JP-2022513798-A5 -

Dates

Publication Date

20221220

Application Date

20191213

Description

Preferred embodiments of the present invention have been shown and described herein, but it will be apparent to those skilled in the art that such embodiments are provided only as examples. Those skilled in the art will be able to conceive of numerous variations, modifications, and substitutions without departing from the present invention. It should be understood that various alternatives to the embodiments of the present invention described herein may be adopted in the practice of the present invention. The following claims define the scope of the present invention and are intended to encompass the methods and structures within these claims and their equivalents. In certain embodiments, for example, the following are provided: (Item 1) A composition comprising an engineered transferrin receptor (TfR) binding peptide, or a variant, homolog, fragment, or analog thereof. (Item 2) A composition comprising a peptide construct, wherein the peptide construct is a) A transferrin receptor (TfR) binding peptide, or its variant, homolog, fragment, or analog, b) comprising an active agent, The composition wherein the peptide is conjugated, linked to, or fused to the active agent. (Item 3) A composition comprising one of SEQ ID NOs: 1 to 32, SEQ ID NOs: 36 to 67, SEQ ID NOs: 136 to 167, SEQ ID NOs: 171 to 202, or SEQ ID NOs: 356 to 358, and an engineered peptide, variant thereof, or functional fragment having at least 75%, at least 80%, at least 85%, at least 90%, at least 92%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity. (Item 4) The composition according to any one of items 1 to 3, wherein the peptide permeates a cell layer including the blood-brain barrier (BBB). (Item 5) The composition according to any one of items 1 to 3, wherein the peptide permeates a membrane, and the membrane is a cell membrane. (Item 6) The composition according to item 5, wherein the cells express TfR. (Item 7) The composition according to item 5, wherein the peptide permeates the cell membrane via TfR-mediated endocytosis. (Item 8) The composition according to any one of items 1 to 3, wherein the peptide is delivered to the CNS across the blood-brain barrier by binding to TfR and then dissociating. (Item 9) The composition according to any one of items 1 to 3, wherein the peptide is delivered across the blood-brain barrier by receptor-mediated transcytosis. (Item 10) The composition according to item 5, wherein the cells are tumor cells. (Item 11) The composition according to any one of items 1 to 3, wherein the cells or organs in which the peptide is localized overexpress TfR. (Item 12) The composition according to any one of items 1 to 3, wherein the peptide comprises SEQ ID NOs. 206 to 224 and SEQ ID NOs. 334 to 344. (Item 13) The composition according to any one of items 1 to 3, wherein the peptide comprises surface interface residues corresponding to G5, A7, S8, N14, L17, E18, E21, L38, L42, L45, D46, H47, S50, and Q51, based on SEQ ID NO: 32, or any combination thereof. (Item 14) The composition according to any one of items 1 to 3, wherein the peptide comprises a hydrophilic surface distal residue corresponding to any one of positions 3, 4, 9, 11, 15, 16, 19, 23, 26, 28, 29, 30, 31, 32, 33, 35, 36, 37, 39, and 40 with respect to SEQ ID NO: 32, or any combination thereof. (Item 15) The composition according to item 14, wherein the hydrophilic distal surface residue is selected from amino acids D, E, H, K, R, N, Q, S, or T. (Item 16) The composition according to item 12, wherein the peptide comprises one of the hydrophilic surface distal residues corresponding to R3, E4, R9, K12, D15, E16, K19, R23, S26, S28, N29, T30, E31, E32, D33, E35, Q36, E37, E39, and D40, based on SEQ ID NO: 32, or any combination thereof. (Item 17) The composition according to any one of items 1 to 3, wherein the peptide contains a hydrophilic residue at a position corresponding to one of 15, 35, 39, or 49, or any combination thereof, based on SEQ ID NO: 32. (Item 18) The composition according to item 14, wherein the hydrophilic residue is selected from amino acids D, E, H, K, R, N, Q, S, or T. (Item 19) The composition according to item 17 or 18, wherein the peptide comprises hydrophilic residues corresponding to D15, E35, E39, and H49, or any combination thereof, based on SEQ ID NO: 32. (Item 20) The composition according to any one of items 1 to 3, wherein the peptide contains a hydrophobic residue at positions corresponding to 11, 25, or 27, or any combination thereof, with reference to SEQ ID NO: 32. (Item 21) The composition according to item 20, wherein the hydrophobic residue is selected from amino acids A, M, I, L, V, F, W, or Y, or any combination thereof. (Item 22) The composition according to item 20, wherein the peptide comprises one of the hydrophobic residues corresponding to M11, M25, and M27, or any combination thereof, based on SEQ ID NO: 32. (Item 23) The composition according to any one o