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91. 发明授权

US08287865B2 Class I anti-CEA antibodies and uses thereof 有权
标题翻译： I类抗CEA抗体及其用途
公开(公告)号：US08287865B2
公开(公告)日：2012-10-16
申请号：US12846062
申请日：2010-07-29
申请人： Hans J. Hansen , Chien-Hsing Chang , David M. Goldenberg
发明人： Hans J. Hansen , Chien-Hsing Chang , David M. Goldenberg
IPC分类号： A61K39/395
CPC分类号： C07K16/3007 , A61K39/39558 , A61K47/55 , A61K47/60 , A61K47/6801 , A61K47/6807 , A61K47/6813 , A61K47/6815 , A61K47/6817 , A61K47/6819 , A61K47/6829 , A61K47/6849 , A61K47/6851 , A61K47/6853 , A61K49/0058 , A61K49/221 , A61K51/088 , A61K51/1027 , A61K51/1093 , A61K51/1096 , A61K2039/505 , A61K2039/545 , C07K14/54 , C07K16/2803 , C07K16/3076 , C07K2317/24 , C07K2317/31 , C07K2317/33 , C07K2317/515 , C07K2317/53 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/76 , C07K2317/92 , C07K2319/00 , C07K2319/30 , A61K2300/00
摘要： The present invention provides compositions and methods of use of humanized, chimeric or human Class I anti-CEA antibodies or fragments thereof, preferably comprising the light chain variable region CDR sequences SASSRVSYIH (SEQ ID NO:1); GTSTLAS (SEQ ID NO:2); and QQWSYNPPT (SEQ ID NO:3); and the heavy chain variable region CDR sequences DYYMS (SEQ ID NO:4); FIANKANGHTTDYSPSVKG (SEQ ID NO:5); and DMGIRWNFDV (SEQ ID NO:6). The Class I anti-CEA antibodies or fragments are useful for treating diseases, such as cancer, wherein the diseased cells express CEACAM5 and/or CEACAM6 antigens. The Class I anti-CEA antibodies or fragments are also of use for interfering with specific processes, such as metastasis, invasiveness and/or adhesion of cancer cells, or for enhancing sensitivity of cancer cells to cytotoxic agents and have favorable effects on the survival of subjects with cancer.
摘要翻译：本发明提供使用人源化，嵌合或人类I类抗CEA抗体或其片段的组合物和方法，优选包含轻链可变区CDR序列SASSRVSYIH（SEQ ID NO：1）; GTSTLAS（SEQ ID NO：2）; 和QQWSYNPPT（SEQ ID NO：3）; 和重链可变区CDR序列DYYMS（SEQ ID NO：4）; FIANKANGHTTDYSPSVKG（SEQ ID NO：5）; 和DMGIRWNFDV（SEQ ID NO：6）。 I类抗CEA抗体或片段可用于治疗诸如癌症的疾病，其中患病细胞表达CEACAM5和/或CEACAM6抗原。 I类抗CEA抗体或片段也可用于干扰特异性过程，例如癌细胞的转移，侵袭和/或粘附，或用于增强癌细胞对细胞毒性剂的敏感性，并且对癌症患者

92. 发明授权

US08287864B2 Structural variants of antibodies for improved therapeutic characteristics 有权
标题翻译：用于改善治疗特征的抗体的结构变体
公开(公告)号：US08287864B2
公开(公告)日：2012-10-16
申请号：US12506996
申请日：2009-07-21
申请人： David M. Goldenberg , Chien-Hsing Chang , Hans J. Hansen
发明人： David M. Goldenberg , Chien-Hsing Chang , Hans J. Hansen
IPC分类号： A61K39/00 , A61K39/395
CPC分类号： A61K39/3955 , A61K39/39558 , A61K51/1093 , A61K2039/505 , C07K16/2887 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/732 , C07K2317/734 , C07K2317/92
摘要： The present invention provides substituted humanized, chimeric or human anti-CD20 antibodies or antigen binding fragments thereof and bispecific antibodies or fusion proteins comprising the substituted antibodies or antigen binding fragments thereof. The antibodies, fusion proteins or fragments are useful for treatment of B-cell disorders, such as B-cell malignancies and autoimmune diseases, as well as GVHD, organ transplant rejection, and hemolytic anemia and cryoglobulinemia. Amino acid substitutions, particularly substitution of an aspartate residue at Kabat position 101 of CDR3 VH (CDRH3), result in improved therapeutic properties, such as decreased dissociation rates, improved CDC activity, improved apoptosis, improved B-cell depletion and improved therapeutic efficacy at very low dosages. Veltuzumab, a humanized anti-CD20 antibody that incorporates such sequence variations, exhibits improved therapeutic efficacy compared to similar antibodies of different CDRH3 sequence, allowing therapeutic effect at dosages as low as 200 mg or less, more preferably 100 mg or less, more preferably 80 mg or less, more preferably 50 mg or less, most preferably 30 mg or less of naked antibody when administered i.v. or s.c.
摘要翻译：本发明提供取代的人源化，嵌合或人抗CD20抗体或其抗原结合片段和包含取代抗体或其抗原结合片段的双特异性抗体或融合蛋白。抗体，融合蛋白或片段可用于治疗B细胞病变，如B细胞恶性肿瘤和自身免疫性疾病，以及GVHD，器官移植排斥，溶血性贫血和冷球蛋白血症。氨基酸取代，特别是取代CDR3 VH（CDRH3）Kabat 101位天冬氨酸残基导致改善的治疗性质，例如降低的解离速率，改善的CDC活性，改善的细胞凋亡，改善的B细胞消耗和改善的治疗功效非常低的剂量 Veltuzumab是与不同CDRH3序列的相似抗体相比具有改善的治疗效果的，具有这种序列变异性的人源化抗-CD20抗体，其能够以低至200mg或更低，更优选为100mg或更少，更优选为80mg mg或更少，更优选50mg或更少，最优选30mg或更少的裸抗体或s.c.

93. 发明申请

US20110311531A1 IMMUNOTHERAPY OF AUTOIMMUNE DISORDERS USING ANTIBODIES WHICH TARGET B-CELLS 审中-公开
公开(公告)号：US20110311531A1
公开(公告)日：2011-12-22
申请号：US13214767
申请日：2011-08-22
申请人： David M. Goldenberg , Hans J. Hansen
发明人： David M. Goldenberg , Hans J. Hansen
IPC分类号： A61K39/395 , A61P37/06 , A61P29/00
CPC分类号： C07K16/2887 , A61K38/00 , A61K39/3955 , A61K45/06 , A61K47/6813 , A61K47/6849 , A61K2039/505 , A61K2039/507 , C07K16/28 , C07K16/2803 , C07K16/2896 , C07K2317/24 , Y10S514/885 , Y10S514/903
摘要： Antibodies that bind with a B-cell antigen provide an effective means to treat autoimmune disorders. Antibodies and fragments, which may be conjugated or naked, are used alone or in multimodal therapies. The antibodies may be bispecific antibodies which may be produced recombinantly as fusion proteins, or as hybrid, polyspecific antibodies.

94. 发明授权

US07951369B2 Chimeric, human and humanized anti-granulocyte antibodies and methods of use 有权
标题翻译：嵌合，人和人源化抗粒细胞抗体及其使用方法
公开(公告)号：US07951369B2
公开(公告)日：2011-05-31
申请号：US12398416
申请日：2009-03-05
申请人： David M. Goldenberg , Hans J. Hansen
发明人： David M. Goldenberg , Hans J. Hansen
IPC分类号： C12P21/08 , C07K16/00 , C07K17/00 , C07K17/14 , A61K39/00 , A61K39/395
CPC分类号： G01N33/57426 , A61K39/395 , A61K51/10 , A61K51/1027 , C07K16/2803 , C07K2317/24 , C07K2317/567 , C07K2319/00 , G01N2500/00 , A61K2300/00
摘要： The present invention provides humanized, chimeric and human MN3 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 granulocyte related disorders and diseases, such as leukemia.
摘要翻译：本发明提供人源化，嵌合和人类MN3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粒细胞相关疾病和疾病如白血病。

95. 发明申请

US20110117010A1 Methods and Compositions for Administering Therapeutic and Diagnostic Agents 有权
标题翻译：用于治疗和诊断试剂的方法和组合物
公开(公告)号：US20110117010A1
公开(公告)日：2011-05-19
申请号：US12985775
申请日：2011-01-06
申请人： William J. McBride , Chien-Hsing Chang , David M. Goldenberg , Hans J. Hansen
发明人： William J. McBride , Chien-Hsing Chang , David M. Goldenberg , Hans J. Hansen
IPC分类号： A61K51/00 , A61K39/395 , A61K49/04 , A61K49/00 , A61P35/00 , A61P43/00
CPC分类号： B82Y5/00 , A61K47/6891 , Y10S435/975
摘要： Methods and compositions are described for targeting therapeutic and diagnostic molecules to particular types of cells using targeting antibodies or other targeting moeities.
摘要翻译：描述了使用靶向抗体或其他靶向动物将治疗和诊断分子靶向特定类型的细胞的方法和组合物。

96. 发明申请

US20110064653A1 Class I Anti-CEA Antibodies and Uses Thereof 有权
标题翻译： I类抗CEA抗体及其用途
公开(公告)号：US20110064653A1
公开(公告)日：2011-03-17
申请号：US12846062
申请日：2010-07-29
申请人： Hans J. Hansen , Chien-Hsing Chang , David M. Goldenberg
发明人： Hans J. Hansen , Chien-Hsing Chang , David M. Goldenberg
IPC分类号： A61K51/10 , A61K51/00 , A61K49/00 , A61K39/395 , C07K16/46 , C07K16/00 , A61P35/00 , A61P35/02
CPC分类号： C07K16/3007 , A61K39/39558 , A61K47/55 , A61K47/60 , A61K47/6801 , A61K47/6807 , A61K47/6813 , A61K47/6815 , A61K47/6817 , A61K47/6819 , A61K47/6829 , A61K47/6849 , A61K47/6851 , A61K47/6853 , A61K49/0058 , A61K49/221 , A61K51/088 , A61K51/1027 , A61K51/1093 , A61K51/1096 , A61K2039/505 , A61K2039/545 , C07K14/54 , C07K16/2803 , C07K16/3076 , C07K2317/24 , C07K2317/31 , C07K2317/33 , C07K2317/515 , C07K2317/53 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/76 , C07K2317/92 , C07K2319/00 , C07K2319/30 , A61K2300/00
摘要： The present invention provides compositions and methods of use of humanized, chimeric or human Class I anti-CEA antibodies or fragments thereof, preferably comprising the light chain variable region CDR sequences SASSRVSYIH (SEQ ID NO:1); GTSTLAS (SEQ ID NO:2); and QQWSYNPPT (SEQ ID NO:3); and the heavy chain variable region CDR sequences DYYMS (SEQ ID NO:4); FIANKANGHTTDYSPSVKG (SEQ ID NO:5); and DMGIRWNFDV (SEQ ID NO:6). The Class I anti-CEA antibodies or fragments are useful for treating diseases, such as cancer, wherein the diseased cells express CEACAM5 and/or CEACAM6 antigens. The Class I anti-CEA antibodies or fragments are also of use for interfering with specific processes, such as metastasis, invasiveness and/or adhesion of cancer cells, or for enhancing sensitivity of cancer cells to cytotoxic agents and have favorable effects on the survival of subjects with cancer.
摘要翻译：本发明提供使用人源化，嵌合或人类I类抗CEA抗体或其片段的组合物和方法，优选包含轻链可变区CDR序列SASSRVSYIH（SEQ ID NO：1）; GTSTLAS（SEQ ID NO：2）; 和QQWSYNPPT（SEQ ID NO：3）; 和重链可变区CDR序列DYYMS（SEQ ID NO：4）; FIANKANGHTTDYSPSVKG（SEQ ID NO：5）; 和DMGIRWNFDV（SEQ ID NO：6）。 I类抗CEA抗体或片段可用于治疗诸如癌症的疾病，其中患病细胞表达CEACAM5和/或CEACAM6抗原。 I类抗CEA抗体或片段也可用于干扰特异性过程，例如癌细胞的转移，侵袭和/或粘附，或用于增强癌细胞对细胞毒性剂的敏感性，并且对癌症患者

97. 发明申请

US20100272636A1 Anti-CD74 Immunoconjugates and Methods of Use 有权
标题翻译：抗CD74免疫缀合物及其使用方法
公开(公告)号：US20100272636A1
公开(公告)日：2010-10-28
申请号：US12789575
申请日：2010-05-28
申请人： John C. Byrd , David M. Goldenberg , Hans J. Hansen
发明人： John C. Byrd , David M. Goldenberg , Hans J. Hansen
IPC分类号： A61K39/44 , A61K9/127 , A61K51/12 , A61K38/19 , A61K38/20 , A61K38/21 , A61P35/00 , A61P35/02 , A61P37/02 , A61P37/06
CPC分类号： A61K47/48823 , A61K39/395 , A61K47/6907 , A61K47/6913 , A61K51/1234 , A61K2039/505 , C07K16/2803 , C07K16/2833 , C07K16/2896 , C07K2317/24 , C07K2317/565 , C07K2317/73 , G01N33/574 , G01N2333/70596 , G01N2800/245 , A61K2300/00
摘要： Disclosed are compositions that include anti-CD74 immunoconjugates and optionally a therapeutic and/or diagnostic agent. In preferred embodiments, the immunoconjugates comprise one or more anti-CD74 antibodies or antigen-binding fragments thereof, conjugated to a liposome or micelle. Also disclosed are methods for preparing the immunoconjugates and using the immunoconjugates in diagnostic and therapeutic procedures. In certain preferred embodiments, the therapeutic methods comprise administering to a subject with a CD74-expressing disease an anti-CD74 immunoconjugate and thereby inducing apoptosis of CD74-expressing cells. In more preferred embodiments, the CD74 immunoconjugate is capable of inducing cell death in the absence of any other therapeutic agent, although such agents may be optionally administered prior to, together with or subsequent to administration of the anti-CD74 immunoconjugate. The compositions may be part of a kit for administering the anti-CD74 immunoconjugates or compositions.
摘要翻译：公开了包含抗CD74免疫缀合物和任选的治疗和/或诊断剂的组合物。在优选的实施方案中，免疫偶联物包含缀合至脂质体或胶束的一种或多种抗CD74抗体或其抗原结合片段。还公开了在诊断和治疗过程中制备免疫缀合物和使用免疫缀合物的方法。在某些优选实施方案中，治疗方法包括向具有表达CD74的疾病的受试者施用抗CD74免疫偶联物，从而诱导表达CD74的细胞的凋亡。在更优选的实施方案中，CD74免疫缀合物能够在不存在任何其它治疗剂的情况下诱导细胞死亡，尽管可以任选地在施用抗CD74免疫缀合物之前，之后或之后施用这些试剂。组合物可以是用于施用抗CD74免疫缀合物或组合物的试剂盒的一部分。

98. 发明申请

US20100196266A1 Humanized Anti-HLA-DR Antibodies 有权
标题翻译：人源化抗HLA-DR抗体
公开(公告)号：US20100196266A1
公开(公告)日：2010-08-05
申请号：US12754140
申请日：2010-04-05
申请人： David M. Goldenberg , Hans J. Hansen , Chien-Hsing Chang
发明人： David M. Goldenberg , Hans J. Hansen , Chien-Hsing Chang
IPC分类号： A61K51/10 , C07K16/30 , C07K19/00 , A61K39/395 , A61K38/19 , A61K38/20 , A61K38/21 , C07H21/04 , A61P35/00 , A61P35/02 , C12N9/96
CPC分类号： C07K16/2833 , A61K39/3955 , A61K39/39558 , A61K45/06 , A61K47/6849 , A61K47/6867 , A61K51/1027 , A61K51/1093 , A61K2039/505 , A61K2039/507 , C07K16/28 , C07K16/2887 , C07K16/4241 , C07K19/00 , C07K2317/24 , C07K2317/52 , C07K2317/56 , C07K2317/565 , C07K2317/71 , C07K2317/73 , C07K2317/732 , C07K2317/734 , C07K2317/75 , C07K2317/92
摘要： The present invention concerns compositions and methods of use of humanized anti-HLA-DR antibodies. In preferred embodiments, the antibodies induce apoptosis and inhibit proliferation of lymphoma cells without inducing CDC or ADCC. In more preferred embodiments, the humanized anti-HLA-DR antibodies bind to the same epitope of HLA-DR as, or compete for binding to HLA-DR with, a murine L243 antibody. Most preferably, the humanized anti-HLA-DR antibody exhibits a higher affinity for HLA-DR than the parental murine antibody. The humanized HLA-DR antibody is of use for therapy of various diseases such as cancer, autoimmune disease or immune dysregulatory function, and is of particular use for therapy of B cell lymphomas and leukemias. In most preferred embodiments, the humanized anti-HLA-DR antibody is capable of inducing at least partial remission of lymphomas that are resistant to other B cell antibodies, such as rituximab.
摘要翻译：本发明涉及使用人源化抗HLA-DR抗体的组合物和方法。在优选的实施方案中，抗体诱导凋亡并抑制淋巴瘤细胞的增殖而不诱导CDC或ADCC。在更优选的实施方案中，人源化抗HLA-DR抗体与鼠L243抗体结合HLA-DR相同的表位或与鼠L243抗体竞争结合HLA-DR。最优选地，人源化抗HLA-DR抗体对亲本鼠抗体的HLA-DR表现出更高的亲和力。人源化HLA-DR抗体可用于治疗各种疾病如癌症，自身免疫疾病或免疫调节功能，并且特别用于治疗B细胞淋巴瘤和白血病。在最优选的实施方案中，人源化抗HLA-DR抗体能够诱导对其它B细胞抗体如利妥昔单抗有抗性的淋巴瘤的至少部分缓解。

99. 发明授权

US07534427B2 Immunotherapy of B cell malignancies and autoimmune diseases using unconjugated antibodies and conjugated antibodies and antibody combinations and fusion proteins 有权
标题翻译：免疫治疗B细胞恶性肿瘤和自身免疫疾病使用非共轭抗体和共轭抗体和抗体组合和融合蛋白
公开(公告)号：US07534427B2
公开(公告)日：2009-05-19
申请号：US10747199
申请日：2003-12-30
申请人： David M. Goldenberg , Hans J. Hansen
发明人： David M. Goldenberg , Hans J. Hansen
IPC分类号： A61K39/395 , A61K39/44 , A61K38/19 , C12P21/08 , C07K16/18 , C07K16/28
CPC分类号： C07K16/2896 , A61K51/1018 , A61K51/1045 , A61K51/109 , A61K51/1093 , C07K16/2812 , C07K16/2815 , C07K16/2821 , C07K16/2827 , C07K16/2845 , C07K16/2851 , C07K16/2878 , C07K16/2887 , C07K16/2893
摘要： The invention is directed to a method for treating a treating and diagnosing a B cell-related disease, T cell-related disease or an autoimmune disease in a mammal by concurrently or sequentially administering to the mammal a therapeutic composition that comprises a pharmaceutically acceptable vehicle and at least one conjugated antibody, wherein predosing with a non-radiolabeled antibody is not performed.
摘要翻译：本发明涉及一种治疗和诊断哺乳动物中B细胞相关疾病或T细胞相关疾病或自身免疫性疾病的方法，该方法是通过向哺乳动物同时或依次施用治疗组合物，其包含药学上可接受的载体和至少一种缀合的抗体，其中未进行非放射性标记的抗体的预处理。

100. 发明申请

US20080241141A1 METHODS AND COMPOSITIONS FOR IMMUNOTHERAPY AND DETECTION OF INFLAMMATORY AND IMMUNE-DYSREGULATORY DISEASE, INFECTIOUS DISEASE, PATHOLOGIC ANGIOGENESIS AND CANCER 审中-公开
公开(公告)号：US20080241141A1
公开(公告)日：2008-10-02
申请号：US11929315
申请日：2007-10-30
申请人： David M. Goldenberg , Hans J. Hansen
发明人： David M. Goldenberg , Hans J. Hansen
IPC分类号： A61K38/02 , A61K39/395 , A61P37/00
CPC分类号： A61K39/3955 , A61K31/513 , A61K38/193 , A61K38/2013 , A61K38/4866 , A61K39/40 , A61K45/06 , A61K49/0002 , A61K2039/505 , A61K2039/507 , C07K16/1203 , C07K16/24 , C07K16/241 , C07K16/248 , C07K16/2803 , C07K16/2896 , C07K16/30 , C07K2317/24 , C07K2317/31 , C07K2317/734
摘要： Methods and compositions for immunotherapy of inflammatory and immune-dysregulatory diseases, using multispecific antagonists that target at least two different markers are disclosed. The different targets include (i) proinflammatory effectors of the innate immune system, (ii) coagulation factors, and (iii) targets specifically associated with an inflammatory or immune-dysregulatory disorder, with a pathologic angiogenesis or cancer, or with an infectious disease, wherein the targets included in group (iii) are neither a proinflammatory effector of the immune system nor a coagulation factor. When the multispecific antagonist reacts specifically with a target associated with an inflammatory or immune-dysregulatory disorder, with a pathologic angiogenesis or cancer, or with an infectious disease, it also binds specifically with at least one proinflammatory effector of the immune system or at least one coagulation factor. Thus, the multispecific antagonist contains at least one binding specificity related to the diseased cell or condition being treated and at least one specificity to a component of the immune system, such as a receptor or antigen of B cells, T cells, neutrophils, monocytes and macrophages, and dendritic cells, a modulator of coagulation, or a proinflammatory cytokine. The multispecific antagonists are used in the treatment of various diseases that are generated or exacerbated by, or otherwise involve, proinflammatory effectors of the innate immune system or coagulation factors. Such diseases more particularly include acute and chronic inflammatory disorders, autoimmune diseases, giant cell arteritis, septicemia and septic shock, coagulopathies (including diffuse intravascular coagulation), neuropathies, graft versus host disease, infectious diseases, acute respiratory distress syndrome, granulomatous diseases, transplant rejection, asthma, cachexia, myocardial ischemia, and atherosclerosis. Other diseases also responsive to these therapies include cancers and conditions with pathological angiogenesis.

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