Jian Zhou: Difference between revisions
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* For additional reference, Jian Zhou has published a total 22 times. His publications have been cited 926 times. He has written with 64 co-authors and has, himself, been cited by 194 authors.<ref>[http://academic.research.microsoft.com/Author/55337878/jian-zhou] A complete bibliography of Dr. Jian Zhou's published papers is here available.</ref> |
* For additional reference, Jian Zhou has published a total 22 times. His publications have been cited 926 times. He has written with 64 co-authors and has, himself, been cited by 194 authors.<ref>[http://academic.research.microsoft.com/Author/55337878/jian-zhou] A complete bibliography of Dr. Jian Zhou's published papers is here available.</ref> |
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==U.S. Patents for |
==U.S. Patents for HPV Vaccine and Technologies== |
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* U.S. 5,993,821, titled ''“Modified Papillomavirus L2 Protein …”'', was granted to Frazer and Zhou (posthumously) on November 30, 1999. The U.S. application for the patent was filed on July 30, 1996. |
* U.S. 5,993,821, titled ''“Modified Papillomavirus L2 Protein …”'', was granted to Frazer and Zhou (posthumously) on November 30, 1999. The U.S. application for the patent was filed on July 30, 1996. |
Revision as of 03:15, 12 March 2013
Jian Zhou (1957-1999) (in Chinese convention Dr. Zhou Jian) is the Chinese virologist and cancer researcher, who with Australia’s Ian Frazer, invented the vaccine for stimulating human immunological resistance to the cervical cancer inducing human papilloma virus (Gardasil®, Cervarix®).[1] Hundreds of millions of young women have now enjoyed the benefits of this life preserving vaccine against HPV, which causes 70%[2] of the World’s 500,000 annual cervical cancers, which cancers originate 80% in developing countries and which cancers cause the deaths of some 250,000 women worldwide annually.[3]
Unlike his co-researcher Ian Frazer, however, Jian Zhou did not live long enough to see any of the fruits of his labors, to contemplate their unquantifiable benefit to human posterity or to enjoy the public adulation, rightly, accorded this sedulous achievement. In 1999, Jian Zhou succumbed to the sequela of a hepatitis, which he had contracted in childhood in his native South East China, where the disease is, unfortunately, still, even, to this day endemic.[4] He did not even live long enough to see the U.S. patent for Ian Frazer’s and his vaccine and its method of production, and for which patent and priority they had both so long fought, finally, issue as U.S. patent 7,476,389, titled “Papilloma Virus Vaccines”, on January 13, 2009, after an Interference battle of over a decades length.[5] Jian Zhou has been called “Vaccines Forgotten Man”.[4]
With Frazer, Zhou postulated a quite novel approach for vaccinating. This theretofore unheard of method for achieving immunization was to use then nascent recombinant DNA technology to replicate a virus’s innocuous, but, antigen laden and immunologically targeted, protein shell sans its pernicious core and, then, to introduce those, of themselves, harmless proteins (now known as VLPs or “virus like particles”) into the human body to stimulate an immunological response thereto. “We basically had the same idea, which was to create a synthetic replica of the human pappilloma virus known as a virus like particle.” – Ian Frazer.[4] Zhou and Frazer began jointly investigating this approach to producing vaccine against and vaccinating against the human papilloma virus at the University of Queensland in 1984.
While on August 20, 2007 delivering the United States Court of Appeal for the Federal Circuit opinion CAFC 2006-1154 (Ian Frazer & Jian Zhou v. Richard Schlegel and A. Bennet), that, finally, decisively, and conclusively ruled in favor of co-inventors Zhou and Frazer as to the Interference and their priority to the invention of VLPs, Circuit Judge Pauline Newman described the VLP invention in more detail as protein structures having an “external icosahedral shape of virus capsid and (which) thereby mimic the papilloma virus but Lack the disease causing genetic material.” and quoting from Zhou’s and Frazier’s July 20, 1992 PTC application in further detail “The method includes a initial step of constructing one or more recombinant DNA molecules which each encode papilloma virus LI protein or a combination of papilloma virus L1 protein and papillloma virus L2 protein followed by a further step of transfecting a suitable host cell with one or more recombinant DNA molecules so that, virus like particles (VLPs) are produced within the cell after expression of the L1 or L1 and L2 proteins. The VLPs are also claimed per se as well as vaccines incorporating the VLPs.”[6]
Ian Frazer has, to his enduring merit, forthrightly, adamantly and consistently credited his deceased friend and colleague Jian Zhou with alone devising the in vitro method and technology which, finally, after some decade of discouraging and demoralizing failures, succeeded at using recombinant DNA technology to fabricate the VLP of the pair’s invention and which was, first, successfully executed by Jian Zhou’s wife and fellow researcher Xiao – Yi Sun.[4] ”From my point of view, I think having full public acknowledgement of Jian’s contribution to the work … is long overdue.” – Ian Frazer speaking at Dr. Jian Zhou’s belated 1 P.M. May 3, 2008 memorial service in Brisbane, Australia.[7][8]
Jian Zhou received his medical degree from South China’s Wenzhou Medical College near Shanghai.[4] Jian Zhou was survived by his wife Xiao-Yi Sun and his and their only child, a son Andreas.
“We owe him (Dr. Jian Zhou) a great deal because not only was he involved in developing the papilloma virus vaccine, but he also has mentored a whole generation of Chinese scientists in Australia, who are now going out there and doing equally interesting science.” – Ian Frazer, M.B.B.S. University of Edinburgh, British-Australian virologist and co-inventor of Gardasil®, also, at belated 1 P.M. May 3, 2008 memorial service for Dr. Jian Zhou in Brisbane, Australia[9]
Early English Language Papers on Possibility of Human Papilloma Virus Vaccine
- Zhou et al “Increased Expression of Vaccinia Recombinant HVP 16 L1 and L2 ORF Proteins in Epithelium Cells Is Sufficient for Assembly of HVP Virion Like Particles”, J. Gen. Virology, 1990, pp. 2185-2190, Vol. 71.
- Zhou et al “Increased Antibody Responses to Human Papilloma Virus Type 16 L1 Protein Expressed by Recombinant Vaccine Virus Lacking Serine Protease Inhibitor Genes”, Chemical Abstracts, Nov. 5, 1990, Vol. 13, No. 19
- Zhou et al “Human Pappilomavirus Type 16 Virions Produced by Recombinant Viccinia Virus”, Abstract from 1991 Papilloma Virus Workshop (Seattle, WA 1991)
- J. Zhou, X.Y. Sun, D.J. Stenzel, I.H. Frazer, “Expression of Vaccinia Recombinant HPV 16 L1 and L2 ORF Proteins in Epithelial Cells”, 185 J. Virology 251 (1991), pp 251-257
- For additional reference, Jian Zhou has published a total 22 times. His publications have been cited 926 times. He has written with 64 co-authors and has, himself, been cited by 194 authors.[10]
U.S. Patents for HPV Vaccine and Technologies
- U.S. 5,993,821, titled “Modified Papillomavirus L2 Protein …”, was granted to Frazer and Zhou (posthumously) on November 30, 1999. The U.S. application for the patent was filed on July 30, 1996.
- U.S. 6,066,324, titled “Carboxyl Terminal of Papillomavirus L1 region is not required…”, was granted on May 23, 2000 to Gissman, Zhou (posthumously), Muller and Painstill. The U.S. application for the patent was filed on October 2, 1997.
- U.S. 6,599,508, titled “Papilloma Virus-Like Particles …”, was granted to Lutz, Zhou (posthumously), Muller and Painstill on July 29, 2003. The U.S. application for the patent was filed (on Zhou’s behalf posthumously) on September 6, 2001.
- U.S. 6,613,557, titled “Papillomavirus HPV 16 L1 polynucleotide”, was granted to Frazer and Zhou (posthumously) on September 2, 2003. The U.S. application for the patent was filed (on Zhou’s behalf posthumously) on September 7, 2001.
- U.S. 6,361,778, titled “Carboxyl Terminal of Papillomavirus L1 region is not required…”, was granted May 26, 2002. The patent was applied for on September 16, 1999 (both for Zhou posthumous).
- U.S. 7,169,585, titled “Papillomavirus Vaccine”, was granted January 30, 2007. The patent was applied for on December 11, 2003 (both for Zhou posthumous).
- U.S. 7,416,732, titled “Papilloma Virus Like Particles …” was granted August 26, 2008. The patent was applied for on February 21, 2006 (both for Zhou posthumous).
- U.S. 7,476,389, titled “Papilloma Virus Vaccines”, was granted Frazer and Zhou (posthumously) on January 13, 2009. Its U.S. application was filed on January 19, 1994 but claimed priority under a July 20, 1992 PTC filing to the date of an initial [AU] Australian patent application filed on July 19, 1991.
- U.S. 7,939,082, titled “Papilloma Virus Vaccine”, was granted May 10, 2011. The patent was applied for on December 22, 2008 (both for Zhou posthumous).
References and Notes
- ^ Gardasil® is a trademark of Merck & Co. and Cervarix® is a trademark of Glaxo Smith Kline. Merck & Co. and Glaxo Smith Kline provided the major funding for Zhou’s and Frazer’s VLP research.
- ^
Lowy DR, Schiller JT (2006). "Prophylactic human papillomavirus vaccines". J. Clin. Invest. 116 (5): 1167–73. doi:10.1172/JCI28607. PMC 1451224. PMID 16670757. Retrieved 2009-11-12.
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ignored (help) - ^ [1] Here also is a wealth of technical information on HPV vaccines.
- ^ a b c d e [www.theaustralian.com.au/news/tribute-to-vaccines-forgotten-man-story-e6frg600-1111116233989]
- ^ Zhou and Frazer had filed an [AU] Australian patent on July 19, 1991, a PTC filing on July 20, 1992 and a subsequent U.S. patent application on January 19, 1994. Competing Georgetown University researchers Richard Schlegel and A. Bennet, who claimed invention priority to the VLP, had filed their original U.S. patent application after the date of Zhou’s and Frazer’s Australian application and priority date of invention, but, before the date of the pairs U.S. application. These “inventors” Schlegel and Bennet filed a patent Interference proceeding in the United States Patent and Trademark Office, while, there, during, making the speciously compelling argument that Zhou and Frazer should not receive the earlier Australian priority date for their invention under the provisions of the PTC, because Zhou and Frazer had failed to “fully disclose” their invention in their PTC filing and that, therefore, Schlegel and Bennet had legal, if not actual, priority to the invention of VLPs (an argument which the United States Court of Appeal for the Federal Circuit decisively detailed as completely meritless in 2006 in Ian Frazer and Dr. Jian Zhou v. Richard Schlegel and A. Bennet Jenson (CAFC 2006-1154), the Court’s opinion reversing the P.T.O. In its September 20, 2005 decision in Interference proceeding No. 104,776 (Bd. Pat. App. & Inter.), the P.T.O. had erroneously earlier ruled in favor of “inventors” Schlegel and Bennet and that Frazer and Zhou were not entitled to the 1991 Australian invention priority date, because their PTC application disclosure was “inadequate”.)
- ^ See, also, U.S. patent 5,993,821, granted on Nov. 30, 1999, “(independent invention claim) 1. A protein consisting of L2 protein which does not bind DNA or which has an impaired ability to bind DNA … (independent invention claim) 15. A method of producing one or more virus like particles comprising a papilloma virus L1 protein and a papilloma virus L2 protein, wherein said papilloma virus L2 protein does not bind to DNA or has an impaired ability to bind to DNA compared to a wild-type papilloma virus L2 protein, said method comprising the steps of: (1) constructing a recombinant DNA molecule comprising a DNA sequence encoding said papilloma virus L2 protein wherein said sequence is operably linked to a promoter; (2) introducing said recombinant DNA molecule into a suitable host cell; (3) expressing said papilloma in said host cell in the presence of said papilloma virus L1 protein to form one or more virus-like-particles; and (4) recovering one or more (unbound) virus-like-particles from said host cell.”
- ^ [2] "Gardasil Developer Remembered", The Age
- ^ Also, Ruth Beran, “Ian Frazer’s patent problem”, Australian Life Scientist, 21 June 2008, quoting Ian Frazer “Jian Zhou died in 1999 but he was an equal partner.”
- ^ again, [3] "Gardasil Developer Remembered", The Age (at [4] go to May 3, 2008 and click “Gardasil developer remembered in Qld” for alternative routing to this archived article.
- ^ [5] A complete bibliography of Dr. Jian Zhou's published papers is here available.
External links
- [6] www.uspto.gov
- [7] This is an archive of an exhaustive and detailed interview with Ian Frazer. Look under title "Making the indispensible virus like particle". Pictures of Jian Zhou can also be there viewed.
- [8] At pages 2-4 here, the VLPs development at various institutions, the convolution of multiple patent Interference proceedings thereon, there ultimate resolution in Zhou's and Frazer's favor and a chronological history of the various VLP patents licensing and crosslicensing by various pharmaceutical manufacturers are succinctly outlined.