Modified Human Growth Hormone

• US 20080107680A1
• Filed: 10/25/2007
• Published: 05/08/2008
• Est. Priority Date: 12/22/2004
• Status: Abandoned Application

• Current Assignee: Ambrx, Inc. (Johnson & Johnson)
• Original Assignee: Ambrx, Inc. (Johnson & Johnson)
• Inventors: Daniel, Thomas, Hays, Anna-Maria, Wilson, Troy, Litzinger, David, DiMarchi, Richard, Cho, Ho Sung, Sim, Bee-Cheng
• Application Number:
  US11/924,056
• Publication Number:
  US 20080107680A1
• Time in Patent Office: Days
• US Class Current: 424/198.1
• 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

1-77. -77. (canceled)

78. A hormone composition comprising a growth hormone (GH) linked via an oxime bond to a PEG.

79. The hormone composition of claim 78, wherein the average serum half-life when administered to a mammal subcutaneously is selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 4, 15, 16, or more than 16 hours.

80. The composition of claim 78, wherein the GH is human growth hormone (hGH).

81. The composition of claim 80, wherein the hGH is recombinantly fused with albumin binding sequence.

82. The composition of claim 81, wherein the albumin binding sequence is an albumin-binding peptide or an albumin binding domain from streptococcal protein G.

83. The composition of claim 80, wherein the hGH is acylated with fatty acids.

84. The composition of claim 83, wherein the fatty acids promote binding to serum albumin.

85. A method of treating a patient with a composition comprising a growth hormone linked via an oxime bond to a PEG.

86. The method of claim 85, wherein the composition produces in the patient an IGF-1 concentration at least 34 ng/mL above patient baseline.

87. The method of claim 85, wherein the patient is a human and the composition produces an area under the concentration-time curve (AUC) above human efficacious levels.

88. The method of claim 87, wherein the area under the concentration-time curve (AUC_0->

inf) is at least 6,000 ng×

hr/mL.

89. The method of claim 85, wherein the patient has increased tibial bone length.

90. A hormone composition comprising hGH linked via an oxime bond to a PEG and a pharmaceutically acceptable carrier, wherein, when the formulation is administered through subcutaneous injection in a dose of between 0.05 mg/kg to 1 mg/kg a mean plasma concentration profile having a mean AUC_∞

of about 362,443 ngXh/mL±

20%, and a mean Cmax of about 4,977 ng/mL±

20% is achieved, and wherein the formulation is effective to increase tibial length, body weight, or both.