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Cambridge Antibody Technology (officially Cambridge Antibody Technology Group Plc, informally CAT) was a biotechnology company headquartered in
Cambridge Cambridge ( ) is a university city and the county town in Cambridgeshire, England. It is located on the River Cam approximately north of London. As of the 2021 United Kingdom census, the population of Cambridge was 145,700. Cambridge bec ...
, England, United Kingdom. Its core focus was on antibody therapeutics, primarily using
Phage Display Phage display is a laboratory technique for the study of protein–protein, protein–peptide, and protein– DNA interactions that uses bacteriophages (viruses that infect bacteria) to connect proteins with the genetic information that encodes ...
and
Ribosome Display Ribosome display is a technique used to perform ''in vitro'' protein evolution to create proteins that can bind to a desired ligand. The process results in translated proteins that are associated with their mRNA progenitor which is used, as a compl ...
technology. Phage Display Technology was used by CAT to create
adalimumab Adalimumab, sold under the brand name Humira, among others, is a monoclonal antibody used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurati ...
, the first fully human antibody blockbuster drug.
Humira Adalimumab, sold under the brand name Humira, among others, is a monoclonal antibody used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativ ...
, the brand name of adalimumab, is an anti-TNF antibody discovered by CAT as D2E7, then developed in the clinic and marketed by
Abbvie AbbVie is an American publicly traded biopharmaceutical company founded in 2013. It originated as a spin-off of Abbott Laboratories. History On October 19, 2011, Abbott Laboratories announced its plan to separate into two publicly traded compani ...
, formerly
Abbott Laboratories Abbott Laboratories is an American multinational medical devices and health care company with headquarters in Abbott Park, Illinois, United States. The company was founded by Chicago physician Wallace Calvin Abbott in 1888 to formulate known dr ...
. CAT was also behind
belimumab Belimumab, sold under the brand name Benlysta, is a human monoclonal antibody that inhibits B-cell activating factor (BAFF), also known as B-lymphocyte stimulator (BLyS). It is approved in the United States, Canada, and the European Union to treat ...
, the anti-BlyS antibody drug marketed as
Benlysta Belimumab, sold under the brand name Benlysta, is a human monoclonal antibody that inhibits B-cell activating factor (BAFF), also known as B-lymphocyte stimulator (BLyS). It is approved in the United States, Canada, and the European Union to tre ...
and the first new approved drug for systemic lupus in more than 50 years. In 2018, the Nobel Prize organisation awarded one quarter of the Nobel Prize in Chemistry to a founding member of CAT, Sir Greg Winter FRS "for the phage display of peptides and antibodies.". Founded in 1989, CAT was acquired by
AstraZeneca AstraZeneca plc () is a British-Swedish multinational pharmaceutical and biotechnology company with its headquarters at the Cambridge Biomedical Campus in Cambridge, England. It has a portfolio of products for major diseases in areas includi ...
for £702m in 2006. AstraZeneca subsequently acquired
MedImmune MedImmune, LLC was a wholly owned subsidiary of AstraZeneca before February 14, 2019, when it was announced that the MedImmune name and branding would be discontinued in favor of AstraZeneca. MedImmune was founded in 1988 as Molecular Vaccines, ...
LLC, which it combined with CAT to form a global biologics R&D division called MedImmune. CAT was often described as the 'jewel in the crown' of the British biotechnology industry and during the latter years of its existence was the subject of frequent acquisition speculation.


History

CAT was founded in 1989 by Dr. David Chiswell OBE and Sir Greg Winter, with major scientific contributions from Dr. John McCafferty and the
Medical Research Council (UK) The Medical Research Council (MRC) is responsible for co-coordinating and funding medical research in the United Kingdom. It is part of United Kingdom Research and Innovation (UKRI), which came into operation 1 April 2018, and brings together t ...
(MRC). Operations began at the MRC laboratories in Cambridge. In May 1990, operations moved to the Daly Research Laboratories at
Babraham Institute The Babraham Institute is a life sciences research institution and a partner organisation of the University of Cambridge. The Babraham Institute is based on the Babraham Research Campus, partly occupying a former manor house, but also labora ...
, Cambridge. In 1992, CAT moved to Beech House on the
Melbourn Science Park Melbourn Science Park is a science park located in the village of Melbourn, England, south of Cambridge. It is owned by Bruntwood SciTech. Melbourn Science Park covers with nine buildings covering over . External links Official website Scie ...
to occupy units B1 and B2. In 1993 the company expanded into unit B3, into B4 into 1995, and in 1998 into units B5, B6, B8 and B9. CAT completed the occupation of Beech House by finally occupying B7 by the late 1990s. CAT listed on the
London Stock Exchange London Stock Exchange (LSE) is a stock exchange in the City of London, England, United Kingdom. , the total market value of all companies trading on LSE was £3.9 trillion. Its current premises are situated in Paternoster Square close to St Pau ...
in 1997, raising £43 million, and went through a second round of funding in 2000, raising over £90 million. In 1999, CAT expanded into a second location in Melbourn called Cambridge House. After leaving Melbourn, CAT sold this location on to housing developers in early 2006. In 2000, after a succession of deals that focussed on harnessing the exploitation of the
human genome The human genome is a complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the ...
, CAT's share price peaked at over £50 per share. Also in 2000, CAT decided to move out of Melbourn to a
science park A science park (also called a "university research park", "technology park”, "technopark", “technopole", or a "science and technology park" (STP)) is defined as being a property-based development that accommodates and fosters the growt ...
called
Granta Park Granta Park is a science, technology and biopharmaceutical park based on the bank of the River Granta in Great Abington near Cambridge, England. The first idea for the park came from the then Chief Executive of The Welding Institute (TWI Ltd) ...
, roughly away. Of the buildings on the park, the first to be occupied was the Franklin Building followed, in late 2002, by a move to a new corporate headquarters at the Milstein Building. The Franklin Building, named after
Rosalind Franklin Rosalind Elsie Franklin (25 July 192016 April 1958) was a British chemist and X-ray crystallographer whose work was central to the understanding of the molecular structures of DNA (deoxyribonucleic acid), RNA (ribonucleic acid), viruses, ...
, was formally opened in 2001 by
David Sainsbury, Baron Sainsbury of Turville David John Sainsbury, Baron Sainsbury of Turville, , raeng.org.uk. Accessed 8 September 2022. (24 October 1940) is a British politician, businessman and philanthropist. From 1992 to 1997, he served as chairman of Sainsbury's, the supermarket c ...
. The Milstein Building was named after
César Milstein César Milstein, CH, FRS (8 October 1927 – 24 March 2002) was an Argentine biochemist in the field of antibody research. Milstein shared the Nobel Prize in Physiology or Medicine in 1984 with Niels Kaj Jerne and Georges J. F. Köhler for d ...
, and had a modular design with separate laboratory (46,000 sq ft) and administration blocks (21,000 sq ft). In the same year, CAT listed on the
NASDAQ The Nasdaq Stock Market () (National Association of Securities Dealers Automated Quotations Stock Market) is an American stock exchange based in New York City. It is the most active stock trading venue in the US by volume, and ranked second ...
. When AstraZeneca acquired CAT in June 2006, plans were announced to occupy a new building on Granta Park, GP15, offering a further . Refurbishment of this building took approximately 18 months and the building was officially opened, in November 2008, with the name Aaron Klug Building.


Acquisitions


Aptein Inc.

On 15 July 1998, CAT completed the acquisition of Aptein Inc. This acquisition "...further strengthened its world leading position in antibody display technology...giving CAT controlling patents in the field of
polysome A polyribosome (or polysome or ergosome) is a group of ribosomes bound to an mRNA molecule like “beads” on a “thread”. It consists of a complex of an mRNA molecule and two or more ribosomes that act to translate mRNA instructions into pol ...
display. Polysome display involves the use of polysomes, a type of molecule responsible for protein synthesis within the human body, to display functional antibody proteins in vitro.". Three years later David Glover, CAT's Chief Medical Officer at the time, summarised the acquisition as one which essentially acquired Aptein's patent estate "Under the terms of the agreement CAT purchased the issued share capital and outstanding share options and warrants of Aptein for a total consideration of up to $11 million satisfied by the issue of up to 2.366 million CAT shares (an implied CAT share price of 278p.) $6 million of the consideration was satisfied by the issue of 1.290 million CAT shares on closing. The balance of the consideration of up to $5 million will be satisfied by the issue of up to 1.076 million CAT shares after Aptein's European patents have been sustained through opposition or appeal. In accordance with accounting standards the cost of acquiring this new technology has been capitalised and will be written off over the lives of the patents concerned.". Aptein was founded by Glenn Kawasaki, who is currently, amongst other positions, CEO at Accium BioSciences. According to an article published in Nature in 2002, that focused on the
automation Automation describes a wide range of technologies that reduce human intervention in processes, namely by predetermining decision criteria, subprocess relationships, and related actions, as well as embodying those predeterminations in machines ...
of
proteomics Proteomics is the large-scale study of proteins. Proteins are vital parts of living organisms, with many functions such as the formation of structural fibers of muscle tissue, enzymatic digestion of food, or synthesis and replication of DNA. I ...
,..."Normally, an
mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the ...
molecule passes through the ribosome-like ticker-tape and is released, along with the newly synthesised
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
molecule, when a sequence of three bases known as a '
stop codon In molecular biology (specifically protein biosynthesis), a stop codon (or termination codon) is a codon (nucleotide triplet within messenger RNA) that signals the termination of the translation process of the current protein. Most codons in mess ...
' is reached. In Aptein's technology, stop codons are eliminated so that the completed antibody and its mRNA remain bound together on the ribosome. The system, which CAT is now optimising, is entirely cell-free and so is more amenable to automation. This should make it possible to construct libraries that are orders of magnitude larger than those created using phage display." CAT published on their optimisation work with Ribosome Display, including: *The discovery of tralokinumab, a therapeutic antibody against IL-13. *An improved method for eukaryotic ribosome display *A comparison of phage and ribosome display approaches for improving antibody affinity and stability showing the advantages of ribosome display * The use of ribosome display to optimise pharmacology and "developability" of therapeutic proteins CAT used extensive data sets from ribosome display to patent protect their anti- IL-13 monoclonal antibody, CAT-354, in a world-first of sequence-activity-relationship claims.


Drug Royalty Corporation Inc.

In 1994, CAT signed a royalty deal with Drug Royalty Corporation Inc. (DRC) such that DRC would receive future royalty revenue from CAT's products. In January 2002, CAT made a share-based offer to buy DRC for £55 million so that it could buy out this royalty obligation. CAT valued DRC at C$3.00 a share, and this offer was initially recommended by the board of directors of DRC. On 8 March 2002 the investment company Inwest made a competing offer valuing DRC at C$3.05 per share. CAT's offer would see DRC
shareholders A shareholder (in the United States often referred to as stockholder) of a corporation is an individual or legal entity (such as another corporation, a body politic, a trust or partnership) that is registered by the corporation as the legal ...
receiving CAT shares whilst Inwest's offer would see the DRC shareholder receiving cash. DRC's board of directors changed their decision and recommended Inwest's offer. After a number of deadline extensions from CAT the offer from Inwest was accepted by the DRC shareholders. Inwest purchased DRC on 2 May 2002, and the company began operating as a private entity that continues operation today as DRI Capital. As a result of this failure to purchase DRC, CAT's right to buy back royalty interest was triggered at a cost to CAT of C$14 million (£6.2 million) by way of 463,818 CAT shares.


Oxford Glycosciences

On 23 January 2003 CAT made a share-based offer for Oxford Glycosciences (OGS) and at an
Extraordinary General Meeting An extraordinary general meeting, commonly abbreviated as EGM, is a meeting of members of an organisation, shareholders of a company, or employees of an official body that occurs at an irregular time.' The term is usually used where the group wou ...
shareholders voted to approve the merger. In March of this year CAT saw a decline in its share price. Discussions regarding the applicability of the royalty offset provisions for HUMIRA with Abbott Laboratories had started, and these had a negative impact on the CAT share price depressing the value of CAT's offer. On 26 February 2003 the British-based biotechnology group
Celltech Celltech Group plc was a leading British-based biotechnology business based in Slough. It was listed on the London Stock Exchange and was a constituent of the FTSE 100 Index. History Celltech was founded by Gerard Fairtlough in 1980 with financ ...
subsequently made a hostile £101 million cash offer for OGS and began buying OGS shares. Some reported that this activity represented the UK biotechnology industry's first-ever bidding war. Despite this improved offer from Celltech, OGS continued to recommend the CAT offer. Celltech continued to buy OGS shares and the OGS board pressed CAT to improve the terms of its offer as the Celltech shareholding reached 10.55%. OGS became alarmed that Celltech's share purchase would prompt CAT to walk away because, under takeover rules, it would not be able to forcibly purchase the 10.55 per cent stake Celltech owned. CAT failed to improve the terms of its bid forcing OGS to abandon the agreement. Celltech continued buying shares and, as their stake reached 25%, so the board of OGS met to reluctantly recommend the Celltech offer. Celltech completed the purchase of OGS in April 2003. Some newspapers reported that the failure of the bid by CAT would means that CAT would have to cut some of its workforce. Celltech was itself purchased by the Belgian drugmaker UCB in mid-2004.


Genencor

On 1 November 2005 CAT announced it was acquiring two
anti-CD22 immunotoxin An anti-CD22 immunotoxin is a monoclonal antibody (targeting CD22) linked to a cytotoxic agent. They are being studied in the treatment of some types of B-cell cancer. They bind to CD22, a receptor protein on the surface of normal B cells and B- ...
products from Genencor, namely GCR-3888 and GCR-8015.
Genencor Genencor is a biotechnology company based in Palo Alto, CA and a subsidiary of IFF. Genencor is a producer of Industrial enzymes and low-priced bulk protein. The name Genencor originates with Genencor, Inc., the original joint venture between Ge ...
is the
biotechnology Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used ...
division of
Danisco Danisco A/S is a Danish bio-based company with activities in food production, enzymes and other bioproducts as well as a wide variety of pharmaceutical grade excipients. It was formed in 1989 from the largest Danish industrial merger ever of t ...
and the acquisition meant CAT would hire certain former Genencor key employees to be responsible for the development of the programmes. GCR-3888 and GCR-8015 were discovered and initially developed by the
National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. T ...
, which is part of the U.S.
National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the lat ...
. Genencor licensed the candidates for
hematological malignancies Tumors of the hematopoietic and lymphoid tissues (American English) or tumours of the haematopoietic and lymphoid tissues (British English) are tumors that affect the blood, bone marrow, lymph, and lymphatic system. Because these tissues are ...
and entered into a
Cooperative Research and Development Agreement In the United States, a cooperative research and development agreement (CRADA or CRDA) is an agreement between a government agency and another government agency, a private company, non-profit, or university to work together on research and develop ...
(CRADA) with the NIH, which will now be continued by CAT. Under the original licence agreement with the NIH, CAT gained the rights to a portfolio of intellectual property associated with the programs and would pay future royalties to the NIH. CAT intended to file an Investigational New Drug (IND) application for GCR-8015 in various CD22 positive B-cell malignancies, including
Non-Hodgkin lymphoma Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tiredne ...
and
chronic lymphocytic leukaemia Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever, nigh ...
, following a period of manufacturing development which is expected to be complete by the end of 2006 and to support the NCI's ongoing development of GCR-3888 in Hairy cell leukaemia (HCL) and paediatric
acute lymphoblastic leukaemia Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruis ...
(pALL). CAT-8015 exhibited a greater affinity for CD22 than its predecessor, CAT-3888 and CAT's language such as "CAT will support the NCI's ongoing development of CAT-3888..." suggested at the time that their focus was on the second generation candidate. On 16 May 2013,
AstraZeneca AstraZeneca plc () is a British-Swedish multinational pharmaceutical and biotechnology company with its headquarters at the Cambridge Biomedical Campus in Cambridge, England. It has a portfolio of products for major diseases in areas includi ...
announced that CAT-8015, now Moxetumumab, has started Phase III clinical trials.


Collaborations

CAT entered into many collaborations with technology and pharmaceutical companies, including: * Searle, 1999 – CAT signed, what was at the time, their biggest deal with Searle, the pharmaceutical arm of
Monsanto The Monsanto Company () was an American agrochemical and agricultural biotechnology corporation founded in 1901 and headquartered in Creve Coeur, Missouri. Monsanto's best known product is Roundup, a glyphosate-based herbicide, developed in ...
. In 2000,
Pharmacia & Upjohn Pharmacia & Upjohn was a global pharmaceutical company formed by the merger of Sweden-based Pharmacia AB and the American company Upjohn in 1995. Today the remainder of the company is owned by Pfizer. In 1997, Pharmacia & Upjohn sold several b ...
merged with Monsanto and Searle to create Pharmacia Corporation. In 2003,
Pfizer Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfize ...
acquired Pharmacia. It is unsure as to whether the deal with Searle generated any clinical candidates. *
Human Genome Sciences Human Genome Sciences (HGS) was a biopharmaceutical corporation founded in 1992 by Craig Venter, Alan Walton and Wally Steinberg. It uses the human DNA sequence to develop protein and antibody drugs. It had drugs under development to treat suc ...
, 2000.
GlaxoSmithKline GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the tent ...
purchased HGSI in 2012. The deal with Cambridge Antibody Technology generated, amongst others; **An anti-BLyS antibody – registered by HGSI as LymphoStat-B, also known as
belimumab Belimumab, sold under the brand name Benlysta, is a human monoclonal antibody that inhibits B-cell activating factor (BAFF), also known as B-lymphocyte stimulator (BLyS). It is approved in the United States, Canada, and the European Union to treat ...
, and subsequently branded as Benlysta. On 16 November 2010 HGSI and GlaxoSmithKline announced the vote of the FDA advisory committee to recommend approval of belimumab for
systemic lupus erythematosus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Commo ...
. On 9 March 2011 the FDA voted 11 to 2 in favour of approving Benlysta "to treat patients with active, autoantibody-positive lupus who are receiving standard therapy, including corticosteroids, antimalarials, immunosuppressives, and nonsteroidal anti-inflammatory drugs". **An
anthrax Anthrax is an infection caused by the bacterium '' Bacillus anthracis''. It can occur in four forms: skin, lungs, intestinal, and injection. Symptom onset occurs between one day and more than two months after the infection is contracted. The s ...
therapeutic antibody – registered by HGSI as ABthrax, also known as raxibacumab. At the 2 November 2012 meeting of the Anti-Infective Drugs Advisory Committee to the US Food and Drug Administration (FDA) members "voted 16 to 1 in support of the clinical benefit of raxibacumab for the treatment of inhalational anthrax, with one abstention. In addition, the committee voted 18 – 0 in favour of the risk-benefit profile of raxibacumab". **Two anti-TRAIL receptor antibodies –
mapatumumab Mapatumumab (HGS-ETR1) is an experimental human monoclonal antibody undergoing clinical trials for the treatment of cancer. It targets TRAIL-R1, also known as DR4, which is expressed on the surface of many tumor cell types. Development histo ...
(HGS-ETR1) and
lexatumumab Lexatumumab (also known as ETR2-ST01) is an experimental agonistic human monoclonal antibody against TRAIL-R2 (DR5, APO-2), intended for the treatment of cancer. HGS-ETR2 antibodies were generated by Human Genome Sciences through a collaborat ...
(HGS-ETR2). Early work by CAT and HGS scientists showed that HGS-ETR1 induces cell death in certain tumour types. Following this data, HGS exercised an option to enter into an exclusive development partnership for the antibody. *
Genzyme Genzyme was an American biotechnology company based in Cambridge, Massachusetts. Since its acquisition in 2011, Genzyme (also known as Genzyme Transgenics Corp or GTC Biotherapeutics) has been a fully owned subsidiary of Sanofi. In 2010, Genzyme ...
, 2000. CAT held significant strength in the area of TGF beta with two products already – lerdelimumab (CAT-152) and metelimumab (CAT-192). The deal with Genzyme was "a broad strategic alliance to develop and commercialise human monoclonal antibodies directed against TGF-beta." All clinical indications, with the exception of ophthalmic uses, were covered by the agreement. **The deal resulted in fresolimumab (GC1008), a pan-neutralizing IgG4 human antibody directed against all three isoforms of TGF beta, which had the "potential for treating a variety of diseases". In particular Genzyme are currently using fresolimumab in trials involving immunogenic tumours. **The takeover of CAT by AstraZeneca initiated a change of control clause in the 2008 agreement that gives Genzyme the right to buy out rights to a jointly developed experimental lung drug. **In February 2011,
Sanofi-Aventis Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Syn ...
purchased Genzyme for approximately US$20bn. *Immunex Corp, 2000. CAT's proprietary antibody phage display library for the discovery, development and potential commercialisation of human monoclonal antibodies was licensed to Immunex, in return for a licence fee. This deal was expanded in May 2001 where CAT shared more of the risk of drug development – a so-called "profit-sharing" deal. In 2002 Immunex was acquired by
Amgen Amgen Inc. (formerly Applied Molecular Genetics Inc.) is an American multinational biopharmaceutical company headquartered in Thousand Oaks, California. One of the world's largest independent biotechnology companies, Amgen was established in T ...
and in December 2003 CAT entered into a new, restructured agreement with Amgen, reportedly focussing in skin disease. It was also reported that, under the terms of the agreement, Amgen had taken responsibility for the further development and marketing of the therapeutic antibody candidates isolated by CAT against two targets on which the parties agreed to collaborate and would bear all the associated costs. In return, CAT received from Amgen an initial fee and potential milestone payments and royalties on future sales. As of February 2004, one candidate had been delivered by CAT to Amgen. A second candidate was the subject of a continuing research program funded by Amgen and conducted by CAT and was to be delivered to Amgen in due course. **Amgen acquired the transgenic mouse company Abgenix meaning that they had access to two different methods of human monoclonal antibody production. As of July 2009, it is not known from which technology any of their monoclonal antibody products in clinical trials have been derived. *AMRAD, 2001. AMRAD subsequently changed its name to Zenyth Therapeutics and, in mid-2006, Zenyth was acquired by
CSL Limited CSL Limited is an Australian multinational specialty biotechnology company that researches, develops, manufactures, and markets products to treat and prevent serious human medical conditions. CSL's product areas include blood plasma derivative ...
. CAT and AMRAD had gone 50:50 with the original deal over the development of an anti-GMCSF-R antibody, which became CAM-3001. After all this corporate manoeuvring, "CSL decided to license its 50% share in the project to MedImmune...MedImmune commenced Phase I clinical trials in December 2007".


Products and pipeline

CAT had a number of significant products in the pipeline. These included: *
Adalimumab Adalimumab, sold under the brand name Humira, among others, is a monoclonal antibody used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurati ...
(D2E7) – a human monoclonal antibody to tumor necrosis factor-alpha (
TNF alpha Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...
). This drug went on to be developed and marketed by Abbott Laboratories as Humira®. The royalties payable on Adalimumab sales were subject to a dispute between the two companies. In 2013, Abbott split it business in half, whereby
AbbVie AbbVie is an American publicly traded biopharmaceutical company founded in 2013. It originated as a spin-off of Abbott Laboratories. History On October 19, 2011, Abbott Laboratories announced its plan to separate into two publicly traded compani ...
became responsible for its research-based pharmaceutical business, and thus Humira. Humira went on to dominate the best-selling drugs lists. In 2016, the best selling drugs list researched by Genetic Engineering & Biotechnology News, published in March 2017, details that Humira occupied the number 1 position for 2015 ($14.012 billion of sales) and 2016 ($16.078 billion). Whilst for 2017, Abbvie reports that Humira achieved $18.427billion of sales in 2017 * Briakinumab (ABT-874) – a human monoclonal antibody to IL-12 and IL-23. This went on to be developed by Abbott Laboratories for treatment of
psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to comple ...
and
Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distensi ...
. On 11 October 2010, Abbott presented positive Phase III data. * Metelimumab (CAT-192) and fresolimumab (GC1008) are human monoclonal antibodies to transforming growth factor beta 1 ( TGF-β1). Initial trials targeted the skin condition
scleroderma Scleroderma is a group of autoimmune diseases that may result in changes to the skin, blood vessels, muscles, and internal organs. The disease can be either localized to the skin or involve other organs, as well. Symptoms may include areas ...
but, after some unsuccessful clinical trial results, the product was dropped in favour of fresolimumab, which was initially developed by
Genzyme Genzyme was an American biotechnology company based in Cambridge, Massachusetts. Since its acquisition in 2011, Genzyme (also known as Genzyme Transgenics Corp or GTC Biotherapeutics) has been a fully owned subsidiary of Sanofi. In 2010, Genzyme ...
. In February 2011,
Sanofi-Aventis Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Syn ...
purchased Genzyme for approximately US$20 billion and, as of March 2013, Sanofi continue to list fresolimumab in their research and development portfolio. * Lerdelimumab is a human monoclonal antibody to TGF beta 2, initially developed to combat fibrotic scarring that results from glaucoma drainage surgery. The drug was branded Trabio, and development was stopped in late 2005 after unsuccessful trial results. * Bertilimumab (CAT-213) is a human monoclonal antibody to
eotaxin The eotaxins are a CC chemokine subfamily of eosinophil chemotactic proteins. Eotaxin is a special CC chemokine because it primarily attracts eosinophils. By being a chemoattractant for eosinophils, eotaxin has a direct relationship with inflammat ...
1. In January 2007, CAT licensed the drug for treatment of allergy disorders to iCo Therapeutics Inc., who renamed it from CAT-213 to iCo-008. * Mavrilimumab (CAM-3001) – a human monoclonal igG4 antibody to the alpha chain of
granulocyte macrophage colony-stimulating factor Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony-stimulating factor 2 (CSF2), is a monomeric glycoprotein secreted by macrophages, T cells, mast cells, natural killer cells, endothelial cells and fibroblas ...
(GM-CSF Receptor). In 2007, some elements of the local press suggested this product could be the next HUMIRA. CAM-3001 is currently being developed by MedImmune in the treatment of rheumatoid arthritis, and mentioned in the rheumatology section of AstraZeneca's pipeline in their 2008 Annual Report. The first clinical trial was initiated by MedImmune in late 2007. In 2017, Kiniksa licensed Mavrilimumab from MedImmune and, in April 2021, Kiniksa outlined the next steps for development of Mavrilimumab – including in COVID-19–related acute respiratory distress syndrome (ARDS), giant cell arteritis (GCA), and rheumatoid arthritis (RA). * Tralokinumab (CAT-354, Adtralza®) – a human monoclonal antibody (IgG4) that potently and specifically neutralises interleukin 13, a T-lymphocyte-derived cytokine that plays a key role in the development and maintenance of the human asthmatic phenotype. CAT-354 was CAT's first antibody to be discovered using ribosome display, and was further developed by developed by
MedImmune MedImmune, LLC was a wholly owned subsidiary of AstraZeneca before February 14, 2019, when it was announced that the MedImmune name and branding would be discontinued in favor of AstraZeneca. MedImmune was founded in 1988 as Molecular Vaccines, ...
. Tralokinumab was licensed by AstraZeneca to LEO Pharma for skin diseases in July 2016. On 15 June 2017, Leo Pharma announced that they were starting phase 3 clinical trials with tralokinumab in atopic dermatitis. In April 2021, Leo Pharma announced that it had received positive
Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regardin ...
(CHMP) of the
European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Eur ...
(EMA) opinion of Adtralza® (tralokinumab) for the treatment of adults with moderate-to-severe atopic dermatitis. On 22 June 2021, LEO Pharma announced that the European Commission had approved "Adtralza® (tralokinumab) as the first and only treatment specifically targeting IL-13 for adults with moderate-to-severe atopic dermatitis". *
Moxetumomab pasudotox Moxetumomab pasudotox, sold under the brand name Lumoxiti, is an anti-CD22 immunotoxin medication for the treatment of adults with relapsed or refractory hairy cell leukemia (HCL) who have received at least two prior systemic therapies, including ...
(CAT-3888) – CAT-3888 (formerly GCR-3888 and BL22) and CAT-8015 (formerly GCR-8015 and HA22) are both anti-CD22 immunotoxins comprising a modified
Pseudomonas exotoxin The Pseudomonas exotoxin (or exotoxin A) is an exotoxin produced by ''Pseudomonas aeruginosa''. ''Vibrio cholerae'' produces a similar protein called the Cholix toxin (). It inhibits elongation factor-2. It does so by ADP-ribosylation of EF2 ...
and an anti-
CD22 CD22, or cluster of differentiation-22, is a molecule belonging to the SIGLEC family of lectins. It is found on the surface of mature B cells and to a lesser extent on some immature B cells. Generally speaking, CD22 is a regulatory molecule that ...
antibody fragment. CAT acquired these two oncology product candidates in November 2005 from
Genencor Genencor is a biotechnology company based in Palo Alto, CA and a subsidiary of IFF. Genencor is a producer of Industrial enzymes and low-priced bulk protein. The name Genencor originates with Genencor, Inc., the original joint venture between Ge ...
, a subsidiary of
Danisco Danisco A/S is a Danish bio-based company with activities in food production, enzymes and other bioproducts as well as a wide variety of pharmaceutical grade excipients. It was formed in 1989 from the largest Danish industrial merger ever of t ...
. CAT-8015 is being developed by MedImmune. In Sept 2018 the
US FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...
approved it (as Lumoxiti) for some cases of relapsed or
refractory In materials science, a refractory material or refractory is a material that is resistant to decomposition by heat, pressure, or chemical attack, and retains strength and form at high temperatures. Refractories are polycrystalline, polyphase, ...
hairy cell leukemia Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. It is usually classified as a subtype of chronic lymphocytic leukemia (CLL). Hairy cell leukemia makes up about 2% of all leu ...
(HCL). * CAT-5001 (formerly SS1P) – a
Pseudomonas exotoxin The Pseudomonas exotoxin (or exotoxin A) is an exotoxin produced by ''Pseudomonas aeruginosa''. ''Vibrio cholerae'' produces a similar protein called the Cholix toxin (). It inhibits elongation factor-2. It does so by ADP-ribosylation of EF2 ...
immunotoxin An immunotoxin is an artificial protein consisting of a targeting portion linked to a toxin. When the protein binds to that cell, it is taken in through endocytosis, and the toxin kills the cell. They are used for the treatment of some kinds of c ...
that targets
mesothelin Mesothelin, also known as MSLN, is a protein that in humans is encoded by the ''MSLN'' gene. Function Mesothelin is a 40 kDa protein that is expressed in mesothelial cells. The protein was first identified by its reactivity with monoclonal ...
, which is a cell surface
glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glyco ...
present on normal mesothelial cells that is over-expressed in numerous cancers including
pleural The pleural cavity, pleural space, or interpleural space is the potential space between the pleurae of the pleural sac that surrounds each lung. A small amount of serous pleural fluid is maintained in the pleural cavity to enable lubrication b ...
and peritoneal mesothelioma,
ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different ...
and
pancreatic cancer Pancreatic cancer arises when cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a mass. These cancerous cells have the ability to invade other parts of the body. A number of types of pancr ...
. CAT-5001 was acquired from Enzon Pharmaceuticals in May 2006. CAT developed their display technologies further into several patented antibody discovery/functional genomics tools which were named Proximol and ProAb. ProAb was announced in December 1997 and involved high throughput screening of antibody libraries against diseased and non-diseased tissue, whilst Proximol used a free radical enzymatic reaction to label molecules in proximity to a given protein. In September 1999, it was announced that CAT's Library product and ProAb would each receive Millennium Products status. Of the 4,000 products submitted to the
Design Council The Design Council, formerly the Council of Industrial Design, is a United Kingdom charity incorporated by Royal Charter. Its stated mission is "to champion great design that improves lives and makes things better". It was instrumental in the prom ...
for these awards, 1,012 were chosen and, to attain Millennium Product status, products had to: open up new opportunities, challenge existing conventions, be environmentally responsible, demonstrate the application of new or existing technology, solve a key problem and show clear user benefits.


Patents

CAT pioneered the application of Phage Display and Ribosome Display technology for the design and development of human monoclonal antibody therapeutics and which was reflected in the breadth of the company's patent portfolio. The Cambridge patent portfolio includes about 40 families of patents, covering both technologies and products. Three main families of major patents cover Cambridge antibody library and Phage Display technology: 'Winter II' and 'Winter/Huse/Lerner' patents cover Medimmune's processes for generating the collections of human antibody genes that comprise MedImmune Cambridge libraries. MedImmune has patents issued in Europe, South Korea, Japan, Australia and the US and a patent application is pending in Canada. These patents are co-owned by the MRC,
The Scripps Research Institute Scripps Research, previously known as The Scripps Research Institute (TSRI), is a nonprofit American medical research facility that focuses on research and education in the biomedical sciences. Headquartered in San Diego, California, the instit ...
and Stratagene and MedImmune currently has exclusive commercial exploitation rights, subject to certain rights held by the Medical Research Council (MRC), Scripps and Stratagene and their pre-existing licensees. 'McCafferty' covers the process by which human antibodies are displayed on phage (Phage Display) and methods of selecting antibodies to desired targets from libraries. MedImmune has patents issued in Europe, Australia, South Korea and Japan and a patent application is pending in Canada. These patents are co-owned by MedImmune and the MRC. 'Griffiths' covers the use of Phage Display technology to isolate human anti-self' antibodies that specifically bind to molecules found in the human body. CAT has patents issued in Australia, Europe and the US and patent applications are pending in Canada and Japan. This patent is co-owned by MedImmune Cambridge and the MRC. In 2011 "''The High Court of England and Wales has ruled that two patents (EP 0774511 and EP 2055777) owned by MedImmune that describe methods of phage display are invalid because of obviousness.''"


List of Patents


Patent Dispute with MorphoSys

The German
biotechnology Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used ...
company
MorphoSys MorphoSys AG is a biopharmaceutical company founded in 1992. The company is headquartered near Munich, Germany and has a wholly owned subsidiaryMorphoSys US Inc. in Boston MA in the US. The company has various antibody, protein and peptide technol ...
generates human antibodies using its phage display-based 'HuCal' (Human Combinatorial Antibody Library) technology. In the late 1990s both companies found themselves jockeying for strong IP position in the area of therapeutic human antibody generation by way of a specific dispute (details on MorphoSys page). The long, and protracted, dispute resulted which was eventually settled in late 2002 when some argued the settlement was enforced by an industry cash crunch. The 'delighted' CEO at the time, Peter Chambré, reflected that the deal put an end to the distraction to both parties caused by the litigation.


Publications

Scientists at CAT pioneered the use of
phage display Phage display is a laboratory technique for the study of protein–protein, protein–peptide, and protein– DNA interactions that uses bacteriophages (viruses that infect bacteria) to connect proteins with the genetic information that encodes ...
such that variable antibody domains could be expressed on filamentous phage antibodies, as reported in a key
Nature Nature, in the broadest sense, is the physical world or universe. "Nature" can refer to the phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. Although humans are ...
publication, "Phage antibodies: filamentous phage displaying antibody variable domains". Other key CAT publications included: * * * * * *


Management and notable people

CAT was founded by David Chiswell MBE and Sir Greg Winter, with major scientific contributions from John McCafferty. Sir Greg Winter FRS is credited with invented techniques to both humanise (1986) and, later, to fully humanise using
phage display Phage display is a laboratory technique for the study of protein–protein, protein–peptide, and protein– DNA interactions that uses bacteriophages (viruses that infect bacteria) to connect proteins with the genetic information that encodes ...
, antibodies for therapeutic uses.Th
Scientific Founders
of Bicycle Therapeutics Ltd. – Christian Heinis and Sir Greg Winter, FRS.
Previously, antibodies had been derived from mice, which made them difficult to use in human therapeutics because the human immune system had anti-mouse reactions to them. For these developments Winter was awarded the 2018
Nobel Prize in Chemistry ) , image = Nobel Prize.png , alt = A golden medallion with an embossed image of a bearded man facing left in profile. To the left of the man is the text "ALFR•" then "NOBEL", and on the right, the text (smaller) "NAT•" then "M ...
along with George Smith and Frances Arnold. Dave Chiswell OBE was responsible for operational management of CAT from 1990 to 2002, including time as chief executive officer from 1996 to 2002. Chiswell announced he was standing down from CAT on 26 November 2001. During his time at CAT, Chiswell had established himself as a significant character in the
biotechnology Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used ...
business. In 2003, Chiswell became chairman of the BioIndustry Association, and in June 2006 was awarded an OBE for services to the UK Bioscience Industry in the UK and Overseas. CAT was governed by a board and, latterly, a Scientific Advisory Board. Members included: * César Milstein CH FRS, a
Nobel prize The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfr ...
-winning biochemist in the field of antibody research. Milstein shared the Nobel Prize in
Physiology Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemic ...
and Medicine in 1984 with
Niels Jerne Niels is a male given name, equivalent to Nicholas, which is common in Denmark, Belgium, Norway (formerly) and the Netherlands. The Norwegian and Swedish variant is Nils. The name is a developed short form of Nicholas or Greek Nicolaos after Saint ...
and
Georges Köhler Georges may refer to: Places *Georges River, New South Wales, Australia *Georges Quay (Dublin) *Georges Township, Fayette County, Pennsylvania Other uses *Georges (name) * ''Georges'' (novel), a novel by Alexandre Dumas * "Georges" (song), a 1977 ...
. * Sir Aaron Klug OM FRS FMedSci HonFRMS, a Nobel prize-winning laureate, was a British chemist and biophysicist, and winner of the 1982
Nobel Prize in Chemistry ) , image = Nobel Prize.png , alt = A golden medallion with an embossed image of a bearded man facing left in profile. To the left of the man is the text "ALFR•" then "NOBEL", and on the right, the text (smaller) "NAT•" then "M ...
for his development of crystallographic
electron microscopy An electron microscope is a microscope that uses a beam of accelerated electrons as a source of illumination. As the wavelength of an electron can be up to 100,000 times shorter than that of visible light photons, electron microscopes have a hi ...
. He sat on both the board and the scientific advisory board. *Professor Peter Garland – appointed as a non-executive director in 1990, then became non-executive chairman of the board in 1995. Garland has been the Chief Executive of
Institute of Cancer Research The Institute of Cancer Research (the ICR) is a public research institute and a member institution of the University of London in London, United Kingdom, specialising in oncology. It was founded in 1909 as a research department of the Royal Ma ...
, 1989–99 and was a fellow of
University College London , mottoeng = Let all come who by merit deserve the most reward , established = , type = Public research university , endowment = £143 million (2020) , budget = ...
. *Dr Paul Nicholson – replaced Peter Garland as chairman in 2003. Nicholson was chairman when AstraZeneca bought CAT. Peter Chambré replaced Dave Chiswell as CEO in early 2002. Chambré had been the CEO of Bespak PLC since May 1994 and, in July 2000, became the chief operating officer of the
genomics Genomics is an interdisciplinary field of biology focusing on the structure, function, evolution, mapping, and editing of genomes. A genome is an organism's complete set of DNA, including all of its genes as well as its hierarchical, three-dim ...
company
Celera Celera is a subsidiary of Quest Diagnostics which focuses on genetic sequencing and related technologies. It was founded in 1998 as a business unit of Applera, spun off into an independent company in 2008, and finally acquired by Quest Diagnosti ...
. After CAT, Chambré went on to hold a number of positions including Chairman of ApaTech Ltd., and, in September 2006, was appointed non-executive director of BTG plc and Spectrics pls and also advisor to 3i Group plc. As of July 2019, Chambré holds seven board and advisor roles including Chairman of the Board of Directors at immatics biotechnologies, Chairman of the Board of Directors at Cancer Research Technology, and Member of the Board of Directors at
Spectris Spectris plc is a supplier of precision instrumentation and controls. It is listed on the London Stock Exchange and is a constituent of the FTSE 250 Index. History The Company was founded by Richard Fairey in 1915, as the '' Fairey Aviation Co ...
plc. John McCafferty developed much of the phage display technology used by CAT. McCafferty left CAT to start a group at the
Wellcome Trust Sanger Institute The Wellcome Sanger Institute, previously known as The Sanger Centre and Wellcome Trust Sanger Institute, is a non-profit British genomics and genetics research institute, primarily funded by the Wellcome Trust. It is located on the Wellcome G ...
where, as part of the ATLAS project, his group demonstrated the potential for large-scale high-throughput generation and validation of
monoclonal antibodies A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ...
. This work built on CAT's ProAb technology. McCafferty founded a new therapeutic antibody discovery biotechnology company
IONTAS Ltd
In 2018, McCafferty's 1990 phage research paper was cited by the
Nobel Nobel often refers to: *Nobel Prize, awarded annually since 1901, from the bequest of Swedish inventor Alfred Nobel Nobel may also refer to: Companies *AkzoNobel, the result of the merger between Akzo and Nobel Industries in 1994 *Branobel, or ...
committee when awarding the chemistry prize to Sir Gregory Winter, George Smith and Frances Arnold. Kevin Johnson joined CAT in 1990, contributed to the discovery of D2E7, played a key role in CAT's
initial public offering An initial public offering (IPO) or stock launch is a public offering in which shares of a company are sold to institutional investors and usually also to retail (individual) investors. An IPO is typically underwritten by one or more investme ...
(IPO) and, by July 1997, was appointed to the Board as Research Director. In 2000, Johnson became Chief Technology Officer responsible for exploitation and development of CAT's technology platforms. In November 2002, CAT announced its intention to seek independent financing for its development of the application of antibodies on
microarrays A microarray is a multiplex lab-on-a-chip. Its purpose is to simultaneously detect the expression of thousands of genes from a sample (e.g. from a tissue). It is a two-dimensional array on a solid substrate—usually a glass slide or silicon ...
for personalised medicine, as this fell outside CAT's focus on therapeutic antibodies and Johnson positively spearheaded this push. In the event it was not possible to procure finance for this activity and, as a result, microarray activity at CAT was terminated. Johnson is currently a partner at medicxi, a
venture capital Venture capital (often abbreviated as VC) is a form of private equity financing that is provided by venture capital firms or funds to startups, early-stage, and emerging companies that have been deemed to have high growth potential or which h ...
firm focused on
life sciences This list of life sciences comprises the branches of science that involve the scientific study of life – such as microorganisms, plants, and animals including human beings. This science is one of the two major branches of natural science, th ...
investments based on the asset-centric approach to investing. He was formerly with
Index Ventures Index Ventures is a European venture capital firm with dual headquarters in San Francisco and London, investing in technology-enabled companies with a focus on e-commerce, fintech, mobility, gaming, infrastructure/ AI, and security. Since ...
, having joined the venture capital firm in 2010. Jane Osbourn OBE joined CAT as a senior scientist in 1993. Osbourn was a co-author of several, high-impact publications to come out of CAT. When merged with MedImmune, after the acquisition by AstraZeneca, Osbourn became the site leader of MedImmune Cambridge. Osbourn went on to chair the UK's BioIndustry Association in 2015 and, in 2019, was awarded the
Order of the British Empire The Most Excellent Order of the British Empire is a British order of chivalry, rewarding contributions to the arts and sciences, work with charitable and welfare organisations, and public service outside the civil service. It was established ...
medal for services to "Human Monoclonal Antibody Drug Research and Development and Biotechnology".


Awards

CAT's most significant award was the Prix Galien, awarded for outstanding achievement in product and technology development, in recognition of its creativity in the development of novel human monoclonal antibody therapeutics especially in relation to its product CAT-152, which was used to treat fibrotic scarring in certain ophthalmology conditions.CAT Prix Galien news release


See also

* Pharmaceutical industry in the United Kingdom


References

{{Pharmaceutical and biotechnology industry in the United Kingdom Pharmaceutical companies disestablished in 2007 British companies established in 1989 Companies based in Cambridge Pharmaceutical companies of England $ AstraZeneca Companies formerly listed on the Nasdaq 1989 establishments in England