Humanized Anti-CD19 Antibody Variable Region Sequences
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Solution Overview
Problem
Monoclonal antibodies targeting CD19, typically made from mouse cells, are often recognized as foreign by the human immune system, leading to an immune response and reduced efficacy over time due to immune system destruction.
Innovation Solution
Development of humanized antibodies or fragments with specific heavy and light chain variable region sequences (e.g., SEQ ID NO: 27 and SEQ ID NO: 34, 35, 36) that bind to human CD19, conjugated to cytotoxic agents or co-stimulatory sequences, produced in cells like HEK293, and used in conjunction with chimeric antigen receptor-modified cells for targeted therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If monoclonal antibodies are made from mouse cells, then they can effectively bind to CD19, but the human immune system recognizes them as foreign and mounts an immune response against them
Solution Approach 1:
The patent applies local quality by humanizing only the variable regions (VH and VL) of the antibody that directly contact the antigen, while keeping the constant regions murine or human. This selective humanization of specific regions maintains antigen binding capability while reducing immunogenicity in the portions of the antibody that circulate in the human body.
Solution Approach 2:
The patent creates composite antibody structures by combining human and murine sequences. The variable regions are constructed as chimeric molecules with human framework regions and murine complementarity-determining regions, or fully human sequences, while constant regions may be from either species. This composite structure achieves both binding efficacy and reduced immunogenicity.
2Productivity
If monoclonal antibodies are made from mouse cells, then they can be produced effectively, but the human immune system destroys these antibodies before the desired treatment takes place after the first time
Solution Approach 1:
The patent applies local quality by humanizing only the variable regions (VH and VL) of the antibody that directly contact the antigen, while keeping the constant regions murine or human. This selective humanization of specific regions maintains antigen binding capability while reducing immunogenicity in the portions of the antibody that circulate in the human body.
Solution Approach 2:
The patent creates composite antibody structures by combining human and murine sequences. The variable regions are constructed as chimeric molecules with human framework regions and murine complementarity-determining regions, or fully human sequences, while constant regions may be from either species. This composite structure achieves both binding efficacy and reduced immunogenicity.
3Reliability
If humanized antibodies with specific HVR and LVR sequences are developed, then immune rejection is reduced and therapeutic efficacy is maintained, but the complexity of antibody design and production increases
Solution Approach 1:
The patent applies local quality by humanizing only the variable regions (VH and VL) of the antibody that directly contact the antigen, while keeping the constant regions murine or human. This selective humanization of specific regions maintains antigen binding capability while reducing immunogenicity in the portions of the antibody that circulate in the human body.
Solution Approach 2:
The patent creates composite antibody structures by combining human and murine sequences. The variable regions are constructed as chimeric molecules with human framework regions and murine complementarity-determining regions, or fully human sequences, while constant regions may be from either species. This composite structure achieves both binding efficacy and reduced immunogenicity.
Data Source
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AI summary
Provided is a humanized anti-CD19 antibody comprising a heavy chain variable region sequence showed as SEQ ID NO: 27 and a light chain variable region sequence showed as SEQ ID NO: 34, SEQ ID NO: 35 or SEQ ID NO: 36, and methods of using such antibody for treating CD19 related disorder or disease.