Antibodies: Timeline of key events

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Heidelberger was one of the founders of immunochemistrty, a branch of biochemistry that investigates the mammalian immune system at the molecular level. He first made his mark in 1923 when he found with Oswald Avery that that the immune system could target bacterial sugars. The two scientists made the discovery while investigating a capsular substance that envelops pneumococcus and other species of bacteria. Their work helped determine that antibodies were proteins. It also paved the way to improving the production of more effective serum therapies for the prevention of bacterial infectious like pneumonia and meningitis.1991-06-25T00:00:00+0000Developed to treat Gram-negative sepsis, Centoxin originated from research conducted by Henry Kaplan and Nelson Teng based at Stanford University. It was licensed to Centocor, a small biotechnology company in Philadelphia. Following the FDA's request for more information, Centocor watched US$1.5 billion of its market capitalisation disappear. The news also had a devastating impact on other companies developing monoclonal antibody drugs. 1992-02-20T00:00:00+0000Interim trial data from trials show unexpectedly high mortality from Centoxin, leading to withdrawal of the drug from the European market. Reinforces general pessimism about the future for monoclonal antibody drugs. 1993-02-01T00:00:00+0000Three groups of scientists separately report the successful generation of different strains of transgenic mice for the generation of human monoclonal antibodies. Two of the teams are based in biotechnology companies: GenPharm (led by Nils Lonsberg), Cell Gensys (led by Larry Green) , and the other involved a collaboration (led by Marian Bruggemann and Michael Neuberger) between scientists at the Laboratory of Molecular Biology, Braham Institute and the University of Cologne.1994-01-01T00:00:00+0000Jerne shared the 1984 Nobel Prize for Medicine for 'theories concerning the specificity in development and control of the immune system'. He developed three important theories for immunology. Firstly, that antibodies are formed during fetal development and are present in the body from birth. Secondly, that white blood cells, lymphocytes, teach themselves to recognise the body's own substances in the thymus gland. Thirdly, he proposed the network theory which depicts the immune system as a complex self-regulating network that can turn itself on and off when needed. Jerne's work paved the way to development of monoclonal antibodies. He was the founder and director of the Basel Institute of Immunology.1994-10-07T00:00:00+0000Abciximab (ReoPro) approved by the FDA and European regulatory authorities to prevent blot clots during coronary artery procedures like angioplasty. The monoclonal antibody was originally developed by Barry Coller at State University of New York and commercially developed by Centocor. The drug showed for the first time that monoclonal antibodies could be used for the treatment of acute disease conditions. 1994-12-22T00:00:00+0000German regulatory authorities approve Panorex as an adjuvant therapy, that is a drug given in addition to primary or main treatment, for postoperative colorectal cancer. The drug originated from resesearch undertaken by Hilary Koprowski and his colleagues at the Wistar Institute. 1995-01-01T00:00:00+0000German regulatory authorities approve edrecolomab (Panorex) as an adjuvant treatment for post-operative colorectal cancer. The monoclonal antibody, originally known as 17-1A, was developed at the Wistar Institute and commercially developed for market by Centocor. 1995-01-01T00:00:00+0000Together with Cesar Milstein, Kohler developed the first unlimited supply of long-lasting monoclonal antibodies. Their technique now underpins the development and application of many diagnostics and therapeutics. Kohler and Milstein devised the method as part of their search for a tool to investigate how the immune system can make so many different kinds antibodies, each able to bind to a highly specific receptor on foreign substances that invade the body. 1995-03-01T00:00:00+0000Ritxuan (rituiximab) is approved for the treatment of non-Hodgkin Lymphoma. The drug arose out of Ronald Levy's research for three decades to find a way of harnessing the power of the body's own immune system to fight cancer. 1997-01-01T00:00:00+0000Koshland was an American immunologist who was a major pioneer in the field of antibodies. Her work was instrumental in showing antibodies to be discrete antibodies and knowledge about the origins of antibody specificity. In the 1960s, she demonstrated that the efficiency and effectiveness with which antibodies can combat foreign invaders is determined by their different amino acid compositions. By the 1990s she had unravelled the process that accompanies and directs B cell activation and maturation. A major role-model for other women scientists, Koshland was nearly not awarded her PhD because her professor thought it would be a waste because she was pregnant. 1997-10-28T00:00:00+0000Daclizumab was approved by the FDA for the prevention of acute rejection of kidney transplants. The monoclonal antibody was developed by Protein Design Labs using a humanising method devised by Cary Queen and marketed together with F. Hoffmann-La Roche. 1997-12-01T00:00:00+0000The drug is a monoclonal antibody that targets cancer cells that overproduce the HER2/neu oncoprotein1998-01-01T00:00:00+0000The company was set up by Perry Fell and Clay Siegall. The two scientists founded Seattle Genetics after their former employer, Bristol-Myers Squibb cuts its antibody cancer research programme.1998-01-01T00:00:00+00001998-01-01T00:00:00+0000Remicade (infliximab) is approved for the treatment of Crohn's disease. Soon after Remicade wins approval for other autoimmune and inflammatory conditions including rheumatoid arthritis and ulcerative colitis. The drug, a monoclonal antibody against TNF alpha, a powerful promoter of inflammation, was developed in 1989 by Jan Vilcek and Jumning Le and developed in collaboration with Centocor, Marc Feldmann and Maini1998-08-01T00:00:00+0000Genentech agreed to help Seattle Genetics develop SGN-40, one of its drugs for CD40 positive cancers. Under the deal Genentech made an upfront payment of $60 million to Seattle Genetics and agreed to make milestone payments in excess of $800 million and double-digit royalties on any sales.1999-01-01T00:00:00+0000Launched by the biotechnology company Medarex in collaboration with Jim Allison. 2000-01-01T00:00:00+0000Michael Smith shared the 1993 Nobel Prize for Chemistry for a technique that enables researchers to introduce specific mutations into genes and, thus, to the proteins that they encode. He developed the method, known as site-directed mutagenesis, in the 1970s, in collaboration with Fred Sanger and Clyde A Hutchinson III. The advantage of the technique was that it allowed comparisons to be made of different protein molecules and provide a means to deliberately alter a specific gene thereby making it possible to modify the characteristics of an organism. His work opened up a new chapter for studying and treating genetic diseases. Site-directed mutagenesis is a pivotal tool today in genetic and protein research and engineering and at the forefront of the development of monoclonal antibody drugs. 2000-10-04T00:00:00+0000The technology allowed for the development of antibody drug conjugates.2001-01-01T00:00:00+0000
Date Event People Places Sciences
25 Jun 1991Michael Heidelberger died in New York City, USAHeidelbergerRockefeller Institute, Columbia UniversityAntibodies, Immunology
Feb 1992Monoclonal antibodies market crashed following FDA's call for more information for Centocor's drug, CentoxinSchoemaker, Koprowski, MilsteinCentocor, WistarMonoclonal antibodies
Feb 1993Centoxin withdrawn from European market CentocorMonoclonal antibodies
1994First transgenic mice strains reported for producing human monoclonal antibodiesBruggemann, S.Green, Lonsberg, NeubergerCell Genesys, GenPharm, Laboratory of Molecular BiologyMonoclonal antibodies, Transgenic animals, Cloning
7 Oct 1994Niels Kaj Jerne diedJerneBasel Institute for ImmunologyImmunology, Monoclonal antibodies
22 Dec 1994First chimeric monoclonal antibody therapeutic approved for marketColler, SchoemakerCentocor, State University of New YorkMonoclonal antibodies, Recombinant DNA
1995First monoclonal antibody drug for cancer approved in EuropeKoprowski Monoclonal antibodies
1995First monoclonal antibody therapeutic for cancer approved for marketKoprowskiWistar Institute, CentocorMonoclonal antibodies
1 Mar 1995Georges Kohler diedKohlerLaboratory of Molecular BiologyMonoclonal antibodies
1997FDA approved the first monoclonal antibody cancer drug for the American marketLevy, RastetterStanford University Medical School, Idec PharmaceuticalsCancer immunotherapy, Monoclonal antibodies
28 Oct 1997Marian E Koshland diedKoshlandBrookhaven National LaboratoryImmunology, Antibodies
Dec 1997First humanised monoclonal antibody approved for marketQueenProtein Design Labs, RocheMonoclonal antibodies, Recombinant DNA
1998FDA approved Trastuzumab (Herceptin) for the treatment of metastatic breast cancer   Monoclonal antibodies, Oncology
Jan 1998Seattle Genetics founded Fell, SiegallSeattle GeneticsMonoclonal antibodies, Oncology
1998Seattle Genetics licensed patents from Bristol-Myers Squibb Seattle GeneticsMonoclonal antibodies, Oncology
Aug 1998FDA and European regulatory authorities approved the first monoclonal antibody drug for an autoimmune diseaseVilcek, Le, Feldmann, Maini, SchoemakerNew York University, Centocor, Kennedy Institute of RheumatologyMonoclonal antibodies
1999Seattle Genetics and Genentech partnership signed Seattle Genetics, GenentechMonoclonal antibodies, Oncology
2000First clinical trials launched to test first immune checkpoint inhibitor drug containing a monoclonal antibody against CTLA-4 (ipilimumab, Yervoy®)AllisonMedarex, University of California BerkleyImmune checkpoint inhibitors, Immunology, Cancer immunotherapy, Oncology, Monoclonal antibodies
4 Oct 2000Michael Smith diedMichael SmithUniversity of British ColumbiaGene editing, Genetics, Monoclonal antibodies
2001Seattle Genetics began licensing out its technology to other companies Seattle GeneticsMonoclonal antibodies, Oncology

25 Jun 1991

Michael Heidelberger died in New York City, USA

Feb 1992

Monoclonal antibodies market crashed following FDA's call for more information for Centocor's drug, Centoxin

Feb 1993

Centoxin withdrawn from European market

1994

First transgenic mice strains reported for producing human monoclonal antibodies

7 Oct 1994

Niels Kaj Jerne died

22 Dec 1994

First chimeric monoclonal antibody therapeutic approved for market

1995

First monoclonal antibody drug for cancer approved in Europe

1995

First monoclonal antibody therapeutic for cancer approved for market

1 Mar 1995

Georges Kohler died

1997

FDA approved the first monoclonal antibody cancer drug for the American market

28 Oct 1997

Marian E Koshland died

Dec 1997

First humanised monoclonal antibody approved for market

1998

FDA approved Trastuzumab (Herceptin) for the treatment of metastatic breast cancer

Jan 1998

Seattle Genetics founded

1998

Seattle Genetics licensed patents from Bristol-Myers Squibb

Aug 1998

FDA and European regulatory authorities approved the first monoclonal antibody drug for an autoimmune disease

1999

Seattle Genetics and Genentech partnership signed

2000

First clinical trials launched to test first immune checkpoint inhibitor drug containing a monoclonal antibody against CTLA-4 (ipilimumab, Yervoy®)

4 Oct 2000

Michael Smith died

2001

Seattle Genetics began licensing out its technology to other companies

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