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1. 发明申请

WO2008052933A2 NOVEL POLYPEPTIDES AND USES THEREOF 审中-公开
标题翻译：新型聚氨酯及其用途
公开(公告)号：WO2008052933A2
公开(公告)日：2008-05-08
申请号：PCT/EP2007/061514
申请日：2007-10-26
申请人： DOMANTIS LIMITED , DE WILDT, Rudolf, M. T. , JAMES, Leo, C. , JONES, Philip, C. , SCHON, Oliver , WINTER, Gregory, Paul
发明人： DE WILDT, Rudolf, M. T. , JAMES, Leo, C. , JONES, Philip, C. , SCHON, Oliver , WINTER, Gregory, Paul
IPC分类号： C07K14/43
CPC分类号： C07K16/22 , C07K16/241 , C07K16/42 , C07K2317/31 , C07K2317/567 , C07K2317/569
摘要： The present invention provides an inhibitor of the aggregation of immunoglobulin chains (or immunoglobulin VL or CHl domains). In preferred embodiments, the inhibitor comprises or consists of a polypeptide which comprises or consists of (a) an amino acid sequence corresponding to the amino acid sequence of the FRl region of an immunoglobulin light chain variable domain, or part thereof which includes amino acid residue 12, (b) an amino acid sequence corresponding to the amino acid sequence of the immunoglobulin-binding domain of bacterial superantigen Protein L, or part thereof, and/or (c) an amino acid sequence corresponding to the amino acid sequence of the immunoglobulin-binding domain of streptococcal protein G (SpG), or part thereof, or a variant, fusion or derivative thereof, or a fusion of a said variant or derivative thereof which retains the ability of the parent polypeptide to inhibit aggregation of immunoglobulin chains, or domains thereof. The invention further provides a non-naturally occurring antibody, or antigen-binding fragment, fusion or derivative thereof comprising a light chain variable domain, or a fusion of a said fragment or derivative, wherein the FRl region of the light chain variable domain is modified (e.g. mutated) so as to inhibit, at least in part, the ability of the antibody, fragment, fusion or derivative to form aggregates. Most preferably, the light chain variable domain is modified at position 12 of the FR1 region by replacing the naturally occurring amino acid (e.g. serine in κ light chains) with proline.
摘要翻译：本发明提供免疫球蛋白链（或免疫球蛋白VL或CH1结构域）聚集的抑制剂。在优选的实施方案中，抑制剂包含或由多肽组成，该多肽包含（a）对应于免疫球蛋白轻链可变结构域的FR1区的氨基酸序列的氨基酸序列或其部分，其部分包括氨基酸残基 12，（b）对应于细菌超抗原蛋白L的免疫球蛋白结合结构域的氨基酸序列或其部分的氨基酸序列，和/或（c）对应于免疫球蛋白的氨基酸序列的氨基酸序列链球菌蛋白G（SpG）或其部分或其变体，融合物或衍生物或其所述变体或衍生物的融合物的结合结构域，其保留母体多肽抑制免疫球蛋白链的聚集的能力，或其领域。本发明还提供非天然存在的抗体或其抗原结合片段，其融合物或衍生物，其包含轻链可变结构域或所述片段或衍生物的融合物，其中轻链可变结构域的FR1区域被修饰（例如突变），以至少部分地抑制抗体，片段，融合物或衍生物形成聚集体的能力。最优选地，通过用脯氨酸替代天然存在的氨基酸（例如轻链中的丝氨酸），轻链可变结构域在FR1区的第12位被修饰。

2. 发明申请

WO2008052933A3 PREVENTION OF AGGREGATION OF IMMUNOGLOBULIN LIGHT OR HEAVY CHAINS 审中-公开
标题翻译：防止聚集免疫球蛋白轻链或重链
公开(公告)号：WO2008052933A3
公开(公告)日：2008-11-13
申请号：PCT/EP2007061514
申请日：2007-10-26
申请人： DOMANTIS LTD , DE WILDT RUDOLF M T , JAMES LEO C , JONES PHILIP C , SCHON OLIVER , WINTER GREGORY PAUL
发明人： DE WILDT RUDOLF M T , JAMES LEO C , JONES PHILIP C , SCHON OLIVER , WINTER GREGORY PAUL
IPC分类号： C07K16/42 , C07K7/00 , C07K14/315 , C07K16/22 , C07K16/24 , C12N15/12 , C12N15/63
CPC分类号： C07K16/22 , C07K16/241 , C07K16/42 , C07K2317/31 , C07K2317/567 , C07K2317/569
摘要： The present invention provides an inhibitor of the aggregation of immunoglobulin chains (or immunoglobulin VL or CHl domains). In preferred embodiments, the inhibitor comprises or consists of a polypeptide which comprises or consists of (a) an amino acid sequence corresponding to the amino acid sequence of the FRl region of an immunoglobulin light chain variable domain, or part thereof which includes amino acid residue 12, (b) an amino acid sequence corresponding to the amino acid sequence of the immunoglobulin-binding domain of bacterial superantigen Protein L, or part thereof, and/or (c) an amino acid sequence corresponding to the amino acid sequence of the immunoglobulin-binding domain of streptococcal protein G (SpG), or part thereof, or a variant, fusion or derivative thereof, or a fusion of a said variant or derivative thereof which retains the ability of the parent polypeptide to inhibit aggregation of immunoglobulin chains, or domains thereof. The invention further provides a non-naturally occurring antibody, or antigen-binding fragment, fusion or derivative thereof comprising a light chain variable domain, or a fusion of a said fragment or derivative, wherein the FRl region of the light chain variable domain is modified (e.g. mutated) so as to inhibit, at least in part, the ability of the antibody, fragment, fusion or derivative to form aggregates. Most preferably, the light chain variable domain is modified at position 12 of the FR1 region by replacing the naturally occurring amino acid (e.g. serine in ? light chains) with proline.
摘要翻译：本发明提供免疫球蛋白链（或免疫球蛋白VL或CH1结构域）聚集的抑制剂。在优选的实施方案中，抑制剂包含或由多肽组成，该多肽包含（a）对应于免疫球蛋白轻链可变结构域的FR1区的氨基酸序列的氨基酸序列或其部分，其部分包括氨基酸残基 12，（b）对应于细菌超抗原蛋白L的免疫球蛋白结合结构域的氨基酸序列或其部分的氨基酸序列，和/或（c）对应于免疫球蛋白的氨基酸序列的氨基酸序列链球菌蛋白G（SpG）或其部分或其变体，融合物或衍生物或其所述变体或衍生物的融合物的结合结构域，其保留母体多肽抑制免疫球蛋白链的聚集的能力，或其领域。本发明还提供非天然存在的抗体或其抗原结合片段，其融合物或衍生物，其包含轻链可变区或所述片段或衍生物的融合物，其中轻链可变结构域的FR1区域被修饰（例如突变），以至少部分地抑制抗体，片段，融合物或衍生物形成聚集体的能力。最优选地，通过用脯氨酸替代天然存在的氨基酸（例如轻链中的丝氨酸），轻链可变结构域在FR1区的第12位被修饰。

3. 发明申请

WO2004101790A1 A PROCESS FOR RECOVERING POLYPEPTIDES THAT UNFOLD REVERSIBLY FROM A POLYPEPTIDE REPERTOIRE 审中-公开
标题翻译：一种从多肽代谢物中反复复制多肽的方法
公开(公告)号：WO2004101790A1
公开(公告)日：2004-11-25
申请号：PCT/GB2004/002102
申请日：2004-05-14
申请人： DOMANTIS LIMITED , JESPERS, Laurent, S. , JONES, Philip, C. , FAMM, Kristoffer, H., J. , WINTER, Gregory, P.
发明人： JESPERS, Laurent, S. , JONES, Philip, C. , FAMM, Kristoffer, H., J. , WINTER, Gregory, P.
IPC分类号： C12N15/13
CPC分类号： C40B40/02 , C07K1/1136 , C07K16/00 , C07K2317/567 , C07K2317/569 , C12N15/1037
摘要： The invention relates to polypeptides that unfold reversibly ( e.g. , unfolds when heated and refolds when cooled), to repertoires containing polypeptides that unfold reversibly and to libraries that contain polypeptides that unfold reversibly or nucleic acids that encode polypeptides that unfold reversibly. The invention further relates to processes for producing a library enriched in polypeptides that unfold reversibly or nucleic acids encoding polypeptides that unfold reversibly, processes for selecting and/or isolating polypeptides that unfold reversibly, and to methods for producing a polypeptide that unfolds reversibly.
摘要翻译：本发明涉及可逆地展开的多肽（例如，当被冷却时被加热和重新折叠时展开），包含可逆地展开的多肽的库和包含可逆展开的多肽的文库或编码可逆展开的多肽的核酸。本发明还涉及产生富含可逆地展开的多肽的文库的方法或编码可逆展开的多肽的核酸的方法，用于选择和/或分离可逆展开的多肽的方法以及用于产生可逆展开的多肽的方法。

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