TL1A antibodies and uses thereof
Disclosed are antibodies that bind specifically to the receptor TNF superfamily member 15 (TNFSF15), also known as TL1A. Methods of making and using the anti-TL1A antibodies are also described.
1. An antibody, or antigen binding fragment thereof, that binds to human TL1A (TNF-like ligand 1A) and comprises:
a) a heavy chain variable domain comprising:
CDRH1 comprising the sequence of SEQ ID NO:7;
CDRH2 comprising the sequence of SEQ ID NO:8; and
CDRH3 comprising the sequence of SEQ ID NO:9;
and
b) a light chain variable domain comprising:
CDRL1 comprising the sequence of SEQ ID NO:12;
CDRL2 comprising the sequence of SEQ ID NO:13; and
CDRL3 comprising the sequence of SEQ ID NO:14;
wherein the antibody or fragment inhibits the binding of human TL1A to DR3.
2. The antibody, or antigen binding fragment of claim 1 that binds to TL1A (SEQ ID NO:20) at an epitope comprising one or more of residues 102-116(SEQ ID NO:16) or 166-180(SEQ ID NO: 17).
3. The antibody or antigen binding fragment of claim 2 that binds to TL1A at an epitope comprising one or more of residues 169 QAGR 172 (SEQ ID NO:21) and one or more of residues 113 KNQF 116 (SEQ ID NO:22).
4. The antibody or antigen binding fragment of claim 2 that binds to TL1A at an epitope comprising the sequence 169 QAGR 172 (SEQ ID NO:21) and/or 113 KNQF 116 (SEQ ID NO:22).
5. The antibody or antigen binding fragment of claim 1 wherein the antibody binds to both human and cynomolgus TL1A.
6. The antibody or antigen binding fragment of claim 1 comprising one or more heavy chains and one or more light chains, wherein:
a) the heavy chain comprises a heavy chain variable region having at least 80% sequence identity with the sequence of SEQ ID NO: 6; and
a) the light chain comprises a light chain variable region having at least 80% sequence identity with the sequence of SEQ ID NO: 11.
7. The antibody of claim 1 , wherein the antibody is a human IgG1 Fc variant with reduced or eliminated effector function.
8. A nucleic acid encoding the heavy and light chain variable region of the antibody of antigen binding fragment of claim 1 .
9. An expression vector comprising the nucleic acid molecule of claim 8 .
10. A host cell transformed with an expression vector of claim 9 .
11. A method of producing an anti-TL1A antibody or antigen binding fragment thereof comprising culturing the host cell of claim 10 under conditions that allows production of the antibody or fragment, and purifying the antibody from the cell.
12. A method of detecting the presence of TL1A in a sample comprising contacting the sample with the antibody, or antigen binding fragment thereof, of claim 1 under conditions that allow for formation of a complex between the antibody, or antigen binding fragment thereof, and TL1A, and detecting the formation of the complex.