Apelin fusion proteins and uses thereof

Patent metadata

Field	Value
Publication number	US-9353163-B2
Application number	US-201414212753-A
Country	US
Kind code	B2
Filing date	Mar 14, 2014
Priority date	Mar 14, 2013
Publication date	May 31, 2016
Grant date	May 31, 2016

Abstract

The invention provides a fusion protein or polypeptide comprising an apelin peptide fused to a multimerizing component. The invention also provides a fusion protein or polypeptide comprising an apelin peptide fused to an Fc domain, a fragment of an Fc domain, or a variant of an Fc domain. Apelin Fc-fusion polypeptides are capable of binding to the apelin receptor (APLNR). Apelin Fc-fusion polypeptides are capable of activating the APLNR and have improved pharmacokinetic properties compared to apelin peptides that are not fused to an Fc or an Fc fragment. Apelin Fc-fusion polypeptides are useful in diseases and conditions related to cardiovascular function, diabetes, cancer, obesity and other apelin-related conditions.

First claim

What is claimed:

1. A polypeptide comprising the amino acid sequence of SEQ ID NO: 2.

2. A composition comprising the polypeptide of claim 1 and at least one pharmaceutically acceptable carrier or diluent.

3. A nucleic acid molecule encoding the polypeptide of claim 1 .

4. The nucleic acid molecule of claim 3 linked to a nucleotide sequence encoding a signal peptide.

5. The nucleic acid molecule of claim 4 comprising the nucleotide sequence consisting of SEQ ID NO: 25.

6. A vector comprising the nucleic acid molecule of claim 5 .

7. A cell comprising the vector of claim 6 .

8. A cell comprising the nucleic acid molecule of claim 5 .

9. The cell of claim 8 , wherein the nucleic acid is stably integrated into the genome of the cell.

10. The cell of claim 9 , wherein the cell is a eukaryotic cell.

11. The cell of claim 10 , wherein the cell is selected from the group consisting of CHO, COS, retinal cell, Vero, CV1, 293, MDCK, HaK, BHK, HeLa, HepG2, WI38, MRC 5, Colo 25, HB 8065, HL-60, Jurkat, Daudi, A431 (epidermal), CV-1, U937, 3T3, L cell, C127 cell, SP2/0, NS-0, MMT cell, and tumor cell.

12. The cell of claim 11 , wherein the cell is an animal cell.

13. The cell of claim 12 , wherein the cell is a mammalian cell.

14. The cell of claim 13 , wherein the cell is a CHO cell.

15. The cell of claim 14 , wherein the cell is a CHO-K1 cell.

Assignees

• Regeneron Pharma

Inventors

• Stevis Panayiotis
• Murphy Andrew

Classifications

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P9/12

  Antihypertensives · CPC title