Tse Wen Chang

Tse Wen Chang (Chinese: 張子文; pinyin: Zhāng Zǐwén, born August 25, 1947) is an immunology researcher, whose career spans across academia and industry. His early research involving the Immunoglobulin E (IgE) pathway and antibody-based therapeutics lead to the development of omalizumab (also known as Xolair), a medication that has been approved for the treatment of severe allergic asthma and severe chronic spontaneous urticaria.[1] Chang is a cofounder of Tanox, a biopharmaceutical company specialized in anti-IgE therapies for the treatment of allergic diseases.[2] After Tanox's tripartite partnership with Genentech and Novartis was forged in 1996, Chang returned to his alma mater, the National Tsing Hua University in Taiwan and served as the Dean (1996–1999) of the College of Life Sciences.[3] Chang was appointed by the Taiwanese government as President of the Development Center for Biotechnology (DCB) in 2000, and served as a Science and Technology Advisor of the Executive Yuan from 2002 to 2006.[4] From 2006 to 2016, he was tenured as Distinguished Research Fellow at the Genomics Research Center, Academia Sinica.[5] He founded Immunwork, Inc. in 2014.

Tse Wen Chang
張子文
Born (1947-08-25) August 25, 1947
Zhongli District, Taoyuan County, Taiwan
EducationNational Tsing Hua University (B.S; M.S)
Harvard University (Ph.D.)
Known forXolair
anti-IgE therapy
Antibody microarray
Scientific career
FieldsImmunology, Biomedicine, Biotechnology
InstitutionsNational Tsing Hua University
Tanox, Inc.
Academia Sinica
Immunwork, Inc.
Doctoral advisorAlfred L. Goldberg

Education

Chang was born and raised in Zhongli District, Taoyuan County, Taiwan in 1947. His ancestry traces back to Mei County, Guangdong Province, China. His father Chang Chun-an (張均安) spent his entire career working for the Taiwan Railroad Bureau. Chang's mother, Yeh Ting-mei (葉丁妹), was an elementary school teacher, who worked as a housewife after marriage to raise five children. Chang obtained a bachelor's degree (1970) and master's degree (1972) in chemistry at the National Tsing Hua University. Afterwards, Chang received a four-year fellowship at Harvard University, where he did thesis research on protein degradation in the muscle during fasting with Alfred L. Goldberg.[6] Chang received his Ph.D. in 1977, and did postdoctoral research on T cell immune mechanisms with Herman Eisen at the Center for Cancer Research at MIT from 1977 to 1980.[7]

Career

Contributions to biomedicine

Chang invented anti-IgE therapeutics in 1987.[8] IgE plays a central role in the initiation of hypersensitivity reactions in the human body, and is responsible for allergic diseases that affect 20-40% of the population in developed countries.[9] Originating from Chang's research, antibodies that target the IgE-mediated allergic pathway have proven effective in the treatment of various allergic diseases. Among these anti-IgE drugs are: Omalizumab (Xolair), approved by the U.S. Food and Drug Administration (FDA) for the treatment of allergic asthma and chronic spontaneous urticaria (primarily an autoimmune disease); Talizumab (TNX-901), shown to be effective in treating allergic rhinitis (hay fever) and peanut allergy; and Ligelizumab, a high-affinity TNX-901 under active clinical development at Novartis.[10][11][12][13] In 1993, Chang's patent was granted for his discovery of CεmX, a unique region on human membrane-bound IgE (mIgE), leading to another therapeutic approach to treating IgE-mediated diseases.[14][15] Apart from anti-IgE therapeutics, Chang also first proposed the concept and methodology of the antibody matrix in 1983.[16] By aligning antibodies of distinct specificities in a matrix-like manner, scientists are able to detect and quantify multiple antigens in one simultaneous attempt. Thereafter, many other types of microarrays emerged, including DNA microarrays and protein microarrays, among others.[17]

Work in biotechnology

In March 1986, Tse Wen and Nancy T. Chang founded Tanox, Inc., where he served as Vice President of Research & Development (1986–1996) and director of the board from 1986 until Tanox was acquired by Genentech in 2007.[18] In order to secure funding for a start-up company based on family funds, the Changs sought collaboration with Genentech in 1989, sending data and samples of early anti-IgE antibody, but talks with Genentech were unsuccessful.[19] In 1990, Tanox partnered with Ciba-Geigy (which later merged with Sandoz to form Novartis) and started developing Talizumab (TNX-901).[20]

A few years later, legal disputes arose as the Changs discovered that Genentech launched its own anti-IgE program, developing what now became known as Omalizumab (Xolair). The Changs took it to the court in 1993 and accused Genentech of misappropriating its work, but the legal battle dragged on.[21] Chang was granted patents in 1995.[22][23] In 1996, Tanox and Genentech settled out of court, with Genentech paying Tanox a compensation. The two companies and Novartis agreed to jointly develop Xolair, under the reasoning that Genentech had better manufacturing processes to produce antibodies in large quantities.[24] Chang not only proposed the theory behind anti-IgE therapeutics, but also actively participated in the phase I and II clinical trials of Talizumab from 1990 to 1996.[25][26]

Meanwhile, after the settlement in 1996, Tanox continued to develop Talizumab, not for allergic asthma but for peanut allergy. In 2001–2003, Talizumab entered phase II clinical trials for peanut allergy, and obtained very positive results.[11][12] Genentech, however, sued Tanox, arguing that their contract in 1996 should prevent Tanox from developing any potential competitor drugs to Xolair. Again, the dispute rose to the court. Although Tanox won the consent in a federal district court, it lost the arbitration that followed, and the development of Talizumab for peanut allergy was suspended.[19][27]

Post-Tanox

In 2014, Chang started the company Immunwork in Taiwan.[28][29]

Investing attempts

Chang tried his hand at investing, purchasing large quantities of derivatives under Deutsche Bank's advice. Unfortunately, his scientific expertise did not translate into financial acumen, and as a result he lost $50 million in total. Chang initiated a counter-claim for the amount lost in response to the bank's claim for a sum of $1.7 million. While successful in his claim at the High Court, the decision was reversed on appeal, where the Singapore Court of Appeal stated that he had the requisite knowledge of shares to not rely on the advice of the bank. He also had to repay a $1.7 million debt incurred from investment losses. This case has since become a point of authority in contract law. [30]

Awards and honors

Selected publications

References
  1. Chang, Tse Wen; Chen, Christina; Lin, Chien-Jen; Metz, Martin; Church, Martin K.; Maurer, Marcus (2015-02-01). "The potential pharmacologic mechanisms of omalizumab in patients with chronic spontaneous urticaria". Journal of Allergy and Clinical Immunology. 135 (2): 337–342.e2. doi:10.1016/j.jaci.2014.04.036. PMID 24948369.
  2. "Tanox, Inc. - Company Profile, Information, Business Description, History, Background Information on Tanox, Inc". Reference for Business. Advameg, Inc. Retrieved 3 May 2017.
  3. "2008年：張子文校友". National Tsing Hua University. Retrieved 3 May 2017.
  4. "張子文 (Dr. Tse-Wen Chang)". Board of Science and Technology, Executive Yuan. Retrieved 3 May 2017.
  5. "Chang, Tse Wen". Genomics Research Center, Academia Sinica. Retrieved 3 May 2017.
  6. "Alfred Goldberg". Harvard University. Retrieved 2017-06-13.
  7. 張, 子文 (2017-03-23). "走上新藥研究與事業新創的心路歷程" (PDF). The Taiwan Society for Biochemistry and Molecular Biology.
  8. 龐, 中培 (September 2005). "從抗體到藥物──專訪 張子文教授" (PDF). Scientific American. Archived from the original (PDF) on July 15, 2020. Retrieved 15 May 2017. Alt URL
  9. Chu, Hsing-Mao; Wright, Jon; Chan, Yueh-Hsuan; Lin, Chien-Jen; Chang, Tse Wen; Lim, Carmay (2014-01-24). "Two potential therapeutic antibodies bind to a peptide segment of membrane-bound IgE in different conformations". Nature Communications. 5: 3139. doi:10.1038/ncomms4139. ISSN 2041-1723. PMID 24457896.
  10. "Xolair – Biological Therapy". Drugdevelopment-technology.com.
  11. Leung DY, Sampson HA, Yunginger JW, et al. (2003). "Effect of anti-IgE therapy in patients with peanut allergy". N. Engl. J. Med. 348 (11): 986–93. doi:10.1056/NEJMoa022613. PMID 12637608.
  12. Leung DY, Shanahan WR, Li XM, Sampson HA (2004). "New approaches for the treatment of anaphylaxis". Novartis Found. Symp. Novartis Foundation Symposia. 257: 248–60, discussion 260–4, 276–85. doi:10.1002/0470861193.ch20. ISBN 978-0-470-86119-6. PMID 15025403.
  13. "Ligelizumab". Adis Insight. May 4, 2017. Retrieved 15 May 2017.
  14. U.S. Patent 5274075 A, Chang, Tse Wen, "Newly identified human epsilon immunoglobulin peptides and related products", published 1993-12-28, assigned to Tanox Biosystems, Inc.
  15. Chan, Yueh-Hsuan; Lee, Yu-Tzu; Chou, Hung-Wen; Wu, Pheidias C.; Chen, Jiun-Bo; Li, Chau-Hong; Cheng, Tien-Tien; Chen, Nien-Yi; Lue, Ko-Haung (2014-05-01). "Developing an antibody targeting CϵmX of mIgE for the treatment of allergic and other IgE-mediated diseases (VAC6P.954)". The Journal of Immunology. 192 (1 Supplement): 140.15. ISSN 0022-1767.
  16. Chang, T. W. (1983-12-16). "Binding of cells to matrixes of distinct antibodies coated on solid surface". Journal of Immunological Methods. 65 (1–2): 217–223. doi:10.1016/0022-1759(83)90318-6. ISSN 0022-1759. PMID 6606681.
  17. Abu-Jamous, Basel; Fa, Rui; Nandi, Asoke K. (2015-04-16). Integrative Cluster Analysis in Bioinformatics. John Wiley & Sons. p. 56. ISBN 978-1-118-90655-2.
  18. "Our Founder". Immunwork. Retrieved 2017-05-16.
  19. Hamilton, David P. (2005-04-05). "How Genentech, Novartis Stifled A Promising Drug". Wall Street Journal. ISSN 0099-9660. Retrieved 2017-05-16.
  20. "Sample Business Contracts". contracts.onecle.com. Retrieved 2017-05-16.
  21. Thorpe, Helen (April 1, 1995). "Drug war. (small drug firm Tanox takes on Genentech over patent rights)". Texas Monthly. Archived from the original on October 29, 2013. Retrieved 2017-06-15 – via HighBeam Business.
  22. U.S. Patent 5422258 A, "Methods for producing high affinity anti-human IgE-monoclonal antibodies which binds to IgE on IgEabearing B cells but not basophils", published 1995-06-06, assigned to Tanox Biosystems, Inc.
  23. U.S. Patent 5428133 A, "Chimeric anti-human IgE-monoclonal antibody which binds to secreted IgE and membrane-bound IgE expressed by IgE-expressing B cells but notto IgE bound to FC receptors on basophils", published 1995-06-27, assigned to Tanox Biosystems, Inc.
  24. Pollack, Andrew (2003-03-13). "Wrangling May Delay Peanut Allergy Drug". The New York Times. ISSN 0362-4331. Retrieved 2017-05-26.
  25. Corne, J.; Djukanovic, R.; Thomas, L.; Warner, J.; Botta, L.; Grandordy, B.; Gygax, D.; Heusser, C.; Patalano, F. (1997-03-01). "The effect of intravenous administration of a chimeric anti-IgE antibody on serum IgE levels in atopic subjects: efficacy, safety, and pharmacokinetics". The Journal of Clinical Investigation. 99 (5): 879–887. doi:10.1172/JCI119252. ISSN 0021-9738. PMC 507895. PMID 9062345.
  26. Racine-Poon, A.; Botta, L.; Chang, T.W. (1997). "Clinical efficacy of CGP 51901, an anti-IgE chimeric monoclonal antibody, in patients with allergic rhinitis: is it related to the extent of IgE suppression and pharmacokinetics". Clinical Pharmacology & Therapeutics. 62 (6): 675–90. doi:10.1016/S0009-9236(97)90087-4. PMID 9433396.
  27. "Genentech, Novartis and Tanox Settle Disputes Surrounding Xolair and TNX-901" (Press release). Genentech. Retrieved 2017-06-15.
  28. "Five Questions with Immunwork" (Blog). Terrapinn. 2016-09-23. Retrieved 2017-05-26.
  29. "Overview". Immunwork. Retrieved 2017-05-26.
  30. http://www.singaporelaw.sg/sglaw/laws-of-singapore/case-law/free-law/court-of-appeal-judgments/15349-deutsche-bank-ag-v-chang-tse-wen-and-another-appeal-2013-sgca-49
  31. "Chang, Tse Wen 張子文" (in Chinese). Genomics Research Center, Academia Sinica. Retrieved 2017-05-26.
  32. Jayaraman, K. S.; Louët, Sabine; Powell, Kendall; Ransom, John; Sheridan, Cormac; Vastag, Brian; Waltz, Emily (2006-03-01). "Who's who in biotech". Nature Biotechnology. 24 (3): 291–300. doi:10.1038/nbt0306-291. ISSN 1087-0156. PMC 7097553. PMID 16525392.
  33. "Past AAAAI Honorary Award Recipients". The American Academy of Allergy, Asthma & Immunology. Retrieved 2017-05-26.
  34. "TWAS announces 2014 Prize winners". TWAS. Retrieved 2017-05-26.
  • "Immunwork", Biotech company founded and directed by Chang.
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