公开(公告)号：US5786456A

公开(公告)日：1998-07-28

申请号：US123772

申请日：1993-09-20

Applicant: Jeffrey A. Ledbetter ,  Edward A. Clark

Inventor： Jeffrey A. Ledbetter ,  Edward A. Clark

IPC: A61K38/00 ,  A61K47/48 ,  C07K14/54 ,  C07K14/715 ,  C07K16/28 ,  C07K16/18 ,  C12N5/12

CPC classification number: C07K16/28 ,  A61K47/48561 ,  C07K14/54 ,  C07K14/715 ,  A61K38/00 ,  C07K2317/74 ,  Y10S530/829

Abstract: A new B-cell receptor, Bp50, a 50 kilodalton polypeptide, that functions in B-cell proliferation is described. Ligands such as lymphokines, antibody molecules or the Fv fragments of antibody molecules that bind to Bp50 and augment the proliferation of activated B-cells can be used to regulate B-cell proliferation or differentiation.

Abstract translation: 描述了在B细胞增殖中起作用的新的B细胞受体Bp50，50千道尔顿多肽。 诸如淋巴因子，抗体分子或与Bp50结合并增加活化的B细胞增殖的抗体分子的Fv片段的配体可用于调节B细胞增殖或分化。

公开(公告)号：US5770197A

公开(公告)日：1998-06-23

申请号：US8898

申请日：1993-01-22

Applicant: Peter S. Linsley ,  Jeffrey A. Ledbetter ,  Nitin K. Damle ,  William Brady ,  Philip M. Wallace

Inventor： Peter S. Linsley ,  Jeffrey A. Ledbetter ,  Nitin K. Damle ,  William Brady ,  Philip M. Wallace

IPC: A61K38/00 ,  A61K38/17 ,  A61K39/00 ,  A61K39/395 ,  A61K45/00 ,  A61P29/00 ,  A61P31/12 ,  A61P31/14 ,  A61P31/18 ,  A61P35/00 ,  A61P37/00 ,  A61P37/02 ,  A61P37/06 ,  A61P37/08 ,  C07K20060101 ,  C07K14/00 ,  C07K14/705 ,  C07K14/715 ,  C07K14/725 ,  C07K16/00 ,  C07K16/28 ,  C07K16/42 ,  C07K19/00 ,  C12N5/06 ,  C12N5/10 ,  C12N15/02 ,  C12N15/09 ,  C12N15/12 ,  C12N15/13 ,  C12P21/02 ,  C12P21/08 ,  C12R1/91 ,  G01N33/53 ,  G01N33/564 ,  G01N33/566 ,  G01N33/577 ,  C07K16/46

CPC classification number: C07K16/2827 ,  C07K14/70521 ,  C07K14/7155 ,  C07K16/2818 ,  A61K38/00 ,  C07K2317/73 ,  C07K2319/02 ,  C07K2319/036 ,  C07K2319/30 ,  C07K2319/32 ,  Y10S424/81 ,  Y10S530/868

Abstract: The invention identifies the CTLA4 receptor as a ligand for the B7 antigen. The complete amino acid sequence encoding human CTLA4 receptor gene is provided. Methods are provided for expressing CTLA4 as an immunoglobulin fusion protein, for preparing hybrid CTLA4 fusion proteins, and for using the soluble fusion proteins, fragments and derivatives thereof, including monoclonal antibodies reactive with B7 and CTLA4, to regulate T cell interactions and immune responses mediated by such interactions.

Abstract translation: 本发明鉴定CTLA4受体作为B7抗原的配体。 提供编码人CTLA4受体基因的完整氨基酸序列。 提供用于表达CTLA4作为免疫球蛋白融合蛋白的方法，用于制备杂合CTLA4融合蛋白，并使用可溶性融合蛋白，其片段和衍生物，包括与B7和CTLA4反应的单克隆抗体调节T细胞相互作用和免疫应答介导 通过这种互动。

公开(公告)号：US5747037A

公开(公告)日：1998-05-05

申请号：US475847

申请日：1995-06-07

Applicant: Randolph J. Noelle ,  Teresa M. Foy ,  Alejandro Aruffo ,  Jeffrey A. Ledbetter

Inventor： Randolph J. Noelle ,  Teresa M. Foy ,  Alejandro Aruffo ,  Jeffrey A. Ledbetter

IPC: A61K39/395 ,  A61K31/00 ,  A61K35/14 ,  A61K35/28 ,  A61K38/00 ,  A61K38/17 ,  A61K39/00 ,  A61P37/00 ,  A61P37/06 ,  C07K14/705 ,  C07K16/28 ,  C07K19/00 ,  C12N5/10 ,  C12N15/02 ,  C12P21/08 ,  C12R1/91 ,  G01N33/68 ,  C12N5/12

CPC classification number: C07K14/70578 ,  C07K16/2875 ,  C07K19/00 ,  G01N33/6854 ,  A61K2039/505 ,  A61K2039/57 ,  A61K38/00 ,  C07K2317/24 ,  C07K2317/73 ,  C07K2319/00

Abstract: Antibodies that bind a protein gp39 (also referred to as CD40 ligand) are disclosed. Preferably, the antibodies are monoclonal antibodies of an IgG1 isotype and bind human gp39. In a preferred embodiment, an antibody of the invention binds an epitope recognized by a monoclonal antibody 24-31, produced by a hybridoma 24-31 (ATTC Accession No. HB11712) or binds an epitope recognized by a monoclonal antibody 89-76, produced by a hybridoma 89-76 (ATCC Accession No.HB11713). Pharmaceutical compositions comprising the antibodies of the invention are also disclosed. The antibodies of the invention are useful for inhibiting B cell proliferation and differentiation, T cell responses and for inducing T cell tolerance. Nucleic acid molecules encoding anti-gp39 antibodies, or portions thereof, as well as expression vectors and host cells incorporating said nucleic acid molecules, are also encompassed by the invention.

Abstract translation: 公开了结合蛋白质gp39（也称为CD40配体）的抗体。 优选地，抗体是IgG1同种型的单克隆抗体并结合人gp39。 在优选的实施方案中，本发明的抗体结合由杂交瘤24-31（ATTC登录号HB11712）产生的单克隆抗体24-31识别的表​​位或结合由单克隆抗体89-76识别的表位，产生 通过杂交瘤89-76（ATCC登录号HB11713）。 还公开了包含本发明抗体的药物组合物。 本发明的抗体可用于抑制B细胞增殖和分化，T细胞应答和诱导T细胞耐受。 编码抗gp39抗体或其部分的核酸分子以及掺入所述核酸分子的表达载体和宿主细胞也包括在本发明中。

公开(公告)号：US20130142793A1

公开(公告)日：2013-06-06

申请号：US13451641

申请日：2012-04-20

Applicant: Jeffrey A. LEDBETTER ,  Martha S. Hayden-Ledbetter

Inventor： Jeffrey A. LEDBETTER ,  Martha S. Hayden-Ledbetter

IPC: C07K16/46

CPC classification number: C07K16/46 ,  A61K2039/505 ,  C07K16/2809 ,  C07K16/2818 ,  C07K16/2878 ,  C07K16/2896 ,  C07K16/462 ,  C07K2317/22 ,  C07K2317/24 ,  C07K2317/53 ,  C07K2317/622 ,  C07K2317/64 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2319/00 ,  C07K2319/30

Abstract: The invention relates to novel binding domain immunoglobulin fusion proteins that feature a binding domain for a cognate structure such as an antigen, a counterreceptor or the like, a hinge region polypeptide having either zero or one cysteine residue, and immunoglobulin CH2 and CH3 domains, and that are capable of ADCC and/or CDC while occurring predominantly as monomeric polypeptides. The fusion proteins can be recombinantly produced at high expression levels. Also provided are related compositions and methods, including immunotherapeutic applications.

Abstract translation: 本发明涉及新颖的结合域免疫球蛋白融合蛋白，其特征在于同源结构如结合抗原，反式受体等的结合结构域，具有零个或一个半胱氨酸残基的铰链区多肽和免疫球蛋白CH2和CH3结构域，以及 其能够主要以单体多肽的形式存在于ADCC和/或CDC。 可以以高表达水平重组产生融合蛋白。 还提供了相关的组合物和方法，包括免疫治疗应用。

公开(公告)号：US20130089546A1

公开(公告)日：2013-04-11

申请号：US13505421

申请日：2010-11-02

Applicant: Jeffrey A. Ledbetter ,  Martha Hayden-Ledbetter ,  Keith Elkon ,  Xizhang Sun

Inventor： Jeffrey A. Ledbetter ,  Martha Hayden-Ledbetter ,  Keith Elkon ,  Xizhang Sun

IPC: C12N11/06

CPC classification number: C12N9/22 ,  A61K38/00 ,  C07K16/18 ,  C07K2319/30 ,  C12N9/96 ,  C12N11/06 ,  C12Y301/27005 ,  Y02P20/582

Abstract: Hybrid nuclease molecules and methods for treating an immune-related disease or disorder in a mammal, and a pharmaceutical composition for treating an immune-related disease in a mammal.

公开(公告)号：US20120213773A1

公开(公告)日：2012-08-23

申请号：US13396147

申请日：2012-02-14

Applicant: Jeffrey A. Ledbetter ,  Martha Hayden-Ledbetter ,  Peter A. Thompson

Inventor： Jeffrey A. Ledbetter ,  Martha Hayden-Ledbetter ,  Peter A. Thompson

IPC: A61K39/395 ,  A61P37/00 ,  A61P29/00 ,  A61P19/02 ,  A61P35/02 ,  A61P3/10 ,  A61P25/00 ,  A61P1/00 ,  A61P1/04 ,  A61P35/00 ,  A61P17/06

CPC classification number: C07K16/3061 ,  A61K38/00 ,  A61K39/0011 ,  A61K2039/505 ,  A61K2039/5152 ,  A61K2039/5156 ,  A61K2039/5158 ,  C07K16/2809 ,  C07K16/2818 ,  C07K16/2878 ,  C07K16/2896 ,  C07K16/462 ,  C07K2317/22 ,  C07K2317/24 ,  C07K2317/53 ,  C07K2317/622 ,  C07K2317/64 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2319/00 ,  C07K2319/30 ,  C12N5/0636 ,  C12N2501/23 ,  C12N2501/51 ,  C12N2501/515 ,  C12N2501/52 ,  C12N2502/11 ,  C12N2510/00

Abstract: The invention relates to novel binding domain-immunoglobulin fusion proteins that feature a binding domain for a cognate structure such as an antigen, a counterreceptor or the like, a wild-type IgG1, IGA or IgE hinge region polypeptide or a mutant IgG1 hinge region polypeptide having either zero, one or two cysteine residues, and immunoglobulin CH2 and CH3 domains, and that are capable of ADCC and/or CDC while occurring predominantly as polypeptides that are compromised in their ability to form disulfide-linked multimers. The fusion proteins can be recombinantly produced at high express levels. Also provided are related compositions and methods, including cell surface forms of the fusion proteins and immunotherapeutic applications of the fusion proteins and of polynucleotides encoding such fusion proteins.

Abstract translation: 本发明涉及新颖的结合域 - 免疫球蛋白融合蛋白，其特征在于用于诸如抗原，反向受体等的同源结构的结合结构域，野生型IgG1，IGA或IgE铰链区多肽或突变型IgG1铰链区多肽 具有零个，一个或两个半胱氨酸残基，以及免疫球蛋白CH2和CH3结构域，并且它们能够以ADCC和/或CDC的形式发生，同时主要作为其形成二硫键连接的多聚体的能力被损害的多肽。 融合蛋白可以以高表达水平重组产生。 还提供了相关的组合物和方法，包括融合蛋白的细胞表面形式和融合蛋白的免疫治疗应用以及编码这种融合蛋白的多核苷酸。

公开(公告)号：US08147835B2

公开(公告)日：2012-04-03

申请号：US12541062

申请日：2009-08-13

Applicant: Jeffrey A. Ledbetter ,  Martha Susan Hayden-Ledbetter

Inventor： Jeffrey A. Ledbetter ,  Martha Susan Hayden-Ledbetter

IPC: A61K39/395 ,  C07K16/00

CPC classification number: C07K16/3061 ,  A61K38/00 ,  A61K39/0011 ,  A61K2039/505 ,  A61K2039/5152 ,  A61K2039/5156 ,  A61K2039/5158 ,  C07K16/2809 ,  C07K16/2818 ,  C07K16/2878 ,  C07K16/2896 ,  C07K16/462 ,  C07K2317/22 ,  C07K2317/24 ,  C07K2317/53 ,  C07K2317/622 ,  C07K2317/64 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2319/00 ,  C07K2319/30 ,  C12N5/0636 ,  C12N2501/23 ,  C12N2501/51 ,  C12N2501/515 ,  C12N2501/52 ,  C12N2502/11 ,  C12N2510/00

Abstract: The invention relates to novel binding domain-immunoglobulin fusion proteins that feature a binding domain for a cognate structure such as an antigen, a counterreceptor or the like, a wild-type IgG1, IGA or IgE hinge region polypeptide or a mutant IgG1 hinge region polypeptide having either zero, one or two cysteine residues, and immunoglobulin CH2 and CH3 domains, and that are capable of ADCC and/or CDC while occurring predominantly as polypeptides that are compromised in their ability to form disulfide-linked multimers. The fusion proteins can be recombinantly produced at high express levels. Also provided are related compositions and methods, including cell surface forms of the fusion proteins and immunotherapeutic applications of the fusion proteins and of polynucleotides encoding such fusion proteins.

Abstract translation: 本发明涉及新颖的结合域 - 免疫球蛋白融合蛋白，其特征在于用于诸如抗原，反向受体等的同源结构的结合结构域，野生型IgG1，IGA或IgE铰链区多肽或突变型IgG1铰链区多肽 具有零个，一个或两个半胱氨酸残基，以及免疫球蛋白CH2和CH3结构域，并且它们能够以ADCC和/或CDC的形式发生，同时主要作为其形成二硫键连接的多聚体的能力被损害的多肽。 融合蛋白可以以高表达水平重组产生。 还提供了相关的组合物和方法，包括融合蛋白的细胞表面形式和融合蛋白的免疫治疗应用以及编码这种融合蛋白的多核苷酸。

公开(公告)号：US20090317397A1

公开(公告)日：2009-12-24

申请号：US12459291

申请日：2009-06-30

Applicant: Peter S. Linsley ,  Jeffrey A. Ledbetter ,  Nitin K. Damle ,  William Brady ,  Philip M. Wallace

Inventor： Peter S. Linsley ,  Jeffrey A. Ledbetter ,  Nitin K. Damle ,  William Brady ,  Philip M. Wallace

IPC: A61K39/395 ,  C07K16/00 ,  C12P21/04 ,  C12N15/63 ,  C07K14/00 ,  C12N5/02 ,  A61K38/16

CPC classification number: C07K16/247 ,  A61K38/00 ,  A61K2039/505 ,  C07K14/70521 ,  C07K14/7155 ,  C07K16/00 ,  C07K16/2818 ,  C07K16/2827 ,  C07K2317/34 ,  C07K2317/73 ,  C07K2319/00 ,  C07K2319/30 ,  Y10S514/885

Abstract: The invention identifies the CTLA4 receptor as a ligand for the B7 antigen. The complete amino acid sequence encoding human CTLA4 receptor gene is provided. Methods are provided for expressing CTLA4 as an immunoglobulin fusion protein, for preparing hybrid CTLA4 fusion proteins, and for using the soluble fusion proteins, fragments and derivatives thereof, including monoclonal antibodies reactive with B7 and CTLA4, to regulate T cell interactions and immune responses mediated by such interactions.

Abstract translation: 本发明鉴定CTLA4受体作为B7抗原的配体。 提供编码人CTLA4受体基因的完整氨基酸序列。 提供用于表达CTLA4作为免疫球蛋白融合蛋白的方法，用于制备杂合CTLA4融合蛋白，并使用可溶性融合蛋白，其片段和衍生物，包括与B7和CTLA4反应的单克隆抗体调节T细胞相互作用和免疫应答介导 通过这种互动。

公开(公告)号：US20090186037A1

公开(公告)日：2009-07-23

申请号：US12207997

申请日：2008-09-10

Applicant: Christian P. Larsen ,  Alejandro A. Aruffo ,  Diane L. Hollenbaugh ,  Peter S. Linsley ,  Jeffrey A. Ledbetter ,  Thomas C. Pearson

Inventor： Christian P. Larsen ,  Alejandro A. Aruffo ,  Diane L. Hollenbaugh ,  Peter S. Linsley ,  Jeffrey A. Ledbetter ,  Thomas C. Pearson

IPC: A61K39/395 ,  A61K38/16 ,  A61P37/06

CPC classification number: C07K16/2878 ,  A61K38/00 ,  A61K39/395 ,  C07K14/70521 ,  C07K14/70532 ,  C07K14/70575 ,  C07K14/70578 ,  C07K16/2818 ,  C07K16/2827 ,  C07K16/2875 ,  C07K2317/73 ,  A61K38/17 ,  A61K2300/00

Abstract: The present invention provides a method for inhibiting an immune response and a method for inhibiting rejection of transplanted tissues. This method comprises preventing an endogenous molecule on a cell selected from the group consisting of gp39 and CD40 antigens from binding its endogenous ligand and preventing an endogenous molecule on a cell selected from the group consisting of CTLA4, CD28, and B7 antigens from binding its endogenous ligand. The prevention of such molecules from binding their ligand thereby blocks two independent signal pathways and inhibits the immune response resulting in transplanted tissue rejection.

Abstract translation: 本发明提供抑制免疫应答的方法和抑制移植组织排斥的方法。 该方法包括防止选自gp39和CD40抗原的细胞上的内源性分子与其内源性配体结合并防止选自CTLA4，CD28和B7抗原的细胞上的内源性分子结合其内源性 配体。 阻止这些分子结合其配体从而阻断两个独立的信号通路并抑制免疫应答导致移植组织排斥反应。

公开(公告)号：US20090175867A1

公开(公告)日：2009-07-09

申请号：US12041590

申请日：2008-03-03

Applicant: Peter A. Thompson ,  Jeffrey A. Ledbetter ,  Martha S. Hayden-Ledbetter ,  William Brady

Inventor： Peter A. Thompson ,  Jeffrey A. Ledbetter ,  Martha S. Hayden-Ledbetter ,  William Brady

IPC: A61K39/395 ,  C07K16/18 ,  C12N15/11 ,  C12N15/00 ,  C12N5/06 ,  C12P21/04 ,  C07H1/00 ,  G01N33/566 ,  G01N33/53 ,  A61P43/00

CPC classification number: C07K16/28 ,  A61K2039/505 ,  A61K2039/507 ,  C07K16/18 ,  C07K16/2803 ,  C07K16/2809 ,  C07K16/2818 ,  C07K16/2827 ,  C07K16/2833 ,  C07K16/2851 ,  C07K16/2875 ,  C07K16/2878 ,  C07K16/2887 ,  C07K16/2896 ,  C07K16/30 ,  C07K16/46 ,  C07K16/468 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/34 ,  C07K2317/52 ,  C07K2317/53 ,  C07K2317/622 ,  C07K2317/64 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2319/30

Abstract: Multivalent binding peptides, including bi-specific binding peptides, having immunoglobulin effector function are provided, along with encoding nucleic acids, vectors and host cells as well as methods for making such peptides and methods for using such peptides to treat or prevent a variety of diseases, disorders or conditions, as well as to ameliorate at least one symptom associated with such a disease, disorder or condition.

Abstract translation: 提供具有免疫球蛋白效应子功能的多价结合肽，包括双特异性结合肽，以及编码核酸，载体和宿主细胞以及制备这些肽的方法和使用这些肽治疗或预防各种疾病的方法 ，疾病或病症，以及改善与这种疾病，病症或病症相关的至少一种症状。