公开(公告)号：US20030198595A1

公开(公告)日：2003-10-23

申请号：US10150654

申请日：2002-05-17

申请人： IMMUNOMEDICS, INC.

发明人： David M. Goldenberg ,  Hans J. Hansen ,  Shui-On Leung ,  William J. McBride ,  Zhengxing Qu

IPC分类号： A61K051/00 ,  C07K016/46

CPC分类号： A61K51/1048 ,  A61K47/665 ,  A61K47/6879 ,  A61K51/1063 ,  A61K2039/505 ,  B82Y5/00 ,  C07K5/0215 ,  C07K5/1016 ,  C07K5/1019 ,  C07K7/06 ,  C07K16/18 ,  C07K16/3007 ,  C07K16/3046 ,  C07K16/44 ,  C07K16/468 ,  C07K2317/12 ,  C07K2317/13 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2317/622 ,  C07K2317/64 ,  C07K2319/00

摘要： The present invention relates to a bi-specific antibody or antibody fragment having at least one arm that specifically binds a targeted tissue and at least one other arm that specifically binds a targetable construct. The targetable construct comprises a carrier portion which comprises or bears at least one epitope recognizable by at least one arm of said bi-specific antibody or antibody fragment. The targetable construct further comprises one or more therapeutic or diagnostic agents or enzymes. The invention provides constructs and methods for producing the bi-specific antibodies or antibody fragments, as well as methods for using them.

摘要翻译： 本发明涉及具有特异性结合目标组织的至少一个臂的特异性抗体或抗体片段以及特异性结合可靶向构建体的至少一个其他臂。 可靶向构建体包含载体部分，其包含或携带至少一个可被所述双特异性抗体或抗体片段的至少一个臂识别的表位。 可靶向构建物还包含一种或多种治疗剂或诊断剂或酶。 本发明提供用于产生双特异性抗体或抗体片段的构建体和方法，以及使用它们的方法。

公开(公告)号：US20020176856A1

公开(公告)日：2002-11-28

申请号：US10114315

申请日：2002-04-03

申请人： Immunomedics, Inc.

发明人： Shui-On Leung ,  Zhengxing Qu

IPC分类号： A61K039/395

CPC分类号： C23C14/3464 ,  A61K38/00 ,  A61K39/00 ,  A61K47/6807 ,  A61K2039/505 ,  C07K16/2803 ,  C07K16/3007 ,  C07K16/3061 ,  C07K16/4266 ,  C07K2317/54 ,  C07K2319/00 ,  C23C14/10

摘要： Humoral and cellular immune responses against tumor cells and infectious agents are induced in a mammal using an antibody that binds with an epitope of an antigen that is associated with a tumor or an infectious agent, and that contains at least one null-galactosyl epitope. Such an antibody is capable of forming a complex with cells that express the target epitope and with antibodies that bind null-galactosyl epitopes. Suitable antibodies include molecules that contain at least one engineered glycosylation site in the constant region of the heavy chain.

公开(公告)号：US20040013607A1

公开(公告)日：2004-01-22

申请号：US10446689

申请日：2003-05-29

申请人： IMMUNOMEDICS, INC.

发明人： Shui-On Leung ,  Hans Hansen

IPC分类号： A61K051/00 ,  C07K016/46

CPC分类号： C07K16/3061 ,  A61K38/00 ,  A61K47/6851 ,  A61K47/6867 ,  A61K47/6877 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/41 ,  C07K2317/77 ,  C07K2319/00

摘要： A chimeric LL2 monoclonal antibody is described in which the complementarity determining regions (CDRs) of the light and heavy chains of the murine LL2 anti-B-lymphoma, anti-leukemia cell monoclonal antibody has been recombinantly joined to the human kappa and IgG1 constant region domains, respectively, which retains the immunospecificity and B-cell lymphoma and leukemia cell internalization capacity of the parental murine LL2 monoclonal antibody, and which has the potential of exhibiting reduced human anti-mouse antibody production activity. A humanized LL2 monoclonal antibody is described in which the CDRs of the light and heavy chains have been recombinantly joined to a framework sequence of human light and heavy chains variable regions, respectively, and subsequently linked to human kappa and IgG1 constant region domains, respectively, which retains the immunospecificity and B-lymphoma and leukemia cell internalization capacities of the parental murine and chimeric LL2 monoclonal antibodies, and which has the potential for exhibiting reduced human anti-mouse antibody production activity. Vectors for producing recombinant chimeric and humanized chimeric monoclonal antibodies are provided. Isolated DNAs encoding the amino acid sequences of the LL2 variable light and heavy chain and CDR framework regions are described. Conjugates of chimeric and humanized chimeric LL2 antibodies with cytotoxic agents or labels find use in therapy and diagnosis of B-cell lymphomas and leukemias.

摘要翻译： 描述了嵌合LL2单克隆抗体，其中鼠LL2抗B淋巴瘤，抗白血病细胞单克隆抗体的轻链和重链的互补决定区（CDR）已经重组连接到人类κ和IgG1恒定区 分别保留亲本鼠LL2单克隆抗体的免疫特异性和B细胞淋巴瘤和白血病细胞内化能力，其具有降低的人抗小鼠抗体生产活性的潜力。 描述了一种人源化的LL2单克隆抗体，其中轻链和重链的CDR分别重组连接到人轻链和重链可变区的框架序列上，并分别与人类κ和IgG1恒定区结构域连接， 其保留亲本鼠和嵌合LL2单克隆抗体的免疫特异性和B淋巴瘤和白血病细胞内化能力，并且其具有降低的人抗小鼠抗体产生活性的潜力。 提供了用于产生重组嵌合和人源化嵌合单克隆抗体的载体。 描述了编码LL2可变轻链和重链和CDR构架区的氨基酸序列的分离的DNA。 具有细胞毒性剂或标签的嵌合和人源化嵌合LL2抗体的缀合物可用于B细胞淋巴瘤和白血病的治疗和诊断。

公开(公告)号：US20030099629A1

公开(公告)日：2003-05-29

申请号：US10153882

申请日：2002-05-24

申请人： Immunomedics, Inc.

发明人： David M. Goldenberg ,  Hans Hansen ,  Shui-On Leung

IPC分类号： A61K038/48 ,  C07H021/04 ,  C12N009/64 ,  C12P021/02 ,  C12N001/21 ,  C12N015/74

CPC分类号： C12N9/22 ,  A61K38/00 ,  C07K2319/00

摘要： Recombinantly-produced Onconase molecules and fusion proteins containing the same are disclosed. The recombinantly-produced Onconase molecule has the sequence of native Onconase, retains the proper folding of native Onconase and has cytotoxic activity similar to that of Onconase purified from oocytes of Rana pipiens. cDNA coding for Onconase is extended by one triplet which codes for N-formyl-methionine. When expressed recombinantly, the mutant Onconase has N-formyl-methionine as the N-terminal amino acid, and glutaminyl as the penultimate N-terminal residue. Following expression, the N-formyl methionine residue is cleaved and the penultimate glutaminyl residues is cyclized to produce Onconase with an N-terminal pyroglutamate residue, and hence the same structure and function as native Onconase.

摘要翻译： 公开了重组产生的Onconase分子和含有它们的融合蛋白。 重组产生的Onconase分子具有天然Onconase的序列，保留天然Onconase的适当折叠，并具有与从Rana pipiens的卵母细胞纯化的Onconase相似的细胞毒活性。 编码Onconase的cDNA延伸一个编码N-甲酰基 - 甲硫氨酸的三联体。 当重组表达时，突变型Onconase具有N-甲酰基 - 甲硫氨酸作为N-末端氨基酸，谷氨酰胺作为倒数第二个N-末端残基。 在表达后，N-甲酰甲硫氨酸残基被切割，倒数第二的谷氨酰胺残基被环化以产生具有N-末端焦谷氨酸残基的Onconase，因此具有与天然Onconase相同的结构和功能。