公开(公告)号：US20090281035A1

公开(公告)日：2009-11-12

申请号：US12305678

申请日：2007-06-22

申请人： Petrus Johannes Louis Spee ,  Soren Berg Padkaer ,  Birgitte Nissen Friedrichsen ,  Inga Sig Nielsen Norby

发明人： Petrus Johannes Louis Spee ,  Soren Berg Padkaer ,  Birgitte Nissen Friedrichsen ,  Inga Sig Nielsen Norby

IPC分类号： A61K38/17 ,  C07K14/705 ,  C07K16/00 ,  C12P21/02

CPC分类号： C12N15/62 ,  C07K14/7056 ,  C07K14/70596 ,  G01N2333/70596

摘要： Soluble versions of heterodimeric receptors, e.g., CD94/NKG2 receptors, and methods of producing and using such constructs, are described. The constructs comprise soluble fragments of, each receptor monomer, and some constructs further comprise at least one immunoglobulin Fc domain. Exemplary constructs are those wherein (1) each soluble fragment is linked to an immunoglobulin Fc domain, which are then allowed to dimerize, (2) each soluble fragment is linked to an immunoglobulin Fc domain mutated to promote forced dimerization with the correct counterpart, and (3) single-chain constructs where the monomeric receptor fragments are linked, and the C-terminal fragment is linked to an Fc domain.

摘要翻译： 描述了异二聚体受体的可溶性形式，例如CD94 / NKG2受体，以及生产和使用这些构建体的方法。 构建体包含每个受体单体的可溶性片段，并且一些构建体还包含至少一个免疫球蛋白Fc结构域。 示例性构建体是其中（1）每个可溶性片段连接到免疫球蛋白Fc结构域，然后允许其二聚化，（2）每个可溶性片段连接到突变的免疫球蛋白Fc结构域以促进与正确对应物的强制二聚化，以及 （3）其中连接单体受体片段的单链构建体，并且C-末端片段连接于Fc结构域。

公开(公告)号：US20080305117A1

公开(公告)日：2008-12-11

申请号：US11813402

申请日：2006-01-06

申请人： Soren Berg Padkaer ,  Peter Andreas Nicolai Reumert Wagtmann ,  Pieter Spee ,  Stefan Zahn ,  Kristian Kjaergaard

发明人： Soren Berg Padkaer ,  Peter Andreas Nicolai Reumert Wagtmann ,  Pieter Spee ,  Stefan Zahn ,  Kristian Kjaergaard

IPC分类号： A61K39/395 ,  C07K16/00 ,  C12N5/00 ,  G01N33/53 ,  C07H21/00 ,  C12N15/63 ,  C12P21/00 ,  A61P37/00

CPC分类号： C07K16/2803 ,  C07K16/28 ,  C07K2299/00 ,  C07K2317/55 ,  C07K2317/73 ,  C07K2317/76

摘要： The present invention relates to agents and methods that are capable of augmenting NK-mediated killing of target cells by reducing inhibitory KIR signalling without reducing the binding of KIR to HLA-C. As described herein, transduction of negative signaling via KIR, 5 upon binding of KIR to its HLA class I ligand, can involve a ligand-binding induced, conformational reorientation of the KIR molecules allowing interactions to form between adjacent KIRs in specific domains, leading to accelerated clustering. Methods and agents such as mono-clonal antibodies for reducing KIR-mediated inhibition of NK cell cytotoxicity without reducing or blocking HLA-binding by, e.g., reducing or blocking dimerization of KIR, are provided.

摘要翻译： 本发明涉及能够通过减少抑制性KIR信号而不降低KIR与HLA-C的结合来增强NK介导的靶细胞杀伤的试剂和方法。 如本文所述，在KIR与其HLA I类配体结合时通过KIR转导负向信号可涉及KIR分子的配体结合诱导的构象重新取向，允许在特定结构域中的相邻KIR之间形成相互作用，从而导致 加速聚类。 提供了用于减少KIR介导的NK细胞细胞毒性抑制的单克隆抗体的方法和试剂，而不通过例如还原或阻断KIR二聚化来降低或阻断HLA结合。

公开(公告)号：US20090182127A1

公开(公告)日：2009-07-16

申请号：US12305669

申请日：2007-06-22

申请人： Kristian Kjaergaard ,  Jens Jacob Hansen ,  Soren Berg Padkaer

发明人： Kristian Kjaergaard ,  Jens Jacob Hansen ,  Soren Berg Padkaer

IPC分类号： C07K16/46 ,  C07K1/00

CPC分类号： C07K16/468 ,  C07K16/2803 ,  C07K16/36 ,  C07K2317/52

摘要： Bispecific antibodies comprising (a) a first light-heavy chain pair having specificity for a first target and a sufficient number of substitutions in its heavy chain constant domain with respect to a corresponding wild-type antibody of the same isotype to significantly reduce the formation of first heavy chain-first heavy chain dimers and (b) a second light-heavy chain pair comprising a heavy chain having a sequence that is complementary to the sequence of the first pair heavy chain sequence with respect to the formation of intramolecular ionic interactions, wherein the first pair or second pair comprises a substitution in the light chain and complementary substitution in the heavy chain that reduces the ability of the light chain to interact with the heavy chain of the other light chain-heavy chain pair are provided. Methods of producing such antibodies in one or more cells also are provided.

摘要翻译： 双特异性抗体包含（a）相对于相同同种型的相应野生型抗体，其第一轻链与第一靶具有特异性的重链和其重链恒定结构域中的足够数量的取代，以显着减少 第一重链首先重链二聚体和（b）第二轻 - 重链对，其包含相对于形成分子内离子相互作用而具有与第一对重链序列互补的序列的重链，其中 第一对或第二对包括轻链中的取代和重链中的互补取代，其降低轻链与另一轻链 - 重链对的重链相互作用的能力。 还提供了在一个或多个细胞中产生此类抗体的方法。

公开(公告)号：US20090081240A1

公开(公告)日：2009-03-26

申请号：US12244170

申请日：2008-10-02

申请人： Alessandro Moretta ,  Mariella Della Chiesa ,  Pascale Andre ,  Laurent Gauthier ,  Francois Romagne ,  Peter Andreas Nicolai Reumert Wagtmann ,  Ivan Svendsen ,  Stefan Zahn ,  Anders Svensson ,  Matthias Thorolfsson ,  Soren Berg Padkaer ,  Kristian Kjaergaard ,  Pieter Spee ,  Michael Wilken

发明人： Alessandro Moretta ,  Mariella Della Chiesa ,  Pascale Andre ,  Laurent Gauthier ,  Francois Romagne ,  Peter Andreas Nicolai Reumert Wagtmann ,  Ivan Svendsen ,  Stefan Zahn ,  Anders Svensson ,  Matthias Thorolfsson ,  Soren Berg Padkaer ,  Kristian Kjaergaard ,  Pieter Spee ,  Michael Wilken

IPC分类号： C07K16/28 ,  C12N15/13 ,  C12N15/85 ,  C12P21/08 ,  A61K39/395 ,  C12N5/10 ,  A61P35/00

CPC分类号： C07K16/42 ,  C07K16/28 ,  C07K16/2803 ,  C07K2299/00 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92

摘要： Compositions and methods for regulating an immune response in a subject are described. More particularly, described are human antibodies that regulate the activity of NK cells and allow a potentiation of NK cell cytotoxicity in mammalian subjects, and antibodies having antigen-binding properties similar to those of human monoclonal antibody 1-7F9 or 1-4F1. Described also are also fragments and derivatives of such antibodies, as well as pharmaceutical compositions comprising the same and their uses, particularly for use in therapy, to increase NK cell activity or cytotoxicity in subjects.

摘要翻译： 描述了用于调节受试者的免疫应答的组合物和方法。 更具体地，描述了调节NK细胞活性并允许哺乳动物受试者中NK细胞细胞毒性增强的抗体，以及具有与人单克隆抗体1-7F9或1-4F1类似的抗原结合特性的抗体。 还描述了这种抗体的片段和衍生物，以及包含其的药物组合物及其用途，特别是用于治疗，以增加受试者的NK细胞活性或细胞毒性。

公开(公告)号：US20090075340A1

公开(公告)日：2009-03-19

申请号：US12244101

申请日：2008-10-02

申请人： Soren Berg Padkaer ,  Peter Andreas Nicolai Reumert Wagtmann ,  Pieter Spee ,  Stefan Zahn ,  Kristian Kjaergaard ,  Anders Svensson

发明人： Soren Berg Padkaer ,  Peter Andreas Nicolai Reumert Wagtmann ,  Pieter Spee ,  Stefan Zahn ,  Kristian Kjaergaard ,  Anders Svensson

IPC分类号： C12P21/00 ,  C07K16/00 ,  A61K39/395 ,  C12N5/06 ,  C40B30/04 ,  A61K39/00 ,  C07H21/00 ,  C12N15/63 ,  C12N5/10

CPC分类号： C07K16/2803 ,  C07K16/28 ,  C07K2299/00 ,  C07K2317/55 ,  C07K2317/73 ,  C07K2317/76

摘要： The present invention relates to agents and methods that are capable of augmenting NK-mediated killing of target cells by reducing inhibitory KIR signalling without reducing the binding of KIR to HLA-C. As described herein, transduction of negative signaling via KIR, upon binding of KIR to its HLA class I ligand, can involve a ligand-binding induced, conformational reorientation of the KIR molecules allowing interactions to form between adjacent KIRs in specific domains, leading to accelerated clustering. Methods and agents such as monoclonal antibodies for reducing KIR-mediated inhibition of NK cell cytotoxicity without reducing or blocking HLA-binding by, e.g., reducing or blocking dimerization of KIR, are provided.

摘要翻译： 本发明涉及能够通过减少抑制性KIR信号而不降低KIR与HLA-C的结合来增强NK介导的靶细胞杀伤的试剂和方法。 如本文所述，在KIR与其HLA I类配体结合时通过KIR转导负向信号可涉及KIR分子的配体结合诱导的构象重新取向，允许在特定结构域中的相邻KIR之间形成相互作用，从而导致 加速聚类。 提供了诸如单克隆抗体的方法和试剂，用于减少KIR介导的NK细胞细胞毒性的抑制，而不通过例如还原或阻断KIR的二聚化来减少或阻断HLA结合。