Combination of anti-CD19 antibody and bruton's tyrosine kinase inhibitor and uses thereof

一种酪氨酸激酶、抑制剂的技术，应用在抗-CD19抗体和布鲁顿酪氨酸激酶抑制剂的组合及其用途领域，能够解决癌症预后不良等问题

Active Publication Date: 2022-06-10
MORFOZIS AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0017]It is clear that despite recent advances in the discovery and development of anticancer agents, many forms of cancer involving CD19-expressing tumors continue to have a poor prognosis

Method used

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  • Combination of anti-CD19 antibody and bruton's tyrosine kinase inhibitor and uses thereof
  • Combination of anti-CD19 antibody and bruton's tyrosine kinase inhibitor and uses thereof
  • Combination of anti-CD19 antibody and bruton's tyrosine kinase inhibitor and uses thereof

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Experimental program
Comparison scheme
Effect test

Embodiment approach

[0078] One aspect of the present disclosure is a combination comprising a CD19 specific antibody and a Bruton's tyrosine kinase (BTK) inhibitor for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and / or acute lymphoblastic leukemia . In an embodiment, the combination is synergistic.

[0079] Herein, the combination of an exemplary anti-CD19 antibody and ibrutinib performed synergistically in an in vitro model associated with CLL. Since CLL is a B cell-associated disease and CD19 is highly expressed on B cells, exemplary combinations should have the same mechanism of action and should also show synergy in the treatment of other B cell-associated disorders such as ALL and NHL. Therefore, the combination of an exemplary CD19-specific antibody and ibrutinib should be effective in the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and / or acute lymphoblastic leukemia in humans. Clinical trials will confirm the expected efficacy of the combi...

Embodiment 1

[0109] Example 1: Cytotoxicity in MEC-1 cells using MOR00208 and ibrutinib alone and in combination

[0110] Material

[0111] Cell line tested: MEC-1 cells (DSMZ #ACC497). Test cell lines: chronic B-cell leukemia cell line; mantle cell lymphoma cell line JVM-2 ( CRL-3002); Ramos cells (ATCC No. CRL-1596); Human Burkitt's Ramos cells (ATCC No. CRL-1596); HG-3 (DSMZ #ACC765) and Cll (DSMZ #ACC773) are chronic lymphoid cell leukemia cell line; Su-DHL 6 (DSMZ #ACC572), U2932 (DSMZ #ACC633) and OCI-LY7 (DSMZ #ACC688) are diffuse large B-cell lymphoma (DLBCL) cell lines; JVM-2 ( CRL-3002) is a mantle cell lymphoma cell line; and BALL-1 (DSMZ #ACC742) is an acute lymphoblastic leukemia cell line.

[0112] The culture conditions of the cell lines used were according to the supplier's information.

[0113] Cell culture medium: Iscove's Modified Dulbecco's medium (IMDM), Invitrogen, catalog number: 31980-048; RPMI1640, Invitrogen, catalog number: 31870-074; GlutaMAX, Invitrog...

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Abstract

The present disclosure describes a pharmaceutical combination of an anti-CD19 antibody and a Bruton's tyrosine kinase (BTK) inhibitor for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and / or acute lymphoblastic leukemia.

Description

[0001] This application is a divisional application of the invention patent application submitted on May 25, 2016. technical field [0002] The present disclosure relates to pharmaceutical combinations of anti-CD19 antibodies and Bruton's tyrosine kinase (BTK) inhibitors for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and / or acute lymphoblastic leukemia . Background technique [0003] B cells are lymphocytes that play an important role in the humoral immune response. They are produced in the bone marrow of most mammals and comprise 5-15% of the circulating lymphatic pool. The main function of B cells is to produce antibodies against various antigens, and B cells are an important component of the adaptive immune system. [0004] Due to the critical role of B cells in regulating the immune system, its dysregulation has been linked to various diseases such as lymphoma and leukemia. These include non-Hodgkin's lymphoma (NHL), chronic lymphocytic leuk...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K39/395A61K31/519A61P35/02A61P35/00
CPCA61K31/519A61K45/06A61K39/3955A61P35/02A61P35/00A61K2300/00A61K39/39558C07K16/2803A61K2039/505C07K2317/24C07K2317/732A61K47/68C07K16/2896
Inventor J·恩德尔R·博克斯哈默M·温德尔里奇
Owner MORFOZIS AG
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