Antibodies from Plants Protect Against Anthrax

BALTIMORE, MD - Scientists have produced, in tobacco plants, human antibodies that could be used to treat anthrax exposure. They report their findings today at the 2005 American Society for Microbiology Biodefense Research Meeting.

”The nature of bioterrorism is such that an aggressor is likely to strike at a time and place calculated to induce maximum terror through mass casualties. The unpredictable nature of such events compels us to develop cost-effective, highly stable medical countermeasures to enable authorities to treat individuals exposed to bioterror agents such as anthrax,” says Les Baillie of the Naval Medical Research Center. Dr. Baillie, who is also associated with the University of Maryland Biotechnology Institute, conducted his research in collaboration with Dr. Vidadi Yusibov, Director of the Fraunhofer USA Center for Molecular Biotechnology (CMB) in Newark, Delaware. Funding for this project at the Fraunhofer USA CMB was obtained through the efforts of a congressional delegation led by Delaware’s Senior Senator Joe Biden.

To create the “plantibodies,” Baillie and his colleagues first collected the cells that make antibodies from individuals who had been vaccinated against anthrax. Then genes that encode the antibody itself were inserted into a bacterium that transfers the gene into the plant cells. “The plant makes the antibody for you in a few days,” says Baillie.

The antibodies were then purified from leaves harvested from the infected plants and tested for their ability to protect mice against anthrax infection. The plant-produced antibodies were just as effective as the antibodies produced by human cells from immunized individuals.

The antibodies can be used either before exposure to prevent infection or after exposure as treatment.

”If you’ve been exposed to an agent, you want protection as soon as possible. Vaccination can take a very long time to build immunity. Antibodies give you immediate protection,” says Baillie. ”Plant-produced antibodies are also safer because there is no risk of contamination by human or animal pathogens, and plant viruses are not known to infect humans,” says Yusibov. ”It is an easy, inexpensive and, very stable system. If you’re looking for a way to stockpile a large amount of antibodies for a long periods of time, plant-produced antibodies are the answer,” says Baillie.

Anthrax antibodies are just the first step for Baillie and his collaborators. Plantibodies against the plague bacterium and botulism are also in development.

March 22, 2004 - Fraunhofer Gesellschaft publication

A short article in the monthly Fraunhofer Gesellschaft publication "Research
News" marked a significant milestone for our Fraunhofer USA Center in
Delaware (see Research News Topic 5 in January, "New Vaccines Harvested from
Plants", at http://www.fraunhofer.de/english/press/pi/index.html ). This
news story represents the first report describing Fraunhofer USA actitivies
to be selected for this publication, according to Dr. Dirk Polter, a member
of the Vorstand (Board of Directors) that guides the Gesellschaft (Society).
We at the Fraunhofer USA Center for Molecular Biotechnology are honored by
this recognition, and we are grateful to Professor Rainer Fischer, Director
of the Fraunhofer Institute for Molecular Biology and Applied Ecology, who
founded our Center and continues to support our activities.

January 15, 2004 - Integrated BioPharma

INTEGRATED BIOPHARMA ACQUIRES TECHNOLOGY
FROM THE FRAUNHOFER CENTER FOR MOLECULAR BIOTECHNOLOGY

HILLSIDE, NJ, Jan.13, 2004—Integrated BioPharma (AMEX:INB) announced today that it has acquired intellectual property developed by the Center for Molecular Biotechnology (CMB) of Fraunhofer USA, Inc. The agreement covers exclusive rights to proprietary technology and intellectual property in the area of expression, engineering, testing, production and validation of human therapeutic proteins in plants.

The Fraunhofer Center for Molecular Biotechnology has a suite of new technologies, including genetically engineered plant viruses for producing veterinary and human vaccines, therapeutic proteins, antibodies and industrial enzymes in plants. INB, through its wholly owned subsidiary NuCycle Therapy, Inc., has an ongoing collaboration with Fraunhofer to produce generic drugs, and in particular therapeutic proteins using CMB’s proprietary technology. “This agreement creates a partnership that will help to facilitate commercialization of the center’s research and development activities and to open new opportunities for Fraunhofer USA in U.S. and world biotech markets,” says Dr. W. Hartman of Fraunhofer USA.

The agreement between INB and CMB grants INB exclusive rights and eventual ownership of all of the intellectual property and proprietary know-how in the field of vaccine, therapeutic protein and antibody production for human use. The Agreement will result in cash and royalties paid to CMB by INB in exchange for broad rights to the technology.

“The agreement with The Center for Molecular Biotechnology significantly increases our portfolio of intellectual property in the use of plants for making high value-high impact products,” says E.Gerald Kay, CEO of INB. “This intellectual property provides us with an opportunity to develop generic drugs and entirely new therapeutic and nutraceutical products at low cost with high quality and higher safety standards.”

Through its biotech subsidiary, NuCycle Therapy, Inc., INB is developing cancer preventive compounds in transgenic plants. INB serves the nutraceutical, biotech and pharmaceutical industries.  Through several wholly owned subsidiaries, INB develops, manufactures and distributes more than 130 products worldwide.  Its recent acquisition of Paxis Pharmaceuticals, Inc., places the Company in the position to be a world leader in the production and sale of paclitaxel and related drugs.  Further information is available at www.iBioPharma.com.

January 14, 2004 - The Dow Chemical Company

Dow enters NIH research agreement to develop rapid vaccine production system

MIDLAND—(January 14, 2004)— The Dow Chemical Company has entered into a 4-year, $5.7 million cooperative research agreement from the National Institutes of Health (NIH) to apply new technology for rapid development of vaccines. Dow will subcontract with Fraunhofer USA Center for Molecular Biotechnology to co-develop the technology and with the University of Maryland to provide screening for efficacy.

NIH requested proposals for new vaccine technologies against infectious diseases, including biowarfare agents. Dow’s approach will be based on new plant viral particle technology, with vaccine protein production taking place on leaves of greenhouse-grown plants.

Speed of production is the most significant advantage according to Carolyn Fritz, Dow’s global business director for Industrial Biotechnology. “We anticipate that our plant technology will cut production time to 3 or 4 months, reduce cost, and produce effective and safe vaccines that can be delivered by capsule or nasal spray. This would be a big improvement over existing technology,” said Fritz.

Fraunhofer USA will be exploring complementary technology and will provide a highly developed plant virus platform system with a wide host range. “This plant-based vaccine system will reduce the risk of contamination by animal pathogens,” said Barry Marrs, Executive Director of Fraunhofer USA. “We have seen excellent results in preliminary animal testing.” The University of Maryland will perform pre-clinical testing.

About Fraunhofer USA

Fraunhofer USA Center for Molecular Biotechnology is part of the Fraunhofer Gesellschaft, the leading non-profit contract research organization in Europe, with annual revenues of one billion euros. Fraunhofer USA offers transient expression of proteins in plants for the production of vaccines or therapeutic proteins, such as antibodies and peptide hormones, and together with its parental Fraunhofer Institute for Molecular Biology and Applied Ecology, can provide a wide range of cutting-edge molecular biology services. For further information, visit the www.fraunhofer-cmb.org website.

About Dow

Dow is a leading science and technology company that provides innovative chemical, plastic and agricultural products and services to many essential consumer markets. With annual sales of $28 billion, Dow serves customers in more than 170 countries and a wide range of markets that are vital to human progress, including food, transportation, health and medicine, personal and home care, and building and construction, among others. Committed to the principles of Sustainable Development, Dow and its approximately 50,000 employees seek to balance economic, environmental and social responsibilities.

More information about Dow is available at the Dow web site at http://www.dow.com.  For further information, please contact Adrianne Proctor, Business Communications Manager, The Dow Chemical Company, on 989-636-5636; or Brian Mahoney of Gibbs & Soell Public Relations, on 212- 697-2600.

More information about Fraunhofer USA is available at www.fraunhofer-cmb.org. For further information, please contact Yvonne Wessel, Executive Assistant, Fraunhofer CMB, on 302-369-8292.

September 25, 2003 - Approved Appropriations Legislation

U.S. House and Senate Approved Appropriations Legislation -- Includes Funding for Fraunhofer Center for Molecular Biotechnology to Develop New Smallpox Vaccine.

Newark, DE (October 30, 2003) – The Delaware Delegation announced on September 25, 2003 that both the U.S. House and Senate approved legislation that funds key Department of Defense initiatives.  Included in this package is $3.5 million to help Fraunhofer Center for Molecular Biotechnology (FhCMB) develop a safer and less expensive smallpox vaccine using plant proteins.

The new vaccine will reduce the health risk of vaccinations, cost less to produce, and be produced more quickly than the current vaccine.  Vaccines are substances that prevent disease by stimulating specific immune responses.  Barry Marrs, Executive Director of FhCMB said, “We think that in 18 months, we can produce a vaccine candidate that is ready to begin clinical trials.  Using plant technology will make the vaccine safer because we won’t use animal tissue cultures which can transmit animal diseases to humans, and we won’t use viruses that could harm people”

The vaccine will be made in greenhouses. The new therapeutics will be manufactured by greenhouse growers in Delaware in partnership with pharmaceutical companies.   

The core platform technologies employed by Fraunhofer CMB are molecular farming and directed evolution. These are applied to vaccine development, therapeutic protein production and industrial enzyme development. FhCMB has assembled an experienced team of technologists and business professionals who push the boundaries of science to help improve global health, provide freedom from bioterrorism, and contribute to sustainable chemical manufacturing.

For additional information, visit the website at www.fraunhofer-cmb.org or contact Yvonne Wessel, Executive Assistant, 9 Innovation Way, Suite 200, Newark, DE 19711, Phone: 302.369.8292,  partnering@fraunhofer-cmb.org

September 11, 2003 - Chemical Heritage Foundation

Barry Marrs, Executive Director, Fraunhofer Center for Molecular Biotechnology, Speaks at Chemical Heritage Foundation

Newark, DE (October 30, 2002) – Barry Marrs, Executive Director, Fraunhofer Center for Molecular Biotechnology (FhCMB) was an invited speaker for the Chemical Heritage Foundation on September 11, 2003.  Dr. Marrs presented as part of the “Symposium on Partnering in Industrial Biotechnology,”

The symposium discussed new research in the production of bioplastics, biocatalysis, and other innovative materials, focusing on ways to create partnerships between traditional chemical companies and small biotech firms to further develop and add markets for new products.

The core platform technologies employed by Fraunhofer CMB are molecular farming and directed evolution. These are applied to vaccine development, therapeutic protein production and industrial enzyme development. FhCMB has assembled an experienced team of technologists and business professionals who push the boundaries of science to help improve global health, provide freedom from bioterrorism, and contribute to sustainable chemical manufacturing.

For additional information, visit the website at www.fraunhofer-cmb.org or contact Yvonne Wessel, Executive Assistant, 9 Innovation Way, Suite 200, Newark, DE 19711,  Phone: 302.369.8292,  partnering@fraunhofer-cmb.org

March 31, 2003 - Open House and Briefing

Council and Fraunhofer focus on cutting edge technology, job development, industry investment and potential partnership with Delaware farmers

Newark, DE (April 09, 2003) – Fraunhofer USA Center for Molecular Biotechnology (FhCMB) and the New Castle County Economic Development Council (NCCEDC) hosted an open house for legislators, business and community representatives on March 31, 2003 at the Delaware Technology Park in Newark, Delaware. More than eighty people attended this unique opportunity to emphasize the value of developing partnerships within state and federal governments, local organizations and businesses.

Michael Bowman, President and CEO of the Delaware Technology Park welcomed the attendees. Bowman reviewed the mission, partnership contributions, and opportunities for interfacing new technology companies with business and university strengths in providing a force for economic development in Delaware.

Dale Ervin, Director of the New Castle County Economic Development Council, explained that the council and Fraunhofer CMB provide unique development initiatives to New Castle County. Ervin stated  “Everybody in the country is trying to attract biotech companies, but I think we can offer several advantages – including the fact that Fraunhofer USA chose the Delaware Technology Park in Newark as the site of their first biotechnology research center in the United States.” 

Fraunhofer CMB’s presence in Delaware will help attract “clusters” of other biotechnology companies to Delaware and our region. This will bring biotech workers, build biotech businesses that fit Delaware, and present opportunities for business growth relating to biotechnology needs and development.  Fraunhofer CMB is building partnerships with Delaware farmers to develop molecular farming, offering cash crops in therapeutics, vaccines and industrial enzymes. In addition, new international business opportunities are being developed.

Dr. Barry Marrs, Executive Director of Fraunhofer CMB said, “The open house and briefing was a great way to bring diverse groups together to consider the economic possibilities and partnerships that will foster economic growth in our near future.”

The core platform technologies employed by Fraunhofer CMB are molecular farming and directed evolution. These are applied to vaccine development, therapeutic protein production and industrial enzyme development. FhCMB helps its partners make protein products that are safer and more cost effective than those made with alternative technologies. FhCMB has assembled an experienced team of technologists and business professionals who push the boundaries of science to help improve global health, provide freedom from bioterrorism, and contribute to sustainable chemical manufacturing.

FhCMB’s mission is to promote partnerships with business, academia, and government agencies to provide rapid, low-cost and safe production of valuable proteins and enzymes that will enhance the quality of life world-wide.

February 10, 2003 - Fraunhofer Molecular Farming Comm. Meets

Fraunhofer Molecular Farming Advisory Committee Meets

On 10 February, the Fraunhofer Molecular Farming Advisory Committee held its first meeting at the Conference Center of the Delaware Department of Agriculture in Dover, Delaware. The meeting was organized jointly with Mike Scuse, the Secretary of Agriculture and Jack Tarburton, Director of Business Development for the Delaware Economic Development Office.

The following organizations were represented: the University of Delaware Extension Service, The Commonwealth Group, AdvanTek, Farmer’s First Services, the Chesapeake Fields Institute, Perdue Farms, Senator Carper’s office, DDA, DEDO and Fraunhofer USA.  

The purpose of the meeting was to examine business models and regulatory issues related to this plan. Subcommittees of the Fraunhofer Molecular Farming Advisory Committee will study each of these areas, and report back to the larger group. We believe Delaware can carve a niche for itself in the competitive biotech marketplace around Molecular Farming.

Molecular farming is the production of proteins and related molecules in plants. It is a form of biotech that is uniquely suited to Delaware’s economic infrastructure, because it brings together greenhouse growers and pharmaceutical companies and field crop farming and chemical companies. 

The pharmaceutical industry needs safer, cheaper ways of manufacturing protein-based therapeutics and vaccines. Current state-of-the-art manufacturing for therapeutics, such as monoclonal antibodies (MAb), involves significant risk of contamination by animal pathogens, such as viruses and prions, and it is capital intensive. Each new MAb manufacturing facility costs about $500 million, and only one type of MAb can be made at any time according to FDA regulations. Production of these exciting new therapeutic proteins in plants would avoid a significant part of the capital expense, and it avoids the animal tissues that are the sources of many worrisome pathogens.

 Plant-virus-based vaccine development builds on the cost and safety advantages described above, but it also offers a highly versatile and speedy way of making potent vaccine candidates. Current vaccines, especially those against bioweapons like smallpox or anthrax, represent very old-fashioned technologies. They are not safe enough for widespread use, because they actually expose the recipient to potentially harmful pathogens or toxins. Some people succumb to these vaccines, but most of the survivors have strong, broad immunity. These vaccines were developed before the era of biotechnology, and safer vaccines against some diseases have subsequently been invented by using subunits of pathogen proteins. However, subunit vaccines were seldom as effective as their cruder predecessors, because they only stimulated an immune response to one or very few targets. By making vaccines based on plant viruses, we can now put multiple targets into highly immunogenic vaccine particles, thus promising both safety and efficacy. We can do this very rapidly, which should discourage enemies from engaging in a bioweapons arms race. Low-cost vaccines made in plants are also of obvious interest to animal growers.

We propose to produce vaccines and therapeutics in greenhouses, using host plants and engineered plant viruses. The greenhouses will provide controlled production conditions and prevent movement of materials in or out of the system. Subsequent purification and product stabilization would be similar to current pharmaceutical manufacturing methodology. Greenhouse growers would need to work as part of the pharmaceutical manufacturing process.

Low-cost protein manufacture is even more critical in the area of industrial biocatalysis: making chemicals and materials using biochemical catalysts. Industrial biocatalysis could account for as much as 30% of the revenues of the chemical industry in the near future, within 10 years by one estimate (McKinsey Quarterly, 2000). One key factor in this market penetration is the cost of industrial enzymes. The current fermentation-based processes for producing enzymes are capital intensive, and the lowest cost industrial enzymes cost about $10/lb (and most are more than $20/lb). Plant protein from field crops costs about $0.10 to 0.20/lb. The technologies of molecular farming can be used to produce industrial enzymes in plants at costs that are expected to easily match the lowest fermentatively produced enzymes, and much lower costs should be attainable. This will accelerate the biochemical transformation of a large part of the chemical industry. Furthermore, biotech-based chemical manufacturing has been demonstrated to be significantly cleaner than the chemical processes that they have displaced.

Making conventional assumptions about yield and enzyme activity, we can estimate that about 500 acres would be required to produce enzyme for a hypothetical commodity chemical with sales of 100,000 tons per year, so this is a Delaware scale agricultural opportunity. On the greenhouse/therapeutics side, only 50 acres would be required to produce all the MAb’s sold in 2002 (1000 kg, worth $3 billion).

Barry L. Marrs

Executive Director

Fraunhofer Center for Molecular Biotechnology

October 15, 2002 - Awarded Diabetes Research Project

FOR IMMEDIATE RELEASE          

Contact:  Fraunhofer Center  for Molecular  Biotechnology (FhCMB)          

               Yvonne Wessel       (302) 369-1708

Fraunhofer Center for Molecular Biotechnology

Awarded Diabetes Research Project

Newark, DE (October 15, 2002) – Fraunhofer Center for Molecular Biotechnolgy (FhCMB) has been awarded a contract from the Delaware Health Care Commission for preparing diagnostic materials to conduct initial trials for developing a screening procedure for early detection of type I or juvenile diabetes. FhCMB will work collaboratively with Dr. Abner L. Notkins, Chief of the Experimental Medicine Section in the Oral Infection and Immunity Branch at the National Institutes of Health.

The Commission is working in collaboration with the Delaware Division of Public Health Diabetes to fight diabetes with support from the Delaware Health Fund.

In the 1980’s researchers discovered that individuals with type 1 diabetes produce antibodies against at least three proteins that are normally found in all individuals, i.e., insulin, glutamic acid decarboxylase (GAD) and IA-2 protein. Autoantibodies to the IA -2 protein are found in 50-75% of type 1 diabetics prior to onset of disease – the appearance of these autoantibodies  occurs years ahead of onset of the classical symptoms associated with type 1 diabetes. Measurement of these antibodies can be useful in assisting physicians with the prediction, diagnosis and management of patients with diabetes.

“Addressing the high rate of diabetes in Delaware is a priority of the Delaware Health Care Commission,” said Lt. Governor John C. Carney Jr., the Commission’s chair.  “We have focused many of our efforts on screening and education and getting people at risk into a doctor’s care.  The work being done by Fraunhofer and NIH holds the potential for identifying people with Type 1 diabetes much sooner.”

Diagnostic tests currently use radioactive, human recombinant protein antigen that is highly reliable. However this assay is not practical for screening large populations due to the limited availability of the human recombinant antigen and logistical problems related to using radioactivity. Executive Director Dr. Barry Marrs stated, “We will use cutting edge technology that utilizes whole plants and a unique recombinant protein expression system derived from plant viruses to produce the protein antigen for use in the diagnostic screening for type 1 diabetes. This new generation system ensures high yields with characteristics similar in nature to those found in the authentic human protein.”

Fraunhofer Center for Molecular Biotechnology is a not-for-profit contract research organization, developing and applying plant science for the production of high valuable proteins. Using the platform of Transient Gene Expression (TGE) provides excellent protein yields in a short time. FhCMB’s mission is to promote partnerships with business, academia, and government agencies to provide rapid, low-cost and safe production of valuable proteins and enzymes that will enhance the quality of life world-wide.

April 4, 2002 - Tech Trends 2002

February 23, 2002-March 2, 2002 - Pursuing Partnership with Taiwan

The Governer of Delaware, Ruth Ann Minner and the Director of the Delaware Economic Development Office (DEDO), John Wik were joined on a business mission to Taiwan by Barry Marrs, Executive Director of Fraunhofer Center for Molecular Biotechnology in late February. The purpose was to pursue business partnership opportunities for Delaware including the biotechnology field which was represented by Dr. Marrs. Dr. Marrs is returning to Taiwan with Scientific Director, Vidadi Yusibov and a contingent of representatives from DEDO and other Delaware businesses to develop strategies for international business relationships.

Dr. Barry Marrs with Governor Minner and other business and government leaders meeting with their counterparts in Taiwan

November 7, 2001 - Fraunhofer Devises Anti-Bioterrorism Strategy