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1. 发明授权

US5609847A Treatment methods using metal-binding targeted polypeptide constructs 失效
标题翻译：使用金属结合靶向多肽构建体的治疗方法
公开(公告)号：US5609847A
公开(公告)日：1997-03-11
申请号：US480370
申请日：1995-06-07
申请人： Benjamin A. Belinka, Jr. , Daniel J. Coughlin , Vernon L. Alvarez , Richard Wood
发明人： Benjamin A. Belinka, Jr. , Daniel J. Coughlin , Vernon L. Alvarez , Richard Wood
IPC分类号： A61K49/08 , A61K51/08 , A61K51/00 , A61M36/14
CPC分类号： A61K49/122 , A61K49/085 , A61K49/14 , A61K51/088 , A61K2121/00 , A61K2123/00
摘要： The invention relates to a method of treating a patient in need thereof, including a need for diagnosis or treatment, comprising the administration of a metal complex of a polypeptide construct. The construct comprises a compound of the formula (I): ##STR1## in which, "B" is a hydrocarbon backbone,"P" is a polypeptide capable of targeting particular-cells, tissues or organs of the body,"A" may be the group --NR'--NR"-- or the group --NR'--NR"--L-- in which L may be an aliphatic or aromatic linker group,R, R', and R" may be the same or different and may be hydrogen or an aliphatic group,m is an integer .gtoreq.2, provided that the groups R, R', R", L and "P" of a given chain may be the same or different from the groups R, R', R", L and "P" of another chain,n is an integer .gtoreq.0;or a pharmaceutically acceptable salt thereof. The constructs of the present invention are capable of binding a variety of metallic species.
摘要翻译：本发明涉及治疗有需要的患者的方法，包括需要诊断或治疗，包括施用多肽构建体的金属络合物。构建体包含式（I）的化合物：ckbone，“P”是能够靶向身体的特定细胞，组织或器官的多肽，“A”可以是-NR'-NR“ - 或其中L可以是脂族或芳族连接基团的基团-NR'-NR“-L-可以相同或不同，并且可以是氢或脂族基团，m是整数> / = 2，条件是给定链的基团R，R'，R“，L和”P“可以相同或不同于基团R，R'，R”，L和“ P“，n是整数> / = 0; 或其药学上可接受的盐。本发明的构建体能够结合各种金属物质。

2. 发明授权

US5449761A Metal-binding targeted polypeptide constructs 失效
标题翻译：金属结合靶向多肽构建体
公开(公告)号：US5449761A
公开(公告)日：1995-09-12
申请号：US127351
申请日：1993-09-28
申请人： Benjamin A. Belinka, Jr. , Daniel J. Coughlin , Vernon L. Alvarez , Richard Wood
发明人： Benjamin A. Belinka, Jr. , Daniel J. Coughlin , Vernon L. Alvarez , Richard Wood
IPC分类号： A61K49/08 , A61K51/08 , C07C337/06 , A61K38/00 , C07C335/16
CPC分类号： A61K49/122 , A61K49/085 , A61K49/14 , A61K51/088 , A61K2121/00 , A61K2123/00
摘要： This invention relates to the preparation and use of novel open-chain or cyclic polypeptide constructs in which two or more polypeptide chains, in an open-chain construct, or one or more chains, in a cyclic construct, are chemically derivatized such that the resulting construct exhibits both metal-binding capability and tissue-, organ- or cell-targeting selectivity. In particular, the polypeptide constructs of the present invention comprise compounds of the formula (I): ##STR1## in which, "B" is a hydrocarbon backbone, "P" is a polypeptide capable of targeting particular cells, tissues or organs of the body, "A" may be the group --NR'--NR"-- or the group --NR'--NR"--L-- in which L may be an aliphatic or aromatic linker group, R, R' and R" may be the same or different and may be hydrogen or an aliphatic group, m is an integer .gtoreq.2, provided that the groups R, R', R', L and "P" of a given chain may be the same or different from the groups R, R', R", L and "P" of another chain, n is an integer .gtoreq.0; or a pharmaceutically acceptable salt thereof. The constructs of the present invention are capable of binding a variety of metallic species.
摘要翻译：本发明涉及新型开链或环状多肽构建体的制备和应用，其中开链构建体中的两个或多个多肽链或环状构建体中的一个或多个链化学衍生化，使得得到构建体表现出金属结合能力和组织，器官或细胞靶向选择性。特别地，本发明的多肽构建体包含式（I）的化合物：其中“B”是烃主链，“P”是能够靶向特定细胞，组织或身体的器官“A”可以是基团-NR'-NR“ - 或基团-NR'-NR”-L-，其中L可以是脂族或芳族连接基团R，R'和 R“可以相同或不同，并且可以是氢或脂族基团，m是≥2的整数，条件是给定链的基团R，R'，R'，L和”P“可以是与另一个链的基团R，R'，R“，L”和“P”相同或不同，n为整数> / = 0; 或其药学上可接受的盐。本发明的构建体能够结合各种金属物质。

3. 发明授权

US5593656A Metal-binding targeted polypeptide constructs 失效
标题翻译：金属结合靶向多肽构建体
公开(公告)号：US5593656A
公开(公告)日：1997-01-14
申请号：US487221
申请日：1995-06-07
申请人： Benjamin A. Belinka, Jr. , Daniel J. Coughlin , Vernon L. Alvarez , Richard Wood
发明人： Benjamin A. Belinka, Jr. , Daniel J. Coughlin , Vernon L. Alvarez , Richard Wood
IPC分类号： A61K49/08 , A61K51/08 , A61K51/00 , A61M36/14
CPC分类号： A61K49/122 , A61K49/085 , A61K49/14 , A61K51/088 , A61K2121/00 , A61K2123/00
摘要： This invention relates to the preparation and use of novel open-chain or cyclic polypeptide constructs in which two or more polypeptide chains, in an open-chain construct, or one or more chains, in a cyclic construct, are chemically derivatized such that the resulting construct exhibits both metal-binding capability and tissue-, organ- or cell-targeting selectivity. In particular, the polypeptide constructs of the present invention comprise compounds of the formula (I): ##STR1## in which, "B" is a hydrocarbon backbone, "P" is a polypeptide capable of targeting particular cells, tissues or organs of the body, "A" may be the group --NR'--NR"-- or the group --NR'--NR"--L-- in which L may be an aliphatic or aromatic linker group, R, R', and R" may be the same or different and may be hydrogen or an aliphatic group, m is an integer.gtoreq.2, provided that the groups R, R', R", L and "P" of a given chain may be the same or different from the groups R, R', R", L and "P" of another chain, n is an integer.gtoreq.0; or a pharmaceutically acceptable salt thereof. The constructs of the present invention are capable of binding a variety of metallic species.
摘要翻译：本发明涉及新型开链或环状多肽构建体的制备和应用，其中开链构建体中的两个或多个多肽链或环状构建体中的一个或多个链化学衍生化，使得得到构建体表现出金属结合能力和组织，器官或细胞靶向选择性。特别地，本发明的多肽构建体包含式（I）的化合物：其中“B”是烃主链，“P”是能够靶向特定细胞，组织或身体的器官“A”可以是基团-NR'-NR“ - 或基团-NR'-NR”-L-，其中L可以是脂族或芳族连接基团，R，R' 并且R“可以相同或不同，并且可以是氢或脂族基团，m是整数> / = 2，条件是给定链的基团R，R'，R”，L和“P” 可以与另一个链的基团R，R'，R“，L和”P“相同或不同，n是整数> / = 0; 或其药学上可接受的盐。本发明的构建体能够结合各种金属物质。

4. 发明授权

US5578288A Metal-binding targeted polypeptide constructs 失效
标题翻译：金属结合靶向多肽构建体
公开(公告)号：US5578288A
公开(公告)日：1996-11-26
申请号：US480367
申请日：1995-06-07
申请人： Benjamin A. Belinka, Jr. , Daniel J. Coughlin , Vernon L. Alvarez , Richard Wood
发明人： Benjamin A. Belinka, Jr. , Daniel J. Coughlin , Vernon L. Alvarez , Richard Wood
IPC分类号： A61K49/08 , A61K51/08 , A61K51/00 , A61K38/00 , C07K2/00
CPC分类号： A61K49/122 , A61K49/085 , A61K49/14 , A61K51/088 , A61K2121/00 , A61K2123/00
摘要： This invention relates to the preparation and use of novel open-chain or cyclic polypeptide constructs in which two or more polypeptide chains, in an open-chain construct, or one or more chains, in a cyclic construct, are chemically derivatized such that the resulting construct exhibits both metal-binding capability and tissue-, organ- or cell-targeting selectivity. In particular, the polypeptide constructs of the present invention comprise compounds of the formula (I): ##STR1## in which, "B" is a hydrocarbon backbone, "P" is a polypeptide capable of targeting particular cells, tissues or organs of the body, "A" may be the group --NR'--NR"-- or the group --NR'-- NR"--L-- in which L may be an aliphatic or aromatic linker group, R, R', and R" may be the same or different and may be hydrogen or an aliphatic group, m is an integer.gtoreq.2, provided that the groups R, R', R", L and "P" of a given chain may be the same or different from the groups R, R', R", L and "P" of another chain, n is an integer.gtoreq.0; or a pharmaceutically acceptable salt thereof. The constructs of the present invention are capable of binding a variety of metallic species.
摘要翻译：本发明涉及新型开链或环状多肽构建体的制备和应用，其中开链构建体中的两个或多个多肽链或环状构建体中的一个或多个链化学衍生化，使得得到构建体表现出金属结合能力和组织，器官或细胞靶向选择性。特别地，本发明的多肽构建体包含式（I）的化合物：其中“B”是烃主链，“P”是能够靶向特定细胞，组织或身体的器官“A”可以是基团-NR'-NR“ - 或基团-NR'-NR”-L-，其中L可以是脂族或芳族连接基团，R，R' 并且R“可以相同或不同，并且可以是氢或脂族基团，m是整数> / = 2，条件是给定链的基团R，R'，R”，L和“P” 可以与另一个链的基团R，R'，R“，L和”P“相同或不同，n是整数> / = 0; 或其药学上可接受的盐。本发明的构建体能够结合各种金属物质。

5. 发明授权

US5585468A Substituted thioureas as bifunctional chelators 失效
标题翻译：取代硫脲作为双功能螯合剂
公开(公告)号：US5585468A
公开(公告)日：1996-12-17
申请号：US204197
申请日：1994-06-27
申请人： Daniel J. Coughlin , Benjamin A. Belinka, Jr.
发明人： Daniel J. Coughlin , Benjamin A. Belinka, Jr.
IPC分类号： G01N33/58 , A61K39/44 , A61K47/48 , A61K51/00 , A61K51/08 , A61K51/10 , C07C335/06 , C07C335/14 , C07C335/16 , C07C335/22 , C07C337/06 , C07D207/44 , C07D207/452 , C07D213/34 , C07D213/71 , C09K3/00
CPC分类号： C07D207/452 , A61K47/48 , A61K51/082 , A61K51/088 , A61K51/1093 , C07C335/22 , C07C337/06 , C07D213/71 , A61K2121/00 , A61K2123/00
摘要： This invention relates to chelating agents useful for coupling metal ions to biologically active molecules. In particular, substantial thioureas for chelating metals such as technetium are provided that can be conjugated to a targeting molecule such as an antibody, a peptide or a protein.
摘要翻译： PCT No.PCT / US93 / 03208 Sec。 371日期1994年6月27日第 102（e）日期1994年6月27日PCT提交1993年4月8日PCT公布。出版物WO93 / 21151 日期：1993年10月28日本发明涉及用于将金属离子与生物活性分子偶联的螯合剂。特别地，提供了用于螯合金属例如锝的大量硫脲，其可以与靶向分子例如抗体，肽或蛋白质缀合。

6. 发明授权

US5527885A Bifunctional isothiocyanate derived thiocarbonyls as ligands for metal binding 失效
标题翻译：双官能异硫氰酸酯衍生的硫代羰基作为金属结合的配体
公开(公告)号：US5527885A
公开(公告)日：1996-06-18
申请号：US268445
申请日：1994-06-30
申请人： Daniel J. Coughlin , Benjamin A. Belinka, Jr.
发明人： Daniel J. Coughlin , Benjamin A. Belinka, Jr.
IPC分类号： G01N33/58 , A61K39/44 , A61K47/48 , A61K51/00 , A61K51/08 , A61K51/10 , C07C335/06 , C07C335/14 , C07C335/16 , C07C335/22 , C07C337/06 , C07D207/44 , C07D207/452 , C07D213/34 , C07D213/71 , C09K3/00 , A61K35/14
CPC分类号： C07D207/452 , A61K47/48 , A61K51/082 , A61K51/088 , A61K51/1093 , C07C335/22 , C07C337/06 , C07D213/71 , A61K2121/00 , A61K2123/00
摘要： This invention relates to chelating agents useful for coupling metal ions to biologically active molecules. In particular, isothiocyanate derived thiocarbonyls for chelating metals such as technetium are provided that can be conjugated to a targeting molecule such as an antibody, a peptide or a protein.
摘要翻译：本发明涉及用于将金属离子与生物活性分子偶联的螯合剂。特别地，提供了用于螯合金属例如锝的异硫氰酸酯衍生的硫代羰基，其可以与靶向分子例如抗体，肽或蛋白质缀合。

7. 发明授权

US5495042A Non-alkaline purification of aminophosphonic acids 失效
标题翻译：氨基膦酸的非碱性纯化
公开(公告)号：US5495042A
公开(公告)日：1996-02-27
申请号：US145591
申请日：1993-11-04
申请人： Benjamin A. Belinka, Jr. , Daniel J. Coughlin
发明人： Benjamin A. Belinka, Jr. , Daniel J. Coughlin
IPC分类号： C07D255/02 , C07F9/02 , C07F9/38 , C07F9/6524
CPC分类号： C07F9/6524 , C07F9/025 , C07F9/3817
摘要： A process for the purification of aminophosphonic acids under non-alkaline conditions is described. In particular, aminophosphonic acids are slurred in neutral or acidic water, heated to reflux, cooled and then filtered. Product purities approaching 100% are thus obtained.
摘要翻译：描述了在非碱性条件下纯化氨基膦酸的方法。特别地，氨基膦酸在中性或酸性水中溶解，加热至回流，冷却，然后过滤。因此获得接近100％的产品纯度。

8. 发明授权

US5326856A Bifunctional isothiocyanate derived thiocarbonyls as ligands for metal binding 失效
标题翻译：双官能异硫氰酸酯衍生的硫代羰基作为金属结合的配体
公开(公告)号：US5326856A
公开(公告)日：1994-07-05
申请号：US866375
申请日：1992-04-09
申请人： Daniel J. Coughlin , Benjamin A. Belinka, Jr.
发明人： Daniel J. Coughlin , Benjamin A. Belinka, Jr.
IPC分类号： G01N33/58 , A61K39/44 , A61K47/48 , A61K51/00 , A61K51/08 , A61K51/10 , C07C335/06 , C07C335/14 , C07C335/16 , C07C335/22 , C07C337/06 , C07D207/44 , C07D207/452 , C07D213/34 , C07D213/71 , C09K3/00 , C07C
CPC分类号： C07D207/452 , A61K47/48 , A61K51/082 , A61K51/088 , A61K51/1093 , C07C335/22 , C07C337/06 , C07D213/71 , A61K2121/00 , A61K2123/00
摘要： This invention relates to chelating agents useful for coupling metal ions to biologically active molecules. In particular, isothiocyanate derived thiocarbonyls for chelating metals such as technetium are provided that can be conjugated to a targeting molecule such as an antibody, a peptide or a protein.
摘要翻译：本发明涉及用于将金属离子与生物活性分子偶联的螯合剂。特别地，提供了用于螯合金属例如锝的异硫氰酸酯衍生的硫代羰基，其可以与靶向分子例如抗体，肽或蛋白质缀合。

9. 发明授权

US5156840A Amine-containing porphyrin derivatives 失效
标题翻译：含胺卟啉衍生物
公开(公告)号：US5156840A
公开(公告)日：1992-10-20
申请号：US327881
申请日：1989-03-20
申请人： John W. F. Goers , Hurley D. King , Chyi Lee , Daniel J. Coughlin , Vernon L. Alvarez , John D. Rodwell , Thomas J. McKearn
发明人： John W. F. Goers , Hurley D. King , Chyi Lee , Daniel J. Coughlin , Vernon L. Alvarez , John D. Rodwell , Thomas J. McKearn
IPC分类号： A61K41/00 , A61K47/48 , A61K51/10 , C07K5/083 , G01N33/531 , G01N33/543
CPC分类号： C07K5/0804 , A61K41/0042 , A61K41/0071 , A61K47/48369 , A61K47/48715 , A61K51/10 , A61K51/1093 , G01N33/531 , G01N33/54353 , A61K2121/00
摘要： The invention relates to amine-containing porphyrin derivatives. Theporphyrins can be used as photosensitizers which are useful as therapeutic agents. Also described are methods for preparing conjugates in which a porphyrin derivative is covalently attached to an antibody or antibody fragment. In vivo therapeutic methods utilizing the conjugates are also desired.
摘要翻译：本发明涉及含胺卟啉衍生物。卟啉可用作可用作治疗剂的光敏剂。还描述了制备其中卟啉衍生物与抗体或抗体片段共价连接的缀合物的方法。还需要使用缀合物的体内治疗方法。

10. 发明授权

US4966999A Radiohalogenated compounds for site specific labeling 失效
标题翻译：用于场地特异性标记的放射性卤化化合物
公开(公告)号：US4966999A
公开(公告)日：1990-10-30
申请号：US203793
申请日：1988-06-07
申请人： Daniel J. Coughlin , Benjamin A. Belinka , Vernon L. Alvarez
发明人： Daniel J. Coughlin , Benjamin A. Belinka , Vernon L. Alvarez
IPC分类号： A61K39/395 , A61K51/00 , A61K51/10 , A61P31/04 , A61P31/12 , A61P35/00 , C07B59/00 , C07C215/76 , C07C217/84 , C07C243/22 , C07C243/38 , C07K1/113 , C07K14/00 , C07K14/705 , C07K16/00
CPC分类号： A61K51/1051 , A61K51/1063 , A61K2121/00
摘要： Radiohalogenated compounds which are useful as intermediates for preparing radiohalogenated antibody conjugates in which the radiohalogenated compound is site specifically attached to an oxidized carbohydrate moiety of an antibody or antibody fragment are disclosed. Methods for making the compounds and the antibody conjugates as well as methods of use of the same are also disclosed In particular, phenolic hydrazide and phenolic amine compounds are disclosed.

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