Antibodies with high affinity for alpha-Klotho
An antibody and/or binding fragment thereof, wherein the antibody and/or binding fragment thereof specifically binds to an epitope of a αKlotho polypeptide, optionally a folded αKiotho or optionally with a dissociation constant (K D ) of about 2 nM or less, as measured by competitive ELISA assay, methods 0 of making and using to diagnose kidney diseases.
1. An antibody and/or binding fragment thereof that specifically binds to an epitope of αKlotho polypeptide, wherein said antibody comprises a light chain variable region and a heavy chain variable region, the light chain variable region comprising complementarity determining regions CDR-L1, CDR-L2 and CDR-L3 and the heavy chain variable region comprising complementarity determining regions CDR-H1, CDR-H2 and CDR-H3, with the amino acid sequences of said CDRs consisting of the sequences set forth below:
CDR-L1
(SEQ ID NO: 9)
QSVSSA;
CDR-L2:
(SEQ ID NO: 10)
SAS;
CDR-L3:
(SEQ ID NO: 5)
QQAGYSPIT;
CDR-H1:
(SEQ ID NO: 6)
GFNISYYS;
CDR-H2:
(SEQ ID NO: 7)
ISPSYGYTS;
and
CDR-H3:
(SEQ ID NO: 8)
ARYYVYASHGWAGYGM.
2. The antibody and/or binding fragment thereof of claim 1 , wherein the antibody and/or binding fragment thereof comprises a light chain with the amino acid sequence set forth in SEQ ID NO: 11 and/or comprises a heavy chain with the amino acid sequence set forth in SEQ ID NO:12.
3. The antibody and/or binding fragment thereof of claim 1 , wherein the antibody and/or binding fragment thereof is selected from the group consisting of a monoclonal antibody, an immunoglobulin molecule, a Fab, a Fab′, a F(ab)2, a F(ab′)2, a Fv, a disulfide-linked Fv, a scFv, a disulfide-linked scFv, a single-chain domain antibody, a diabody, a dimer, a minibody, a bispecific antibody fragment, a chimeric antibody, a humanized antibody and a polyclonal antibody.
4. The antibody and/or binding fragment thereof of claim 1 , wherein the folded αKlotho polypeptide is soluble αKlotho polypeptide found in urine, plasma, and/or serum.
5. The antibody and/or binding fragment thereof of claim 1 , wherein the antibody and/or binding fragment thereof binds a complex comprising folded αKlotho polypeptide and a fibroblast growth factor (FGF) receptor, and optionally FGFR1c.
6. The antibody and/or binding fragment of claim 1 , wherein the antibody and/or binding fragment is labeled with a detectable tag.
7. An antibody complex comprising the antibody and/or binding fragment thereof of claim 1 and αKlotho, optionally further comprising FGFR1c.
8. A composition or kit comprising the antibody and/or binding fragment thereof of claim 1 .