Abstract: The invention provides a cDNA sequence of a new type II human hepatoma derived growth factor (HDGF2). The protein encoded by such sequence is a homology of type I HDGF. The present invention also relates to peptides encoded by the nucleotide sequences, to uses of these polynucleotide and the polypeptides, and methods for producing the polynucleotides and the polypeptides.

Abstract: Recombinant nucleotide sequences encoding mutated prolactin are described. Expression of the sequences result in mimics of a phosphorylated prolactin corresponding to a selected species. A particularly preferred mimic is mutated at serine 179 (corresponding to human PRL) where serine is substituted by an aspartate residue. This aspartate mutant is a very effective antagonist and shows no ability to stimulate Nb2 to cell proliferation.

Abstract: A mini-proinsulin, in which the amino acid Arg bridges the A and the B chain instead of the C chain, shows insulin activity and is suitable for the preparation of pharmaceuticals for the treatment of diabetes mellitus. It can furthermore be converted into an insulin derivative simply using trypsin, the B chain of which is lengthened by Arg. This can be converted into insulin using carboxypeptidase B. Advantageously, however, the mini-proinsulin can also be converted to insulin directly in a one-pot process.

Abstract: The present invention relates to pharmaceutical compositions and methods to improve expression of exogenous polypeptides into vertebrate cells in vivo, utilizing delivery of polynucleotides encoding such polypeptides. More particularly, the present invention provides the use of salts, in particular sodium and potassium salts of phosphate, in aqueous solution, and auxiliary agents, in particular detergents and surfactants, in pharmaceutical compositions and methods useful for direct polynucleotide-based polypeptide delivery into the cells of vertebrates.

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: A process for producing high amount of proteins or polypeptides in yeast is disclosed. The process makes use of the CIT1 yeast promoter or a functional part or variant thereof. Examples of polypeptides which are expressed in high yields are insulin or insulin analogues or GLP1.

Abstract: The invention relates to a polypeptide including (1) a receptor binding domain of a Pseudomonas exotoxin A, and (2) at least two copies of a peptide sequence.

Abstract: The present invention is directed to novel chimpanzee erythropoietin polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, and antibodies which bind to the polypeptides of the present invention.

Abstract: A novel human gene having a significant homology with a VEGF-C gene, a member of the VEGF family, has been isolated by the PCR method using primers designed based on the sequence of EST that is assumed to be homologous with the C-terminal region of the VEGF-C gene. Mouse and rat genes have been isolated based on the human gene isolated as above. A protein encoded by the above human gene has been isolated by introducing the gene into Escherichia coli and expressing it. The isolated protein and genes can be applied to, for example, gene therapy for the VEGF-D deficiency, wound healing, and promotion of collateral vessel formation. Furthermore, VEGF-D protein inhibitors can be used as a novel anticancer drug, etc.

Abstract: A method of screening a subject for increased likelihood of having a favorable response to estrogen replacement therapy comprises detecting the presence of the rare form of at least one estrogen receptor alpha polymorphism in the subject, the presence of the estrogen receptor alpha polymorphism indicating the subject is more likely to have a favorable response to estrogen replacement therapy (e.g., with respect to cardiovascular health, heart disease, and/or HDL levels).

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 is directed to a lentiviral vector system that can be used for episomal replication of a desired gene. The vector system contains a first vector containing a lentiviral gag gene encoding a lentiviral gag protein, a second vector containing an env gene encoding a functional envelope protein, and a lentiviral pol gene encoding a lentiviral pol protein. The pol protein is at least integrase, but that the integrase has been modified so that it is not capable of integration. This pol gene can be on the first or second vectors or on a third vector. The lentiviral gag and pol and the envelope protein are not on a single vector, and these vectors do not contain nucleotides to effectively package lentiviral RNA. The system also contains another vector having a nucleic acid sequence encoding a target molecule operably linked to a component of an episomal replicon and a lentiviral packaging sequence.

Abstract: The present invention relates to methods and compositions for the treatment of biological disorders regulatable by the controlled expression or inhibition of the described NHP.

Abstract: Disclosed is a human Fibroblast growth factor-14 polypeptide and DNA(RNA) encoding such polypeptide. Also provided is a procedure for producing such polypeptide by recombinant techniques. Also disclosed are methods for utilizing such polypeptide for promoting wound healing for example as a result of burns and ulcers, to prevent neuronal damage due to associated with stroke and promote neuronal growth, and to prevent skin aging and hair loss, to stimulate angiogenesis, mesodermal induction in early embryos and limb regeneration. Antagonists against such polypeptides and their use as a therapeutic to prevent abnormal cellular proliferation, hyper-vascular diseases and epithelial lens cell proliferation are also disclosed. Diagnostic methods for detecting mutations in the coding sequence and alterations in the concentration of the polypeptides in a sample derived from a host are also disclosed.

Abstract: The present invention relates to DNA molecules which encode antagonists of vertebrate growth hormones obtained by mutation of at least the amino acid corresponding to Glu-119 in bovine growth hormone. The DNA molecules may be used to express the antagonists, either in cell culture, or in the cells of the patient of interest. The antagonist so expressed may be used to inhibit GH activity in a subject.

Abstract: The invention provides methods for the systematic analysis of the structure and function of polypeptides by identifying active domains which influence the activity of the polypeptide with a target substance. Such active domains are determined by substituting selected amino acid segments of the polypeptide with an analogous polypeptide segment from an analog to the polypeptide. The analog has a different activity with the target substance as compared to the parent polypeptide. The activities of the segment-substituted polypeptides are compared to the same activity for the parent polypeptide for the target. A comparison of such activities provides an indication of the location of the active domain in the parent polypeptide. The invention also provides methods for identifying the active amino acid residues within the active domain of the parent polypeptide.

Abstract: The present invention relates to the use of a class of genes called oil body protein genes that have unique features. The discovery of these features allowed the invention of methods for the production of recombinant proteins wherein a protein of interest can be easily separated from other host cell components. The invention is further exemplified by methods for exploitation of the unique characteristics of the oil body proteins and oil body genes for expression of polypeptides of interest in many organisms, particularly plant seeds. Said polypeptides may include but are not limited to: seed storage proteins, enzymes, bioactive peptides, antibodies and the like. The invention can also be modified to recover recombinant polypeptides fused to oil body proteins from non-plant host cells. Additionally the invention provides a method of using recombinant proteins associated with seed oil bodies released during seed germination for expression of polypeptides that afford protection to seedlings from pathogens.

Abstract: The subject matters of this invention are the hormone-dependent forms of Rep 78 and Rep 68 proteins of the Adeno-associated virus (AAV), obtained by the fusion of their specific mutants with the hormone binding domain (HBD) of steroid hormone receptors, and the DNA sequences coding for them. The invention also refers to a method for the hormonal regulation of the activity of the fusion products Rep78/68-HBD, inserted into eucaryotic cells utilizing viral or non-viral systems, in order to direct the stable integration of DNA sequences in specific regions of the host human genome for therapeutic purposes. The fusion products Rep78/68-HBD are also utilized to generate viral hybrid vectors (i.e. adenovirus vectors AAV) and for generating recombinant vectors AAV.

Abstract: The present invention pertains to isolated DNA encoding avian interleukin-15 and to purified interleukin-15 polypeptides.

Abstract: Provided are methods of stimulating the growth of lymphatic endothelia using an Flt4 ligand.

Abstract: Disclosed are a DNA which encodes murine trehalase, a polypeptide expressed by the DNA, and a transgenic- and knockout- animals which have been genetically engineered with the DNA. The DNA comprises a part or the whole of the nucleotide sequence of SEQ ID NO:1.

Abstract: PDGF-D, a new member of the PDGF/VEGF family of growth factors, is described, as well as the nucleotide sequence encoding it, methods for producing it, antibodies and other antagonists to it, transfected and transformed host cells expressing it, pharmaceutical compositions containing it, and uses thereof in medical and diagnostic applications.

Abstract: The present invention relates to a vector for expression of a heterologous protein by a Gram negative bacteria, wherein the vector includes a nucleic acid such as DNA encoding the following: an origin of replication region; optionally and preferably a selection marker; a promoter; an initiation region such as translation initiation region and/or a ribosome binding site, at least one restriction site for insertion of heterologous nucleic acid, e.g. DNA, encoding the heterologous protein, and a transcription terminator. The inventive vector may contain DNA encoding the heterologous protein, e.g., pro-insulin such as pro-insulin with a His tag.

Abstract: A DNA fragment coding for a modified nuclear glucocorticoid receptor, particularly one mutated in the region coding for the ligand binding domain, so that receptor activity is more strongly inducible by a synthetic glucocorticoid ligand than by a natural glucocorticoid ligand, is disclosed. A recombination system inducible in mammals by means of a fusion protein produced between a recombinase and the binding domain of the ligand derived from the modified glucocorticoid receptor of which the activity is more strongly inducible by synthetic glucocorticoids than by natural glucocorticoids, is also disclosed.

Abstract: A DNA comprising a deoxynucleotide sequence coding for bovine growth hormone is described. A transfer vector and an expression vector containing this DNA and microorganisms transformed by these vectors are also described.

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: The Apa I restriction fragment of the human erythropoietin gene, for producing high titers of biologically active hormone from stably transfected cell lines.

Abstract: The present invention is directed to methods of using and compositions comprising amelogenin peptides capable of inducing chondrogenesis and osteogenesis when implanted in vivo, a chondrogenesis in cultures in vitro. Compositions and methods of enhancing bone and cartilage growth using these peptides are described.

Abstract: The invention provides a cDNA sequence of a new human growth differentiation factor (hGDF3-2). The protein encoded by such sequence is a splice variant of hGDF3. The present invention also relates to peptides encoded by the nucleotide sequences, to uses of these polynucleotides and polypeptides, and methods for producing the said polynucleotides and polypeptides.

Abstract: The present invention is based in part on the novel observation that two different types of nuclear receptors, retinoic acid receptors (RAR) and thyroid receptors (TR) dimerize with a RX receptor (RXR) to form a heterodimer which is capable of binding to retinoic acid response elements (RARE) or thyroid receptor response elements (TRE) at physiological conditions. In addition, the present invention discloses that RXR homodimers are capable of binding to RARE's. Based on this observation, the present invention provides novel dimeric proteins, methods of identifying agents capable of binding the dimers of the present invention, methods of identifying DNA sequences capable of being bound by the dimers and methods to identify RA metabolic enzymes and proteins which are required for the activation function of nuclear receptors.

Abstract: A mouse cDNA is illustrated by FIG. 3 (SEQ ID NO:1) which, when knocked out or prevented from expression, results in high growth. This mouse cDNA is highly homologous to genes of other species, such as human and cattle.

Abstract: The present invention relates to nucleic acid sequences encoding ciliary neurotrophic factor (CNTF) and to the proteins, peptides, and derivatives produced therefrom. In various embodiments of the invention, the nucleic acid sequences, proteins, and peptides of the invention may be used in the treatment of a variety of neurological diseases and disorders, including Alzheimer's disease. In a specific embodiment of the invention, CNTF may be used to support the growth of spinal cord neurons, thereby providing a method of treating spinal cord damage caused by trauma infarction, infection, nutritional deficiency or toxic agents. The present invention also relates to a novel method for producing substantilly pure CNTF. The invention also relates to pharmaceutical compositions comprising effective amounts of CNTF gene products which may be used in the diagnosis and treatment of a variety of neurologial diseases and disorders.

Abstract: An isolated cDNA encoding a growth-inducing protein, Frzb, capable of stimulating bone, cartilage, muscle and nerve tissue formation. The CDNA and protein sequences of human and bovine frzb are provided. Production and purification of recombinant Frzb are also described.

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 relates to flea peritrophin proteins; to flea peritrophin nucleic acid molecules, including those that encode such flea peritrophin proteins; to antibodies raised against such proteins; and to compounds that inhibit the activity of such proteins. The present invention also includes methods to obtain and use such proteins, nucleic acid molecules, antibodies, and inhibitory compounds. The present invention also includes therapeutic compositions comprising such inhibitory compounds, particularly those that specifically inhibit flea peritrophin activity, as well as the use of such therapeutic compositions to treat animals.

Abstract: Provided herein are methods and compositions relating to the attachment of water soluble polymers to proteins. Provided are novel methods for N-terminally modifying proteins or analogs thereof, and resultant compositions, including novel chemically modified G-CSF compositions and related methods of preparation.

Abstract: The present invention relates to a novel truncated forms of hepatocyte growth factor (HGF) which specifically antagonizes the activity of HGF and to a novel truncated form of HGF that is a partial HGF agonist. In particular, the present invention relates to the purification, molecular cloning, recombinant expression of the truncated HGF variants and related pharmaceutical compositions. The present invention further relates to the utilization of the small HGF variants to either inhibit HGF mitogenesis or stimulate HGF mitogenesis in cells expressing the receptor for HGF.

Abstract: The present invention relates to a method of treatment of patients by administration of human growth hormone. Also disclosed are DNA (or RNA) polynucleotide sequences that encode naturally occurring splice variants of human growth hormone, hGHV-2(88) and hGV-3(53), as well as analogs and derivatives thereof, which both lack nucleotide sequences normally present in the gene which codes for wild-type human growth hormone. The growth hormone variants of the present invention are of human origin and are useful for diagnostic, preventive and therapeutic purposes with respect to certain human diseases. Also disclosed is a method for producing the human growth hormone variants of the present invention by recombinant DNA techniques, as well as a method for generating antibodies directed against (and therefore inhibiting the activity of) wild-type growth hormone.

Abstract: A novel polypeptide, designated neurotrophic factor-4 (NT-4), has been identified by PCR amplification of human genomic DNA. Provided herein is nucleic acid encoding NT-4 useful in diagnostics and in the recombinant preparation of NT-4. Also provided herein are nucleic acids encoding naturally occurring amino acid sequence variants of NT-4, designated NT-4&bgr;, NT-4&ggr;, and NT-4&Dgr;. The neurotropic factors of the invention are useful in the treatment of nerve cells and in diagnostic assays.

Abstract: The present invention provides peptides which can interact with VEGF and inhibit VEGF interaction with KDR or anti-VEGF antibody thereby inhibiting VEGF mediated angiogenesis or angiogeneis related diseases, polynucleotide encoding the peptides, vectors containing the polynucleotides, pharmaceutical compositions containing the peptides, and methods of inhibiting angiogenesis with the peptides.

Abstract: Mammalian Interleukin-4 receptor proteins, DNAs and expression vectors encoding mammalian IL-4 receptors, and processes for producing mammalian IL-4 receptors as products of cell culture, are disclosed. A method for suppressing an IL-4-dependent immune or inflammatory response in a mammal, including a human, by administering an effective amount of soluble IL-4 receptor (sIL-4R) and a suitable diluent or carrier.

Abstract: Nucleic acids encoding a new family of chemokines, the CX3C family, from a mammal, reagents related thereto, including specific antibodies, and purified proteins are described. Methods of using said reagents and related diagnostic kits are also provided.

Abstract: The invention relates to methods for the isolation of metastatic sequences and the isolated sequences. Cells from a cell line or an animal tissue are treated to form a cell line predisposed to cancer. Treated cells are implanted in an animal and incubated for a period of time sufficient for the cells to proliferate and develop malignant transplants. RNA from the malignant transplant and the primary tumor are analyzed by differential display polymerase chain reaction. Differentially expressed genes are cloned, reanalyzed, and sequenced. These genes and sequences can be used as probes in the diagnosis of neoplastic disorders, as probes to isolate metastatic sequences and as a therapeutic agent in the treatment of neoplastic disorders. The metastatic sequence may be a dominant metastatic sequence or a recessive metastatic sequence.

Abstract: The invention relates to a precursor of human insulin or of an insulin analog of the formula I: Fus-B(1-30)-RDVP-Yn-A(1-21)  (I); wherein Fus is an optionally present fusion portion; B(1-30) is a B chain of human insulin, Y is an amino acid chain which terminates with a basic amino acid at the C terminus; n is from 2 to 50 and indicates the length of the amino acid chain Y; and A(1-21) is an A chain of human insulin, and the A chain and/or the B chain can be modified by amino acid substitution, deletions and/or additions. The present invention also provides DNA coding for the above precursors, preparation and use of the instant precursors and DNA, and a process for preparing human insulin or an insulin analog.

Abstract: The present invention relates to novel fusion proteins, DNA molecules encoding the same, vectors comprising the DNA molecules, and host cells containing the vectors for use in measuring protease activity using a novel transcriptional assay. This invention also relates to a method for determining the inhibitory activity of a compound against a protease and to a method for comparing the activity of two proteases which recognize the same cleavage site. Kits for assaying protease activity comprising DNA molecules encoding the fusion protein substrates of this invention are also contemplated.

Abstract: A purified preparation of a peptide consisting essentially of an amino acid sequence identical to that of a segment of a naturally-occurring human protein, said segment being of 10 to 30 residues in length, inclusive, wherein said peptide binds to a human major histocompatibility complex (MHC) class II allotype.

Abstract: This invention relates to a DNA comprising a nucleotide sequence encoding a fusion protein, wherein the fusion protein comprises: a sequence of signal peptide for Bacillus cell wall protein (CWP); a tag sequence for separation and purification of the fusion protein; a linker sequence; a sequence for chemical or enzymatic cleavage; and an exogenous polypeptide sequence, the sequences being linked in order, the signal peptide, tag and linker being optional sequences; and wherein the nucleotide sequence encoding a fusion protein is ligated to 3′-end of a nucleic acid sequence comprising a Bacillus promoter region; to a vector comprising the DNA; to a bacterium belonging to the genus Bacillus comprising the vector; and to a process for preparation of a useful polypeptide by culture of the bacterium.

Abstract: Nucleic acids encoding a new family of small cysteine rich soluble proteins, from a mammal, reagents related thereto, including specific antibodies, and purified proteins are described. Methods of using said reagents and related diagnostic kits are also provided.

Abstract: The present invention relates to polypeptides expressed and processed in yeast, a DNA construct comprising a DNA sequence encoding such polypeptides, vectors carrying such DNA fragments and yeast cells transformed with the vectors, as well as a process of producing heterologous proteins in yeast.

Abstract: The present invention is directed to DNA encoding human endothelial cell growth factors, and to plasmids comprising said DNA. In particular, the invention relates to DNA encoding a cleavable signal peptide and an endothelial cell growth factor, wherein removal of said signal peptide yields a mature form of the growth factor.