Anti-PAR2 antibodies and uses thereof
The present disclosure provides antibodies and antigen-binding fragments capable of binding PAR2. In some embodiments, the anti-PAR2 antibodies or antigen-binding fragments thereof bind PAR2 in a pH-dependent manner. The disclosure further provides methods for making and using the antibodies and antigen-binding fragments.
1. An antibody or antigen-binding fragment thereof that binds to PAR2 comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein the VH comprises:
i) a VH-CDR1 having the amino acid sequence of SEQ ID NO: 13,
ii) a VH-CDR2 having the amino acid sequence of SEQ ID NO: 14,
iii) a VH-CDR3 having the amino acid sequence of SEQ ID NO: 15,
and wherein the VL comprises:
i) a VL-CDR1 having the amino acid sequence of SEQ ID NO: 18,
ii) a VL-CDR2 having the amino acid sequence of SEQ ID NO: 19,
iii) a VL-CDR3 having the amino acid sequence of SEQ ID NO: 20.
2. The antibody or antigen-binding fragment thereof of claim 1 , wherein the VH comprises an amino acid sequence that is at least 80%, 85%, 90%, 92%, 93%, 95%, 97%, 99% or 100% identical to SEQ ID NO: 12 and wherein the VL comprises an amino acid sequence that is at least 80%, 85%, 90%, 92%, 93%, 95%, 97%, 99% or 100% identical to SEQ ID NO: 17.
3. The antibody or antigen-binding fragment of claim 1 , wherein the antigen-binding fragment is an scFv or a Fab′.
4. The antibody or antigen-binding fragment of claim 1 , wherein the antibody is a monoclonal antibody.
5. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment prevents trypsin, tryptase and/or matriptase from interacting with PAR2.
6. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment binds to PAR2 with greater affinity at a pH of 7.4 than at a pH of 6.0.
7. A composition comprising a pharmaceutically acceptable carrier and the antibody or antigen-binding fragment of claim 1 .
8. A kit comprising the composition of claim 7 .
9. A kit comprising the antibody or antigen-binding fragment of claim 1 .
10. The antibody or antigen-binding fragment of claim 1 , wherein the VH comprises an amino acid sequence corresponding to SEQ ID NO: 12 and wherein the VL comprises an amino acid sequence corresponding to SEQ ID NO: 17.
11. A composition comprising a pharmaceutically acceptable carrier and the antibody or antigen-binding fragment of claim 10 .
12. A method for treating pain in a subject in need thereof, comprising administering to the subject a pharmaceutically effective amount of the antibody or antigen-binding fragment of claim 10 .
13. A method for treating pain in a subject in need thereof, comprising administering to the subject a pharmaceutically effective amount of the antibody or antigen-binding fragment of claim 1 .