Modified human growth horomone polypeptides and their uses

• US 7,939,496 B2
• Filed: 12/21/2005
• Issued: 05/10/2011
• 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., DiMarchi, Richard D., Hays, Anna-Maria, Sim, Bee-Cheng, Daniel, Thomas O., Wilson, Troy E., Cho, Ho Sung
• Primary Examiner(s): Saoud; Christine J
• Application Number:
  US11/316,534
• Publication Number:
  US 20060189529A1
• Time in Patent Office: 1,966 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

Modified growth hormone polypeptide and uses thereof are provided.

Claims

1. A hormone composition comprising a human growth hormone (hGH) having the amino acid sequence of SEQ ID NO:

2, covalently linked to one 30 k Dalton linear polyethylene glycol (PEG) molecule via an oxime bond formed between a non-naturally encoded amino acid substituted at position 35 of SEQ ID NO;

2 and said PEG molecule, wherein said hormone composition is at least 95% pure hGH and wherein the hGH has an average serum half-life of at least about 7-fold the serum half-life of a composition comprising the hGH without the PEG when administered to a mammal subcutaneously.

2. A pharmaceutical composition comprising

(i) the growth hormone composition of claim 1;

and

(ii) a pharmaceutically acceptable excipient.

3. The pharmaceutical composition of claim 2 wherein the composition comprises a pharmaceutically acceptable formulation liquid for injection.

4. The hormone composition of claim 1 wherein the average serum half-life is at least about 12 hours when administered to a mammal subcutaneously.