Oligonucleotide—containing pharmacological compositions and their use
The present invention relates to methods and compositions containing oligonucleotides suitable for administration to humans and other mammals.
1. A composition suitable for oral administration to a mammal suffering from a pathological disorder or disease comprising a first and a second modified oligonucleotide, wherein
(a) said first and said second modified oligonucleotide each comprise about seven to seventy-five nucleotides containing seven or more contiguous ribose groups linked by achiral 5′ to 3′ internucleotide phosphate linkages, wherein said ribose groups of said modified oligonucleotides have a 2′ modification, and wherein the 5′ and/or 3′ ends of said modified oligonucleotides are blocked;
(b) said first modified oligonucleotide is complementary to a region of a first gene associated with said pathological disorder or disease and said second modified oligonucleotide is complementary to a region of a second gene associated with said pathological disorder or disease, wherein the nucleotide sequence of said first modified oligonucleotide comprises SEQ ID NO:1 and the nucleotide sequence of said second modified oligonucleotide comprises SEQ ID NO:6; and
(c) wherein said pathological disorder or disease comprises inflammation.
2. The composition of claim 1 , wherein the mammal is a human.
3. The composition of claim 1 , wherein the 2′ position of each of said ribose groups comprises a substituent selected from the group consisting of hydrogen, methoxy, propoxy, methoxy-ethoxy, fluorine, chlorine, bromine, and iodine.
4. The composition of claim 1 , wherein the composition is a pharmaceutical composition.
5. A method of treating a patient with inflammation comprising administering to said patient the composition of claim 1 .
6. The method of claim 5 , wherein the composition of claim 1 is orally administered.
7. The method of claim 5 , wherein the 2′ position of each of said ribose groups comprises a substituent selected from the group consisting of hydrogen, methoxy, propoxy, methoxy-ethoxy, fluorine, chlorine, bromine, and iodine.
8. The method of claim 5 , wherein said first and said second modified oligonucleotide are 3′ end-blocked.
9. The method of claim 5 , wherein said first and said second modified oligonucleotide are 5′ end-blocked.
10. The method of claim 5 , wherein at least three different modified oligonucleotides are administered.
11. The composition of claim 1 , further comprising a third modified oligonucleotide, wherein said third modified oligonucleotide is complementary to a region of a third gene associated with said pathological disorder or disease, and wherein the nucleotide sequence of said third modified oligonucleotide comprises SEQ ID NO:10.
12. The composition of claim 11 , further comprising a fourth modified oligonucleotide, wherein said fourth modified oligonucleotide is complementary to a region of a fourth gene associated with said pathological disorder or disease, and wherein the nucleotide sequence of said fourth modified oligonucleotide comprises SEQ ID NO:12.