Long-acting polypeptides and methods of producing and administering same

• US 9,908,924 B2
• Filed: 11/26/2014
• Issued: 03/06/2018
• Est. Priority Date: 02/03/2006
• Status: Active Grant

• Current Assignee: Opko Biologics Ltd. (Opko Health, Inc.)
• Original Assignee: Opko Biologics Ltd. (Opko Health, Inc.)
• Inventors: Fares, Fuad, Fima, Udi Eyal
• Primary Examiner(s): Kemmerer, Elizabeth C
• Assistant Examiner(s): Deberry, Regina M
• Application Number:
  US14/555,246
• Publication Number:
  US 20150093358A1
• Time in Patent Office: 1,196 Days
• Field of Search: None
• CPC Class Codes: A61K 38/1816 Erythropoietin [EPO]
• CPC Class Codes: C07K 14/505 Erythropoietin [EPO]
• CPC Class Codes: C07K 14/555 Interferons [IFN]
• CPC Class Codes: C07K 14/59 Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g.hCG [human chorionic gonadotropin]; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
• CPC Class Codes: C07K 14/605 Glucagons
• CPC Class Codes: C07K 14/61 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/31 fusions, other than Fc, for prolonged plasma life, e.g. albumin

Abstract

A polypeptide and polynucleotides comprising at least two carboxy-terminal peptides (CTP) of chorionic gonadotrophin attached to a non-human peptide-of-interest are disclosed. Pharmaceutical compositions comprising the non-human polypeptides and polynucleotides of the invention and methods of using both human and non-human polypeptides and polynucleotides are also discarded.

Claims

1. A chorionic gonadotropin carboxy terminal peptide (CTP)-modified polypeptide consisting of a peptide of interest, wherein a first chorionic gonadotropin carboxy terminal peptide (CTP) is attached to the amino terminus of said peptide of interest, and a second and third chorionic gonadotropin carboxy terminal peptide are attached to the carboxy terminus of said peptide of interest, wherein said peptide of interest is an erythropoietin (EPO) peptide, and wherein the amino acid sequence of said polypeptide is set forth in SEQ ID NO:

51.

2. The polypeptide of claim 1, wherein said peptide of interest is glycosylated.

3. The polypeptide of claim 1, wherein said peptide of interest is non-glycosylated.

4. The polypeptide of claim 1, wherein at least 1 of said chorionic gonadotrophin carboxy terminal peptides is glycosylated.

5. A pharmaceutical formulation comprising the polypeptide of claim 1, wherein said formulation further comprises a buffer, and a tonicity agent.

6. The formulation of claim 5, wherein said buffer is citrate or acetate.

7. The formulation of claim 5, wherein said tonicity agent is sodium chloride.

8. The formulation of claim 5, wherein said formulation is formulated for injection in a multidose container, with optionally, a preservative.

9. The formulation of claim 8, wherein said preservative is benzalkonium chloride or thimerosal.

10. A liquid formulation, comprising the formulation of claim 5.

11. The liquid formulation of claim 10, wherein said formulation is at a pH between about 6 to 7.

12. A method of improving a biological half life of a peptide of interest, wherein said peptide of interested is an erythropoietin peptide (EPO), said method comprising the step of attaching a first chorionic gonadotrophin carboxy terminal peptide (CTP) to an amino terminus of said peptide of interest and a second and third chorionic gonadotrophin carboxy terminal peptide (CTP) to a carboxy terminus of said peptide of interest, wherein the amino acid sequence of said CTP-modified peptide of interest is set forth in SEQ ID NO:

51, thereby improving a biological half life of a peptide of interest.