公开(公告)号：WO2022162164A1

公开(公告)日：2022-08-04

申请号：PCT/EP2022/052085

申请日：2022-01-28

Applicant: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  CENTRE HOSPITALIER UNIVERSITAIRE DE TOULOUSE ,  UNIVERSITÉ TOULOUSE III – PAUL SABATIER

Inventor： AMAR, Jacques ,  BRASSAT, David ,  PIGNOLET, Béatrice

IPC: C12Q1/6883 ,  C12Q1/689

Abstract: Natalizumab a monoclonal antibody is associated with the risk of progressive multifocal leukoencephalopathy (PML), an infection caused by the John Cunningham (JC) virus. The inventors explored the hypothesis that bacteria should be involved in the onset of PML in connection to the HLA-DR haplotype in multiple sclerosis (MS) patients. Thus 625 MS patients starting Natalizumab therapy from the BIONAT study were followed prospectively. Among those patients, 12 developed a PML. Outside the BIONAT cohort, we included nine additional MS patients with PML who had been referred to our center. For each patient, blood metagenomics sequencing and sequencing-based typing for HLA-DRB1*15:01 ancestral haplotype were determined. HLA-DRB1*15:01 haplotype carriers show a protection against PML (p=0.03). Among blood taxa, at genus level, Phyllobacterium was only significantly associated in HLA-DRB1*15:01 haplotype carriers with an inflammatory marker (p 2% have an odds ratio of 4.55 (95% confidence intervals 1.82-11.37; p=0.001) of developing or having PML under NTZ treatment. In conclusion, the inventors showed a relation between the HLA-DRB1*15:01 haplotype, the circulating microbiota and the risk of PML. The interaction between blood microbiota and the HLA-DRB1*15:01 haplotype may play a role in the virulence of the viruses.

公开(公告)号：WO2020053380A1

公开(公告)日：2020-03-19

申请号：PCT/EP2019/074472

申请日：2019-09-13

Applicant: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  UNIVERSITÉ PAUL SABATIER TOULOUSE III ,  CENTRE HOSPITALIER UNIVERSITAIRE DE TOULOUSE

Inventor： SCHANSTRA, Joost ,  KLEIN, Julie ,  BREUIL, Benjamin ,  DECRAMER, Stéphane ,  BUFFIN-MEYER, Bénédicte

IPC: G01N33/68

Abstract: Bilateral congenital anomalies of the kidney and urinary tract (CAKUT) are the main cause of childhood chronic kidney disease (CKD). Accurate and non-biased prenatal prediction of postnatal disease evolution is currently lacking, but is essential for prenatal counseling and disease management. Here the inventors aimed to develop an objective and quantifiable risk prediction method based on amniotic fluid (AF) peptides. 178 fetuses with bilateral CAKUT were included in a prospective multicenter study. The AF peptide content was studied using capillary electrophoresis coupled to mass spectrometry. The endpoint was early-onset renal failure (CKD stage 3-5) or death due to end-stage renal disease at two years of age. Among the ~7000 peptide candidates, 98 were associated with early severe renal failure. The most frequently found peptides associated with severe disease were fragments from extracellular matrix proteins and thymosin-P4. Combination of those 98 peptides in a classifier lead to the prediction of postnatal renal outcome in a blinded validation set of 51 patients with a 88% (95%CI: 64-98) sensitivity, 97% (95%CI: 85-100) specificity and an AUC of 0.96 (95%CI: 0.87-1.00), outperforming predictions based on currently used clinical methods. The classifier also predicted normal postnatal renal function in 75% of terminated pregnancies where fetopathology showed kidneys compatible with normal life. Analysis of AF peptides thus allows a precise and quantifiable prediction of postnatal renal function in bilateral CAKUT with potential major impact on pre- and postnatal disease management.

公开(公告)号：WO2019115473A1

公开(公告)日：2019-06-20

申请号：PCT/EP2018/084217

申请日：2018-12-10

Applicant: INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM) ,  UNIVERSITE PAUL SABATIER TOULOUSE III ,  CENTRE HOSPITALIER UNIVERSITAIRE DE TOULOUSE

Inventor： MORO, Cédric ,  LANGIN, Dominique ,  CRAMPES, François ,  CALMELS, Yann

IPC: A61B5/08 ,  G01N33/00 ,  G01N33/497

CPC classification number: A61B5/0803 ,  G01N33/0006 ,  G01N33/497

Abstract: This breathing simulator (2) is used for calibrating a gas analyzer (6) which is designed for determining a variable rate of oxygen consumption and/or a variable rate of carbon dioxide production of a living subject. The breathing simulator includes a first inlet (22) for connection to a reservoir (4) of a gas mixture with a predetermined composition, a second inlet (24) for connection to the ambient atmosphere, an outlet (26) for connection to the gas analyzer (6) and a gas mixer (28) for mixing the gas mixture coming from the first inlet (22) with air coming from the second inlet (24). The breathing simulator also includes a first fluid line (32) connecting the first inlet (22) to the gas mixer (28), a second fluid line (34) connecting the second inlet (24) to the gas mixer and a third fluid line (36) connecting the gas mixer to the outlet. A first flow regulator (42) is mounted on the first fluid line (32), while a second flow regulator (46) and a metering pump (48) are mounted on the third fluid line (36). An electronic control unit (50) pilots at least the first and second flow regulators (42,46) for simulating different breathing regimes.

公开(公告)号：WO2018146171A1

公开(公告)日：2018-08-16

申请号：PCT/EP2018/053123

申请日：2018-02-08

Applicant: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  UNIVERSITÉ PAUL SABATIER TOULOUSE III ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  CENTRE HOSPITALIER UNIVERSITAIRE DE TOULOUSE

Inventor： ESPINOSA, Eric ,  PAUL, Carle ,  BULAI LIVIDEANU, Christina

IPC: A61K31/4706 ,  A61P11/06 ,  A61P17/00 ,  A61P37/00 ,  A61P27/14

Abstract: The present invention relates to the treatment of mast cell activation diseases (MCAD). The present invention is based on the discovery that aminoquinoline compound (such) can improve clinical symptoms present in several MCAD patients. In all patients, six months after HCQ treatment initiation, a significant improvement of MC activation symptoms was observed. These clinical observations prompted to investigate the biological effects of hydroxychloroquine (HCQ) treatment on human mast cells (MCs) in vitro. The results indicate that HCQ treatment modifies key features of MC biology and induces a profound alteration of MC granules homeostasis (storage of inactive tryptase and decreased expression of key MC inflammatory mediator). Taken together, the HCQ induced dramatic reduction of MC inflammatory capabilities contributing to the observed efficacy of HCQ in MCAD patients. Accordingly, the present invention relates to an aminoquinoline compound (such HCQ) for use in the treatment of MACD such as mastocytosis and mast cell activation syndromes (MCAS).

公开(公告)号：WO2018020000A1

公开(公告)日：2018-02-01

申请号：PCT/EP2017/069174

申请日：2017-07-28

Applicant: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  UNIVERSITÉ PAUL SABATIER TOULOUSE III ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  CENTRE HOSPITALIER UNIVERSITAIRE DE TOULOUSE ,  INSTITUT CLAUDIUS REGAUD

Inventor： POUPOT, Mary ,  YSEBAERT, Loïc ,  TOSOLINI, Marie ,  FOURNIE, Jean-Jacques ,  BROUSSET, Pierre ,  ROCHAIX, Philippe

IPC: C07K16/28

Abstract: The present invention relates to antibodies targeting Tumor Associated Macrophages (TAMs) and uses thereof. The inventors investigated specific marker exposed on the surface of the macrophages associated to tumor in order to detect and target TAMs. They showed that sideroflexin 3, which is absent in normal macrophage, is expressed by tumor associated macrophages. The inventors further demonstrated that using antibody directed to sideroflexin 3, they depleted TAMs in PBMC sample obtained from LCC patient, and strongly reduced leukemic B cells number.

Abstract translation: 本发明涉及靶向肿瘤相关巨噬细胞（TAM）的抗体及其用途。 发明人研究了暴露在与肿瘤相关的巨噬细胞表面上的特异性标记物，以检测和靶向TAM。 他们表明，在正常巨噬细胞中不存在的sideroflexin 3由肿瘤相关巨噬细胞表达。 本发明人进一步证明，使用针对sideroflexin 3的抗体，它们耗尽了从LCC患者获得的PBMC样品中的TAM，并且强烈地降低了白血病B细胞数量。

公开(公告)号：WO2017191300A1

公开(公告)日：2017-11-09

申请号：PCT/EP2017/060756

申请日：2017-05-05

Applicant: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  UNIVERSITÉ PAUL SABATIER TOULOUSE III ,  CENTRE HOSPITALIER UNIVERSITAIRE DE TOULOUSE

Inventor： SARRY, Jean-Emmanuel ,  RECHER, Christian ,  DE TONI-COSTES, Fabienne ,  AROUA, Nesrine

IPC: A61K45/06 ,  A61K31/00 ,  A61K31/663 ,  A61K31/704 ,  A61K31/7068 ,  A61K33/24 ,  A61P35/02

Abstract: The present invention relates to pharmaceutical compositions for use in the treatment of chemoresistant acute myeloid leukemia (AML). The inventors have established a powerful preclinical model to screen in vivo responses to conventional genotoxics and to mimic the chemoresistance and minimal residual disease as observed in AML patients after chemotherapy. The inventors showed that cytarabine-resistance mechanism involves the CD39-dependent crosstalk between energetic niche and AML mitochondrial functions through CD39-P2Y13-cAMP-PKA signaling axis. In particular, the present invention relates to an inhibitor of the CD39-P2Y13-cAMP-PKA signaling axis for use in a method of treating chemoresistant acute myeloid leukemia (AML) in a patient in need thereof comprising administering to the patient a therapeutically effective amount of said inhibitor.

Abstract translation: 本发明涉及用于治疗化学抗性急性骨髓性白血病（AML）的药物组合物。 发明人已经建立了强大的临床前模型来筛选对常规基因毒素的体内应答，并且模拟化疗后在AML患者中观察到的化学抗性和微小残留疾病。 发明人表明，阿糖胞苷抗性机制涉及通过CD39-P2Y13-cAMP-PKA信号轴在高能生态位和AML线粒体功能之间的CD3​​9依赖性串扰。 具体而言，本发明涉及CD39-P2Y13-cAMP-PKA信号轴的抑制剂，用于在需要治疗的患者中治疗化学抗性急性骨髓性白血病（AML）的方法中，所述方法包括向患者施用治疗有效量 的所述抑制剂。

公开(公告)号：WO2017122039A1

公开(公告)日：2017-07-20

申请号：PCT/IB2016/000099

申请日：2016-01-13

Applicant: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  UNIVERSITÉ PAUL SABATIER TOULOUSE III ,  CENTRE HOSPITALIER UNIVERSITAIRE DE TOULOUSE

Inventor： CORDELIER, Pierre ,  BUSCAIL, Louis ,  LOPEZ, Frédéric

IPC: C12Q1/68 ,  G01N33/574

CPC classification number: C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/178 ,  G01N33/57438 ,  G01N2800/52

Abstract: The present invention relates to methods for predicting pancreatic cancer treatment response.

Abstract translation: 本发明涉及预测胰腺癌治疗应答的方法。

公开(公告)号：WO2016151018A1

公开(公告)日：2016-09-29

申请号：PCT/EP2016/056383

申请日：2016-03-23

Applicant: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  UNIVERSITÉ PAUL SABATIER TOULOUSE III ,  CENTRE HOSPITALIER UNIVERSITAIRE DE TOULOUSE

Inventor： VALET, Philippe ,  LAURELL, Isabelle ,  CAZALS, Laurent ,  GOURDY, Pierre

IPC: A61K38/17 ,  A61P3/10

CPC classification number: A61K38/1709 ,  A61K9/0019 ,  A61P3/10

Abstract: The present invention relates to an APJ receptor agonist for use in the treatment or the prevention of diabetes.

Abstract translation: 本发明涉及用于治疗或预防糖尿病的APJ受体激动剂。

公开(公告)号：WO2015155323A1

公开(公告)日：2015-10-15

申请号：PCT/EP2015/057800

申请日：2015-04-10

Applicant: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  UNIVERSITÉ PAUL SABATIER TOULOUSE III ,  CENTRE HOSPITALIER UNIVERSITAIRE DE TOULOUSE ,  ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP)

Inventor： CHARBONNEAU, Hélène ,  MAYEUR, Nicolas ,  TACK, Ivon

IPC: A61K38/08 ,  A61K31/402 ,  A61K31/445 ,  A61K31/4709 ,  A61K31/496 ,  A61P9/00

CPC classification number: A61K38/08 ,  A61K31/402 ,  A61K31/4468 ,  A61K31/4709 ,  A61K31/496 ,  A61K45/06 ,  A61K2300/00

Abstract: The present invention relates to a method of preventing and/or treating the hypotensive effect of angiotensin-converting enzyme inhibitors (ACEl) in a patient treated with ACEl, said patient being under a critical condition. More specifically, it concerns the use of a Bradykinin 2 receptor (BR2) antagonist for the prevention and treatment of the hypotensive effect of ACEl in a patient treated with ACEl undergoing emergency anaesthesia or shock resuscitation like hypovolemic shock (i.e. hemorrhagic shock (HS), or vasoplegic shock (i.e. septic shock).

Abstract translation: 本发明涉及一种预防和/或治疗血管紧张素转换酶抑制剂（ACEI）在用ACE1治疗的患者中的低血压作用的方法，所述患者处于临界状态。 更具体地说，它涉及使用缓激肽2受体（BR2）拮抗剂来预防和治疗ACE1在接受紧急麻醉或休克复苏如血容量异常休克（即出血性休克（HS））治疗的患者中的降血压作用， 或痉挛性休克（即败血性休克）。

公开(公告)号：WO2015104284A1

公开(公告)日：2015-07-16

申请号：PCT/EP2015/050154

申请日：2015-01-07

Applicant: INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  UNIVERSITÉ PAUL SABATIER TOULOUSE III ,  CENTRE HOSPITALIER UNIVERSITAIRE DE TOULOUSE ,  UNIVERSITÉ DE BOURGOGNE ,  UNIVERSITÉ DE RENNES ,  UNIVERSITÉ DES ANTILLES ET DE LA GUYANE ,  ECOLE DES HAUTES ETUDES EN SANTÉ PUBLIQUE (EHESP)

Inventor： LEGEMBRE, Patrick ,  SEGUI, Bruno ,  LEVADE, Thierry ,  MICHEAU, Olivier

IPC: A61K31/164 ,  A61P35/04 ,  G01N33/50

CPC classification number: G01N33/57484 ,  A61K9/127 ,  A61K31/164 ,  G01N33/57415 ,  G01N2800/52

Abstract: The present invention relates to methods and pharmaceutical compositions for preventing or reducing metastatic dissemination (i.e. reducing motility of cancer cells). In particular, the present invention relates to a method for preventing or reducing metastatic dissemination (i.e. reducing motility of cancer cells) in a subject suffering from a cancer comprising the steps consisting of i) determining the expression level of at least one biomarker selected from the group consisting of soluble CD95L and EMT promoting factors in a sample obtained from the subject, ii) comparing the expression level determined at step i) with a predetermined reference value and iii) administering the subject with a therapeutically effective amount of C16-ceramide or derivatives such as C16-sphingomyelin and C16- glycosphingolipids when the expression level determined at step i) is higher than the predetermined reference value.

Abstract translation: 本发明涉及用于预防或减少转移性传播的方法和药物组合物（即降低癌细胞的运动性）。 特别地，本发明涉及一种用于预防或减少患有癌症的受试者的转移性扩散（即降低癌细胞的运动性）的方法，包括以下步骤：i）确定至少一种选自以下的生物标志物的表达水平： 在从受试者获得的样品中组成可溶性CD95L和EMT促进因子的组，ii）将步骤i）中测定的表达水平与预定参考值进行比较，和iii）给予受试者治疗有效量的C16-神经酰胺或衍生物 例如当步骤i）确定的表达水平高于预定参考值时，例如C16-鞘磷脂和C16-糖鞘蛋白。