Understanding the market dynamics of biosimilars

Biosimilars represent an attractive market opportunity in the pharmaceutical industry. In order to understand the underlying market dynamics and to identify the success factors of the biosimilars market, a PEST (political, economic, social, technological) analysis was conducted based on desk research and expert interviews with market participants and stakeholders. The regulatory environment for biosimilars seems to be well established and both the required manufacturing technology and the necessary analytical capabilities for biosimilar development are available. The potential market is expected to grow due to the overall dynamics in the biologics market and the patent expiration of blockbuster drugs. The perspective of the scientific community towards biosimilars has changed from skeptical to rather positive in the last 10 years, probably reflecting the evolution of regulatory guidelines and technological progress. However, physicians, responsible for the prescription of drugs, are still rather skeptical about biosimilars and need to be better informed in order to increase the currently low market penetration of biosimilars. Taken together, the biosimilars industry is expected to step out of its infancy stage and now enter the growth phase

On the current practice of New Business Development in the German chemical industry

The results of a survey on the practice of new business development conducted in 17 chemical industry companies and related business sectors, such as service providers, are presented in this article. The objectives and organizational setup of New Business Development were found to be exceptionally heterogeneous and to cover a broad spectrum. The differentiation between New Business Development and Innovation Management was also not consistent between the companies. All the companies underlined the importance of technical and scientific know-how for new business development staff, but also emphasized the relevance of interdisciplinary competencies at the interface between natural science and business. Small companies follow a rather opportunistic New Business Development approach without dedicated organizational structures. Larger companies, on the other hand, employ a Stage-Gate process and largely derive their ideas from megatrends. Differences between small and larger companies are discussed in the article at hand

ESI-IMS-MS: A method for rapid analysis of protein aggregation and its inhibition by small molecules.

Electrospray ionisation-ion mobility spectrometry-mass spectrometry (ESI-IMS-MS) is a powerful method for the study of conformational changes in protein complexes, including oligomeric species populated during protein self-aggregation into amyloid fibrils. Information on the mass, stability, cross-sectional area and ligand binding capability of each transiently populated intermediate, present in the heterogeneous mixture of assembling species, can be determined individually in a single experiment in real-time. Determining the structural characterisation of oligomeric species and alterations in self-assembly pathways observed in the presence of small molecule inhibitors is of great importance, given the urgent demand for effective therapeutics. Recent studies have demonstrated the capability of ESI-IMS-MS to identify small molecule modulators of amyloid assembly and to determine the mechanism by which they interact (positive, negative, non-specific binding, or colloidal) in a high-throughput format. Here, we demonstrate these advances using self-assembly of Aβ40 as an example, and reveal two new inhibitors of Aβ40 fibrillation

Etude de complexes protéiques non covalents par spectrométrie de masse FT-ICR.

The outstanding analytical performances of electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FT-ICR MS) were applied to study non-covalent interactions in protein complexes. In a first part, the application of this technique to the detection of intact protein complexes was developed on the system of Creatine kinase (CK) and its ligands ADP and ATP, leading to the observation of these complexes in the gas phase. Specific and non- specific contributions of these interaction were separated by means of a statictical model, yielding interaction constants (K1,ADP=11.8 ± 1.5 μM, K2,ADP=48 ± 6 μM, K1,ATP=27 ± 7 μM, K2,ATP=114 ± 27 μM) that are in fair agreement with literature values. In a second part, methods to study the surface accessibility of protein complexes by chemical modification in solution, either reversible (H/D exchange) or irreversible (specific modification of His and Lys by DEPC) were developed and implemented. The modification site was identified either by a bottom-up (enzymatic digestion followed by mass measurement of the resulting peptides) or a top-down approach (gas phase fragmentation of the entire protein by electron capture dissociation [ECD]). Within the framework of the current instrumentation, the latter approach yields reasonable results for proteins as large as 17 kDa and should be extendible to 25 kDa. Application of the different analytical strategies yielded insight into the structure and conformational dynamics of prion protein (PrP) oligomers that were obtained by partial thermal denaturation of the monomeric species in vitro. Increase in deuterium incorporation in some regions of the oligomeric species (compared to the monomer) reflects partial unfolding of the protein, as indicated by the unfolding of an α helix.Les qualités analytiques de la spectrométrie de masse à résonance cyclotronique ionique et à transformée de Fourier, combinée à une source d'électronébulisation (ESI-FT-ICR) ont été mises à profit pour l'étude d'interactions non-covalentes dans des assemblages protéiques. Dans une première partie, l'utilisation de cette technique pour la détection de complexes protéiques intacts a été développée sur le système constitué de la créatine kinase (CK) et de ses ligands ADP et ATP, conduisant à l'observation de ces complexes en phase gazeuse. Les parts spécifiques et non spécifiques de ces interactions ont été séparées par un modèle statistique, conduisant à la détermination des constantes de dissociation (K1,ADP=11.8 ± 1,5 μM, K2,ADP=48 ± 6 μM, K1,ATP=27 ± 7 μM, K2,ATP=114 ± 27 μM ) qui sont en accord avec la littérature. Dans une seconde partie, des techniques pour l'étude de l'accessibilité de surface de complexes de protéines par modification chimique en solution, aussi bien réversibles (échanges H/D) qu'irréversibles (modification spécifique d'histidine et de lysine par le DEPC) ont été mises au point et appliquées. Les sites de modification ont été localisés soit par une approche « bottom-up » (digestion enzymatique suivie d'une mesure de masse des peptides résultants) soit par une approche « top-down » (fragmentation en phase gazeuse de la protéine intacte par dissociation par capture d'électrons [ECD]). Dans le cadre de l'instrumentation actuelle, cette dernière approche a conduit à des résultats pour des protéines allant jusqu'à 17 kDa et pourrait être étendue jusqu'à des protéines de 25 kDa. Ces différentes stratégies analytiques ont été appliquées à des oligomères de la protéine du prion (PrP) obtenus par dénaturation thermique partielle in vitro de l'espèce monomérique. L'accroissement de l'incorporation de deutérium dans certaines régions de la forme oligomèrique (par rapport au monomère) reflète un dépliement partiel de la protéine, en particulier au niveau d'une hélice

Comprehensive Virtual Mathematics Training - A Crucial Support to Bridge the Gap for Undergraduate Students

We present an integrated virtual learning based approach to support undergraduate students in developing their mathematical knowledge and skills. The approach consists of three elements. First, a pre-study web-based mathematics training course for pre-assessment and self-study. Secondly, the traditional classroom lecture that is supplemented with specific examples from application fields involving dedicated literature and case examples from other courses (e.g., physical chemistry). Finally, lectures have been recorded using an easy-to-use system to provide the students with after-class self-learning material. The latter proves especially useful for extra-occupational students. The approach has been developed and implemented for chemistry undergraduate courses but can be easily adapted for any kind of engineering study course

On the contentious sequence and glycosylation motif of the ribosome inactivating plant protein gelonin

International audienceThe amino acid sequence and the glycosylation motif of the ribosome inactivating protein (RIP) gelonin are identified by Fourier transform ion cyclotron resonance mass spectrometry. Intact gelonin as isolated from the seeds of Gelonium multiflorum consists of at least three different post-translational modified forms: analysis of gelonin peptides as obtained by proteolytic digestion is consistent with the amino acid sequence published by Nolan et al. High resolution mass determination established a glycosylation pattern of GlcNAc2Man3-5Xyl. N189 was identified as glycosylation site. The proposed glycan structure is consistent with a standard plant N-glycosylation pattern as found in other RIP. Based on these results we suggest that gelonin is located in the vacuole of Gelonium multiflorum seeds. © 2005 Elsevier Inc. All rights reserved

Comprehensive Virtual Mathematics Training - A Crucial Support to Bridge the Gap for Undergraduate Students

We present an integrated virtual learning based approach to support undergraduate students in developing their mathematical knowledge and skills. The approach consists of three elements. First, a pre-study web-based mathematics training course for pre-assessment and self-study. Secondly, the traditional classroom lecture that is supplemented with specific examples from application fields involving dedicated literature and case examples from other courses (e.g., physical chemistry). Finally, lectures have been recorded using an easy-to-use system to provide the students with after-class self-learning material. The latter proves especially useful for extra-occupational students. The approach has been developed and implemented for chemistry undergraduate courses but can be easily adapted for any kind of engineering study course

A deconvolution method for the separation of specific versus nonspecific interactions in noncovalent protein-ligand complexes analyzed by ESI-FT-ICR mass spectrometry.

A method to separate specific and nonspecific noncovalent interactions observed in ESI mass spectra between a protein and its ligands is presented. Assuming noncooperative binding, the specific ligand binding is modeled as a statistical distribution on identical binding sites. For the nonspecific fraction we assume a statistical distribution on a large number of "nonspecific" interacting sites. The model was successfully applied to the noncovalent interaction between the protein creatine kinase (CK) and its ligands adenosine diphosphate (ADP) and adenosine triphosphate (ATP) that both exhibit nonspecific binding in the mass spectrum. The two sequential dissociation constants obtained by applying our method are K(1,diss) = 11.8 +/- 1.5 microM and K(2,diss) = 48 +/- 6 microM for ADP. For ATP, the constants are K(1,diss) = 27 +/- 7 microM and K(2,diss) = 114 +/- 27 microM. All constants are in good correlation with reported literature values. The model should be valuable for systems with a large dissociation constant that require high ligand concentrations and thus have increased potential of forming nonspecific adducts

Tradition vs. Moderne: Möglichkeiten und Limitationen eines neuen Vorlesungskonzepts in der curricularen HNO-Lehre

Background!#!Due to steadily dwindling student attendance, a new blended learning lecture format was piloted at the Department of Otorhinolaryngology of the University Medical Center Freiburg in the winter semester (WS) 2017/18: the ENT 3D series. In order to present complex ENT topics (e.g., middle ear) in a more understandable, appealing, and clinically relevant manner, the clinical disciplines of otorhinolaryngology and radiology cooperated with the preclinical specialty of anatomy. The aim of the study was to evaluate this teaching format and investigate preferences that could encourage students to attend lectures.!##!Methods!#!In all lectures, participants of the ENT block internship in the 2017/18 WS were asked about the quality of the lecture using an evaluation card. In addition, the increase in knowledge was examined in each of the newly designed lectures. A final questionnaire asked the students about their preferences regarding teaching methods.!##!Results!#!Overall, the new courses were not rated better than the regular ones, although the new concept was generally rated positively. It was not possible to attract more lecture attendees. However, the traditional teaching format 'lecture' is still regarded as up to date by a defined group of students.!##!Conclusion!#!Despite a principally positive student assessment of a new lecture format, the 3D lectures did not achieve top marks in any category. This can be explained by the accumulation of unexpected student criticisms (quantity of the course content). Thus, the parameters intended as indicators (e-learning, quality of the course, use of modern teaching methods) could not fulfil their task. The result of the evaluation requires critical reflection and, if necessary, partial reorganization of the course (streamlining of content)