Combination therapy of tumor-targeted il-2 variant immunocytokines and antibodies against human pd-l1

Patent metadata

Field	Value
Publication number	US-2016175397-A1
Application number	US-201514839410-A
Country	US
Kind code	A1
Filing date	Aug 28, 2015
Priority date	Aug 29, 2014
Publication date	Jun 23, 2016
Grant date	—

Abstract

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

First claim

1 . A tumor-targeted IL-2 variant immunocytokine in combination with an antibody which binds to human PD-L1 for use as a combination therapy in the treatment of cancer, for use as a combination therapy in the prevention or treatment of metastasis, for use as a combination therapy in the treatment of inflammatory diseases, for use as a combination therapy in treating or delaying progression of an immune related disease such as tumor immunity, or for use as a combination therapy in stimulating an immune response or function, such as T cell activity,
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 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 l) 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.

2 . The tumor-targeted IL-2 variant immunocytokine in combination with an antibody which binds to human PD-L1 according to claim 1 , for use in the treatment of cancer.

3 . The tumor-targeted IL-2 variant immunocytokine in combination with an antibody which binds to human PD-L1 according to claim 2 , for use in the treatment of breast cancer, lung cancer, colon cancer, ovarian cancer, melanoma cancer, bladder cancer, renal cancer, kidney cancer, liver cancer, head and neck cancer, colorectal cancer, melanoma, pancreatic cancer, gastric carcinoma cancer, esophageal cancer, mesothelioma, prostate cancer, leukemia, lymphomas, myelomas.

4 . The tumor-targeted IL-2 variant immunocytokine in combination with an antibody which binds to human PD-L1 according to claim 1 , for use in the prevention or treatment of metastasis.

5 . The tumor-targeted IL-2 variant immunocytokine in combination with an antibody which binds to human PD-L1 according to claim 1 , for use in the treatment of inflammatory diseases.

6 . The tumor-targeted IL-2 variant immunocytokine in combination with an antibody which binds to human PD-L1 according to claim 1 , for use in treating or delaying progression of an immune related disease such as tumor immunity.

7 . The tumor-targeted IL-2 variant immunocytokine in combination with an antibody which binds to human PD-L1 according to claim 1 for use in stimulating an immune response or function, such as T cell activity.

8 . A tumor-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 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
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
l) 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 S

Assignees

• Hoffmann La Roche

Inventors

• Umana Pablo
• Klein Christian
• Nicolini Valeria G

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title