Abstract: The present invention relates to compounds with an extended duration of action at the glucagon receptor as compared to native glucagon. Specifically provided are glucagon receptor agonists with modifications to the structure of native glucagon introduced to selectively agonize the glucagon receptor over an extended period of time.

Abstract: Methods for detecting or capturing low-avidity autoantibodies in a biological sample are provided. Target antigen used to assay for the low-avidity autoantibodies of interest is immobilized on a solid phase. The biological sample is contacted under low conductivity condition with the target antigen for which the autoantibodies has specific binding affinity. Binding of the target antigen to the autoantibodies of interest in the biological sample is then detected to ascertain the presence or concentration of the autoantibodies of interest.

Abstract: The present invention relates to gastrin derivatives comprising gastrin or an analogue or fragment thereof and a derivatisation group and therapeutic use thereof.

Abstract: This invention pertains to the discovery that pentagastrin, when administered in conjunction with a proton pump inhibitor (PPI) is synergistic with the PPI and significantly increases the efficacy of the PPI in reducing/mitigating excess gastric acid secretion.

Abstract: A novel group of gastrokines called Gastric Antrum Mucosal Protein is characterized. A member of the group is designated AMP-18. AMP-18 genomic DNA, cDNA and the AMP-18 protein are sequenced for human, mouse and pig. The AMP-18 protein and active peptides derived from it are cellular growth factors. Surprisingly, peptides capable of inhibiting the effects of the complete protein, are also derived from the AMP-18 protein. Cytoprotection and control of mammalian gastro-intestinal tissue growth and repair (restitution) is facilitated by the use of the proteins, making the proteins candidates for therapies in inflammatory bowel disease, mucositis, and gastric ulcers.

Abstract: This invention relates to novel compositions comprising analogs of naturally occurring polypeptides, wherein the analog comprises an a-amino acid and at least one ?-amino acid. Administration of the compositions may be used for effecting treatment or prevention of a plurality of disease states caused by dysfunctional biochemical or biological pathways. The compositions and methods of this invention are particularly useful to identify novel therapeutic modulators of in-vivo receptor activity with extended half-lives and relevant bioactivity as compared to the naturally translated polypeptides upon which the analogs are derived.

Abstract: The present invention relates to gastrin derivatives comprising gastrin or an analogue or fragment thereof and a derivatisation group and therapeutic use thereof.

Abstract: Provided herein are monomers incorporating folate or other targeting agent, polymers prepared therefrom, polymers prepared therefrom having a therapeutic agent covalently coupled thereto, as well as micelles and therapeutic compositions thereof.

Abstract: Stabilized radiopharmaceutical formulations are disclosed. Methods of making and using stabilized radiopharmaceutical formulations are also disclosed. The invention relates to stabilizers that improve the radiostability of radiotherapeutic and radiodiagnostic compounds and formulations containing them. In particular, it relates to stabilizers useful in the preparation and stabilization of targeted radiodiagnostic and radiotherapeutic compounds, and, in a preferred embodiment, to the preparation and stabilization of radiodiagnostic and radiotherapeutic compounds that are targeted to the Gastrin Releasing Peptide Receptor (GRP-Receptor).

Abstract: An intracellular selection system allows screening for peptide bioactivity and stability. Randomized recombinant peptides are screened for bioactivity in a tightly regulated expression system, preferably derived from the wild-type lac operon. Bioactive peptides thus identified are inherently protease- and peptidase-resistant. Also provided are bioactive peptides stabilized by a stabilizing group at the N-terminus, the C-terminus, or both. The stabilizing group can be a small stable protein, such as the Rop protein, glutathione sulfotransferase, thioredoxin, maltose binding protein, or glutathione reductase, an ?-helical moiety, or one or more proline residues.

Abstract: The invention provides a method for introducing 1,4,7,10-tetraazacyclododecane-N,N?,N?,N??-tetraacetic acid (DOTA) into a compound such as a peptide. The method comprises a first step for preparing a mixed liquid of DOTA having no protecting group and dimethylsulfoxide, and a second step for contacting the mixed liquid with the compound carried on a solid-phase carrier.

Abstract: A method for treating a Parkinson's patient with digestive/pancreatic enzymes involves administering an effective amount of digestive/pancreatic enzymes to an individual having the disorder in order to improve a symptom of the disorder. In addition, a method is provided for determining whether an individual has, or may develop, Parkinson's disease or related dysautonomic disorders and for determining whether an individual will benefit from the administration of pancreatic/digestive enzymes to treat the dysautonomic disorder.

Abstract: Non-aggregating resorbable calcium phosphosilicate nanoparticles (CPNPs) are bioconjugated to targeting molecules that are specific for particular cells. The CPNPs are stable particles at normal physiological pH. Chemotherapy and imaging agents may be integrally formed with the CPNPs so that they are compartmentalized within the CPNPs. In this manner, the agents are protected from interaction with the environment at normal physiological pH. However, once the CPNPs have been taken up, at intracellular pH, the CPNPs dissolve releasing the agent. Thus, chemotherapeutic or imaging agents are delivered to specific cells and permit the treatment and/or imaging of those cells. Use of the bioconjugated CPNPs both limits the amount of systemic exposure to the agent and delivers a higher concentration of the agent to the cell. The methods and principals of bioconjugating CPNPs are taught by examples of bioconjugation of targeting molecules for breast cancer, pancreatic cancer, and leukemia.

Abstract: The invention is based on the finding that the secretin receptor is expressed in tissues present in the distal lung of humans. In patient with CF, levels of the receptor are elevated compared to the normal tissue. Treatment of tissue by secretin stimulates the movement of negative ions in the tissue. The invention provide method of treating cystic fibrosis or COPD in a patient by administering to said patient an effective amount of an agent which triggers anion efflux in respiratory tissue via the activation of the secretin receptor.

Abstract: The present invention concerns six novel variants of alternative splicing of the CD40 receptor The invention provides a pharmaceutical composition comprising a gastrin compound having an extended activity upon administration to a subject in comparison with native gastrin. Methods are provided of conjugating portions of the amino acid sequence of gastrin having functional ability to bind to the gastrin/CCK receptor, to various carrier moieties, including the use of amino acid spacer regions, and use of bifunctional cross-linking reagents. Methods of treating a diabetes patient with the compositions are provided.

Abstract: The invention concerns the use of a bombesin/gastrin releasing peptide antagonist in the treatment of inflammatory and immune-mediated inflammatory conditions, in particular sepsis, acute lung injury and rheumatoid arthritis as well as for the treatment or prophylaxis of brain disorders, preferably bipolar disorder, and in particular the different forms and/or subforms of bipolar disorder, such as mania, acute mania, severe mania, hypomania, depression, moderate depression, dysthymia, severe depression, episodes of mania and/or depression, psychosis/psychotic symptoms (e.g. hallucinations, delusions), mixed bipolar state, bipolar I disorder, bipolar II disorder and/or rapid-cycling bipolar disorder. In particular, specific nonapeptides with antagonist properties against bombesin or bombesin-like peptides, such as the gastrin releasing peptide, may be used in the treatment of inflammatory and immune-mediated inflammatory conditions as well as brain disorders.

Abstract: The present invention is directed to the use of the peptide compound Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 as a therapeutic agent for the prophylaxis and/or treatment of cancer, autoimmune diseases, fibrotic diseases, inflammatory diseases, neurodegenerative diseases, infectious diseases, lung diseases, heart and vascular diseases and metabolic diseases. Moreover the present invention relates to pharmaceutical compositions preferably in form of a lyophilisate or liquid buffer solution or artificial mother milk formulation or mother milk substitute containing the peptide Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 optionally together with at least one pharmaceutically acceptable carrier, cryoprotectant, lyoprotectant, excipient and/or diluent.

Abstract: Compositions and methods for islet neogenesis therapy comprising an EGF and a gastrin in combination with immune suppression, and for treating or preventing early stage diabetes with a gastrin/CCK receptor ligand and an immunosuppressant are provided.

Abstract: The present invention concerns six novel variants of alternative splicing of the CD40 receptor.

Abstract: An intracellular selection system allows screening for peptide bioactivity and stability. Randomized recombinant peptides are screened for bioactivity in a tightly regulated expression system, preferably derived from the wild-type lac operon. Bioactive peptides thus identified are inherently protease- and peptidase-resistant. Also provided are bioactive peptides stabilized by a stabilizing group at the N-terminus, the C-terminus, or both. The stabilizing group can be a small stable protein, such as the Rop protein, glutathione sulfotransferase, thioredoxin, maltose binding protein, or glutathione reductase, an ?-helical moiety, or one or more proline residues.

Abstract: Methods for aiding in the diagnosis of dysautonomic disorders and dysautonomic conditions and methods for treating individuals diagnosed as having a dysautonomic disorder or a dysautonomic condition. In one aspect, a diagnosis method comprising analyzing a stool sample of an individual for the presence of a biological marker wherein the quantity of the biological marker is an indication of whether the individual has, or can develop, a dysautonomic disorder or dysautonomic condition, as well as a therapeutic method for treating a dysautonomic disorder or dysautonomic condition by administration of, e.g., secretin, neuropeptides, peptides and/or digestive enzymes.

Abstract: A tumor antigen gene is identified by screening a cDNA library derived from a gastric cancer cell line that can induce gastric cancer antigen specific cytotoxic T cell (CTL) by means of hybridization and PCR utilizing an amino acid sequence of peptide fragment of a known gastric cancer antigen protein, introducing a selected cDNA clone into a cell of gastric cancer cell line that cannot induce gastric cancer antigen specific CTL so that the clone should be expressed in the cell, and selecting a transgenic cell that has acquired the ability to induce CTL. According to the present invention, there are provided a protein capable of inducing immune response against human gastric cancer, DNA encoding the protein, as well as vaccine for treatment and prevention of human gastric cancer, and agent for treatment and prevention of human gastric cancer.

Abstract: Compositions and methods are provided for achieving in vivo islet cell regeneration in subjects with preexisting diabetes. The methods comprise short term treatment with a composition having a gastrin/cholecystokinin receptor ligand and an EGF receptor ligand. Treatment with such a composition for a short term resulted in a prolonged period of increased insulin release, decreased fasting blood glucose, and improved glucose tolerance, the prolonged efficacy, the period being considered from the time of cessation of treatment.

Abstract: A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

Abstract: The sequences of 5′ ESTs derived from mRNAs encoding secreted proteins are disclosed. The 5′ ESTs may be to obtain cDNAs and genomic DNAs corresponding to the 5′ ESTs. The 5′ ESTs may also be used in diagnostic, forensic, gene therapy, and chromosome mapping procedures. Upstream regulatory sequences may also be obtained using the 5′ ESTs. The 5′ ESTs may also be used to design expression vectors and secretion vectors.

Abstract: Methods for aiding in the diagnosis of dysautonomic disorders and dysautonomic conditions and methods for treating individuals diagnosed as having a dysautonomic disorder or a dysautonomic condition. In one aspect, a diagnosis method comprising analyzing a stool sample of an individual for the presence of a biological marker wherein the quantity of the biological marker is an indication of whether the invidual has, or can develop, a dysuatonic disorder or dysautonomic condition, as well as a therapuetic method for treating a dysautonomic disorder or dysautonomic condition by administration of, e.g., secretin, neuropeptides, peptides and/or digestive enzymes.

Abstract: An intracellular selection system allows screening for peptide bioactivity and stability. Randomized recombinant peptides are screened for bioactivity in a tightly regulated expression system, preferably derived from the wild-type lac operon. Bioactive peptides thus identified are inherently protease- and peptidase-resistant. Also provided are bioactive peptides stabilized by a stabilizing group at the N-terminus, the C-terminus, or both. The stabilizing group can be a small stable protein, such as the Rop protein, glutathione sulfotransferase, thioredoxin, maltose binding protein, or glutathione reductase, an &agr;-helical moiety, or one or more proline residues.

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: Methods and compositions for treating diabetes mellitus in a patient in need thereof are provided. The methods include administering to a patient a composition providing a gastrin/CCK receptor ligand, e.g., a gastrin, and/or an epidermal growth factor (EGF) receptor ligand, e.g., TGF-&agr;, in an amount sufficient to effect differentiation of pancreatic islet precursor cells to mature insulin-secreting cells. The composition can be administered systemically or expressed in situ by cells transgenically supplemented with one or both of a gastrin/CCK receptor ligand gene, e.g., a preprogastrin peptide precursor gene and an EGF receptor ligand gene, e.g., a TGF-&agr; gene. The methods also include transplanting into a patient cultured pancreatic islets in which mature insulin-secreting beta cells are proliferated by exposure to a gastrin/CCK receptor ligand and an EGF receptor ligand.

Abstract: The invention relates to the use of peptides individually or in combination, for treating and/or preventing angiogenesis. It also relates to the use of peptide analogs or a combination of peptides referred to as MuJ-7 as anticancer drugs in restricting the tumor growth and spread by inhibiting tumor angiogenesis. MuJ-7, in addition inhibits metastasis through its antiangiogenic activity in all cancers. The invention also relates to a pharmaceutical composition containing either individual peptides or in combination, and methods of treatment of human beings and animals for curing and/or preventing angiogenesis.

Abstract: The present invention is directed to polynucleotides, polypeptides 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 and host cells expressing the cDNA encoding the novel motilin homologs.

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: A method for treating diabetes mellitus by administering composition providing a gastrin/CCK receptor ligand, e.g. a gastrin, and an EGF receptor ligand, e.g. TGF&agr;, in an amount sufficient to effect differentiation of pancreatic islet precursor cells to mature insulin-secreting cells. The composition can be administered systemically or expressed in situ by cells transgenically supplemented with one or both of a gastrin/CCK receptor ligand gene, e.g. a preprogastrin peptide precursor gene and an EGF receptor ligand gene, e.g. a TGF&agr; gene.

Abstract: A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

Abstract: A pharmaceutical composition useful for killing or inhibiting multiplication of cancer cells. It is expected that the pharmaceutical composition will be useful in preventing, inhibiting, or modulating the hypersecretion of VIP, somatostatin, bombesin, Substance P, or a combination of VIP, somatostatin, bombesin, or Substance P. The composition may suitably comprise, consist of, or consist essentially of a therapeutically effective combination of peptide analogs of somatostatin, VIP, bombesin, and Substance P. Also provided is a method of treatment for humans or other animals suffering from cancer, the method comprising administering a therapeutically effective dose of the pharmaceutical composition so as to kill or inhibit the multiplication of cancer cells. The method of treatment may be particularly useful in the treatment of cancers of the colon and rectum.

Abstract: A method for treating diabetes mellitus by administering composition providing a gastrin/CCK receptor ligand, e.g. a gastrin, and an EGF receptor ligand, e.g. TGF.alpha., in an amount sufficient to effect differentiation of pancreatic islet precursor cells to mature insulin-secreting cells. The composition can be administered systemically or expressed in situ by cells transgenically supplemented with one or both of a gastrin/CCK receptor ligand gene, e.g. a preprogastrin peptide precursor gene and an EGF receptor ligand gene, e.g. a TGF.alpha. gene.

Abstract: The present invention relates to a composition comprising exogenous human or animal IGF-I or IGF-II or both or effective analogs thereof comprising foodstuff for oral administration wherein the foodstuff is selected from the group consisting of artificial milk, natural milk and colostrum.

Abstract: A method of lowering the pulmonary blood pressure of a subject suffering from pulmonary hypertension. The method includes administering to the subject an effective amount of a bombesin antagonist.

Abstract: Immunogenic compositions useful for the treatment or prevention of gastric or duodenal ulcer disease are disclosed. The immunogenic compositions effectively operate by inducing antibodies in a subject which selectively neutralize specific peptide gastric hormones and inhibit the binding of the hormones to physiological receptors thus limiting the secretion of stomach acid. Pharmaceutical compositions comprising effective amounts of the immunogenic compositions and methods of treatment using the compositions are also disclosed.

Abstract: Immunogenic compositions useful for the treatment of ulcers or tumors whose growth is dependent on or stimulated by gastrin hormones are disclosed. The immunogenic compositions induce antibodies in a subject which selectively neutralize the specific hormones. Pharmaceutical compositions comprising effective amounts of the immunogenic compositions and methods of treatment using the compositions are disclosed. A method of reversing the inventive treatments by neutralizing the antibodies induced in vivo is also disclosed.

Abstract: This invention relates to improved methods and novel compositions for enzyme complementation assays for qualitative and quantitative determination of a suspected analyte in a sample. The use of enzyme-acceptor and enzyme-donor polypeptides prepared by recombinant DNA techniques, DNA synthesis or chemical polypeptide synthesis techniques which are capable of interacting to form an active enzyme complex having catalytic activity characteristic of .beta.-galactosidase is described. Both homogeneous and heterogeneous assays utilizing these polypeptides are described.

Abstract: Peptide derivatives containing one or more substituents separately linked by an amide, amino or sulfonamide bond to an amino group on either the N-terminal end or side chain of a biologically active peptide moiety. The peptide derivatives have relatively enhanced biological activity when compared to the corresponding peptide alone.

Abstract: Methods of preparing a peptide having a C-terminal amide group from peptides having a C-terminal carboxyl group are provided.

Abstract: A stabilized conjugated peptide complex comprising a peptide conjugatively coupled to a polymer including lipophilic and hydrophilic moieties, wherein the peptide may for example be selected from the group consisting of insulin, calcitonin, ACTH, glucagon, somatostatin, somatotropin, somatomedin, parathyroid hormone, erythropoietin, hypothalamic releasing factors, prolactin, thyroid stimulating hormones, endorphins, enkephalins, vasopressin, non-naturally occurring opioids, superoxide dismutase, interferon, asparaginase, arginase, arginine deaminease, adenosine deaminase, ribonuclease, trypsin, chymotrypsin, and papain.

Abstract: Specific, selective inhibitors of catalytic antibodies both synthetic and naturally occurring, their use and compositions thereof are disclosed. In particular, an inhibitor preventing the hydrolysis of the peptide bond between amino acid residues 16 and 17 in the neurotransmitter vasoactive intestinal peptide (VIP) by an anti-VIP catalytic autoantibody is disclosed.

Abstract: Conjugates of trichothecenes and agents that bind to a defined population of cells are disclosed. Preferred are conjugates of trichothecene molecules with polyclonal or monoclonal antibodies or fragments thereof that recognize antigens that are present only on tumor cells or are augmented in their expression on tumor cells as compared to normal tissues. Trichothecene molecules are coupled to the agent through non-covalent and covalent linkages, such as peptide bonds, disulfide bonds, thioester bonds, or thioether bonds. A method for inhibiting the growth and metabolism of antigen-positive cells is also disclosed.

Abstract: A linear (i.e., non-cyclic) analog of biologically active amphibian bombesin, mammalian gastrin-releasing peptide (GRP), or mammalian growth hormone releasing factor (GRF), having an active site and a binding site responsible for the binding of the peptide to a receptor on a target cell. Cleavage of a peptide bond in the active site of naturally occurring bombesin, GRP, or GRF is unnecessary for in vivo biological activity. The analog has one of the following modifications: (a) a deletion of an amino acid residue within the active site and a modification of an amino acid residue outside of the active site, (b) a replacement of two amino acid residues within the active site with a synthetic amino acid, a .beta.-amino acid, or a .gamma.-amino acid residue, or (c) a non-peptide bond instead of a peptide bond between an amino acid residue of the active site and an adjacent amino acid residue.

Abstract: Novel benzhydrylamine derivatives represented by general formulas (I) and (II) are useful as reaction reagents for the solid-phase synthesis of polypeptide amides making use of 9-fluorenylmethyloxycarbonyl group ("Fmoc"). An intermediate for these derivatives represented by the general formula (III) is also disclosed: ##STR1## where R.sub.1 and R.sub.2 each independently represents a C.sub.1-3 lower alkyl; n is an integer of 1-4; l is 1 or 2; and m is 1 or 2.

Abstract: Small cell lung carcinoma cells (SCLC) contain gastrin releasing peptide (GRP) receptors. The response of the cells to GRP is rapid growth. We have found a group of peptide derivatives that act as GRP antagonists by blocking the binding of GRP to its receptor thereby inhibiting the growth of cells that are sensitive to the growth promoting activity of GRP.

Abstract: Small cell lung carcinoma cells (SCLC) contain gastrin releasing peptide (GRP) receptors. The response of the cells to GRP is rapid growth. We have found a group of peptide derivatives that act as GRP antagonists by blocking the binding of GRP to its receptor thereby inhibiting the growth of cells that are sensitive to the growth promoting activity of GRP.