Abstract: The present invention provides novel transgenic nonhuman mammals capable of producing human sequence antibodies, as well as methods of producing and using these antibodies.

Abstract: A method of forming a hybridoma cell includes acoustically focusing antibody producing cells in a first channel having a first acoustic field so as to produce a single file line of antibody producing cells; acoustically focusing immortal cells in a second channel having a second acoustic field so as to produce a single file line of immortal cells; flowing the acoustically focused single file lines of antibody producing cells and immortal cells to a third channel having a third acoustic field configured to bring at least one antibody cell and at least one immortal cell into close enough proximity to permit them to fuse; and fusing the antibody producing cell and the immortal cell together by at least one of a chemical and an electrical means to form at least one hybridoma cell.

Abstract: Disclosed herein are methods for improving the efficiency of the production of hybridomas, e.g., through enrichment of IgG expressing B cells. Also disclosed are hybridoma compositions produced using these methods as well as methods for producing antibodies with the hybridomas.

Abstract: The invention relates generally to compositions and methods of using transgenic non-human animals expressing human SIRP? that are engrafted with a human hematopoietic system. In various embodiments, the human hematopoietic system engrafted, human SIRP? transgenic non-human animals of the invention are useful as systems for the in vivo evaluation of the growth and differentiation of hematopoietic and immune cells, for the in vivo assessment of an immune response, for the in vivo evaluation of vaccines and vaccination regimens, for in vivo production and collection of immune mediators, including human antibodies, and for use in testing the effect of agents that modulate hematopoietic and immune cell function.

Abstract: The present invention provides a novel method to distinguish between HCG ? type I and type II gene expression using specific antibody. The specific recognition of HCG? encoded by type II genes and expressed by trophoblastic and neoplastic cells might improve the clinical usefulness of assays aimed at either diagnosing tumors or screening Down's syndrome. The present invention also provides a diagnostic kit for determining the amount of HCG? type II in a biological sample. The present invention additionally provides process of preparation and screening hybridoma capable of specifically recognizing HCG? type II and recombinant antibody thereof. Finally, the present invention provides methods for detecting trophoblast or non-trophoblast malignancy in a sample.

Abstract: A method of manipulating a living cell is disclosed. The method comprises, directing a pulsed optical field to at least one conductive nanoparticle present in the vicinity of the cell, so as to generate cavitations at or near the conductive nanoparticle at sufficient amount to effect at least one cell modification selected from the group consisting of cell-damage and cell-fusion.

Abstract: Materials and Method for treating cancer and screening for anti-neoplastic agents are provided. These materials and methods can include sphingosine 1-phosphate antagonists that bind to sphingosine-1 phosphate receptor subtype 3. Antibodies and aptamers that selectively bind to an epitope in the extracellular loop between transmembrane domains two and three of sphingosine-1-phosphate receptor subtype 3 are provided.

Abstract: Provided herein is disclosure about the development and characterization of an antibody that binds to antigen EphA2 which is present on a variety of human cancers from breast, lung, prostate, and colons. Methods of diagnosing and treating various cancers by using such antibodies directed against this antigen are also disclosed.

Abstract: The present invention concerns a method of testing a subject thought to be predisposed to having a metastatic cancer which comprises: analyzing a biological sample from said subject for detecting the presence of a p53 isoform selected from the group consisting of ?133p53, ?133p53? and ?133p53?, the presence of said p53 isoform being indicative of a metastatic cancer.

Abstract: The present invention relates to cellular differentiation and, in particular to hybrid cells that exhibit phenotypic plasticity and methods for producing these cells. The invention also relates to methods for generating specific cells of a desired phenotype. The invention still further relates to methods of producing hybrid cells with a capacity to de-differentiate into an earlier progenitor state. The invention further contemplates the use of hybrid cells in a range of applications, for example tissue generation.

Abstract: Monoclonal antibodies that are specific for vascular endothelial growth factor receptor 1 (VEGFR-I). This invention also provides nucleotide sequences encoding and amino acid sequences comprising variable heavy and light chain immunoglobulin molecules, including sequences corresponding to the complementarity determining regions of CDR1, CDR2, and CDR3. The invention also provides methods for generation and expression of anti-VEGFR-I antibodies and methods of treating angiogenic-related disorders and reducing tumor growth by administering anti-VEGFR-I antibodies.

Abstract: A process for purifying an antibody is provided. In this process, a mixture containing the antibody and a contaminant is subjected to low pH hydrophobic interaction chromatography (LPHIC) at low salt concentration. The antibody is eluted from the column in the fraction which does not bind thereto. This process can be preceded and followed by other purification steps.

Abstract: The invention concerns a process for the production of a hybridoma, and of a monoclonal antibody or fragments thereof able to recognize 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3.

Abstract: The invention reflects enhanced antibody expression of an antibody of interest by cell lines transformed by random homozygous gene perturbation methods to either increase or decrease the expression pattern of a gene of the cell line other than the antibody of interest. The transformed cell line exhibits specific productivity rates, SPR, for the RHGP transformed cell liens of 1.5 or more, as compared with the antibody expressing cell line parents prior to transformation by RHGP. A knock out or anti-sense construct may be devised to reduce expression of the target gene, a promoter may be inserter to enhance expression of the target gene. The antibodies expressed by the transformed cell lines exhibit the binding properties of their parent cell lines prior to transformation with RHGP, and increase Total Volumetric Production of said antibody by said cells in a given volume.

Abstract: A variant of a polypeptide comprising a human IgG Fc region is described, which variant comprises an amino acid substitution at one or more of amino acid positions 270, 322, 326, 327, 329, 331, 333 or 334 of the human IgG Fc region. Such variants display altered effector function. For example, C1q binding and/or complement dependent cytotoxicity (CDC) activity may be altered in the variant polypeptide. The application also discloses a variant of a parent polypeptide comprising a human IgG Fc region, which variant has a better binding affinity for human C1q than the parent polypeptide.

Abstract: The present invention provides methods of enhancing hybridoma fusion efficiencies through cell synchronization of the fusion partners, in order to aid in production of antibodies.

Abstract: Embodiments of the present invention are directed to quantitative analysis of tissues enabling the measurement of objects and parameters of objects found in images of tissues including perimeter, area, and other metrics of such objects. Measurement results may be input into a relational database where they can be statistically analyzed and compared across studies. The measurement results may be used to create a pathological tissue map of a tissue image, to allow a pathologist to determine a pathological condition of the imaged tissue more quickly.

Abstract: The present application relates to immunoglobulin polypeptides comprising at least two immunoglobulin complementarity determining regions, one that binds to an immune receptor and the other which comprises an idiotype to which an immune response is desired.

Abstract: There is provided a human myeloma cell tine for use in a method for producing a human monoclonal antibody.

Abstract: Disclosed are antibodies that inhibit proteolytic release of a soluble KIM-1 polypeptide from KIM-1 expressing cells. Also disclosed are methods of using the antibodies to inhibit shedding of the KIM-1 polypeptide.

Abstract: This invention provides: a heteromyeloma, other than B6B11, capable of producing a trioma when fused with a human lymphoid cell, wherein the trioma is capable of producing a monoclonal antibody-secreting tetroma when fused with a second, antibody-secreting human lymphoid cell; a trioma fusion partner which does not produce antibody, obtained by fusing a heteromyeloma which does not produce antibody with a human lymphoid cell; a monoclonal antibody-secreting tetroma, obtained by fusing a trioma which does not produce antibody with an antibody-secreting human lymphoid cell; a method of producing a monoclonal antibody that specifically recognizes an antigen associated with a condition; a method of identifying an antigen associated with a condition using the trioma fusion partner; a method of diagnosing a condition using the trioma fusion partner; a method for preventing a condition; and compositions and therapeutic compositions comprising monoclonal antibodies produced using the trioma fusion partner.

Abstract: The present invention provides for a method of selecting an antibody against a target substance to be measured, which comprises selecting the antibody against the target substance by antigen-antibody reaction in the presence of a substance interfering with the antigen-antibody reaction. That is, an antigen and a labeled antigen are reacted with the antibody in the presence of an interfering substance, such as an environment pollutant, and on the basis of the degree of reaction thereof, the antibody against the target substance, which is highly resistant to the interfering substance, is selected. Thereby, even if a test sample is contaminated with a substance interfering with antigen-antibody reaction, the antibody, which is highly resistant to the substance interfering with antigen-antibody reaction, is not influenced by the interfering substance and gives a correct value in the quantification.

Abstract: The invention provides methods for fusing a first cell with a second cell to form a hybrid cell. The methods involve incubating a first parental cell producing a first partner of a fusogenic binding partner pair on its surface with a second parental cell producing a second partner of the fusogenic binding partner pair on its surface. In certain embodiments, the parental cells are incubated with a known fusogen such as polyethylene glycol and the fusogenic binding partner pair increases the rate of cell fusion. In many embodiments, the first cell is an antibody producing cell, the second cell is an immortal cell, and the hybrid cell is a hybridoma cell that produces a monoclonal antibody. Also provided by the invention are methods for producing hybridoma cells, and methods for screening those cells for production of a monoclonal antibody of interest. The invention further provides systems and kits for carrying out the subject methods.

Abstract: The present invention features methods of producing a multimeric protein in a hybrid, recombinant cell, as well as for identifying recombinant cells expressing heavy chain which cells are useful in production of such hybrid cells. In the method of the invention, at least first and second recombinant cells are engineered to contain a first and second expression cassette, respectively, which expression cassettes contain an amplifiable marker and encode first and second components of the multimeric protein. The recombinant cells are then fused to produce a hybrid cell expressing the multimeric protein. The hybrid cell is then cultured to provide for amplification of the DNA encoding the first and second multimeric protein components. The methods of the invention are widely applicable to the production of proteins having two or more components.

Abstract: The present invention features methods of producing a multimeric protein in a hybrid, recombinant cell, as well as for identifying recombinant cells expressing heavy chain which cells are useful in production of such hybrid cells. In the method of the invention, at least first and second recombinant cells are engineered to contain a first and second expression cassette, respectively, which expression cassettes contain an amplifiable marker and encode first and second components of the multimeric protein. The recombinant cells are then fused to produce a hybrid cell expressing the multimeric protein. The hybrid cell is then cultured to provide for amplification of the DNA encoding the first and second multimeric protein components. The methods of the invention are widely applicable to the production of proteins having two or more components.

Abstract: The present invention provides in one aspect novel fusion partner cells that ectopically express one or more genes that alter the phenotype of a hybrid cell made from a fusion of the fusion partner cell and a fusion cell, hybrid cell lines produced using the fusion partner cells. The invention in another aspect provides antibodies produced by certain hybrid cell lines, and compositions containing one or a combination of such antibodies or antigen-binding fragments thereof. The invention also provides in another aspect methods of using the antibodies or antigen-binding fragments thereof for diagnosis and treatment of diseases characterized by the antigens specifically bound by the antibodies.

Abstract: This invention relates to immunological reagents and methods specific for a mammalian, transmembrane protein termed Pgp, having a non-specific efflux pump activity established in the art as being a component of clinically-important multidrug resistance in cancer patients undergoing chemotherapy. The invention provides methods for developing and using immunological reagents specific for certain mutant forms of Pgp and for wild-type Pgp in a conformation associated with substrate binding or in the presence of ATP depleting agents. The invention also provides improved methods for purifying hematopoietic stems cells expressing Pgp and diagnostic and therapeutic methods for cancer cells expressing Pgp.

Abstract: Commercially feasible methods for synthesizing various epothilones precursors needed for the preparation of final epothilones are provided, including techniques for the synthesis of epothilone segment A and C precursors. Segment C precursors are prepared using starting nitriles, which can alternately be oxidized to ketones and converted, or reacted to form the diol with subsequent conversion to the segment. Segment A precursors are prepared by reacting a starting enone with a chiral catalyst to give an intermediate alcohol in high enantomeric excess, followed by conversion of the alcohol to the desired Segment A precursor.

Abstract: A system for the immune mediated in vivo hydrolysis of the nerve agent sarin, comprising metalloantibodies capable of hydrolyzing the nerve agent sarin, a cell culture method of raising these antibodies, an artificial antigen capable of stimulating the production of these antibodies, and a hapten analogue of sarin. A hapten analogue to sarin is formed by conjugating a Cr(III) trien with N&agr;, N&egr;-di(O,O-diisopropyl) phosphoryl L-lysine (DIP). This hapten is conjugated with key limpet hemocyanin (KLH) to form an antigen capable of eliciting antibodies with reactive sites for both metals and sarin. Antibodies formed in response to this antigen are cultured in an immortal cell line and purified. The steric proximity of binding sites on the antibody for the metal trien and sarin allows hydrolyzation of the F− moiety from sarin and sarin's resultant bioactive neutralization. Antibody hydrolysis activity is monitored by measurement of produced F−.

Abstract: The present invention relates to a method of producing a plurality of dendritic cell/tumor cell hybrids which induce an anti-tumor response when applied to a patient. The present invention further relates to a method of producing a dendritic cell/tumor cell hybridoma which induces an anti-tumor response when applied to a patient.

Abstract: The present invention features a method of producing a multimeric protein from a hybrid cell formed from the fusion of two or more cells, each of which cell is engineered to express one component of the multimeric protein, as well as a method for screening for successful fusion of the cells to produce a desired hybrid cell. The methods of the invention are widely applicable to the production of proteins having two or more components.

Abstract: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.

Abstract: The present invention features a method of producing a multimeric protein from a hybrid cell formed from the fusion of two or more cells, each of which cell is engineered to express one component of the multimeric protein, as well as a method for screening for successful fusion of the cells to produce a desired hybrid cell. The methods of the invention are widely applicable to the production of proteins having two or more components.

Abstract: A new and useful apparatus for producing cell electrofusion is provided. The apparatus comprises: a. a chamber with a substrate disposed therein, b. means for directing the cells to be fused toward one side of the substrate; and c. a device for inducing fusion of the portion of the cells.

Abstract: According to the invention, there is provided a human or animal cell expressing an antibody directed against a surface antigen on an antigen-presenting cell (APC) and lacking parental tumor-derived immunoglobulin.

Abstract: A monoclonal antibody which is specific to a polypeptide having a molecular weight of 18, 500±3,000 daltons on SDS-PAGE and a pI of 4.9±1.0 on chromatofocusing. The monoclonal antibody is obtainable from hybridomas and can be used for the purification and detection of the polypeptide. The polypeptide strongly induces the IFN-&ggr; production by immunocompetent cells with only a small amount, and does not cause serious side effects even when administered to human in a relatively-high dose.

Abstract: The invention is directed to a method for the preparation of a conditionally immortalized immortalization-helper cell (fuseme), the fusemes generated by said method, hybridoma cells prepared using said fusemes as well as a method for immortalization of mammalian cells using said fuseme cells. Further, the invention relates to the generation of T cells directed agaist tumor cells using a fuseme cell.

Abstract: Compositions of, genetic constructions coding for, and methods for producing multivalent antigen-binding proteins are described and claimed. The methods include purification of compositions containing both monomeric and multivalent forms of single polypeptide chain molecules, and production of multivalent proteins from purified monomers. Production of multivalent proteins may occur by a concentration-dependent association of monomeric proteins, or by rearrangement of regions involving dissociation followed by reassociation of different regions. Bivalent proteins, including homobivalent and heterobivalent proteins, are made in the present invention. Genetic sequences coding for bivalent single-chain antigen-binding proteins are disclosed. Uses include all those appropriate for monoclonal and polyclonal antibodies and fragments thereof, including use as a bispecific antigen-binding molecule.

Abstract: A monoclonal or other antibody to the carbohydrate antigen Tn can be used to inhibit or slow the progression of AIDS or ARC. The antigen can be used in a vaccine, for immunisation.