Industrie pharmaceutique

L'industrie pharmaceutique est le secteur économique qui regroupe les activités de recherche, de fabrication et de commercialisation des médicaments pour la médecine humaine ou vétérinaire. Cette activité est exercée par les laboratoires pharmaceutiques et les sociétés de biotechnologie. Historique La pharmacie la plus ancienne recensée dans l’histoire date de 754. Ouverte à Bagdad par des pharmaciens arabes, sous le califat Abbasside, les sayadilas, elle a rapidement été rejointe par d’autres, initialement dans le monde médiéval islamique et, par la suite, en Europe. Au , nombre de pharmacies européennes et nord-américaines sont devenues des sociétés pharmaceutiques à part entière, et, de fait, la plupart des sociétés pharmaceutiques actuelles ont été fondées à cette époque. Aux , les découvertes centrales des années 1920 et des années 1930 dans le domaine de la médecine, telles que la pénicilline et l’insuline, commencent alors à être produites en quantité industrielle

Peptide-Polymer Conjugates for Therapeutic Applications

Ana Maria Raduta

Over the last ten years the attention of the pharmaceutical industry has shifted away from small molecules to focus on new biologics such as antibodies, proteins and therapeutic peptides. Herein, peptides have emerged as a particularly interesting category that fills a niche between small molecule chemicals and the larger proteins. Although they have great potential for drug development, their use is still limited due to their intrinsic low systemic stability, rapid renal elimination and poor membrane permeability. Various formulations have been developed to take advantage of their therapeutic properties, one of the most promising strategies being chemical conjugation to a polymer. Peptide-polymer conjugates are hybrid materials that consist of one or more synthetic polymers covalently attached to one or more peptide fragments. The aim of this thesis was to provide an insight into the requirements for the design of peptide-polymer conjugates for therapy. Chapter 1 illustrates the state of the art in the development of peptides for therapeutic applications, exemplifies the different architectures and structures of peptide-polymer conjugates and discusses ongoing efforts to improve and diversify the range and applications of these conjugates. Chapter 2 describes a novel synthetic strategy to prepare PHPMA based peptide-polymer conjugates via thiol chemistry starting from poly(pentafluorophenyl methacrylate). By varying the feed composition, the extent of side chain modification could be controlled. Further modification of the reactive copolymer scaffolds led to the site specific attachment of model peptides. This method was used to synthesize stable as well as pH and redox sensitive peptide-polymer conjugates and the release of the peptide from the polymer backbone was studied in acidic and redox conditions. In Chapter 3, the aim was to construct a peptide-polymer conjugate that could serve to promote intracellular delivery and drug release but also play a role in the intracellular trafficking of the drug. To this end, coiled coil peptides E3/K3 was attached to a PHPMA polymer backbone and was used to facilitate release from the backbone at acidic pH and further endosomal escape. Initially, the membrane lytic properties of E3/K3 and three newly designed E3/K3X motifs on model membranes were investigated as a function of pH. Secondly, the potential application of E3/K3 peptide-polymer conjugate for cytoplasmic delivery was evaluated in vitro. Chapter 4 explores the synthesis and in vitro therapeutic activity of synthetic peptide-polymer conjugates focusing on the inhibition of an oncogenic transcription factor (AP-1). To this end, AFosW peptide, a peptide binder that can interfere with AP-1 formation was attached to a polymer backbone via a redox or pH sensitive linker using a strategy developed in Chapter 2. Fluorescent microscopy and flow cytometry provided an insight into the cellular uptake of these conjugates. Their ability to interfere with AP-1 formation in vitro was quantified. Chapter 5 describes the synthesis of a second generation of peptide-polymer conjugates for AP-1 inhibition that along the FosW dominant negative peptide also incorporates a motif that facilitates endosomal escape and a nuclear localization sequence. To investigate the potential application for therapy, the conjugates were evaluated and compared with regard to their ability to inhibit AP-1 formation in living cells.

EPFL2015

Essays on the Economics of Innovation: Incentives, Diffusion, and Disparity

Ling Zhou

As an important policy instrument for guiding innovation, the patent system involves a long-standing tension between creating economic rewards for the original innovators and stifling subsequent R&D activities. The availability of new data allows us to provide unique sights into understanding how effective patents are in providing incentives for innovation and how firms' disclosure of proprietary assets affects the dissemination of knowledge. On the other hand, innovation per se is the fruit of human intellect. The knowledge workforce is, therefore, a crucial component of a country's innovative capacity. The persistent gap in the participation in innovative activities between men and women reflects a misallocation of talented human capital and leaves opportunities for policy implementation. This dissertation ties the questions mentioned above and presents novel evidence on the incentives, diffusion, and disparity in innovative activities. The first essay (chapter 2), in collaboration with Gaétan de Rassenfosse, provides empirical evidence on the real effect of patent expiration on monopoly prices and explores how this effect varies with product market competition. We compile a novel dataset that links patents to consumer products and retail prices for these products from Amazon.com. We find that patent expiration leads to a 7--8 percent drop in product prices. This effect is heterogeneous by patent type and importance and starts one year in advance. We also find a more substantial decline in prices in product markets where competition is intense, consistent with evidence from the pharmaceutical industry. We argue that incumbent innovators lower prices preemptively in the face of generic competition. The second essay (chapter 3), in collaboration with Gaétan de Rassenfosse, studies how firms' disclosure of innovative assets affects the diffusion of inventions. We focus the empirical setting on firms' provision of constructive notice through virtual patent marking (VPM) and exploit patent-level variation in the marking dates. With data collected on marked patents from the VPM web documents of 16 firms, we find an overall effect of VPM is small. However, conditional firms' strong reliance on patents as an appropriability regime, our findings suggest that while VPM induces firms to build subsequent internal inventions on the ones that are commercially valuable, it fends off diffusion to external firms and reduces similarity between inventions. Last but not least, in the third essay (chapter 4), collaborated with Mary Kaltenberg, we explore the role of family policies in closing the innovation gender gap. By matching inventor data to web-scraped inventor age information, we exploit the staggered passage of maternity leave policies across the U.S. and evaluate its impact on the retention and productivity of female inventors. Our findings suggest that maternity leave policy supports women of reproductive ages stay longer in patenting but has little impact on their productivity.

EPFL2021

Essays on the Economics of Innovation: Incentives, Diffusion, and Disparity

Ling Zhou

EPFL2021

Peptide-Polymer Conjugates for Therapeutic Applications

Ana Maria Raduta

EPFL2015

Demand forecast for pharmaceutical company

Peptide-Polymer Conjugates for Therapeutic Applications

Essays on the Economics of Innovation: Incentives, Diffusion, and Disparity

Essays on the Economics of Innovation: Incentives, Diffusion, and Disparity

Demand forecast for pharmaceutical company

Peptide-Polymer Conjugates for Therapeutic Applications