavy chain variable region selected from the group consisting of SEQ ID NO:121, 123, 125, 127, 129 and 131.