Abstract: The invention provides a human preproneurotensin/neuromedin N (HPPN) and polynucleotides which identify and encode HPPN. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for treating or preventing disorders associated with expression of HPPN.

Abstract: NGF variants which have trkC-binding activity and trkC-signal inducing activity are provided. The variants optionally have trkA or trkB binding and signal induction activity. The NGF variants of the present invention are useful in the treatment of neuronal disorders. Nucleic acids and expression vectors encoding the NGF variant neurotrophins are also provided.

Abstract: The present invention concerns the discovery that proteins encoded by a family of vertebrate genes, termed here hedgehog-related genes, comprise morphogenic signals produced by embryonic patterning centers, and are involved in the formation of ordered spatial arrangements of differentiated tissues in vertebrates. The present invention makes available compositions and methods that can be utilized, for example to generate and/or maintain an array of different vertebrate tissue both in vitro and in vivo.

Abstract: The invention relates to novel human DNA sequences, targeting constructs, and methods for producing novel genes encoding thrombopoietin, DNase I, and &bgr;-interferon by homologous recombination. The targeting constructs comprise at least: a) a targeting sequence; b) a regulatory sequence; c) an exon; and d) a splice-donor site. The targeting constructs, which can undergo homologous recombination with endogenous cellular sequences to generate a novel gene, are introduced into cells to produce homologously recombinant cells. The homologously recombinant cells are then maintained under conditions which will permit transcription of the novel gene and translation of the mRNA produced, resulting in production of either thrombopoietin, DNase I, or &bgr;-interferon.

Abstract: An isolated clone consisting of sequences transcribed from the TNF-delta gene is disclosed. Also provided are human polypeptides translated from said TNF-delta sequences and a procedure for producing such polypeptide by recombinant techniques. Also provided are a procedure for producing soluble biologically active TNF-delta, which may be used to treat deficiencies of TNF-delta and diseases conditions ameliorated by TNF-delta. Antibodies, antagonists and inhibitors of such polypeptide which may be used to prevent the action of such polypeptide and therefore may be used therapeutically to treat TNF-delta associated diseases, tumors or metastastases are disclosed. Also disclosed is the use of said antibodies, agonists and inhibitors as well as the nucleic acid sequences to screen for, diagnose, prognosticate, stage and monitor conditions and diseases attributable to TNF-delta, especially inflammation.

Abstract: Disclosed are 1) osteogenic devices comprising a matrix containing osteogenic protein and methods of inducing endochondral bone growth in mammals using the devices; 2) amino acid sequence data, amino acid composition, solubility properties, structural features, homologies and various other data characterizing osteogenic proteins, 3) methods of producing osteogenic proteins using recombinant DNA technology, and 4) osteogenically and chondrogenically active synthetic protein constructs.

Abstract: Provided are ligands for the receptor tyrosine kinase, Flt4. Also provided are cDNAs and vectors encoding the ligands, pharmaceutical compositions and diagnostic reagents.

Abstract: The invention is directed to liquid and lyophilized forms of Keratinocyte Growth Factor-2 (KGF-2) and derivatives thereof. This invention further relates to the formulation of KGF-2 for therapeutic use, for example, to promote or accelerate wound healing.

Abstract: The invention relates to nucleotide sequences encoding human interleukin-3 (hIL-3) as well as recombinant DNAs, expression cassettes, transformed host cells, and recombinant expression methods comprising such sequences. Additionally, the invention describes proteins having hIL-3 activity, as purified, recombinantly produced, or fusion protein forms of hIL-3, as well as methods of using such proteins to produce antibodies capable of immunospecific reaction with hIL-3.

Abstract: The present invention provides a novel polypeptide which has fish growth hormone-like activity and which can be widely used no matter what the species of fish is.

Abstract: The present invention provides an isolated and purified DNA molecule comprising a single coding region encoding (a) a turkey vasoactive intestinal peptide (VIP); (b) a turkey prepro vasoactive intestinal peptide or (c) a biologically active subunit of (a) or (b).

Abstract: The present invention relates to novel cortistatin polypeptides, and to polynucleotides encoding these polypeptides. More specifically, isolated nucleic acid molecules are provided encoding a Human Cortistatin polypeptide. Cortistatin polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. Also provided are diagnostic methods for detecting variations in Human Cortistatin gene expression and therapeutic methods for treating individuals in need of an increased level of Human Cortistatin activity.

Abstract: The present invention relates to strains of E coli adapted to produce bovine growth hormone, being the result of extraction of RNA from bovine pituitaries, transcription of DNA on such RNA templates, splicing of DNA into plasmids, insertion of spliced plasmid into microorganisms, and further subjecting the microorganisms to selection and isolating the colonies producing the desired fused or modified growth hormone and to modified bovine growth hormone obtained by the cultivation of such modified E. coli strains and recovery of the desired product.

Abstract: The present invention relates to the ligand polypeptide for the human pituitary- and mouse pancreas-derived G protein-coupled receptor proteins. The ligand polypeptide or the DNA which codes for the ligand polypeptide can be used for (1) development of medicines such as pituitary function modulators, central nervous system function modulators, and pancreatic function modulators, and (2) development of recombinant receptor proteins and screening of pharmaceutical candidate compounds. In particular, by the receptor binding assay systems utilizing the expression of recombinant G protein-coupled receptor proteins in accordance with the invention, agonists and antagonists of G protein-coupled receptors which are specific to human and other warm-blooded animals can be screened and the agonists or antagonists obtained can be used as therapeutic and prophylactic agents for various diseases.

Abstract: The present invention relates to insulin derivatives which in comparison to human insulin, have an accelerated onset of action, to a process for their preparation and to their use, in particular in pharmaceutical preparations for the treatment of diabetes mellitus. In particular, the present invention relates to insulin derivatives or physiologically tolerable salts thereof in which asparagine (Asn) in position B3 of the B chain is replaced by a naturally occurring basic amino acid residue and at least one amino acid residue in the positions B27, B28 or B29 of the B chain is replaced by another naturally occurring amino acid residue, it optionally being possible for asparagine (Asn) in position 21 of the A chain to be replaced by Asp, Gly, Ser, Thr or Ala and for phenylalanine (Phe) in position B1 of the B chain and the amino acid residue in position B30 of the B chain to be absent.

Abstract: Specific netrin proteins, nucleic acids which encode netrin proteins and hybridization reagents, probes and primers capable of hybridizing with netrin genes and methods for screening chemical libraries for lead compounds for pharmacological agents useful in the diagnosis or treatment of disease associated undesirable cell growth are provided. An exemplary screen involves forming a mixture comprising a recombinant netrin protein, a natural intracellular netrin protein binding target, and a candidate pharmacological agent; incubating the mixture under conditions whereby, but for the presence of said candidate pharmacological agent, said netrin protein selectively binds said binding target; and detecting the presence or absence of specific binding of said netrin protein to said binding target.

Abstract: A polypeptide which has a molecular weight of 18,500±3,000 daltons on SDS-PAGE and a pI of 4.9±1.0 on chromatofocusing. 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. It can be used to treat and/or prevent malignant tumors, viral diseases, bacterial infectious diseases, and immune diseases.

Abstract: Urocortin (Ucn) is a native mammalian peptide generally related to Urotensin I and Corticotropin Releasing Factor (CRF). Human Ucn has the formula: Asp-Asn-Pro-Ser-Leu-Ser-Ile-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Thr-Leu-Leu-Glu-Leu-Ala-Arg-Thr-Gln-Ser-Gln-Arg-Glu-Arg-Ala-Glu-Gln-Asn-Arg-Ile-Ile-Phe-Asp-Ser-Val-NH2 (SEQ ID NO:15). Rat-derived Ucn is identical but for 2 substitutions, Asp2 for Asn2 and Pro4 for Ser4. Ucn or analogs thereof or pharmaceutically acceptable salts can be administered to humans and other mammals to achieve substantial elevation of ACTH, &bgr;-endorphin, &bgr;-lipotropin, other products of the pro-opiomelanocortin gene and corticosterone. They can also be used to lower blood pressure over an extended period of time, as stimulants to elevate mood and to improve memory and learning performance, as well as diagnostically. Shortened fragments may be administered to release endogenous CRF and/or Ucn in the brain and peripherally.

Abstract: A method for preparing polypeptides in bacteria with an alanine rather than a methionine at the N-terminus. The DNA sequence expressed has an alanine codon immediately following from one to about three contiguous methionine codons including a translation start signal and allows for the expression of polypeptides having the amino acid sequence of, for example, naturally occurring eucaryotic proteins such as various bovine and porcine somatotropin species.

Abstract: Novel peptide hormones which influence the release of gonadotropins by the pituitary gland in fish are disclosed. Methods in which such peptides may be administered to fish to control their reproduction are also described. Furthermore, novel isolated cDNA encoding the precursor of the novel gonadotropin-releasing hormone is disclosed. The use of such cDNA in controlling the gonadal development and spawning of fish is also described.

Abstract: The invention features a nucleic acid molecule encoding a chondrosarcoma associated polypeptide and methods for diagnosing patients with chondrosarcoma. the gene.

Abstract: The present invention provides a novel human tubby homolog (NHT) and polynucleotides which identify and encode NHT. The invention also provides expression vectors, host cells, agonists, antibodies, or antagonists. The invention also provides methods for treating disorders associated with appetite and eating.

Abstract: An isolated nucleic acid molecule that hybridizes under stringent conditions, or shares at least 80% sequence identity, with a defined genomic region upstream of the coding region of a FSH&bgr; gene, and a DNA construct containing that nucleic acid molecule as a targeting sequence for homologous recombination.

Abstract: EGF muteins in which the histidine at position 16 is replaced with a neutral or acidic amino acid exhibit activity at pHs lower than obtainable with wild type EGF.

Abstract: The present invention is directed to compositions and methods for selective induction of apoptosis in cancer cells, particularly malignant cancer cells, by delivery of a IL-1&agr; propiece polypeptide (e.g., a native IL-1&agr; propiece polypeptide, including IL-1&agr; propiece polypeptide variant) to a cancer cell.

Abstract: The present invention provides testis-specific insulin homolog polypeptides and polynucleotides encoding the polypeptides, as well as related compositions and methods are disclosed. The polypeptides and polynucleotides may be used within methods for enhancing viability of cryopreserved sperm, for enhancing sperm motility, to enhance fertilization in methods of assisted reproduction, as contraceptives and other related uses.

Abstract: The CC type chemokines belong to a family of polypeptides which have proven to be mediators of immune reactions, and they have recently attracted attention due to their antiviral activity with respect to HIV. The cloning and molecular characterization of a human tandem gene is disclosed which contains the closely linked coding regions for two new CC type chemokines the sequences of which are highly homologous with that of MIP-1&agr;. The transcription of the tandem gene leads to a bicistronic mature transcript which contains the non-overlapping open reading frames for the recently described factor HCC-1 and an as yet unknown CC type chemokine, designated as CC-2. Moreover, alternative splicing of the primary transcript yields at least one additional CC type chemokine, cytokine CC-3. Two functional promoter regions were identified within the tandem gene.

Abstract: A method for linking strongly negatively charged biological macromolecules like deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and glycosaminoglycans (GAG) to plastic substrates, comprising contacting the macromolecules and the plastics with a non chaotropic solution containing a salt in an amount of at least 20% of its saturation concentration, or having a pH below the pKa of the charged groups of the macromolecules to be linked. Also disclosed are the products of the method, in particular a microtiter plate with plastic wells coated with the negatively charged non-proteinaceous macrobiomolecules.

Abstract: Therapeutic hybrid cytokines, having a size ranging from about 10 to about 30 kDa, comprise portions of cytokines: leukemia inhibitory factor (LIF), granulocyte-colony stimulating factor (G-CSF), interleukin-6 (IL-6), interleukin-11 (IL-11), oncostatin-M (OSM), and ciliaryneurotrophic factor (CNTF). Hybrid cytokines comprise three or four &agr;-helical sequences selected from &agr;-helical sequences of IL-6, G-CSF, LIF, IL-11, CNTF and OSM and linking sequences of 5-40 amino acids in length, selected from the linking sequences of IL-6, G-CSF, LIF, IL-11, CNTF and OSM or other, desirable linking sequences. In the hybrid cytokines, at least one &agr;-helical sequence is derived from a different cytokine than at least one other &agr;-helical sequence; or, at least one linking sequence of a cytokine differentiates the hybrid cytokine from a corresponding cytokine.