Methods of treatment with long-acting growth hormone

• US 10,351,615 B2
• Filed: 08/02/2012
• Issued: 07/16/2019
• 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): Borgeest, Christina M
• Application Number:
  US14/236,509
• Publication Number:
  US 20140371144A1
• Time in Patent Office: 2,539 Days
• Field of Search: None
• 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 14/61 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/02 containing a signal sequence

Abstract

Use of a growth hormone protein and polynucleotides encoding same comprising an amino-terminal carboxy-terminal peptide (CTP) of chorionic gonadotrophin and two carboxy-terminal chorionic gonadotrophin CTPs attached to the growth hormone in methods of inducing weight loss or body fat reduction, methods of increasing insulin-like growth factor (IGF-1) levels, and methods of reducing the dosing frequency of a growth hormone in a human subject are disclosed. Pharmaceutical compositions comprising the growth hormone and polynucleotides encoding the growth hormone of the invention and methods of using same are also disclosed.

Claims

1. A method of treating growth hormone deficiency in a human adult subject as measured by maintaining insulin-like growth factor (IGF-1) levels within a normal therapeutic range in said growth hormone deficient human subject, the method comprising

administering to said human adult subject a therapeutically effective amount of a CTP-modified polypeptide consisting of (i) a human growth hormone, (ii) a single chorionic gonadotropin carboxy terminal peptide (CTP) attached to the amino terminus of said growth hormone, and (iii) two chorionic gonadotropin CTPs attached to the carboxy terminus of said growth hormone, wherein optionally (iv) a signal peptide is attached to the amino terminus of said amino terminal CTP,

measuring IGF-1 levels to determine the maintenance of IGF-1 in said human adult subject,

wherein said CTP-modified polypeptide consists of the amino acid sequence set forth in amino acids 27-301 of SEQ ID NO:

11 when said signal peptide is not attached,

wherein said therapeutically effective amount consists of a single dose of approximately 1.8-2 mg/week of the CTP-modified polypeptide,

wherein said administration maintains IGF-1 levels within a normal therapeutic range and treats said growth hormone deficient human subject.

2. The method of claim 1, wherein said CTP-modified polypeptide is administered at a dose of approximately 2 mg/administration.

3. The method of claim 1, wherein said CTP-modified polypeptide is administered subcutaneously to said subject.

4. The method of claim 1, wherein said CTP-modified polypeptide is encoded by the nucleotide sequence set forth in SEQ ID NO:

16.

5. The method of claim 1, wherein at least one CTP is glycosylated.

6. The method of claim 1, wherein said maintaining is for at least one week.

7. The method of claim 1, wherein the amino acid sequence of said signal peptide is set forth in SEQ ID NO:

3.

8. The method of claim 1, wherein said CTP-modified polypeptide is administered at a dose of approximately 1.8 mg/administration.

9. The method of claim 1, wherein said adult subject is male.