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71. 发明申请

US20130315821A1 Methods and Compositions for Improved F-18 Labeling of Proteins, Peptides and Other Molecules 有权
公开(公告)号：US20130315821A1
公开(公告)日：2013-11-28
申请号：US13897849
申请日：2013-05-20
申请人： Immunomedics, Inc.
发明人： Christopher A. D'Souza , William J. McBride , David M. Goldenberg
IPC分类号： A61K51/10 , A61K51/08
CPC分类号： A61K49/0004 , A61B5/004 , A61K47/6897 , A61K49/06 , A61K51/02 , A61K51/0406 , A61K51/0491 , A61K51/08 , A61K51/082 , A61K51/083 , A61K51/088 , A61K51/109 , A61K2123/00 , B82Y5/00
摘要： The present application discloses compositions and methods of synthesis and use of 18F- or 19F-labeled molecules of use in PET, SPECT and/or MR imaging. Preferably, the 18F or 19F is conjugated to a targeting molecule by formation of a complex with a group IIIA metal and binding of the complex to a bifunctional chelating agent, which may then be directly or indirectly attached to the targeting molecule. In other embodiments, the 18F or 19F labeled moiety may comprise a targetable construct used in combination with a bispecific antibody to target a disease-associated antigen. The disclosed methods and compositions allow the simple and reproducible labeling of molecules at very high efficiency and specific activity in 30 minutes or less. In preferred embodiments, the bifunctional chelating agent bound to 18F- or 19F-metal complex may be conjugated to the molecule to be labeled at a reduced temperature, e.g. room temperature.

72. 发明授权

US08501909B2 Polypeptides having affinity for HER2 有权
标题翻译：对HER2具有亲和力的多肽
公开(公告)号：US08501909B2
公开(公告)日：2013-08-06
申请号：US12735068
申请日：2008-12-22
申请人： Lars Abrahmsén , Nina Herne , Joachim Feldwisch , Christofer Lendel , Vladimir Tolmachev
发明人： Lars Abrahmsén , Nina Herne , Joachim Feldwisch , Christofer Lendel , Vladimir Tolmachev
IPC分类号： A61K38/00 , A61K51/08 , A61K49/00
CPC分类号： A61K51/08 , A61K38/00 , A61K51/088 , C07K16/32
摘要： HER2 binding polypeptides comprising the amino acid sequence EX1 RNAYWEIA LLPNLTNQQK RAFIRKLYDD PSQSSELLX2E AKKLNDSQ wherein X1 in position 2 is M, I or L, and X2 in position 39 is S or C (SEQ ID NO: 1) are disclosed. Moreover, such peptides comprising a chelating environment are disclosed. Also radiolabeled polypeptides formed by the peptides comprising a chelating environment and radionuclides are disclosed. Furthermore, methods of in vivo imaging of the body of a mammalian subject having or suspected of having a cancer characterized by overexpression of HER2 comprising administration of such a radiolabeled polypeptide followed by obtainment of an image of the body using a medical imaging instrument and also methods of treating such cancer are disclosed. Furthermore, the use of such a radiolabeled polypeptide in diagnosis and treatment of cancer characterized by overexpression of HER2. Nucleic acids encoding the polypeptides, expression vectors comprising the nucleic acids and host cells comprising the expression vectors are also disclosed.
摘要翻译： HER2结合多肽包含氨基酸序列EX1 RNAYWEIA LLPNLTNQQK RAFIRKLYDD PSQSSELLX2E AKKLNDSQ，其中位置2中的X1是M，I或L，而位置39的X2是S或C（SEQ ID NO：1）。此外，公开了包含螯合环境的这些肽。还公开了由包含螯合环境和放射性核素的肽形成的放射性标记的多肽。此外，具有或怀疑具有HER2过表达的哺乳动物受试者的身体的体内成像方法包括施用这种放射性标记的多肽，然后使用医学成像仪获得身体的图像，以及方法公开了治疗这种癌症的方法。此外，这种放射性标记的多肽在诊断和治疗HER2过表达的癌症中的应用。还公开了编码多肽的核酸，包含核酸的表达载体和包含表达载体的宿主细胞。

73. 发明申请

US20130149239A1 5-PYRROLIDINYLSULFONYL-ISATIN DERIVATIVES 审中-公开
标题翻译： 5-吡咯烷基磺酰脲 - 衍生物衍生物
公开(公告)号：US20130149239A1
公开(公告)日：2013-06-13
申请号：US13685414
申请日：2012-11-26
申请人： Universitatsklinikum Munster
发明人： Klaus Kopka , Bodo Levkau , Michael Schafers
IPC分类号： A61K51/08 , A61K51/04
CPC分类号： A61K51/087 , A61K51/0446 , A61K51/08 , C07D401/14 , C07D403/12
摘要： The present invention relates to novel 5-pyrrolidinylsulfonyl isatin derivatives, non-peptidyl Caspase binding Radioligands (CbRs) and CbR-transporter conjugates derived from said isatin derivatives, diagnostic compositions comprising said compounds of the invention and their use for non-invasive diagnostic imaging.
摘要翻译：本发明涉及新型5-吡咯烷基磺酰靛红衍生物，衍生自所述靛红衍生物的非肽肽半胱氨酸蛋白酶结合放射性配体（CbR）和CbR-转运蛋白缀合物，包含本发明化合物的诊断组合物及其用于非侵入性诊断成像的用途。

74. 发明授权

US08435490B2 Small peptides specifically bind to colorectal cancers 有权
标题翻译：小肽特异性结合结肠直肠癌
公开(公告)号：US08435490B2
公开(公告)日：2013-05-07
申请号：US12664302
申请日：2008-06-04
申请人： John Martin Abraham , Stephen J. Meltzer
发明人： John Martin Abraham , Stephen J. Meltzer
IPC分类号： A61K51/00 , A61M36/14
CPC分类号： A61K51/08 , C12Q1/485 , G01N33/60
摘要： Cancers are extremely heterogeneous in terms of the frequency and types of mutations present in different malignant tumors. Thus, it is likely that uniform clinical treatment is not optimal for all patients, and that the development of individualized therapeutic regimens may be beneficial. Multiple, unique small peptides bind to cell lines derived from different colon adenocarcinomas. Within two hours of contact, the colorectal cancer cells are able to transfer a 32P radioisotope from the small peptides to cellular proteins; the transfer occurs at a substantially higher rate than in the colorectal cancer cells than in cell lines derived from other cancers or from normal tissues.
摘要翻译：在不同恶性肿瘤中存在的突变的频率和类型方面，癌症是非常不均匀的。因此，对于所有患者来说，统一的临床治疗可能不是最佳的，个体化治疗方案的发展可能是有益的。多个独特的小肽结合来自不同结肠腺癌的细胞系。在接触两小时后，结肠直肠癌细胞能够将32P放射性同位素从小肽转移到细胞蛋白质; 转移发生在比结肠直肠癌细胞中显着更高的速率，而不是来源于其他癌症或来自正常组织的细胞系。

75. 发明授权

US08343458B2 Probes for in vivo targeting of active cysteine proteases 有权
标题翻译：用于体内靶向活性半胱氨酸蛋白酶的探针
公开(公告)号：US08343458B2
公开(公告)日：2013-01-01
申请号：US12418116
申请日：2009-04-03
申请人： Matthew S. Bogyo , Galia Blum , Alicia Berger , Zhen Cheng , Sanjiv S. Gambhir
发明人： Matthew S. Bogyo , Galia Blum , Alicia Berger , Zhen Cheng , Sanjiv S. Gambhir
IPC分类号： A61K51/00 , A61M36/14
CPC分类号： A61K51/08 , A61B6/508 , A61K49/0032 , A61K49/0056 , A61K51/0495 , A61K51/088
摘要： Activity-based probes, which are specific for certain active cysteine proteases (caspase, cathepsin and legumain) and carry radioactive labels, are disclosed. The present probes comprise an acyloxymethyketone (AOMK) “warhead” that binds only to active enzyme. The probes further comprise peptide-like structure that targets the probe to a specific cysteine protease or protease family, and a radiolabel on the probe, which is bound to the targeted enzyme. It has been found that the present probes are stable in vivo and give specific target images distinguishable over background. The preferred probes are labeled with a positron-emitting agent such as 64Cu, 125I (SPECT) and 99mTc (PET). The probes show in vivo half-life and stability well suited for imaging.
摘要翻译：公开了基于活性的探针，其特异于某些活性半胱氨酸蛋白酶（半胱天冬酶，组织蛋白酶和legumain）和携带放射性标记。本发明的探针包括只与活性酶结合的酰氧基甲基酮（AOMK）弹头。探针进一步包含将探针靶向特定半胱氨酸蛋白酶或蛋白酶家族的肽样结构，以及与靶向酶结合的探针上的放射性标记。已经发现本发明的探针在体内是稳定的，并且可以在背景下区分特定的目标图像。优选的探针用正电子发射剂如64Cu，125I（SPECT）和99mTc（PET）标记。探针显示体内半衰期和稳定性，非常适合成像。

76. 发明授权

US08268781B2 Peptide derivatives of exendin-4 有权
标题翻译：毒蜥外泌肽-4的肽衍生物
公开(公告)号：US08268781B2
公开(公告)日：2012-09-18
申请号：US11712978
申请日：2007-03-02
申请人： Martin Gotthardt , Martin Béhé , Thomas Behr , Burkhard J. Göke
发明人： Martin Gotthardt , Martin Béhé , Thomas Behr , Burkhard J. Göke
IPC分类号： C07K14/575
CPC分类号： C07K14/605 , A61K51/08 , C07K14/57563 , G01N33/74
摘要： In the current invention peptides, which are derived from GLP-1 (glucagon-like peptide-1) and exendin-3 and/or exendin-4, are provided which bond to the GLP-receptor and can be used, labeled or unlabeled, for the production of an agent for diagnostic and therapy of benign and malignant diseases, in which GLP-1 receptor expression plays a role.
摘要翻译：在本发明中，提供了衍生自GLP-1（胰高血糖素样肽-1）和毒蜥外泌肽-3和/或毒蜥外泌肽-4的肽，其与GLP-受体结合并可以使用，标记或未标记，用于生产GLP-1受体表达起作用的良性和恶性疾病的诊断和治疗药物。

77. 发明申请

US20120207676A1 NEUROTENSIN ANALOGUES FOR RADIOISOTOPE TARGETING TO NEUROTENSIN RECEPTOR-POSITIVE TUMORS 有权
标题翻译：用于神经递质受体阳性肿瘤的放射线照射的神经递质模拟物
公开(公告)号：US20120207676A1
公开(公告)日：2012-08-16
申请号：US13384418
申请日：2010-07-16
申请人： Anne Gruaz-Guyon , Didier Pelaprat , Jacques Barbet , Dirk Tourwe
发明人： Anne Gruaz-Guyon , Didier Pelaprat , Jacques Barbet , Dirk Tourwe
IPC分类号： A61K51/08 , G01N33/574 , A61K38/17 , C07K14/47
CPC分类号： C07K7/083 , A61K38/00 , A61K51/08 , A61K51/085 , A61K51/088
摘要： The invention relates to a new neurotensin analogue, or a salt thereof, useful for targeting to neurotensin receptor-positive tumors, like ductal pancreatic adenocarcinoma, exocrine pancreatic cancer, invasive ductal breast cancers, colon adeno-carcinoma, small cell lung carcinoma, Ewing sarcoma, meningioma, medulloblastoma and astrocytoma.
摘要翻译：本发明涉及可用于靶向神经降压素受体阳性肿瘤的新型神经降压素类似物或其盐，例如导管胰腺腺癌，外分泌胰腺癌，浸润性导管乳腺癌，结肠腺癌，小细胞肺癌，尤文肉瘤，脑膜瘤，成神经管细胞瘤和星形细胞瘤。

78. 发明授权

US08202509B2 Methods and compositions for improved F-18 labeling of proteins, peptides and other molecules 有权
标题翻译：用于改进蛋白质，肽和其他分子的F-18标记的方法和组合物
公开(公告)号：US08202509B2
公开(公告)日：2012-06-19
申请号：US12958889
申请日：2010-12-02
申请人： William J. McBride , Christopher A. D'Souza , David M. Goldenberg
发明人： William J. McBride , Christopher A. D'Souza , David M. Goldenberg
IPC分类号： A61K51/00 , A61M36/14
CPC分类号： C07K19/00 , A61K47/6897 , A61K51/0406 , A61K51/0491 , A61K51/08 , A61K51/082 , A61K51/083 , A61K51/088 , A61K51/109 , B82Y5/00
摘要： The present application discloses compositions and methods of synthesis and use of 68Ga, 18F or 19F labeled molecules of use in PET or MRI imaging. Preferably, the 18F or 19F is conjugated to a targeting molecule by formation of a complex with a group IIIA metal and binding of the complex to a chelating moiety, which may be directly or indirectly attached to the targeting molecule. In other embodiments, the 68Ga, 18F or 19F labeled moiety may comprise a targetable construct used in combination with a bispecific antibody to target a disease-associated antigen. In more preferred embodiments, a chelating moiety or targetable construct may be conjugated to a targeting molecule, such as an antibody or antibody fragment.
摘要翻译：本申请公开了在PET或MRI成像中合成和使用68Ga，18F或19F标记分子的组合物和方法。优选地，18F或19F通过与IIIA族金属形成络合物并将该复合物与可以直接或间接连接到靶向分子的螯合部分结合而与靶向分子缀合。在其它实施方案中，68Ga，18F或19F标记的部分可以包含与靶向疾病相关抗原的双特异性抗体组合使用的可靶向构建体。在更优选的实施方案中，螯合部分或可靶向构建体可以与靶向分子缀合，例如抗体或抗体片段。

79. 发明申请

US20120141375A1 Anti-Mucin Antibodies for Early Detection and Treatment of Pancreatic Cancer 有权
标题翻译：抗粘蛋白抗体用于早期检测和治疗胰腺癌
公开(公告)号：US20120141375A1
公开(公告)日：2012-06-07
申请号：US13371969
申请日：2012-02-13
申请人： David V. Gold , David M. Goldenberg
发明人： David V. Gold , David M. Goldenberg
IPC分类号： A61K49/00 , A61K49/16 , A61K51/10 , G01N33/574
CPC分类号： A61K47/486 , A61K47/48569 , A61K47/48746 , A61K47/6851 , A61K47/6859 , A61K47/6897 , A61K51/0406 , A61K51/0491 , A61K51/08 , A61K51/088 , A61K51/1045 , A61K51/1057 , A61K51/109 , A61K51/1096 , A61K2039/505 , A61K2039/507 , B82Y5/00 , B82Y15/00 , C07K16/303 , C07K16/3092 , C07K16/44 , C07K2317/24 , C07K2317/31 , C07K2317/54 , C07K2317/55 , C07K2317/565 , C07K2317/76 , G01N33/6854
摘要： Described herein are compositions and methods of use of anti-pancreatic cancer antibodies or fragments thereof, such as murine, chimeric, humanized or human PAM4 antibodies. The antibodies show novel and useful diagnostic characteristics, such as binding with high specificity to pancreatic and other cancers, but not to normal or benign pancreatic tissues and binding to a high percentage of early stage pancreatic cancers. Preferably, the antibodies bind to pancreatic cancer mucins such as MUC1 or MUC5ac and are of use for the detection and diagnosis of early stage pancreatic cancer. In more preferred embodiments, the anti-pancreatic cancer antibodies can be used for immunoassay of serum samples, wherein the immunoassay detects a marker for early stage pancreatic cancer in serum. Most preferably, the serum is extracted with an organic phase, such as butanol, before immunoassay. Alternatively, immunoassay with PAM4 and anti-CA19.9 antibodies may be utilized to improve sensitivity for pancreatic cancer.
摘要翻译：本文描述了使用抗胰腺癌抗体或其片段的组合物和方法，例如鼠，嵌合，人源化或人PAM4抗体。抗体显示出新的和有用的诊断特征，例如对胰腺癌和其他癌症具有高特异性结合，但不对正常或良性胰腺组织结合并结合高百分比的早期胰腺癌。优选地，抗体结合胰腺癌粘蛋白如MUC1或MUC5ac，并且可用于早期胰腺癌的检测和诊断。在更优选的实施方案中，抗胰腺癌抗体可用于血清样品的免疫测定，其中免疫测定检测血清中早期胰腺癌的标志物。最优选地，在免疫测定之前，用有机相如丁醇萃取血清。或者，可以使用具有PAM4和抗CA19.9抗体的免疫测定来提高胰腺癌的敏感性。

80. 发明申请

US20120087863A1 Peptide Derivative and Use of the Same 有权
标题翻译：肽衍生物及其用途
公开(公告)号：US20120087863A1
公开(公告)日：2012-04-12
申请号：US13269345
申请日：2011-10-07
申请人： Hideo Saji , Nobuya Inagaki , Hiroyuki Kimura , Kentaro Toyoda , Konomu Hirao , Hirokazu Matsuda
发明人： Hideo Saji , Nobuya Inagaki , Hiroyuki Kimura , Kentaro Toyoda , Konomu Hirao , Hirokazu Matsuda
IPC分类号： A61K51/08 , A61K49/00 , C07K14/00
CPC分类号： A61K51/08 , A61K51/088 , C07K14/57563
摘要： A new peptide derivative is provided. The peptide derivative is represented by the following general formula (I), where polypeptide ExP is polypeptide that contains completely or partially the amino acid sequence of exendin-4, and a -L-Z group represents a group represented by the following formula (II) that is bonded to an amino acid side chain of or the α-amino group at the N-terminus of the polypeptide ExP,
摘要翻译：提供了一种新的肽衍生物。肽衍生物由以下通式（I）表示，其中多肽ExP是完全或部分含有毒蜥外泌肽-4的氨基酸序列的多肽，-LZ基团表示由下式（II）表示的基团，与多肽ExP的N末端的氨基酸侧链或α-氨基键合，

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