Modified human four helical bundle polypeptides and their uses

• US 8,906,676 B2
• Filed: 01/28/2005
• Issued: 12/09/2014
• Est. Priority Date: 02/02/2004
• Status: Active Grant

• 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): Shafer, Shulamith H
• Application Number:
  US10/587,371
• Publication Number:
  US 20080300163A1
• Time in Patent Office: 3,602 Days
• Field of Search: None
• US Class Current: 435/325
• 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 four helical bundle (4HB) polypeptides and uses thereof are provided.

Claims

1. An isolated nucleic acid comprising at least one N-terminal selector codon that is recognized by an orthogonal translation system and wherein the polynucleotide is translated by the translation system to produce a four helical bundle (4HB) polypeptide selected from the group consisting of human growth hormone, interferon, erythropoietin, and granulocyte cell stimulating factor, and wherein said orthogonal translation system translates the selector codon for a para-acetyl phenylalanine, and wherein the para-acetyl phenylalanine is post-translationally acylated, and wherein the 4HB polypeptide has increased serum half-life as compared to a wild type 4HB polypeptide of the same type.

2. The isolated nucleic acid of claim 1, wherein the selector codon is selected from the group consisting of an amber codon, ochre codon, opal codon, a unique codon, a rare codon, and a four-base codon.

3. An isolated cell comprising the nucleic acid of claim 1.

4. The isolated cell of claim 3, wherein the cell comprises an orthogonal tRNA synthetase or an orthogonal tRNA.