.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Details for Patent: 6,280,932

« Back to Dashboard

Details for Patent: 6,280,932

Title: High affinity nucleic acid ligands to lectins
Abstract:This invention discloses high-affinity oligonucleotide ligands to lectins, specifically nucleic acid ligands having the ability to bind to the lectins, wheat germ agglutinin, L-selectin and P-selectin. Also disclosed are the methods for obtaining such ligands.
Inventor(s): Parma; David H (Boulder, CO), Hicke; Brian (Boulder, CO), Bridonneau; Philippe (Boulder, CO), Gold; Larry (Boulder, CO)
Assignee: Gilead Sciences, Inc. (Foster City, CA)
Filing Date:Nov 21, 1997
Application Number:08/952,793
Claims:1. A method for identifying modified, single-stranded ribonucleic acid ligands to a lectin comprising:

a) contacting a candidate mixture of modified, single-stranded ribonucleic acids with a lectin, said modified ribonucleic acids selected from the group consisting of 2'-amino (2'-NH.sub.2) modified ribonucleic acids and 2'-fluoro (2'-F) modified ribonucleic acids, wherein ribonucleic acids having an increased affinity to said lectin relative to the candidate mixture may be partitioned from the remainder of the candidate mixture;

b) partitioning the increased affinity ribonucleic acids from the remainder of the candidate mixture; and

c) amplifying the increased affinity ribonucleic acids to yield a mixture of ribonucleic acids enriched for ribonucleic acid sequences with relatively high affinity and specificity for binding to said lectin, whereby modified, single-stranded ribonucleic acid ligands to said lectin may be identified.

2. A method for forming a multivalent Complex of nucleic acid ligands to a lectin comprising:

a) contacting a candidate mixture of nucleic acids with a lectin, wherein nucleic acids having an increased affinity to said lectin relative to the candidate mixture may be partitioned from the remainder of the candidate mixture;

b) partitioning the increased affinity nucleic acids from the remainder of the candidate mixture; and

c) amplifying the increased affinity nucleic acids to yield a mixture of nucleic acids enriched for nucleic acid sequences with relatively higher affinity and specificity for binding to said lectin, whereby nucleic acid ligands to said lectin may be identified; and

d) forming a multivalent Complex comprising two nucleic acid ligands identified in step c).

3. A method for identifying single-stranded ribonucleic acid ligands and producing modified ribonucleic acid ligands to a lectin comprising:

a) contacting a candidate mixture of single-stranded ribonucleic acids with a lectin, wherein ribonucleic acids having an increased affinity to said lectin relative to the candidate mixture may be partitioned from the remainder of the candidate mixture;

b) partitioning the increased affinity ribonucleic acids from the remainder of the candidate mixture; and

c) amplifying the increased affinity ribonucleic acids to yield a mixture of single-stranded ribonucleic acids enriched for ribonucleic acid sequences with relatively higher affinity and specificity for binding to said lectin, whereby the ribonucleic acid ligands to said lectin may be identified; and

d) substituting 2'-O-methyl ribonucleic acids for 2'-OH ribonucleic acids in the ribonucleic acid ligands identified in step c), whereby the modified ribonucleic acids to a ligand are produced.

4. A method for identifying nucleic acid ligands and nucleic acid ligand sequences to a lectin comprising:

a) contacting a candidate mixture of nucleic acids with a lectin, wherein nucleic acids having an increased affinity to said lectin relative to the candidate mixture may be partitioned from the remainder of the candidate mixture;

b) partitioning the increased affinity nucleic acids from the remainder of the candidate mixture; and

c) amplifying the increased affinity nucleic acids to yield a mixture of nucleic acids enriched for nucleic acid sequences with relatively higher affinity and specificity for binding to said lectin, whereby nucleic acid ligands to said lectin may be identified, wherein said lectin is a selectin.

5. The method of claim 4 wherein said selectin is selected from the group consisting of L-selectin, E-selectin, and P-selectin.

6. A purified and isolated non-naturally occurring nucleic acid ligand to a lectin.

7. The nucleic acid ligand of claim 6 which is a non-naturally occurring nucleic acid ligand having a specific binding affinity for said lectin, such lectin being a three dimensional chemical structure other than a polynucleotide that binds to said nucleic acid ligand through a mechanism which predominantly depends on Watson/Crick base pairing or triple helix binding, wherein said nucleic acid ligand is not a nucleic acid having the known physiological function of being bound by said lectin.

8. The nucleic acid ligand of claim 6 wherein said lectin is selected from the group consisting of a mammalian lectin, a plant lectin, a microbial lectin and a viral lectin.

9. The nucleic acid ligand of claim 6 wherein said lectin is selected from the group consisting of wheat germ agglutinin, L-selectin, E-selectin and P-selectin.

10. The nucleic acid ligand of claim 6 wherein said lectin is wheat germ agglutinin.

11. The nucleic acid ligand to wheat germ agglutinin of claim 10 wherein said nucleic acid ligand is a ribonucleic acid (RNA) ligand.

12. The nucleic acid ligand of claim 11 which comprises a modified ribonucleic acid.

13. The nucleic acid ligand of claim 12 wherein said modified ribonucleic acid is a 2'-amino (NH.sub.2) modified ribonucleic acid.

14. The nucleic acid ligand to wheat germ agglutinin of claim 13 wherein said ligand is an RNA ligand selected from the group consisting of the nucleotide sequences set forth in Table 2.

15. The nucleic acid ligand of claim 14 wherein said ligand is selected from the group consisting of SEQ ID NOS: 4-55.

16. The nucleic acid ligand of claim 11 wherein said ligand comprises sequences selected from the group consisting of SEQ ID NOS: 56-63.

17. The nucleic acid ligand to wheat germ agglutinin of claim 10 wherein said ligand is substantially homologous to a ligand selected from the group consisting of the sequences set forth in Table 2.

18. The nucleic acid ligand to wheat germ agglutinin of claim 10 wherein said ligand has substantially the same structure as a ligand selected from the group consisting of the sequences set forth in Table 2.

19. The nucleic acid ligand of claim 6 wherein said lectin is a selectin.

20. The nucleic acid ligand of claim 19 wherein said selectin is selected from the group consisting of L-selectin, E-selectin and P-selectin.

21. The nucleic acid ligand of claim 20 wherein said selectin is L-selectin.

22. The nucleic acid ligand to L-selectin of claim 21 wherein said nucleic acid ligand is ribonucleic acid (RNA) ligand.

23. The nucleic acid ligand of claim 22 which comprises a modified ribonucleic acid.

24. The nucleic acid ligand of claim 23 wherein said modified ribonucleic acid is selected from the group consisting of a 2'-amino (2'-NH.sub.2) modified ribonucleic acid and a 2'-fluoro (2'-F) modified ribonucleic acid.

25. The nucleic acid ligand to L-selectin of claim 24 wherein said ligand is an RNA ligand selected from the group consisting of the nucleotide sequences set forth in Tables 8 and 16.

26. The nucleic acid ligand of claim 25 wherein said ligand is selected from the group consisting of SEQ ID NOS: 67-117 and 293-388.

27. The nucleic acid ligand of claim 22 wherein said ligand comprises sequences selected from the group consisting of SEQ ID NOS: 118-125.

28. The nucleic acid ligand to L-selectin of claim 21 wherein said ligand is substantially homologous to a ligand selected from the group consisting of the sequences set forth in Tables 8, 12 and 16.

29. The nucleic acid ligand to L-selectin of claim 21 wherein said ligand has substantially the same structure as a ligand selected from the group consisting of the sequences set forth in Tables 8, 12 and 16.

30. The nucleic acid ligand to L-selectin of claim 21 wherein said nucleic acid ligand is deoxyribonucleic acid (DNA).

31. The nucleic acid ligand to L-selectin of claim 30 wherein said ligand is an DNA ligand selected from the group consisting of the nucleotide sequences set forth in Table 12.

32. The nucleic acid ligand of claim 31 wherein said ligand is selected from the group consisting of SEQ ID NOS: 129-180 and 185-196.

33. The nucleic acid ligand of claim 30 wherein said ligand comprises sequences selected from the group consisting of SEQ ID NOS: 181-184.

34. The nucleic acid ligand of claim 20 wherein said selectin is P-selectin.

35. The nucleic acid ligand to P-selectin of claim 34 wherein said nucleic acid ligand is ribonucleic acid (RNA) ligand.

36. The nucleic acid ligand of claim 35 which comprises a modified ribonucleic acid.

37. The nucleic acid ligand of claim 36 wherein said modified ribonucleic acid is selected from the group consisting of a 2'-amino (2'-NH.sub.2) modified ribonucleic acid, a 2'-fluoro (2'-F) modified ribonucleic acid, and a 2'-O-Methyl (2'-O-Me) modified ribonucleic acid.

38. The nucleic acid ligand to P-selectin of claim 37 wherein said ligand is an RNA ligand selected from the group consisting of the nucleotide sequences set forth in Tables 19, 21 and 25.

39. The nucleic acid ligand of claim 38 wherein said ligand is selected from the group consisting of SEQ ID NOS: 199-219 and 236-290.

40. The nucleic acid ligand of claim 35 wherein said ligand comprises sequences selected from the group consisting of SEQ ID NO: 291.

41. A nucleic acid ligand to P-selectin of claim 34 wherein said ligand is substantially homologous to a ligand selected from the group consisting of the sequences set forth in Tables 19, 21 and 25.

42. The nucleic acid ligand to P-selectin of claim 34 wherein said ligand has substantially the same structure as a ligand selected from the group consisting of the sequences set forth in Tables 19, 21 and 25.

43. The nucleic acid ligand to P-selectin of claim 37 wherein said nucleic acid ligand is deoxyribonucleic acid (DNA).

44. The nucleic acid ligand of claim 6 wherein said ligand is a ribonucleic acid ligand.

45. The nucleic acid ligand of claim 44 which comprises a modified ribonucleic acid.

46. The nucleic acid ligand of claim 45 wherein said modified ribonucleic acid is selected from the group consisting of 2'-amino (2'-NH.sub.2) modified ribonucleic acids, 2'-fluoro (2'-F) modified ribonucleic acids and 2'-O-Methyl (2'-O-Me) modified ribonucleic acids.

47. The nucleic acid ligand of claim 6 wherein said ligand is a deoxyribonucleic acid.

48. The nucleic acid ligand of claim 6 wherein said ligand has been chemically modified at a sugar and/or phosphate and/or base.

49. A multivalent Complex comprising a plurality of ligands of claim 6.

50. A nucleic acid ligand to a lectin identified according to the method comprising:

a) contacting a candidate mixture of nucleic acids with a lectin, wherein nucleic acids having an increased affinity to said lectin relative to the candidate mixture may be partitioned from the remainder of the candidate mixture;

b) partitioning the increased affinity nucleic acids from the remainder of the candidate mixture; and

c) amplifying the increased affinity nucleic acids to yield a mixture of nucleic acids enriched for nucleic acid sequences with relatively higher affinity and specificity for binding to said lectin, whereby nucleic acid ligand of said lectin may be identified.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc