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Details for Patent: 7,399,752

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Details for Patent: 7,399,752

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, E-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 Science, Inc. (Foster City, CA)
Filing Date:Apr 07, 2003
Application Number:10/409,627
Claims:1. A method of inhibiting binding between L-selectin and a carbohydrate ligand of said L-selectin, comprising the step of contacting a nucleic acid ligand to said L-selectin with said L-selectin wherein said nucleic acid ligand to L-selectin is selected from the group consisting of SEQ ID NO: 67-117, 129-196, and 293-388.

2. A method of inhibiting binding between P-selectin and a carbohydrate ligand of said P-selectin, comprising the step of contacting a nucleic acid ligand to said P-selectin with said P-selectin wherein said nucleic acid ligand to P-selectin is selected from the group consisting of SEQ ID NO: 199-247, and 251-290.

3. A method of modulating leukocyte adhesion or migration, comprising inhibiting binding between a P- or L-selectin on a first cell and a ligand to said selectin on a second cell, said inhibiting comprising the step of permitting a nucleic acid ligand to the selectin to interact with the first cell, wherein the first cell is a leukocyte selected from the group consisting of neutrophils and monocytes, the second cell is a vascular endothelial cell and wherein said nucleic acid ligand is selected from the group consisting of SEQ ID NO: 67-117, 129-196, 199-247, 251-290 and 293-388.

4. A method for modulating platelet adhesion, comprising inhibiting binding between a P-selectin on a first cell and a ligand to said P-selectin on a second cell, said inhibiting comprising the step of permitting a nucleic acid ligand to said P-selectin to interact with the first cell, wherein the first cell is a platelet, wherein said nucleic acid ligand to said P-selectin is selected from the group consisting of SEQ ID NO:199-247 and 251-290.

5. A method of modulating leukocyte adhesion or migration, comprising inhibiting binding between an L-selectin on a first cell and a ligand to said L-selectin on a second cell, said inhibiting comprising the step of permitting a nucleic acid ligand to said L-selectin to interact with the first cell, wherein the first cell is a leukocyte selected from the group consisting of lymphocytes, granulocytes, neutrophils and monocytes, the second cell is a vascular endothelial cell or a lymphatic cell and wherein said nucleic acid ligand to said L-selectin is selected from the group consisting of SEQ ID NO: 67-117, 129-196 and 293-388.

6. A method of modulating lymphocyte adhesion, migration or activation comprising inhibiting binding between an L-selectin on a first cell and a ligand to said L-selectin on a second cell, said inhibiting comprising the step of permitting a nucleic acid ligand to said L-selectin to interact with the first cell, wherein the first cell is a lymphocyte, the second cell is a vascular endothelial cell and wherein said nucleic acid ligand is selected from the group consisting of SEQ ID NO: 67-117, 129-196 and 293-388.

7. A method of inhibiting binding between P-selectin and a carbohydrate ligand of said P-selectin, comprising the step of contacting a nucleic acid ligand to said P-selectin with said P-selectin wherein said nucleic acid ligand to P-selectin comprises SEQ ID NO: 223.

8. The method of claim 7 wherein SEQ ID NO: 223 further comprises at least one 2'-O-methyl purine.

9. The method of claim 7 wherein SEQ ID NO: 223 further comprises 2'-OMe purines at positions 7, 8, 9, 15, 27, 28 and 31.

10. The method of claim 9 wherein SEQ ID NO: 223 further comprises a 2'-OMe purine at one or more of the following positions 13, 14, 16, 18, 21, 22, 24 and 30.

11. The method of claim 9 wherein SEQ ID NO: 223 further comprises 2'-OMe purines at positions 13, 14, 18, 21, 22, and 24.

12. A method of modulating leukocyte adhesion or migration, comprising inhibiting binding between a P-selectin on a first cell and a ligand to said P-selectin on a second cell, said inhibiting comprising the step of permitting a nucleic acid ligand to the selectin to interact with the first cell, wherein the first cell is a leukocyte selected from the group consisting of neutrophils and monocytes, the second cell is a vascular endothelial cell and wherein said nucleic acid ligand comprises SEQ ID NO: 223.

13. The method of claim 12 wherein SEQ ID NO: 223 further comprises at least one 2'-O-methyl purine.

14. The method of claim 12 wherein SEQ ID NO: 223 further comprises 2'-OMe purines at positions 7, 8, 9, 15, 27, 28 and 31.

15. The method of claim 14 wherein SEQ ID NO: 223 further comprises a 2'-OMe purine at one or more of the following positions 13, 14, 16, 18, 21, 22, 24 and 30.

16. The method of claim 14 wherein SEQ ID NO: 223 further comprises 2'-OMe purines at positions 13, 14, 18, 21, 22, and 24.

17. A method for modulating platelet adhesion, comprising inhibiting binding between a P-selectin on a first cell and a ligand to said P-selectin on a second cell, said inhibiting comprising the step of permitting a nucleic acid ligand to said P-selectin to interact with the first cell, wherein the first cell is a platelet, wherein said nucleic acid ligand to said P-selectin comprises SEQ ID NO: 223.

18. The method of claim 17 wherein SEQ ID NO: 223 further comprises at least one 2'-O-methyl purine.

19. The method of claim 17 wherein SEQ ID NO: 223 further comprises 2'-OMe purines at positions 7, 8, 9, 15, 27, 28 and 31.

20. The method of claim 19 wherein SEQ ID NO: 223 further comprises a 2'-OMe purine at one or more of the following positions 13, 14, 16, 18, 21, 22, 24 and 30.

21. The method of claim 19 wherein SEQ ID NO: 223 further comprises 2'-OMe purines at positions 13, 14, 18, 21, 22, and 24.
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