Long-acting coagulation factors and methods of producing same

• US 9,663,778 B2
• Filed: 05/09/2014
• Issued: 05/30/2017
• Est. Priority Date: 07/09/2009
• Status: Active Grant

• Current Assignee: Opko Biologics Ltd. (Opko Health, Inc.)
• Original Assignee: Opko Biologics Ltd. (Opko Health, Inc.)
• Inventors: Hart, Gili, Fima, Udi Eyal
• Primary Examiner(s): Kemmerer, Elizabeth C
• Assistant Examiner(s): Deberry, Regina M
• Application Number:
  US14/274,061
• Publication Number:
  US 20150079063A1
• Time in Patent Office: 1,117 Days
• Field of Search: None
• 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: C07K 14/505 Erythropoietin [EPO]
• 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 14/745 Blood coagulation or fibrinolysis factors
• CPC Class Codes: C07K 2319/31 fusions, other than Fc, for prolonged plasma life, e.g. albumin
• CPC Class Codes: C12N 9/6437 Coagulation factor VIIa (3.4.21.21)
• CPC Class Codes: C12N 9/644 Coagulation factor IXa (3.4.21.22)
• CPC Class Codes: C12N 9/96 Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates

Abstract

Polypeptides comprising at least one carboxy-terminal peptide (CTP) of chorionic gonadotropin attached to the carboxy terminus but not to the amino terminus of a coagulation factor and polynucleotides encoding the same are disclosed. Pharmaceutical compositions comprising the polypeptides and polynucleotides of the invention and methods of using and producing same are also disclosed.

Claims

1. A polynucleotide molecule consisting of a coding portion encoding a CTP-modified polypeptide consisting of a coagulation factor and three chorionic gonadotropin carboxy terminal peptides (CTPs) attached to the carboxy terminus of said coagulation factor, wherein said coagulation factor is Factor IX, or is Factor VII, or is activated Factor VII (FVIIa), and wherein said encoded CTP-modified polypeptide has coagulation activity.

2. The polynucleotide molecule of claim 1, wherein the sequence of at least one CTP is selected from the group consisting of:

SEQ ID NO;

1 and SEQ ID NO;

2.

3. The polynucleotide molecule of claim 1, wherein at least one CTP is truncated.

4. The polynucleotide molecule of claim 1, wherein said coagulation factor is a vitamin K dependent glycoprotein.

5. The polynucleotide molecule of claim 1, wherein said coagulation factor is Factor IX, and said polynucleotide molecule has the sequence set forth in SEQ ID NO:

30.

6. The polynucleotide molecule of claim 1, wherein said coagulation factor is Factor VII, and said polynucleotide molecule has the sequence set forth in SEQ ID NO:

24.

7. The polynucleotide molecule of claim 1, wherein said coagulation factor is activated FVII (FVIIa), and said polynucleotide molecule has the sequence set forth in SEQ ID NO:

24.

8. An expression vector comprising the polynucleotide molecule of claim 1.

9. An isolated cell comprising the expression vector of claim 8.

10. A composition comprising the expression vector of claim 9.