Smithkline Beckman Corporation

Zynaxis, Inc.

Smithkline Beecham Corporation

Phanos Technologies, Inc.

Zynaxis Technologies, Inc.

Paul K Horan

Sue Ellen Slezak

Bruce D Jensen

Katharine A Muirhead

Meryle J Melnicoff

David E Troutner

Brian D Gray

Gregory A Kopia

William Wong

Martin D Summers

Zhizhou Yu

Chia-En Lin

Kamleshkumar A Sheth

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.

The presence or quantity of a selected subset of cells, which is part of a subpopulation of a mixed cell population, is determined by a method in which a detectable reporter substance is uniformly incorporated into substantially all cells of the subpopulation containing the subset of interest. The subset of interest is then affinity-separated by incubating a test sample of the mixed cell population containing the labeled subpopulation with a specific binding substance which selectively binds to characteristic determinants of the cell subset of interest. Occurrence of the reporter substance in the separated fraction is then detected, and correlated to a predetermined standard to determine the presence or quantity of the subset of interest within the cell population. According to another aspect of the invention a method is provided for quantitating two or more selected subsets of cells within a subpopulation of a mixed cell population. After labeling, the entire subpopulation is affinity-separated from the mixed cell population, and occurrence of the reporter substance in the separated fraction is detected. Next, subsets of interest within the subpopulation are affinity-separated as described above, and the level of detected reporter substance in each subset is compared to the level detected in the entire subpopulation. According to further aspects of the invention test kits are provided for performing the above-described methods.

Methods for detection and quantification of cell subsets within

Analytes, having a characteristic determinant that selectively interacts with a specific binding substance, are determined by coupling a reporter substance to the analyte, or to the specific binding substance, causing complex formation between the analyte and the specific binding substance in a test medium, separating the complexes thus formed from the test medium, and determining the presence or quantity of the analyte of interest by detecting the occurrence of the reporter substance in the complexes or the separated test medium. The determination is preferably performed on biomembrane-containing entities, such as cell subpopulations and/or subsets thereof, the reporter substance being stably associated with the lipid component of the biomembrane. Reagents and test kits are disclosed for performing the analyte determination.

Methods, reagents and test kits for determination of subpopulations of

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.

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Downingtown, PA, United States of America

Paul K Horan