::::: SCIENCE :::::

  :: ABOUT RABBIT ::

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

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

The animal of choice to produce human therapeutic glycoproteins and vaccines. Rabbit mammary gland has the ability to make the post-translational modifications necessary for the functionality of human recombinant proteins. The rabbit is therefore suitable for the production of complex glycosylated proteins or recombinant 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 (1 month) and sexual maturity period (only 4 months for rabbit females and 5 months for rabbit males), BioProtein Technologies can generate transgenic rabbit lines within short timeframe. From there, rabbit becomes an amazing bioreactor allowing the production of human therapeutic proteins and vaccines within very competitive timelines compared to other mammals.

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, the expression yield in milk varies between 0.1 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 an extremely efficient and competitive system, allowing fast, safe, and cost-effective production of human therapeutic proteins.

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 :: EXPERTISE ::

BioProtein Technologies masters :

     Molecular and Cellular Biology
Transgene constructs used for the expression of the protein of interest under the control of a milk protein promoter (WAP promoter) are designed and by BioProtein Technologies and are the result of a 10 years experience in the area of milk protein expression regulation.
BioProtein Technologies’ capabilities in gene expression in the milk of transgenic rabbits are protected by worldwide patents. --> More…

     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 through 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.

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. Milk containing the desired recombinant protein or recombinant vaccine is obtained with a unique milking system developed in collaboration with INRA.
This milking system allows optimum milk extraction while complying with animal welfare standards. -->More…

     Downstream Processing
Protein characterisation and purification is outsourced to contract manufacturers specialized in DSP. Alternatively and when our customers have their own purification capabilities in house, milk is provided by BioProtein and DSP is performed directly by our customers.

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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 4 major R&D programs:

     Improvement of protein expression in milk.
     Use of bacterial artificial chromosomes for transgenesis.
     Cloning by nuclear transfer including rabbits.
     Development of transgenic lines with improved bioproduction capabilities.

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. --> More...

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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.

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