Canji Inc.

Halozyme, Inc.

Innovata Limited

University of California

Genzyme Corporation

Daniel C Maneval

Richard J Gregory

Ken N Wills

H Michael Shepard

Heidrun Engler

Curtis B Thompson

Susan E Conroy

Seng H Cheng

Craig S Siegel

David J Harris

John Marshall

Edward R Lee

Wen-Hwa Lee

Ronald K Scheule

Simon J Eastman

Paul W Shabram

Chau-Dung Chang

Rebecca G Bagley

Eva Y-hp Lee

Engler Heidrun

S Catherine Hubbard

G William Demers

Bernard G Huyghe

Nan-Ping Wang

David Goodrich

Jo Ann Horowitz

Duane E Johnson

Loretta Nielsen

Provided herein is combination cancer therapy effected by administering a polymer-conjugated hyaluronidase, and a tumor-targeted taxane, and optionally a further chemotherapeutic agent such as a nucleoside analog. The combination therapy can be used in methods of treating cancers, and in particular solid tumor cancers.

Combination therapy with an anti-hyaluronan agent and therapeutic agent

Provided herein is combination therapy containing an anti-hyaluronan agent, such as a polymer-conjugated hyaluronan-degrading enzyme, and a tumor-targeted taxane, and optionally a further chemotherapeutic agent such as a nucleoside analog. The combination therapy can be used in methods of treating cancers, and in particular solid tumor cancers.

The present invention provides formulations and methods to enhance the delivery of nucleic acids to cells. Formulations comprising dextrin polymers in combination with sugars provide enhanced delivery of nucleic acids, particularly eucaryotic expression vectors, demonstrate enhanced delivery of nucleic acids to cells in vivo. The present invention also provides methods of treatment in combination with such formulations.

Nucleic acid delivery

In one embodiment, this invention provides methods of treating mammalian cancer or hyperproliferative cells, said method comprising contacting said cells with a tumor suppressor protein or tumor suppressor nucleic acid and also contacting said cell with at least one adjunctive anti-cancer agent. The invention also provides for a pharmacological composition comprising a tumor suppressor protein or a tumor suppressor nucleic acid and at least one adjunctive anti-cancer agent, and a kit for the treatment of mammalian cancer or hyperproliferative cells.

Combined tumor suppressor gene therapy and chemotherapy in the treatment of neoplasms

Disclosed are methods of controlling cell cycle progression by introducing into a cell to be controlled a composition selected from the group consisting of p56protein, a fragment of the p56protein, and the gene encoding p56protein to alter the cell cycle progression while maintaining the viability of the cell. The p56protein has been found to have the unexpected and surprising characteristic of being soluble in low concentrations of glycerol, thereby enhancing its value in pharmaceutical applications and the gene encoding p56when delivered to the hyperproliferating cell inhibits cellular proliferation.

Method of using an adenoviral vector encoding a retinoblastoma protein to treat hyperproliferating cells

This invention provides a recombinant adenovirus expression vector characterized by the partial or total deletion of the adenoviral protein IX DNA and having a gene encoding a foreign protein or a functional fragment or mutant thereof. Transformed host cells and a method of producing recombinant proteins and gene therapy also are included within the scope of this invention. Thus, for example, the adenoviral vector of this invention can contain a foreign gene for the expression of a protein effective in regulating the cell cycle, such as p53, Rb, or mitosin, or in inducing cell death, such as the conditional suicide gene thymidine dinase. (The latter must be used in conjunction with a thymidine kinase metabolite in order to be effective.)

Recombinant adenoviral vector and method of use

This invention provides a recombinant adenovirus expression vector characterized by the partial or total deletion of the adenoviral protein IX DNA and having a gene encoding a foreign protein or a functional fragment or mutant thereof. Transformed host cells and a method of producing recombinant proteins and gene therapy also are included within the scope of this invention. Thus, for example, the adenoviral vector of this invention can contain a foreign gene for the expression of a protein effective in regulating the cell cycle, such as p53, Rb, or mitosin, or in inducing cell death, such as the conditional suicide gene thymidine kinase. (The latter must be used in conjunction with thymidine kinase metabolite in order to be effective).

Recombinant adenoviral vector and methods of use

Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. The amphiphiles contain lipophilic groups derived from steroids, from mono or dialkylamines, or from alkyl or acyl groups; and cationic groups, protonatable at physiological pH, derived from amines, alkylamines or polyalkylamines. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile. Novel and highly effective plasmid constructs are also disclosed, including those that are particularly effective at providing gene therapy for clinical conditions complicated by inflammation. Additionally, targeting of organs for gene therapy by intravenous administration of therapeutic compositions is described.

Organ-specific targeting of cationic amphiphile / DNA complexes for gene therapy

This invention provides a recombinant adenovirus expression vector characterized by the partial or total deletion of the adenoviral protein IX DNA and having a gene encoding a foreign protein or a functional fragment or mutant thereof. Transformed host cells and a method of producing recombinant proteins and gene therapy also are included within the scope of this invention. Thus, for example, the adenoviral vector of this invention can contain a foreign gene for the expression of a protein effective in regulating the cell cycle, such as p53, Rb, or mitosin, or in inducing cell death, such as the conditional suicide gene thymidine kinase. (The latter must be used in conjunction with a thymidine kinase metabolite in order to be effective).

A method and pharmaceutical composition for the treatment of cancer using a gene delivery system, such as a viral vector delivery system, comprising a therapeutic gene such as p53 or a retinoblastoma tumor suppressor gene wherein the gene delivery system is formulated in a buffer comprising a delivery-enhancing agent such as ethanol or a detergent.

Compositions and methods for therapeutic use

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San Diego, CA, United States of America

Daniel C Maneval