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Antibody-drug conjugates including antibody against human dlk1, and use thereof

A technology of antibody conjugates and antibodies, applied in medical preparations containing active ingredients, anti-animal/human immunoglobulins, anti-tumor drugs, etc.

Pending Publication Date: 2020-12-25
LEGOCHEM BIOSCIENCES INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At the heart of the issue is the identification of appropriate antigens for antibody-based therapeutics

Method used

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  • Antibody-drug conjugates including antibody against human dlk1, and use thereof
  • Antibody-drug conjugates including antibody against human dlk1, and use thereof
  • Antibody-drug conjugates including antibody against human dlk1, and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0453] Production of Compounds 1, 2, 3 and 4

[0454]

[0455]

[0456] The compounds 1, 2, 3 and 4 were produced by the method described in International Publication Patent WO2017-089895.

[0457] Among the compounds 1, 2, 3 and 4, the structure of MMAE (Monomethyl Auristatin E) is as follows.

[0458]

Embodiment 2

[0459] Production of Compounds 5, 6, 7 and 8

[0460]

[0461]

[0462] The compounds 5, 6 and 7 were produced by the method described in Korean Laid-Open Patent No. 10-2018-0110645.

[0463]

[0464] The compound 8 was produced by the method described in Korean Application No. 10-2019-0000514.

Embodiment 3

[0465] Production of ADC

[0466] ADCs were produced in the following two steps, and LCB14-0511 and LCB14-0606, which are commonly used, were produced by the method described in Korean Laid-Open Patent No. 10-2014-0035393. The structural formulas of LCB14-0511 and LCB14-0606 are as follows:

[0467]

[0468] Step 1: Production of prenylated antibody

[0469] A prenylation reaction mixture of the antibody (18A5) produced by the method described in Korean Application No. 10-2018-0107639 was prepared and reacted at 30°C for 16 hours. The reaction mixture contained 24 μM antibody (18A5), and 200 nM FTase (Calbiochem, #344145) and 0.144 mM LCB14-0511 or LCB14-0606 buffer solution (50 mM Tris-HCl (pH 7.4), 5 mM MgCl 2 , 10μM ZnCl 2 , 0.144 mM DTT (Dithiothreitol, dithiothreitol)). After the reaction, the prenylated antibody was desalted using a G25 Sepharose column (AKTA purifier, GE healthcare) equilibrated with PBS (Phosphate Buffer Saline, phosphate buffer saline) buffer...

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Abstract

The present invention relates to: novel antibody-drug conjugates (ADC) targeting DLK1; active metabolites of the ADCs; a method for producing the ADCs; a use of the ADCs for treating and / or preventingdiseases; and a use of the ADCs for producing medicaments for treating and / or preventing diseases, more specifically, hyperproliferative and / or angiogenic diseases such as cancer. More particularly,the present invention relates to an antibody-drug conjugate comprising an antibody binding to DLK1 or an antigen-binding fragment thereof, and to a pharmaceutical composition including same.

Description

technical field [0001] The present invention relates to a novel antibody-drug conjugate (antibody-drug conjugate, ADC) targeting DLK1 (Delta-like 1 homolog, ADC), an active metabolite of the ADC, The method for producing the ADC, the use of the ADC for the treatment and / or prevention of diseases, and the use of the ADCs for the production of medicaments for the treatment and / or prevention of diseases, more specifically proliferation and / or angiogenic diseases, such as cancer, more specifically, an antibody-drug conjugate comprising an antibody that binds to DLK1 or an antigen-binding fragment of said antibody, and an antibody-drug conjugate comprising said antibody-drug conjugate Pharmaceutical compositions of substances. Background technique [0002] Cancer refers to a disease caused by an abnormally formed mass formed by autonomous excessive growth of human tissue, which is the result of cell growth that cannot be regulated in various tissues. Primary tumors can be remov...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/68A61K47/65A61K31/5517A61P35/00C07K16/28A61K45/06
CPCY02A50/30A61K31/5517A61K45/06A61K47/65A61K47/68A61P35/00C07K16/28A61K47/6851A61K47/6889C07K2317/70C07K2317/565C07K2317/567
Inventor 朴昌植崔敏智张太翼朴允姬宋昊永白周烈金星民李炫政李柱泳金炯來李建重金容柱李昌宣蔡济旭李相弼申智英尹善河崔允瑄朴哉垠李智秀朴范灿朴荣佑
Owner LEGOCHEM BIOSCIENCES INC
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