Anti-TNF Antibodies for Ankylosing Spondylitis

Solution Overview

Problem

Current anti-TNF antibodies and fragments used for treating diseases like ankylosing spondylitis face challenges due to immunogenicity, low specificity, and pharmaceutical unsuitability, leading to reduced therapeutic benefits and increased risks of immune responses such as serum sickness and anaphylaxis.

Innovation Solution

Development of anti-TNF antibodies with specific heavy chain and light chain complementarity-determining region (CDR) amino acid sequences, administered via intravenous infusion, which achieve significant improvements in disease activity indices and patient-reported outcomes for ankylosing spondylitis, with the option of co-administration with methotrexate, sulfasalazine, or hydroxychloroquine.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current anti-TNF antibodies are used for treating ankylosing spondylitis, then therapeutic benefits are achieved, but immunogenicity increases leading to serum sickness and anaphylaxis

Engineering Contradiction:

Improvetherapeutic benefitVSAvoidimmunogenicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by modifying the amino acid sequences of the antibody's complementarity-determining regions (CDRs) to create variants with reduced immunogenicity. Specifically, the patent describes engineering anti-TNF antibodies with optimized CDR sequences that maintain therapeutic efficacy while reducing the risk of immune responses such as serum sickness and anaphylaxis.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If current anti-TNF antibodies are used, then some disease suppression is achieved, but specificity is low leading to reduced therapeutic benefits

Engineering Contradiction:

Improvedisease suppressionVSAvoidspecificity

Core Design Contradiction:

ReliabilityVSMeasurement precision

Solution Approach 1:

The patent applies local quality by optimizing specific regions of the antibody molecule, particularly the complementarity-determining regions (CDRs), to enhance binding specificity to TNF-alpha. The patent describes engineering antibodies with optimized CDR sequences that maintain therapeutic efficacy while reducing the risk of immune responses.

Inventive Principle:

Principle #3Local quality

3Ease of operation

If current anti-TNF antibodies are used, then treatment is provided, but pharmaceutical suitability is reduced due to immune responses

Engineering Contradiction:

Improvetreatment availabilityVSAvoidpharmaceutical suitability

Core Design Contradiction:

Ease of operationVSEase of manufacture

Solution Approach 1:

The patent applies parameter changes by modifying the amino acid sequences of the antibody's complementarity-determining regions (CDRs) to create variants with reduced immunogenicity. Specifically, the patent describes engineering anti-TNF antibodies with optimized CDR sequences that maintain therapeutic efficacy while reducing the risk of immune responses such as serum sickness and anaphylaxis.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20220195028A1Anti-TNF Antibodies, Compositions, and Methods for the Treatment of Active Ankylosing Spondylitis

Publication Date: 2022.06.23 JANSSEN BIOTECH INC

AI summary

The present invention relates to compositions and methods utilizing anti-TNF antibodies or antigen binding fragments thereof in a treatment of active Ankylosing Spondylitis (AS), e.g., a treatment utilizing the anti-TNF antibody having heavy chain complementarity-determining region (CDR) amino acid sequences SEQ ID NOS:40-42 and light chain CDR amino acid sequences SEQ ID NOS:43-45.