RNAi-mediated inhibition of HIF1A for treatment of ocular angiogenesis

• US 8,940,887 B2
• Filed: 05/29/2013
• Issued: 01/27/2015
• Est. Priority Date: 12/29/2005
• Status: Active Grant

• Current Assignee: Arrowhead Pharmaceuticals, Inc.
• Original Assignee: Alcon Research Limited (Nestle SA)
• Inventors: Chatterton, Jon E., Bingaman, David P.
• Primary Examiner(s): Bowman, Amy
• Application Number:
  US13/904,431
• Publication Number:
  US 20130245098A1
• Time in Patent Office: 608 Days
• Field of Search: None
• US Class Current: 536/24.5
• CPC Class Codes: A61K 31/7105 Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 7/10 Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• 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 15/1136 against growth factors, growth regulators, cytokines, lymphokines or hormones
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2320/30 Special therapeutic applications
• CPC Class Codes: C12N 2320/31 Combination therapy

Abstract

RNA interference is provided for inhibition of HIF1A mRNA expression for treating patients with ocular angiogenesis, particularly for treating retinal edema, diabetic retinopathy, sequela associated with retinal ischemia, posterior segment neovascularization (PSNV), and neovascular glaucoma, and for treating patients at risk of developing such conditions.

Claims

1. A pharmaceutical composition comprising:

an interfering RNA that contains one or more chemically modified nucleotides, one or more deoxyribonucleotides, and/or one or more non-phosphodiester linkages, and a pharmaceutically acceptable carrier, wherein the interfering RNA has a sense strand and an antisense strand, wherein each strand is 19-49 nucleotides in length, and wherein the sense strand comprises the RNA sequence corresponding to SEQ ID NO;

11, wherein the interfering RNA inhibits HIF1A.

2. The pharmaceutical composition of claim 1 wherein the interfering RNA is an shRNA, siRNA, or miRNA.