Antibody EXO 6A10 Targeting Carbonic Anhydrase XII
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Solution Overview
Problem
Current systemic carbonic anhydrase inhibitors for treating diseases associated with carbonic anhydrase activity, such as cancer and eye diseases, are associated with adverse side effects like acid-base disturbances and hypersensitivity reactions, necessitating the development of alternative therapeutic and diagnostic means.
Innovation Solution
Development of an antibody specifically binding to carbonic anhydrase XII (CA-XII) with defined complementarity-determining regions (CDRs) that inhibits the enzyme activity more effectively than existing inhibitors, including sulfonamide azetazolamide, and is designed to target the extracellular domain of CA-XII.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If systemic carbonic anhydrase inhibitors are used to treat diseases associated with CA activity, then therapeutic effect is achieved, but adverse side effects occur
Solution Approach 1:
The antibody is designed to specifically target CA-XII in the extracellular space and tumor microenvironment, rather than systemically inhibiting all carbonic anhydrase isoforms. This localized action provides therapeutic benefit to tumors while sparing normal tissues expressing other CA isoforms, thereby reducing adverse side effects like acid-base disturbances and hypersensitivity reactions
Solution Approach 2:
The patent uses an antibody as an intermediary molecule to selectively bind and inhibit CA-XII. This antibody-mediated approach provides more targeted delivery of inhibition to tumor cells expressing CA-XII, reducing off-target effects compared to small molecule systemic inhibitors that non-specifically inhibit multiple CA isoforms throughout the body
2Reliability
If existing carbonic anhydrase inhibitors are used, then some therapeutic effect is achieved, but enzyme inhibition efficiency is insufficient
Solution Approach 1:
The antibody exhibits significantly higher inhibition efficiency against CA-XII compared to conventional sulfonamide inhibitors like azetazolamide. The patent reports that the antibody inhibits CA-XII enzyme activity 40 times better than azetazolamide, representing a substantial improvement in the inhibitory parameter and therapeutic potency
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The antibody EXO 6A10 inhibits CA-XII enzyme activity 40 times better than sulfonamide azetazolamide and shows promise in reducing tumor cell growth under hypoxic conditions, providing a more targeted and potentially safer therapeutic option for diseases related to CA-XII activity.
Implementation Method 1
an antibody binding to carbonic anhydrase XII, wherein the antibody comprises (a) the amino acid sequences SEQ ID NOS. 1 (CDR 1), 2 (CDR 2) and 3 (CDR 3) determining the CDRs of the V H region, and/or the amino acid sequences SEQ ID NOS. 4 (CDR 1), 5 (CDR 2) and 6 (CDR 3) determining the CDRs of the V L region
Implementation Method 2
Carbonic anhydrases are a family of enzymes that catalyze the reversible hydration of carbonic acid to bicarbonate and protons
Data Source
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AI summary
The present invention relates to an antibody binding to a carbonic anhydrase, wherein the antibody comprises (a) the amino acid sequences SEQ ID NOS. 1 (CDR 1 ), 2 (CDR 2) and 3 (CDR 3) determining the CDRs of the VH region, and the amino acid sequences SEQ ID NOS. 4 (CDR 1 ), 5 (CDR 2) and 6 (CDR 3) determining the CDRs of the VL region; or (b) the amino acids sequences of (a), wherein at least one amino acid is conservatively substituted in any one of the amino acid sequences SEQ ID NOS. 1 to 6.