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：US20210308106A1

公开(公告)日：2021-10-07

申请号：US17324690

申请日：2021-05-19

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： A61K31/4196 ,  A61K31/506 ,  A61P37/00 ,  A61K31/397 ,  A61K31/4245

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：US20170020847A1

公开(公告)日：2017-01-26

申请号：US15039230

申请日：2014-11-18

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

发明人： Olivier HERMINE ,  Flavia GUILLEM ,  Jean-Benoit ARLET ,  Genevieve COURTOIS

IPC分类号： A61K31/4196 ,  G01N33/50 ,  A61K31/497

CPC分类号： A61K31/4196 ,  A61K31/397 ,  A61K31/4245 ,  A61K31/433 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/497 ,  A61K31/5377 ,  A61K31/55 ,  G01N33/5073 ,  G01N2500/02 ,  G01N2500/10

摘要： The present invention relates to methods and pharmaceutical compositions for the treatment of beta-thalassemias. In particular, the present invention relates to an XPO1 inhibitor for use in a method for treating beta-thalassemia in a subject in need thereof.

摘要翻译： 本发明涉及用于治疗β-地中海贫血的方法和药物组合物。 特别地，本发明涉及用于治疗有需要的受试者中的β-地中海贫血的方法中的XPO1抑制剂。

公开(公告)号：US20220073626A1

公开(公告)日：2022-03-10

申请号：US17420537

申请日：2020-01-02

申请人： INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHECHE MÉDICALE (INSERM) ,  ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS ,  FONDATION IMAGINE ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE ,  UNIVERSITÉ DE PARIS ,  UNIVERSITÉ PARIS-SACLAY

发明人： Olivier HERMINE ,  Julien ROSSIGNOL ,  Zakia BELAID-CHOUCAIR ,  Guillemette FOUQUET ,  Lucile COURONNE ,  Michael DUSSIOT ,  Rachel RIGNAULT-BRICARD ,  Tereza COMAN ,  Flavia GUILLEM ,  Yves LEPELLETIER ,  Amédée RENAND ,  Pierre MILPIED

IPC分类号： C07K16/28 ,  A61K38/17 ,  A61P35/00 ,  C12N5/0783 ,  A61K35/17

摘要： Targeting immune checkpoints, such as Programmed cell Death 1 (PD1), has improved survival in cancer patients by unleashing exhausted CD8+ T-cell thereby restoring anti-tumor immune responses. Most patients, however, relapse or are refractory to immune checkpoint blocking therapies. Here, the inventors show that NRP1 is recruited in the cytolytic synapse of PD1+CD8+ T-cells, interacts and enhances PD-1 activity. In mice, CD8+ T-cell specific deletion of Nrp1 improves spontaneous and anti PD1 antibody anti-tumor immune responses. Likewise, in human metastatic melanoma, the expression of NRP1 in tumor infiltrating CD8+ T-cells QI predicts poor outcome of patients treated with anti-PD1 (e.g. pembrolizumab). Finally, the combination of anti-NRP1 and anti-PD1 antibodies is synergistic in human, specifically in CD8+ T-cells anti-tumor response. Thus the therapeutic inhibition of NRP1 alone or combined with an immune checkpoint inhibitor (e.g. anti-PD1 antibody) could efficiently repress tumor growth in human cancer. The present invention also relates to multispecific antibodies comprising at least one binding site that specifically binds to an immune checkpoint molecule (e.g. PD-1), and at least one binding site that specifically binds to NRP-1. The present invention also relates to a population of cells engineered to express a chimeric antigen receptor (CAR) and wherein the expression of NRP-1 in said cells is repressed.