Humanized Anti-TNF Antibody Sequences for Psoriatic Arthritis
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Solution Overview
Problem
Current anti-TNF antibodies used in treating diseases mediated by TNF alpha often elicit an immune response, leading to reduced therapeutic benefits due to immunogenicity, low affinity, and production challenges, making repeated administration unsuitable.
Innovation Solution
A composition comprising a pharmaceutically acceptable carrier and an isolated mammalian anti-TNF antibody with specific heavy and light chain amino acid sequences (SEQ ID NO:36 and SEQ ID NO:37) for intravenous infusion, administered at specific doses and intervals, effectively reducing disease activity in patients with active Psoriatic Arthritis as measured by modified van der Heijde-Sharp scores.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current anti-TNF antibodies are administered to treat diseases mediated by TNF alpha, then therapeutic benefits are achieved, but immune response is elicited leading to reduced therapeutic benefits and limited re-administration
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequences of the anti-TNF antibody to achieve humanization. The antibody heavy chain and light chain sequences are engineered to have human-like characteristics, changing the immunogenicity parameter from high (in non-human antibodies) to low (in humanized antibodies), thereby reducing immune response while maintaining therapeutic efficacy
Solution Approach 2:
The patent uses copying by creating a humanized version of the anti-TNF antibody that replicates the therapeutic function of non-human antibodies while copying human antibody characteristics. The humanized antibody copies the essential binding properties needed for TNF alpha inhibition while adopting human sequence features to avoid immune recognition
2Reliability
If non-human mammalian antibodies are used to treat human diseases, then therapeutic activity is achieved, but serum sickness and anaphylaxis can occur upon repeated administration
Solution Approach 1:
The patent changes the immunogenicity parameter by humanizing the antibody sequences. The heavy chain amino acid sequence (SEQ ID NO:36) and light chain amino acid sequence (SEQ ID NO:37) are designed to resemble human antibodies, reducing the immunological difference between the therapeutic agent and the patient's immune system, thereby preventing serum sickness and anaphylaxis
Solution Approach 2:
The humanized antibody acts as an intermediary between non-human therapeutic antibodies and the human immune system. It maintains the therapeutic functionality of non-human antibodies while presenting human-like molecular features to the immune system, serving as a bridge that prevents harmful immune responses
3Object-generated harmful factors
If chimeric and humanized antibodies are developed to reduce immunogenicity, then immune response is reduced, but affinity and production challenges remain
Solution Approach 1:
The patent optimizes multiple parameters simultaneously by carefully designing the humanized antibody sequences to maintain high affinity for TNF alpha while reducing immunogenicity. The specific amino acid sequences (SEQ ID NO:36 and SEQ ID NO:37) are engineered to preserve critical binding interactions with TNF alpha despite humanization modifications
Solution Approach 2:
The patent applies local quality by making targeted modifications to specific regions of the antibody while preserving other regions. The humanization process selectively modifies certain amino acid positions in the heavy and light chains to reduce immunogenicity while maintaining the integrity of the antigen-binding sites and overall antibody structure
Data Source
AI summary
The present invention relates to compositions and methods utilizing anti-TNF antibodies having a heavy chain (HC) comprising amino acid sequence SEQ ID NO:36 and a light chain (LC) comprising amino acid sequence SEQ ID NO:37 in a treatment for active Psoriatic Arthritis (PsA).