Compositions and methods related to miRNA modulation of neovascularization or angiogenesis

• US 9,365,852 B2
• Filed: 05/05/2015
• Issued: 06/14/2016
• Est. Priority Date: 05/08/2008
• Status: Expired due to Fees

• Current Assignee: Johns Hopkins University, Mirna Therapeutics, Inc. (Synlogic, Inc.)
• Original Assignee: Mirna Therapeutics, Inc. (Synlogic, Inc.)
• Inventors: Shen, Jikui, Kelnar, Kevin, Shelton, Jeffrey, Brown, David, Campochiaro, Peter
• Primary Examiner(s): Bowman, Amy
• Application Number:
  US14/704,458
• Publication Number:
  US 20150344880A1
• Time in Patent Office: 406 Days
• US Class Current: 1/1
• 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 15/113 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: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/141 MicroRNAs, miRNAs
• CPC Class Codes: C12N 2310/32 of the sugar
• CPC Class Codes: C12N 2310/351 Conjugate
• CPC Class Codes: C12N 2310/531 Stem-loop; Hairpin
• CPC Class Codes: C12N 2320/30 Special therapeutic applications
• CPC Class Codes: C12N 2320/32 Special delivery means, e.g. tissue-specific
• CPC Class Codes: C12Q 1/6809 Methods for determination or identification of nucleic acids involving differential detection
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2525/207 siRNA, miRNA
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/118 Prognosis of disease development
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: C12Q 2600/16 Primer sets for multiplex assays
• CPC Class Codes: C12Q 2600/178 miRNA, siRNA or ncRNA

Abstract

The present invention concerns methods and compositions for diagnosing and/or treating vascular diseases including cancer, cardiac diseases, vascular diseases of the eye, and inflammatory diseases. The methods involve measuring the levels of one or multiple miRNAs in patient samples and using the test results to diagnose and/or predict an optimal treatment regimen for the patient. Compositions described in the invention include nucleic acids that function as miRNAs or miRNA inhibitors that can be introduced to a patient to reduce or increase vascularization as needed.

Claims

1. A method for reducing unwanted neovascularization in an individual in need thereof comprising administering to the individual a therapeutically-effective amount of an inhibitor of miR-21-comprising a single-stranded oligonucleotide that is complementary to a sequence of mature miR-21 (SEQ ID NO:

71).

2. The method of claim 1, wherein the inhibitor of miR-21 is 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or 30 nucleotides in length.

3. The method of claim 1, wherein the inhibitor of miR-21 comprises a nucleotide analog or a modified nucleotide.

4. The method of claim 3, wherein the modified nucleotide comprises a sugar modification.

5. The method of claim 1, wherein the inhibitor of miR-21 is administered parenterally.

6. The method of claim 1, wherein the inhibitor of miR-21 has a sulfur modification.