Anti-CD38 Antibodies Modulating Enzymatic Activity
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Solution Overview
Problem
Current therapeutic antibodies for CD38 do not effectively modulate specific functions of CD38, particularly in autoimmune and inflammatory diseases, as they lack strong stimulating effects on cADPR hydrolase activity and inhibition of NAADP formation.
Innovation Solution
Development of a new class of anti-CD38 antibodies that interact with specific amino acids to stimulate cADPR hydrolase activity and inhibit NAADP formation, reducing cADPR levels and modulating enzymatic activities of CD38.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapeutic antibodies for CD38 are used, then CD38 binding is achieved, but strong stimulation of cADPR hydrolase activity and inhibition of NAADP formation is not achieved
Solution Approach 1:
The patent applies parameter changes by modifying the antibody structure to alter its functional interaction with CD38. The new antibody class is designed with specific variable regions that change the binding parameters to simultaneously achieve CD38 binding, cADPR hydrolase stimulation, and NAADP formation inhibition - properties that current antibodies fail to achieve together.
Solution Approach 2:
The patent segments the functional requirements into distinct binding interactions. The antibody is designed with specific CDR regions that independently target different functional sites on CD38: one region binds to stimulate cADPR hydrolase activity while another region binds to inhibit NAADP formation, allowing simultaneous achievement of multiple therapeutic effects.
2Adaptability or versatility
If antibodies bind to CD38 without specific amino acid interaction, then general CD38 binding occurs, but specific modulation of enzymatic activities (cADPR hydrolase stimulation and NAADP formation inhibition) is not achieved
Solution Approach 1:
The patent applies local quality by designing specific regions of the antibody (variable regions and CDRs) with unique properties to interact with specific amino acids on CD38. These localized structural features enable selective stimulation of cADPR hydrolase activity and inhibition of NAADP formation, rather than general non-specific binding.
Solution Approach 2:
The antibody acts as an intermediary molecule that mediates between the therapeutic goal and the CD38 enzyme. By specifically interacting with certain amino acids on CD38, the antibody transmits a modulatory signal that selectively enhances cADPR hydrolase activity while suppressing NAADP formation, achieving precise enzymatic control.
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
These antibodies provide a unique therapeutic approach for treating autoimmune and inflammatory diseases by reducing neutrophil and dendritic cell migration, offering anti-inflammatory effects and potential treatments for conditions like Type 1 and 2 diabetes, thyroiditis, and asthma.
Implementation Method 1
CD38 uses NAD as substrate for the formation of cyclic ADP-ribose (cADPR) and ADPR... The anti-CD38 antibodies provide a unique therapeutic approach by stimulating cADPR hydrolase activity and inhibiting the ability of CD38 to catalyze the formation of NAADP
Data Source
AI summary
Isolated monoclonal antibodies which bind to human CD38 and related antibody-based compositions and molecules, are disclosed. Also disclosed are pharmaceutical compositions comprising the antibodies and therapeutic and diagnostic methods for using the antibodies.