Novartis AG
METHODS AND COMPOSITIONS USING KLOTHO VARIANT POLYPEPTIDES

Abstract:

The present disclosure is directed to compositions and methods related to an alpha sKlotho variant or fragment, in which 1 to up to about 20 amino acids have been deleted from the C-terminus, optionally also having mutations at V563 and/or K795. The present disclosure also pertains to an alpha sKlotho polypeptide variant or fragment, having mutations at V563 and/or K795, wherein the polypeptide variant or fragment is full-length, or optionally 1 to up to about 20 amino acids have been deleted from the C-terminus. The present disclosure also pertains to fusion polypeptides comprising: (a) an alpha sKlotho, in which 1 to up to about 20 amino acids have been deleted from the C-terminus, optionally also having mutations at V563 and/or K795; (b) a linker; and (c) FGF23, optionally having a mutation at R179, C206 and/or C244, or (c) serum albumin.