A Novel Cystic Fibrosis Therapeutic: Process Development

Period of Performance: 09/10/2000 - 03/09/2002


Phase 1 SBIR

Recipient Firm

Immune Disease Institute, Inc.
Boston, MA 02115
Principal Investigator


DESCRIPTION (Adapted from the Investigator's Abstract): Cystic fibrosis (CF) is an inherited ion channel defect affecting 23,000 children and young adults in the U.S. The major cause of suffering and early death of CF patients is lung disease, i.e., a destructive process of chronic airway inflammation and recurring infections. Neutrophils are continually present in the lungs of CF patients, and neutrophil proteases, particularly elastase, are major agents of inflammatory damage. The overall goal of the project is to bring a clinical practice a novel therapy to block neutrophil proteases and intervene in the destructive inflammatory cycle by aerosol administration of recombinant Monocyte/Neutrophil Elastase Inhibitor (rM/NEI). M/NEI, a naturally occurring anti-inflammatory agent, is an efficient and specific inhibitor of all three major neutrophil proteases. Efficacy of rM/NEI was demonstrated in preclinical studies with insect cell-derived rM/NEI. The proposed Phase I study will examine whether the Pichai system can support commercial production of rM/NEI. Specific aims will: 1) Optimize rM/NEI expression in small scale Pichia cultures; 2) Develop assays: 3) Establish a scheme to purify rM/NEI from Pichia-cell lysates; and 4) Generate a mid-size batch (grams) of research grade rM/NEI. In Phase II, the PI will produce GMP grade rM/NEI in Pichia for clinical trials of efficacy in CF patients. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE