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Therapy for drug-resistant cancer by administration of anti-HER2 antibody/drug conjugate

A technology of drug conjugates and conjugates, applied in the direction of antibody medical components, antibodies, drug combinations, etc., can solve the problems of insufficient adaptability of responsiveness and activity intensity

Pending Publication Date: 2019-05-21
DAIICHI SANKYO CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, responsiveness, intensity of activity, and scope of adaptation are still insufficient, and the need for targeting HER2 has not been met

Method used

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  • Therapy for drug-resistant cancer by administration of anti-HER2 antibody/drug conjugate
  • Therapy for drug-resistant cancer by administration of anti-HER2 antibody/drug conjugate
  • Therapy for drug-resistant cancer by administration of anti-HER2 antibody/drug conjugate

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0424] (1) Antigen preparation

[0425] Examples of antigens for producing anti-HER2 antibodies include HER2 or polypeptides containing partial amino acid sequences of at least 6 consecutive amino acids, or derivatives obtained by adding arbitrary amino acid sequences and carriers to them.

[0426] HER2 can be directly purified and used from human tumor tissue or tumor cells, or can be obtained by synthesizing HER2 in vitro or producing HER2 in host cells through genetic manipulation.

[0427] In genetic manipulation, specifically, after integrating the cDNA of HER2 into an expressible vector, it is synthesized in a solution containing enzymes, substrates and energy substances required for transcription and translation, or other prokaryotes or Eukaryotic host cells are transformed to express HER2, and antigens can be obtained.

[0428] Alternatively, the antigen can also be obtained as a secreted protein by expressing a fusion protein obtained by linking the extracellular reg...

Embodiment

[0671] The present invention will be specifically described by the examples shown below, but the present invention is not limited by them. Also, these examples are not to be construed as limiting in any way.

manufacture example

[0672] [Manufacturing example: Preparation of antibody-drug conjugate]

[0673] According to the production method described in Patent Document 8 (International Publication No. 2015 / 115091), an antibody-drug conjugate represented by the following formula (hereinafter referred to as "antibody-drug conjugate (1)" or "ADC (1) )”).

[0674] [chemical formula 28]

[0675]

[0676] Here, the drug-linker structure is connected to the antibody through a thioether bond, and n is in the range of 7-8.

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Abstract

A therapeutic agent and therapeutic method for HER2 expression cancers, which are resistant to or are not easily cured by conventional anti-HER2 drugs, are provided in which use is made of an antibody / drug conjugate comprising a linker and a drug, which are represented by the formula -(Succinimid-3-yl-N)-CH2CH2CH2CH2CH2-C(=O)-GGFG-NH-CH2-O-CH2-C(=O)-(NH-DX), and an anti-HER2 antibody bonded thereto. The therapeutic agent and method are effective against HER2 expression cancers, which are resistant to or are not easily cured by conventional anti-HER2 drugs.

Description

technical field [0001] The present invention relates to treatment of drug-resistant cancer (hereinafter simply referred to as "resistant cancer"), especially acquired-resistant cancer, based on an antibody in which an anti-HER2 antibody is linked to exatecan via a linker structure - drug conjugates. Background technique [0002] Antibody-drug conjugates (Antibody-Drug Conjugates; ADCs), which link cytotoxic drugs to antibodies that bind to antigens expressed on the surface of cancer cells and can be internalized into cells, can selectively introduce By delivering the drug, it is expected that the drug will be accumulated in the cancer cells to kill the cancer cells (Non-Patent Documents 1 to 3). As an ADC, for example, Mylotarg (registered trademark; INN: Gemtuzumab), which is obtained by linking calicheamicin to an anti-CD33 antibody, has been approved as a therapeutic drug for acute myeloid leukemia. In addition, Adcetris (registered trademark; INN: Brentuximab vedotin),...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K47/68A61P35/00
CPCA61K47/68A61P35/00C07K16/32A61K2039/505A61K2039/545A61K47/68037A61K47/6851A61K47/6857A61K47/6863A61K47/6889A61K31/4015A61K31/4741
Inventor 慈幸贵洋扇谷祐辅吉原一孝远藤圣子藤崎良彦
Owner DAIICHI SANKYO CO LTD
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