Human blood-brain barrier targeting antibodies

An isolated blood-brain barrier (BBB)-selective antibody or antigen-binding fragment thereof 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).