US2005169888A1PendingUtilityA1
Methods related to immunostimulatory nucleic acid-induced interferon
Est. expirySep 27, 2019(expired)· nominal 20-yr term from priority
A61P 31/20A61P 31/14C12N 2501/056C12N 2501/23A61K 38/21C12N 2501/22A61P 35/00A61P 31/18A61K 2039/55561A61P 31/22C12N 15/117A61K 40/4252A61K 40/4217A61K 40/421A61K 40/10C12N 5/0639
56
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
Methods and compositions are provided for extending the clinical utility of IFN-α in the treatment of a variety of viral and proliferative disorders. Among other aspects, the invention provides methods which increase the efficacy of IFN-α treatment and reduce IFN-α treatment-related side effects. In addition, methods are provided for supporting the survival and for activating natural interferon producing cells (IPCs) in vitro without exogenous IL-3 or GM-CSF. The invention is based on the discovery that certain CpG and non-CpG ISNAs promote survival and stimulation of IPCs.
Claims
exact text as granted — not AI-modified1 - 46 . (canceled)
47 . A method of treating a subject to activate interferon-producing cells (IPCs) of the subject comprising
isolating IPCs from a subject in need of such treatment, culturing the IPCs in vitro, contacting the IPCs in vitro with an effective amount of an isolated immunostimulatory nucleic acid, and returning the contacted IPCs to the subject.
48 . The method of claim 47 , further comprising contacting the IPCs in vitro with a growth factor.
49 . The method of claim 47 , further comprising contacting the IPCs in vitro with IL-3.
50 . The method of claim 47 , further comprising contacting the IPCs in vitro with GM-CSF.
51 . The method of claim 47 , wherein the IPCs are cultured in vitro in the absence of IL-3.
52 . The method of claim 47 , wherein the IPCs are cultured in vitro in the absence of GM-CSF.
53 . The method of claim 47 , wherein the immunostimulatory nucleic acid is modified.
54 . The method of claim 47 , wherein the immunostimulatory nucleic acid comprises a backbone with at least one nuclease-resistant intemucleotide linkage selected from the group consisting of: phosphorothioate, phosphorodithioate, methylphosphonate, and peptide.
55 . The method of claim 47 , wherein the immunostimulatory nucleic acid comprises at least one nucleotide analog or derivative.
56 . The method of claim 47 , wherein the immunostimulatory nucleic acid is not a palindrome.
57 . The method of claim 47 , wherein the immunostimulatory nucleic acid is a CpG nucleic acid.
58 . The method of claim 47 , wherein the immunostimulatory nucleic acid is a non-CpG nucleic acid.
59 . The method of claim 58 , wherein the non-CpG immunostimulatory nucleic acid is a T-rich nucleic acid.
60 . The method of claim 58 , wherein the non-CpG immunostimulatory nucleic acid is a poly-G nucleic acid.
61 . The method of claim 47 , wherein the immunostimulatory nucleic acid is any combination of at least two nucleic acids selected from the group consisting of: CpG nucleic acids, T-rich nucleic acids, and poly-G nucleic acids.
62 . The method of claim 47 , wherein the immunostimulatory nucleic acid is between 8 and 100 nucleotides in length.
63 . The method of claim 47 , wherein the immunostimulatory nucleic acid is between 12 and 40 nucleotides in length.
64 . The method of claim 47 , wherein the immunostimulatory nucleic acid has a sequence selected from the group consisting of
ggGGTCAACGTTGAgggggG
ODN 1585
SEQ ID NO:1
tcgtcgttttgtcgttttgtcgtt
ODN 2022
SEQ ID NO:2
ggggtcgtcgttttgggggg
ODN 2184
SEQ ID NO:3
tcgtcgttttgtcgttttgggggg
ODN 2185
SEQ ID NO:4
ggggtcgacgtcgagggggg
ODN 2192
SEQ ID NO:5
ggggtcatcgatgagggggg
ODN 2204
SEQ ID NO:6
ggGGGACGATCGTCgggggG
ODN 2216
SEQ ID NO:7
gggggtcgtacgacgggggg
ODN 2217
SEQ ID NO:8
ggGGGACGATATCGTCgggggG
ODN 2245
SEQ ID NO:9
ggGGGACGACGTCGTCgggggG
ODN 2246
SEQ ID NO:10
ggGGGACGAGCTCGTCgggggG
ODN 2247
SEQ ID NO:11
ggGGGACGTACGTCgggggG
ODN 2248
SEQ ID NO:12
ggGGGACGATCGTTGggggG
ODN 2252
SEQ ID NO:13
ggGGAACGATCGTCgggggG
ODN 2253
SEQ ID NO:14
ggGGGGACGATCGTCgggggG
ODN 2254
SEQ ID NO:15
ggGGGACGATCGTCGgggggG
ODN 2255
SEQ ID NO:16
ggGGGTCATCGATGAgggggG
ODN 2260
SEQ ID NO:17
ggGGTCGTCGACGAgggggG
ODN 2293
SEQ ID NO:18
ggGGTCGTTCGAACGAgggggG
ODN 2294
SEQ ID NO:19
ggGGACGTTCGAACGTgggggG
ODN 2295
SEQ ID NO:20
ggGGAACGACGTCGTTgggggG
ODN 2297
SEQ ID NO:21
ggGGAACGTACGTCgggggG
ODN 2298
SEQ ID NO:22
ggGGAACGTACGTACGTTgggggG
ODN 2299
SEQ ID NO:23
ggGGTCACCGGTGAgggggG
ODN 2300
SEQ ID NO:24
ggGGTCGACGTACGTCGAgggggG
ODN 2301
SEQ ID NO:25
ggGGACCGGTACCGGTgggggG
ODN 2302
SEQ ID NO:26
ggGTCGACGTCGAgggggG
ODN 2303
SEQ ID NO:27
ggGGTCGACGTCGagggg
ODN 2304
SEQ ID NO:28
ggGGAACGTTAACGTTgggggG
ODN 2305
SEQ ID NO:29
ggGGACGTCGACGTggggG
ODN 2306
SEQ ID NO:30
ggGGGTCGTTCGTTgggggG
ODN 2311
SEQ ID NO:31
ggGACGATCGTCGgggggG
ODN 2328
SEQ ID NO:32
ggGTCGTCGACGAggggggG
ODN 2329
SEQ ID NO:33
ggTCGTCGACGAGgggggG
ODN 2330
SEQ ID NO:34
ggGGACGATCGTCGgggggG
ODN 2332
SEQ ID NO:35
ggGGTCGACGTCGACGTCGAGgggggG,
ODN 2334
SEQ ID NO:36
and
ggGGACGACGTCGTGgggggG,
ODN 2336
SEQ ID NO:37
wherein each lower case letter represents phosphorothioate linkage and each upper case letter indicates phosphodiester linkage.
65 - 121 . (canceled)
122 . A method of enhancing efficacy of IFN-α treatment in a subject in need of such treatment, comprising
administering to a subject in need of such treatment an amount of a pharmaceutical composition comprising IFN-α effective for treating a condition of the subject; isolating natural interferon-producing cells (IPCs) from a donor; contacting the isolated IPCs ex vivo with an amount of a pharmaceutical composition comprising an immunostimulatory nucleic acid effective for inducing the IPCs to release IFN-α; and administering the contacted cells to the subject.
123 . The method of claim 122 , wherein the donor is the subject.
124 . The method of claim 122 further comprising contacting the isolated IPCs with an antigen.
125 . The method of claim 122 , wherein the administering the contacted cells comprises local injection.
126 . The method of claim 125 , wherein the local injection is via a blood vessel supplying a target tissue.
127 . The method of claim 126 , wherein the blood vessel is selected from the group consisting of a hepatic artery, a portal vein, a celiac artery, and a splenic artery.
128 . The method of claim 122 , wherein the immunostimulatory nucleic acid is modified.
129 . The method of claim 122 , wherein the immunostimulatory nucleic acid comprises a backbone with at least one nuclease-resistant intemucleotide linkage selected from the group consisting of: phosphorothioate, phosphorodithioate, methylphosphonate, and peptide.
130 . The method of claim 122 , wherein the immunostimulatory nucleic acid comprises at least one nucleotide analog or derivative.
131 . The method of claim 122 , wherein the immunostimulatory nucleic acid is not a palindrome.
132 . The method of claim 122 , wherein the immunostimulatory nucleic acid is a CpG nucleic acid.
133 . The method of claim 122 , wherein the immunostimulatory nucleic acid is a non-CpG nucleic acid.
134 . The method of claim 133 , wherein the non-CpG immunostimulatory nucleic acid is a T-rich nucleic acid.
135 . The method of claim 133 , wherein the non-CpG immunostimulatory nucleic acid is a poly-G nucleic acid.
136 . The method of claim 122 , wherein the immunostimulatory nucleic acid is any combination of at least two nucleic acids selected from the group consisting of: CpG nucleic acids, T-rich nucleic acids, and poly-G nucleic acids.
137 . The method of claim 122 , wherein the immunostimulatory nucleic acid is between 8 and 100 nucleotides in length.
138 . The method of claim 122 , wherein the immunostimulatory nucleic acid is between 12 and 40 nucleotides in length.
139 . The method of claim 122 , wherein the immunostimulatory nucleic acid has a sequence selected from the group consisting of
ggGGTCAACGTTGAgggggG
ODN 1585
SEQ ID NO:1
tcgtcgttttgtcgttttgtcgtt
ODN 2022
SEQ ID NO:2
ggggtcgtcgttttgggggg
ODN 2184
SEQ ID NO:3
tcgtcgttttgtcgttttgggggg
ODN 2185
SEQ ID NO:4
ggggtcgacgtcgagggggg
ODN 2192
SEQ ID NO:5
ggggtcatcgatgagggggg
ODN 2204
SEQ ID NO:6
ggGGGACGATCGTCgggggG
ODN 2216
SEQ ID NO:7
gggggtcgtacgacgggggg
ODN 2217
SEQ ID NO:8
ggGGGACGATATCGTCgggggG
ODN 2245
SEQ ID NO:9
ggGGGACGACGTCGTCgggggG
ODN 2246
SEQ ID NO:10
ggGGGACGAGCTCGTCgggggG
ODN 2247
SEQ ID NO:11
ggGGGACGTACGTCgggggG
ODN 2248
SEQ ID NO:12
ggGGGACGATCGTTGggggG
ODN 2252
SEQ ID NO:13
ggGGAACGATCGTCgggggG
ODN 2253
SEQ ID NO:14
ggGGGGACGATCGTCgggggG
ODN 2254
SEQ ID NO:15
ggGGGACGATCGTCGgggggG
ODN 2255
SEQ ID NO:16
ggGGGTCATCGATGAgggggG
ODN 2260
SEQ ID NO:17
ggGGTCGTCGACGAgggggG
ODN 2293
SEQ ID NO:18
ggGGTCGTTCGAACGAgggggG
ODN 2294
SEQ ID NO:19
ggGGACGTTCGAACGTgggggG
ODN 2295
SEQ ID NO:20
ggGGAACGACGTCGTTgggggG
ODN 2297
SEQ ID NO:21
ggGGAACGTACGTCgggggG
ODN 2298
SEQ ID NO:22
ggGGAACGTACGTACGTTgggggG
ODN 2299
SEQ ID NO:23
ggGGTCACCGGTGAgggggG
ODN 2300
SEQ ID NO:24
ggGGTCGACGTACGTCGAgggggG
ODN 2301
SEQ ID NO:25
ggGGACCGGTACCGGTgggggG
ODN 2302
SEQ ID NO:26
ggGTCGACGTCGAgggggG
ODN 2303
SEQ ID NO:27
ggGGTCGACGTCGagggg
ODN 2304
SEQ ID NO:28
ggGGAACGTTAACGTTgggggG
ODN 2305
SEQ ID NO:29
ggGGACGTCGACGTggggG
ODN 2306
SEQ ID NO:30
ggGGGTCGTTCGTTgggggG
ODN 2311
SEQ ID NO:31
ggGACGATCGTCGgggggG
ODN 2328
SEQ ID NO:32
ggGTCGTCGACGAggggggG
ODN 2329
SEQ ID NO:33
ggTCGTCGACGAGgggggG
ODN 2330
SEQ ID NO:34
ggGGACGATCGTCGgggggG
ODN 2332
SEQ ID NO:35
ggGGTCGACGTCGACGTCGAGgggggG,
ODN 2334
SEQ ID NO:36
and
ggGGACGACGTCGTGgggggG,
ODN 2336
SEQ ID NO:37
wherein each lower case letter represents phosphorothioate linkage and each upper case letter indicates phosphodiester linkage.
140 . The method of claim 122 , wherein the subject has a condition selected from the group consisting of a proliferative disorder and a viral infection.
141 . The method of claim 122 , wherein the subject has a proliferative disorder selected from the group consisting of: hairy cell leukemia, chronic myelogenous leukemia, cutaneous T-cell leukemia, multiple myeloma, follicular lymphoma, malignant melanoma, squamous cell carcinoma, AIDS-related Kaposi's sarcoma, renal cell carcinoma, prostate carcinoma, bladder cell carcinoma, cervical dysplasia, and colon carcinoma.
142 . The method of claim 122 , wherein the subject has a viral infection selected from the group consisting of: hepatitis B, hepatitis C, condyloma acuminatum, human immunodeficiency virus, herpes, cytomegalovirus, Epstein-Barr virus, and papillomavirus.
143 - 203 . (canceled)Join the waitlist — get patent alerts
Track US2005169888A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.