Smithkline Beckman Corporation

Zynaxis, Inc.

Smithkline Beecham Corporation

Lehigh University

Phanos Technologies, Inc.

Sue Ellen Slezak

Paul K Horan

Bruce D Jensen

Brian D Gray

Gregory A Kopia

David E Troutner

Kathy L Gottlund

Katharine A Muirhead

John H Abel

Barbara Obrepalska-Bielska

Eugene A Nau

Zhizhou Yu

Chia-En Lin

Kamleshkumar A Sheth

The present invention provides methods and reagents for assessing lipoprotein metabolism. The methods provided are applicable for use on multiple samples in a clinical laboratory, thus obviating the need for sophisticated instrumentation, such as flow cytometry. Selected cell types in a test sample are uniformly labelled with a detectable reporter substance, so that they may later be enumerated. Pre-determined lipoprotein receptors associated with the cells of interest are labelled with a receptor-selective marker, thereby to determine the number of lipoprotein receptors per cell in the test sample. Selected cells of interest are conveniently separated from the test sample by binding thereto a specific binding substance attached to a solid support. The specific binding substance binds specifically with a characteristic determinant of the cell subset of interest. The remainder of the test sample may be washed away or discarded. The separated cells of interest may then be enumerated by measuring the amount of detectable label associated therewith, hence to determine the number of lipoprotein receptors per cell in each test sample.

Method and reagents for assessing lipoprotein metabolism

Compounds are provided having the capability of binding therapeutically active substances to lipid containing bio-compatible particles, such as cells or viruses. These compounds include a bio-affecting moiety, comprising a therapeutically active substance, which is linked via a linking moiety to at least one hydrocarbon substituent selected so that the compounds is sufficiently non-polar to impart lipid binding capability to the compound. Thus, compounds of the invention are useful for site-selective delivery of therapeutic agents, and retention thereof at the selected site. Methods are provided for using various compounds of the invention in treatment of diseases or other pathological conditions. For example, methods are provided for treatment of: (1) post-angioplasty restenosis; (2) rheumatoid arthritis; (3) tumor cell proliferation, particularly tumor cells associated with ovarian cancer; and (4) psoriasis.

Compounds, compositions and methods for binding bio-affecting substances

Compounds, compositions, their methods of preparation and use in binding bio-affecting substances to the surface membrane of bioparticles, such as enkaryotic cells, without producing appreciable detrimental effect on morphology or physiological function of cells.

A separation method for use in conjunction with bio-analytical techniques, such as cell screening and blood flow measurement, in which a carrier bearing a bio-affecting compound comprising a reporter moiety is contacted with an organic extractant which is immiscible with the carrier, so as to produce distinct extractant and carrier phases, with a major amount of the bio-affecting compound originally associated with the carrier being transferred to the extractant phase. The separation method is particularly useful in performing bio-analytical techniques involving fluorometric determinations, as fluorescence efficiency is increased substantially by transfer of a fluorescent reporter from an aqueous carrier phase to the organic extractant phase, and concentration of the fluorescent reporter in the extractant phase prior to fluorescence measurement.

Bio-analytical separation method

Methods for distinguishing multiple subpopulations of biological particles in a single sample based upon quantitative differences in the fluorescence intensity attributable to one or two fluorochromes with which the biological particles are labelled. The method is used with flow cytometric particle counting techniques to count and sort and biological particles such as the formed elements of blood and other tissue cells. Also disclosed are reagents containing fluorochrome-conjugated antibodies used in the methods.

Method and reagents for performing subset analysis using quantitative

Methods for determining growth rate of cells growing in vivo and in vitro. Cells are labelled with cyanine dyes and changes in plasma membrane cyanine dye levels are used to determine growth rate. Cell growth rate determinations are utilized to monitor transplanted bone marrow cell engraftment and post-surgical corneal epitheal cell growth. The invented methods also are used to determine tumor cell sensitivity to cancer therapeutic agents, yeast sensitivity to antifungal agents, and bacteria sensitivity to antibacterial agents.

Cell growth rate determination by measurement of changes in cyanine dye

Methods for reproducibly labelling viable cells with cyanine dyes that do not significantly affect cell viability. Applications for labelled cells include using labelled red blood cells to distinguish post-transfusional bleeding from immunologic reaction and using dilution to measure growth rate of cultured cells.

Viable cell labelling

Methods of tracking cells in vivo and for determining in vivo cell lifetimes. Cells are labelled with cyanine dyes and detection is by measuring fluorescence, absorbance, or by detecting nuclear magnetic resonance probes included in the cyanine dyes. Using the invented methods, for example, red blood cell and platelet lifetimes are determined. Also, cells are tracked to determine sites of primary or metastatic tumors, or sites of occult infection. Further, rates at which cells pass through vessels is used to determine blood vessel patency and platelet aggregation.

Growing community of inventors

Downingtown, PA, United States of America

Sue Ellen Slezak