Abstract: A method for improving clinical outcome in focal ischemic stroke in a mammal by increasing cerebral blood flow and/or reducing infarct size is described which involves administering an effective amount of an anti-CD18 antibody to the mammal, in the absence of removal of the arterial obstruction.

Abstract: The present invention relates to amino acid sequence variants of human DNase I that have increased DNA-hydrolytic activity. The invention provides nucleic acid sequences encoding such hyperactive variants, thereby enabling the production of these variants in quantities sufficient for clinical use. The invention also relates to pharmaceutical compositions and therapeutic uses of hyperactive-variants of human DNase I.

Abstract: The invention provides novel inhibitors of IAP that are useful as a therapeutic agents for treating malignancies where the compounds have the general formula I: X1 and X2 are independently O or S; L is a bond or —C(X3)—, —C(X3)NR12, —C(X3)O— wherein X3 is O or S and R12 is H or R1; R1 is alkyl, a carbocycle, carbocycle-substituted alkyl, a heterocycle or heterocycle-substituted alkyl, wherein each is optionally substituted with halogen, hydroxyl, mercapto, carboxyl, alkyl, haloalkyl, alkoxy, alkylsulfonyl, amino, nitro, aryl and heteroaryl; R2 is alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, a heterocycle or heterocyclylalkyl; R3 is H or alkyl; R4 and R4? are independently H, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, or heteroaralkyl wherein each is optionally substituted with halogen, hydroxyl, mercapto, carboxyl, alkyl, alkoxy, amino and nitro; R5, and R5? are each independently H or alkyl; R6 is H or alkyl; and salts and solvates thereof.

Abstract: DNA isolates coding for human DNase and methods of obtaining such DNA are provided, together with expression systems for recombinant production of human DNase useful in therapeutic or diagnostic compositions.

Abstract: Provided are compounds of formula (I) wherein A, Q, W, X, Y, Z, R1 to R4, m and n are as defined herein. Compounds of the invention bind to ?4 integrin receptors and thereby inhibit binding of ligands for ?4 integrins which is useful for prophylactic and/or therapeutic treatment of diseases and conditions associated with ?4 integrins or their ligands.

Abstract: The invention provides novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies where the compounds have the general formula I: wherein X, Y, A, R1, R2, R3, R4, R4?, R5, R5?, R6 and R6? are as described herein.

Abstract: A compaction assay measuring the viscoelasticity of sputum samples of patients subject to respiratory disease is provided. This assay is useful in determining the therapeutic efficacy of DNase, antibiotic and other respiratory disease treatments in improving lung function.

Abstract: The invention provides novel thiocarbamate alpha-4 inhibitors of the general formula (I) that are resistant to metabolism having improved half-life and/or clearance properties compared to corresponding carbamate compounds wherein substituents L, X, Y, Z, R1–R4, m, n, o and p are as defined herein. Also provided are compositions comprising compounds of formula I and a carrier, diluent or excipient as well as methods of treating a disease or condition mediated by the binding interaction of alpha-4 integrins to its ligands such as inflammatory diseases.

Abstract: Halo-alkoxycarbonyl derivatives are provided as prodrug moieties for pharmaceutical agents containing a basic or polar nitrogen containing functionality. The prodrugs are provided as pharmaceutical compositions as well as in methods of treatment.

Abstract: The present invention comprises growth hormone releasing peptides/peptidomimetics (GHRP) capable of causing release of growth hormone from the pituitary. Compositions containing the GHRP's of this invention are used to promote growth in mammals either alone or in combination with other growth promoting compounds, especially IGF-1. In a method of this invention GHRP's in combination with IGF-1 are used to treat Type II diabetes.

Abstract: The present invention relates to the use of calcium ion and/or sugars to minimize thermal aggregation of DNase and to the use of calcium ion to stabilize liquid solutions of DNase, the solutions having a pH of less than neutral. DNase is the active pharmaceutical principle and the solutions may contain other pharmaceutically acceptable excipients making them suitable for pharmaceutical administration. In the first instance, calcium ion/sugar minimizes the effects of thermal aggregation in the solution. In the second aspect, calcium ion stabilizes the lower pH solutions from protein precipitation.

Abstract: The invention provides novel thiocarbamate alpha-4 inhibitors of the general formula (I) that are resistant to metabolism having improved half-life and/or clearance properties compared to corresponding carbamate compounds wherein substituents L, X, Y, Z, R1–R4, m, n, o and p are as defined herein. Also provided are compositions comprising compounds of formula I and a carrier, diluent or excipient as well as methods of treating a disease or condition mediated by the binding interaction of alpha-4 integrins to its ligands such as inflammatory diseases.

Abstract: Provided are compounds of formula (I) wherein A, Q, W, X, Y, Z, R1 to R4, m and n are as defined herein. Compounds of the invention bind to ?4 integrin receptors and thereby inhibit binding of ligands for ?4 integrins which is useful for prophylactic and/or therapeutic treatment of diseases and conditions associated with ?4 integrins or their ligands.

Abstract: The present invention provides the identification and characterization of two components of a recombinant preparation of DNase. These components are the purified deamidated and non-deamidated human DNases. Taught herein are the separation of these components and the use of the non-deamidated species as a pharmaceutical per se, and in particular in compositions wherein the species is disclosed within a plastic vial, for use in administering to patients suffering from pulmonary distress.

Abstract: Compounds having the structure shown below are useful to inhibit serine protease enzymes, such as TF/factor VIIa, factor Xa, thrombin and kallikrein. These compounds may be used in methods of preventing and/or treating clotting disorders.

Abstract: The invention relates to novel compounds having formula (I) wherein Cy, X, Y, L and R1-6 are as defined herein. The compounds bind CD11/CD18 adhesion receptors such as Lymphocyte Function-associated Antigen-1 (LFA-1) and are therefore useful for treating disorders mediated by LFA-1 such as inflammation and autoimmune diseases.

Abstract: Inhibitors of serine proteases are provided having formula (I) wherein X, R1, R2, R3, R4 and R5 are as defined herein. In particular, the compounds bind to factor VIIa, tissue factor/factor Xa complex, thrombin, trypsin, plasmin and kallikrein and have anticoagulant activity. Pharmaceutical compositions comprising the compounds are useful for inhibiting the formation of veinous and/or arterial thrombi in vivo.

Abstract: Provided are compounds of formula (I) wherein A, Q, W, X, Y, Z, R1 to R4, m and n are as defined herein. Compounds of the invention bind to &agr;4 integrin receptors and thereby inhibit binding of ligands for &agr;4 integrins which is useful for prophylactic and/or therapeutic treatment of diseases and conditions associated with &agr;4 integrins or their ligands.

Abstract: The invention relates to novel compounds having formula (I) wherein Cy, X, Y, L and R1-6 are as defined herein. The compounds bind CD11/CD18 adhesion receptors such as Lymphocyte Function-associated Antigen-1 (LFA-1) and are therefore useful for treating disorders mediated by LFA-1 such as inflammation and autoimmune diseases.

Abstract: This invention relates to a novel human deoxyribonuclease, referred to as human DNase II. The invention provides nucleic acid sequences encoding human DNase II, thereby enabling the production of human DNase II by recombinant DNA methods in quantities sufficient for clinical use. The invention also relates to pharmaceutical compositions and diagnostic and therapeutic uses of human DNase II.