Modified human growth hormone formulations with an increased serum half-life

• US 8,178,494 B2
• Filed: 10/25/2007
• Issued: 05/15/2012
• Est. Priority Date: 12/22/2004
• Status: Expired due to Fees

• Current Assignee: Ambrx, Inc. (Johnson & Johnson)
• Original Assignee: Ambrx, Inc. (Johnson & Johnson)
• Inventors: Hays, Anna-Maria, Buechler, Ying, Litzinger, David C.
• Primary Examiner(s): STOICA, ELLY GERALD
• Application Number:
  US11/924,242
• Publication Number:
  US 20080113914A1
• Time in Patent Office: 1,664 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 47/26 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 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• 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 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 5/10 of the posterior pituitary hormones, e.g. oxytocin, ADH
• CPC Class Codes: C07K 14/61 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: C08G 65/33396 having oxygen in addition to nitrogen

Abstract

Formulations of modified growth hormone polypeptides are provided, including human growth hormone polypeptides with one or more non-naturally encoded amino acids with an increased half-life.

Claims

1. A pharmaceutical formulation of human growth hormone (hGH) polypeptide comprising a non-naturally encoded amino acid wherein the non-naturally encoded amino acid is substituted at a position corresponding to a position selected from the group 35, 92, 131, 134, 143, and 145 of SEQ ID NO:

2 and wherein the non-naturally encoded amino acid is linked to a linear polyethylene glycol through an oxime bond and wherein the polyethylene glycol has a molecular weight of at least 20 kDa-40 kDa, wherein said formulation is liquid, and wherein the serum half-life of the PEGylated hGH is at least two-fold greater than the serum half-life of a naturally occurring, unPEGylated version of an hGH protein.

2. The pharmaceutical formulation of claim 1, wherein the concentration of the formulation is at least 14 mg/mL hGH.

3. A pharmaceutical formulation of human growth hormone (hGH) polypeptide comprising a non-naturally encoded amino acid wherein the non-naturally encoded amino acid is substituted at a position corresponding to a position selected from the group 35, 92, 131, 134, 143, and 145 of SEQ ID NO:

2 and wherein the non-naturally encoded amino acid is linked to a linear polyethylene glycol through an oxime bond and wherein the polyethylene glycol has a molecular weight of at least 20 kDa-40 kDa and wherein the serum half-life of the PEGylated hGH is at least two-fold greater than the serum half-life of a naturally occurring, unPEGylated hGH protein and wherein said formulation is lyophilized.