Amino Acid Sequences Modulating B7:CD28 Superfamily Interactions
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Solution Overview
Problem
Current therapies for autoimmune diseases, allergies, and immune-related disorders often have limitations in modulating T-cell responses effectively, particularly in blocking the B7:CD28 superfamily interactions, which are critical for regulating T-cell activation and tolerance.
Innovation Solution
Development of amino acid sequences and polypeptides that specifically bind to APC targets or T-cell targets within the B7:CD28 superfamily, such as B7-1, B7-2, CD28, CTLA-4, ICOS, PD-1, PD-L1, and PD-L2, to modulate their interactions and signaling pathways, thereby inhibiting or enhancing T-cell activation as needed.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional therapies are used to modulate T-cell responses, then some immune modulation is achieved, but the effectiveness in blocking B7:CD28 superfamily interactions is insufficient
Solution Approach 1:
The patent applies parameter changes by identifying and targeting specific amino acid sequences and structural features of the B7:CD28 superfamily members. By focusing on conserved regions and specific epitopes across different members of this family, the invention modifies the parameters of interaction specificity and affinity to achieve more effective blocking of T-cell activation pathways.
Solution Approach 2:
The patent segments the B7:CD28 superfamily into distinct members (B7-1, B7-2, B7RP-1, PD-L1, PD-L2, B7H-3, B7x) and their respective receptors, allowing for targeted interference with specific interaction pathways. This segmentation enables selective blocking of individual members while preserving others, thereby improving the reliability of immune modulation.
2Reliability
If selective blockade of costimulatory molecule interactions is implemented, then T-cell activation is inhibited, but the complexity of managing multiple B7:CD28 superfamily members increases
Solution Approach 1:
The patent applies universality by identifying conserved amino acid sequences and structural motifs that are common across multiple B7:CD28 superfamily members. By targeting these conserved regions, a single therapeutic agent can potentially interfere with multiple members of the family simultaneously, reducing the complexity of managing multiple targets while maintaining reliable inhibition of T-cell activation.
Solution Approach 2:
The patent introduces intermediary compounds or constructs that specifically bind to conserved regions of B7:CD28 superfamily members, acting as mediators that block their interactions with T-cell receptors. These intermediaries simplify the therapeutic approach by providing a unified mechanism to target multiple family members through a single agent class.
Data Source
AI summary
The present invention relates to amino acid sequences that block the interaction between (a target on) an antigen presenting cell (APC) and (a target on) a T-cell. More particularly, the present invention relates to amino acid sequences that are directed against (as defined herein) a target on an APC (also referred to herein as “APC target”) or a target on a T-cell (also referred to herein as “T-cell target”). The invention further relates to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences.