Sanofi Genzyme is an American biotechnology company based in Cambridge, Massachusetts. Since its acquisition in 2011, Genzyme has been a owned subsidiary of Sanofi. In 2010, Genzyme was the world’s third-largest biotechnology company, employing more than 11,000 people around the world; as a subsidiary of Sanofi, Genzyme has a presence in 65 countries, including 17 manufacturing facilities and 9 genetic-testing laboratories. Its products are sold in 90 countries. In 2007, Genzyme generated $3.8 billion in revenue with more than 25 products in the market. In 2006 and 2007, Genzyme was named one of Fortune Magazine’s “100 Best Companies to Work for”; the company donated $83 million worth of products worldwide. In 2005, Genzyme was awarded the National Medal of Technology, the highest level of honor awarded by the president of the United States to America’s leading innovators; the company was started by Sheridan Snyder and George M. Whitesides in 1981. Genzyme's scientific founder was Henry Blair who had a contract with the National Institutes of Health to produce modified enzymes for the NIH to test in clinical trials.
Blair was a technician at the New England Enzyme Center at Tufts Medical School. Genzyme's first office was an old clothing warehouse adjacent to Tufts Medical School. In 1981,with the help of venture capital funding, the company made its first acquisition. In 1982, it made its second acquisition, British-based Koch-Light Laboratories becoming Genzyme Pharmaceutical and Fine Chemicals. Henri Termeer joined Genzyme as its president in 1983 and worked to redirect the company, which by this time had reached a valuation of $100 million, from its focus on diagnostic enzymes to modified enzymes for use as human therapeutics. In 1984, Robin Berman, MD, who volunteered at the NIH, had a three-year-old son Brian, who had Gaucher's disease, he was scheduled for a spleen removal but his mother pleaded with Roscoe Brady, MD, expert in Gaucher's disease, to include Brian in the clinical trial of Ceredase along with the other seven patients who were all adults. This trial failed due to use of too low a dose of the enzyme, but Ceredase went on to "become the company's most important product line", receiving FDA approval in 1991In 1985, Termeer became the company's Chief executive officer and in 1986, he took the company public.
In 1989, Termeer acquired Integrated Genetics, strengthening the company's presence in molecular biology, protein chemistry, carbohydrate engineering, nucleic acid chemistry, enzymology. Following the approval and success of Ceredase in 1991, Genzyme became devoted to finding drugs, involving recombinant human enzymes that would treat enzyme deficiency conditions that were essential to human survival and which afflict a small percentage of the world’s population. Drugs used to treat such conditions are considered to be orphan drugs. Ceredase was the first effective treatment for Gaucher's disease, a rare and fatal genetic disorder. At the time, Ceredase drew criticism for being the most expensive drug sold, on average $150,000 per patient a year. In 1991, Genzyme took IG laboratories, acquired in 1989, public raising $14 million on IPO. Genzyme's sold off its interest in GENE-TRAK systems for $10 million and acquired Genecore International's diagnostic enzyme division. In 1992, Genzyme acquired Medix Biotech, Inc. a producer and supplier of monoclonal and polyclonal antibodies, immunoassay components, immunodiagnostic services.
In the same year, Genzyme Limited, acquired Enzymatix Ltd and genetics testing laboratory Vivigen. In 1993, the company acquired German distributor of invitro diagnostic kits and immunobiological products manufacturer Omni Res srl. In 1994 Genzyme received FDA approval to market Cerezyme, a genetically engineered replacement for Ceredase; the company acquired Sygena Ltd, BioSurface Technology Inc. and TSI Inc.. TSI was acquired by Genzyme Transgenics Corp., 73 percent owned by Genzyme. In 1997 the company acquired Inc. creating Genzyme Molecular Oncology. In 1999 Genzyme Surgical Products is established within the wider Group. In 2000 the company announced its plan to acquire Inc.. In August 2003, the company acquired SangStat Medical Corp. and its principal anti-organ rejection drug named Thymoglobulin for $600 million. In 2004 the company acquired Ilex Oncology Inc.. Genzyme acquired several of Impath's laboratories and cancer-testing technologies in May 2004, after Impath sought Chapter 11 bankruptcy protection.
In 2005 the company acquired Bone Care International Inc for $600 million. In 2006 the company acquired AnorMED Inc. for $580 millionIn 2007, the company agreed to acquire Bioenvision for $345 million, motivated by the potential of the leukemia treatment clofarabine. In 2010, the year before the company's acquisition by Sanofi-Aventis, Genzyme had more than $400 million on net income on revenue of $4 billion and was the fourth-largest American biopharmaceutical company. By this time, enzyme therapies accounted for about 40% of revenues, a portfolio managed by the "Personalized Genetic Health" unit, the largest of five operating units. In the same year the company sold Genzyme Genetics for $925 million to LabCorp. In 2011 Sanofi acquired the company for $20.1 billion. The following is an illustration of the company's major mergers and acquisitions and historical predecessors: Genzyme focuses on six areas of medicine relating to lysosomal storage diseases, renal disease, orthopedics and immune diseases, oncology and diagnostics.
The first orphan-drug for Genzyme that FDA approved was Ceredase, a drug for treating Gaucher disease. Ceredase
A lymphocyte is one of the subtypes of a white blood cell in a vertebrate's immune system. Lymphocytes include natural killer cells, T cells, B cells, they are the main type of cell found in lymph, which prompted the name "lymphocyte". The three major types of lymphocyte are B cells and natural killer cells. Lymphocytes can be identified by their large nucleus. T cells and B cells are the major cellular components of the adaptive immune response. T cells are involved in cell-mediated immunity, whereas B cells are responsible for humoral immunity; the function of T cells and B cells is to recognize specific "non-self" antigens, during a process known as antigen presentation. Once they have identified an invader, the cells generate specific responses that are tailored to maximally eliminate specific pathogens or pathogen-infected cells. B cells respond to pathogens by producing large quantities of antibodies which neutralize foreign objects like bacteria and viruses. In response to pathogens some T cells, called T helper cells, produce cytokines that direct the immune response, while other T cells, called cytotoxic T cells, produce toxic granules that contain powerful enzymes which induce the death of pathogen-infected cells.
Following activation, B cells and T cells leave a lasting legacy of the antigens they have encountered, in the form of memory cells. Throughout the lifetime of an animal, these memory cells will "remember" each specific pathogen encountered, are able to mount a strong and rapid response if the same pathogen is detected again. NK cells are a part of the innate immune system and play a major role in defending the host from tumors and virally infected cells. NK cells distinguish infected cells and tumors from normal and uninfected cells by recognizing changes of a surface molecule called MHC class I. NK cells are activated in response to a family of cytokines called interferons. Activated NK cells release cytotoxic granules which destroy the altered cells, they are named "natural killer cells" because they do not require prior activation in order to kill cells which are missing MHC class I. Mammalian stem cells differentiate into several kinds of blood cell within the bone marrow; this process is called haematopoiesis.
All lymphocytes originate, during this process, from a common lymphoid progenitor before differentiating into their distinct lymphocyte types. The differentiation of lymphocytes follows various pathways in a hierarchical fashion as well as in a more plastic fashion; the formation of lymphocytes is known as lymphopoiesis. B cells mature into B lymphocytes in the bursa equivalent, which in humans is the GALT, thought to be located in the Peyer's patches of the intestine, while T cells migrate to and mature in a distinct organ, called the thymus. Following maturation, the lymphocytes enter the circulation and peripheral lymphoid organs where they survey for invading pathogens and/or tumor cells; the lymphocytes involved in adaptive immunity differentiate further after exposure to an antigen. Effector lymphocytes function to eliminate the antigen, either by releasing antibodies, cytotoxic granules or by signaling to other cells of the immune system. Memory T cells remain in the peripheral tissues and circulation for an extended time ready to respond to the same antigen upon future exposure.
Microscopically, in a Wright's stained peripheral blood smear, a normal lymphocyte has a large, dark-staining nucleus with little to no eosinophilic cytoplasm. In normal situations, the coarse, dense nucleus of a lymphocyte is the size of a red blood cell; some lymphocytes show a clear perinuclear zone around the nucleus or could exhibit a small clear zone to one side of the nucleus. Polyribosomes are a prominent feature in the lymphocytes and can be viewed with an electron microscope; the ribosomes are involved in protein synthesis, allowing the generation of large quantities of cytokines and immunoglobulins by these cells. It is impossible to distinguish between B cells in a peripheral blood smear. Flow cytometry testing is used for specific lymphocyte population counts; this can be used to determine the percentage of lymphocytes that contain a particular combination of specific cell surface proteins, such as immunoglobulins or cluster of differentiation markers or that produce particular proteins.
In order to study the function of a lymphocyte by virtue of the proteins it generates, other scientific techniques like the ELISPOT or secretion assay techniques can be used. In the circulatory system, they move from lymph node to lymph node; this contrasts with macrophages. A lymphocyte count is part of a peripheral complete blood cell count and is expressed as the percentage of lymphocytes to the total number of white blood cells counted. A general increase in the number of lymphocytes is known as lymphocytosis, whereas a decrease is known as lymphocytopenia. An increase in lymphocyte concentration is a sign of a viral infection. A high lymphocyte count wi
Monoclonal antibodies are antibodies that are made by identical immune cells that are all clones of a unique parent cell. Monoclonal antibodies can have monovalent affinity. In contrast, polyclonal antibodies bind to multiple epitopes and are made by several different plasma cell lineages. Bispecific monoclonal antibodies can be engineered, by increasing the therapeutic targets of one single monoclonal antibody to two epitopes. Given any substance, it is possible to produce monoclonal antibodies that bind to that substance; this has become an important tool in biochemistry, molecular biology, medicine. When used as medications, non-proprietary drug names end in -mab and many immunotherapy specialists use the word mab anacronymically; the idea of "magic bullets" was first proposed by Paul Ehrlich, who, at the beginning of the 20th century, postulated that, if a compound could be made that selectively targeted a disease-causing organism a toxin for that organism could be delivered along with the agent of selectivity.
He and Élie Metchnikoff received the 1908 Nobel Prize for Physiology or Medicine for this work, which led to an effective syphilis treatment by 1910. In the 1970s, the B-cell cancer multiple myeloma was known, it was understood. This was used to study the structure of antibodies, but it was not yet possible to produce identical antibodies specific to a given antigen. In 1975, Georges Köhler and César Milstein succeeded in making fusions of myeloma cell lines with B cells to create hybridomas that could produce antibodies, specific to known antigens and that were immortalized, they shared the Nobel Prize in Medicine in 1984 for the discovery. In 1988, Greg Winter and his team pioneered the techniques to humanize monoclonal antibodies, eliminating the reactions that many monoclonal antibodies caused in some patients. Much of the work behind production of monoclonal antibodies is rooted in the production of hybridomas, which involves identifying antigen-specific plasma/plasmablast cells that produce antibodies specific to an antigen of interest and fusing these cells with myeloma cells.
Rabbit B-cells can be used to form a rabbit hybridoma. Polyethylene glycol is used to fuse adjacent plasma membranes, but the success rate is low, so a selective medium in which only fused cells can grow is used; this is possible because myeloma cells have lost the ability to synthesize hypoxanthine-guanine-phosphoribosyl transferase, an enzyme necessary for the salvage synthesis of nucleic acids. The absence of HGPRT is not a problem for these cells unless the de novo purine synthesis pathway is disrupted. Exposing cells to aminopterin, makes them unable to use the de novo pathway and become auxotrophic for nucleic acids, thus requiring supplementation to survive; the selective culture medium is called HAT medium because it contains hypoxanthine and thymidine. This medium is selective for fused cells. Unfused myeloma cells cannot grow because they lack HGPRT and thus cannot replicate their DNA. Unfused spleen cells cannot grow indefinitely because of their limited life span. Only fused hybrid cells, referred to as hybridomas, are able to grow indefinitely in the medium because the spleen cell partner supplies HGPRT and the myeloma partner has traits that make it immortal.
This mixture of cells is diluted and clones are grown from single parent cells on microtitre wells. The antibodies secreted by the different clones are assayed for their ability to bind to the antigen or immuno-dot blot; the most productive and stable clone is selected for future use. The hybridomas can be grown indefinitely in a suitable cell culture medium, they can be injected into mice. There, they produce; the medium must be enriched during in vitro selection to further favour hybridoma growth. This can be achieved by the use of a layer of feeder fibrocyte cells or supplement medium such as briclone. Culture-media conditioned by macrophages can be used. Production in cell culture is preferred as the ascites technique is painful to the animal. Where alternate techniques exist, ascites is considered unethical. Several monoclonal antibody technologies had been developed such as phage display, single B cell culture, single cell amplification from various B cell populations and single plasma cell interrogation technologies.
Different from traditional hybridoma technology, the newer technologies use molecular biology techniques to amplify the heavy and light chains of the antibody genes by PCR and produce in either bacterial or mammalian systems with recombinant technology. One of the advantages of the new technologies is applicable to multiple animals, such as rabbit, llama and other common experimental animals in the laboratory. After obtaining either a media sample of cultured hybridomas or a sample of ascites fluid, the desired antibodies must be extracted. Cell culture sample contaminants consist of media components such as growth factors and transferrins. In contrast, the in vivo sample is to have host antibodies, nucleases, nucleic acids and viruses. In both cases, other secretions by the hybridomas such as cytokines may be present. There may be b
Immunoglobulin G is a type of antibody. Representing 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are released by plasma B cells; each IgG has two antigen binding sites. Antibodies are major components of humoral immunity. IgG is the main type of antibody found in blood and extracellular fluid, allowing it to control infection of body tissues. By binding many kinds of pathogens such as viruses and fungi, IgG protects the body from infection, it does this through several mechanisms: IgG-mediated binding of pathogens causes their immobilization and binding together via agglutination. IgG antibodies are generated following class switching and maturation of the antibody response, thus they participate predominantly in the secondary immune response. IgG is secreted as a monomer, small in size allowing it to perfuse tissues, it is the only antibody isotype that has receptors to facilitate passage through the human placenta, thereby providing protection to the fetus in utero.
Along with IgA secreted in the breast milk, residual IgG absorbed through the placenta provides the neonate with humoral immunity before its own immune system develops. Colostrum contains a high percentage of IgG bovine colostrum. In individuals with prior immunity to a pathogen, IgG appears about 24–48 hours after antigenic stimulation. Therefore, in the first six months of life, the newborn has the same antibodies as the mother and the child can defend itself against all the pathogens that the mother encountered in her life until these antibodies are degraded; this repertoire of immunoglobulins is crucial for the newborns who are sensitive to infections above all for the respiratory and digestive systems. IgG are involved in the regulation of allergic reactions. According to Finkelman, there are two pathways of systemic anaphylaxis: antigens can cause systemic anaphylaxis in mice through classic pathway by cross-linking IgE bound to the mast cell receptor FcεRI, stimulating the release of both histamine and platelet activating factor.
In the alternative pathway antigens form complexes with IgG, which cross-link macrophage receptor FcγRIII and stimulates only PAF release. IgG antibodies can prevent IgE mediated anaphylaxis by intercepting a specific antigen before it binds to mast cell–associated IgE. IgG antibodies block systemic anaphylaxis induced by small quantities of antigen but can mediate systemic anaphylaxis induced by larger quantities. IgG antibodies are large molecules with a molecular weight of about 150 kDa made of four peptide chains, it contains two identical class γ heavy chains of about 50 kDa and two identical light chains of about 25 kDa, thus a tetrameric quaternary structure. The two heavy chains are linked to a light chain each by disulfide bonds; the resulting tetramer has two identical halves. Each end of the fork contains an identical antigen binding site; the various regions and domains of a typical IgG are depicted in the figure to the left. The Fc regions of IgGs bear a conserved N-glycosylation site.
The N-glycans attached to this site are predominantly core-fucosylated diantennary structures of the complex type. In addition, small amounts of these N-glycans bear bisecting GlcNAc and α-2,6-linked sialic acid residues. There are four IgG subclasses in humans, named in order of their abundance in serum. Note: IgG affinity to Fc receptors on phagocytic cells is specific to individual species from which the antibody comes as well as the class; the structure of the hinge regions contributes to the unique biological properties of each of the four IgG classes. Though there is about 95% similarity between their Fc regions, the structure of the hinge regions is different. Given the opposing properties of the IgG subclasses, the fact that the immune response to most antigens includes a mix of all four subclasses, it has been difficult to understand how IgG subclasses can work together to provide protective immunity; the Temporal Model of human IgE and IgG function was proposed. This model suggests; the IgG3, though of low affinity, allows IgG-mediated defences to join IgM-mediated defences in clearing foreign antigens.
Subsequently, higher affinity IgG1 and IgG2 are produced. The relative balance of these subclasses, in any immune complexes that form, helps determine the strength of the inflammatory processes that follow. If antigen persists, high affinity IgG4 is produced, which dampens down inflammation by helping to curtail FcR-mediated processes; the relative ability of different IgG subclasses to fix complement may explain why some anti-donor antibody responses do harm a graft after organ transplantation. In a mouse model of autoantibody mediated anemia using IgG isotype swit
Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus Rattus. Other rat genera include Neotoma and Dipodomys. Rats are distinguished from mice by their size; when someone discovers a large muroid rodent, its common name includes the term rat, while if it is smaller, its name includes the term mouse. The common terms rat and mouse are not taxonomically specific. In other words, rat is not a scientific term; the best-known rat species are the brown rat. This group known as the Old World rats or true rats, originated in Asia. Rats are bigger than most Old World mice, which are their relatives, but weigh over 500 grams in the wild; the term rat is used in the names of other small mammals that are not true rats. Examples include the North American pack rats, a number of species loosely called kangaroo rats, others. Rats such as the bandicoot rat are murine rodents related to true rats but are not members of the genus Rattus.
Male rats are called bucks. A group of rats is referred to as a mischief; the common species are opportunistic survivors and live with and near humans. They may cause substantial food losses in developing countries. However, the distributed and problematic commensal species of rats are a minority in this diverse genus. Many species of rats are island endemics, some of which have become endangered due to habitat loss or competition with the brown, black, or Polynesian rat. Wild rodents, including rats, can carry many different zoonotic pathogens, such as Leptospira, Toxoplasma gondii, Campylobacter; the Black Death is traditionally believed to have been caused by the microorganism Yersinia pestis, carried by the tropical rat flea, which preyed on black rats living in European cities during the epidemic outbreaks of the Middle Ages. Another zoonotic disease linked to the rat is foot-and-mouth disease. Rats become sexually reach social maturity at about 5 to 6 months of age; the average lifespan of rats varies by species.
The black and brown rats diverged from other Old World rats in the forests of Asia during the beginning of the Pleistocene. The characteristic long tail of most rodents is a feature, extensively studied in various rat species models, which suggest three primary functions of this structure: thermoregulation, minor proprioception, a nocifensive-mediated degloving response. Rodent tails—particularly in rat models—have been implicated with a thermoregulation function that follows from its anatomical construction; this particular tail morphology is evident across the family Muridae, in contrast to the bushier tails of Sciuridae, the squirrel family. The tail is hairless and thin skinned but vascularized, thus allowing for efficient countercurrent heat exchange with the environment; the high muscular and connective tissue densities of the tail, along with ample muscle attachment sites along its plentiful caudal vertebrae, facilitate specific proprioceptive senses to help orient the rodent in a three-dimensional environment.
Lastly, murids have evolved a unique defense mechanism termed degloving that allows for escape from predation through the loss of the outermost integumentary layer on the tail. However, this mechanism is associated with multiple pathologies that have been the subject of investigation. Multiple studies have explored the thermoregulatory capacity of rodent tails by subjecting test organisms to varying levels of physical activity and quantifying heat conduction via the animals' tails. One study demonstrated a significant disparity in heat dissipation from a rat's tail relative to its abdomen; this observation was attributed to the higher proportion of vascularity in the tail, as well as its higher surface-area-to-volume ratio, which directly relates to heat's ability to dissipate via the skin. These findings were confirmed in a separate study analyzing the relationships of heat storage and mechanical efficiency in rodents that exercise in warm environments. In this study, the tail was a focal point in measuring heat modulation.
On the other hand, the tail's ability to function as a proprioceptive sensor and modulator has been investigated. As aforementioned, the tail demonstrates a high degree of muscularization and subsequent innervation that ostensibly collaborate in orienting the organism; this is accomplished by coordinated flexion and extension of tail muscles to produce slight shifts in the organism's center of mass, etc. which assists it with achieving a state of proprioceptive balance in its environment. Further mechanobiological investigations of the constituent tendons in the tail of the rat have identified multiple factors that influence how the organism navigates its environment with this structure. A particular example is that of a study in which the morphology of these tendons is explicated in detail. Namely, cell viability tests of tendons of the rat's tail demonstrate a higher proportion of living fibroblasts that produce the collagen for these fibers; as in humans, these tendons contain a high density of golgi tendon organs that help the animal assess stretching of muscle in situ and adjust accordingly by relaying the information to higher cortical areas associated with balance and movement.
Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to determine the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as: pharmaceutical drugs, food additives, etc, it attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, whereas pharmacodynamics is the study of how the drug affects the organism. Both together influence dosing and adverse effects, as seen in PK/PD models. Pharmacokinetics describes how the body affects a specific xenobiotic/chemical after administration through the mechanisms of absorption and distribution, as well as the metabolic changes of the substance in the body, the effects and routes of excretion of the metabolites of the drug. Pharmacokinetic properties of chemicals are affected by the route of administration and the dose of administered drug.
These may affect the absorption rate. Models have been developed to simplify conceptualization of the many processes that take place in the interaction between an organism and a chemical substance. One of these, the multi-compartmental model, is the most used approximations to reality; the various compartments that the model is divided into are referred to as the ADME scheme: Liberation – the process of release of a drug from the pharmaceutical formulation. See IVIVC. Absorption – the process of a substance entering the blood circulation. Distribution – the dispersion or dissemination of substances throughout the fluids and tissues of the body. Metabolism – the recognition by the organism that a foreign substance is present and the irreversible transformation of parent compounds into daughter metabolites. Excretion – the removal of the substances from the body. In rare cases, some drugs irreversibly accumulate in body tissue; the two phases of metabolism and excretion can be grouped together under the title elimination.
The study of these distinct phases involves the use and manipulation of basic concepts in order to understand the process dynamics. For this reason in order to comprehend the kinetics of a drug it is necessary to have detailed knowledge of a number of factors such as: the properties of the substances that act as excipients, the characteristics of the appropriate biological membranes and the way that substances can cross them, or the characteristics of the enzyme reactions that inactivate the drug. All these concepts can be represented through mathematical formulas that have a corresponding graphical representation; the use of these models allows an understanding of the characteristics of a molecule, as well as how a particular drug will behave given information regarding some of its basic characteristics such as its acid dissociation constant and solubility, absorption capacity and distribution in the organism. The model outputs for a drug can be used in industry or in the clinical application of pharmacokinetic concepts.
Clinical pharmacokinetics provides many performance guidelines for effective and efficient use of drugs for human-health professionals and in veterinary medicine. The following are the most measured pharmacokinetic metrics: In pharmacokinetics, steady state refers to the situation where the overall intake of a drug is in dynamic equilibrium with its elimination. In practice, it is considered that steady state is reached when a time of 4 to 5 times the half-life for a drug after regular dosing is started; the following graph depicts a typical time course of drug plasma concentration and illustrates main pharmacokinetic metrics: Pharmacokinetic modelling is performed by noncompartmental or compartmental methods. Noncompartmental methods estimate the exposure to a drug by estimating the area under the curve of a concentration-time graph. Compartmental methods estimate the concentration-time graph using kinetic models. Noncompartmental methods are more versatile in that they do not assume any specific compartmental model and produce accurate results acceptable for bioequivalence studies.
The final outcome of the transformations that a drug undergoes in an organism and the rules that determine this fate depend on a number of interrelated factors. A number of functional models have been developed in order to simplify the study of pharmacokinetics; these models are based on a consideration of an organism as a number of related compartments. The simplest idea is to think of an organism as only one homogenous compartment; this monocompartmental model presupposes that blood plasma concentrations of the drug are a true reflection of the drug's concentration in other fluids or tissues and that the elimination of the drug is directly proportional to the drug's concentration in the organism. However, these models do not always reflect the real situation within an organism. For example, not all body tissues have the same blood supply, so the distribution of the drug will be slower in these tissues than in others with a better blood supply. In addition, there are some tissues (s
Sanofi S. A. is a French multinational pharmaceutical company headquartered in Paris, France, as of 2013 the world's fifth-largest by prescription sales. The company was formed as Sanofi-Aventis in 2004 by the merger of Aventis and Sanofi-Synthélabo, which were each the product of several previous mergers, it changed its name to Sanofi in May 2011. The company is a component of the Euro Stoxx 50 stock market index. Sanofi engages in the research and development and marketing of pharmaceutical drugs principally in the prescription market, but the firm develops over-the-counter medication; the company covers seven major therapeutic areas: cardiovascular, central nervous system, internal medicine, oncology and vaccines. In February 2019, Sanofi appointed Dr. Ameet Nathwani as its Chief Digital Officer. Sanofi was founded in 1973 as a subsidiary of Elf Aquitaine, when Elf Aquitaine took control of the Labaz group, a pharmaceutical company formed in 1947 by Societe Belge de l'Azote et des Produits Chimiques du Marly.
In 1993 Sanofi made a move into the Eastern Europe market by acquiring a controlling interest in Chinoin, a Hungarian drug company that had about US$104 million in sales in 1992. In that same year, Sanofi's made its first significant venture into the U. S. and strengthened its presence in Eastern Europe, by first partnering with Sterling Winthrop and acquiring the prescription pharmaceuticals business in 1994. Sanofi was incorporated under the laws of France in 1994 as a société anonyme, a form of limited liability company. Synthélabo was founded in 1970 through the merger of two French pharmaceutical laboratories, Laboratoires Dausse and Laboratoires Robert & Carrière. In 1973, the French cosmetics group L’Oréal acquired the majority of its share capital. In 1991, Synthelabo acquired Laboratories Delalande and Laboratoires Delagrange, through this deal picked up the product metoclopramide. Sanofi-Synthélabo was formed in 1999; the merged company was based in France. The merged companies focused on pharmaceuticals, divesting several businesses soon after the merger, including beauty, animal health and nutrition, custom chemicals, two medical equipment businesses.
Aventis was formed in 1999 when French company Rhône-Poulenc S. A. merged with the German corporation Hoechst Marion Roussel, which itself was formed from the 1995 merger of Hoechst AG with Cassella, Roussel Uclaf and Marion Merrell Dow. The merged company was based near Strasbourg, France. At the time of the merger, Rhône-Poulenc's business included the pharmaceutical businesses Rorer and Pasteur Merieux, the plant and animal health businesses Rhône-Poulenc Agro, Rhône-Poulenc Animal Nutrition, Merial, a 67 percent share in Rhodia, a speciality chemicals company. Hoechst, one of the companies resulting from the post-WWII split of IG Farben, had seven primary businesses: Hoechst Marion Roussel, AgrEvo, HR Vet, Dade Behring, Centeon and Messer. Merieux has been in the business of selling blood products, In the 1980s during the AIDS epidemic and other companies were involved in scandals related to HIV-contaminated haemophilia blood products that were sold to developing nations. In mid 2000 Aventis and Millennium Pharmaceuticals, a US biotechnology company formed to discover new drugs based on the then-new science of genomics, announced that Aventis would make a $250M investment in Millennium and would pay $200M to Millennium in research fees over five years, one of the largest such deals between a big pharmaceutical company and a biotech company at the time.
In late 2000, in the midst of the recall of Starlink, its genetically modified maize product, Aventis announced that it had determined to sell off Aventis Cropscience, the seed and pesticide business unit it had created from the agriculture businesses of its predecessors. In October 2001, Bayer and Aventis announced that Bayer would acquire the unit for about $6.6 billion, with the unit becoming Bayer CropScience and making Bayer the world's second-largest agrochemical company behind Syngenta. In 2003 Aventis entered into a collaboration with Regeneron, a New York biotechnology company, to develop Regeneron's VEGF-inhibiting drug, aflibercept, in the field of cancer, in Phase I clinical trials. Aventis made an upfront payment of $80 million in cash. Regeneron partnered the drug with Bayer Healthcare in the field of proliferative eye diseases, under the name Eylea it was approved by the FDA in 2011. Sanofi-Aventis was formed in 2004. In early 2004, Sanofi-Synthélabo made. Aventis rejected the bid because it felt that the bid offered inferior value based on the company's share value, the board of Aventis went so far as to enact poison pill provisions and to invite Novartis to enter merger negotiations.
The three-month takeover battle concluded when Sanofi-Synthélabo launched a friendly bid of €54.5 billion in place of