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1. WO2014164913 - COMPOSITIONS AND METHODS FOR INDUCING APOPTOSIS

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CLAIMS

What is claimed is:

1. A method of inducing apoptosis, the method comprising:

(i) contacting a population of cells with a first complex comprising a targeting moiety and a morpholino; and

(ii) contacting a population of cells with a second complex comprising a copolymer carrier and one or more morpholinos;

wherein the contacting of the cells with the first complex and the second complex induces apoptosis of the cells.

2. The method of Claim 1, further comprising repeating step (i) and step (ii).

3. The method of Claim 1, further comprising (iii) confirming apoptosis of the cells.

4. The method of Claim 1, wherein the cells are B-cells.

5. The method of Claim 1, wherein the cells are in a subject.

6. The method of Claim 5, wherein the subject has non-Hodgkin's lymphoma.

7. The method of Claim 1, wherein the targeting moiety is specific for a non- internalizing cell surface molecule or slowly internalizing cell surface molecule.

8. The method of Claim 7, wherein the non-internalizing cell surface molecule or slowly internalizing cell surface molecule is a CD20 receptor, a protein tyrosine phosphatase receptor type C, a cell surface death receptor, a prostate stem cell antigen receptor, or a receptor belonging to the tumor necrosis factor receptor superfamily.

9. The method of Claim 7, wherein the targeting moiety is a polysaccharide, a peptide ligand, an aptamer, a Fab' fragment, or a single-chain variable fragment.

10. The method of Claim 9, wherein the targeting moiety is a Fab' fragment.

11. The method of Claim 10, wherein the Fab' fragment is derived from an anti-CD20 receptor antibody.

12. The method of Claim 1 1, wherein the anti-CD20 receptor antibody is 1F5, rituximab, tositumomab, ibritumomab, ofatumumab, veltuzumab, ocrelizumab, ocaratuzumab, obinutuzumab, PR0131921, BCD-020, IBI-301, ublituximab, or BLX-301.

13. The method of Claim 1, wherein the morpholino of the first complex and the one or more morpholinos of the second complex are complementary.

14. The method of Claim 1, wherein the morpholino of the first complex is 5' GAG TAA GCC AAG GAG AAT CAA TAT A 3 ' (SEQ ID NO:25) and wherein the one or more morpholinos of the second complex are 5' TAT ATT GAT TCT CCT TGG CTT ACT C 3' (SEQ ID O:26).

15. A method of inducing apoptosis, the method comprising:

contacting a population of cells with a composition comprising a first complex comprising a targeting moiety and a morpholino and a second complex comprising a complex comprising a copolymer carrier and one or more morpholinos, wherein the contacting of the cells with the composition induces apoptosis of the cells.

16. The method of Claim 15, further comprising repeating the contacting of the cells with the composition.

17. The method of Claim 15, wherein the cells are B-cells.

18. The method of Claim 15, wherein the cells are in a subject.

19. The method of Claim 18, wherein the subject has non-Hodgkin's lymphoma.

20. The method of Claim 15, wherein the targeting moiety is specific for a non- internalizing cell surface molecule or slowly internalizing cell surface molecule.

21. The method of Claim 20, wherein the non- internalizing cell surface molecule or slowly internalizing cell surface molecule is a CD20 receptor, a protein tyrosine phosphatase receptor type C, a cell surface death receptor, a prostate stem cell antigen receptor, or a receptor belonging to the tumor necrosis factor receptor superfamily.

22. The method of Claim 15, wherein the targeting moiety is a polysaccharide, a peptide ligand, an aptamer, a Fab' fragment, or a single-chain variable fragment.

23. The method of Claim 22, wherein the targeting moiety is a Fab' fragment.

24. The method of Claim 23, wherein the Fab' fragment is derived from an anti-CD20 receptor antibody.

25. The method of Claim 24, wherein the anti-CD20 receptor antibody is 1F5, rituximab, tositumomab, ibritumomab, ofatumumab, veltuzumab, ocrelizumab, ocaratuzumab, obinutuzumab, PR0131921, BCD-020, IBI-301, ublituximab, or BLX-301.

26. The method of Claim 15, wherein the morpholino of the first complex and the one or more morpholinos of the second complex are complementary.

27. The method of Claim 15, wherein the morpholino of the first complex is 5' GAG TAA GCC AAG GAG AAT CAA TAT A 3 ' (SEQ ID NO:25) and wherein the one or more morpholinos of the second complex are 5' TAT ATT GAT TCT CCT TGG CTT ACT C 3' (SEQ ID O:26).

28. A kit comprising (i) a first complex comprising a targeting moiety and a morpholino, and (ii) a second complex comprising a copolymer carrier and one or more morpholinos.

29. The kit of Claim 28, further comprising (iii) instructions for administering the complex of (i) and the complex of (ii).

30. The kit of Claim 28, wherein the first complex and the second complex are co- formulated.

31. The kit of Claim 28, wherein the targeting moiety is specific for a non- internalizing cell surface molecule or slowly internalizing cell surface molecule.

32. The kit of Claim 31, wherein the non-internalizing cell surface molecule or slowly internalizing cell surface molecule is on a cell.

33. The kit of Claim 32, wherein the cell is a B cell.

34. The kit of Claim 31, wherein the non- internalizing cell surface molecule or slowly internalizing cell surface molecule is a CD20 receptor, a protein tyrosine phosphatase receptor type C, a cell surface death receptor, a prostate stem cell antigen receptor, or a receptor belonging to the tumor necrosis factor receptor superfamily.

35. The kit of Claim 28, wherein the targeting moiety is a polysaccharide, a peptide ligand, an aptamer, a Fab' fragment, or a single-chain variable fragment.

36. The kit of Claim 35, wherein the Fab' fragment is derived from an anti-CD20 receptor antibody.

37. The kit of Claim 36, wherein the anti-CD20 receptor antibody is 1F5, rituximab, tositumomab, ibritumomab, ofatumumab, veltuzumab, ocrelizumab, ocaratuzumab, obinutuzumab, PR0131921, BCD-020, IBI-301, ublituximab, or BLX-301.

38. The kit of Claim 28, wherein the morpholino of the first complex and the one or more morpholinos of the second complex are complementary.

39. The kit of Claim 28, wherein the morpholino of the first complex is 5' GAG TAA GCC AAG GAG AAT CAA TAT A 3' (SEQ ID NO:25) and wherein the one or more morpholinos of the second complex are 5' TAT ATT GAT TCT CCT TGG CTT ACT C 3' (SEQ ID O:26).