公开(公告)号：US20210246469A1

公开(公告)日：2021-08-12

申请号：US17224367

申请日：2021-04-07

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  GENETHON ,  SORBONNE UNIVERSITÉ ,  UNIVERSITÉ DE PARIS ,  SPARK THERAPEUTICS, INC.

发明人： Sébastien LACROIX-DESMAZES ,  Federico MINGOZZI ,  Jordan DIMITROV ,  Christian LEBORGNE ,  Sean ARMOUR

IPC分类号： C12N15/86 ,  A61K38/48

摘要： Disclosed herein are methods for treating patients that may develop or already have pre-existing gene therapy neutralizing antibodies by administering a protease that cleaves peptide bonds present in immunoglobulins or by administering a glycosidase that cleaves carbohydrate residues present on immunoglobulins, or other similar enzymatic cleavage of immunoglobulins in vivo. Also disclosed are methods for utilizing IdeS and other immunoglobulin G-degrading enzyme polypeptides for gene therapy treatment of a disease in a patient in need thereof.

公开(公告)号：US20210220481A1

公开(公告)日：2021-07-22

申请号：US17265554

申请日：2019-07-24

申请人： INSERM (Institut National de la Santé et de la Recherche Médicale) ,  Assistance Publique - Hopitaux de Paris ,  Université Paris 13 ,  Université de Paris ,  Centre National de la Recherche Scienifique (CNRS)

发明人： Peter VAN ENDERT ,  Laurence MOTTE ,  Chloé DUBREIL

IPC分类号： A61K47/69 ,  A61K38/28 ,  A61K47/60

摘要： The present invention relates to nanoparticles, methods and compositions which are suitable for the detection and/or follow-up and/or treatment of type 1 diabetes. In particular, it relates to biocompatible tolerogenic nanoparticles comprising at least: (i) a ligand which can bind to an aryl hydrocarbon receptor (AHR) transcription factor; an (ii) a diabetes autoantigen selected from: insulin, preproinsulin, proinsulin, or an immunologically active fragment thereof The inventors have shown that such biocompatible tolerogenic nanoparticles are efficient for the identification of type-1 diabetes. It has also been shown that they can accumulate into the pancreas, and induce temporary or lasting remission of disease in spontaneously diabetic NOD mice. Kits and compositions are further provided.

公开(公告)号：US10947323B2

公开(公告)日：2021-03-16

申请号：US16329423

申请日：2016-09-05

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

发明人： Matthieu Sollogoub ,  Vincent Calvez ,  Anne-Geneviève Marcelin ,  Laurent Bouteiller ,  Mickaël Menand ,  Pierre Evenou ,  Adélie Gothland ,  Dmitri Colesnic ,  Julien Rossignol

IPC分类号： C08B37/16 ,  A61K47/69 ,  C12N15/113

摘要： The invention relates to a capped cyclodextrin-hydrophobic moiety conjugate, to a supramolecular polymer formed of capped cyclodextrin-hydrophobic moiety conjugates according to the invention and to a siRNA-cyclodextrin complex comprising a supramolecular polymer according to the invention. The invention also relates to a method for manufacturing the capped cyclodextrin-hydrophobic moiety conjugate, the supramolecular polymer, the siRNA-cyclodextrin complex according to the invention. The capped cyclodextrin-hydrophobic moiety conjugate of the invention comprises a capped cyclodextrin group and at least one hydrophobic moiety bound by a first linker to one of the carbon atoms of the cap. The invention can be used for various applications in particular in the pharmaceutical field.

公开(公告)号：US20210000889A1

公开(公告)日：2021-01-07

申请号：US16977274

申请日：2019-02-28

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

发明人： Fatima-Soraya TALEB ,  Harry SOKOL ,  Ludivine LAURANS

IPC分类号： A61K35/741 ,  A23L33/135 ,  A61P3/04 ,  A23L33/00

摘要： The present invention relates to methods for prognosing and treating metabolic diseases. The inventors demonstrated the association of obesity with the increase of intestinal IDO activity, which shifts tryptophan (Trp) metabolism from indole derivative but also IL-22 production towards kynurenine (Kyn) production. The inventors showed that the rewiring of Tip metabolism is possible towards a microbiota-dependent production of IL-22. In particular, the present invention relates to a method of treating metabolic diseases in a subject in need thereof comprising administering to the subject a therapeutically effective amount of probiotics

公开(公告)号：US20240285626A1

公开(公告)日：2024-08-29

申请号：US18589498

申请日：2024-02-28

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： Laurence LEGEAI-MALLET

IPC分类号： A61K31/506 ,  A61P19/00

CPC分类号： A61K31/506 ,  A61P19/00

摘要： FGFR3 gain-of-function mutations are responsible for a family of chondrodysplasias namely, achondroplasia (ACH) the most common form of dwarfism, a lethal form of dwarfism thanatophoric dysplasia (TD) as well as and hypochondroplasia. Recent data demonstrate that Infigratinib (NVP-BGJ398) corrects pathological hallmarks of ACH and support it as a 10 potential therapeutic approach for FGFR3-related skeletal diseases. Now the inventors has investigated the feasibility to treat the defective growth of the skeleton during the pregnancy with the drug. They treated pregnant female Fgfr3Nco/Y67C mice with the drug (4 mg/kg) that was injected subcutaneously at day E14.5 continuing daily through day 1 (after birth). The data indicated that BGJ398 treatment during 5 days in pregnant mice successfully repressed skeletal 15 anomalies that occurred during embryonic stages. Accordingly, the present invention relates to methods for treatment of FGFR3-related skeletal diseases during pregnancy with Infigratinib.

公开(公告)号：US20230054300A1

公开(公告)日：2023-02-23

申请号：US16955596

申请日：2018-12-21

申请人： PARIS SCIENCES ET LETTRES - QUARTIER LATIN ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  ECOLE NORMALE SUPERIEURE ,  UNIVERSITÉ DE PARIS ,  INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)

发明人： Térence STRICK ,  Charlie GOSSE ,  Dorota KOSTRZ ,  Jinglong WANG ,  Marc NADAL

IPC分类号： G01N33/543 ,  G01N33/68 ,  C12Q1/6825

摘要： The present application relates to a double-stranded DNA molecule comprising a first double-stranded DNA molecule (1) connected to a second double-stranded DNA molecule (2) by at least one covalent bond which is not a phosphodiester, phosphorothioate, phosphoramidate or phosphorodiamidate bond, preferably by a tether, said tether preferably being a double-stranded DNA molecule.

公开(公告)号：US20230008495A1

公开(公告)日：2023-01-12

申请号：US17852595

申请日：2022-06-29

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

发明人： Etienne JACOTOT ,  Elodie BOSC

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

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：US20220356525A1

公开(公告)日：2022-11-10

申请号：US17764642

申请日：2020-10-15

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) ,  ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP) ,  UNIVERSITÉ DE PARIS

发明人： Alexandre PUISSANT ,  Raphaël ITZYKSON

IPC分类号： C12Q1/6883 ,  A61K31/517 ,  A61K31/551 ,  A61K31/55 ,  A61K31/5517 ,  A61K31/5377 ,  A61P35/02

摘要： Deciphering the impact of metabolic intervention on response to anticancer therapy represents a path toward improved clinical responses. Here, the inventors identify amino acid-related pathways connected to the folate cycle whose activation predicts sensitivity to MYC-targeting therapies in acute myeloid leukemia (AML). They establish that folate restriction and deficiency of the rate-limiting folate-cycle enzyme, MTHFR—which exhibits reduced-function polymorphisms in about 10% of Caucasians—enhance resistance to MYC targeting by BET and CDK7 inhibitors in cell lines, primary patient samples and syngeneic mouse models of AML. Further, this effect is abrogated by supplementation with the MTHFR enzymatic product, CH3-THF. Mechanistically, folate cycle disturbance reduces H3K27/K9 histone methylation, and activates a SPI1 transcriptional program counteracting the effect of BET inhibition. Thus the data provide a rationale for screening MTHFR polymorphisms and the folate cycle status to exclude patients least likely and nominate those most likely to benefit from MYC-targeting therapies.

公开(公告)号：US20220340901A1

公开(公告)日：2022-10-27

申请号：US17606574

申请日：2020-04-24

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

发明人： Jean-Michel Rozet ,  Xavier GERARD ,  Iris BARNY ,  Isabelle PERRAULT ,  Josseline KAPLAN

IPC分类号： C12N15/113

摘要： The invention relates to the skipping of the CEP290 exon 36 in an individual suffering from a retinal dystrophy accounted for by a nonsense mutation or a premature termination codon generated by a frameshift mutation in exon 36 or an upstream exon, including the c.4723A>T, c.4771C>T, c.4714G>T, c.4786_4790del, c.4791_4794del, c.4732G>T, c.4625_4626insCATG (35), c.4792_4795del, c.4801C>T, c.4805C>T, or c.4811G>A mutations, to bypass protein truncation and lessen retinal damages. Here, studying fibroblasts from control individuals, and two patients carrying the CEP290 c.4723A>T nonsense mutation, they show low levels of spontaneous skipping of exon 36 arising from both endogenous basal skipping and mutation-induced skipping. The minimally shortened and mutation-free CEP290 mRNA produced by skipping of exon 36 in the fibroblasts of the two patients is translated into a protein isoform that localizes at the centrosome and allows the formation of primary cilia, yet with elongated axonemes. Using an AON consisting of a sequence set forth as SEQ ID NO: 1, complementary to a nucleic acid sequence of CEP290 pre-mRNA, wherein said AON targeting an mRNA encoding the donor splice site (H36D) is capable to alter splicing by blocking the recognition of exon 36 and bypass protein truncation while maintaining the open reading frame, leading to the production of near full-length CEP290 protein, they were able to increase the abundance of the alternatively spliced mRNA and shortened protein and to reduce axonemal length in patient cells.

公开(公告)号：US11473145B2

公开(公告)日：2022-10-18

申请号：US16633912

申请日：2018-07-26

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  FONDATION IMAGINE ,  Université de Paris ,  ASSISTANCE PUBLIQUE-HÔPITAUX DE PARIS (APHP) ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS)

发明人： Pascale De Lonlay-Debeney ,  Peter Van Endert ,  Marine Madrange ,  Yamina Hamel ,  François-Xavier Mauvais

IPC分类号： C12Q1/68 ,  C12Q1/6883 ,  C12Q1/686

摘要： The inventors initially participated to the identification of LPIN1 mutations as a cause for massive rhabdomyolysis episodes in children, triggered by febrile illness. The inventors have suggested that TLR9 antagonists would be suitable for the treatment of rhabdomyolysis (WO2017085115). The inventors thus treated 2 patients with lipin-1 disease by a TRL9 antagonist (hydroxychloroquine). They showed that the accumulation of mtDNA in plasma of the two patients before treatment decreases under treatment. When the treatment was stopped, the accumulation of mtDNA reappeared, then normalized when treatment was resumed. Accordingly, the present invention relates to a method for determining whether a patient suffering from rhabdomyolysis achieves a response with a TLR9 antagonist comprising determining the amount of mitochondrial DNA (mtDNA) in a blood sample obtained from the patient (e.g. by PCR).