RELAXIN FUSION POLYPEPTIDES AND USES THEREOF

• US 20140187491A1
• Filed: 06/29/2012
• Published: 07/03/2014
• Est. Priority Date: 07/01/2011
• Status: Active Grant

• Current Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Original Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Inventors: Wilmen, Andreas, Haupts, Ulrich, Freiberg, Christoph, Tinel, Hanna, Trautwein, Mark, Linden, Lars, Leineweber, Kirsten
• Granted Patent: US 9,382,305 B2
• Time in Patent Office: Days
• US Class Current: 514/12.7
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 14/64 Relaxins
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2319/31 fusions, other than Fc, for prolonged plasma life, e.g. albumin
• CPC Class Codes: C07K 2319/75 containing a fusion for activation of a cell surface receptor, e.g. thrombopoeitin, NPY and other peptide hormones

Abstract

The present invention provides Relaxin fusion polypeptides A-L-B with a non-wild type array of the Relaxin A-chain and Relaxin B-chain, wherein the A- and B-chains are connected by a linker peptide. The invention further provides Relaxin fusion polypeptides with extended half-life. Furthermore, the invention provides nucleic acid sequences encoding the foregoing fusion polypeptides, vectors containing the same, pharmaceutical compositions and medical use of such fusion polypeptides.

Claims

1. A fusion polypeptide having Relaxin activity comprising A-L-B,

wherein

B comprises a Relaxin B chain polypeptide or a functional variant thereof,

A comprises a Relaxin A chain poylpeptide or a functional variant thereof, and

L is a linker polypeptide.

2. A fusion polypeptide according to claim 1, wherein the fusion polypeptide further comprises at least one half-life extending moiety.

3. A fusion polypeptide according to claim 2, wherein half-life extending moiety is an IgG1 Fc domain, PEG or HES.

4. A fusion polypeptide according to claim 1, wherein the linker polypeptide L is 6-14 amino acids in length.

5. A fusion polypeptide according claim 1, wherein the Relaxin A chain is human Relaxin 2 A chain (SEQ ID NO:

117) and the Relaxin B chain is human Relaxin 2 B chain (SEQ ID NO;

     119).

6. A fusion polypeptide according to claim 1 that is a fusion polypeptide as depicted in table 3.

7. A fusion polypeptide according to claim 1, wherein A-L-B is selected from the group of A-L-B polypeptides consisting of scR3, scR4, scR5, scR3 w/o Tag, scR4 w/o Tag, scR5 w/o Tag, scR-Fc5, scR-Fc6 and scR-Fc7.

8. A polynucleotide encoding a fusion polypeptide according to claim 1.

9. A vector comprising a polynucleotide according to claim 8.

10. A host cell comprising a polynucleotide according to claim 8.

11. A method of producing a polypeptide comprising the steps of cultivating a host cell according to claim 10 and isolating the polypeptide produced by the host cell.

12. A pharmaceutical composition comprising a fusion polypeptide according to claim 1.

15. A method of treating a cardiovascular disease, lung disease, fibrotic disorder or kidney disease comprising the administration of a therapeutically effective dose of a fusion polypeptide according to claim 1.

16. A method according to claim 15, wherein the cardiovascular disease is coronary heart disease, acute coronary syndrome, heart failure, or myocardial infarction.

13-14. -14. (canceled)