Ultra-long acting insulin-Fc fusion protein and methods of use
The present disclosure relates to compositions of insulin-Fc fusion proteins and their use to treat feline diabetes.
1. A fusion protein comprising an insulin polypeptide and an Fc fragment, wherein the insulin polypeptide and the Fc fragment are connected by a peptide linker, wherein the Fc fragment comprises the sequence:
(SEQ ID NO: 21)
GEGPKCPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLVVDLGPDDSNV
QITWFVDNTEMHTAKTRPREEQFKSTYRVVSVLPILHQDWLKGKEFKCKV
NSKSLPSAMERTISKAKGQPHEPQVYVLPPTQEELSENKVSVTCLIKGFH
PPDIAVEWEITGQPEPENNYQTTPPQLDSDGTYFLYSRLSVDRSHWQRGN
TYTCSVSHEALHSHHTQKSLTQSPG.
2. The fusion protein of claim 1 , wherein the insulin polypeptide and the Fc fragment are connected by a peptide linker comprising the sequence:
(SEQ ID NO: 10)
GGGGSGGGG.
3. The fusion protein of claim 1 , wherein the insulin polypeptide comprises the sequence:
(SEQ ID NO: 4)
FVNQHLCGSDLVEALYLVCGERGFFYTDPTGGGPRRGIVEQCCHSICSLY
QLENYCN.
4. A fusion protein comprising an insulin polypeptide and an Fc fragment, wherein the insulin polypeptide and the Fc fragment are connected by a peptide linker, wherein the fusion protein comprises the sequence:
(SEQ ID NO: 36)
FVNQHLCGSDLVEALYLVCGERGFFYTDPTGGGPRRGIVEQCCHSICSLY
QLENYCNGGGGSGGGGGEGPKCPVPEIPGAPSVFIFPPKPKDTLSISRTP
EVTCLVVDLGPDDSNVQITWFVDNTEMHTAKTRPREEQFKSTYRVVSVLP
ILHQDWLKGKEFKCKVNSKSLPSAMERTISKAKGQPHEPQVYVLPPTQEE
LSENKVSVTCLIKGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGTYF
LYSRLSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQSPG.
5. The fusion protein of claim 1 , wherein the fusion protein is a homodimer comprising two identical monomers bound together via one or more disulfide bonds.
6. The fusion protein of claim 5 , wherein the percentage homodimer of insulin-Fc fusion protein is greater than or equal to 80%.
7. The fusion protein of claim 5 , wherein the duration of activity of the fusion protein is longer than about 2 hours, 6 hours, 9 hours, 12 hours, 18 hours, 1 day, 1.5 days, 2 days, 2.2 days, 2.5 days, 3 days, 5 days or longer.