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--------------------------------------------------------------------------------------------------------------------------------------------Address: IMMUNOTECH S.A. Av. Pavn 2885 Ciudad Autnoma de Buenos Aires (C1248AAK), Argentina Phone: 54-11-4941-1859 Fax: 54-11-4942-0041 E-mail: rlopez@immunotech-sa.com
Company
Immunotech S. A. (IMT) is a private biotech company with headquarters in Buenos Aires, Argentina. It is focused on discovering and developing innovative pharmaceutical products to accelerate organ and tissue repair, cancer treatment and prevention of infectious diseases. Currently, IMT efforts are based on proprietary molecules (synthetic oligonucleotides) with bio-regulatory properties. IMT staff members include biologists, biochemists, physicians, pharmacists and financial experts. They are highly motivated to aggressively drive IMT potential products through clinical trials, in order to make them available to patients worldwide. IMT adheres to GCPs and maintains a high level of quality standards regarding data management.
Technology
IMT oligonucleotides (IMT ODNs) are approximately 24 nucleotides long and contain the sequence PyNTTTTGT, wherein Py is C or T and N any deoxynucleotide, as the active portion of the molecule. IMT studies have demonstrated that these ODNs, mainly in their phosphorothioate version, could interact with certain human cells modifying their behaviour. Primary target cells of IMT ODNs include mesenchymal stem cell progenitors, B lymphocytes, plasmacytoid dendritic cells, NK and NKT cells. Upon interaction with IMT ODNs these cells release cytokines and express cell surface markers. These molecules orchestrate the answer of the body to damage caused by micro-organisms, by trauma, or by unfavourable genetic changes like the ones that lead to cancer. Therefore, IMT ODNs may be used as adjuvant in vaccines, for the treatment of cancer and for tissue repair medical procedures.
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Vaccine 23(2005): 3597-3603 Fig. 1: Anti-HBs responses in monkeys (Cebus apella) using the regular vaccine or the vaccine adjuvated with the ODN IMT504
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Vaccine 24 ( 2006) :2701 Fig. 2: Anti-Flu antigen responses in rats vaccinated with a regular flu vaccine or the vaccine adjuvated with ODN IMT504.
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Data on File Anti-rabies virus responses in rats vaccinated with a regular Vero cell vaccine or the vaccine adjuvated with ODN IMT504.
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Data on File Fig. 4: Anti-rabies virus responses in humans (pilot study) vaccinated with a regular Vero cell vaccine or the vaccine adjuvated with ODN IMT504. Titers at 90 days after a three shots schedule.
Intellectual property
IMT ODNs and their uses are protected by the following patents and patent applications Immunostimulatory oligonucleotides and uses thereof . Patent Application PCT- (WO 03/101375 A2; May 30th, 2003, WIPO; Priority date with patent CA-2388049; May 30th, 2002, Canada); granted.
AUSTRALIA: Immunostimulatory oligonucleotides and uses thereof; Nov 25th, 2004; AU 2003250334 CANADA: Immunostimulatory oligonucleotides and uses thereof; Nov 30th, 2004; EUROPE: Immunostimulatory oligonucleotides and uses thereof; Dec 27th, 2004; EP03755959.8 INDIA: Immunostimulatory oligonucleotides and uses thereof; Nov 29th, 2004; In: 3773/DLNP72004 ISRAEL: Immunostimulatory oligonucleotides and uses thereof; Nov 29th, 2004; Il: 165466 JAPAN: Immunostimulatory oligonucleotides and uses thereof; Nov 29th, 2004; JP: 2004508733 KOREA: Immunostimulatory oligonucleotides and uses thereof; Nov 30th, 2004; KO:102004-7019524 MEXICO: Oligonucleotidos inmunoestimuladores y sus usos; Nov 30th, 2004; PA/a/2004/011937 NEW ZEALAND: Immunostimulatory oligonucleotides and uses thereof; Nov 25th, 2004; NZ:536962 PHILIPPINES: Immunostimulatory oligonucleotides and uses thereof; Nov 25th, 2004
U. S. OF AMERICA: Immunostimulatory oligonucleotides and uses thereof; Apr 12th, 2002; US: 10/309,775; granted.
Osteogenic oligonucleotides and uses thereof. Patent Application -Set 27th, 2004, EP04077653.6 Oligonucleotides that induce the secretion of GM-CSF. Patent Application -Nov 16th, 2004, EP04105792.8 Oligonucleotides stimulatory of the mesenchymal stem cell proliferation and uses thereof. Patent Application - June 3th, 2005, EP05104854.4
Publications
- Elias, F., Flo, J., Lopez, R.A., Zorzopulos, J., Montaner, A., Rodrguez, J.M. 2003. Strong Cytosine- Guanosine- Independent Immunostimulation in Humans and Other Primates by Synthetic Oligonucleotides with PyNTTTTGT Motifs. J.
Immunol.171:3697.
Elias F, Flo J, Rodriguez JM, Nichilo AD, Lopez RA, Zorzopulos J, Nagle C,
Lahoz M, Montaner A. 2005. PyNTTTTGT prototype oligonucleotide IMT504 is a potent adjuvant for the recombinant Hepatitis B vaccine that enhances the Th1 response. Vaccine, 23:3597-603.
- Rodriguez JM, Elias F, Montaner A, Flo J, Lopez RA, Zorzopulos J, Franco RJ, Lenial SP, Lopez Salon M, Pirpignani ML, Solimano J, Garay G, Riveros D, Fernandez J, Cacchione R, Dupont J. Oligonucleotide IMT504 induces an immunogenic phenotype and apoptosis in chronic lymphocytic leukemia cells. Medicina (B. Aires). 2006; 66:916.
- Lopez RA, Zorzopulos J. Vaccine shortage for pandemic influenza: can it be solved? Vaccine. 2006; 24:2701.
- Rodriguez JM, Elias F, Flo J, Lopez RA, Zorzopulos J, Montaner AD. Immunostimulatory PyNTTTTGT Oligodeoxynucleotides: Structural Properties and Refinement of the Active Motif. Oligonucleotides. 2006; 16: 275-85.
- Insua, A.H., Montaner, A.D., Rodrguez, J.M., Elias,F., Flo, J., Lopez, R.A., Zorzopulos, J., Hofer, E.L., Chasseing, N.A. 2006. IMT504, the Prototype of the Immunostimulatory Oligonucleotides of the PyNTTTTGT Class is a Potent Signal for Mesenchymal Stem Cells Expansion In Vitro and In Vivo with Potential Use in Medicine in Tissue Repair Therapy. Stem Cell (in publication).
-Montaner A., Elias F., Juan Fl, Lpez R.A., Zorzopulos J. Rodriguez J.M. Strong CpG Independent Immunostimulation in Humans and other Primates by Synthetic Oligodeoxynucleotides with PyNTTTTGT Motifs. Sixth Annual Conference on Vaccine Research. National Foundation for Infectious Disease. May 2003. Arlington, Virginia. USA.
-Rodriguez J.M., Elias F., Fl J., Lpez R.A., Montaner A. and Zorzopulos J. Potent (non-CpG) Immunostimulatory Oligonucleotides. 90th Anniversary Meeting,
Federation of American Societies for Experimental Biology. The American Association of Immunologists. May 2003. Denver, Colorado. USA.
-Elias F., Fl J., Lpez R.A., Zorzopulos J., Montaner A. and Rodriguez J. Immunostimulation in Primates by Synthetic Oligodeoxynucleotides with PyNTTTTGT Motifs. 90th Anniversary Meeting, Federation of American Societies for Experimental Biology. The American Association of Immunologists. May 2003. Denver, Colorado. USA.
-Elas F., Montaner A., Rodrguez J, Denichilo A., Fl J, Lpez R. and Zorzopulos J. PyNTTTTGT Oligonucleotide IMT504 is a Potent Vaccine Adjuvant. Experimental Biology. XXX International Congress of Physiological Sciences. March 2005. San Diego, CA. USA
-Rodrguez J.M., Elas F., Lpez Saln M., Montaner A., Franco R.J., Genial S.P., Pirpignani M., Fl J., Lpez R.A. and Zorzopulos J. Immunostimulatory PyNTTTTGT Oligonucleotide IMT504 Induce an Immunogenic Phenotype and Apoptosis in Chronic Lymphocytic Leukemia Cells: Synergy with IL2 and Independency of the Mutational
Status of the Ig VH Genes. Experimental Biology. XXX International Congress of Physiological Sciences. March 2005. San Diego, CA. USA
-Rodrguez J.M., Marchisio J., Lpez Saln M., Elas F., Montaner A., Fl J., Lpez R.A. and Zorzopulos J. Induction of high levels of GM-CSF Secretion in Human Peripheral Blood Mononuclear Experimental Cells by XXX non-CpG Immunostimulatory Congress of
Oligonucleotides.
Biology.
International
Physiological Sciences March 31. April 2005. San Diego, CA. USA -Montaner A.D., Elias F., Rodrguez J.M., Flo J., Lopez R. and Zorzopulos J. PyNTTTTGT Oligonucleotide IMT504 is a Potent Vaccine Adjuvant. Eighth Annual Conference on Vaccine Research. May 2005. Baltimore, Maryland. USA.
- Montaner A.D., Hernando Insa A, Rodriguez J, Elas F, Fl J, Hofer E, Lpez R, Chasseing N, Zorzopulos J. IMT504 the Prototype of the Immunostimulatory Oligonucleotides of the PYNTTTGT Class Is a Potent Signal for Mesenchymal Stem Cells Expansion. 4th ISSCR Annual Meeting International Society for Stem Cell Research. June 29-July 1, 2006, Toronto- Canada
- Zorzopulos, Jorge. Synthetic Oligonucleotide IMT504 is a Potent Signal for Adult Stem Cell Expansion in Vitro and in Vivo with Potential use in Tissue Repair Therapy. Partnerships & Technologies. Partnering Venture Ready Stem Cell Research, Tissue Modeling Technology, and BioProcessing Developments. August 17-19, 2006, Boston, MA.
Conclusions
IMT ODNs are potent stimulators of the immune system. In consequence, they can be use as adjuvant in vaccines. IMT ODNs are very easy to synthesize and manufacture. Preclinical trials have demonstrated that IMT ODNs are very safe drugs.