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1. 发明申请

WO1996040915A2 NOVEL CTLA4/CD28 LIGANDS AND USES THEREFOR 审中-公开
标题翻译：新CTLA4 / CD28配对及其用途
公开(公告)号：WO1996040915A2
公开(公告)日：1996-12-19
申请号：PCT/US1996009052
申请日：1996-06-06
申请人： DANA-FARBER CANCER INSTITUTE , REPLIGEN CORPORATION
发明人： DANA-FARBER CANCER INSTITUTE , REPLIGEN CORPORATION , FREEMAN, Gordon, J. , NADLER, Lee, M. , GRAY, Gary, S.
IPC分类号： C12N15/12
CPC分类号： C07K16/2827 , A01K67/0276 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/075 , A01K2217/30 , A01K2227/105 , A01K2267/01 , A01K2267/03 , A01K2267/0325 , A01K2267/0331 , A01K2267/0381 , A61K38/00 , C07K14/70503 , C07K14/70532 , C07K2317/73 , C07K2319/00 , C07K2319/02 , C07K2319/30 , C12N15/8509
摘要： Nucleic acids encoding novel CTLA4/CD28 ligands which costimulate T cell activation are disclosed. In one embodiment, the nucleic acid has a sequence which encodes a fusion protein consisting of at least part of the B lymphocyte antigen, B7-2, fused to one or more constant domains of immunoglobulin heavy chain. Preferably, the nucleic acid is a DNA molecule comprising at least a portion of a nucleotide sequence shown in Figure 8, SEQ ID NO:1 or Figure 14, SEQ ID NO:23. The nucleic acid sequences of the invention can be integrated into various expression vectors, which in turn direct the synthesis of the corresponding proteins or peptides in a variety of hosts, particularly eukaryotic cells, such as mammalian and insect cell culture. Also disclosed are host cells transformed to produce proteins or peptides encoded by the nucleic acid sequences of the invention and isolated proteins and peptides which comprise at least a portion of a novel B lymphocyte antigen. Proteins and peptides described herein can be administered to subjects to enhance or suppress T cell-mediated immune responses.
摘要翻译：公开了编码协同T细胞活化的新型CTLA4 / CD28配体的核酸。在一个实施方案中，所述核酸具有编码由与免疫球蛋白重链的一个或多个恒定结构域融合的至少部分B淋巴细胞抗原B7-2组成的融合蛋白的序列。优选地，核酸是包含图8所示核苷酸序列的至少一部分的DNA分子，SEQ ID NO：1或图14，SEQ ID NO：23。本发明的核酸序列可以整合到各种表达载体中，这又指导了多种宿主，特别是真核细胞如哺乳动物和昆虫细胞培养物中的相应蛋白质或肽的合成。还公开了转化以产生由本发明的核酸序列编码的蛋白质或肽的宿主细胞和包含至少一部分新型B淋巴细胞抗原的分离的蛋白质和肽。本文所述的蛋白质和肽可以施用于受试者以增强或抑制T细胞介导的免疫应答。

2. 发明申请

WO1995003408A1 B7-2: CTL A4/CD 28 COUNTER RECEPTOR 审中-公开
标题翻译： B7-2：CTL A4 / CD 28计数器受体
公开(公告)号：WO1995003408A1
公开(公告)日：1995-02-02
申请号：PCT/US1994008423
申请日：1994-07-26
申请人： DANA-FARBER CANCER INSTITUTE , REPLIGEN CORPORATION
发明人： DANA-FARBER CANCER INSTITUTE , REPLIGEN CORPORATION , FREEMAN, Gordon, J. , NADLER, Lee, M. , GRAY, Gary, S. , GREENFIELD, Edward
IPC分类号： C12N15/12
CPC分类号： C12N15/8509 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/075 , A01K2227/105 , A01K2267/03 , A01K2267/0331 , A01K2267/0381 , A61K38/00 , C07K14/70532 , C07K16/2827 , C07K2319/30
摘要： Nucleic acids encoding novel CTLA4/CD28 ligands which costimulate T cell activation are disclosed. In one embodiment, the nucleic acid has a sequence which encodes a B lymphocyte antigen, B7-2. Preferably, the nucleic acid is a DNA molecule comprising at least a portion of a nucleotide sequence shown in Figure 8, SEQ ID NO: 1 or Figure 14, SEQ ID NO: 23. The nucleic acid sequences of the invention can be integrated into various expression vectors, which in turn direct the synthesis of the corresponding proteins or peptides in a variety of hosts, particularly eukaryotic cells, such as mammalian and insect cell culture. Also disclosed are host cells transformed to produce proteins or peptides encoded by the nucleic acid sequences of the invention and isolated proteins and peptides which comprise at least a portion of a novel B lymphocyte antigen. Proteins and peptides described herein can be administered to subjects to enhance or suppress T cell-mediated immune responses.
摘要翻译：公开了编码协同T细胞活化的新型CTLA4 / CD28配体的核酸。在一个实施方案中，核酸具有编码B淋巴细胞抗原B7-2的序列。优选地，核酸是包含图8，SEQ ID NO：1或图14，SEQ ID NO：23所示核苷酸序列的至少一部分的DNA分子。本发明的核酸序列可以整合到各种表达载体，其又指导多种宿主，特别是真核细胞如哺乳动物和昆虫细胞培养物中的相应蛋白质或肽的合成。还公开了转化以产生由本发明的核酸序列编码的蛋白质或肽的宿主细胞和包含至少一部分新型B淋巴细胞抗原的分离的蛋白质和肽。本文所述的蛋白质和肽可以施用于受试者以增强或抑制T细胞介导的免疫应答。

3. 发明申请

WO1995033823A1 METHODS FOR SELECTIVELY STIMULATING PROLIFERATION OF T CELLS 审中-公开
标题翻译：选择性刺激T细胞增殖的方法
公开(公告)号：WO1995033823A1
公开(公告)日：1995-12-14
申请号：PCT/US1994013782
申请日：1994-12-01
申请人： THE UNITED STATES OF AMERICA, represented by THE SECRETARY OF THE NAVY , THE REGENTS OF THE UNIVERSITY OF MICHIGAN , REPLIGEN CORPORATION , DANA-FARBER CANCER INSTITUTE
发明人： THE UNITED STATES OF AMERICA, represented by THE SECRETARY OF THE NAVY , THE REGENTS OF THE UNIVERSITY OF MICHIGAN , REPLIGEN CORPORATION , DANA-FARBER CANCER INSTITUTE , JUNE, Carl, H. , THOMPSON, Craig, B. , NABEL, Gary, J. , GRAY, Gary, S. , RENNERT, Paul, D. , FREEMAN, Gordon, J.
IPC分类号： C12N05/08
CPC分类号： C07K16/2818 , A61K2039/5158 , C07K14/705 , C07K16/2806 , C07K16/2809 , C07K16/2896 , C07K2317/34 , C12N5/0636 , C12N2501/51 , C12N2501/515 , C12N2501/599
摘要： Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population of T cells, an accessory molecule on the surface of the T cells, such as CD9 or CD28, is stimulated with a ligand (e.g. monoclonal antibody ES5.2D8) specific for CD9 which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.
摘要翻译：描述了通过激活T细胞群并用结合附属分子的配体刺激T细胞表面上的辅助分子来诱导T细胞群体增殖的方法。 T细胞增殖发生在没有外源生长因子或附属细胞的情况下。通过刺激T细胞受体（TCR）/ CD3复合物或CD2表面蛋白来完成T细胞活化。为了诱导T细胞活化群体的增殖，T细胞表面如CD9或CD28上的辅助分子被用于结合辅助分子的CD9特异性配体（例如单克隆抗体ES5.2D8）刺激。通过本发明方法扩增的T细胞群体可以被遗传转导并用于免疫治疗，或可用于诊断方法。

4. 发明申请

WO1995033770A1 LIGANDS FOR INDUCTION OF ANTIGEN SPECIFIC APOPTOSIS IN T CELLS 审中-公开
标题翻译：用于诱导T细胞中抗原特异性宿主的配体
公开(公告)号：WO1995033770A1
公开(公告)日：1995-12-14
申请号：PCT/US1995006726
申请日：1995-06-02
申请人： REPLIGEN CORPORATION , DANA FARBER CANCER INSTITUTE
发明人： REPLIGEN CORPORATION , DANA FARBER CANCER INSTITUTE , GRIBBEN, John, G. , FREEMAN, Gordon, J. , NADLER, Lee, M. , RENNERT, Paul , JELLIS, Cindy, L. , GREENFIELD, Edward , GRAY, Gary, S.
IPC分类号： C07K14/705
CPC分类号： C07K14/70521 , A61K38/00 , C07K14/70532 , C07K16/2818 , C07K2317/34
摘要： Isolated ligands which bind a molecule expressed on the surface of T cells and induce antigen specific apoptosis in activated T cells are disclosed. Preferably, the T cell surface molecule is CTLA4 and the ligand is a monoclonal anti-CTLA4 antibody that binds to an epitope of CTLA4 distinct from the binding sites of B7-1 and B7-2. Upon binding of the antibody to CTLA4 on an activated T cell, in the presence of an antigenic signal, antigen specific apoptosis is induced. The invention also describes a novel natural CTLA4 ligand, distinct from B7-1 and B7-2, which mediates induction of apoptosis. Pharmaceutical compositions of anti-CTLA4 antibodies or other isolated CTLA4 ligands which can be administered to subjects to induce T cell apoptosis, thereby clonally deleting antigen specific T cells, such as alloreactive T cells in transplantation situations or autoreactive T cells in autoimmune disorders, are also disclosed. Methods for inducing T cell apoptosis in vitro with an anti-CTLA4 antibody or other ligand of the invention together with an antigen specific signal are also disclosed, e.g., for use in purging alloreactive T cells from donor bone marrow prior to bone marrow transplantation to inhibit graft versus host disease.
摘要翻译：公开了结合在T细胞表面上表达并在活化的T细胞中诱导抗原特异性凋亡的分子的分离的配体。优选地，T细胞表面分子是CTLA4，并且配体是结合与B7-1和B7-2的结合位点不同的CTLA4的表位的单克隆抗CTLA4抗体。当抗体与CTLA4在活化的T细胞上结合时，在抗原信号存在下，诱导抗原特异性凋亡。本发明还描述了一种与介导细胞凋亡诱导的B7-1和B7-2不同的新型天然CTLA4配体。抗CTLA4抗体或其他分离的CTLA4配体的药物组合物也可以被给予受试者诱导T细胞凋亡，从而克隆地删除抗原特异性T细胞，例如移植情况下的同种异体反应性T细胞或自身免疫性疾病中的自身反应性T细胞，披露。还公开了用本发明的抗CTLA4抗体或其他配体与抗原特异性信号一起体外诱导T细胞凋亡的方法，例如用于在骨髓移植之前从供体骨髓中清除同种异体反应性T细胞以抑制移植物抗宿主病。

5. 发明申请

WO1996014865A1 METHODS FOR INHIBITING GRAFT VERSUS HOST DISEASE IN BONE MARROW TRANSPLANTATION 审中-公开
标题翻译：在骨髓移植中抑制维生素HOST疾病的方法
公开(公告)号：WO1996014865A1
公开(公告)日：1996-05-23
申请号：PCT/US1995014774
申请日：1995-11-09
申请人： REPLIGEN CORPORATION , DANA-FARBER CANCER INSTITUTE
发明人： REPLIGEN CORPORATION , DANA-FARBER CANCER INSTITUTE , GRIBBEN, John, G. , NADLER, Lee, M. , GRAY, Gary, S.
IPC分类号： A61K39/00
CPC分类号： C07K16/2827 , A61K38/1774
摘要： Methods for inhibiting antigen-specific T cell responses in vitro by use of an agent which inhibits a costimulatory signal in T cells, such as a CTLA4Ig fusion protein or an anti-B7-1 antibody or an anti-B7-2 are disclosed. The methods of the invention are particularly useful for inhibiting graft versus host disease which results from allogeneic bone marrow transplantation.
摘要翻译：公开了通过使用抑制T细胞如CTLA4Ig融合蛋白或抗B7-1抗体或抗B7-2的共刺激信号的试剂在体外抑制抗原特异性T细胞应答的方法。本发明的方法对于抑制由同种异体骨髓移植引起的移植物抗宿主病特别有用。

6. 发明申请

WO1996013587A1 CHEMOKINE-LIKE PROTEINS AND METHODS OF USE 审中-公开
标题翻译： CHEMOKINE-like蛋白质和使用方法
公开(公告)号：WO1996013587A1
公开(公告)日：1996-05-09
申请号：PCT/US1995013897
申请日：1995-10-26
申请人： REPLIGEN CORPORATION
发明人： REPLIGEN CORPORATION , DALY, Thomas, J. , LAROSA, Gregory, J.
IPC分类号： C12N15/19
CPC分类号： C07K14/522 , A61K38/00 , C07K14/5421
摘要： The invention relates to novel chemokine-like proteins that include two or more newly discovered active domains from different chemokines. Active domains are regions of several contiguous amino acids that are necessary for chemokines' ability to suppress the proliferation of actively dividing myeloid cells, e.g., myeloid progenitor cells, myeloid stem cells, and leukemic cells. The new chemokine-like proteins provide higher myelosuppressive activity than naturally occurring, wild-type chemokines.
摘要翻译：本发明涉及包含来自不同趋化因子的两个或多个新发现的活性结构域的新型趋化因子样蛋白。活性结构域是趋化因子抑制主动分裂骨髓细胞例如髓样祖细胞，骨髓干细胞和白血病细胞增殖的能力所必需的几个连续氨基酸的区域。新的趋化因子样蛋白提供比天然存在的野生型趋化因子更高的骨髓抑制活性。

7. 发明申请

WO1992018641A1 INTERLEUKIN-8 RECEPTORS AND RELATED MOLECULES AND METHODS 审中-公开
标题翻译：白细胞介素-8受体及相关分子及方法
公开(公告)号：WO1992018641A1
公开(公告)日：1992-10-29
申请号：PCT/US1992002977
申请日：1992-04-10
申请人： THE TRUSTEES OF BOSTON UNIVERSITY , REPLIGEN CORPORATION
发明人： THE TRUSTEES OF BOSTON UNIVERSITY , REPLIGEN CORPORATION , NAVARRO, Javier , THOMAS, Kathleen, M. , WITT, Daniel, P.
IPC分类号： C12P21/06
CPC分类号： C07K14/7155 , A61K38/00
摘要： Disclosed are cDNAs encoding IL-8 receptors and the recombinant proteins expressed from such cDNAs. The recombinant receptor and receptor fragments and analogs are used in methods of screening candidate compounds for their ability to antagonize interaction between IL-8 and an IL-8 receptor; antagonists are used as therapeutics to reduce inflammation. Antibodies specific for IL-8 receptor (or receptor fragment or analog) and their use as a therapeutic are also disclosed.
摘要翻译：公开了编码IL-8受体的cDNA和从这些cDNA表达的重组蛋白。重组受体和受体片段和类似物用于筛选候选化合物拮抗IL-8和IL-8受体之间相互作用的能力的方法中; 拮抗剂用作治疗剂以减轻炎症。还公开了对IL-8受体（或受体片段或类似物）特异性的抗体及其作为治疗剂的用途。

8. 发明申请

WO1987000564A1 USE OF rLDMTM 1-6 AND OTHER LIGNINOLYTIC ENZYMES 审中-公开
标题翻译：使用rLDM TM 1-6和其他木质素酶
公开(公告)号：WO1987000564A1
公开(公告)日：1987-01-29
申请号：PCT/US1986001476
申请日：1986-07-11
申请人： REPLIGEN CORPORATION
发明人： REPLIGEN CORPORATION , FARRELL, Roberta
IPC分类号： D21C09/00
CPC分类号： C12N9/0065 , C02F3/342 , D21C5/005
摘要： A novel enzymatic process for (a) bleaching kraft pulp, or (b) enhancing the strength properties and brightness stability of mechanical pulps, or (c) decolorization of E1 effluent. Specifically, novel enzymes, designated rLDM , and other ligninolytic enzymes present are used.
摘要翻译：（a）漂白牛皮纸浆的新型酶法，或（b）增强机械纸浆的强度性能和亮度稳定性，或（c）E1流出物的脱色。具体来说，使用了称为rLDM TM的新型酶和存在的其它木质素分解酶。

9. 发明申请

WO1997028267A1 ANTIBODIES AND IMMUNOGLOBULIN FUSION PROTEINS HAVING MODIFIED EFFECTOR FUNCTIONS AND USES THEREFOR 审中-公开
标题翻译：具有改良效应功能的抗体和免疫球蛋白融合蛋白及其用途
公开(公告)号：WO1997028267A1
公开(公告)日：1997-08-07
申请号：PCT/US1997001698
申请日：1997-02-03
申请人： REPLIGEN CORPORATION , GRAY, Gary, S. , CARSON, Jerry , JAVAHERIAN, Kashi , JELLIS, Cindy, L. , RENNERT, Paul, D. , SILVER, Sandra
发明人： REPLIGEN CORPORATION
IPC分类号： C12N15/62
CPC分类号： C07K14/70503 , A61K38/00 , A61K2039/5154 , C07K2319/00
摘要： CTLA4-immunoglobulin fusion proteins having modified immunoglobulin constant region-mediated effector functions, and nucleic acids encoding the fusion proteins, are described. The CTLA4-immunoglobulin fusion proteins comprise two components: a first peptide having a CTLA4 activity and a second peptide comprising an immunoglobulin constant region which is modified to reduce at least one constant region-mediated biological effector function relative to a CTLA4-IgG1 fusion protein. The nucleic acids of the invention can be integrated into various expression vectors, which in turn can direct the synthesis of the corresponding proteins in a variety of hosts, particularly eukaryotic cells. The CTLA4-immunoglobulin fusion proteins described herein can be administered to a subject to inhibit an interaction between a CTLA4 ligand (e.g., B7-1 and/or B7-2) on an antigen presenting cell and a receptor for the CTLA4 ligand (e.g., CD28 and/or CTLA4) on the surface of T cellsto thereby suppress an immune response in the subject, for example to inhibit transplantation rejection, graft versus host disease or autoimmune responses.
摘要翻译：描述了具有修饰的免疫球蛋白恒定区介导的效应子功能的CTLA4-免疫球蛋白融合蛋白，以及编码融合蛋白的核酸。 CTLA4免疫球蛋白融合蛋白包含两个组分：具有CTLA4活性的第一肽和包含免疫球蛋白恒定区的第二个肽，其被修饰以相对于CTLA4-IgG1融合蛋白减少至少一个恒定区介导的生物效应子功能。本发明的核酸可以整合到各种表达载体中，这又可以指导各种宿主，特别是真核细胞中相应的蛋白质的合成。本文所述的CTLA4-免疫球蛋白融合蛋白可以施用于受试者以抑制抗原呈递细胞上的CTLA4配体（例如B7-1和/或B7-2）与CTLA4配体的受体（例如， CD28和/或CTLA4），从而抑制受试者的免疫应答，例如抑制移植排斥反应，移植物抗宿主病或自身免疫应答。

10. 发明申请

WO1994018232A1 METHODS FOR GENERATING BROADLY NEUTRALIZING ANTI-HIV ANTIBODIES AND ANTIGENS CAPABLE OF ELICITING SAME 审中-公开
标题翻译：用于产生广泛抗中性抗体抗体的抗生素和抗精子抗体的方法
公开(公告)号：WO1994018232A1
公开(公告)日：1994-08-18
申请号：PCT/US1994001458
申请日：1994-02-09
申请人： REPLIGEN CORPORATION , THE SCRIPPS RESEARCH INSTITUTE
发明人： REPLIGEN CORPORATION , THE SCRIPPS RESEARCH INSTITUTE , PROFY, Albert, T. , WILSON, Ian, A.
IPC分类号： C07K07/00
CPC分类号： C07K14/005 , A61K38/00 , A61K39/00 , C07K16/1045 , C12N2740/16122 , G01N33/56988
摘要： This invention features methods for identifying molecules which will act as antigens capable of eliciting broadly neutralizing anti-HIV antibodies, and methods for producing recombinant, broadly neutralizing anti-HIV antibodies.
摘要翻译：本发明的特征在于鉴定能够起到广泛中和抗HIV抗体的抗原的分子的方法以及用于产生重组的，广泛中和的抗HIV抗体的方法。

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