Abstract: Disclosed are conjugates exhibiting VLA-4 antagonistic properties. Certain of these conjugates also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. The conjugates of this invention are characterized as containing more than one VLA-4 inhibiting compound covalently attached to a bio-compatible polymer, such as polyethylene glycol. Conjugates of the invention are defined by formula I, wherein A, B, and q are described in the specification. Such conjugates are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis, and myocardial ischemia. The conjugates can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

Abstract: The invention provides methods for detecting alpha-synuclein. The invention also identifies preferred epitopes of alpha synuclein for use in such detection, and provides antibodies specifically binding to such epitopes.

Abstract: Disclosed are compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a human or animal subject such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

Abstract: The invention relates to compounds of formula (I). Useful in treating Alzheimer's disease and other similar diseases. These compounds include inhibitors of the beta-secretase enzyme that are useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of A beta peptide in a mammal. The compounds of the invention are useful in pharmaceutical compositions and methods of treatment to reduce A beta peptide formation.

Abstract: This invention is directed to acylated amino acid amidyl pyrazoles and related compounds of Formula I. The invention is also directed to a pharmaceutical formation comprising such compound or in a pharmaceutically acceptable salt form thereof. The invention is further directed to a method for inhibiting ?-amyloid peptide release and/or synthesis, a method for inhibiting ?-secretase activity, and a method for treating neurological disorders associated with ?-amyloid peptide production. The method comprises administering to a host a pharmaceutical formulation comprising an effective amount of a compound of Formula I. The compounds of Formula I are useful in the prevention and treatment of Alzheimer's disease.

Abstract: The invention provides N-cyclic sulfonamido compounds and salts of Formula I: wherein A is as described in the specification and R1 and R2 combine to form a [3.3.1] or a [3.2.1] ring system, where the nitrogen is attached to the two bridgehead carbons, and the [3.3.1] or [3.2.1] ring systems are optionally fused with an heteroaryl or heterocycloalkyl ring. Compounds of Formula I are useful in treating or preventing cognitive disorders, such as Alzheimer's Disease. The invention also encompasses pharmaceutical compositions comprising compounds of Formula I, methods of treating cognitive disorders, such as Alzheimer's disease, and the intermediates useful in preparing the compounds of Formula I.

Abstract: Disclosed are certain alpha amino acid compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

Abstract: Disclosed are compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

Abstract: The invention provides methods for efficient recombinant expression, refolding, and purification of Beta-site APP cleaving enzyme (BACE) polypeptides. In various aspects, the method includes the steps of expressing a recombinant construct in bacteria, dissolving inclusion bodies with a denaturant at high pH in the presence of a reducing agent, diluting the solubilized BACE polypeptide in an aqueous solution at a temperature of about 1° C. to 15° C., and incubating the diluted sample at a temperature of about 4° C. to 15° C. until the recombinant BACE polypeptide folds into an active enzyme.

Abstract: The invention provides N-cyclic sulfonamido compounds of Formula I wherein A, B, R1, R1a, R2, R2a, R3 and R3a are as described in the specification. Compounds of Formula I are useful in treating or preventing cognitive disorders, such as Alzheimer's disease. The invention also encompasses pharmaceutical compositions comprising compounds of Formula I, methods of preparing compounds of formula I, and methods of treating cognitive disorders, such as Alzheimer's disease.

Abstract: Disclosed are compounds of the formula wherein the variables RN, RC, R1, R25, R2, and R3 are as defined herein. These compounds have activity as inhibitors of beta-secretase and are therefore useful in treating a variety of disorders such as Alzheimer's Disease.

Abstract: Disclosed are compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

Abstract: Human BACE polypeptides having modifications to the N-linked glycosylation sites including one or more of the following amino acid substitutions: S174I, N223A, N153Q and N354S. DNA sequences, vectors, and host cells for producing the polypeptides. Crystalline protein compositions formed from the purified polypeptides. Methods of screening for compounds that inhibit A? using the polypeptides.

Abstract: This invention provides methods useful in aiding in the diagnosis of Alzheimer's disease. The methods involve measuring the amount of amyloid-? peptide (x-?41) in the cerebrospinal fluid of a patient. High levels of the peptide generally are inconsistent with a diagnosis of Alzheimer's. Low levels of the peptide are consistent with the disease and, with other tests, can provide a positive diagnosis. Other methods involve measuring the amounts of both A?(x-?41) and tau. Low levels of A?(x-?41) and high levels of tau are a positive indicator of Alzheimer's disease, while high levels of A?(x-?41) and low levels of tau are a negative indication of Alzheimer's disease.

Abstract: The invention provides improved agents and methods for treatment of diseases associated with synucleinopathic diseases, including Lewy bodies of alpha-synuclein in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the Lewy body. The methods are particularly useful for prophylactic and therapeutic treatment of Parkinson's disease.

Abstract: The invention provides methods of treatment using humanized immunoglobulins that specifically bind to alpha-4 integrin. The methods are useful for treatment of asthma, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, transplant rejection, graft versus host disease, tumor metastasis, nephritis, atopic dermatitis, psoriasis, myocardial ischemia, and acute leukocyte mediated lung injury.

Abstract: The invention provides methods for detecting alpha-synuclein. The invention also identifies preferred epitopes of alpha synuclein for use in such detection, and provides antibodies specifically binding to such epitopes.

Abstract: The invention provides a novel human protein, FISH adaptor protein, involved in amyloid ?-protein-mediated cell death. Also provided are methods for modulating amyloid ?-protein-mediated cell death using agents that interfere with the activity of FISH adaptor protein.

Abstract: The invention provides improved agents and methods for treatment of diseases associated with synucleinopathic diseases, including Lewy bodies of alpha-synuclein in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the Lewy body. The methods are particularly useful for prophylactic and therapeutic treatment of Parkinson's disease.

Abstract: A stable aqueous pharmaceutical formulation comprising a therapeutically effective amount of an antibody, polysorbate 80, a buffer which inhibits polysorbate oxidation is described along with methods of making the preparation. Also described are formulations with high antibody concentrations which maintain fixed volumes and which may be used on patients of variable weight.