US2017218363A1PendingUtilityA1

Morpholino-mediated increase in soluble flt-1 expression results in decreased ocular and tumor neovascularization

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Assignee: UNIV UTAH RES FOUNDPriority: Apr 19, 2012Filed: Nov 29, 2016Published: Aug 3, 2017
Est. expiryApr 19, 2032(~5.7 yrs left)· nominal 20-yr term from priority
Inventors:Balamurali K. AmbatiHironori Uehara
C12N 2320/33A61P 35/00C12N 2310/11C12N 2310/113C12N 15/1138C12N 2310/3233C12N 15/113
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Claims

Abstract

Methods of inhibiting lymphangiogenesis and/or angiogenesis in a subject are provided. In one aspect, for example, a method of inhibiting angiogenesis in a subject can include binding an antisense morpholino to an mRNA splicing site of VEGFR1 selected from exon13_intron13 junction, intron13_exon14 junction, or a combination thereof. In another aspect, the morpholino includes a member selected from VEGFR1_MOe13, VEGFR1_MOi13, or a combination thereof.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method of inhibiting angiogenesis in a subject, comprising:
 binding an antisense morpholino to a splicing site of VEGFR1 mRNA selected from the group consisting of exon13_intron13 junction, intron13_exon14 junction, or a combination thereof such that the VEGFR1 mRNA is spliced into an sFlt-1 isoform.   
     
     
         2 . The method of  claim 1 , wherein the morpholino has a sequence similarity to the splicing site of greater than about 75%. 
     
     
         3 . The method of  claim 1 , wherein the morpholino has a sequence similarity to the splicing site of greater than about 95%. 
     
     
         4 . The method of  claim 1 , wherein the morpholino includes a member selected from the group consisting of VEGFR1_MOe13 (SEQ ID NO: 001), VEGFR1_MOi13 (SEQ ID NO: 002), or a combination thereof. 
     
     
         5 . The method of  claim 1 , wherein the morpholino has a sequence that has at least about 75% sequence similarity to SEQ ID NO: 001. 
     
     
         6 . The method of  claim 1 , wherein the morpholino has a sequence that has at least about 95% sequence similarity to SEQ ID NO: 001. 
     
     
         7 . The method of  claim 1 , wherein the morpholino has a sequence of SEQ ID NO: 001. 
     
     
         8 . The method of  claim 1 , wherein the morpholino has a sequence that has at least about 75% sequence similarity to SEQ ID NO: 002. 
     
     
         9 . The method of  claim 1 , wherein the morpholino has a sequence that has at least about 95% sequence similarity to SEQ ID NO: 002. 
     
     
         10 . The method of  claim 1 , wherein the morpholino has a sequence of SEQ ID NO: 002. 
     
     
         11 . A pharmaceutical composition for inhibiting angiogenesis in a subject, comprising:
 a pharmaceutically effective carrier including a morpholino capable of binding to a splicing site of VEGFR1 mRNA selected from the group consisting of exon13_intron13 junction, intron13_exon14 junction, or a combination thereof to facilitate increased expression of sFlt-1.   
     
     
         12 . The composition of  claim 11 , wherein the morpholino includes a member selected from the group consisting of VEGFR1_MOe13 (SEQ ID NO: 001), VEGFR1_MOi13 (SEQ ID NO: 002), or a combination thereof. 
     
     
         13 . The composition of  claim 11 , wherein the morpholino has a sequence similarity to the splicing site of greater than about 75%. 
     
     
         14 . The composition of  claim 11 , wherein the morpholino has a sequence similarity to the splicing site of greater than about 95%. 
     
     
         15 . The composition of  claim 11 , wherein the morpholino has a sequence that has at least about 75% sequence similarity to SEQ ID NO: 001. 
     
     
         16 . The composition of  claim 11 , wherein the morpholino has a sequence that has at least about 95% sequence similarity to SEQ ID NO: 001. 
     
     
         17 . The composition of  claim 11 , wherein the morpholino has a sequence of SEQ ID NO: 001. 
     
     
         18 . The composition of  claim 11 , wherein the morpholino has a sequence that has at least about 75% sequence similarity to SEQ ID NO: 002. 
     
     
         19 . The composition of  claim 11 , wherein the morpholino has a sequence that has at least about 95% sequence similarity to SEQ ID NO: 002. 
     
     
         20 . The composition of  claim 11 , wherein the morpholino has a sequence of SEQ ID NO: 002.

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