公开(公告)号：US10435665B2

公开(公告)日：2019-10-08

申请号：US15538184

申请日：2015-12-23

申请人： INSTITUT PASTEUR ,  FONDATION IMAGINE ,  ASSISTANCE PUBLIQUE—HOPITAUX DE PARIS ,  UNIVERSITE PARIS DESCARTES ,  INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (IN-SERM)

发明人： Eberl Gerard ,  Bikard David ,  Schnupf Pamela ,  Cerf Bensussan Nadine ,  Gaboriau-Routhiau Valerie ,  Sansonetti Philippe

IPC分类号： C12N1/20 ,  C12N15/74 ,  C12N13/00

摘要： The present invention relates to an in vitro method of culturing a segmented filamentous bacterium strain, comprising co-culturing said segmented filamentous bacterium strain with a eukaryotic host cell, wherein the culture is performed at an O2 level inferior to 5% in a rich tissue culture liquid medium containing bacterial medium components including iron. The present invention also relates to methods for genetically modifying a segmented filamentous bacterium strain comprising a step a culturing the strain in vitro.

公开(公告)号：US20190247416A1

公开(公告)日：2019-08-15

申请号：US16330956

申请日：2017-09-15

申请人： INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE) ,  FONDATION IMAGINE ,  UNIVERSITE PARIS DESCARTES ,  ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS (APHP) ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  UNIVERSITE DE CAEN NORMANDIE ,  CENTRE HOSPITALIER REGIONAL UNIVERSITAIRE DE CAEN

发明人： Olivier HERMINE ,  Flavia GUILLEM ,  Gandhi DAMAJ ,  Sophia LADRAA

IPC分类号： A61K31/7105 ,  A61K31/497

CPC分类号： A61K31/7105 ,  A61K31/497 ,  A61K31/713 ,  A61P35/00 ,  A61P35/04 ,  C12N15/00 ,  C12N15/113 ,  C12N2310/14 ,  C12N2310/531

摘要： The present invention relates to methods and pharmaceutical compositions for the treatment of systemic mastocytosis. The inventors showed the effect of KPT-251 treatment on SCF-dependent human Mast cell (MC) line without KIT mutation (WT ROSA) and on two factor-independent MC lines with KIT mutations : ROSA Δ 417-419 insY and ROSA D816V. KPT is a Selective Inhibitor of Nuclear Export (SINE) that specifically inhibits the activity of the exportin-1 (XPO1). KPT-251 treatment induces minimal toxicity in non-cancerous hematopoietic cells both in vitro and in vivo. In particular, the present invention relates a method of treating systemic mastocytosis in patient in need thereof comprising administering to the patient a therapeutically effective amount of a XPO1 inhibitor.

公开(公告)号：US20190037583A2

公开(公告)日：2019-01-31

申请号：US14903477

申请日：2014-07-08

申请人： INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE) ,  FONDATION IMAGINE ,  UNIVERSITE PARIS DESCARTES ,  ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS (APHP)

发明人： Jean-Michel ROZET ,  Isabelle PERRAULT ,  Xavier GERARD ,  Josseline KAPLAN ,  Arnold MUNNICH

IPC分类号： H04W72/12 ,  H04W28/02 ,  H04L5/00

摘要： The present invention relates to methods for performing antisense oligonucleotide-mediated exon skipping in the retina of a subject in need thereof. In particular, the present invention relates to a method for performing antisense oligonucleotide-mediated exon skipping in a retina cell of a subject comprising the step of injecting into the vitreous of the subject an amount of the antisense oligonucleotide.

公开(公告)号：US20180353486A1

公开(公告)日：2018-12-13

申请号：US15780722

申请日：2016-11-30

申请人： INSERM (Institut National de la Sante et de la Recherche Medicale) ,  Assistance Publique-Hopitaux de Paris (APHP) ,  Universite Paris Descartes ,  Fondation Imagine

发明人： Alain Hovnanian ,  Marina Simon

IPC分类号： A61K31/436 ,  A61K38/13 ,  A61P17/12

CPC分类号： A61K31/436 ,  A61K38/13 ,  A61P17/12

摘要： The present invention relates to methods and pharmaceutical composition for the treatment of Darier disease. In particular, the present invention relates to a method of treating Darier disease in a subject in need thereof comprising administering the subject with a therapeutically effective amount of a calcineurin inhibitor.

公开(公告)号：US20180237424A1

公开(公告)日：2018-08-23

申请号：US15554749

申请日：2016-03-02

申请人： INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE) ,  UNIVERSITE PARIS DESCARTES ,  FONDATION IMAGINE ,  ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS (APHP) ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS)

发明人： Laurence LEGEAI-MALLET ,  Ludovic MARTIN ,  Patricia BUSCA ,  Laurent CORRE

IPC分类号： C07D413/04 ,  C07D413/14

CPC分类号： C07D413/04 ,  A61K31/4245 ,  A61K45/06 ,  C07D413/14

摘要： The invention pertains to novel FG-FR3antagonists of general formula (I), The compounds are useful for the treatments and prevention of achondroplasia and cancer.

公开(公告)号：US20180031579A1

公开(公告)日：2018-02-01

申请号：US15550394

申请日：2016-02-11

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  UNIVERSITÉ PARIS DESCARTES ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  FONDATION IMAGINE ,  ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP) ,  UNIVERSITÉ DE NANTES ,  UNIVERSITÉ D'ANGERS ,  CENTRE HOSPITALIER UNIVERSITAIRE D'ANGERS

发明人： Ivan CRUZ-MOURA ,  Valérie BARDET ,  Michaël DUSSIOT ,  Thiago TROVATI MACIEL ,  Jérôme TAMBURINI ,  Norbert IFRAH ,  Olivier HERMINE

IPC分类号： G01N33/74 ,  A61K39/395 ,  C07K16/22

CPC分类号： G01N33/74 ,  A61K39/3955 ,  C07K16/22 ,  C07K2317/76 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/158 ,  G01N33/57426 ,  G01N2333/475 ,  G01N2333/51 ,  G01N2800/22 ,  G01N2800/52

摘要： The present invention relates to antagonists of GDF11, for use in the treatment of malignant hematological disease, such as Acute Myeloid Leukemia (AML). The present invention also relates to a method for predicting the responsiveness of a patient affected with malignant haematological disease, such as Acute Myeloid Leukemia, to a chemotherapy treatment.

公开(公告)号：US20160368975A1

公开(公告)日：2016-12-22

申请号：US15161603

申请日：2016-05-23

申请人： Institut National de la Sante et de la Recherche Medicale (INSERM) ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  Universite Paris Descartes - Paris V ,  Assistance Publique - Hopitaux de Paris ,  Fondation Imagine

发明人： Olivier HERMINE ,  Genevieve COURTOIS ,  Jean-Benoit ARLET ,  Jean-Antoine RIBEIL

IPC分类号： C07K16/18 ,  G01N33/68 ,  A61K31/70 ,  G01N33/50 ,  A61K38/02 ,  A61K31/7088

CPC分类号： C07K16/18 ,  A61K31/70 ,  A61K31/7088 ,  A61K38/02 ,  G01N33/5094 ,  G01N33/6893 ,  G01N33/80 ,  G01N2333/805 ,  G01N2500/02 ,  G01N2800/22

摘要： Methods and compositions for the treatment of β-thalassemia are provided. Methods and compositions restore or increase erythrocyte maturation in individuals afflicted with β-TM by preventing proteolysis of GATA-1 protein. Screening methods for identifying agents which bind heat shock protein 70 (HSP-70) and inhibit HSP-70 α-globin binding, but which allow GATA-1 protein-HSP-1 binding in a manner that prevents GATA-1 proteolysis.

摘要翻译： 提供了治疗β-地中海贫血的方法和组合物。 方法和组合物通过预防GATA-1蛋白的蛋白水解来恢复或增加患有β-TM的个体的红细胞成熟。 用于鉴定结合热休克蛋白70（HSP-70）并抑制HSP-70α-珠蛋白结合但允许以防止GATA-1蛋白水解的方式进行GATA-1蛋白-HSP-1结合的试剂的筛选方法。

公开(公告)号：US20160051674A1

公开(公告)日：2016-02-25

申请号：US14781353

申请日：2014-04-17

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  FONDATION IMAGINE ,  UNIVERSITÉ PARIS DESCARTES ,  ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP) ,  THE UNIVERSTY OF MANCHESTER

发明人： Sylvain LATOUR ,  Alain FISCHER ,  Emmanuel MARTIN ,  Peter ARKWRIGHT

IPC分类号： A61K39/395 ,  A61K31/7068 ,  A61K31/713 ,  A61K45/06 ,  A61K31/655 ,  A61K31/436 ,  A61K31/185 ,  A61K31/353 ,  A61K31/404 ,  A61K31/215 ,  A61K31/4015 ,  A61K31/5377 ,  A61K31/52 ,  A61K38/13 ,  G01N33/50 ,  A61K31/42

CPC分类号： A61K39/3955 ,  A61K31/185 ,  A61K31/215 ,  A61K31/353 ,  A61K31/4015 ,  A61K31/404 ,  A61K31/42 ,  A61K31/436 ,  A61K31/52 ,  A61K31/5377 ,  A61K31/655 ,  A61K31/7068 ,  A61K31/7072 ,  A61K31/713 ,  A61K38/13 ,  A61K45/06 ,  G01N33/5023 ,  G01N33/505

摘要： The present invention relates to methods and pharmaceutical compositions for inhibiting lymphocyte proliferationin a subject in need thereof. In particular, the invention relates to a CTP synthase 1 (CTPS1) inhibitor for use in a method for inhibiting lymphocyte proliferationin a subject in need thereof. The invention also relates to a method for screening a plurality of test substances useful for inhibiting lymphocyte proliferationin a subject in need thereof comprising the steps consisting of i) testing each of the test substances for its ability to inhibit CTPS1 activity or expression and ii) identifying the test substance which inhibits CTPS1 activity or expression thereby to identify a test substance useful for inhibiting lymphocyte proliferationin a subject in need thereof.

摘要翻译： 本发明涉及在有需要的受试者中抑制淋巴细胞增殖的方法和药物组合物。 特别地，本发明涉及一种用于抑制有需要的受试者的淋巴细胞增殖的方法中的CTP合酶1（CTPS1）抑制剂。 本发明还涉及一种筛选用于抑制需要的受试者的淋巴细胞增殖的多种测试物质的方法，包括以下步骤：i）测试每种测试物质以抑制CTPS1活性或表达的能力，以及ii）鉴定 抑制CTPS1活性或表达的测试物质，从而鉴定在有需要的受试者中可用于抑制淋巴细胞增殖的测试物质。

公开(公告)号：US20240229139A9

公开(公告)日：2024-07-11

申请号：US18546611

申请日：2022-02-16

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE ,  UNIVERSITÉ PARIS CITÉ ,  FONDATION IMAGINE ,  ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP)

发明人： Mickaël MENAGER ,  Julie TOUBIANA ,  Darragh DUFFY ,  Frédéric LAUCAT

IPC分类号： C12Q1/6883

CPC分类号： C12Q1/6883 ,  C12Q2600/118 ,  C12Q2600/158

摘要： SARS-CoV-2 infection in children is generally milder than in adults, yet a proportion of cases result in hyperinflammatory conditions often including myocarditis. To better understand these cases, the inventors applied a multi-parametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. The most severe forms of MIS-C (multisystem inflammatory syndrome in children related to SARS-CoV-2), that resulted in myocarditis, were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. This phenotype was associated with TNF-α signaling, sustained NF-κB signaling in monocytic/dendritic cells, alongside increased HIF-1α and VEGF signaling. Single-cell transcriptomic analyses identified

公开(公告)号：US11857532B2

公开(公告)日：2024-01-02

申请号：US17418981

申请日：2019-12-27

申请人： INSERM (Institut National de la Santé et de la Recherche Médicale) ,  Université de Paris ,  Assistance Publique—Hôpitaux de Paris (APHP) ,  Fondation Imagine

发明人： Anne Agnès Rotig ,  Arnold Munnich ,  Floriane Petit

IPC分类号： A01N43/04 ,  A61K31/70 ,  A61K31/357 ,  A61K31/194 ,  A61K31/7076

CPC分类号： A61K31/357 ,  A61K31/194 ,  A61K31/7076

摘要： Friedreich ataxia (FRDA) is caused by a GAA repeat expansion in FXN gene that encodes a mitochondrial protein, frataxin, involved in iron sulfur complex (ISC) assembly. Frataxin deficiency results in abnormal ISC containing proteins, namely respiratory chain complex I-III and aconitases and accumulation of iron in brain and heart of patients. Here, the inventors show that FRDA fibroblasts are unable to limit iron uptake inducing a massive cytosolic iron accumulation and to a lesser extent in mitochondria. The inventors also observed increased transferrin receptor (TfR1) steady state levels and membrane TfR1 accumulation that they ascribed to impaired post-translational modification by palmitoylation as well as delayed transferrin recycling. Finally, the inventors showed that artesunate, dichloroacetate and Coenzyme-A improved TfR1 palmitoylation and thus represent candidate molecules for the treatment of patients with Friedreich ataxia. Thus the present invention relates to methods of treating Friedreich ataxia (FRDA) as well as to methods of predicting whether a patient suffering from FRDA will achieve a therapeutic response.