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PDGF and VEGF aptamers having improved stability and their use in treating PDGF and VEGF mediated diseases and disorders

  • US 9,994,857 B2
  • Filed: 05/15/2017
  • Issued: 06/12/2018
  • Est. Priority Date: 09/09/2013
  • Status: Active Grant
First Claim
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1. A nucleic acid molecule comprising the nucleic sequence5′

  • -C1-G-A-C1,2-A-G1-C1-A-Z2-G2-Z2-A2-Z-G1-C1-A1-C1-A1-Z-C1-Z1-3′

    (SEQ ID NO;

         833),wherein,C1 is independently, for each occurrence, selected from the group consisting of a cytidine, a deoxycytidine and a 2′

    -O-methylcytidine;

    C1,2 is independently, for each occurrence, selected from the group consisting of a cytidine, a cytidine comprising a phosphorothioate linkage, a deoxycytidine, a deoxycytidine comprising a phosphorothioate linkage, a 2′

    -O-methylcytidine and a 2′

    -O-methylcytidine comprising a phosphorothioate linkage;

    G1 is independently, for each occurrence, selected from the group consisting of a guanosine, a deoxyguanosine and a 2′

    -O-methylguanosine;

    G2 is independently, for each occurrence, selected from the group consisting of a guanosine, a guanosine comprising a phosphorothioate linkage, a deoxyguanosine and a deoxyguanosine comprising a phosphorothioate linkage;

    Z1 is independently, for each occurrence, selected from the group consisting of a uridine, a deoxyuridine, a 2′

    -O-methyluridine, a 5-(N-naphthylmethylcarboxyamide)-2′

    -deoxyuridine (NapdU) and a 5-(N-naphthylmethylcarboxyamide)-2′

    -deoxyuridine (NapdU) comprising a 2′

    -O-methyl group;

    Z2 is independently, for each occurrence, selected from the group consisting of a uridine, a uridine comprising a phosphorothioate linkage, a deoxyuridine, a deoxyuridine comprising a phosphorothioate linkage, a 5-(N-naphthylmethylcarboxyamide)-2′

    -deoxyuridine (NapdU) and a 5-(N-naphthylmethylcarboxyamide)-2′

    -deoxyuridine (NapdU)comprising a phosphorothioate linkage;

    Z is independently, for each occurrence, selected from the group consisting of a uridine, a deoxyuridine and a 5-(N-naphthylmethylcarboxyamide)-2′

    -deoxyuridine (NapdU);

    A1 is independently, for each occurrence, selected from the group consisting of an adenosine, a deoxyadenosine and a 2′

    -O-methyladenosine;

    A2 is independently, for each occurrence, selected from the group consisting of an adenosine, an adenosine comprising a phosphorothioate linkage, a deoxyadenosine and a deoxyadenosine comprising a phosphorothioate linkage; and

    wherein, the nucleic acid molecule comprises at least one, two, three, four or five phosphorothioate linkages.

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