The Brigham and Women's Hospital, Inc.

University of Southern California

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Bruce D Levy

Charles Nicholas Serhan

Nicos A Petasis

Michael S Singer

A method to determine the severity of a disease of chronic inflammation in a patient, comprising the steps of (1) collection or preparation of a bodily fluid, tissue or lavage and (2) measurement of ALX receptor ligands or ALX receptor expression in the fluid, tissue, or lavage, wherein the level of ALX receptor ligands predicts a clinical outcome or choice of treatment modality, is disclosed.

ALX receptor ligands define a biochemical endotype for inflammation-based diseases

The invention describes novel isolated, purified, 10,17-dihydroxy-docosahexaenoic acids, esters, derivatives and their preparation.

Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers

The present invention is generally drawn to novel isolated therapeutic agents, termed resolvins, generated from the interaction between a dietary omega-3 polyunsaturated fatty acid (PUFA) such as eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), cyclooxygenase-II (COX-2) and an analgesic, such as aspirin (ASA). Surprisingly, careful isolation of compounds generated from the combination of components in an appropriate environment provide di- and tri-hydroxy EPA or DHA compounds having unique structural and physiological properties. The present invention therefore provides for many new useful therapeutic di- or tri-hydroxy derivatives of EPA or DHA (resolvins) that diminish, prevent, or eliminate inflammation or PMN migration, for example. The present invention also provides methods of use, methods of preparation, and packaged pharmaceuticals for use as medicaments for the compounds disclosed throughout the specification.

Use of docasatrienes, resolvins, and their stable analogs in the treatment of airway diseases and asthma

Use of docosatrienes, resolvins, and their stable analogs in the treatment of airway diseases and asthma

The present invention is directed to devices, systems, and methods for monitoring inhaled drug usage to predict when an acute attack or exacerbation of a disease, such as a respiratory disease, is imminent. Instrumented inhalers that use modular designs with standard components are disclosed, as are systems for monitoring the instrumented inhalers. Also disclosed are methods for determining whether or not a patient's inhaled drug usage pattern indicates that an acute attack or disease exacerbation is imminent, and notifying appropriate medical personnel of any usage patterns indicative of an attack or disease exacerbation. If such an attack or exacerbation is imminent, additional therapeutic agents may be dispensed to the patient or other interventions made.

Instrumented metered-dose inhaler and methods for predicting disease exacerbations

(Neuro)protectin D1 (1OR,17S-dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid) and 15,16-dehydro-PD1 and their derivatives are useful in the treatment of airway inflammation, especially asthma.

Anti-inflammatory actions of neuroprotectin D1/protectin D1 and it's natural stereoisomers

The use of lipoxin analogs for the treatment or prevention of asthma and asthma related diseases is described. In particular, acetylenic lipoxin analogs are effective for the treatment and prevention of eosinophil recruitment involved with the inflammation processes associated with asthma, asthma like conditions, and lung injuries associated from airway inflammation or infection as brought about by leukocyte-mediated injury from within.

Method for treating airway hyper-responsiveness with lipoxin analogs

The present invention is generally drawn to novel isolated therapeutic agents, termed resolving, generated from the interaction between a dietary omega-3 polyunsaturated fatty acid (PUFA) such as eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), cyclooxygenase-II (COX-2) and an analgesic, such as aspirin (ASA). Surprisingly, careful isolation of compounds generated from the combination of components in an appropriate environment provide di- and tri-hydroxy EPA or DHA compounds having unique structural and physiological properties. The present invention therefore provides for many new useful therapeutic di- or tri-hydroxy derivatives of EPA or DHA (resolvins) that diminish, prevent, or eliminate inflammation or PMN migration, for example. The present invention also provides methods of use, methods of preparation, and packaged pharmaceuticals for use as medicaments for the compounds disclosed throughout the specification.

Use of docosatrienes, resolvins and their stable analogs in the treatment of airway diseases and asthma

The present invention is directed to presqualene diphosphate (PSDP) analogs having an active region of natural PSDP and a metabolic transformation region resistant to rapid intracellular inactivation in vivo. For example, PSDP and its stable analogs can inhibit neutrophil signal transduction events in cellular activation that result in the generation of active oxygen species, regulation of leukocyte adherence, both homotypic (leukocyte&mdash;leukocyte) or heterotypic adherence with leukocytes and epithelial cells of mucosal origin or endothelial cells of vascular origin. These analogs can also be used to regulate leukocyte-dependent tissue injury.

Screening methods for presqualene disphosphate analogs

The present invention is directed to presqualene diphosphate (PSDP) analogs having an active region of natural PSDP and a metabolic transformation region resistant to rapid intracellular inactivation in vivo. For example, PSDP and its stable analogs can inhibit neutrophil signal transduction events in cellular activation that result in the generation of active oxygen species, regulation of leukocyte adherence, both homotypic (leukocyte-leukocyte) or heterotypic adherence with leukocytes and epithelial cells of mucosal origin or endothelial cells of vascular origin. These analogs can also be used to regulate leukocyte-dependent tissue injury.

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West Roxbury, MA, United States of America

Bruce D Levy