Patents Assigned to The Liposome Company
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Patent number: 6015716Abstract: Endotoxin incorporated into liposomes, lipid bilayers or lipid complexes can be detected by combining an aqueous suspension of the liposomes, lipid complexes or lipid bilayers with a suitable detergent. Preferable detergents, e.g., Lubrol-PX.TM. or a polyoxyethylene ether, solubilize the lipid bilayers, liposomes or lipid complexes at acceptable lipid concentrations, forming micelles therefrom which contain lipid bilayer, liposome or lipid complex lipid, detergent and endotoxin, should it be present. The micelles are then assayed for the presence of endotoxin.Type: GrantFiled: July 12, 1996Date of Patent: January 18, 2000Assignee: The Liposome Company, Inc.Inventors: Paul A. Harmon, Donna J. Cabral-Lilly, J. Craig Franklin, Robert A. Reed, Andrew S. Janoff
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Preparation of pharmaceutical compositions containing etherlipid-containing multiple lipid liposomes
Patent number: 6007839Abstract: Described herein are methods of preparing liposome-containing pharmaceutical compositions, the liposomes containing headgroup-derivatized lipids and etherlipids having the formula: ##STR1## Such compositions are useful in the treatment of a variety of conditions, including various cancers and inflammatory disorders.Type: GrantFiled: February 2, 1998Date of Patent: December 28, 1999Assignee: The Liposome Company, Inc.Inventors: Eric Mayhew, Andrew S. Janoff, Imran Ahmad, Suresh K. Bhatia -
Patent number: 5965159Abstract: Described herein are liposomes containing etherlipids of the formula: ##STR1## as well as a phosphatidylcholine, a sterol, and a headgroup-derivatized lipid. These liposomes are useful in a variety of therapeutic regimens, including the treatment of cancers and inflammatory disorders.Type: GrantFiled: February 2, 1998Date of Patent: October 12, 1999Assignee: The Liposome Company, Inc.Inventors: Eric Mayhew, Andrew S. Janoff, Imran Ahmad, Suresh K. Bhatia
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Patent number: 5948441Abstract: Tangential flow filtration is used in the size separation of particles, such as liposomes and lipid particles. These particles may be passed through a tangential flow filtration device of any pore size desired. Tangential flow filter systems of various pore sizes may be used sequentially to obtain particles such as lipid particles or liposomes having a defined size range.Type: GrantFiled: January 3, 1995Date of Patent: September 7, 1999Assignee: The Liposome Company, Inc.Inventors: Robert P. Lenk, Anthony G. Durning, Robert J. Klimchak, Joel Portnoff, Michelle L. Tomsho
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Patent number: 5942246Abstract: Liposomes are provided which contain etherlipids having the formula: ##STR1## as well as an unsaturated or partially unsaturated phospholipid, a sterol, and a phosphatidylethanolamine-based headgroup-derivatized lipid. These liposomes are useful in a variety of therapeutic regimens, including the treatment of cancers and inflammatory disorders.Type: GrantFiled: February 2, 1998Date of Patent: August 24, 1999Assignee: The Liposome Company, INc.Inventors: Eric Mayhew, Andrew S. Janoff, Imran Ahmad, Suresh K. Bhatia
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Patent number: 5939567Abstract: This invention provides a taxane derivative of the formula: ##STR1## wherein a hydrophobic organic moiety is attached to a taxane. R and R.sup.1 is each indepently H or a hydrophobic organic moiety, as long as at least one of R and R.sup.1 is not H. Attachment of a hydrophobic organic moiety to the taxane so as to obtain a taxane derivative generally stabilizes the association of the derivative with a lipid, including a liposomal lipid, carrier in the plasma of animals to which the derivative-carrier association is administered. Also provided herein is a composition containing the taxane derivative and a pharmaceutically acceptable medium; desirably, the medium also contains a lipid carrier, and the derivative is associated with the carrier. Further provided herein is a method of administering taxane derivatives to animals, for example, animals afflicted with cancers.Type: GrantFiled: December 10, 1997Date of Patent: August 17, 1999Assignee: The Liposome Company, Inc.Inventors: Eric Mayhew, J. Craig Franklin, Suresh Bhatia, Paul A. Harmon, Andrew S. Janoff
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Patent number: 5932242Abstract: Pharmaceutical compositions are provided herein that contain, in addition to a pharmaceutically acceptable carrier, a lamellar lipid. The lipid is composed of an ether lipid and a lipid having a molecular shape that is complementary to the molecular shape of the glycerolipid. These compositions can be used therapeutically, for example, in the treatment of cancers and inflammatory conditions.Type: GrantFiled: October 15, 1996Date of Patent: August 3, 1999Assignee: The Liposome Company, Inc.Inventors: J. Craig Franklin, Eric Mayhew, Walter Perkins, Andrew Janoff
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Patent number: 5925375Abstract: This invention provides a multilamellar liposome containing an arachidonic acid metabolite, two or more lipid-containing bilayers and two or more aqueous compartments containing a release-inhibiting buffer. Preferred arachidonic acid metabolites are the prostaglandins, particularly PGE.sub.1. The liposomal formulations can be used to treat animals, particularly humans, for diseases, disorders or conditions which can be ameliorated by prostaglandins, e.g., disorders characterized by cellular activation and adhesion, inflammation and/or toxemia.Type: GrantFiled: November 3, 1994Date of Patent: July 20, 1999Assignee: The Liposome Company, Inc.Inventors: Robert P. Lenk, Michelle L. Tomsho, Robert L. Suddith, Robert J. Klimchak, Andrew S. Janoff, Sharma R. Minchey, Marc J. Ostro
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Patent number: 5922350Abstract: Dehydrated liposomes are prepared by drying liposome preparations under reduced pressure in the presence of one or more protective sugars, e.g., the disaccharides trehalose and sucrose. Preferably, the protective sugars are present at both the inside and outside surfaces of the liposome membranes. Freezing of the liposome preparation prior to dehydration is optional. Alternatively, the protective sugar can be omitted if: (1) the liposomes are of the type which have multiple lipid layers; (2) the dehydration is done without prior freezing; and (3) the dehydration is performed to an end point which results in sufficient water being left in the preparation (e.g., at least 12 moles water/mole lipid) so that the integrity of a substantial portion of the multiple lipid layers is retained upon rehydration.Type: GrantFiled: June 16, 1997Date of Patent: July 13, 1999Assignee: The Liposome Company, Inc.Inventors: Andrew S. Janoff, Pieter R. Cullis, Marcel B. Bally, Michael W. Fountain, Richard S. Ginsberg, Michael J. Hope, Thomas D. Madden, Hugh P. Schieren, Regina L. Jablonski
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Patent number: 5916588Abstract: A high integrity liposome comprising at least one stabile lipid and at least one peptide-like therapeutic agent associated with the liposome, adapted for parenteral administration to an animal, including a human, and method according to manufacture and use.Immunizing dosage forms comprising a liposome and an immunogen, wherein the liposome and immunogen are present in an immunization dose. Additionally, a dosage form, including such form particularly adapted to producing an immune response, comprising a salt according to an organic acid derivative of a sterol and an immunogen are present in an immunization dose, and method according to uses is disclosed. Further, a dosage form, including such form particularly adapted to producing an immune response, comprising dimyristolyphosphatidylcholine (DMPC)/cholesterol liposomes, optionally in an aluminum hydroxide gel, and an immunogen wherein the DMPC/cholesterol and immunogen are present in an immunization dose, and method according to use.Type: GrantFiled: May 25, 1995Date of Patent: June 29, 1999Assignee: The Liposome Company, Inc.Inventors: Mircea C. Popescu, Alan L. Weiner, Marie S. Recine, Andrew S. Janoff, Leonard Estis, Lynn D. Keyes, Carl R. Alving
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Patent number: 5897873Abstract: Disclosed is a vaccine against an infective agent, the vaccine comprising a liposome having an exterior and an interior and having externally disposed affinity associated antigen material of at least one, preferably nonpartitioning, antigen representative of said infective agent. Also disclosed is a method of preparation and use of this vaccine.Type: GrantFiled: February 23, 1995Date of Patent: April 27, 1999Assignee: The Liposome Company, Inc.Inventor: Mircea Popescu
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Patent number: 5840328Abstract: A composition comprises a free arachidonic acid metabolite and endocystosable particles such as phagocytosable or opsonizable particles, or particles binding to phagocytic receptors to serum proteins, and the like. The composition, in the form of a therapeutic formulation may be administered alone, or with other bioactive agents, for the treatment of a disorder characterized by cell activation/adhesion, inflammation or toxemia. A second method of treating such disorders comprises the administration of an endocytosable particle.Type: GrantFiled: January 11, 1995Date of Patent: November 24, 1998Assignee: The Liposome Company, Inc.Inventors: Andrew S. Janoff, David F. Eierman
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Patent number: 5820848Abstract: This invention provides a composition containing a sized liposome comprising a lipid and an induce; the sized liposome has a diameter of at most about 1 micoron and the induces is present in an amount effective to induce interdigitation-fusion of the sized liposome. Also provided herein are interdigitation-fusion liposomes and gels, and methods of making the same.Type: GrantFiled: September 30, 1994Date of Patent: October 13, 1998Assignee: The Liposome Company, Inc.Inventors: Lawrence T. Boni, Andrew S. Janoff, Sharma R. Minchey, Walter R. Perkins, Christine E. Swenson, Patrick L. Ahl, Thomas S. Davis
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Patent number: 5811118Abstract: This invention provides a method of administering an arachidonic acid metabolite, such as prostaglandin E1, to an animal. The metabolite is given to the animal, typically a human, in association with a unilamellar liposome comprising a lipid and a release-inhibiting aqueous buffer. This method can be used to treat animals afflicted with disorders characterized by cell activation and adhesion, inflammation or toxemia.Type: GrantFiled: November 3, 1994Date of Patent: September 22, 1998Assignee: The Liposome Company, Inc.Inventors: Marc J. Ostro, Andrew S. Janoff, Sharma R. Minchey
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Patent number: 5795589Abstract: A method for encapsulation of antineoplastic agents in liposomes is provided, having preferably a high drug:lipid ratio. Liposomes may be made by a process that loads the drug by an active mechanism using a transmembrane ion gradient, preferably a tranamembrane pH gradient. Using this technique, trapping efficiencies approach 100%, and liposomes may be loaded with drug immediately prior to use, eliminating stability problem related to drug retention in the liposomes. Drug:lipid ratios employed are about 3-80 fold higher than for traditional liposome preparations, and the release rate of the drug from the liposomes is reduced. An assay method to determine free antineoplastic agents in a liposome preparation is also disclosed.Type: GrantFiled: February 5, 1997Date of Patent: August 18, 1998Assignee: The Liposome Company, Inc.Inventors: Lawrence D. Mayer, Marcel B. Bally, Pieter R. Cullis, Richard S. Ginsberg, George N. Mitilenes
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Patent number: 5783210Abstract: A composition having equal to or greater than about 97 percent by weight phosphatidylcholine and about equal to or less than about 3 percent by weight to about 0.5% sphingomylin and equal to or less than about 0.5% lysophosphatidylcholine (undetectable by UV at 205 nm) has been found to result in liposomes having improved stability. Methods for preparing the composition are disclosed whereby the phospholipids are extracted and then purified using silica chromatography.Type: GrantFiled: May 24, 1995Date of Patent: July 21, 1998Assignee: The Liposome Company, Inc.Inventors: Paul A. Tremblay, Robert L. Suddith, John J. Kearns
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Patent number: 5762958Abstract: Liposomes are provided which contain ether lipids having the formula: ##STR1## as well as an underivatized phosphatidylethanolamine, a sterol, and a phosphatidylethanolamine-dicarboxylic acid headgroup-derivatized lipid. These liposomes are useful in a variety of therapeutic regimens, including the treatment of cancers and inflammatory disorders.Type: GrantFiled: February 16, 1996Date of Patent: June 9, 1998Assignee: The Liposome Company, Inc.Inventors: Eric Mayhew, Andrew S. Janoff, Imran Ahmad, Suresh K. Bhatia
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Patent number: 5744158Abstract: A method for encapsulation of antineoplastic agents in liposomes is provided, having preferably a high drug:lipid ratio. Liposomes may be made by a process that loads the drug by an active mechanism using a transmembrane ion gradient, preferably a transmembrane pH gradient. Using this technique, trapping efficiencies approach 100%, and liposomes may be loaded with drug immediately prior to use, eliminating stability problems related to drug retention in the liposomes. Drug:lipid ratios employed are about 3-80 fold higher than for traditional liposome preparations, and the release rate of the drug from the liposomes is reduced. An assay method to determine free antineoplastic agents in a liposome preparation is also disclosed.Type: GrantFiled: May 25, 1995Date of Patent: April 28, 1998Assignee: The Liposome Company, Inc.Inventors: Lawrence D. Mayer, Marcel B. Bally, Pieter R. Cullis, Richard S. Ginsberg, George N. Mitilenes
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Patent number: 5736155Abstract: Methods for encapsulating ionizable antineoplastic agents in liposomes using transmembrane potentials are provided. Trapping efficiencies approaching 100% and rapid loading are readily achieved. Dehydration protocols which allow liposomes to be conveniently used in the administration of antineoplastic agents in a clinical setting are also provided. In accordance with other aspects of the invention, transmembrane potentials are used to reduce the rate of release of ionizable drugs from liposomes.Type: GrantFiled: June 5, 1995Date of Patent: April 7, 1998Assignee: The Liposome Company, Inc.Inventors: Marcel B. Bally, Pieter R. Cullis, Michael J. Hope, Thomas D. Madden, Lawrence D. Mayer
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Patent number: 5716526Abstract: The invention provides a method of separating liposomes or lipid complexes from a fluidic medium. The method involves passage of a fluidic medium containing liposomes or lipid complexes through a composite filter which retains the liposomes or lipid complexes while allowing the fluidic medium to pass through. The filter is composed of a ceramic membrane and a ceramic substrate that is thicker than the ceramic membrane. Moreover, the average pore size of the ceramic membrane, from about 0.1 to about 0.2 microns, is less than the average pore size of the substrate.Type: GrantFiled: February 12, 1996Date of Patent: February 10, 1998Assignee: The Liposome Company, Inc.Inventors: Robyne J. Kelemen, Anthony G. Durning