June 23, 2011 – Ventria announced that Company representatives will attend the Annual BIO Convention in Washington DC, June 27^th-30^th, 2011.  This is the largest international event for the biotechnology industry with over 15,000 attendees from 60 countries. 

Ventria will be exhibiting as part of the Kansas Pavilion at booth number 4637 and will be participating in BIO’s One-on-One partnering sessions.  

“Ventria is excited to be joining the biotech industry in Washington, DC. The innovative spirit of the biotech industry thrives when we collaborate and create win-win relationships that deliver better healthcare outcomes for patients around the world,” said Scott Deeter, President and CEO, Ventria Bioscience. 

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June 2, 2011 – Ventria Bioscience will showcase its ExpressTec^TM biomanufacturing technology at the 4^th International Plant-Based Vaccines & Antibodies (PBVA) Conference.  Scott Deeter, President and CEO, will present “High Yielding and Scalable Plant-based Recombinant Protein Production in Monocots,” as part of the Facilities and Production plenary session on Friday, June 10^th, 2011.  The PBVA conference provides an international forum for the medical, veterinary, and plant biotechnology research communities to discuss the current state-of-the art in plant-based biologics technology and research and development related to new product development.

 At the conference, Ventria Bioscience will discuss its experience scaling up a plant-based cGMP manufacturing system to commercial scale exceeding 1,000 kilograms of recombinant protein.  To accomplish this scale, Ventria employs its proprietary recombinant protein manufacturing technology called ExpressTec^TM.  ExpressTec^TM provides a safe, affordable, and sustainable manufacturing platform that produces target protein yields more than ten times higher than alternative systems.

 “Ventria is the first company to commercialize recombinant proteins derived from a plant-based manufacturing system and has proven this technology at large scale,” said Scott Deeter, President and CEO for Ventria Bioscience. “ExpressTec^TM achieves protein yields, cost-effectiveness and safety advantages that are the foundation of a portfolio of products that were previously not available to a global customer base.” 

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Expression, purification, and characterization of recombinant human transferrin from rice (Oryza sativa L.).

Zhang D, Nandi S, Bryan P, Pettit S, Nguyen D, Santos MA, Huang N.

Transferrin is an essential ingredient used in cell culture media due to its crucial role in regulating cellular iron uptake, transport, and utilization. It is also a promising drug carrier used to increase a drug’s therapeutic index via the unique transferrin receptor-mediated endocytosis pathway. Due to the high risk of contamination with blood-borne pathogens from the use of human or animal plasma-derived transferrin, recombinant transferrin is preferred for use as a replacement for native transferrin. We expressed recombinant human transferrin in rice (Oryza sativa L.) at a high level of 1% seed dry weight (10 g/kg). The recombinant human transferrin was able to be extracted with saline buffers and then purified by a one step anion exchange chromatographic process to greater than 95% purity. The rice-derived recombinant human transferrin was shown to be not only structurally similar to the native human transferrin, but also functionally the same as native transferrin in terms of reversible iron binding and promoting cell growth and productivity. These results indicate that rice-derived recombinant human transferrin should be a safe and low cost alternative to human or animal plasma-derived transferrin for use in cell culture-based biopharmaceutical production of protein therapeutics and vaccines.

PubMed Link – Click Here

A rice-derived recombinant human lactoferrin stimulates fibroblast proliferation, migration, and sustains cell survival.

Tang L, Cui T, Wu JJ, Liu-Mares W, Huang N, Li J.

Human lactoferrin (hLF), a glycoprotein of the transferrin family, has recently been shown to stimulate wound repair through its antimicrobial effect and inflammation modulation. A recent study with several non-skin cell lines indicated that hLF may also have a stimulatory effect on cell proliferation. To explore the role of hLF in wound healing, we used recombinant human lactoferrin (holo-rhLF), derived from transgenic rice, to examine the effects of holo-rhLF on cell proliferation, migration, attachment, and survival in a human primary skin fibroblast culture system. This study revealed that holo-rhLF not only significantly stimulates fibroblast proliferation but also has synergistic effects with fibroblast growth factor-2 and antagonistic effects with transforming growth factor-beta1 on cell proliferation. Furthermore, using a chamber migration assay, our results demonstrate that holo-rhLF promotes fibroblast migration in a dosage-dependent manner. More importantly, holo-rhLF significantly increased cell viability and protected cells from death when they were stressed by either serum depletion or 12-O-tetradecanoylphorbol-13-acetate exposure. No significant effect was observed on cell attachment. In conclusion, these findings reveal the multiple functions of holo-rhLF in human skin fibroblasts and indicate its potential application in wound therapy by enhancing cell proliferation and migration as well as protecting cells from apoptosis.

PubMed Link – Click Here

28-Day repeated dose oral toxicity of recombinant human apo-lactoferrin or recombinant human lysozyme in rats.

Cerven D, DeGeorge G, Bethell D.

Lactoferrin and lysozyme are important proteins of the human innate immune system. These proteins are found in breast milk and have been associated with improved infant health. Recombinant human apo-lactoferrin (apo-rhLF), 1800 and 180mg/kg bw/day, and recombinant human lysozyme (rhLZ), 360 and 36mg/kg bw/day, were orally administered to Wistar rats for 28 days. Apo-rhLF and rhLZ were expressed in rice grain, extracted, purified; the lactoferrin was iron desaturated. The animals were examined for evidence of toxicity; there were no deaths and in-life physical signs were normal. Transient differences in mean food consumption occurred in high dose apo-rhLF and low dose LZ females at week three. There were no biologically significant differences in hematological or clinical chemistry parameters. Necropsy results were normal and microscopic evaluation showed no treatment related changes in animals dosed with 1800mg/kg/day apo-rhLF or 360mg/kg/day rhLZ. The results of the 28-day oral administration demonstrate a lack of toxicity of apo-rhLF and rhLZ in rats. There were no treatment related, toxicologically relevant changes in clinical signs, growth, food consumption, hematology, clinical chemistry, organ weight and pathology. The no observed adverse effect level (NOAEL) is greater than 1800mg/kg/day for apo-rhLF and 360mg/kg/day for rhLZ.

PubMed Link – Click Here

Assessment of the Potential Cross-Allergenicity between Hen’s Egg Lysozyme and Recombinant Human Lysozyme

D. A. Moneret-Vautrin1, C. M. N. Astier2, P. Franck1, M. Morisset1, F. Codreanu1, O. Roitel3, S. L. Taylor4, D. R. Bethell5; 1University Hospital, Nancy, FRANCE, 2INPL, Vandoeuvre-Les-Nancy, FRANCE, 3Laboratory
of Molecular Medicine and Therapeutics, Vandoeuvre-Les-Nancy, FRANCE, 4University of Nebraska, Lincoln, NE, 5Ventria Bioscience, Sacramento, CA.

RATIONALE: Human lysozyme (rhu lys) extracted from genetically modified rice is available and regulatory strategies are currently under evaluation. Since the sequence of human lysozyme shows 60% homology with hen’s egg lysozyme, and because egg lysozyme is recognized by 35% of sera from egg allergic patients, searching for a possible cross-allergenicity between human and egg lysozyme is needed. This is in keeping with the recommendations from the WHO/FAO Joint Expert Committee and the Codex Alimentarius Commission.

METHODS: Forty-one sera from egg allergic patients, with specific IgE to egg lysozyme were screened by ELISA inhibition using egg lysozyme and rhu lys. Basophil activation tests (BAT) were performed in 28 egg lysozyme-sensitized patients using 3 preparations of rhu lys with a purity of 85%, 95% and 99%, human milk lysozyme, and rice proteins. Sera from 5 patients not allergic to egg were used as controls.

RESULTS: In the tested sera, ELISA inhibition showed no cross-reactivity between human and hen egg lysozyme. Positive BAT to rhu lys in patients was associated to positive BAT to rice extract. The percentage of basophil activation decreased with the increase of the purity of rhu lys, consistent with the notion that contaminating rice proteins are responsible for the BAT positive responses. No positive BAT test was observed with human milk lysozyme.

CONCLUSIONS: Our data support the conclusion that rhu lys does not cross react with human IgE directed against hen egg lysozyme.

Journal Link – Click Here

Efficacy of rice-based oral rehydration solution containing recombinant human lactoferrin and lysozyme in Peruvian children with acute diarrhea.

Zavaleta N, Figueroa D, Rivera J, Sánchez J, Alfaro S, Lönnerdal B.

Erratum in:
J Pediatr Gastroenterol Nutr. 2008 Jan;46(1):121.

Comment in:
J Pediatr Gastroenterol Nutr. 2007 Mar;44(3):298-9.

Abstract
OBJECTIVE: To compare glucose and rice-based oral rehydration solution with rice-based oral rehydration solution containing recombinant human lactoferrin and recombinant human lysozyme in diarrhea outcomes.

PATIENTS AND METHODS: We conducted a randomized, double-blind controlled trial in children with acute diarrhea and dehydration. One hundred and forty children 5 to 33 months old were block randomized to receive low osmolarity WHO-ORS (G-ORS), rice-based ORS (R-ORS), or rice-based ORS plus lactoferrin and lysozyme (Lf/Lz-R-ORS). Intake and output were monitored for 48 h in the ORU, with continued monitoring through home and clinic follow-up for 14 d.

RESULTS: The G-ORS and R-ORS groups did not show any differences in diarrhea outcomes and were therefore combined as the control group. Intent-to-treat analysis showed a significant decrease in duration of diarrhea (3.67 d vs 5.21 d, P = 0.05) in the Lf/Lz-R-ORS group as compared with the control group and a significant increase in the number of children who achieved 48 h with solid stool, 85% vs 69% (P < 0.05). There were no significant differences [corrected] in volume of diarrhea or [corrected] the percentage of children who had a new diarrhea episode after achieving the endpoint.

CONCLUSIONS: Addition of recombinant human lactoferrin and lysozyme to a rice-based oral rehydration solution had beneficial effects on children with acute diarrhea.

PubMed Link – Click Here

Recombinant Human Milk Proteins

Bo Lönnerdal
Department of Nutrition, University of California, Davis, CA, USA

Human milk provides proteins that benefit newborn infants. They not only provide amino acids, but also facilitate the absorption of nutrients, stimulate growth and development of the intestine, modulate immune function, and aid in the digestion of other nutrients. Breastfed infants have a lower prevalence of infections than formulafed infants. Since many women in industrialized countries choose not to breastfeed, and an increasing proportion of women in developing countries are advised not to breastfeed because of the risk of HIV transmission, incorporation of recombinant human milk proteins into infant foods is likely to be beneficial. We are expressing human milk proteins known to have anti-infective activity in rice. Since rice is a normal constituent of the diet of infants and children, limited purification of the proteins is required. Lactoferrin has antimicrobial and iron-binding activities. Lysozyme is an enzyme that is bactericidal and also acts synergistically with lactoferrin. These recombinant proteins have biological activities identical to their native counterparts. They are equally resistant to heat processing, which is necessary for food applications, and to acid and proteolytic enzymes which are needed to maintain their biological activity in the gastrointestinal tract of infants. These recombinant human milk proteins may be incorporated into infant formulas, baby foods and complementary foods, and used with the goal to reduce infectious diseases. Copyright © 2006 Nestec Ltd., Vevey/S. Karger AG, Basel

PubMed Link – Click Here

International Academy of Life Sciences Applauds Novel Product for Diarrhea

New Study Finds Ventria Bioscience’s Oral Rehydration Solution is Effective Against the Number Two Infectious Killer of Children

HANOVER, Germany (June 23, 2006) – A new approach to fighting diarrhea that fortifies the standard product, oral rehydration solution, with two key protective breast milk proteins is a revolutionary development that could save the lives of millions of children around the world, the head of an international group of medical and academic researchers said today.
The proteins were developed by U.S.-based Ventria Bioscience, which through a plant-based system is able to cost-efficiently produce significant quantities of lactoferrin and lysozyme, two proteins found naturally in breast milk.
“Our academic community supports the development of plant-made pharmaceuticals because of their tremendous potential to treat life-threatening illness,” said Hilmar Stolte, M.D., president of the International Academy of Life Sciences (IALS). “Now we have a study that provides tangible proof of what is possible with this technology.”
Diarrhea is the number-two infectious killer of children under five in the world and its effects are particularly acute in developing countries such as Peru, where more than 20 percent of the 36,000 children who die every year are victims of diarrhea.
A study conducted by investigators in the US and Peru found that by adding Ventria’s proteins to the standard treatment for diarrhea, oral rehydration solution, both the length and the severity of diarrhea decreased.
The study, which was conducted following World Health Organization protocols, found that children consuming oral rehydration solution with lactoferrin and lysozyme were sick for 3.67 days on average, as compared to 5.21 days for children receiving oral rehydration solution without the added proteins. Children receiving the enhanced oral rehydration solution had 30 percent shorter duration of the diarrhea. In addition, the children who received Ventria’s proteins had a higher rate of recovery and reduced incidence of another episode of diarrhea.
Leading researchers in the field have said that the development is a significant breakthrough in a condition that kills more than 2 million children every year.
“We know that babies that drink breast milk do not get diarrhea with anywhere near the same frequency as children who are not breast fed, so if you can take the important components of breast milk and extend them to children who are not breastfeeding and older people this would be a huge advantage,” William Greenough III, MD, professor of medicine at Johns Hopkins University and an international expert in pediatric and geriatric diarrhea, has said. “This is what
we call the Holy Grail: We’d like to have something that both hydrated people and could shorten the illness.”
According to the World Health Organization there are 4 billion episodes of diarrhea in children each year. Many of these are repeat instances that can create chronic health problems including malnutrition, which in turn can weaken children’s immune systems and expose them to additional health risks such as infection, pneumonia and anemia.
“Diarrhea is a dreadful disease that preys worldwide upon the most innocent and the most vulnerable groups of people: children, the elderly and the poor,” Dr. Stolte said. “This innovative science promises to provide new solutions to a long-standing public health problem. We applaud this effort.”
Stolte, IALS and its U.S. partner, the Biomedical Exchange Program (BMEP), host http://www.plantpharma.org, an online community dedicated to a science-based, medically oriented discussion on PMPs and their potential to help combat life-threatening illness.
IALS is a global network of universities, medical schools, and related institutions that are dedicated to education, training and research in key issues associated with the life sciences.

Resources:
http://www.plantpharma.org
http://www.ventria.com
http://www.lifesciences.net
WHO guidelines on treatment of diarrhea: http://www.who.int/child-adolescent-health/publications/referral_care/chap4/chap41.htm