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1. 发明授权

US5597707A Tumor associated antigen recognized by the murine monoclonal antibody L6, its oligonucleotide sequence and methods for their use 失效
标题翻译：由鼠单克隆抗体L6识别的肿瘤相关抗原，其寡核苷酸序列及其使用方法
公开(公告)号：US5597707A
公开(公告)日：1997-01-28
申请号：US48700
申请日：1993-04-15
申请人： John Marken , Gary L. Schieven , Ingegerd Hellstrom , Karl E. Hellstrom , Alejandro Aruffo
发明人： John Marken , Gary L. Schieven , Ingegerd Hellstrom , Karl E. Hellstrom , Alejandro Aruffo
IPC分类号： A61K38/00 , C07K14/47 , G01N33/574 , C07H21/00 , C12N15/00 , C12P21/06
CPC分类号： G01N33/57492 , C07K14/4748 , A61K38/00 , G01N2333/705
摘要： The present invention definitively identifies and characterizes the tumor-associated antigen immunologically recognized by the murine monoclonal antibody L6. Further, the present invention provides the nucleotide sequence which encodes the L6 antigen. Various diagnostic, prophylactic and therapeutic methods comprising the L6 antigen and the nucleotide sequence which encodes the L6 antigen are also provided.
摘要翻译：本发明明确地鉴定和表征由鼠单克隆抗体L6免疫识别的肿瘤相关抗原。此外，本发明提供编码L6抗原的核苷酸序列。还提供了包含L6抗原和编码L6抗原的核苷酸序列的各种诊断，预防和治疗方法。

2. 发明授权

US5242824A Monoclonal antibody to human carcinomas 失效
标题翻译：人类癌症的单克隆抗体
公开(公告)号：US5242824A
公开(公告)日：1993-09-07
申请号：US443696
申请日：1989-11-29
申请人： Ingegerd Hellstrom , Karl E. Hellstrom
发明人： Ingegerd Hellstrom , Karl E. Hellstrom
IPC分类号： G01N33/574 , A61K38/00 , A61K39/395 , A61K45/00 , A61K47/48 , A61K49/00 , A61K51/00 , A61P35/00 , C07K14/00 , C07K14/52 , C07K16/00 , C07K16/30 , C07K16/46 , C07K19/00 , C12N5/10 , C12N15/02 , C12P21/08 , C12R1/91 , G01N33/577
CPC分类号： C07K16/468 , A61K47/48569 , A61K47/48669 , A61K49/0004 , C07K16/30 , A61K38/00 , C07K2317/732 , C07K2317/77
摘要： The present invention relates to a novel monoclonal antibody reactive with human carcinoma cells. More particularly, the antibody of the invention is a monoclonal antibody reactive with a glycolipid cell membrane antigen on the surface of human carcinomas. The antibody displays a high degree of selectivity for carcinoma cells, showing a low degree of reactivity with certain normal human cells and no detectable reactivity with other types of tumors such as lymphomas, sarcomas or melanomas. In addition, the antibody of the invention is capable of internalizing within the carcinoma cells to which it binds and is therefore particularly useful for therapeutic applications, for example, as the antibody component of antibody-drug or antibody-toxin conjugates.

3. 发明授权

US5165922A Synergistic tumor therapy with combinations of biologically active anti-tumor antibodies and chemotherapy 失效
标题翻译：与生物活性抗肿瘤抗体和化疗相结合的协同肿瘤治疗
公开(公告)号：US5165922A
公开(公告)日：1992-11-24
申请号：US527227
申请日：1990-05-22
申请人： Karl E. Hellstrom , Ingegerd Hellstrom , Gary E. Goodman
发明人： Karl E. Hellstrom , Ingegerd Hellstrom , Gary E. Goodman
IPC分类号： A61K38/00 , A61K39/395 , A61K45/06 , A61K47/48 , A61P35/00 , A61P43/00 , C07K16/30 , C12P21/08
CPC分类号： C07K16/30 , A61K39/395 , A61K45/06 , A61K47/48569 , A61K38/00
摘要： The present invention relates to the use of combinations of antibody therapy and chemotherapy in the treatment of malignant disease. More particularly, the invention relates to novel methods of treating patients who have malignant disease and who have shown an unresponsiveness to treatment with standard chemotherapy regimens by administering to those patients (i) an antibody that binds to the malignant cells of the patient and (ii) a chemotherapeutic agent. According to particular embodiments of the invention, anti-glycolipid antibodies are administered to patients who are subsequently treated with standard chemotherapy regimens.
摘要翻译：本发明涉及抗体治疗和化疗联合治疗恶性疾病的用途。更具体地说，本发明涉及治疗患有恶性疾病的患者的新方法，并且通过给予那些患者（i）与患者的恶性细胞结合的抗体，以及（ii）与标准化疗方案治疗无关）化疗剂。根据本发明的具体实施方案，将抗糖脂抗体施用于随后用标准化疗方案治疗的患者。

4. 发明授权

US5091178A Tumor therapy with biologically active anti-tumor antibodies 失效
标题翻译：肿瘤治疗与生物活性抗肿瘤抗体
公开(公告)号：US5091178A
公开(公告)日：1992-02-25
申请号：US473137
申请日：1990-01-30
申请人： Karl E. Hellstrom , Ingegerd Hellstrom
发明人： Karl E. Hellstrom , Ingegerd Hellstrom
IPC分类号： A61K38/00 , C07K16/30
CPC分类号： C07K16/30 , A61K38/00 , C07K2317/73 , C07K2317/732 , C07K2317/734 , Y10S424/804 , Y10S530/808 , Y10S530/828 , Y10S530/861
摘要： A method for identifying and using antibodies which are directed against tumor-associated glycolipid antigens and which are capable of activating serum complement or antibody dependent cellular cytotoxicity. These antibodies find use in the therapy of tumors. Administration of the antibodies results in lysis of the tumor cells in vivo.
摘要翻译：用于鉴定和使用针对肿瘤相关糖脂抗原的能够激活血清补体或抗体依赖性细胞毒性的抗体的方法。这些抗体可用于治疗肿瘤。抗体的施用导致体内肿瘤细胞裂解。

5. 发明授权

US4918164A Tumor immunotherapy using anti-idiotypic antibodies 失效
标题翻译：使用抗独特型抗体的肿瘤免疫治疗
公开(公告)号：US4918164A
公开(公告)日：1990-04-17
申请号：US116802
申请日：1987-11-04
申请人： Ingegerd Hellstrom , Karl E. Hellstrom , Maria S. Kahn
发明人： Ingegerd Hellstrom , Karl E. Hellstrom , Maria S. Kahn
IPC分类号： A61K38/00 , A61K39/00 , C07K16/28 , C07K16/30 , C07K16/42 , G01N33/574 , G01N33/68
CPC分类号： G01N33/686 , C07K16/2809 , C07K16/30 , C07K16/4266 , G01N33/57423 , G01N33/5743 , G01N33/57476 , G01N33/57488 , A61K38/00 , A61K39/00 , C07K2317/732 , C07K2317/734 , Y10S530/806 , Y10S530/808 , Y10S530/828 , Y10S530/866
摘要： The present invention relates to methods which utilize anti-idiotypic antibodies, or fragments thereof, for tumor immunotherapy or immunoprophylaxis. Monoclonal anti-idiotypic antibodies which recognize an idiotype present on a second antibody or on a T lymphocyte or on an immune suppressor factor which is directed against a defined tumor antigen, can be used for immunization against a tumor, for immune anti-tumor activation or inhibition of suppression, or for in vitro activation of lymphocytes to be used in adoptive immunotherapy. The anti-idiotypic antibodies, or fragments thereof, can also be used to monitor anti-antibody induction in patients undergoing passive immunization to a tumor antigen by administration of anti-tumor antibody. In another embodiment, administration of T lymphocytes which express an idiotype directed against a defined tumor antigen can be used to transfer delayed-type hypersensitivity to the tumor. In another method of the invention, the induction of anti-idiotypic antibodies in vivo by administration of anti-tumor antibody or immune cells or factors exhibiting an anti-tumor idiotype can be therapeutically valuable.
摘要翻译：本发明涉及利用抗独特型抗体或其片段用于肿瘤免疫治疗或免疫预防的方法。识别存在于第二抗体或T淋巴细胞上的独特型单克隆抗独特型抗体或针对定义的肿瘤抗原的免疫抑制因子的单克隆抗独特型抗体可用于针对肿瘤的免疫，用于免疫抗肿瘤活化或抑制或抑制用于过继免疫治疗的淋巴细胞的体外活化。抗独特型抗体或其片段也可用于通过施用抗肿瘤抗体来监测对肿瘤抗原进行被动免疫的患者的抗 - 抗体诱导。在另一个实施方案中，可以使用表达针对定义的肿瘤抗原的独特型的T淋巴细胞的施用来将延迟型超敏反应转移至肿瘤。在本发明的另一种方法中，通过施用抗肿瘤抗体或免疫细胞或显示抗肿瘤独特型的因子在体内诱导抗独特型抗体是有治疗价值的。

6. 发明授权

US5185432A Monoclonal antibodies and antigen for human non-small cell lung carcinoma and other certain human carcinomas 失效
标题翻译：人类非小细胞肺癌和其他某些人类癌症的单克隆抗体和抗原
公开(公告)号：US5185432A
公开(公告)日：1993-02-09
申请号：US834172
申请日：1986-02-26
申请人： Karl E. Hellstrom , Joseph P. Brown , Ingegerd Hellstrom , Hans Marquardt
发明人： Karl E. Hellstrom , Joseph P. Brown , Ingegerd Hellstrom , Hans Marquardt
IPC分类号： C12N15/02 , A61K38/00 , A61K39/395 , A61P35/00 , C07K14/00 , C07K14/005 , C07K14/195 , C07K14/47 , C07K14/705 , C07K16/00 , C07K16/30 , C12N5/00 , C12N5/10 , C12N5/20 , C12P21/00 , C12P21/08 , C12R1/91 , G01N33/574 , G01N33/577
CPC分类号： C07K16/3023 , C07K14/4748 , C07K16/3015 , C07K16/3046 , C12N5/163 , G01N33/57423 , A61K38/00
摘要： The present invention is concerned with novel monoclonal antibodies which bind strongly to a protein antigen associated with human non-small cell lung carcinomas ("NSCLC") human small cell lung carcinomas and certain other human carcinomas including many carcinomas of the colon and breast. The antibodies bind to normal human cells to a much lesser degree than to tumor cells. The antibodies find use both in diagnostic methods such as the detection of malignant cells associated with NSCLC and in therapeutic methods for treatment of human in NSCLC and certain other human carcinomas. Also disclosed is a novel 110,000 dalton glycoprotein antigen found on the cell surface of human non-small lung carcinoma tumor cells and on cells from certain other human cancers. The amino terminal amino acid sequence of this antigen is: ##STR1## in which X represents an unidentified amino acid.
摘要翻译：本发明涉及与人类非小细胞肺癌（“NSCLC”）人类小细胞肺癌和某些其他人类癌症（包括结肠和乳腺癌）相关的蛋白质抗原强烈结合的新型单克隆抗体。抗体与正常人细胞结合的程度远低于肿瘤细胞。抗体可用于诊断方法，例如检测与NSCLC相关的恶性细胞，以及用于治疗NSCLC和某些其他人类癌症的治疗方法。还公开了在人非小细胞肺癌肿瘤细胞的细胞表面和某些其他人类癌症的细胞上发现的新颖的110,000道尔顿糖蛋白抗原。该抗原的氨基末端氨基酸序列为：其中X代表不明氨基酸。

7. 发明授权

US5171665A Monoclonal antibody to novel antigen associated with human tumors 失效
标题翻译：单克隆抗体与人类肿瘤相关的新型抗原
公开(公告)号：US5171665A
公开(公告)日：1992-12-15
申请号：US339142
申请日：1989-04-17
申请人： Ingegerd Hellstrom , Karl E. Hellstrom , Hans Marquardt
发明人： Ingegerd Hellstrom , Karl E. Hellstrom , Hans Marquardt
IPC分类号： A61K39/00 , A61K38/00 , A61K39/12 , A61K39/395 , A61K45/00 , A61K47/48 , A61K49/00 , A61K51/00 , A61K51/10 , A61P35/00 , C07K1/22 , C07K14/00 , C07K14/47 , C07K14/705 , C07K16/00 , C07K16/30 , C07K19/00 , C12N5/10 , C12N15/02 , C12P21/08 , C12R1/91 , G01N33/574 , G01N33/577
CPC分类号： A61K51/1045 , A61K47/48569 , C07K14/4748 , C07K16/30 , A61K2123/00 , A61K38/00 , A61K39/00 , C07K2317/34 , Y10S436/813
摘要： The present invention is concerned with a novel monoclonal antibody which binds strongly to a protein antigen associated with human tumors, including carcinomas of the colon and lung. The antibody binds to normal human cells to a much lesser degree than to tumor cells. The antibody finds use both in diagnostic methods such as the detection of malignant cells associated with tumors and in therapeutic methods for treatment of humans with tumors. Also disclosed is a novel 66,000 dalton glycoprotein antigen found on the cell surface of human tumor cells. The amino terminal amino acid sequence of this antigen is: ##STR1## in which X represents an unidentified amino acid.
摘要翻译：本发明涉及与人肿瘤相关的蛋白质抗原（包括结肠和肺癌）强烈结合的新型单克隆抗体。该抗体与正常人类细胞结合的程度远低于肿瘤细胞。该抗体可用于诊断方法，例如检测与肿瘤相关的恶性细胞和用于治疗患有肿瘤的人的治疗方法。还公开了在人肿瘤细胞的细胞表面上发现的新颖的66,000道尔顿糖蛋白抗原。该抗原的氨基末端氨基酸序列为：其中X代表不明氨基酸。

8. 发明授权

US5811098A Antibodies to HER4, human receptor tyrosine kinase 失效
标题翻译： HER4抗体，人受体酪氨酸激酶
公开(公告)号：US5811098A
公开(公告)日：1998-09-22
申请号：US484438
申请日：1995-06-07
申请人： Gregory D. Plowman , Jean-Michel Culouscou , Mohammed Shoyab , Clay B. Siegall , Ingegerd Hellstrom , Karl E. Hellstrom
发明人： Gregory D. Plowman , Jean-Michel Culouscou , Mohammed Shoyab , Clay B. Siegall , Ingegerd Hellstrom , Karl E. Hellstrom
IPC分类号： A61K47/48 , C07K14/475 , C07K16/28 , A61K39/00
CPC分类号： C07K14/4756 , A61K47/48561 , C07K16/2863 , G01N2333/4756
摘要： The molecular cloning, expression, and biological characteristics of a novel receptor tyrosine kinase related to the epidermal growth factor receptor, termed HER4/p180.sup.erbB4, are described. Antibodies to HER4 are disclosed. A HER4 ligand capable of inducing cellular differentiation of breast cancer cells is also disclosed. In view of the expression of HER4 in several human cancers and in certain tissues of neuronal and muscular origin, various diagnostic and therapeutic uses of HER4-derived and HER4-related biological compositions are provided.
摘要翻译：描述了与表皮生长因子受体相关的新受体酪氨酸激酶的分子克隆，表达和生物学特征，称为HER4 / p180erbB4。公开了HER4抗体。还公开了能够诱导乳腺癌细胞的细胞分化的HER4配体。鉴于HER4在几种人类癌症和神经元和肌肉起源的某些组织中的表达，提供了HER4衍生和HER4相关生物组合物的各种诊断和治疗用途。

9. 发明授权

US5084560A Immunoconjugates and methods for their use in tumor therapy 失效
标题翻译：免疫缀合物及其在肿瘤治疗中的应用
公开(公告)号：US5084560A
公开(公告)日：1992-01-28
申请号：US564387
申请日：1990-08-07
申请人： Karl E. Hellstrom , Ingegerd E. Hellestrom , Efraim Lavie
发明人： Karl E. Hellstrom , Ingegerd E. Hellestrom , Efraim Lavie
IPC分类号： A61K47/48
CPC分类号： A61K47/48692 , A61K47/48715
摘要： Novel pH-sensitive immunoconjugates which dissociate in low-pH tumor tissue, comprising a chemotherapeutic agent and an antibody reactive with a tumor-associated antigen are described. The chemotherapeutic agent is coupled to the antibody by a link which is unstable in low pH. The link may comprise a spacer consisting of a polyamino acid. Representative antibodies for use in these immunoconjugates include monoclonal antibodies which are not internalized by tumor cells.
摘要翻译：描述了在包含化学治疗剂和与肿瘤相关抗原反应的抗体的低pH肿瘤组织中解离的新型pH敏感性免疫偶联物。化学治疗剂通过低pH不稳定的连接物与抗体偶联。连接可以包括由聚氨基酸组成的间隔物。用于这些免疫缀合物的代表性抗体包括不被肿瘤细胞内化的单克隆抗体。

10. 发明授权

US4997913A pH-sensitive immunoconjugates and methods for their use in tumor therapy 失效
标题翻译： pH敏感免疫缀合物及其用于肿瘤治疗的方法
公开(公告)号：US4997913A
公开(公告)日：1991-03-05
申请号：US47161
申请日：1987-05-12
申请人： Karl E. Hellstrom , Ingegerd E. Hellstrom , Efraim Lavie
发明人： Karl E. Hellstrom , Ingegerd E. Hellstrom , Efraim Lavie
IPC分类号： A61K39/395 , A61K45/08 , A61K47/48 , A61P35/00 , C07K1/113 , C07K14/00 , C07K14/76 , C07K16/00 , C07K19/00
CPC分类号： A61K47/48715 , A61K47/48692 , Y10S514/885 , Y10S530/81 , Y10S530/812
摘要： Novel pH-sensitive immunoconjugates which dissociate in low-pH tumor tissue, comprising a chemotherapeutic agent and an antibody reactive with a tumor-associated antigen are described. The chemotherapeutic agent is coupled to the antibody by a link which is unstable in low pH. The link may comprise a spacer consisting of a polyamino acid. Representative antibodies for use in these immunoconjugates include monoclonal antibodies which are not internalized by tumor cells.

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