Abstract: Inactive precursor forms of PSA (pPSA) have been identified to exist in serum and tissues of patients with prostate cancer. Antibodies specific for pPSA are provided. Methods for detecting inactive precursors of PSA in human physiological fluid and tissues are also provided, as well as diagnostic kits and methods useful in the diagnosis and management of prostate cancer.

Abstract: Inactive precursor forms of PSA (pPSA) have been identified to exist in serum and tissues of patients with prostate cancer. Antibodies specific for pPSA are provided. Methods for detecting inactive precursors of PSA in human physiological fluid and tissues are also provided, as well as diagnostic kits and methods useful in the diagnosis and management of prostate cancer.

Abstract: Methods for detecting BRCA1 mutations are provided. The methods include the steps of determining the amount of the BRCA1 polypeptide contained in a sample of the subject, and correlating the amount of BRCA1 to the presence of the BRCA1 gene mutation in the subject, wherein the amount below a predetermined cutoff value is an indication of the presence of the mutation in the BRCA1 gene of the subject. The methods of the present invention are well suited for use to determine a condition associated with BRCA1 mutation, such as a predisposition to breast cancer, ovarian cancer, colorectal, and prostate cancers, and the presence or prognosis of breast cancer, ovarian cancer, colorectal, and prostate cancers.

Abstract: A substantially pure and isolated novel form of prostate specific antigen (PSA) is provided. The novel form of PSA of the present invention comprises at least one clip at Lys 182 of the amino acid sequence of a mature form of PSA. Preferably, the novel form of PSA additionally comprises one or more clips at a location selected from a group consisting of Ile 1, Lys 145, and Lys 146. More preferably, the form of PSA contains at least two clips at Lys 145 and Lys 182 of the amino acid sequence of a mature form of PSA. The novel forms of PSA exist at an elevated level in patients suspected of having benign prostatic hyperplasia (BPH) and therefore may be used as a serum mark or an immunohistological marker to help distinguish BPH from prostate cancer. Antibodies recognizing the novel forms of PSA and immunoassays that detect and determine the novel forms of PSA of the present invention in a sample are also provided.

Abstract: A method of distinguishing prostate cancer from benign prostatic hyperplasia (BPH) is provided. The mathematical combination or ratio of proPSA and BPSA serum or tissue markers may be used for distinguishing benign prostatic hyperplasia (BPH) from prostate cancer. It is the discovery of the present invention that BPSA is preferentially elevated in transition zone prostate tissue whereas pPSA is elevated in the peripheral zone of prostate tissue. A kit for aiding in distinguishing BPH from prostate cancer is also provided.

Abstract: The present invention provides a novel complex of hK2 and PI-6 and methods of using the novel complex. The novel complexes of hK2 and PI-6 of the present invention exist at an elevated level in prostate cancer tissues. Therefore, the hK2-PI6 complexes of the present invention may be used as a serum marker for detecting prostate cancer. They may also be used as an immunohistological marker to detect prostate cancer tissues. In accordance with the present invention, the hK2-PI6 complexes of the present invention may be detected in patient tissue samples by immunohistochemical and/or in patient fluid samples by in vitro immunoassay procedures. Diagnostic kits and diagnostic methods for detecting the existence of prostate cancer are also provided.

Abstract: An isolated, purified variant hK2 polypeptide useful in preparing immunogenic compositions and vaccines is provided. The variant hK2 polypeptides are more stable to purification than wild type mature hK2 polypeptide.

Abstract: An isolated, substantially homogenous pre-pro, pro or mature hK2 polypeptide is provided as well as biologically active variants or subunits thereof, including a biologically active variant pre-pro hK2 polypeptide having SEQ ID NO:19.

Abstract: Isolated nucleic acid molecules encoding variant hK2 polypeptides and fragments thereof, as well as expression cassettes and host cells comprising said nucleic acid molecules, are provided. Also provided is a method to express a nucleic acid molecule encoding a variant hK2 polypeptide.

Abstract: Monoclonal antibodies highly specific for human bone alkaline phosphatase, especially in the presence of human liver alkaline phosphatase, and their use in assays for human bone alkaline phosphatase are disclosed. A kit using the antibodies in an assay for human bone alkaline phosphatase is also disclosed.

Abstract: The present invention has multiple aspects that include an intermediate composition (i.e., a marked stock calibrator solution) for preparing diluted calibrator solutions that are marked in proportion to the amount of calibrator contained therein; a diluted (i.e., working) calibrator solution made therefrom, a series of diluted calibrator solutions that are visually colored in proportion to the concentration of calibrator therein; a method for performing a diagnostic assay that employs a series of marked calibrator solutions; a method for confirming that a stock solution of calibrator has been diluted correctly; and a method for indirectly confirming the concentration of calibrator in a working calibrator solution.

Abstract: A chelating agent is covalently bonded to a biologically active molecule such as an enzyme or antibody, the biologically active molecule is contacted with a support containing a bound transition metal ion whereby the metal ion is chelated by the chelating agent and the oxidation state of the metal ion is changed by treatment with an oxidizing or a reducing agent to provide a kinetically inert: oxidation state to immobilize the biologically active molecule on the support. The transition metal ion is preferably Co(II), Cr(II) or Ru(III) and the oxidation state of the metal ion is changed to Co(III), Cr(III) or Ru(II), respectively. The chelating agent can be iminodiacetic acid, nitrilotriacetic acid, terpyridine, bipyridine, triethylenetetraamine, biethylenetriamine, 1,4,7-triazacyclonane or a chelating peptide. Certain chelating agents can immobilize more than one biologically active molecule at a metal ion site on the support.

Abstract: The present invention is directed to a membrane-based immunoassay method for an analyte of interest having at least two sterically separate antigenic sites. The method comprises providing a reactive membrane having a calibration zone and a test zone, wherein the calibration zone is characterized by having a predetermined amount of the analyte of interest immobilized via a first antibody as a first specific binding pair to a solid phase, the immobilized first binding pair being covalently cross-linked such that any remaining binding sites on said first immobilized antibody are substantially incapable of further specifically binding to any additional analyte, but at least some of said analyte is capable of specifically binding to a preselected amount of a labelled second antibody.

Abstract: The present invention has multiple aspects. In its first aspect the present invention is directed to a trifunctional antibody-like compound that has tissue, organ, cell or molecule specificity and which is capable of being bifunctional when immobilized, via binding, at the tissue, organ, cell or molecule for which it has specificity. In particular, the present invention is directed to a trifunctional antibody-like compound of Formula I:F.sub.1 ab'--L--F.sub.2 ab'--L--F.sub.3 ab' (1)wherein L is the same or two different moieties for cross-linking F.sub.1 ab', F.sub.2 ab' and F.sub.3 ab';wherein F.sub.1 ab' is an Fab'-like fragment of a polyclonal or monoclonal antibody having specificity for an antigen expressed by the organ, tissue, cell or molecule of interest;wherein F.sub.2 ab' is an Fab'-like fragment of a polyclonal or monoclonal antibody having the same specificity as F.sub.

Abstract: The present invention is directed to a method for extending the length of one of the three linker arms of the compound of Formula I in the production of novel trifunctional antibody-like compounds. Formula I is defined as follows: ##STR1## wherein X is ##STR2## wherein k=1 or 0; wherein Z is ##STR3## wherein s=1 or 0; wherein n=1 or 0;wherein q=1 or 0;wherein Y is ##STR4## wherein Y' is ##STR5## wherein p or m may be the same or different and are integers ranging from 0 to 20 with the provisos that when n=0, the sum of m and p is an integer ranging from 1 to 20, whereas when n=1, p and m are each an integer that is at least 1 and the sum of p and m is an integer ranging from 2 to 20;wherein R.sup.1 is straight or branched chain lower alkyl having from 1 to 6 carbon atoms or lower alkoxy having from 1-6 carbon atoms; andwherein R.sup.

Abstract: A novel tumor-associated antigen expressed by lung adenocarcinoma is disclosed. The antigen, characterized by monoclonal antibody LA20207, has a molecular weight in the range of about 50,000 to about 80,000 daltons and an isoelectric point in the range of about 4.9 to about 6.5. Antibodies directed against the antigen, methods for their production and diagnostic and therapeutic uses therefor are also provided.

Abstract: Processes for preparing stable natural matrices for prostrate specific antigen (PSA) are disclosed. Biological carrier fluids for PSA obtained from a suitable mammal are modified to inhibit the activity of components of the biological fluids destabilizing to PSA. The stable natural matrices, prepared in accordance with the present invention, are useful in the measurement of PSA in a sample by means of an immunoassay.

Abstract: Novel methods for reducing the heterogeneity of secreted monoclonal antibodies are disclosed. The first method comprises incubating the heterogeneous antibodies at low pH for a length of time sufficient to convert the heterogeneous forms of antibodies into substantially homogeneous forms. Another method produces the same result using ascites fluid, while yet another method produces the same result using carboxypeptidase. The homogeneous antibodies can then be purified in high yield.

Abstract: Disclosed herein is an improved apparatus for conducting immunoassays. The apparatus comprises a container, and a test zone to which is bound an antibody, typically a monoclonal antibody, or which is capable of extracting cells from a fluid sample. The test zone may be a membrane, filter or a porous matrix in which microspheres to which are bound antibody are entrapped. The apparatus further comprises a liquid absorbing zone which is composed of absorbent material which acts when in contact with the test zone to induce flow through the test zone when a fluid sample is added to it. At least one port in communication with the liquid absorbing zone and the opening of the container is provided to allow gas displaced by the addition of fluid to be discharged from the container. The flow of the displaced gas being in a direction opposite to the flow of assay reagents through the liquid absorbing zone.

Abstract: The present invention provides a method for the separation of anti-metal chelate antibodies from non-specific proteins, including antibodies, by applying a preparation containing the anti-metal chelate antibodies to an oxo acid derivatized solid support and eluting first with an elution buffer containing sufficient salt concentration to elute non-specific proteins but not sufficient to elute the anti-metal chelate antibodies and then increasing the salt concentration of the elution solution so as to elute the anti-metal chelate antibodies. In one embodiment, the oxo acid derivatized solid support is a sulfopropyl resin. Appropriate salts include sodium phosphate, sodium chloride and sodium acetate. The method can be used to separate monoclonal or polyclonal anti-metal chelate antibodies from non-specific proteins as well as to separate bifunctional anti-metal chelate antibodies from monoclonal anti-metal chelate antibodies and other non-specific proteins.