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Test Kit for personalized treatment
Novel predictive marker for Hydroxyurea (HU) resistance
in treatment of Leukemia
Aarhus University
October, 2009
Technical Field
Hydroyurea - Hydrea (HU) is a widely use Biotechnology – health, medico-technical agent in the treatment of Leukemia. Potentially all patient diagnosed with leukemia could Business opportunity
benefit from individual testing securing optimal monitoring of disease progression due to HU resistances.
Current state of technology
A plant chemo-resistance discovery model has opportunity for companies and investors for early involvement working alongside the Proof- mutations inducing drug resistance due to altered enzyme activity. A correlation between this plant enzyme activity and drug response The Technology
was confirmed by mammalian patient in vitro Blood cancers are often treated with cytotoxic data. The technology has applied for further agents that prevent cell division. However, relapses are frequent due to development of Prototype of a prognostic test kit for screening of personalized drug applicability is expected in 2010 together with a first clinical trial of 150 This technology allows the development of a test-kit able to predict cancer sensitivity toward the chemotherapeutic agent hydroxyurea Applications
(HU). A specific enzyme activity is used as a • The prognostic test kit will be part of a predictive marker for blood cancer response to standard pre-treatment procedure, aiding HU treatment.
clinicians in making rational decisions allowingpersonalized patient treatment.
The test-kit will allow clinicians to determine whether or not a specific blood cancer patient • Potential for the development of additional will benefit from treatment with HU and allow test-kits thereby increasing the potential product resistance, ensuring a shift to alternative treatment before severe disease progression.
Commercial Value
Leukemia prevalence in the seven major
Intellectual Property Rights
markets (France, Germany, Italy, Spain, A Danish patent application has been filed UK,US, Japan) is expected to research 227,180 August 2009 and has received the application Treatment with chemotherapy continues to application is unpublished. Aarhus University present clinical challenges due to chemotherapy is the full owner of the all Intellectual Property resistances and a lack of technology for accurately predicting the chemo-sensitivity of individual cancers.
Inventors
Jan-Elo Jørgensen
Associate professor,Department of Molecular Biology, Aarhus University
I have researched and lectured extensively on the topic of Molecular Biology of Plants for 24 years. I
was a Post-Doc at the Salk Institute, La Jolla, California 1991-1993. In 2001 I founded and managed
Plantic ApS, a Danish biotechnology company in cancer therapeutics.
My key focus has been cell cycle and development as well as cancer.

Trine Juul
Postdoc, Department of Molecular Biology, Aarhus University
I have 13 years of experience in the field of plant molecular biology of which five years have been
spent abroad at the John Innes Institute, UK and INRA, France. For two years I was employed as a
researcher at the biotech company Plantic Aps. During my career I have been interested in plant
growth and development working with several different plant species and am now involved in setting
up a system where plants can be used to get a better understanding of human cancer diseases.

Stig Uggerhøj Andersen
Postdoc, Department of Moleculær Biology, Aarhus University
During my PhD, I studied symbiotic nitrogen fixation in legumes. As a post doc, my research activity
has been centered on regulation of cell cycle and stem cell activity using the plant Arabidopsis as a
model system. I have pursued this interest first at Plantic ApS and then at the Max Planck Institute,
Tübingen, Germany, before returning to Aarhus University. Currently, I focus on studying the effects
of chemotherapeutic agents by combining genetic and pharmacological intervention and on
optimizing the Arabidopsis platform for this purpose by taking advantage of deep sequencing

References
• Fulton, L., Batoux, M., Vaddepalli, P., Yadav, R.K., Busch, W., Andersen, S.U., Jeong, S., Lohmann, J.U., Schneitz, K. 2009, 'DETORQUEO, QUIRKY, and ZERZAUST represent novel components involved in organ development mediated by the receptor-like kinaseSTRUBBELIG in Arabidopsis thaliana', PLoS Genetics, vol. 5 no. 1, pp. e1000355.* ) • Schneeberger, K., Ossowski, S., Lanz, C., Juul, T., Petersen, A.H., Nielsen, K.L., Jørgensen, J.-E., Weigel, D., Andersen, S.U. 2009, 'SHOREmap: simultaneous mapping and mutation identification by deep sequencing', Nature Methods, vol. 6 no. 8, p. 550-1. • Andersen, S.U., Buechel, S., Zhao, Z., Ljung, K., Novák, O., Busch, W., Schuster, C., Lohmann, J.U. 2008, 'Requirement of B2-Type Cyclin-Dependent Kinases for Meristem Integrity in Arabidopsis thaliana ', Plant Cell, vol. 20, pp. 88-100.* ) • Andersen, S.U., Algreen-Petersen, R.G., Hödl, M., Jurkiewicz, A., Cvitanich, C., Braunschweig, U., Schauser, L., Oh, S.-A., Twell, D., Jensen, E.Ø. 2007, 'The conserved cysteine-rich domain of a tesmin/TSO1-like protein binds zinc in vitro and TSO1 is required for both male and female fertility in Arabidopsis thaliana ', Journal of Experimental Botany, vol. 58, pp. 3657-3670. • Andersen, S.U., Cvitanich, C., Busk, H., Jensen, D.B., Jensen, E.Ø., Grønlund, M. 2005, 'Vectors for reverse genetics and expressionanalysis', in Lotus japonicus Handbook, Contribution to scientific book/anthology • Andersen, S.U., Cvitanich, C., Hougaard, B.K., Roussis, A., Grønlund, M., Bødker Jensen, D., Frøkjær, L.A., Jensen, E.Ø. 2003, 'The glucocorticoid-inducible GVG system causes severe growth defects in both root and shoot of the model legume Lotus japonicus ', Mol. Plant-Microbe Interact., vol. 16, pp. 1069-1076. • Jacobsen-Lyon, K., Jensen, E.Ø., Jørgensen, J.-E., Marcker, K.A., Peacock, W., Dennis, E. 1995, 'Symbiotic and nonsymbiotic hemoglobingenes of Casuarina glauca.', Plant Cell, vol. 7 no. 2, pp. 213-23. • Borg S, Brandstrup B, Jensen TJ, Poulsen C.,”Identification of new protein species among 33 different small GTP-binding proteins encoded by cDNAs from Lotus japonicus, and expression of corresponding mRNAs in developing root nodules” Plant J. 1997 vol.11(2):237-50.
• Kapranov P, Jensen TJ, Poulsen C, de Bruijn FJ, Szczyglowski K.,” A protein phosphatase 2C gene, LjNPP2C1, from Lotus japonicusinduced during root nodule development” Proc Natl Acad Sci U S A. 1999 vol.96(4):1738-43.
• Borg S, Pødenphant L, Jensen TJ, Poulsen C., ”Plant cell growth and differentiation may involve GAP regulation of Rac activity”, FEBS Lett. 1999 vol.453(3):341-5.
• Gaudin V, Libault M, Pouteau S, Juul T, Zhao G, Lefebvre D, Grandjean O, “Mutations in LIKE HETEROCHROMATIN PROTEIN 1 affect flowering time and plant architecture in Arabidopsis” Development. 2001 vol.128(23):4847-58.
• Germann S, Juul-Jensen T, Letarnec B, Gaudin V., “DamID, a new tool for studying plant chromatin profiling in vivo, and its use to identify putative LHP1 target loci”, Plant J. 2006 vol.48(1):153-63.

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