Abstract: The present invention relates to antibodies including human antibodies and antigen-binding portions thereof that specifically bind to c-Met, preferably human c-Met, and that function to inhibit c-Met. The invention also relates to human anti-c-Met antibodies and antigen-binding portions thereof. The invention also relates to antibodies that are chimeric, bispecific, derivatized, single chain antibodies or portions of fusion proteins. The invention also relates to isolated heavy and light chain immunoglobulins derived from human anti-c-Met antibodies and nucleic acid molecules encoding such immunoglobulins. The present invention also relates to methods of making human anti-c-Met antibodies, compositions comprising these antibodies and methods of using the antibodies and compositions for diagnosis and treatment. The invention also provides gene therapy methods using nucleic acid molecules encoding the heavy and/or light immunoglobulin molecules that comprise the human anti-c-Met antibodies.

Abstract: The present disclosure provides compositions and methods relating to antigen binding proteins, in particular, antibodies which specifically bind to the human glucagon receptor. The disclosure provides nucleic acids encoding such antigen binding proteins and antibodies and methods of making and using such antibodies including methods of treating and preventing type 2 diabetes and related disorders by administering such antibodies to a subject in need of such treatment.

Abstract: The invention is directed to human IL-4 muteins numbered in accordance with wild-type IL-4 having T cell activating activity, but having reduced endothelial cell activating activity. In particular, the invention is related to human IL-4 muteins wherein the surface-exposed residues of the D helix of the wild-type IL-4 are mutated whereby the resulting mutein causes T cell proliferation, and causes reduced IL-6 secretion from HUVECs, relative to wild-type IL-4. This invention realizes a less toxic IL-4 mutant that allows greater therapeutic use of this interleukin. Further, the invention is directed to IL-4 muteins having single, double and triple mutations represented by the designators R121A, R121D, R121E, R121F, R121H, R121I, R121K, R121N, R121P, R121T, R121W; Y124A, Y124Q, Y124R, Y124S, Y124T; Y124A/S125A, T13D/R121E; and R121T/E122F/Y124Q, when numbered in accordance with wild type IL-4 (His=1).

Abstract: This invention describes a protein-free production process for proteins having factor VIII procoagulant activity. The process includes the derivation of stable human cell clones with high productivity for B-domain deleted Factor VIII, and (2) the adaptation of cells to grow in a medium free of plasma-derived proteins.

Abstract: Glycosylated interleukin-2 muteins are described. A method of producing the muteins using mammalian cells is included. The muteins may be incorporated into pharmaceutical preparations useful for, e.g., cancer therapy.

Abstract: A cell culture medium which is low in dissolved carbon dioxide is disclosed. The medium contains less than about 1 g/L added sodium bicarbonate and includes an organic buffer and a metal complexing agent. The medium is preferably essentially free of added sodium bicarbonate. Methods of use of the medium in culturing mammalian cells, particularly cells engineered to produce recombinant factor VIII, are also disclosed.

Abstract: This invention realizes a less toxic IL-4 mutant that allows greater therapeutic use of interleukin 4. Further, the invention is directed to IL-4 muteins having single and double mutations represented by the designators R121E and T13D/R121E, numbered in accordance with wild type IL-4 (His=1). The invention also includes polynucleotides coding for the muteins of the invention, vectors containing the polynucleotides, transformed host cells, pharmaceutical compositions comprising the muteins, and therapeutic methods of treatment.

Abstract: A recombinant human IL-4 mutein numbered in accordance with wild-type IL-4 wherein the mutein comprises at least one amino acid substitution in the binding surface of either the A- or C-alpha helices of the wild-type IL-4 whereby the mutein binds to the IL-4R&agr; receptor with at least greater affinity than native IL-4. The substitution is more preferably selected from the group of positions consisting of, in the A-helix, positions 13 and 16, and in the C-helix, positions 81 and 89. A most preferred embodiment is the recombinant human IL-4 mutein wherein the substitution at position 13 is Thr to Asp. Pharmaceutical compositions, amino acid and polynucleotide sequences encoding the muteins, transformed host cells, antibodies to the muteins, and methods of treatment are also described.

Abstract: This invention provides a novel antibody, designated the .alpha.EM10 antibody. Also provided are methods of determining hematopoietic stem cell content. The methods employ using antibodies (.alpha.EM10) specific for a unique cell marker (EM10) that is expressed on stem cells.

Abstract: Myeloproliferative leukemia receptor (mpl) ligands, such as thrombopoietin, act on a primitive subpopulation of human stem cells having the characteristics of self-renewal and ability to give rise to all hematopoietic cell lineages. Thrombopoietin supports both megakaryocytic differentiation and primitive progenitor cell expansion of CD34.sup.+ and CD34.sup.+ sub-populations (CD34.sup.+ Lin.sup.-, CD34.sup.+ Thy-1.sup.+ Lin.sup.-, and CD34.sup.+ Lin.sup.- Rh123.sup.lo). Thrombopoietin also stimulated quiescent human stem cells to begin cycling. Thus, mpl ligands are useful for expanding primitive stem cells for restoration of hematopoietic capabilities and for providing modified human stem cells for gene therapy applications.

Abstract: A device is provided for use in a centrifuge to separate or isolate material (such as pelleted cells, particulates, aggregates, compounds, blood components, and the like) from the liquid in which they are suspended while limiting or preventing loss of any of the resulting separated or pelleted material during further manipulations. The device can be inserted into a standard centrifugation bucket in a centrifuge and holds a flexible centrifuge bag. The device includes at least one damp assembly, which includes a partition that is maintained in an open position during centrifugation and in a closed position at unit gravity, thus isolating separated or pelleted material at the bottom of the flexible bag in the device after centrifugation and preventing the isolated material from being disturbed during liquid changes and other manipulations.

Abstract: This invention provides a method for obtaining a recombinant retroviral packaging cell capable of producing retroviral vectors as well as the recombinant packaging cell obtained by the method. Also provided is a method of producing recombinant retroviral particles obtained by introducing into the packaging cells obtained according to the methods disclosed herein, a recombinant retroviral vector and propagating the resulting producer cells under conditions favorable for the production and secretion of retroviral vector supernatant. The retroviral supernatant produced by these methods also is claimed herein. This invention further provides a method for screening retroviral vector supernatant for high transduction efficiency and methods for producing retroviral vector supernatant for transducing cells with high efficiency in gene therapy applications.

Abstract: The invention relates to methods of enriching for hematopoietic cell populations enriched in myeloid and/or lymphoid progenitor cells based on cell specific markers. The methods also provide an enriched population of prethymic lymphoid-committed progenitor population lacking long-term hematopoietic reconstitution potential. Compositions enriched for the cells and populations of cells obtained therefrom are also provided by the invention. Methods of use of the cells are also included. Methods of genetically modifying the cells are provided as are cells obtained thereby.

Abstract: The invention relates to methods of enriching for hematopoietic cell populations enriched in myeloid and/or lymphoid progenitor cells based on cell specific markers. The methods also provide an enriched population of prethymic lymphoid-committed progenitor population lacking long-term hematopoietic reconstitution potential. Compositions enriched for the cells and populations of cells obtained therefrom are also provided by the invention. Methods of use of the cells are also included. Methods of genetically modifying the cells are provided as are cells obtained thereby.

Abstract: The invention relates to methods of enriching for hematopoietic cell populations enriched in myeloid and/or lymphoid progenitor cells based on cell specific markers. The methods also provide an enriched population of prethymic lymphoid-committed progenitor population lacking long-term hematopoietic reconstitution potential. Compositions enriched for the cells and populations of cells obtained therefrom are also provided by the invention. Methods of use of the cells are also included. Methods of genetically modifying the cells are provided as are cells obtained thereby.

Abstract: The present invention provides a method for optimizing gene transfer into hematopoietic stem cells (HSCs) by contacting the cells with hydroxyurea prior to gene transfer to induce HSCs in G0 into active cell cycle. This method is useful for treating patients suffering from a disease that is suitably treated by gene therapy or involves hematopoietic cells. A method is also provided for enhancing the efficacy of bone marrow transplantation by administering hydroxyurea to increase HSC yields.

Abstract: The invention provides a modified tubulin comprising a tubulin polypeptide which confers resistance to an anti-tubulin agent when expressed within a biological organism, said polypeptide having at least one amino acid substitution such that hydrophobicity is increased at one or more positions in the polypeptide. DNA sequences encoding such modified tubulins may be used to confer resistance on organisms which otherwise would be susceptible to one or more anti-tubulin agents. For example, a plant which is resistant to a herbicide that disrupts microtubule structure or function may be produced.

Abstract: The chemically-inducible 27 kD subunit of the enzyme glutathione-S-transferase, isoform II (GST-II-27) and sequences encoding it are provided. In particular, a genomic DNA sequence encoding the gene promoter for the GST-II-27 subunit is provided. Then linked to an exogenous gene and introduced into a plant by transformation, and GST-II-27 promoter provides a means for the external regulation of expression of that exogenous gene. Transformation with DNA encoding glutathione-S-transferase polypeptides produces herbicide resistance transgenic plants.

Abstract: Compounds, useful as plant fungicides, having the formula (I): ##STR1## or a stereoisomer thereof, wherein A is CH or N, B is OCH.sub.3 or NHCH.sub.3, X is CH.sub.2, CH.sub.2 O, O or S, Y is R.sup.1 --C.dbd.C--R.sup.2 or R.sup.1 --CH--CH--R.sup.2 wherein R.sup.1 and R.sup.2 are independently H, halo, hydroxy, alkyl, haloalkyl, alkoxy, haloalkoxy, cyano, nitro, amino, mono- or dialkylamino, alkanoylamino, carboxy, alkoxycarbonyl, aminocarbonyl, mono- or di-alkylaminocarbonyl, alkylcarbonyloxy, optionally substituted aryl, optionally substituted aralkyl or optionally substituted aryloxy or R.sup.1 and R.sup.2 join to form with the carbon atoms to which they are attached an optionally substituted benzene ring, and Z is CH.sub.2, CHCH.sub.3, C(CH.sub.3).sub.2 or C.dbd.O.

Abstract: This invention relates to substituted N-benzotriazoles of the formula ##STR1## in which: R.sup.1, R.sup.2, R.sup.3,R.sup.4, R.sup.5,R.sup.6, R.sup.7, X are as defined in the specification. The compounds exhibit herbicidal activity.