Abstract: The present invention concerns two human nucleic acids comprising sequences which code two novel isoforms of human somatostatin receptor type 5 produced by alternative adjustment, called sst5B and sst5C and with possible uses in tumoral processes. Additionally, the invention concerns oligonucleotide pairs used for the differential detection of said isoforms by means of the PCR technique in different tissues.

Abstract: The present invention relates to polymer conjugated releasable lipids and nanoparticle compositions containing the same for the delivery of nucleic acids and methods of modulating gene expression using the same. In particular, this invention relates to releasable polymeric lipids containing an acid-labile linker based on a ketal or acetal-containing linker, or an imine-containing linker.

Abstract: SRIF peptide antagonists, which are selective for SSTR2 in contrast to the other cloned SRIF receptors and which bind with high affinity to the cloned human receptor SSTR2 but do not activate the receptor, have many useful functions. Because they do not bind with significant affinity to SSTR1, SSTR3, SSTR4 or SSTR5, their administration avoids potential undesirable side effects. By incorporating radioiodine or the like in these SSTR2-selective SRIF antagonists, a labeled compound useful in drug-screening methods is provided. Alternatively, for use in therapy, highly radioactive moieties can be N-terminally coupled, complexed or chelated thereto. Because they block the receptor function, they can be used therapeutically to block certain physiological effects which SSTR2 mediates.

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: The present invention is directed to fusion proteins that can be used to assay gene transfer and expression both in vitro and in vivo. The fusion proteins contain a reporter protein, e.g. a somatostatin receptor, fused to a second protein, which may be a protein fusion tag. Alternatively, a fusion protein may be fused to a leader sequence. A leader sequence may localize an expressed protein, e.g localize a fusion protein to the cell membrane. The invention includes nucleic acids encoding the fusion proteins and methods of assaying for gene expression.

Abstract: The invention describes compositions of peptide analogs that are active in blood or cleavable in blood to release an active peptide. The peptide analogs have a general formula: A-(Cm)x-Peptide (SEQ ID NO: 76), wherein A is hydrophobic moiety or a metal binding moiety, e.g., a chemical group or moiety containing 1) an alkyl group having 6 to 36 carbon units, 2) a nitrilotriacetic acid group, 3) an imidodiacetic acid group, or 4) a moiety of formula (ZyHisw)p (SEQ ID NO: 50), wherein Z is any amino acid residue other than histidine, His is histidine, y is an integer from 0-6; w is an integer from 1-6; and p is an integer from 1-6; wherein if A has alkyl group with 6 to 36 carbon units x is greater than 0; and Cm is a cleavable moiety consisting of glycine or alanine or lysine or arginine or N-Arginine or N-lysine, wherein x is an integer between 0-6 and N may be any amino acid or none. The peptide analogs are complexed with polymeric carrier to provide enhanced half-life.

Abstract: Provided are therapeutic and diagnostic somatostatin analogs including radiotherapeutic and radiodiagnostic reagents, and methods of making and use thereof.

Abstract: Chimeric somatostatin-based polypeptides, polynucleotides used to encode the polypeptides, the methods for isolating and producing the polypeptides and the uses thereof are provided. In addition, low cost adjuvants for enhanced immunogenic response are provided. Vaccinations that include both chimeric somatostatin-based polypeptides and novel adjuvants are included, useful in facilitating farm animal productivity.

Abstract: The invention provides cyclo[{4-(NH2—C2H4—NH—CO—O—)Pro}-Phg-DTrp-Lys-Tyr(4-Benzyl)-Phe], optionally in protected form, or a pharmaceutically acceptable salt or complex thereof, which has interesting pharmaceutical properties.

Abstract: The present invention is directed to improvements in compositions containing a somatostatin-dopamine conjugate which retains both somatostatin and dopamine activity in vivo, methods for preparing such compositions, and method of using such compositions to treat mammals. In particular, the present invention relates to a pharmaceutical composition comprising Dop2-DLys(Dop2)-cyclo[Cys-Tyr-DTrp-Lys-Abu-Cys]-Thr-NH2 (SEQ ID NO: 1), in which the somatostatin-dopamine conjugate precipitates in vivo at physiological pH to form an in situ deposit that is slowly dissolved and released into the body fluid and bloodstream. The present invention may further comprise an organic component such as dimethylacetamide (DMA) or polyethylene glycol with an average molecular weight of 400 (PEG400).

Abstract: The present invention concerns methods and compositions for forming cytokine-antibody complexes using dock-and-lock technology. In preferred embodiments, the bispecific immunocytokine DNL construct comprises an IgG antibody attached to a Fab antibody fragment and a cytokine, wherein the IgG and the Fab bind to different target antigens which may be expressed on the same target cell. The bispecific immunocytokine DNL construct exhibits improved pharmacokinetics, with a longer serum half-life and significantly greater efficacy compared to cytokine alone, antibody alone, unconjugated cytokine plus antibody or even other types of cytokine-antibody DNL constructs. In a most preferred embodiment the construct comprises an anti-CD20 IgG antibody conjugated to an anti-HLA-DR Fab and IFN?2b, although other combinations of antibodies, antibody fragments and cytokines may be used to form the subject DNL complexes.

Abstract: The present invention relates to a new class of cyclopeptides of formula (1), reported here below, which are non-selective functional analogues of somatostatin.

Abstract: The present invention provides conjugates of disorazoles and their derivatives with cell-binding molecules, such as peptides, proteins, hormones, blood proteins and antibodies. The present invention further provides novel disorazole derivatives and processes of manufacturing such conjugates and disorazole derivatives. These compounds can be used as medicaments for the treatment of physiological and/or pathophysiological conditions in mammals, in particular for the treatment of various tumors.

Abstract: The invention relates to methods for the preparation of polypeptides. The polypeptides are prepared in high purity of at least about 98.5%, and preferably at least about 99% by HPLC.

Abstract: A solid phase method for synthesizing a peptide containing three or more amino acid residues utilizing both Boc and Fmoc protected amino acids and a chloromethylated polystyrene resin.

Abstract: Chimeric somatostatin-based polypeptides, polynucleotides used to encode the polypeptides, the methods for isolating and producing the polypeptides and the uses thereof are provided. In addition, low cost adjuvants for enhanced immunogenic response are provided. Vaccinations that include both chimeric somatostatin-based polypeptides and novel adjuvants are included, useful in facilitating farm animal productivity.

Abstract: Novel photo-active labeled diagnostic and therapeutic peptides which are conformationally constrained backbone cyclized somatostatin analogs, having improved somatostatin receptor subtype affinity and selectivity are disclosed. The backbone cyclized peptide analogs disclosed possess unique and superior properties over other analogs, such as chemical and metabolic stability, selectivity, increased bioavailability and improved pharmacokinetics. Furthermore, the unique patterns of receptor subtype selectivity provide compounds having improved diagnostic and therapeutic utilities. Pharmaceutical compositions comprising the photo-active backbone cyclized somatostatin analogs, reagents for synthesizing same, and methods of using such compositions for diagnostic and therapeutic purposes including optical imaging and photodynamic therapy are also disclosed.

Abstract: The invention primarily relates to the use of somatostatin or one of the agonistic analogs thereof for producing a medicament serving to regulate the ovarian follicular reserve and, in particular, to reduce the depletion of the ovarian follicular reserve over time in non-menopausal women or to the use of an antagonistic analog of somatostatin for producing a medicament serving to accelerate the start of growing of quiescent follicles in non-menopausal women. The invention also relates to in vitro applications of somatostatin and of agonistic and antagonistic analogs thereof.

Abstract: Improved sst-receptor binding peptidic ligands for diagnostic and therapeutic applications in nuclear medicine are provided. The improved ligands contain either natural or unnatural amino acids or peptidomimetic structures that are modified at either the N-terminal or the C-terminal end or at both termini, a carbohydrate unit and a chelator or prosthetic group to provide a complexation of a radioisotope binding or holding the radioisotope. The sst- or SSTR-receptor binding peptidic ligands may also contain one or more multifunctional linker units optionally coupling the peptide, and/or the sugar moiety and/or the chelator and/or the prosthetic group. Upon administering the ligand to a mammal through the blood system the ligand provides improved availability, clearance kinetics, sst-receptor targeting and internalization over the non-carbohydrated ligands.

Abstract: Disclosed is a series of somatostatin-dopamine chimeric analogs which retain both somatostatin and dopamine activity in vivo. An example is: 6-n-propyl-8?-ergolinglmethylthioacetyl-D-Phe-c-(Cys-Tyr-D-Trp-Lys-Abu-Cys)-Thr-NH2.

Abstract: Disclosed is a series of somatostatin-dopamine chimeric analogs which retain both somatostatin and dopamine activity in vivo.

Abstract: The invention features somatostatin antagonists having a D-amino acid at the second residue.

Abstract: The present invention provides methods and compositions for increasing the growth rates, alleviating the symptoms, or improving the metabolism of human patients having insulin-like growth factor-1 deficiency (IGFD). The invention relates to methods comprising administering insulin-like growth factor-I to a patient having a height which, at the time of treatment or prior to initial treatment with IGF-1, is at least about 2 standard deviations below normal for a subject of the same age and gender, a blood level of insulin-like growth factor-I that, and at the time of treatment or prior to initial treatment with IGF-1, is below normal mean levels, usually at least about 1 standard deviations below normal mean levels, for age and gender.

Abstract: The invention provides cyclo[{4-(NH2—C2H4—NH—CO—O—)Pro}-Phg-DTrp-Lys-Tyr(4-Benzyl)-Phe], optionally in protected form, or a pharmaceutically acceptable salt or complex thereof, which has interesting pharmaceutical properties.

Abstract: Compositions comprising activatable recombinant neurotoxins and polypeptides derived therefrom. The invention also comprises nucleic acids encoding such polypeptides, and methods of making such polypeptides and nucleic acids.

Abstract: The invention provides cyclo[{4-(NH2—C2H4—NH—CO—O—)Pro}-Phg-DTrp-Lys-Tyr(4-Benzyl)-Phe], optionally in protected form, or a pharmaceutically acceptable salt or complex thereof, which has interesting pharmaceutical properties.

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: SRIF peptide antagonists, which are selective for SSTR2 in contrast to the other cloned SRIF receptors and which bind with high affinity to the cloned human receptor SSTR2 but do not activate the receptor, have many useful functions. Because they do not bind with significant affinity to SSTR1, SSTR3, SSTR4 or SSTR5, their administration avoids potential undesirable side effects. Because they block the receptor function, they can be used therapeutically to block certain physiological effects which SSTR2 mediates. By incorporating radioiodine or the like in these SSTR2-selective SRIF antagonists, a labeled compound useful in drug-screening methods is provided. Alternatively, for use in therapy, highly radioactive moieties can be N-terminally coupled, complexed or chelated thereto.

Abstract: The invention relates to compounds of formula (I): and their use as targeting vectors that bind to receptors associated with angiogenesis. Such compounds may thus be used for diagnosis or therapy of, for example, malignant diseases, heart diseases, endometriosis, inflammation-related diseases, rheumatoid arthritis and Kaposi's sarcoma.

Abstract: The present invention is directed to a somatostatin antagonist according to formula (I): A1-cyclo {D-Cys-A2-D-Trp-A3-A4-Cys}-A5Y1, wherein A1 is an optionally substituted aromatic a-amino acid; A2 is an optionally substituted aromatic ?-amino acid; A3 is Dab, Dap, Lys or Om; A4 is ?-Hydroxyvaline, Ser, Hser, or Thr; A5 is an optionally substituted D- or L-aromatic amino acid; and Y1 is OH, NH2 or NHR1? where RI is (C1-6)alkyl; wherein each said optionally substituted aromatic amino acid is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, NO2, OH, CN, (C1-6) alkyl, (C2-6) alkenyl, (C2-6) alkynyl, (C1-6)alkoxy, Bzl, O-Bzl, and NR9R10? wherein R9 ad R10 each is independently H, O, or (C1-6) alkyl; and wherein the amine nitrogen of each of amide peptide bond and the amino group of A1 of formula (I) is optionally substituted with a methyl group, provided that there is at least one said methyl group; or a pharmaceutically acceptable salt thereof,

Abstract: A novel class of analogs which exhibit both high affinity and selectivity for Neuromedin B and Somatostatin receptors are claimed. One example is Nal-Tyr-cyclo(D-Cys-D-Trp-Lys-D-Cys)-Abu-Nal-NH2.

Abstract: The present invention is directed to a somatostatin antagonist according to formula (I), wherein A1 is an optionally substituted aromatic ?-amino acid; A2 is an optionally substituted aromatic ?-amino acid; A3 is Dab, Dap, Lys or Orn; A4 is ?-Hydroxyvaline, Ser, Hser, or Thr; A5 is an optionally substituted D- or L-aromatic -amino acid; and Y1 is OH, NH2 or NHR1, or NHR1, where R1 is (C1-6)alkyl; wherein each said optionally substituted aromatic -amino acid is optionally substituted with one or more substituents substituents each independently selected from the group consisting of halogen, NO2, OH, CN, (C1-6)alkyl, (c2-6)alkenyl, (c2-6)alkynyl, (C1-6)alkoxy, Bzl, O-Bzl, and NR9R10, where R9 ad R10 each is independently H, O, or (C1-6)alkyl; and wherein the amine nitrogen of each of amide peptide bond and the amino group of A1 of formula (I) is optionally substituted with a methyl group, provided that there is at least one said methyl group; or a pharmaceutically acceptable salt thereof, and to uses thereof.

Abstract: A composition and a method of increasing growth hormone (“GH”) values in a canine or dog, and more specifically, a canine- or dog-specific growth hormone releasing hormone (“dGHRH”), or functional biological equivalent thereof. The dGHRH is an isolated composition or a nucleic acid molecule that encodes the dGHRH or functional biological equivalent. Also, a method for delivering the composition of this invention to a subject, wherein the dGHRH increases the level of growth hormone (“GH”) secretion in a recipient subject, such as a canine or dog.

Abstract: The present invention features MCH antagonists active at the MCH-1R. The antagonists are optionally modified peptides able to inhibit the effect of MCH at MCH-1R. MCH antagonists have a variety of uses including being used as a research tool and being used to achieve a beneficial effect in a subject.

Abstract: Positron emitting compounds and methods of their production are provided. The compounds have the formula: (F)m G (R)n wherein each R is a group comprising at least one carbon, nitrogen, phosphorus or sulfur atom and G is joined to R through said carbon, nitrogen, phosphorus or sulfur atom; G is silicon or boron; m is 2 to 5 and n is 1 to 3 with m+n=3 to 6 when G is silicon; m is 1 to 3 and n is 1 to 3 with m+n=3 to 4 when G is boron; and wherein the compound further comprises one or more counterions when the above formula is charged; and wherein at least one F is 18 F.

Abstract: Disclosed are peptide agents and uses thereof that are analogs of biologically active peptides such as somatostatin and bombesin. The compounds of the invention have the general formula X-Y-Z-Q, where X is a cytotoxic agent, therapeutic agent, detectable label or chelating group, and Q is a biologically active peptide. In peptide agents of the invention Y is optionally a hydrophilic polymer or peptide, and Z is a linking peptide bonded to Q at the amino terminus of Q, having two, three, four, or five, amino acid residues selected to link X to Q, while retaining the biological activity of Q. Methods of using these peptide agents in the diagnosis and treatment of diseases are also disclosed.

Abstract: A sustained-release drug composition consisting essentially of microparticles of hyaluronic acid having a high molecular weight or an inorganic salt thereof and a protein or peptide drug encased in said microparticles, wherein the average size of said microparticles ranges from 0.1 to 40 ?m.

Abstract: The present invention provides methods and compositions for increasing the growth rates, alleviating the symptoms, or improving the metabolism of human patients having insulin-like growth factor-1 deficiency (IGFD). The invention relates to methods comprising administering insulin-like growth factor-I to a patient having a height which, at the time of treatment or prior to initial treatment with IGF-1, is at least about 2 standard deviations below normal for a subject of the same age and gender, a blood level of insulin-like growth factor-I that, and at the time of treatment or prior to initial treatment with IGF-1, is below normal mean levels, usually at least about 1 standard deviations below normal mean levels, for age and gender.

Abstract: The present invention is directed to a novel class of cyclic polypeptides of the formula: (R1)a-AA1-cyclo[AA2-AA3-AA4-AA5-AA6-Cys]-AA7-R2, pharmaceutically acceptable salts thereof, wherein the variables are as defined in the specification, which inhibit the effects of urotensin-II and are useful for treating a variety of diseases and/or conditions characterized by an excess of urotensin-II including ischaemic heart disease, congestive heart failure, portal hypertension, variceal bleeding, hypotension, angina pectoris, myocardial infarction, ulcers, anxiety, schizophrenia, manic depression, delirium, dementia, mental retardation and/or dyskinesias.

Abstract: Analogs of SRIF which are selective for SSTR4 in contrast to the other cloned SRIF receptors are useful in determining tissue and cellular expression of the receptor SSTR4 and its biological role in regulating tumor growth. SRIF analog peptides, such as des-AA1,2,4,5,12,13[Ala7]-SRIF; des-AA1,2,4,5,12,13[Aph7]-SRIF, des-AA1,2,4,5,12,13[Aph7]Cbm-SRIF; des-AA1,2,4,5,12,13[Tyr2,Ala7]-Cbm-SRIF, and des-AA1,2,4,5,12,13[Tyr7,C?Me-L-2Nal8]-SRIF, and counterparts incorporating D-Cys3 and/or D-Trp8 and/or Ala11, bind with high affinity to the cloned human receptor SSTR4 and activate the receptor, but they do not bind with significant affinity to human SSTR1, SSTR2, SSTR3 or SSTR5. By incorporating an iodinated tyrosine in position-2 in these SSTR4-selective SRIF analogs, a labeled compound useful in drug-screening methods is provided. Alternatively, for use in therapy, cytotoxins or highly radioactive elements can be N-terminally coupled or complexed thereto.

Abstract: The invention relates to compounds having a binding affinity for both the ?v?3 receptor and a (neuro)peptide receptor, in particular the somatostatin receptor, which compound comprises a first peptide part comprising at least once the amino acid sequence Arg-Gly-Asp, and a second peptide part coupled thereto, optionally via a linker, which second peptide part is a (neuro)peptide.

Abstract: In one embodiment, a composition of somatostatin analogues having the general formula: is provided wherein Z may be absent or present and when present is selected from DOTA- and DTPA-based chelators, NOTA-based chelators, carbonyl compounds, hydrazino nicotinamide, N4-chelators, desferrioxamine, NxSy-chelators, optionally complexed or labeled with a radioisotope, tyrosine for halogenation, a fluorescent dye, or biotin. The composition further provides that L may or may not be present and when present is a linker molecule, X1 is glutamic acid or a symmetric or asymmetric diamino acid containing 3 or 4 consecutive C atoms, X2 is a positively charged natural or unnatural amino acid, an arginine mimic, citrulline, or a neutral amino acid, X3 is phenylalanine, Ala-[3-(2-thienyl)], ?-naphthylalanine, or ?-naphthylalanine, X4 is an aromatic amino acid, X5 is threonine or serine, and X6 is phenylalanine, Ala-[3-(2-thienyl)], ?-naphthylalanine, or ?-naphthylalanine.

Abstract: The present invention relates to binding moieties comprising at least one monomeric V-like domain (VLD) derived from a non-antibody ligand, the at least one monomeric V-like domain being characterized in that at least one CDR loop structure or part thereof is modified or replaced such that the solubility of the modified VLD is improved when compared with the unmodified VLD.

Abstract: The present invention is directed to cyclic peptides of formula (I): X-A1-cyclo(D-Cys-A3-A4-Lys-A6-A7)-A8-Y, or a pharmaceutically acceptable salt thereof. The peptides bind selectively to the somatostatin subtype receptor type-5 and elicit an agonist effect from the somatostatin subtype receptors.

Abstract: The invention relates to a peptide compound having an improved binding affinity to somatostatin receptors, comprising a somatostatin analogue as the peptide and a chelating group covalently linked to the N-terminal free amino group of said peptide, wherein said somatostatin analogue carries an 1-naphthylalanine or a 3-benzothienylalanine residue in its 3-position. The invention further relates to said peptide compound labeled with a detectable element or with a therapeutic radionuclide, as well as to a diagnostic method and to a method for the therapeutic treatment of tumors, by using the labeled compounds.

Abstract: Template-fixed ?-hairpin loop mimetics comprising a template corresponding to one of the structures (a), (b), (c), (d), (e), (f), (g), (h) and a template-fixed chain of 4 to 20 ?-amino acid residues which, if their ?-C atom is asymmetric, have L-configuration can be manufactured by a novel process which is based on a mixed solid- and solution phase synthetic strategy. If desired, this process can be modified to give the enantiomers of these template-fixed ?-hairpin loop mimetics. These enantiomers are novel compounds, and many of said template-fixed ?-hairpin loop mimetics themselves are also novel compounds. The template-fixed ?-hairpin loop mimetics and their enantiomers can mimic flat surfaces of proteins and thus be used to probe large surface protein-protein interactions. Accordingly they can serve as lead finding tools for protein targets where it is difficult to find small-molecular-weight lead compounds.

Abstract: The present invention relates to a method of treating vascular proliferation in a patient in need thereof. The method includes the step of administering a therapeutically effective amount of a type-1 somatostatin agonist to said patient.

Abstract: The peptides and precursors thereof, inclusive salts thereof, of the present invention are useful as a pharmaceutical composition, for example as therapeutic or prophylactic agents for hormone-producing tumors, acromegaly, gigantism, dementia, gastric ulcer and the like, hormone secretion inhibitors, tumor growth inhibitors, neural activity or sleep modulators, etc. The DNAs coding for the peptides or precursors of the invention are useful as a pharmaceutical composition, for example as agents for the gene therapy or prevention of hormone-producing tumors, acromegaly, gigantism, dementia, gastric ulcer and the like, hormone secretion inhibitors, tumor growth inhibitors, neural activity or sleep modulators, etc. Furthermore, the DNAs coding for the peptides or precursors of the invention are useful as agents for the gene diagnosis of various diseases, for example, hormone-producing tumors, acromegaly, gigantism, dementia, gastric ulcer, etc.

Abstract: The present invention relates to a method of decreasing body weight in a patient. The method includes the step of administering a therapeutically effective amount of a somatostatin or a somatostatin agonist to said patient. A pharmaceutical/cosmetic composition comprises the somatostatin or somatostatin agonist. Such products are used to prepare such compositions for the reduction of body weight in a human or mammalian animal.

Abstract: The present invention relates to a method of treating hyperlipidemia and to reducing triacylglycerols, glycerol and cholesterol in a patient. The method includes the step of administering a therapeutically effective amount of a type-5 selective somatostatin agonist to said patient. A pharmaceutical composition comprises said agonist and such product is used in the preparation of the composition for use in treating hyperlipidemia or reducing triacylglycerols, glycerol and cholesterol in a patient's body.

Abstract: Sialic acid binding proteins, sialic acid-binding peptides and sialic acid containing oligo-saccharides are active ingredients of a novel bacterial enterotoxin neutralizer and interfere with the binding of enterotoxins, including cholera toxin, to receptors so as to exert an effect of neutralizing the toxicity, thus being utilized as an effective neutralizer and are safe and available cheaply and abundantly from by-products produced during the processing of cow's milk which renders the enterotoxin neutralizer economically advantageous for commercial use.