Denali Therapeutics has patented a method to generate polypeptides that target transferrin receptor-expressing cells, including those across the blood-brain barrier. By mutating specific amino acid sequences, the variant polypeptides show enhanced brain uptake. GlobalData’s report on Denali Therapeutics gives a 360-degree view of the company including its patenting strategy. Buy the report here.
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According to GlobalData’s company profile on Denali Therapeutics, Cancer treatment biomarkers was a key innovation area identified from patents. Denali Therapeutics's grant share as of February 2024 was 19%. Grant share is based on the ratio of number of grants to total number of patents.
Polypeptides targeting transferrin receptor for brain delivery
A recently granted patent (Publication Number: US11912778B2) outlines a method for generating variant polypeptides that can specifically bind to the transferrin receptor protein and effectively transport across the blood-brain barrier. The method involves identifying a specific region of a native polypeptide for mutation, creating a library of sequence variants through genetic manipulation, expressing these variants, screening for those that bind to the transferrin receptor protein, and isolating the most effective ones. The identified region of the native polypeptide does not initially bind to the transferrin receptor protein, and the isolated variant polypeptides demonstrate significantly improved brain uptake compared to the native polypeptide.
Furthermore, the patent details additional steps that can be incorporated into the method, such as identifying conserved amino acid positions, mutating adjacent amino acid positions, and shuffling polynucleotide fragments to enhance the effectiveness of the variant polypeptides. The method aims to improve brain uptake by more than 10-fold compared to the native polypeptide and increase the affinity for the transferrin receptor protein by about 100-fold when tested under the same conditions. The variant polypeptides generated through this method exhibit specific binding to the transferrin receptor protein's apical domain, ensuring efficient transport across the blood-brain barrier without competing with transferrin for binding, thus offering a promising approach for targeted drug delivery to the brain.
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