Abstract: The present invention provides materials and methods for predicting the response of a disease state to a therapeutic agent. A targeting moiety specific for a biological marker is labeled with a reporter moiety and used to analyze cells characteristic of the disease state. The output of the reporter moiety, which may be fluorescence intensity, is compared to the output of reference standard analyzed under similar or identical conditions. The use of a reference standard allows biomarker reporting to be normalized. Biomarker values can then be correlated from sample to sample and from laboratory to laboratory based on quantitative calibration on a universal reference standard.

Abstract: The present invention provides materials and methods for predicting the response of a disease state to a therapeutic agent. A targeting moiety specific for a biological marker is labeled with a reporter moiety and used to analyze cells characteristic of the disease state. The output of the reporter moiety, which may be fluorescence intensity, is compared to the output of reference standard analyzed under similar or identical conditions. The use of a reference standard allows biomarker reporting to be normalized. Biomarker values can then be correlated from sample to sample and from laboratory to laboratory based on quantitative calibration on a universal reference standard.

Abstract: A conjugate of formula A-L-P, in which: A represents a glycosylated/galactosylated peptide that binds to a cell-surface receptor, L represents a bifunctional linker, which does not comprise a naturally occurring amino acid and is covalently bonded to A and P in a regiospecific manner, and P represents a monomer, homopolymer or heteropolymer comprising at least one nucleotide or an analogue thereof, which inhibits the intracellular biosynthesis of nucleotides or nucleic acids in a sequence-independent manner, wherein either or both of the covalent bond between A and L and the covalent bond between L and P can be cleaved intracellularly; a composition comprising such a conjugate; and a method of inhibiting abnormal cellular proliferation in a mammal; and a method of inhibiting replication of a virus in a mammal.

Abstract: The present invention relates to the identification and characterization of classes and subclasses of circulating cancer cells, including microtumors from body fluid samples using molecular, cytological, and morphological analyses, and methods for staging patients and measuring the efficacy of medical treatments.

Abstract: A conjugate of formula A-L-P, in which: A represents a glycosylated/galactosylated peptide that binds to a cell-surface receptor, L represents a bifunctional linker, which does not comprise a naturally occurring amino acid and is covalently bonded to A and P in a regiospecific manner, and P represents a monomer, homopolymer or heteropolymer comprising at least one nucleotide or an analogue thereof, which inhibits the intracellular biosynthesis of nucleotides or nucleic acids in a sequence-independent manner, wherein either or both of the covalent bond between A and L and the covalent bond between L and P can be cleaved intracellularly; a composition comprising such a conjugate; and a method of inhibiting abnormal cellular proliferation in a mammal; and a method of inhibiting replication of a virus in a mammal.

Abstract: The present invention provides materials and methods for predicting the response of a disease state to a therapeutic agent. A targeting moiety specific for a biological marker is labeled with a reporter moiety and used to analyze cells characteristic of the disease state. The output of the reporter moiety, which may be fluorescence intensity, is compared to the output of reference standard analyzed under similar or identical conditions. The use of a reference standard allows biomarker reporting to be normalized. Biomarker values can then be correlated from sample to sample and from laboratory to laboratory based on quantitative calibration on a universal reference standard.

Abstract: The present invention provides for enriching rare cells in a fluid comprising the rare cells and non-rare cells. Examples of rare cells enriched include prostate cancer cells.

Abstract: The present invention relates to the design and synthesis of homogeneous A-L-P constructs, which contain a hepatic ligand to direct an oligomer or “payload” to a hepatocyte intracellularly via a receptor-mediated, ligand-directed pathway.

Abstract: A conjugate of formula A-L-P, in which:

Abstract: The present invention relates to the identification and characterization of classes and subclasses of circulating cancer cells, including microtumors from body fluid samples using molecular, cytological, and morphological analyses, and methods for staging patients and measuring the efficacy of medical treatments.

Abstract: A method of treating HSV-2 infection which comprises administering to a host subject to said infection an effective amount of a polynucleotide of the formula polyrI.polyr(C.sub.12 U) where n is an integer from 4 to 29. The polynucleotide is advantageously administered intranasally.

Abstract: Acid resistant Oligomers suitable for oral administration, orally acceptable formulations of such Oligomers and preparation of pharmaceutical formations of such Oligomers are provided.

Abstract: Oligodeoxynucleoside methylphosphonate neoglycopeptide conjugates and related compounds for tissue specific delivery of biologically stable, nonionic oligodeoxynucleoside analogs into cells.

Abstract: A method for enriching cancer cells such as prostate cancer cells in a bodily fluid sample is disclosed comprising (a) obtaining the sample comprising cancer cells and non-rare cells; (b) subjecting the sample to multiple density gradient separation comprising a first density gradient and a second density gradient, wherein the second density gradient is greater than the first density gradient, and producing a first fluid comprising an increased concentration of cancer cells of a first density, and a second fluid comprising an increased concentration of cancer cells of a second density, wherein the second density is greater than the first density; wherein subjecting the sample to multiple density gradient separation includes producing a plasma layer, a first interface layer, a first gradient layer, a second interface layer, a second gradient layer, and a cell pellet; wherein producing the first fluid includes combining the first interface layer and the first gradient layer and forming a first suspension; and w

Abstract: A composition for inactivating a target nucleic acid which comprises an oligonucleoside alkyl or arylphosphonate analogue which is complementary to the sequence of the target nucleic acid and includes a functional group which reacts with the target nucleic acid to render the target nucleic acid inactive or nonfunctional.

Abstract: A process for selectively controlling or interfering with the effect or function of foreign nucleic acid in the presence of otherwise normal living cells which comprises determining the base sequence for said nucleic acid and binding the said nucleic acid with an appropriately prepared nonionic oligonucleoside alkyl or arylphosphonate analogue which is complementary to the indicated sequence of the foreign nucleic acid.

Abstract: A nucleic acid-protein conjugate which is specific with respect to a selected living cell is prepared by linking said nucleic acid to a protein specific to said living cell.

Abstract: A process for selectively controlling or interfering with the effect or function of foreign nucleic acid in the presence of otherwise normal living cells which comprises determining the base sequence for the nucleic acid and binding the nucleic acid with an appropriately prepared nonionic oligonucleoside alkyl or arylphosphonate analogue which is complementary to the indicated sequence of the foreign nucleic acid.

Abstract: Process for synthesizing deoxyribonucleoside methylphosphonates on polystyrene polymer supports which involves condensing 5'-dimethoxytrityldeoxynucleoside 3'-methylphosphonates. The oligomers are removed from the support and the base protecting groups hydrolyzed by treatment with ethylenediamene in ethanol, which avoids hydrolysis of the methylphosphonate linkages. Two types of oligomers are synthesized: those containing only methylphosphonate linkages, d-Np(Np).sub.n N, and those which terminate with a 5' nucleotide residue, dNp(Np).sub.n N. The latter oligomers can be phosphorylated by polynucleotide kinase, and are separated by polyacrylamide gel electrophoresis according to their chain length. Piperidine randomly cleaves the oligomer methylphosphonate linkages and generates a series of shorter oligomers whose number corresponds to the length of the original oligomer. Apurinic sites introduced by acid treatment spontaneously hydrolyze to give oligomers which terminate with free 3' and 5'-OH groups.

Abstract: Oligonucleoside alkyl-- or aryl phosphonates are nonionic analogues of nucleic acid which possess unique physical and biological properties. These properties enable the analogues to enter living cells intact and to bind with specifically selected nucleic acids within the cell. As a result, the analogues can specifically inhibit the function or expression of a preselected nucleic acid sequence. Thus the analogues could be used to specifically inhibit the growth of tumor cells or replication of viruses in infected cells.