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公开(公告)号：US07319139B2
公开(公告)日：2008-01-15
申请号：US10058069
申请日：2002-01-29
IPC分类号： C12P21/08 , C07K16/00 , A61K39/395 , C12P21/04 , C12N5/06
CPC分类号： C12P21/02 , A61K47/6849 , A61K47/6851 , A61K47/6869 , A61K47/6901 , A61K51/1027 , A61K51/1045 , A61K51/1072 , A61K2039/505 , C07K16/00 , C07K16/2896 , C07K16/30 , C07K16/3069 , C07K2317/24 , C07K2317/52 , C07K2319/00 , C12N15/85
摘要： Methods, compositions and kits comprising dimeric antibodies for the treatment of neoplastic, autoimmune or other disorders are provided. The dimeric antibodies of the instant invention may comprise two antibody molecules (H4L4) having the same antigen binding specificity (homodimers) or, alternatively, may comprise two different antibody molecules having binding specificity for two distinct antigens (heterodimers). In preferred embodiments the antibody molecules comprising the dimers are non-covalently associated.
摘要翻译： 提供了包含用于治疗肿瘤，自身免疫或其它病症的二聚抗体的方法，组合物和试剂盒。 本发明的二聚体抗体可以包含具有相同抗原结合特异性（同源二聚体）的两个抗体分子（H 4 S 4 L 4），或者可以包含两种不同的抗体 对两种不同抗原（异二聚体）具有结合特异性的分子。 在优选的实施方案中，包含二聚体的抗体分子是非共价缔合的。
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公开(公告)号：US06897044B1
公开(公告)日：2005-05-24
申请号：US09238741
申请日：1999-01-28
IPC分类号： C12N15/09 , A61K39/395 , A61K47/48 , A61P1/00 , A61P11/00 , A61P11/02 , A61P11/06 , A61P17/00 , A61P35/00 , A61P37/02 , A61P37/08 , C07K16/28 , C07K16/46 , C12P21/08 , C12N15/00
CPC分类号： C07K16/2887 , A61K47/6835 , A61K2039/505 , C07K16/2851 , C07K16/468 , C07K2317/31 , C07K2317/734
摘要： The present invention relates to a novel process for the preparation of biologically active antibody dimers in a pharmaceutically acceptable composition. The dimers can be composed of two antibody molecules having the same antigen binding specificity and linked through reducible, disulfide, or a non-reducible thioether, bond (homodimer). Alternatively, the dimers can be composed of two different antibody molecules having binding specificity for two distinct antigens (heterodimer). These dimers are useful for inducing hyper-cross-linking of membrane antigens. The present invention further relates to the use of biologically active antibody dimers for the preferential killing or inhibition of selected cell populations in the treatment of diseases such as cancer and autoimmune disorders.
摘要翻译： 本发明涉及一种用于在药学上可接受的组合物中制备生物活性抗体二聚体的新方法。 二聚体可以由具有相同抗原结合特异性的两个抗体分子组成并通过可还原的二硫键或不可还原的硫醚键（同二聚体）连接。 或者，二聚体可以由对两种不同抗原（异二聚体）具有结合特异性的两种不同抗体分子组成。 这些二聚体可用于诱导膜抗原的超交联。 本发明还涉及生物活性抗体二聚体在优先杀死或抑制所选细胞群体治疗诸如癌症和自身免疫疾病的疾病中的用途。
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公开(公告)号：US5606017A
公开(公告)日：1997-02-25
申请号：US468162
申请日：1995-06-06
申请人： David Willner , Pamela A. Trail , H. Dalton King , Sandra J. Hofstead , Robert S. Greenfield , Gary R. Braslawsky
发明人： David Willner , Pamela A. Trail , H. Dalton King , Sandra J. Hofstead , Robert S. Greenfield , Gary R. Braslawsky
IPC分类号： A61K31/70 , A61K31/7028 , A61K31/7034 , A61K31/704 , A61K31/7042 , A61K31/7048 , A61K39/395 , A61K47/48 , A61P35/00 , A61P35/04 , C07G11/00 , C07H15/252 , C07H17/04 , C07K1/113 , C07K14/00 , C07K14/42 , C07K14/485 , C07K14/495 , C07K14/52 , C07K14/54 , C07K14/55 , C07K14/575 , C07K14/62 , C07K14/65 , C07K14/705 , C07K16/00 , C07K19/00 , C07K5/00 , C07D475/00 , C07H15/24 , C07H19/00
CPC分类号： A61K47/48684 , A61K47/48407 , A61K47/48692 , A61K47/48715
摘要： Provided are drug/ligand compounds of Formula (I): ##STR1## in which D is a drug moiety;n is an integer from 1 to 10;p is an integer from 1 to 6;Y is O or NH.sub.2.sup.+ Cl.sup.- ;z is 0 or 1;q is about 1 to about 10;X is a ligand; and,A is a Michael Addition Adduct.In a preferred embodiment, the ligand is an immunoglobulin, preferably a chimeric antibody or fragment thereof. Also provided are formulations comprising as an active ingredient a compound of Formula (I), intermediates useful for preparing the compounds of Formula (I), processes for preparing the compounds of Formula (I), and methods for using the compounds of the invention.
摘要翻译： 提供式（I）的药物/配体化合物：其中D是药物部分; n是1至10的整数; p是1至6的整数; Y是O或NH2 + Cl-; z为0或1; q为约1至约10; X是配体; A是迈克尔加成加成物。 在优选的实施方案中，配体是免疫球蛋白，优选嵌合抗体或其片段。 还提供了包含作为活性成分的式（I）化合物，可用于制备式（I）化合物的中间体，制备式（I）化合物的方法和使用本发明化合物的方法的制剂。
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4.发明授权
公开(公告)号：US5349066A
公开(公告)日：1994-09-20
申请号：US865062
申请日：1992-04-08
IPC分类号： A61K31/70 , A61K31/7028 , A61K31/7034 , A61K31/704 , A61K39/395 , A61K47/48 , A61P35/00 , C07C323/42 , C07C323/44 , C07D213/71 , C07D309/30 , C07H15/252 , C07K16/00 , C12N15/02 , C12P21/08 , C07D211/72 , C07C229/00 , C07C241/00
CPC分类号： C07H15/252 , A61K47/48338 , A61K47/48407 , A61K47/48715 , C07C323/44 , C07D213/71
摘要： The present invention provides novel N-substituted hydrazine bifunctional compounds, novel N-substituted hydrazone derivatives of a cytotoxic reagent incorporating the bifunctional compounds, novel conjugates containing at least one cytotoxic reagent molecule reacted with the bifunctional compound and bound to a molecule reactive with a target cell population, methods for their production, and pharmaceutical compositions and methods for delivering cytotoxic reagents to a target population of cells. The hydrazone bonds of the conjugates of the invention permit the release of free cytotoxic reagent from the conjugates in the acidic external or internal environment of the target cells. The bifunctional compounds, derivatives, conjugates and methods of the invention are useful in antibody-or ligand-mediated drug delivery systems for the preferential killing of a target cell population to treat diseases such as cancers, infections and autoimmune disorders.
摘要翻译： 本发明提供新型N-取代肼双功能化合物，结合双功能化合物的细胞毒性试剂的新N-取代腙衍生物，含有至少一种与双功能化合物反应的细胞毒性试剂分子的结合物，并结合至与靶标反应的分子 细胞群，其生产方法，以及用于将细胞毒性试剂递送至靶细胞群的药物组合物和方法。 本发明的轭合物的腙键可以在靶细胞的酸性外部或内部环境中从缀合物释放游离的细胞毒素试剂。 本发明的双功能化合物，衍生物，缀合物和方法可用于抗体或配体介导的药物递送系统，用于优先杀死靶细胞群以治疗疾病如癌症，感染和自身免疫性疾病。
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公开(公告)号：US20090022658A1
公开(公告)日：2009-01-22
申请号：US12032424
申请日：2008-02-15
申请人： Gary R. Braslawsky , Nabil Hanna , Paul Chinn
发明人： Gary R. Braslawsky , Nabil Hanna , Paul Chinn
IPC分类号： A61K51/10 , C07K16/18 , A61P35/00 , A61K39/395
CPC分类号： C07K16/2887 , A61K47/6849 , A61K47/6851 , A61K47/6869 , A61K47/6901 , A61K51/1027 , A61K51/1045 , A61K51/1072 , A61K2039/505 , C07K16/00 , C07K16/30 , C07K2317/24 , C07K2317/52 , C07K2319/00 , C12N15/85 , C12P21/02
摘要： Novel compounds, compositions and methods comprising modified antibodies are provided. In preferred embodiments the disclosed modified antibodies comprise antibodies having one or more of the constant region domains altered or deleted to afford beneficial physiological properties such as enhanced target localization and rapid blood clearance. The disclosed compounds are particularly useful for the treatment of neoplastic disorders in myelosuppressed patients.
摘要翻译： 提供了包含修饰抗体的新型化合物，组合物和方法。 在优选的实施方案中，所公开的修饰抗体包含具有一个或多个恒定区结构域改变或缺失的抗体，以提供有益的生理特性，例如增强的靶标定位和快速血液清除。 所公开的化合物特别可用于治疗骨髓抑制患者的肿瘤性疾病。
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公开(公告)号：US20080213167A1
公开(公告)日：2008-09-04
申请号：US11840573
申请日：2007-08-17
IPC分类号： A61K51/10 , A61K39/395 , A61P35/04
CPC分类号： A61K39/39541 , A61K39/39558 , A61K47/6829 , A61K47/6849 , A61K2039/505 , A61K2039/507 , C07K16/283 , C07K16/2851 , C07K16/2887 , C07K16/2896 , C07K2317/24 , C07K2317/73 , C07K2317/732 , C07K2317/75 , A61K2300/00
摘要： Methods and kits for the treatment of neoplastic disorders comprising the use of a CD23 antagonist are provided. The CD23 antagonist may be used alone or in combination with chemotherapeutic agents. In particularly preferred embodiments the CD23 antagonists may be used to treat B cell chronic lymphocytic leukemia (B-CLL).
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公开(公告)号：US20110020222A1
公开(公告)日：2011-01-27
申请号：US12789955
申请日：2010-05-28
申请人： Gary R. Braslawsky , Nabil Hanna , Paul Chinn
发明人： Gary R. Braslawsky , Nabil Hanna , Paul Chinn
IPC分类号： A61K51/10 , C07K16/30 , A61K49/00 , A61K39/395 , A61P35/00
CPC分类号： C07K16/2887 , A61K47/6849 , A61K47/6851 , A61K47/6869 , A61K47/6901 , A61K51/1027 , A61K51/1045 , A61K51/1072 , A61K2039/505 , C07K16/00 , C07K16/30 , C07K2317/24 , C07K2317/52 , C07K2319/00 , C12N15/85 , C12P21/02
摘要： Novel compounds, compositions and methods comprising modified antibodies are provided. In preferred embodiments the disclosed modified antibodies comprise antibodies having one or more of the constant region domains altered or deleted to afford beneficial physiological properties such as enhanced target localization and rapid blood clearance. The disclosed compounds are particularly useful for the treatment of neoplastic disorders in myelosuppressed patients.
摘要翻译： 提供了包含修饰抗体的新型化合物，组合物和方法。 在优选的实施方案中，所公开的修饰抗体包含具有一个或多个恒定区结构域改变或缺失的抗体，以提供有益的生理特性，例如增强的靶标定位和快速血液清除。 所公开的化合物特别可用于治疗骨髓抑制患者的肿瘤性疾病。
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公开(公告)号：US07700097B2
公开(公告)日：2010-04-20
申请号：US10880320
申请日：2004-06-28
CPC分类号： C07K16/2896 , A61K2039/505 , C07K16/00 , C07K16/18 , C07K16/2851 , C07K16/30 , C07K2317/24 , C07K2317/52 , C07K2317/53 , C07K2317/622 , C07K2317/624 , C07K2319/00
摘要： The instant invention describes methods of separating or preferentially synthesizing dimers which are linked via at least one interchain disulfide linkage from dimers which are not linked via at least one interchain disulfide linkage from a mixture comprising the two types of polypeptide dimers. These forms can be separated from each other using hydrophobic interaction chromatography. In addition, the invention pertains to connecting peptides that result in the preferential biosynthesis of dimers that are linked via at least one interchain disulfide linkage or that are not linked via at least one interchain disulfide linkage. The invention also pertains to compositions in which a majority of the dimers are linked via at least one interchain disulfide linkage or are not linked via at least one interchain disulfide linkage. The invention still further pertains to novel binding molecules, e.g., comprising connecting peptides of the invention.
摘要翻译： 本发明描述了分离或优先合成二聚体的方法，二聚体通过至少一个链间二硫键连接，二聚体不通过至少一个链间二硫键与包含两种类型的多肽二聚体的混合物连接。 这些形式可以使用疏水相互作用色谱法彼此分离。 此外，本发明涉及连接导致通过至少一个链间二硫键连接或不通过至少一个链间二硫键连接的二聚体的优先生物合成的肽。 本发明还涉及其中大多数二聚体通过至少一个链间二硫键连接或不通过至少一个链间二硫键连接的组合物。 本发明还涉及新颖的结合分子，例如包含连接本发明的肽。
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公开(公告)号：US20080213260A1
公开(公告)日：2008-09-04
申请号：US11840576
申请日：2007-08-17
IPC分类号： A61K39/395 , A61P35/00
CPC分类号： A61K39/39541 , A61K39/39558 , A61K47/6829 , A61K47/6849 , A61K2039/505 , A61K2039/507 , C07K16/283 , C07K16/2851 , C07K16/2887 , C07K16/2896 , C07K2317/24 , C07K2317/73 , C07K2317/732 , C07K2317/75 , A61K2300/00
摘要： Methods and kits for the treatment of neoplastic disorders comprising the use of a CD23 antagonist are provided. The CD23 antagonist may be used alone or in combination with chemotherapeutic agents. In particularly preferred embodiments the CD23 antagonists may be used to treat B cell chronic lymphocytic leukemia (B-CLL).
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公开(公告)号：US20080213168A1
公开(公告)日：2008-09-04
申请号：US11840580
申请日：2007-08-17
IPC分类号： A61K51/10 , A61K39/395 , A61P35/04
CPC分类号： A61K39/39541 , A61K39/39558 , A61K47/6829 , A61K47/6849 , A61K2039/505 , A61K2039/507 , C07K16/283 , C07K16/2851 , C07K16/2887 , C07K16/2896 , C07K2317/24 , C07K2317/73 , C07K2317/732 , C07K2317/75 , A61K2300/00
摘要： Methods and kits for the treatment of neoplastic disorders comprising the use of a CD23 antagonist are provided. The CD23 antagonist may be used alone or in combination with chemotherapeutic agents. In particularly preferred embodiments the CD23 antagonists may be used to treat B cell chronic lymphocytic leukemia (B-CLL).
摘要翻译： 提供了用于治疗包括使用CD23拮抗剂的肿瘤性疾病的方法和试剂盒。 CD23拮抗剂可以单独使用或与化学治疗剂组合使用。 在特别优选的实施方案中，CD23拮抗剂可用于治疗B细胞慢性淋巴细胞白血病（B-CLL）。
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