公开(公告)号：US20060191024A1

公开(公告)日：2006-08-24

申请号：US11143737

申请日：2005-06-03

申请人： William Kloetzer ,  Nabil Hanna

发明人： William Kloetzer ,  Nabil Hanna

IPC分类号： A01K67/027 ,  C07H21/04 ,  C12P21/06 ,  C07K16/24 ,  C12N5/06

CPC分类号： A01K67/0276 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/01 ,  A01K2267/0331 ,  A61K39/3955 ,  A61K2039/505 ,  C07K14/52 ,  C07K16/24 ,  C12N15/8509 ,  A61K31/00 ,  A61K2300/00

摘要： The specification provides methods of preparing high-affinity antibodies to a macrophage migration inhibitory factor (MIF) in animals in which the MIF gene has been homozygously knocked-out (MIF−/−). Also provided are methods of preparing hybridomas which produce the anti-MIF antibodies, methods of administering the antibodies to treat inflammatory or cancerous conditions and/or diseases modulated by MIF, as well as compositions comprising said high-affinity anti-MIF antibodies.

摘要翻译： 本说明书提供了在MIF基因已经被纯合敲除的动物中制备巨噬细胞迁移抑制因子（MIF）的高亲和力抗体的方法（MIF）。 还提供了制备产生抗MIF抗体的杂交瘤的方法，施用抗体以治疗炎性或癌性病症和/或由MIF调节的疾病的方法，以及包含所述高亲和力抗MIF抗体的组合物的方法。

公开(公告)号：US07510713B2

公开(公告)日：2009-03-31

申请号：US11840597

申请日：2007-08-17

申请人： Darrell R. Anderson ,  Nabil Hanna ,  Peter Brams

发明人： Darrell R. Anderson ,  Nabil Hanna ,  Peter Brams

IPC分类号： A61K39/395 ,  C07K16/28

CPC分类号： C07K16/2827 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/55 ,  C07K2317/73 ,  C07K2317/76 ,  C07K2317/92

摘要： The present invention relates to the identification of antibodies which are specific to human B7.1 antigen (CD80) and which are capable of inhibiting the binding of B7.1 to a CD28 receptor and which are not capable of inhibiting the binding of B7.1 to a CTLA-4 receptor. Two of these antibodies, 16C10 and 7C10, significantly inhibit the production of IL-2, in spite of the existence of a second activating ligand B7.2 (CD86). Blocking of the primary activation signal between CD28 and B7.1 (CD80) with these antibodies while allowing the unimpaired or coincident interaction of CTLA-4 and B7.1 and/or B7.2 represents a combined antagonistic effect on positive co-stimulation with an agonistic effect on negative signalling. These antibodies may be used as specific immunosuppressants, e.g., for the treatment of autoimmune diseases and to prevent organ transplant rejection.

摘要翻译： 本发明涉及对人B7.1抗原（CD80）特异性并且能够抑制B7.1与CD28受体的结合并且不能抑制B7.1结合的抗体的鉴定 到CTLA-4受体。 尽管存在第二活化配体B7.2（CD86），但是这些抗体16C10和7C10中的两个显着抑制了IL-2的产生。 阻断CD28和B7.1（CD80）之间的主要激活信号与这些抗体同时允许CTLA-4和B7.1和/或B7.2的未受损或一致的相互作用代表对阳性共刺激的组合拮抗作用， 对负信号的激动作用。 这些抗体可以用作特异性免疫抑制剂，例如用于治疗自身免疫性疾病和预防器官移植排斥。

公开(公告)号：US20080095769A1

公开(公告)日：2008-04-24

申请号：US11840591

申请日：2007-08-17

申请人： Darrell Anderson ,  Nabil Hanna ,  Peter Brams

发明人： Darrell Anderson ,  Nabil Hanna ,  Peter Brams

IPC分类号： A61K39/395 ,  A61P31/00 ,  A61P37/00 ,  C07K16/18 ,  C07K16/28

CPC分类号： C07K16/2827 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/55 ,  C07K2317/73 ,  C07K2317/76 ,  C07K2317/92

摘要： The present invention relates to the identification of antibodies which are specific to human B7.1 antigen (CD80) and which are capable of inhibiting the binding of B7.1 to a CD28 receptor and which are not capable of inhibiting the binding of B7.1 to a CTLA-4 receptor. Two of these antibodies, 16C10 and 7C10, significantly inhibit the production of IL-2, in spite of the existence of a second activating ligand B7.2 (CD86). Blocking of the primary activation signal between CD28 and B7.1 (CD80) with these antibodies while allowing the unimpaired or coincident interaction of CTLA-4 and B7.1 and/or B7.2 represents a combined antagonistic effect on positive co-stimulation with an agonistic effect on negative signalling. These antibodies may be used as specific immunosuppressants, e.g., for the treatment of autoimmune diseases and to prevent organ transplant rejection.

公开(公告)号：US07319139B2

公开(公告)日：2008-01-15

申请号：US10058069

申请日：2002-01-29

申请人： Gary R Braslawsky ,  Nabil Hanna ,  Paul Chinn ,  Kandasamy Hariharan

发明人： Gary R Braslawsky ,  Nabil Hanna ,  Paul Chinn ,  Kandasamy Hariharan

IPC分类号： C12P21/08 ,  C07K16/00 ,  A61K39/395 ,  C12P21/04 ,  C12N5/06

CPC分类号： C12P21/02 ,  A61K47/6849 ,  A61K47/6851 ,  A61K47/6869 ,  A61K47/6901 ,  A61K51/1027 ,  A61K51/1045 ,  A61K51/1072 ,  A61K2039/505 ,  C07K16/00 ,  C07K16/2896 ,  C07K16/30 ,  C07K16/3069 ,  C07K2317/24 ,  C07K2317/52 ,  C07K2319/00 ,  C12N15/85

摘要： Methods, compositions and kits comprising dimeric antibodies for the treatment of neoplastic, autoimmune or other disorders are provided. The dimeric antibodies of the instant invention may comprise two antibody molecules (H4L4) having the same antigen binding specificity (homodimers) or, alternatively, may comprise two different antibody molecules having binding specificity for two distinct antigens (heterodimers). In preferred embodiments the antibody molecules comprising the dimers are non-covalently associated.

摘要翻译： 提供了包含用于治疗肿瘤，自身免疫或其它病症的二聚抗体的方法，组合物和试剂盒。 本发明的二聚体抗体可以包含具有相同抗原结合特异性（同源二聚体）的两个抗体分子（H 4 S 4 L 4），或者可以包含两种不同的抗体 对两种不同抗原（异二聚体）具有结合特异性的分子。 在优选的实施方案中，包含二聚体的抗体分子是非共价缔合的。

公开(公告)号：US20070065436A1

公开(公告)日：2007-03-22

申请号：US11464447

申请日：2006-08-14

申请人： Kandasamy Hariharan ,  Nabil Hanna

发明人： Kandasamy Hariharan ,  Nabil Hanna

IPC分类号： A61K39/395 ,  A61K39/00

CPC分类号： C07K16/2827 ,  A61K39/39558 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/76 ,  C07K2319/30 ,  A61K2300/00

摘要： Methods for treating B cell malignancies, in particular B cell leukemia and lymphoma, using an anti-CD80 antibody alone or in combination with an anti-CD20 antibody or chemotherapy is provided. These methods result in a synergistic anti-tumor response.

摘要翻译： 提供了使用单独的抗CD80抗体或与抗-CD20抗体或化疗联合治疗B细胞恶性肿瘤，特别是B细胞白血病和淋巴瘤的方法。 这些方法导致协同的抗肿瘤反应。

公开(公告)号：US20060275291A1

公开(公告)日：2006-12-07

申请号：US11464133

申请日：2006-08-11

申请人： Darrell Anderson ,  Nabil Hanna ,  Peter Brams

发明人： Darrell Anderson ,  Nabil Hanna ,  Peter Brams

IPC分类号： A61K39/395 ,  C07K16/28

CPC分类号： C07K16/2827 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/55 ,  C07K2317/73 ,  C07K2317/76 ,  C07K2317/92

摘要： The present invention relates to the identification of antibodies which are specific to human B7.1 antigen (CD80) and which are capable of inhibiting the binding of B7.1 to a CD28 receptor and which are not capable of inhibiting the binding of B7.1 to a CTLA-4 receptor. Two of these antibodies, 16C10 and 7C10, significantly inhibit the production of IL-2, in spite of the existence of a second activating ligand B7.2 (CD86). Blocking of the primary activation signal between CD28 and B7.1 (CD80) with these antibodies while allowing the unimpaired or coincident interaction of CTLA-4 and B7.1 and/or B7.2 represents a combined antagonistic effect on positive co-stimulation with an agonistic effect on negative signalling. These antibodies may be used as specific immunosuppressants, e.g., for the treatment of autoimmune diseases and to prevent organ transplant rejection.

摘要翻译： 本发明涉及对人B7.1抗原（CD80）特异性并且能够抑制B7.1与CD28受体的结合并且不能抑制B7.1结合的抗体的鉴定 到CTLA-4受体。 尽管存在第二活化配体B7.2（CD86），但是这些抗体16C10和7C10中的两个显着抑制了IL-2的产生。 阻断CD28和B7.1（CD80）之间的主要激活信号与这些抗体同时允许CTLA-4和B7.1和/或B7.2的未受损或一致的相互作用代表对阳性共刺激的组合拮抗作用， 对负信号的激动作用。 这些抗体可以用作特异性免疫抑制剂，例如用于治疗自身免疫性疾病和预防器官移植排斥。

公开(公告)号：US07122187B2

公开(公告)日：2006-10-17

申请号：US10171681

申请日：2002-06-17

申请人： Amelia Black ,  Nabil Hanna ,  Eduardo A. Padian ,  Roland A. Newman

发明人： Amelia Black ,  Nabil Hanna ,  Eduardo A. Padian ,  Roland A. Newman

IPC分类号： A61K39/395 ,  C07K16/28

CPC分类号： C07K16/467 ,  A61K9/0014 ,  A61K9/0019 ,  A61K9/0048 ,  A61K9/008 ,  A61K38/00 ,  A61K39/395 ,  A61K2039/505 ,  C07K16/2875 ,  C07K2317/24 ,  C07K2317/73 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/00 ,  G01N33/564 ,  G01N2333/70578 ,  G01N2800/24 ,  G01N2800/245

摘要： The present invention is directed to humanized antibodies which bind human gp39 and their use as therapeutic agents. These humanized antibodies are especially useful for treatment of autoimmune diseases; and an immunosuppressant during transplantation of heterologous cells, tissues or organs, cell therapy, and gene therapy.

摘要翻译： 本发明涉及结合人gp39的人源化抗体及其作为治疗剂的用途。 这些人源化抗体特别适用于治疗自身免疫疾病; 和异种细胞，组织或器官移植期间的免疫抑制剂，细胞治疗和基因治疗。

公开(公告)号：US20060153848A1

公开(公告)日：2006-07-13

申请号：US11298567

申请日：2005-12-12

申请人： Nabil Hanna ,  Gary Braslawsky ,  Kandasamy Hariharan

发明人： Nabil Hanna ,  Gary Braslawsky ,  Kandasamy Hariharan

IPC分类号： A61K39/395 ,  A61K39/12 ,  A61K38/17

CPC分类号： A61K39/00 ,  A61K9/1075 ,  A61K39/0011 ,  A61K39/12 ,  A61K39/39 ,  A61K39/39558 ,  A61K2039/505 ,  A61K2039/55516 ,  A61K2039/55522 ,  A61K2039/55555 ,  A61K2039/55566 ,  A61K2039/57 ,  A61K2039/585 ,  C07K16/22 ,  C07K2317/76 ,  C12N2710/20034 ,  Y02A50/412 ,  Y02A50/464 ,  A61K2300/00

摘要： The present invention provides a synergistic composition and methods for treating neoplastic or cancerous growths as well as for treating such patients in order to restore or boost hematopoiesis. The present invention comprises administration of the combination of a cytotoxic T-lymphocyte inducing composition and at least one agent which is capable of neutralizing or down regulating the activity of tumor secreted immunosuppressive factors, separately or in combination.

摘要翻译： 本发明提供了用于治疗肿瘤或癌性生长以及用于治疗这些患者以恢复或增强造血作用的协同组合物和方法。 本发明包括施用细胞毒性T淋巴细胞诱导组合物和能够分别或组合地中和或下调肿瘤分泌的免疫抑制因子的活性的至少一种试剂的组合。

公开(公告)号：US20050129688A1

公开(公告)日：2005-06-16

申请号：US10986780

申请日：2004-11-15

申请人： Darrell Anderson ,  Peter Brams ,  Nabil Hanna ,  William Shestowsky ,  Cheryl Heard

发明人： Darrell Anderson ,  Peter Brams ,  Nabil Hanna ,  William Shestowsky ,  Cheryl Heard

IPC分类号： C12N15/02 ,  A61K38/00 ,  A61K39/395 ,  A61P17/00 ,  A61P29/00 ,  A61P35/00 ,  A61P37/00 ,  C07K14/705 ,  C07K16/18 ,  C07K16/28 ,  C12N5/10 ,  C12N15/09 ,  C12P21/08 ,  C07K16/44 ,  C12N5/06

CPC分类号： C07K14/70532 ,  A61K38/00 ,  C07K16/2827

摘要： The present invention relates to the identification of macaque antibodies to human B7.1 and B7.2 by screening of phage display libraries or monkey heterohybridomas obtained using B lymphocytes from B7.1 and/or B7.2 immunized monkeys. More specifically, the invention provides four monkey monoclonal antibodies 7B6, 16C10, 7C10 and 20C9 which inhibit the B7:CD28 pathway and thereby function as effective immunosuppressants. The invention further provides the complete DNA and amino acid sequences of the light and heavy chain of three primatized antibodies derived from those monkey monoclonal antibodies which bind B7.1 and possibly B7.2, primatized 7C10, primatized 7B6 and primatized 16C10. These primatized and monkey antibodies may be used as specific immunosuppressants, e.g., for the treatment of autoimmune diseases and to prevent organ transplant rejection.

摘要翻译： 本发明涉及通过筛选使用B7.1和/或B7.2免疫的猴子的B淋巴细胞获得的噬菌体展示文库或猴杂合杂交瘤来鉴定人B7.1和B7.2的猕猴抗体。 更具体地，本发明提供四种抑制B7：CD28途径的猴单克隆抗体7B6,16C10,7C10和20C9，从而起到有效的免疫抑制剂的作用。 本发明进一步提供衍生自结合B7.1和可能B7.2，灵长类化7C10，灵长类化7B6和灵长类16C10的猴单克隆抗体的三种灵长类抗体轻链和重链的完整DNA和氨基酸序列。 这些灵长类和猴抗体可以用作特异性免疫抑制剂，例如用于治疗自身免疫性疾病和预防器官移植排斥。

公开(公告)号：US06897044B1

公开(公告)日：2005-05-24

申请号：US09238741

申请日：1999-01-28

申请人： Gary R Braslawsky ,  Nabil Hanna ,  Kandasamy Hariharan ,  Michael J LaBarre ,  Tri B Huynh

发明人： Gary R Braslawsky ,  Nabil Hanna ,  Kandasamy Hariharan ,  Michael J LaBarre ,  Tri B Huynh

IPC分类号： C12N15/09 ,  A61K39/395 ,  A61K47/48 ,  A61P1/00 ,  A61P11/00 ,  A61P11/02 ,  A61P11/06 ,  A61P17/00 ,  A61P35/00 ,  A61P37/02 ,  A61P37/08 ,  C07K16/28 ,  C07K16/46 ,  C12P21/08 ,  C12N15/00

CPC分类号： C07K16/2887 ,  A61K47/6835 ,  A61K2039/505 ,  C07K16/2851 ,  C07K16/468 ,  C07K2317/31 ,  C07K2317/734

摘要： The present invention relates to a novel process for the preparation of biologically active antibody dimers in a pharmaceutically acceptable composition. The dimers can be composed of two antibody molecules having the same antigen binding specificity and linked through reducible, disulfide, or a non-reducible thioether, bond (homodimer). Alternatively, the dimers can be composed of two different antibody molecules having binding specificity for two distinct antigens (heterodimer). These dimers are useful for inducing hyper-cross-linking of membrane antigens. The present invention further relates to the use of biologically active antibody dimers for the preferential killing or inhibition of selected cell populations in the treatment of diseases such as cancer and autoimmune disorders.

摘要翻译： 本发明涉及一种用于在药学上可接受的组合物中制备生物活性抗体二聚体的新方法。 二聚体可以由具有相同抗原结合特异性的两个抗体分子组成并通过可还原的二硫键或不可还原的硫醚键（同二聚体）连接。 或者，二聚体可以由对两种不同抗原（异二聚体）具有结合特异性的两种不同抗体分子组成。 这些二聚体可用于诱导膜抗原的超交联。 本发明还涉及生物活性抗体二聚体在优先杀死或抑制所选细胞群体治疗诸如癌症和自身免疫疾病的疾病中的用途。