公开(公告)号：US20120129710A1

公开(公告)日：2012-05-24

申请号：US13165300

申请日：2011-06-21

Applicant: John McCafferty ,  Anthony Richard Pope ,  Kevin Stuart Johnson ,  Hendricus Renerus Jacobus Mattheus Hoogenboom ,  Andrew David Griffiths ,  Ronald Henry Jackson ,  Kasper Philipp Holliger ,  James David Marks ,  Timothy Piers Clackson ,  David John Chiswell ,  Gregory Paul Winter ,  Timothy Peter Bonnert

Inventor： John McCafferty ,  Anthony Richard Pope ,  Kevin Stuart Johnson ,  Hendricus Renerus Jacobus Mattheus Hoogenboom ,  Andrew David Griffiths ,  Ronald Henry Jackson ,  Kasper Philipp Holliger ,  James David Marks ,  Timothy Piers Clackson ,  David John Chiswell ,  Gregory Paul Winter ,  Timothy Peter Bonnert

IPC: C40B30/04 ,  C12N7/01 ,  G01N33/53 ,  C12N15/63

CPC classification number: C07K16/005 ,  B01J2219/00718 ,  C07K16/00 ,  C07K16/18 ,  C07K16/26 ,  C07K16/34 ,  C07K16/40 ,  C07K16/44 ,  C07K16/462 ,  C07K16/468 ,  C07K19/00 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2317/55 ,  C07K2317/62 ,  C07K2317/622 ,  C07K2317/92 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/41 ,  C07K2319/735 ,  C12N15/1037 ,  C12N15/62 ,  C12N15/73 ,  C40B40/02 ,  G01N33/53 ,  G01N33/6857 ,  Y10S530/867

Abstract: A member of a specific binding pair (sbp) is identified by expressing DNA encoding a genetically diverse population of such sbp members in recombinant host cells in which the sbp members are displayed in functional form at the surface of a secreted recombinant genetic display package (rgdp) containing DNA encoding the sbp member or a polypeptide component thereof, by virtue of the sbp member or a polypeptide component thereof being expressed as a fusion with a capsid component of the rgdp. The displayed sbps may be selected by affinity with a complementary sbp member, and the DNA recovered from selected rgdps for expression of the selected sbp members. Antibody sbp members may be thus obtained, with the different chains thereof expressed, one fused to the capsid component and the other in free form for association with the fusion partner polypeptide. A phagemid may be used as an expression vector, with said capsid fusion helping to package the phagemid DNA. Using this method libraries of DNA encoding respective chains of such multimeric sbp members may be combined, thereby obtaining a much greater genetic diversity in the sbp members than could easily be obtained by conventional methods.

Abstract translation: 特异性结合对（sbp）的成员通过在重组宿主细胞中表达编码这种sbp成员的遗传多样性群体的DNA来鉴定，其中sbp成员以分泌重组遗传显示包（rgdp）的表面以功能形式显示 ），其含有编码sbp成员或其多肽组分的DNA，其中sbp成员或其多肽组分被表达为与rgdp的衣壳组分的融合物。 显示的sbps可以通过与补充sbp成员的亲和力来选择，并且从所选的rgdps中恢复的DNA用于表达所选择的sbp成员。 因此可以获得抗体sbp成员，其中不同的链表达，一个与衣壳组分融合，另一个与游离形式融合，用于与融合伴侣多肽结合。 噬菌粒可以用作表达载体，所述衣壳融合有助于包装噬菌粒DNA。 使用这种方法，可以组合编码这种多聚体sbp成员的各个链的DNA文库，从而获得在sbp成员中比通过常规方法容易地获得的更大的遗传多样性。

公开(公告)号：US20100183616A1

公开(公告)日：2010-07-22

申请号：US12456660

申请日：2009-06-19

Applicant: Larry Green ,  Raffaella Faggioni ,  Orit Foord ,  Scott L. Klakamp ,  Giorgio Senaldi ,  Amy K. Schneider

Inventor： Larry Green ,  Raffaella Faggioni ,  Orit Foord ,  Scott L. Klakamp ,  Giorgio Senaldi ,  Amy K. Schneider

IPC: A61K39/395 ,  A61P35/02 ,  A61P35/04 ,  A61P19/10 ,  A61P9/10 ,  A61P29/00 ,  C07H21/04 ,  C07K16/00 ,  C12N15/63 ,  C12N5/10

CPC classification number: C07K16/245 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/34 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/567 ,  C07K2317/76 ,  C07K2317/92 ,  Y10S424/801 ,  Y10S530/867

Abstract: Antibodies directed to the antigen IL-1β and uses of such antibodies are described. In particular, fully human monoclonal antibodies directed to the antigen IL-1β. Nucleotide sequences encoding, and amino acid sequences comprising, heavy and light chain immunoglobulin molecules, particularly sequences corresponding to contiguous heavy and light chain sequences spanning the framework regions and/or complementarity determining regions (CDR's), specifically from FR1 through FR4 or CDR1 through CDR3. Hybridomas or other cell lines expressing such immunoglobulin molecules and monoclonal antibodies.

Abstract translation: 针对抗原IL-1和bgr的抗体 并描述了这些抗体的用途。 特别是针对抗原IL-1和bgr的完全人单克隆抗体。 编码的核苷酸序列和包含重链和轻链免疫球蛋白分子的氨基酸序列，特别是对应于跨越框架区和/或互补决定区（CDR）的连续重链和轻链序列的序列，特别是从FR1至FR4或CDR1至CDR3 。 表达这种免疫球蛋白分子和单克隆抗体的杂交瘤或其它细胞系。

公开(公告)号：US07744877B2

公开(公告)日：2010-06-29

申请号：US10238681

申请日：2002-09-11

Applicant: Darrell R. Anderson ,  Nabil Hanna ,  John E. Leonard ,  Roland A. Newman ,  Mitchell E. Reff ,  William H. Rastetter

Inventor： Darrell R. Anderson ,  Nabil Hanna ,  John E. Leonard ,  Roland A. Newman ,  Mitchell E. Reff ,  William H. Rastetter

IPC: A61K39/395 ,  C07K16/28 ,  C07K16/30

CPC classification number: C07K16/2887 ,  A61K38/00 ,  A61K47/6849 ,  C07K2317/24 ,  C07K2319/00 ,  Y10S530/867

Abstract: Disclosed herein are methods of depleting peripheral blood B cells in a human host comprising administering to the host an immunologically active anti-CD20 antibody in an amount effective to deplete peripheral blood B cells in the host.

Abstract translation: 本文公开了消耗人宿主中的外周血B细胞的方法，包括向宿主施用有效消耗宿主中外周血B细胞的量的免疫活性抗CD20抗体。

公开(公告)号：US20090035322A1

公开(公告)日：2009-02-05

申请号：US12183274

申请日：2008-07-31

Applicant: Joel H. MARTIN ,  Li-Hsien Wang ,  Sean Stevens ,  Erin M. Allison

Inventor： Joel H. MARTIN ,  Li-Hsien Wang ,  Sean Stevens ,  Erin M. Allison

IPC: A61K39/395 ,  C07K16/18 ,  C12N15/11 ,  A61P37/00 ,  C12N15/00 ,  C12P21/04

CPC classification number: C07K16/2887 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/92 ,  Y10S530/808 ,  Y10S530/866 ,  Y10S530/867

Abstract: A human antibody or antigen-binding fragment of an antibody that specifically binds human CD20 and is capable of inducing complement dependent cytotoxicity (CDC), and is capable of increasing symptom free survival time between about 2-fold to about 9-fold or more, relative to control-treated animals in a mouse model of human lymphoma. The antibody or antigen-binding fragment thereof is useful in a therapeutic method for treating a CD20-mediated disease or condition, such as for example, non-Hodgkin's lymphoma, rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, chronic lymphocytic leukemia, and inflammatory diseases.

Abstract translation: 特异性结合人CD20并能够诱导补体依赖性细胞毒性（CDC）的抗体的人抗体或抗原结合片段，并且能够增加约2倍至约9倍或更多的无症状存活时间， 相对于人淋巴瘤的小鼠模型中的对照处理的动物。 抗体或其抗原结合片段可用于治疗CD20介导的疾病或病症的治疗方法，例如非霍奇金淋巴瘤，类风湿性关节炎，系统性红斑狼疮，克罗恩病，慢性淋巴细胞性白血病和炎性反应 疾病

公开(公告)号：US20090010921A1

公开(公告)日：2009-01-08

申请号：US11889975

申请日：2007-08-17

Applicant: Pablo Umana ,  Peter Brunker ,  Claudia Ferrara ,  Tobias Suter ,  Ursula Puntener ,  Ekkehard Mossner

Inventor： Pablo Umana ,  Peter Brunker ,  Claudia Ferrara ,  Tobias Suter ,  Ursula Puntener ,  Ekkehard Mossner

IPC: A61K39/395 ,  C07K16/46 ,  C07K16/28 ,  C07K14/00

CPC classification number: C07K16/2887 ,  A61K2039/505 ,  C07K2317/14 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/41 ,  C07K2317/52 ,  C07K2317/53 ,  C07K2317/56 ,  C07K2317/567 ,  C07K2317/72 ,  C07K2317/73 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/92 ,  C07K2319/01 ,  C12N9/1051 ,  C12N15/11 ,  C12N15/63 ,  C12Y204/01144 ,  Y10S530/808 ,  Y10S530/866 ,  Y10S530/867

Abstract: The present invention relates to antigen binding molecules (ABMs). In particular embodiments, the present invention relates to recombinant monoclonal antibodies, including chimeric, primatized or humanized antibodies specific for human CD20. In addition, the present invention relates to nucleic acid molecules encoding such ABMs, and vectors and host cells comprising such nucleic acid molecules. The invention further relates to methods for producing the ABMs of the invention, and to methods of using these ABMs in treatment of disease. In addition, the present invention relates to ABMs with modified glycosylation having improved therapeutic properties, including antibodies with increased Fc receptor binding and increased effector function.

Abstract translation: 本发明涉及抗原结合分子（ABM）。 在具体实施方案中，本发明涉及重组单克隆抗体，包括对人CD20特异性的嵌合，灵长类或人源化抗体。 此外，本发明涉及编码这种ABM的核酸分子以及包含该核酸分子的载体和宿主细胞。 本发明还涉及生产本发明的ABM的方法以及使用这些ABM在治疗疾病中的方法。 此外，本发明涉及具有改善的治疗性质的具有改性糖基化的ABM，包括具有增加的Fc受体结合和增加的效应子功能的抗体。

公开(公告)号：US07422739B2

公开(公告)日：2008-09-09

申请号：US09911703

申请日：2001-07-25

Applicant: Darrell R. Anderson ,  Nabil Hanna ,  Roland A. Newman ,  Mitchell E. Reff ,  William H. Rastetter

Inventor： Darrell R. Anderson ,  Nabil Hanna ,  Roland A. Newman ,  Mitchell E. Reff ,  William H. Rastetter

IPC: A61K39/396 ,  C07K16/28 ,  C07K16/30

CPC classification number: C07K16/2887 ,  A61K38/00 ,  A61K47/6849 ,  A61K51/1027 ,  A61K51/1093 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/56 ,  C07K2317/732 ,  C07K2319/00 ,  C12N2799/028 ,  Y10S424/80 ,  Y10S424/801 ,  Y10S530/808 ,  Y10S530/809 ,  Y10S530/867

Abstract: Disclosed are chimeric, immunologically active, isolated, and radiolabeled antibodies directed against the CD20 antigen. The antibodies are useful for treating and diagnosing B cell disorders.

Abstract translation: 公开了针对CD20抗原的嵌合，免疫活性，分离和放射性标记的抗体。 该抗体可用于治疗和诊断B细胞疾病。

公开(公告)号：US20080050359A1

公开(公告)日：2008-02-28

申请号：US11625750

申请日：2007-01-22

Applicant: Andrew Griffiths ,  Hendricus Renerus Jacobus Hoogenboom ,  James Marks ,  John McCafferty ,  Gregory Winter ,  Geoffrey Grigg

Inventor： Andrew Griffiths ,  Hendricus Renerus Jacobus Hoogenboom ,  James Marks ,  John McCafferty ,  Gregory Winter ,  Geoffrey Grigg

IPC: A61K31/395 ,  A61P43/00 ,  C07K16/00 ,  C40B20/08

CPC classification number: C40B40/02 ,  B01J2219/00718 ,  C07K16/005 ,  C07K16/18 ,  C07K16/22 ,  C07K16/241 ,  C07K16/26 ,  C07K16/28 ,  C07K16/2812 ,  C07K16/2863 ,  C07K16/2866 ,  C07K16/3007 ,  C07K16/3092 ,  C07K16/34 ,  C07K16/40 ,  C07K16/4208 ,  C07K16/4241 ,  C07K16/44 ,  C07K16/462 ,  C07K16/468 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/55 ,  C07K2317/622 ,  C07K2317/92 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/41 ,  C07K2319/735 ,  C12N15/1037 ,  C12N15/62 ,  Y10S530/867

Abstract: Methods are disclosed for the production of anti-self antibodies and antibody fragments, being antibodies or fragments of a particular species of mammal which bind self antigens of that species. Methods comprise providing a library of replicable genetic display packages (rgdps), such as filamentous phage, each rgdp displaying at its surface member of a specific binding pair which is an antibody or antibody fragment, and each rgdp containing nucleic acid sequence derived from a species of mammal. The nucleic acid sequence in each rgdp encodes a polypeptide chain which is a component part of the sbp member displayed at the surface of that rgdp. Anti-self antibody fragments are selected by binding with a self antigen from said species of mammal. The displayed antibody fragments may be scFv, Fd, Fab or any other fragment which has the capability of binding antigen. Nucleic acid libraries used may be derived from rearranged V-gene sequences of unimmunised mammal. Synthetic or artificial libraries are described and shown to be useful.

Abstract translation: 公开了用于产生抗自身抗体和抗体片段的方法，其是结合该物种的自身抗原的特定哺乳动物种类的抗体或片段。 方法包括提供可复制的遗传显示包（rgdps）文库，例如丝状噬菌体，每个rgdp在其作为抗体或抗体片段的特异性结合对的表面成员显示，并且每个含有rgdp的核酸序列衍生自物种 的哺乳动物。 每个rgdp中的核酸序列编码多肽链，其是在该rgdp的表面显示的sbp成员的组成部分。 通过与来自所述哺乳动物物种的自身抗原结合来选择抗自身抗体片段。 显示的抗体片段可以是scFv，Fd，Fab或具有结合抗原能力的任何其它片段。 所用的核酸文库可能来源于未免疫哺乳动物的重排的V基因序列。 描述和显示合成或人造文库是有用的。

公开(公告)号：US20070232790A1

公开(公告)日：2007-10-04

申请号：US11625769

申请日：2007-01-22

Applicant: ANDREW GRIFFITHS ,  Hendricus Renerus Hoogenboom ,  James Marks ,  John McCafferty ,  Gregory Winter ,  Geoffrey Grigg

Inventor： ANDREW GRIFFITHS ,  Hendricus Renerus Hoogenboom ,  James Marks ,  John McCafferty ,  Gregory Winter ,  Geoffrey Grigg

IPC: C07K16/18

CPC classification number: C40B40/02 ,  B01J2219/00718 ,  C07K16/005 ,  C07K16/18 ,  C07K16/22 ,  C07K16/241 ,  C07K16/26 ,  C07K16/28 ,  C07K16/2812 ,  C07K16/2863 ,  C07K16/2866 ,  C07K16/3007 ,  C07K16/3092 ,  C07K16/34 ,  C07K16/40 ,  C07K16/4208 ,  C07K16/4241 ,  C07K16/44 ,  C07K16/462 ,  C07K16/468 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/55 ,  C07K2317/622 ,  C07K2317/92 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/41 ,  C07K2319/735 ,  C12N15/1037 ,  C12N15/62 ,  Y10S530/867

Abstract: Methods are disclosed for the production of anti-self antibodies and antibody fragments, being antibodies or fragments of a particular species of mammal which bind self antigens of that species. Methods comprise providing a library of replicable genetic display packages (rgdps), such as filamentous phage, each rgdp displaying at its surface member of a specific binding pair which is an antibody or antibody fragment, and each rgdp containing nucleic acid sequence derived from a species of mammal. The nucleic acid sequence in each rgdp encodes a polypeptide chain which is a component part of the sbp member displayed at the surface of that rgdp. Anti-self antibody fragments are selected by binding with a self antigen from said species of mammal. The displayed antibody fragments may be scFv, Fd, Fab or any other fragment which has the capability of binding antigen. Nucleic acid libraries used may be derived from rearranged V-gene sequences of unimmunised mammal. Synthetic or artificial libraries are described and shown to be useful.

Abstract translation: 公开了用于产生抗自身抗体和抗体片段的方法，其是结合该物种的自身抗原的特定哺乳动物种类的抗体或片段。 方法包括提供可复制的遗传显示包（rgdps）文库，例如丝状噬菌体，每个rgdp在其作为抗体或抗体片段的特异性结合对的表面成员显示，并且每个含有rgdp的核酸序列衍生自物种 的哺乳动物。 每个rgdp中的核酸序列编码多肽链，其是在该rgdp的表面显示的sbp成员的组成部分。 通过与来自所述哺乳动物物种的自身抗原结合来选择抗自身抗体片段。 显示的抗体片段可以是scFv，Fd，Fab或具有结合抗原能力的任何其它片段。 所用的核酸文库可能来源于未免疫哺乳动物的重排的V基因序列。 描述和显示合成或人造文库是有用的。

公开(公告)号：US07157562B1

公开(公告)日：2007-01-02

申请号：US10414555

申请日：2003-04-14

Applicant: Gilbert G. Olsen, II ,  William E. Bentley

Inventor： Gilbert G. Olsen, II ,  William E. Bentley

IPC: A23J1/00 ,  C07K1/00 ,  C07K14/00 ,  C07K16/00

CPC classification number: C07K16/00 ,  Y10S530/866 ,  Y10S530/867

Abstract: A process for producing recombinant anti-botulinum toxin antibody comprising the steps of fermenting recombinant E. Coli cells in broth, concentrating the cells by removing the broth, crushing the concentrated cells, separating a permeate derived from the crushed cells from cell debris, purifying a recombinant antibotulinum antibody (Fab) from said permeate, and separating said Fab from impurities by diafiltration.

Abstract translation: 一种生产重组抗肉毒杆菌毒素抗体的方法，包括以下步骤：在肉汤中发酵重组大肠杆菌细胞，通过去除培养液浓缩细胞，粉碎浓缩细胞，从细胞碎片中分离源自破碎细胞的渗透物，纯化 来自所述渗透物的重组抗微生物素抗体（Fab），并通过渗滤将所述Fab与杂质分离。

公开(公告)号：US20040234515A9

公开(公告)日：2004-11-25

申请号：US09972473

申请日：2001-10-04

Applicant: Millennium Pharmaceuticals, Inc.

Inventor： Sean A. McCarthy

IPC: C07H021/04 ,  A61K038/51 ,  C12N009/12 ,  C12P021/02 ,  C12N005/06

CPC classification number: C07K14/4718 ,  A61K38/00 ,  C07K14/47 ,  C07K2319/00 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/136 ,  Y10S530/866 ,  Y10S530/867

Abstract: Novel Dkk and Dkk-related polypeptides, proteins, and nucleic acid molecules are disclosed. In addition to isolated, full-length Dkk and Dkk-related proteins, the invention further provides isolated fusion proteins, antigenic peptides and antibodies. The invention also provides Dkk and Dkk-related nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced and non-human transgenic animals in which a Dkk and Dkk-related gene has been introduced or disrupted. Diagnostic, screening and therapeutic methods utilizing compositions of the invention are also provided.

Abstract translation: 公开了新的Dkk和Dkk相关多肽，蛋白质和核酸分子。 除了分离的全长Dkk和Dkk相关蛋白之外，本发明还提供分离的融合蛋白，抗原肽和抗体。 本发明还提供了Dkk和Dkk相关核酸分子，含有本发明的核酸分子的重组表达载体，已经引入了表达载体的宿主细胞和其中Dkk和Dkk相关基因的非人转基因动物 已被引入或中断。 还提供利用本发明组合物的诊断，筛选和治疗方法。