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Details for Patent: 6,713,616

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Details for Patent: 6,713,616

Title: High affinity TGF.beta. nucleic acid ligands and inhibitors
Abstract:Methods are described for the identification and preparation of high-affinity nucleic acid ligands to TGF.beta.2. Included in the invention are specific RNA ligands to TGF.beta.2 identified by the SELEX method. Also included are RNA ligands that inhibit the interaction of TGF.beta.2 with its receptor.
Inventor(s): Pagratis; Nikos (Boulder, CO), Lochrie; Michael (Louisville, CO), Gold; Larry (Boulder, CO)
Assignee: Gilead Sciences, Inc. (Foster City, CA)
Filing Date:Feb 23, 2001
Application Number:09/791,301
Claims:1. A purified and isolated non-naturally occurring RNA ligand to transforming growth factor .beta.1 (TGF.beta.1) wherein said ligand is selected from the group consisting of the sequences set forth in Table 22 (SEQ ID NOS:194-215).

2. A complex comprised of a TGF.beta.1 nucleic acid ligand and a non-immunogenic, high molecular weight compound or lipophilic compound, wherein said ligand is selected from the group consisting of the sequences set forth in claim 1.

3. The complex of claim 2 further comprising a linker between said ligand and said non-immunogenic, high molecular weight compound or lipophilic compound.

4. The complex of claim 2 wherein said non-immunogenic, high molecular weight compound is polyalkylene glycol.

5. The complex of claim 4 wherein said polyalkylene glycol is polyethylene glycol (PEG).

6. The complex of claim 5 wherein said PEG has a molecular weight of about between 10-80 K.

7. The complex of claim 6 wherein said PEG has a molecular weight of about 20-45 K.

8. The complex of claim 7 wherein said complex is: ##STR1##

LIGAND=5'mGmGmGrUrGrCrCrUrUrUrUrGrCrCrUmAmGmGrUrUmGrUmGmArUrU rUmGrUmAmArCrCrUrUrCrUrGrCrCrCmA3'-3'rU (SEQ ID NO:210)

wherein r prefix indicates unmodified ribonucleoside, m prefix indicates 2'-O-methyl substituted ribonucleotide.

9. A complex comprised of a TGF.beta.2 nucleic acid ligand, and a non-immunogenic, high molecular weight compound or lipophilic compound, wherein said ligand is selected from the group consisting of the sequences set forth in Tables 5, 7, 8, 11, 13, 14, 16-19, and FIG. 9 (SEQ ID NOS:21-121 and 128-193).

10. The complex of claim 9 further comprising a linker between said ligand and said non-immunogenic, high molecular weight compound or lipophilic compound.

11. The complex of claim 9 wherein said non-immunogenic, high molecular weight compound is a polyalkylene glycol.

12. The complex of claim 11 wherein said polyalkylene glycol is polyethylene glycol (PEG).

13. The complex of claim 12 wherein said PEG has a molecular weight of about between 10-80 K.

14. The complex of claim 13 wherein said PEG has a molecular weight of about 20-45 K.
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