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1. WO2020112129 - ENHANCED TARGETED DELIVERY OF THERAPEUTIC AGENTS

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[ EN ]

CLAIMS

1. A targeted drug conjugate composition, comprising a carrier and a precision targeted drug conjugate comprised of a therapeutic agent and a targeting agent, wherein (i) the therapeutic potency or therapeutic index of the targeted drug conjugate is at least about 10-fold more than the therapeutic potency or therapeutic index of an untargeted drug composition comprising the same therapeutic agent in non-targeted form, and (ii) the targeting agent specifically binds to an extracellular domain of a protein displayed on an outer surface of a cell membrane of a cell, and wherein optionally the therapeutic agent is conjugated to the targeting agent.

2. A targeted drug conjugate composition according to claim 1 wherein the therapeutic agent is selected from the group consisting of a small molecule, a peptide, a protein, a nucleic acid, a radionuclide, and a gene delivery vehicle.

3. A targeted drug conjugate composition according to claim 1 wherein the therapeutic agent is selected from the group consisting of chemotherapeutic agent, an immune stimulatory agent, an anti-neoplastic agent, a pro-coagulant, a toxin, an antibiotic, a hormone, an enzyme, and a lytic agent.

4. A targeted drug conjugate composition according to claim 1 wherein the targeting agent is one member of a high-affinity binding pair, optionally a molecule selected from the group consisting of an antibody, an antigen-binding antibody fragment, a receptor, a ligand-binding receptor fragment, a receptor ligand, a small molecule, and an aptamer.

5. A targeted drug conjugate composition according to claim 1 wherein the targeted drug conjugate further comprises a linker disposed between the therapeutic agent and targeting agent.

6. A targeted drug conjugate composition according to claim 1 wherein the targeted drug conjugate is a nanoparticle, optionally a nanoparticle having a mean diameter of less than about 20 nm.

7. A pharmaceutical composition, comprising a targeted drug conjugate composition according to claim 1 wherein the carrier is a pharmaceutically acceptable carrier.

8. A targeted drug conjugate composition according to claim 1 wherein the effective amount of the therapeutic agent is present in an amount that is at least about 100 times less than the effective amount of the therapeutic agent when the therapeutic agent is a non-targeted therapeutic agent.

9. A targeted drug conjugate composition according to claim 1 wherein:

the targeting agent specifically binds to an extracellular domain of a protein displayed on the outer surface of a cell membrane of a cell that is a vascular endothelial cell;

the extracellular domain of the protein is capable of mediating active transvascular pumping of the targeted drug conjugate across the cell into underlying diseased tissue; and

the extracellular domain of the protein that is displayed on the surface of the vascular endothelial cell is predominantly located in or translocated to caveolae.

10. A method of decreasing the amount of a therapeutic agent needed to effect therapy, comprising administering a targeted drug conjugate composition according to claim 1 to a subject having a disease or condition amenable to treatment by the therapeutic agent, thereby decreasing the amount of the therapeutic agent needed to treat the disease or condition, whereby the amount of the therapeutic agent administered to the subject via the targeted drug conjugate composition is at least about 10-fold less than when the therapeutic agent present in the targeted drug conjugate is administered in a non-targeted form to treat the disease or condition.

11. A method according to claim 10 wherein the amount of the therapeutic agent is at least about 100-fold less than when the therapeutic agent present in the targeted drug conjugate composition is administered in a non-targeted form to treat the disease or condition.

12. A method according to claim 10 wherein the therapeutic agent is selected from the group consisting of a small molecule, a peptide, a protein, a nucleic acid, a radionuclide, and a gene delivery vehicle, optionally a virus.

13. A method according to claim 1 wherein the targeting agent is one member of a high-affinity binding pair, optionally a molecule selected from the group consisting of an antibody, an antigen-binding antibody fragment, a receptor, a ligand-binding receptor fragment, a receptor ligand, a small molecule, and an aptamer.

14. A method according to claim 10 wherein the disease or condition is selected from the group consisting of a non-hematologic cancer, an infection, inflammation, fibrosis, acute injury, infarction, and a pathological malfunction that is not one of the foregoing.

15. A method of treating a disease or condition, comprising administering to a subject suspected of or having a disease or condition a targeted drug conjugate composition according to claim 1, thereby treating the disease or condition.

16. A method according to claim 15 wherein the subject is a human or another mammal, optionally a mammal selected from the group consisting of an bovine, canine, equine, feline, ovine, and porcine animal.

17. A method according to claim 15 wherein the disease or condition is selected from the group consisting of a non-hematologic cancer, an infection, inflammation, fibrosis, acute injury, infarction, and a pathological malfunction that is not one of the foregoing.

18. A method according to claim 17 wherein the non-hematologic cancer is a solid cancer selected from the group consisting of a sarcoma, carcinoma, lymphoma, and metastatic lesion.