Antibodies: Timeline of key events

Mouseover the event title for a more detailed description of the event (if available). To search for particular terms in the description of the event enter the term in the box below 'Event' on the table and press 'enter'. Alternatively use the dropdown lists to filter by Person, Place or Science. Click here to clear the filter.

Orthoclone OKT3 (muromonamb0CD3) was approved as an immunosuppressant drug to reduce patients rejection of their kidney transplants. It is a mouse-derived (murine) monoclonal antibody (Muromonab-CD3) that targets a membrane protein on the surface of T cells. OKT3 was first developed in 1979 by Patrick Kung at Ortho Diagnostics as tool to identify different T-cell subsets in humans. It took Kung time to persuade his company to develop the monoclonal antibody as a drug. 1986-06-19T00:00:00+0000Campath-1G is humanised, resulting in Campath-1H. It is accomplished with technology developed by Greg Winter.1988-01-01T00:00:00+0000This patent is filed on the basis of work reported in M Brüggeman, HM Caskey, C Teale, H Waldmann, Williams, Surani, and MS Neuberger, A repertoire of monoclonal antibodies with human heavy chains from transgenic mice, Proc Natl Acad Sci USA, 86 (Sept 1989), 6709-13. 1988-01-01T00:00:00+0000Gregory Winter at the Laboratory of Molecular Biology develops the technique as part of his strategy to create an artificial immune system for generating monoclonal antibodies. The technique is published in R Olandi, DH, Gussow, PT Jones and G Winter, 'Cloning immunoglobulin variable domains for expression by polymerase chain reaction', Proc Natl Acad Sci USA, 86 (May 1989), 3833-7. 1988-11-01T00:00:00+0000Gregory Winter together with David Chiswell set up CAT to develop phage display technology for monoclonal antibodies1989-01-01T00:00:00+0000Gregory Winter together with CAT create the first phage monoclonal antibodies, laying the foundation for the generation of diverse libraries of randomly shaped human antibodies. With this scientists are no longer dependent on the natural immune system of animals or humans and the limitations this poses for the production of monoclonal antibodies. 1990-01-01T00:00:00+0000This is achieved by Richard Lerner and Carlos Barbas at the Scripps Research Institute with the backing of Stratagene, an American biotechnology specialising in antibody engineering.1991-01-01T00:00:00+0000European Committee for Proprietary Medicinal Products recommends the approval of Centoxin (Nebacumab) , a drug originally developed by Henry Kaplan and Nelson Tang at Stanford University and prepared for market by Centocor. Based on this recommendation the drug was subsequently approved for market in The Netherlands, Britain, Germany and France between March and December 1991.1991-03-01T00:00:00+0000Heidelberger 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' and laying the foundation for the production of monoclonal antibodies.1994-10-07T00:00:00+0000ReoPro (abciximab), developed by Centocor, approved for use during and after coronary artery procedures like angioplasty. A chimeric antibody (Abciximab) created by Barry Koller to study platelet behaviour, the antibody was found to be more effective than aspirin in prevent platelets from sticking together and causing thrombus (blood clot) formation within the coronary artery. Today the drug is the most commonly used treatment for angioplasty patients, making the procedure safer for use during heart attacks and as a preventative measure. 1994-12-01T00:00:00+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. 1994-12-01T00:00:00+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+0000Daclizumab was approved by the FDA for the preventition 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+0000
Date Event People Places Sciences
Jun 1986First monoclonal antibody approved as a drug for use in humansChang, Kung, Gringas, Schlossman, GoldsteinOrtho DiagnosticsMonoclonal antibodies, Transplantation
1988Campath-1H is created - the first clinically useful humanised monoclonal antibody.Winter, Waldmann, Reichmann, ClarkCambridge University, Laboratory of Molecular BiologyMonoclonal antibodies, Recombinant DNA, Campath
1988Patent application filed for a method to create transgenic mice for the production of human antibodiesBruggeman, Caskey, Neuberger, Surani, Teale, Waldmann, WilliamsLaboratory of Molecular Biology, Babraham Institute, Cambridge UniversityMonoclonal antibodies, gene cloning, transgenic animals
Nov 1988Patent application filed for the the use of PCR to create a library of antibody fragmentsGussow, Jones, Olandi, WinterLaboratory of Molecular Biology, Istituto Nazionale dei TumoriMonoclonal antibodies, PCR
1989Cambridge Antibody Technology (CAT) foundedWinter, ChiswellLaboratory of Molecular Biology, CATMonoclonal antibodies, Phage Display
1990Phage display monoclonal antibodies createdWinterLaboratory of Molecular Biology, CATMonoclonal antibodies, Phage Display
1991First display and selection of human antibodies phageBarbas, LernerScripps Research InstituteMonoclonal antibodies, Phage Display
Mar 1991Monoclonal antibody drug approved in Europe for the treatment of septic shockKaplan, TangStanford University Medical School, CentocorMonoclonal antibodies
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, Gene cloning
7 Oct 1994Niels Kaj Jerne diedJerneBasel Institute for ImmunologyImmunology, Monoclonal antibodies
Dec 1994Second monoclonal antibody drug approvedCollerStony Brook University, CentocorMonoclonal antibodies
1994First chimeric monoclonal antibody therapeutic approved for marketCollerCentocor, 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
Dec 1997First humanised monoclonal antibody approved for marketQueenProtein Design Labs, RocheMonoclonal antibodies, Recombinant DNA

Jun 1986

First monoclonal antibody approved as a drug for use in humans

1988

Campath-1H is created - the first clinically useful humanised monoclonal antibody.

1988

Patent application filed for a method to create transgenic mice for the production of human antibodies

Nov 1988

Patent application filed for the the use of PCR to create a library of antibody fragments

1989

Cambridge Antibody Technology (CAT) founded

1990

Phage display monoclonal antibodies created

1991

First display and selection of human antibodies phage

Mar 1991

Monoclonal antibody drug approved in Europe for the treatment of septic shock

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

Dec 1994

Second monoclonal antibody drug approved

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

Dec 1997

First humanised monoclonal antibody approved for market