Patent ID: 11912778
Assignee: DENALI THERAPEUTICS INC.
Field: Pharmaceuticals (Chemistry)
Classification: CPC C  A | IPC C

Claim 0:
1. A method of generating one or more variant polypeptides that specifically bind transferrin receptor protein and transport across the blood brain barrier, comprising:
(a) identifying a contiguous surface exposed register of about 7 to 15 amino acids of a native polypeptide for mutation;
(b) generating one or more polynucleotides comprising a nucleotide sequence that encodes for a library of sequence variants of the native polypeptide, wherein the nucleotide sequence encodes for one or more mutations in the identified register of the native polypeptide;
(c) expressing the one or more polynucleotides to produce the library of sequence variants;
(d) screening the library of sequence variants to identify one or more variant polypeptides that specifically bind transferrin receptor protein; and
(e) isolating the variant polypeptides,
wherein the identified register of the native polypeptide does not bind transferrin receptor protein; and the isolated variant polypeptides exhibit substantially improved brain uptake compared to the native polypeptide.