Human blood-brain barrier targeting antibodies

Patent metadata

Field	Value
Publication number	US-2026062480-A1
Application number	US-202519384776-A
Country	US
Kind code	A1
Filing date	Nov 10, 2025
Priority date	Jan 28, 2020
Publication date	Mar 5, 2026
Grant date	—

Abstract

The present invention provides antibodies or antigen-binding fragments thereof including single chain variable fragment (scFv) antibodies that specifically bind to and translocate the blood-brain barrier and methods of use.

First claim

What is claimed:

1 . A nucleic acid sequence encoding a BBB-selective antibody or antigen-binding fragment comprising:
(a) a heavy chain domain comprising a CDRH1 region comprising SEQ ID NO: 26 (GFTFSGYW), a CDHR2 region comprising SEQ ID NO: 27 (IKGDGTDI), and a CDHR3 region comprising SEQ ID NO: 28 (ARDLRQTHWFDS), and a light chain domain comprising CDRL1 region comprising SEQ ID NO: 29 (SLRSYY), a CDRL2 region comprising the amino acid sequence GE, and a CDRL3 comprising SEQ ID NO:30 (SSRDTSGNHVL); (b) a heavy chain domain comprising a CDRH1 region comprising SEQ ID NO: 2 (GFTFSSYA), a CDHR2 region comprising SEQ ID NO: 3 (ISYDGSNK), and a CDHR3 region comprising SEQ ID NO: 4 (ARDSKGQSVRNRFDP), and a light chain domain comprising a CDRL1 region comprising SEQ ID NO: 5 (NLRSYY), a CDRL2 region comprising the amino acid sequence AN, and a CDRL3 comprising SEQ ID NO:6 (NSRDSSGNLVV); (c) a heavy chain domain comprising a CDRH1 region comprising SEQ ID NO: 8 (GFTFSSYA), a CDHR2 region comprising SEQ ID NO: 9 (ISGSGGST), and a CDHR3 region comprising SEQ ID NO: 10 (ARGWKYFDY), and a light chain domain comprising a CDRL1 region comprising SEQ ID NO: 11 (EGIYHW), a CDRL2 region comprising the amino acid sequence KA, and a CDRL3 comprising SEQ ID NO: 12 (QQYHTISRT); (d) a heavy chain domain comprising a CDRH1 region comprising SEQ ID NO: 14 (GFTFSSST), a CDHR2 region comprising SEQ ID NO: 15 (VSYDGNTQ), and a CDHR3 region comprising SEQ ID NO: 16 (AGLWGSLLGYFQH), and a light chain domain comprising a CDRL1 region comprising SEQ ID NO: 17 (QGVNNY), a CDRL2 region comprising the amino acid sequence AA, and a CDRL3 comprising SEQ ID NO: 18 (QQAHSFPPT); (e) a heavy chain domain comprising a CDRH1 region comprising SEQ ID NO: 20 (GFTFSTYW), a CDHR2 region comprising SEQ ID NO: 21 (INQDGTAE), and a CDHR3 region comprising SEQ ID NO: 22 (ATPTGDSDY), and a light chain domain comprising a CDRL1 region comprising SEQ ID NO: 23 (SLRSYY), a CDRL2 region comprising the amino acid sequence GQ, and a CDRL3 comprising SEQ ID NO: 24 (HSRDSSGNHVL); (f) a heavy chain domain comprising a CDRH1 region comprising SEQ ID NO: 32 (GFTFSTYW), a CDHR2 region comprising SEQ ID NO: 33 (INQDGTAE), and a CDHR3 region comprising SEQ ID NO: 34 (ATPTGDSDY), and a light chain domain comprising a CDRL1 region comprising SEQ ID NO: 35 (QDIGNY), a CDRL2 region comprising the amino acid sequence DA, and a CDRL3 comprising SEQ ID NO: 36 (QKLSSYPLT); (g) a heavy chain domain comprising a CDRH1 region comprising SEQ ID NO: 38 (GFTFSNYA), a CDHR2 region comprising SEQ ID NO: 39 (ISGSGSST), and a CDHR3 region comprising SEQ ID NO: 40 (AKTSGWPYYFDY), and a light chain domain comprising a CDRL1 region comprising SEQ ID NO: 41 (SSNIGNNY), a CDRL2 region comprising the amino acid sequence DN, and a CDRL3 comprising SEQ ID NO: 42 (CSYAGSSTLV); (h) a heavy chain domain comprising a CDRH1 region comprising SEQ ID NO: 44 (GFTFSSYA), a CDHR2 region comprising SEQ ID NO: 45 (VSGTGVST), and a CDHR3 region comprising SEQ ID NO: 46 (ARGLDWKSTPIDY), and a light chain domain comprising a CDRL1 region comprising SEQ ID NO: 47 (QSISGW), a CDRL2 region comprising the amino acid sequence GA, and a CDRL3 comprising SEQ ID NO: 48 (LQDYNGWT); (i) a heavy chain domain comprising a CDRH1 region comprising SEQ ID NO: 50 (GFTVSSNY), a CDHR2 region comprising SEQ ID NO: 51 (IKQDGSEK), and a CDHR3 region comprising SEQ ID NO: 52 (ARGGEEKNSGYYGDY), and a light chain domain comprising a CDRL1 region comprising SEQ ID NO: 53 (SLRSYY), a CDRL2 region comprising the amino acid sequence QD, and a CDRL3 comprising SEQ ID NO: 54 (QAWDSSTAHYV); (j) a heavy chain domain comprising a CDRH1 region comprising SEQ ID NO: 56 (GFTFSSYV), a CDHR2 region comprising SEQ ID NO: 57 (ISGSGGST), and a CDHR3 region comprising SEQ ID NO: 58 (AKQNWYFDL), and a light chain domain comprising a CDRL1 region comprising SEQ ID NO: 59 (SLRSYY), a CDRL2 region comprising the amino acid sequence GE, and a CDRL3 comprising SEQ ID NO: 60 (NSRDSRGTHLEV); (k) a heavy chain domain comprising a CDRH1 region comprising SEQ ID NO: 62 (GFTFSSYA), a CDHR2 region comprising SEQ ID NO: 63 (ISGSGGST), and a CDHR3 region comprising SEQ ID NO: 64 (AKSQGWAGDFDF), and a light chain domain comprising a CDRL1 region comprising SEQ ID NO: 65 (SSDIGTYNY), a CDRL2 region comprising the amino acid sequence EV, and a CDRL3 comprising SEQ ID NO: 66 (CSYAGSSTLV); or (l) a heavy chain domain comprising a CDRH1 region comprising SEQ ID NO: 68 (GFTFSSYA), a CDHR2 region comprising SEQ ID NO: 69 (ISSNGAIT), and a CDHR3 region comprising SEQ ID NO: 70 (VKDLKPSSWPPIYFDY), and a light chain domain comprising a CDRL1 region comprising SEQ ID NO: 71 (SLRTYY), a CDRL2 region comprising the amino acid sequence AN, and a CDRL3 comprising SEQ ID NO: 72 (NSRDSSGNHHVV).

2 . The nucleic acid sequence of claim 1 , wherein the BBB-selective antibody or antigen-binding fragment comprises an amino acid sequence selected from:
(a) SEQ ID NO: 25 or a sequence having at least 90% identity to SEQ ID NO: 25; (b) SEQ ID NO: 1 or a sequence having at least 90% identity to SEQ ID NO: 1; (c) SEQ ID NO: 7 or a sequence having at least 90% identity to SEQ ID NO: 7; (d) SEQ ID NO: 13 or a sequence having at least 90% identity to SEQ ID NO: 13; (e) SEQ ID NO: 19 or a sequence having at least 90% identity to SEQ ID NO: 19; (f) SEQ ID NO: 31 or a sequence having at least 90% identity to SEQ ID NO: 31; (g) SEQ ID NO: 37 or a sequence having at least 90% identity to SEQ ID NO: 37; (h) SEQ ID NO: 43 or a sequence having at least 90% identity to SEQ ID NO: 43; (i) SEQ ID NO: 49 or a sequence having at least 90% identity to SEQ ID NO: 49; (j) SEQ ID NO: 55 or a sequence having at least 90% identity to SEQ ID NO: 55; (k) SEQ ID NO: 61 or a sequence having at least 90% identity to SEQ ID NO: 61; and (l) SEQ ID NO: 67 or a sequence having at least 90% identity to SEQ ID NO: 67.

3 . The nucleic acid sequence of claim 1 , wherein the BBB-selective antibody or antigen-binding fragment comprises an amino acid sequence selected from: (a) SEQ ID NO: 25; (b) SEQ ID NO: 1; (c) SEQ ID NO: 7; (d) SEQ ID NO: 13; (e) SEQ ID NO: 19; (f) SEQ ID NO: 31; (g) SEQ ID NO: 37; (h) SEQ ID NO: 43; (i) SEQ ID NO: 49; (j) SEQ ID NO: 55; (k) SEQ ID NO: 61; and (l) SEQ ID NO: 66.

4 . The nucleic acid sequence of claim 1 , wherein the BBB-selective antibody or antigen-binding fragment is a humanized antibody or humanized antigen-binding fragment thereof.

5 . The nucleic acid of claim 1 , wherein the BBB-selective antibody or antigen-binding fragment is engrafted within a full IgG scaffold of human or other species origin or a scFv scaffold of human or other species of origin.

6 . The nucleic acid sequence of claim 1 , wherein the BBB-selective antibody or antigen-binding fragment is a single chain variable fragment (scFv).

7 . The nucleic acid sequence of claim 1 , wherein the BBB-selective antibody or antigen-binding fragment can bind the BBB and translocate across the BBB.

8 . The nucleic acid sequence of claim 1 , wherein the BBB-selective antibody or antigen-binding fragment specifically binds to the brain.

9 . The nucleic acid sequence of claim 1 , wherein the nucleic acid is linked to a nucleic acid encoding an agent.

10 . The nucleic acid of claim 9 , wherein the agent is selected from the group consisting of a therapeutic agent, a pharmaceutical agent, a diagnostic agent, an imaging agent, a detection agent, an immunological therapeutic construct, and a combination thereof.

11 . The nucleic acid sequence of claim 9 , wherein the BBB-selective antibody or antigen-binding fragment and the agent are able to translocate the BBB.

Assignees

• Wisconsin Alumni Res Found

Inventors

• Shusta Eric V
• Stutz Charles C
• Goulatis Loukas
• Georgieva Julia

Classifications

• C12N15/63

  Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• A61K2039/505

  comprising antibodies · CPC title