Winter, Gregory P.

Gregory P. Winter, in full Sir Gregory Paul Winter, (born April 14, 1951, Leicester, England), British biochemist known for his development of the first humanized antibodies, his research on the directed evolution of antibodies, and his application of phage display technology for the development of fully human therapeutic antibodies. Winter was awarded the 2018 Nobel Prize in Chemistry, shared with American biochemists George P. Smith and Frances H. Arnold, for his scientific breakthroughs relating to the development of therapeutic antibodies.

Winter spent his youth in West Africa, thriving in the warm climate after a sickly infanthood in England. He later returned to England for undergraduate studies at Trinity College, Cambridge, completing a degree in 1973, and in 1976 earned a Ph.D. from the Medical Research Council (MRC) Laboratory of Molecular Biology at Cambridge. In 1981, following postdoctoral fellowships at Imperial College London, and the Institute of Genetics at Cambridge, Winter joined the faculty at the MRC Laboratory of Molecular Biology. He remained there for the duration of his career, eventually serving as its deputy director and, in 2014, being made professor emeritus.

In the early 1980s, after investigating relationships between gene mutation and protein function, Winter focused his research on site-directed mutagenesis in antibodies. At the time, therapeutic antibodies developed for use in humans were derived from mouse proteins, which could cause potentially dangerous immune reactions in human patients. To overcome this problem, Winter engineered so-called humanized antibodies, in which the sections of the mouse antibody that stimulated unwanted immune reactions were replaced by human antibody fragments. The breakthrough facilitated the eventual development of drugs such as trastuzumab (Herceptin), approved for the treatment of breast cancer, and bevacizumab (Avastin), approved for use against certain types of cancer and for age-related macular degeneration.

Winter later refined phage display technology, originally developed by Smith, to allow for the generation of fully human antibody proteins by fusion phages (bacteriophages) produced in the laboratory, circumventing potential limitations associated with his previously developed humanization process. Phage display technology proved critical to the process of directed evolution, whereby researchers are able to derive variant antibody proteins with improved binding affinity and high selectivity for their therapeutic targets using directed mutagenic approaches. The first fully human antibody produced using Winter’s phage display technique to be marketed for use in humans was adalimumab (Humira), which was approved by the U.S. Food and Drug Administration in 2002 for the treatment of rheumatoid arthritis. The drug was later approved for the treatment of inflammatory bowel disease, psoriasis, and certain other inflammatory conditions.

Over the course of Winter’s career, he founded or cofounded several biotech companies to facilitate the development of his novel therapeutic agents. Among them were Cambridge Antibody Technology in 1989, which was later purchased by AstraZeneca; Domantis in 2000, which was acquired by GlaxoSmithKline in 2006; and Bicycle Therapeutics in 2009, which focused on the chemical synthesis and therapeutic development of small compounds known as bicyclic peptides. Winter received numerous awards and honours throughout his career, including the King Faisal International Prize for Medicine (1995) and the Royal Medal (2011). He was a fellow of multiple organizations, including Trinity College and the Royal Society. He received a knighthood for his contributions to molecular biology in 2004, and in 2012 he was made Master of Trinity at Trinity College.