Antibody-drug conjugate comprising antibody against human ror1 and use for same

A technology of conjugates and antibodies, applied in drug combinations, medical preparations containing active ingredients, anti-tumor drugs, etc., can solve problems such as unwanted side effects and toxicity

Pending Publication Date: 2021-10-22
CSTONE PHARM (SUZHOU) CO LTD +3
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Most chemotherapeutic agents administered parenterally may induce unwanted side effects or severe toxicity due to systemic administration

Method used

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  • Antibody-drug conjugate comprising antibody against human ror1 and use for same
  • Antibody-drug conjugate comprising antibody against human ror1 and use for same
  • Antibody-drug conjugate comprising antibody against human ror1 and use for same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0728] Example 1: Preparation of ROR1 Antibody

Embodiment 1-1

[0729] Example 1-1: Antigen

[0730] As an antigen, a ROR1 ECD-Fc type protein in which Fc is linked to the C-terminus of the extracellular domain (ECD) of human ROR1 was used.

[0731] Specifically, for preparing the antigen, residues including the extracellular domain of ROR1 and corresponding to amino acid 1 to amino acid 406 of the ROR1 amino acid sequence represented by NCBI reference number NP_0050032 were used. As for the gene encoding the extracellular domain of ROR1, cDNA from Origene (Origene, RC214967) was purchased and used. Furthermore, in order to purify the ROR1 extracellular domain thereafter, a gene encoding a human IgG1-derived Fc protein was synthesized and linked to the 3' end of the gene encoding the ROR1 extracellular domain (hereinafter referred to as 'ROR1-Fc'). A vector encoding ROR1-Fc nucleic acid in a mammalian cell line was obtained by introducing the gene into the pcDNA3.1 vector.

[0732] The expression vector was transiently transfected into...

Embodiment 1-2

[0733] Example 1-2: Selection of antibodies by phage library screening

[0734] Prepare library phage

[0735] Escherichia coli 2 × 10 with a human-derived single-chain variable fragment (scFv) library (Yang et al., 2009 Molecular Cells (Mol. Cells) 27:225) was incubated at 37°C. 10 Cultured in a medium containing 2×YT (Amresco, J902-500G), benzyl penicillin (Duchefa, C01090025) 100 μg / mL and 2% glucose (Sigma, G7021) for 2 to 3 hours (OD600=0.5 to 0.7 ), then transfected with helper phage, and incubated at 30°C in 2×YT medium [2×YT, benzyl penicillin, 70 μg / mL kanamycin (Duchefa, K0126), 1 mM IPGTG (Duchefa, I1401)] Incubate for 16 hours to induce phage encapsulation. Thereafter, the cultured cells were centrifuged (6000rpm, 15 minutes, 4° C.), and then 4% PEG8000 (Sigma, P2139) and 3% NaCl (Samchun, S2097) were added to the supernatant and thoroughly dissolved and placed in React on ice for 1 hour. After recentrifugation (8000 rpm, 20 min, 4°C), PBS (phosphate buffered...

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Abstract

The invention relates to an antibody-drug conjugate comprising antibody against human ROR1 and use for the same. The present invention relates to new antibody-drug conjugates (ADCs) targeting ROR1, active metabolites of such ADCs, methods for preparation of such ADCs, uses for such ADCs in treatment and / or prevention of illnesses, and uses for such ADCs in production of drugs for treatment and / or prevention of diseases, more specifically diseases associated with over-expression of ROR1, for example cancer. More specifically, the present invention relates to an antibody-drug conjugate comprising an antibody that binds to ROR1 or an antigen-binding fragment thereof, and a pharmaceutical composition comprising the same.

Description

[0001] This application is a divisional application with an application date of August 21, 2020, an application number of 202010852078.1, and an invention title of "Antibody-Drug Conjugate Containing Anti-Human ROR1 Antibody and Its Use". [0002] related application [0003] This application claims priority from Korean Application No. 10-2019-0109807 filed September 4, 2019, which is hereby incorporated by reference in its entirety. technical field [0004] The present invention relates to novel antibody-drug conjugate ADCs targeting ROR1; active metabolites of such ADCs; methods of preparing such ADCs; uses of such ADCs in the treatment and / or prevention of diseases; Use in a medicament for the treatment and / or prevention of diseases, more specifically diseases associated with the overexpression of ROR1, such as cancer. More specifically, the present invention relates to an antibody-drug conjugate comprising an antibody or antigen-binding fragment thereof that binds to ROR...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/68A61K45/00A61P35/00A61P35/02
CPCA61K47/6801A61K45/00A61P35/00A61P35/02C07K16/2803A61K47/6849A61K47/6851A61K47/6889A61K47/68031A61K47/68035A61K47/6803A61K31/706
Inventor 朴允姬宋昊永柳贤敏金星民白周烈吴智惠韩娜拉金炯來朴庆恩李炫政李柱泳姜大赫杨勇材刘智娜金容柱李昌宣蔡济旭郑振元金珠熙李宝拉宋大海盛秉济廉东勋
Owner CSTONE PHARM (SUZHOU) CO LTD
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