US2003049266A1PendingUtilityA1

Immunomodulatory polynucleotides and methods of using the same

47
Priority: Dec 27, 2000Filed: Dec 27, 2001Published: Mar 13, 2003
Est. expiryDec 27, 2020(expired)· nominal 20-yr term from priority
Inventors:Karen L. FearonDino Dina
A61P 37/08A61P 31/00A61P 33/06A61P 31/16A61P 33/02A61P 31/04A61P 33/12A61P 31/12A61P 33/00A61P 37/02A61P 35/00A61P 31/22A61P 43/00A61P 11/00A61P 11/06C12N 2310/315A61P 21/00C12N 2310/18C12N 15/117A61K 2039/55561C12N 2310/334C12N 15/00C12N 15/10Y02A50/30
47
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

The invention provides immunomodulatory polynucleotides and methods for immunomodulation of individuals using the immunomodulatory polynucleotides.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . An immunomodulatory polynucleotide comprising an immunostimulatory sequence (ISS), wherein the ISS comprises the formula:  
       5′-X 1 X 2  A X 3  C G X 4  T C G-3′ (SEQ ID NO: 62)  wherein X 1  is T, G, C or Z, wherein Z is 5-bromocytosine;    wherein X 2  is T, G, A or U;    wherein X 3  is T, A or C;    wherein X 4  is T, G or U; and    wherein the ISS is not 5′-TGAACGTTCG-3′ (SEQ ID NO: 63) or 5′-GGAACGTTCG-3′ (SEQ ID NO: 64).    
     
     
         2 . An immunomodulatory polynucleotide according to  claim 1 , wherein the ISS is selected from the group consisting of TGAACGUTCG (SEQ ID NO: 67), TGACCGTTCG (SEQ ID NO: 68), TGATCGGTCG (SEQ ID NO: 69), TGATCGTTCG (SEQ ID NO: 70), TGAACGGTCG (SEQ ID NO: 71), GTAACGTTCG (SEQ ID NO: 72), GTATCGGTCG (SEQ ID NO: 73), GTACCGTTCG (SEQ ID NO: 74), GAACCGTTCG (SEQ ID NO: 75), ZGACCGTTCG (SEQ ID NO: 76), wherein Z is 5-bromocytosine, CGAACGTTCG (SEQ ID NO: 77), CGACCGTTCG (SEQ ID NO: 78), ZGAACGTTCG (SEQ ID NO: 79), wherein Z is 5-bromocytosine, TTAACGUTCG (SEQ ID NO: 82), TUAACGUTCG (SEQ ID NO: 81) and TTAACGTTCG (SEQ ID NO: 80).  
     
     
         3 . An immunomodulatory polynucleotide according to  claim 2 , wherein the ISS is selected from the group consisting of TGAACGUTCG (SEQ ID NO: 67), GAACCGTTCG (SEQ ID NO: 75) and CGAACGTTCG (SEQ ID NO: 77).  
     
     
         4 . An immunomodulatory polynucleotide according to  claim 3  comprising a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 18, SEQ ID NO: 19 and SEQ ID NO: 132.  
     
     
         5 . An immunomodulatory polynucleotide comprising an immunostimulatory sequence (ISS), wherein the ISS comprises the formula:  
       5′-X 1 X 2  A X 3  Z G X 4  T C G-3′ (SEQ ID NO: 65)  wherein Z is 5-bromocytosine;    wherein X 1  is T, G, C or Z, wherein Z is 5-bromocytosine;    wherein X 2  is T, G, A or U;    wherein X 3  is T, A or C;    wherein 4 is T, G or U; and    wherein the ISS is not 5′-TGAAZGTTCG-3′ (SEQ ID NO: 66), wherein Z is 5-bromocytosine.    
     
     
         6 . An immunomodulatory polynucleotide according to  claim 5 , wherein the ISS is selected from the group consisting of TGAAZGUTCG, (SEQ ID NO: 83) TGACZGTTCG (SEQ ID NO: 84), TGATZGGTCG (SEQ ID NO: 85), GTATZGGTCG (SEQ ID NO: 86), GTACZGTTCG (SEQ ID NO: 87), GAACZGTTCG (SEQ ID NO: 88), GAAAZGUTCG (SEQ ID NO: 89), ZGACZGTTCG (SEQ ID NO: 90), CGAAZGTTCG (SEQ ID NO: 91), ZGAAZGTTCG (SEQ ID NO: 92), ZGAAZGUTCG (SEQ ID NO: 93), TTAAZGUTCG (SEQ ID NO: 94), TUAAZGUTCG (SEQ ID NO: 95) and TTAAZGTTCG (SEQ ID NO: 96), wherein Z is 5-bromocytosine.  
     
     
         7 . An immunomodulatory polynucleotide according to  claim 6 , wherein the ISS is selected from the group consisting of ZGAAZGUTCG (SEQ ID NO: 93) and GAAAZGUTCG (SEQ ID NO: 89), wherein Z is 5-bromocytosine.  
     
     
         8 . An immunomodulatory polynucleotide according to  claim 7  comprising a sequence selected from the group consisting of SEQ ID NO: 35 and SEQ ID NO: 36.  
     
     
         9 . An immunomodulatory polynucleotide according to  claim 1  or  claim 5 , wherein the immunomodulatory polynucleotide further comprises at least one TCG sequence.  
     
     
         10 . An immunomodulatory polynucleotide according to  claim 9 , wherein the TCG sequence is adjacent to the 5′ end of the ISS.  
     
     
         11 . An immunomodulatory polynucleotide according to  claim 1  or  claim 5 , wherein the immunomodulatory polynucleotide further comprises a TCGA sequence.  
     
     
         12 . An immunomodulatory polynucleotide according to  claim 1  or  claim 5 , wherein the immunomodulatory polynucleotide further comprises at least one T, 5-bromocytosine, G sequence.  
     
     
         13 . An immunomodulatory polynucleotide according to  claim 12 , wherein the T, 5-bromocytosine, G sequence is adjacent to the 5′ end of the ISS.  
     
     
         14 . An immunomodulatory polynucleotide according to  claim 1  or  claim 5 , wherein the immunomodulatory polynucleotide further comprises a T, 5-bromocytosine, G, A sequence.  
     
     
         15 . An immunomodulatory polynucleotide according to  claim 1  or  claim 5 , wherein the immunomodulatory polynucleotide is less than about 150 bases or base pairs in length.  
     
     
         16 . An immunomodulatory polynucleotide according to  claim 1  or  claim 5 , wherein the immunomodulatory polynucleotide is less than about 100 bases or base pairs in length.  
     
     
         17 . An immunomodulatory polynucleotide according to  claim 1  or  claim 5 , wherein the immunomodulatory polynucleotide is less than about 50 bases or base pairs in length.  
     
     
         18 . An immunomodulatory polynucleotide according to  claim 1  or  claim 5 , wherein the immunomodulatory polynucleotide is single-stranded.  
     
     
         19 . An immunomodulatory polynucleotide according to  claim 1  or  claim 5 , wherein the immunomodulatory polynucleotide is double-stranded.  
     
     
         20 . An immunomodulatory polynucleotide according to  claim 1  or  claim 5 , wherein the immunomodulatory polynucleotide is stabilized.  
     
     
         21 . An immunomodulatory polynucleotide according to  claim 20 , wherein the polynucleotide comprises a phosphorothioate bond.  
     
     
         22 . An immunomodulatory composition comprising an immunomodulatory polynucleotide according to  claim 1  or  claim 5 .  
     
     
         23 . An immunomodulatory composition according to  claim 22  further comprising a pharmaceutically acceptable excipient.  
     
     
         24 . An immunomodulatory composition according to  claim 22  further comprising an antigen.  
     
     
         25 . An immunomodulatory composition according to  claim 24  further comprising a pharmaceutically acceptable excipient.  
     
     
         26 . An immunomodulatory polynucleotide/microcarrier (IMP/MC) complex, comprising: 
 a polynucleotide according to  claim 1  linked to a biodegradable microcarrier (MC), wherein said MC is less than 10 μm in size.    
     
     
         27 . An immunomodulatory polynucleotide/microcarrier (IMP/MC) complex, comprising: 
 a polynucleotide according to  claim 5  linked to a biodegradable microcarrier (MC), wherein said MC is less than 10 μm in size.    
     
     
         28 . A method of modulating an immune response in an individual comprising administering to an individual an immunomodulatory polynucleotide according to  claim 1  or  claim 5  in an amount sufficient to modulate an immune response in said individual.  
     
     
         29 . The method of  claim 28 , wherein said individual suffers from a disorder associated with a Th2-type immune response.  
     
     
         30 . The method of  claim 29 , wherein said disorder associated with a Th2-type immune response is an allergy or asthma.  
     
     
         31 . The method of  claim 28 , wherein said individual has an infectious disease.  
     
     
         32 . A method of increasing interferon-gamma (IFN-γ) in an individual, comprising: 
 administering an immunomodulatory polynucleotide according to  claim 1  or  claim 5  to said individual in an amount sufficient to increase IFN-γ in said individual.  
 
     
     
         33 . The method of  claim 32 , wherein said individual has idiopathic pulmonary fibrosis.  
     
     
         34 . A method of increasing interferon-alpha (IFN-α) in an individual, comprising: 
 administering an immunomodulatory polynucleotide according to  claim 1  or  claim 5  to said individual in an amount sufficient to increase IFN-α in said individual.  
 
     
     
         35 . The method of  claim 34 , wherein said individual has a viral infection.  
     
     
         36 . A method of increasing interferon-alpha (IFN-α) in an individual, comprising: 
 administering an immunomodulatory polynucleotide according to  claim 9  to said individual in an amount sufficient to increase IFN-α in said individual.  
 
     
     
         37 . The method of  claim 35 , wherein said individual has a viral infection.  
     
     
         38 . A method of increasing interferon-alpha (IFN-α) in an individual, comprising: 
 administering an immunomodulatory polynucleotide according to  claim 11  to said individual in an amount sufficient to increase IFN-α in said individual.  
 
     
     
         39 . The method of  claim 38 , wherein said individual has a viral infection.  
     
     
         40 . A method of ameliorating a symptom of an infectious disease in an individual, comprising: 
 administering an effective amount of an immunomodulatory polynucleotide according to  claim 1  or  claim 5  to the individual, wherein an effective amount is an amount sufficient to ameliorate a symptom of said infectious disease.    
     
     
         41 . The method of  claim 40 , wherein said infectious disease is an infectious disease caused by a cellular pathogen.  
     
     
         42 . The method of  claim 41 , wherein said infectious disease caused by a cellular pathogen is selected from the group consisting of mycobacterial disease, malaria, leishmaniasis, toxoplasmosis, schistosomiasis and clonorchiasis.  
     
     
         43 . A method of ameliorating a symptom of an IgE-related disorder in an individual, comprising: 
 administering an effective amount of an immunomodulatory polynucleotide according to  claim 1  or  claim 5  to an individual having an IgE-related disorder, wherein an effective amount is an amount sufficient to ameliorate a symptom of said IgE-related disorder.    
     
     
         44 . The method of  claim 43 , wherein said IgE-related disorder is allergy.  
     
     
         45 . The method of  claim 43 , wherein said IgE-related disorder is an allergy-related disorder.  
     
     
         46 . The method of  claim 43 , wherein said IgE-related disorder is asthma.  
     
     
         47 . A kit comprising an immunomodulatory polynucleotide according to  claim 1  or  claim 5 .  
     
     
         48 . The kit of  claim 47 , further comprising instructions for use of the immunomodulatory polynucleotide for immunodulation of an individual.

Join the waitlist — get patent alerts

Track US2003049266A1 — get alerts on status changes and closely related new filings.

We store only your email — no account needed. See our privacy policy.