Molecular Bilayer Structure (e.g., Vesicle, Liposome) Patents (Class 424/1.21)
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Patent number: 7056653Abstract: The extent of binding of a moiety, such as a biomolecule, to a surface, where the local environment at the surface has a pH or surface potential which is altered upon binding of the moiety, is determined by stably incorporating at the surface a probe which contains a pH- or potential-sensitive fluorophore.Type: GrantFiled: February 8, 2001Date of Patent: June 6, 2006Assignee: Yissum Research Development Company of the Hebrew University of JerusalemInventors: Yechezkel Barenholz, Danielle Hirsch-Lerner, Rivka Cohen, Arie Dagan, Shimon Gatt
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Patent number: 6991805Abstract: The present invention provides a liposomal composition for targeted delivery of drugs. The composition comprises poloxamer molecules and liposomes encapsulating one or more delivery agents. At above the critical micellar temperature of the poloxamer, a fraction of the poloxamer molecules form micelles and another fraction becomes incorporated into the liposome surface, thereby inhibiting their adhesion to cells. At a temperature below the critical micellar temperature, the poloxamer molecules dissociate into monomers allowing the liposomes to adhere to adjacent cells and effecting retention of the liposomes in the surrounding tissue. A method is provided for delivery of agents to target site comprising administering the composition to an individual and cooling the target site to cause retention of the liposomes at or near the target site.Type: GrantFiled: September 6, 2002Date of Patent: January 31, 2006Assignee: Health Research, Inc.Inventors: Sek Wen Hui, Arindam Sen
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Patent number: 6989196Abstract: Microencapsulation methods and products are provided. The method includes forming, at a first temperature, a emulsion which comprises aqueous microdroplets, including the agent (e.g., a magnetic material or drug) and a cross-linkable matrix material (e.g., a protein such as albumin), dispersed in a hydrophobic continuous phase comprising an oil and an oil-soluble surfactant, the first temperature being below the temperature effective to initiate cross-linking of the matrix material, and then heating the emulsion to a temperature and for a time effective to cause the matrix material to self-crosslink, to form microparticles comprising the agent encapsulated by the crosslinked matrix material.Type: GrantFiled: October 1, 2003Date of Patent: January 24, 2006Assignee: Florida State University Research FoundationInventors: Jhunu Chatterjee, Yousef Haik, Ching-Jen Chen
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Patent number: 6989153Abstract: The present invention relates to a radiation sensitive liposome, and the use of this liposome as carrier for therapeutic and diagnostic agent(s). In particular, the invention encompasses a liposomal delivery system, comprising a stable liposome-forming lipid and a polymerizable colipid, a fraction of which polymerizable colipid polymerizes upon exposure to ionizing radiation, thereby destabilizing the liposomal membrane. Destabilization of liposomes allows for leakage of liposomal contents. The present invention further contemplates methods of diagnosing and treating conditions and diseases that are responsive to liposome-encapsulated or associated agents.Type: GrantFiled: November 30, 2000Date of Patent: January 24, 2006Assignees: Varian Medical Systems Technologies, Inc., Arizona Board of Regents on Behalf of the University of ArizonaInventors: David F. O'Brien, Kathy A. McGovern, Bruce Bondurant, Robert Sutherland
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Patent number: 6986902Abstract: The present invention relates generally to the amphiphilic polyelectrolyte, poly(2-ethylacrylic acid) and covalently bonded lipids to generate Lipo-PEAA. These Lipo-PEAA are then used to make pH-sensitive liposomes which become unstable, permeable or fusogenic with certain pH changes. In addition, this invention generally describes methods for delivering therapeutic compounds and drugs to target cells by administering to a host the pH-sensitive liposomes of the present invention.Type: GrantFiled: April 27, 1999Date of Patent: January 17, 2006Assignee: Inex Pharmaceuticals CorporationInventors: Tao Chen, Yuehua He, Peter Cullis, Thomas Madden, Peter Scherrer, David Tirrell, Phalgun Joshi, Jung Soo Kim
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Patent number: 6979460Abstract: A novel amphiphilic lipid compound having a cleavable, vinyl ether linked hydrophilic headgroup is described. Also described are liposomes containing the vinyl ether lipid compound, which may be triggered to release their contents and/or permeablize or fuse with target lipid membranes. The cleavable vinyl ether linkage allows the hydrophilic headgroup to be dissociated from the hydrophobic tailgroup(s) of the lipid compound to facilitate phase transitions in the lipid bilayer.Type: GrantFiled: July 17, 2000Date of Patent: December 27, 2005Assignee: Purdue Research FoundationInventors: David H. Thompson, Jeremy A. Boomer, Robert Haynes
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Patent number: 6974589Abstract: A lipid represented by the formula: wherein each of R1 and R2 is an alkyl or alkenyl chain having between about 8 to about 24 carbon atoms; n=0–20; L is selected from the group consisting of (i) —X—(C?O)—Y—, (ii) —X—(C?O)—, and (iii) —X—CH2—, wherein X and Y are independently selected from oxygen, NH, and a direct bond; and Z is a weakly basic moiety that has a pK of less than about 7.4 and greater than about 4.0 is described.Type: GrantFiled: October 10, 2000Date of Patent: December 13, 2005Assignee: Miza CorporationInventors: Shi Kun Huang, Samuel Zalipsky, Wei-Ming Zhang, Bei Jin, Yolanda P. Quinn
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Patent number: 6962747Abstract: The present invention is a self-assembling material comprised of stacks of lipid bilayers formed in a columnar structure, where the assembly process is mediated and regulated by chemical recognition events. The material, through the chemical recognition interactions, has a self-regulating system that corrects the radial size of the assembly creating a uniform diameter throughout most of the structure. The materials form and are stable in aqueous solution. These materials are useful as structural elements for the architecture of materials and components in nanotechnology, efficient light harvesting systems for optical sensing, chemical processing centers, and drug delivery vehicles.Type: GrantFiled: October 23, 2001Date of Patent: November 8, 2005Assignee: Sandia CorporationInventors: Darryl Y. Sasaki, Tina A. Waggoner, Julie A. Last
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Patent number: 6962784Abstract: This invention discloses a method for preparing a complex comprised of a VEGF Nucleic Acid Ligand and a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound by identifying a VEGF Nucleic Acid Ligand by SELEX methodology and associating the VEGF Nucleic Acid Ligand with a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound. The invention further discloses Complexes comprising one or more VEGF Nucleic Acid Ligands in association with a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound. The invention further includes a Lipid construct comprising a VEGF Nucleic Acid Ligand or Complex and methods for making the same.Type: GrantFiled: July 25, 2002Date of Patent: November 8, 2005Assignee: Gilead Sciences, Inc.Inventors: Nebojsa Janjic, Larry Gold, Paul Schmidt, Chandra Vargeese, Michael Willis
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Patent number: 6958160Abstract: A liposome suspension forms spontaneously upon adding a lipid composition to an aqueous solution. The liposomes include diacylglycerol-PEG compounds. The melting point of the diacylglycerol-PEG is below about 40 degrees C., and the acyl chains of the diacylglycerol-PEG are greater than or equal to 14 carbons in length. Such liposome suspensions are useful for a variety of purposes, including the delivery of therapeutic agents.Type: GrantFiled: September 30, 2002Date of Patent: October 25, 2005Assignee: BioZone Technologies, Inc.Inventors: Brian Charles Keller, Alenka Lasic, legal representative, Dan D. Lasic, deceased
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Patent number: 6949537Abstract: The invention provides novel prodrugs of inhibitors of PI-3 kinase. The novel compounds are LY294002 and analogs thereof comprising a reversibly quaternized amine.Type: GrantFiled: April 5, 2004Date of Patent: September 27, 2005Assignee: Semafore Pharmaceuticals, Inc.Inventors: Joseph R. Garlich, Donald L. Durden, Mary Patterson, Jingdong Su, Robert G. Suhr
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Patent number: 6916488Abstract: Vesicles made from amphiphilic copolymers are disclosed. The amphiphilic copolymers can be ABA copolymers, where one of A and B is hydrophilic and the other is hydrophobic. AB copolymers can also be used. The copolymers may be crosslinked to form nanocapsules. Crosslinking can be accomplished using a variety of methods, including end to end polymerization of copolymers having terminal unsaturated groups. Molecules, such as membrane proteins, can be incorporated into the wall of the vesicles or nanocapsules.Type: GrantFiled: July 13, 2000Date of Patent: July 12, 2005Assignee: BioCure, Inc.Inventors: Wolfgang Meier, Thomas Hirt, Corinne Nardin
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Patent number: 6899863Abstract: This invention relates to a method of preparing membrane vesicles from a biological sample, characterised in that it comprises at least one anion exchange and/or gel permeation chromatography treatment of the sample. The invention is used to prepare vesicles of varied origins and types, particularly from antigen presenting cells or tumoral cells. The invention also relates to the vesicles obtained in this way and their uses.Type: GrantFiled: January 19, 2000Date of Patent: May 31, 2005Inventors: Olivier Dhellin, Sebastian Amigorena, Philippe Rameau, Joël Crouzet
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Patent number: 6890901Abstract: Pharmaceutical compositions comprising a mixture of hyaluronic acid and liposomes. Preferably, the pharmaceutical compositions further include a pharmaceutically active substance such as cyclosporin A encapsulated in the liposomes. A method for preparing a pharmaceutical composition includes producing liposomes from phospholipids, preferably in the presence of a pharmaceutically active substance (most preferably cyclosporin A) to be encapsulated within the liposomes, and mixing the liposomes with hyaluronic acid. Pharmaceutical compositions of this invention are used, for example, to topically administer pharmaceutical agents effective to treat skin disorders by deposition of that agent in the dermis or sub-dermis while minimizing systemic circulation thereof. These compositions are also administered orally, parenterally and intrarectally.Type: GrantFiled: September 29, 1997Date of Patent: May 10, 2005Assignee: Jagotec AGInventors: Christopher Marriott, Gary Peter Martin, Marc Barry Brown
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Patent number: 6835394Abstract: The present invention provides biocompatible vesicles comprising semi-permeable, thin-walled encapsulating membranes which are formed in an aqueous solution, and which comprise one or more synthetic super-amphiphilic molecules. When at least one super-amphiphile molecule is a block copolymer, the resulting synthetic vesicle is termed a “polymersome.” The synthetic, reactive nature of the amphiphilic composition enables extensive, covalent cross-linking of the membrane, while maintaining semi-permeability. Cross-linking of the polymer building-block components provides mechanical control and long-term stability to the vesicle, thereby also providing a means of controlling the encapsulation or release of materials from the vesicle by modifying the composition of the membrane. Thus, the encapsulating membranes of the present invention are particularly suited for the reliable, durable and controlled transport, delivery and storage of materials.Type: GrantFiled: December 14, 1999Date of Patent: December 28, 2004Assignee: The Trustees of the University of PennsylvaniaInventors: Dennis E. Discher, Bohdana M. Discher, You-Yeon Won, James C-M. Lee, Frank S. Bates, Daniel A. Hammer
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Patent number: 6818227Abstract: A method for administering a radiosensitizer to a tumor site in a subject is described. The method includes preparing liposomes composed of a vesicle-forming lipid and a lipid-derivatized radiosensitizer. In one embodiment, the radiosensitizer is dipalmitoyl-5-iodo-2′-deoxyuridine. A method for preparing the liposome composition including the lipid-derivatized radiosensitizer is also disclosed.Type: GrantFiled: February 7, 2000Date of Patent: November 16, 2004Assignee: Alza CorporationInventors: Paul S. Uster, Adam A. Zetter, Kristen M. Hjortsvang, James L. Slater, George Z. Zhu
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Publication number: 20040223911Abstract: Stabilized lipid construct comprising a liposome or polymerized vesicle, a targeting entity, a therapeutic entity, and a stabilizing entity are provided, as well as methods for their preparation and use.Type: ApplicationFiled: June 8, 2004Publication date: November 11, 2004Inventors: Mark David Bednarski, Neal Edward DeChene, John S. Pease, Charles Aaron Wartchow, Karen J. Brunke
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Patent number: 6794152Abstract: An improved reagent system for preparation of cells for flow cytometry having a physiologically compatible salt solution composition including a lysing agent, an agent for minimizing white blood cell lysis, and optionally a preservative.Type: GrantFiled: December 22, 2000Date of Patent: September 21, 2004Assignee: Streck Laboratories Inc.Inventors: Wayne L. Ryan, Paula B. Turpen
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Patent number: 6787154Abstract: The present invention is directed to artificial antigen presenting cells and methods of making artificial antigen presenting cells. Such artificial antigen presenting cells may be used in certain methods of isolating and expanding T cell populations as well as modulating T cell responses. Additionally, the present invention provides novel methods for the identification and isolation of antigen-specific T cells. The methods provide for the construction of liposomes containing MHC:peptide complexes, accessory molecules, co-stimulatory molecules, adhesion molecules, and other molecules irrelevant to T cell binding or modulation that are used in the binding of artificial antigen presenting cells to solid support systems that may be used in the retrieval and identification of antigen-specific T cells.Type: GrantFiled: January 9, 2001Date of Patent: September 7, 2004Inventor: Salvatore Albani
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Patent number: 6749831Abstract: Compare core LPS (lacking O-polysaccharide side chains) from Gram-negative bacteria are incorporated into a vaccine typically in liposomes. The complete core of E. coli K 12 is particularly useful. Upon administration to a mammal the vaccine stimulates synthesis of antibodies which are cross-protective against smooth and rough forms of LPS from at least two different Gram-negative bacterial strains having different core structures.Type: GrantFiled: April 25, 2000Date of Patent: June 15, 2004Assignee: Medical Defense Technology, LLCInventors: Elliott Bennett-Guerrero, George Robin Barclay, Ian Raymond Poxton, Thomas James McIntosh, David Scott Snyder
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Patent number: 6726894Abstract: The invention relates to new compounds with the general formula I for use as a tool to introduce macromolecules into cells. The invention further relates to compositions for introducing macromolecules into cells, comprising vesicles formed by at least one compound in a solvent. The macromolecule can be incorporated in the vesicles and/or bound to the vesicles or another aggregate of the new compounds.Type: GrantFiled: December 28, 1998Date of Patent: April 27, 2004Assignee: Synvolux IP B.V.Inventors: Jan Bernard Frederik Nicolaas Engberts, Anno Wagenaar, Dirk Hoekstra, Irene Van Der Woude, Marcel Herman Jozef Ruiters
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Patent number: 6726925Abstract: A liposome contains an active agent and has a gel-phase lipid bilayer membrane comprising phospholipid and a surface active agent. The phospholipids are the primary lipid source for the lipid bilayer membrane and the surface active agent is contained in the bilayer membrane in an amount sufficient to increase the percentage of active agent released at the phase transition temperature of the lipid bilayer, compared to that which would occur in the absence of the surface active agent. The surface active agent is present in the lipid bilayer membrane so as to not destabilize the membrane in the gel phase.Type: GrantFiled: December 9, 1999Date of Patent: April 27, 2004Assignee: Duke UniversityInventor: David Needham
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Patent number: 6699499Abstract: Disclosed is a new structural class of amphiphilic molecules which incorporate a hydrophilic material or polymer attached, at spatially distinct sites, to at least two hydrophobic residues. Certain of the amphiphilic molecules comprise a plurality of hydrophobic moieties. All such amphiphilic molecules have a common structural motif and, in contact with water, display surface activity and self-assemble into multimolecular aggregates and liquid crystalline phases. Also disclosed are enhanced stability liposomes that incorporate such amphiphilic molecules via unique interactions, and methods of using such formulations in a variety of applications including drug delivery, nutrition, bio-diagnostics, cosmetics, blood products and related applications.Type: GrantFiled: June 11, 2001Date of Patent: March 2, 2004Assignee: Nutrimed BiotechInventor: Rajindra Aneja
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Patent number: 6685911Abstract: The object of the invention is a novel sensitization process for antigen-presenting cells, novel means for implementing the process and novel membrane vesicles possessing immunogenic potency. The invention relates in particular to texosomes (vesicles derived from tumor cells) and dexosomes (vesicles derived from dendritic cells loaded or not with antigens), and their use for the vectorization and presentation of antigens in vitro or in vivo as well as in methods or compositions for the treatment of cancers and infectious, parasitic or autoimmune diseases in particular.Type: GrantFiled: March 15, 1999Date of Patent: February 3, 2004Assignees: Institut National de la Sante et de la Recherche Medicale, Institut Gustave Roussy, Centre National de la Recherche Scientifique, Institut CurieInventors: Laurence Zitvogel, Graça Raposo, Armelle Regnault, Sebastian Amigorena
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Patent number: 6680047Abstract: Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, comprising a suspension in an aqueous carrier liquid of a reporter comprising gas-containing or gas-generating material, said agent being capable of forming at least two types of binding pairs with a target.Type: GrantFiled: August 10, 2001Date of Patent: January 20, 2004Assignee: Amersham Health ASInventors: Jo Klaveness, Pål Rongved, Anders Høgset, Helge Tolleshaug, Alan Cuthbertson, Aslak Godal, Lars Hoff, Geir Gogstad, Klaus Bryn, Anne Nævestad, Dagfinn Løvhaug, Halldis Hellebust, Magne Solbakken
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Patent number: 6676963Abstract: A composition for use in delivering a bioactive agent to targeted tissues or cells comprises: (a) a site-specific targeting ligand; (b) a lipid encapsulated oil in water emulsion; and (c) a bioactive agent in or on the surface of the outer monolayer of the emulsion; the ligand being conjugated directly or indirectly to the emulsion and the composition providing facilitated delivery of the bioactive agent through prolonged association and increased contact of the ligand-bound lipid encapsulated emulsion particles with the lipid bilayer of the target tissues or cells. The composition may also comprise a lipid encapsulated oil in water emulsion and a combination site-specific targeting ligand/bioactive agent. Methods for improved delivery of a bioactive agent to targeted tissues or cells are also disclosed.Type: GrantFiled: October 27, 2000Date of Patent: January 13, 2004Assignee: Barnes-Jewish HospitalInventors: Gregory M. Lanza, Samuel A. Wickline
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Patent number: 6645463Abstract: A surface-modified lipoprotein-like oil-in-water emulsion useful as a blood-pool selective delivery vehicle for lipophilic imaging agents or lipophilic derivatives of water-soluble imaging agents. The blood-pool selective delivery vehicle remains in the blood for several hours, shows very little early hepatic sequestration, and is cleared from the blood within 24 hours. The mean diameter of the oil phase is less than 150 nm which minimizes sequestration by the reticuloendothelial system. The surface of the oil phase is modified with a polyethyl glycol-modified phospholipid to prevent normal interactions with the receptor sites of the hepatocytes.Type: GrantFiled: April 10, 1998Date of Patent: November 11, 2003Assignee: The Board of Regents of the University of MichiganInventors: Raymond E. Counsell, Marc A. Longino, Jamey P. Weichert
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Patent number: 6635234Abstract: Processes for the preparation, prepared solutions, and the use of radium-223 for the treatment of calcified tumors, bone tumors, treatment of bones, bone surfaces and soft tissues is described.Type: GrantFiled: January 3, 2000Date of Patent: October 21, 2003Assignee: Anticancer Therapeutic Inventions ASInventors: Roy H. Larsen, Gjermund Henriksen, Øyvind S. Bruland
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Patent number: 6627218Abstract: A stable aqueous dispersion which comprises a cationic lipid which is a molecule which comprises a cholesterol-derived lipophilic group, a linker bond which is hydrolyzable by cellular enzymes and relatively resistant to base-catalyzed hydrolysis, a spacer arm and a cationic amino group, and an appropriate co-lipid. The invention also includes the cationic lipids and mammalian plasmid DNA or other cells in admixture with the aqueous dispersion.Type: GrantFiled: August 22, 2002Date of Patent: September 30, 2003Assignees: The University of Tennessee Research Foundation, McMaster UniversityInventors: Leaf Huang, Richard M. Epand, Remo Bottega
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Patent number: 6596543Abstract: The present invention relates generally to the field of prothrombin time reagents for determining dysfunction in the coagulation system and more specifically to reagents made from native thromboplastin or purified or recombinant tissue factor and phospholipids from a natural or synthetic source. The present invention relates to methods to make a diagnostic reagent that includes a membrane-bound protein incorporated into a liposome and having additional empty liposomes (liposomes without membrane-bound protein incorporated therein) added to the solution.Type: GrantFiled: March 22, 2001Date of Patent: July 22, 2003Assignee: Dade Behring Inc.Inventors: Jianfang Wang, Kevin Bruce Johnson, Liliana Maria Tejidor, Hema Doobay
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Patent number: 6592843Abstract: The present invention relates to a conjugator system comprising liposomes with ionophores, and with chelator solution and alpha-particle emitting radionuclide(s) located inside of the liposome. Furthermore, a the method for the preparation of this type of radioactive liposomes is described, as well as use of the system and a kit for preparing the system.Type: GrantFiled: February 21, 2001Date of Patent: July 15, 2003Assignee: Anticancer Therapeutic Inventions ASInventors: Roy H. Larsen, Gjermund Henriksen
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Patent number: 6582918Abstract: This invention discloses a method for preparing a complex comprised of a PDGF Nucleic Acid Ligand and a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound by identifying a PDGF Nucleic Acid Ligand by SELEX methodology and associating the PDGF Nucleic Acid Ligand with a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound. The invention further discloses Complexes comprising one or more PDGF Nucleic Acid Ligands in association with a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound. The invention further includes a Lipid construct comprising a PDGF Nucleic Acid Ligand or Complex and methods for making the same.Type: GrantFiled: May 8, 2001Date of Patent: June 24, 2003Assignee: Gilead Sciences, Inc.Inventors: Nebojsa Janjic, Larry Gold
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Patent number: 6569451Abstract: Polymerized liposome particles which are linked to a targeting agent and may also be linked to a contrast enhancement agent and/or linked to or encapsulating a treatment agent. The targeting imaging enhancement polymerized liposome particles interact with biological targets holding the image enhancement agent to specific sites providing in vitro and in vivo study by magnetic resonance, radioactive, x-ray or optical imaging of the expression of molecules in cells and tissues during disease and pathology. Targeting polymerized liposomes may be linked to or encapsulate a treatment agent, such as, proteins, drugs or hormones for directed delivery to specific biological sites for treatment.Type: GrantFiled: February 26, 2002Date of Patent: May 27, 2003Assignee: Targesome, Inc.Inventors: King Chuen Li, Mark David Bednarski, Richard Wood Storrs, Henry Y. Li, Francois Daniel Tropper, Curtis Kang Hoon Song, Dorothy Anna Sipkins, Jeremy Kenji Kuniyoshi
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Patent number: 6562316Abstract: The present invention relates to a drug delivery system with two-step targeting, which comprises a combination: (a) a lipid carrier provided with cell targeting agent(s) to target the drug delivery system to specific cells or tissues; and (b) a drug enclosed in said lipid carrier and provided with a DNA targeting agent to target the drug to the nuclei of specific target cells. Furthermore, the invention relates to a method of cancer therapy in which the above drug delivery system is administered to a cancer patient. The goal is to treat or analyse both large tumour masses as well as small tumour cell clusters and single spread tumour cells. According to the invention, drug uptake in tumours will be markedly increased at the same time as the interaction of the drug with healthy organs and tissues can be minimized. The invention gives potential to convert palliative into curative treatment.Type: GrantFiled: September 1, 2000Date of Patent: May 13, 2003Inventors: Katarina Edwards, Jörgen Carlsson, Stefan Sjöberg
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Patent number: 6562371Abstract: This invention provides a liposome having a drug included therein, which has active targeting property and ensured stability in blood and can be used effectively in the diagnosis and/or treatment of diseases, particularly renal diseases, that accompany production of proteoglycan, comprising (1) a basic compound which takes positive charge within a physiological pH range, (2) a lipid derivative of a hydrophilic polymer and (3) a lipid which constitutes the liposome, as its membrane constituting components, wherein their constituting ratios are from 1 to 20 mol % of (1) based on (3) and from 0.2 to 5 mol % of (2) based on the total of (1) and (3).Type: GrantFiled: September 21, 2000Date of Patent: May 13, 2003Assignee: Terumo Kabushiki KaishaInventors: Kazuo Kawahara, Hideto Ushijima, Hideki Uchiyama, Junji Kimura
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Patent number: 6517808Abstract: Boron neutron capture therapy can be used to destroy tumors. This treatment modality is enhanced by delivering compounds to the tumor site where the compounds have high concentrations of boron, the boron compounds being encapsulated in the bilayer of a liposome or in the bilayer as well as the internal space of the liposomes. Preferred compounds, include carborane units with multiple boron atoms within the carborane cage structure. Liposomes with increased tumor specificity may also be used.Type: GrantFiled: April 18, 2001Date of Patent: February 11, 2003Assignee: The Regents of the University of CaliforniaInventors: M. Frederick Hawthorne, Debra A. Feaks, Kenneth J. Shelly
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Patent number: 6475515Abstract: A process for increasing the stability of liposome suspensions that contain hydrophilic active ingredients is described, which is characterized in that the active ingredient that is to be encapsulated in the liposomes is metered such that 5% to 95% by weight of the active ingredient is present in unencapsulated form.Type: GrantFiled: September 30, 1996Date of Patent: November 5, 2002Assignee: Schering AktiengesellschaftInventors: Andreas Sachse, Georg Rossling, Jens Leike
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Patent number: 6447800Abstract: This invention provides methods of loading preformed liposomes by transmembrane permeation induced by alcohols. Solutes loaded into liposomes by this ethanol mediated process include both small nonpolar molecules and larger species, such as proteins and carbohydrates.Type: GrantFiled: January 18, 1996Date of Patent: September 10, 2002Assignee: The University of British ColumbiaInventor: Michael J. Hope
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Patent number: 6440393Abstract: The present invention provides a method of increasing the deposition of aerosolized drug in the respiratory tract of an individual or animal, comprising the step of administering said aerosolized drug in an air mixture containing up to about 10% carbon dioxide gas.Type: GrantFiled: December 4, 2000Date of Patent: August 27, 2002Assignee: Research Development FoundationInventors: J. Clifford Waldrep, J. Vernon Knight, Nadezhda Koshkina
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Patent number: 6426086Abstract: This invention relates to the field of liposomes. In particular, this invention provides novel liposomes that are pH-sensitive, yet are also stable in serum. The liposomes are complexed with a molecule comprising a thermally-sensitive polymer showing lower critical solution temperature behavior in aqueous solutions, said thermally-sensitive polymer bearing a hydrophobic substituent and a pH sensitive substituent, wherein said hydrophobic substituent is less than 10 kD and which pH sensitive substituent remains ionizable following said covalent bonding to said thermally-sensitive polymer, and whose pH sensitive does not depend on cleavage of the covalent bond to said thermally-sensitive polymer. The invention further relates to methods of conferring pH sensitivity upon liposomes by complexing the liposomes with such molecules.Type: GrantFiled: February 2, 1999Date of Patent: July 30, 2002Assignee: The Regents of the University of CaliforniaInventors: Demetrios Papahadjopoulos, Olivier Meyer, Jean-Christophe Leroux
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Patent number: 6403117Abstract: Novel archaeosome compositions and their use in vaccine formulations as adjuvants and/or delivery systems, to enhance the immune response to immunogens in an animal such as a human, are described. Another aspect relates to the use of these archaeosomes to enhance the delivery of compounds such as pharmaceuticals to specific cell types and tissues in animals and other life forms, via various routes of administration such as subcutaneous, intramuscular, and oral. The efficacy of the archaeosomes and also of conventional liposomes can be further improved in these applications, by incorporation of coenzyme Q10 and/or polyethyleneglycol-lipid conjugate into liposomes made from these archaeosomes.Type: GrantFiled: July 6, 2000Date of Patent: June 11, 2002Assignee: National Research Council of CanadaInventors: G. Dennis Sprott, Girishchandra B. Patel, Boby Makabi-Panzu
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Patent number: 6375980Abstract: The present invention provides a liposomal aerosol composition, comprising a pharmaceutical compound, a cationic lipid, a neutral co-lipid; and tryptone. Also provided is a nebulized cationic lipid: neutral co-lipid: DNA suspension useful for lipid-DNA transfections, wherein the cationic lipid is bis(guanidinium)-tren-cholesterol and the neutral co-lipid is dioleoylphosphatidylethanolamine (DOPE).Type: GrantFiled: July 19, 1999Date of Patent: April 23, 2002Assignee: Research Development FoundationInventors: Charles L. Densmore, Jr., J. Vernon Knight, J. Clifford Waldrep, Berma M. Kinsey
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Publication number: 20020039556Abstract: The stability of phospholipid compositions is enhanced by the inclusion of a buffer system comprising ammonia or a water soluble amine having a pH at 15° C. of less than or equal to 9.5.Type: ApplicationFiled: October 19, 2001Publication date: April 4, 2002Inventors: Kari Dyvik, Harald Dugstad, Jo Klaveness, Roald Skurtveit, Jonny Ostensen, Kiyoto Yachi
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Patent number: 6352716Abstract: Methods and compositions are described for the preparation of bioactive agents entrapped in lipid vesicles the bilayers of which comprise a salt form of an organic acid derivative of a sterol, such as the tris-salt form of a sterol hemisuccinate, and to bompositions comprising a mixtue of tris(hydroxymethyl)aminomethane salt of cholesteryl hemisuccinate with either an antifungal compound or a peptide. These compositions have various applications in vivo.Type: GrantFiled: August 18, 1993Date of Patent: March 5, 2002Assignee: The Liposome Company Inc.Inventors: Andrew S. Janoff, Mircea C. Popescu, Alan L. Weiner, Lois E. Bolcsak, Paul A. Tremblay, Christine E. Swenson
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Patent number: 6350466Abstract: Polymerized liposome particles which are linked to a targeting agent and may also be linked to a contrast enhancement agent and/or linked to or encapsulating a treatment agent. The targeting imaging enhancement polymerized liposome particles interact with biological targets holding the image enhancement agent to specific sites providing in vitro and in vivo study by magnetic resonance, radioactive, x-ray or optical imaging of the expression of molecules in cells and tissues during disease and pathology. Targeting polymerized liposomes may be linked to or encapsulate a treatment agent, such as, proteins, drugs or hormones for directed delivery to specific biological sites for treatment.Type: GrantFiled: August 29, 2000Date of Patent: February 26, 2002Assignee: Targesome, Inc.Inventors: King Chuen Li, Mark David Bednarski, Richard Wood Storrs, Henry Y. Li, Francois Daniel Tropper, Curtis Kang Hoon Song, Dorothy Anna Sipkins, Jeremy Kenji Kuniyoshi
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Patent number: 6331289Abstract: Targetable diagnostic and/or therapeutically active agents, e.g. ultrasound contrast agents, comprising a suspension in an aqueous carrier liquid of a reporter comprising gas-containing or gas-generating material, said agent being capable of forming at least two types of binding pairs with a target.Type: GrantFiled: October 28, 1997Date of Patent: December 18, 2001Assignee: Nycomed Imaging ASInventors: Jo Klaveness, Pål Rongved, Anders Høgset, Helge Tolleshaug, Alan Cuthbertson, Lars Hoff, Klaus Bryn, Halldis Hellebust, Magne Solbakken
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Patent number: 6322810Abstract: Provided are methods for preparing improved biologically active micelle and crystalline products comprising a biologically active amphipathic compound in association with a micelle or crystalline product. Methods for producing the micelle or crystalline products as well as methods of using the micelle or crystalline products in therapeutic, diagnostic, and cosmetic, applications are also provided.Type: GrantFiled: May 18, 2000Date of Patent: November 27, 2001Inventors: Hayat Alkan-Onyuksel, Israel Rubinstein
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Patent number: 6319516Abstract: A stable aqueous dispersion which comprises a cationic lipid which is a molecule which comprises a cholesterol-derived lipophilic group, a linker bond which is hydrolyzable by cellular enzymes and relatively resistant to base-catalyzed hydrolysis, a spacer arm and a cationic amino group, and an appropriate co-lipid. The invention also includes the cationic lipids and mammalian plasmid DNA or other cells in admixture with the aqueous dispersion.Type: GrantFiled: June 16, 1999Date of Patent: November 20, 2001Assignees: The University of Tennessee Research Corporation, McMaster UniversityInventors: Leaf Huang, Richard M. Epand, Remo Bottega
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Patent number: 6319517Abstract: The present invention to relates to a pharmaceutical preparation comprising lyophilized liposomes encapsulating a biologically-active principle which is highly insoluble in water and stable over time.Type: GrantFiled: November 3, 1999Date of Patent: November 20, 2001Assignee: Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.p.A.Inventors: Giovanni Cavallo, Leonardo Marchitto
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Patent number: RE38407Abstract: Liposome-encapsulated opioid analgesic agents delivered by the pulmonary route provide local, or systemic analgesia superior to that produced by the solution form of these agents administered by parentral (intravenous, intramuscular, or subcutaneous injection) or oral routes.Type: GrantFiled: June 14, 2001Date of Patent: January 27, 2004Assignee: Delex Therapeutics Inc.Inventors: Michael Mezel, Orlando Hung