Abstract: The present invention provides methods that can be used to identify &bgr;-amyloid reducing compounds. The present invention is based on the use of organotypic brain slice culturing methods to simultaneously assess the toxicity and &bgr;-amyloid reducing activity of a test compound.

Abstract: Compositions and devices for the controlled release delivery of a peptide or protein drug are produced by dispersing a glassy matrix phase comprising the peptide or protein drug and a thermoprotectant in a bioerodable, biocompatible polymer at a temperature that is below the glass transition temperature of the glassy matrix phase and above the melting point of the polymer. The method and composition of the invention may be employed for the local delivery of angiogenic amounts of basic fibroblast growth factor or vascular endothelial growth factor.

Abstract: The invention describes compounds of the formula and the pharmaceutically acceptable salts thereof and the pharmaceutically acceptable salts thereof wherein each R2 is independently a noninterfering substituent; m is an integer of 0-4; Z is CH or N; R1 is H, alkyl (1-6C) or arylalkyl optionally substituted on the aryl group with 1-3 substituents independently selected from alkyl (1-6C), halo, OR, NR2, SR, —OOCR, —NROCR, RCO, —COOR, —CONR2, —SO2NR2, CN, CF3, and NO2, wherein each R is independently H or lower alkyl (1-4C); n is 0, 1 or 2; Ar is phenyl, pyridyl, indolyl, or pyrimidyl, each optionally substituted with a group selected from the group consisting of optionally substituted alkyl (1-6C), halo, OR, NR2, SR, —OOCR, —NROCR, RCO, —COOR, —CONR2, SO2NR2, CN, CF3, and NO2, wherein each R is independently H or lower alkyl (1-4C); and R3 is a branched or cyclic alkyl group (5-7C) or is phenyl optionally substituted with 1-2 substi

Abstract: The present invention provides reagents and assays for the quantification of hBNP in biological fluid samples such as plasma or serum. Antibodies are provided which are monospecific to epitopes comprising the amino acid sequences 5-13, 1-10 and 15-25 of hBNP. These antibodies, and peptide fragments containing these sequences, can be employed in the assays of the invention, which may be carried out in a sandwich format or a competition format.

Abstract: The invention is directed to compounds of the formula ##STR1## and the pharmaceutically acceptable salts thereof wherein Ar.sup.1 is indole, benzimidazole, or benzotriazole, optionally substituted with lower alkyl (1-4C), halo, or lower alkoxy (1-4C);X.sup.1 is CO or an isostere thereof;Y is optionally substituted alkyl, optionally substituted aryl, or optionally substituted arylalkyl;n is 0 or 1;Z is CH or N;X.sup.2 is CH, CH.sub.2 or an isostere thereof; andAr.sup.2 consists of one or two phenyl moieties directly coupled to X.sup.2 and optionally substituted by halo, nitro, alkyl (1-6C), CN or CF.sub.3, or by RCO, COOR, CONR.sub.2, NR.sub.2, OR or SR, wherein R is H or alkyl (1-6C) or by phenyl, itself optionally substituted by the foregoing substituents;with the proviso that if Z is N, X.sup.1 is CO, and Ar.sup.1 is indole, Ar.sup.1 must be coupled to X.sup.1 through the 2-, 5-, 6- or 7-position.These compounds are useful in the treatment of conditions associated with inflammation.

Abstract: The present invention provides reagents and assays for the quantification of hBNP in biological fluid samples such as plasma or serum. Antibodies are provided which are monospecific to epitopes comprising the amino acid sequences 5-13, 1-10 and 15-25 of hBNP. These antibodies, and peptide fragments containing these sequences, can be employed in the assays of the invention, which may be carried out in a sandwich format or a competition format.

Abstract: Analogues of the Kunitz Protease Inhibitor (KPI) domain of amyloid precursor protein bind to and inhibit activity of serine proteases, including kallikrein, plasmin and coagulation factors such as factors VIIa, IXa, Xa, XIa, and XIIa. Pharmaceutical compositions containing the KPI analogues, along with methods for using such compositions, are useful for ameliorating and treating clinical conditions associated with increased serine protease activity, such as blood loss related to cardiopulmonary bypass surgery. Nucleic acid sequences encoding these analogues and systems for expression of the peptides of the invention are provided.

Abstract: Peptides of the formula R.sup.1 -Cys-Phe-Gly-Arg-Arg-Leu-Asp-Arg-Ile-Gly-Ser-Leu-Ser-Gly-Leu-Gly-Cys-R.sup .2wherein R.sup.1 is selected from the group consisting of:(H);Gly-;Ser-Gly-;Lys-Ser-Gly-;His-Lys-Ser-Gly-;Met-His-Lys-Ser-Gly-;Thr-Met-His-Lys-Ser-Gly-;Lys-Thr-Met-His-Lys-Ser-Gly-;Pro-Lys-Thr-Met-His-Lys-Ser-Gly-;Ser-Pro-Lys-Thr-Met-His-Lys-Ser-Gly-;or is the amino acid sequence of the dog prepro sequence upstream of position 100 shown in FIG. 8 herein or a C-terminal portion thereof;R.sup.2 is (OH), NH.sub.2, or NR.sub.2 wherein each R is independently H or lower alkyl (1-4C) or isAsn;Asn-Val;Asn-Val-Leu;Asn-Val-Leu-Arg;Asn-Val-Leu-Arg-Lys;Asn-Val-Leu-Arg-Lys-Tyr;or the amides thereof are useful in treating conditions characterized by high levels of extracellular fluid.

Abstract: Cloned recombinant or synthetic DNA sequences related to the pathology of Alzheimer's disease are injected into fertilized mammalian eggs (preferably mouse eggs). The injected eggs are implanted in pseudo pregnant females and are grown to term to provide transgenic mice whose cells express proteins related to the pathology of Alzheimer's disease. The injected sequences are constructed having promoter sequences connected so as to express the desired protein in specific tissues of the transgenic mammal (most notably in nerve tissue). The proteins which are preferably ubiquitously expressed include: (1) .beta.-amyloid core precursor proteins; (2) .beta.-amyloid related precursor proteins; and (3) serine protease inhibitor. The transgenic mice provide useful models for studying compounds being tested for their usefulness in treating Alzheimer's disease, and for studying the in vivo interrelationships of these proteins to each other.

Abstract: The invention provides bradykinin antagonist compounds wherein many (or all) of the peptide bonds of bradykinin are eliminated to yield compounds which specifically compete with bradykinin for binding to the bradykinin receptor. More particularly, the invention relates to compounds having, in appropriate spatial arrangement, two positively charged moieties flanking a hydrophobic organic moiety and a moiety which mimics a beta turn conformation.

Abstract: The present invention relates to the development of an efficacious vaccine against Feline Infectious Peritonitis Virus (FIPV). The invention provides the tools for the synthesis and manipulation of the structural and non-structural proteins of FIPV. These proteins are able to elicit an immune response in cats against FIPV. The recombinant virus vectors which express the E1 or N proteins of the virus or the recombinant produced viral proteins themselves are able to elicit an immune response.

Abstract: The present invention provides tools which are useful for the diagnosis of an animal's exposure to feline infectious peritonitis virus (FIPV) or susceptibility to FIPV. The diagnostic tools are composed of nucleic acid sequences which encode structural and nonstructural FIPV proteins and antibodies generated against FIPV proteins. The FIPV proteins may also be useful as subunit vaccines.

Abstract: Pseudopeptide compounds based on a modified bradykinin sequence are potent bradykinin receptor antagonist. All or a portion of the amino acids at positions 2 through 5 of the bradykinin sequence are replaced by 2-pyrrolidinyl and/or amino-alkanoic acid or related olefinic derivatives to reduce the peptidic nature of the compounds.The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected such as by insect bites.

Abstract: The cDNA sequence encoding porcine brain natriuretic peptide and related genes encoding canine and human peptides with natriuretic activity are disclosed. The gene is shown to make accessible the DNAs encoding analogous natriuretic peptides in other vertebrate species. The genes encoding these NPs can be used to effect modifications of the sequence to produce alternate forms of the NPs and to provide practical amounts of these proteins. The NPs of the invention can also be synthesized chemically.

Abstract: Novel compounds with as few as three natural amino acids that incorporate a substituted 4-keto-1,3,8-triazaspiro[4.5]decan-3-alkanoyl bridge in place of selected fragments of peptidic bradykinin receptor antagonists are pseudopeptides with potent bradykinin receptor antagonist actions. These pseudopeptides and their pharmaceutical compositions are of benefit in treating conditions and diseases of mammals, including humans, in which an excess of bradykinin or a related kinin is produced endogenously or is received exogenously, for example via insect bite.

Abstract: The DNA sequences encoding human and bovine acidic and basic fibroblast growth factors (FGF) can be recombinantly expressed to obtain practical amounts of proteins useful in effecting wound healing and related tissue repair.

Abstract: There are disclosed neurotrophic factors which are capable of being expressed as polypeptides lacking the microheterogeneity associated with a related native-sequence factor, CNTF. Also disclosed are DNA sequences encoding the neurotrophic factors and methods for expressing and recovering the factors as homogeneous polypeptides.

Abstract: Human insulin analogs are disclosed. These analogs are tissue-selective. Accordingly, pharmaceutical formulations containing the analogs of the invention provide superior clinical benefits as compared to human insulin when used in the treatment of patients suffering from diabetes. The analogs are modified at amino residue A12, A15 or A19, are different from the naturally occurring residue at said position, and are hepatoselective. Also disclosed are human insulin analogs modified at amino acid residues A12 or A14 or amino acid residues A10 and A13 different from naturally occurring residues or residues at said position or positions and are peripheral selective. DNA sequences and microorganisms comprising sequences coding for human insulin analogs are also provided. Processes for preparing the human insulin analogs are described.