Critical Therapeutics is Awarded U.S. Patents for Methods to Diagnose and Treat Inflammatory Disease.

Business Editors & Health/Medical Writers

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Dec. 2, 2002

Cambridge company establishes strong portfolio of patents

covering new disease mediator associated with illnesses

including sepsis and rheumatoid arthritis

Critical Therapeutics, Inc. (CTI) today announced that it has been awarded three U.S. patents covering methods to diagnose, predict the severity of and treat serious inflammatory diseases including sepsis, a bloodstream infection that is the nation's tenth leading cause of death.

The patents, which were issued by the United States Patent and Trademark Office, relate to a protein within the High Mobility Group (HMGB) family of nuclear proteins. This protein, HMGB1, has been identified as an important mediator of the body's inflammatory response to infection, ischemia and injury. Increased levels of HMGB1 have been implicated in sepsis and other major inflammatory diseases including rheumatoid arthritis.

"Therapies targeting HMGB1 can potentially afford significant benefits to critically ill patients stricken with serious systemic inflammatory disease," said Walter Newman, Ph.D., CTI's chief scientific officer. "As a result, these patents give CTI a strong intellectual property foothold as we move forward with discovery and development initiatives related to this protein."

U.S. patent number 6,468,533 B1, "Antagonists of HMGB1 for Treating Inflammatory Conditions," provides a pharmaceutical composition comprised of an antibody that binds HMGB1. The antibody, in turn, is believed to dramatically reduce the "cytokine cascade," or overproduction, of HMGB1 that triggers sepsis and other inflammatory diseases.

U.S. patent number 6,448,223 B1, "Antagonists of HMGB1 for Treating Inflammatory Conditions," covers a method of administering antibodies to treat the inflammatory illness. These antibodies neutralize the pro-inflammatory effect of HMGB1.

U.S. patent number 6,303,321 B1, "Methods of Diagnosing Sepsis," provides for a method to diagnose the disease and to predict its severity by measuring the concentration of HMGB1 in the serum.

The Society of Critical Care Medicine defines sepsis as an overwhelming infection that causes heart, blood vessel and cell dysfunction.

High levels of HMGB1 have been found in the serum of patients with critical illness and sepsis. (Wang et al., 1999; Ombrellino et al, 1999) and in the synovial fluid of patients with rheumatoid arthritis (Kokkola et al., 2002). In animal models, neutralization of the protein has been associated with improvement in collagen-induced arthritis and increased survival in endotoxemia and sepsis, even when treatment begins after the onset of disease.

According to the Society of Critical Care Medicine, severe sepsis strikes approximately 750,000 people in the U.S. annually. The disease, which is expected to cause 215,000 deaths in the U.S. this year, is the leading cause of death in the non-coronary intensive care unit.

About Critical Therapeutics

Critical Therapeutics, based in Cambridge, Massachusetts, is a privately held biotechnology company focused on critical care medicine. CTI's mission is the discovery and clinical development of novel therapies for the treatment of acute trauma, cardiopulmonary disease and infectious and inflammatory illness.

Glossary of terms(a)

Cytokine cascade (systemic inflammatory response syndrome): A progressive state of systemic inflammation characterized by a white blood cell count greater than 12,000/mm3 or less than 4000/mm3, temperature greater than 38 degrees Celsius or less than 36 degrees Celsius, tachycardia, tachypnea, and decreased blood carbon dioxide levels.

Endotoxemia: A systemic inflammatory response to infection, in which there is fever or hypothermia, tachycardia, tachypnea, and evidence of inadequate blood flow to internal organs.

Ischemia: A temporary deficiency of blood flow to an organ or tissue. The deficiency may be caused by diminished blood flow either through a regional artery or throughout the circulation.

Sepsis: A systemic inflammatory response to infection, in which there is fever or hypothermia, tachycardia, tachypnea, and evidence of inadequate blood flow to internal organs.

Serum: The watery portion of the blood after coagulation 

(a)(Taber's Cyclopedic Medical Dictionary)