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1. 发明授权

US5804157A Peptide compositions and method of radiolabeling 失效
标题翻译：肽组合物和放射性标记方法
公开(公告)号：US5804157A
公开(公告)日：1998-09-08
申请号：US989434
申请日：1997-12-12
申请人： Ananthachari Srinivasan , Mary Marmion Dyszlewski , Joseph E. Bugaj
发明人： Ananthachari Srinivasan , Mary Marmion Dyszlewski , Joseph E. Bugaj
IPC分类号： A61K51/00 , A61K51/08 , A61P35/00 , C07K14/655 , A61M36/14
CPC分类号： C07K14/6555 , A61K51/083 , A61K51/088
摘要： This invention relates to radiolabeled peptide compositions for radiopharmaceutical use and, more specifically, to radiolabeled peptides for diagnostic or therapeutic use having an unmodified carboxy terminal amino acid. The radiopharmaceutical composition may be used for targeting a selected biological site. The radiolabeled peptide is characterized by having its carboxy terminal amino acid in its carboxylic acid form and the peptide is coupled to a diagnostic or therapeutic radionuclide by a chelating agent. The radiopharmaceutical composition preferably comprises a radiolabeled peptide selected from the group consisting of somatostatin, an analog of somatostatin, a derivative of somatostatin and peptides capable of binding to the somatostatin receptor, where the peptide is coupled to a diagnostic or therapeutic radionuclide by a chelating agent has its carboxy terminal amino acid in its carboxylic acid form.
摘要翻译：本发明涉及用于放射性药物用途的放射性标记肽组合物，更具体地，涉及具有未修饰的羧基末端氨基酸的用于诊断或治疗用途的放射性标记肽。放射性药物组合物可以用于靶向选定的生物部位。放射性标记的肽的特征在于其羧基末端氨基酸为羧酸形式，肽通过螯合剂偶联至诊断或治疗放射性核素。放射性药物组合物优选包含选自生长抑素，生长抑素类似物，生长抑素衍生物和能够结合生长抑素受体的肽的放射性标记的肽，其中肽通过螯合剂偶联至诊断或治疗放射性核素其羧基末端氨基酸呈羧酸形式。

2. 发明授权

US5830431A Radiolabeled peptide compositions for site-specific targeting 失效
标题翻译：用于位点特异性靶向的放射性标记肽组合物
公开(公告)号：US5830431A
公开(公告)日：1998-11-03
申请号：US480373
申请日：1995-06-07
申请人： Ananthachari Srinivasan , Mary Marmion Dyszlewski , Joseph E. Bugaj , Jack L. Erion
发明人： Ananthachari Srinivasan , Mary Marmion Dyszlewski , Joseph E. Bugaj , Jack L. Erion
IPC分类号： A61K51/00 , A61K51/08 , A61P35/00 , C07K14/655 , A61M36/14
CPC分类号： C07K14/6555 , A61K51/083 , A61K51/088
摘要： This invention relates to radiolabeled peptide compositions for radiopharmaceutical use and, more specifically, to radiolabeled peptides for diagnostic or therapeutic use having an unmodified carboxy terminal amino acid. The radiopharmaceutical composition may be used for targeting a selected biological site. The radiolabeled peptide is characterized by having its carboxy terminal amino acid in its carboxylic acid form and the peptide is coupled to a diagnostic or therapeutic radionuclide by a chelating agent. The radiopharmaceutical composition preferably comprises a radiolabeled peptide selected from the group consisting of somatostatin, an analog of somatostatin, a derivative of somatostatin and peptides capable of binding to the somatostatin receptor, where the peptide is coupled to a diagnostic or therapeutic radionuclide by a chelating agent has its carboxy terminal amino acid in its carboxylic acid form.
摘要翻译：本发明涉及用于放射性药物用途的放射性标记肽组合物，更具体地，涉及具有未修饰的羧基末端氨基酸的用于诊断或治疗用途的放射性标记肽。放射性药物组合物可以用于靶向选定的生物部位。放射性标记的肽的特征在于其羧基末端氨基酸为羧酸形式，肽通过螯合剂偶联至诊断或治疗放射性核素。放射性药物组合物优选包含选自生长抑素，生长抑素类似物，生长抑素衍生物和能够结合生长抑素受体的肽的放射性标记的肽，其中肽通过螯合剂偶联至诊断或治疗放射性核素其羧基末端氨基酸呈羧酸形式。

3. 发明申请

US20050191240A1 LABELED NEUROTENSIN DERIVATIVES 失效
标题翻译：标记的神经递质衍生物
公开(公告)号：US20050191240A1
公开(公告)日：2005-09-01
申请号：US10036918
申请日：2001-12-21
申请人： Ananthachari Srinivasan , Jack Erion , Michelle Schmidt
发明人： Ananthachari Srinivasan , Jack Erion , Michelle Schmidt
IPC分类号： A61K38/00 , A61K47/48 , A61K51/00 , A61K51/08 , C07K7/06 , C07K7/08
CPC分类号： A61K51/088 , A61K38/00 , A61K47/6425 , A61K51/085 , C07K7/083
摘要： Peptide analogs of neurotensin are disclosed which are resistant to enzymatic degradation and which retain high binding affinity for neurotensin receptors. Pharmaceutical compositions of these compounds are useful for diagnostic and therapeutic purposes.
摘要翻译：公开了对酶促降解具有抗性并且对神经降压素受体保持高结合亲和力的神经降压素的肽类似物。这些化合物的药物组合物可用于诊断和治疗目的。

4. 发明授权

US5623077A Imidazole based nitrogen sulfur ligands useful in radiographic imaging agents 失效
标题翻译：用于放射成像剂的咪唑基氮硫配体
公开(公告)号：US5623077A
公开(公告)日：1997-04-22
申请号：US420612
申请日：1995-04-10
申请人： Raghavan Rajagopalan , Ananthachari Srinivasan
发明人： Raghavan Rajagopalan , Ananthachari Srinivasan
IPC分类号： C07D233/64 , A61K51/00 , A61K51/04 , C07D233/54 , C07D233/91 , C07D405/12 , C07F13/00
CPC分类号： C07F13/005 , A61K51/0478 , C07D233/64 , C07D405/12 , A61K2123/00
摘要： The present invention relates particularly to novel imidazole based nitrogen-sulfur ligands that are suitable for complexing with a radionuclide, and are useful as general imaging agents for diagnostic purposes.
摘要翻译：本发明特别涉及适用于与放射性核素络合的新型咪唑基氮硫配体，并且可用作用于诊断目的的一般成像剂。

5. 发明授权

US5606028A Anchimeric radiometal chelating compounds 失效
标题翻译：嵌合型放射金属螯合化合物
公开(公告)号：US5606028A
公开(公告)日：1997-02-25
申请号：US532041
申请日：1995-09-21
申请人： Alan R. Fritzberg , Ananthachari Srinivasan
发明人： Alan R. Fritzberg , Ananthachari Srinivasan
IPC分类号： A61K51/00 , A61K51/04 , A61K51/10 , C07C313/28 , C07C323/25 , C07C323/41 , C07C323/60 , C07C331/28 , C07K1/113 , C07K5/06 , C07K14/00 , C07K16/00 , C09K3/00 , G01N33/534 , G01N33/60 , C07K17/02 , A61K51/08
CPC分类号： G01N33/534 , A61K51/0478 , A61K51/1093 , C07C313/28 , C07C331/28 , A61K2123/00
摘要： Anchimeric chelates are disclosed which are capable of rapidly forming stable chelates with radionuclide metals at or below physiological temperature. Bifunctional anchimeric chelates having these same properties are also disclosed which are useful for radiolabeling target specific molecules such as monoclonal antibodies and fragments thereof.
摘要翻译：公开了能够在或低于生理温度下用放射性核素金属快速形成稳定的螯合物的嵌合螯合物。还公开了具有这些相同特性的双功能锚定螯合物，其可用于放射性标记靶特异性分子，例如单克隆抗体及其片段。

6. 发明授权

US5283342A Biotinylated small molecules 失效
标题翻译：生物素化小分子
公开(公告)号：US5283342A
公开(公告)日：1994-02-01
申请号：US895588
申请日：1992-06-09
申请人： Linda M. Gustavson , Ananthachari Srinivasan , Alan R. Fritzberg , John M. Reno , Donald B. Axworthy
发明人： Linda M. Gustavson , Ananthachari Srinivasan , Alan R. Fritzberg , John M. Reno , Donald B. Axworthy
IPC分类号： A61K47/48 , A61K51/04 , A61K51/12 , A61K43/00 , A61K49/02 , C07D235/00 , C07D495/04
CPC分类号： B82Y5/00 , A61K47/48146 , A61K47/48353 , A61K47/48707 , A61K47/4873 , A61K47/48753 , A61K51/0497 , A61K51/1268 , A61K2121/00 , A61K2123/00 , Y10S436/804 , Y10S436/808
摘要： Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin and for improved radiohalogenation of biotin, as well as related compounds, are described.
摘要翻译：公开了与诊断和治疗剂的预靶向递送相关的方法，化合物，组合物和试剂盒。特别地，描述了用于生物素的放射性金属标记和改善生物素的放射性卤化的方法以及相关化合物。

7. 发明授权

US5066789A Targeting substance-diagnostic/therapeutic agent conjugates having Schiff base linkages 失效
标题翻译：具有希夫碱连接的靶向物质 - 诊断/治疗剂缀合物
公开(公告)号：US5066789A
公开(公告)日：1991-11-19
申请号：US415154
申请日：1989-09-29
申请人： Ananthachari Srinivasan , Diana I. Brixner , Vivekananda M. Vrudhula
发明人： Ananthachari Srinivasan , Diana I. Brixner , Vivekananda M. Vrudhula
IPC分类号： A61K47/48 , A61K51/10 , C07D207/40 , C07D207/404 , C07D207/44 , C07D207/452 , C07H15/203 , C07H15/252
CPC分类号： C07D207/404 , A61K47/48338 , A61K47/48715 , A61K51/1093 , C07D207/452 , C07H15/203 , C07H15/252 , A61K2123/00
摘要： Targeting substance-diagnostic/therapeutic agent conjugates joined by stabilized Schiff base or hydrazone linkages are disclosed. In addition, slow release carrier-drug pharmaceuticals are described. The diagnostic and therapeutic conjugates and pharmaceuticals of the present invention provide certain advantages relating to in vivo administration, including controlled release of the active agent at a target site.
摘要翻译：公开了通过稳定的席夫碱或腙键连接的靶向物质 - 诊断/治疗剂缀合物。此外，描述了缓释载体药物药物。本发明的诊断和治疗性缀合物和药物提供与体内施用有关的某些优点，包括活性剂在靶位点的受控释放。

8. 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.

9. 发明授权

US5017693A Methods for introducing a sulfhydryl amino or hydroxyl groups to a compound 失效
标题翻译：将巯基氨基或羟基引入化合物的方法
公开(公告)号：US5017693A
公开(公告)日：1991-05-21
申请号：US454295
申请日：1989-12-19
申请人： Mark D. Hylarides , Ananthachari Srinivasan , Jeffrey N. Fitzner , Vivekananda M. Vrudhula
发明人： Mark D. Hylarides , Ananthachari Srinivasan , Jeffrey N. Fitzner , Vivekananda M. Vrudhula
IPC分类号： A61K47/48
CPC分类号： A61K47/48715 , A61K2121/00 , A61K2123/00
摘要： The present invention provides cleavable conjugates whose linkers contain a labile bond that is cleavable under a variety of mild conditions, including weakly acidic. Since the agent may be bonded directly to the linker, cleavage can result in release of native agent. The invention also provides methods for producing cleavable conjugates. Preferred agents include drugs, toxins, biological response modifiers, radiodiagnostic compounds, radiotherapeutic compounds, and derivatives thereof. The targeting molecule employed in the invention may be an intact molecule, a fragment thereof, or a functional equivalent thereof. In a particularly preferred embodiment, the targeting molecule is a monoclonal antibody directed towards a tumor-associated antigen in man. The invention further provides methods for delivering to the cytoplasm of target cell an agent free of its targeting molecular carrier. A diagnostically therapeutically effective dose of a cleavable conjugate is administered to a warm-blooded animal such as man.Another aspect of the invention provides methods for isolating a compound. The compound binds covalently to a solid phase which has been derivatized with the linkers described above and is released in native form by a variety of mild conditions.An additional aspect of the invention provides methods for introducing into a compound a free sulfhydryl, amino, or hydroxyl group by use of reagents structurally related to the linkers described above. Preferred uses of the method are to add a free amino or a free sulfhydryl group to a protein, such as an antibody, or a drug.
摘要翻译：本发明提供了可切割的缀合物，其接头含有在多种温和条件下可裂解的不稳定键，包括弱酸性。由于试剂可以直接与接头键合，所以裂解可导致天然试剂的释放。本发明还提供了用于产生可切割缀合物的方法。优选的试剂包括药物，毒素，生物反应调节剂，放射性诊断化合物，放射治疗化合物及其衍生物。本发明中使用的靶向分子可以是完整分子，其片段或其功能等同物。在特别优选的实施方案中，靶向分子是针对人类中与肿瘤相关抗原的单克隆抗体。本发明还提供了向靶细胞的细胞质递送不含靶向分子载体的试剂的方法。将可切割缀合物的诊断治疗有效剂量施用于温血动物如人。本发明的另一方面提供了分离化合物的方法。该化合物共价结合到已经用上述接头衍生化的固相，并且通过各种温和条件以天然形式释放。本发明的另一方面提供了通过使用与上述接头结构相关的试剂将化合物引入游离巯基，氨基或羟基的方法。该方法的优选用途是将游离氨基或游离巯基添加到蛋白质例如抗体或药物中。

10. 发明授权

US4988496A 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：US4988496A
公开(公告)日：1991-01-29
申请号：US201134
申请日：1988-05-31
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 comjugates 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.

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