Human growth hormone modified at position 35

• US 8,778,880 B2
• Filed: 01/28/2005
• Issued: 07/15/2014
• Est. Priority Date: 02/02/2004
• Status: Expired due to Fees

• Current Assignee: Ambrx, Inc. (Johnson & Johnson)
• Original Assignee: Ambrx, Inc. (Johnson & Johnson)
• Inventors: Cho, Ho Sung, Daniel, Thomas O., DiMarchi, Richard D., Hays, Anna-Maria, Wilson, Troy E., Sim, Bee-Cheng, Litzinger, David C.
• Primary Examiner(s): Saoud, Christine J
• Application Number:
  US11/046,432
• Publication Number:
  US 20050170404A1
• Time in Patent Office: 3,455 Days
• Field of Search: None
• US Class Current: 514/11.4
• CPC Class Codes: A61K 38/21 Interferons [IFN]
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• 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: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• 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: A61P 5/12 : for decreasing, blocking or antagonising the activity of the posterior pituitary hormones
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07H 21/04 : with deoxyribosyl as saccharide radical
• CPC Class Codes: C07K 14/475 : Growth factors; Growth regulators
• CPC Class Codes: C07K 14/52 : Cytokines; Lymphokines; Interferons
• CPC Class Codes: C07K 14/575 : Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin C07K14/665, e.g. corticotropin C07K14/695
• CPC Class Codes: C07K 14/61 : Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: C08G 65/33396 : having oxygen in addition to nitrogen
• CPC Class Codes: G01N 2500/00 : Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 33/6875 : Nucleoproteins

Abstract

Modified human growth hormone polypeptides and uses thereof are provided.

Claims

1. A human growth hormone (hGH) polypeptide comprising an amino acid sequence of SEQ ID NO:

2, wherein said hGH polypeptide comprises one or more polyethylene glycol moieties wherein the molecular weight of said polyethylene glycol is in a range of 10 k-40 k Dalton and wherein at least one polyethylene glycol moiety is attached to a para-acetyl-phenylalanine that is ribosomally incorporated into the hGH polypeptide at position 35 of SEQ ID NO;

2 and wherein the hGH polypeptide has a serum half-life at least three-fold greater than the serum half-life of an unmodified hGH polypeptide.

2. The hGH polypeptide of claim 1, wherein the polypeptide is linked to a bifunctional polymer, bifunctional linker, or at least one additional hGH polypeptide.

3. The hGH polypeptide of claim 2, wherein the bifunctional linker or polymer is linked to a second polypeptide.

4. The hGH polypeptide of claim 3, wherein the second polypeptide is a hGH polypeptide.

5. A composition comprising the hGH polypeptide of claim 1 and a pharmaceutically acceptable carrier.