Formulations of human growth hormone comprising a non-naturally encoded amino acid at position 35

• US 7,816,320 B2
• Filed: 12/21/2005
• Issued: 10/19/2010
• Est. Priority Date: 12/22/2004
• Status: Expired due to Fees

• Current Assignee: Ambrx, Inc. (Johnson & Johnson)
• Original Assignee: Ambrx, Inc. (Johnson & Johnson)
• Inventors: Litzinger, David C., Hays, Anna-Maria, Buechler, Ying
• Primary Examiner(s): Spector; Lorraine
• Assistant Examiner(s): STOICA, ELLY GERALD
• Application Number:
  US11/316,483
• Publication Number:
  US 20060135427A1
• Time in Patent Office: 1,763 Days
• Field of Search: None
• US Class Current: 514/11.4
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 39/06 Free radical scavengers or antioxidants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/06 of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
• CPC Class Codes: A61P 9/02 Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: C07K 14/61 Growth hormone [GH], i.e. somatotropin

Abstract

Formulations of modified human growth hormone polypeptides are provided.

Claims

1. A pharmaceutical formulation of a human growth hormone (hGH) variant wherein said formulation comprises:

a) a buffer;

b) at least one carrier, excipient, or stabilizer, and;

c) a pharmaceutically effective quantity of the hGH variant wherein the hGH variant comprises a non-naturally encoded amino acid at position 35 and wherein the non-naturally encoded amino acid is p-acetyl phenylalanine.

2. The formulation of claim 1 wherein the hGH is PEGylated.

3. The formulation of claim 1, wherein the pH of the buffer is between about pH 4.0 and about pH 8.5.

4. The formulation of claim 1, wherein the pH of the buffer is between about pH 6.0 and about pH 7.3.

5. The formulation of claim 1, wherein the pH of the buffer is between about pH 5.5 and about 8.0.

6. The formulation of claim 1, wherein the pharmaceutically effective quantity of hGH is between about 2mg/mL and about 50 mg/mL.

7. The formulation of claim 1, wherein the buffer is between about pH 5.0 and about pH 7.5.

8. The formulation of claim 1, wherein the buffer is histidine.

9. The formulation of claim 8, wherein the histidine is at a concentration of about 0.1 mM to about 200 mM.

10. The formulation of claim 9, wherein the histidine is at a concentration of about 1 mM to about 75 mM.

11. The formulation of claim 10, wherein the histidine is at a concentration of about 5 mM to about 30 mM.

12. The formulation of claim 1, wherein the formulation further comprises d) a surfactant.

13. The formulation of claim 12, wherein the surfactant is a non-ionic surfactant.

14. The formulation of claim 13, wherein the non-ionic surfactant is at about 0.0001% to about 10%.

15. The formulation of claim 13, wherein the non-ionic surfactant is at about 0.01% to about 10%.

16. The formulation of claim 13, wherein the non-ionic surfactant is at about 0.1% to about 5%.

17. The formulation of claim 13, wherein the non-ionic surfactant is at about 0.1% to about 1%.

18. The formulation of claim 13, wherein the non-ionic surfactant is at about 0.0001% to about 1%.