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]