CLAIMS

What is claimed is:

1. A targeted drug delivery conjugate comprising:

(i) a targeting ligand;
(ii) an affinity ligand linked to said targeting ligand; and
(iii) a therapeutic agent linked to said affinity ligand via a linker.
2. The drug delivery conjugate of claim 1, wherein said affinity ligand is covalently connected to said therapeutic agent.

3. The drug delivery conjugate of claim 1, wherein said affinity ligand is non-covalently connected to said targeting ligand.

4. The targeted drug delivery conjugate of claim 1, wherein the targeting ligand is selected from the group consisting of monoclonal antibodies, polyclonal antibodies, antigens, folates, EGF, albumin, receptor ligands, carbohydrates, aptamers, integrin receptor ligands, chemokine receptor ligands, transferrin, biotin, serotonin receptor ligands, PSMA, endothelin, GCPII, somatostatin, LDL ligands, HDL ligands, polylysine (PLL), poly L aspartic acid, poly L-glutamic acid, lectins, glycoproteins, surfactant protein A, mucin, transferrin, sugar-albumin conjugates, peptides (e.g., an alpha helical peptide, amphipathic peptide, RGD peptide, cell permeation peptide, endosomolytic/fusogenic peptide), transport/absorption facilitators (e.g., naproxen, aspirin, vitamin E, folic acid), hormones, multivalent carbohydrates, vitamins (e.g., vitamin A, vitamin E, vitamin K, vitamin B, e.g., folic acid, B12, riboflavin, biotin and pyridoxal), D-galactose, multivalent galactose, N-acetyl-D-galactose (GalNAc), multivalent GalNAc, D-mannose, multivalent mannose, multivalent lactose, N-acetyl-galactosamine, N-acetyl-gulucosamine, multivalent fucose, glycosylated polyaminoacids, and any combinations thereof.

5. The targeted drug delivery conjugate of claim 1 wherein the targeting ligand binds a protein, receptor, or marker expressed on the surface of a cancer cell.
6. The targeted drug delivery conjugate of claim 1, wherein the affinity ligand binds with high affinity and/or specificity with the targeting ligand.

7. The targeted drug delivery conjugate of claim 1, wherein the affinity ligand is selected from the group consisting of small organic or inorganic molecules, peptides, proteins, peptide derivatives and analogs, peptidomimetics, nucleic acids, nucleic acid derivatives and acid

analogs, saccharines, oligosaccharides, polysaccharides, lipids, glycoproteins, glycopeptides, and any combinations thereof.

8. The targeted drug delivery conjugate of claim 1 wherein the affinity ligand is selected from the group consisting of 4-mercaptoethyl pyridine, triazines, 2-mercapto-5-benzymidazole sulfonic acid, peptides, protein A, protein G, protein L, protein A/G/L mimetics, domains and sub-domains, Fc receptor, Fc receptor mimetics, phenyl boronic acid, boronic acid derivatives, N-benzyl-N-methyl ethanolamine, N-benzoyl-homocysteine, TRIM21 and its mimetics, Clusterin and its mimetics, histidyl-aminohexyl based, 2-mercaptoimidazole, 2-mercapto-1 -methyl-imidazole, 2-benzamido-4-mercaptobutanoic acid, phenylpropylamine, hexylamine, 3-(2-mercaptoethyl)quinazoline-2,4(lH,3H)dione, ficolin and its mimetics, 4'-terpyridinylsulfanylethylamine, 4-(lH-imidazol-l-yl) aniline, Poly(4-vinylpyridine), ligands used for antibody purification which specifically bind to antibodies non-covalently, any combinations or parts or modifications thereof.

9. The targeted drug delivery conjugate of claim 1, wherein the linker is selected from the group consisting of a bond, hydrocarbons, amino acids, peptides, polyethylene glycols, cyclodextrin, and any derivatives and combinations thereof.

10. The targeted drug delivery conjugate of claim 1, wherein the therapeutic agent is linked to the linker via a non-cleavable linking group.

11. The targeted drug delivery conjugate of claim 1, wherein the therapeutic agent is linked to the linker via a cleavable linking group.

12. The targeted drug delivery conjugate of claim 1, wherein the affinity ligand is linked to the linker via a non-cleavable linking group.

13. The targeted drug delivery conjugate of claim 1, wherein the affinity ligand is linked to the linker via a cleavable linking group.

14. The targeted drug delivery conjugate of claim 1, wherein the linker is a branched linker.

15. The targeted drug delivery conjugate of claim 14, wherein the conjugate comprises at least two therapeutic agents linked to the affinity molecule via the branched linker.

16. The targeted drug delivery conjugate of claim 14, wherein the conjugate comprises two or more affinity ligands linked to the therapeutic agent via the branched linker.

17. The targeted drug delivery conjugate of claim 16, wherein the therapeutic agent is an anticancer agent or a cytotoxic drug.

18. The targeted drug delivery conjugate of any of claims 1-17, wherein the linker comprises a cleavable group.

19. The targeted drug delivery conjugate of any of claims 1-18, wherein two or more affinity ligands are connected together via a linker.

20. The targeted drug delivery conjugate of claim 19, wherein the two or more affinity ligands are each linked to a biomolecule.

21. The targeted drug delivery conjugate of any of claims 1-20, wherein the affinity ligand is linked to two or more biomolecules.

22. The targeted drug delivery conjugate of claim 21, wherein a first biomolecule is covalently linked to the affinity ligand and a second biomolecule is non-covalently linked to the affinity ligand.

23. The targeted drug delivery conjugate of any of claims 20-22, wherein the biomolecules comprise the targeting ligand, the therapeutic agent, or a combination thereof.

24. A conjugate comprising:

(i) a first biomolecule;
(ii) a first affinity ligand linked to said first biomolecule;
(iii) a second affinity ligand linked to said first affinity molecule; and
(iv) a second biomolecule linked to said second affinity ligand.

25. The conjugate of claim 24, wherein the first affinity ligand and the second affinity ligand are linked to each other via a linker.

26. The conjugate of claim 25, wherein the linker comprises a cleavable group.

27. The conjugate of claim 25 or 26, wherein the first affinity ligand is linked to the linker via a cleavable linking group.

28. The conjugate of any of claims 25-27, wherein the second affinity ligand is linked to the linker via a cleavable linking group.

29. The conjugate of any of claims 25-28, wherein the first affinity ligand is non-covalently linked to the first biomolecule.

30. The conjugate of any of claims 25-29, wherein the second affinity ligand is non-covalently linked to the second biomolecule.

31. The conjugate of any of claims 25-30, wherein the first biomolecule and/or the second biomolecule comprises a targeting ligand, a therapeutic agent or a combination thereof.

32. A conjugate comprising:

(i) a first biomolecule;
(ii) an affinity ligand linked to said first biomolecule; and
(iii) a second biomolecule linked to said affinity ligand.

33. The conjugate of claim 32, wherein the affinity ligand is non-covalently connected to said first biomolecule.

34. The conjugate of claim 32, wherein the affinity ligand is covalently connected to said second biomolecule.

35. The conjugate of any of claims 32-34, wherein the affinity ligand is linked to the second biomolecule via a linker.

36. The conjugate of claim 35, wherein the linker comprises a cleavable group.

37. The conjugate of claim 35 or 36, wherein the affinity ligand is linked to the linker via a cleavable linking group.

38. The conjugate of any of claims 35-37, wherein the second biomolecule is linked to the linker via a cleavable linking group.

39. The conjugate of any of claims 32-38, wherein the first biomolecule and/or the second biomolecule comprises a targeting ligand, a therapeutic agent or a combination thereof.

40. A conjugate comprising at least two affinity ligands linked to a therapeutic agent, wherein said at least two affinity ligands are linked to the therapeutic agent via a branched linker.

41. The conjugate of claim 40, wherein said at least two affinity ligands are different affinity ligands.

42. The conjugate of claim 40, wherein said at least two affinity ligands are same.

43. The conjugate of any of claims 40-42, wherein the therapeutic agent is an anticancer agent or a cytotoxic drug.

44. The conjugate of any of claims 40-43, wherein said at least two affinity ligands are selected independently from the group consisting of small organic or inorganic molecules, peptides, proteins, peptide derivatives and analogs, peptidomimetics, nucleic acids, nucleic acid derivatives and acid analogs, saccharines, oligosaccharides, polysaccharides, lipids, glycoproteins, glycopeptides, and any combinations thereof.

45. The conjugate of any of claims 40-44, wherein said at least two affinity ligands are selected independently from the group consisting of 4-mercaptoethyl pyridine, triazines, 2-mercapto-5-benzymidazole sulfonic acid, peptides, protein A, protein G, protein L, protein A/G/L mimetics, domains and sub-domains, Fc receptor, Fc receptor mimetics, phenyl boronic acid, boronic acid derivatives, N-benzyl-N-methyl ethanolamine, N-benzoyl-homocysteine, TRIM21 and its mimetics, Clusterin and its mimetics, histidyl-aminohexyl based, 2-mercaptoimidazole, 2-mercapto-1 -methyl-imidazole, 2-benzamido-4-mercaptobutanoic acid, phenylpropylamine, hexylamine, , 3-(2-mercaptoethyl)quinazoline-2,4(lH,3H)dione, ficolin

and its mimetics, 4'-terpyridinylsulfanylethylamine, 4-(lH-imidazol-l-yl) aniline, Poly(4-vinylpyridine), ligands used for antibody purification which specifically bind to antibodies non-covalently, any combinations or parts or modifications thereof.

46. The conjugate of any of claims 40-45, wherein the linker is selected from the group consisting of a bond, hydrocarbons, amino acids, peptides, polyethylene glycols, cyclodextrin, and any derivatives and combinations thereof.

47. The conjugate of any of claims 40-46, wherein the linker comprises a cleavable group.

48. The conjugate of any of claims 40-46, wherein the linker is a non-cleavable linker.

49. The conjugate of any of claims 40-48, wherein at least one of said at least two affinity ligands is linked to the linker via a cleavable linking group.

50. The conjugate of any of claims 40-49, wherein at least one of said at least two affinity ligands is linked to the linker via a non-cleavable linking group.

51. The conjugate of any of claims 40-50, wherein the therapeutic agent is linked to the linker via a cleavable linking group.

52. The conjugate of any of claims 40-51, wherein the therapeutic agent is linked to the linker via a non-cleavable linking group.

53. The conjugate of any of claims 40-52, wherein at least one of said at least two affinity ligands is linked to a targeting ligand.

54. The conjugate of any of claims 40-53, wherein at least two of said at least affinity ligands are linked to a targeting ligand.

55. The conjugate of any of claims 40-54, wherein at least two of said at least affinity ligands are linked to a same targeting ligand.

56. The conjugate of any of claims 40-55, wherein at least one of said at least two affinity ligands is linked to a first targeting agent and at least one of said at least two affinity ligands is linked to a second targeting ligand, and wherein the first and second targeting ligands are different.

57. The conjugate of any of claims 53-56, wherein the targeting ligand is selected from the group consisting of monoclonal antibodies, polyclonal antibodies, antigens, folates, EGF, albumin, receptor ligands, carbohydrates, aptamers, integrin receptor ligands, chemokine receptor ligands, transferrin, biotin, serotonin receptor ligands, PSMA, endothelin, GCPII, somatostatin, LDL ligands, HDL ligands, polylysine (PLL), poly L-aspartic acid, poly L-glutamic acid, lectins, glycoproteins, surfactant protein A, mucin, transferrin, sugar-albumin conjugates, peptides (e.g., an alpha helical peptide, amphipathic peptide, RGD peptide, cell permeation peptide, endosomolytic/fusogenic peptide), transport/absorption facilitators (e.g.,

naproxen, aspirin, vitamin E, folic acid), hormones, multivalent carbohydrates, vitamins (e.g., vitamin A, vitamin E, vitamin K, vitamin B, e.g., folic acid, B12, riboflavin, biotin and pyridoxal), D-galactose, multivalent galactose, N-acetyl-D-galactose (GalNAc), multivalent GalNAc, D-mannose, multivalent mannose, multivalent lactose, N-acetyl-galactosamine, N-acetyl-gulucosamine, multivalent fucose, glycosylated polyaminoacids, and any combinations thereof.

58. The conjugate of any of claims 53-57, wherein the targeting ligand binds a protein, receptor, or marker expressed on the surface of a cancer cell.

59. A pharmaceutical composition comprising a conjugate of any of claims 1-58 and a pharmaceutically acceptable carrier.

60. A method of treating a cancer in a subject in need thereof, the method comprising administering an effective amount of a conjugate of any of claims 1-58.