Abstract: The present invention provides monoclonal antibodies that selectively bind to and inhibit activated protein C without binding to or inhibiting unactivated protein C. Other antibodies inhibit both activated protein C and activation of unactivated protein C. Methods of treatment employing these antibodies are described herein as are methods of screening for and detecting these antibodies.

Abstract: A method of in vitro fucosylation of selectin ligands on cord blood-derived hematopoietic stem cells for bone marrow transplantation is disclosed. In this method, an effective amount of an ?1,3-fucosyltransferase, e.g., ?1,3-fucosyltransferase VI, is used in vitro to treat cord blood-derived hematopoietic stem cells to convert non-functional PSGL-1 or other ligands on the cell surface into functional forms that bind selectins, especially P-selectin or E-selectin. The treated cells have enhanced effectiveness in reconstituting bone marrow in patients in need of such therapy.

Abstract: The present invention provides methods for the prediction and diagnosis of autoimmune diseases, including Systemic Lupus Erythematosus, using single nucleotide polymorphism in TNFAIP3 (A20).

Abstract: This application pertains to antibodies which specifically bind to immunogenic memapsin 2?-secretase peptides for use in the treatment of Alzheimer's disease and memapsin 2?-secretase disorders. The application also pertains to immunogenic compositions comprising memapsin 2?-secretase peptides and uses thereof.

Abstract: Biomarkers useful for diagnosing and assessing inflammatory disease are provided, along with kits for measuring their expression. The invention also provides predictive models, based on the biomarkers, as well as computer systems, and software embodiments of the models for scoring and optionally classifying samples. The biomarkers include at least two biomarkers selected from the DAIMRK group and the score is a disease activity index (DAI).

Abstract: Compositions and methods effective for eliciting an immune response for preventing or reducing infection or improving clinical outcomes caused by Bacillus anthracis are provided. The compositions include a naturally occurring or synthetic protein, peptide, or protein fragment containing all or an active portion of an antigenic epitope associated with anthrax toxin proteins optionally combined with a pharmaceutically acceptable carrier. The preferred antigenic epitopes correspond to immunogenic regions of protective antigen, lethal factor or edema factor, either individually or in combination. In addition, methods and compositions containing antibodies for reducing the effects of anthrax toxins are described. The methods involve administering to a human or animal the compositions described herein in a dosage sufficient to elicit an immune response or treat the anthrax infection.

Abstract: ACTH analog compounds of the present invention include compounds comprising an ACTH peptide sequence with one or more structural modifications that can have one or more of the following preferred ACTH analog biological functions: (1) reduction of corticosteroid secretion by adrenal membrane in the presence of the ACTH analog compared to unmodified ACTH, (2) reduction of corticosteroid secretion by adrenal membrane in the presence of endogenous ACTH and (3) increased MC-2R binding affinity with reduced activation of the MC-2R receptor compared to unmodified ACTH binding to the MC-2R melanocortin. The ACTH analog compounds of the present invention are therefore useful for treatment or prevention of diseases and disorders related to ACTH, ACTH receptors or corticosteroid secretion, such as premature labor and Cushing's Disease.

Abstract: Methods for the production of purified, catalytically active, recombinant memapsin 2 have been developed. The substrate and subsite specificity of the catalytically active enzyme have been determined. The substrate and subsite specificity information was used to design substrate analogs of the natural memapsin 2 substrate that can inhibit the function of memapsin 2. The substrate analogs are based on peptide sequences, shown to be related to the natural peptide substrates for memapsin 2. The substrate analogs contain at least one analog of an amide bond which is not capable of being cleaved by memapsin 2. Processes for the synthesis of two substrate analogues including isosteres at the sites of the critical amino acid residues were developed and the substrate analogues, OMR99-1 and OM99-2, were synthesized. OM99-2 is based on an octapeptide Glu-Val-Asn-Leu-Ala-Ala-Glu-Phe (SEQ ID NO:28) with the Leu-Ala peptide bond substituted by a transition-state isostere hydroxyethylene group (FIG. 1).

Abstract: It has now been found that N-L-alpha-aspartyl-L-phenylalanine 1-methyl ester (APM) and/or one of its lower alkyl derivatives can be used to treat allergic contact dermatitis associated with irritating oils such as catechol-containing plant-derived antigens such as poison ivy, poison oak, poison sumac and Asian lacquer tree and oils containing capsaicin. Topical application of APM and/or derivative can reduce or alleviate the symptoms associated with irritation of the skin and/or mucous membranes caused by contact or inhalation of these oils or fumes from burning vegetation containing these oils.

Abstract: Compositions and methods effective for eliciting an immune response for preventing or reducing infection or improving clinical outcomes caused by Bacillus anthracis are provided. The compositions include a naturally occurring or synthetic protein, peptide, or protein fragment containing all or an active portion of an antigenic epitope associated with anthrax toxin proteins optionally combined with a pharmaceutically acceptable carrier. The preferred antigenic epitopes correspond to immunogenic regions of protective antigen, lethal factor or edema factor, either individually or in combination. In addition, methods and compositions containing antibodies for reducing the effects of anthrax toxins are described. The methods involve administering to a human or animal the compositions described herein in a dosage sufficient to elicit an immune response or treat the anthrax infection.

Abstract: A method of in vitro fucosylation of selectin ligands on cord blood-derived hematopoietic stem cells for bone marrow transplantation is disclosed. In this method, an effective amount of an ?1,3-fucosyltransferase, e.g., ?1,3-fucosyltransferase VI, is used in vitro to treat cord blood-derived hematopoietic stem cells to convert non-functional PSGL-1 or other ligands on the cell surface into functional forms that bind selectins, especially P-selectin or E-selectin. The treated cells have enhanced effectiveness in reconstituting bone marrow in patients in need of such therapy.

Abstract: Compositions and methods effective for eliciting an immune response for preventing or reducing infection or improving clinical outcomes caused by Bacillus anthracis are provided. The compositions include a naturally occurring or synthetic protein, peptide, or protein fragment containing all or an active portion of an antigenic epitope associated with anthrax toxin proteins optionally combined with a pharmaceutically acceptable carrier. The preferred antigenic epitopes correspond to immunogenic regions of protective antigen, lethal factor or edema factor, either individually or in combination. In addition, methods and compositions containing antibodies for reducing the effects of anthrax toxins are described. The methods involve administering to a human or animal the compositions described herein in a dosage sufficient to elicit an immune response or treat the anthrax infection.

Abstract: The present invention provides compositions comprising lanthionine ketimine derivatives and thiomorpholine dicarboxylic acid derivatives, as well as processes for the preparation of such compounds. The invention also concerns the use of lanthionine, lanthionine ketimine (LK), LK derivatives, thiomorpholine dicarboxylic acid (TMDCA), and TMDCA derivatives. It concerns the use of these compounds for the treatment and/or prevention diseases, including diseases affecting the central nervous system. The invention provides for compounds and methods having anti-oxidant, anti-neuroinflammatory and neuroprotective activities. It also provides for compounds having the ability to pass through and/or be transported through cellular membranes, such the blood-brain barrier.

Abstract: Methods for the production of purified, catalytically active, recombinant memapsin 2 have been developed. The substrate and subsite specificity of the catalytically active enzyme have been determined. The substrate and subsite specificity information was used to design substrate analogs of the natural memapsin 2 substrate that can inhibit the function of memapsin 2. The substrate analogs are based on peptide sequences, shown to be related to the natural peptide substrates for memapsin 2. The substrate analogs contain at least one analog of an amide bond which is not capable of being cleaved by memapsin 2. Processes for the synthesis of two substrate analogues including isosteres at the sites of the critical amino acid residues were developed and the substrate analogues, OMR99-1 and OM99-2, were synthesized. OM99-2 is based on an octapeptide Glu-Val-Asn-Leu-Ala-Ala-Glu-Phe (SEQ ID NO:28) with the Leu-Ala peptide bond substituted by a transition-state isostere hydroxyethylene group (FIG. 1).

Abstract: The present invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating of Alzheimer's disease.

Abstract: Methods for regulating body weight and/or regulating weight gain are provided herein. The methods are useful, for instance, for treating or preventing obesity. Specifically, methods of administering varying levels of various alpha melanocyte stimulating hormone (?-MSH) analog compounds to an animal are provided for reducing body weight and/or reducing the rate of body weight gain.

Abstract: The invention provides methods for diagnosing, treating, or evaluating inflammatory and autoimmune diseases by sampling peripheral blood, serum, plasma, tissue, cerebrospinal fluit, or other bodily fluids from a human subject having a suspected diagnosis. The sample is analyzed for the presence and amount of certain cytokines, which provides the diagnosis, prognosis or evaluation of therapeutic response.

Abstract: The discovery of Toll-like receptors (TLRs) on the surface of hematopoietic cells provides new methods for the stimulation and differentiation of various classes of progenitor cells. TLR2 and TLR4 agonists (natural ligands, mimetics, antibodies) are particularly useful in these methods. The cells can be isolated and used for various purpose including tissue regeneration and grafting. In contrast, antagonists of TLRs can be used to protect cells from various insults such as chemo- and radiotherapy, acute and chronic infection, and transplantation by inhibiting activation and differentiation. TLR2, TLR4 and TLR9 pathway antagonists (soluble TLR, mimetics, antibodies) are particularly useful in these methods. Cells can be isolated and used for various purposes including transplantation.

Abstract: The present invention provides novel methods of reducing memapsin 2 ?-secretase activity in a subject, decreasing levels of ?-amyloid peptide in the brain of a subject, treating Alzheimer's disease and/or reducing the size and/or number of ?-amyloid plaques in the brain of a subject. The methods may include the step of administering an effective amount of truncated memapsin 2 protein, anti-truncated memapsin 2 antibody, and/or nucleic acid encoding a truncated memapsin 2 protein or anti-truncated memapsin 2 antibody. The present invention also provides related pharmaceutical compositions and uses thereof.

Abstract: A method for determining the concentration of factor VIIa-antithrombin complexes is disclosed which has application to estimating the level of intravascular exposure of tissue factor, assessing patient risk for hypercoagulation or other coagulopathies, and monitoring patients for factor VIIa-antithrombin complexes over time which can reveal changes in risk for hypercoagulation or other coagulopathies and/or effectiveness of anticoagulant therapy. Antibodies suitable for use in an in vitro assay for determining the concentration of factor VIIa-antithrombin complexes and methods for making the same are also disclosed.