Patents by Inventor Pieter R. Cullis

Pieter R. Cullis has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Patent number: 5252263
    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: March 17, 1992
    Date of Patent: October 12, 1993
    Assignee: The Liposome Company, Inc.
    Inventors: Michael J. Hope, Pieter R. Cullis
  • 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: 5171578
    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: June 6, 1991
    Date of Patent: December 15, 1992
    Assignee: The Liposome Company, Inc.
    Inventors: Marcel B. Bally, Helen Loughrey, Pieter R. Cullis
  • 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: 5059421
    Abstract: The present invention relates to a general method for producing sized protein-liposome conjugates exhibiting enhanced blood circulation times. The present invention also relates to the sized protein-liposome conjugate compositions produced by the method of the present invention. The protein-liposome conjugates of the present invention preferably range in size from about 75 nm to about 200 nm.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 antineplastic agents, and may be used in diagnostic assays.
    Type: Grant
    Filed: June 23, 1989
    Date of Patent: October 22, 1991
    Assignee: The Liposome Company, Inc.
    Inventors: Helen C. Loughrey, Pieter R. Cullis, Marcel B. Bally, Lewis S. L. Choi, Kim F. Wong
  • Patent number: 5008050
    Abstract: A method for reducing the lamellarity of a population of liposomes is provided which comprises repeatedly passing the liposomes under pressure through a filter which has a pore size equal to or less than about 100 nm. In certain embodiments, the method is used to convert a population of previously formed multilamellar liposomes into a population of substantially unilamellar liposomes. In accordance with other aspects of the disclosure, liposomes are prepared directly from a lipid powder or pellet and buffer without the use of any solvents, detergents or other extraneous materials.
    Type: Grant
    Filed: February 13, 1989
    Date of Patent: April 16, 1991
    Assignee: The Liposome Company, Inc.
    Inventors: Pieter R. Cullis, Michael J. Hope, Marcel B. Bally
  • 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