JPWO2019213668A5 - - Google Patents

Claims (15)

One or more in the amino acid sequence of an epitope selected from at least one of epitope 1, epitope 2, epitope 3, epitope 4, epitope 5, epitope 6, epitope 7, epitope 8, epitope 9, or epitope 10. AAVx-derived epitope containing a mutation. The epitopes are 439-469 (Epitope 1), 650-672 (Epitope 2), 700-728 (Epitope 3), 243-271 (Epitope 4), 320-337 (Epitope 5), 498-516 (Epitope 6). ), 523-533, 534-560 (Epitope 8), 570-596 (Epitope 9), or 409-422 (Epitope 10) corresponding to the AAV2 amino acid position according to claim 1. .. The AAVx-derived capsid according to claim 1, wherein the amino acid sequence of the epitope is randomized. The AAVx-derived capsid according to claim 1, wherein the one or more mutations in the amino acid sequence of the epitope are derived from an AAV strain other than AAVx. The AAVx-derived capsid according to claim 1, wherein the AAVx is AAV2. The AAVx-derived capsid of claim 5, wherein the one or more mutations in the amino acid sequence of the epitope are randomized. The AAVx-derived capsid according to claim 5, wherein the one or more mutations in the amino acid sequence of the epitope are derived from an AAV strain other than AAV2. The one or more mutations in the amino acid sequence in the epitope
Epitope 1: 439-DQYLYLSRTNTPSGTTTQSRLQFSQAGASD-469 (SEQ ID NO: 5);
Epitope 2: 650-NTPVPANPSTTFSAAKFASFITQ-672 (SEQ ID NO: 6);
Epitope 3: 700-YTSNYNKSVNVDFTVDTNGVYSEPPRIGT-728 (SEQ ID NO: 7);
Epitope 4: 243-STRTWALPTYNNHLYKQISSQSGASNDNNH-721 (SEQ ID NO: 9);
Epitope 5: 320-VKEVTQNDGTTTIANNLT-337 (SEQ ID NO: 10);
Epitope 6: 498-SEYSWTGATKYHLNGRDSL-516 (SEQ ID NO: 11);
Epitope 7: 523-MASHKDDEEKF-533 (SEQ ID NO: 12);
Epitope 8: 534-FPQSGVLIFGKQGSEKTNVDIEKVMIT-560 (SEQ ID NO: 13);
Epitope 9: 570-PVATEQYGSVSTNLQRGNRQAATADVN-596 (SEQ ID NO: 8); or
The AAVx-derived capsid according to claim 1, which is selected from at least one of Epitope 10: 409-FTFSYTFEDVPFHS-422 (SEQ ID NO: 52). It comprises a variant epitope 1 amino acid sequence, wherein the variant epitope 1 amino acid sequence is GGTATE (SEQ ID NO: 14), TQEARPG (SEQ ID NO: 20), TPTPQFS (SEQ ID NO: 22), TLEPLIT (SEQ ID NO: 24), PFETDLM. (SEQ ID NO: 26), LQEAHLT (SEQ ID NO: 28), EEGGRPK (SEQ ID NO: 29), EGDGGCL (SEQ ID NO: 31), DGGAGSW (SEQ ID NO: 32), AEGGGGG (SEQ ID NO: 34), AGGGEMG (SEQ ID NO: 36), GEAAAPA (SEQ ID NO: 26). The AAVx-derived capsid according to claim 1, comprising SEQ ID NO: 37), SVEGGAW (SEQ ID NO: 38), or SLASTLE (SEQ ID NO: 40). It comprises a variant epitope 2 amino acid sequence, wherein the variant epitope 2 amino acid sequence is PARQL (SEQ ID NO: 15), PRPVQ (SEQ ID NO: 19), PSALM (SEQ ID NO: 21), ADSLL (SEQ ID NO: 23), PASVM. (SEQ ID NO: 25), PRPLM (SEQ ID NO: 27), AQPVM (SEQ ID NO: 30), SEKQL (SEQ ID NO: 33), APAMC (SEQ ID NO: 35), DRRLL (SEQ ID NO: 39), or TLPMK (SEQ ID NO: 41). , AAVx-derived capsid according to claim 1. The AAVx-derived capsid according to claim 1, which comprises a mutant epitope 3 amino acid sequence, wherein the mutant epitope 3 amino acid sequence comprises SVDGN (SEQ ID NO: 16). The capsid derived from AAVx according to any one of claims 8 to 11, wherein AAVx is AAV2. AAVx derived from any one of claims 8 to 11, wherein AAVx is selected from the group consisting of AAV1, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, and AAV13. Capsid. The capsid derived from AAVx according to any one of claims 8 to 11, wherein AAVx is a capsid engineering variant. An AAV vector comprising the AAVx-derived capsid according to any one of claims 1 to 14.