Patents Represented by Attorney Catherine L. Kurtz
  • Patent number: 5204112
    Abstract: Methods are described for controlling the transbilayer distribution of ionizable lipids and proteins in vesicles. Control of the ion gradient of the exterior bathing medium in relation to that of the interior entrapped aqueous compartment of the vesicles induces migration of ionizable lipids or proteins to one or the other of the monolayers comprising the bilayer. This can result in an asymmetric distribution of the ionizable lipid or ionizable protein. The basic ionizable lipids, such as stearylamine and sphingosine, are sequestered into the inner monolayer when the liposome interior is acidic relative to the liposome exterior. Conversely, acidic ionizable lipids such as oleic acid and stearic acid are sequestered into the inner monolayer when the liposome interior is basic relative to the liposome exterior bathing solution.
    Type: Grant
    Filed: June 12, 1987
    Date of Patent: April 20, 1993
    Assignee: The Liposome Company, Inc.
    Inventors: Michael J. Hope, Pieter R. Cullis
  • Patent number: 5084215
    Abstract: A process for the separation and purification of individual phospholipids, especially phosphatidylcholine or lecithin and phosphatidylethanolaine, from mixtures containing members of the sub-class of phosphatides, incorporating methods of solvent extraction appropriate to the scale of the sample and utilizing an acetonitrile, acetonitrile-hydrocarbon, or acetonitrile-fluorocarbon solvent, which exhibit differential solubility properties towards the individual phospholipids.
    Type: Grant
    Filed: October 20, 1988
    Date of Patent: January 28, 1992
    Assignee: The Liposome Company, Inc.
    Inventors: John J. Kearns, Paul A. Tremblay
  • Patent number: 5082664
    Abstract: A liposome composition and methods for making same are disclosed, such compositions comprise an arachidonic acid metabolite such as a prostaglandin, preferably prostaglandin E.sub.1, a lipid, and a drying protectant such as a saccharide. The liposomes may be loaded with prostaglandin passively, or using a transmembrane concentration gradient, preferably using a transmembrane pH gradient. Using this transmembrane loading technique, trapping efficiencies of 50% to 100% are achieved, and the release rate of the prostaglandin from the liposomes is reduced. The liposome size is maintained after lyophilization and reconstitution.
    Type: Grant
    Filed: May 18, 1988
    Date of Patent: January 21, 1992
    Assignee: The Liposome Company, Inc.
    Inventors: Robert P. Lenk, Michelle L. Tomsho, Robert L. Suddith, Robert J. Klimchak
  • Patent number: 5077056
    Abstract: 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: Grant
    Filed: December 12, 1988
    Date of Patent: December 31, 1991
    Assignee: The Liposome Company, Inc.
    Inventors: Marcel B. Bally, Pieter R. Cullis, Michael J. Hope, Thomas D. Madden, Lawrence D. Mayer
  • Patent number: 5059591
    Abstract: Preparations of drugs in admixture with certain ligands are described which, when administered to animals or humans, are less toxic than conventional drug preparations. Although the toxicity of the drug-ligand preparations described is greatly reduced, the drug retains pharmacological activity.
    Type: Grant
    Filed: September 12, 1989
    Date of Patent: October 22, 1991
    Assignee: The Liposome Company, Inc.
    Inventors: Andrew S. Janoff, Mircea C. Popescu, Carl R. Alving, Michael W. Fountain, Robert P. Lenk, Marc J. Ostro, Paul A. Tremblay, Alan L. Weiner
  • Patent number: 5047245
    Abstract: The present invention describes a composition consisting of liposomes covalently or non-covalently coupled to the glycoprotein streptavidin. The streptavidin may additionally be coupled to biotinated proteins such as Immunoglobulin G or monoclonal antibodies. The liposomes of the invention may have a transmembrane potential across their membranes, and may be dehydrated. In addition, the composition may contain ionizable bioactive agents such as antineoplastic agents, and may be used in diagnostic assays.This is a divisional application of copending application Ser. No. 941,913, filed Dec. 15, 1986, which is now U.S. Pat. No. 4,885,172, which is a continuation-in-part of copending application Ser. No. 811,037, which in turn is a continuation-in-part of copending application Ser. No. 749,161, filed June 26, 1985, both now abandoned and copending application Ser. No. 759,419, filed July 26, 1985 now U.S. Pat. No. 4,870,635.
    Type: Grant
    Filed: August 28, 1989
    Date of Patent: September 10, 1991
    Assignee: The Liposome Company, Inc.
    Inventors: Marcel B. Bally, Helen Loughrey, Pieter R. Gullis
  • Patent number: 5009819
    Abstract: A taste moderating composition comprising a liposome associated flavorant and method of preparation and use.
    Type: Grant
    Filed: November 12, 1987
    Date of Patent: April 23, 1991
    Assignee: The Liposome Company, Inc.
    Inventors: Mircea C. Popescu, Edgar T. Mertz
  • Patent number: 4975282
    Abstract: A multilamellar vesicle dispersed in an aqueous phase comprising an aqueous medium, a lipid concentration of at least about 50 mg/ml and a trapping efficiency of at least about 40 percent. The vesicle can be prepared by dispersing the lipid in an aqueous phase to form a multilamellar vesicle, rapidly freezing the multilamellar vesicle to obtain a frozen lipid-aqueous medium mixture, and warming the mixture to obtain a frozen and thawed multilamellar vesicle dispersed in an aqueous phase.
    Type: Grant
    Filed: November 17, 1987
    Date of Patent: December 4, 1990
    Assignee: The Liposome Company, Inc.
    Inventors: Pieter R. Cullis, Marcel B. Bally, Michael J. Hope, Andrew S. Janoff, Lawrence D. Mayer
  • Patent number: 4923854
    Abstract: A method and composition are described for the solubilization of hydrophobic materials using a lysophospholipid. The method includes drying a composition comprising a hydrophobic material-solubilizing effective amount of phospholipid from organic solvent and hydrating the resulting film with an aqueous medium at either a pH of between about 8.5 and about 14.0, or at pH 7.0 followed by reduction of the temperature to less then 0.degree. C.
    Type: Grant
    Filed: January 22, 1986
    Date of Patent: May 8, 1990
    Assignee: The Liposome Company, Inc.
    Inventors: Colin P. S. Tilcock, Pieter R. Cullis, Michael J. Hope, Andrew S. Janoff
  • Patent number: 4885172
    Abstract: The present invention describes a composition consisting of liposomes covalently or non-covalently coupled to the glycoprotein streptavidin. The streptavidin may additionally be coupled to biotinated proteins such as Immunoglobulin G or monoclonal antibodies.The liposomes of the invention may have a transmembrane potential across their membranes, and may be dehydrated. In addition, the composition may contain ionizable bioactive agents such as antineoplastic agents, and may be used in diagnostic assays.
    Type: Grant
    Filed: December 15, 1986
    Date of Patent: December 5, 1989
    Assignee: The Liposome Company, Inc.
    Inventors: Marcel B. Bally, Helen Loughrey, Pieter R. Cullis
  • Patent number: 4880635
    Abstract: 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: Grant
    Filed: July 26, 1985
    Date of Patent: November 14, 1989
    Assignee: 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
  • Patent number: 4861580
    Abstract: Methods and compositions are described for the preparation of alpha-tocopherol vesicles, the bilayers of which comprise a salt form of an organic acid derivative of alpha-tocopherol such as the Tris salt form of alpha-tocopherol hemisuccinate. The method is rapid and efficient and does not require the use of organic solvents. The alpha-tocopherol vesicles may be used to entrap compounds which are insoluble in aqueous solutions. Such preparations are especially useful for entrapping bioactive agents of limited solubility, thus enabling administration in vivo.
    Type: Grant
    Filed: September 24, 1986
    Date of Patent: August 29, 1989
    Assignee: The Liposome Company, Inc.
    Inventors: Andrew S. Janoff, Lois E. Bolcsak, Alan L. Weiner, Paul A. Tremblay, Michael V. W. Bergamini, Robert L. Suddith
  • Patent number: 4698299
    Abstract: Lipid-dependent diagnostic assays are provided wherein the test sample to be assayed is pre-incubated with one or more phospholipids having a hexagonal (H.sub.II) organization, with lipidic particles, or with bilayer-forming lysophospholipids such as monooleoylphosphatidylethanolamine (MOPE). The pre-incubation results in reduced false positives due to antiphospholipid antibodies, such as, lupus anticoagulants, which may be present in the test sample, without changing the overall character, including the normal baseline, of the assay. Surprisingly, in accordance with the invention, it has been found that only hexagonal phospholipids, lipidic particles, and bilayer-forming lysophospholipids can be used, and, in particular, lamellar (bilayer) phospholipids (other than such lysophospholipids) cannot be used. An assay for diagnosing systemic lupus erythematosus (SLE) is also provided.
    Type: Grant
    Filed: February 19, 1986
    Date of Patent: October 6, 1987
    Assignee: The Liposome Company, Inc.
    Inventors: Andrew S. Janoff, Joyce Rauch, Colin P. S. Tilcock