Alexion Pharmaceuticals, Inc.

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

Louis A Matis

Yi Wang

Scott A Rollins

John P Mueller

Russell P Rother

Mark James Evans

Stephen P Squinto

Steven H Nye

James A Wilkins

Eileen Elliott Mueller

Michael J Lenardo

Jeremy P Springhorn

Henry McFarland

Thomas C Thomas

Clara M Pelfrey

Eileen Mueller

Novel chimeric fusion proteins comprising immunodominant epitopes of GAD and insulin are provided. Also provided are immunomodulatory methods for the use of such proteins for both the prevention and treatment of Type 1 diabetes mellitus. The chimeric fusion proteins of the invention are useful in predicting risk of onset of Type 1 diabetes, determining prognosis of Type 1 diabetes patients early in disease progression, and in evaluating patients for suitability as recipients of transplants of pancreatic cells or tissues. The administration of the proteins of the invention in accordance with the immunomodulatory methods of the invention results in beneficial effects on disease development and severity in patients suffering from or predicted to be at risk of developing Type 1 diabetes, as well as on the outcome of transplants of pancreatic cells or tissues in Type 1 diabetes patients.

Chimeric proteins for diagnosis and treatment of diabetes

Novel chimeric fusion proteins comprising immunodominant epitopes of GAD and insulin are provided. Also provided are immunomodulatory methods for the use of such proteins for both the prevention and treatment of Type 1 diabetes mellitus. The chimeric fusion proteins of the invention are useful in predicting risk of onset of Type I diabetes, determining prognosis of Type 1 diabetes patients early in disease progression, and in evaluating patients for suitability as recipients of transplants of pancreatic cells or tissues. The administration of the proteins of the invention in accordance with the immunomodulatory methods of the invention results in beneficial effects on disease development and severity in patients suffering from or predicted to be at risk of developing Type 1 diabetes, as well as on the outcome of transplants of pancreatic cells or tissues in Type I diabetes patients.

Chimeric insulin-gad proteins for treating patients with type 1 diabetes or at risk of developing type 1 diabetes

The use of compounds that block complement component C5 or its active fragments C5and/or C5(such compounds collectively referred to as 'C5 blockers') to treat established joint inflammation (arthritis) is disclosed. Administration of such C5 blockers has been found to: 1) arrest and/or reduce inflammation in joints which are already inflamed, and 2) inhibit the spread of inflammation to unaffected joints.

Methods for the treatment of inflammatory joint disease

Compositions and methods are provided for the clinical assessment, diagnosis, and treatment of multiple sclerosis. The compositions of the invention are molecules related to the 21.5 kDa fetal isoform of human myelin basic protein, and include nucleic acids and polypeptides. The nucleic acid molecules of the invention are useful in the efficient production of modified and unmodified 21.5 kDa myelin basic protein polypeptides, such polypeptides being useful for assaying T cells for responsiveness to myelin basic protein epitopes. The polypeptides of the invention are also useful as therapeutic agents that act by inducing T cell responses, including apoptosis, as a means of treating multiple sclerosis.

Modified myelin basic protein molecules

The use of anti-C5 antibodies, e.g., monoclonal antibodies, to treat glomerulonephritis (GN) is disclosed. The administration of such antibodies at low dosage levels has been found to significantly reduce glomerular inflammation/enlargement and other pathologic conditions associated with GN. Also disclosed are anti-C5 antibodies and anti-C5 antibody-encoding nucleic acid molecules. These antibodies are useful in the treatment of GN and other inflammatory conditions involving pathologic activation of the complement system.

C5-specific antibodies for the treatment of inflammatory diseases

The use of anti-C5 antibodies, e.g., monoclonal antibodies, to treat glomerulonephritis (GN) is disclosed. The administration of such antibodies at low dosage levels has been found to significantly reduce glomerular inflammation/enlargement and other pathologic conditions associated with GN.

Use of antibodies specific to human complement component C5 for the

A porcine E-selectin protein, its amino acid sequence, the sequence of a cDNA encoding the protein, antibodies reactive with the protein, and methods for the use of these molecules are disclosed. The molecules are used to diagnose the rejection of xenotransplanted pig organs, as well as to prevent and treat such transplant rejection.

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Southport, CT, United States of America

Louis A Matis