Anti-IL-2 antibodies and compositions and uses thereof
The present invention provides antibodies, or antigen-binding portions thereof, which specifically bind to IL-2 and reduce the affinity of IL-2 binding to IL-2Rα and IL-2Rβ. The invention further provides a method of obtaining such antibodies and nucleic acids encoding the same. The invention further relates to compositions and therapeutic methods for use of these antibodies for the treatment and/or prevention of autoimmune diseases, disorders or conditions and for immunosuppression, including, but not limited to, administering a complex comprising the antibody and IL-2.
1. An isolated antibody or antigen-binding portion thereof that specifically binds human IL-2, said antibody comprising: a heavy chain complementarity determining region 1 (HCDR1) comprising SEQ ID NO:127, a heavy chain complementarity determining region 2 (HCDR2) comprising SEQ ID NO:130, a heavy chain complementarity determining region 3 (HCDR3) comprising SEQ ID NO:132, a light chain complementarity determining region 1 (LCDR1) comprising SEQ ID NO:133, a light chain complementarity determining region 2 (LCDR2) comprising SEQ ID NO:134, and a light chain complementarity determining region 3 (LCDR3) comprising SEQ ID NO:135.
2. The antibody or antigen-binding portion of claim 1 , wherein the antibody is an lgG antibody.
3. The antibody or antigen-binding portion of claim 2 , further comprising a heavy chain constant region comprising the amino acid sequence of SEQ ID NO:33 with or without the C-terminal lysine.
4. The antibody or antigen-binding portion of claim 1 , further comprising a light chain constant region comprising the amino acid sequence of SEQ ID NO: 35.
5. The antibody or antigen-binding portion of claim 1 , wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence that is at least 95% identical to SEQ ID NO:13 and a light chain variable region comprising an amino acid sequence that is at least 95% identical to SEQ ID NO:14.
6. A pharmaceutical composition comprising the antibody or antigen-binding portion of claim 1 , and a pharmaceutically acceptable carrier or excipient.
7. A method for treating an inflammatory condition in a human subject, wherein the condition is caused by and/or associated with IL-2 activity, comprising administering to the subject an effective amount of the antibody or antigen-binding portion of claim 1 .
8. A method for inducing immunosuppression in a human subject in need thereof, wherein the subject suffers from a condition caused by and/or associated with IL-2 activity, comprising administering to the subject an effective amount of the antibody or antigen-binding portion of claim 1 .
9. The antibody or antigen-binding portion of claim 1 , for use in treating a human subject having an inflammatory condition or in need of immunosuppression.
10. The method of claim 8 , wherein the subject has an autoimmune disease or graft versus host disease.
11. The method of claim 8 , wherein the antibody is administered in complex with IL-2.
12. The method of claim 8 , wherein the subject has type 1 diabetes.
13. A composition comprising the antibody or antigen-binding portion of claim 1 complexed with human IL-2.
14. A pharmaceutical composition comprising the antibody or antigen-binding portion of claim 1 , complexed with human IL-2, and a pharmaceutically acceptable carrier or excipient.
15. A method for treating an inflammatory condition in a human subject, wherein the condition is caused by and/or associated with IL-2 activity, comprising administering to the subject an effective amount of the antibody or antigen-binding portion of claim 1 complexed with human IL-2.
16. The antibody or antigen-binding portion of claim 1 , wherein the antibody or antigen-binding portion is a monoclonal antibody.
17. The antibody or antigen-binding portion of claim 1 , wherein the antibody or antigen-binding portion is a humanized antibody.
18. The antibody or antigen-binding portion of claim 1 , wherein the antibody or antigen-binding portion is a human antibody.
19. The antibody or antigen-binding portion of claim 1 , comprising a heavy chain variable region that comprises SEQ ID NO:13 and a light chain variable region that comprises SEQ ID NO:14.
20. An isolated nucleic acid encoding the heavy chain variable region and/or the light chain variable region of the antibody or antigen-binding portion of claim 19 .
21. A vector comprising the nucleic acid of claim 20 .
22. A host cell comprising the nucleic acid of claim 21 .
23. The host cell of claim 22 , wherein the cell is a mammalian cell.
24. A method of producing an antibody or an antigen-binding portion thereof that specifically binds human interleukin-2 (hIL-2), said method comprising:
a) culturing the host cell of claim 23 under conditions that allow said antibody or antigen-binding portion to be expressed, wherein the host cell comprises nucleotide sequences coding the heavy chain and light chain of the antibody or antigen-binding portion, and
b) isolating said antibody or antigen-binding portion from the culture.