Transthyretin Fusion Antibody Multimerization
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Solution Overview
Problem
There is a need for multimerized proteins, such as multimerized whole antibodies and antibody fragments, which demonstrate enhanced biological and therapeutic properties, including increased antibody avidity and enhanced antigen clustering compared to their non-multimerized counterparts.
Innovation Solution
The development of homodimer and homotetramer fusion proteins using a TTR protein complex, where antigen binding proteins, such as antibodies or Fab fragments, are linked to the TTR protein complex, either directly or via a linker, to enhance their biological and therapeutic properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibodies are multimerized using TTR protein complex, then antibody avidity and antigen clustering are improved, but device complexity increases
Solution Approach 1:
The TTR protein complex serves as an intermediary mediator that facilitates the multimerization of antibodies. By linking multiple antibody molecules to the TTR complex, the invention achieves enhanced antibody avidity and antigen clustering without requiring direct complex antibody-antibody interactions, thus resolving the technical contradiction between improved reliability and increased device complexity.
2Reliability
If antibodies are multimerized using TTR protein complex, then therapeutic effects are enhanced, but manufacturing precision requirements increase
Solution Approach 1:
The invention employs parameter changes by modifying the TTR protein complex structure and antibody linkage parameters to optimize fusion protein homogeneity. By controlling the molecular weight, subunit composition, and linkage characteristics of the TTR-antibody fusion, the invention achieves enhanced therapeutic effects while maintaining manufacturable precision standards.
Data Source
AI summary
The present invention relates to transthyretin (TTR) fusions useful in the dimerization and tetramerization of antibodies and antibody fragments, such as Fabs. The TTR fusions proteins described herein are particularly useful in increasing antibody avidity and in enhancing antigen clustering. Methods for treating diseases using the fusion proteins of the present invention are described herein.