Therapeutic gene-switch constructs and bioreactors for the expression of biotherapeutic molecules, and uses thereof

• US 9,724,430 B2
• Filed: 09/24/2015
• Issued: 08/08/2017
• Est. Priority Date: 09/28/2007
• Status: Active Grant

• Current Assignee: Intrexon Corporation
• Original Assignee: Intrexon Corporation
• Inventors: Tretiakova, Anna P., Peterson, Richard E., Beech, Robert P., Merenick, Bethany Lynn, Reed, Thomas D.
• Primary Examiner(s): Nguyen, Quang
• Application Number:
  US14/864,265
• Publication Number:
  US 20160114059A1
• Time in Patent Office: 684 Days
• Field of Search: 536 241, 4353201, 435455
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 48/0066 Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C12N 15/635 Externally inducible repressor mediated regulation of gene expression, e.g. tetR inducible by tetracyline
• CPC Class Codes: C12N 15/85 for animal cells
• CPC Class Codes: C12N 2510/02 Cells for production
• CPC Class Codes: C12N 2830/002 : inducible enhancer/promoter combination, e.g. hypoxia, iron, transcription factor
• CPC Class Codes: C12N 2830/15 : chimeric enhancer/promoter combination

Abstract

The present invention relates to methods and compositions for treating, ameliorating or preventing a disease or disorder in a subject by introducing into cells of the subject a therapeutic gene switch construct that controls expression of one or more therapeutic products.

Claims

1. A composition comprising:

(1) a first polynucleotide encoding a gene switch, said gene switch comprising at least one transcription factor sequence, wherein said at least one transcription factor sequence encodes a ligand-dependent transcription factor in operable association with a hypoxia-inducible promoter, wherein the hypoxia-inducible promoter is a nucleic acid sequence at least 95% identical to the sequence from nucleotide 4958 to nucleotide 5535 of SEQ ID NO;

7, and

(2) a second polynucleotide encoding a therapeutic polypeptide or therapeutic polynucleotide operably associated with a transcription factor-regulated promoter which is activated by said ligand-dependent transcription factor, wherein a ligand is capable of inducing expression of said therapeutic polypeptide or therapeutic polynucleotide, wherein said composition is for use in treating, ameliorating, or preventing a disease or disorder.

2. The composition of claim 1, wherein said first and second polynucleotides are part of one larger polynucleotide.

3. The composition of claim 1, wherein the ligand capable of inducing expression of said therapeutic polypeptide or therapeutic polynucleotide is a diacylhydrazine.

4. The composition of claim 1, wherein the ligand capable of inducing expression of said therapeutic polypeptide or therapeutic polynucleotide is selected from the group consisting of RG-115819, RG-115932, and RG-115830.