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Medicament for treating cancer

A drug and prodrug technology, applied in the field of drugs for the treatment of hepatocellular carcinoma, can solve the problems of limited therapeutic effect, unconfirmed effect, low effective rate, etc., and achieve the effect of lasting anti-tumor effect and strong anti-tumor effect

Pending Publication Date: 2021-11-16
CHIOME BIOSCIENCE INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Thus, lenvatinib showed a high response rate of 40.6% against unresectable HCC, but no effect was confirmed in the remaining approximately 60% of patients
In addition, the effective rate of Sorafenib, another initial treatment drug, is even as low as 12.4%, and the therapeutic effect of monotherapy with multikinase inhibitors is limited

Method used

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  • Medicament for treating cancer
  • Medicament for treating cancer
  • Medicament for treating cancer

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0073] (i) Antigen preparation

[0074] Information on the amino acid sequence (SEQ ID NO: 2) of hDLK-1 is published, for example, on the website of NCBI (GenBank) (http: / / www.ncbi.nlm.nih.gov / ) as "Accession Number: NP_003827". Also, information on the base sequence (SEQ ID NO: 1) encoding the amino acid sequence of hDLK-1 is published on the same website as "Accession No.: NM_003836".

[0075] As the antigen, a polypeptide or peptide (also simply referred to as a peptide) containing at least a part (all or part) of the amino acid sequence of hDLK-1 can be used, preferably an amino acid sequence containing the extracellular domain (FA-1) of hDLK-1 at least a part (all or part) of the peptide. The extracellular region of hDLK-1 is a region containing six EGF-like motifs (EGF-1 to EGF-6) as described above, and contains the 24th to 244th positions in the amino acid sequence shown in SEQ ID NO: 2 The amino acid region is preferably a region consisting of amino acids from "24th...

Embodiment 1

[0184] Using the Hep3B xenograft tumor model, the combined effect of lenvatinib mesylate and anti-hDLK-1 antibody in tumor formation inhibitory activity was investigated.

[0185] Here, a commercially available lenvatinib mesylate was used (hereinafter, simply referred to as "lenvatinib" in this Example.). The anti-hDLK-1 antibody used in this example is the "HuBA-1-3D-1-A24G / T73K antibody" described in WO2014 / 054820 (hereinafter referred to as "HuBA-1-3D antibody" in this example for short). ), the DNA encoding the antibody protein was constructed according to the method described in the same publication (Example in the specification), and then, for the production / production of the antibody protein using host cells, GlymaxX (registered trademark) technology was used (cf. ProBioGen AG; https: / / www.probiogen.de / genetic-glyco-engineering-adcc-glymaxx.html). It should be noted that the HuBA-1-3D-1-A24G / T73K antibody used in this example is composed of the amino acids shown in SE...

Embodiment 2

[0191] Using the HepG2 xenograft tumor model, the combined effect of lenvatinib mesylate and anti-hDLK-1 antibody in tumor formation inhibitory activity was investigated.

[0192] Here, a commercially available lenvatinib mesylate was used (hereinafter, simply referred to as "lenvatinib" in this Example.). The anti-hDLK-1 antibody used in this example is the "HuBA-1-3D-1-A24G / T73K antibody" described in WO2014 / 054820 (hereinafter referred to as "HuBA-1-3D antibody" in this example for short). ), the DNA encoding the antibody protein was constructed according to the method described in the same publication (Example in the specification), and then, for the production / production of the antibody protein using host cells, GlymaxX (registered trademark) technology was used (cf. ProBioGen AG; https: / / www.probiogen.de / genetic-glyco-engineering-adcc-glymaxx.html). It should be noted that the HuBA-1-3D-1-A24G / T73K antibody used in this example is composed of the amino acids shown in SE...

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Abstract

Provided are a liver cell cancer therapeutic agent, a therapeutic method, etc., which can exhibit more potent and sustained antitumor effects than a conventional multi-kinase inhibitor. The medicament is characterized by including, as a combination medicament for treating liver cell cancer: lenvatinib or a prodrug thereof, or a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof; and an antibody against human DLK-1 having an in-vivo anti-tumor activity or antibody fragments derived from said antibody.

Description

technical field [0001] The present invention relates to medicines and methods for treating hepatocellular carcinoma and the like. Background technique [0002] Liver cancer is the second leading cause of cancer-related death in the world, and about 750,000 people die from liver cancer every year. There are about 780,000 new patients every year, about 80% of which are concentrated in Asia including Japan and China. It is reported that hepatocellular carcinoma accounts for 85-90% of all liver cancers. In Japan, the number of patients with hepatocellular carcinoma is about 42,000, and the annual death toll is about 26,000. Unresectable hepatocellular carcinoma has limited treatment options, has a very poor prognosis, and is a disease with high unmet medical need. [0003] As therapeutic agents for unresectable progressive hepatocellular carcinoma, multikinase inhibitors against multiple receptor tyrosine kinases are generally used. Specifically, sorafenib and lenvatinib are ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61P1/16A61P35/00A61P43/00C07K16/28A61K47/68C12N15/13A61K31/47
CPCA61K31/47A61K39/395A61P1/16A61P35/00A61P43/00C07K16/28C07K2317/73A61K2300/00A61K45/06A61K2039/505A61K39/3955
Inventor 中村康司高桥恒太坂口泉张灵逸
Owner CHIOME BIOSCIENCE INC
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