JAK/STAT INHIBITORS AND MAPK/ERK INHIBITORS FOR RSV INFECTION

• US 20140065133A1
• Filed: 11/06/2013
• Published: 03/06/2014
• Est. Priority Date: 12/19/2003
• Status: Abandoned Application

• Current Assignee: University of South Florida (State University System of Florida)
• Original Assignee: University of South Florida (State University System of Florida)
• Inventors: MOHAPATRA, SHYAM S.
• Application Number:
  US14/073,387
• Publication Number:
  US 20140065133A1
• Time in Patent Office: Days
• US Class Current: 424/130.1
• CPC Class Codes: A61K 2039/525 Virus
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/277 having a ring, e.g. verapamil
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61K 38/005 Enzyme inhibitors protease inhibitors A61K38/55
• CPC Class Codes: A61K 38/02 Peptides of undefined number of amino acids; Derivatives thereof
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12Q 1/485 involving kinase
• CPC Class Codes: C12Q 1/70 involving virus or bacteriophage immunoassay for viruses G01N33/56983

Abstract

The present invention concerns a method for treating or reducing the likelihood of developing a respiratory syncytial virus (RSV) infection in a subject by administering an effective amount of an inhibitor of the janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway or the mitogen-activated kinase (MAPK)/extracellular signal-regulated kinase (ERK1/2) signaling pathway to the subject. Another aspect of the invention concerns a pharmaceutical composition that includes an inhibitor of JAK/STAT or MAPK/ERK signaling to the subject; and a pharmaceutically acceptable carrier. Another aspect of the invention concerns a method for identifying agents useful for treating or reducing the likelihood of developing an RSV infection

Claims

1. A pharmaceutical composition comprising an inhibitor of janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling pathway or the mitogen-activated kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway;

and a pharmaceutically acceptable carrier.

2. The pharmaceutical composition of claim 1, wherein the inhibitor is a polynucleotide.

3. The pharmaceutical composition of claim 1, wherein the inhibitor is a polypeptide.

4. The pharmaceutical composition of claim 1, wherein the inhibitor is an antibody.

5. The pharmaceutical composition of claim 1, wherein the inhibitor is a small molecule.

6. The pharmaceutical composition of claim 1, wherein the inhibitor is a polynucleotide, and wherein the polynucleotide encodes a polypeptide which, when expressed, inhibits JAK/STAT or MAPK/ERK signaling.

7. The pharmaceutical composition of claim 1, wherein the inhibitor is a polynucleotide, and wherein the polynucleotide is an antisense molecule or a small interfering RNA (siRNA) molecule.

8. The pharmaceutical composition of claim 7, wherein the inhibitor reduces expression of STAT-1 or STAT-3.

9. The pharmaceutical composition of claim 7, wherein the inhibitor reduces expression of ERK1 or ERK2.

10. The pharmaceutical composition of claim 1, wherein the composition is formulated for intranasal administration.

11. The pharmaceutical composition of claim 1, wherein the composition is formulated for inhalation.

12. The pharmaceutical composition of claim 1, wherein the composition further comprises an agent that promotes internalization of the inhibitor by respiratory epithelial cells.

13. The pharmaceutical composition of claim 1, wherein the inhibitor is selected from the group consisting of AG490, PIAS protein, cytokine-inducible Src homology 2-containing (CIS) protein, CIS-related protein, suppressor of cytokine signaling-I protein (SOCS-1), tyrphostin, 4,5-dimethoxy-2-nitrobenzoic acid, 4,5-dimehtoxy-2-nitrobenzamide, 4-(phenyl)-amino-6,7-dimethoxyquinazoline, 4-(4′

-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline, 4-(3′

-bromo-4′

-hydroxylphenyl)-amino-6,7-dimethoxyquinalzoline, forskolin, and 3-isobutyl-1-methylxanthine (IBMX).

14. The pharmaceutical composition of claim 1, wherein the inhibitor is a MAPK/ERK signaling inhibitor selected from the group consisting of GW5074, BAY 43-9006, ISIS 5132, PD98059, PD184352, U0126, Ro 09-2210, L-783,277, purvalanol, and imidazolium trans-imidazoledimethyl sulfoxide-tetrachlororuthenate (NAMI-A).