公开号/公开日

WO2016030350 A1 2016-03-03 [WO201630350] / 2016-03-03

申请号/申请日

2015WO-EP69399 / 2015-08-25

发明人

UMANA PABLO;KLEIN CHRISTIAN;NICOLINI VALERIA G;

申请人

HOFFMANN LA ROCHE;

主分类号

IPC分类号

A61K-047/48A61P-035/00C07K-014/55C07K-016/28C07K-016/30C07K-016/40

摘要

(WO201630350) The present invention relates to the combination therapy of specific tumor-targeted IL-2 variant immunocytokines with specific antibodies which bind human PD-L1.

机翻摘要

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地址

代理人

代理机构

;

优先权号

2014EP-0182778 2014-08-29

主权利要求

(WO201630350) 8. A tumor- targeted IL-2 variant immunocytokine in combination with an antibody which binds to human PD-Ll for use in i) inhibition of tumor growth in a tumor expressing the target of the immunocytokine; and/or ii) enhancing median and/or overall survival of subjects with a tumor expressing the target of the immunocytokine; wherein the target is presented on a tumor cell or in a tumor cell environment, wherein the tumor-targeted IL-2 variant immunocytokine used in the combination therapy is characterized in comprising a) a heavy chain variable domain VH of SEQ ID NO:68 and a light chain variable domain VL of SEQ ID NO:67, and the polypeptide sequence of SEQ ID NO:3, or b) a polypeptide sequence of SEQ ID NO: 84 or SEQ ID NO: 86 or SEQ ID NO:88, or c) the polypeptide sequences of SEQ ID NO: 84, and SEQ ID NO:86 and SEQ ID NO:88, or d) the polypeptide sequences of SEQ ID NO: 108, and SEQ ID NO: 109 and SEQ ID NO: 110, or e) a heavy chain variable domain VH of SEQ ID NO:42 and a light chain variable domain VL of SEQ ID NO:41, and the polypeptide sequence of SEQ ID NO:3, or f) a polypeptide sequence of SEQ ID NO:79 or SEQ ID NO: 80 or SEQ ID NO: 81, or g) the polypeptide sequences of SEQ ID NO:79, and SEQ ID NO: 80 and SEQ ID NO:81, or h) the polypeptide sequences of SEQ ID NO: 124, and SEQ ID NO: 125 and SEQ ID NO: 126; and the antibody which binds to human PD-L1 used in the combination therapy is characterized in comprising a) a heavy chain variable domain VH of SEQ ID NO: 89 and a light chain variable domain VL of SEQ ID NO:92, or b) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO:93, or c) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO:94, or d) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO:95, or e) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO:96, or 5 f) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO:97, or g) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO:98, or h) a heavy chain variable domain VH of SEQ ID NO:90 and a 10 light chain variable domain VL of SEQ ID NO:99, or i) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 100, or j) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 101, or 15 k) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 102, or 1) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 103, or m) a heavy chain variable domain VH of SEQ ID NO:90 and a 20 light chain variable domain VL of SEQ ID NO: 104, or n) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 105, or o) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 106, or p) a heavy chain variable domain VH of SEQ ID NO:91 and a light chain variable domain VL of SEQ ID NO: 107.  9. A CEA-targeted IL-2 variant immunocytokine in combination with an antibody which binds to human PD-L1 for use in i) inhibition of tumor growth in a CEA-expressing tumors; and/or ii) enhancing median and/or overall survival of subjects with a CEA- expressing tumor, wherein the CEA-targeted IL-2 variant immunocytokine is administered in combination with an antibody which binds to human PD-L1; wherein the CEA-targeted IL-2 variant immunocytokine used in the combination therapy is characterized in comprising a) a heavy chain variable domain VH of SEQ ID NO:68 and a light chain variable domain VL of SEQ ID NO:67, and the polypeptide sequence of SEQ ID NO:3, or b) a polypeptide sequence of SEQ ID NO: 84 or SEQ ID NO: 86 or SEQ ID NO:88, or c) the polypeptide sequences of SEQ ID NO: 84, and SEQ ID NO:86 and SEQ ID NO:88, or d) the polypeptide sequences of SEQ ID NO: 108, and SEQ ID NO: 109 and SEQ ID NO: 110; and the antibody which binds to human PD-L1 used in the combination therapy is characterized in comprising a) a heavy chain variable domain VH of SEQ ID NO: 89 and a light chain variable domain VL of SEQ ID NO:92, or b) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO:93, or 5 c) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO:94, or d) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO:95, or e) a heavy chain variable domain VH of SEQ ID NO:90 and a 10 light chain variable domain VL of SEQ ID NO:96, or f) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO:97, or g) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO:98, or 15 h) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO:99, or i) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 100, or j) a heavy chain variable domain VH of SEQ ID NO:90 and a 20 light chain variable domain VL of SEQ ID NO: 101, or k) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 102, or 1) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 103, or m) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 104, or n) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 105, or o) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 106, or p) a heavy chain variable domain VH of SEQ ID NO:91 and a light chain variable domain VL of SEQ ID NO: 107.  10. A FAP-targeted IL-2 variant immunocytokine in combination with an antibody which binds to human PD-L1 for use in i) inhibition of tumor growth in a FAP-expressing tumor; and/or ii) enhancing median and/or overall survival of subjects with a FAP- expressing tumor; wherein the FAP-targeted IL-2 variant immunocytokine used in the combination therapy is characterized in comprising a) a heavy chain variable domain VH of SEQ ID NO:42 and a light chain variable domain VL of SEQ ID NO:41, and the polypeptide sequence of SEQ ID NO:3, or b) a polypeptide sequence of SEQ ID NO:79 or SEQ ID NO: 80 or SEQ ID NO:81, or c) the polypeptide sequences of SEQ ID NO:79, and SEQ ID NO: 80 and SEQ ID NO:81, or d) the polypeptide sequences of SEQ ID NO: 124, and SEQ ID NO: 125 and SEQ ID NO: 126; and the antibody which binds to human PD-L1 used in the combination therapy is characterized in comprising a) a heavy chain variable domain VH of SEQ ID NO: 89 and light chain variable domain VL of SEQ ID NO:92, or b) a heavy chain variable domain VH of SEQ ID NO:90 and light chain variable domain VL of SEQ ID NO:93, or c) a heavy chain variable domain VH of SEQ ID NO:90 and light chain variable domain VL of SEQ ID NO:94, or d) a heavy chain variable domain VH of SEQ ID NO:90 and light chain variable domain VL of SEQ ID NO:95, or e) a heavy chain variable domain VH of SEQ ID NO:90 and light chain variable domain VL of SEQ ID NO:96, or f) a heavy chain variable domain VH of SEQ ID NO:90 and light chain variable domain VL of SEQ ID NO:97, or g) a heavy chain variable domain VH of SEQ ID NO:90 and light chain variable domain VL of SEQ ID NO:98, or h) a heavy chain variable domain VH of SEQ ID NO:90 and light chain variable domain VL of SEQ ID NO:99, or i) a heavy chain variable domain VH of SEQ ID NO:90 and light chain variable domain VL of SEQ ID NO: 100, or j) a heavy chain variable domain VH of SEQ ID NO:90 and light chain variable domain VL of SEQ ID NO: 101, or k) a heavy chain variable domain VH of SEQ ID NO:90 and light chain variable domain VL of SEQ ID NO: 102, or 1) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 103, or m) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 104, or n) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 105, or o) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 106, or p) a heavy chain variable domain VH of SEQ ID NO:91 and a light chain variable domain VL of SEQ ID NO: 107. A tumor-targeted IL-2 variant immunocytokine, for use in the treatment of a patient having a CEA-expressing tumor or a tumor characterized by expression or overexpression of CEA, having a FAP-expressing tumor or a tumor characterized by expression or overexpression of FAP or having a tumor associated with expression or overexpression of CEA or FAP, and wherein the immunocytokine is administered in combination with an antibody which binds to human PD-L1, wherein the tumor-targeted IL-2 variant immunocytokine used in the combination therapy is characterized in comprising a) a heavy chain variable domain VH of SEQ ID NO:68 and a light chain variable domain VL of SEQ ID NO:67, and the polypeptide sequence of SEQ ID NO:3, or b) a polypeptide sequence of SEQ ID NO: 84 or SEQ ID NO: 86 or SEQ ID NO:88, or c) the polypeptide sequences of SEQ ID NO: 84, and SEQ ID NO:86 and SEQ ID NO:88, or d) the polypeptide sequences of SEQ ID NO: 108, and SEQ ID NO: 109 and SEQ ID NO: 110, or e) a heavy chain variable domain VH of SEQ ID NO:42 and a light chain variable domain VL of SEQ ID NO:41, and the polypeptide sequence of SEQ ID NO:3, or f) a polypeptide sequence of SEQ ID NO:79 or SEQ ID NO: 80 or SEQ ID NO:81, or g) the polypeptide sequences of SEQ ID NO:79, and SEQ ID NO: 80 and SEQ ID NO:81, or h) the polypeptide sequences of SEQ ID NO: 124, and SEQ ID NO: 125 and SEQ ID NO: 126; and the antibody which binds to human PD-L1 used in the combination therapy is characterized in comprising a) a heavy chain variable domain VH of SEQ ID NO: 89 and a light chain variable domain VL of SEQ ID NO:92, or b) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO:93, or c) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO:94, or d) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO:95, or e) a heavy chain variable domain VH of SEQ ID NO:90 and chain variable domain VL of SEQ ID NO:96, or f) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO:97, or g) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO:98, or h) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO:99, or i) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 100, or j) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 101, or k) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 102, or 1) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 103, or m) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 104, or n) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 105, or o) a heavy chain variable domain VH of SEQ ID NO:90 and a light chain variable domain VL of SEQ ID NO: 106, or p) a heavy chain variable domain VH of SEQ ID NO:91 and a light chain variable domain VL of SEQ ID NO: 107.

法律状态

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专利类型码

A1

国别省市代码

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