Methods of making and using multispecific antibody panels and antibody analog panels

    公开(公告)号:US10584181B2

    公开(公告)日:2020-03-10

    申请号:US13510145

    申请日:2010-12-03

    摘要: Multispecific antibodies that specifically bind at least two different epitopes are provided. Structural variants of native antibodies (antibody analogs) are also provided. Also provided are multispecific antibodies and antibody analogs having a range of biological activities. Agonist and antagonist multispecific antibodies and agonist and antagonist antibody analogs are provided. Multispecific antibodies and antibody analogs conjugated with therapeutic and/or diagnostic agents are also provided, as are multispecific antibodies and antibody analogs conjugated with agents to increase in vivo half-life compared to multispecific antibodies and antibody analogs lacking such agents. In addition, methods of making multispecific antibodies and antibody analogs and compositions comprising multispecific antibodies and antibody analogs are provided. Therapeutic, research, and diagnostic uses of multispecific antibodies and antibody analogs are also provided.

    Polynucleotides encoding polypeptides that bind to the P185HER2 receptor
    14.
    发明授权
    Polynucleotides encoding polypeptides that bind to the P185HER2 receptor 失效
    编码结合P185HER2受体的多肽的多核苷酸

    公开(公告)号:US07601827B2

    公开(公告)日:2009-10-13

    申请号:US11225400

    申请日:2005-09-12

    IPC分类号: C12N15/18

    CPC分类号: C07K14/4756 A61K38/00

    摘要: Novel 2 polypeptides with binding affinity for the p185HER2 receptor, designated heregulin 2-α and heregulin 2-β, have been identified and purified from human tissue. The cDNA encoding the novel heregulin 2-α has been isolated from human tissue and sequenced. Provided herein is nucleic acid sequence of the heregulin 2-α useful in the production of heregulin 2-α by recombinant means. Further provided an amino acid sequence of heregulin 2-α and heregulin 2-β. Heregulins and their antibodies are useful as therapeutic agents and in diagnostic methods.

    摘要翻译: 已经从人体组织中鉴定并纯化了具有对p185HER2受体(称为asgulin 2-α和asgulin 2-β)的结合亲和力的新型2多肽。 已经从人体组织中分离出编码新型胰岛素2-α的cDNA并进行测序。 本文提供了可用于通过重组方法产生拟胰岛素2-α的调节蛋白2-α的核酸序列。 进一步提供了asgulin 2-α和asgulin 2-β的氨基酸序列。 本土及其抗体可用作治疗剂和诊断方法。

    Antibodies to heregulin 2
    16.
    发明授权
    Antibodies to heregulin 2 失效
    对asgulin的抗体2

    公开(公告)号:US06953842B2

    公开(公告)日:2005-10-11

    申请号:US10022609

    申请日:2001-12-17

    CPC分类号: C07K14/4756 A61K38/00

    摘要: Novel 2 polypeptides with binding affinity for the p185HER2 receptor, designated heregulin 2-α and heregulin 2-β, have been identified and purified from human tissue. The cDNA encoding the novel heregulin 2-α has been isolated from human tissue and sequenced. Provided herein is nucleic acid sequence of the heregulin 2-α useful in the production of heregulin 2-α by recombinant means. Further provided an amino acid sequence of heregulin 2-α and heregulin 2-β. Heregulins and their antibodies are useful as therapeutic agents and in diagnostic methods.

    摘要翻译: 从人体组织中鉴定并纯化具有与p185 HER2受体结合亲和力的新型2多肽,命名为heregulin 2-α和asgulin 2-β。 已经从人体组织中分离出编码新型胰岛素2-α的cDNA并进行测序。 本文提供了可用于通过重组方法产生拟胰岛素2-α的调节蛋白2-α的核酸序列。 进一步提供了asgulin 2-α和asgulin 2-β的氨基酸序列。 本土及其抗体可用作治疗剂和诊断方法。

    Method of using HRG2-.alpha. to stimulate P185.sup.HeR2
    17.
    发明授权
    Method of using HRG2-.alpha. to stimulate P185.sup.HeR2 失效
    使用HRG2-α刺激P185HeR2的方法

    公开(公告)号:US5856110A

    公开(公告)日:1999-01-05

    申请号:US440401

    申请日:1995-05-12

    CPC分类号: C07K14/4756 A61K38/00

    摘要: Novel 2 polypeptides with binding affinity for the p185.sup.HER2 receptor, designated heregulin 2-.alpha. and heregulin 2-.beta., have been identified and purified from human tissue. The cDNA encoding the novel heregulin 2-.alpha. has been isolated from human tissue and sequenced. Provided herein is nucleic acid sequence of the heregulin 2-.alpha. useful in the production of heregulin 2-.alpha. by recombinant means. Further provided an amino acid sequence of heregulin 2-.alpha. and heregulin 2-.beta.. Heregulins and their antibodies are useful as therapeutic agents and in diagnostic methods.

    摘要翻译: 已经从人体组织中鉴定并纯化具有与p185HER2受体结合亲和力的新型2多肽,称为asgulin 2-α和asgulin 2-β。 已经从人组织中分离出编码新型拟胰岛素2-α的cDNA并测序。 本文提供了可用于通过重组方法产生拟胰岛素2-α的asgulin 2-α的核酸序列。 进一步提供了asgulin 2-α和asgulin 2-beta的氨基酸序列。 本土及其抗体可用作治疗剂和诊断方法。

    Method for purifying heregulin
    18.
    发明授权
    Method for purifying heregulin 失效
    纯化蛋白质的方法

    公开(公告)号:US5641869A

    公开(公告)日:1997-06-24

    申请号:US456201

    申请日:1995-05-31

    CPC分类号: C07K14/4756 A61K38/00

    摘要: A novel polypeptide with binding affinity for the p185.sup.HER2 receptor, designated heregulin-.alpha., has been identified and purified from cultured human cells. DNA sequences encoding additional heregulin polypeptides, designated heregulin-.alpha., heregulin-.beta.1, heregulin-.beta.2, heregulin-.beta.2-like, and heregulin-.beta.3, have been isolated, sequenced and expressed. Provided herein are nucleic acid sequences encoding the amino acid sequences of heregulins useful in the production of heregulins by recombinant means. Further provided are the amino acid sequences of heregulins and purification methods therefor. Heregulins and their antibodies are useful as therapeutic agents and in diagnostic methods.

    摘要翻译: 已经鉴定并从培养的人细胞中纯化了对p185HER2受体具有结合亲和力的新型多肽,命名为asgulin-α。 已经分离,测序和表达编码附加的调节蛋白多肽的DNA序列,称为asgulin-α,asgulin-β1,heregulin-β2,heregulin-β2样和asgulin-β3。 本文提供了通过重组方法编码可用于生产本身的古菌素的氨基酸序列的核酸序列。 此外还提供了本文的氨基酸序列及其纯化方法。 本土及其抗体可用作治疗剂和诊断方法。

    Processes and compositions for the isolation of human relaxin
    19.
    发明授权
    Processes and compositions for the isolation of human relaxin 失效
    用于分离人类松弛素的方法和组合物

    公开(公告)号:US5464756A

    公开(公告)日:1995-11-07

    申请号:US908766

    申请日:1992-07-01

    摘要: A process is provided for cleaving a polypeptide into at least two polypeptide components comprising treating a reduced, free-cysteine form of the polypeptide with a cleaving agent under conditions for cleaving the polypeptide at a desired junction between the polypeptide cleavage products. More preferably, the process for cleaving comprises culturing cells containing DNA encoding said polypeptide, wherein at least one Asp codon is present in said DNA at a desired junction between the components to be cleaved from each other, said culturing resulting in expression of the DNA to produce the polypeptide in the host cell culture; and treating a reduced, free-cysteine form of the polypeptide with dilute acid under conditions for cleaving the polypeptide at the Asp junction. In particular embodiments, a DNA sequence is provided that encodes a relaxin precursor and includes codons encoding aspartic acid-containing linkers at novel positions within the precursor, allowing the ready cleavage of relaxin A peptides by treatment with dilute acid.

    摘要翻译: 提供了一种用于将多肽切割成至少两种多肽组分的方法,包括在多肽切割产物之间的所需连接处切割多肽的条件下用切割剂处理还原的游离半胱氨酸形式的多肽。 更优选地,所述切割方法包括培养含有编码所述多肽的DNA的细胞,其中至少一个Asp密码子存在于所述DNA中在待切割的组分之间的所需连接处,所述培养导致DNA的表达 在宿主细胞培养物中产生多肽; 以及在Asp连接处切割多肽的条件下用稀酸处理还原的游离半胱氨酸形式的多肽。 在具体实施方案中,提供了编码松弛素前体的DNA序列,并且包括在前体内的新位置编码含有天冬氨酸的接头的密码子,从而允许通过用稀酸处理来快速切割松弛素A肽。

    ErbB2 and ErbB3 chimeric heteromultimer receptors
    20.
    发明授权
    ErbB2 and ErbB3 chimeric heteromultimer receptors 有权
    ErbB2和ErbB3嵌合异源多聚体受体

    公开(公告)号:US08226935B2

    公开(公告)日:2012-07-24

    申请号:US12639822

    申请日:2009-12-16

    摘要: Chimeric heteromultimer adhesins that bind the ligand of natural heromultimeric receptors and uses therefor are disclosed. The chimeric molecules of the heteromultimer adhesins comprise an extracellular domain of a heteromultimeric receptor monomer and a multimerization domain for the stable interaction of the chimeric molecules in the adhesin. Specifically disclosed are heteromultimeric adhesins comprising the extracellular domains of the ErbB2 and ErbB3 and ErbB2 and ErbB4. The chimeric ErB heteromultimer adhesins of the present invention are useful as competitive antagonists or agonists of a neuregulin for the treatment of diseases such as various cancers.

    摘要翻译: 公开了结合天然heromultimeric受体的配体的嵌合杂多聚体粘附素及其用途。 杂多聚体粘附素的嵌合分子包含异源多聚体受体单体的细胞外结构域和用于粘附素中嵌合分子的稳定相互作用的多聚化结构域。 具体公开的是包含ErbB2和ErbB3以及ErbB2和ErbB4的细胞外结构域的异源多聚体粘附素。 本发明的嵌合ErB异源多聚体粘附素可用作神经调节蛋白的竞争性拮抗剂或激动剂,用于治疗各种癌症等疾病。