Combination Of An Anti-Cd19 Antibody And A Bruton's Tyrosine Kinase Inhibitor And Uses Thereof

A tyrosine kinase and inhibitor technology, which is applied in the combination of an anti-CD19 antibody and Bruton's tyrosine kinase inhibitor and its application field, can solve problems such as poor cancer prognosis

Active Publication Date: 2018-02-02
MORFOZIS AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0016] Clearly, despite recent advances in the discovery and development of anticancer agents, many forms of cancer involving CD19-expressing tumors still have a poor prognosis

Method used

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  • Combination Of An Anti-Cd19 Antibody And A Bruton's Tyrosine Kinase Inhibitor And Uses Thereof
  • Combination Of An Anti-Cd19 Antibody And A Bruton's Tyrosine Kinase Inhibitor And Uses Thereof
  • Combination Of An Anti-Cd19 Antibody And A Bruton's Tyrosine Kinase Inhibitor And Uses Thereof

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Experimental program
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Embodiment approach

[0077] 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.

[0078] 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

[0108] Example 1: Cytotoxicity in MEC-1 cells using MOR00208 and ibrutinib alone and in combination

[0109] Material

[0110] 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.

[0111] The culture conditions of the cell lines used were according to the supplier's information.

[0112] Cell culture medium: Iscove's Modified Dulbecco's medium (IMDM), Invitrogen, catalog number: 31980-048; RPMI1640, Invitrogen, catalog number: 31870-074; GlutaMAX, Invitrogen...

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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

technical field [0001] 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 [0002] 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. [0003] 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 leukemia (CLL) and acute lymphoblastic leukemia (ALL). [0004] NHL is a heterogeneous malignancy derived from lymphocyt...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K31/519A61P35/00A61P35/02C07K16/28
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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