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31:, as each antibody in the mixture is produced from one carefully selected clone. Their three main areas of therapeutic research are immunoglobulin replacement, cancer, and infectious diseases. The company was founded in 2000 and has patents on a drug discovery platform called Symplex and a drug manufacturing platform called Sympress. By 2009, ten drugs were being developed with
119:, since the latter bind to different epitopes of the target molecule. By producing mixtures of the monoclonal antibodies, Symphogen avoids the major drawback of the polyclonal antibodies, which quality is difficult to control due to the diversity in their biophysical characteristics and biological activity.
311:, a monoclonal antibody used to block ligands from accessing the EGFR, because Sym004 induces removal of the receptor from the cell surface. Sym004 also inhibits tumor cell growth because removal of the EGFR prevents it from cooperating with other receptors and signaling molecules in the tumor cell.
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According to
Symphogen, their proprietary monoclonal antibody mixtures reflect both the diversity of immunoglobulins and specificity of monoclonal antibodies. It is possible to produce an unlimited supply of these antibodies using traditional large-scale biological manufacturing techniques; these
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antibodies are produced with no risk of viral or prion transmission according to
Symphogen. This new class of therapeutic antibodies could be effective in treating complex diseases such as cancer for it allows the combination of several treatment modalities in one drug.
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were used in preclinical studies. Dose range finding studies showed an increase in cynomolgus monkey kidney weight and decrease in body weight in respect to the control group, but both effects were reversible. The clearance of Sym004 is dependent on antibody mediated
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Sympress
Technology is the manufacturing platform used to produce recombinant polyclonal antibodies in high yields. This technology enables the production of consistent mixtures of polyclonal antibodies with high batch-to-batch consistency at an industrial scale.
302:(EGFR) and the EGFR is rapidly internalized and undergoes degradation. Alone, these mAbs are unable to effectively induce degradation of EGFR and inhibit tumor growth. mAb 992 and 1024 are thought to work synergistically. The antibodies bind to different
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Friedman LM, Rinon A, Schechter B, Lyass L, Lavi S, Bacus SS, Sela M, and Yarden Y. (2005) "Synergistic down-regulation of receptor tyrosine kinases by combinations of mAbs: Implications for cancer immunotherapy" PNAS (102) 1915–20 Retrieved 17 November
344:. Phase II trials were announced on 23 August 2011 and are continuing for 24 weeks, beginning at Antwerp University Hospital in Belgium. Patients are receiving weekly doses, and the drug is being evaluated on "safety, efficacy, and pharmacokinetics".
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are typically used due to their effectiveness in binding to many kinds of pathogens as well as protecting the body against the pathogens by immobilization, complement activation, opsonization for phagocytosis and neutralization of their toxins.
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Pedersen MW, Jacobsen HJ, Koefoed K, Hey A, Pyke C, Haurum JS, et al. (2010) "Sym004: a novel synergistic anti–epidermal growth factor receptor antibody mixture with superior anticancer efficacy" Cancer Res (70) 588-97 Retrieved 17 November
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Skartved NJØ, Jacobsen HJ, Pedersen MW, et al. (2011) "Preclinical
Pharmacokinetics and Safety of Sym004: A Synergistic Antibody Mixture Directed against Epidermal Growth Factor Receptor" Clin Cancer Res (17) 5962-72. Retrieved 17 November
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Meijer PJ, Andersen PS, Haahr Hansen M, et al. (2006). "Isolation of human antibody repertoires with preservation of the natural heavy and light chain pairing" Journal of
Molecular Biology. 358 (3) 764-72 Retrieved 17 November
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for a recombinant polyclonal antibody against smallpox. The grant enables
Symphogen to complete pre-clinical development of Sym002, which allows submission of an Investigational New Drug application for new safety studies.
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Tolstrup AB, Frandsen TP, Bregenholt S. (2006) " Development of recombinant human polyclonal antibodies for the treatment of complex human diseases" Expert
Opinion on Biological Theory 6 (9) 905-12 Retrieved 17 November
155:
Symplex
Technology is a process used to discover antibodies that are customized from plasma cells for a particular therapeutic application, and it involves direct isolation of the antibody genes from the immune system.
114:
Multi-clonal antibodies developed at
Symphogen are mixtures of monoclonal antibodies, where each of the mAbs binds specifically to one unique epitope of the target. Technically, Symphogen products are not
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Wiberg FC, Rasmussen SK, Frandsen TP, et al.(June 2006) "Production of target-specific recombinant human polyclonal antibodies in mammalian cells" Biotechnol Bioeng. 94 (2): 396–405 Retrieved 29 November
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Recombinant monoclonal antibody mixtures mimic the diversity, specificity and binding capability of the natural immune system and increase the likelihood of the rapid elimination of the desired antigens.
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on the EGFR and their cooperation shows a statistically significant improvement on tumor growth inhibition over non-synergistic use of the antibodies. Alone, Sym004 has been shown to be more potent than
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rate was higher than
Cetuximab. Because EGFR is expressed in the skin and gastrointestinal tract, the only toxic side effects observed were rash and diarrhea, and presented much earlier than Cetuximab.
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Of the ten products that Symphogen is in the process of developing, two have completed pre-clinical phases and have entered clinical trials. Both Sym001 and Sym004 are in Phase 2 clinical trials.
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Sympress I Technology has been used to develop the product Sym001. Recently, Sympress II Technology has been developed, and it uses random gene integration to improve the expression yield.
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Mendelsohn J and Baselga J. (2003) "Status of Epidermal Growth Factor Receptor Antagonists in the Biology and Treatment of Cancer" J Clin Oncol (21) 2787–2799 Retrieved 17 November 2011.
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399:"Servier signed a definitive agreement to acquire Symphogen, a leading antibody discovery company, to boost its antibody capabilities and leverage its R&D pipeline"
271:, is a recombinant polyclonal antibody consisting of twenty-five monoclonal antibodies that is being developed for treatment of various hematological diseases such as,
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294:(mAB), 992 and 1024, discovered and developed using the Symplex process that inhibits tumor growth in a number of cancerous cell lines including A431NS (
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435:
Meijer PJ, Nielsen LS, Lantto J, et al. (2009). " Human antibody repertoires" Methods of Molecular Biology 525(3) 261-77. Retrieved 17 November 2010.
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which enables both companies to utilize Symplex technology to help discover new antibodies against three undisclosed infectious disease targets.
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create a higher density of antibodies on target surfaces enhancing downstream effector functions such as complement lysis,
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The cloned antibodies are placed into wells and specifically chosen for further development based on antibody expression
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that develops protein drugs based on recombinant monoclonal antibody mixtures. These drugs are different from the
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498:"Symphogen initiates Sym004 Phase 2 trial in squamous cell carcinoma of head and neck cancer website: News"
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Recombinant multi-clonal antibodies, or mixtures of mAbs, could be advantageous for the following reasons:
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The individual cell lines encoding the highest quality antibodies are mixed and produced in high yields
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Heavy and light chains are amplified and conservatively paired back together in natural configuration
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Antibodies are placed into a well (repertoire arraying) and the DNA is extracted and prepared
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Cells where the antibody is most highly expressed are selected through fluorescent tagging
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Antibody of choice from the original gene pairs (conjugate pairs) is chosen by screening
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that establishes a collaboration of research, development, and commercialization.
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Immune cells are isolated from the spleen of mice or purified from human blood
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Antibodies are encoded on plasmids using Chinese hamster ovary cell lines
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less sensitive to target diversification such as viral escape mutants
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is cloned, placed into a bacterial vector and stored in a library
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create large immune complexes that activate effector functions
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Cells are individually sorted and antibodies are isolated
78:: A co-development and commercialization agreement with
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Phase I trials finished in June 2011 in patients with
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A fully human antigen-specific antibody is produced
244:Cell lines are preserved and stored in cell banks
171:are separated using differences in cell densities
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68:: Sym006 development and license agreement with
298:). When used together, 992 and 1024 cross link
86:granted an orphan drug designation to Sym001.
383:Symphogen. Copenhagen 2008 ; Available from:
145:antibody-dependent cell-mediated cytotoxicity
342:squamous cell carcinoma of the head and neck
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545:Life science companies based in Copenhagen
362:"Symphogen Collaboration Information - US"
84:United States Food and Drug Administration
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550:Companies based in Ballerup Municipality
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290:Sym004 is a combination of two chimeric
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92:: Sym002 developmental grant with the
19:is a biotechnology company located in
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555:Danish companies established in 2000
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273:Idiopathic Thrombocytopenic Purpura
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540:Biotechnology companies of Denmark
385:http://www.symphogen.com/web/guest
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35:(Sym001) being the lead product.
300:epidermal growth factor receptor
277:Hemolytic disease of the newborn
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397:A/S, Symphogen (3 April 2020).
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94:National Institutes of Health
39:acquired Symphogen in 2020.
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267:Rozrolimupab (Sym001), an
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58:: Collaboration pact with
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204:and antibodies are cloned
323:receptor internalization
403:GlobeNewswire News Room
66:Meiji Seika Kaisha, Ltd
101:Multiclonal antibodies
51:Partner collaborations
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46:Founder Kirsten Drejer
292:monoclonal antibodies
183:reverse transcription
117:polyclonal antibodies
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29:polyclonal antibodies
366:www.thermofisher.com
37:Laboratoires Servier
218:Sympress technology
318:Cynomolgus monkeys
151:Symplex technology
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338:colorectal cancer
315:Clinical Results:
227:Sympress Process:
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33:rozrolimupab
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269:orphan drug
70:Meiji Seika
534:Categories
348:References
296:A431 cells
288:Mechanism:
21:Copenhagen
327:clearance
309:Cetuximab
90:NIAID/NIH
80:Biovitrum
76:Biovitrum
60:Genentech
17:Symphogen
304:epitopes
192:antibody
177:Symplex
202:protein
25:Denmark
283:Sym004
263:Sym001
478:2011.
465:2011.
455:2011.
445:2010.
426:2010.
416:2010.
190:Each
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340:and
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Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
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