Anti-PD-1 Monoclonal Antibody CDR Optimization for Binding Affinity

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Solution Overview

Problem

Current anti-PD-1 monoclonal antibodies exhibit weak selectivity and low affinity, limiting their effectiveness in targeting the PD-1/PD-L1 pathway for tumor immunotherapy and autoimmune disease treatment.

Innovation Solution

Development of a novel anti-human PD-1 monoclonal antibody with specific heavy and light chain complementarity determining regions, encoded by nucleotide sequences, expressed using an expression vector in a host cell, and purified using conventional methods to enhance binding affinity and specificity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing anti-PD-1 monoclonal antibodies are used, then the PD-1/PD-L1 pathway can be targeted for tumor immunotherapy, but the selectivity and binding affinity are weak

Engineering Contradiction:
Improvebinding affinityVSAvoidantibody structure complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies local quality by specifically optimizing the complementarity determining regions (CDRs) of the antibody - CDRH1, CDRH2, CDRH3 for the heavy chain and CDRL1, CDRL2, CDRL3 for the light chain - to enhance binding affinity to PD-1. By focusing modifications on these specific local regions rather than the entire antibody structure, the patent achieves improved selectivity and affinity without unnecessarily increasing overall structural complexity.

Inventive Principle:
Principle #3Local quality

2Reliability

If existing anti-PD-1 monoclonal antibodies are used, then tumor immunotherapy can be performed, but the selectivity is weak leading to off-target effects

Engineering Contradiction:
ImproveselectivityVSAvoidantibody sequence complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the antibody into distinct functional components with specifically defined CDR regions for the heavy chain (CDRH1, CDRH2, CDRH3) and light chain (CDRL1, CDRL2, CDRL3). This segmentation allows each CDR region to be independently optimized for binding specificity to PD-1, thereby enhancing selectivity while maintaining a manageable overall structure through modular design.

Inventive Principle:
Principle #1Segmentation

Data Source

PatentEP3575322B1Anti-PD-1 monoclonal antibody, and preparation method therefor and application thereof
Publication Date: 2024.11.27 SUNSHINE GUOJIAN PHARMA (SHANGHAI) CO LTD
  • EP3575322B1 patent drawingFigure 1~2
  • EP3575322B1 patent drawingFigure 3~4
  • EP3575322B1 patent drawingFigure 5

AI summary

An anti-human PD-1 monoclonal antibody, and a preparation method therefor and an application thereof. The anti-human PD-1 monoclonal antibody has good bioactivity, can effectively bind with an extracellular region of a human PD-1 protein receptor, and can effectively seal PD-1 protein at protein level and cellular level and block the binding of the PD-1 protein with a ligand PD-L1, thereby effectively enhancing immunity. The monoclonal antibody can be applied independently or jointly with other antitumor drugs to tumor immunotherapy and the diagnosis and screening of patients with PD-L1 positive tumors; and the monoclonal antibody has a promising prospect in the preparation of drugs for treating tumors, resisting autoimmune diseases and the like.