POLYNUCLEOTIDE MOLECULES AND USES THEREOF

US 20160237108A1
Filed: 10/02/2014
Published: 08/18/2016
Est. Priority Date: 10/02/2013
Status: Active Grant

First Claim

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1. A compound of Formula I:

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Abstract

The present disclosure provides alternative sugar moieties and polynucleotides comprising such sugar moieties, and methods of use thereof.

91 Citations

483 Claims

1. A compound of Formula I:
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118)
- - 2. The compound of claim 1, wherein said compound has the structure:
  - 3. The compound of claim 2, wherein said nucleobase is uracil.
  - 4. The compound of claim 2, wherein said nucleobase is pseudouracil.
  - 5. The compound of claim 2, wherein said nucleobase is 1-methylpseudouracil.
  - 6. The compound of claim 2, wherein said nucleobase is 5-methoxyuracil.
  - 7. The compound of claim 2, wherein said nucleobase is cytosine.
  - 8. The compound of claim 2, wherein said nucleobase is 5-methylcytosine.
  - 9. The compound of claim 2, wherein said nucleobase is guanine.
  - 10. The compound of claim 2, wherein said nucleobase is adenine.
  - 11. The compound of claim 1, wherein said compound has the structure:
  - 12. The compound of claim 11, wherein said nucleobase is uracil.
  - 13. The compound of claim 11, wherein said nucleobase is pseudouracil.
  - 14. The compound of claim 11, wherein said nucleobase is 1-methylpseudouracil.
  - 15. The compound of claim 11, wherein said nucleobase is 5-methoxyuracil.
  - 16. The compound of claim 11, wherein said nucleobase is cytosine.
  - 17. The compound of claim 11, wherein said nucleobase is 5-methylcytosine.
  - 18. The compound of claim 11, wherein said nucleobase is guanine.
  - 19. The compound of claim 11, wherein said nucleobase is adenine.
  - 20. The compound of claim 1, wherein said compound has the structure:
  - 21. The compound of claim 20, wherein said nucleobase is uracil.
  - 22. The compound of claim 20, wherein said nucleobase is pseudouracil.
  - 23. The compound of claim 20, wherein said nucleobase is 1-methylpseudouracil.
  - 24. The compound of claim 20, wherein said nucleobase is 5-methoxyuracil.
  - 25. The compound of claim 20, wherein said nucleobase is cytosine.
  - 26. The compound of claim 20, wherein said nucleobase is 5-methylcytosine.
  - 27. The compound of claim 20, wherein said nucleobase is guanine.
  - 28. The compound of claim 20, wherein said nucleobase is adenine.
  - 29. The compound of claim 1, wherein said compound has the structure:
  - 30. The compound of claim 29, wherein said nucleobase is uracil.
  - 31. The compound of claim 29, wherein said nucleobase is pseudouracil.
  - 32. The compound of claim 29, wherein said nucleobase is 1-methylpseudouracil.
  - 33. The compound of claim 29, wherein said nucleobase is 5-methoxyuracil.
  - 34. The compound of claim 29, wherein said nucleobase is cytosine.
  - 35. The compound of claim 29, wherein said nucleobase is 5-methylcytosine.
  - 36. The compound of claim 29, wherein said nucleobase is guanine.
  - 37. The compound of claim 29, wherein said nucleobase is adenine.
  - 38. The compound of claim 1, wherein said compound has the structure:
  - 39. The compound of claim 38, wherein said nucleobase is uracil.
  - 40. The compound of claim 38, wherein said nucleobase is pseudouracil.
  - 41. The compound of claim 38, wherein said nucleobase is 1-methylpseudouracil.
  - 42. The compound of claim 38, wherein said nucleobase is 5-methoxyuracil.
  - 43. The compound of claim 38, wherein said nucleobase is cytosine.
  - 44. The compound of claim 38, wherein said nucleobase is 5-methylcytosine.
  - 45. The compound of claim 38, wherein said nucleobase is guanine.
  - 46. The compound of claim 38, wherein said nucleobase is adenine.
  - 47. The compound of claim 1, wherein said compound has the structure:
  - 48. The compound of claim 47, wherein said nucleobase is uracil.
  - 49. The compound of claim 47, wherein said nucleobase is pseudouracil.
  - 50. The compound of claim 47, wherein said nucleobase is 1-methylpseudouracil.
  - 51. The compound of claim 47, wherein said nucleobase is 5-methoxyuracil.
  - 52. The compound of claim 47, wherein said nucleobase is cytosine.
  - 53. The compound of claim 47, wherein said nucleobase is 5-methylcytosine.
  - 54. The compound of claim 47, wherein said nucleobase is guanine.
  - 55. The compound of claim 47, wherein said nucleobase is adenine.
  - 56. The compound of claim 1, wherein said compound has the structure:
  - 57. The compound of claim 56, wherein said nucleobase is uracil.
  - 58. The compound of claim 56, wherein said nucleobase is pseudouracil.
  - 59. The compound of claim 56, wherein said nucleobase is 1-methylpseudouracil.
  - 60. The compound of claim 56, wherein said nucleobase is 5-methoxyuracil.
  - 61. The compound of claim 56, wherein said nucleobase is cytosine.
  - 62. The compound of claim 56, wherein said nucleobase is 5-methylcytosine.
  - 63. The compound of claim 56, wherein said nucleobase is guanine.
  - 64. The compound of claim 56, wherein said nucleobase is adenine.
  - 65. The compound of claim 1, wherein said compound has the structure:
  - 66. The compound of claim 65, wherein said nucleobase is uracil.
  - 67. The compound of claim 65, wherein said nucleobase is pseudouracil.
  - 68. The compound of claim 65, wherein said nucleobase is 1-methylpseudouracil.
  - 69. The compound of claim 65, wherein said nucleobase is 5-methoxyuracil.
  - 70. The compound of claim 65, wherein said nucleobase is cytosine.
  - 71. The compound of claim 65, wherein said nucleobase is 5-methylcytosine.
  - 72. The compound of claim 65, wherein said nucleobase is guanine.
  - 73. The compound of claim 65, wherein said nucleobase is adenine.
  - 74. The compound of claim 1, wherein said compound has the structure:
  - 75. The compound of claim 74, wherein said nucleobase is uracil.
  - 76. The compound of claim 74, wherein said nucleobase is pseudouracil.
  - 77. The compound of claim 74, wherein said nucleobase is 1-methylpseudouracil.
  - 78. The compound of claim 74, wherein said nucleobase is 5-methoxyuracil.
  - 79. The compound of claim 74, wherein said nucleobase is cytosine.
  - 80. The compound of claim 74, wherein said nucleobase is 5-methylcytosine.
  - 81. The compound of claim 74, wherein said nucleobase is guanine.
  - 82. The compound of claim 74, wherein said nucleobase is adenine.
  - 83. The compound of claim 1, wherein said compound has the structure:
  - 84. The compound of claim 83, wherein said nucleobase is uracil.
  - 85. The compound of claim 83, wherein said nucleobase is pseudouracil.
  - 86. The compound of claim 83, wherein said nucleobase is 1-methylpseudouracil.
  - 87. The compound of claim 83, wherein said nucleobase is 5-methoxyuracil.
  - 88. The compound of claim 83, wherein said nucleobase is cytosine.
  - 89. The compound of claim 83, wherein said nucleobase is 5-methylcytosine.
  - 90. The compound of claim 83, wherein said nucleobase is guanine.
  - 91. The compound of claim 83, wherein said nucleobase is adenine.
  - 92. The compound of claim 1, wherein said compound has the structure:
  - 93. The compound of claim 92, wherein said nucleobase is uracil.
  - 94. The compound of claim 92, wherein said nucleobase is pseudouracil.
  - 95. The compound of claim 92, wherein said nucleobase is 1-methylpseudouracil.
  - 96. The compound of claim 92, wherein said nucleobase is 5-methoxyuracil.
  - 97. The compound of claim 92, wherein said nucleobase is cytosine.
  - 98. The compound of claim 92, wherein said nucleobase is 5-methylcytosine.
  - 99. The compound of claim 92, wherein said nucleobase is guanine.
  - 100. The compound of claim 92, wherein said nucleobase is adenine.
  - 101. The compound of claim 1, wherein said compound has the structure:
  - 102. The compound of claim 101, wherein said nucleobase is uracil.
  - 103. The compound of claim 101, wherein said nucleobase is pseudouracil.
  - 104. The compound of claim 101, wherein said nucleobase is 1-methylpseudouracil.
  - 105. The compound of claim 101, wherein said nucleobase is 5-methoxyuracil.
  - 106. The compound of claim 101, wherein said nucleobase is cytosine.
  - 107. The compound of claim 101, wherein said nucleobase is 5-methylcytosine.
  - 108. The compound of claim 101, wherein said nucleobase is guanine.
  - 109. The compound of claim 101, wherein said nucleobase is adenine.
  - 110. The compound of claim 1, wherein said compound has the structure:
  - 111. The compound of claim 110, wherein said nucleobase is uracil.
  - 112. The compound of claim 110, wherein said nucleobase is pseudouracil.
  - 113. The compound of claim 110, wherein said nucleobase is 1-methylpseudouracil.
  - 114. The compound of claim 110, wherein said nucleobase is 5-methoxyuracil.
  - 115. The compound of claim 110, wherein said nucleobase is cytosine.
  - 116. The compound of claim 110, wherein said nucleobase is 5-methylcytosine.
  - 117. The compound of claim 110, wherein said nucleobase is guanine.
  - 118. The compound of claim 110, wherein said nucleobase is adenine.

119. A polynucleotide comprising at least one backbone moiety of Formula III:
- View Dependent Claims (120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241)
- - 120. The polynucleotide of claim 119, wherein said backbone moiety comprises:
  - 121. The polynucleotide of claim 120, wherein said nucleobase is uracil.
  - 122. The polynucleotide of claim 120, wherein said nucleobase is pseudouracil.
  - 123. The polynucleotide of claim 120, wherein said nucleobase is 1-methylpseudouracil.
  - 124. The polynucleotide of claim 120, wherein said nucleobase is 5-methoxyuracil.
  - 125. The polynucleotide of claim 120, wherein said nucleobase is cytosine.
  - 126. The polynucleotide of claim 120, wherein said nucleobase is 5-methylcytosine.
  - 127. The polynucleotide of claim 120, wherein said nucleobase is guanine.
  - 128. The polynucleotide of claim 120, wherein said nucleobase is adenine.
  - 129. The polynucleotide of claim 119, wherein said backbone moiety comprises:
  - 130. The polynucleotide of claim 129, wherein said nucleobase is uracil.
  - 131. The polynucleotide of claim 129, wherein said nucleobase is pseudouracil.
  - 132. The polynucleotide of claim 129, wherein said nucleobase is 1-methylpseudouracil.
  - 133. The polynucleotide of claim 129, wherein said nucleobase is 5-methoxyuracil.
  - 134. The polynucleotide of claim 129, wherein said nucleobase is cytosine.
  - 135. The polynucleotide of claim 129, wherein said nucleobase is 5-methylcytosine.
  - 136. The polynucleotide of claim 129, wherein said nucleobase is guanine.
  - 137. The polynucleotide of claim 129, wherein said nucleobase is adenine.
  - 138. The polynucleotide of claim 119, wherein said backbone moiety comprises:
  - 139. The polynucleotide of claim 138, wherein said nucleobase is uracil.
  - 140. The polynucleotide of claim 138, wherein said nucleobase is pseudouracil.
  - 141. The polynucleotide of claim 138, wherein said nucleobase is 1-methylpseudouracil.
  - 142. The polynucleotide of claim 138, wherein said nucleobase is 5-methoxyuracil.
  - 143. The polynucleotide of claim 138, wherein said nucleobase is cytosine.
  - 144. The polynucleotide of claim 138, wherein said nucleobase is 5-methylcytosine.
  - 145. The polynucleotide of claim 138, wherein said nucleobase is guanine.
  - 146. The polynucleotide of claim 138, wherein said nucleobase is adenine.
  - 147. The polynucleotide of claim 119, wherein said backbone moiety comprises:
  - 148. The polynucleotide of claim 147, wherein said nucleobase is uracil.
  - 149. The polynucleotide of claim 147, wherein said nucleobase is pseudouracil.
  - 150. The polynucleotide of claim 147, wherein said nucleobase is 1-methylpseudouracil.
  - 151. The polynucleotide of claim 147, wherein said nucleobase is 5-methoxyuracil.
  - 152. The polynucleotide of claim 147, wherein said nucleobase is cytosine.
  - 153. The polynucleotide of claim 147, wherein said nucleobase is 5-methylcytosine.
  - 154. The polynucleotide of claim 147, wherein said nucleobase is guanine.
  - 155. The polynucleotide of claim 147, wherein said nucleobase is adenine.
  - 156. The polynucleotide of claim 119, wherein said backbone moiety comprises:
  - 157. The polynucleotide of claim 156, wherein said nucleobase is uracil.
  - 158. The polynucleotide of claim 156, wherein said nucleobase is pseudouracil.
  - 159. The polynucleotide of claim 156, wherein said nucleobase is 1-methylpseudouracil.
  - 160. The polynucleotide of claim 156, wherein said nucleobase is 5-methoxyuracil.
  - 161. The polynucleotide of claim 156, wherein said nucleobase is cytosine.
  - 162. The polynucleotide of claim 156, wherein said nucleobase is 5-methylcytosine.
  - 163. The polynucleotide of claim 156, wherein said nucleobase is guanine.
  - 164. The polynucleotide of claim 156, wherein said nucleobase is adenine.
  - 165. The polynucleotide of claim 119, wherein said backbone moiety comprises:
  - 166. The polynucleotide of claim 165, wherein said nucleobase is uracil.
  - 167. The polynucleotide of claim 165, wherein said nucleobase is pseudouracil.
  - 168. The polynucleotide of claim 165, wherein said nucleobase is 1-methylpseudouracil.
  - 169. The polynucleotide of claim 165, wherein said nucleobase is 5-methoxyuracil.
  - 170. The polynucleotide of claim 165, wherein said nucleobase is cytosine.
  - 171. The polynucleotide of claim 165, wherein said nucleobase is 5-methylcytosine.
  - 172. The polynucleotide of claim 165, wherein said nucleobase is guanine.
  - 173. The polynucleotide of claim 165, wherein said nucleobase is adenine.
  - 174. The polynucleotide of claim 119, wherein said backbone moiety comprises:
  - 175. The polynucleotide of claim 174, wherein said nucleobase is uracil.
  - 176. The polynucleotide of claim 174, wherein said nucleobase is pseudouracil.
  - 177. The polynucleotide of claim 174, wherein said nucleobase is 1-methylpseudouracil.
  - 178. The polynucleotide of claim 174, wherein said nucleobase is 5-methoxyuracil.
  - 179. The polynucleotide of claim 174, wherein said nucleobase is cytosine.
  - 180. The polynucleotide of claim 174, wherein said nucleobase is 5-methylcytosine.
  - 181. The polynucleotide of claim 174, wherein said nucleobase is guanine.
  - 182. The polynucleotide of claim 174, wherein said nucleobase is adenine.
  - 183. The polynucleotide of claim 119, wherein said backbone moiety comprises:
  - 184. The polynucleotide of claim 183, wherein said nucleobase is uracil.
  - 185. The polynucleotide of claim 183, wherein said nucleobase is pseudouracil.
  - 186. The polynucleotide of claim 183, wherein said nucleobase is 1-methylpseudouracil.
  - 187. The polynucleotide of claim 183, wherein said nucleobase is 5-methoxyuracil.
  - 188. The polynucleotide of claim 183, wherein said nucleobase is cytosine.
  - 189. The polynucleotide of claim 183, wherein said nucleobase is 5-methylcytosine.
  - 190. The polynucleotide of claim 183, wherein said nucleobase is guanine.
  - 191. The polynucleotide of claim 183, wherein said nucleobase is adenine.
  - 192. The polynucleotide of claim 119, wherein said backbone moiety comprises:
  - 193. The polynucleotide of claim 192, wherein said nucleobase is uracil.
  - 194. The polynucleotide of claim 192, wherein said nucleobase is pseudouracil.
  - 195. The polynucleotide of claim 192, wherein said nucleobase is 1-methylpseudouracil.
  - 196. The polynucleotide of claim 192, wherein said nucleobase is 5-methoxyuracil.
  - 197. The polynucleotide of claim 192, wherein said nucleobase is cytosine.
  - 198. The polynucleotide of claim 192, wherein said nucleobase is 5-methylcytosine.
  - 199. The polynucleotide of claim 192, wherein said nucleobase is guanine.
  - 200. The polynucleotide of claim 192, wherein said nucleobase is adenine.
  - 201. The polynucleotide of claim 119, wherein said backbone moiety comprises:
  - 202. The polynucleotide of claim 201, wherein said nucleobase is uracil.
  - 203. The polynucleotide of claim 201, wherein said nucleobase is pseudouracil.
  - 204. The polynucleotide of claim 201, wherein said nucleobase is 1-methylpseudouracil.
  - 205. The polynucleotide of claim 201, wherein said nucleobase is 5-methoxyuracil.
  - 206. The polynucleotide of claim 201, wherein said nucleobase is cytosine.
  - 207. The polynucleotide of claim 201, wherein said nucleobase is 5-methylcytosine.
  - 208. The polynucleotide of claim 201, wherein said nucleobase is guanine.
  - 209. The polynucleotide of claim 201, wherein said nucleobase is adenine.
  - 210. The polynucleotide of claim 119, wherein said backbone moiety comprises:
  - 211. The polynucleotide of claim 210, wherein said nucleobase is uracil.
  - 212. The polynucleotide of claim 210, wherein said nucleobase is pseudouracil.
  - 213. The polynucleotide of claim 210, wherein said nucleobase is 1-methylpseudouracil.
  - 214. The polynucleotide of claim 210, wherein said nucleobase is 5-methoxyuracil.
  - 215. The polynucleotide of claim 210, wherein said nucleobase is cytosine.
  - 216. The polynucleotide of claim 210, wherein said nucleobase is 5-methylcytosine.
  - 217. The polynucleotide of claim 210, wherein said nucleobase is guanine.
  - 218. The polynucleotide of claim 210, wherein said nucleobase is adenine.
  - 219. The polynucleotide of claim 119, wherein said backbone moiety comprises:
  - 220. The polynucleotide of claim 219, wherein said nucleobase is uracil.
  - 221. The polynucleotide of claim 219, wherein said nucleobase is pseudouracil.
  - 222. The polynucleotide of claim 219, wherein said nucleobase is 1-methylpseudouracil.
  - 223. The polynucleotide of claim 219, wherein said nucleobase is 5-methoxyuracil.
  - 224. The polynucleotide of claim 219, wherein said nucleobase is cytosine.
  - 225. The polynucleotide of claim 219, wherein said nucleobase is 5-methylcytosine.
  - 226. The polynucleotide of claim 219, wherein said nucleobase is guanine.
  - 227. The polynucleotide of claim 219, wherein said nucleobase is adenine.
  - 228. The polynucleotide of claim 119, wherein said backbone moiety comprises:
  - 229. The polynucleotide of claim 228, wherein said nucleobase is uracil.
  - 230. The polynucleotide of claim 228, wherein said nucleobase is pseudouracil.
  - 231. The polynucleotide of claim 228, wherein said nucleobase is 1-methylpseudouracil.
  - 232. The polynucleotide of claim 228, wherein said nucleobase is 5-methoxyuracil.
  - 233. The polynucleotide of claim 228, wherein said nucleobase is cytosine.
  - 234. The polynucleotide of claim 228, wherein said nucleobase is 5-methylcytosine.
  - 235. The polynucleotide of claim 228, wherein said nucleobase is guanine.
  - 236. The polynucleotide of claim 228, wherein said nucleobase is adenine.
  - 237. The polynucleotide of any one of claims 119 to 236, further comprising:
    - (a) a 5′
      
      UTR comprising at least one Kozak sequence;
      
      (b) a 3′
      
      UTR; and
      
      (c) at least one 5′
      
      cap structure.
  - 238. The polynucleotide of claim 237, wherein at least one 5′
    - cap structure is Cap0, Cap1, ARCA, inosine, N1-methyl-guanosine, 2′
      
      -fluoro-guanosine, 7-deaza-guanosine, 8-oxo-guanosine, 2-amino-guanosine, LNA-guanosine, or 2-azido-guanosine.
  - 239. The polynucleotide of any one of claims 119 to 238, further comprising a poly-A tail.
  - 240. The polynucleotide of any one of claims 119 to 239, wherein said polynucleotide encodes a protein of interest.
  - 241. The polynucleotide of any one of claims 119 to 240, which is purified.

242. A compound of Formula IA:
- View Dependent Claims (243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360)
- - 243. The compound of claim 242, wherein, if n is 0, X is O, R¹, R², R⁴, R⁵, and R⁶are hydrogen, and Y⁵is O, then at least one of Y¹and Y⁴is optionally substituted amino, and, if m is 0, n is 1, Y¹is optionally substituted amino, Y²is optionally substituted C₁-C₆heteroalkyl, Y³is absent, Y⁷is O, X is O, and R¹, R², R⁴, R⁵, and R⁶are hydrogen, and R³is hydroxyl, then Y⁴is optionally substituted amino.
  - 244. The compound of claim 242, wherein said compound has the structure:
  - 245. The compound of claim 244, wherein said nucleobase is uracil.
  - 246. The compound of claim 244, wherein said nucleobase is pseudouracil.
  - 247. The compound of claim 244, wherein said nucleobase is 1-methylpseudouracil.
  - 248. The compound of claim 244, wherein said nucleobase is 5-methoxyuracil.
  - 249. The compound of claim 244, wherein said nucleobase is cytosine.
  - 250. The compound of claim 244, wherein said nucleobase is 5-methylcytosine.
  - 251. The compound of claim 244, wherein said nucleobase is guanine.
  - 252. The compound of claim 244, wherein said nucleobase is adenine.
  - 253. The compound of claim 242, wherein said compound has the structure:
  - 254. The compound of claim 253, wherein said nucleobase is uracil.
  - 255. The compound of claim 253, wherein said nucleobase is pseudouracil.
  - 256. The compound of claim 253, wherein said nucleobase is 1-methylpseudouracil.
  - 257. The compound of claim 253, wherein said nucleobase is 5-methoxyuracil.
  - 258. The compound of claim 253, wherein said nucleobase is cytosine.
  - 259. The compound of claim 253, wherein said nucleobase is 5-methylcytosine.
  - 260. The compound of claim 253, wherein said nucleobase is guanine.
  - 261. The compound of claim 253, wherein said nucleobase is adenine.
  - 262. The compound of claim 242, wherein said compound has the structure:
  - 263. The compound of claim 262, wherein said nucleobase is uracil.
  - 264. The compound of claim 262, wherein said nucleobase is pseudouracil.
  - 265. The compound of claim 262, wherein said nucleobase is 1-methylpseudouracil.
  - 266. The compound of claim 262, wherein said nucleobase is 5-methoxyuracil.
  - 267. The compound of claim 262, wherein said nucleobase is cytosine.
  - 268. The compound of claim 262, wherein said nucleobase is 5-methylcytosine.
  - 269. The compound of claim 262, wherein said nucleobase is guanine.
  - 270. The compound of claim 262, wherein said nucleobase is adenine.
  - 271. The compound of claim 242, wherein said compound has the structure:
  - 272. The compound of claim 271, wherein said nucleobase is uracil.
  - 273. The compound of claim 271, wherein said nucleobase is pseudouracil.
  - 274. The compound of claim 271, wherein said nucleobase is 1-methylpseudouracil.
  - 275. The compound of claim 271, wherein said nucleobase is 5-methoxyuracil.
  - 276. The compound of claim 271, wherein said nucleobase is cytosine.
  - 277. The compound of claim 271, wherein said nucleobase is 5-methylcytosine.
  - 278. The compound of claim 271, wherein said nucleobase is guanine.
  - 279. The compound of claim 271, wherein said nucleobase is adenine.
  - 280. The compound of claim 242, wherein said compound has the structure:
  - 281. The compound of claim 280, wherein said nucleobase is uracil.
  - 282. The compound of claim 280, wherein said nucleobase is pseudouracil.
  - 283. The compound of claim 280, wherein said nucleobase is 1-methylpseudouracil.
  - 284. The compound of claim 280, wherein said nucleobase is 5-methoxyuracil.
  - 285. The compound of claim 280, wherein said nucleobase is cytosine.
  - 286. The compound of claim 280, wherein said nucleobase is 5-methylcytosine.
  - 287. The compound of claim 280, wherein said nucleobase is guanine.
  - 288. The compound of claim 280, wherein said nucleobase is adenine.
  - 289. The compound of claim 242, wherein said compound has the structure:
  - 290. The compound of claim 289, wherein said nucleobase is uracil.
  - 291. The compound of claim 289, wherein said nucleobase is pseudouracil.
  - 292. The compound of claim 289, wherein said nucleobase is 1-methylpseudouracil.
  - 293. The compound of claim 289, wherein said nucleobase is 5-methoxyuracil.
  - 294. The compound of claim 289, wherein said nucleobase is cytosine.
  - 295. The compound of claim 289, wherein said nucleobase is 5-methylcytosine.
  - 296. The compound of claim 289, wherein said nucleobase is guanine.
  - 297. The compound of claim 289, wherein said nucleobase is adenine.
  - 298. The compound of claim 242, wherein said compound has the structure:
  - 299. The compound of claim 298, wherein said nucleobase is uracil.
  - 300. The compound of claim 298, wherein said nucleobase is pseudouracil.
  - 301. The compound of claim 298, wherein said nucleobase is 1-methylpseudouracil.
  - 302. The compound of claim 298, wherein said nucleobase is 5-methoxyuracil.
  - 303. The compound of claim 298, wherein said nucleobase is cytosine.
  - 304. The compound of claim 298, wherein said nucleobase is 5-methylcytosine.
  - 305. The compound of claim 298, wherein said nucleobase is guanine.
  - 306. The compound of claim 298, wherein said nucleobase is adenine.
  - 307. The compound of claim 242, wherein said compound has the structure:
  - 308. The compound of claim 307, wherein said nucleobase is uracil.
  - 309. The compound of claim 307, wherein said nucleobase is pseudouracil.
  - 310. The compound of claim 307, wherein said nucleobase is 1-methylpseudouracil.
  - 311. The compound of claim 307, wherein said nucleobase is 5-methoxyuracil.
  - 312. The compound of claim 307, wherein said nucleobase is cytosine.
  - 313. The compound of claim 307, wherein said nucleobase is 5-methylcytosine.
  - 314. The compound of claim 307, wherein said nucleobase is guanine.
  - 315. The compound of claim 307, wherein said nucleobase is adenine.
  - 316. The compound of claim 242, wherein said compound has the structure:
  - 317. The compound of claim 316, wherein said nucleobase is uracil.
  - 318. The compound of claim 316, wherein said nucleobase is pseudouracil.
  - 319. The compound of claim 316, wherein said nucleobase is 1-methylpseudouracil.
  - 320. The compound of claim 316, wherein said nucleobase is 5-methoxyuracil.
  - 321. The compound of claim 316, wherein said nucleobase is cytosine.
  - 322. The compound of claim 316, wherein said nucleobase is 5-methylcytosine.
  - 323. The compound of claim 316, wherein said nucleobase is guanine.
  - 324. The compound of claim 316, wherein said nucleobase is adenine.
  - 325. The compound of claim 242, wherein said compound has the structure:
  - 326. The compound of claim 325, wherein said nucleobase is uracil.
  - 327. The compound of claim 325, wherein said nucleobase is pseudouracil.
  - 328. The compound of claim 325, wherein said nucleobase is 1-methylpseudouracil.
  - 329. The compound of claim 325, wherein said nucleobase is 5-methoxyuracil.
  - 330. The compound of claim 325, wherein said nucleobase is cytosine.
  - 331. The compound of claim 325, wherein said nucleobase is 5-methylcytosine.
  - 332. The compound of claim 325, wherein said nucleobase is guanine.
  - 333. The compound of claim 325, wherein said nucleobase is adenine.
  - 334. The compound of claim 242, wherein said compound has the structure:
  - 335. The compound of claim 334, wherein said nucleobase is uracil.
  - 336. The compound of claim 334, wherein said nucleobase is pseudouracil.
  - 337. The compound of claim 334, wherein said nucleobase is 1-methylpseudouracil.
  - 338. The compound of claim 334, wherein said nucleobase is 5-methoxyuracil.
  - 339. The compound of claim 334, wherein said nucleobase is cytosine.
  - 340. The compound of claim 334, wherein said nucleobase is 5-methylcytosine.
  - 341. The compound of claim 334, wherein said nucleobase is guanine.
  - 342. The compound of claim 334, wherein said nucleobase is adenine.
  - 343. The compound of claim 242, wherein said compound has the structure:
  - 344. The compound of claim 343, wherein said nucleobase is uracil.
  - 345. The compound of claim 343, wherein said nucleobase is pseudouracil.
  - 346. The compound of claim 343, wherein said nucleobase is 1-methylpseudouracil.
  - 347. The compound of claim 343, wherein said nucleobase is 5-methoxyuracil.
  - 348. The compound of claim 343, wherein said nucleobase is cytosine.
  - 349. The compound of claim 343, wherein said nucleobase is 5-methylcytosine.
  - 350. The compound of claim 343, wherein said nucleobase is guanine.
  - 351. The compound of claim 343, wherein said nucleobase is adenine.
  - 352. The compound of claim 242, wherein said compound has the structure:
  - 353. The compound of claim 352, wherein said nucleobase is uracil.
  - 354. The compound of claim 352, wherein said nucleobase is pseudouracil.
  - 355. The compound of claim 352, wherein said nucleobase is 1-methylpseudouracil.
  - 356. The compound of claim 352, wherein said nucleobase is 5-methoxyuracil.
  - 357. The compound of claim 352, wherein said nucleobase is cytosine.
  - 358. The compound of claim 352, wherein said nucleobase is 5-methylcytosine.
  - 359. The compound of claim 352, wherein said nucleobase is guanine.
  - 360. The compound of claim 352, wherein said nucleobase is adenine.

361. A polynucleotide comprising at least one backbone moiety of Formula IIA:
- View Dependent Claims (362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483)
- - 362. The polynucleotide of claim 361, wherein said backbone moiety comprises:
  - 363. The polynucleotide of claim 362, wherein said nucleobase is uracil.
  - 364. The polynucleotide of claim 362, wherein said nucleobase is pseudouracil.
  - 365. The polynucleotide of claim 362, wherein said nucleobase is 1-methylpseudouracil.
  - 366. The polynucleotide of claim 362, wherein said nucleobase is 5-methoxyuracil.
  - 367. The polynucleotide of claim 362, wherein said nucleobase is cytosine.
  - 368. The polynucleotide of claim 362, wherein said nucleobase is 5-methylcytosine.
  - 369. The polynucleotide of claim 362, wherein said nucleobase is guanine.
  - 370. The polynucleotide of claim 362, wherein said nucleobase is adenine.
  - 371. The polynucleotide of claim 361, wherein said backbone moiety comprises:
  - 372. The polynucleotide of claim 371, wherein said nucleobase is uracil.
  - 373. The polynucleotide of claim 371, wherein said nucleobase is pseudouracil.
  - 374. The polynucleotide of claim 371, wherein said nucleobase is 1-methylpseudouracil.
  - 375. The polynucleotide of claim 371, wherein said nucleobase is 5-methoxyuracil.
  - 376. The polynucleotide of claim 371, wherein said nucleobase is cytosine.
  - 377. The polynucleotide of claim 371, wherein said nucleobase is 5-methylcytosine.
  - 378. The polynucleotide of claim 371, wherein said nucleobase is guanine.
  - 379. The polynucleotide of claim 371, wherein said nucleobase is adenine.
  - 380. The polynucleotide of claim 361, wherein said backbone moiety comprises:
  - 381. The polynucleotide of claim 380, wherein said nucleobase is uracil.
  - 382. The polynucleotide of claim 380, wherein said nucleobase is pseudouracil.
  - 383. The polynucleotide of claim 380, wherein said nucleobase is 1-methylpseudouracil.
  - 384. The polynucleotide of claim 380, wherein said nucleobase is 5-methoxyuracil.
  - 385. The polynucleotide of claim 380, wherein said nucleobase is cytosine.
  - 386. The polynucleotide of claim 380, wherein said nucleobase is 5-methylcytosine.
  - 387. The polynucleotide of claim 380, wherein said nucleobase is guanine.
  - 388. The polynucleotide of claim 380, wherein said nucleobase is adenine.
  - 389. The polynucleotide of claim 361, wherein said backbone moiety comprises:
  - 390. The polynucleotide of claim 389, wherein said nucleobase is uracil.
  - 391. The polynucleotide of claim 389, wherein said nucleobase is pseudouracil.
  - 392. The polynucleotide of claim 389, wherein said nucleobase is 1-methylpseudouracil.
  - 393. The polynucleotide of claim 389, wherein said nucleobase is 5-methoxyuracil.
  - 394. The polynucleotide of claim 389, wherein said nucleobase is cytosine.
  - 395. The polynucleotide of claim 389, wherein said nucleobase is 5-methylcytosine.
  - 396. The polynucleotide of claim 389, wherein said nucleobase is guanine.
  - 397. The polynucleotide of claim 389, wherein said nucleobase is adenine.
  - 398. The polynucleotide of claim 361, wherein said backbone moiety comprises:
  - 399. The polynucleotide of claim 398, wherein said nucleobase is uracil.
  - 400. The polynucleotide of claim 398, wherein said nucleobase is pseudouracil.
  - 401. The polynucleotide of claim 398, wherein said nucleobase is 1-methylpseudouracil.
  - 402. The polynucleotide of claim 398, wherein said nucleobase is 5-methoxyuracil.
  - 403. The polynucleotide of claim 398, wherein said nucleobase is cytosine.
  - 404. The polynucleotide of claim 398, wherein said nucleobase is 5-methylcytosine.
  - 405. The polynucleotide of claim 398, wherein said nucleobase is guanine.
  - 406. The polynucleotide of claim 398, wherein said nucleobase is adenine.
  - 407. The polynucleotide of claim 361, wherein said backbone moiety comprises:
  - 408. The polynucleotide of claim 407, wherein said nucleobase is uracil.
  - 409. The polynucleotide of claim 407, wherein said nucleobase is pseudouracil.
  - 410. The polynucleotide of claim 407, wherein said nucleobase is 1-methylpseudouracil.
  - 411. The polynucleotide of claim 407, wherein said nucleobase is 5-methoxyuracil.
  - 412. The polynucleotide of claim 407, wherein said nucleobase is cytosine.
  - 413. The polynucleotide of claim 407, wherein said nucleobase is 5-methylcytosine.
  - 414. The polynucleotide of claim 407, wherein said nucleobase is guanine.
  - 415. The polynucleotide of claim 407, wherein said nucleobase is adenine.
  - 416. The polynucleotide of claim 361, wherein said backbone moiety comprises:
  - 417. The polynucleotide of claim 416, wherein said nucleobase is uracil.
  - 418. The polynucleotide of claim 416, wherein said nucleobase is pseudouracil.
  - 419. The polynucleotide of claim 416, wherein said nucleobase is 1-methylpseudouracil.
  - 420. The polynucleotide of claim 416, wherein said nucleobase is 5-methoxyuracil.
  - 421. The polynucleotide of claim 416, wherein said nucleobase is cytosine.
  - 422. The polynucleotide of claim 416, wherein said nucleobase is 5-methylcytosine.
  - 423. The polynucleotide of claim 416, wherein said nucleobase is guanine.
  - 424. The polynucleotide of claim 416, wherein said nucleobase is adenine.
  - 425. The polynucleotide of claim 361, wherein said backbone moiety comprises:
  - 426. The polynucleotide of claim 425, wherein said nucleobase is uracil.
  - 427. The polynucleotide of claim 425, wherein said nucleobase is pseudouracil.
  - 428. The polynucleotide of claim 425, wherein said nucleobase is 1-methylpseudouracil.
  - 429. The polynucleotide of claim 425, wherein said nucleobase is 5-methoxyuracil.
  - 430. The polynucleotide of claim 425, wherein said nucleobase is cytosine.
  - 431. The polynucleotide of claim 425, wherein said nucleobase is 5-methylcytosine.
  - 432. The polynucleotide of claim 425, wherein said nucleobase is guanine.
  - 433. The polynucleotide of claim 425, wherein said nucleobase is adenine.
  - 434. The polynucleotide of claim 361, wherein said backbone moiety comprises:
  - 435. The polynucleotide of claim 434, wherein said nucleobase is uracil.
  - 436. The polynucleotide of claim 434, wherein said nucleobase is pseudouracil.
  - 437. The polynucleotide of claim 434, wherein said nucleobase is 1-methylpseudouracil.
  - 438. The polynucleotide of claim 434, wherein said nucleobase is 5-methoxyuracil.
  - 439. The polynucleotide of claim 434, wherein said nucleobase is cytosine.
  - 440. The polynucleotide of claim 434, wherein said nucleobase is 5-methylcytosine.
  - 441. The polynucleotide of claim 434, wherein said nucleobase is guanine.
  - 442. The polynucleotide of claim 434, wherein said nucleobase is adenine.
  - 443. The polynucleotide of claim 361, wherein said backbone moiety comprises:
  - 444. The polynucleotide of claim 443, wherein said nucleobase is uracil.
  - 445. The polynucleotide of claim 443, wherein said nucleobase is pseudouracil.
  - 446. The polynucleotide of claim 443, wherein said nucleobase is 1-methylpseudouracil.
  - 447. The polynucleotide of claim 443, wherein said nucleobase is 5-methoxyuracil.
  - 448. The polynucleotide of claim 443, wherein said nucleobase is cytosine.
  - 449. The polynucleotide of claim 443, wherein said nucleobase is 5-methylcytosine.
  - 450. The polynucleotide of claim 443, wherein said nucleobase is guanine.
  - 451. The polynucleotide of claim 443, wherein said nucleobase is adenine.
  - 452. The polynucleotide of claim 361, wherein said backbone moiety comprises:
  - 453. The polynucleotide of claim 452, wherein said nucleobase is uracil.
  - 454. The polynucleotide of claim 452, wherein said nucleobase is pseudouracil.
  - 455. The polynucleotide of claim 452, wherein said nucleobase is 1-methylpseudouracil.
  - 456. The polynucleotide of claim 452, wherein said nucleobase is 5-methoxyuracil.
  - 457. The polynucleotide of claim 452, wherein said nucleobase is cytosine.
  - 458. The polynucleotide of claim 452, wherein said nucleobase is 5-methylcytosine.
  - 459. The polynucleotide of claim 452, wherein said nucleobase is guanine.
  - 460. The polynucleotide of claim 452, wherein said nucleobase is adenine.
  - 461. The polynucleotide of claim 361, wherein said backbone moiety comprises:
  - 462. The polynucleotide of claim 461, wherein said nucleobase is uracil.
  - 463. The polynucleotide of claim 461, wherein said nucleobase is pseudouracil.
  - 464. The polynucleotide of claim 461, wherein said nucleobase is 1-methylpseudouracil.
  - 465. The polynucleotide of claim 461, wherein said nucleobase is 5-methoxyuracil.
  - 466. The polynucleotide of claim 461, wherein said nucleobase is cytosine.
  - 467. The polynucleotide of claim 461, wherein said nucleobase is 5-methylcytosine.
  - 468. The polynucleotide of claim 461, wherein said nucleobase is guanine.
  - 469. The polynucleotide of claim 461, wherein said nucleobase is adenine.
  - 470. The polynucleotide of claim 361, wherein said backbone moiety comprises:
  - 471. The polynucleotide of claim 470, wherein said nucleobase is uracil.
  - 472. The polynucleotide of claim 470, wherein said nucleobase is pseudouracil.
  - 473. The polynucleotide of claim 470, wherein said nucleobase is 1-methylpseudouracil.
  - 474. The polynucleotide of claim 470, wherein said nucleobase is 5-methoxyuracil.
  - 475. The polynucleotide of claim 470, wherein said nucleobase is cytosine.
  - 476. The polynucleotide of claim 470, wherein said nucleobase is 5-methylcytosine.
  - 477. The polynucleotide of claim 470, wherein said nucleobase is guanine.
  - 478. The polynucleotide of claim 470, wherein said nucleobase is adenine.
  - 479. The polynucleotide of any one of claims 361 to 478, further comprising:
    - (a) a 5′
      
      UTR comprising at least one Kozak sequence;
      
      (b) a 3′
      
      UTR; and
      
      (c) at least one 5′
      
      cap structure.
  - 480. The polynucleotide of claim 479, wherein at least one 5′
    - cap structure is Cap0, Cap1, ARCA, inosine, N1-methyl-guanosine, 2′
      
      -fluoro-guanosine, 7-deaza-guanosine, 8-oxo-guanosine, 2-amino-guanosine, LNA-guanosine, or 2-azido-guanosine.
  - 481. The polynucleotide of any one of claims 361 to 480, further comprising a poly-A tail.
  - 482. The polynucleotide of any one of claims 479 to 481, wherein said polynucleotide encodes a protein of interest.
  - 483. The polynucleotide of any one of claims 361 to 482, which is purified.

Specification

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Litigation Campaign Assessment

Current Assignee
Moderna TX, Inc. (Moderna, Inc.)
Original Assignee
Moderna Therapeutics, Inc. (Moderna, Inc.)
Inventors
FRALEY, Andrew W., ROY, Atanu, STANTON, Matthew

Granted Patent

US 10,385,088 B2
Time in Patent Office

Days
Field of Search
US Class Current

1/1
CPC Class Codes

C07H 19/067   with ribosyl as the sacchar...

C07H 19/10   with the saccharide radical...

C07H 19/167   with ribosyl as the sacchar...

C07H 19/20   with the saccharide radical...

C07H 21/02   with ribosyl as saccharide ...

C07K 14/525   Tumour necrosis factor [TNF]

C07K 14/535   Granulocyte CSF; Granulocyt...

C07K 14/565   IFN-beta

POLYNUCLEOTIDE MOLECULES AND USES THEREOF

First Claim

4 Assignments

0 Petitions

Accused Products

Abstract

91 Citations

483 Claims

Specification

Solutions

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POLYNUCLEOTIDE MOLECULES AND USES THEREOF

First Claim

4 Assignments

Subscription Required

Subscription Required

0 Petitions

Subscription Required

Accused Products

Subscription Required

Abstract

91 Citations

483 Claims

Specification

Subscription Required

Solutions

Use Cases

Quick Links