Abstract: Novel receptor polypeptides, polynucleotides encoding the polypeptides, and related compositions and methods are disclosed. The polypeptides comprise an extracellular domain of a cell-surface receptor that is expressed in kidneys, pancreas, prostate, adrenal cortex and nervous tissue. The polypeptides may be used within methods for detecting ligands that promote the proliferation and/or differentiation of these organs.

Abstract: The present invention relates to chimeric fatty body-pro-GRF analogs with increased biological potency, their application as anabolic agents and in the diagnosis and treatment of growth hormone deficiencies. The chimeric fatty body-pro-GRF analogs include an hydrophobic moiety (tail), and can be prepared, either by anchoring one or several hydrophobic tails to the GRF, or by substituting one or several amino-acids by a pseudomicellar residue in the chemical synthesis of GRF. The GRF analogs of the present invention are biodegradable, non-immunogenic and exhibit an improved anabolic potency with a reduced dosage and prolonged activity.

Abstract: A recombinant human IL-12 receptor complex produced on the surface of a non-human mammalian cell and free from other human proteins, the complex comprising the beta1 receptor protein complexed with a beta2 receptor protein, which complex is capable of binding to human IL-12 with high affinity. A recombinant human IL-12 beta2 receptor protein produced on the surface of a non-human mammalian cell, free from other human proteins, in its active form. In addition, a non-human mammalian cell having expressed on its surface the recombinant human IL-12 beta2 receptor protein or the recombinant human IL-12 receptor complex, which cell proliferates in the presence of human IL-12. A non-human mammalian cell having the human IL-12 beta2 receptor protein or the complex expressed on its surface and which proliferates in response to human IL-12 is useful for determining whether a given compound inhibits biological activity of human IL-12 or is an IL-12 agonist.

Abstract: This invention is a method for treating human erectile dysfunction using therapeutic amounts of human growth hormone (GH) administered systemically. Severing the parasympathetic nerves that regulate the erectile function during the course of surgery produces erectile dysfunction. Damage to these nerves by diseases such as diabetes mellitus and alcoholism and during aging may also produce erectile dysfunction. GH stimulates the regeneration of severed parasympathetic nerves that regulate the erectile function restoring potency. GH may act directly or by stimulating the production of insulin-like growth factor-I (IGF-I). The combination of GH plus an IGF (with or without one of the IGF binding proteins) may provide a better response than GH alone.

Abstract: The invention relates to a purified growth factor protein which is obtained from Spirometra mansonoides, and a pharmaceutical composition which includes the same. The protein has a molecular weight of 27,500 and an isoelectric point of 4.5. The amino acid sequence has been characterized as well as the DNA sequence which encodes it.

Abstract: Pharmaceutical compositions containing hGH stabilized by means of saccharose. The formulation is particularly suitable for stabilizing a lyophilisate of recombinant hGH.

Abstract: This invention relates to composite somatotropin peptides comprising somatotropin epitopic amino acid sequences, and fusion proteins thereof, useful in potentiating growth hormone activity. Also disclosed are vectors and host cells useful in the recombinant production of such molecules. Vaccines containing the composite somatotropin peptides and fusion proteins of the present invention, and methods of using the same, are disclosed.

Abstract: Substantially pure heparin-binding growth factor polypeptides (HBGFs), nucleic acids encoding the HBGFs and antibodies which bind to the HBGFs of the invention are provided. The HBGF polypeptides are useful in methods for the induction of bone, cartilage and tissue formation, growth and development of the endometrium and in the acceleration of wound healing. HBGF is related to Connective Tissue Growth Factor (CTGF).

Abstract: Mature Human Growth Hormone is prepared by enzymatic hydrolysis of a soluble precursor with immobilized Factor Xa. The soluble precursor contains a cleavage recognition sequence, Ile--Glu--Gly--Arg, for Factor Xa. The Factor Xa is preferably immobilized on CNBr activated Sepharose Cl-4B containing cyclic imido carbonate groups. Immobilization is carried out by reaction of amine groups on Factor X with the cyclic imido carbonate groups of the CNBr activated Sepharose Cl-4B to form covalently immobilized Factor X, which is then activated to Factor Xa with a protein contained in Russell's viper venom (RVV) in the presence of Ca.sup.++ ions.

Abstract: The present invention relates to methods and compositions for the treatment of body weight disorders, including, but not limited to, obesity. Specifically, the present invention identifies and describes genes which are differentially expressed in body weight disorder states, relative to their expression in normal, or non-body weight disorder states, and/or in response to manipulations relevant to appetite and/or weight regulation. Further, the present invention identifies and describes genes via the ability of their gene products to interact with gene products involved in body weight disorders and/or appetite and/or body weight regulation. Still further, the present invention provides methods for the identification and therapeutic use of compounds as treatments of body weight disorders. Additionally, the present invention describes methods for the diagnostic evaluation and prognosis of various body weight disorders, and for the identification of subjects exhibiting a predisposition to such conditions.

Abstract: The present invention relates to chimeric fatty body-pro-GRF analogs with increased biological potency, their application as anabolic agents and in the diagnosis and treatment of growth hormone deficiencies. The chimeric fatty body-pro-GRF analogs include an hydrophobic moiety (tail), and can be prepared, either by anchoring one or several hydrophobic tails to the GRF, or by substituting one or several amino-acids by a pseudomicellar residue in the chemical synthesis of GRF. The GRF analogs of the present invention are biodegradable, non-immunogenic and exhibit an improved anabolic potency with a reduced dosage and prolonged activity.

Abstract: The present invention relates to a compound having the formula:Ra--X--Rb Ior a pharmaceutically acceptable salt thereof,wherein,X is selected from the group consisting of ##STR1## Ra is a fluorophore selected from the group consisting of fluorescein, rhodamine, Texas red, any BODIPY.TM., CASCADE BLUE.TM., coumarin, phycoerithryn, eosin and rosamine; and Rb is a polypeptide moiety for binding to GRF receptors which allows for receptor physiological studies in vivo or in vitro and for distinguishing cell surface from intracellular receptor components. The present invention also relates to a method for the labeling of GRF receptors on cell surface.

Abstract: The present invention provides a stable and bioactive recombinant small-loop modified somatotropin which has its small-loop cysteines changed to other amino acids or deleted altogether and a method for producing such a small-loop modified somatotropin. Also provided by the present invention are DNA sequences coding for such small-loop modified somatotropins, plasmids containing such sequences, and organisms containing such plasmids. Furthermore, pharmaceutical compositions including small-loop modified somatotropins and methods for using such pharmaceutical compositions are disclosed.

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 invention provides for synthetic ligands that bind to class I receptor tyrosine kinases. The ligands are analogous in structure to naturally occurring ligands. The modified ligands however, have eliminated the mid-sequence (B) domain present in the native ligands and replaced it with a peptide bridge which links the amino (A) and carboxy (C) domains.

Abstract: A method for selecting novel proteins such as growth hormone and antibody fragment variants having altered binding properties for their respective receptor molecules is provided. The method comprises fusing a gene encoding a protein of interest to the carboxy terminal domain of the gene III coat protein of the filamentous phage M13. The gene fusion is mutated to form a library of structurally related fusion proteins that are expressed in low quantity on the surface of a phagemid particle. Biological selection and screening are employed to identify novel ligands useful as drug candidates. Disclosed are preferred phagemid expression vectors and selected human growth hormone variants.

Abstract: The present invention is directed to compositions comprising endothelial cell growth factor, an acceptable carrier and, optionally, an extracellular matrix protein, a glycosaminoglycan or serum albumin. The compositions are useful for wound repair.

Abstract: The invention provides an isolated cDNA sequence coding for murine interleukin 5 receptor, murine secretory interleukin 5 receptor, human interleukin 5 receptor, and human secretory interleukin 5 receptor and products including murine interleukin 5 receptor, murine secretory interleukin 5 receptor, and human interleukin 5 receptor which are produced using the isolated cDNA sequence. These products may be useful for a therapeutic agent for autoimmune disorders and diseases with eosinophilia in which human IL-5 is believed to be involved.

Abstract: Novel GRF PEPTIDES having Thr, Val or Ile at position 2, having an amino acid selected from the group consisting of Ala, Val, Leu, Ile or Gly at position 15, and optionally substituted with Val or Ile at position 19 are described. Compositions and the method of stimulating the release of growth hormone utilizing GRF PEPTIDES having Thr, Val or Ile at position 2 and having an amino acid selected from the group consisting of Ala, Val, Leu, Ile or Gly at position 15 are also described. The GRF PEPTIDES of the present invention have enhanced stability in plasma.

Abstract: Purified Bone Morphogenetic Protein-10 (BMP-10) proteins and processes for producing them are disclosed. DNA molecules encoding the BMP-10 proteins are also disclosed. The proteins may be used in the treatment of bone and cartilage defects and in wound healing and related tissue repair.

Abstract: Purified Bone Morphogenetic Protein-11(BMP-11) proteins and processes for producing them are disclosed. Recombinant DNA molecules encoding the BMP-11 proteins are also disclosed. The proteins may be useful in regulating follicle stimulating hormone, such as for contraception. In addition, the proteins may be useful for the induction of bone, cartilage and/or other connective tissue.

Abstract: An isolated polynucleotide of anti-dorsalizing morphogenetic protein (ADMP-1) is obtained from Xenopus. The protein is most closely related to human BMP-3. ADMP-1 functions as a modulator for dorsalizing influences, and prevents syndromes involving inappropriate proliferation of tissues.

Abstract: The invention relates to a neurite-promoting factor released by glial cells, to related proteins and fragments thereof retaining their neurite-promoting activity, to DNAs coding for the amino acid sequence of the neurite-promoting factor and fragments thereof, to hybrid vectors containing such DNAs, to hosts transformed with such a hybrid vector, to processes for the preparation of the DNAs, vectors and transformed hosts, to processes for the manufacture of the neurite-promoting factor, related proteins and its fragments, and to their use in the treatment of lesions in the nervous system.

Abstract: An isolated, synthetic preparation of a novel neutrophil-specific chemotactic factor (NCF), monoclonal antibodies having specific binding affinity for NCF and a clone containing the complete cDNA coding sequence for NCF are disclosed.

Abstract: An isolated protein having the amino terminal sequence of SEQ ID No. 1 and having a molecular weight of about 200 KDa is described. This animal brain-derived protein binds to OSF-1 (HBGF-8), which is a heparin-binding growth factor that has neuronal differentiation-enhancing activity, and a proliferative action on osteoblasts.

Abstract: Endothelial cell growth factor is achieved through the application of recombinant DNA technology to prepare cloning vehicles encoding the ECGF protein and procedures are disclosed for recovering ECGF protein essentially free of other proteins of human origin. The product is useful for, among other purposes, diagnostic applications and as potential in the treatment of damaged blood vessels or other endothelial cell-lined structures.

Abstract: GRF(1-44)-NH.sub.2 is prepared by the trypsin catalyzed enzymatic coupling of Leu-NH.sub.2 to GRF(1-43)-OH. The latter compound may be obtained by recombinant DNA synthesis. Thus the present method provides an economical pathway to the clinically important GRF(1-44)-NH.sub.2 compound.

Abstract: Bovine .beta.-endothelial cell growth factor (.beta.-ECGF) having an apparent molecular weight of 20,000 daltons can be purified at least 16,300 fold from bovine brain using heparin-Sepharose affinity chromatography. ECGF is useful for, among other purposes, diagnostic applications and has potential in the treatment of damaged blood vessels or other endothelial cell-lined structures.

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.

Abstract: Autocrine growth factors and isoforms of those factors have been identified, isolated, purified and manipulated. Nucleic acid segments coding for the factors, and antibodies directed to the factors are also aspects of the present invention. The effect of these growth factors on cells is to enhance their growth by increasing mitogenesis. In particular, the growth factors stimulate kidney epithelial cell growth. The growth factors differ from others previously reported in their molecular weights and other properties, for example, resistance to denaturation by dithiothreitol. Methods of preparation and use of the factors are also described. The growth factors are released from kidney epithelial cells by short exposures to a low-sodium environment. The factors have potential for treatment of kidney disease.

Abstract: A heterodimeric form of TGF-.beta. is described. This 25 KD molecule is active in an in vitro assay of inhibition of epithelial cell growth. The protein may be isolated from bone. When reduced, the protein elutes in two peaks by RP-HPLC. In immunoblots, the reduced protein from the earlier eluting peak reacts predominately with antibodies directed against TGF-.beta.3, while reduced protein from the later eluting peak reacts predominately with antibodies directed against TGF-.beta.2. The N-terminal amino acid sequence and immunoreactivity of the native protein are consistent with a heterodimer of TGF-.beta.2 and TGF-.beta.3.

Abstract: The invention describes antagonists for PDGF. The antagonists contain amino acids, and may be monomers or dimers. Especially preferred are dimers which bind the PDGF receptors, but prevent dimerization of the bound receptors. Dimerization is necessary for PDGF effect, hence the antagonistic effect. Also described are nucleic acid sequences for making the antagonists, as well as cell lines transfected with the material.

Abstract: The invention relates to peptides corresponding to regions of the amino acid sequence of TGF-.beta.1 or TGF-.beta.2 which retain, either in monomeric or polymeric forms, at least some of the biological activity of the respective full length TGF-.beta.. The monomeric form of the peptide derived from TGF-.beta.1 comprises the following amino acid sequence: CVRQLYIDFRKDLGWKWIHEPKGYHANFCLGP (SEQ ID NO: 1). The monomeric form of the peptide derived from TGF-.beta.2 comprises the following amino acid sequence: CLRPLYIDFKRDLGWKWIHEPKGYNANFCAGA (SEQ ID NO: 2). Dimers may be formed via disulfide bonds between the amino-terminal cysteine residues, the carboxy-terminal cysteine residues, or amino- and carboxy-terminal cysteine residues of the monomer subunits.

Abstract: A novel chemotactic and mitogenic protein, Connective Tissue Growth Factor (CTGF), a polynucleotide that encodes CTGF and antibodies that bind to CTGF are provided. Diagnostic and therapeutic methods using CTGF are also described.

Abstract: A combined formulation for IGF-I and growth hormone (GH) is useful for enhancing growth of a mammal. This formulation, which may be administered by infusion or injection to enhance growth, comprises IGF-I and GH, each in amounts of 0.1 to 100 mg/ml, in a pharmaceutically acceptable carrier at a pH of about 5-6 containing a surfactant, wherein the amounts of IGF-I and GH in the composition are effective to promote growth of a mammal more than an equivalent dose of IGF-I or GH alone, and wherein the weight ratio of IGF-I to GH in the composition ranges from 0.002:1 to 240:1.

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: The present invention relates to somatotropin analogues with amino acid changes in the .alpha.-helix 3 regions of said somatotropins, changes in the .alpha.-helix 2 regions, combinations thereof plus combinations with other changes to the native amino acid sequence of somatotropins. The resulting analogues are stable for formulation in sustained release, formulations, while maintaining biological activity. Further, methods for conducting site-directed mutagenesis on DNA encoding proteins and/or polypeptides also are provided.

Abstract: The present invention relates to the production of large quantities of a novel chimeric TGF-.beta., termed TGF-.beta.1/.beta.2, by eucaryotic host cells transfected with recombinant DNA vectors containing the TGF-.beta.1/.beta.2 precursor coding sequence controlled by expression regulatory elements. Simian TGF-.beta.1 cDNA (Sharples et al., 1987, DNA 6:239-244) was modified so that the nucleotides encoding amino acid residue numbers 9-13, 17, 19, 25 and 26 of the mature TGF-.beta.1 sequence were hanged to the nucleotides encoding the corresponding amino acids of the mature TGF-.beta.2 structure. Simian codon usage was maintained. The chimeric TGF-.beta.1/.beta.2 of the invention induces effects on the proliferation of vascular endothelial cells equivalent to those induced by TGF-.beta.1.

Abstract: Human epidermal growth factor is provided in an ultrapure form characterized by the absence of protein contaminants detectable by capillary electrophoresis analysis. A method for obtaining such ultrapure human epidermal growth factor includes fractionation of a human epidermal growth factor preparation by reversed phase high performance liquid chromatography in the presence of a cationic ion-pairing agent.

Abstract: Antagonists to basic fibroblast growth factor, a 146 amino acid residue polypeptide, are produced. These antagonists are generally between 10 and 45 residues in length and are characterized by their ability to interact with the FGF receptor and/or inhibit and therefore modulate endothelial and other cell growth in vitro and also in vivo. These antagonists includes the sequence of bovine basic FGF(106-115), namely Tyr-Arg-Ser-Arg-Lys-Tyr-Ser-Ser-Trp-Tyr or a sequence having equivalent residues substituted therein. These peptides are also antagonistic to acidic FGF and other members of the family of FGF peptides. They are effective to combat FGF-promoted mitosis in melanomas and the like.

Abstract: Disclosed are a growth-inhibitory factor which is a pure protein extracted from human brain and having inhibitory action against neurotrophic activity and a cDNA coding for a protein existing in human brain and the lysate from E. coli transfected with the cDNA having growth-inhibitory action, and also a method of inducing growth-inhibiting activity for treatment of Alzheimer disease by using the protein.

Abstract: The present invention deals with LHRH antagonists which possess improved water solubility and while having the high antagonist potency of the basic peptides, are free of the edematogenic effects. These compounds are highly potent in inhibiting the release of gonadotropins from the pituitary gland in mammals, including humans.The compounds of this invention are represented by the formulaX--R.sup.1 --R.sup.2 --R.sup.3 --Ser--Tyr--R.sup.6 --Leu--Arg--Pro--R.sup.10 --NH.sub.2whereinX is an acyl group derived from straight or branched chain aliphatic or alicyclic carboxylic acids having from 1 to 7 carbon atoms, or H.sub.2 N--CO,R.sup.1 is D-- or L--Pro, D-- or L--.DELTA..sup.3 --Pro, D--Phe, D--Phe(4--H1), D--Ser, D--Thr, D--Ala, D--Nal(1) or D--Nal (2),R.sup.2 is D--Phe or D--Phe(4--C1)R.sup.3 is D--Trp, D--Phe, D--Pal(3), D--Nal(1) or D--Nal(2),R.sup.6 is D--Cit, D--Hci, D--Cit(Q) or D--Hci(Q) andR.sup.

Abstract: A recombinant natural killer cell activating factor is disclosed, preferably having a peptide of the following amino acid sequence in its molecule. The invention provides a cDNA coding for a recombinant natural killer cell activating factor, a expression plasmid involving the cDNA, a host transformed with the plasmid, an antitumor agent containing the recombinant natural killer cell activating factor and a pharmaceutical composition which comprises a pharmacologically effective amount of the antitumor agent and a pharmacologically acceptable carrier.

Abstract: Peptide analogues of insulin-like growth factor 1 and growth factor 2 are disclosed. When the analogue is an analogue of growth factor 1 the glutamic acid residue is absent from position 3 of the N-terminal and either the glutamic acid residue or the threonine residue adjacent to glutamic acid residue at position 3 is replaced by a different amino acid residue. When the peptide analogue is an analogue of insulin growth factor 2 the glutamic acid residue position 5 is absent. Preferred peptide analogues are disclosed. Methods of use in pharmaceutical and veterinary preparations are described.

Abstract: The present invention provides both agonist and antagonist nerve growth factor peptides. The NGF blocking peptides can be used to inhibit the expression of mRNA and their encoded proteins whose expression is stimulated by NGF, such as .beta.-protein precursor and prion proteins, which proteins or their products are associated with neurodegenerative disorders, whereas the NGF agonist peptides can be used to treat neoplastic disorders such as neuroblastomas.

Abstract: The present invention relates to peptides having adenylate cyclase stimulating activity. The peptides all have at least the sequence His-Ser-Asp-Gly-Ile-Phe-Thr-Asp-Ser-Tyr-Ser-Arg-Tyr- Arg-Lys-Gln-Met-Ala-Val-Lys-Lys-Tyr-Leu-Ala-Ala-Val-Leu-.

Abstract: This invention provides novel growth hormone-releasing peptides and a method for increasing the release and raising the levels of growth hormone in mammals. The invention also provides a method for increasing the growth rate of meat producing animals, treating the symptoms of growth hormone deficiencies in mammals and improving the efficiency of feed utilization by meat producing and dairy animals.

Abstract: A composition for the promotion of cell proliferation and tissue repair in animals having as active ingredients a TGF-.beta. which is activated by either a TGF-.alpha. or an EGF or both; and methods for administration. As another embodiment these active ingredients can be admixed with other (secondary) growth factors.

Abstract: A process for treating a wound in a host which comprises administering to the host having a wound at least one biologically active amphiphilic peptide. The peptide is an ion channel-forming peptide and is administered in an amount effective for treating a wound in a host.