::::: SCIENCE :::::

  :: ABOUT RABBIT ::

Contrary to common opinion, rabbits are phylogenically closer to primates than rodents, which makes them :

A better animal model than rodents for the study of human diseases

The animal of choice to produce human therapeutic proteins and vaccines. Rabbit mammary gland has the ability to make the post-translational modifications necessary for the functionality of human proteins. The rabbit is therefore suitable for the production of complex glycosylated proteins or VLP-based multivalent vaccines.

Indeed rabbits do not belong to the order of rodents like mice and rats even though they share many common characteristics with them. A significant difference exists between rabbits and rodents: rabbits possess two pairs of incisors on the upper jaw whereas rodents only have one. This distinction has lead them to be classified in a different order: lagomorphs.
With a short gestation time (one month) and sexual maturity period (only four months for females and five months for males), rabbits can be seen as a fast bioreactor for the production of therapeutic proteins and vaccines.

One female rabbit can give up to 8-10 broods per year with an average brood of 8 young rabbits, and can produce up to 250 ml of milk per day of lactation. Yearly, up to 10-15 liters of milk can be collected from each lactating female).

Depending on the protein expressed, transgenic rabbit milk contain in average 1 to 10 g per liter of recombinant proteins.

The low costs of breeding and production allows BioProtein Technologies to reduce significantly the cost of developing therapeutic proteins and vaccines in the milk of transgenic rabbits compared to industry standards.

There is no known prion disease in rabbit and no known serious disease transmission to humans, which makes the rabbit safer than other dairy animals.

Transmission tests of the prion disease to the rabbit (examples):
LOFTUS B., ROGERS M. 1997. Characterization of a prion protein (PrP) gene from rabbit; a species with apparent resistance to infection by prions. Gene 184: 215-219
GIBBS C.J., GAJDUSEK D.C., AMYX H. 1979. Strain variation in the viruses of Creutzfeldt-Jacob disease and kuru. In Pathogenesis, immunobiology, virology, and molecular biology of the spongiform encephalopathies /edited by S.B. Prusiner and W.J. Hadlow, New York : Academic Press, 1979. (Slow transmissible diseases of the nervous system ; vol.2)
BARLOW R.M., RENNIE J.C. 1976. The fat of ME7 scrapie infection in rat, guinea pig, and rabbit. Research in Veterinary Science. 21, 110-111
GIBBS C.J., GAJDUSEK D.C. 1973. Experimental subacute spongiform virus encephalopathie in primates and other laboratory
animals. Science.182(107) : 67-8

For all of these reasons, rabbits appear to be the system of choice for a fast, safe, and cost-effective production of human therapeutic proteins.

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 :: EXPERTISE ::

BioProtein Technologies masters :

     Molecular and Cellular Biology

Gene constructs allowing the expression of the protein of interest under the control of a milk protein promoter (WAP promoter) are made by BioProtein Technologies molecular and cellular biology team, which is highly experienced in the milk-specific regulation and expression of proteins.

BioProtein Technologies’ unique capabilities in gene expression in the milk of transgenic rabbits are protected by worldwide patents.
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     Embryology

A privileged partnership with INRA allows BioProtein Technologies to access cutting-edge technology and know-how to generate transgenic rabbits. Transgenic rabbits are generated by a well-adapted micro-injection method, where the expression vector is directly injected into the pronucleus of a single-cell fertilized ovocyte. The transgenic embryos are then transferred to recipient female rabbits.
The method used by the Company is well established and shows a high success rate as 4000 embryos can be micro-injected in a month.
20 transgenic embryos will be transfered into each recipient female, meaning that the company is able to performed up to 200 implantations.
Moreover the transgenic animals that are produced show a stable expression of the transgene from one generation to the next.

 

     Rabbit husbandry and milking

Scientists at BioProtein Technologies also have the expertise in dairy science and animal husbandry. The milk containing the desired recombinant protein or VLP-based vaccine is obtained with a unique milking system developed in collaboration with INRA. This milking system allows optimum milk extraction while complying with GMP requirements and animal welfare standards.
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     Downstream Processing

BioProtein Technologies has developed a partnership with Eurogentec, a Belgian company specialized in protein purification under GMP requirements.
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 :: RESEARCH & DEVELOPMENT ::

BioProtein Technologies scientists develop new ways to refine and improve the efficiency of the transgenic process. The Company is currently conducting four major R&D programs:

     Improvement of protein expression in milk
     Use of Bacterial Artificial Chromosomes & homologous recombination for transgenesis
     Cloning by nuclear transfer including rabbits
     Generation of transgenic animals obtained by spermatotransgenesis

These programs will keep BioProtein Technologies at the forefront of technologies that are applied for generating recombinant therapeutic proteins and vaccines in the milk of transgenic rabbits.

BioProtein Technologies benefits from the invaluable know-how of INRA, which created one of the world’s first cloned transgenic cattle in 1999 and cloned the first rabbit in 2002.
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 :: ETHICAL POLICY ::

BioProtein Technologies focuses on the production of bio-engineered pharmaceuticals (ideally, drugs addressing diseases for which no treatments exist, on behalf of reputable pharmaceutical and biotechnology companies).

BioProtein Technologies will, on adequate occasion, develop animal models on behalf of reputable pharmaceutical and/or biotech companies. Such models shall be developed to understand the action of one or several genes on the generation and/or the development of unexplained human diseases.

BioProtein Technologies will conduct an ethical assessment of each project proposal and exclude all possible applications of its technologies to projects that are not socially acceptable.

:: REGULATORY ::

BioProtein Technologies complies with relevant legislation in each of its facilities, its endeavor to apply the highest standards of animal care usually exceeds national requirements.

Animal rearing facilities hosted by INRA have been accredited by the French Regulatory Committee (Commission du Génie Génétique) for the breeding of transgenic animals.

BioProtein Technologies warrants that all existing premises are in compliance with all relevant legislations. This encompasses particularly all relevant (National, European and US) authorizations and all relevant (National, European and US) directives relating to transgenic animals bioreactors as well as to the commercialization of pharmaceutical products.

:: OPERATIONS ::

BioProtein Technologies shall develop and implement state of the art quality control and quality assurance procedures in order to continually improve the quality of its products and comply with national and international regulations for the development and production of pharmaceuticals.
BioProtein Technologies ensures that further production procedures and security will adhere to European and US legal standards regarding animal welfare.

:: BIOPROTEIN TECHNOLOGIES AND PUBLIC CONCERNS ::

One independent member of the Scientific Advisory Board is specifically in charge of ethical issues, particularly of the on-going evaluation of the
full compliance of BioProtein Technologies’ activities and operations with the present Charter. The same person will also be in charge of proposing modifications to the present Charter in response to further changes in technology or in public opinion.

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