Helix Biopharma Corporation

Heman Chao

Wah Yau Wong

Jerry McElroy

Donald Segal

John M Docherty

Jodi Dickstein

Baomin Tian

Praveen Kumar

Don Segal

Kimberly Jayne Gaspar

John Docherty

Pharmaceutical compositions comprising antibody-urease conjugates and substantially free of unconjugated urease are disclosed. These compositions are prepared by a method that does not require chromatographic purification. These pharmaceutical compositions have utility in the treatment of cancer by antibody-directed enzyme prodrug therapy wherein the urease converts endogenous urea into ammonia in situ to induce cytotoxicity.

Antibody-urease conjugates for therapeutic purposes

This disclosure provides antibody-urease conjugates having therapeutic and diagnostic utility. More specifically, the disclosure relates to diagnostic and/or therapeutic conjugates that are prepared by conjugating one or more whole antibodies to urease.

Antibody-urease conjugates

Improvements in methods of treating cancer with weakly basic anti-cancer compounds are provided. In one aspect, the invention provides an improvement in a method of treating cancer cells whose extracellular environment contains 1&#x2013;8 mM urea, by exposing the cells to a weakly basic anti-cancer compound which is effective in inhibiting the growth of the cells. The improvement includes (a) exposing the cells to a urease enzyme composition and, (b) by step (a), reducing the amount of anti-cancer compound required to produce a given extent of inhibition in the growth of the cells when the cells are exposed to the anti-cancer agent. Methods of potentiating the specific therapeutic activity of a weakly basic anti-cancer compound in the treatment of a given mammalian cancer which is responsive to the compound are provided as are pharmaceutical compositions for use in intravenous administration to a subject are also provided.

Method and composition for inhibiting cancer cell growth

A pharmaceutical composition and method for use in inhibiting growth of cancer cells in a mammalian subject are disclosed. The composition includes a urease enzyme, and associated therewith, a chemical entity effective to enhance the delivery of the enzyme to cancer cells, when the composition is administered to the subject. Also disclosed are a method of enhancing the effectiveness of weakly basic anti-tumor compounds, a method assessing the presence, size or condition a solid tumor in a subject, and a gene therapy composition for treating a cancer in a subject.

A diagnostic method and device for use in detecting or quantitating an analyte present in a liquid sample. The method includes reacting an analyte-containing sample with reagents capable of generating a first coil-forming peptide in solution form. This peptide is then contacted with a biosensor whose detection surface has surface-bound molecules of a second, oppositely charged coil-forming peptide, under conditions effective to form a stable &agr;-helical coiled-coil heterodimer on the detection surface. The formation of the coiled-coil heterodimer produces a measurable change in biosensor signal, which is measured to detect the presence of or quantitate the amount of analyte in a sample. Also disclosed is a biosensor device for carrying out the reaction.

Biosensor method for detecting analytes in a liquid

A diagnostic card device for use in detecting or quantitating an analyte present in a liquid sample, comprising a card substrate having a sample introduction region, a biosensor, and a sample-flow pathway communicating between the sample-introduction region and the biosensor, circuitry for generating an analyte-dependent electrical signal from the biosensor; and a signal-responsive element for recording such signal. In one embodiment, the biosensor includes a detection surface with surface-bound molecules of a first charged, coil-forming peptide capable of interacting with a second, oppositely charged coil-forming peptide to form a stable &agr;-helical coiled-coil heterodimer, where the binding of the second peptide to the first peptide, to form such heterodimer, is effective to measurably alter a signal generated by the biosensor. The sample-flow pathway contains diffusibly bound conjugate of the second coil-forming peptide and the analyte (or an analyte analog) and immobilized analyte-binding agent. The analyte in the liquid sample and the conjugate compete for binding with the immobilized analyte-binding agent. Unbound conjugate migrates by capillarity to the biosensor. Liquid sample containing conjugate migrates in the sample flow pathway by capillary action or is driven by a micro-pump. In another embodiment, the biosensor includes an electrode substrate coated with a high-dielectric hydrocarbon-chain monolayer, and having analyte-binding agent attached to the exposed monolayer surface. Binding of analyte to the monolayer-bound analyte-binding agent, and the resultant perturbation of the monolayer structure, causes ion-mediated electron flow across the monolayer.

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Aurora, Canada

Heman Chao