University of California

Other

Genentech, Inc.

Ira D Goldfine

Michael S German

Stephen S Rothman

Betty A Maddux

Timothy Andrew Stewart

Steven A Spencer

Andrew Grupe

Peter J Kushner

Riccardo Vigneri

Vincenzo Trischitta

Antonio Pizzuti

Michael Campbell

Lucia A Frittitta

Jack F Youngren

John Kerner

Denise M Harrison

A method of treatment is disclosed whereby cancer cells are brought into contact with a formulation comprising an inhibitor of tyrosine kinase receptors. The formulation may be comprised of an injectable carrier and two or more tyrosine kinase receptor inhibitors which may be nordihydroguaiarectic acid (NDGA) and doxorubicin.

Tyrosine kinase receptor antagonists and methods of treatment for breast cancer

The present invention provides methods of delivering a secreted protein into the bloodstream of a mammal. A nucleic acid molecule encoding the protein is introduced into the gastrointestinal tract of the mammal, and the nucleic acid molecule enters an intestinal epithelial cell, where the protein is produced and secreted into the bloodstream of the mammal.

Delivery of therapeutic gene products by intestinal cell expression

Secretory gland cells, particularly pancreatic and salivary gland cells, are genetically altered to operatively incorporate a gene which expresses a protein which has a desired therapeutic effect on a mammalian subject. The expressed protein is secreted directly into the gastrointestinal tract and/or blood stream to obtain therapeutic blood levels of the protein thereby treating the patient in need of the protein. The transformed secretory gland cells provide long term therapeutic cures for diseases associated with a deficiency in a particular protein or which are amenable to treatment by overexpression of a protein.

Gene therapy by secretory gland expression

The invention features methods for delivering a polypeptide to the bloodstream of a subject by introduction of a nucleic acid construct into secretory gland cells(e.g., cells of salivary gland, pancreas, or liver). In general, the method involves introduction of a nucleic acid construct into a secretory gland duct, which introduction results in expression of a gene product encoded by the introduced construct and delivery of the gene product into the bloodstream of the subject.

Delivery of polynucleotides by secretory gland expression

A novel polymorphism in the human PC-1 gene is characterized, which is associated with an increased predisposition to developing insulin resistance. The polymorphism affects heterozygous and homozygous carriers of the allele. The subject nucleic acids and fragments thereof, encoded polypeptides, and antibodies specific for the polymorphic amino acid sequence are useful in determining a genetic predisposition to insulin resistance. The encoded protein is useful in drug screening for compositions that affect the activity of PC-1 and insulin receptor activity or expression.

Polymorphic human PC-1 sequences associated with insulin resistance

Intestinal epithelial cells of a mammalian subject are genetically altered to operatively incorporate a gene which expresses a protein which has a desired effect. The method of the invention comprises administration of a formulation containing DNA to the gastrointestinal tract, preferably by an oral route. The expressed recombinant protein is secreted directly into the bloodstream. Of particular interest is the use of the method of the invention to provide for short term delivery of gene products to the bloodstream.

Delivery of gene products by intestinal cell expression

Gene delivery by secretory gland expression

Intestinal epithelial cells of a mammalian subject are genetically altered to operatively incorporate a gene which expresses a protein which has a desired therapeutic effect. Intestinal cell transformation is accomplished by administration of a formulation composed primarily of naked DNA, and is preferably administered orally. Oral or other intragastrointestinal routes of administration provide a simple method of administration, while the use of naked nucleic acid avoids the complications associated with use of viral vectors to accomplish gene therapy. The expressed protein is secreted directly into the gastrointestinal tract and/or blood stream to obtain therapeutic blood levels of the protein thereby treating the patient in need of the protein. The transformed intestinal epithelial cells provide short or long term therapeutic cures for diseases associated with a deficiency in a particular protein or which are amenable to treatment by overexpression of a protein.

Systemic gene therapy by intestinal cell transformation

Secretory gland cells, particularly pancreatic, hepatic, and salivary gland cells, are genetically altered to operatively incorporate a gene which expresses a protein which has a desired therapeutic effect on a mammalian subject. The expressed protein is secreted directly into the bloodstream to obtain therapeutic levels of the protein thereby treating the patient in need of the protein. The transformed secretory gland cells provide long term or short term therapies for diseases associated with a deficiency in a particular protein or which are amenable to treatment by overexpression of a protein.

Protein delivery by secretory gland expression

A method of diagnosing insulin resistance and related disorders is provided. Additionally, methods of treating mammals with insulin resistance and related disorders is provided. The methods employ antagonists to an insulin receptor tyrosine kinase inhibitor protein.

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Kentfield, CA, United States of America

Ira D Goldfine