Humanized antibodies against TL1A

1. An isolated antigen-binding polypeptide that binds specifically to TL1A, comprising:

(a) a humanized heavy chain variable region comprising:

(1) a CDR-H1 comprising the amino acid sequence of TSNMGVV (SEQ ID NO:7);

(2) a CDR-H2 comprising the amino acid sequence of HILWDDREYSNPALKS (SEQ ID NO:8); and

(3) a CDR-H3 comprising the amino acid sequence of MSRNYYGSSYVMDY (SEQ ID NO:9); and

(b) a humanized light chain variable region comprising:

(1) a CDR-L1 comprising the amino acid sequence of SASSSVNYMH (SEQ ID NO:35);

(2) a CDR-L2 comprising the amino acid sequence of STSNLAS (SEQ ID NO:36); and

(3) a CDR-L3 comprising the amino acid sequence of HQWNNYGT (SEQ ID NO:37).

2. The polypeptide of claim 1 , wherein the polypeptide is selected from the group consisting of an antibody molecule, a Fab fragment, a Fab′ fragment, a F(ab′) 2 fragment, and an scFv molecule.

3. The polypeptide of claim 2 , wherein the polypeptide is an antibody molecule.

4. The polypeptide of claim 3 , wherein the antibody is a chimeric antibody comprising a human heavy chain constant region and a human light chain constant region.

5. The polypeptide of claim 3 , wherein the antibody is an IgG molecule.

6. The polypeptide of claim 2 , wherein the polypeptide is an scFv molecule.

7. The polypeptide of claim 6 , wherein the scFv has a formula selected from the group consisting of NH 2 -L-VH-X-VK-COOH and NH 2 -L-VK-X-VH-COOH; wherein L is a leader sequence; VH is the humanized antibody heavy chain variable region; X is a linking polypeptide; and VK is the humanized antibody light chain variable region.

8. The polypeptide of claim 2 , wherein the polypeptide is a Fab HSA fusion molecule.

9. The polypeptide of claim 8 , wherein the Fab HSA fusion has a formula selected from the group consisting of: NH 2 -VH-CH1-HSA-COOH and NH 2 -HSA- CH1-VH-COOH combined with NH 2 -VK-CK-COOH;wherein the VH-CH1-HSA or HSA- CH1-VH is the humanized antibody heavy chain variable region (VH) and human constant heavy chain domain 1 (CH1) produced as a fusion protein with human serum albumin (HSA) which folds with its cognate humanized antibody light chain variable region (VK) and human constant kappa domain (CK) to form the Fab-HSA or HSA-Fab fusion protein.

10. The polypeptide of claim 1 , conjugated to a therapeutic or diagnostic agent.

11. The polypeptide of claim 10 , wherein the therapeutic agent is selected from the group consisting of a cytotoxic agent, a radioactive label, an immunomodulator, a hormone, an enzyme, an oligonucleotide, a photoactive therapeutic agent or a combination thereof.

12. The polypeptide of claim 10 , wherein the diagnostic agent is selected from the group consisting of a radioactive label, a photoactive diagnostic agent, an ultrasound-enhancing agent or a non-radioactive label.

13. The polypeptide of claim 1 , wherein the polypeptide is an antagonist of TL1A.

14. The polypeptide of claim 1 , wherein the polypeptide is not an agonist of TL1A.

15. The polypeptide of claim 1 , wherein the polypeptide binds to TL1A with an affinity constant of at least about 10 6 M −1 .

16. A pharmaceutical composition comprising the polypeptide of claim 1 , and a carrier.

17. The pharmaceutical composition of claim 16 , further comprising an additional therapeutic or diagnostic agent.

18. An antigen binding polypeptide that binds specifically to TL1A, comprising:

(a) a humanized variable light chain region comprising the amino acid sequence:

DIQLTQSPSFLSASVGDRVTITCSASSSVNYMHWYQQKPGKAPKLLIYSTSNLASGVP SRFSGSGSGTEFTLTISSLQPEDFATYYCHQWNNYGTFGQGTKVEIKR (SEQ ID NO:38); and

(b) a humanized variable heavy chain region comprising the amino acid sequence:

QVTLKESGPALVKPTQTLTLTCTFSGFSLSTSNMGVVWIRQPPGKALEWLAHILWDD REYSNPALKSRLTISKDTSKNQVVLTMTNMDPVDTATYYCARMSRNYYGSSYVMD YWGQGTLVTVSS (SEQ ID NO: 10).