RNAi-RELATED INHIBITION OF TNFa SIGNALING PATHWAY FOR TREATMENT OF OCULAR ANGIOGENESIS
AssigneeAlcon Research, Ltd.
InventorsJon E. Chatterton, Abbot F. Clark, David P. Bingaman, Martin B. Wax, Adrian M. Timmers
Life of this patent
Estimating the term…
Abstract
RNA interference is provided for inhibition of tumor necrosis factor α (TNFα) by silencing TNFα cell surface receptor TNF receptor-1 (TNFR1) mRNA expression, or by silencing TNFα converting enzyme (TACE/ADAM17) mRNA expression. Silencing such TNFα targets, in particular, is useful for treating patients having a TNFα-related condition or at risk of developing a TNFα-related condition, such as ocular angiogenesis, retinal ischemia, and diabetic retinopathy.
Claims20
A method of treating a TNFα-related ocular disorder in a patient in need thereof, comprising administering to the patient an interfering RNA molecule that attenuates expression of the TNFR1 or TACE mRNA via RNA interference, wherein the TNFα-related ocular disorder is ocular angiogenesis, ocular neovascularization, proliferative diabetic retinopathy, sequela associated with retinal ischemia, or posterior segment neovascularization (PSNV).
An interfering RNA molecule having a length of about 19 to about 49 nucleotides, the interfering RNA molecule comprising:
- (a) a region of at least 13 contiguous nucleotides having at least 90% sequence complementarity to, or at least 90% sequence identity with, the penultimate 13 nucleotides of the 3′ end of a mRNA corresponding to any one of SEQ ID NO:3 and SEQ ID NO:14-SEQ ID NO:58;
- (b) a region of at least 14 contiguous nucleotides having at least 85% sequence complementarity to, or at least 85% sequence identity with, the penultimate 14 nucleotides of the 3′ end of an mRNA corresponding to any one of SEQ ID NO:3 and SEQ ID NO:14-SEQ ID NO:58;
- or
- (c) a region of at least 15, 16, 17, or 18 contiguous nucleotides having at least 80% sequence complementarity to, or at least 80% sequence identity with, the penultimate 15, 16, 17, or 18 nucleotides, respectively, of the 3′ end of an mRNA corresponding to any one of SEQ ID NO:3 and SEQ ID NO:14-SEQ ID NO:58.
An interfering RNA molecule having a length of about 19 to about 49 nucleotides, the interfering RNA molecule comprising:
- (a) a region of at least 13 contiguous nucleotides having at least 90% sequence complementarity to, or at least 90% sequence identity with, the penultimate 13 nucleotides of the 3′ end of a mRNA corresponding to any one of SEQ ID NO:155-SEQ ID NO:201;
- (b) a region of at least 14 contiguous nucleotides having at least 85% sequence complementarity to, or at least 85% sequence identity with, the penultimate 14 nucleotides of the 3′ end of an mRNA corresponding to any one of SEQ ID NO:155-SEQ ID NO:201;
- or
- (d) a region of at least 15, 16, 17, or 18 contiguous nucleotides having at least 80% sequence complementarity to, or at least 80% sequence identity with, the penultimate 15, 16, 17, or 18 nucleotides, respectively, of the 3′ end of an mRNA corresponding to any one of SEQ ID NO:155-SEQ ID NO:201.
Dependencies are inferred from the claim text.