公开(公告)号：US20200317647A1

公开(公告)日：2020-10-08

申请号：US16650629

申请日：2018-09-26

申请人： UNIVERSITÉ DE PARIS ,  INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM) ,  SORBONNE UNIVERSITE ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS)

发明人： Etienne JACOTOT ,  Elodie BOSC

IPC分类号： C07D405/12 ,  C07D401/12 ,  C07D417/14 ,  C07D207/16

摘要： The present invention relates to a compound of formula (I): wherein P1, P3, P4 and P5 are amino acid residues or amino acid like structures. The invention also relates to a compound of formula (I) for its use as a Caspase-2 inhibitor and for its therapeutical use. It also concerns the use of a compound of formula (I) as activity base probe to selectively detect Caspase-2 activity.

公开(公告)号：US20240118268A1

公开(公告)日：2024-04-11

申请号：US18257244

申请日：2021-12-17

申请人： CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE ,  UNIVERSITÉ DE PARIS CITÉ ,  YSLAB

发明人： Patrice RAT ,  Elodie OLIVIER ,  Melody DUTOT ,  Anaïs WAKX

IPC分类号： G01N33/50 ,  C12N5/073 ,  G01N33/74

CPC分类号： G01N33/5044 ,  C12N5/0605 ,  G01N33/743 ,  G01N2333/705 ,  G01N2333/90245

摘要： The invention relates to a cell culture comprising a placental cell and a culture medium consisting of minimal essential nutriments and a low amount of serum. The invention also relates to a method using the cell culture for identifying endocrine disruptor.

公开(公告)号：US20230357769A1

公开(公告)日：2023-11-09

申请号：US18246270

申请日：2021-09-21

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

发明人： Annarita MICCIO ,  Fulvio MAVILIO ,  Mario AMENDOLA ,  Marina CAVAZZANA ,  Megane BRUSSON

IPC分类号： C12N15/113 ,  C12N15/86 ,  A61K35/28 ,  A61P7/06

CPC分类号： C12N15/113 ,  C12N15/86 ,  A61K35/28 ,  A61P7/06 ,  C12N2310/141 ,  C12N2310/531 ,  C12N2740/15043

摘要： Gene therapy of SCO is based on the transplantation of genetically modified HSCs. Several LV approaches based on gene addition consist in transducing patient HSCs with a lentiviral vector expressing an anti-sickling β-like globin chain such as use of βAS3 HBB anti-sickling variants. Here, the inventors have improved the design of the LV-AS3 vector to treat SCO patients. These LVs allow the simultaneous expression of the potent anti-sickling βAS3-globin and an artificial miR (amiR) silencing the βS-globin. The reduction of βS-globin levels will increase the incorporation of βAS3-globin in Hb tetramers, which should increase the proportion of corrected RBCs in SCO patients. The inventors selected the best-performing miRs, and modified the therapeutic βAS3-globin transgene by inserting silent mutations to avoid the recognition by the amiR and the silencing of the transgene.

公开(公告)号：US20230290436A1

公开(公告)日：2023-09-14

申请号：US18006030

申请日：2021-07-23

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  UNIVERSITE DE NANTES ,  ASSISTANCE PUBLIQUE HOPITAUX DE PARIS ,  UNIVERSITÉ DE PARIS ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - CNRS - ,  UNIVERSITÉ DE LORRAINE ,  SORBONNE UNIVERSITE

发明人： Maria MITEV ,  Marie-Anne LORIOT ,  Arnaud NICOT ,  Elodie GOLDWASER ,  Christian JELSCH ,  Catherine LAURENT

IPC分类号： G16B15/30 ,  G16B40/20 ,  G06F18/2411

CPC分类号： G16B15/30 ,  G16B40/20 ,  G06F18/2411

摘要： The present invention relates to the prediction of drug metabolizing enzymes (DME) inhibitors. Inhibition of DMEs leads to adverse drug-drug interaction, hence predicting inhibition of DMEs by determined molecules is critical for preventing drug toxicity. Inventors elaborated a protocol of integrated in silico protein structure-based and machine learning approach to predict inhibition of DMEs. In particular, the present invention relates to a method for training a model for predicting inhibition of DMEs, comprising a selection of a number of descriptors among an initial set comprising physicochemical descriptors and binding energies on at least one enzyme configuration, and a training of a classification model on a learning database of known inhibitors or non-inhibitors based on the selected descriptors as inputs. This approach successfully predicted inhibition of CYP2C9, CYP2D6, SULT1A1, SULT1A3 and UGT1 A1.

公开(公告)号：US11723956B2

公开(公告)日：2023-08-15

申请号：US16327543

申请日：2017-08-31

申请人： Institut National de la Sante et de la Recherche Medicale (INSERM) ,  Centre National de la Recherche Scientifique (CNRS) ,  UNIVERSITÉ DE PARIS ,  Assistance Publique—Hopitaux de Paris ,  Ecole Nationale Superieure de Chimie de Paris ,  Universite de Versailles—St Quentin en Yvelines

发明人： Robert Malafosse ,  Nathalie Mignet ,  Vincent Boudy ,  Johanne Seguin ,  Kathia Lemdani ,  Claude Capron

IPC分类号： A61K38/19 ,  A61K39/07 ,  A61K41/00 ,  A61K47/10 ,  A61K47/36 ,  A61P35/00 ,  A61K47/34 ,  A61K9/00 ,  A61K39/04 ,  A61K9/06 ,  C07K16/28 ,  A61K31/765 ,  A61K39/395 ,  A61K38/38 ,  A61K39/00

CPC分类号： A61K38/193 ,  A61K9/0019 ,  A61K9/0024 ,  A61K9/06 ,  A61K31/765 ,  A61K38/385 ,  A61K39/04 ,  A61K39/07 ,  A61K39/39541 ,  A61K41/0028 ,  A61K41/0052 ,  A61K47/10 ,  A61K47/34 ,  A61K47/36 ,  A61P35/00 ,  C07K16/2818 ,  A61K2039/505 ,  A61K2039/522 ,  A61K2039/54 ,  A61K2039/55522 ,  A61K2039/585 ,  A61K2039/82 ,  C07K2317/76 ,  A61K39/39541 ,  A61K2300/00

摘要： The present invention concerns a thermosensitive polymeric hydrogel comprising at least one thermosensitive copolymer, one aqueous solution, and a mucoadhesive excipient, wherein said thermosensitive polymeric hydrogel further comprises at least one immunostimulatory adjuvant and/or at least one cytokine and/or at least one chemokine and/or atleast one heat shockprotein. Another object of the invention is a thermosensitive polymeric hydrogel according to the invention for use in the treatment of tumors or metastasis in a subject having a cancer, preferably a metastatic cancer.

公开(公告)号：US11668729B2

公开(公告)日：2023-06-06

申请号：US17627239

申请日：2020-07-16

申请人： Paris Sciences et Lettres ,  Centre National de la Recherche Scientifique (CNRS) ,  Sorbonne Universite ,  Université de Paris

发明人： Antoine Niguès ,  Alessandro Siria

IPC分类号： G01Q30/20 ,  G01Q30/14

CPC分类号： G01Q30/20 ,  G01Q30/14

摘要： The present invention relates to an atomic force microscope for evaluating a surface of a sample, comprising a sample holder, having a first zone suitable for receiving the sample mounted in a stationary manner, a probe having a tip able to be positioned facing the surface of the sample, the microscope being configured to allow an adjustment of a position of the tip relative to the surface, and a support, the sample holder having at least one second zone, separate from the first zone and stationary relative to the support, the sample holder being deformable so as to allow a relative movement of the first zone with respect to the second zone, and the microscope comprising a detector able to detect a movement of the first zone relative to the second zone.

公开(公告)号：US20220348660A1

公开(公告)日：2022-11-03

申请号：US17760557

申请日：2020-10-01

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

发明人： Vahid ASNAFI ,  Olivier HERMINE ,  Ambroise MARÇAIS ,  Jacques GHYSDAEL

IPC分类号： C07K16/28 ,  A61P35/02

摘要： Adult T-cell leukemia/lymphoma (ATL) is an aggressive proliferation of mature activated CD4+ T cells associated with the human T-cell lymphotropic virus type I (HTLV-I). The inventors performed an integrated genomic analysis of a retrospective cohort of 62 ATL patients mainly originating from Africa and the Caribbean area. In particular, they identified a subset of mutations in the TCR/NF-KB pathway (PLCG1, CARD11, PRKCB, CBLB, IRF4, CSNK1A1, FYN, RHOA, VAV1). Furthermore, the inventors investigated the effects of an anti-CD3 antibody (OKT3) exposure on 4 ATL samples including 2 cases harboring CARD 11 and PRKCB gain of function alterations and 2 cases without any TCR pathway mutation. The data suggest that ATL harboring TCR pathway mutations clearly responded to anti-CD3 (FIG. 1B, red+OKT3) and died by apoptosis possibly by a mechanism resembling AICD. Importantly, these TCR-pathway/NFKB mutated patients also showed poorer outcome as compared to unmutated cases. Accordingly, the present invention relates to a method of treating adult T-cell leukemia/lymphoma (ATL) in a patient in need thereof comprising administering to the patient a therapeutically effective amount of an anti-CD3 antibody.

公开(公告)号：US20220307021A1

公开(公告)日：2022-09-29

申请号：US17614437

申请日：2020-06-03

申请人： INSERM (Institut National de la santé et de la Recherche Médicale) ,  Université de Paris ,  Centre National de la Recherche Scientifique (CNRS) ,  Assistance Publique-Hôpitaux de Paris (APHP) ,  Fondation Imagine ,  Conservatoire National des Arts et Métiers (CNAM)

发明人： Yves LEPELLETIER ,  Matthieu MONTES ,  Luc DEMANGE ,  François RAYNAUD ,  Rachel RIGNAULT-BRICARD ,  Olivier HERMINE ,  Nicolas LOPEZ

IPC分类号： C12N15/113 ,  A61P35/00 ,  C07K16/28

摘要： Neuropilin-1 is henceforth a relevant target in cancer treatment, however way-of-action is remains partly elusive and the development of small inhibitory molecules is therefore required for its study. Here, the inventors report that two neuropilin small-sized antagonists (NRPa-47, NRPa-48), VEGF-A165/NRP-1 binding inhibitors, are able to decrease VEGF-Rs phosphorylation and to modulate their downstream cascades in triple negative breast cancer cell line (MDA-MB-231). In particular, the inventors showed for the first time, how NRPa may altered tumor cell signaling and contributed in the down-modulation of the cancer therapeutic key factor p38α-kinase phosphorylation. More importantly, the association of NRPa with a p38α inhibitor leads to additional and/or synergistic effect of these drugs (depending of the dose used) for significantly reducing breast cancer cell proliferation Thus, the efficient association of NRPa and p38α-kinase inhibitors are thus credible for the treatment of cancer.

公开(公告)号：US20220298578A1

公开(公告)日：2022-09-22

申请号：US17596758

申请日：2020-06-25

申请人： UNIVERSITÉ DE PARIS ,  INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE

发明人： Véronique BAUD

IPC分类号： C12Q1/6886

摘要： The invention relates to a method for predicting the prognosis of a patient suffering from a B-cell lymphoma, through the detection of the status of activation of the RelB protein, in a biological sample of said patient. The inventors indeed identified an associated gene expression signature in the biological sample. Some genes from said signature are over-expressed and other are under-expressed and allow detecting RelB activation and predicting a worse prognosis in B-cell lymphoma.

公开(公告)号：US20220296674A1

公开(公告)日：2022-09-22

申请号：US17625006

申请日：2020-07-03

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  UNIVERSITÉ DE PARIS

发明人： Jean-Luc POYET ,  Anne MARIE-CARDINE ,  Justine HABAULT ,  Claire FRASER

IPC分类号： A61K38/08 ,  A61K47/64 ,  A61P35/00

摘要： The inventors have identified a novel cell-penetrating sequence, termed hAP10, from the C-terminus of the human protein Acinus. hAP10 was able to efficiently enter various normal and cancerous cells, likely through an endocytosis pathway, and to deliver an EGFP cargo to the cell interior. Cell penetration of a peptide, hAP10DR, derived from hAP10 by mutation of an aspartic acid residue to an arginine was dramatically increased. Interestingly, a peptide containing a portion of the heptad leucine repeat region domain of the survival protein AAC-11 (residues 377-399) fused to either hAP10 or hAP10DR was able to induce tumor cells death in vitro and to inhibit tumor growth in vivo in a sub-cutaneous xenograft mouse model for the Sézary syndrome. Combined, the results indicate that hAP10 and hAP10DR may represent promising vehicles for in vitro or in vivo delivery of bioactive cargos, with potential use in clinical settings. Thus the present invention relates to cell penetrating peptides and uses thereof for intracellularly delivery of molecules.