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    ANTI-ANTITHROMBIN SINGLE-DOMAIN ANTIBODIES AND POLYPEPTIDES COMPRISING THEREOF
    105.
    发明申请
    ANTI-ANTITHROMBIN SINGLE-DOMAIN ANTIBODIES AND POLYPEPTIDES COMPRISING THEREOF 审中-公开

    公开(公告)号：US20190100602A1

    公开(公告)日：2019-04-04

    申请号：US16086146

    申请日：2017-03-17

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

    发明人： Peter LENTING ,  Cécile DENIS ,  Olivier CHRISTOPHE ,  Gabriel AYME

    IPC分类号： C07K16/36 ,  C07K16/38 ,  A61P7/04 ,  A61K38/17 ,  C07K14/47 ,  C12N15/62

    摘要： The present invention relates to isolated single-domain antibodies (sdAb) directed against Antithrombin (AT) to prolong the half-life of the proteins. Inventors have generated isolated single domain antibodies (sdAbs) directed against antithrombin. They observed that in amidolytic assays, sdAbs are incapable of blocking the inhibitory antithrombin activity towards thrombin and factor Xa in the presence of heparin. The different combinations of sdAb were able to block the inhibitory antithrombin activity towards thrombin and factor Xa in mice. Thus, the inventors propose to use different combinations of sdAb to block the inhibitory function of antithrombin in order to promote thrombin generation and thus treat haemophilia and other conditions that are associated with bleeding. Accordingly, the invention relates also to a method of preventing or treating bleeding disorders in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of the single domain antibodies or the drug conjugate of the invention.

    Humanized Anti-Claudin-1 Antibodies and Uses Thereof
    106.
    发明申请
    Humanized Anti-Claudin-1 Antibodies and Uses Thereof 审中-公开

    公开(公告)号：US20190100586A1

    公开(公告)日：2019-04-04

    申请号：US16086934

    申请日：2017-03-21

    申请人： INSERM (Institut National de la Santé et de la Recherche Médicale) ,  Université de Strasbourg ,  Chu Strasbourg, Les Hôpitaux Universitaires de Strasbourg

    发明人： Thomas Baumert ,  Rajeevkumar Tawar

    IPC分类号： C07K16/28 ,  A61P31/14 ,  A61P1/16 ,  C12N15/62

    摘要： The present invention relates to humanized anti-claudin-1 antibodies and uses thereof. Hepatitis C virus infection is a leading cause of chronic liver disease and a major indication for liver transplantation. The tight junction protein claudin-1 (CLDN1) is an essential entry factor for HCV and a promising target for therapy. For clinical development, the inventors have humanized a rat anti-CLDN1 antibody produced by genetic immunization that prevent HCV infection and also cure chronically infected human liver chimeric mice. The lead humanized anti-CLDN1 antibody (H3L3) pan-genotypically inhibited HCV pseudoparticle infection of primary human hepatocytes (PHH) without detectable escape. H3L3 efficiently inhibited infection by diverse HCV genotype 3 strains and exhibited marked synergy with direct-acting antivirals (DAAs). The inventors also demonstrate that anti-CLDN1 H3L3 cures persistent HCV infection in human-liver chimeric uPA-SCID mice in monotherapy. Thus, the present invention relates to humanized anti-claudin-1 antibodies and uses thereof, in particular for the prevention and treatment of hepatitis C virus infection, virus-induced liver diseases, hepatocellular carcinoma (HCC), nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

    ANTI-NEUROTENSIN LONG FRAGMENT ANTIBODIES AND USES THEREOF
    108.
    发明申请
    ANTI-NEUROTENSIN LONG FRAGMENT ANTIBODIES AND USES THEREOF 审中-公开

    公开(公告)号：US20190077854A1

    公开(公告)日：2019-03-14

    申请号：US16191559

    申请日：2018-11-15

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

    发明人： Patricia Forgez

    IPC分类号： C07K16/18 ,  C07K16/30 ,  A61K45/06 ,  C07K16/26 ,  A61K33/24 ,  A61K39/395 ,  A61K39/00

    摘要： The present invention relates to a neutralising antibody which is capable of binding to neurotensin with high affinity. The antibody of the present invention neutralises the activity of neurotensin, in particular the oncogenic activities of neurotensin. In particular, the present invention relates to a neutralising antibody which binds to the human neurotensin long fragment, and having a heavy chain variable region which comprises a H-CDR1 region having at least 90% of identity with SEQ ID NO:2, a H-CDR2 region having at least 90% of identify with SEQ ID NO:3 and a H-CDR3 region having at least 90% of identity with SEQ ID NO:4; and a light chain variable region comprising a L-CDR1 region having at least 90% of identity with SEQ ID NO:6, a L-CDR2 having at least 90% of identity with SEQ ID NO:7 and a L-CDR3 region having at least 90% of identity with SEQ ID NO:8. The present invention also provides the use of such antibodies in the treatment of cancer.