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31. 发明授权

US07820164B2 Chimeric, human and humanized anti-CSAP monoclonal antibodies 有权
标题翻译：嵌合，人和人源化抗CSAP单克隆抗体
公开(公告)号：US07820164B2
公开(公告)日：2010-10-26
申请号：US12686011
申请日：2010-01-12
申请人： Hans J. Hansen , David M. Goldenberg
发明人： Hans J. Hansen , David M. Goldenberg
IPC分类号： A61K39/395 , C07K16/30
CPC分类号： C07K16/3076 , A61K45/06 , A61K47/6803 , A61K47/6851 , A61K47/6863 , A61K47/6879 , A61K47/6897 , A61K51/1045 , A61K51/1048 , A61K51/1063 , A61K2039/505 , B82Y5/00 , C07K16/18 , C07K16/30 , C07K16/3007 , C07K16/3046 , C07K16/3092 , C07K16/44 , C07K16/468 , C07K2317/12 , C07K2317/13 , C07K2317/21 , C07K2317/24 , C07K2317/31 , C07K2317/55 , C07K2317/622 , C07K2319/00 , Y10S436/813 , Y10S436/819
摘要： The present invention provides humanized, chimeric and human anti-CSAp antibodies and anti-CSAp antibody fusion proteins that are useful for the treatment and diagnosis of various cancers, including colon cancer.
摘要翻译：本发明提供可用于治疗和诊断包括结肠癌在内的各种癌症的人源化，嵌合和人抗CSAp抗体和抗CSAp抗体融合蛋白。

32. 发明授权

US07803372B2 Antibody therapy 有权
标题翻译：抗体治疗
公开(公告)号：US07803372B2
公开(公告)日：2010-09-28
申请号：US10680734
申请日：2003-10-08
申请人： David M. Goldenberg , Hans J. Hansen
发明人： David M. Goldenberg , Hans J. Hansen
IPC分类号： C07K16/18 , C07K16/30 , A61K39/395 , A61K51/10
CPC分类号： A61K39/39558 , A61K31/437 , A61K31/4545 , A61K31/4745 , A61K31/475 , A61K31/513 , A61K31/519 , A61K31/555 , A61K31/655 , A61K31/675 , A61K31/704 , A61K38/164 , A61K38/168 , A61K38/1816 , A61K38/191 , A61K38/193 , A61K38/196 , A61K38/20 , A61K38/217 , A61K51/1045 , A61K51/1048 , A61K51/1096 , A61K2039/505 , C07K16/3007 , C07K2317/24 , A61K2300/00
摘要： The present invention provides a composition comprising naked humanized, chimeric, and human anti-CEA antibodies and a therapeutic agent, which is useful for treatment of CEA expressing cancers and other diseases, and methods of use in treatment using this composition.
摘要翻译：本发明提供了包含裸体人源化，嵌合和人抗CEA抗体和治疗剂的组合物，其可用于治疗表达CEA的癌症和其它疾病，以及使用该组合物的治疗方法。

33. 发明授权

US07785880B2 Mammalian cell lines for increasing longevity and protein yield from cell culture 有权
标题翻译：哺乳动物细胞系增加细胞培养的寿命和蛋白质产量
公开(公告)号：US07785880B2
公开(公告)日：2010-08-31
申请号：US12405733
申请日：2009-03-17
申请人： David M. Goldenberg , Zhengxing Qu , Chien-Hsing Chang , Edmund A. Rossi , Jeng-Dar Yang , Diane Nordstrom
发明人： David M. Goldenberg , Zhengxing Qu , Chien-Hsing Chang , Edmund A. Rossi , Jeng-Dar Yang , Diane Nordstrom
IPC分类号： C12N5/00 , C12N15/00 , C12P21/00
CPC分类号： C07K16/2896 , A61K2039/505 , C07K14/005 , C07K14/4747 , C07K16/00 , C07K16/18 , C07K16/2803 , C07K16/3007 , C07K2317/24 , C07K2317/31 , C12N5/0694 , C12N15/85 , C12N15/86 , C12N2500/90 , C12N2501/48 , C12N2510/02 , C12N2710/20022 , C12N2740/10043 , C12P21/02
摘要： Disclosed are compositions and methods for increasing the longevity of a cell culture and permitting the increased production of proteins, preferably recombinant proteins, such as antibodies, peptides, enzymes, growth factors, interleukins, interferons, hormones, and vaccines. Cells transfected with an apoptosis-inhibiting gene or vector, such as a triple mutant Bcl-2 gene, can survive longer in culture, resulting in extension of the state and yield of protein biosynthesis. Such transfected cells exhibit maximal cell densities that equal or exceed the maximal density achieved by the parent cell lines. Transfected cells can also be pre-adapted for growth in serum-free medium, greatly decreasing the time required to obtain protein production in serum-free medium. In certain methods, the pre-adapted cells can be used for protein production following transformation under serum-free conditions. The method preferably involves eukaryotic cells, more preferably mammalian cells.
摘要翻译：公开了用于增加细胞培养物的寿命并允许增加蛋白质生产的组合物和方法，优选重组蛋白，例如抗体，肽，酶，生长因子，白细胞介素，干扰素，激素和疫苗。用凋亡抑制基因或载体如三重突变体Bcl-2基因转染的细胞可以在培养物中更长时间地存活，导致蛋白质生物合成的状态和产量的延长。这样的转染细胞表现出最大的细胞密度，其等于或超过由亲本细胞系实现的最大密度。转染的细胞也可以预先适应于无血清培养基中生长，大大减少了在无血清培养基中获得蛋白质产生所需的时间。在某些方法中，预先调节的细胞可以在无血清条件下转化后用于蛋白质生产。该方法优选涉及真核细胞，更优选哺乳动物细胞。

34. 发明授权

US07776311B1 D-amino acid peptides 有权
标题翻译： D-氨基酸肽
公开(公告)号：US07776311B1
公开(公告)日：2010-08-17
申请号：US11640790
申请日：2006-12-18
申请人： William J. McBride , David M. Goldenberg
发明人： William J. McBride , David M. Goldenberg
IPC分类号： A61K38/08 , A61K38/16 , A61K39/00 , A61K36/395 , A61K51/10 , C07K5/02 , C12P21/08
CPC分类号： C07K5/0815 , A61K38/00 , A61K47/6897 , A61K49/0002 , A61K51/109 , B82Y5/00 , C07K5/1008 , C07K5/1016 , C07K5/1019 , C07K5/1021 , C07K7/06 , Y02A50/411
摘要： The present invention provides compounds of the formula X—R1-D-[Dpr, Orn or Lys](A)-R2(Z)-D-[Dpr, Orn or Lys](B)—R3(Y)—NR4R5; or R1(X)-D-[Dpr, Orn or Lys](A)-R2(Z)-D-[Dpr, Orn or Lys](B)—R3(Y)—NR4R5, in which X is a hard acid cation chelator, a soft acid cation chelator or Ac-, R1, R2 and R3 are independently selected from a covalent bond or one or more D-amino acids that can be the same or different, Y is a hard acid cation chelator, a soft acid cation chelator or absent, Z is a hard acid cation chelator, a soft acid cation chelator or absent, and A and B are haptens or hard acid cation chelators and can be the same or different, and R4 and R5 are independently selected from the group consisting of hard acid cation chelators, soft acid cation chelators, enzymes, therapeutic agents, diagnostic agents and H. The present invention also provides methods of using these compounds and kits containing the compounds.
摘要翻译：本发明提供式X-R1-D- [Dpr，Orn或Lys]（A）-R2（Z）-D- [Dpr，Orn或Lys]（B）-R3（Y）-NR4R5的化合物; 或R 1（X）-D- [Dpr，Orn或Lys]（A）-R2（Z）-D- [Dpr，Orn或Lys]（B）-R3（Y）-NR4R5，其中X为硬酸阳离子螯合剂，软酸阳离子螯合剂或Ac-，R1，R2和R3独立地选自共价键或一个或多个可以相同或不同的D-氨基酸，Y是硬酸阳离子螯合剂，软酸阳离子螯合剂或不存在，Z是硬酸阳离子螯合剂，软酸阳离子螯合剂或不存在，A和B是半抗原或硬酸阳离子螯合剂，可以相同或不同，并且R 4和R 5独立地选自由硬酸阳离子螯合剂，软酸阳离子螯合剂，酶，治疗剂，诊断剂和H组成的组。本发明还提供使用这些化合物和含有该化合物的试剂盒的方法。

35. 发明授权

US07772373B2 Internalizing anti-CD74 antibodies and methods of use 有权
标题翻译：内化抗CD74抗体及其使用方法
公开(公告)号：US07772373B2
公开(公告)日：2010-08-10
申请号：US11867775
申请日：2007-10-05
申请人： Hans J. Hansen , Zhengxing Qu , David M. Goldenberg
发明人： Hans J. Hansen , Zhengxing Qu , David M. Goldenberg
IPC分类号： C07K16/00
CPC分类号： A61K45/06 , A61K38/00 , A61K47/6849 , A61K51/1027 , A61K2039/505 , C07K16/2833 , C07K16/2896 , C07K2317/24 , C07K2317/77
摘要： The present invention provides humanized, chimeric and human anti-CD74 antibodies, CD74 antibody fusion proteins, immunoconjugates, vaccines and bispecific that bind to CD74, the major histocompatibility complex (MHC) class-II invariant chain, Ii, which is useful for the treatment and diagnosis of B-cell disorders, such as B-cell malignancies, other malignancies in which the cells are reactive with CD74, and autoimmune diseases, and methods of treatment and diagnosis.
摘要翻译：本发明提供人源化，嵌合和人抗CD74抗体，CD74抗体融合蛋白，免疫缀合物，疫苗和结合CD74的双特异性，主要组织相容性复合体（MHC）II类不变链I 1可用于治疗 B细胞病变，B细胞恶性肿瘤，其他细胞与CD74反应的其他恶性肿瘤，以及自身免疫性疾病以及治疗和诊断方法的诊断。

36. 发明授权

US07683044B2 Sphingomyelin therapy of autoimmune disease 有权
标题翻译：鞘磷脂治疗自身免疫性疾病
公开(公告)号：US07683044B2
公开(公告)日：2010-03-23
申请号：US11857303
申请日：2007-09-18
申请人： David E. Modrak , David M. Goldenberg
发明人： David E. Modrak , David M. Goldenberg
IPC分类号： A01N57/26
CPC分类号： A61K31/66
摘要： Autoimmune disease therapy in a patient treated with apoptosis-inducing agents is enhanced by co-administration of sphingomyelin. The combination most likely enhances an autoimmune disease cell's ability to undergo ceramide-induced apoptosis by increasing the levels of sphingomyelin in all cellular compartments, thereby providing sufficient substrate for activated sphingomyelinase. In alternative embodiments, sphingomyelin may be administered alone, in combination with corticosteroids, and/or in combination with a apoptosis-inducing agent.
摘要翻译：用凋亡诱导剂治疗的患者中的自身免疫疾病治疗通过共同施用鞘磷脂增强。该组合最有可能增强自身免疫疾病细胞通过增加所有细胞区室中鞘磷脂水平进行神经酰胺诱导的细胞凋亡的能力，从而为活化的鞘磷脂酶提供足够的底物。在替代实施方案中，鞘磷脂可以与皮质类固醇组合施用，和/或与细胞凋亡诱导剂组合施用。

37. 发明申请

US20090299033A1 Methods and Compositions for F-18 Labeling of Proteins, Peptides and Other Molecules 有权
标题翻译：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：US20090299033A1
公开(公告)日：2009-12-03
申请号：US12485998
申请日：2009-06-17
申请人： William J. McBride , David M. Goldenberg
发明人： William J. McBride , David M. Goldenberg
IPC分类号： C07K7/54 , C07K7/08 , C07K5/103 , C07K16/00 , C07K16/30
CPC分类号： A61K51/082 , A61K47/6897 , A61K51/0406 , A61K51/0491 , A61K51/08 , A61K51/088 , A61K51/109 , B82Y5/00 , C07B59/008
摘要： The present application discloses compositions and methods of synthesis and use of F-18 labeled molecules of use, for example, in PET imaging techniques. In particular embodiments, the labeled molecules may be peptides or proteins, although other types of molecules including but not limited to aptamers, oligonucleotides and nucleic acids may be labeled and utilized for such imaging studies. In preferred embodiments, the F-18 label may be conjugated to a targeting molecule by formation of a metal complex and binding of the F-18-metal complex to a chelating moiety, such as DOTA, NOTA, DTPA, TETA or NETA. In other embodiments, the metal may first be conjugated to the chelating group and subsequently the F-18 bound to the metal. In other preferred embodiments, the F-18 labeled moiety may comprise a targetable conjugate that may be used in combination with a bispecific or multispecific antibody to target the F-18 to an antigen expressed on a cell or tissue associated with a disease, medical condition, or pathogen. Exemplary results show that F-18 labeled targetable conjugate peptides are stable in human serum at 37° C. for several hours, sufficient time to perform PET imaging analysis.
摘要翻译：本申请公开了用于例如PET成像技术的F-18标记分子的合成和使用的组合物和方法。在具体实施方案中，标记的分子可以是肽或蛋白质，尽管其他类型的分子包括但不限于适体，寡核苷酸和核酸可以被标记并用于这种成像研究。在优选的实施方案中，F-18标记可以通过形成金属络合物和F-18-金属络合物与螯合部分如DOTA，NOTA，DTPA，TETA或NETA的结合而与靶向分子缀合。在其它实施方案中，金属可以首先与螯合基团缀合，随后F-18与金属结合。在其它优选的实施方案中，F-18标记的部分可以包含可靶向的缀合物，其可以与双特异性或多特异性抗体组合使用，以将F-18靶向在与疾病相关的细胞或组织上表达的抗原，医学病症，或病原体。示例性结果表明，F-18标记的可靶向缀合物肽在人血清中在37℃下稳定数小时，足够的时间进行PET成像分析。

38. 发明授权

US07550143B2 Methods for generating stably linked complexes composed of homodimers, homotetramers or dimers of dimers and uses 有权
标题翻译：用于产生由同型二聚体，同三聚体或二聚体二聚体和用途组成的稳定连接络合物的方法
公开(公告)号：US07550143B2
公开(公告)日：2009-06-23
申请号：US11389358
申请日：2006-03-24
申请人： Chien Hsing Chang , David M. Goldenberg , William J. McBride , Edmund A. Rossi
发明人： Chien Hsing Chang , David M. Goldenberg , William J. McBride , Edmund A. Rossi
IPC分类号： C07K16/46 , C07K16/28 , C07K16/30 , A61K38/01 , A61K38/19 , A61K39/395
CPC分类号： C12N9/12 , B82Y5/00 , B82Y10/00 , C07K16/18 , C07K16/2803 , C07K16/2887 , C07K16/3007 , C07K16/3092 , C07K2317/31 , C07K2317/55 , C07K2319/00 , C07K2319/70 , C12Y207/11011
摘要： The present invention concerns methods and compositions for stably tethered structures of defined compositions, which may have multiple functionalities and/or binding specificities. Particular embodiments concern homodimers comprising monomers that contain a dimerization and docking domain attached to a precursor. The precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc. Other embodiments concern tetramers comprising a first and second homodimer, which may be identical or different. The disclosed methods and compositions provide a facile and general way to obtain homodimers, homotetramers and heterotetramers of virtually any functionality and/or binding specificity.
摘要翻译：本发明涉及可以具有多种功能和/或结合特异性的限定组合物的稳定的束缚结构的方法和组合物。具体实施方案涉及包含单体的同型二聚体，其含有连接到前体的二聚化和对接结构域。前体实际上可以是任何分子或结构，例如抗体，抗体片段，抗体类似物或模拟物，适体，结合肽，结合蛋白的片段，蛋白质或其他分子的已知配体，酶，可检测标记或标签，治疗剂，毒素，药物，细胞因子，白细胞介素，干扰素，放射性同位素，蛋白质，肽，肽模拟物，多核苷酸，RNAi，寡糖，天然或合成聚合物质，纳米颗粒，量子点，有机或无机化合物等。其他实施方案涉及四聚体，和第二同二聚体，其可以相同或不同。所公开的方法和组合物提供了获得实质上任何功能性和/或结合特异性的同源二聚体，同源四聚体和异源四聚体的简便且一般的方式。

39. 发明授权

US07501498B2 Alpha-fetoprotein Immu31 antibodies and fusion proteins 有权
标题翻译：甲胎蛋白Immu31抗体和融合蛋白
公开(公告)号：US07501498B2
公开(公告)日：2009-03-10
申请号：US11870627
申请日：2007-10-11
申请人： Hans J. Hansen , Zhengxing Qu , David M. Goldenberg
发明人： Hans J. Hansen , Zhengxing Qu , David M. Goldenberg
IPC分类号： C07K16/00 , C12P21/08 , C12P21/04 , A61K39/395 , C07H21/04
CPC分类号： C07K16/30 , A61K41/0095 , A61K47/6843 , A61K49/0002 , A61K51/1018 , A61K2039/505 , C07K16/18 , C07K16/3076 , C07K2317/24 , C07K2317/56 , G01N33/57484 , G01N33/689
摘要： The present invention provides humanized, chimeric and human anti-alpha-fetoprotein antibodies, fusion proteins, and fragments thereof. The antibodies, fusion proteins, and fragments thereof, as well as combinations with other suitable antibodies, are useful for the treatment and diagnosis of hepatocellular carcinoma, hepatoblastoma, germ cell tumors carcinoma and other AFP-producing tumors.
摘要翻译：本发明提供人源化，嵌合和人抗甲胎蛋白抗体，融合蛋白及其片段。抗体，融合蛋白及其片段以及与其它合适抗体的组合可用于治疗和诊断肝细胞癌，肝母细胞瘤，生殖细胞肿瘤癌和其他产生AFP的肿瘤。

40. 发明申请

US20090060862A1 PEGylation by the Dock and Lock (DNL) Technique 有权
标题翻译：通过Dock和Lock（DNL）技术进行PEG化
公开(公告)号：US20090060862A1
公开(公告)日：2009-03-05
申请号：US11925408
申请日：2007-10-26
申请人： Chien-Hsing Chang , David M. Goldenberg , William J. McBride , Edmund A. Rossi
发明人： Chien-Hsing Chang , David M. Goldenberg , William J. McBride , Edmund A. Rossi
IPC分类号： A61K38/20 , C07K14/00 , C12N9/00 , C07K14/805 , C07K16/00 , C07K14/54 , A61K38/28 , A61K38/18 , C07K14/555 , C07K14/62 , C07K14/505 , A61K38/16 , A61K38/21
CPC分类号： A61K47/6835 , A61K38/1816 , A61K38/193 , A61K38/212 , A61K47/60 , A61K47/65 , A61K47/6853 , A61K51/1048 , B82Y5/00 , B82Y10/00 , C07K2319/00 , C07K2319/70
摘要： The present invention concerns methods and compositions for forming PEGylated complexes of defined stoichiometry and structure. In preferred embodiments, the PEGylated complex is formed using dock-and-lock technology, by attaching a target agent to a DDD sequence and attaching a PEG moiety to an AD sequence and allowing the DDD sequence to bind to the AD sequence in a 2:1 stoichiometry, to form PEGylated complexes with two target agents and one PEG moiety. In alternative embodiments, the target agent may be attached to the AD sequence and the PEG to the DDD sequence to form PEGylated complexes with two PEG moieties and one target agent. In more preferred embodiments, the target agent may comprise any peptide or protein of physiologic or therapeutic activity. The PEGylated complexes exhibit a significantly slower rate of clearance when injected into a subject and are of use for treatment of a wide variety of diseases.
摘要翻译：本发明涉及用于形成定义化学计量和结构的聚乙二醇化配合物的方法和组合物。在优选的实施方案中，使用对接和锁定技术形成聚乙二醇化复合物，通过将目标试剂连接到DDD序列并将PEG部分连接到AD序列并允许DDD序列以2： 1化学计量，以形成与两个靶剂和一个PEG部分的聚乙二醇化复合物。在替代实施方案中，靶物质可以连接到AD序列，并将PEG连接到DDD序列以形成具有两个PEG部分和一个目标试剂的PEG化复合物。在更优选的实施方案中，靶剂可以包含生理或治疗活性的任何肽或蛋白质。当注射到受试者中时，聚乙二醇化复合物表现出明显较慢的清除率，并且可用于治疗各种各样的疾病。

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