Grenoble, France
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Sabatier V.,Pierre Mendès-France University | Sabatier V.,Grenoble Graduate School of Business | Mangematin V.,Grenoble Graduate School of Business | Rousselle T.,PxTherapeutics
Production Planning and Control | Year: 2010

The biopharmaceutical industry has been one of the most dynamic and promising sectors. The entry of Biotechnology start-ups in the 1980s led to the reconfiguration of the drug development value chain and the emergence of new competences. As the sector evolved, specialised firms appeared. As the industry matures, the production process becomes more specialised to support optimisation of technological steps. Our case studies reveal that the coordination of networks can be specialised, with the emergence of Dedicated Coordinating Firms. On the basis of four case studies of European biotechnology companies within a business model approach, this article helps understanding how coordinating a network can be successful and how small hub firms can do it.


Pritchard D.I.,University of Nottingham | Telford G.,University of Nottingham | Diab M.,PXTherapeutics | Low W.,PXTherapeutics
Biotechnology Progress | Year: 2012

Previously, we demonstrated the effectiveness of a research grade recombinant chymotrypsin,1 derived from the larvae of Lucilia sericata, in "debriding" slough/eschar from venous leg ulcers ex vivo. Furthermore, we were able to formulate this enzyme for successful delivery to in vitro wound healing assays, from a prototype hydrogel wound dressing,2 and showed that enzyme delivered in this way could degrade wound tissue ex vivo.3 Recently, to progress biotechnological development of the enzyme as a potential therapeutic product, we explored expression using current good manufacturing practice (cGMP) guidelines, and now report that a recombinant chymotrypsin I zymogen from L. sericata can be expressed in the cGMP acceptable strain of Escherichia coli (BLR-DE3). In addition, the conditions required for purification, refolding and activation of the chymotrypsinogen have been determined. The activated enzyme was stable, and effective in digesting wound slough/eschar tissue. To summarise, we have successfully initiated the production and characterisation of a novel cGMP compatible product for use in future clinical trials. © 2012 American Institute of Chemical Engineers (AIChE).


Crespillo S.,University of Granada | Camara-Artigas A.,University of Almeria | Casares S.,University of Granada | Morel B.,University of Granada | And 9 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

During HIV-1 fusion to the host cell membrane, the N-terminal heptad repeat (NHR) and the C-terminal heptad repeat (CHR) of the envelope subunit gp41 become transiently exposed and accessible to fusion inhibitors or Abs. In this process, the NHR region adopts a trimeric coiled-coil conformation that can be a target for therapeutic intervention. Here, we present an approach to rationally design single-chain protein constructs that mimic the NHR coiled-coil surface. The proteins were built by connecting with short loops two parallel NHR helices and an antiparallel one with the inverse sequence followed by engineering of stabilizing interactions. The constructs were expressed in Escherichia coli, purified with high yield, and folded as highly stable helical coiled coils. The crystal structure of one of the constructs confirmed the predicted fold and its ability to accurately mimic an exposed gp41 NHR surface. These single-chain proteins bound to synthetic CHR peptides with very high affinity, and furthermore, they showed broad inhibitory activity of HIV-1 fusion on various pseudoviruses and primary isolates. © 2014, National Academy of Sciences. All rights reserved.


Bomsel M.,French National Center for Scientific Research | Bomsel M.,French Institute of Health and Medical Research | Bomsel M.,University of Paris Descartes | Tudor D.,French National Center for Scientific Research | And 26 more authors.
Immunity | Year: 2011

Human immunodeficiency virus (HIV)-1 is mainly transmitted mucosally during sexual intercourse. We therefore evaluated the protective efficacy of a vaccine active at mucosal sites. Macaca mulatta monkeys were immunized via both the intramuscular and intranasal routes with an HIV-1 vaccine made of gp41-subunit antigens grafted on virosomes, a safe delivery carrier approved in humans with self-adjuvant properties. Six months after 13 vaginal challenges with simian-HIV (SHIV)-SF162P3, four out of five vaccinated animals remained virus-negative, and the fifth was only transiently infected. None of the five animals seroconverted to p27. gag-SIV. In contrast, all 6 placebo-vaccinated animals became infected and seroconverted. All protected animals showed gp41-specific vaginal IgAs with HIV-1 transcytosis-blocking properties and vaginal IgGs with neutralizing and/or antibody-dependent cellular-cytotoxicity activities. In contrast, plasma IgGs totally lacked virus-neutralizing activity. The protection observed challenges the paradigm whereby circulating antiviral antibodies are required for protection against HIV-1 infection and may serve in designing a human vaccine against HIV-1-AIDS. © 2011 Elsevier Inc.


Tsimafeyeu I.,Kidney Cancer Research Bureau | Zaveleva E.,OncoMax Ltd | Stepanova E.,Nn Blokhin Russian Cancer Research Center | Low W.,PxTherapeutics
Investigational New Drugs | Year: 2013

Fibroblast growth factor (FGF) receptor 1 (FGFR1) is a potential therapeutic target for treatment of metastatic renal cell carcinoma (RCC). We investigated the preclinical activity of OM-RCA-01, a novel therapeutic humanized anti-FGFR1 antibody in RCC. OM-RCA-01 has been shown to inhibit in vitro kinase activity of FGFR1 and has high affinity (Kd of 1.59 nM). In human renal carcinoma Caki-1 FGFR1-expressing cells, OM-RCA-01 potently inhibited FGF-mediated signaling and proliferation. In vivo, the tumors in untreated mice or mice treated with non-specific IgG continued their aggressive growth to reach the size of 2,000 cm3, at which point the mice were killed. In contrast, treatment with OM-RCA-01 not only significant arrested further growth of the tumors (P < 0.01) but also demonstrated differences in tumor volume compared with vehicle already on Day 13. A similar anti-tumor activity of OM-RCA-01 was observed when the antibody was given in low (1 mg/kg) or high (10 mg/kg) doses (P = 0.917). In Matrigel assay, OM-RCA-01 significantly inhibited FGF-induced endothelial cell migration, capillary-like tubular structure and mature vessels formation. Administration of 10 mg/kg antibody for up to 35 days resulted in minimal body weight loss and no observations of gross toxicity were made. Collectively, the data obtained with OM-RCA-01 are consistent with potent inhibition of FGFR1-signaling, angiogenesis, and tumor growth. OM-RCA-01 is being developed clinically as an intravenous therapy for the treatment of clear cell RCC. © 2013 Springer Science+Business Media New York.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2007-2.3.2-6 | Award Amount: 15.92M | Year: 2008

There is now an increasingly solid body of scientific evidence which demonstrates that the binding of small molecular weight compounds, peptides and antibodies (Abs) to fusion-intermediate conformations of gp41 leads to an inhibition of HIV cell entry. The principal aim of this project is to exploit this information by establishing a platform where gp41-derived vaccine candidates will be designed to elicit neutralising Abs. Several families of immunogens which mimic gp41 in its fusion intermediate conformations are already available and others will be designed using modelisation approaches. Candidates will be submitted to a thorough biophysical characterisation followed by a preclinical development in order to identify the most promising for clinical evaluation. A crucial selection parameter is the capacity of antigens to elicit neutralising Abs using internationally standardized assays. Since sexual transmission accounts for more than 90% of HIV infection, the capacity of Abs to inhibit infection at the mucosal level will also be determined. This cross-disciplinary project gathers top European scientists with expertise in protein engineering and characterisation, adjuvantation, formulation for systemic and mucosal delivery, evaluation of functional antibody response, efficacy testing in animal models, medium to large scale vaccine production as well as conduct of clinical trials in both developed and third-world countries. In contrast to previous more empirical attempts, this project is based on the rational exploitation of the knowledge on the mechanism of HIV entry and is thus a promising approach to generate a protective vaccine. It will be the first European project targeting intermediate conformations of gp41 and it could complement/synergize other international strategies focusing on the membrane proximal region of gp41 or gp140 trimer to induce neutralising Abs or aiming at reducing the viral load by eliciting a cellular immunity against HIV.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-TP | Phase: HEALTH-2007-2.3.3-4 | Award Amount: 3.64M | Year: 2008

Influenza is an extremely contagious infection that is caused by distinct virus types and subtypes. Early diagnosis is crucial for disease treatment and control as it reduces the inappropriate use of antibiotics and provides the indication for antiviral therapy. Rapid diagnosis is also a key component of surveillance activity. This requires the ability to detect and accurately diagnose infection at or close to the source/outbreak with minimum delay, a tactic consistent with the global experience during the SARS epidemic in 2003. This experience underlines the need for specific, sensitive point-of-care testing capable of discriminating between influenza subtypes. None of the available influenza diagnostic assays combines a point-of-care format with the multiplex capability to identify a large repertoire of human and animal viruses. This project exploits the knowledge and the expertise of the partners to convert microarray assays, that have a powerful multiplex capability but are laborious, complex and expensive to perform, into a simple, robust and affordable automated point-of-care system for the diagnosis of influenza. The system will utilize three components: 1) a microarray immunoassay that distinguishes influenza A and B virus as well as A subtypes; 2) an innovative self-contained disposable lateral-flow device that allows the addition of specimens and reagents in a temporally-controlled manner; 3) a robust automated processing reading instrument of novel conception that employs a low cost, high performance optical module. This project will provide small laboratories, health offices, veterinary clinics and outposts (airports) with the diagnostic capability of major research institutions and reference centres, thus providing better care for patients and most importantly, facilitating the implementation of surveillance activities and guiding response measures that are being built to face a possible influenza pandemic caused by a highly virulent virus.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-IAPP | Phase: PEOPLE-2007-3-1-IAPP | Award Amount: 1.87M | Year: 2008

People living in malaria endemic areas develop, with time, a form of immunity to infection and clinical disease mediated by antibodies directed against P. falciparum antigens. Currently there are no assays or clinical parameters that predict whether an exposed person is protected against malaria. This represents a major obstacle for vaccine development. Here research institutions and industrial partners, combining cutting edge expertise in protein microarrays, immunoassay development, immunology, protein expression and epidemiology join their efforts with the objective of translating the genome sequence information of Plasmodium falciparum into a tool to unravel correlates of protection against human malaria. Recombinant P. falciparum proteins, encompassing the repertoire of secreted and surface antigens, will be printed onto microarrays to develop an immunoassay capable of unraveling antibodies directed against a vast number of parasite molecules. This assay will be utilized to compare the antigen-antibody recognition profiles of protected and non-protected persons in malaria-exposed communities, thus facilitating the identification of the antigens that either alone or in combination function as targets of protective immunity. The underlying project structure in terms of research activities, task distribution and management has been planned with the priority of facilitating the interactions of human resources, between academic institutions and industry. Exchange of staff and networking activities will bridge the scientific and cultural differences existing between the academic and industrial partners. Exchange of scientific knowledge and technical skill will unleash the full potential of the collective expertise of the participating laboratories towards the objectives of the proposal and will be instrumental in building collaborative links that will extend beyond the duration of the project.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-2.3.2-2 | Award Amount: 19.00M | Year: 2010

With 14.4 million prevalent cases and 1.7 million deaths tuberculosis (TB) remains one of the most serious infectious diseases to date. An estimated 2 billion people are believed to be infected with Mycobacterium tuberculosis and at risk of developing disease. Multi- and extensively drug resistant strains are increasingly appearing in many parts of the world, including Europe. While with current control measures the Millennium Development Goals (MDGs) set for 2015 may be achieved, reaching these would still leave a million people per year dying from TB. Much more effective measures, particularly more effective vaccines will be essential to reach the target of eliminating TB in 2050. Two successive FP5 and FP6 funded projects, Tuberculosis (TB) Vaccine Cluster (2000-2003) and TBVAC (2004-2008), have in the recent decade made significant contributions to the global TB vaccine pipeline, with four vaccines (out of nine globally) being advanced to clinical stages. Both projects strongly contributed to the strengthening and integration of expertise and led to a European focus of excellence that is unique in the area of TB vaccine development. In order to sustain and accelerate the TB vaccine developments and unique integrated excellence of TBVAC, a specific legal entity was created named TuBerculosis Vaccine Initiative (TBVI). The NEWTBVAC proposal is the FP7 successor of TBVAC, and will be coordinated by TBVI. The proposal has the following objectives : 1) To sustain and innovate the current European pipeline with new vaccine discoveries and advance promising candidates to clinical stages; 2) To design new, second generation vaccines based new prime-boost strategies and/or new (combinations of) promising subunit vaccines, that will impact on reduction of disease in exposed individuals; 3) To sustain and innovate discovery, evaluation and testing of new biomarkers, that will be critically important for future monitoring of clinical trials.


Trademark
Pxtherapeutics | Date: 2012-04-03

Chemical preparations for use in industry and science, other than medical science; chemical preparations for use in agriculture, horticulture, and forestry, except fungicides, herbicides, insecticides and parasiticides; chemical preparations for food preserving for the food industry; biochemical preparations for use in industry and science, other than medical science; protein-based biological preparations for use in industry and science, other than medical science, namely, proteins, purified proteins and cells in raw form for scientific research; biochemical for use in agriculture, horticulture, and forestry, except fungicides, herbicides, insecticides and parasiticides; protein-based biological preparations, namely, proteins, purified proteins and cells used as raw materials for the manufacture of food; non-nutritive mixture of protein in the nature of collagen and water for use as an ingredient in the manufacture of food, namely, for forming an edible, external layer on food products during the co-extrusion processing of foodstuffs. Pharmaceutical preparations for therapeutic use for the treatment of human diseases namely, metabolic disorders, immune diseases, oncology, infectious diseases within the context of therapeutic and prophylactic applications; veterinary preparations for therapeutic use for treatment of animal diseases for therapeutic and prophylactic applications, namely, preparations for the treatment of metabolic disorders, immune diseases, oncology, infectious diseases for livestock, pets and wildlife ; chemical, biochemical and biological protein based preparations for medical or veterinary use, namely, cells, purified proteins and proteins used as active pharmaceutical ingredients, namely, biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function for use in the treatment of metabolic disorders, immune diseases, oncology, infectious diseases, cells; protein for medical or veterinary use, namely, bone morphogenetic protein for use as a bone growth media for people. Scientific and industrial research, especially in the fields of chemistry, biochemistry, biotechnology and biology; computer programming, design, development, rental, updating and maintenance of computer software; technical appraisals, advice, consulting and information, particularly in the fields of chemistry, biochemistry, biotechnology and biology; testing of materials and chemical, biochemical, biotechnological and biological substances; laboratory research services in the fields of chemistry, biochemistry, biotechnology and biology.

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