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Patent
Multiplicom | Date: 2015-06-19

The present invention relates to the technical field of nucleic acid amplification using a Polymerase Chain Reaction (PCR). Specifically, the present invention relates to Polymerase Chain Reaction (PCR) primers and Polymerase Chain Reaction (PCR) nucleic acid amplification mixture and the use thereof in (quantitative) Polymerase Chain Reactions (PCR). Specifically, the present invention relates to Polymerase Chain Reaction (PCR) primers suitable for use in Restriction Mediated quantitative PCR (RM-qPCR) nucleic acid amplification reactions comprising a 5 Acceptor representing one member of a fluorescence resonance energy transfer (FRET) pair; A representing a nucleic acid sequence motif of 10 to 30 bp; 3-C representing a linker region comprised of at least three carbon atoms; B representing a double stranded restriction enzyme recognition site or a random nucleic acid sequence; A representing a nucleic acid sequence motif of 10 to 30 bp being complementary to the nucleic acid sequence motif of A; and R-prim representing a nucleic acid sequence complementary to a target sequence in a nucleic acid sequence to be amplified.


The present invention relates to the technical field of organ and tissue transplantation and specifically to methods allowing rejection of transplanted organs and tissues by a transplant patient. The present invention provides methods for non-invasive and ex vivo or in vitro detection of the presence or absence of transplant rejection, i.e. transplant health or rejection. The present methods allow for effective and continuous monitoring of transplant status with a minimal or absent discomfort for a transplant patient.


The present invention relates to the technical field of organ and tissue transplantation and specifically to methods allowing rejection of transplanted organs and tissues by a transplant patient. The present invention provides methods for non-invasive and ex vivo or in vitro detection of the presence or absence of transplant rejection, i.e. transplant health or rejection. The present methods allow for effective and continuous monitoring of transplant status with a minimal or absent discomfort for a transplant patent.


Patent
Multiplicom | Date: 2017-04-26

The present invention relates to the technical field of nucleic acid amplification using a Polymerase Chain Reaction (PCR). Specifically, the present invention relates to Polymerase Chain Reaction (PCR) primers and Polymerase Chain Reaction (PCR) nucleic acid amplification mixture and the use thereof in (quantitative) Polymerase Chain Reactions (PCR). Specifically, the present invention relates to Polymerase Chain Reaction (PCR) primers suitable for use in Restriction Mediated quantitative PCR (RM-qPCR) nucleic acid amplification reactions comprising a 5 Acceptor representing one member of a fluorescence resonance energy transfer (FRET) pair; A representing a nucleic acid sequence motif of 10 to 30 bp; 3-C representing a linker region comprised of at least three carbon atoms; B representing a double stranded restriction enzyme recognition site or a random nucleic acid sequence; A representing a nucleic acid sequence motif of 10 to 30 bp being complementary to the nucleic acid sequence motif of A; and R-prim representing a nucleic acid sequence complementary to a target sequence in a nucleic acid sequence to be amplified.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.4.1-1 | Award Amount: 8.10M | Year: 2013

Colorectal cancer (CRC) is the 3rd most common cancer in Europe, and with approximately 200,000 deaths per year, it remains the 2nd most common cause of cancer death. More than half of all CRC patients develop distant metastases and have 5-year overall survival (OS) of less than 5% because of ineffective treatments. Increased understanding of cancer biology, coupled with the implementation of omics-based approaches, has revealed that cancer must be considered a heterogeneous disease. Historically, one-size-fits-all approaches have been standard practice in CRC treatment, but with the increased understanding of the molecular/genetic heterogeneity of CRC, it is clear that novel treatments must be developed and tested in selected subgroups to maximize the benefit of these new developments. MErCuRIC is a multicentre phase Ib/II clinical trial which will assess a novel therapeutic strategy (combined treatment of a MEK inhibitor PD-0325901 with a MET inhibitor PF-02341066) to combat metastasis, improve survival and change current clinical practice for CRC patients with KRAS mutant (MT) and KRAS wild type (WT) (with aberrant c-MET) tumours. The consortium will go beyond the current state-of-the-art by (i) employing a novel treatment strategy targeting the biology of the disease and by (ii) using next generation sequencing (NGS) and xenopatients to identify CRC patient subgroups who will maximally benefit from this novel treatment strategy.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2012.2.1.1-1-B | Award Amount: 15.82M | Year: 2012

EURenOmics will integrate several established consortia devoted to rare kidney diseases with eminent need and potential for diagnostic and therapeutic progress (i.e. steroid resistant nephrotic syndrome, membranous nephropathy, tubulopathies, complement disorders such a haemolytic uraemic syndrome, and congenital kidney malformations). The Consortium has access to the largest clinical cohorts assembled to date (collectively >10,000 patients) with detailed phenotypic information and comprehensive biorepositories containing DNA, blood, urine, amniotic fluid and kidney tissue. The project aims to (1) identify the genetic and epigenetic causes and modifiers of disease and their molecular pathways; (2) define a novel mechanistic disease ontology beyond phenotypical or morphological description; (3) develop innovative technologies allowing rapid diagnostic testing; (4) discover and validate biomarkers of disease activity, prognosis and treatment responses; and (5) develop in vitro and in vivo disease models and apply high-throughput compound library screening. For these purposes we will integrate comprehensive data sets from next generation exome and whole-genome sequencing, ChiP-sequencing, tissue transcriptome and antigen/epitope profiling, and miRNome, proteome/peptidome, and metabolome screening in different body fluids within and across conventional diagnostic categories. These data will be combined in a systems biology approach with high-resolution clinical phenotyping and findings obtained with a large array of established and novel in vitro, ex vivo and in vivo disease models (functiomics) to identify disease-associated genetic variants involved in monogenic or complex genetic transmission, disease-defining molecular signatures, and potential targets for therapeutic intervention. These efforts will converge in the development of innovative diagnostic tools and biomarkers and efficient screening strategies for novel therapeutic agents.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2012.2.1.1-2 | Award Amount: 15.18M | Year: 2013

The ageing of the European population represents a rapidly rising social and economic challenge. Especially cardiovascular morbidity increases with age, but unfortunately, elderly patients are often difficult to diagnose due to confounding factors, leading to uncertainties in clinical decision making with huge impact on patients outcomes. Hence, there is an unmet need for novel biomarkers for more accurate diagnosis, risk assessment, and clinical outcome prediction for both acute and chronic cardiovascular diseases in the elderly. The BestAgeing consortium aims to improve this lack of diagnostic capabilities by developing and validating innovative omics-based biomarkers particularly for elderly patients supporting healthy ageing in Europe. Our study design addresses the most frequent and severe cardiovascular diseases of elderly patients by incorporating the appropriate disease cohorts and biomaterials from European populations. We aim to develop new omics-assays to diagnose cardiovascular disease, estimate risk, and monitor the response to treatment in elderly. This is envisaged to enable a more stratified and economic delivery of medicine. We expect that BestAgeing will generate novel European medical technologies that can improve the efficacy and efficiency of our care for elderly patients, which will also impact on socioeconomic wealth in Europe.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.1.4-1 | Award Amount: 3.74M | Year: 2012

The presence of donor specific HLA antibodies is a contra-indication for renal transplantation. Highly sensitized patients accumulate and often die on the transplant waiting lists as it is almost impossible to find donors towards which they dont have antibodies. The acceptable mismatch program of Eurotransplant has shown to be an effective tool to enhance successful transplantation of highly sensitized patients. However, 35% of the patients have rare HLA phenotypes and no suitable donor can be found. HLA phenotype frequencies vary amongst European populations. Rare HLA phenotypes in one population are more frequent in other populations. The major objective of the 10 partners in this project is to analyze the feasibility and requirements for a Europe-wide acceptable mismatch program to enhance transplantation of patients with rare HLA phenotypes in their own population. Long waiting patients will be matched with virtual donors based on known HLA frequencies of different European populations and with actual donors from the different transplant organizations. If successful, the logistics will be tested by transplanting some of these patients with donors from elsewhere in Europe. Second objective is to simplify the definition of acceptable HLA mismatches. Although almost 4000 HLA class I antigens are known, only 150 polymorphic residues differentially spread over the different HLA antigens are responsible for the induction of antibodies. An innovative typing and matching strategy based on the definition of acceptable HLA epitopes will facilitate the identification of suitable donors. Third objective is to define whether antibodies against non-HLA targets on the donor endothelium affect the results of transplants in highly sensitized patients. The aims of this collaborative project are fully compatible with those required for the program Health.2012.1.4-1. In objectives 2 and 3 two partners belonging to the SME sector of the European industry are involved.


Patent
Multiplicom | Date: 2012-10-18

The invention relates to prenatal detection methods using non-invasive techniques. In particular, it relates to prenatal diagnosis of a fetal chromosomal aneuploidy by detecting fetal and maternal nucleic acids in a maternal biological sample. More particularly, the invention applies multiplex PCR to amplify selected fractions of the respective chromosomes of maternal and fetal chromosomes. Respective amounts of suspected aneuploid chromosomal regions and reference chromosomes are determined from massive sequencing analysis followed by a statistical analysis to detect a particular aneuploidy.


Grant
Agency: European Commission | Branch: H2020 | Program: SME-1 | Phase: PHC-12-2014-1 | Award Amount: 71.43K | Year: 2015

Multiplicom will draft a business plan that is composed of the following parts: (i) selection of miRNAs for which there is substantial scientific evidence that such may be important for the diagnosis, treatment and/or prognosis of triple-negative breast cancer (TNBC) patients; (ii) perform a thorough analysis of the intellectual property on the selected miRNAs; (iii) start in-licensing negotiations with licensors regarding relevant intellectual property (iv) select a suitable quantitative multiplex miRNA analysis; (v) plan a European-wide, multi-center, clinical validation of the selected miRNAs using the selected multiplex quantification method (Validation Study); and (vi) perform a marketing study regarding the use of miRNA diagnosis/prognosis in TNBC patients; (vii) develop a competitive strategy. For part (i) Multiplicom has the support of top-notch clinical scientists (KOLs) in the field of miRNA in TNBC. Multiplicom will rely on its internal expertise, and expertise of its consultants to perform (ii) to (vi). This is supported by its track record of developing and commercializing novel highly multiplexed diagnostics (ISO 13485 & CE/IVD). The global 170,000 cases of TNBC (new cases in 2012) constitute the target patient population to be monitored by the validated multiplex miRNA test kit (Kit) such that they can be offered the best treatment of what is a multi-billion Euro pharmaceutical opportunity. From presently available data Multiplicom estimates the annual peak sales of the Kit in excess of 5M, with a gross margin of >80%, allowing further expansion of the company including new hires in all departments.

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