Lpl-gpihbp1 fusion polypeptides
AssigneeNovartis AG
InventorsJiaping GAO, Amitabh NIMONKAR, John TRAUGER, Andrei Igorevich VOZNESENSKY, Stephen Craig WELDON
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Abstract
This disclosure relates to fusion polypeptides comprising lipoprotein lipase (LPL) and glycosylphosphatidylinositol-anchored High Density Lipoprotein-binding protein 1 (GPIHBP1). The disclosure also relates to uses of such fusion polypeptides in treating disease such as familial chylomicronemia syndrome (FCS).
Claims31
A fusion polypeptide comprising:
- (i) a lipoprotein lipase (LPL) polypeptide, or a functional variant thereof;
- and
- (ii) a glycosylphosphatidylinositol-anchored High Density Lipoprotein-binding protein 1 (GPIHBP1) polypeptide, or a functional variant thereof.
The fusion polypeptide according to any one of the previous claims, wherein the functional variant of the LPL polypeptide comprises an amino acid sequence having at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, at least about 98%, or at least about 99% sequence identity to SEQ ID NO:
- 1 or SEQ ID NO:2.
The fusion polypeptide according to any one of the previous claims, wherein the functional variant of the LPL polypeptide comprises the amino acid sequence of
- (i) SEQ ID NO:
- 2 having one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) point mutations that add to, delete, or substitute any of the amino acids of SEQ ID NO:
- 2, or
- (ii) SEQ ID NO:
- 1 having one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) point mutations that add to, delete, or substitute any of amino acids 157-189 of SEQ ID NO:
- 1.
The fusion polypeptide according to any one of the previous claims, wherein the functional variant of the GPIHBP1 polypeptide comprises an amino acid sequence having at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 97%, at least about 98% or at least about 99% sequence identity to the GPIHBP1 polypeptide of SEQ ID NO:
- 5, SEQ ID NO:
- 6 or SEQ ID NO:
- 7.
The fusion polypeptide according to any one of the previous claims, wherein the functional variant of the GPIHBP1 polypeptide comprises the amino acid sequence of SEQ ID NO:
- 7 having one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) point mutations that add to, delete, or substitute any of the amino acids of SEQ ID NO:
- 7.
The fusion polypeptide according to any one of the previous claims, wherein the LPL polypeptide and GPIHBP1 polypeptide are joined by a linker C.
The fusion polypeptide according to any one of the previous claims, wherein the fusion polypeptide comprises an N-terminal sequence A.
The fusion polypeptide according to any one of the previous claims, wherein the fusion polypeptide comprises a C-terminal sequence E.
The fusion polypeptide according to any one of the previous claims, wherein the N-terminal or C-terminal sequence comprises a moiety to increase the half-life of the fusion polypeptide in vivo,
- and wherein the N-terminal or C-terminal sequence comprises a PEG sequence, a PAS sequence or an antibody sequence, optionally selected from a Fab or ScFv molecule.
Dependencies are inferred from the claim text.