# US 10,765,632 B2 · Methods of improving delivery of compounds for therapy, prophylaxis or diagnosis > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,765,632 B2 - Document ID: US10765632B2 - Status: Granted - Kind: B2 - Application number: 15/529,106 - Filed: 2015-11-24 - Published: 2017-09-14 - Granted: 2020-09-08 - Earliest claimed: 2014-11-25 - Assignees: Curadigm SAS - Applicants: Curadigm SAS - Inventors: Matthieu Germain; Marie-Edith Meyre; Agnes Pottier; Laurent Levy - Web page: https://patentgrep.com/patent/US10765632B2 ## CPC - A61K 9/1271: Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) - A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant - A61K 9/51: Nanocapsules; {Nanoparticles; (nanotubes A61K9/0092; polymeric micelles A61K9/1075; polymersomes A61K9/1273; pure drug nanoparticles A61K9/14; drug nanoparticles with adsorbed surface modifiers A61K9/141; conjugates, e.g. between drug and non-active nanoparticles, A61K47/50; preparations for in vivo diagnosis A61K49/00; with radioactive substances A61K51/00)} - A61K 31/704: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} - A61K 47/6911: {the form being a liposome} - A61P 35/00: Antineoplastic agents - A61K 9/0009: {involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis} - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention relates to a pharmaceutical composition comprising the combination of (i) at least one biocompatible nanoparticle and (ii) at least one carrier comprising at least one pharmaceutical compound, to be administered to a subject in need of such a pharmaceutical compound, wherein the combination of the at least one biocompatible nanoparticle and of the at least one carrier comprising the pharmaceutical compound(s) potentiates the compound(s) of interest effectiveness in therapy, prophylaxis or diagnosis. The invention also relates to such a composition for use for administering the pharmaceutical compound(s) in a subject in need thereof, wherein the at least one biocompatible nanoparticle and the at least one carrier comprising the at least one pharmaceutical compound are to be administered separately in a subject in need of said pharmaceutical compound, typically between more than 5 minutes and about 72 hours one from each other. ## Claims ### Claim 1 A method for treating cancer in a subject, the method comprising a step of intravenously administering to the subject at least one carrier comprising at least one pharmaceutical compound, the at least one pharmaceutical compound being encapsulated in the at least one carrier, and the at least one pharmaceutical compound being a chemotherapeutic agent, and a distinct step of intravenously administering to the subject at least one biocompatible lipid-based nanoparticle, wherein the at least one carrier is devoid of any surface sterically stabilizing agent and wherein the longest dimension of the at least one biocompatible nanoparticle is between about 4 nm and about 500 nm, the surface charge value of the at least one biocompatible nanoparticle is a negative surface charge value below −10 mV, the at least one biocompatible nanoparticle is not used as a pharmaceutical compound, and said at least one biocompatible nanoparticle is administered to the subject about 10 minutes, or more than 10 minutes, and less than about 72 hours before administering the at least one carrier comprising the at least one pharmaceutical compound. ### Claim 2 (depends on 1) The method according to claim 1, wherein the nanoparticle is further covered with a biocompatible coating. ### Claim 3 (depends on 1) The method according to claim 1, wherein the carrier is a plain carrier. ### Claim 4 (depends on 1) The method according to claim 1, wherein the carrier is a hollow carrier. ### Claim 5 (depends on 1) The method according to claim 1, wherein the carrier's surface is devoid of any hydrophilic polymer. ### Claim 6 (depends on 1) The method according to claim 1, wherein the carrier's surface is devoid of polyethylene glycol (PEG) polymer. ### Claim 7 (depends on 1) The method according to claim 1, wherein the administration of the at least one biocompatible nanoparticle and of the at least one carrier comprising the pharmaceutical compound(s) maintains the therapeutic benefit of said pharmaceutical compound(s) and reduces toxicity, or increases the therapeutic benefit of said pharmaceutical compound(s) for an equivalent or reduced toxicity, for the subject, when compared to therapeutic benefit and toxicity induced by the standard therapeutic dose(s) of said compound(s) in the absence of any biocompatible nanoparticle and/or carrier. ### Claim 8 (depends on 1) The method according to claim 1, wherein the administration of the at least one biocompatible nanoparticle and of the at least one carrier comprising the pharmaceutical compound(s) allows a reduction of at least 10% of the administered pharmaceutical compound(s) therapeutic dose(s) when compared to the standard therapeutic dose(s) of said compound(s) while maintaining the same therapeutic benefit for an equivalent toxicity or a reduced toxicity for the subject or while increasing the therapeutic benefit for an equivalent or reduced toxicity for the subject in the absence of any biocompatible nanoparticle and/or carrier. ### Claim 9 (depends on 1) The method according to claim 1, wherein the nanoparticle is cleared from the subject to whom it has been administered within one hour and six weeks after its administration to a subject in need of said at least one pharmaceutical compound. ### Claim 10 (depends on 1) The method according to claim 1, wherein the chemotherapeutic agent is selected from a small molecule, a targeted small molecule, a cytotoxic compound and a transition metal coordination complex. ### Claim 11 (depends on 1) The method according to claim 1, wherein the pharmaceutical compound is released from the carrier by temporal-controlled diffusion, carrier erosion and/or carrier degradation. ### Claim 12 (depends on 1) The method according to claim 1, wherein the pharmaceutical compound is released from the carrier in response to an intracellular or an extracellular stimulus. ### Claim 13 (depends on 1) The method according to claim 1, wherein the pharmaceutical compound is released from the carrier when said carrier is exposed to electromagnetic radiation, ultrasound or a magnetic field. ### Claim 14 (depends on 1) The method according to claim 1, wherein said at least one biocompatible nanoparticle is administered to the subject about 10 minutes before administering the at least one carrier comprising at least one pharmaceutical compound. ### Claim 15 (depends on 1) The method according to claim 1, wherein said at least one biocompatible nanoparticle is administered to the subject more than 10 minutes and less than about 24 hours before administering the at least one carrier comprising at least one pharmaceutical compound. ### Claim 16 (depends on 1) The method according to claim 1, wherein said carrier is devoid of a surface sterically stabilizing agent selected from Dextran, polysialic acid (PSA), hyaluronic acid, chitosan, heparin, polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), polyacrylamide, poly(ethylene glycol) (PEG), poloxamer, poloxamine or polysorbate.