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41. 发明授权

US5106955A Process for preparation of antibody conjugates 失效
标题翻译：制备抗体的方法
公开(公告)号：US5106955A
公开(公告)日：1992-04-21
申请号：US304987
申请日：1988-11-23
申请人： Noriaki Endo , Yumiko Takeda , Yoshinori Kato , Takeshi Hara
发明人： Noriaki Endo , Yumiko Takeda , Yoshinori Kato , Takeshi Hara
IPC分类号： G01N33/531 , A61K39/395 , A61K45/00 , A61K47/48 , A61P35/00 , C07K1/107 , C07K1/113 , C07K14/00 , C07K16/00
CPC分类号： A61K47/48715 , A61K39/395 , A61K47/48369 , A61K47/48707
摘要： A process for production of antibody conjugates which comprises modification of a part of the amino groups in an antibody or its fragment whose antigen-binding activity is lowered by the modification of its amino groups, with a reversible modifier for protein amino groups, reaction of the antibody or its fragment with a substance bearing a group reactive with the amino group and removal of the residues of the reversible modifier from the amino groups and, when necessary, the residues of the substance bearing a group reactive with the amino group in case they are introduced onto groups other than amino groups. The process according to the present invention gives antibody conjugates with retention of antigen-binding activity and these conjugates have a possibility of being used in affinity chromatography or as a diagnostic agent or a drug for cancer therapy.

42. 发明授权

US5075099A Metal radionuclide chelating compounds for improved chelation kinetics 失效
标题翻译：用于改善螯合动力学的金属放射性核素螯合化合物
公开(公告)号：US5075099A
公开(公告)日：1991-12-24
申请号：US589449
申请日：1990-09-27
申请人： Ananthachari Srinivasan , Alan R. Fritzberg , David S. Jones
发明人： Ananthachari Srinivasan , Alan R. Fritzberg , David S. Jones
IPC分类号： A61K47/48 , A61K51/10 , C07C327/30 , C07C327/32 , C07D207/46 , C07D209/48 , C07D307/18 , C07D405/12
CPC分类号： C07D209/48 , A61K47/48707 , A61K51/1093 , C07C327/30 , C07C327/32 , C07D207/46 , C07D307/18 , C07D405/12 , A61K2121/00 , A61K2123/00
摘要： The present invention provides metal chelating compounds, to chelates and chelate-targeting agent conjugates formed from the chelating compounds, and to methods for making and using these compositions. The chelating compounds incorporate two nitrogen atoms and three sulfur atoms ("N.sub.2 S.sub.3 "), two nitrogen atoms and four sulfur atoms ("N.sub.2 S.sub.4 "), or three nitrogen atoms and three sulfur atoms ("N.sub.3 S.sub.3 "). Metals, and metal oxides, capable of being chelated by the compounds include those that are radionuclides, such as .sup.99m Tc and .sup.186/188 Re.The targeting agent portion of the chelate-targeting agent conjugates provided includes antibodies, peptides, hormones, enzymes and biological response modifiers. Methods for making the conjugates are provided and encompass the addition of a metal, or metal oxide, to a chelating compound prior to attachment to a targeting agent as well as subsequent to the attachment.Another aspect of the invention provides kits for producing chelate-targeting agent conjugates for radiopharmaceutical use.An additional aspect of the invention provides methods for using the chelate-targeting agent conjugates for diagnostic and therapeutic purposes, such as detection of a target site and delivery of a radionuclide to the site, respectively.
摘要翻译：本发明提供金属螯合化合物，由螯合化合物形成的螯合物和螯合靶向试剂缀合物，以及制备和使用这些组合物的方法。螯合化合物包含两个氮原子和三个硫原子（“N2S3”），两个氮原子和四个硫原子（“N2S4”）或三个氮原子和三个硫原子（“N3S3”）。能够被化合物螯合的金属和金属氧化物包括那些是放射性核素，例如99mTc和186 / 188Re。提供的螯合靶向药物缀合物的靶向剂部分包括抗体，肽，激素，酶和生物反应调节剂。提供了制备缀合物的方法，并且包括在附着到靶向剂之前以及在附着之后将金属或金属氧化物加入到螯合化合物中。本发明的另一方面提供了用于制备用于放射性药物用途的螯合靶向剂缀合物的试剂盒。本发明的另一方面提供了用于诊断和治疗目的的螯合靶向试剂缀合物的使用方法，例如分别检测靶位点和将放射性核素递送至位点。

43. 发明授权

US5064956A Process for preparing mono-n-alkylated polyazamacrocycles 失效
标题翻译：制备单正烷基化多氮杂环丙烷的方法
公开(公告)号：US5064956A
公开(公告)日：1991-11-12
申请号：US549791
申请日：1990-07-09
申请人： William J. Kruper, Jr.
发明人： William J. Kruper, Jr.
IPC分类号： A61K47/48 , A61K49/00 , A61K51/04 , A61K51/10 , C07D257/02 , C07D259/00 , C07D403/06 , C07D487/08 , C07F15/00
CPC分类号： C07F15/008 , A61K47/48707 , A61K49/0002 , A61K51/04 , A61K51/1045 , A61K51/109 , A61K51/1093 , C07D257/02 , C07D259/00 , C07D403/06 , C07D487/08 , A61K2121/00 , A61K2123/00
摘要： The invention relates to a novel process to prepare selectively mono-N-alkylated polyazamacrocycles which requires an electrophile with between about one and five equivalents of a suitable macrocycle in a solvent which will not promote a proton transfer.
摘要翻译：本发明涉及一种选择性制备单-N-烷基化多氮杂异丙酰基的新方法，其需要在不会促进质子转移的溶剂中约1至5当量的合适大环的亲电子试剂。

44. 发明授权

US4994560A Functionalized polyamine chelants and radioactive rhodium complexes thereof for conjugation to antibodies 失效
标题翻译：功能化的多胺螯合剂和其放射性铑络合物用于与抗体缀合
公开(公告)号：US4994560A
公开(公告)日：1991-02-19
申请号：US65739
申请日：1987-06-24
申请人： William J. Kruper, Jr. , Douglas K. Pollock , William A. Fordyce , Michael J. Fazio , Muthiah N. Inbasekaran
发明人： William J. Kruper, Jr. , Douglas K. Pollock , William A. Fordyce , Michael J. Fazio , Muthiah N. Inbasekaran
IPC分类号： A61K39/395 , A61K47/48 , A61K49/00 , A61K51/00 , A61K51/10 , C07C211/14 , C07C211/49 , C07C211/50 , C07D257/02 , C07F15/00
CPC分类号： C07D257/02 , A61K47/48707 , A61K49/0002 , A61K51/1093 , C07F15/008 , A61K2123/00
摘要： A group of functionalized polyamine chelants that form complexes with radioactive rhodium are disclosed. The rhodium complexes can be attached to an antibody or antibody fragment and used for therapeutic or diagnostic purposes.

45. 发明授权

US4466951A Intracellular trapping of therapeutics or tracer agents 失效
标题翻译：细胞内捕获治疗剂或示踪剂
公开(公告)号：US4466951A
公开(公告)日：1984-08-21
申请号：US441275
申请日：1982-11-12
申请人： Ray C. Pittman
发明人： Ray C. Pittman
IPC分类号： A61K9/127 , A61K47/48 , A61K51/04 , A61K51/12 , A61K43/00 , A61K49/00
CPC分类号： A61K51/0491 , A61K41/0095 , A61K47/48238 , A61K47/48707 , A61K51/04 , A61K51/0497 , A61K51/1234 , A61K9/1275 , A61K2123/00 , Y10S530/81
摘要： A method is provided for trapping therapeutic or tracer agents within cells to maximize their therapeutic effect or detectability. Primary amine containing therapeutic or tracer agents are bound by reductive deamination to the active carbonyl of cellobiose. The resulting adduct is attached to a targeting agent for introduction into a selected cell. Due to the cellobiose, the adduct remains trapped within the cell to maximize therapeutic or tracer activity. Novel adducts and targeting agent-adduct conjugates are disclosed. A new double label method for measuring protein metabolism is also disclosed.
摘要翻译：提供了一种用于在细胞内捕获治疗剂或示踪剂以最大化其治疗效果或可检测性的方法。含伯胺的治疗或示踪剂通过还原脱氨结合到纤维二糖的活性羰基上。将所得加合物连接到靶向剂以引入所选择的细胞。由于纤维二糖，加合物仍然被捕获在细胞内以最大化治疗或示踪剂活性。公开了新型加合物和靶向剂 - 加合物缀合物。还公开了用于测量蛋白质代谢的新的双标记方法。

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