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: 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 provides a fusion polypeptide capable of binding a cytokine to form a nonfunctional complex. It also provides a nucleic acid sequence encoding the fusion polypeptide and methods of making and uses for the fusion polypeptide.

Abstract: Modified ciliary neurotrophic factors and methods for their production and therapeutic use. Also described is a method of screening for novel therapeutic proteins by determining altered electrophoretic binding properties.

Abstract: The present invention relates to the ciliary neurotrophic factor (CNTF) receptor, and provides for CNTF receptor nucleic acid and amino acid sequences. It also relates to (i) assay systems for detecting CNTF activity; (ii) experimental model systems for studying the physiologic role of CNTF; (ii) diagnostic techniques for identifying CNTF-related neurologic conditions; (iv) therapeutic techniques for the treatment of CNTF-related neurologic and muscular conditions, and (v) methods for identifying molecules homologous to CNTF and CNTFR.

Abstract: The present invention relates to methods for identifying therapeutic agents that enhance the effect of leptin, an adipocyte-derived cytokine that regulates food intake and body weight. The invention further provides for use of agents identified using this assay system to enhance the interaction between leptin and its receptor, OB-R, thereby boosting leptin's weight-reducing effects in obese individuals.

Abstract: The present invention provides for a method of promoting motor neuron survival, growth or differentiation comprising treating motor neurons with an effective amount of HGF. The invention also provides for a method of promoting motor neuron survival, growth or differentiation comprising treating motor neurons with an effective amount of HGF and an effective amount of CNTF. The invention further provides for a method of alleviating the toxic effects of vincristine on motor neurons comprising treating motor neurons with an effective amount of HGF and an effective amount of CNTF. The methods may be carried out in vitro or in vivo. The invention also provides a method of treating a motor neuron disorder in a patient comprising administering to the patient an effective amount of HGF and CNTF. The invention further provides a pharmaceutical composition for treating a motor neuron disorder in a patient comprising HGF and CNTF in a pharmacologically acceptable carrier.

Abstract: The present invention provides for a stable, biologically active CNTF/receptor complex, and hybrids or mutants thereof. The invention is also based in part on the discovery that the CNTF/receptor complex promotes differentiation through a signal transduction pathway on target cells that do not express the CNTF receptor. The invention further provides for a specific CNTFR mutant that promotes signal transduction without binding CNTF. The invention also provides for a CNTF/receptor blocking mutant, a mutant possessing a high binding affinity to CNTF, but possessing no signal transducing function. The present invention also identifies receptor components shared by the IL-6, CNTF, LIF and OSM signal transduction pathways, and the assay systems based on the use of such components.

Abstract: The present invention relates to the ciliary neurotropic factor (CNTF) receptor, and provides for CNTF receptor antibodies. It also relates to diagnostic techniques for identifying CNTF-related neurologic conditions.

Abstract: Neurotrophins having activities of multiple parental neurotrophins are described, as well as DNA for their production and pharmaceutical preparations thereof.

Abstract: The present invention relates to the ciliary neurotrophic factor (CNTF) receptor, and provides for CNTF receptor nucleic acid and amino acid sequences. It also relates to (i) assay systems for detecting CNTF activity; (ii) experimental model systems for studying the physiologic role of CNTF; (ii) diagnostic techniques for identifying CNTF-related neurologic conditions; (iv) therapeutic techniques for the treatment of CNTF-related neurologic and muscular conditions, and (v) methods for identifying molecules homologous to CNTF and CNTFR.

Abstract: Modified ciliary neurotrophic factors and methods for their production and therapeutic use. Also described is a method of screening for novel therapeutic proteins by determining altered electrophoretic binding properties.

Abstract: Novel dorsal growth inducing factors, complexes including the factors, and DNA or RNA coding sequences for the factors are described. Hybridoma cell lines and antibodies that bind to the dorsal growth inducing factor noggin, having the amino acid sequence set forth in SEQ ID NO:2, are also described.

Abstract: A method of altering the receptor binding properties and the stability of neurotrophic factors is set forth. Mutant neurotrophic factors having altered receptor binding specificities are described. Specific embodiments include neurotrophic factors that bind trk receptors but do not bind to the low affinity NGF receptor.

Abstract: Trk neurotrophin binding motifs consisting of 24 amino acid, leucine rich domains are described as well as nucleic acid sequences encoding such peptides. The leucine rich motifs are useful in screens for novel agonists and antagonists of the neurotrophins.

Abstract: Photoreceptor injury or cell death (retinal degeneration) is prevented by the introduction into the living mammalian eye of specific, survival-promoting factors. These specific factors prevent damage and degeneration of photoreceptors when introduced into the living eye prior to, during or after exposure to the damaging effects of light and delay photoreceptor damage caused by inherited disease.

Abstract: The present invention provides for a gene, designated as dmk, that encodes a novel tyrosine kinase receptor expressed in high levels in denervated muscle. The invention also provides assay systems that may be used to detect and/or measure ligands that bind the dmk gene product. The present invention also provides for diagnostic and therapeutic methods based on the interaction between Dmk and agents that initiate signal transduction through binding to Dmk.

Abstract: The present invention provides for TIE-2 ligand substantially free of other proteins. The invention also provides for an isolated nucleic acid molecule encoding TIE-2 ligand. In addition, the invention provides for a receptor body which specifically binds TIE-2 ligand. The invention also provides an antibody which specifically binds TIE-2 ligand. The invention further provides for therapeutic compositions as well as a method of blocking blood vessel growth, a method of promoting neovascularization and a method of promoting the growth or differentiation of a cell expressing the TIE-2 receptor.

Abstract: The present invention provides for assay systems that may be used to detect and/or measure neurotrophin activity or to identify agents that exhibit neurotrophin-like activity, and for methods of using such assay systems. It is based, at least in part, on the discovery that the trkB protooncogene encodes a tyrosine kinase receptor that may serve as a functional binding protein for BDNF and NT-3. Such assay systems may be of particular value in identifying new neurotrophins or agents with neurotrophin-like activity. In various embodiments, the assay systems and methods of the invention may be used to detect and/or measure the binding of neurotrophin to trkB, either using direct binding studies or the detection of the secondary affects of trkB/neurotrophin binding. The present invention also has diagnostic and therapeutic utilities. In particular embodiments of the invention, methods of detecting aberrancies in trkB function or expression may be used in the diagnosis of neurological disorders.

Abstract: The present invention relates to chimeric neurotrophic factors which comprise at least a portion of a naturally occurring cellular factor and a portion of at least one other molecule such that the resulting chimeric molecule has neurotrophic activity. It is based, in part, on the discovery that chimeric molecules comprising portions of both NGF and BDNF are likely to possess neurotrotrophic activity, and in some cases exhibit a spectrum of activity larger than that of either parent molecule. It is further based on the discovery that chimeric molecules comprising neurotrophic factor sequences as well as additional peptide sequences may retain neurotrophic activity, and in some cases may exhibit a more potent activity than the parent factor. The chimeric neurotrophic factor molecules of the invention provide a number of advantages relative to naturally occurring neurotrophic factors.