Anti-latent tgf-beta1 antibodies and methods of use

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By designing antibodies with specific amino acid sequences and modified Fc regions, the problem of existing antibodies affecting integrin activation when inhibiting protease-mediated latent TGF-β1 activation was resolved, achieving efficient inhibitory effects with pH-dependent binding and broad species applicability.

CN120835902APending Publication Date: 2025-10-24CHUGAI PHARMA CO LTD

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Patent Information

Application Number: CN202480014986.X
Authority / Receiving Office: CN · China
Patent Type: Applications(China)
Current Assignee / Owner
Priority Date: 2023-02-10
Filing Date: 2024-02-09
Publication Date: 2025-10-24

Application Information

Patent Timeline

10 Feb 2023

Priority

09 Feb 2024

Application

CN202480014986.X

24 Oct 2025

Publication

CN120835902A

IPC: C07K16/30; A61K39/395; A61P35/00; C12N1/15; C12N1/19; C12N1/21; C12N5/10; C12N15/13

CPC: A61P35/00; C12N15/85; C07K16/22; C07K2317/24; C07K2317/92; C07K2317/76; C07K2317/94; A61K2039/505

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Application Domain

Fungi Bacteria

Technology Topics

Antibody SuppressionAntiendomysial antibodies

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AI Technical Summary

Technical Problem

Existing antibodies have difficulty in effectively inhibiting protease-mediated activation of latent TGF-β1 without affecting integrin-mediated activation and lack pH-dependent binding affinity.

Method used

Develop a cross-species, humanized anti-latent TGF-β1 antibody containing HVR and Fc region modifications with specific amino acid sequences, which can specifically bind to latent TGF-β1 in a pH-dependent manner, inhibit protease-mediated activation, and have little effect on integrin-mediated activation.

Benefits of technology

It achieves efficient inhibition of protease-mediated latent TGF-β1 activation under different pH conditions, reduces the impact on integrin-mediated activation, and has wide species applicability and high affinity.

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Abstract

It is an object of the present invention to provide anti-latent TGF-beta 1 antibodies and methods of using such antibodies. The present invention provides an anti-latent TGF-[beta] 1 antibody which inhibits protease-mediated activation of latent TGF-[beta] 1 without inhibiting integrin-mediated activation of latent TGF-[beta] 1 or which partially inhibits activation of integrin-mediated latent TGF-[beta] 1, or the antibody inhibits protease-mediated latent TGF-beta 1 activation but has a small effect on inhibition of integrin-mediated latent TGF-beta 1 activation. The present invention also provides optimized anti-latent TGF-beta 1 antibodies wherein the pH dependent binding properties are improved. The anti-latent TGF-beta 1 antibody can be used to treat fibrosis or cancer. For example, the anti-latent TGF-beta1 antibodies may be used to treat renal fibrosis, hepatic fibrosis, and pulmonary fibrosis.

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