An Overview of FDA-Approved Biologics Medicines

Total Page:16

File Type:pdf, Size:1020Kb

An Overview of FDA-Approved Biologics Medicines Drug Discovery Today Volume 20, Number 4 April 2015 PERSPECTIVE feature An overview of FDA-approved biologics medicines Michael S. Kinch, [email protected], [email protected] Recombinant DNA technologies revolutionized medicine. Herein, the approvals and mechanistic basis of biologics-based medicines are analyzed. The overall and relative rate of FDA approvals for recombinant proteins grew from the 1980s through the first half-decade of the new millennium. Over time, the number of biologics gaining approval for an orphan indication has climbed to more than 50% in the current decade. The field has been dynamic in terms of the types of biologics, indications targeted and the mechanistic basis of drug activity. Despite impressive increases in recombinant-protein-based medicine, the rate of new biologics approvals could have leveled out. PERSPECTIVE Current analysis concerns that science would outpace society’s established pharmaceutical company (Eli Lilly) Recombinant DNA technology fundamentally ability to control new technology safely. and gained FDA approval for the first recombi- 1 Features changed the way medicines are discovered and Research of more-controversial aspects of nant DNA product (Humulin ; 1982) [5,6]. This developed. In a remarkable convergence of recombinant DNA research was voluntarily sus- aggressive timeline set a standard that continues timing and talent, Stanford University was the pended shortly after the publication of the first to be associated with the biotechnology industry epicenter of a revolution in the early 1970s, papers on recombinant DNA technology. This today. which first led to the concept, and rapidly self-imposed curtailment was an impressive An assessment of biologics drugs over time thereafter the successful demonstration, that demonstration of the potential impact associ- was achieved by compiling a list of all recom- genes from one organism could be isolated and ated with biotechnology, as was the decision of binant biologics-based medicines approved by cloned into vectors for expression in unrelated prominent scientists to request that The National the FDA from 1982 through 2013. Information organisms [1,2]. The resulting scientific Academy of Science evaluated the implications was gleaned initially from the FDA Orange Book knowledge and its commercial applications of the emerging new field of biotechnology [3]. and supplemented with data regarding with- gave rise to the modern biopharmaceutical The resulting Asilomar Conference on Recom- drawn products using the same approaches industry. binant DNA (1975) provided guidelines, many of detailed previously [7]. These results have also This revolution almost did not happen. Wor- which persist today, and gave rise to the ever- been verified against well-established resources 1 ries about the consequences of utilizing tumor- accelerating use of recombinant DNA technol- such as Citeline , PubMed and additional online derived DNA components raised concerns about ogies [4]. resources [8]. Please note that recombinant transmitting cancer among individuals working Within seven years of the Asilomar Confer- products approved outside the USA were not with DNA vectors or recombinant proteins. ence, the first recombinant medicine had been included nor were products (including proteins) Compounding this, popular culture at the time developed and approved by the FDA. Within this purified from sera and other human and non- was highly critical of the potential for science time frame, a key pioneer of recombinant human sources. 1 gone awry. Books and films such as The Biological DNA research (Herbert Boyer) had founded Since the approval of Humulin , a total of 91 Time Bomb (1968), The Andromeda Strain (1969) Genentech (1976), developed a recombinant recombinant-protein-based new molecular en- and Future Shock (1970) had primed public form of human insulin (1978) partnered with an tities (NMEs) have been approved by the FDA as 1359-6446/06/$ - see front matter ß 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.drudis.2014.09.003 www.drugdiscoverytoday.com 393 PERSPECTIVE Drug Discovery Today Volume 20, Number 4 April 2015 TABLE 1 Comparison of small molecule and biologic-based NMEs (1982–2013). NME type Total IND to approval (years) Withdrawn because of safety concerns (%) Small molecule 777 8.5 (n = 200) 26 (3.3%) Biologic 91 7.4 (n = 30) 2 (2.2%) -Monoclonal antibody 34 7.8 (n = 18) 2 (5.9%) -Enzyme modulator 26 5.9 (n = 8) 0 -Receptor modulator 31 8.3 (n = 4) 0 The total number of new molecular entities (NMEs) approved from 1982 through 2013 is indicated, as are the average times from investigational new drug (IND) to approval and the number and fraction of the molecules approved that were subsequently withdrawn for reasons of safety (noninclusive of withdrawals because of obsolescence or lack of sales). Please note that IND submission dates were available only for a relative small proportion of NMEs approved in this time period as indicated in parentheses. therapeutics (Table 1, Fig. 1a). These biologics application of monoclonal antibodies was emerging technologies to enhance drug safety can be almost evenly divided into three cate- hampered by the need to minimize immuno- and efficacy. gories: monoclonal antibodies, replacement or genicity and thus required new breakthroughs. The proportion of biologics-based approvals modulators of enzymes and replacement or A pioneering Cambridge University study (relative to small molecules) generally increased modulators of cell surface receptor function. The demonstrated replacement of murine antibody through the 1980s and 1990s and represented first five approvals within each category are complementarity-determining regions with one-third of all NME approvals in the early 2000s shown in Table 2. human versions and thereby provided a means (Fig. 1b) and again during 2009–2010. Although The first monoclonal antibody, muromonab to decrease immunogenicity [10]. Such break- the absolute number of biologics approvals has CD3, gained approval in 1982 as a murine throughs facilitated approval of the second remained relatively stable (with the exceptions protein approved for use in acute organ trans- monoclonal antibody, abciximab (1993), and noted below), the relative fraction of approvals, plant rejection [9]. The mechanistic basis of thereafter ignited a revolution in protein engi- as compared with small molecules, declined suppressive immune function minimized neering technology. The advances continue over the past three years (2011–2013). One the risk of immunogenicity. However, broad today and include fully human antibodies and potential explanation is that these changes (a) 100 Features Biologics 80 mAb Enzym e PERSPECTIVE 60 Receptor modifier 40 Cumulative NMEs 20 0 1982 1992 2002 2012 Year (b) (c) 35% 60% Biologics 30% 50% Non-bio logics 25% 40% 20% 30% 15% 20% 10% % Biologics NME Orphan approvals 10% 5% 0% 0% 1982 1987 1992 1997 2002 2007 2012 Year 1981-19851986-19901991-19951996-20002001-20052006-20102011-2013 Drug Discovery Today FIGURE 1 Accumulation of FDA-approved biologics. (a) The accumulation of the three major categories of biologics-based new molecular entities (NMEs) is shown over time W since the initial approval of Humulin in 1982. (b) The proportion of biologics-based NMES (relative to all NMEs) is shown on a half-decade basis. (c) The proportion of biologics-based and non-biologics-based orphan approvals is shown over time. 394 www.drugdiscoverytoday.com Drug Discovery Today Volume 20, Number 4 April 2015 PERSPECTIVE TABLE 2 First five biologics approved in major categories. Monoclonal antibody Receptor modulator Enzyme modulator Muromonab CD3 rhInsulin Dornase alfa (Ortho, 1982) (Eli Lilly, 1982) Genentech (1993) Abciximab Interferon alpha-2a Pegaspargase (Centocor, 1993) (Roche, 1986) (Enzon, 1994) Rituximab Epoetin alfa Imiglucerase IDEC (1997) (Amgen, 1989) (Genzyme, 1994) Basiliximab Filgrastim Alteplase (Novartis, 1998) (Amgen, 1991) (Genentech, 1996) Palivizumab Sagramostim Reteplase (MedImmune, 1998) (Immunex, 1991) (Boehringer-Mannheim, 1996) reflect capacity levels within the regulatory restricted to FDA-approved NMEs (and thus 2006. The first enzyme replacement and mod- agency (e.g. FDA Center for Biologics Evaluation could not address the question of how many ulators gained approval in the early 1990s and and Research; CBER). At this early stage, it cannot clinical candidates had been rejected as a result tended to favor metabolic disorders, including be excluded that this recent trend simply reflects of toxicity concerns). Nevertheless, one view of inborn genetic errors of metabolism (Fig. 2c, random chance and it remains to be seen post-approval safety was achieved by assessing other data not shown). The approval rate for whether such findings will persist over the the number of NMEs later withdrawn from enzyme modifiers has been remarkably steady coming years. the market owing to concerns about toxicity over time. The first monoclonal antibodies were To identify factors relevant to the growing (Table 1). When evaluating small molecule pro- approved in the early 1990s but were heavily popularity of biologics, the development and ducts approved since 1982, 3.3% (26 in total) weighted toward oncology and inflammatory regulatory histories of FDA-approved, small- have subsequently been withdrawn because of disorders (Fig. 2d). Like enzyme modifiers, the molecule- and biologics-based medicines were safety concerns. Biologics generally tended to approval rate for new
Recommended publications
  • Biopharmaceutical Sector Update: Market Outlook for 2021
    Biopharmaceutical Sector Update Market Outlook for 2021 January 11, 2021 © 2021. All rights reserved. Securities offered in the United States are offered through Torreya Capital LLC, Member FINRA/SIPC. In Europe such services are offered through Torreya Partners (Europe) LLP, which is authorized and regulated by the UK Financial Conduct Authority. Table of Contents An Extraordinary Year: Top 10 Biopharma Events of 2020 4 Biopharma Sector Outlook for 2021 20 The Evolving World of Biotech Company Formation 26 Implications of the U.S. Election on the Biopharma Sector 31 Update on Covid-19, Capital Markets and M&A Activity 39 About Torreya 50 Key Topics in This Update In this report we discuss three topics that are front of mind in our industry: We have lived through an Given the exceptional performance of the biopharma extraordinary year for the #1 market in 2020, what does 2021 hold? biopharmaceutical industry. Given excellent protection data on two COVID-19 vaccines we now appear It appears likely that with widespread vaccination, #2 the COVID-19 pandemic will recede in 2021. What to be at the beginning of the end of does this imply for the biopharma sector? the COVID-19 pandemic. A “return to normalcy” appears possible in 2021 despite a very challenging situation What are the implications of the U.S. political #3 situation for the global biopharmaceutical sector? at present with the pandemic. 3 An Extraordinary Year: Top 10 Biopharma Events of 2020 4 Event #1 COVID-19 Vaccines Portend a New Normal The FDA has approved two COVID-19 vaccines as of Jan 2021 and more vaccine approvals are likely.
    [Show full text]
  • Hybridoma Technology History of Hybridoma Technology
    Hybridoma Technology History of Hybridoma Technology What is hybridoma technology? Hybridoma technology is a well-established method to produce monoclonal antibodies (mAbs) specific to antigens of interest. Hybridoma cell lines are formed via fusion between a short-lived antibody-producing B cell and an immortal myeloma cell. Each hybridoma constitutively expresses a large amount of one specific mAb, and favored hybridoma cell lines can be cryopreserved for long-lasting mAb production. As a result, researchers usually prefer generating hybridomas over other mAb production methods in order to maintain a convenient, never-ending supply of important mAbs. Fig 1. Hybridoma technology Inventor: Georges Kohler and Cesar Milstein Hybridoma technology was discovered in 1975 by two scientists, Georges Kohler and Cesar Milstein. They wanted to create immortal hybrid cells by fusing normal B cells from immunized mice with their myeloma cells. For incidental reasons, they had all the requirements fulfilled and it worked in the first attempt. By cloning individual hybrid cells, they established the first hybridoma cell lines which can produce single type of antibody specific to the specific antigen. Their discovery is considered one of the greatest breakthroughs in the field of biotechnology. For the past decades, hybridomas have fueled the discovery and production of antibodies for a multitude of applications. By utilizing hybridoma technology, Sino Biological provides cost-effective mouse monoclonal antibody service, and we can deliver you purified antibodies in 60 days. Steps Involved in Hybridoma Technology Hybridoma technology is composed of several technical procedures, including antigen preparation, animal immunization, cell fusion, hybridoma screening and subcloning, as well as characterization and production of specific antibodies.
    [Show full text]
  • The Future for Biosensors in Biopharmaceutical Production
    Pharmaceutical Commentary BRACEWELL & POLIZZI The future for biosensors in biopharmaceutical production 2 Commentary The future for biosensors in biopharmaceutical production Pharm. Bioprocess. Keywords: bioprocess monitoring • bioprocess control • in-vivo biosensor • PAT Daniel G Bracewell*,1 • synthetic biology & Karen M Polizzi2 1The Advanced Centre for Biochemical Engineering, Department of Biochemical A defining feature of bioprocesses is the need straightforward. This is not to say there have Engineering, University College London, for measurement, monitoring and control; in not been significant successes: Torrington Place, London, WC1E 7JE, UK the context of biopharmaceuticals this need 2Department of Life Sciences & Centre • The world’s diabetic population depends is further heightened by the absolute require- for Synthetic Biology & Innovation, on blood glucose measurements to admin- Imperial College London, London, UK ment to ensure the quality of the product [1] . ister insulin based on an amperometric *Author for correspondence: This is evidenced by the size of bioanalytical based biosensor technology (enzyme elec- [email protected] endeavor found within the R&D programs trodes). This represents the largest single of the major biopharmaceutical companies biosensor application in terms of numbers and the supplier industry that caters for this of devices and market size; instrumentation need. It is a need that grows at a pace reflected in the initiatives involv- • Optical biosensors, largely surface plas- ing the regulatory authorities such as PAT mon resonance (BIAcore) has become central to the larger vision of QbD. At the the default method to directly mea- core of these attempts to improve biophar- sure protein–protein interactions in the maceutical production is the need for rapid, laboratory.
    [Show full text]
  • Biopharmaceutical Notes
    An Overview of the BioPharmaceutical Products and Market By Paul DiMarco, Vice President, Global Commercial Program, BioSpectra Inc. Table of Contents INTRODUCTION: ........................................................................................................................................ 2 History ....................................................................................................................................................... 2 Background information ........................................................................................................................... 3 Defining biological products ..................................................................................................................... 4 Small vs. Large Molecule Regulation and Registration in the USA and EU ............................................... 6 Controversial Regulatory Concepts: ......................................................................................................... 7 Extrapolation: ........................................................................................................................................ 7 Switching: .............................................................................................................................................. 8 Interchangeability: ................................................................................................................................ 9 Harmonization: ....................................................................................................................................
    [Show full text]
  • Identification of Small Molecule Modulators of Diguanylate Cyclase
    bioRxiv preprint doi: https://doi.org/10.1101/402909; this version posted August 28, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Identification of Small Molecule Modulators of Diguanylate Cyclase by FRET-based High-Throughput-Screening Matthias Christen1, , Cassandra Kamischke2, Hemantha D. Kulasekara2, Kathleen C. Olivas3, Bridget R. Kulasekara4, Beat Christen1, Toni Kline5, and Samuel I. Miller2,4,6, 1Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH) Zürich, CH-8093 Zürich, Switzerland 2Department of Microbiology, University of Washington, Seattle, United States 3Seattle Genetics, Inc., 21823 30th Drive SE, Bothell, Washington 98021 4Department of Genome Sciences, University of Washington, Seattle 5Sutro Biopharma, 310 Utah Avenue, South San Francisco, CA 94080 6Department of Medicine, University of Washington, Seattle The bacterial second messenger cyclic diguanosine monophos- parent role of c-di-GMP in the cell cycle and the presence of phate (c-di-GMP) is a key regulator of cellular motility, the cell many paralogous DGC enzymes controlling diverse cellular cycle, and biofilm formation with its resultant antibiotic tol- functions indicate that there is likely tight spatial and tem- erance, which may make chronic infections difficult to treat. poral regulation of c-di-GMP (10–12). Bacterial genomes Therefore, diguanylate cyclases, which regulate the spatiotem- encode multiple GGDEF domains in proteins with signal- poral production of c-di-GMP, may be attractive drug tar- sensing domains (13).
    [Show full text]
  • Hybridoma Technology
    HYBRIDOMA TECHNOLOGY Subject : Dr. KRISHNA KUMAR V M.sc,Ph.D,PGDCS Govt. Degree College ,NAIDUPET Email. Id : [email protected] HYBRIDOMA TECHNOLOGY LEARNING OBJECTIVES • TO UNDERSTAND THE NATURE OF ANTIBODY • DISTINGUISH BETWEEN POLYCLONAL AND MONOCLONAL ANTIBODIES • TO LEARN THE TECHNIQUE INVOLVED IN HYBRIDOMA TECHNOLOGY • STEPS INVOLVED IN I) CELL- FUSION III) ANTIBODY PRODUCTION INTRODUCTION ANTIBODY : • Antibodies are specialised proteins that are recruited by the immune system in response to an antigenic stimulus. • Antibodies identify and recognise the foreign antigens and remove them from the body. • Antibodies are produced B lymphocytes (or) B-cells • The production of antibodies is the main function of the humoral response (or) adaptive Immune system TYPES OF ANTIBODIES POLYCLONAL ANTIBODIES: • Antibodies derived from different B lymphocyte cell lines. • Heterogeneous in nature collected from multiple B cell clones. • Recognise and bind to many different epitopes of single antigen. • Primary role is to detect unknown antigens. Monoclonal antibody MONOCLONAL ANTIBODIES (Mabs) : • Antibodies are identical as they are produced by one type of immune cell (or) Clones of single parent cell. • Homogeneous in nature with affinity towards a specific antigen MONOCLONAL ANTIBODIES (Mabs) • Monoclonal antibodies possess two important characteristics, namely high specificity and high reproducibility. • widely used in diagnostic, clinical and therapeutic applications. • Plays a key role in immunotherapy HYBRIDOMA TECHNOLOGY MONOCLONAL ANTIBODIES : • Production of monoclonal antibodies using hybridoma technology was discovered in 1975 by GEORGE KOHLER & CESAR MILSTEIN. • They shared the NOBEL PRIZE in the year,1984. nobelprize.org • In 1990 MILSTEIN produced the first monoclonal antibodies HYBRIDOMA TECHNOLOGY HYBRIDOMA TECHNIQUE : • Well established method to produce monoclonal antibodies specific to desired antigens.
    [Show full text]
  • Advances in BIOPHARMACEUTICAL TECHNOLOGY in CHINA New Second Edition!
    Establish China partnerships Create Effective Strategies to EXPAND YOUR GLOBAL REACH! Advances in BIOPHARMACEUTICAL TECHNOLOGY in CHINA New Second Edition! A great opportunity exists in working with Chinese companies to establish scientific and business partnerships, and to create effective strategies. However, success in Asia in the new millennium will require changes in partnerships between Western and Asian companies. Every company faces the question “What should our China strategy be?” This volume, a co-publication of the Society for Industrial BY THE NUMBERS Microbiology and Biotechnology and BioPlan Associates, Inc., provides an overview of the biopharmaceutical industry, ● 102 Internationally and the state of technology in China. Recognized Authors ● 21 Peer-Reviewers Readers will be able to: ● 1,139 Pages 1. Assess the state of biopharmaceutical development in China ● 70 Translated Chapters 2. Understand general business practices ● 5 Case Studies and China Briefs 3. Analyze business opportunities and identify potential partners ● 200+ Tables and Figures A peer-reviewed, ready reference for all aspects of ● 300+ References biopharmaceuticals in China, including an understanding of the ● Over 2,000 Index Entries China biopharma current situation, and future opportunities. Readers receive a comprehensive assessment of the state-of-the- This authoritative, peer-reviewed study industry, trends, and analysis. Information on all types of organizations is produced in collaboration with the involved in biopharma in China, whether they
    [Show full text]
  • Producing a Peptide for Use in a Blood Biosensor for Injury
    Producing A Peptide For Use In A Blood Biosensor For Injury Detection By Errek Mạnh Trung Phạm Submitted in Partial Fulfillment of the Requirements for the Degree of Master of Science in the Biological Sciences Program YOUNGSTOWN STATE UNIVERSITY December 2020 Producing A Peptide For Use In A Blood Biosensor For Injury Detection Errek Mạnh Trung Phạm I hereby release this thesis to the public. I understand that this thesis will be made available from the OhioLINK ETD Center and the Maag Library Circulation Desk for public access. I also authorize the University or other individuals to make copies of this thesis as needed for scholarly research. Signature: ____________________________________________________________ Errek M.T. Phạm, Master’s Student Date Approvals: ____________________________________________________________ Dr. Diana L. Fagan, Thesis Advisor Date ____________________________________________________________ Dr. Jonathan J. Caguiat, Committee Member Date ____________________________________________________________ Dr. David K. Asch, Committee Member Date ____________________________________________________________ Dr. Salvatore A. Sanders, Dean of Graduate Studies Date ii Abstract Conventional hybridoma technology has been used for the selection and production of proteins for biosensor development. However, hybridoma technology is typically a slower and more costly procedure than phage display and produces a less durable end- product. Quicker and more efficient production of a small peptide using phage display has been
    [Show full text]
  • How Scientist/Founders Lead Successful Biopharmaceutical
    Antioch University AURA - Antioch University Repository and Archive Student & Alumni Scholarship, including Dissertations & Theses Dissertations & Theses 2008 How Scientist/Founders Lead Successful Biopharmaceutical Organizations: A Study of Three Companies Lynn Johnson Langer Antioch University - PhD Program in Leadership and Change Follow this and additional works at: http://aura.antioch.edu/etds Part of the Business Administration, Management, and Operations Commons, Medicine and Health Sciences Commons, and the Organizational Behavior and Theory Commons Recommended Citation Langer, Lynn Johnson, "How Scientist/Founders Lead Successful Biopharmaceutical Organizations: A Study of Three Companies" (2008). Dissertations & Theses. 138. http://aura.antioch.edu/etds/138 This Dissertation is brought to you for free and open access by the Student & Alumni Scholarship, including Dissertations & Theses at AURA - Antioch University Repository and Archive. It has been accepted for inclusion in Dissertations & Theses by an authorized administrator of AURA - Antioch University Repository and Archive. For more information, please contact [email protected], [email protected]. HOW SCIENTIST/FOUNDERS LEAD SUCCESSFUL BIOPHARMACEUTICAL ORGANIZATIONS: A STUDY OF THREE COMPANIES Lynn Johnson Langer A DISSERTATION Submitted to the Ph.D. in Leadership & Change Program of Antioch University in partial fulfillment of the requirements for the degree of Doctor of Philosophy May, 2008 This is to certify that the dissertation entitled: HOW SCIENTIST/FOUNDERS
    [Show full text]
  • Addressing 360O of Biochemical Imbalances to Restore Balance and Relieve Symptoms
    Addressing 360o of biochemical imbalances to restore balance and relieve symptoms. Product Guide Effective June 2015 Product availability subject to change without notice. View the most current catalog electronically at www.neuroscienceinc.com/productcatalog Dr. Gottfried Kellermann and Mieke Kellermann Ushering in a New Age of Personalized Care As NeuroScience, Inc. enters its 15th year in business, we reflect on the driving force behind our services- providing you, the practitioner, with tools that allow you to more efficiently and effectively care for your patients. Together with our laboratory partner, Pharmasan Labs, Inc. we pioneered the Assess and Address™ approach for personalized patient care. New and Exciting Direction We recognize the evolving changes in patient care and patient expectation from their healthcare practitioners. More than ever, patients are taking control of their health and demanding care that allows them to get better faster and enjoy the healthy lifestyle they deserve. NeuroScience, along with Pharmasan Labs, has taken the lead in focusing on a model that not only identifies the imbalances behind many symptoms but how the network of those imbalances indicates deeper issues. This network approach points you in the direction of the root cause of patient symptoms, which when resolved can lead to improved, long-term health outcomes. Never satisfied with the status quo, we will continue to innovate to provide you with unparalleled support toward this end. A Provider of Personalized, Clinical Solutions…this is WHO WE ARE. Together, NeuroScience and Pharmasan are committed to providing you with the clinical assessments and tools you need to thrive in this rapidly changing healthcare market while better serving your patients.
    [Show full text]
  • Hybridoma Technology & Monoclonal Antibody Production Definition
    Sanjib Kr Das B.Sc Hons. In ZOOLOGY 06.06.2020 Assistant Professor (WBES) SEM-IV Dept. of Zoology Paper- CC-10 Immunology Jhargram Raj College UNIT-4 Immunoglobulin Hybridoma Technology & Monoclonal Antibody Production Definition: Hybridoma A clone of hybrid cells formed by fusion of normal lymphocytes with myeloma cells. It retains the properties of the normal cell to produce antibodies or T-cell receptors but exhibits the immortal growth characteristic of myeloma cells. Hybridomas are used to produce monoclonal antibody (mAB). Monoclonal antibody Homogeneous preparation of antibody molecules, produced by a single clone of B lineage cells, often a hybridoma, all of which have the same antigenic specificity. (The term monoclonal refers to the fact that all of the cells in a given hybridoma culture are derived from the single clone of cells, and therefore carry the same DNA). A hybridoma is a fusion product of two cells. B-cell hybridomas are generated by artificially fusing antibody-producing, short-lived lymphocytes with long-lived tumor cells in order to generate long-lived daughter cells secreting large amounts of monoclonal antibodies. In 1975, Georges Köhler and Cesar Milstein figured out how to generate large quantities of antibodies derived from a single B-cell clone. By fusing a normal, activated, antibody-producing B cell with a myeloma cell (a cancerous plasma cell), they were able to generate a hybridoma that possessed the immortal growth properties of the myeloma cell parent and secreted the unique antibody produced by the B-cell parent. Over time, myeloma-cell partners were generated that had lost the ability to synthesize their own immunoglobulin, thus ensuring that the only antibodies secreted into the culture medium were those from the B-cell fusion partner.
    [Show full text]
  • The Economic Impact of the US Biopharmaceutical
    THE ECONOMIC IMPACT OF THE U.S. BIOPHARMACEUTICAL INDUSTRY: 2017 National and State Estimates DECEMBER 2019 TEConomy Partners, LLC is a global leader in research, analysis, and strategy for innovation-driven economic development. Today we’re helping nations, states, regions, universities, and industries blueprint their future and translate knowledge into prosperity. The Pharmaceutical Research and Manufacturers of America (PhRMA) represents the country’s leading innovative pharmaceutical research and biotechnology companies, which are devoted to developing medicines that allow patients to live longer, healthier, and more productive lives. PhRMA companies are leading the way in the search for new treatments and cures. TEConomy Partners, LLC (TEConomy) endeavors at all times to produce work of the highest quality, consistent with our contract commitments. However, because of the research and/or experimental nature of this work, the client undertakes the sole responsibility for the consequence of any use or misuse of, or inability to use, any information or result obtained from TEConomy, and TEConomy, its partners, or employees have no legal liability for the accuracy, adequacy, or efficacy thereof. TABLE OF CONTENTS Executive Summary ......................................................................................................1 Introduction: An Industry Defined by Innovation .................................................... 3 The Broad Scope and Scale of the Biopharmaceutical Industry ............................5 Defining the
    [Show full text]