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1. 发明授权

US5175343A Metal radionuclide labeled proteins for diagnosis and therapy 失效
标题翻译：金属放射性核素标记的蛋白质用于诊断和治疗
公开(公告)号：US5175343A
公开(公告)日：1992-12-29
申请号：US065017
申请日：1987-06-19
申请人： Alan R. Fritzberg , Sudhakar Kasina , Ananthachari Srinivasan , Daniel S. Wilbur
发明人： Alan R. Fritzberg , Sudhakar Kasina , Ananthachari Srinivasan , Daniel S. Wilbur
IPC分类号： A61K51/04 , A61K51/10 , A61K51/12 , C07C227/08 , C07C271/22
CPC分类号： C07C271/22 , A61K51/0478 , A61K51/1093 , A61K51/12 , B82Y5/00 , C07C227/08 , A61K2123/00
摘要： Protein conjugated chelated metal radionuclides are provided for use in vivo. Intermediates are provided for preparing the polypeptide compositions efficiently.
摘要翻译：提供蛋白质共轭螯合金属放射性核素用于体内。提供中间体有效地制备多肽组合物。

2. 发明授权

US5120526A Method of producing metal radionuclide labeled proteins for diagnosis and therapy 失效
标题翻译：生产用于诊断和治疗的金属放射性核素标记蛋白质的方法
公开(公告)号：US5120526A
公开(公告)日：1992-06-09
申请号：US650834
申请日：1991-02-04
申请人： Alan R. Fritzberg , Sudhakar Kasina , Ananthachari Srinivasan , Daniel S. Wilbur
发明人： Alan R. Fritzberg , Sudhakar Kasina , Ananthachari Srinivasan , Daniel S. Wilbur
IPC分类号： A61K51/04 , A61K51/10 , A61K51/12 , C07C227/08 , C07C271/22
CPC分类号： C07C271/22 , A61K51/04 , A61K51/0478 , A61K51/1093 , A61K51/12 , B82Y5/00 , C07C227/08 , A61K2123/00 , Y10S530/866
摘要： Protein conjugated chelated metal radionuclides are provided for use in vivo. Intermediates are provided for preparing the polypeptide compositions efficiently.
摘要翻译：提供蛋白质共轭螯合金属放射性核素用于体内。提供中间体有效地制备多肽组合物。

3. 发明授权

US4885153A Radiohalogenated for proteins 失效
标题翻译：放射性卤化蛋白质
公开(公告)号：US4885153A
公开(公告)日：1989-12-05
申请号：US338497
申请日：1989-04-13
申请人： Daniel S. Wilbur , Alan R. Fritzberg , David S. Jones
发明人： Daniel S. Wilbur , Alan R. Fritzberg , David S. Jones
IPC分类号： C07F3/12 , C07F7/22
CPC分类号： C07F7/2212 , C07F3/12
摘要： Haloaryl compounds bearing a defined functional group or precursor are metalated with either Sn(n-Bu).sub.3 or SnMe.sub.3. The resulting aryltin compound may be transmetalated in site-specific reaction with one of the following organometallic groups: HgX.sub.2, Hg(OAc).sub.2, BX.sub.3, or BZ.sub.3, wherein X is Cl, Br, or I, and Z is alkyl or alkoxy. The stannylated or otherwise metalated compounds are subsequently radiohalogenated via a demetalation reaction. The Stannylated or otherwise metalated compounds are subsequently radiohalogenated via a demetalation reaction. The functional group is suitable for conjugation to protein and can be present or be added subsequent, but most preferably prior, to the radiohalogenation.Also compounds of the formula: R.sub.1 --Ar--R.sub.2, wherein R.sub.1 is either a radiohalogen or any one of the organometallic groups stated above, Ar is aromatic or heteroaromatic ring, and R.sub.2 is a short-chain substituent that does not highly activate the aromatic ring an that bears a functional group suitable for conjugation to protein under conditions that preserve the biological activity of the protein. The radiohalogenated small nolecules are conjugated to proteins such as monoclonal antibodies for use in diagnosis and therapy.
摘要翻译：带有限定官能团或前体的卤代芳基化合物与Sn（n-Bu）3或SnMe 3金属化。所得的芳基锡化合物可以与以下有机金属基团之一的位置特异性反应转金属：HgX2，Hg（OAc）2，BX3或BZ3，其中X为Cl，Br或I，Z为烷基或烷氧基。然后通过脱金属反应使经卤化或其它金属化的化合物放射性卤化。然后通过脱金属反应使经卤化或其它金属化的化合物放射性卤化。该官能团适用于与蛋白质缀合，并且可以存在或随后添加，但最优选之前为放射性卤化。还有下式的化合物：R1-Ar-R2，其中R1是放射性卤素或上述有机金属基团中的任一个，Ar是芳族或杂芳族环，R2是不高度活化芳族的短链取代基在保护蛋白质的生物活性的条件下，具有适合于与蛋白质缀合的官能团。放射性卤化的小分子与蛋白质缀合，例如用于诊断和治疗的单克隆抗体。

4. 发明授权

US5059541A Minimal derivatization of proteins 失效
标题翻译：蛋白质的最小衍生物
公开(公告)号：US5059541A
公开(公告)日：1991-10-22
申请号：US187714
申请日：1988-04-29
申请人： Alan R. Fritzberg , Daniel S. Wilbur , Ananthachari Srinivasan , Dennis W. Wester
发明人： Alan R. Fritzberg , Daniel S. Wilbur , Ananthachari Srinivasan , Dennis W. Wester
IPC分类号： A61K51/10
CPC分类号： A61K51/1093 , A61K2123/00 , Y10S436/804 , Y10S436/819
摘要： There is disclosed a process for minimally derivatizing a targeting protein with a radionuclide such that the predominant species of derivatized targeting protein contains one radionuclide group as a single radiolabeled ligand, and whereby the binding characteristics of the targeting protein are minimally affected. There is further disclosed ligands that can chelate a metal radionuclide or bind a halogen radionuclide while providing a means for separating radiolabeled ligand from unradiolabeled ligand.

5. 发明授权

US5045303A Radiohalogenated small molecules for protein labeling 失效
标题翻译：用于蛋白标记的放射性卤代小分子
公开(公告)号：US5045303A
公开(公告)日：1991-09-03
申请号：US137952
申请日：1987-11-23
申请人： Daniel S. Wilbur , Alan R. Fritzberg
发明人： Daniel S. Wilbur , Alan R. Fritzberg
IPC分类号： C07F3/12 , C07F7/22
CPC分类号： C07F7/2212 , C07F3/12
摘要： Haloaryl compounds are lithiated and thereafter metalated with one of the following organometallic groups: Sn(n-Bu).sub.3 or SnMe.sub.3. The resulting aryltin compound can be transmetalated in site-specific reaction with one of the following organometallic groups: HgX, Hg(OAc).sub.2, BX.sub.3, or BZ.sub.2, wherein X is Cl, Br, or I, and Z is alkyl or alkoxy. The metalated compounds are subsequently radiohalogenated via a demetalation reaction. A functional group suitable for conjugation to protein can be added subsequent of preferably prior to the radiohalogenation.Also compounds of the formula: R.sub.1 -Ar-R.sub.2, wherein R.sub.1 is either a radiohalogen or any one of the organometallic groups stated above, Ar is aromatic or heteroaromatic ring, and R.sub.2 is a short-chain substituent that does not activate the aromatic ring and that bears a functional group, or a precursor thereof, suitable for conjugation to protein under conditions that preserve the biological activity of the protein.The radiohalogenated small molecules are conjugated to proteins such as monoclonal antibodies for use in diagnosis and therapy.
摘要翻译：卤代芳基化合物被锂化，然后用以下有机金属组之一金属化：Sn（n-Bu）3或SnMe 3。所得的芳基锡化合物可以在以下有机金属基团之一的位置特异性反应中转金属：HgX，Hg（OAc）2，BX3或BZ2，其中X为Cl，Br或I，Z为烷基或烷氧基。金属化合物随后通过脱金属反应放射卤化。适合于与蛋白质缀合的官能团可以随后优选在放射性卤化之前加入。还有下式的化合物：R1-Ar-R2，其中R1是放射性卤素或上述有机金属基团中的任何一个，Ar是芳族或杂芳族环，R2是不活化芳环的短链取代基并且在保持蛋白质的生物活性的条件下具有适合于与蛋白质缀合的官能团或其前体。放射性卤化的小分子与蛋白质缀合，例如用于诊断和治疗的单克隆抗体。

6. 发明授权

US5213787A Radiohalogenated small molecules for protein labeling 失效
标题翻译：放射性蛋白标记的小分子
公开(公告)号：US5213787A
公开(公告)日：1993-05-25
申请号：US627806
申请日：1990-12-12
申请人： Daniel S. Wilbur , Alan R. Fritzberg
发明人： Daniel S. Wilbur , Alan R. Fritzberg
IPC分类号： C07F3/12 , C07F7/22
CPC分类号： C07F7/2212 , C07F3/12
摘要： Haloaryl compounds are lithiated and thereafter metalated with one of the following organometallic groups: Sn(n-Bu).sub.3 or SnMe.sub.3. The resulting aryltin compound can be transmetalated in site-specific reaction with one of the following organometallic groups: HgX, Hg(OAc).sub.2, BX.sub.3, or BZ.sub.2, wherein X is Cl, Br, or I, and Z is alkyl or alkoxy. The metalated compounds are subsequently radiohalogenated via a demetalation reaction. A functional group suitable for conjugation to protein can be added subsequent or preferably prior to the radiohalogenation.Also compounds of the formula: R.sub.1 -Ar-R.sub.2, wherein R.sub.1 is either a radiohalogen or any one of the organometallic groups stated above, Ar is aromatic or heteroaromatic ring, and R.sub.2 is a short-chain substituent that does not activate the aromatic ring and that bears a functional group, or a precursor thereof, suitable for conjugation to protein under conditions that preserve the biological activity of the protein.The radiohalogenated small molecules are conjugated to proteins such as monoclonal antibodies for use in diagnosis and therapy.
摘要翻译：卤代芳基化合物被锂化，然后用以下有机金属组之一金属化：Sn（n-Bu）3或SnMe 3。所得的芳基锡化合物可以在以下有机金属基团之一的位置特异性反应中转金属：HgX，Hg（OAc）2，BX3或BZ2，其中X为Cl，Br或I，Z为烷基或烷氧基。金属化合物随后通过脱金属反应放射卤化。适于与蛋白质缀合的官能团可以随后或优选在放射性卤化之前添加。还有下式的化合物：R1-Ar-R2，其中R1是放射性卤素或上述有机金属基团中的任何一个，Ar是芳族或杂芳族环，R2是不活化芳环的短链取代基并且在保持蛋白质的生物活性的条件下具有适合于与蛋白质缀合的官能团或其前体。放射性卤化的小分子与蛋白质缀合，例如用于诊断和治疗的单克隆抗体。

7. 发明授权

US5037630A Metal radionuclide labeled proteins for diagnosis and therapy 失效
标题翻译：金属放射性核素标记的蛋白质用于诊断和治疗
公开(公告)号：US5037630A
公开(公告)日：1991-08-06
申请号：US423180
申请日：1989-10-18
申请人： Alan R. Fritzberg , Sudhakar Kasina , Ananthachari Srinivasan , Daniel S. Wilbur
发明人： Alan R. Fritzberg , Sudhakar Kasina , Ananthachari Srinivasan , Daniel S. Wilbur
IPC分类号： A61K51/04 , A61K51/10 , A61K51/12 , C07C227/08 , C07C271/22
CPC分类号： C07C271/22 , A61K51/0478 , A61K51/1093 , A61K51/12 , B82Y5/00 , C07C227/08 , A61K2123/00 , Y10S530/866
摘要： Protein conjugated chelated metal radionuclides are provided for use in vivo. Intermediates are provided for preparing the polypeptide compositions efficiently.
摘要翻译：提供蛋白质共轭螯合金属放射性核素用于体内。提供中间体有效地制备多肽组合物。

8. 发明授权

US5242679A Metal radionuclide labeled proteins for diagnosis and therapy 失效
标题翻译：金属放射性核素标记的蛋白质用于诊断和治疗
公开(公告)号：US5242679A
公开(公告)日：1993-09-07
申请号：US576343
申请日：1990-08-31
申请人： Alan R. Fritzberg , Sudhakar Kasina , Ananthachari Srinivasan , Daniel S. Wilbur
发明人： Alan R. Fritzberg , Sudhakar Kasina , Ananthachari Srinivasan , Daniel S. Wilbur
IPC分类号： A61K51/04 , A61K51/10 , A61K51/12 , C07C227/08 , C07C271/22
CPC分类号： C07C271/22 , A61K51/0478 , A61K51/1093 , A61K51/12 , B82Y5/00 , C07C227/08 , A61K2123/00
摘要： Protein conjugated chelated metal radionuclides are provided for use in vivo. Intermediates are provided for preparing the polypeptide compositions efficiently.
摘要翻译：提供蛋白质共轭螯合金属放射性核素用于体内。提供中间体有效地制备多肽组合物。

9. 发明授权

US4897255A Metal radionuclide labeled proteins for diagnosis and therapy 失效
公开(公告)号：US4897255A
公开(公告)日：1990-01-30
申请号：US65011
申请日：1987-06-19
申请人： Alan R. Fritzberg , Sudhakar Kasina , Ananthachari Srinivasan , Daniel S. Wilbur
发明人： Alan R. Fritzberg , Sudhakar Kasina , Ananthachari Srinivasan , Daniel S. Wilbur
IPC分类号： A61K51/04 , A61K51/10 , A61K51/12 , C07C227/08 , C07C271/22
CPC分类号： C07C271/22 , A61K51/0478 , A61K51/1093 , A61K51/12 , B82Y5/00 , C07C227/08 , A61K2123/00 , Y10S530/866
摘要： Protein conjugated chelated metal radionuclides are provided for use in vivo. Intermediates are provided for preparing the polypeptide compositions efficiently.

10. 发明授权

US07744853B2 Radiolabeled annexins 失效
标题翻译：放射性标记的膜联蛋白
公开(公告)号：US07744853B2
公开(公告)日：2010-06-29
申请号：US11236272
申请日：2005-09-27
申请人： Sudhakar Kasina , John M. Reno , Alan R. Fritzberg , Jonathan Tait
发明人： Sudhakar Kasina , John M. Reno , Alan R. Fritzberg , Jonathan Tait
IPC分类号： A61K51/00 , C07F13/00 , C07K1/00 , C07H1/00
CPC分类号： C07K7/06 , A61K47/54 , A61K47/547 , A61K47/549 , A61K51/087 , A61K51/088 , A61K2123/00 , C07K1/13 , C07K14/4721
摘要： Radiolabeled annexin and modified annexin conjugates useful for imaging vascular thrombi are described. Methods for making and using such radiolabeled annexin conjugates are also provided.
摘要翻译：描述了可用于成像血管血栓的放射性标记的膜联蛋白和修饰的膜联蛋白缀合物。还提供了制备和使用这种放射性标记的膜联蛋白缀合物的方法。

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