公开(公告)号：EP3512515A1

公开(公告)日：2019-07-24

申请号：EP17764845.8

申请日：2017-09-15

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) ,  Centre National de la Recherche Scientifique (CNRS) ,  Université de Caen Normandie ,  Centre Hospitalier Régional Universitaire De Caen

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

IPC分类号： A61K31/4196 ,  A61K31/497 ,  A61K31/7088 ,  A61P35/00

公开(公告)号：EP3074007A1

公开(公告)日：2016-10-05

申请号：EP14808905.5

申请日：2014-11-28

申请人： INSERM (Institut National de la Santé et de la Recherche Médicale) ,  Université Paris Descartes ,  Assistance Publique-Hôpitaux de Paris (APHP) ,  Fondation Imagine ,  Centre National de la Recherche Scientifique (CNRS)

发明人： HERMINE, Olivier ,  GUILLEM, Flavia ,  ARLET, Jean-Benoît ,  COURTOIS, Geneviève

IPC分类号： A61K31/396 ,  A61P7/00

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的β-地中海贫血的方法中的XPO1抑制剂。

公开(公告)号：EP3906415A1

公开(公告)日：2021-11-10

申请号：EP20700002.7

申请日：2020-01-02

申请人： INSERM (Institut National de la Santé et de la Recherche Médicale) ,  Assistance Publique-Hôpitaux de Paris (APHP) ,  Fondation Imagine ,  Université Paris Descartes ,  Centre National de la Recherche Scientifique (CNRS) ,  Université Paris-Saclay

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

IPC分类号： G01N33/574

公开(公告)号：EP3074007B1

公开(公告)日：2019-07-03

申请号：EP14808905.5

申请日：2014-11-28

申请人： INSERM (Institut National de la Santé et de la Recherche Médicale) ,  Université Paris Descartes ,  Assistance Publique-Hôpitaux de Paris (APHP) ,  Fondation Imagine ,  Centre National de la Recherche Scientifique (CNRS)

发明人： HERMINE, Olivier ,  GUILLEM, Flavia ,  ARLET, Jean-Benoît ,  COURTOIS, Geneviève

IPC分类号： A61K31/396 ,  A61P7/00

公开(公告)号：EP3154536A1

公开(公告)日：2017-04-19

申请号：EP15731531.8

申请日：2015-06-09

申请人： Institut National de la Santé et de la Recherche Médicale (INSERM) ,  Fondation Imagine ,  Assistance Publique-Hôpitaux de Paris (APHP) ,  Université Paris Descartes ,  Centre National de la Recherche Scientifique (C.N.R.S.)

发明人： HERMINE, Olivier ,  ARLET, Jean-Benoit ,  GUILLEM, Flavia ,  COURTOIS, Genevève ,  FONTENAY, Michaela

IPC分类号： A61K31/165 ,  A61P35/02

CPC分类号： A61K31/422 ,  A61K31/00 ,  A61K31/366

摘要： The present invention provides methods and pharmaceutical compositions designed to intervene in this defective process and to promote or restore erythrocyte maturation in individuals suffering from a myelodysplastic syndrome. The methods involve maintaining the activity of GATA-1 by preventing sequestration of Hsp70 in the cytoplasm. Accordingly, it is an object of this invention to provide methods of restoring or increasing erythrocyte maturation in a subject suffering from a myelodysplastic syndrome by preventing proteolytic inactivation of GATA-1. In some embodiments, preventing is achieved by administering to the subject a compound that inhibits the XPO1 nuclear transporter.

摘要翻译： 本发明提供了设计用于干预该缺陷过程并促进或恢复患有骨髓增生异常综合征的个体的红细胞成熟的方法和药物组合物。 该方法涉及通过防止细胞质中Hsp70的螯合来维持GATA-1的活性。 因此，本发明的目的是通过预防GATA-1的蛋白水解失活来提供恢复或增加患有骨髓增生异常综合征的受试者的红细胞成熟的方法。 在一些实施方案中，通过向受试者施用抑制XPO1核转运蛋白的化合物来实现预防。

公开(公告)号：EP4059569A1

公开(公告)日：2022-09-21

申请号：EP22157031.0

申请日：2020-01-02

申请人： INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM) ,  Assistance Publique-Hôpitaux de Paris ,  Fondation Imagine ,  Centre national de la recherche scientifique ,  Université de Paris ,  Université Paris-Saclay

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

IPC分类号： A61P35/00 ,  C07K16/28 ,  G01N33/574

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 predicts poor outcome of patients treated with anti-PDl (e.g. pembrolizumab). Finally, the combination of anti-NRPl and anti-PDl 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-PDl 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.