Abstract: The present invention relates to ligands which bind to human tumour necrosis factor alpha (TNF) in a manner such that upon binding of these ligands to TNF the biological activity of TNF is modified. In preferred forms the ligand binds to TNF in a manner such that the induction of endothelial procoagulant activity of the TNF is inhibited; the binding of TNF to receptors on endothelial cells is inhibited; the induction of fibrin deposition in the tumour and tumour regression activities of the TNF are enhanced; and the cytotoxicity and receptor binding activities of the TNF are unaffected or enhanced on tumour cells. The ligand is preferably an antibody, F(ab) fragment, single domain antibody (dABs) single chain antibody or a serum binding protein. It is preferred, however, that the ligand is a monoclonal antibody or F(ab) fragment thereof.

Abstract: Isolated nucleic acid molecules are provided which encode Fkhsf, as well as mutant forms thereof. Also provided are expression vectors suitable for expressing such nucleic acid molecules, and host cells containing such expression vectors.

Abstract: The invention relates to Cytostatin III polypeptides, polynucleotides encoding the polypeptides, methods for producing the polypeptides, in particular by expressing the polynucleotides, and agonists and antagonists of the polypeptides. The invention further relates to methods for utilizing such polynucleotides, polypeptides, agonists and antagonists for applications, which relate, in part, to research, diagnostic and clinical arts.

Abstract: The invention relates to human cells which are capable, on the basis of an activation of the endogenous human EPO gene, of producing EPO in a sufficient amount and purity to make possible a cost-effective production of human EPO as a pharmaceutical preparation. The invention furthermore relates to a method for the preparation of such human EPO-producing cells, DNA constructs for the activation of the endogenous EPO inhuman cells, and a method for the large technical production of EPO in human cells.

Abstract: The present invention relates to an antibody or functional fragment thereof which binds to a mammalian (e.g., human) CC-chemokine receptor 2 (CCR2) or a portion of the receptor and blocks binding of a ligand to the receptor. The invention further relates to a method of inhibiting the interaction of a cell bearing mammalian CCR2 with a ligand thereof, and to use of the antibodies and fragments in therapeutic, prophylactic and diagnostic methods.

Abstract: The invention relates to the treatment of subjects for the purpose inhibiting vaso-occlusive events, including thrombosis and embolism, by administering agents which reduce the number of circulating platelets to low or below normal levels. Methods and pharmaceutical preparations comprising such agents are provided.

Abstract: The present invention provides methods for isolating biological target materials, particularly nucleic acids, such as DNA or RNA or hybrid molecules of DNA and RNA, from other substances in a medium using silica magnetic particles. The methods of the present invention involve forming a complex of the silica magnetic particles and the biological target material in a mixture of the medium and particles, separating the complex from the mixture using external magnetic force, and eluting the biological target material from the complex. The preferred embodiments of magnetic silica particles used in the methods and kits of the present invention are capable of forming a complex with at least 2 &mgr;g of biological target material per milligram of particle, and of releasing at least 60% of the material from the complex in the elution step of the method.

Abstract: The present invention provides Fibroblast Growth Factor-Like (FGF-L) polypeptides and nucleic acid molecules encoding the same. The invention also provides selective binding agents, vectors, host cells, and methods for producing FGF-L polypeptides. The invention further provides pharmaceutical compositions and methods for the diagnosis, treatment, amelioration, and/or prevention of diseases, disorders, and conditions associated with FGF-L polypeptides.

Abstract: The present invention concerns a method of treating sepsis comprising administering a therapeutically effective amount of anti-CD14 antibody molecules. A therapeutic composition comprising anti-CD14 antibody molecules in a pharmaceutically acceptable excipient is also contemplated.

Abstract: Two kinds of antibody antagonists of the binding of human IL-4 to cellular receptors are provided by this invention. Some of the antagonists bind to specific regions of IL-4 which are believed to be involved in interactions between IL-4 and its receptors. Because of this specific binding by the antibodies to the IL-4, the binding of the IL-4 to the receptors is substantially inhibited. The other antibody antagonists of the invention are anti-idiotypic antibodies which, while lacking IL-4 activity, appear to mimic IL-4 and to compete directly with it for binding to the cellular receptors. Polypeptides used to make the antibody antagonists are also provided, together with methods for using the antagonists to inhibit the binding of IL-4 to its cellular receptors.

Abstract: The present invention relates to the detection of HLA-G. Antibodies to both soluble and membrane bound HLA-G are disclosed. Exemplary antibodies include 2C/C8, 3C/G4, and 4H84. 2C/C8 and 4H84 antibodies bind to the same region of HLA-G, which is a different region than that bound by 3C/G4. Methods of detection and diagnosis are disclosed as well as kits, including a miniaturized assay suitable for a clinical setting. Further, a method of selecting an embryos for in vitro fertilization is disclosed. A sandwich ELISA test is provided using two antibodies that bind to HLA-G at different regions. The HLA-G test according to the invention is over 1000 times more selective in binding to HLA-G than to antigens HLA-A2, HLA-B4, HLA-C, or mixed WBC preparations.

Abstract: The IL-1H4 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing IL-1H4 polypeptides and polynucleotides in therapy, and diagnostic assays for such.

Abstract: Disclosed are antibodies that specifically inhibit VEGF binding to only one (VEGFR2) of the two VEGF receptors. The antibodies effectively inhibit angiogenesis and induce tumor regression, and yet have improved safety due to their specificity. The present invention thus provides new antibody-based compositions, methods and combined protocols for treating cancer and other angiogenic diseases. Advantageous immunoconjugate and prodrug compositions and methods using the new VEGF-specific antibodies are also provided.

Abstract: To increase the effective affinity of soluble analogs of peptide/MHC molecules for their cognate ligands, divalent peptide/MHC complexes were constructed. Using a recombinant DNA strategy, DNA encoding the MHC class I was ligated to DNA coding for murine Ig heavy chain. MHC/Ig complexes were exploited to homogeneously load with peptides of interest. The results of flow cytometry demonstrated that the pepMHC/Ig complexes bound specifically with high affinity to cells bearing their cognate receptors.

Abstract: A method for the culture of hematopoietic cells and/or production of human cytokines using immortalized human stromal cell lines is provided. These immortalized stromal cell lines condition media such that the ability of the hematopoietic stem cells to self-replicate and/or differentiate is maintained by the media or the ability of the committed progenitors to expand and/or differentiate is maintained by the media. Further provided are irradiated and non-irradiated immortalized human stromal cells that synthesize cytokines, such as, IL-7, IL-8, IL-11, FLT3L, SCF, LIF, M-CSF, TGF-beta 1, GM-CSF, MIP-1alpha, G-CSF, and MCP-1.

Abstract: The present invention provides a human leukotriene B4 receptor that acts as a coreceptor for HIV viruses, polynucleotides encoding the receptor, recombinant cells expressing the receptor, and antibodies against the receptor. The invention also provides methods of identifying drugs that can block viral infection of cells and methods of facilitating infection of cells with HIV viruses.

Abstract: A method for inhibiting T-lymphocyte-mediated immune responses, including those directed against autologous and/or heterologous tissues, e.g., by a recipient mammal of a transplanted tissue, said method comprising providing the recipient mammal with Fas ligand. The Fas ligand may be provided to the recipient mammal by a variety of means, including by pump implantation or by transplantation of transgenic tissue expressing Fas ligand. Also provided is a method for diagnostic use of Fas ligand expression in improving transplantation success.

Abstract: An effective anti-IL-5 recombinant antibody molecule comprising heavy and/or light chain antigen-binding residues from a donor antibody.

Abstract: The invention provides TCCV-1 or TCCV-2 from human, reagents related thereto including polynucleotides encoding TCCV-1 or TCCV-2, purified polypeptides, and specific antibodies. Methods of making and using these reagents, in particular, methods for screening compounds which modulate TCCV-1 or TCCV-2 activity are provided. Also provided are methods of diagnosis and kits.

Abstract: The present invention concerns a method of treating sepsis comprising administering a therapeutically effective amount of anti-CD14 antibody molecules. A therapeutic composition comprising anti-CD14 antibody molecules in a pharmaceutically acceptable excipient is also contemplated.

Abstract: The in vivo circulating life and/or absorption of cationic therapeutic proteins, including but not limited to basic proteins such as NT-3, can be increased by generating analogs that have a lower isoelectric point and, preferably, also a lower protein charge relative to the protein of native sequence.

Abstract: In the course of therapy following an allogeneic bone marrow transplant (allo-BMT) in which lymphocytes were removed from the transplant, donor lymphocytes are introduced after a delay to reconstitute immunity in the patient. According to the invention, these donor lymphocytes are transduced with a detectable cell surface marker and a suicide gene prior to introducing them into the patient. Introduction of these transduced lymphocytes after allo-BMT, serves to treat or prevent complications from the BMT, including disease relapse, reactivation of viral infection and Graft versus Host disease.

Abstract: Human antibodies, preferably recombinant human antibodies, that specifically bind to human tumor necrosis factor &agr;(hTNF&agr;) are disclosed. These antibodies have high affinity for hTNF&agr; (e.g., Kd=10−8 M or less), a slow off rate for hTNF&agr; dissociation (e.g., Koff=10−3sec−1 or less) and neutralize hTNF&agr; activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hTNF&agr; and for inhibiting hTNF&agr; activity, e.g., in a human subject suffering from a disorder in which hTNF&agr; activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.

Abstract: The invention relates to anti-procalcitonin antibodies, their preparation and use, in particular in therapy and diagnostics. The antibodies comprise binding to procalcitonin but not to free calcitonin, free katacalcin and free N-procalcitonin.

Abstract: A method of assaying the growth hormone status of an individual by immuno-assay for the 150 KDa Insulin-like Growth Factor ternary complex (IGF/IGFBP-3/ALS). Alternatively, a binary complex may be assayed. The method involves capturing the IGFBP complex with a first antibody coupled to a solid phase and detecting the complex with a second antibody coupled to a label. A set of monoclonal and polyclonal antibodies usefutl for the assay is also provided.

Abstract: A method for treating neoplastic disease comprising the steps of: administering to a patient receiving radiation therapy or chemotherapy, an effective amount of an NK cell activating cytokine or an NK cell activating flavonoid, wherein said NK cell activating cytokine is not IL-2 or IFN-&agr;; and administering to the patient a compound effective to inhibit the production or release of intracellular hydrogen peroxide selected from the group consisting of histamine, other H2 receptor agonists, and serotonin.

Abstract: The present invention relates to tissue graft constructs useful in promoting regrowth and healing of damaged or diseased nuerological related tissue structures. More particularly this invention is directed to a submucosa tissue graft construct and a method of inducing the formation of endogenous neurological structures at a site in need of endogenous neurological related tissue growth.

Abstract: Mammalian genes and proteins, designated cytokine synthesis inhibitory factors (CSIFs) or interleukin 10 (IL-10), as well as antibodies which specifically bind IL-10, are provided. These proteins, and antibodies, may be used to treat various disease states associated with cytokine imbalances.

Abstract: A specific method has been developed to produce an autoimmune response and resulting clinical symptoms for a particular disease process. Peptides or other structures derived from an autoantigen and which are bound by auto antibody or T cell receptors are identified and used to induce an immune response. This immune response evolves into an autoimmune response directed against the other portions of the protein from which the peptide was derived. Subsequently, clinical manifestations may appear that are also found in the clinical illness. selected from the group including viruses, bacteria, fungi, parasites, rickettsia, plasmids, and insects which contains a structure or a peptide sequence that is similar to a structure or peptide sequence that has been identified by the method of claim 1 to the extent that it is bound by one of the group selected from antigen specific B cell surface receptors, and antigen specific T cell receptors.

Abstract: Canine interleukin 12 and a method for producing it by genetic engineering are disclosed. The canine interleukin 12 includes a protein having an amino acid sequence substantially the same as SEQ ID NO:1 or SEQ ID NO:11 or corresponds to part of either of SEQ ID NOS:1 and 11, and a protein having an amino acid sequence substantially the same as SEQ ID NO:2 or SEQ ID NO:12 or corresponds to part of either of SEQ ID NOS:2 and 12, and relates to a production method thereof. There is also an immune disease remedy and preventive agent for dogs and cats containing canine interleukin 12, and a method of treating immune disease and a preventive method for dogs and cats using the immune disease remedy or preventive agent.

Abstract: The present invention relates to novel p75 heterodimer specific anti-human IL-12 antibodies that are characterized by a higher potency and greater efficacy in neutralizing human IL-12 bioactivity than known heterodimer specific IL-12 monoclonal antibodies. The heterodimer specific antibodies recognize one or more epitopes of the human IL-12 p75 heterodimer, but do not bind to the p40 subunit alone. The heterodimer specific IL-12 antibodies neutralize rhesus monkey IL-12 bioactivity with a potency similar to their potency for neutralizing human IL-12 bioactivity making them useful IL-12 antagonists for in vivo studies in the rhesus monkey.

Abstract: Nucleic acid sequences which encode biologically active ETF, expression vectors which direct the expression of ETF, ETF polypeptides, antibodies which specifically bind ETF and processes for preparing the same are disclosed. Also disclosed are methods for treating or preventing gastrointestinal diseases and HIV or HIV-associated diseases.

Abstract: The present invention is based on the observation that HIV does not only interact with the CD4 receptor of target cells but that there exists a different type of interaction between HIV envelope protein and the IFN receptor of the target cell. Thus, blocking such interaction can be useful for preventing or treating retroviral infections. Accordingly, the present invention relates to pharmaceutical compositions for competitively inhibiting the binding of a retrovirus, preferably HIV, to the IFN-receptor of a target cell. Preferably, said pharmaceutical compositions comprise a protein, polypeptide or equivalent molecule or a combination thereof which binds to the IFN-.alpha./.beta.-receptor or to HIV-gp41. Furthermore, the present invention relates to the use of said protein, polypeptide or equivalent molecule or IFN-.beta. or a combination thereof for the preparation of a pharmaceutical composition for preventing or treating retroviral infections.

Abstract: Human/human hybrid cells were made via fusion of human embryonic kidney cells (293S) and modified Burkitt's lymphoma cells (2B8). The fusion cells are useful as host cells for the recombinant expression of mammalian genes. The advantages of using these hybrid clones of human kidney- and B-cells, called HKBs, for mammalian gene expression, include (i) the cells are negative for immunoglobulin expression, (ii) the cells grow easily in plasma protein-free medium (with or without the addition of recombinant insulin) as suspension cultures in a shake flask or in a fermenter (iii) the cells are very susceptible for transfection of DNA, and (iv) the cells secrete high levels of heterologous recombinant proteins, such as recombinant monoclonal antibodies, soluble ICAM-1, rIL-4, and rFVIII.

Abstract: The present invention relates generally to the control of body weight of animals including mammals and humans, and more particularly to materials identified herein as modulators of body weight, and to diagnostic and therapeutic uses of such modulators. In its broadest aspect, the present invention relates to nucleotide sequences corresponding to the murine and human OB gene, and two isoforms thereof, and proteins expressed by such nucleotides or degenerate variations thereof, that demonstrate the ability to participate in the control of mammalian body weight and that have been postulated to play a critical role in the regulation of body weight and adiposity. The present invention further provides nucleic acid molecules for use as molecular probes or as primers for polymerase chain reaction (PCR) amplification. In further aspects, the present invention provides cloning vectors and mammalian expression vectors comprising the nucleic acid molecules of the invention.

Abstract: The invention relates to antibodies which is capable of binding the monocyte chemoattractant protein 1 (MCP-1) receptor CCR2, especially those which are capable of acting either as an antagonist or agonist. The claimed antobodies can be used for in vitro and/or in vivo diagnostic, for screening and detection of tissues and classes of cells expressing the MCP-1 receptor, for screening for new drugs and for therapeutic use. The invention also relates to a preparation comprising the claimed antibody and a micro-organism or cell-line capable of producing the claimed antibody.

Abstract: The invention provides for a method for the modification of (poly)peptides for facilitating purification thereof, which modification method comprises the insertion of at least one specifically cleavable amino acid at the end of the (poly)peptide chain during synthesis thereof and protecting the same amino acid(s) within the (poly)peptide, if present, against cleavage, in order to allow for specific cleavage precisely at the specifically cleavable amino acid(s). The invention further relates to a process for the preparation of purified (poly)peptides using the modification method.

Abstract: A cancer prognostic having particular utility in the prognosis of head and neck squamous cell cancer, in which the expression levels of either or both of Transforming Growth Factor Alpha (TGF-.alpha.) or Epidermal Growth Factor Receptor (EGFR) are assayed directly from a sample of tumor tissue. The expression level once quantitated is normalized as to standard, and the standardized expression level is compared to the prognostic threshold of about 83% of standard for TGF-.alpha. or of about 23% of standard for EGFR, or the corresponding upper threshold of the "low" tertile regardless of how calculated. Virtually all if not all patients demonstrating this low expression level survive at least five years after initial diagnosis, assuming completion of treatment with standard surgical tumor excision and radiation protocols for squamous cell head and neck cancer. Whether an individual patient's expression levels of TGF-.alpha.

Abstract: A monoclonal antibody is provided which specifically binds to human interleukin-5. Also provided are a hybridoma which produces the monoclonal antibody; complementary DNAs which encode the heavy and light chain variable regions of the monoclonal antibody and CDRs therefrom; humanized monoclonal antibodies; and pharmaceutical compositions comprising the monoclonal antibody or anti-idiotypic antibodies directed against it, humanized monoclonal antibodies, binding fragments, binding compositions or single-chain binding proteins derived from the antibody and a physiologically acceptable carrier.

Abstract: Monoclonal antibodies immunospecific for the neutrophil chemotactic factor, IL-8, have been humanized by reshaping the variable regions to conform more closely to human counterparts. These antibodies are useful in immunoassays to detect IL-8 and as ligands on immunoaffinity columns for purification of human IL-8. In addition, the humanized antibodies have an antiinflammatory effect in patients.

Abstract: A novel cytokine, designated Apo-2 ligand, which induces mammalian cell apoptosis is provided. The Apo-2 ligand is believed to be a member of the TNF cytokine family. Compositions including Apo-2 ligand chimeras, nucleic acid encoding Apo-2 ligand, and antibodies to Apo-2 ligand are also provided. Methods of using Apo-2 ligand to induce apoptosis and to treat pathological conditions such as cancer, are further provided.

Abstract: The present invention relates to the identification and characterization of a novel, membrane-anchored chemokine, neurotactin. Sequence analysis of neurotactin reveals that, while it includes an amino terminal domain which resembles that of other chemokines, it has an overall structure which distinguishes it from all presently identified chemokines. Neurotactin is highly expressed in normal mammalian brain. Inhibitors of neurotactin expression or activity can be used to treat inflammation.

Abstract: The present invention relates to peptides and polypeptides derived from the submaxillary gland of the rat. In particular, the present invention discloses a purified peptide of formuls:X-His-Asn-Pro-Yin which X represents a Gln or Pro-Glu residue and Y represents an OH group or residue of a basic amino acid. The present invention also relates to corresponding polyclonal and monoclonal antibodies as well as corresponding hybridomas. The products of the present invention are useful for therapeutic, diagnosis and detection purposes.

Abstract: DNA encoding human neuronal nicotinic acetylcholine receptor alpha and beta subunits, mammalian and amphibian cells containing said DNA, methods for producing alpha and beta subunits and recombinant (i.e., isolated or substantially pure) alpha subunits (specifically .alpha..sub.4 and .alpha..sub.7) and beta subunits (specifically .beta..sub.4) are provided. In addition, combinations of subunits (i.e., .alpha..sub.1, .alpha..sub.2, .alpha..sub.3, .alpha..sub.4, and/or .alpha..sub.7 subunits in combination with .beta..sub.4 subunits; or .beta..sub.2, .beta..sub.3 and/or .beta..sub.4 subunits in combination with .alpha..sub.4 and/or .alpha..sub.7 subunits) are provided.

Abstract: The invention concerns novel inhibitors of tumor necrosis factor receptor associated factor-(TRAF) mediated signal transduction. The invention encompasses the novel inhibitor proteins (I-TRAFs), nucleic acid encoding them, methods for their recombinant production, and their use in screening assays and as pharmaceuticals.

Abstract: An effective anti-IL-5 recombinant antibody molecule comprising heavy and/or light chain antigen-binding residues from a donor antibody.

Abstract: The present invention discloses a reshaped human antibody against human IL-8 comprising:(A) L chains each comprising:(1) a human L chain C region; and,(2) an L chain V region comprising a human Lchain FR, and an L chain CDR of mouse monoclonal antibody against human IL-8; and,(B) H chains each comprising:(1) a human H chain C region; and,(2) an H chain V region comprising a human Hchain FR, and an H chain CDR of mouse monoclonal antibody against human IL-8. Since the majority of this reshaped human antibody originates in human antibody and the CDR has low antigenicity, the reshaped human antibody of the present invention has low antigenicity to humans, and can therefore be expected to be useful in medical treatment. The present invention further discloses polynucleotides which encode reshaped antibodies against IL-8, as well as host cells and methods to produce these antibodies.

Abstract: A human epidermal differentiation factor polypeptide and DNA (RNA) encoding such polypeptide and a procedure for producing such polypeptide by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptide for treating and/or preventing skin diseases. Diagnostic assays for detecting mutations in a nucleic acid sequence encoding a polypeptide of the present invention and for detecting altered levels of the polypeptide of the present invention are also disclosed.

Abstract: Two novel cytokines which are involved in an inflammatory response (inflammatory cytokines) are disclosed. The inflammatory cytokines have been isolated from activated peripheral blood, preferably monocytes adhered to plastic; or peripheral blood leukocytes induced with calcium ionophore and mezerin. The two cytokines are Gro .beta. and .gamma., and their cDNA and amino acid sequences are disclosed. The expression of the genes in various cells is presented. Assay and diagnostic utilities using the cytokines; recombinant materials and procedures; purification procedures; and monoclonal antibodies to the cytokines are also shown.

Abstract: Antibodies specific for a hek-L may be generated, using a hek-L polypeptide or fragment thereof as an immunogen. The antibodies may be monoclonal.