Promega Corporation

Columbia University

Uwm Research Foundation, Inc.

Ophidian Pharmaceuticals, Inc.

Ochidian Pharmaceuticals, Inc.

Avaxia Biologics, Inc.

Douglas C Stafford

John A Kink

James M Cook

Barbara S Fox

Alexander E Arnold

Katherine L Worledge

Charles W Emala

Michael Rajesh Stephen

Guanguan Li

Bruce S Thalley

Gloria Forkuo

Rajwana Jahan

Revathi Kodali

Sean B Carroll

Charles Vernon Pugh

Mohammed Saleh Shekhani

Margaret B Van Boldrik

Joseph R Firca

Nisha V Padhye

Robert W Schatz

Nicholas Panasik, Jr

George Gallos

The present invention describes substituted benzo[f]imidazo[1,5-a][1,4]diazepines of the formula (I): wherein R, R, R, R, and X are as disclosed herein. These compounds target alpha-4 and alpha-5 GABAa receptors and are useful for the treatment of airway hyperresponsiveness and inflammation in asthma.

Substituted benzo[f]imidazo[1,5-a][1,4]diazepines as GABA(a) receptor modulators

Substituted benzo[f]imidazo[1,5-&#x3b1;][1,4]diazepines of formula (I') target alpha-4 and alpha-5 GABAreceptors for use in the treatment of airway hyperresponsiveness and inflammation in asthma. Compounds selectively partition to the peripheral compartment and have reduced CNS effects. 

Novel methods of treating inflammation and airway constriction using GABAergic compounds with reduced benzo-diazepine-like CNS activity are provided. Novel compounds which selectively target alpha-4 and alpha-5 GABAreceptors and methods of using those compounds to treat bronchoconstriction and inflammation are provided herein.

GABAA agonists and methods of using to control airway hyperresponsiveness and inflammation in asthma

Methods are described for treating inflammatory bowel disease in animals, including humans. Specific avian polyclonal antibodies directed to proinflammatory cytokines (such as IL-6 and TNF) are shown to have a beneficial effect in animal models predictive of human therapy for the treatment of colitis, including Crohn's disease.

Antibodies to cytokines in the prevention and treatment of inflammatory bowel disease

Effective antitoxins are demonstrated for prophylactic or causal immunotherapy. A method of generating antitoxin composed of highly-pure antibodies is described as an important defense against naturally-occurring plant and/or bacterial toxins.

Antitoxins and methods for making antitoxins

Compositions and methods are described for preventing and treating sepsis in humans and other animals. Surgical patients, low birth weight infants, burn and trauma victims, as well as other individuals at risk can be treated prophylactically. Methods for treating acute infections with advantages over current therapeutic approaches are provided.

Polymyxin B conjugates

Methods are described for treating inflammatory bowel disease in animals, including humans. Specific avian polyclonal antibodies directed to TNF are shown to have a beneficial effect in animal models predictive of human therapy for the treatment of colitis.

Prevention and treatment of inflammatory bowel disease

The prevention and treatment of autoimmune disease in humans (as well as other animals) is described through the use of ligands directed to cytokines. Antibodies and receptors to the proinflammatory cytokines IL-2, TNF, IL-12 and IFN-gamma are employed (along with other ligands to such cytokines). Such ligands administered luminally are effective (as demonstrated in two experimental models of autoimmune disease) at delaying the onset of autoimune disease.

Prevention and treatment of autoimmune disease with luminally administered polyclonal antibodies

The present investion provides vaccines capable of protecting a vaccinated recipient from the morbidity and mortality associated with,infection. These vaccines are produced with portions of,Toxin A, or Toxin B, or both. These portions of Toxins A and B may be fusion proteins with at least one non-toxin protein sequence, and may also be soluble and substantially endotoxin-free. These vaccines are useful for administration to humans and other animals at risk of exposure to,toxins.

Vaccine and antitoxin for the treatment of C. difficile disease

The present provides neutralizing antitoxin directed against C. difficile toxins. These antitoxins are produced in arian species using soluble recombinant C. difficile toxin proteins. The avian antitoxins are designed so as to be orally administrable in therapeutic amounts and may be in any form (i.e., as a solid or in aqueous solution). Solid forms of the antitoxin may comprise an enteric coating. These antitoxins are useful in the treatment of humans and other animals intoxicated with at least one bacterial toxin. The invention further provides vaccines capable of protecting a vaccinated recipient from the morbidity and mortality associated with C. difficile infection. These vaccines are useful for administration to humans and other animals at risk of exposure to C. difficile toxins.

Growing community of inventors

Madison, WI, United States of America

Douglas C Stafford