Aptamers that bind to IL-6 and their use in treating or diagnosing IL-6 mediated conditions

1. An aptamer that specifically binds IL-6, wherein the aptamer comprises a sequence selected from:

(SEQ ID NO: 705)

5′-YXAXGYARQ a MGYAAGSCGRY-3′ (VI);

and

(SEQ ID NO: 706)

5′-MGYAAGSCGRYQ b YXAXGYAR-3′ (VII);

wherein each Y is independently selected from a modified pyrimidine; each X is independently selected from a modified pyrimidine; M is selected from C and A; S is selected from C and G; each R is independently selected from G and A; each Q is independently selected from a linker, a modified nucleotide, and an unmodified nucleotide; a is 1 to 30; and / or b is 1 to 30.

2. The aptamer of claim 1 , comprising the sequence:

(SEQ ID NO: 701)

5′-GGGYXAXGYAGCL b GZGCGYAAGGCGGY-3′ (II);

wherein Z is selected from U, T, and a modified pyrimidine; each Y is independently selected from a modified pyrimidine; each X is independently selected from a modified pyrimidine; each L is independently selected from a linker, a modified nucleotide, and an unmodified nucleotide; b is 1 to 20.

3. The aptamer of claim 2 , wherein the each Q or L is independently selected from a substituted or unsubstituted C 2 -C 20 linker, an alkylene glycol, and a polyalkylene glycol.

4. The aptamer of claim 3 , wherein each Q or L is independently selected from a substituted or unsubstituted C 2 -C 20 linker, a 1,3-propane diol, a poly(1,3-propane diol) having from 2 to 100 1,3-propane diol units, an ethylene glycol, and a polyethylene glycol having from 2 to 100 ethylene glycol units.

5. The aptamer of claim 1 wherein each X is independently selected from an aromatic modified pyrimidine.

6. The aptamer of claim 1 wherein each Y is independently selected from the modified pyrimidines shown in FIG. 20 and FIG. 24 .

7. The aptamer of claim 4 wherein each substituted or unsubstituted C 2 -C 20 linker is a substituted or unsubstituted C 2 -C 8 linker, a substituted or unsubstituted C 2 -C 6 linker, a substituted or unsubstituted C 2 -C 5 linker, a substituted or unsubstituted C 2 -C 4 linker, or a substituted or unsubstituted C 3 linker.

8. The aptamer of claim 1 wherein each X is independently selected from:

5-(N-1-naphthylmethylcarboxyamide)-2′-deoxyuridine (NapdU),

5-(N-1-naphthylmethylcarboxyamide)-2′-O-methyluridine,

5-(N-1-naphthylmethylcarboxyamide)-2′-fluorouridine,

5-(N-2-naphthylmethylcarboxyamide)-2′-deoxyuridine (2NapdU),

5-(N-2-naphthylmethylcarboxyamide)-2′-O-methyluridine,

5-(N-2-naphthylmethylcarboxyamide)-2′-fluorouridine,

5-(N-1-naphthylethylcarboxyamide)-2′-deoxyuridine (NEdU),

5-(N-1-naphthylethylcarboxyamide)-2′-O-methyluridine,

5-(N-1-naphthylethylcarboxyamide)-2′-fluorouridine,

5-(N-2-naphthylethylcarboxyamide)-2′-deoxyuridine (2NEdU),

5-(N-2-naphthylethylcarboxyamide)-2′-O-methyluridine,

5-(N-2-naphthylethylcarboxyamide)-2′-fluorouridine,

5-(N-3-benzofuranylethylcarboxyamide)-2′-deoxyuridine (BFdU),

5-(N-3-benzofuranylethylcarboxyamide)-2′-O-methyluridine,

5-(N-3-benzofuranylethylcarboxyamide)-2′-fluorouridine,

5-(N-3-benzothiophenylethylcarboxyamide)-2′-deoxyuridine (BTdU),

5-(N-3-benzothiophenylethylcarboxyamide)-2′-O-methyluridine, and

5-(N-3-benzothiophenylethylcarboxyamide)-2′-fluorouridine.

9. A pharmaceutical composition comprising at least one aptamer of claim 1 , or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

10. A method of treating a disease or condition mediated by IL-6 comprising administering the pharmaceutical composition of claim 9 .

11. The method of claim 10 , wherein the disease or condition mediated by IL-6 is selected from an inflammatory disease, a malignant disease, an infection, and an autoimmune disease.