Combination motif immune stimulatory oligonucleotides with improved activity
AssigneesUniversity of Iowa Research Foundation, Coley Pharmaceutical GmbH
InventorsArthur M. Krieg, Jorg Vollmer
Life of this patent
Estimating the term…
Abstract
A class of immunostimulatory nucleic acids having at least two functionally and structurally defined domains is provided. This class of combination motif immunostimulatory nucleic acids activates an immune response and is useful for treating a variety of immune realted disorders such as cancer, infectious disease, and allergic disorders. The nucleic acids also stimulate activation of natural killer cells and production of type 1 interferon.
Claims72
An immunostimulatory nucleic acid of 14-100 nucleotides in length comprising the formula:
- 5′ X1DCGHX2 3′
- wherein X1 and X2 are independently any sequence 0 to 10 nucleotides long, D is a nucleotide other than C, C is cytosine, G is guanine, H is a nucleotide other than G, further comprising a nucleic acid sequence selected from the group consisting of P and N positioned immediately 5′ to X1 or immediately 3′ to X2, and N is a B-cell neutralizing sequence, wherein N begins with a CGG trinucleotide and is at least 10 nucleotides long, and P is a GC-rich palindrome containing sequence at least 10 nucleotides long.
An immunostimulatory nucleic acid of 13-100 nucleotides in length comprising the formula:
- 5′ N1PyGN2P 3′
- wherein N1 is any sequence 1 to 6 nucleotides long, Py is a pyrimidine, G is guanine, N2 is any sequence 0 to 30 nucleotides long, and P is a GC-rich palindrome containing sequence at least 10 nucleotides long.
An immunostimulatory nucleic acid of 13-100 nucleotides in length comprising the formula:
- 5′ N1PyG/IN2P 3′
- wherein N1 is any sequence 1 to 6 nucleotides long, Py is a pyrimidine, G/I refers to single nucleotide which is either a G or an I, G is guanine and I is inosine, N2 is any sequence 0 to 30 nucleotides long, and P is a palindrome containing sequence at least 10 nucleotides long.
An immunostimulatory nucleic acid comprising a sequence selected from the group consisting of:
- TCGTCGTTTTCGGCGCGCGCCG (SEQ ID NO:
- 1),
- TCGTCGTTTTCGGCGGCCGCCG (SEQ ID NO:
- 4),
- TCGTCGTTTTCGGCGCGCCGCG (SEQ ID NO:
- 5),
- TCGTCGTTTTCGGCGCCGGCCG (SEQ ID NO:
- 6),
- TCGTCGTTTTCGGCCCGCGCGG (SEQ ID NO:
- 7),
- TCGTCGTTTTCGGCGCGCGCCGTTTTT (SEQ ID NO:
- 12),
- TCCTGACGTTCGGCGCGCGCCG (SEQ ID NO:
- 13),
- TZGTZGTTTTZGGZGZGZGZZG (SEQ ID NO:
- 14), wherein Z is 5-methylcytosine,
- TCCTGACGTTCGGCGCGCGCCC (SEQ ID NO:
- 19), and
- TCGGCGCGCGCCGTCGTCGTTT (SEQ ID NO:
- 11).
Dependencies are inferred from the claim text.