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1. 发明授权

US07135457B1 Random peptides that bind to gastro-intestinal tract (GIT) transport receptors and related methods 失效
标题翻译：结合胃肠道（GIT）转运受体的随机肽和相关方法
公开(公告)号：US07135457B1
公开(公告)日：2006-11-14
申请号：US09079819
申请日：1998-05-15
申请人： Vernon L. Alvarez , Daniel J. O'Mahony , Imelda J. Lambkin , Catherine A. Patterson , Judith Singleton , Benjamin A. Belinka, Jr. , John M. Carter , Gerard M. Cagney
发明人： Vernon L. Alvarez , Daniel J. O'Mahony , Imelda J. Lambkin , Catherine A. Patterson , Judith Singleton , Benjamin A. Belinka, Jr. , John M. Carter , Gerard M. Cagney
IPC分类号： A61K38/00 , A61K39/00 , C07K5/00 , C07K7/00
CPC分类号： A61K38/28 , A61K9/1635 , A61K9/5153 , A61K47/593 , A61K47/60 , A61K47/62 , A61K47/6937 , B82Y5/00 , C07K14/001
摘要： This invention relates to proteins (e.g., peptides) that are capable of facilitating transport of an active agent through a human or animal gastro-intestinal tissue, and derivatives (e.g., fragments) and analogs thereof, and nucleotide sequences coding for said proteins and derivatives. The proteins of the invention have use in facilitating transport of active agents from the lumenal side of the GIT into the systemic blood system, and/or in targeting active agents to the GIT. Thus, for example, by binding (covalently or noncovalently) a protein of the invention to an orally administered drug, the drug can be targeted to specific receptor sites or transport pathways which are known to operate in the human gastrointestinal tract, thus facilitating its absorption into the systemic system.
摘要翻译：本发明涉及能够促进活性剂通过人或动物胃肠组织及其衍生物（例如片段）及其类似物以及编码所述蛋白质和衍生物的核苷酸序列的蛋白质（例如肽）。本发明的蛋白质用于促进活性剂从GIT的内腔侧输送到全身血液系统中，和/或将活性剂靶向GIT。因此，例如，通过将本发明的蛋白质（共价或非共价）结合到口服给药的药物，该药物可以靶向已知在人胃肠道中操作的特异性受体位点或转运途径，从而有助于其吸收进入系统系统。

2. 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。

3. 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。

4. 发明授权

US07053177B1 Random peptides that bind to gastro-intestinal tract (GIT) transport receptors and related methods 失效
标题翻译：结合胃肠道（GIT）转运受体的随机肽和相关方法
公开(公告)号：US07053177B1
公开(公告)日：2006-05-30
申请号：US09079678
申请日：1998-05-15
申请人： Vernon L. Alvarez , Daniel J. O'Mahony , Imelda J. Lambkin , Catherine A. Patterson , Judith Singleton , Benjamin A. Belinka, Jr. , John M. Carter , Gerard M. Cagney
发明人： Vernon L. Alvarez , Daniel J. O'Mahony , Imelda J. Lambkin , Catherine A. Patterson , Judith Singleton , Benjamin A. Belinka, Jr. , John M. Carter , Gerard M. Cagney
IPC分类号： A61K38/00
CPC分类号： A61K38/28 , A61K47/58 , A61K47/593 , A61K47/60 , A61K47/62 , A61K47/6937
摘要： This invention relates to proteins (e.g., peptides) that are capable of facilitating transport of an active agent through a human or animal gastrointestinal tissue, and derivatives (e.g., fragments) and analogs thereof, and nucleotide sequences coding for said proteins and derivatives. The proteins of the invention have use in facilitating transport of active agents from the lumenal side of the GIT into the systemic blood system, and/or in targeting active agents to the GIT. Thus, for example, by binding (covalently or noncovalently) a protein of the invention to an orally administered drug, the drug can be targeted to specific receptor sites or transport pathways which are known to operate in the human gastrointestinal tract, thus facilitating its absorption into the systemic system.
摘要翻译：本发明涉及能够促进活性剂通过人或动物胃肠组织及其衍生物（例如片段）及其类似物以及编码所述蛋白质和衍生物的核苷酸序列的蛋白质（例如肽）。本发明的蛋白质用于促进活性剂从GIT的内腔侧进入全身血液系统，和/或将活性剂靶向GIT。因此，例如，通过将本发明的蛋白质（共价或非共价）结合到口服给药的药物，该药物可以靶向已知在人胃肠道中操作的特异性受体位点或转运途径，从而有助于其吸收进入系统系统。

5. 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。

6. 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。

7. 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。

8. 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。

9. 发明授权

US06703362B1 Random peptides that bind to gastro-intestinal tract (GIT) transport receptors and related methods 失效
标题翻译：结合胃肠道（GIT）转运受体的随机肽和相关方法
公开(公告)号：US06703362B1
公开(公告)日：2004-03-09
申请号：US09079723
申请日：1998-05-15
申请人： Vernon L. Alvarez , Daniel J. O'Mahony , Imelda J. Lambkin , Catherine A. Patterson , Judith Singleton , Benjamin A. Belinka, Jr. , John M. Carter , Gerard M. Cagney
发明人： Vernon L. Alvarez , Daniel J. O'Mahony , Imelda J. Lambkin , Catherine A. Patterson , Judith Singleton , Benjamin A. Belinka, Jr. , John M. Carter , Gerard M. Cagney
IPC分类号： C12D2106
CPC分类号： C07K7/08 , A61K38/00 , C07K1/047 , C07K5/1013 , C07K5/1016 , C07K14/001
摘要： This invention relates to proteins (e.g., peptides) that are capable of facilitating transport of an active agent through a human or animal gastro-intestinal tissue, and derivatives (e.g., fragments) and analogs thereof, and nucleotide sequences coding for said proteins and derivatives. The proteins of the invention have use in facilitating transport of active agents from the lumenal side of the GIT into the systemic blood system, and/or in targeting active agents to the GIT. Thus, for example, by binding (covalently or noncovalently) a protein of the invention to an orally administered drug, the drug can be targeted to specific receptor sites or transport pathways which are known to operate in the human gastrointestinal tract, thus facilitating its absorption into the systemic system.
摘要翻译：本发明涉及能够促进活性剂通过人或动物胃肠组织及其衍生物（例如片段）及其类似物以及编码所述蛋白质和衍生物的核苷酸序列的蛋白质（例如肽）。本发明的蛋白质用于促进活性剂从GIT的内腔侧输送到全身血液系统中，和/或将活性剂靶向GIT。因此，例如，通过将本发明的蛋白质（共价或非共价）结合到口服给药的药物，该药物可以靶向已知在人胃肠道中操作的特异性受体位点或转运途径，从而有助于其吸收进入系统系统。

10. 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。

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