Alpha v Beta 8 Integrin Antibody for Selective TGFbeta Inhibition
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Solution Overview
Problem
Current treatments for fibroinflammatory airway disease and other TGFβ-associated disorders lack effective methods to selectively target TGFβ activation, which is mediated by integrin αvβ8.
Innovation Solution
Development of an antibody that specifically binds to human αvβ8, blocking the binding of TGFβ peptide to αvβ8, thereby inhibiting TGFβ activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used for fibroinflammatory airway disease, then general TGFβ inhibition is achieved, but selective targeting of TGFβ activation mediated by integrin αvβ8 is lacking
Solution Approach 1:
The patent uses a humanized antibody as an intermediary molecule that specifically binds to integrin αvβ8 and blocks its interaction with latent TGFβ. This antibody mediator provides selective inhibition of TGFβ activation by targeting the specific integrin receptor, thereby resolving the contradiction between general inhibition and selective targeting.
Solution Approach 2:
The invention applies local quality by designing an antibody that targets specifically to integrin αvβ8 expressed in certain tissues (such as airway epithelia), rather than globally inhibiting all TGFβ activity. This localized targeting allows selective blockade of pathogenic TGFβ activation while preserving physiological TGFβ functions in other contexts.
2Ease of manufacture
If integrin αvβ8 is targeted to block TGFβ activation, then TGFβ-associated disorders can be treated, but current methods lack effective selective targeting
Solution Approach 1:
The patent employs parameter changes by humanizing the antibody structure (changing species origin from murine to human) to improve both therapeutic effectiveness and binding selectivity. The humanized antibody maintains high affinity for human integrin αvβ8 while reducing immunogenicity, thereby achieving both ease of manufacture as a therapeutic and manufacturing precision in terms of specific binding.
3Object-affected harmful factors
If TGFβ activation is inhibited by blocking integrin αvβ8, then fibroinflammatory airway disease can be treated, but non-covalent interactions of latent TGFβ complex must be disrupted
Solution Approach 1:
The antibody extracts or removes the integrin αvβ8 from its normal function of activating TGFβ by blocking its binding site. This extraction of the integrin's activating function prevents the formation of the active TGFβ complex without requiring direct disruption of the latent TGFβ complex itself, thereby simplifying the therapeutic mechanism while effectively treating the disease.
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 effectively blocks TGFβ activation, providing a potential therapeutic approach for treating TGFβ-associated disorders by inhibiting the integrin αvβ8-mediated activation of TGFβ.
Implementation Method 1
an antibody that specifically binds human αvβ8 and blocks binding of TGFβ peptide to αvβ8
Data Source
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AI summary
Provided is an antibody that specifically binds human ανββ and blocks binding of TGFp peptide to ανβ8, wherein the antibody binds to the specificity determining loop (SDL) of human β8. In some embodiments, the antibody further binds to one, two, or all three of the human av-head domain, the a1 helix of human β8, or the a1 helix of human β8. In some embodiments, the antibody is humanized or chimeric. In some embodiments, the antibody is linked to a detectable label. Also provided is a method of enhancing an immune response in a human individual, comprising administering a sufficient amount of the antibody to the individual, thereby enhancing an immune response. Also provided are pharmaceutical compositions comprising the anti-ανββ antibodies or antigen-binding molecules thereof.