System for targeted delivery of therapeutic agents
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-009/14
A61K-038/00
C12N-015/11
출원번호
US-0239136
(2008-09-26)
등록번호
US-8709483
(2014-04-29)
발명자
/ 주소
Farokhzad, Omid C.
Cheng, Jianjun
Teply, Benjamin A.
Langer, Robert S.
Zale, Stephen E.
출원인 / 주소
Massachusetts Institute of Technology
대리인 / 주소
Pabst Patent Group LLP
인용정보
피인용 횟수 :
52인용 특허 :
191
초록▼
The present invention provides a drug delivery system for targeted delivery of therapeutic agent-containing particles to tissues, cells, and intracellular compartments. The invention provides targeted particles comprising a particle, one or more targeting moieties, and one or more therapeutic agents
The present invention provides a drug delivery system for targeted delivery of therapeutic agent-containing particles to tissues, cells, and intracellular compartments. The invention provides targeted particles comprising a particle, one or more targeting moieties, and one or more therapeutic agents to be delivered and pharmaceutical compositions comprising inventive targeted particles. The present invention provides methods of designing, manufacturing, and using inventive targeted particles and pharmaceutical compositions thereof.
대표청구항▼
1. A targeted particle comprising polymer conjugated to a surfactant, hydrophilic polymer or lipid, the particle having bound thereto a plurality of small molecule targeting moieties that specifically bind to the Zn2+ NAAG/PSMA binding pocket within prostate specific membrane antigen (PSMA) selected
1. A targeted particle comprising polymer conjugated to a surfactant, hydrophilic polymer or lipid, the particle having bound thereto a plurality of small molecule targeting moieties that specifically bind to the Zn2+ NAAG/PSMA binding pocket within prostate specific membrane antigen (PSMA) selected from the group consisting of 2-PMPA, GPI5232, VA-033 2MPPA, thiol and indole thiol based PSMA inhibitors, 3-(2-mercaptoethyl)-1H-indole-2-carboxylic acid derivative PSMA inhibitors, hydroxamate derivative PSMA inhibitors, PDBA-based PSMA inhibitors, and urea-based PSMA inhibitors, andhaving encapsulated or dispersed therein a therapeutic, diagnostic or prophylactic agent,wherein at least 80% of the particles have a greatest dimension less than 250 nm and have enhanced permeation through tumor vasculature and retention in tumor tissue as compared to particles greater than 250 nm. 2. The targeted particle of claim 1, wherein the polymer is selected from the group consisting of poly(lactide-co-glycolide) (PLGA), poly(lactic acid) (PLA), poly(glycolic acid) (PGA), polycaprolactone, and polyanhydrides. 3. The targeted particle of claim 1, wherein the polymer is PLA. 4. The targeted particle of claim 1, wherein the particle comprises two or more polymers. 5. The targeted particle of claim 4, wherein at least one polymer is selected from the group consisting of polyethylenes, polycarbonates, polyanhydrides, polyhydroxyacids, polypropylfumerates, polycaprolactones, polyamides, polyacetals, polyethers, polyesters, poly(orthoesters), polycyanoacrylates, polyvinyl alcohols, polyurethanes, polyphosphazenes, polyacrylates, polymethacrylates, polycyanoacrylates, polyureas, polystyrenes, polyamines, and combinations thereof. 6. The targeted particle of claim 4, wherein at least one polymer is selected from the group consisting of polyesters, polyanhydrides, polyethers, polyurethanes, polymethacrylates, polyacrylates, and polycyanoacrylates. 7. The targeted particle of claim 4, wherein at least one polymer is polyalkylene glycol. 8. The targeted particle of claim 4, wherein at least one polymer is polyethylene glycol (PEG). 9. The targeted particle of claim 1, wherein the conjugated polymer comprises a copolymer of two or more polymers. 10. The targeted particle of claim 9, wherein the conjugated copolymer is a copolymer of PLA and PEG. 11. The targeted particle of claim 1, wherein the targeted particle comprises a protein, lipid, or carbohydrate. 12. The targeted particle of claim 1, wherein the small molecule targeting moiety is selected from the group consisting of urea-based inhibitors. 13. The targeted particle of claim 1, wherein the therapeutic agent is selected from the group consisting of small molecules, proteins, nucleic acids, carbohydrates, lipids, and combinations thereof. 14. The targeted particle of claim 1, wherein the therapeutic agent is an anti-cancer agent. 15. The targeted particle of claim 1, wherein the therapeutic agent is selected from the group consisting of antibodies, recombinant antibodies, humanized antibodies, characteristic portions thereof, and combinations thereof. 16. The targeted particle of claim 1, wherein the therapeutic agent is an enzyme. 17. The targeted particle of claim 1, wherein the therapeutic agent is a small interfering RNA, a small hairpin RNA, or a microRNA. 18. The targeted particle of claim 1, wherein at least 90% of the particles have a greatest dimension less than 200 nm in diameter. 19. The targeted particle of claim 1, wherein the prophylactic agent is a vaccine. 20. The targeted particle of claim 1, wherein the therapeutic agent is docetaxel. 21. The targeted particle of claim 1, wherein the targeting moiety is associated with the particle via at least one covalent linkage. 22. A method of treating prostate cancer in a subject, comprising administering an effective amount to a subject in need thereof of particles comprising polymer conjugated to a surfactant, hydrophilic polymer or lipid, the particle having bound thereto a plurality of small molecule targeting moieties that specifically bind to the Zn2+ NAAG/PSMA binding pocket within prostate specific membrane antigen (PSMA) selected from the group consisting of 2-PMPA, GPI5232, VA-033, thiol and indole thiol based PSMA inhibitors, 3-(2-mercaptoethyl)-1H-indole-2-carboxylic acid derivative PSMA inhibitors, hydroxamate derivative PSMA inhibitors, PDBA-based PSMA inhibitors, and urea-based PSMA inhibitors,having encapsulated or dispersed therein a therapeutic, diagnostic or prophylactic agent,wherein at least 80% of the particles have a greatest dimension less than 250 nm and have enhanced permeation through tumor vasculature and retention in tumor tissue as compared to particles greater than 250 nm. 23. The method of claim 22, wherein the targeted particle further comprises a pharmaceutically acceptable excipient. 24. The method of claim 22, wherein the targeted particle is administered to the subject by an intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, subcutaneous, or intraventricular, route. 25. The method of claim 22, wherein the targeted particle is administered directly to the prostate. 26. The method of claim 22, wherein the targeted particle is administered directly to prostate cancer cells. 27. The method of claim 26, wherein the targeted particle is administered directly to prostate cancer cells by topical administration. 28. The method of claim 26, wherein the targeted particle is administered directly to prostate cancer cells by injection into tissue comprising the prostate cancer cells. 29. The method of claim 26, wherein the targeted particle is administered to the subject by implantation of targeted particles at or near prostate cancer cells by stereotactic surgery. 30. The method of claim 26, wherein the targeted particle is administered to the subject by implantation of targeted particles at or near prostate cancer cells during surgical removal of a tumor. 31. A method of preparing particles comprising polymer conjugated to a surfactant, hydrophilic polymer or lipid, the particle having bound thereto a plurality of protein or small molecule targeting moieties that specifically bind to the particle having bound thereto a plurality of small molecule targeting moieties that specifically bind to the Zn2+ NAAG/PSMA binding pocket within prostate specific membrane antigen (PSMA) selected from the group consisting of 2-PMPA, GPI5232, VA-033, thiol and indole thiol based PSMA inhibitors, 3-(2-mercaptoethyl)-1H-indole-2-carboxylic acid derivative PSMA inhibitors, hydroxamate derivative PSMA inhibitors, PDBA-based PSMA inhibitors, and urea-based PSMA inhibitors, andhaving encapsulated or dispersed therein a therapeutic, diagnostic or prophylactic agent,wherein at least 80% of the particles have a greatest dimension less than 250 nm and have enhanced permeation through tumor vasculature and retention in tumor tissue as compared to particles greater than 250 nm, comprising nanoprecipitation or flow focusing fluidic channels of polymer conjugated to a surfactant, hydrophilic polymer or lipid, in combination with a therapeutic, diagnostic or prophylactic agent and targeting moieties that specifically binding to prostate specific membrane antigen selected from the group consisting of 2-PMPA, GPI5232, VA-033, thiol and indole thiol based PSMA inhibitors, 3-(2-mercaptoethyl)-1H-indole-2-carboxylic acid derivative PSMA inhibitors, hydroxamate derivative PSMA inhibitors, PDBA-based PSMA inhibitors, and urea-based PSMA inhibitors, and selecting the particles having a greatest dimension less than 250 nm. 32. A population of targeted particles, comprising a particle comprising a polymeric matrix, wherein the polymeric matrix comprises a polyester;a targeting moiety wherein the targeting moiety is a urea-based prostate specific membrane antigen (PSMA) inhibitor; anda therapeutic agent;wherein at least 80% of the particles have a greatest dimension less than 250 nm,having encapsulated or dispersed therein a therapeutic, diagnostic or prophylactic agent, andhaving enhanced permeation through tumor vasculature and retention in tumor tissue as compared to particles greater than 250 nm. 33. The targeted particle of claim 32, wherein the urea-based inhibitor is selected from the group consisting of ZJ 43, ZJ 11, ZJ 17, and ZJ 38. 34. The targeted particle of claim 1, wherein the conjugated polymer is a copolymer of PLA and PEG, and wherein the therapeutic agent is docetaxel. 35. The targeted particle of claim 34, wherein the greatest dimension of the particles is between 25 nm and 200 nm in diameter. 36. The targeted particle of claim 1, wherein the therapeutic agent is a taxane. 37. The targeted particle of claim 1, wherein the targeting moiety increases intratumor levels of the therapeutic agent by at least three-fold. 38. The targeted particle of claim 32, wherein at least 90% of the particles have a greatest dimension less than 250 nm. 39. The targeted particle of claim 1, wherein at least 80% of the particles have a greatest dimension less than 200 nm. 40. The targeted particle of claim 1, wherein at least 90% of the particles have a greatest dimension less than 200 nm. 41. The targeted particle of claim 32, wherein at least 80% of the particles have a greatest dimension less than 200 mm. 42. The targeted particle of claim 32, wherein at least 90% of the particles have a greatest dimension less than 200 nm. 43. The targeted particle of claim 1 having bound thereto a plurality of small molecule targeting moieties that specifically bind to the Zn2+ NAAG/PSMA binding pocket within prostate specific membrane antigen (PSMA) selected from the group consisting of 2-PMPA, GPI5232, VA-033, and 2-MPPA.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (191)
Gerster John F. (Woodbury MN) Crooks Stephen L. (Mahtomedi MN) Lindstrom Kyle J. (Houlton WI), 1-substituted, 2-substituted 1H-imidazo[4,5-c]quinolin-4-amines.
Schmitz,Juergen; Dzionek,Andrzej; Buck,David William, Antigen-binding fragments specific for dendritic cells, compositions and methods of use thereof antigens recognized thereby and cells obtained thereby.
Arimilli Murty N. ; Cundy Kenneth C. ; Dougherty Joseph P. ; Kim Choung U. ; Oliyai Reza ; Stella Valentino J., Antiviral phosphonomethoxy nucleotide analogs having increased oral bioavailability.
Hubbard Vance M. (Bedford) Brunson Welton K. (Bedford) Saied V. C. (Wichita Falls TX), Apparatus and method for raising a skin wheal and anesthetizing skin.
Mikos Antonios G. (Houston TX) Sarakinos Georgios (Boston MA) Vacanti Joseph P. (Winchester MA) Langer Robert S. (Newton MA) Cima Linda G. (Lexington MA), Biocompatible polymer membranes and methods of preparation of three dimensional membrane structures.
Barrera Denise (Oakdale MN) Langer Robert S. (Newton MA) Lansbury ; Jr. Peter T. (Brookline MA) Vacanti Joseph P. (Winchester MA), Biodegradable polymers for cell transplantation.
Vacanti Joseph P. ; Vacanti Charles A. ; Langer Robert S., Biodegradable synthetic polymeric fibrous matrix containing chondrocyte for in vivo production of a cartilaginous struct.
D\Amore Patricia (Brookline MA) Leong Kam W. (Cambridge MA) Langer Robert S. (Somerville MA), Bioerodible articles useful as implants and prostheses having predictable degradation rates.
Skwierczynski Raymond D. ; Phares Kenneth R. ; Miller Richard L. ; Li Zheng Jane ; Jozwiakowski Michael J. ; Busch Terri F., Formulations and methods for treatment of mucosal associated conditions with an immune response modifier.
Dalton,James T.; Miller,Duane D.; Steiner,Mitchell S.; Veverka,Karen A., Halogenated selective androgen receptor modulators and methods of use thereof.
Swain Philip A. ; Schad Victoria C. ; Greenstein Julia L. ; Exley Mark A. ; Fox Barbara S. ; Powers Stephen P. ; Gefter Malcolm L., Hapten-carrier conjugates for use in drug-abuse therapy and methods for preparation of same.
Kedl,Ross M.; Griesgraber,George W.; Zarraga,Isidro Angelo E.; Wightman,Paul D., Immunostimulatory compositions and methods of stimulating an immune response.
Lilley Stephen J. (Sawston GBX) Taylor Hugh F. (Sawston GBX) Theobald David R. (Huntingdon GBX) Carlson Craig J. (Andover MA) Rosen David I. (Arlington MA) Johnson Thomas R. (Milford NH), Medical injection system and method, gas spring thereof and launching device using gas spring.
Tice Thomas R. ; Gilley Richard M. ; Eldridge John H. ; Staas Jay K., Method for delivering bioactive agents into and through the mucosally-associated lymphoid tissues and controlling their.
Bengs, Holger; Grande, Jürgen; Schuth, Silke; Böhm, Gitte; Schneller, Arnold; Brunner, Anette, Method for preparing smooth-surface spherical microparticles completely or partially made of at least one water-insoluble linear polysaccharide and microparticles produced according to this method.
Bomberger David C. ; Catz Paul G. ; Smedley Mark I. ; Stearns Paul C., Method for producing drug-loaded microparticles and an ICAM-1 dosage form so produced.
Deming, Timothy J.; Yu, Miaoer; Curtin, Scott A.; Hwang, Jungyeon; Wyrsta, Michael D.; Nowak, Andrew; Seidel, Scott W., Methods and compositions for controlled polypeptide synthesis.
Speaker Tully J. (Philadelphia PA) Sultzbaugh Kenneth J. (Philadelphia PA), Microcapsules of predetermined peptide(s) specificity (ies), their preparation and uses.
Jacobson Stephen C. ; Ramsey J. Michael, Microfabricated device and method for multiplexed electrokinetic focusing of fluid streams and a transport cytometry method using same.
Horoszewicz Julius S. (Williamsville NY), Monoclonal antibodies to a new antigenic marker in epithelial prostatic cells and serum of prostatic cancer patients.
Domb Abraham J. (Efrat ILX) Gref Ruxandra (Nancy FRX) Minamitake Yoshiharu (Ota JPX) Peracchia Maria T. (Parma ITX) Langer Robert S. (Newton MA), Nanoparticles and microparticles of non-linear hydrophilic-hydrophobic multiblock copolymers.
Domb Abraham J.,ILX ; Gref Ruxandra,FRX ; Minamitake Yoshiharu,JPX ; Peracchia Maria Teresa,ITX ; Langer Robert S., Nanoparticles and microparticles of non-linear hydrophilic-hydrophobic multiblock copolymers.
Mirkin, Chad A.; Letsinger, Robert L.; Mucic, Robert C.; Storhoff, James J.; Elghanian, Robert; Taton, Thomas A.; Garimella, Viswanadham; Li, Zhi, Nanoparticles having oligonucleotides attached thereto and uses therefor.
McKinnon ; Jr. Charles N. (Laguna Niguel CA) Peterson Steven F. (West Linn OR) Smith Paul E. (Tualatin OR) Nakagawa Takaaki (Tigard OR) Bartholomew Victor L. (Tigard OR), Needleless hypodermic injection device.
Peterson Steven F. (West Linn OR) McKinnon ; Jr. Charles N. (Laguna Niguel CA) Smith Paul E. (Tualatin OR) Nakagawa Takaaki (Tigard OR) Bartholomew Victor L. (Tigard OR), Needleless hypodermic injection methods and device.
Bischofberger Norbert W. ; Jones Robert J. ; Arimilli Murty N. ; Lin Kuei-Ying ; Louie Michael S. ; McGee Lawrence R. ; Prisbe Ernest J. ; Lee William A. ; Cundy Kenneth C., Nucleotide analogs.
Santus Giancarlo (Milan ITX) Bottoni Giuseppe (Bergamo ITX) Sala Giovanni (Verona ITX), Pharmaceutical controlled-release composition with bioadhesive properties.
Fessi Curt (Paris FRX) Devissaguet Jean-Philippe (Neuilly S/Seine FRX) Puisieux Francis (Maisons Alfort MO FRX) Thies Curt (St. Louis MO), Process for the preparation of dispersible colloidal systems of a substance in the form of nanoparticles.
Cech Thomas R. (Boulder CO) Zaug Arthur J. (Louisville CO) Been Michael D. (Boulder CO), RNA ribozyme polymerases, dephosphorylases, restriction endoribo-nucleases and methods.
Hirosue Sachiko ; Mueller Bernhard G.,CHX ; Langer Robert S. ; Mulligan Richard C., Sub-100nm biodegradable polymer spheres capable of transporting and releasing nucleic acids.
Larry Gold ; Michael Willis ; Tad Koch ; Steven Ringquist ; Kirk Jensen ; Brent Atkinson, Systematic evolution of ligands by exponential enrichment: photoselection of nucleic acid ligands.
Gold Larry ; Willis Michael ; Koch Tad ; Ringquist Steven ; Jensen Kirk ; Atkinson Brent, Systematic evolution of ligands by exponential enrichment: photoselection of nucleic acid ligands and solution selex.
Gold Larry ; Willis Michael ; Koch Tad ; Ringquist Steven ; Jensen Kirk ; Atkinson Brent, Systematic evolution of ligands by exponential enrichment: photoselection of nucleic acid ligands and solution selex.
Kunz Lawrence L. ; Klein Richard A. ; Reno John M. ; Grainger David J.,GBX ; Metcalfe James C.,GBX ; Weissberg Peter L.,GBX ; Anderson Peter G., Therapeutic inhibitor of vascular smooth muscle cells.
Setterstrom, Jean A.; Tice, Thomas R.; Jacob, Elliot; Reid, Robert H.; van Hamont, John; Boedecker, Edgar C.; Jeyanthi, Ramassubbu; Friden, Phil; Roberts, F. Donald; McQueen, Charles E.; Bhattacharje, Therapeutic treatment and prevention of infections with a bioactive material(s) encapuslated within a biodegradable-bio-compatable polymeric matrix.
Bancel, Stephane; Chakraborty, Tirtha; de Fougerolles, Antonin; Elbashir, Sayda M.; John, Matthias; Roy, Atanu; Whoriskey, Susan; Wood, Kristy M.; Hatala, Paul; Schrum, Jason P.; Ejebe, Kenechi; Ellsworth, Jeff Lynn; Guild, Justin, In vivo production of proteins.
Bancel, Stephane; Chakraborty, Tirtha; de Fougerolles, Antonin; Elbashir, Sayda M.; John, Matthias; Roy, Atanu; Whoriskey, Susan; Wood, Kristy M.; Hatala, Paul; Schrum, Jason P.; Ejebe, Kenechi; Ellsworth, Jeff Lynn; Guild, Justin, Modified polynucleotides for the production of biologics and proteins associated with human disease.
Bancel, Stephane; Chakraborty, Tirtha; de Fougerolles, Antonin; Elbashir, Sayda M.; John, Matthias; Roy, Atanu; Whoriskey, Susan; Wood, Kristy M.; Hatala, Paul; Schrum, Jason P.; Ejebe, Kenechi; Ellsworth, Jeff Lynn; Guild, Justin, Modified polynucleotides for the production of biologics and proteins associated with human disease.
Bancel, Stephane; Chakraborty, Tirtha; de Fougerolles, Antonin; Elbashir, Sayda M.; John, Matthias; Roy, Atanu; Whoriskey, Susan; Wood, Kristy M.; Hatala, Paul; Schrum, Jason P.; Ejebe, Kenechi; Ellsworth, Jeff Lynn; Guild, Justin, Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins.
Bancel, Stephane; Chakraborty, Tirtha; de Fougerolles, Antonin; Elbashir, Sayda M.; John, Matthias; Roy, Atanu; Whoriskey, Susan; Wood, Kristy M.; Hatala, Paul; Schrum, Jason P.; Ejebe, Kenechi; Ellsworth, Jeff Lynn; Guild, Justin, Modified polynucleotides for the production of oncology-related proteins and peptides.
Bancel, Stephane; Chakraborty, Tirtha; de Fougerolles, Antonin; Elbashir, Sayda M.; Ellsworth, Jeff Lynn; Ejebe, Kenechi; Guild, Justin; John, Matthias; Hatala, Paul; Roy, Atanu; Schrum, Jason P.; Whoriskey, Susan; Wood, Kristy M., Modified polynucleotides for the production of proteins.
Bancel, Stephane; Chakraborty, Tirtha; de Fougerolles, Antonin; Elbashir, Sayda M.; John, Matthias; Roy, Atanu; Whoriskey, Susan; Wood, Kristy M.; Hatala, Paul; Schrum, Jason P.; Ejebe, Kenechi; Ellsworth, Jeff Lynn; Guild, Justin, Modified polynucleotides for the production of proteins.
Bancel, Stephane; Chakraborty, Tirtha; de Fougerolles, Antonin; Elbashir, Sayda M.; John, Matthias; Roy, Atanu; Whoriskey, Susan; Wood, Kristy M.; Hatala, Paul; Schrum, Jason P.; Ejebe, Kenechi; Ellsworth, Jeff Lynn; Guild, Justin, Modified polynucleotides for the production of proteins associated with human disease.
Bancel, Stephane; Chakraborty, Tirtha; de Fougerolles, Antonin; Elbashir, Sayda M.; John, Matthias; Roy, Atanu; Whoriskey, Susan; Wood, Kristy M.; Hatala, Paul; Schrum, Jason P.; Ejebe, Kenechi; Ellsworth, Jeff Lynn; Guild, Justin, Modified polynucleotides for the production of secreted proteins.
Bagrodia, Shubha; Lafontaine, Jennifer; Lovatt, Zach; Shin, Eyoung; Song, Young Ho; Troiano, Greg; Wang, Hong, Therapeutic nanoparticles comprising a therapeutic agent and methods of making and using the same.
Bagrodia, Shubha; Lafontaine, Jennifer; Lovatt, Zach; Shin, Eyoung; Song, Young Ho; Troiano, Greg; Wang, Hong, Therapeutic nanoparticles comprising a therapeutic agent and methods of making and using the same.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.