Anti-PCSK9-GLP-1 fusions and methods for use

Patent metadata

Field	Value
Publication number	US-10077319-B2
Application number	US-201515117985-A
Country	US
Kind code	B2
Filing date	Feb 20, 2015
Priority date	Feb 21, 2014
Publication date	Sep 18, 2018
Grant date	Sep 18, 2018

Abstract

This application provides anti-PCSK9˜GLP-1 fusions and methods for use.

First claim

What is claimed is:

1. A dual active fusion molecule for the treatment of diabetes comprising an anti-PCSK9 antibody stably fused to a GLP-1 peptide, wherein the anti-PCSK9 antibody binds a PCSK9 polypeptide and the GLP-1 peptide binds a GLP-1 receptor.

2. The fusion molecule of claim 1 , wherein the GLP-1 peptide comprises the amino acid sequence of SEQ ID NO: 3.

3. A method of treating Type 2 Diabetes, cardiovascular disease or metabolic syndrome comprising administering to a subject in need thereof, a fusion molecule of claim 1 .

4. A method of promoting weight loss, controlling glucose or reducing LDL in a subject comprising administering to a subject in need thereof, a fusion molecule of claim 1 .

5. An isolated polynucleotide encoding the fusion molecule of claim 1 .

6. A vector comprising the polynucleotide of claim 5 .

7. A host cell comprising the polynucleotide of claim 5 .

8. A method of making a fusion molecule, comprising culturing the host cell of claim 7 under conditions allowing expression of the fusion molecule, and recovering the fusion molecule.

9. A pharmaceutical composition comprising the fusion molecule of claim 1 , and a carrier.

10. A kit comprising the composition of claim 9 .

11. A dual active fusion molecule for the treatment of diabetes comprising an anti-PCSK9 antibody stably fused to a GLP-1 peptide comprising the amino acid sequence of SEQ ID NO: 3, wherein the C-terminus of the GLP-1 peptide is fused via a peptide linker to the anti-PCSK9 antibody, and wherein the anti-PCSK9 antibody binds a PCSK9 polypeptide and the GLP-1 peptide binds a GLP-1 receptor.

12. A dual active fusion molecule comprising an anti-PCSK9 antibody stably fused to a GLP-1 peptide comprising the amino acid sequence of SEQ ID NO: 3, wherein the C-terminus of the GLP-1 peptide is fused via a peptide linker to the anti-PCSK9 antibody, and wherein the anti-PCSK9 antibody binds a PCSK9 polypeptide and the GLP-1 peptide hinds a GLP-1 receptor.

13. The dual active fusion molecule of claim 12 , wherein the GLP-1 peptide is fused via a peptide linker to the light chain of the anti-PCSK9 antibody.

14. The dual active fusion molecule of claim 13 , wherein the light chain of the anti-PCSK9 antibody is at least 90% identical to the amino acid sequence of SEQ ID NO: 2.

15. The dual active fusion molecule of claim 14 , wherein the light chain of the anti-PCSK9 antibody comprises the amino acid sequence of SEQ ID NO: 2.

16. The dual active fusion molecule of claim 12 , wherein the GLP-1 peptide is fused via a peptide linker to the heavy chain of the anti-PCSK9 antibody.

17. The dual active fusion molecule of claim 16 , wherein the heavy chain of the anti-PCSK9 antibody is at least 90% identical to the amino acid sequence of SEQ ID NO: 1.

18. The dual active fusion molecule of claim 17 , wherein the heavy chain of the anti-PCSK9 antibody comprises the amino acid sequence of SEQ ID NO: 1.

19. The dual active fusion molecule of claim 12 , wherein the light chain of the anti-PCSK9 antibody comprises the amino acid sequence of SEQ ID NO: 2 and the heavy chain of the anti-PCSK9 antibody comprises the amino acid sequence of SEQ ID NO: 1.

20. A dual active fusion molecule for the treatment of diabetes comprising an anti-PCSK9 antibody stably fused to a GLP-1 peptide that has reduced potency at the human GLP-1 receptor compared to a GLP-1 peptide comprising the amino acid sequence of SEQ ID NO: 28 or SEQ ID NO: 29, wherein the C-terminus of the GLP-1 peptide is fused via a peptide linker to the anti-PCSK9 antibody, and wherein the anti-PCSK9 antibody binds a PCSK9 polypeptide and the GLP-1 peptide binds a GLP-1 receptor.

Assignees

• Medimmune Llc
• Medimmune Ltd

Inventors

• Celeste Anthony
• Chodorge Matthieu
• Buchanan Andrew
• Rondinone Cristina
• Grimsby Joseph
• Ravn Peter
• Seaman Jonathan
• Fairman David

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P3/08

  for glucose homeostasis (pancreatic hormones A61P5/48) · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title