US2018127750A1PendingUtilityA1

Mir-155 inhibitors for treating cutaneous t cell lymphoma (ctcl)

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Assignee: MIRAGEN THERAPEUTICS INCPriority: Jun 5, 2015Filed: Aug 15, 2017Published: May 10, 2018
Est. expiryJun 5, 2035(~8.9 yrs left)· nominal 20-yr term from priority
Inventors:David RodmanAnita SetoChristina DalbyAimee JacksonXuan Beatty
A61P 35/00A61K 45/06C12N 15/113A61K 48/00C12Q 1/6886A61P 43/00A61P 35/02C12N 2310/315C12N 2310/344C12N 2310/113C12N 2320/31C12N 2310/3231C12Q 2600/158C12N 2310/3531C12N 2310/322
57
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Claims

Abstract

The present invention provides oligonucleotide inhibitors of miR-155 and compositions thereof. The invention further provides methods for treating cancer such as a T cell lymphoma in a subject by administering to the subject an oligonucleotide inhibitor of miR-155. The invention also provides methods for reducing or inhibiting the proliferation of malignant T cells by administering an oligonucleotide inhibitor of miR-155.

Claims

exact text as granted — not AI-modified
1 - 30 . (canceled) 
     
     
         31 . A method for treating cutaneous T cell lymphoma (CTCL) in a subject in need thereof, comprising administering to the subject an oligonucleotide inhibitor of miR-155 having a length of 11-14 nucleotides, wherein
 said oligonucleotide inhibitor is at least about 75% complementary to a mature sequence of miR-155 and has a full phosphorothioate backbone; and   wherein at least the first three nucleotides from the 3′ end of said oligonucleotide inhibitor are locked nucleotides.   
     
     
         32 . The method of  claim 31 , wherein said oligonucleotide inhibitor has a length of 12-14 nucleotides. 
     
     
         33 . The method of  claim 31 , wherein said oligonucleotide inhibitor has a length of 13-14 nucleotides. 
     
     
         34 . The method of  claim 31 , wherein said oligonucleotide inhibitor has a length of 12 nucleotides. 
     
     
         35 . The method of  claim 31 , wherein said oligonucleotide inhibitor has a length of 13 nucleotides. 
     
     
         36 . The method of  claim 31 , wherein said oligonucleotide inhibitor has a length of 14 nucleotides. 
     
     
         37 . The method of  claim 31 , wherein at least the second, fourth, sixth, and/or the eighth nucleotide from the 5′ end of said oligonucleotide inhibitor is a deoxyribonucleic acid (DNA) nucleotide. 
     
     
         38 . The method of  claim 31 , wherein at least the second nucleotide from the 5′ end of said oligonucleotide inhibitor is a deoxyribonucleic acid (DNA) nucleotide. 
     
     
         39 . The method of  claim 31 , wherein at least the fourth nucleotide from the 5′ end of said oligonucleotide inhibitor is a deoxyribonucleic acid (DNA) nucleotide. 
     
     
         40 . The method of  claim 31 , wherein at least the second and the fourth nucleotides from the 5′ end of said oligonucleotide inhibitor are deoxyribonucleic acid (DNA) nucleotides. 
     
     
         41 . The method of  claim 31 , wherein at least the second, fourth, and the sixth nucleotides from the 5′ end of said oligonucleotide inhibitor are deoxyribonucleic acid (DNA) nucleotides. 
     
     
         42 . The method of  claim 31 , wherein at least the second, fourth, sixth, and the eighth nucleotides from the 5′ end of said oligonucleotide inhibitor are deoxyribonucleic acid (DNA) nucleotides. 
     
     
         43 . The method of  claim 31 , wherein at least the second, sixth, and the eighth nucleotides from the 5′ end of said oligonucleotide inhibitor are deoxyribonucleic acid (DNA) nucleotides. 
     
     
         44 . The method of  claim 31 , wherein the fourth nucleotide from the 3′ end of said oligonucleotide inhibitor is a locked nucleotide. 
     
     
         45 . The method of  claim 31 , wherein said oligonucleotide inhibitor contains at least 7, 8, 9, or 10 locked nucleotides. 
     
     
         46 . The method of  claim 36 , wherein said oligonucleotide inhibitor comprises a sequence of 5′-1Cs.dAs.1Cs.dGs.dAs.1Ts.1Ts.dAs.1Gs.dCs1As.1Ts.1Ts.1A-3′ (SEQ ID NO: 25). 
     
     
         47 . The method of  claim 36 , wherein said oligonucleotide inhibitor comprises a sequence of 5′-1Cs;1As;dCs;dGs;dAs;1Ts;1Ts;dAs;1Gs;dCs;1As;1Ts;1Ts;1A-3′ (SEQ ID NO: 47). 
     
     
         48 . The method of  claim 36 , wherein said oligonucleotide inhibitor comprises a sequence of 5′-1Cs;dAs;1Cs;dGs;dAs;1Ts;1Ts;dAs;1Gs;1Cs;dAs;1Ts;1Ts;1A-3′ (SEQ ID NO: 53). 
     
     
         49 . The method of  claim 36 , wherein said oligonucleotide inhibitor comprises a sequence of 5′-1Cs.dAs.1Cs.dGs.dAs.1Ts.1Ts.dAs.1Gs.dCs.dAs.1Ts.1Ts.1A-3′ (SEQ ID NO: 42). 
     
     
         50 . The method of  claim 35 , wherein said oligonucleotide inhibitor comprises a sequence of 5′-dAs;1Cs;dGs;dAs;1Ts;1Ts;dAs;1Gs;dCs;1As;1Ts;1Ts;1A-3′ (SEQ ID NO: 57). 
     
     
         51 . The method of  claim 35 , wherein said oligonucleotide inhibitor comprises a sequence of 5′-1As;dCs;dGs;dAs;1Ts;1Ts;dAs;1Gs;dCs;1As;1Ts;1Ts;1A-3′ (SEQ ID NO: 58). 
     
     
         52 . The method of  claim 35 , wherein said oligonucleotide inhibitor comprises a sequence of 5′-1As.1Cs.dGs.dAs.1Ts.1Ts.dAs.1Gs.dCs.1As.1Ts.1Ts.1A-3′ (SEQ ID NO: 54). 
     
     
         53 . The method of  claim 35 , wherein said oligonucleotide inhibitor comprises a sequence of 5′-1As;1Cs;dGs;dAs;1Ts;1Ts;dAs;1Gs;1Cs;dAs;1Ts;1Ts;1A-3′ (SEQ ID NO: 76). 
     
     
         54 . The method of  claim 35 , wherein said oligonucleotide inhibitor comprises a sequence of 5′-1As.1Cs.dGs.dAs.1Ts.1Ts.dAs.1Gs.dCs.dAs.1Ts.1Ts.1A-3′ (SEQ ID NO: 66). 
     
     
         55 . The method of  claim 34 , wherein said oligonucleotide inhibitor comprises a sequence of 5′-1Cs.dGs1As.1Ts.1Ts.1As.1Gs.dCs.1As.1Ts.1Ts.1A-3′ (SEQ ID NO: 22). 
     
     
         56 . The method of  claim 34 , wherein said oligonucleotide inhibitor comprises a sequence of 5′-1Cs.dGs1As.1Ts.1Ts.dAs.1Gs.dCs.1As.1Ts.1Ts.1A-3′ (SEQ ID NO: 23). 
     
     
         57 . The method of  claim 34 , wherein said oligonucleotide inhibitor comprises a sequence of 5′-1Cs.dGs.dAs.1Ts.1Ts.dAs.1Gs.dCs.dAs.1 Ts.1 Ts.1A-3′ (SEQ ID NO: 85). 
     
     
         58 . The method of  claim 34 , wherein said oligonucleotide inhibitor comprises a sequence of 5′-1Cs.dGs.dAs.1Ts.1Ts.dAs.1Gs.1Cs.dAs.1Ts.1Ts.1A-3′ (SEQ ID NO: 94). 
     
     
         59 . The method of  claim 31 , wherein said oligonucleotide inhibitor reduces proliferation of CTCL cells. 
     
     
         60 . The method of  claim 31 , wherein said oligonucleotide inhibitor induces apoptosis of CTCL cells. 
     
     
         61 . The method of  claim 31 , wherein said oligonucleotide inhibitor is administered to the subject via injection. 
     
     
         62 . The method of  claim 55 , wherein the oligonucleotide inhibitor reduces proliferation of CTCL cells by about 30-90% compared to untreated cells. 
     
     
         63 . The method of  claim 31 , wherein the oligonucleotide inhibitor is at least about 80%, 85%, 90%, or 95% complementary to a mature sequence of miR-155. 
     
     
         64 . The method of  claim 31 , wherein the oligonucleotide inhibitor is fully complementary to a mature sequence of miR-155.

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