Abstract: Canine CCK1 receptor materials are described, such as polypeptides having amino acid sequences corresponding to SEQ ID Nos.: 14, 15, and 16 or functional variants thereof and polynucleotides expressing them having nucleic acid sequences corresponding to SEQ ID Nos.: 11, 12, and 13 or complements thereof. Such materials are useful as reagents in drug screening assays to identify compounds having CCK1R-modulating activity.

Abstract: The invention provides compositions and methods of identifying, modifying and producing modified target molecules, including therapeutic molecules by modification with non-natural amino acids. Certain aspects of the invention include methods of adding a chemical moiety to a target molecule, and the compositions resulting therefrom. Certain aspects of the invention also relate to kits for identifying, modifying and producing modified target molecules described herein.

Abstract: Disclosed are methods and compositions to genetically modify substantially intact cells having cosmetic function to enhance the cosmetic appearance in mammals so as to enhance and/or maintain a biochemical and/or physiological process that has a positive effect on cosmetic appearance. The methods and compositions may provide cosmetic benefits such as reduced skin sagging, increased skin thickness, reduced wrinkles, increased skin thickness and collagen content, increased skin tone and elasticity, increased skin hydration, and improved skin texture and color.

Abstract: Chimeric proteins constructed from the fusion of the naturally occurring form of the soluble IL-6 receptor and IL-6 which are useful for treatment of cancer and liver disorders, enhancement of bone marrow transplantation, and treatment of other IL-6 related conditions are provided.

Abstract: The present invention relates to mutants of human growth hormone, which contain newly introduced N-linked or O-linked glycosylation site(s), such that these recombinantly produced polypeptides have glycosylation patterns distinctly different from that of the naturally occurring human growth hormone. The polynucleotide coding sequences for the mutants, expression cassettes comprising the coding sequences, cells expressing the mutants, and methods for producing the mutants are also disclosed. Further disclosed are pharmaceutical compositions comprising the mutants and method for using the mutants.

Abstract: The present invention is directed to polynucleotides, peptides, variants, and uses thereof for a novel peptide fragment designated TML peptides. Binding of the peptide fragment has been shown in kidney and small intestine. The present invention further includes agonists, antagonists, variants, antibodies, host cells expressing the cDNA encoding the novel TML peptides and methods for increasing gastric motility and secretion of digestive proteins and hormones using the novel TML peptides.

Abstract: The present invention relates to a canine pre-proGHRH polypeptide, a canine mature GHRH peptide, an isolated polynucleotide which encodes the canine pre-proGHRH or the canine mature GHRH. The invention also encompasses vectors encoding and expressing the canine pre-proGHRH or the canine GHRH which can be used to treat disease and growth hormone deficiencies by gene therapy in vertebrates, in particular in dogs.

Abstract: The present invention relates to the field of obesity research. Obesity is a public health problem that is serious and widespread. A compound, globular OBG3, has been identified that reduces weight gain in animals. This compound should be effective for reducing body mass and for treating obesity-related diseases and disorders. These obesity-related diseases and disorders include hyperlipidemias, atherosclerosis, diabetes, and hypertension.

Abstract: The inventors have designed novel FSH mutants with increased glycosylation and longer half-lives for use in inducing folliculogenesis in human patients. The use of a FSH mutant preparation of the invention permits the use of lower cumulative doses of FSH to achieve the same or better clinical result.

Abstract: Methods for increasing and maintaining hematocrit in a mammal comprising administering a hyperglycosylated analog of erythropoietin are disclosed. An analog may be administered less frequently than an equivalent molar amount of recombinant human erythropoietin to obtain a comparable target hematocrit and treat anemia. Alternatively, a lower molar amount of a hyperglycosylated analog may be administered to obtain a comparable target hematocrit and treat anemia. Also disclosed are new hyperglycosylated erythopoietin analogs, methods of production of the analogs, and compositions comprising the analogs.

Abstract: The invention provides isolated nucleic acid and amino acid sequences of sensory cell specific G-protein coupled receptors, antibodies to such receptors, methods of detecting such nucleic acids and receptors, and methods of screening for modulators of sensory cell specific G-protein coupled receptors.

Abstract: The invention provides isolated nucleic acid and amino acid sequences of sensory cell specific G-protein coupled receptors, antibodies to such receptors, methods of detecting such nucleic acids and receptors, and methods of screening for modulators of sensory cell specific G-protein coupled receptors.

Abstract: Constructs and methods are provided for expressing peptides derived from eukaryotic organisms in plant plastids. Constructs have a promoter functional in a plant plastid, a DNA sequence encoding a peptide derived from an eukaryotic organism and a transcription termination region. Other elements include a selectable marker for selection of plant cells comprising a plastid expressing the marker and DNA regions of homology to the genome of the plastid and optionally a ribosome binding site joined to the promoter. By methods using such constructs high levels of eukaryotic peptides, such as mammalian proteins, are produced in a plant cell by growing plant cells under conditions whereby the DNA encoding sequences are expressed to produce eukaryotic peptide in said plastid.

Abstract: The invention pertains to polypeptide variants with increased heparin-binding ability. Increased heparin-binding ability is achieved by addition, insertion, and/or substitution of an amino acid sequence X1X2X3X4X5X6 (SEQ ID NO. 1 or NO.2). Polypeptide variants according to the invention are particularly suited for stimulation of chondrogenesis, osteogenesis, and wound healing. The invention also pertains to amino acid molecules that encode said polypeptide variants, host cells containing said nucleic acid molecules, and processes for producing the polypeptide variants.

Abstract: The present invention provides compositions and methods for modulating the secretion of transcriptionally regulated proteins from recombinant cells. More particularly, the present invention provides compositions and methods for accelerating the secretion dynamics of human insulin from recombinant cells using nonsense mediated mRNA decay of the preproinsulin mRNA transcript.

Abstract: Novel Saccharomyces Cerevisiae mutant strains are provided for producing human parathyroid hormone. The novel strains acre genetically disrupted in at least one of the genes encoding the yapsin family of proteases Yapsin 1, Yapsin 2 and Yapsin 3 and harbor a human parathyroid hormone gene in their genomes. Culturing the novel strains results in the secretion of intact hPTH into culture media at high yield.

Abstract: Novel parathyroid hormone (PTH) peptides and analogs thereof of the PTH(1–34) fragment are disclosed that combine the N-terminal signaling domain (residues 1–9) and the C-terminal binding domain (residues 15–31) via a linker. Nucleic acid molecules and peptides for PTH(1–9)-(Gly)5-PTH(15–31) (PG5) and PTH(1–9)-(Gly)7-PTH(15–31) and a novel PTH receptor are disclosed. Additionally, methods of screening for PTH agonists, pharmaceutical compositions and methods of treatment are disclosed.

Abstract: Use of a negative-sense RNA virus vector has enabled transfer of nucleic acid into nerve cells. The method of this invention can be used for introducing a gene efficiently into nerve cells including the central nerve tissue in gene therapy, etc.

Abstract: This invention relates to newly identified polynucleotides, polypeptides encoded by such polynucleotides, the use of such polynucleotides and polypeptides, as well as the production of such polynucleotides and polypeptides. More particularly, the polypeptide of the present invention is a Keratinocyte Growth Factor, sometimes hereinafter referred to as “KGF-2” also formerly known as Fibroblast Growth Factor 12 (FGF-12). This invention further relates to the therapeutic use of KGF-2 to promote or accelerate wound healing. This invention also relates to novel mutant forms of KGF-2 that show enhanced activity, increased stability, higher yield or better solubility.

Abstract: Disclosed is a chemically inducible promoter for transforming plants or plant cells with genes which are regulatable by adding the plants or cells to a medium containing an inducer or by removing them from such medium. The promoter is inducible by a glucocorticoid, estrogen or inducer not endogenous to plants. Such promoters may be used with any plant genes that can promote shoot regeneration and development to induce shoot formation in the presence of a glucocorticoid, estrogen or inducer. The promoter may be used with antibiotic or herbicide resistance genes or other genes which are regulatable by the presence or absence of a given inducer. Also presented are organisms or cells comprising a gene wherein the natural promoter of the gene is disrupted and the gene is placed under the control of a transgenic inducible promoter. These organisms and cells and their progeny are useful for screening for conditional gain of function and loss of function mutations.

Abstract: A novel neurotrophic factor referred to as glial cell line-derived neurotrophic factor (GDNF) has been identified and isolated from serum free growth conditioned medium of B49 glioblastoma cells. Rat and human genes encoding GDNF have been cloned and sequenced. A gene encoding GDNF has been subcloned into a vector, and the vector has been used to transform a host cell in order to produce biologically active GDNF in a recombinant DNA process.

Abstract: The invention relates to novel nucleic acids encoding a fibroblast growth factor-23(FGF23) and proteins encoded thereby, mutations in which are associated with autosomal dominant rickets (ADHR). The invention further relates to methods of diagnosing and treating hypophosphatemic and hyperphosphatemic disorders comprising inhibiting or stimulating, respectively, the biological activity of FGF23 in a patient. The invention also relates to methods of treating osteoporosis, dermatomyositis, and coronary artery disease comprising stimulating the biological activity of FGF23 in a patient.

Abstract: Erythropoietin analogs having at least one additional site for glycosylation, or a rearrangement of at least one site for glycosylation are disclosed. The invention also relates to DNA sequences encoding said erythropoietin analogs, and recombinant plasmids and host cells for analog expression.

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 in human cells, and a method for the large technical production of EPO in human cells.

Abstract: Nucleic acids encoding the neurotrophic protein known as pigment epithelium derived factor (PEDF), a truncated version of PEDF referred to as rPEDF, and equivalent proteins, vectors comprising such nucleic acids, host cells into which such vectors have been introduced, recombinant methods for producing PEDF, rPEDF, and equivalent proteins, the rPEDF protein and equivalent proteins of rPEDF and PEDF-BP, -BX and BA, and the PEDF protein produced by recombinant methods. Effects and uses of these variants on 1) neuronal differentiation (neurotrophic effect) 2) neuron survival (neuronotrophic effect) and 3) glial inhibition (gliastatic effect) are described.

Abstract: The present invention concerns a protein produced from an alternative splice form of the human Ghrelin gene, an obesity and/or diabetes related gene.

Abstract: A nucleic acid formulation for use in gene delivery comprising a nucleic acid and an anionic polymer is disclosed. Examples of the anionic polymer includes aniionic amino acid polymer or poly-amino acid (such as poly-L-glutamic acid, poly-D-glutamic acid, poly-L-aspartic acid, poly-D-aspartic acid), poly-acrylic acid, polynucleotides, poly galacturonic acid, and poly vinyl sulfate.

Abstract: Inadequate growth due to deficiencies in growth hormone (GR), growth hormone releasing hormone (GHRH), or genetic diseases can be ameliorated utilizing recombinant protein therapy with a novel GHRH analog having a sequence (SEQ ID NO:1). Also included is (1) a method of treating growth hormone-related deficiencies associated with the growth hormone pathway; (2) a method for treating growth hormone-related deficiencies associated with genetic disease; (3) a method to improve growth performance in an animal; (4) a method of treating an animal having a growth deficiency disease; (5) a method of increasing the efficiency of an animal used for food; and (6) a method to enhance growth in an animal.

Abstract: Novel parathyroid hormone peptide (PTH) and parathyroid hormone related peptide (PTHrP) or derivatives thereof which are biologically active are disclosed, as are pharmaceutical compositions containing such peptides, and synthetic and recombinant methods for producing such peptides. Also disclosed are methods for treating mammalian conditions characterized by decreases in bone mass using therapeutically effective pharmaceutical compositions containing such peptides. Also disclosed are methods for screening candidate compounds of the invention for antagonistic or agonistic effects on parathyroid hormone receptor action. Also disclosed are diagnostic and therapeutic methods of such compounds.

Abstract: It is shown here that hedgehog proteins possess novel activities beyond phenotype specification. Using cultures derived from the embryonic day 14.5 (E14.5) rat ventral mesencephalon, we show that hedgehog is also trophic for dopaminergic neurons. Interestingly, hedgehog not only promotes dopaminergic neuron survival, but also promotes the survival of midbrain GABA-immunoreactive (GABA-ir) neurons.

Abstract: A chromosome DNA which codes for human hepatocyte growth factor, a recombinant expression vector capable of expressing the DNA, a transformant transformed with the expression vector and a method of producing recombinant human hepatocyte growth factor. The DNA and polypeptide of the present invention are expected to serve well for hepatocyte cultivation reagents, liver regeneration promoters, various researches, clinical diagnostic reagents and therapeutic drugs for liver diseases.

Abstract: VEGF-D, a new member of the PDGF family of growth factors, which among other things stimulates endothelial cell proliferation and angiogenesis and increases vascular permeability, as well as nucleotide sequences encoding it, methods for producing it, antibodies and other antagonists to it, transfected or transformed host cells for expressing it, pharmaceutical compositions containing it, and uses thereof in medical and diagnostic applications.

Abstract: Proteins consisting of two PDGF-D polypeptide chains, polynucleotides encoding the polypeptides, and materials and methods for making the proteins are disclosed. Each of the polypeptide chains consists of, from amino terminus to carboxyl terminus, the following operably linked segments: P1-P2-h-CH2-CH3; P1-P2-CH2-CH3; h-CH2-CH3-P2-P1; or CH2-CH3-P2-P1. Within these polypeptide chains, P1 is a first polypeptide segment as shown in SEQ ID NO:2 or SEQ ID NO:4 from amino acid x to amino acid y, wherein x is an integer from 246 to 258, inclusive, and y is an integer from 365–370, inclusive; P2 is a second polypeptide segment consisting of from 4 to 20 amino acid residues; h is an immunoglobulin hinge region or portion thereof; and CH2 and CH3 are CH2 and CH3 domains of an immunoglobulin heavy chain, respectively. Within the protein, the two polypeptide chains are joined by one or more disulfide bonds, each of the chains is optionally glycosylated, and the protein binds to and activates cell-surface PDGF receptors.

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 VEGF variants having one or more amino acid mutations in the KDR and/or FLT-1 receptor binding domains in the native VEGF sequence and selective binding affinity for either the KDR receptor or the FLT-1 receptor. Methods of making the VEGF variants and methods of using the VEGF variants are also provided.

Abstract: The present invention provides a method of preparing epidermal growth factors in plants and transgenic plant seeds containing epidermal growth factors. The method provides an economical way to produce epidermal growth factors.

Abstract: The invention is directed toward a human glycoprotein hormone having at least one, two, three, four, or five basic amino acids in the ?-subunit at positions selected from the group consisting of positions 11, 13, 14, 16, 17, and 20. The inventions is also directed to a human glycoprotein where at least one of the amino acids at position 58, 63, and 69 of the ?-subunit of the human thyroid stimulating hormone are basic amino acids. The invention is further directed to a modified human glycoprotein hormone having increased activity over a wild-type human glycoprotein hormone, where the modified human glycoprotein comprises a basic amino acid substituted at a position corresponding to the same amino acid position in a non-human glycoprotein hormone having an increased activity over the wild-type human glycoprotein hormone.

Abstract: The present invention provides delivery vectors for transferring a nucleic acid sequence to a cell in vitro, ex vivo or in vivo. The delivery vector comprises a segment encoding a secretory signal peptide. In embodiments of the invention, the delivery vector is an adeno-associated virus (AAV) vector. In other embodiments, the secretory signal peptide is a fibronectin secretory signal peptide (including variations and modifications, thereof). The delivery vectors of the invention may further comprise a heterologous nucleic acid sequence encoding a polypeptide of interest for transfer to a target cell, where the polypeptide of interest is operably associated with the secretory signal. Also disclosed are methods of transferring a nucleic acid of interest to a cell using the delivery vectors of the invention.

Abstract: The present invention is directed to a novel method of detecting a function or activity of a polypeptide which is related to bone metabolism, in particular, differentiation (maturation) of osteoblast or morphological change (retraction), specifically relating to a polypeptide which comprises an amino acid sequence shown by SEQ ID NO: 2 or SEQ ID NO: 4, an amino acid sequence in which one or several amino acids are deleted, substituted or added in the amino acid sequence shown by SEQ ID NO: 2 or SEQ ID NO: 4, or a polypeptide encoded by a nucleic acid which is capable of hybridizing under stringent condition with a nucleic acid comprising a nucleotide sequence shown by SEQ ID NO: 1 or SEQ ID NO: 3, or a complement sequence thereof.

Abstract: The present invention relates to use of peptide to which G-protein coupled receptor protein recognizes as a ligand. Since the ligand polypeptide of the present invention has a stimulating action on oxytocin secretion, it is useful as a drug for ameliorating, preserving or treating various diseases related to oxytocin secretion such as uterine inertia, atonic hemorrhage, placental expulsion, subinvolution and the like.

Abstract: A novel growth factor, persephin, which belongs to the GDNF/neurturin family of growth factors, is disclosed. The human, mouse and rat amino acid sequences have been identified. Human, mouse and rat persephin genomic DNA sequences have been cloned and sequenced and the respective cDNA sequences identified. In addition, methods for treating degenerative conditions using persephin, methods for detecting persephin gene alterations and methods for detecting and monitoring patient levels of persephin are provided. Methods for identifying additional members of the persephin-neurturin-GDNF family of growth factors are also provided.

Abstract: Disclosed are a novel hedgehog protein, i.e., a Desert hedgehog protein of human origin including mature and precursor forms, a DNA encoding the protein, a monoclonal antibody recognizing the protein, a process for producing the protein, and a method for detecting the protein. The hedgehog protein is useful in establishment of hybridomas which produce antibodies recognizing the protein, and the monoclonal antibody is useful in detection and purification of the protein. The hedgehog protein, DNA, and monoclonal antibody of this invention have efficacy in elucidation of hereditary morphological abnormalities in humans to establish their treatments and diagnoses.

Abstract: The present invention provides novel expression vectors which permit tight regulation of gene expression in eucaryotic cells. More specifically, the invention provides DNA vectors comprising nucleotide sequences that are transcribed to form RNA molecules which are then replicated by a temperature-sensitive replicase to form additional RNA molecules. The RNA molecules produced by replication contain a nucleotide sequence which may be translated to produce a protein of interest or which encode one or more untranslated RNA molecules. Also provided are methods for producing heterologous proteins and untranslated RNA molecules. Further provided are methods for administering heterologous proteins and untranslated RNA molecules to individuals. In addition, pharmaceutical compositions are provided comprising the DNA and RNA molecules of the invention and a pharmaceutically acceptable carrier.

Abstract: Disclosed are novel multi-functional chimeric hematopoietic receptor agonist proteins, DNAs which encode the multi-functional chimeric hematopoietic receptor agonist proteins, methods of making the multi-functional chimeric hematopoietic receptor agonist proetiens and methods of using the multi-functional chimeric hematopoietic receptor agonist proteins.

Abstract: Polypeptide growth factors, methods of making them, polynucleotides encoding them, antibodies to them, and methods of using them are disclosed. The polypeptides comprise an amino acid segment that is at least 70% identical to residues 52-179 of SEQ ID NO:2 or residues 258-370 of SEQ ID NO:2. Multimers of the polypeptides are also disclosed. The polypeptides, multimeric proteins, and polynucleotides can be used in the study and regulation of cell and tissue development, as components of cell culture media, and as diagnostic agents.

Abstract: Novel isolated cDNA encoding the precursor of the novel gonadotropin-releasing hormones in four species of the fish lamprey is disclosed. The use of such cDNA's in studying the phylogenetic relationship of various species of fish and vertebrates overall; and the use of such cDNA's for controlling the gonadal development and spawning of fish, including inducing and inhibiting maturation, spawning and reproduction, is also described. Methods by which the novel peptides may be administered to fish to control their reproduction are also described.

Abstract: The invention relates to novel growth hormone activity (GHA) proteins and nucleic acids. The invention further relates to the use of the GHA proteins in the treatment of growth hormone related disorders.

Abstract: The present invention is directed to polynucleotides, polypeptides and peptide fragments thereof, and uses thereof for a novel cDNA sequence which has homology to motilin. Tissue distribution of the mRNA for the novel polypeptide is specific to the stomach, small intestine and pancreas. The present invention further includes agonists, antagonists, antibodies, host cells expressing the cDNA encoding the novel motilin homologs and methods for increasing gastric motility using the novel molecules.

Abstract: We have discovered that growth hormones from ternary complexes with their receptors in which site 1 on the hormone first binds to one molecule of receptor and then hormone site 2 then binds to another molecule of receptor, thereby producing a 1:2 complex. We believe this phenomenon is shared by other ligands having similar conformational structure. Assays based on this phenomenon are useful for identifying ligand agonists and antagonists. Sites 1 and 2 are structurally identified to facilitate generation of amino acid sequence variants of ternary complex-forming ligands. Novel variants of growth hormone, prolactin placental lactogen and other related ligands are provided. As a result of our studies with the ternary complex we have determined that selected antibodies to the receptor for these ligands are capable of acting as ligand agonists or antagonists. Novel growth hormones and novel uses for anti-growth hormone receptor antibodies are described.

Abstract: The invention provides an isolated and purified nucleic acid molecule encoding mammalian immunoglobulin A inducing protein (IGIP), and methods of using the IGIP nucleic acid molecule and IGIP.