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1. 发明申请

US20120107293A1 METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER 审中-公开
标题翻译：治疗癌症的方法和组合
公开(公告)号：US20120107293A1
公开(公告)日：2012-05-03
申请号：US13282832
申请日：2011-10-27
申请人： Zheng Cui , Mark C. Willingham
发明人： Zheng Cui , Mark C. Willingham
IPC分类号： A61K35/14 , C40B30/06 , A61P35/00 , C12Q1/02
CPC分类号： A61K35/17 , A61K35/15 , A61K2300/00
摘要： A method of treating cancer comprises: (a) providing allogenic or autologous white blood cells from a suitable donor; and then (b) administering the white blood cells to the subject in an amount effective to treat the cancer. Preferably the white blood cells comprise innate immune cells. Preferably the white blood cells comprise less than 10% by number of cytotoxic T lymphocytes. Preferably the white blood cells, or more particularly the innate immune cells, are preselected in vitro to kill cancer cells in vitro (for example, by collecting white blood cells from the patient and determining that the white blood cells kill cancer cells in vitro before and thereby pre-selecting the donor, before collecting a subsequent population of cells from the donor for administration).
摘要翻译：治疗癌症的方法包括：（a）从合适的供体提供同种异体或自体白细胞; 然后（b）以有效治疗癌症的量给受试者施用白细胞。优选地，白细胞包含先天免疫细胞。优选地，白细胞包含少于10个数量的细胞毒性T淋巴细胞。优选地，在体外预先选择白细胞，或更特别是先天免疫细胞，以在体外杀死癌细胞（例如，通过从患者中收集白细胞并确定白细胞在体外杀死癌细胞，从而在从供体施用之前收集随后的细胞群体之前预先选择供体）。

2. 发明授权

US5846535A Methods for reducing tumor cell growth by using antibodies with broad tumor reactivity and limited normal tissue reactivity 失效
标题翻译：通过使用具有广泛肿瘤反应性和有限正常组织反应性的抗体来减少肿瘤细胞生长的方法
公开(公告)号：US5846535A
公开(公告)日：1998-12-08
申请号：US467959
申请日：1995-06-06
申请人： Ira Pastan , Mark C. Willingham
发明人： Ira Pastan , Mark C. Willingham
IPC分类号： A61K38/00 , C07K16/30 , A61K39/395
CPC分类号： C07K16/3046 , A61K38/00 , C07K2317/24 , C07K2317/56 , C07K2317/622
摘要： The subject invention relates to methods for reducing tumor cell growth in a mammal by administering compositions which include an antibody having the binding specificity of a monoclonal antibody selected from the group comprising one of those referred to as B1, B3 or B5 conjugated to a toxin, radionuclide or drug.
摘要翻译：本发明涉及通过施用组合物来减少哺乳动物肿瘤细胞生长的方法，所述组合物包括具有与毒素缀合的被称为B1，B3或B5的那些之一的单克隆抗体的结合特异性的抗体，放射性核素或药物。

3. 发明授权

US5817313A Monoclonal antibodies and conjugates thereof useful for the treatment of cancer 失效
标题翻译：用于治疗癌症的单克隆抗体及其缀合物
公开(公告)号：US5817313A
公开(公告)日：1998-10-06
申请号：US629053
申请日：1996-04-08
申请人： Mark C. Willingham , Kai Chang , Ira Pastan
发明人： Mark C. Willingham , Kai Chang , Ira Pastan
IPC分类号： A61K39/395 , A61K38/00 , A61K47/48 , A61K51/10 , A61P35/00 , C07K16/30 , C12N5/10 , C12N15/02 , C12P21/08 , C12R1/91 , G01N33/53 , G01N33/574 , G01N33/577
CPC分类号： A61K47/48638 , A61K47/48569 , A61K51/1045 , C07K16/30 , C07K16/3069 , A61K38/00
摘要： The invention provides a novel treatment of cancer using a monoclonal antibody that recognizes cell surface antigens present on a number of tumor cells, including ovarian, esophageal and cervical carcinomas. A preferred monoclonal antibody is secreted by a hybridoma deposited with the ATCC and has Accession NO. HB 10570.
摘要翻译：本发明提供使用识别存在于多个肿瘤细胞（包括卵巢，食管和宫颈癌）上的细胞表面抗原的单克隆抗体的癌症的新型治疗。优选的单克隆抗体由保藏于ATCC的杂交瘤分泌并具有登录号。 HB 10570。

4. 发明授权

US5525337A Monoclonal antibody binding cell surface antigens for diagnosing cancer 失效
标题翻译：用于诊断癌症的单克隆抗体结合细胞表面抗原
公开(公告)号：US5525337A
公开(公告)日：1996-06-11
申请号：US239101
申请日：1994-05-06
申请人： Mark C. Willingham , Kai Chang , Ira Pastan
发明人： Mark C. Willingham , Kai Chang , Ira Pastan
IPC分类号： A61K39/395 , A61K38/00 , A61K47/48 , A61K51/10 , A61P35/00 , C07K16/30 , C12N5/10 , C12N15/02 , C12P21/08 , C12R1/91 , G01N33/53 , G01N33/574 , G01N33/577 , A61K35/16 , A61K39/00
CPC分类号： A61K47/48638 , A61K47/48569 , A61K51/1045 , C07K16/30 , C07K16/3069 , A61K38/00
摘要： Monoclonal antibody K1 binds to an epitope on the surface of cells of some human tumors, but not to many important normal tissues. Unlike similar antigenic sites such as CA125, this epitope is not shed into the plasma of patients with mesothelioma, e.g. with ovarian cancer. Since the K1 monoclonal antibody is therefore not neutralized by circulating antigen immediately upon injection into the bloodstream, and since K1 allows efficient entry of coupled toxins into cells, the K1 monoclonal antibody can be used in the diagnosis of mesotheliomas.
摘要翻译：单克隆抗体K1结合一些人肿瘤细胞表面上的表位，但不与许多重要的正常组织结合。与类似的抗原性位点如CA125不同，该表位不会流入患有间皮瘤的患者的血浆中，例如，与卵巢癌。因为K1注射单克隆抗体在血液注射后不会立即循环抗原中和，因为K1能有效地将毒素进入细胞，所以K1单克隆抗体可用于诊断间皮瘤。

5. 发明授权

US4958009A Anti-human ovarian cancer immunotoxins and methods of use thereof 失效
标题翻译：抗人卵巢癌免疫毒素及其使用方法
公开(公告)号：US4958009A
公开(公告)日：1990-09-18
申请号：US69867
申请日：1987-07-06
申请人： Michael J. Bjorn , David J. FitzGerald , Arthur E. Frankel , Walter J. Laird , Ira H. Pastan , David B. Ring , Mark C. Willingham , Jeffrey L. Windelhake
发明人： Michael J. Bjorn , David J. FitzGerald , Arthur E. Frankel , Walter J. Laird , Ira H. Pastan , David B. Ring , Mark C. Willingham , Jeffrey L. Windelhake
IPC分类号： C12N15/02 , A61K38/00 , A61K39/395 , A61K47/00 , A61K47/48 , A61P35/00 , C07K14/00 , C07K14/195 , C07K14/37 , C07K14/41 , C07K14/415 , C07K16/00 , C07K16/30 , C07K19/00 , C12N5/00 , C12N5/10 , C12P21/00 , C12P21/08 , C12R1/91 , G01N33/574 , G01N33/577
CPC分类号： C07K16/30 , A61K47/48638 , A61K38/00 , Y10S424/804 , Y10S424/807 , Y10S514/885 , Y10S530/808 , Y10S530/864
摘要： Immunotoxins comprising a cytotoxic moiety and monoclonal antibodies which bind to human ovarian cancer tissue having at least one of the following capabilities are claimed: cytotoxic ID.sub.50 of 10 nM or less against human ovarian cancer cells, retardation of human ovarian cancer tumor growth in mammals or extension of survival of a mammal carrying a human ovarian cancer tumor. Antigens to which the monoclonal antibody of the immunotoxin bind are identified and characterize the immunotoxins. Methods of killing human ovarian cancer cells, retarding the growth of human ovarian cancer tumors in mammals or extending the survival of mammals carrying human ovarian cancer tumors are claimed.
摘要翻译：包含细胞毒素部分的免疫毒素和结合至少具有以下能力之一的人卵巢癌组织的单克隆抗体是要求保护的：针对人卵巢癌细胞的10nM或更小的细胞毒性ID50，哺乳动物或延伸中人卵巢癌肿瘤生长的延迟携带人卵巢癌肿瘤的哺乳动物的存活。识别免疫毒素结合的单克隆抗体的抗原并表征免疫毒素。要求杀死人类卵巢癌细胞的方法，延缓哺乳动物中人卵巢癌肿瘤的生长或延长携带人卵巢癌肿瘤的哺乳动物的存活。

6. 发明授权

US4545985A Pseudomonas exotoxin conjugate immunotoxins 失效
标题翻译：假单胞菌外毒素结合物免疫毒素
公开(公告)号：US4545985A
公开(公告)日：1985-10-08
申请号：US574173
申请日：1984-01-26
申请人： Ira Pastan , Mark C. Willingham , David J. Fitzgerald
发明人： Ira Pastan , Mark C. Willingham , David J. Fitzgerald
IPC分类号： A61K47/48 , A61K39/00 , A23J1/06 , A61K37/00 , A61K39/02
CPC分类号： A61K47/48484 , Y10S530/806 , Y10S530/807 , Y10S530/825 , Y10S530/826 , Y10S530/828
摘要： A method of modifying Pseudomonas exotoxin (PE) with methyl-4-mercaptobutyrimidate is disclosed so that after conjugating the exotoxin to a monoclonal antibody (ab) such as the antibody to the transferrin receptor, the PE-ab conjugate becomes a highly potent immunotoxin suitable for use against human tumor cells. This same method has been used to conjugate PE to epidermal growth factor (EGF) to create a highly potent growth factor-toxin conjugate for use against cells having large numbers of EGF receptors. Also disclosed are the immunotoxin conjugates for Pseudomonas exotoxin coupled to anti-TFR (antibody to the transferrin receptor) and anti-TAC (antibody to the human T-cell growth factor receptor) and to EGF.
摘要翻译：公开了用甲基-4-巯基丁酰亚胺酸酯修饰假单胞菌外毒素（PE）的方法，使得在将外毒素与转运蛋白受体的抗体结合到单克隆抗体（ab）之后，PE-ab缀合物变成高度有效的免疫毒素用于对抗肿瘤细胞。已经使用相同的方法将PE与表皮生长因子（EGF）缀合以产生用于对具有大量EGF受体的细胞的高效生长因子 - 毒素缀合物。还公开了与抗TFR（针对转铁蛋白受体的抗体）和抗TAC（针对人T细胞生长因子受体的抗体）和EGF偶联的假单胞菌外毒素的免疫毒素偶联物。

7. 发明授权

US5612032A Method for diagnosing tumors using mouse monoclonal antibodies 失效
标题翻译：使用小鼠单克隆抗体诊断肿瘤的方法
公开(公告)号：US5612032A
公开(公告)日：1997-03-18
申请号：US363203
申请日：1994-12-22
申请人： Ira Pastan , Mark C. Willingham
发明人： Ira Pastan , Mark C. Willingham
IPC分类号： A61K39/395 , A61K38/00 , A61K47/48 , A61P35/00 , C07K16/18 , C07K16/30 , C12N5/10 , C12N15/02 , C12P21/08 , G01N33/53 , G01N33/574 , G01N33/577 , A61K51/10 , C07K16/00 , C07K16/28
CPC分类号： C07K16/30 , A61K47/48569 , C07K16/18 , G01N33/57419 , G01N33/57446 , G01N33/57449 , G01N33/57492 , A61K38/00 , C07K2317/24 , C07K2317/56 , C07K2317/622
摘要： The subject invention relates to monoclonal antibodies and uses thereof. In particular, the invention relates to three monoclonal antibodies, referred to as B1, B3, and B5, which are useful in the treatment and diagnosis of many forms of cancer.
摘要翻译：本发明涉及单克隆抗体及其用途。特别地，本发明涉及称为B1，B3和B5的三种单克隆抗体，其可用于治疗和诊断许多形式的癌症。

8. 发明授权

US5320956A Monoclonal antibody useful for the diagnosis of cancer 失效
标题翻译：用于诊断癌症的单克隆抗体
公开(公告)号：US5320956A
公开(公告)日：1994-06-14
申请号：US977727
申请日：1992-11-16
申请人： Mark C. Willingham , Kai Chang , Ira Pastan
发明人： Mark C. Willingham , Kai Chang , Ira Pastan
IPC分类号： A61K39/395 , A61K38/00 , A61K47/48 , A61K51/10 , A61P35/00 , C07K16/30 , C12N5/10 , C12N15/02 , C12P21/08 , C12R1/91 , G01N33/53 , G01N33/574 , G01N33/577 , A61K35/00 , A61K35/16 , C07K15/28
CPC分类号： A61K47/48638 , A61K47/48569 , A61K51/1045 , C07K16/30 , C07K16/3069 , A61K38/00
摘要： The invention provides novel monoclonal antibodies and the hybridomas that secrete them. The antibodies can be used for the diagnosis of a number of cancers, such as ovarian, esophageal and cervical carcinomas. A preferred antibody is secreted by a hybridoma deposited with the ATCC and has Accession No. HB 10570.
摘要翻译：本发明提供新型单克隆抗体和分泌它们的杂交瘤。抗体可用于诊断许多癌症，如卵巢癌，食道癌和子宫颈癌。优选的抗体由保藏于ATCC的杂交瘤分泌并具有登录号HB 10570。

9. 发明授权

US5242813A Mouse monoclonal antibodies specific for normal primate tissue, malignant human cultural cell lines human tumors 失效
标题翻译：正常组织组织，恶性肿瘤细胞系人类肿瘤特异性小鼠单克隆抗体
公开(公告)号：US5242813A
公开(公告)日：1993-09-07
申请号：US596289
申请日：1990-10-12
申请人： Ira Pastan , Mark C. Willingham
发明人： Ira Pastan , Mark C. Willingham
IPC分类号： A61K39/395 , A61K38/00 , A61K47/48 , A61P35/00 , C07K16/18 , C07K16/30 , C12N5/10 , C12N15/02 , C12P21/08 , G01N33/53 , G01N33/574 , G01N33/577
CPC分类号： C07K16/30 , A61K47/48569 , C07K16/18 , G01N33/57419 , G01N33/57446 , G01N33/57449 , G01N33/57492 , A61K38/00 , C07K2317/24 , C07K2317/56 , C07K2317/622
摘要： The subject invention relates to monoclonal antibodies and uses thereof. In particular, the invention relates to three monoclonal antibodies, referred to as B1, B3, and B5, which are useful in the treatment and diagnosis of many forms of cancer.
摘要翻译：本发明涉及单克隆抗体及其用途。特别地，本发明涉及称为B1，B3和B5的三种单克隆抗体，其可用于治疗和诊断许多形式的癌症。

10. 发明授权

US4396628A Antiviral activities of dansylcadaverine and closely related compounds 失效
标题翻译：丹参酰胺和密切相关化合物的抗病毒活性
公开(公告)号：US4396628A
公开(公告)日：1983-08-02
申请号：US352599
申请日：1982-02-26
申请人： Ira H. Pastan , Mark C. Willingham
发明人： Ira H. Pastan , Mark C. Willingham
IPC分类号： A61K31/18
CPC分类号： A61K31/18
摘要： The entry of animal viruses into their host cells proceeds via a specialized internalization pathway involving clathrin coated regions of the plasma membrane. In the present invention, there has been examined the effect of dansylcadaverine compared with amantadine and other antiviral agents as to the entry of vesicular stomatitis virus (VSV) into mouse cells. It was found that both compounds inhibit VSV entry. Both compounds inhibit the uptake of .alpha..sub.2 macroglobulin (.alpha.2M), a protein that binds to specific membrane receptors and follows the same route of internalization. Dansylcadaverine is 20 fold more potent than amantadine to the blocking virus and also to the .alpha..sub.2 macroglobulin uptake.
摘要翻译：动物病毒进入其宿主细胞通过涉及质膜的网格蛋白包被的区域的专门的内化途径进行。在本发明中，已经研究了丹参酰胺素与金刚烷胺和其他抗病毒剂相比，对水泡性口炎病毒（VSV）进入小鼠细胞的效果。发现两种化合物都抑制VSV进入。两种化合物均抑制α2巨球蛋白（α2M）的摄取，α2是一种与特异性膜受体结合并遵循相同的内化途径的蛋白质。丹参酰胺素比金刚烷胺对阻断病毒的效力高20倍，而且对于α2巨球蛋白摄取更有效。

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