Compositions and methods for oligonucleotide formulations
First Claim
Patent Images
1. An immunostimulatory oligonucleotide comprising:
- a 5′
TLR activation domain and at least two palindromic regions, one palindromic region being a 5′
palindromic region of at least 6 nucleotides in length and connected to a 3′
palindromic region of at least 8 nucleotides in length either directly or through a spacer, wherein the oligonucleotide includes at least one YpR dinucleotide, and wherein the oligonucleotide is not T*C_G*T*C_G*A*C_G*T*T*C_G*G*C*G*C_G*C*G*C*C*G (SEQ ID NO;
335).
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Abstract
The present invention relates generally to immunostimulatory nucleic acids, compositions thereof and methods of using the immunostimulatory nucleic acids. In particular the invention relates to palindrome-containing immunostimulatory nucleic acids and the use of these nucleic acids in treating disease.
231 Citations
215 Claims
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1. An immunostimulatory oligonucleotide comprising:
a 5′
TLR activation domain and at least two palindromic regions, one palindromic region being a 5′
palindromic region of at least 6 nucleotides in length and connected to a 3′
palindromic region of at least 8 nucleotides in length either directly or through a spacer, wherein the oligonucleotide includes at least one YpR dinucleotide, and wherein the oligonucleotide is not T*C_G*T*C_G*A*C_G*T*T*C_G*G*C*G*C_G*C*G*C*C*G (SEQ ID NO;
335).- 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, 193, 198, 200, 204, 213, 214)
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56. An immunostimulatory oligonucleotide comprising:
a 5′
TLR activation domain and at least two complementarity-containing regions, a 5′ and
a 3′
complementarity-containing region, each complementarity-containing region being at least 8 nucleotides in length and connected to one another either directly or through a spacer, wherein the oligonucleotide includes at least one pyrimidine-purine (YpR) dinucleotide, and wherein at least one of the complementarity-containing regions is not a perfect palindrome.
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57-148. -148. (canceled)
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149. A composition comprising:
a mixture of duplex forming oligonucleotides formulated in a low salt buffer and including a solute. - View Dependent Claims (150, 151, 160, 161, 163)
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152-159. -159. (canceled)
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162. (canceled)
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164-169. -169. (canceled)
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170. A method for preparing a substantially homogenous mixture of oligonucleotides, comprising:
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identifying duplex forming immunostimulatory oligonucleotides, formulating the duplex forming immunostimulatory oligonucleotides in a low salt buffer and a solute to produce a substantially homogenous mixture of oligonucleotides.
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171. A composition comprising a mixture of at least two different duplex forming immunostimulatory oligonucleotides, wherein the at least two different duplex forming immunostimulatory oligonucleotides each have a 5′
- TLR activation domain including an unmethylated CpG dinucleotide and a 3′
duplex forming sequence of at least 8 nucleotides in length, wherein the 3′
duplex forming sequence of each of the at least two different duplex forming immunostimulatory oligonucleotides are complementary to one another, and wherein the at least two different duplex forming immunostimulatory oligonucleotides are 11-100 nucleotides in length.
- TLR activation domain including an unmethylated CpG dinucleotide and a 3′
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172-192. -192. (canceled)
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194-197. -197. (canceled)
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199. (canceled)
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201-203. -203. (canceled)
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205-212. -212. (canceled)
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215-217. -217. (canceled)
Specification