Assays for TIMP2 having improved performance in biological samples
The present invention relates to antibodies or antigen binding fragments thereof that binds to human “TIMP2. Further provided are methods for treating subjects, including human subjects, in need of treatment with the isolated TIMP2 antibodies or antigen-binding fragments thereof disclosed herein. Further provided are pharmaceutical or sterile compositions of anti-TIMP2 antibodies and antigen-binding fragments of the invention, the antibody or antigen-binding fragment thereof is admixed with a pharmaceutically acceptable carrier or excipient. Further provided are kits comprising one or more components that include an anti-TIMP2 antibody or antigen-binding fragment thereof of the invention or a pharmaceutical composition thereof.
1. A monoclonal antibody that binds to human tissue inhibitor of metalloproteinases 2 (TIMP2) protein, wherein the antibody comprises:
(a) a light chain variable region complementarity determining region 1 (CDR1) comprising the amino acid sequence
ESISGW (SEQ ID NO: 1),
a light chain variable region CDR2 comprising the amino acid sequence RAS (SEQ ID NO: 2), and
a light chain variable region CDR3 comprising the amino acid sequence QCSYGINGNSEHGNP (SEQ ID NO: 3); and
(b) a heavy chain variable region CDR1 comprising the amino acid sequence GFTISSNYY (SEQ ID NO:4),
a heavy chain variable region CDR2 comprising the amino acid sequence ILGGSGTYT (SEQ ID NO:5), and
a heavy chain variable region CDR3 comprising the amino acid sequence ARQAPADTYLYGGYGPFNL (SEQ ID NO:6).
2. The monoclonal antibody of claim 1 , wherein the light chain variable region comprises an amino acid sequence at least 90% identical to that set forth as SEQ ID NO: 7 and the heavy chain variable region comprises an amino acid sequence at least 90% identical to that set forth as SEQ ID NO: 8.
3. The monoclonal antibody of claim 2 , wherein the light chain variable region comprises an amino acid sequence set forth as SEQ ID NO: 7 and the heavy chain variable region comprises an amino acid sequence set forth as SEQ ID NO: 8.
4. The monoclonal antibody of claim 1 , wherein the light chain comprises an amino acid sequence at least 90% identical to that set forth as SEQ ID NO: 16 and the heavy chain comprises an amino acid sequence at least 90% identical to that set forth as SEQ ID NO: 10.
5. The monoclonal antibody of claim 4 , wherein the light chain comprises an amino acid sequence set forth as SEQ ID NO: 16 and the heavy chain comprises an amino acid sequence set forth as SEQ ID NO: 10.
6. The monoclonal antibody of claim 1 , wherein the antibody is a rabbit antibody.
7. A method for determining the presence or amount of human tissue inhibitor of metalloproteinases 2 (TIMP2) protein in a biological sample, the method comprising:
performing an immunoassay on the biological sample with first and second monoclonal antibodies which together form sandwich complexes with human TIMP2 protein, wherein the immunoassay provides a detectable signal that is related to the presence or amount of human TIMP2 protein in the biological sample bound in the sandwich complexes; and
relating the detectable signal to the presence or amount of human TIMP2 protein in the biological sample,
wherein the first monoclonal antibody comprises:
the monoclonal antibody as in any of claims 1 - 6 .
8. The method of claim 7 , wherein the minimum detectable concentration is 10 ng/mL or less.