„We work together on an multisite project on vaccine development, particularly on the analytical developement. Olivier was a good partner for the international collaboration, sharing information and experience participating actively to the success of the project.“
Olivier Marcq
München, Bayern, Deutschland
1098 Follower:innen
500+ Kontakte
Aktivitäten
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Und in diesem Bereich haben wir in Deutschland tolle Innovationen und Start-Ups, siehe Firmen wie Cardior Pharmaceuticals, Tubulis GmbH, Tacalyx…
Und in diesem Bereich haben wir in Deutschland tolle Innovationen und Start-Ups, siehe Firmen wie Cardior Pharmaceuticals, Tubulis GmbH, Tacalyx…
Beliebt bei Olivier Marcq
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🇫🇷 FÉLIX LEBRUN EN BRONZE ❤️ PREMIÈRE MÉDAILLE OLYMPIQUE À SEULEMENT 17 ANS 🥉 HISTORIQUE 🤩 #Paris2024 📸 CNOSF / KMSP
🇫🇷 FÉLIX LEBRUN EN BRONZE ❤️ PREMIÈRE MÉDAILLE OLYMPIQUE À SEULEMENT 17 ANS 🥉 HISTORIQUE 🤩 #Paris2024 📸 CNOSF / KMSP
Beliebt bei Olivier Marcq
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🇫🇷 Les plus beaux JO de l'histoire 🤩 C'était grandiose ✨ #Paris2024 📸 CNOSF / KMSP
🇫🇷 Les plus beaux JO de l'histoire 🤩 C'était grandiose ✨ #Paris2024 📸 CNOSF / KMSP
Beliebt bei Olivier Marcq
Berufserfahrung
Ehrenamt
Veröffentlichungen
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Enabling 5T4 for targeted cancer therapy: TUB-030, a novel ADC built with ethynylphosphonamidate conjugation chemistry, shows long-lasting anti-tumor activity via Topoisomerase-I inhibition with an optimized therapeutic index
American Association for Cancer Research
TUB-030 is a novel Antibody-Drug Conjugate (ADC) targeting the oncofetal 5T4 antigen, a glycoprotein, that is functionally involved in regulation of the Wnt signalling pathway and promoting cellular motility and adhesion. Immunohistochemical analysis identified 5T4 overexpressed in many types of cancers, including bladder, lung, breast, stomach, esophagus, head and neck, colon, and ovarian. Analysis in fresh frozen healthy human tissue with the therapeutic mAb candidate of TUB-030 revealed…
TUB-030 is a novel Antibody-Drug Conjugate (ADC) targeting the oncofetal 5T4 antigen, a glycoprotein, that is functionally involved in regulation of the Wnt signalling pathway and promoting cellular motility and adhesion. Immunohistochemical analysis identified 5T4 overexpressed in many types of cancers, including bladder, lung, breast, stomach, esophagus, head and neck, colon, and ovarian. Analysis in fresh frozen healthy human tissue with the therapeutic mAb candidate of TUB-030 revealed limited cross reactivity. Ethynylphosphonamidate conjugation chemistry was used to build TUB-030 with a homogenous DAR (drug-antibody-ratio) of 8 and the Topoisomerase I inhibitor Exatecan as payload, which is connected to a humanized, Fc-silenced IgG1 antibody targeting 5T4 using a cleavable linker system. Overall, TUB-030 contrasts previous ADC designs targeting 5T4, implementing several layers of differentiation in terms of antibody, payload and conjugation technology. In vitro, TUB-030 is characterized by sub-nanomolar affinity to 5T4, efficient target-mediated internalization and strong cytotoxicity towards cancer cells from different tumor indications with a broad range of 5T4 expression levels. Differently to previous 5T4-targeting ADCs, TUB-030 has efficient bystander activity against co-cultured target-negative cells, which facilitates targeting of tumors with heterogenous 5T4 expression. Pharmacokinetic analysis showed that TUB-030 is highly stable - and does not lose or transfer its linker-payload to serum proteins during blood circulation and antibody-like clearance profile contrasting maleimide-conjugated ADCs and enabling most efficient and continued delivery of Exatecan to the tumor site. Single-dose treatment with TUB-030 results in long-lasting tumor regression with high complete remission rates across a variety of both cell-line derived xenograft (CDX) and patient-derived xenograft (PDX) cancer models of multiple tumor indications in vivo, including models ……
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TUB-040, a novel Napi2b-targeting ADC built with ethynylphosphonamidate conjugation chemistry, demonstrates high and long-lasting anti-tumor efficacy via Topoisomerase-I inhibition and excellent tolerability predictive of a wide therapeutic
Cancer Research
Abstract 2622 - Cancer Research Annual Meeting 2024
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Addition of Lauryldimethylamine N-Oxide (LDAO) to a Copper-Free Click Chemistry Reaction Improves the Conjugation Efficiency of a Cell-Free Generated CRM197 Variant to Clinically Important Streptococcus pneumoniae Serotypes
Strain-promoted azide–alkyne cycloaddition (SPAAC) reactions like click chemistry have the potential to be highly scalable, robust, and cost-effective methods for generating small- and large-molecule conjugates for a variety of applications. However, despite method improvements, the rates of copper-based click chemistry reactions continue to be much faster than the rates of copper-free click chemistry reactions, which makes broader deployment of click chemistry challenging from a safety and…
Strain-promoted azide–alkyne cycloaddition (SPAAC) reactions like click chemistry have the potential to be highly scalable, robust, and cost-effective methods for generating small- and large-molecule conjugates for a variety of applications. However, despite method improvements, the rates of copper-based click chemistry reactions continue to be much faster than the rates of copper-free click chemistry reactions, which makes broader deployment of click chemistry challenging from a safety and compatibility standpoint. In this study, we used a zwitterionic detergent, namely, lauryldimethylamine N-oxide (LDAO), in a copper-free click chemistry reaction to investigate its impact on the generation of conjugate vaccines (CVs). For this, we utilized an Xpress cell-free protein synthesis (CFPS) platform to generate a proprietary variant of CRM197 (eCRM) containing non-native amino acids (nnAA) with azide-containing side chains as a carrier protein for conjugation to several clinically relevant dibenzocyclooctyne (DBCO)-derivatized S. pneumoniae serotypes (types 3, 5, 18C, and 19A). For conjugation, we performed copper-free click chemistry in the presence and absence of LDAO. Our results show that the addition of LDAO significantly enhanced the reaction kinetics to generate larger conjugates, which were similarly immunogenic and equally stable to conjugates generated without LDAO. Most importantly, the addition of LDAO substantially improved the efficiency of the conjugation process. Thus, our results for the first time show that the addition of a zwitterionic surfactant to a copper-free click chemistry reaction can significantly accelerate the reaction kinetics along with improving the efficiency of the conjugation process.
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Development of a Next Generation 30+ Valent Pneumococcal Conjugate Vaccine (VAX-XP) Using Site-Specific Carrier Protein Conjugation
Oxford Academics
Open Forum Infectious Diseases, Volume 8, Issue Supplement_1, November 2021, Page S615, https://doi.org/10.1093/ofid/ofab466.1241
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Non-clinical immunological comparison of a Next-Generation 24-valent pneumococcal conjugate vaccine (VAX-24) using site-specific carrier protein conjugation to the current standard of care (PCV13 and PPV23)
Elsevier - Vaccine
Jeff Fairman, Paresh Agarwal, Sandrine Barbanel, Christopher Behrens, Aym Berges, John Burky, Peter Davey, Phil Fernsten, Chris Grainger, Sherry Guo, Sam Iki, Mark Iverson, Martin Kane, Neeraj Kapoor, Olivier Marcq, Thi-Sau Migone, Paul Sauer, James Wassil*
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Glycoconjugates: What It Would Take To Master These Well-Known yet Little-Understood Immunogens for Vaccine Development
M-Sphere
Glycoconjugate vaccines are a critical component of the medical arsenal against infectious diseases. This established field continues, however, to experience failures in the clinic. The lack of fundamental understanding of factors controlling clinical efficacy of glycoconjugate vaccines is discussed while key parameters demanding focused and collaborative research are identified.
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(2R,3S,4S,5S)-6,6-bis(ethylthio)hexane-1,2,3,4,5-pentaol CCDC 1937683
CSD Communication
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Marcq O. (2018) Outlook on Next Generation Technologies and Strategy Considerations for ADC Process Development and Manufacturing. In: Damelin M. (eds) Innovations for Next-Generation Antibody-Drug Conjugates. Cancer Drug Discovery and Development.
Humana Press
In the chapter, we review new conjugation technologies from the standpoints of process development and manufacturability and identify potential process hotspots. We briefly review recent progress in conventional conjugation methods and assess, for instance, how new linkers impact process. We also consider antibody modeling and its untapped potential to help design ADCs. We address outsourcing options and trends and provide an overview of single use technologies. Finally, strategies for…
In the chapter, we review new conjugation technologies from the standpoints of process development and manufacturability and identify potential process hotspots. We briefly review recent progress in conventional conjugation methods and assess, for instance, how new linkers impact process. We also consider antibody modeling and its untapped potential to help design ADCs. We address outsourcing options and trends and provide an overview of single use technologies. Finally, strategies for efficient early process development to ensure CMC consistency across clinical phases and manufacturing scales and ensure readiness for accelerated regulatory approval paths are discussed
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Characterization and Higher-Order Structure Assessment of an Interchain Cysteine-Based ADC: Impact of Drug Loading and Distribution on the Mechanism of Aggregation
Bioconjugate Chemistry / American Chemical Society
The impact of drug loading and distribution on higher order structure and physical stability of an interchain cysteine-based antibody drug conjugate (ADC) has been studied. An IgG1 mAb was conjugated with a cytotoxic auristatin payload following the reduction of interchain disulfides. The 2-D LC-MS analysis shows that there is a preference for certain isomers within the various drug to antibody ratios (DARs). The physical stability of the unconjugated monoclonal antibody, the ADC, and isolated…
The impact of drug loading and distribution on higher order structure and physical stability of an interchain cysteine-based antibody drug conjugate (ADC) has been studied. An IgG1 mAb was conjugated with a cytotoxic auristatin payload following the reduction of interchain disulfides. The 2-D LC-MS analysis shows that there is a preference for certain isomers within the various drug to antibody ratios (DARs). The physical stability of the unconjugated monoclonal antibody, the ADC, and isolated conjugated species with specific DAR, were compared using calorimetric, thermal, chemical denaturation and molecular modeling techniques, as well as techniques to assess hydrophobicity. The DAR was determined to have a significant impact on the biophysical properties and stability of the ADC. The CH2 domain was significantly perturbed in the DAR6 species, which was attributable to quaternary structural changes as assessed by molecular modeling. At accelerated storage temperatures, the DAR6 rapidly forms higher molecular mass species whereas the DAR2 and the unconjugated mAb were largely stable. Chemical denaturation study indicates that DAR6 may form multimers while DAR2 and DAR4 primarily exist in monomeric forms in solution at ambient conditions. The physical state differences were correlated with a dramatic increase in the hydrophobicity and a reduction in the surface tension of the DAR6 compared to lower DAR species. Molecular modeling of the various DAR species and their conformers demonstrates that the auristatin-based linker payload directly contributes to the hydrophobicity of the ADC molecule. Higher order structural characterization provides insight into the impact of conjugation on the conformational and colloidal factors that determine the physical stability of cysteine-based ADCs, with implications for process and formulation development.
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NMR structural analysis of the capsular polysaccharide from Streptococcuspneumoniae serotype 6C
Carbohydrate Research
The original structure of Streptococcuspneumoniae capsular polysaccharide (CPS) serotype 6C was proposed based on chemical degradation and tandem mass analysis [J. Clin. Microbiol.2007, 45, 1225–1233]. In order to confirm the repeat unit structure and assign the stereochemical structure, the CPS 6C and the known CPS 6A were fully characterized by NMR spectroscopy. Full 1H and 13C NMR spectra assignments of CPS 6C and CPS 6A were achieved based on DQCOSY, TOCSY, HSQC, HMBC, and NOESY analysis…
The original structure of Streptococcuspneumoniae capsular polysaccharide (CPS) serotype 6C was proposed based on chemical degradation and tandem mass analysis [J. Clin. Microbiol.2007, 45, 1225–1233]. In order to confirm the repeat unit structure and assign the stereochemical structure, the CPS 6C and the known CPS 6A were fully characterized by NMR spectroscopy. Full 1H and 13C NMR spectra assignments of CPS 6C and CPS 6A were achieved based on DQCOSY, TOCSY, HSQC, HMBC, and NOESY analysis. These analyses confirmed the published structure of CPS 6A and established the repeat unit structure of the CPS 6C as:
→2)-α-d-Glcp-(1→3)-α-d-Glcp-(1→3)-α-l-Rhap-(1→3)-d-Ribitol-(5→phosphate-Andere Autor:innenVeröffentlichung anzeigen -
Reaction pathways of glucose oxidation by ozone under acidic conditions
Carbohydrate Research
The ozonation of d-glucose-1-13C, 2-13C, and 6-13C was carried out at pH 2.5 in a semi-batch reactor at room temperature. The products present in the liquid phase were analyzed by GC–MS, HPAEC-PAD, and 13C NMR spectroscopy. Common oxidation products of glucose have also been submitted to identical ozonation conditions. For the first time, a pentaric acid was identified and its formation quantitatively correlated to the loss of C-6 of glucose in the form of carbon dioxide. Potential mechanisms…
The ozonation of d-glucose-1-13C, 2-13C, and 6-13C was carried out at pH 2.5 in a semi-batch reactor at room temperature. The products present in the liquid phase were analyzed by GC–MS, HPAEC-PAD, and 13C NMR spectroscopy. Common oxidation products of glucose have also been submitted to identical ozonation conditions. For the first time, a pentaric acid was identified and its formation quantitatively correlated to the loss of C-6 of glucose in the form of carbon dioxide. Potential mechanisms for the formation of this pentaric acid are discussed. The well-accepted pathway involving the anomeric position in glucose, gluconic acid, arabinose, and carbon dioxide is reinvestigated. The origin of small molecules such as tartaric, erythronic, and oxalic acids is clarified. Finally, new reaction pathways and tentative mechanisms consistent with the formation of ketoaldonic acids and smaller acids are proposed
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Origin and significance of the production of carbon dioxide during the ozonization of 13C-labeled d-glucose at different pH values
Carbohydrate Research
[1-13C], [2-13C] and [6-13C] d-glucose were, respectively, ozonized in a semi-batch reactor in acidic and basic conditions. The composition of the gas phase was evaluated by on-line mass spectrometry measurements. The quantitative and isotopic analyses of the carbon dioxide formed during ozonization are presented and discussed. The data, correlated with previous literature results, clearly show that at pH 2.5 the production of carbon dioxide from C-6 and C-1 carbon atoms is nearly equivalent…
[1-13C], [2-13C] and [6-13C] d-glucose were, respectively, ozonized in a semi-batch reactor in acidic and basic conditions. The composition of the gas phase was evaluated by on-line mass spectrometry measurements. The quantitative and isotopic analyses of the carbon dioxide formed during ozonization are presented and discussed. The data, correlated with previous literature results, clearly show that at pH 2.5 the production of carbon dioxide from C-6 and C-1 carbon atoms is nearly equivalent. Conversely, at higher pH values, CO2 is released with a greater selectivity from the reducing end. The importance of the decarboxylation reaction in the formation of by-products with fewer than six carbon atoms is also demonstrated.
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Patente
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IMPROVED PROCESSES FOR PREPARING PEPTIDE CONJUGATES AND LINKERS
Ausgestellt am US WO/2013/093705
The present invention provides a process for preparing a compound of Formula 5b, as well as intermediates thereof, and novel classes of compounds useful in process for preparing these and similar compounds.
Andere Erfinder:innenPatent anzeigen -
IMPROVED METHODS FOR THE PREPARATION OF IMMUNOGENIC CONJUGATES
Angemeldet am US WO/2020/010000
Improved methods are provided for preparing immunoconjugates from a saccharide antigen and a carrier protein in which the saccharide antigen is activated by functionalization with a reactive moiety capable of participating in a click chemistry reaction with a second reactant comprising a bio-orthogonal reactive moiety, and the activated antigen so provided is then covalently conjugated to a carrier protein. The carrier protein comprises a polypeptide having at least one T-cell activating…
Improved methods are provided for preparing immunoconjugates from a saccharide antigen and a carrier protein in which the saccharide antigen is activated by functionalization with a reactive moiety capable of participating in a click chemistry reaction with a second reactant comprising a bio-orthogonal reactive moiety, and the activated antigen so provided is then covalently conjugated to a carrier protein. The carrier protein comprises a polypeptide having at least one T-cell activating epitope and at least one non-natural amino acid (nnAA) bearing the bio-orthogonal reactive moiety. Improved methods for activating saccharide antigens in preparation for covalent conjugation to a carrier protein are also provided.
Andere Erfinder:innenPatent anzeigen
Kurse
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Foundational ICH-Good Clinical Practice (GCP) E6 (R2) Training
E522 (ECCRT)
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MIT - Professional Education
Downstream Processing
Auszeichnungen/Preise
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BioTx PharmSci Quality Team Award for ADC process Development
Pfizer
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Globe Award
Wyeth Vaccine Research
“Prevenar 13 CBER response team”
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Jetzt anmelden und ansehenWeitere Aktivitäten von Olivier Marcq
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Peu d'êtres humains peuvent se targuer d'avoir sauvé autant de leurs semblables que Louis Adrian. Cet ingénieur polytechnicien et intendant…
Peu d'êtres humains peuvent se targuer d'avoir sauvé autant de leurs semblables que Louis Adrian. Cet ingénieur polytechnicien et intendant…
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L’un a gagné sa première médaille olympique il y a 16 ans, l’autre il y a 5 jours. Ce soir ils entrent dans la légende en devenant les 2 athlètes…
L’un a gagné sa première médaille olympique il y a 16 ans, l’autre il y a 5 jours. Ce soir ils entrent dans la légende en devenant les 2 athlètes…
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A review of immunotherapy for opioid use disorders (OUD) was just published. Careful development of the hapten and the linker is critical, as are the…
A review of immunotherapy for opioid use disorders (OUD) was just published. Careful development of the hapten and the linker is critical, as are the…
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I discovered the Malaysian flag cupcake among the Olympic-themed treats at the Sanofi Waltham site yesterday!! Flags hold such power to inspire and…
I discovered the Malaysian flag cupcake among the Olympic-themed treats at the Sanofi Waltham site yesterday!! Flags hold such power to inspire and…
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🌴 Bonnes vacances ! 🌞 J'avais jamais eu une année comme celle qui vient de s'écouler. 🎯 En moins d'un an, nous avons ✅ créé la start-up CXS…
🌴 Bonnes vacances ! 🌞 J'avais jamais eu une année comme celle qui vient de s'écouler. 🎯 En moins d'un an, nous avons ✅ créé la start-up CXS…
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My Omniose colleague Christian Harding was recently featured in a BioSTL newsletter. BioSTL is a St.Louis-based non-profit promoting the regional…
My Omniose colleague Christian Harding was recently featured in a BioSTL newsletter. BioSTL is a St.Louis-based non-profit promoting the regional…
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