TRAPPING REAGENTS FOR REACTIVE METABOLITES SCREENING

    公开(公告)号:US20170183378A1

    公开(公告)日:2017-06-29

    申请号:US15397523

    申请日:2017-01-03

    Applicant: Biogen MA Inc.

    Inventor: Natalia Penner

    Abstract: The present invention provides compounds of Formula (I) and (II): wherein R1, R2, R4, R5, R6, X and n are as defined herein, and wherein R3 is hydrogen or a sulfur protecting group. Compounds of Formula (I) and (II), wherein R3 is hydrogen, may be useful in methods for detecting a reactive metabolite in a sample, e.g., wherein the metabolite is generated from the metabolism of a test compound, and wherein the metabolite and the compound of Formula (I) or (II) react to form a detectable adduct, e.g., detectable by mass spectrometry.

    Macrocyclic compounds as IRAK4 inhibitors for the treatment of inflammatory diseases

    公开(公告)号:US09617282B2

    公开(公告)日:2017-04-11

    申请号:US14770030

    申请日:2014-03-14

    Applicant: BIOGEN MA INC.

    Abstract: Provided are compounds of Formula (I), or pharmaceutically acceptable salts thereof, wherein i.a. Ring A is phenylene or 5- to 6-membered heteroarylene; Ring B is phenylene, 5- to 6-membered heterocycloalkylene or 5- to 6-membered heteroarylen; R4 is absent, heteroarylene, arylene, C1-3 alkylene, or R4 and R3 taken together with the nitrogen to which they are bound form a 3- to 7-membered heterocycloalkyl ring; R5 is absent, C(O)NR51, NR52 or O; R6 is C2-10 alkylene or alkenylene, wherein one or two of the carbon atoms in the alkylene chain is optionally replaced by an O, S, SO, SO2 or NR61, and wherein two of the carbon atoms in the alkylene chain are optionally connected by a two or three carbon atom alkylene chain to form a 5- to 7-membered ring; R7 is absent, NR71 or O. The compounds are IRAK4 inhibitors useful for the treatment of inflammatory diseases.

    GAS DELIVERY DEVICES AND ASSOCIATED SYSTEMS AND METHODS

    公开(公告)号:US20170081623A1

    公开(公告)日:2017-03-23

    申请号:US15126332

    申请日:2015-03-17

    Abstract: Systems, devices, and methods for the delivery of gas bubbles to liquids are generally described. The devices can include a primary conduit (102) comprising a plurality of openings (104) fluidically connecting an internal flow pathway (106) of the primary conduit to an environment outside the primary conduit. The devices may also include, in some instances, a secondary conduit (114) located at least partially within the primary conduit, the secondary conduit configured to redistribute the pressure of the gas delivered to the openings of the primary conduit, and comprising a plurality of openings (116) fluidically connecting an internal flow pathway (118) of the secondary conduit to a portion of the internal flow pathway (106) of the primary conduit outside the secondary conduit. Certain of the gas delivery systems and methods described herein are capable of delivering gas at relatively uniform linear flow velocities across multiple gas outlet openings. Certain embodiments are related to inventive configurations (e.g., spacings and/or sizing) of gas outlet openings in one or more conduits of the gas delivery device (e.g., the primary conduit and/or, when present, the secondary conduit). In addition, some embodiments are related to inventive arrangements for joining a gas delivery device is to a vessel, which may be part of for example, a reactor such as a bioreactor. Certain embodiments are related to the orientation of the gas delivery device and/or its components (e.g., during operation).

    JCV neutralizing antibodies
    86.
    发明授权
    JCV neutralizing antibodies 有权
    JCV中和抗体

    公开(公告)号:US09567392B2

    公开(公告)日:2017-02-14

    申请号:US14386262

    申请日:2013-03-15

    Applicant: Biogen MA Inc.

    Abstract: In one aspect, the disclosure provides neutralizing antibodies against JCV and methods for the treatment of PML. In some embodiments, aspects of the invention relate to an isolated JC-vims neutralizing monoclonal antibody against JCV capsid protein VPI (JCV-VP1). In some embodiments, the antibody suppresses infectivity of the JC-vims. In some embodiments, the antibody binds the sialic acid binding pocket of JCV-VP1.

    Abstract translation: 一方面,本公开提供了针对JCV的中和抗体和用于治疗PML的方法。 在一些实施方案中,本发明的方面涉及针对JCV衣壳蛋白VPI(JCV-VP1)的分离的JC-vim中和单克隆抗体。 在一些实施方案中,抗体抑制JC-vims的感染性。 在一些实施方案中,抗体结合JCV-VP1的唾液酸结合口袋。

    Compositions Comprising Antibodies to Lingo or Fragments Thereof
    87.
    发明申请
    Compositions Comprising Antibodies to Lingo or Fragments Thereof 有权
    包含针对Lingo或其片段的抗体的组合物

    公开(公告)号:US20160368984A1

    公开(公告)日:2016-12-22

    申请号:US15165279

    申请日:2016-05-26

    Applicant: Biogen MA Inc.

    Abstract: Endogenous LINGO-1 is a negative regulator for neuronal survival, axon regeneration, oligodendrocyte differentiation and myelination. Molecules that block endogenous LINGO-1 function, such anti-LINGO-1 antibodies can be used as therapeutics for the treatment of neuron and oligodendrocyte dysfunction. The present invention provides antibodies specific for LINGO-1, and methods of using such antibodies as antagonists of endogenous LINGO-1 function. The invention further provides specific hybridoma and phage library-derived monoclonal antibodies, nucleic acids encoding these antibodies, and vectors and host cells comprising these antibodies. The invention further provides methods of promoting oligodendrocyte survival and myelination in a vertebrate, comprising administering to a vertebrate in need of such treatment an effective amount of an anti-LINGO-1 antibody

    Abstract translation: 内源性LINGO-1是神经元存活,轴突再生,少突胶质细胞分化和髓鞘形成的负调节因子。 阻断内源性LINGO-1功能的分子,如抗LINGO-1抗体可用作治疗神经元和少突胶质细胞功能障碍的治疗剂。 本发明提供对LINGO-1特异性的抗体,以及使用这些抗体作为内源性LINGO-1功能的拮抗剂的方法。 本发明还提供特异性杂交瘤和源自噬菌体文库的单克隆抗体,编码这些抗体的核酸,以及包含这些抗体的载体和宿主细胞。 本发明还提供了在脊椎动物中促进少突胶质细胞存活和髓鞘形成的方法,包括对需要这种治疗的脊椎动物施用有效量的抗LINGO-1抗体

    Stable liquid interferon beta formulations

    公开(公告)号:US09522174B2

    公开(公告)日:2016-12-20

    申请号:US14564637

    申请日:2014-12-09

    Applicant: Biogen MA Inc.

    Abstract: Liquid interferon compositions having a pH between 4.0 and 7.2 are described. The compositions comprise interferon-beta and a stabilizing agent at between about 0.3% and 5% by weight which is an amino acid selected from the group consisting of acidic amino acids, arginine and glycine. If needed, salt is added to provide sufficient ionic strength. The liquid composition has not been previously lyophilized or previously cavitated. The liquid is preferably contained within a vessel having at least one surface in contract with the liquid that is coated with a material inert to adsorption of interferon-beta. A kit for parenteral administration of a liquid interferon formulation and a method for stabilizing liquid interferon compositions are also described.

    Use of Perfusion Seed Cultures to Improve Biopharmaceutical Fed-Batch Production Capacity and Product Quality
    89.
    发明申请
    Use of Perfusion Seed Cultures to Improve Biopharmaceutical Fed-Batch Production Capacity and Product Quality 审中-公开
    使用灌注种子培养提高生物制药饲料分批生产能力和产品质量

    公开(公告)号:US20160289633A1

    公开(公告)日:2016-10-06

    申请号:US15038698

    申请日:2014-12-19

    Applicant: Biogen MA Inc.

    Abstract: Methods of improving the efficiency of production of a protein product of interest in mammalian cell culture are presented. In particular, the methods result in an increase in the quantity of a protein product produced, or decreases protein product production time in a manufacturing-scale bioreactor cell culture. The disclosed methods comprise: (a) culturing the N-1 bioreactor culture to high viable cell densities; and (b) seeding the production bioreactor culture at high viable cell seeding densities.

    Abstract translation: 提出了提高哺乳动物细胞培养中感兴趣的蛋白质产品生产效率的方法。 特别地,所述方法导致产生的蛋白质产物的量的增加,或减少制造规模的生物反应器细胞培养物中的蛋白质产物生产时间。 所公开的方法包括:(a)将N-1生物反应器培养物培养成高活细胞密度; 和(b)将生产生物反应器培养物以高活细胞播种密度接种。

    PURIFICATION OF CHIMERIC FVIII MOLECULES
    90.
    发明申请
    PURIFICATION OF CHIMERIC FVIII MOLECULES 审中-公开
    纯化FVIII分子

    公开(公告)号:US20160185817A1

    公开(公告)日:2016-06-30

    申请号:US14910555

    申请日:2014-08-08

    Applicant: Biogen MA Inc.

    CPC classification number: C07K1/36 C07K14/755 C07K2319/31

    Abstract: The invention is directed to methods of purifying a chimeric protein comprising subjecting the chimeric protein to a factor VIII-specific affinity chromatography, and subjecting the chimeric protein to an AEX chromatography; wherein the chimeric protein comprises a factor VIII protein or a fragment thereof. The chimeric protein purified by the present methods shows improved factor VIII activity.

    Abstract translation: 本发明涉及纯化嵌合蛋白的方法,包括使嵌合蛋白进行因子VIII特异性亲和层析,并使嵌合蛋白进行AEX色谱; 其中所述嵌合蛋白包含因子VIII蛋白或其片段。 通过本方法纯化的嵌合蛋白显示出改善的因子VIII活性。

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