公开(公告)号：US07575923B2

公开(公告)日：2009-08-18

申请号：US11418058

申请日：2006-05-05

申请人： Bernd Dorken ,  Gert Riethmuller ,  Peter Kufer ,  Ralf Lutterbuse ,  Ralf Bargou ,  Anja Loffler

发明人： Bernd Dorken ,  Gert Riethmuller ,  Peter Kufer ,  Ralf Lutterbuse ,  Ralf Bargou ,  Anja Loffler

IPC分类号： C12N5/10 ,  C07H21/02 ,  C07H21/04 ,  C12P21/08 ,  A61K39/395

CPC分类号： C07K16/2809 ,  A61K38/00 ,  A61K48/00 ,  A61K2039/505 ,  C07K16/2803 ,  C07K2317/31 ,  C07K2317/34 ,  C07K2319/00

摘要： Described are novel single-chain multifunctional polypeptides comprising at least two binding sites specific for the CD19 and CD3 antigen, respectively. Further provided are polypeptides, wherein the above-described polypeptide comprises at least one further domain, preferably of pre-determined function. Furthermore, polynucleotides encoding said polypeptides as well as to vectors comprising said polynucleotides and host cells transformed therewith and their use in the production of said polypeptides are described. In addition, compositions, preferably pharmaceutical and diagnostic compositions are provided comprising any of the afore-described polypeptides, polynucleotides or vectors. Described is also the use of the afore-mentioned polypeptides, polynucleotides and vectors for the preparation of pharmaceutical compositions for immunotherapy, preferably against B-cell malignancies such as non-Hodgkin lymphoma.

摘要翻译： 描述了分别包含至少两个特异于CD19和CD3抗原的结合位点的新型单链多功能多肽。 还提供多肽，其中上述多肽包含至少一个其它结构域，优选预定义的功能。 此外，描述了编码所述多肽的多核苷酸以及包含所述多核苷酸和由其转化的宿主细胞的载体及其在所述多肽的制备中的用途。 此外，提供组合物，优选药物和诊断组合物，其包含任何上述多肽，多核苷酸或载体。 还描述了上述多肽，多核苷酸和载体用于制备用于免疫治疗的药物组合物，优选抗B细胞恶性肿瘤例如非霍奇金淋巴瘤的用途。

公开(公告)号：US07235641B2

公开(公告)日：2007-06-26

申请号：US10743697

申请日：2003-12-22

申请人： Peter Kufer ,  Meera Berry ,  Patrick Baeuerle ,  Christian Itin

发明人： Peter Kufer ,  Meera Berry ,  Patrick Baeuerle ,  Christian Itin

IPC分类号： C07K16/18 ,  C07K16/28 ,  G01N33/53

CPC分类号： C07K16/30 ,  C07K14/70567 ,  C07K16/2809 ,  C07K2317/31 ,  C07K2317/569 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/21 ,  C07K2319/33 ,  C12N15/8509 ,  C12N2830/008 ,  C12N2830/48

摘要： The present invention discloses bispecific antibodies comprising two antibody variable domains on a single polypeptide chain, wherein a first portion of the bispecific antibody is capable of recruiting the activity of a human immune effector cell by specifically binding to an effector antigen on the human immune effector cell, the first portion consisting of one antibody variable domain, and a second portion of the bispecific antibody specifically binding to a target antigen other than the effector antigen, the target antigen on a target cell other than the human immune effector cell, the second portion comprising one antibody variable domain.

摘要翻译： 本发明公开了在单个多肽链上包含两个抗体可变结构域的双特异性抗体，其中双特异性抗体的第一部分能够通过特异性结合人免疫效应细胞上的效应物抗原募集人免疫效应细胞的活性 ，第一部分由一个抗体可变结构域组成，第二部分特异性结合除效应物抗原之外的靶抗原的双特异性抗体，除人免疫效应细胞以外的靶细胞上的靶抗原，第二部分包含 一个抗体可变结构域。

公开(公告)号：US20070123479A1

公开(公告)日：2007-05-31

申请号：US10554852

申请日：2004-05-26

申请人： Peter Kufer ,  Ralf Lutterbuse ,  Birgit Kohleisen ,  Steven Zeman ,  Patrick Bauerle

发明人： Peter Kufer ,  Ralf Lutterbuse ,  Birgit Kohleisen ,  Steven Zeman ,  Patrick Bauerle

IPC分类号： A61K39/395 ,  A61K48/00

CPC分类号： C07K16/2803 ,  A61K2039/505 ,  C07K2317/31 ,  C07K2317/34 ,  C07K2317/622

摘要： The present invention relates to a pharmaceutical composition comprising a bispecific single chain antibody construct, said bispecific single chain antibody construct comprising binding domains specific for human CD3 and human CD19, wherein the corresponding variable heavy chain regions (VH) and the corresponding variable light chain regions (VL) regions are arranged, from N-terminus to C-terminus, in the order, VH(CD19)-VL(CD19)-VH(CD3)-VL(CD3), VH(CD3)-VL-(CD3)-VH(CD19)-VL(CD19) or VH(CD3)-VL(CD3)-VL(CD19)-VH(CD19). Furthermore, processes for the production of said pharmaceutical compositions as well as medical/pharmaceutical uses for the specific bispecific single chain antibody molecules bearing specificities for the human CD3 antigen and the human CD19 antigen are disclosed.

摘要翻译： 本发明涉及包含双特异性单链抗体构建体的药物组合物，所述双特异性单链抗体构建体包含对人CD3和人CD19特异的结合结构域，其中相应的可变重链区（V H H H） ）和相应的可变轻链区域（V L L）区域从N末端到C末端按顺序排列，V H（CD19）-V （CD19）-V H（CD 3）-V L（CD 3），V H（CD 3） - （CD3）-V H（CD19）-VLL（CD19）或V H（H） （CD 3）-V L（CD 3）-V L（CD 19）-V H（CD 19）。 此外，公开了用于生产所述药物组合物的方法以及对于人CD3抗原和人CD19抗原具有特异性的特异性双特异性单链抗体分子的医学/药物用途。

公开(公告)号：US20060193852A1

公开(公告)日：2006-08-31

申请号：US11418058

申请日：2006-05-05

申请人： Bernd Dorken ,  Gert Riethmuller ,  Peter Kufer ,  Ralf Lutterbuse ,  Ralf Bargou ,  Anja Loffler

发明人： Bernd Dorken ,  Gert Riethmuller ,  Peter Kufer ,  Ralf Lutterbuse ,  Ralf Bargou ,  Anja Loffler

IPC分类号： A61K39/395 ,  C07K16/28

CPC分类号： C07K16/2809 ,  A61K38/00 ,  A61K48/00 ,  A61K2039/505 ,  C07K16/2803 ,  C07K2317/31 ,  C07K2317/34 ,  C07K2319/00

摘要： Described are novel single-chain multifunctional polypeptides comprising at least two binding sites specific for the CD19 and CD3 antigen, respectively. Further provided are polypeptides, wherein the above-described polypeptide comprises at least one further domain, preferably of pre-determined function. Furthermore, polynucleotides encoding said polypeptides as well as to vectors comprising said polynucleotides and host cells transformed therewith and their use in the production of said polypeptides are described. In addition, compositions, preferably pharmaceutical and diagnostic compositions are provided comprising any of the afore-described polypeptides, polynucleotides or vectors. Described is also the use of the afore-mentioned polypeptides, polynucleotides and vectors for the preparation of pharmaceutical compositions for immunotherapy, preferably against B-cell malignancies such as non-Hodgkin lymphoma.

摘要翻译： 描述了分别包含至少两个特异于CD19和CD3抗原的结合位点的新型单链多功能多肽。 还提供多肽，其中上述多肽包含至少一个其它结构域，优选预定义的功能。 此外，描述了编码所述多肽的多核苷酸以及包含所述多核苷酸和由其转化的宿主细胞的载体及其在所述多肽的制备中的用途。 此外，提供组合物，优选药物和诊断组合物，其包含任何上述多肽，多核苷酸或载体。 还描述了上述多肽，多核苷酸和载体用于制备用于免疫治疗的药物组合物，优选抗B细胞恶性肿瘤例如非霍奇金淋巴瘤的用途。

公开(公告)号：US20110262439A1

公开(公告)日：2011-10-27

申请号：US13122271

申请日：2009-10-01

申请人： Peter Kufer ,  Claudia Blümel ,  Roman Kischel

发明人： Peter Kufer ,  Claudia Blümel ,  Roman Kischel

IPC分类号： A61K39/395 ,  C12N15/63 ,  C12N1/00 ,  A61P35/02 ,  C07K16/28 ,  C12P21/02 ,  C07H21/04 ,  A61P35/00 ,  G01N33/566 ,  C12N5/10

CPC分类号： C07K16/2809 ,  A61K39/39558 ,  A61K2039/505 ,  C07K16/005 ,  C07K16/2851 ,  C07K16/2863 ,  C07K16/3069 ,  C07K2317/31 ,  C07K2317/34 ,  C07K2317/622 ,  C07K2317/732 ,  C12N15/1037

摘要： The present invention provides a method for the selection of bispecific single chain antibodies comprising a first binding domain capable of binding to an epitope of CD3 and a second binding domain capable of binding to the extracellular domain cell surface antigens with a high molecular weight extracellular domain. Moreover, the invention provides bispecific single chain antibodies produced by the use of the method of the invention, nucleic acid molecules encoding these antibodies, vectors comprising such nucleic acid molecules and methods for the production of the antibodies. Furthermore, the invention provides pharmaceutical compositions comprising bispecific single chain antibodies of the invention, medical uses of the same and methods for the treatment of diseases comprising the administration of bispecific single chain antibodies of the invention.

摘要翻译： 本发明提供了选择双特异性单链抗体的方法，其包含能够结合CD3表位的第一结合结构域和能够与高分子量细胞外结构域结合细胞外结构域细胞表面抗原的第二结合结构域。 此外，本发明提供了通过使用本发明的方法产生的双特异性单链抗体，编码这些抗体的核酸分子，包含该核酸分子的载体和用于产生抗体的方法。 此外，本发明提供包含本发明的双特异性单链抗体的药物组合物，其医学用途以及治疗包括施用本发明的双特异性单链抗体的疾病的方法。

公开(公告)号：US20080305105A1

公开(公告)日：2008-12-11

申请号：US11754792

申请日：2007-05-29

申请人： Peter Kufer ,  Meera Berry ,  Patrick Baeuerle ,  Christian Itin

发明人： Peter Kufer ,  Meera Berry ,  Patrick Baeuerle ,  Christian Itin

IPC分类号： A61K39/395 ,  C07K16/18 ,  A61P31/00

摘要： The present invention discloses bispecific antibodies comprising two antibody variable domains on a single polypeptide chain, wherein a first portion of the bispecific antibody is capable of recruiting the activity of a human immune effector cell by specifically binding to an effector antigen on the human immune effector cell, the first portion consisting of one antibody variable domain, and a second portion of the bispecific antibody specifically binding to a target antigen other than the effector antigen, the target antigen on a target cell other than the human immune effector cell, the second portion comprising one antibody variable domain.

摘要翻译： 本发明公开了在单个多肽链上包含两个抗体可变结构域的双特异性抗体，其中双特异性抗体的第一部分能够通过特异性结合人免疫效应细胞上的效应物抗原募集人免疫效应细胞的活性 ，第一部分由一个抗体可变结构域组成，第二部分特异性结合除效应物抗原之外的靶抗原的双特异性抗体，除人免疫效应细胞以外的靶细胞上的靶抗原，第二部分包含 一个抗体可变结构域。

公开(公告)号：US20080213256A1

公开(公告)日：2008-09-04

申请号：US10588734

申请日：2005-02-16

申请人： Peter Kufer ,  Ulla Lenkkeri-Schutz ,  Ralf Lutterbuse ,  Birgit Kohleisen

发明人： Peter Kufer ,  Ulla Lenkkeri-Schutz ,  Ralf Lutterbuse ,  Birgit Kohleisen

IPC分类号： A61K39/395 ,  C07K16/18 ,  C12N15/11 ,  C12N15/00 ,  A61K35/00 ,  A61P37/00 ,  A61K31/70 ,  G01N33/567 ,  C12P21/04 ,  C12N5/06

CPC分类号： C07K16/2809 ,  C07K16/2803 ,  C07K16/30 ,  C07K2317/31 ,  C07K2317/34 ,  C07K2317/622

摘要： The present invention provides a bispecific binding molecule, wherein said molecule comprises or consists of at least two domains whereby one of said at least two domains specifically binds to/interacts with the human CD3 complex and said domain comprises an amino acid sequence of an antibody derived light chain, wherein said amino acid sequence is a particularly identified amino acid sequence comprising specific amino acid substitutions, and a second domain is or contains at least one further antigen-interaction-site and/or at least one further effector domain. The invention further provides nucleic acid molecules encoding the bispecific binding molecules of the invention, vectors comprising said nucleic acid molecules and host cells transformed or transfected with said vectors. Moreover, the invention concerns a method for the production of bispecific binding molecules of the invention and compositions comprising the bispecific binding molecules of the invention, the nucleic acid molecules of the invention or the host cells of the invention.

摘要翻译： 本发明提供双特异性结合分子，其中所述分子包含至少两个结构域或由至少两个结构域组成，其中所述至少两个结构域之一与人CD3复合物特异性结合/相互作用，并且所述结构域包含抗体衍生的氨基酸序列 轻链，其中所述氨基酸序列是特别鉴定的包含特定氨基酸取代的氨基酸序列，第二结构域是或含有至少一个其它抗原相互作用位点和/或至少一个其它效应子结构域。 本发明还提供了编码本发明的双特异性结合分子的核酸分子，包含所述核酸分子的载体和用所述载体转化或转染的宿主细胞。 此外，本发明涉及生产本发明的双特异性结合分子的方法和包含本发明的双特异性结合分子，本发明的核酸分子或本发明的宿主细胞的组合物。

公开(公告)号：US20080044413A1

公开(公告)日：2008-02-21

申请号：US11645290

申请日：2006-12-21

申请人： Scott Hammond ,  Peter Kiener ,  Elizabeth Bruckheimer ,  Michael Kinch ,  Shannon Roff ,  Ralf Lutterbuese ,  Petra Lutterbuese ,  Bernd Schlereth ,  Patrick Baeuerle ,  Peter Kufer

发明人： Scott Hammond ,  Peter Kiener ,  Elizabeth Bruckheimer ,  Michael Kinch ,  Shannon Roff ,  Ralf Lutterbuese ,  Petra Lutterbuese ,  Bernd Schlereth ,  Patrick Baeuerle ,  Peter Kufer

IPC分类号： A61K39/395 ,  A61P31/00 ,  A61P35/00 ,  A61P43/00 ,  C07K16/28

CPC分类号： C07K16/2866 ,  C07K16/2809 ,  C07K16/30 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/92 ,  C07K2319/30

摘要： The present invention relates to bispecific single chain antibodies comprising a first binding domain that immunospecifically binds to the T-cell antigen CD3 and a second binding domain that immunospecifically binds to the EphA2 receptor. Such bispecific single chain antibodies are encompassed by the term “EphA2-BiTEs.” The present invention further relates to methods and compositions designed for the treatment, prevention and/or management of disorders associated with aberrant expression and/or activity of EphA2. Such disorders include, but are not limited to, cancer, non-cancer hyperproliferative cell disorders, and infections. The invention further relates to vectors comprising polynucleotides encoding the EphA2-BiTEs of the invention, host cells transformed therewith, and their use in the production of said EphA2-BiTEs. The invention also provides compositions, including pharmaceutical compositions, comprising any of the aforementioned EphA2-BiTEs, polynucleotides or vectors either alone or in combination with one or more prophylactic or therapeutic agents. Also disclosed are methods of screening for said EphA2-BiTEs and kits comprising any of the aforementioned compositions and diagnostic reagents.

摘要翻译： 本发明涉及双特异性单链抗体，其包含免疫特异性结合T细胞抗原CD3的第一结合结构域和免疫特异性结合EphA2受体的第二结合结构域。 这种双特异性单链抗体包括在术语“EphA2-BiTEs”中。 本发明还涉及设计用于治疗，预防和/或控制与EphA2的异常表达和/或活性相关的病症的方法和组合物。 这些疾病包括但不限于癌症，非癌症过度增殖性细胞病症和感染。 本发明还涉及包含编码本发明的EphA2-BiTE的多核苷酸，转化的宿主细胞的载体及其在所述EphA2-BiTE的生产中的用途。 本发明还提供包含单独或与一种或多种预防或治疗剂组合的任何上述EphA2-BiTE，多核苷酸或载体的组合物，包括药物组合物。 还公开了筛选所述EphA2-BiTE和包含任何上述组合物和诊断试剂的试剂盒的方法。

公开(公告)号：US07112324B1

公开(公告)日：2006-09-26

申请号：US09673735

申请日：1999-04-21

申请人： Bernd Dorken ,  Gert Riethmuller ,  Peter Kufer ,  Ralf Lutterbuse ,  Ralf Bargou ,  Anja Loffler

发明人： Bernd Dorken ,  Gert Riethmuller ,  Peter Kufer ,  Ralf Lutterbuse ,  Ralf Bargou ,  Anja Loffler

IPC分类号： C07K16/00

CPC分类号： C07K16/2809 ,  A61K38/00 ,  A61K48/00 ,  A61K2039/505 ,  C07K16/2803 ,  C07K2317/31 ,  C07K2317/34 ,  C07K2319/00

摘要： Described are novel single-chain multifunctional polypeptides comprising at least two binding sites specific for the CD19 and CD3 antigen, respectively. Further provided are polypeptides, wherein the above-described polypeptide comprises at least one further domain, preferably of pre-determined function. Furthermore, polynucleotides encoding said polypeptides as well as to vectors comprising said polynucleotides and host cells transformed therewith and their use in the production of said polypeptides are described, In addition, compositions, preferably pharmaceutical and diagnostic compositions are provided comprising any of the afore-described polypeptides, polynucleotides or vectors. Described is also the use of the afore-mentioned polypeptides, polynucleotides and vectors for the preparation of pharmaceutical compositions for immunotherapy, preferably against B-cell malignancies such as non-Hodgkin lymphoma.

摘要翻译： 描述了分别包含至少两个特异于CD19和CD3抗原的结合位点的新型单链多功能多肽。 还提供多肽，其中上述多肽包含至少一个其它结构域，优选预定义的功能。 此外，还描述了编码所述多肽的多核苷酸以及包含所述多核苷酸和由其转化的宿主细胞的载体及其在产生所述多肽中的用途。此外，提供组合物，优选药物和诊断组合物，包括任何上述 多肽，多核苷酸或载体。 还描述了上述多肽，多核苷酸和载体用于制备用于免疫治疗的药物组合物，优选抗B细胞恶性肿瘤例如非霍奇金淋巴瘤的用途。

公开(公告)号：US06475727B1

公开(公告)日：2002-11-05

申请号：US09402690

申请日：1999-12-17

申请人： Peter Kufer ,  Alfred Zippelius

发明人： Peter Kufer ,  Alfred Zippelius

IPC分类号： C12Q168

CPC分类号： C12Q1/6886 ,  C12Q2600/158

摘要： The present invention relates to primers that specifically hybridize to nucleic acid molecules complementary to the messenger RNA transcribed from genes encoding MAGE tumor-specific antigens or a part thereof or to a complementary strand thereof encoding MAGE tumor specific antigens as well as to diagnostic compositions comprising said antigens. The present invention further relates to methods for detecting disseminated tumor cells employing the primers of the invention as well as methods for preparing a tumor adjuvant vaccine.

摘要翻译： 本发明涉及与编码MAGE肿瘤特异性抗原或编码MAGE肿瘤特异性抗原或其部分或编码MAGE肿瘤特异性抗原的互补链转录的信使RNA互补的核酸分子特异性杂交的引物，以及包含所述 抗原。 本发明还涉及使用本发明的引物检测播散性肿瘤细胞的方法以及制备肿瘤佐剂疫苗的方法。