Abstract: A method for delivering an isolated polynucleotide to the interior of a cell in a vertebrate, comprising the interstitial introduction of an isolated polynucleotide into a tissue of the vertebrate where the polynucleotide is taken up by the cells of the tissue and exerts a therapeutic effect on the vertebrate. The method can be used to deliver a therapeutic polypeptide to the cells of the vertebrate, to provide an immune response upon in vivo translation of the polynucleotide, to deliver antisense polynucleotides, to deliver receptors to the cells of the vertebrate, or to provide transitory gene therapy.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
March 15, 2005
Assignee:
Vical Incorporated
Inventors:
Philip L. Felgner, Jon Asher Wolff, Gary H. Rhodes, Robert Wallace Malone, Dennis A. Carson
Abstract: The invention is related to polynucleotide-based cytomegalovirus vaccines. In particular, the invention is plasmids operably encoding HCMV antigens, in which the naturally-occurring coding regions for the HCMV antigens have been modified for improved translation in human or other mammalian cells through codon optimization. HCMV antigens which are useful in the invention include, but are not limited to pp65, glycoprotein B (gB), IE1, and fragments, variants or derivatives of either of these antigens. In certain embodiments, sequences have been deleted, e.g., the Arg435-Lys438 putative kinase in pp65 and the membrane anchor and endocellular domains in gB. The invention is further directed to methods to induce an immune response to HCMV in a mammal, for example, a human, comprising delivering a plasmid encoding a codon-optimized HCMV antigen as described above.
Type:
Application
Filed:
December 19, 2003
Publication date:
October 21, 2004
Applicant:
Vical Incorporated
Inventors:
Gary G. Hermanson, Andrew J. Geall, Mary Kopke Wloch
Abstract: The present invention relates to a novel method for producing formulations comprising a polynucleotide, block copolymer and cationic surfactant. The formulations produced by the current method are suitable for use in polynucleotide based medicaments. A suitable method of production disclosed herein additionally comprises cold filtering a mixture of a polynucleotide, block copolymer and cationic surfactant, thereby sterilizing the formulation. The method of the present invention also eliminates the need for thermal cycling of the formulation, thereby reducing the time and expense required to produce large quantities of a formulation during commercial manufacturing. The present invention also relates to novel cationic lipids.
Abstract: This invention relates generally to the freeze-drying of formulations comprising a polynucleotide, a block copolymer and a cationic surfactant. In the presence of a cryoprotectant or bulking agent, a formulation can be freeze-dried, whereby upon reconstitution of the dried formulation, the microparticles maintain their optimal size and aggregation or fusion is avoided.
Abstract: The invention relates to a process for purifying plasmid DNA. The invention also relates to a DNA product made by the process of the invention. The DNA product is suitable for pharmaceutical use.
Abstract: A method for delivering a naked or isolated polynucleotide to the interior of a cell in a vertebrate, comprising the interstitial introduction of a naked polynucleotide into a tissue of the vertebrate where the polynucleotide is taken up by the cells of the tissue and exerts a therapeutic effect on the vertebrate. The method can be used to deliver a therapeutic polypeptide to the cells of the vertebrate, to provide an immune response upon in vivo translation of the polynucleotide, to deliver antisense polynucleotides, to deliver receptors to the cells of the vertebrate, or to provide transitory gene therapy.
Type:
Application
Filed:
December 11, 2003
Publication date:
July 8, 2004
Applicant:
Vical Incorporated
Inventors:
Philip L. Felgner, Jon Asher Wolff, Gary H. Rhodes, Robert Wallace Malone, Dennis A. Carson
Abstract: A method for delivering an isolated polynucleotide to the interior of a cell in a vertebrate, comprising the interstitial introduction of an isolated polynucleotide into a tissue of the vertebrate where the polynucleotide is taken up by the cells of the tissue and exerts a therapeutic effect on the vertebrate. The method can be used to deliver a therapeutic polypeptide to the cells of the vertebrate, to provide an immune response upon in vivo translation of the polynucleotide, to deliver antisense polynucleotides, to deliver receptors to the cells of the vertebrate, or to provide transitory gene therapy.
Type:
Grant
Filed:
December 2, 1999
Date of Patent:
March 23, 2004
Assignees:
Vical Incorporated, Wisconsin Alumni Research Foundation
Inventors:
Philip L. Felgner, Jon Asher Wolff, Gary H. Rhodes, Robert Wallace Malone, Dennis A. Carson
Abstract: The present invention provides a method for delivering a pharmaceutical polypeptide to the interior of a cardiac cell of a vertebrate in vivo, comprising the step of introducing a preparation comprising a pharmaceutically acceptable injectable carrier and naked polynucleotide operatively coding for the polypeptide into the interstitial space of the heart, whereby the naked polynucleotide is taken up into the interior of the cell and has a pharmacological effect on the vertebrate. In a preferred embodiment wherein the polynucleotide encodes polypeptide immunologically foreign to the vertebrate, the delivery method preferably comprises delivering an immunosuppressive agent to the vertebrate to limit immune responses directed to the polypeptide.
Type:
Grant
Filed:
June 6, 2000
Date of Patent:
March 16, 2004
Assignees:
Vical Incorporated, Wisconsin Alumni Research Foundation
Inventors:
Jon A. Wolff, David J. Duke, Philip L. Felgner
Abstract: A composition is provided comprising a novel cationic lipid compound having hydrophobic tails and two quaternary ammonium headgroups bridged by a linker. The composition is useful as a cytofectin for facilitating delivery and transfection of biologically active agents, particularly anionic bioactive agents such as DNA, into cells. The composition is useful also as an adjuvant for enhancing the humoral immune response of a vertebrate to an immunogen, especially an immunogen encoded by a polynucleotide-based vaccine. In certain preferred embodiments, the cationic lipid compound is a dimer containing quaternary ammonium headgroups bridged by a linker having DNA and/or cell receptor binding affinity, such as a polypeptide or polyamine. Also disclosed is an immunogenic composition comprising an immunogen and the composition of the present invention.
Abstract: A method for delivering a naked or isolated polynucleotide to the interior of a cell in a vertebrate, comprising the interstitial introduction of a naked polynucleotide into a tissue of the vertebrate where the polynucleotide is taken up by the cells of the tissue and exerts a therapeutic effect on the vertebrate. The method can be used to deliver a therapeutic polypeptide to the cells of the vertebrate, to provide an immune response upon in vivo translation of the polynucleotide, to deliver antisense polynucleotides, to deliver receptors to the cells of the vertebrate, or to provide transitory gene therapy.
Type:
Application
Filed:
March 14, 2003
Publication date:
February 5, 2004
Applicants:
Vical Incorporated, Wisconsin Alumni Research Foundation
Inventors:
Philip L. Felgner, Jon Asher Wolff, Gary H. Rhodes, Robert Wallace Malone, Dennis A. Carson
Abstract: A method for delivering an isolated polynucleotide to the interior of a cell in a vertebrate, comprising the interstitial introduction of an isolated polynucleotide into a tissue of the vertebrate where the polynucleotide is taken up by the cells of the tissue and exerts a therapeutic effect on the vertebrate. The method can be used to deliver a therapeutic polypeptide to the cells of the vertebrate, to provide an immune response upon in vivo translation of the polynucleotide, to deliver antisense polynucleotides, to deliver receptors to the cells of the vertebrate, or to provide transitory gene therapy.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
January 6, 2004
Assignees:
Vical Incorporated, Wisconsin Alumni Research Foundation
Inventors:
Philip L. Felgner, Jon Asher Wolff, Gary H. Rhodes, Robert Wallace Malone, Dennis A. Carson
Abstract: Cationic lipids having a derivatized quaternary ammonium head group that provide improved cell targeting ability and enhanced transfective efficacy for introducing molecules into cells are provided.
Abstract: The present invention provides a method for delivering a pharmaceutical polypeptide to the interior of a cardiac cell of a vertebrate in vivo, comprising the step of introducing a preparation comprising a pharmaceutically acceptable injectable carrier and naked polynucleotide operatively coding for the polypeptide into the interstitial space of the heart, whereby the naked polynucleotide is taken up into the interior of the cell and has a pharmacological effect on the vertebrate. In a preferred embodiment wherein the polynucleotide encodes polypeptide immunologically foreign to the vertebrate, the delivery method preferably comprises delivering an immunosuppressive agent to the vertebrate to limit immune responses directed to the polypeptide.
Type:
Application
Filed:
February 10, 2003
Publication date:
October 2, 2003
Applicants:
Vical Incorporated, Wisconsin Alumni Research Foundation
Inventors:
Jon A. Wolff, David J. Duke, Philip L. Felgner
Abstract: The invention provides adjuvants, immunogenic compositions, and methods useful for polynucleotide-based vaccination and immune response. In particular, the invention provides an adjuvant of cytofectin:co-lipid mixture wherein cytofectin is GAP-DMORIE.
Abstract: The present invention relates to methods of treating an autoimmune disease or an inflammatory condition, and in particular multiple sclerosis, in a mammal comprising administering a therapeutically effective amount of a non-infectious, non-integrating polynucleotide construct encoding a &bgr; interferon or an active fragment or variant thereof, wherein said construct is not associated with transfection-facilitating viral particles, liposomal formulations, or charged lipids.
Abstract: A method for delivering an isolated polynucleotide to the interior of a cell in a vertebrate, comprising the interstitial introduction of an isolated polynucleotide into a tissue of the vertebrate where the polynucleotide is taken up by the cells of the tissue and exerts a therapeutic effect on the vertebrate. The method can be used to deliver a therapeutic polypeptide to the cells of the vertebrate, to provide an immune response upon in vivo translation of the polynucleotide, to deliver antisense polynucleotides, to deliver receptors to the cells of the vertebrate, or to provide transitory gene therapy.
Type:
Application
Filed:
July 26, 2002
Publication date:
February 13, 2003
Applicant:
Vical Incorporated
Inventors:
Philip L. Felgner, Jon Asher Wolff, Gary H. Rhodes, Robert Wallace Malone, Dennis A. Carson
Abstract: The present invention relates to pharmaceutical compositions and methods to improve expression of exogenous polypeptides into vertebrate cells in vivo, utilizing delivery of polynucleotides encoding such polypeptides. More particularly, the present invention provides the use of salts, in particular sodium and potassium salts of phosphate, in aqueous solution, and auxiliary agents, in particular detergents and surfactants, in pharmaceutical compositions and methods useful for direct polynucleotide-based polypeptide delivery into the cells of vertebrates.
Type:
Application
Filed:
April 23, 2001
Publication date:
February 14, 2002
Applicant:
Vical Incorporated
Inventors:
Marston Manthorpe, Jukka Hartikka, Loretta Sukhu
Abstract: The present invention provides a method for delivering a pharmaceutical polypeptide to the interior of a cardiac cell of a vertebrate in vivo, comprising the step of introducing a preparation comprising a pharmaceutically acceptable injectable carrier and naked polynucleotide operatively coding for the polypeptide into the interstitial space of the heart, whereby the naked polynucleotide is taken up into the interior of the cell and has a pharmacological effect on the vertebrate such as inducing vascular growth. In a preferred embodiment wherein the polynucleotide encodes polypeptide immunologically foreign to the vertebrate, the delivery method preferably comprises delivering an immunosuppressive agent to the vertebrate to limit immune responses directed to the polypeptide.
Type:
Grant
Filed:
November 26, 1997
Date of Patent:
May 8, 2001
Assignees:
Vical Incorporated, Wisconsin Alumni Research Foundation
Inventors:
Jon A. Wolff, David J. Duke, Philip L. Felgner