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US 2016/0237108 A1Published application
Polynucleotide molecules and uses thereof
AssigneeModerna Therapeutics, Inc.
InventorsAndrew W. FRALEY, Atanu ROY, Matthew STANTON
Life of this patent
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Abstract
The present disclosure provides alternative sugar moieties and polynucleotides comprising such sugar moieties, and methods of use thereof.
Claims483
A compound of Formula I:
- wherein the dotted line represents an optional double bond;
- B is a nucleobase;
- m and n are independently an integer from 0 to 3;
- X is S, CH2, SO2, O, or NR7;
- R1 is hydrogen or fluorine;
- R2 is hydrogen, fluorine, cyano, azido, or optionally substituted C1-C6 alkyl;
- R3 and R4 are independently hydrogen, optionally substituted hydroxyl, or fluorine;
- R5 and R6 are independently hydrogen or optionally substituted C1-C6 alkyl, or R5 and R6 are combined to form an optionally substituted C3-C6 cycloalkyl, provided that one of R5 and R6 is absent when the dotted line is a double bond;
- R7 is hydrogen or optionally substituted C1-C6 alkyl;
- Y1 and Y4 are independently hydroxyl, protected hydroxyl, or optionally substituted amino;
- each Y2 is independently hydroxyl or optionally substituted C1-C6 heteroalkyl;
- each Y3 is independently absent, O, or S;
- each Y5 is independently O, NH, or CR8R9;
- each Y6 is O or S;
- each Y7 is O or NH and
- each R8 and R9 is independently hydrogen, fluorine, or optionally substituted C1-C6 alkyl, or R8 and R9 are combined to form an optionally substituted C3-C6 cycloalkyl, provided that one of R8 and R9 is absent when the dotted line is a double bond;
- wherein if n is 0, X is O, R1, R2, R4, R5, and R6 are hydrogen, and Y5 is O, then at least one of Y1 and Y4 is optionally substituted amino, and, if m is 0, n is 1, Y1 is optionally substituted amino, Y2 is optionally substituted C1-C6 heteroalkyl, Y3 is absent, Y7 is O, X is O, and R1, R2, R4, R5, and R6 are hydrogen, then Y4 is optionally substituted amino;
- or a salt thereof.
15 more elements
A polynucleotide comprising at least one backbone moiety of Formula III:
- wherein the dotted line represents an optional double bond;
- B is a nucleobase;
- m and n are independently an integer from 0 to 3;
- X is S, CH2, SO2, O, or NR7;
- R1 is hydrogen or fluorine;
- R2 is hydrogen, fluorine, cyano, azido, or optionally substituted C1-C6 alkyl;
- R3 and R4 are independently hydrogen, optionally substituted hydroxyl, or fluorine;
- R5 and R6 are independently hydrogen or optionally substituted C1-C6 alkyl, or R5 and R6 are combined to form an optionally substituted C3-C6 cycloalkyl, provided that one of R5 and R6 is absent when the dotted line is a double bond;
- R7 is hydrogen or optionally substituted C1-C6 alkyl;
- each Y2 is independently hydroxyl or optionally substituted C1-C6 heteroalkyl;
- each Y3 is independently absent, O, or S;
- each Y5 is independently O, NH, or CR8R9;
- each Y6 is independently O or S;
- each Y7 is independently O or NH;
- and
- each R8 and R9 is independently hydrogen, fluorine, or optionally substituted C1-C6 alkyl, or R8 and R9 are combined to form an optionally substituted C3-C6 cycloalkyl, provided that one of R8 and R9 is absent when the dotted line is a double bond;
- wherein if X is O and R1, R2, R4, R5, and R6 are hydrogen, then at least one of Y5 and Y7 is NH or Y5 is CR8R9;
- provided that m and n are both 1 when the backbone moiety is not a 3′ or 5′ terminal moiety;
- or a salt thereof.
16 more elements
A compound of Formula IA:
- wherein the dotted line represents an optional double bond;
- B is a nucleobase;
- m and n are independently an integer from 0 to 3;
- X is S, CH2, SO2, O, or NR7;
- R1 is hydrogen or fluorine;
- R2 is hydrogen, fluorine, cyano, azido, or optionally substituted C1-C6 alkyl;
- R3 and R4 are independently hydrogen, optionally substituted hydroxyl, or fluorine;
- R5 and R6 are independently hydrogen or optionally substituted C1-C6 alkyl, or R5 and R6 are combined to form an optionally substituted C3-C6 cycloalkyl, provided that one of R5 and R6 is absent when the dotted line is a double bond;
- R7 is hydrogen or optionally substituted C1-C6 alkyl;
- Y1 and Y4 are independently hydroxyl, protected hydroxyl, or optionally substituted amino;
- each Y2 is independently hydroxyl or optionally substituted C1-C6 heteroalkyl;
- each Y3 is independently absent, O, or S;
- each Y5 is independently O, NH, or CR8R9;
- each Y6 is O or S;
- each Y7 is O or NH;
- and
- each R8 and R9 is independently hydrogen, fluorine, or optionally substituted C1-C6 alkyl, or R8 and R9 are combined to form an optionally substituted C3-C6 cycloalkyl, provided that one of R8 and R9 is absent when the dotted line is a double bond;
- or a salt thereof.
15 more elements
A polynucleotide comprising at least one backbone moiety of Formula IIA:
- wherein the dotted line represents an optional double bond;
- B is a nucleobase;
- m and n are independently an integer from 0 to 3;
- X is S, CH2, SO2, O, or NR7;
- R1 is hydrogen or fluorine;
- R2 is hydrogen, fluorine, cyano, azido, or optionally substituted C1-C6 alkyl;
- R3 and R4 are independently hydrogen, optionally substituted hydroxyl, or fluorine;
- R5 and R6 are independently hydrogen or optionally substituted C1-C6 alkyl, or R5 and R6 are combined to form an optionally substituted C3-C6 cycloalkyl, provided that one of R5 and R6 is absent when the dotted line is a double bond;
- R7 is hydrogen or optionally substituted C1-C6 alkyl;
- each Y2 is independently hydroxyl or optionally substituted C1-C6 heteroalkyl;
- each Y3 is independently absent, O, or S;
- each Y5 is independently O, NH, or CR8R9;
- each Y6 is independently O or S;
- each Y7 is independently O or NH;
- and
- each R8 and R9 is independently hydrogen, fluorine, or optionally substituted C1-C6 alkyl, or R8 and R9 are combined to form an optionally substituted C3-C6 cycloalkyl, provided that one of R8 and R9 is absent when the dotted line is a double bond;
- provided that m and n are both 1 when the backbone moiety is not a 3′ or 5′ terminal moiety;
- or a salt thereof.
15 more elements
Dependencies are inferred from the claim text.