Collaboration for new therapies: maximizing health and innovation.

Introduction: Innovative medicines and vaccines can provide direct health benefits to patients and populations by preventing, treating and curing diseases, and also drive wider socioeconomic and productivity gains. However, researching and developing them is complex and risky. Funding for life sciences R&D has different sources: public, charitable/NGO, and private sector.

The Innovative Medicines Initiative -10 Years of Public-Private Collaboration.

The Innovative Medicines Initiative (IMI) is a public-private partnership between the European Union and the European pharmaceutical industry. Born of the necessity to foster collaboration between different stakeholders in order to address growing challenges in bringing new medicines to market and the rapidly evolving healthcare landscape, IMI has successfully delivered the radical collaboration needed to address these challenges. In this article we reflect on some of the major achievements of the programme by highlighting a few of the key projects funded and the progress they have made, as well as some of the lessons learnt in delivering such an ambitious partnership.

How to Harness Big Data for the Benefit of Patients.

IMI is a large public private partnership which has committed Euro 5 Billion from the European Commission, the European Pharmaceutical sector and other partners, to enable and accelerate bringing medical innovation to patients. IMI is now 10 years old and already has changed the ecosystem and way of working in developing innovative medicines across the public/private divide. Big data represents a significant piece of this investment and projects in this area are attempting to provide solutions to major challenges including: 1.

Global implementation of genomic medicine: We are not alone.

Around the world, innovative genomic-medicine programs capitalize on singular capabilities arising from local health care systems, cultural or political milieus, and unusual selected risk alleles or disease burdens. Such individual efforts might benefit from the sharing of approaches and lessons learned in other locales. The U.

Complications/adverse effects of maxillomandibular advancement for the treatment of OSA in regard to outcome.

Objective: To evaluate adverse effects/postoperative complications and surgical response rate of maxillomandibular advancement for the treatment of severe obstructive sleep apnea syndrome.

Study Design: Case series with chart review.

Setting: Otolaryngology Head and Neck Surgery Department in a teaching hospital.

[Retrospective cephalometric analysis for surgically treated obstructive sleep apnea: therapeutic deductions].

Purpose Of The Study: The goal of surgical treatment for severe sleep apnea syndrome is to alleviate the upper airway obstruction. The narrowing site must be precisely determined during the preoperative evaluation to ensure success. We suggest that cephalometric analysis using a lateral cephalic radiograph to evaluate bony structures combined with magnetic resonance imaging (MRI) to study soft tissues may achieve this goal.

Identification of a human epitope in hepatitis C virus (HCV) core protein using a molecularly cloned antibody repertoire from a non-symptomatic, anti-HCV-positive patient.

Healthy carriers of hepatitis C virus (HCV) infection exhibit a specific antibody response against all HCV antigens, which could play a role in disease control. Generation of panels of human antibodies may permit a thorough characterization of this response and further identify particular antibodies with potential clinical value. To this effect, we have established a human phage-display antibody library from a patient exhibiting a high antibody response against HCV antigens and no clinical symptoms of disease.

Intradermal DNA immunization by using jet-injectors in mice and monkeys.

We have used spring powered jet injectors to deliver a solution of a naked DNA vaccine encoding the influenza hemagglutinin HA into the skin of mice and monkeys. We compared the immune responses induced by this needleless injection technique into the skin to the responses induced by a classical i.m.

DNA issues.

For many years the debate surrounding the potential danger of contaminating cellular DNA in biological products has focussed on the possibility that this DNA could give rise to tumours in the recipient host. Current knowledge of the nature and the fate of this DNA after in vivo administration allows us to conclude that this material represents a minimal risk to the patient.

Induction of virus-specific cytotoxic T lymphocytes in vivo by liposome-entrapped mRNA.

The induction of anti-influenza cytotoxic T lymphocytes (CTL) in vivo by immunizing mice with liposomes containing messenger RNA (mRNA) encoding the influenza virus nucleoprotein (NP) is described. NP mRNA, obtained by in vitro transcription, was encapsulated into simple cholesterol/phosphatidylcholine/phosphatidylserine liposomes by the detergent removal technique. The dependence of the route of mRNA-liposomes delivery on CTL induction was studied.

Processing and characterization of recombinant von Willebrand factor expressed in different cell types using a vaccinia virus vector.

The cloning of the cDNA encoding von Willebrand factor (vWF) has revealed that it is synthesized as a large precursor (pre-pro-vWF) molecule and it is now clear that the prosequence or vWAgII is responsible for the intracellular multimerization of vWF. We have cloned the complete vWF cDNA and expressed it using a recombinant vaccinia virus as vector. We have characterized the structure and function of the recombinant vWF (rvWF) secreted from five different cell types: baby hamster kidney (BHK), Chinese hamster ovary (CHO), human fibroblasts (143B), mouse fibroblasts (L) and primary embryonic chicken cells.

Characterization of recombinant human factor IX expressed in transgenic mice and in derived trans-immortalized hepatic cell lines.

Transgenic mice were generated in which 5 kb of the 5' flanking promoter region of the human Factor IX (FIX) gene fused to various FIX constructs (gene, minigene and cDNA) were stably integrated in the germ line. Several transgenic mouse lines expressed high circulating levels of active and correctly processed recombinant human FIX. The presence of at least one FIX intron had a positive effect on the expression.

Expression in Escherichia coli of a recombinant fragment (Ile 914-Leu 1364) of human von Willebrand factor containing a collagen binding domain.

Previous studies have shown that a collagen binding domain of human von Willebrand factor (vWF) resides on a fragment named SpI obtained by digestion with Staphylococcus aureus V8 protease which corresponds to residues Gly 911-Glu 1365 of the mature plasma vWF subunit. We have subcloned a fragment of a full-length cDNA encoding vWF into an expression vector which uses an inducible lambda PL promoter. The predicted product expressed by this plasmid is a fusion protein consisting of 16 amino acids (aa) of the lambda cII protein and aa Ile 914-Leu 1364 of human vWF.

Increased biological activity of a recombinant factor IX variant carrying alanine at position +1.

In attempts to improve the post-translational modification and processing of recombinant factor IX (FIX) we have altered the cDNA sequence encoding pre-pro-FIX using site-directed mutagenesis and have expressed the variant cDNAs in BHK21 cells using a vaccinia-virus-derived vector. We find that substitution of the tyrosine residue at +1 for an alanine increases the biological activity of the recombinant molecules 2-fold. On the other hand, substitution of the proline at -3 for a valine results in no significant change to the specific activity of the protein.

[Control of the incisor axis in the vestibulo-lingual direction using an original titanium-molybdenum alloy arch].

In order to restore the vestibulo-lingual orientation of the incisor axis while controlling the position of the crowns, the author suggests using a simple original arch, compatible with any of the multi-clip technics used by orthodontists. This arch is made of Titanium-Molybdenum Alloy and presents the distinctive feature of being specially shaped, on the ribbon side, so as to be introduced edgewise. Practical ease, efficiency in obtaining large amplitude, precisely controlled movements, as well as accurate measurement of torque make of this instrument a practical tool for controlling the incisor axis in the vestibulo-lingual orientation, and for improving the I/i angle warranteeing the stability of the results.

Production in Escherichia coli of a biologically active subfragment of von Willebrand factor corresponding to the platelet glycoprotein Ib, collagen and heparin binding domains.

A full-length cDNA for vWF has been cloned from a human lung cDNA library and a fragment of this cDNA has been modified to allow its expression in E. coli. This fragment, which corresponds to Val 449-Asn 730 of vWF and includes the GPIb-binding domain and binding sites for collagen and heparin, was subcloned into an expression vector containing an inducible lambda PL promoter.

Localization within the 106 N-terminal amino acids of von Willebrand factor (vWF) of the epitope corresponding to a monoclonal antibody which inhibits vWF binding to factor VIII.

We have used an in vitro transcription-translation system to localize the epitope corresponding to a monoclonal antibody (MAb 418) to vWF which specifically inhibits its binding to F. VIII. We have subcloned 1.

[Constraints of means, technics and results in orthodontics?].

Like all health professionals, Orthodontic Physicians, are constantly seeking or are urged to obtain the best therapeutic results possible by their professional bodies such as Universities, Learned societies, Ordre des Medecins and Professional Associations and by extra-professional bodies such as the Social Security, the Law, the Media and the general Public. The divergence between technical progress and patient care resources is currently creating tension in all western countries; thereby producing difficulties in conditions of practice.

[Retro-maxillary sequellae of craniofacial stenosis. The value of fronto-facial advancement using the Tessier monobloc technic].

Monobloc fronto-facial advancement (TESSIER's technic) seems to be the best therapeutic to correct retromaxillia, sequellae of cranio-facio-stenosis. From an aesthetical and functional point of view the result is more satisfactory than with a simple LE FORT III osteotomy advancement. Intermaxillary fixation is not necessary.