Sponsor: Revivicor, Inc.

• Project duration: 10/1/2004 - 9/30/2007
• Total project (est.): $2,488,727
• Requested ATP funds: $1,843,502

Infectious disease is the leading health problem worldwide. In addition to the spread of new, emergent diseases, a severe and growing problem is the increase in antibiotic-resistant strains. More than 30 percent of infections caused by streptococcus pneumonia, the major cause of bacterial pneumonia, meningitis and ear infections, are now resistant to penicillin. In addition, most viruses, including influenza, HIV and hepatitis cannot be treated by antibiotics, nor can the majority of fungal and parasitic inflections, including malaria. To address this serious and worsening problem, Revivicor proposes an ambitious project to develop transgenic cloned pigs capable of producing fully human polyclonal antibodies, in place of their native porcine immunoglobulins (Igs). The company, which pioneered the development of transgenic pigs for therapeutic purposes, proposes a gene modification and cloning program to replace the native immunoglobulin genes in the pigs with large strands of human DNA containing human Ig genes. This involves the complete replacement of very large segments of DNA - in excess of a million base pairs - far larger than any previous gene transfer with pigs. The project involves a complex, multi-stage process culminating in a combination of cloning and conventional mating to produce homozygous "Immunopigs" that produce polyclonal antibodies with fully human protein sequences. Because the DNA transfer would include all the Ig genes, the pigs would produce broad-spectrum antibodies, rather than single, targeted monoclonal antibodies. Any immunogen could be used to induce the production of antibodies. Since a pig can provide up to 50 liters of blood per year, from which one could obtain large amounts of a specific antibody, a small herd in principle could supply the needs of the entire therapeutic market. The antibodies produced this way should be therapeutically superior to antibiotics, and unlike antibiotics also would be effective against viral and fungal infections as well as venoms and toxins. The project addresses a $5 billion market and a significant unmet clinical need in the prevention of infectious disease, including for patients that are immunosuppressed (such as transplant patients), those with antibiotic-resistant infections, and those with autoimmune disorders. The technology also could have broad-based benefits beyond infectious disease, including the production of anti-Rh factor, treatment of autoimmune disease, diagnostics and cancer treatments. It also has significant potential for producing biowarfare counteragents. It would create a new agri-medicine and protein production and purification infrastructure. ATP support is necessary for the project to go forward because Revivicor is a small company and has been unable to secure other funding for the work because of the complexity of the process and the high-risk challenge of completely replacing very large segments of DNA in a higher animal.

For project information:

David Ayares, PhD, (540) 961-5559
dayares@revivicor.com

ATP Project Manager

Gradimir Georgevich, 301-975-2180
gradimir.georgevich@nist.gov

This is the fact sheet for this project as it was announced on September 28, 2004.
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