公开(公告)号：US20070015250A1

公开(公告)日：2007-01-18

申请号：US11487215

申请日：2006-07-14

申请人： David Goldenberg ,  Zhengxing Qu ,  Chien Chang ,  Edmund Rossi ,  Jeng-Dar Yang ,  Diane Nordstrom

发明人： David Goldenberg ,  Zhengxing Qu ,  Chien Chang ,  Edmund Rossi ,  Jeng-Dar Yang ,  Diane Nordstrom

IPC分类号： C12P21/08 ,  C07H21/04 ,  C12P21/06 ,  C12N9/99 ,  C12N5/06 ,  C07K16/18

CPC分类号： C07K16/2896 ,  A61K2039/505 ,  C07K14/005 ,  C07K14/4747 ,  C07K16/00 ,  C07K16/18 ,  C07K16/2803 ,  C07K16/3007 ,  C07K2317/24 ,  C07K2317/31 ,  C12N5/0694 ,  C12N15/85 ,  C12N15/86 ,  C12N2500/90 ,  C12N2501/48 ,  C12N2510/02 ,  C12N2710/20022 ,  C12N2740/10043 ,  C12P21/02

摘要： Disclosed are compositions and methods for increasing the longevity of a cell culture and permitting the increased production of proteins, preferably recombinant proteins, such as antibodies, peptides, enzymes, growth factors, interleukins, interferons, hormones, and vaccines. Cells transfected with an apoptosis-inhibiting gene or vector, such as a triple mutant Bcl-2 gene, can survive longer in culture, resulting in extension of the state and yield of protein biosynthesis. Such transfected cells exhibit maximal cell densities that equal or exceed the maximal density achieved by the parent cell lines. Transfected cells can also be pre-adapted for growth in serum-free medium, greatly decreasing the time required to obtain protein production in serum-free medium. In certain methods, the pre-adapted cells can be used for protein production following transformation under serum-free conditions. The method preferably involves eukaryotic cells, more preferably mammalian cells.

摘要翻译： 公开了用于增加细胞培养物的寿命并允许增加蛋白质生产的组合物和方法，优选重组蛋白，例如抗体，肽，酶，生长因子，白细胞介素，干扰素，激素和疫苗。 用凋亡抑制基因或载体如三重突变体Bcl-2基因转染的细胞可以在培养物中更长时间地存活，导致蛋白质生物合成的状态和产量的延长。 这样的转染细胞表现出最大的细胞密度，其等于或超过由亲本细胞系实现的最大密度。 转染的细胞也可以预先适应于无血清培养基中生长，大大减少了在无血清培养基中获得蛋白质产生所需的时间。 在某些方法中，预先调节的细胞可以在无血清条件下转化后用于蛋白质生产。 该方法优选涉及真核细胞，更优选哺乳动物细胞。

公开(公告)号：US20060228357A1

公开(公告)日：2006-10-12

申请号：US11389358

申请日：2006-03-24

申请人： Chien Chang ,  David Goldenberg ,  William McBride ,  Edmund Rossi

发明人： Chien Chang ,  David Goldenberg ,  William McBride ,  Edmund Rossi

IPC分类号： C12Q1/70 ,  G01N33/574 ,  A61K39/395 ,  C07K14/82 ,  C07K16/30 ,  C07K14/415 ,  A61K39/00 ,  C07K16/46

CPC分类号： C12N9/12 ,  B82Y5/00 ,  B82Y10/00 ,  C07K16/18 ,  C07K16/2803 ,  C07K16/2887 ,  C07K16/3007 ,  C07K16/3092 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2319/00 ,  C07K2319/70 ,  C12Y207/11011

摘要： The present invention concerns methods and compositions for stably tethered structures of defined compositions, which may have multiple functionalities and/or binding specificities. Particular embodiments concern homodimers comprising monomers that contain a dimerization and docking domain attached to a precursor. The precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc. Other embodiments concern tetramers comprising a first and second homodimer, which may be identical or different. The disclosed methods and compositions provide a facile and general way to obtain homodimers, homotetramers and heterotetramers of virtually any functionality and/or binding specificity.

公开(公告)号：US20060228300A1

公开(公告)日：2006-10-12

申请号：US11391584

申请日：2006-03-28

申请人： Chien Chang ,  David Goldenberg ,  William McBride ,  Edmund Rossi

发明人： Chien Chang ,  David Goldenberg ,  William McBride ,  Edmund Rossi

IPC分类号： A61K51/00 ,  A61K39/395

CPC分类号： C07K16/18 ,  A61K39/395 ,  A61K47/65 ,  A61K47/6853 ,  A61K51/088 ,  A61K51/1048 ,  B82Y5/00 ,  B82Y10/00 ,  B82Y30/00 ,  C07K16/283 ,  C07K16/3007 ,  C07K16/468 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2317/569 ,  C07K2319/00 ,  C07K2319/70

摘要： The present invention concerns methods and compositions for stably tethered structures of defined compositions with multiple functionalities and/or binding specificities. Particular embodiments concern stably tethered structures comprising a homodimer of a first monomer, comprising a dimerization and docking domain attached to a first precursor, and a second monomer comprising an anchoring domain attached to a second precursor. The first and second precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc. The disclosed methods and compositions provide a simple, easy to purify way to obtain any binary compound attached to any monomeric compound, or any trinary compound.

公开(公告)号：US20060110793A1

公开(公告)日：2006-05-25

申请号：US11187863

申请日：2005-07-25

申请人： David Goldenberg ,  Zhengxing Qu ,  Eva Horak ,  Ivan Horak ,  Chien Chang ,  Edmund Rossi ,  Jeng-Dar Yang

发明人： David Goldenberg ,  Zhengxing Qu ,  Eva Horak ,  Ivan Horak ,  Chien Chang ,  Edmund Rossi ,  Jeng-Dar Yang

IPC分类号： C07H21/04 ,  C12P21/06 ,  C12N9/00 ,  C07K14/52 ,  C07K14/54 ,  C07K14/56 ,  C07K14/475 ,  C07K16/18 ,  C07K14/505

CPC分类号： C07K16/00 ,  A61K2039/505 ,  C07K14/4747 ,  C07K16/18 ,  C07K16/2803 ,  C07K16/3007 ,  C07K2317/24 ,  C07K2317/31 ,  C12N5/0694 ,  C12N2500/90 ,  C12N2501/48 ,  C12N2510/02 ,  C12P21/02

摘要： Disclosed herein are compositions and methods for increasing the longevity of a cell culture and permitting the increased production of proteins, preferably recombinant proteins, such as antibodies, peptides, enzymes, growth factors, interleukins, interferons, hormones, and vaccines. By transfecting cells in culture with an apoptosis-inhibiting gene or vector, cells in culture can survive longer, resulting in extension of the state and yield of protein biosynthesis. Expression of the apoptosis-inhibitor within the cells, because it does not kill the cells, allows the cells, or an increased fraction thereof, to be maintained in culture for longer periods. This invention then allows for controlled, enhanced protein production of cell lines for commercial and research uses, particularly the enhanced production of growth factors, interferons, interleukins, hormones, enzymes, and monoclonal antibodies, and the like. The method preferentially involves eukaryotic cells in culture, and more advantageously mammalian cells in culture.

公开(公告)号：US20070086942A1

公开(公告)日：2007-04-19

申请号：US11478021

申请日：2006-06-29

申请人： Chien Chang ,  David Goldenberg ,  William McBride ,  Edmund Rossi

发明人： Chien Chang ,  David Goldenberg ,  William McBride ,  Edmund Rossi

IPC分类号： A61K51/00 ,  C12Q1/68 ,  G01N33/53 ,  G01N33/554 ,  C07K16/46

CPC分类号： A61K47/48438 ,  A61K31/00 ,  A61K38/00 ,  A61K47/48415 ,  A61K47/48484 ,  A61K47/485 ,  A61K47/48538 ,  A61K47/48546 ,  A61K47/48561 ,  A61K47/48569 ,  A61K47/6811 ,  A61K47/6817 ,  A61K47/6829 ,  A61K47/6833 ,  A61K47/6843 ,  A61K47/6845 ,  A61K47/6849 ,  A61K47/6851 ,  A61K2039/505 ,  B82Y5/00 ,  B82Y10/00 ,  B82Y15/00 ,  C07K14/475 ,  C07K16/18 ,  C07K16/22 ,  C07K16/28 ,  C07K16/2803 ,  C07K16/2833 ,  C07K16/2851 ,  C07K16/2863 ,  C07K16/2881 ,  C07K16/2887 ,  C07K16/2896 ,  C07K16/3007 ,  C07K16/3092 ,  C07K16/32 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2317/76 ,  C07K2319/30 ,  C07K2319/35 ,  C07K2319/70 ,  C07K2319/74 ,  C12N9/12 ,  C12N9/22 ,  C12N9/96 ,  C12Y207/11001 ,  G01N33/54353 ,  G01N33/588 ,  Y02A50/491

摘要： The present invention concerns methods and compositions for making and using bioactive assemblies of defined compositions, which may have multiple functionalities and/or binding specificities. In particular embodiments, the bioactive assembly is formed using dock-and-lock (DNL) methodology, which takes advantage of the specific binding interaction between dimerization and docking domains (DDD) and anchoring domains (AD) to form the assembly. In various embodiments, one or more effectors may be attached to a DDD or AD sequence. Complementary AD or DDD sequences may be attached to an adaptor module that forms the core of the bioactive assembly, allowing formation of the assembly through the specific DDD/AD binding interactions. Such assemblies may be attached to a wide variety of effector moieties for treatment, detection and/or diagnosis of a disease, pathogen infection or other medical or veterinary condition.

摘要翻译： 本发明涉及用于制备和使用具有多种功能和/或结合特异性的限定组合物的生物活性组合物的方法和组合物。 在特定的实施方案中，生物活性组件使用对接和锁定（DNL）方法形成，其利用二聚化和对接结构域（DDD）和锚定结构域（AD）之间的特异性结合相互作用形成组件。 在各种实施方案中，一个或多个效应物可以连接到DDD或AD序列。 互补AD或DDD序列可以连接到形成生物活性组件核心的适配器模块，从而允许通过特定的DDD / AD结合相互作用形成组装体。 这些组合物可以连接到各种各样的效应部分，用于治疗，检测和/或诊断疾病，病原体感染或其他医学或兽医病症。

公开(公告)号：US20060014245A1

公开(公告)日：2006-01-19

申请号：US11056182

申请日：2005-02-14

申请人： David Goldenberg ,  Hans Hansen ,  Chien-Hsing Chang ,  Sailaja Vanama ,  Edmund Rossi

发明人： David Goldenberg ,  Hans Hansen ,  Chien-Hsing Chang ,  Sailaja Vanama ,  Edmund Rossi

IPC分类号： C07H21/04 ,  C12P21/06 ,  C12N9/22 ,  C12N5/06

CPC分类号： C07K16/2803 ,  A61K47/6817 ,  A61K47/6877 ,  C07K16/2833 ,  C07K2317/24 ,  C07K2317/41 ,  C07K2319/00 ,  C07K2319/33 ,  C12N9/22 ,  C12N2510/02

摘要： Recombinant immunotoxins containing a cytotoxic RNAse fused to an antibody or antibody fragment may be produced in mammalian cell culture. Surprisingly, immunotoxins containing a cytotoxic RNAse fused to the N-terminus of one antibody variable domain can be prepared and retain the ability to specifically bind antigen. The immunotoxins may be used in a variety of therapeutic methods for treating diseases or syndromes associated with unwanted or inappropriate cell proliferation or activation.

公开(公告)号：US20050003403A1

公开(公告)日：2005-01-06

申请号：US10829388

申请日：2004-04-22

申请人： Edmund Rossi ,  Chien Chang ,  William McBride

发明人： Edmund Rossi ,  Chien Chang ,  William McBride

IPC分类号： A61K39/395 ,  C07H21/04 ,  C07K14/475 ,  C07K14/52 ,  C07K16/00 ,  C07K16/30 ,  C07K16/44 ,  C07K16/46 ,  C12N20060101 ,  C12N15/00 ,  C12P21/04 ,  C12Q1/68

CPC分类号： C07K16/44 ,  A61K2039/505 ,  C07K16/3007 ,  C07K16/468 ,  C07K2317/24 ,  C07K2317/626 ,  C07K2318/20 ,  C07K2319/00

摘要： The invention provides for a polyvalent protein complex (PPC) comprising two polypeptide chains generally arranged laterally to one another. Each polypeptide chain typically comprises 3 or 4 “v-regions”, which comprise amino acid sequences capable of forming an antigen binding site when matched with a corresponding v-region on the opposite polypeptide chain. Up to about 6 “v-regions” can be used on each polypeptide chain. The v-regions of each polypeptide chain are connected linearly to one another and may be connected by interspersed linking regions. When arranged in the form of the PPC, the v-regions on each polypeptide chain form individual antigen binding sites.

摘要翻译： 本发明提供了包含两条多肽链的多价蛋白质复合物（PPC），其通常彼此横向排列。 每个多肽链通常包含3或4个“v区”，其包含当与相对的多肽链上的相应v-区域匹配时能够形成抗原结合位点的氨基酸序列。 每个多肽链可以使用多达约6个“v区”。 每个多肽链的v-区域彼此线性连接并且可以通过散在的连接区域连接。 当以PPC的形式排列时，每个多肽链上的v-区域形成单独的抗原结合位点。

公开(公告)号：US09184781B2

公开(公告)日：2015-11-10

申请号：US12250396

申请日：2008-10-13

申请人： Hans Hansen ,  Edmund Rossi ,  Chien-Hsing Ken Chang ,  David M. Goldenberg

发明人： Hans Hansen ,  Edmund Rossi ,  Chien-Hsing Ken Chang ,  David M. Goldenberg

IPC分类号： A61K39/395 ,  H04B1/48

CPC分类号： H04B1/48

摘要： Humanized, chimeric and human anti-CD20 antibodies and CD20 antibody fusion proteins that bind to a human B cell marker, referred to as CD20, which are useful for the treatment and diagnosis of B-cell disorders, such as B-cell malignancies and autoimmune diseases, and methods of treatment and diagnosis are disclosed. Methods of making the humanized, chimeric and human anti-CD20 antibodies are disclosed. A humanized anti-HSG (histamine-succinyl-glycyl) monoclonal antibody designated h679 which binds with high affinity to molecules containing the moiety histamine-succinyl-glycyl (HSG), and methods of making the humanized anti-HSG antibody also are disclosed.

摘要翻译： 结合人B细胞标记（称为CD20）的人源化，嵌合和人抗CD20抗体和CD20抗体融合蛋白，其可用于治疗和诊断B细胞病症，例如B细胞恶性肿瘤和自身免疫 疾病，治疗和诊断方法。 公开了制备人源化，嵌合抗体和人抗CD20抗体的方法。 公开了以高亲和力结合含有组胺 - 琥珀酰 - 甘氨酰（HSG）部分的分子结合的命名为h679的人源化抗HSG（组胺 - 琥珀酰 - 甘氨酰）单克隆抗体，以及制备人源化抗HSG抗体的方法。

公开(公告)号：US20090240037A1

公开(公告)日：2009-09-24

申请号：US12250396

申请日：2008-10-13

申请人： Edmund ROSSI ,  Chien-Hsing Ken CHANG ,  David M. GOLDENBERG ,  Hans HANSEN

发明人： Edmund ROSSI ,  Chien-Hsing Ken CHANG ,  David M. GOLDENBERG ,  Hans HANSEN

IPC分类号： C07K16/00

CPC分类号： H04B1/48

摘要： Humanized, chimeric and human anti-CD20 antibodies and CD20 antibody fusion proteins that bind to a human B cell marker, referred to as CD20, which are useful for the treatment and diagnosis of B-cell disorders, such as B-cell malignancies and autoimmune diseases, and methods of treatment and diagnosis are disclosed. Methods of making the humanized, chimeric and human anti-CD20 antibodies are disclosed. A humanized anti-HSG (histamine-succinyl-glycyl) monoclonal antibody designated h679 which binds with high affinity to molecules containing the moiety histamine-succinyl-glycyl (HSG), and methods of making the humanized anti-HSG antibody also are disclosed.

摘要翻译： 结合人B细胞标记（称为CD20）的人源化，嵌合和人抗CD20抗体和CD20抗体融合蛋白，其可用于治疗和诊断B细胞病症，例如B细胞恶性肿瘤和自身免疫 疾病，治疗和诊断方法。 公开了制备人源化，嵌合抗体和人抗CD20抗体的方法。 公开了以高亲和力结合含有组胺 - 琥珀酰 - 甘氨酰（HSG）部分的分子结合的命名为h679的人源化抗HSG（组胺 - 琥珀酰 - 甘氨酰）单克隆抗体，以及制备人源化抗HSG抗体的方法。

公开(公告)号：US20070092947A1

公开(公告)日：2007-04-26

申请号：US11253666

申请日：2005-10-20

申请人： David Goldenberg ,  Zhengxing Qu ,  Eva Horak ,  Ivan Horak ,  Chien Chang ,  Edmund Rossi ,  Jeng-Dar Yang

发明人： David Goldenberg ,  Zhengxing Qu ,  Eva Horak ,  Ivan Horak ,  Chien Chang ,  Edmund Rossi ,  Jeng-Dar Yang

IPC分类号： C07H21/04 ,  C12P21/02 ,  C07K14/53 ,  C07K14/54 ,  C07K14/56 ,  C12N5/06 ,  C12N5/08

CPC分类号： C12P21/02 ,  C12N2510/02

摘要： Disclosed herein are compositions and methods for increasing the longevity of a cell culture and permitting the increased production of proteins, preferably recombinant proteins, such as antibodies, peptides, enzymes, growth factors, interleukins, interferons, hormones, and vaccines. By transfecting cells in culture with an apoptosis-inhibiting gene or vector, cells in culture can survive longer, resulting in extension of the state and yield of protein biosynthesis. Expression of the apoptosis-inhibitor within the cells, because it does not kill the cells, allows the cells, or an increased fraction thereof, to be maintained in culture for longer periods. This invention then allows for controlled, enhanced protein production of cell lines for commercial and research uses, particularly the enhanced production of growth factors, interferons, interleukins, hormones, enzymes, and monoclonal antibodies, and the like. The method preferentially involves eukaryotic cells in culture, and more advantageously mammalian cells in culture.

摘要翻译： 本文公开了用于增加细胞培养物的寿命并允许增加蛋白质生产的组合物和方法，优选重组蛋白，例如抗体，肽，酶，生长因子，白细胞介素，干扰素，激素和疫苗。 通过用细胞凋亡抑制基因或载体转染培养细胞，培养中的细胞可以长时间存活，导致蛋白质生物合成的状态和产量的延长。 凋亡抑制剂在细胞内的表达，因为它不杀死细胞，允许细胞或其增加的部分在培养物中保持较长时间。 本发明然后允许用于商业和研究用途的细胞系的受控增强的蛋白质生产，特别是生长因子，干扰素，白细胞介素，激素，酶和单克隆抗体的增强生产等。 该方法优先涉及培养中的真核细胞，更有利于培养中的哺乳动物细胞。