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: 208; a heavy chain complementarity determining region 2 (HCDR2) comprising SEQ ID NO: 211; a heavy chain complementarity determining region 3 (HCDR3) comprising SEQ ID NO: 213; a light chain complementarity determining region 1 (LCDR1) comprising SEQ ID NO: 214; a light chain complementarity determining region 2 (LCDR2) comprising SEQ ID NO: 215; and a light chain complementarity determining region 3 (LCDR3) comprising SEQ ID NO: 216.
2. The antibody or antigen-binding portion of claim 1 , wherein the antibody is an IgG 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. An isolated nucleic acid encoding the heavy chain, the light chain, or both, of the antibody or antigen-binding portion of claim 1 .
6. A vector comprising the nucleic acid of claim 5 .
7. A host cell comprising the vector of claim 6 .
8. The host cell of claim 7 , wherein the cell is a mammalian cell.
9. A pharmaceutical composition comprising the antibody or antigen-binding portion of claim 1 , and a pharmaceutically acceptable carrier or excipient.
10. A composition comprising the antibody or antigen-binding portion thereof of claim 1 complexed with human IL-2.
11. A pharmaceutical composition comprising the antibody or antigen-binding portion thereof of claim 1 , complexed with human IL-2, and a pharmaceutically acceptable carrier or excipient.
12. 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:31 and a light chain variable region comprising an amino acid sequence that is at least 95% identical to SEQ ID NO:32.
13. The antibody or antigen-binding portion of claim 1 , wherein the antibody or antigen-binding portion is a monoclonal antibody.
14. The antibody or antigen-binding portion of claim 1 , wherein the antibody or antigen-binding portion is a humanized antibody.
15. The antibody or antigen-binding portion of claim 1 , wherein the antibody or antigen-binding portion is a human antibody.