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    • 2. 发明申请
    • METHODS FOR THE GENERATION OF MULTISPECIFIC AND MULTIVALENT ANTIBODIES
    • 用于产生多重和多重抗体的方法
    • WO2012023053A3
    • 2012-05-24
    • PCT/IB2011002664
    • 2011-08-16
    • NOVIMMUNE SAFISCHER NICOLASMAGISTRELLI GIOVANNIGUENEAU FRANCKRAVN ULLAELSON GREG
    • FISCHER NICOLASMAGISTRELLI GIOVANNIGUENEAU FRANCKRAVN ULLAELSON GREG
    • C07K16/00C07K16/46
    • C07K16/468C07K16/005C07K16/248C07K16/249C07K16/2866C07K2317/31C07K2317/32C07K2317/622C07K2317/92C12N15/1037C12N15/1075
    • The invention provides novel bispecific monoclonal antibodies carrying a different specificity for each binding site of the immunoglobulin molecule and methods for producing novel bispecific monoclonal antibodies carrying a different specificity for each binding site of the immunoglobulin molecule. The antibodies are composed of a single heavy chain and two different light chains, one containing a Kappa constant domain and the other of a Lambda constant domain. The invention provides methods for the isolation of antibodies of different specificities but sharing a common heavy chain. The invention also provides methods for the controlled co-expression of two light chains and a single heavy chain leading to the assembly of monospecific and bispecific antibodies. The invention provides a mean of producing a fully human bispecific and bivalent antibody that is unaltered in sequence and does not involve the use of linkers or other non-human sequences, as well as antibody mixtures of two monospecific antibodies and one bispecific antibody. The invention also provides the means of efficiently purifying the bispecific antibody.
    • 本发明提供对免疫球蛋白分子的每个结合位点携带不同特异性的新型双特异性单克隆抗体以及用于产生对免疫球蛋白分子的每个结合位点具有不同特异性的新型双特异性单克隆抗体的方法。 抗体由单个重链和两个不同的轻链组成,一个含有κ恒定结构域,另一个是λ恒定结构域。 本发明提供了分离不同特异性但共享共同重链的抗体的方法。 本发明还提供了两个轻链和单个重链的受控共表达的方法,导致单特异性和双特异性抗体的组装。 本发明提供了产生完全人双特异性和二价抗体的平均值,其依次不变,不涉及使用接头或其它非人序列,以及两种单特异性抗体和一种双特异性抗体的抗体混合物。 本发明还提供有效纯化双特异性抗体的方法。
    • 5. 发明申请
    • READILY ISOLATED BISPECIFIC BINDING MOLECULES WITH NATIVE FORMAT HAVING MUTATED CONSTANT REGIONS
    • 准备隔离的双特异性结合分子与本地格式具有变异的恒定区域
    • WO2015033223A3
    • 2015-10-29
    • PCT/IB2014002388
    • 2014-09-03
    • NOVIMMUNE SA
    • FISCHER NICOLASMAGISTRELLI GIOVANNIROUSSEAU FRANÇOISMASTERNAK KRZYSZTOFMALINGE PAULINE
    • C07K16/24C07K1/00C07K16/28C07K16/46
    • C07K16/468C07K16/244C07K16/2809C07K2317/21C07K2317/31C07K2317/50C07K2317/522C07K2317/526C07K2317/622C07K2317/94
    • The invention provides heterodimer bispecific antigen-binding molecules that include a first polypeptide thai does not include an IgG CH1 domain and a second polypeptide having an immunoglobulin constant region where there is at least one mutation in the IgG CH3 domain that abolishes the ability of the second polypeptide to bind CH3- specific affinity media such that the first and second polypeptides have different affinities with respect to CH1 and CH3 specific affinity reagents that allows rapid isolation by differential binding of the first and second polypeptides to these affinity reagents. The invention also provides bispeeific antibodies that have IgG CH1 and CH3 regions with different affinities with respect to affinity reagents that allows rapid isolation by differential binding of the IgG regions to these affinity reagents. The invention also concerns bispeeific antibodies which are heterodimers of heavy chains, i.e., two immunoglobulin heavy chains that differ by at least two amino acids that allowr for the isolation of the bispeeific antibody based on a differential affinity of one mutated immunoglobulin heavy chain and a second mutated immunoglobulin heavy chain toward two different affinity reagents.
    • 本发明提供了异二聚体双特异性抗原结合分子,其包括不包含IgG CH1结构域的第一多肽和具有免疫球蛋白恒定区的第二多肽,其中IgG CH3结构域中存在至少一个突变,其消除了第二 多肽结合CH3特异性亲和介质,使得第一和第二多肽对于CH1和CH3特异性亲和试剂具有不同的亲和力,其允许通过第一和第二多肽与这些亲和试剂的差异结合来快速分离。 本发明还提供具有对于亲和试剂具有不同亲和力的IgG CH1和CH3区的双特异性抗体,其允许通过IgG区与这些亲和试剂的差异结合来快速分离。 本发明还涉及作为重链异二聚体的双特异性抗体,即两条免疫球蛋白重链相差至少两个氨基酸,允许基于一种突变的免疫球蛋白重链与第二种突变的免疫球蛋白重链的差异亲和力分离双特异性抗体 突变的免疫球蛋白重链朝向两种不同的亲和试剂。