Adeno-associated virus compositions having increased brain enrichment

Abstract

Described herein are compositions and kits comprising recombinant adeno-associated viruses (rAAVs) with increased transduction enrichment in the brain. The rAAV compositions described herein encapsidate a transgene, such as a therapeutic nucleic acid. Gene therapy using the rAAVs is described. Also described are methods of treating brain-related diseases and conditions.

Description

[0001] Patent Application CAPS-041 / 01 WO 35847 / 197

[0002] ADENO-ASSOCIATED VIRUS COMPOSITIONS HAVING INCREASED BRAIN ENRICHMENT

[0003] BACKGROUND

[0004] Recombinant adeno-associated viruses (rAAVs) are widely used as vectors for gene delivery in therapeutic applications because of their ability to transduce both dividing and non¬ dividing cells, their long-term persistence as episomal DNA in infected cells, and their low immunogenicity. These characteristics make them appealing for therapeutic applications, such as gene therapy. However, there is a need to significantly improve the performance of existing AAV serotypes to selectively and efficiently express in distinct cell-types, upon systemic delivery to a subject. This need is especially acute when the AAV must be expressed in the brain.

[0005] SUMMARY OF THE INVENTION

[0006] Disclosed herein are rAAVs with engineered transduction into the capsid structure through iterative rounds of selection in non-human primates (NHPs), yielding variants having increased transduction when measured in the brain.

[0007] The present invention provides rAAVs with widespread transduction to the brain and central nervous system (CNS).

[0008] Formula I

[0009] Aspects of the present invention provide an adeno-associated virus (AAV) capsid protein comprising an amino acid sequence having at least 80% identity to a sequence of Formula 1:

[0010] X1A-H-Q-X4A-X5A-X6A- X7A-XSA-G-X]0A-X11 A-X12A-I- A

[0011]

[0012] -X15. A-X16A-X17A-X18A-X19A-X20A-X21A-X22A-X23A-X24A-X25A (I)

[0013] wherein,

[0014] XIA is an amino acid selected from N or T;

[0015] X4 is an amino acid selected from S, G, M, or A; Patent Application CAPS-041 / 01 WO 35847 / 197 XSA is an amino acid selected from A, S, or N;

[0016] X6A is an amino acid selected from T, S, or V,

[0017] X7A is an amino acid selected from K or R;

[0018] X8A is an amino acid selected from N or D;

[0019] XIOA is an amino acid selected from E or H;

[0020] XUA is an amino acid selected from V or 1;

[0021] X12A is an amino acid selected from F, Y, L, or H;

[0022] XU is an amino acid selected from Q, M, I, or N;

[0023] Xi6A is an amino acid selected from A or S;

[0024] Xi 7A is an amino acid selected from Q, S, N, T, or A;

[0025] X18A is an amino acid selected from T, V, R, S, Q, I, N, or A;

[0026] X19A is an amino acid from G, S, A, N, Q, M, T, V, Y, L, K, I, H, F, D, or E,

[0027] X20A is an amino acid selected from W, A, Q, S, G, N, P, M, T, L, Y, F, K„ V, H, R, D, I, or E;

[0028] X21A is an amino acid selected from V, A, I, S, C, T, N, M, L, Q, G, or D;

[0029] X22A is an amino acid selected from Q, N, II, Y, T, S, G, or F;

[0030] X23 is an amino acid selected from N, S, G, Q, Y, A, F, M, D, V, E, C, I, H, L, or W; X?4A is an amino acid selected from Q, C, M, or I; and

[0031] X25A is an amino acid selected from G or A.

[0032] In preferred aspects of the invention,

[0033] X4Amay be selected from among S, G, or M;

[0034] Xi2A ay be selected from among F, Y, or L;

[0035] XisAmay be selected from among Q, M, or I;

[0036] Xi7Amay be selected from among Q, S, or N;

[0037] Xi8A ay be selected from among T, V, or R;

[0038] Xi9Ainay be selected from among G, S, or A,

[0039] X20Amay be selected from among W, A, or Q;

[0040] XiiAinay be selected from among V, A, or I;

[0041] X22 may be selected from among Q, N, or H; Patent Application CAPS-041 / 01 WO 35847 / 197 X23Amay be selected from among N, S, or G; and / or

[0042] X24Amay be selected from among Q, C, or M.

[0043] In aspects of the invention, XI is located at parental residue 583 and X25A is located at > parental residue 600 in reference to a parental AAV9 capsid or equivalent residue position in another AAV capsid, wherein in Formula I:

[0044] XI A is a parental or substituted amino acid;

[0045] H and Q are parental amino acids;

[0046] X4 and XSA are parental or substituted amino acids;

[0047] X6A is a substituted amino acid located at parental residue 588;

[0048] X? A, XSA, G, XIOA. XHA, X12A, I are an insertion between parental or substituted residues 588 and 589;

[0049] A is a parental amino acid located at parental residue 589, now residue 596;

[0050] XISA, X16A, X17A, XJXA, X]9A, ZOA, X21A, X22A, X23A. X24. A are parental or substituted amino acids; and

[0051] X25A is a parental or substituted amino acid located at parental residue 600, now residue 607.

[0052] For example, as described above, residue 583 may be substituted or remain the parental amino acid, residues 584-585 remain the parental amino acid, residues 586-587 may be substituted or remain the parental amino acids, and residue 588 is substituted. A 7-mer amino acid is inserted between parental amino acid residues 588 and 589.

[0053] Residue 589 (now 596) remains the parental amino acid. Residues 590-600 (now 596-607) may be substituted or remain the parental amino acid.

[0054] Capsids of the present invention comprising a sequence of Formula I may comprise the following sequences:

[0055] Table 1: Formula I sequences Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0056] ID ID NO NO

[0057] 2 NHQSAVKDGHVLIAMAQTAGVQNQG 41 NHQSATRNGEVHIAMAQTMA VQNQG *3 NHQSAVKDGHVLIAMAQTSNVQNQG 42 NHQS AVKDGHVL1AMAQTGQ VQNQG 4 NHQSAVKDGHVLIAMAQTNAVQNQG 43 NHQS AVKDGH VLIAMAQTNQ VQNQG 5 NHQSASRNGEVYIAQAQTAQVQNQG 44 NHQSASRNGEVYIAQAQTNQVQNQG 6 NHQSAVKDGHVLIAMAQTSPVQNQG 45 NHQSATKNGEVFIAQAQTGGVQNQG 7 NHQSAVKDGHVLIAMAQTGSAQNQG 46 NHQSSTKNGEVFIAQASTGYVQNQG 8 NHQSAVKDGHVL1AMAQTGTAQNQG 47 NHQSAVKDGHVLIAMAQTGGTQNQG 9 NHQSAVKDGHVLIAMAQTGNAQNQG 48 NHQSAVKDGHVLIAMAQTATVQNQG 10 NHQSASRNGEVYIAQAQTSA VQNQG 49 NHQSASRNGEVYIAQAQTQQVQNQG 11 NHQSASRNGEVY1AQAQTSQVQNQG 50 NHQSASRNGEVYIAQAQTIQVQNQG 12 NHQS ASRN GE V Y1AQAQTDKVQN QG 51 NHQSASRNGEVYIAQAQTGQCQNQG 13 NHQSASRNGEVYIAQAQTEKVQNQG 52 NHQSAVKDGHVLIAMAQTGATQNQG 14 NHQSAVKDGHVLIAMAQTTGVQNQG 53 NHQSASRNGEVYIAQAQTVQVQNQG 15 NHQSAVKDGHVLIAMAQTGSNQNQG 54 NHQSAVKDGHVLIAMAQTGGVQNQG 16 NHQSAVKDGHVLIAMAQTAQVQNQG 55 NHQSAVKDGHVLIAMAQTGSVQNQG 17 N HQS ATRN GE VH1AMAQTSGVQN QG 56 NHQSASRNGEVYIAQAQTAWVQNQG 18 NIIQSAVKDGHVLIAMAQTQSVQNQG 57 NHQSSTKNGEVF1AQAQTGWVQNCG 19 NHQSASRNGEVYIAQAQTTAVQNQG 58 NHQSATRNGEVHIAMAQTMGVQNQG 20 NHQSAVKDGHVLIAMAQTGSCQNQG 59 NHQSAVKDGHVLIAMAQTGMTQNQG 21 NHQSSTKNGEVF1AQAQTSN VQNQG 60 NHQSAVKDGHVLIAMAQTSTVQNQG 22 NHQS AVKDGH VLIAMAQTS A VQNQG 61 NHQSASRNGEVYIAQAQTNMVQNQG 23 NHQS AVKDGHVLIAMAQTGG1QN QG 62 NHQSASRNGEVYIAQAQTAYVQNQG 24 NHQSASRNGEVYIAQAQTGQVQNQG 63 NHQSASRNGEVYIAQAQTLQVQNQG 25 NHQSASRNGEVYIAQAQTGWCHNQG 64 NHQSAVKDGHVLIAMAQTGAIQNQG 26 NHQS AVKDGHVLIAMAQTSS VQNQG 65 NHQSAVKDGHVLIAMAQTQQVQNQG 27 NHQSATRNGEVHIAMAQTSMVQNQG 66 NHQSAVKDGHVLIAMAQTGQCQNQG 28 NHQS ASRNGEV YIA QAQTTKVQN QG 67 NHQSAVKDGHVLIAMAQTGVAQNQG 29 N H QS AVKDGHVL 1 AM AQTGNTQN QG 68 NHQSSTKNGEVFIAQAQTGNVQNQG 30 NHQSAVKDGHVLIAMAQTQNVQNQG 69 NHQSASRNGEVYIAQAQTGWVQNQA 31 NHQSASRNGEVYIAQAQTAGVQNQG 70 NHQSAVKDGHVLIAMAQTTQVQNQG 32 NI-IQSASRNGEVYIAQAQTTQVQNQG 71 NHQSASRNGEVYIAQAQTSMVQNQG 33 NHQSAVKDGHVLIAMAQTGTVQNQG 72 NHQSATKNGEVFIAQAQTGWVQNQG 34 NHQSASRNGEVYIAQAQTGWVNSQG 73 NHQSAVKDGHVLIAMAQTASVQNQG 35 NHQSASRNGEVY1AQAQTSGVQNQG 74 NHQSASRNGEVYIAQAQTGWVNQQG 36 NHQSAVKDGHVLIAMAQTGGAQNQG 75 NHQSSTKNGEVFIAQAQTAWVQNQG 37 NHQSSTKNGEVFIAQAQTGSVQNQG 76 NHQSAVKDGHVL1AMAQTGQMQNQG 38 NHQSATRNGEVHIAMAQTSYVQNQG 77 NHQSATRNGEVH1AMAQTNAVQNQG 39 NHQSAVKDGHVLIAMAQTGPAQNQG 78 NHQSAVKDGHVLIAMAQTGPTQNQG 40 NHQSSTKNGEVFIAQAQTGWVQNQG 79 NHQSASRNGEVYIAQAQTQKVQNQG

[0058]

[0059]

[0060] Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0061] ID ID NO NO

[0062] 80 NHQSASRNGEVYIAQAQTGWVNNQG 119 NHQSAVKDGHVLIAMAQTGLAQNQG 81 NHQSAVKDGHVLIAMAQTGMAQNQG 120 NHQSSTKNGEVF1AQSQTGSVQNQG 82 NHQSAVKDGHVL1AMAQTGAAQNQG 121 NHQSSTKNGEVFIAQAQTNQVQNQG 83 NHQSASRNGEVYIAQAQTMGVQNQG 122 NHQSSTKNGEVF1AQAQTGAAQNQG 84 NHQSASRNGEVYIAQAQTGWVYNQG 123 NHQSSTKNGEVF1AQAQTTGVQNQG 85 NIIQSAVKDGHVLIAMAQTSQVQNQG 124 NHQSASRNGEVY1AQAQTGWCNNQG 86 NHQSASRNGEVYIAQAQTNKVQNQG 125 NHQSATRNGEVHIAMAQTIGVQNQG 87 NHQSSTKNGEVFIAQAQTYQVQNQG 126 NHQSATRNGEVHIAMAQTMSVQNQG 88 NHQSATKNGEVFIAQAQTGWVTNQG 127 NHQSASRNGEVYIAQAQTNFVQNQG 89 NHQSAVKDGHVLIAMAQTGPSQNQG 128 NHQSAVKDGHVL1AMAQTGQAQNQG 90 NHQSAVKDGHVLIAMAQTGSIQNQG 129 NHQSAVKDGHVL1AMAQTGQTQNQG 91 NHQSASRNGEVYIAQAQTNSVQNQG 130 NHQSATRNGEVHIAMAQTGYVQNQG 92 NHQSSTKNGEVFIAQAQTAGVQNQG 131 NHQSSTKNGEVFIAQAQTGMVQNQG 93 NHQSAVKDGHVLIAMAQTGAVQNQG 132 NHQSASRNGEVYIAQAQTVKVQNQG 94 NHQSAVKDGHVLIAMAQTSGVQNQG 133 NHQSAVKDGHVLIAMAQTGQSQNQG 95 N HQS ATRN GE VH1AMAQTAYVQNQG 134 NHQSAVKDGHVLIAMAQTGMVQNQG 96 NHQSAVKDGHVL1AMAQTGANQNQG 135 NHQSSTKNGEVF1AQAQTQAVQNQG 97 NI-IQSAVKDGHVLIAMAQTNSVQNQG 136 NHQSATRNGEVHIAMAQTSAVQNQG 98 NHQSAVKDGHVLIAMAQTGNIQNQG 137 NHQSASRNGEVYIAQAQTSWVQNQG 99 NHQSSTKNGEVFIAQAQTNHVQNQG 138 NHQSASRNGEVYIAQAQTGWINNQG 100 NHQSAVKDGHVLIAMAQTSMVQNQG 139 NHQGSTRN GE VF1AQ AQTGW VNNQG 101 NHQSASRNGEVYIAQAQTGWANNQG 140 NHQSSTKNGEVFIAQAQTTQVQNQG 102 NHQSAVKDGHVLIAMAQTGSTQNQG 141 NHQSATRNGEVHIAIAQTGYVQNQG 103 NHQSSTKNGEVFIAQAQTKQVQNQG 142 NHQSATKNGEVFIAQAQTGWHNQG 104 NHQSASRNGEVYIAQAQTQFVQNQG 143 NHQSASRNGEVYLAQAQTGWVNDQG 105 NHQSASRNGEVYIAQAQTASVQNQG 144 NHQSASRNGEVYIAQAQTVSVQNQG 106 NHQSATRNGEVHIAMAQTNSVQNQG 145 NHQSASRNGEVYIAQAQTGANQNQG 107 NHQSSTKNGEVFIAQAQTQLVQNQG 146 NHQSASRNGEVYIAQAQTKMVQNQG 108 N HQS ASRNGE V YIA QAQTGWNNNQG 147 NHQSASRNGEVYIAQAQTNGVQNQG 109 NHQS ATRN GEVH1AIAQTGWV SNQG 148 NHQSSTKNGEVF1AQAQTVNVQNQG 110 NI-IQSAVKDGHVLIAMAQTAPVQNQG 149 NHQSASRNGEVYIAQAQTGWX'QNQG 111 NHQSSTKNGEVFIAQAQTGWVNYQG 150 THQSAVKDGI-IVLIAMAQTGWVQNQG 112 NHQSAVKDGHVLIAMAQTGSMQNQG 151 NHQSASRNGEVYIAQAQTGPSQNQG 113 NHQSATRNGEVHIAMAQTASVQNQG 152 NHQSAVKDGHVLIAMAQTGMSQNQG 114 NHQSATRNGEVHIAMAQTNGVQNQG 153 NHQSAVKDGHVL1AMAQTGSSQNQG 115 NHQSAVKDGHVLIAMAQTGLVQNQG 154 NHQSATKNGEVFIAQAQTGQVQNQG 116 NHQSSTKNGEVF1AQAQTNMVQNQG 155 NHQSASRNGEVYIAQAQTGYVQNQG 117 NHQSSTKNGEVFIAQAQTGWVYNQG 156 NHQSSTKNGEVFIAQAQTAQVQNQG 118 NHQSASRNGEVYIAQAQTNWVQNQG 157 NHQSAVKDGHVLIAMAQTGNVQNQG

[0063]

[0064]

[0065] Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0066] ID ID NO NO

[0067] 158 NHQSATRNGEVHIAMAQTAQVQNQG 197 NHQSASRNGEVYIAQAQTAPVQNQG 159 NHQS ASRNGEV YTA QAQTGW AHNQG 198 NHQSSTKNGEVF1AQAQTTA VQNQG 160 N HQS ASRNGEV YIA QAQTMQ VQNQG 199 NHQS AVKDGHVLIAMAQTGV VQNQG 161 NHQS ATRN GEVH1AMAQTGLSQNQG 200 NHQSATRNGEVHIAMAQTTSVQNQG 162 NHQSAVKDGHVLIAMAQTGQIQNQG 201 NHQSASRNGEVYIAQAQTAKVQNQG 163 NFIQSSTKNGEVFIAQAQTGWVNNQG 202 NHQSASRNGEVYIAQAQTGWVNGQG 164 NHQSASRNGEVYIAQAQTMMVQNQG 203 NHQSATRNGEVHIAMAQRGPVQNQG 165 NHQSASRNGEVYIAQAQTGWSYNQG 204 NHQSASRNGEVYIAQAQTGWVNMQG 166 NHQSSTKNGEVFIAQAQV GA VQNQG 205 NHQSSTKNGEVFIAQAQTFQVQNQG 167 NHQS A SRNGE V Y1 AQ AQT VP VQNQG 206 NHQSSTKNGEVFIAQAQTGWVNSQG 168 NHQSASRNGEVY1AQAQTGGAQNQG 207 NHQSSTKNGEVFIAQAQTAMVQNQG 169 NHQSASRNGEVYIAQAQTGKVQNQG 208 NHQSATRNGEVHIAMAQTSQVQNQG 170 NHQSATRNGEVHIAMAQTQQVQNQG 209 NHQSASRNGEVYIAQAQTGQAQNQG 171 NHQSSTKNGEVFIAQSQTGGVQNQG 210 NHQSASRNGEVYIAQAQTQGVQNQG 172 NHQSASRNGEVYIAQAQTLSVQNQG 211 NHQSSTKNGEVFIAQAQTGAVQNQG 173 NHQSSTKNGEVFIAQAQTVHVQNQG 212 NHQSATKNGEVF1AQAQTMWVQNQG 174 NHQSSTKNGEVFIAQAQTGWVNMQG 213 NHQSAVKDGHVLIAMAQTGPIQNQG 175 NHQSSTKNGEVFIAQAQTSWVQNQG 214 NHQSASRNGEVYIAQAQTLNVQNQG 176 NHQSASRNGEVYIAQAQTNNVQNQG 215 NHQSSTKNGEVFIAQASTNWVQNQG 177 NHQSASRNGEVYIAQAQVGWVQNQG 216 NHQSSTKNGEVFIAQAQVGQVQNQG 178 NHQSASRNGEVY1AQAQTGAAQNQG 217 NHQS ATRN GE VH1AMAQTGSV QN QG 179 NHQSSTKNGEVF1AQAQTIQVQNQG 218 NHQS ATRN GE VH1AIAQTGWVHNQG 180 NHQSAVKDGHVLIAMAQTGQNQNQG 219 NHQSASRNGEVYIAQAQTSNVQNQG 181 NHQSASRNGEVYIAQAQTGGNQNQG 220 NHQSAVKDGHVLIAMAQTTSVQNQG 182 NHQSASRNGEVYIAQAQTGWQHNQG 221 NHQSATRNGEVHIAMAQTGWVNSQG 183 THQSSTKNGEVFIAQAQTGWVQNQG 222 NHQSSTKNGEVFIAQAQTNTVQNQG 184 NHQSASRNGEVYIAQAQTVAVQNQG 223 NHQSSTKNGEVFIAQAQTVSVQNQG 185 NHQSAVKDGHVL1AMAQTGTIQNQG 224 NHQSSTKNGEVFIAQSQTGA VQNQG 186 NHQSSTKNGEVFIAQAQTSGVQNQG 225 NHQSSTKNGEVF1AQAQTGNNQNQG 187 NHQSASRNGEVYIAQAQTGWGNNQG 226 NHQSSTKNGEVF1AQAQTKMVQNQG 188 NI-IQSASRNGEVYIAQAQTGQIQNQG 227 NHQSSTKNGEVFIAQAQTQMVQNQG 189 NHQSSTKNGEVFIAQAQTQNVQNQG 228 NHQSATRNGEVHIAmQTGWVNFQG 190 NHQSAVKDGHVLIAMAQTGWINNQG 229 NHQSSTKNGEVFIAQAQTGQVQNQG 191 NHQSASRNGEVYIAQAQTSLVQNQG 230 NHQSAVKDGHVLIAMAQTQGVQNQG 192 NHQSASRNGEVYIAQAQTGWVTSQG 231 NHQSASRNGEVYIAQAQTMAVQNQG 193 NHQSASRNGEVYIAQAQTGWVNFQG 232 NHQSATRNGEVHIAMAQTQSVQNQG 194 NHQSAVKDGHVLIAMAQTGGNQNQG 233 NHQSASRNGEVYIAQAQTAMVQNQG 195 NHQSSTKNGEVFIAQAQTGSTQNQG 234 NHQSSTKNGEVFIAQAQTSTVQNQG 196 NHQSATRNGEVHIAMAQTSNVQNQG 235 NHQSATKNGEVFIAQAQTSAWQNQG

[0068]

[0069]

[0070] Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0071] ID ID NO NO

[0072] 236 NHQSASRNGEVYIAQAQTKQVQNQG 275 NHQSSTKNGEVFIAQANTGKVQNQG 237 NHQSASRNGEVYTAQAQTYAVQNQG 276 NHQS ASRNGEVY1 AQAQTTYVQNQG 238 N HQGSTRN GE V YIAQ AQTGWVQN QG 277 NHQSASRNGEVYIAQAQTERVQNQG 239 NHQS ATRN GEVHIAIAQTGGVQNQG 278 NHQSAVKDGHVLIAMAQTGPVQNQG 240 NHQSATRNGEVHIAMAQTAAVQNQG 279 NHQSAVKDGHVLIAMAQTGNSQNQG 241 NHQSASRNGEVYIAQAQTSFVQNQG 280 NHQSAVKDGHVL1AMAQTQAVQNQG 242 NHQSSTKNGEVFIAQAQTNGVQNQG 281 NHQSATKNGEVFIAQAQTGSVQNQG 243 NHQSASRNGEVYIAQAQTGWMNNQG 282 NHQSATRNGEVHIAMAQTGNAQNQG 244 NHQSSTKNGEVFIAQAQTGVVQNQG 283 NHQSSTKNGEVFIAQAQTANVQNQG 245 NHQGSTRNGEVFIAQAQTAWVQNQG 284 NHQSASRNGEVYIAQAQTGWVHSQG 246 NHQS ASRN GE V Y1AQAQTNHVQN QG 285 NHQSASRNGEVYIAQAQTGAVQNQG 247 NHQSSTKNGEVFIAQAQTLAVQNQG 286 NHQSAVKDGHVLIAMAQTGWVSNQG 248 NHQS AVKDGI IVLIAMAQTNPVQNQG 287 NHQSATRNGEVHIAMAQTNNVQNQG 249 NHQSAVKDGHVLIAMAQTTAVQNQG 288 NHQSSTKNGEVFIAQAQTKWVQNQG 250 NHQSSTKNGEVFIAQAQTMGVQNQG 289 NHQSSTKNGEVFIAQAQTVPVQNQG 251 N HQS ATRN GE VHIAMAQTGSAQN QG 290 NHQSSTKNGEVFIAQAQTGWVNFQG 252 NHQSAVKDGHVLIAMAQTGPVQNQG 291 NHQSSTKNGEVF1AQAQTAPVQNQG 253 NI-IQSAVKDGHVLIAMAQTAAVQNQG 292 NHQSASRNGEVYIAQAQTSKVQNQG 254 NHQSATKNGEVFIAQAQTGAVQNQG 293 NHQSASRNGEVYIAQAQTGWVHAQG 255 NHQSSTKNGEVFIAQAQRGNVQNQG 294 NHQSASRNGEVYIAQAQTGACQNQG 256 NHQS ASRNGEV YIAQ AQTGFVQNQG 295 NHQSASRNGEVYIAQAQTKAVQNQG 257 NHQSATRNGEVHIAMAQTGAVQNQG 296 NHQS ATRN GE VH1AMAQTGWVQNQG 258 NHQSSTKNGEVFIAQAQTGWVNDQG 297 NHQSAVKDGHVL1AMAQTNNVQNQG 259 NHQSASRNGEVYIAQAQTTGVQNQG 298 NHQSATRNGEVHIAMAQTYAVQNQG 260 NHQSSTKNGEVFIAQAQTGPVQNQG 299 NHQSASRNGEVYIAQAQTVGVQNQG 261 NHQSASRNGEVYIAQAQTGWVNAQG 300 NHQSAVKDGHVL1AMAQTGASQYQG 262 NHQSSTKNGEVFIAQAQRGPVQNQG 301 NHQSSTKNGEVFIAQAQTGHVQNQG 263 N H QS AS RNGE V YT A Q A QTGWDNNQG 302 NHQSAVKDGHVLIAMAQTTPVQNQG 264 N HQS ATRN GE VH1 AMAQTMQVQNQG 303 NHQSAVKDGHVLIAMAQTGQQQNQG 265 NHQSSTKNGEVFIAQAQTGWVNHQG 304 NHQSASRNGEVYIAQAQTGPCQNQG 266 NHQSAVKDGHVLIAMAQTGLTQNQG 305 NHQSASRNGEVYIAQAQTANVQNQG 267 NHQSAVKDGHVLIAMAQTAMVQNQG 306 NHQSSTKNGEVFIAQAQTNWVQNQG 268 NHQSSTKNGEVFIAQAQTGWVQNQA 307 NHQSSTKNGEVFIAQAQTGWVNFQG 269 NHQSSTKNGEVFIAQAQTGNTQNQG 308 NHQSATRNGEVHIAMAQTSSVQNQG 270 NHQSSTKNGEVF1AQSQTGPVQNQG 309 NHQSSTKNGEVFIAQAQTTNVQNQG 271 NHQSASRNGEVYIAQAQTSFVQNQG 310 NHQSAVKDGHVL1AMAQTGGSQNQG 272 NHQSSTKNGEVF1AQAQTSWQNQG 311 NHQSAVKDGHVL1AMAQTGAMQNQG 273 NHQSSTKNGEVFIAQAQTGWVNQQG 312 NHQSAVKDGHVLIAMAQTANVQNQG 274 NHQSSTKNGEVFIAQAQTGWVSNQG 313 NHQSSTKNGEVFIAQAQVGLVQNQG

[0073]

[0074]

[0075] Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0076] ID ID NO NO

[0077] 314 NHQSSTKNGEVFIAQAQVGNVQNQG 353 NHQSSTKNGEVFIAQAQTGNAQNQG 315 NHQSSTKNGEVFIAQAQTKLVQNQG 354 NHQSATRNGEVHIAMAQTVGVQNQG 316 NHQSSTKNGEVF1AQAQTQSVQNQG 355 NHQSSTKNGEVF1AQAQTGWVNAQG 317 NHQSASRNGEVYIAQAQTGWMHNQG 356 NHQSASRNGEVYIAQAQTGQNQNQG 318 NHQSASRNGEVYIAQAQTGHCQNQG 357 NHQSSTKNGEVFIAQAQTGLSQNQG 319 NI-IQSAVKDGHVLIAMAQTAVVQNQG 358 NHQSSTKNGEVFIAQAQTMQVQNQG 320 NHQSSTKNGEVFIAQAQTGWVHNQG 359 NHQSATRNGEVHIAMAQTAFVQNQG 321 NHQSATKNGEVF1AQSQTGWVQNQG 360 NHQSASRNGEVYIAQAQTGWVNLQG 322 NHQSSTKNGEVFIAQAQTVQVQNQG 361 NHQSASRNGEVYIAQAQTHMVQNQG 323 NHQSSTKNGEVFIAQSQTNWVQNQG 362 NHQSASRNGEVYIAQAQTGWLHNQG 324 NHQSASRNGEVY1AQAQTQAVQNQG 363 NHQSASRNGEVYIAQAQTGSCQNQG 325 NHQSASRNGEVYIAQAQQGWVQNQG 364 NHQSSTKNGEVFIAQAQTAAVQNQG 326 NHQSSTKNGEVFIAQAQTMLVQNQG 365 NHQSATKNGEVFIAQAQTTWVQNQG 327 NHQSSTKNGEVFIAQAQTKPVQNQG 366 NHQSASRNGEVYIAQAQTYQVQNQG 328 NHQSSTKNGEVFIAQAQTNNVQNQG 367 NHQSASRNGEVYIAQAQTNAVQNQG 329 NHQSSTKNGEVFIAQAQTYAVQNQG 368 NHQSSTKNGEVF1AQAQTQWVQNQG 330 NHQSSTKNGEVFIAQAQTGSCQNQG 369 NHQSSTKNGEVF1AQAQTKGVQNQG 331 NI-IQSASRNGEVYIAQAQTNPVQNQG 370 NHQSSTKNGEVFIAQAQTMWVQNQG 332 NHQSASRNGEVYIAQAQTGFIQNQG 371 NHQSASRNGEVYIAQAQTNLVQNQG 333 NHQSASRNGEVYIAQAQTTSVQNQG 372 NHQSSTKNGEVFIAQSQTGQVQNQG 334 NHQSASRNGEVY1AQAQTGSSQNQG 373 NHQSATRN GE VH1AMAQTGWVHN QG 335 NHQSAVKDGHVLIAMAQ'TGVNQNQG 374 NHQSASRNGEVY1AQAQTSSVQNQG 336 NHQSSTKNGEVFIAQAQTQTVQNQG 375 NHQSATRN GE VFIAQAQTGWVQNQG 337 NHQSSTKNGEVFIAQAQTQQVQNQG 376 NHQSAVKDGHVLIAMAQTGFAQNQG 338 NHQSSTKNGEVFIAQAQTGLVQNQG 377 NHQSSTKNGEVFIAQAQTMPVQNQG 339 NHQSATRNGEVHIAMAQTQYVQNQG 378 NHQSASRNGEVYIAQAQTNINVQNQG 340 NHQSATRNGEVHIAIAQTGWVQNQG 379 NHQSASRNGEVYIAQAQTGWVGSQG 341 NHQSATKNGEVF1AQAQTGLVQNQG 380 NHQSATRNGEVFTAQAQTGSVQNQG 342 NHQSASRNGEVYIAQAQTGPAQNQG 381 NHQSSTKNGEVF1AQAQTLMVQNQG 343 NHQSSTKNGEVFIAQAQTIAVQNQG 382 NHQSATRNGEVHIAMAQTTAVQNQG 344 NHQSSTKNGEVFIAQAQTGASQNQG 383 NHQSSTKNGEVFIAQAQTNAVQNQG 345 NHQSSTKNGEVFIAQAQTYAVQNQG 384 THQSASRNGEVYIAQAQTGWVQNQG 346 NHQSATKNGEVFIAQAQTAWVQNQG 385 NHQSATRNGEVH1AMAQTAGVQNQG 347 NHQSSTKNGEVFIAQSQTGTVQNQG 386 NHQSSTKNGEVFIAQAQTGSIQNQG 348 NHQSSTKNGEVF1AQAQTKVVQNQG 387 NHQSSTKNGEVFIAQAQTGGVQNQG 349 NHQSSTKNGEVFIAQAQTLSVQNQG 388 NHQSSTKNGEVFIAQAQTLGVQNQG 350 NHQSASRNGEVY1AQAQTAHVQNQG 389 NHQSSTKNGEVFIAQAQ1GQVQNQG 351 NHQSSTKNGEVFIAQAQTVGVQNQG 390 NHQSSTKNGEVFIAQAQVGHVQNQG 352 NHQSSTKNGEVFIAQAQTNSVQNQG 391 NHQSASRNGEVYIAQAQTQWVQNQG

[0078]

[0079]

[0080] Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0081] ID ID NO NO

[0082] 392 NHQSSTKNGEVFIAQAQTIGVQNQG 431 NHQSSTKNGEVFIAQAQTTMVQNQG 393 NHQS ASRNGEV YIA QSQTGWVQN QG 432 NHQSATRNGEVHIAMAQTGTAQNQG 394 NHQSAVKDGHVLIAMAQTGTNQNQG 433 NHQSSTKNGEVF1AQASTGFVQNQG 395 NHQS ATRN GEVHIAMAQTNWVQN QG 434 NHQSNSRNGEVYIAQAQTGWVQNQG 396 NHQSSTKNGEVFIAQAQTMSVQNQG 435 NHQSASRNGEVYIAQAQTQSVQNQG 397 NHQSATKNGEVFIAQAQTGNVQNQG 436 NHQSSTKNGEVFIAQASTQWVQNQG 398 NHQSAVKDGHVLIAMAQTGALQNQG 437 NHQSAVKDGHVLIAMAQTGWTNNQG 399 NHQSASRNGEVYIAQAQTGWCYNQG 438 NHQSSTKNGEVFIAQAQTGMIQNQG 400 NHQSSTKNGEVFIAQAQTSLVQNQG 439 NHQSASRNGEVY1AQAQTGMNQNQG 401 NHQGSTRNGEVFIAQAQTSWVQNQG 440 NHQSSTKNGEVFIAQAQTSMVQNQG 402 NHQSAVKDGHVLIAMAQTGACQNQG 441 NHQSASRNGEVYIAQAQTYGVQNQG 403 NHQSATRNGEVHIAMAQTQAVQNQG 442 NHQSSTKNGEVFIAQAQTMNVQNQG 404 NHQSSTKNGEVFIAQAQTGWVTNQG 443 NHQSSTKNGEVFIAQAQTGWCNNQG 405 NHQSSTKNGEVFIAQAQTGWX^QNMG 444 NHQSSTKNGEVFIAQAQSSWVQNQG 406 NHQSATRNGEVHIAMAQTQGVQNQG 445 NHQSSTKNGEVFIAQAQTGATQNQG 407 NHQSASRNGEVYIAQAQTTRVQNQG 446 NHQSASRNGEVYIAQAQTTRVQNQG 408 NHQSSTKNGEVFIAQAQTKAVQNQG 447 NHQSATRNGEVHIAMAQTGFVQNQG 409 NHQSAVKDGHVLIAMAQTNGVQNQG 448 NHQSASRNGEVYIAQAQTIPVQNQG 410 NHQSAVKDGHVLIAMAQTMQVQNQG 449 NHQSASRNGEVYIAQAQTGSAQNQG 411 NHQSASRNGEVYIAQAQTMYVQNQG 450 NHQSATRNGEVHIAMAQRGNVQNQG 412 NHQSAVKDGHVLIAMAQTGWMNNQG 451 NHQS ATRN GE VH1A1 AQTGS VQN QG 413 NHQSSTKNGEVFIAQAQTGWTNNQG 452 NHQSAVKDGHVL1AMAQTGPCQNQG 414 NHQSSTKNGEVFIAQAQTISVQNQG 453 NHQSASRNGEVYIAQAQTGWVNYQG 415 NHQSASRNGEVYIAQAQTGWSNNQG 454 NHQSASRNGEVYIAQAQTSYVQNQG 416 NHQSATRNGEVHIAMAQTGWANNQG 455 NHQSATKNGEVFIAQAQTGWAQNQG 417 NHQSAVKDGHVLIAMAQTGVIQNQG 456 NHQSAVKDGHVLIAMAQTSLVQNQG 418 NHQSSTKNGEVFIAQAQTGPAQNQG 457 NHQSATRNGEVH1AMAQTSPVQNQG 419 NHQSSTKNGEVFIAQAQTGQTQNQG 458 NHQSASRNGEVY1AQAQTGLAQNQG 420 NHQSASRNGEVYTAQAQTGWVTGQG 459 NHQS ASRNGEVYIAQAQTKF VQNQG 421 NHQSASRNGEVYIAQAQTGWVQGQG 460 NHQSSTKNGEVF1AQAQTGVIQNQG 422 NHQSASRNGEVYIAQAQTQNVQNQG 461 NHQSSTKNGEVFIAQAQTGWVQNIG 423 NHQSSTKNGEVFIAQAQTGWVQYQG 462 NHQSATKNGEVFIAQAQTGWVSNQG 424 NHQSATRNGEVHIAIAQTGQVQNQG 463 NHQGSTRNGEVFIAQATTGWVQNQG 425 NHQSSTKNGEVFIAQAQSGYVQNQG 464 NHQSSTKNGEVFIAQAQTGSAQNQG 426 NHQSSTKNGEVFIAQAQTKTVQNQG 465 NHQSATKNGEVFIAQAQTGWTQNQG 427 NHQSATRNGEVHIAMAQTSWVQNQG 466 NHQSASRNGEVYIAQAQQNWVQNQG 428 NHQSATRNGEVHIAMAQTNPVQNQG 467 NHQSSTKNGEVFIAQAQTSSVQNQG 429 NHQSSTKNGEVFIAQAQIGAVQNQG 468 NHQSSTKNGEVFIAQAQTSPVQNQG 430 NHQSSTKNGEVFIAQAQTGFIQNQG 469

[0083]

[0084]

[0085] NHQGSTRNGEVFIAQAQTGWVHNQG Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0086] ID ID NO NO

[0087] 470 NHQMSTKNGEVFIAQAQTGWVQNQG 509 NHQSAVKDGHVL1AMAQTGTTQNQG 471 NHQSSTKNGEVFIAQAQTLNVQNQG 510 NHQSASRNGEVYIAQAQTGSVQNQG 472 NHQSATKNGEVFIAQAQTGWVNNQG 511 NHQSSTKNGEVFIAQAQTGGNQNQG 473 NHQSSTKNGEVFIAQAQTALVQNQG 512 NHQSSTKNGEVFIAQAQTGMAQNQG 474 NHQS ATRN GEVH1AMAQTAMVQNQG 513 NHQSATRNGEVHIAIAQTGAVQNQG 475 NIIQSASRNGEVYIAQAQTGNVQNQG 514 NHQSSTKNGEVFIAQAQTGNIQNQG 476 NHQSATRNGEVHIAMAQTTGVQNQG 515 NHQSSTKNGEVFIAQAQTGGTQNQG 477 NHQSASRNGEVYIAQAQTNYVQNQG 516 NHQSASRNGEVYIAQAQTGGSQNQG 478 NHQSSTKNGEVFIAQSQTGWVQNQG 517 NHQSSTKNGEVFIAQAQTGWVHSQG 479 NHQS A SRNGE V Y1 AQ AQTSTVQNQG 518 NHQSASRNGEVYIAQAQTGWAYNQG 480 NHQSASRNGEVY1AQAQTGWVYGQG 519 NHQSSTKNGEVFIAQAQTHLVQNQG 481 NHQSATRNGEVHIAMAQTTGVQNQG 520 NHQSSTKNGEVFIAQAQVGWVQNQG 482 NHQSASRNGEVYIAQAQSMWVQNQG 521 NHQSATRNGEVHIAMAQTGSIQNQG 483 NHQSASRNGEVYIAQAQTTMVQNQG 522 NHQSSTKNGEVFIAQAQTGTAQNQG 484 NHQSAVKDGHVLIAMAQTQTVQNQG 523 NHQSASRNGEVYIAQAQTGWVTNQG 485 NHQSSVKNGEVF1AQAQTGWVQNQG 524 NHQSASRNGEVYIAQAQTYSVQNQG 486 NHQS ATRN GEVH1AMAQTGMVQNQG 525 NHQSASRNGEVYIAQAQTTGVQNQG 487 NHQSASRNGEVYIAQAQTYNVQNQG 526 NHQSSTKNGEVFIAQSQTGMVQNQG 488 NHQSSTKNGEVFIAQAQTGWLHNQG 527 NHQSATRNGEVHIAMAQTMNVQNQG 489 NHQSSTKNGEVFIAQAQTGWITNQG 528 NHQSATRNGEVHIAMAQTGWVNNQG 490 NHQSSTKNGEVF1AQAQTMAVQNQG 529 NHQS ATRN GE VH1AMAQTQNV QNQG 491 NHQSATRNGEVHIAMAQTTMVQNQG 530 NHQSASRNGEVYIAQASTGWVQNQG 492 NHQSAVKDGHVLIAMAQTGVTQNQG 531 NHQSSTKNGEVFIAQAQTAHVQNQG 493 NHQSSTKNGEVFIAQAQTGWVYGQG 532 NHQSAVKDGHVLIAMAQTGLCQNQG 494 NHQSAVKDGHVLIAMAQTGPMQNQG 533 NHQSASRNGEVYLAQAQTGWTNNQG 495 NHQSASRNGEVYIAQAQTGWAQNQG 534 NHQSSTKNGEVFIAQAQTMMVQNQG 496 NHQSATRNGEVHIAMAQTNYVQNQG 535 NHQSSTKNGEVFIAQAQTGPSQNQG 497 NHQSATRNGEVH1AMAQTSFVQNQG 536 NHQSAVKDGHVLIAMAQTGPNQNQG 498 NHQSSTKNGEVFIAQAQTSAVQNQG 537 NHQS AVKDGH VLIAMAQTMS VQNQG 499 NHQGSTRNGEVF1AQAQTGWVQNQG 538 NHQS ATKN GEVY1AQAQTGWVQN QG 500 NHQSASRNGEVYIAQAQTSHVQNQG 539 NHQSSTKNGEVFIAQAQVSWVQNQG 501 NI-IQSASRNGEVYIAQAQTGWVHGQG 540 NHQSAVKDGHVLIAMAQTGNLQNQG 502 NHQSASRNGEVYIAQAQTMPVQNQG 541 NHQSSTKNGEVFIAQAQQAWVQNQG 503 NHQSSTKNGEVFIAQAQTKSVQNQG 542 NHQSATRNGEVHIAMAQTTQVQNQG 504 NHQSSTKNGEVFIAQAQTGAIQNQG 543 NHQSSTKNGEVFIAQAQTTSVQNQG 505 NHQSSTKNGEVFIAQAQTGLNQNQG 544 NHQS ATRN GE VFIAQAQTGGVQNQG 506 NHQSATRNGEVHIAMAQRGSVQNQG 545 NHQSSTKNGEVFIAQAQTFNVQNQG 507 NHQSSTKNGEVFIAQAQTGTAQNQG 546 NHQSATRNGEVHIAMAQTGQVQNQG 508 NHQSASRNGEVYIAQAQTTWVQNQG 547

[0088]

[0089]

[0090] NHQSASRNGEVYLAQAQTQTVQNQG Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0091] ID ID NO NO

[0092] 548 NHQSSTKNGEVFIAQAQTGYVQNQG 587 NHQSASRNGEVYIAQAQTIGVQNQG 549 NHQSSTKNGEVFIAQSQTSWVQNQG 588 NHQS AVKDGH VL1A MAQTGMMQN QG 550 NHQSAVKDGHVLIAMAQTGSLQNQG 589 NHQS ASRN GEVYIAQAQTGQTQNQG 551 NHQS ATRN GEVH1AMAQTGQCQNQG 590 NHQSASRNGEVYIAQAQTGWTHNQG 552 NHQS ATRN GEVH1AMAQTGWVNMQG 591 NHQSATRNGEVHIAMAQTAWVQNQG 553 NHQSSTKNGEVFIAQAQTGWMNNQG 592 NHQSATRNGEVHIAMAQTGGAQNQG 554 NHQGSTRNGEVFIAQAQTGWVSNQG 593 NHQSSTKNGEVFIAQAQTQPVQNQG 555 NHQSSTKNGEVFIAQAQTGWVSQQG 594 NHQSATRNGEVHIAMAQVGQVQNQG 556 NHQSSTKNGEVFIAQAQTAVVQNQG 595 NHQSASRNGEVYIAQAQTSVVQNQG 557 NHQSSTKNGEVFIAQAQTGWWWQG 596 NHQSASRNGEVYIAQAQTQMVQNQG 558 NHQSSTKNGEVFIAQAQAGFVQNQG 597 NHQSSTKNGEVFIAQAQTGWAYNQG 559 NHQSSTKNGEVFIAQAQSGWVQNQG 598 NHQSATRNGEVFIAQAQTGAVQNQG 560 NHQSASRNGEVYIAQAQTGMSQNQG 599 NHQSAVKDGHVLIAMAQTGFSQNQG 561 NHQSASRNGEVYIAQAQTGSIQNQG 600 NHQSSTKNGEVFIAQAQTGWVTQQG 562 NHQSATRNGEVHIAMAQTGAAQNQG 601 NHQSSTKNGEVFIAQASTSWVQNQG 563 NHQSSTKNGEVFIAQAQTATVQNQG 602 NHQSSTKNGEVF1AQAQTTTVQNQG 564 NHQSASRNGEVYIAQAQTGHSQNQG 603 NHQS ATKN GEVFIAQAQTGWV YN QG 565 NI-IQSAVKDGHVLIAMAQTGYIQNQG 604 NHQSATRNGEVHIAMAQTTPVQNQG 566 NHQSASRNGEVYIAQAQTTLVQNQG 605 NHQSSTKNGEVFTAQAQTGWVTSQG 567 NHQSATRNGEVFIAQAQTGPVQNQG 606 NHQSASRNGEVYIAQAQTIAVQNQG 568 NHQSSTKNGEVFIAQAQTHNVQNQG 607 NHQSSTKNGEVFIAQAQTSHVQNQG 569 NHQSATRNGEVHIAMAQTYGVQNQG 608 NHQS ATRN GE VH1AMAQTAPVQN QG 570 NHQSAVKDGHVLIAMAQTGYTQNQG 609 NHQSAVKDGHVL1AMAQTGMTQNQG 571 NHQSASRNGEVYIAQAQTGWSHNQG 610 NHQSASRNGEVYIAQAQTGWIHNQG 572 NHQSATRNGEVHIAMAQTNMVQNQG 611 NHQSASRNGEVYIAQAQTHQVQNQG 573 NHQSSTKNGEVFIAQAQTNPVQNQG 612 NHQSSTKNGEVFIAQSQTGLVQNQG 574 NHQSSTKNGEVFIAQAQSNWQNQG 613 NHQSATKNGEVFIAQAQTGV< ArQNQA 575 NHQSATRNGEVH1AMAQTVQVQNQG 614 NHQSASRNGEVYIAQAQTGWVQSQG 576 NHQSSTKNGEVFIAQAQTGMSQNQG 615 NHQSSTKNGEVF1AQAQT1PVQNQG 577 NHQSSTKNGEIFIAQAQTGWVQNQG 616 NHQMNTRNGEVFIAQAQTGWVNNQG 578 NHQSSTKNGEVFIAQAQTGPIQNQG 617 NHQSATRNGEVFIAQAQTGQVQNQG 579 NHQSSTKNGEVFIAQAQIGTVQNQG 618 NHQSASRNGEVYIAQAQTLWQNQG 580 NHQSATRNGEVHIAMAQTNTVQNQG 619 NHQSATRNGEVFIAQASTGWVQNQG 581 NHQSSTKNGEVFIAQAQTGWVQGQG 620 NHQSATRNGEVHIAMAQTGQQQNQG 582 NHQSATKNGEVFIAQAQTGFVQNQG 621 NHQSSTKNGEVFIAQAQRGLVQNQG 583 NHQSATRNGEVHIAMAQTSTVQNQG 622 NHQSSTKNGEVYIAQAQTGWVQNQG 584 NHQSASRNGEVY1AQAQTMLVQNQG 623 NHQSSTKNGEVFIAQAQTLHVQNQG 585 NHQSASRNGEVYIAQAQTYPVQNQG 624 NHQSASRNGEVYIAQAQTGMVQNQG 586 NHQSASRNGEVYIAQAQTGGVQNQG 625 NHQSSTKNGEVFIAQSQTAWVQNQG

[0093]

[0094]

[0095] Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0096] ID ID NO NO

[0097] 626 NHQSAVKDGHVLIAMAQTGLSQNQG 665 NHQSASRNGEVYIAQAQTATVQNQG 627 NHQSATRNGEVHIAMATTGDVQNQG 666 NHQSSTKNGEVFIAQSQTGVVQNQG 628 N HQS ATRN GE VH1 AMAQTERVQN QG 667 NHQSSTKNGEVFIAQAQTYNVQNQG 629 NHQSSTKNGEVFIAQAQTGLCQNQG 668 NHQSSTKNGEVF1AQAQIGGVQNQG 630 NHQS ASRNGEV YIAQAQRDWVQN QG 669 NHQSAVKDGHVLIAMAQTGTLQNQG 631 NHQSSTKNGEVFIAQAQVGMVQNQG 670 NHQSAVKDGHVL1AMAQTGMNQNQG 632 NHQASTKNGEVFIAQAQTGWVQNQG 671 NHQSSTKNGEVFIAQASTGKVQNQG 633 NHQSASRNGEVYIAQAQTGWVHNQG 672 NHQSAVKDGHVLIAMAQTYAVQNQG 634 NHQSATRNGEVHIAIAQTGN VQNQG 673 NHQGATRNGEVY1AQAQTGAVQNQG 635 NHQS A SRNGE V Y1 AQ AQQQWV QNQG 674 NHQSATRNGEVHIAMAQTGMAQNQG 636 NHQSAVKDGHVLIAMAQTMPVQNQG 675 NHQSSTKNGEVFIAQAQTTPVQNQG 637 NHQSAVKDGHVLIAMAQTGWIHNQG 676 NHQSASRNGEVYIAQAQTFAVQNQG 638 NHQSATKNGEVFIAQAQTGYVQNQG 677 NHQSSTKNGEVFIAQAQSGFVQNQG 639 NHQSSTKNGEVFIAQAQTLTVQNQG 678 NHQSSTKNGEVFIAQAQTGWVNCQG 640 NHQSSTKNGEVFIAQAQNGYVQNQG 679 NHQSSTKNGEVFIAQAQTGWIQNQG 641 N HQS ATRN GE VH1AMAQTGN CQNQG 680 NHQSSTKNGEVF1AQAQTHGVQNQG 642 NHQSATKNGEVFIAQAQTQWVQNQG 681 NHQSASRNGEVYIAQAQTGSNQNQG 643 NHQSSTKNGEVFIAQAQTQGVQNQG 682 NHQSSTKNGEVFIAQAQSAWVQNQG 644 NHQSASRNGEVYIAQAQTGWIYNQG 683 NHQSATRNGEVHIAMAQTGWAHNQG 645 NHQSSTKNGEVFIAQAQIGSVQNQG 684 NHQSSTKNGEVFIAQAQTGWVHQQG 646 NHQSATRNGEVHIAMAQTSLVQNQG 685 NHQSSTKNGEVFIAQAQTGIVQNQG 647 NHQSSTKNGEVF1AQAQTGWVHEQG 686 NHQSASRNGEVYIAQAQTGWVHQQG 648 NHQSSTKNGEVFIAQASTGSVQNQG 687 NHQSAVKDGHVL1AMAQTMAVQNQG 649 NHQSASRNGEVYIAQAQTQRVQNQG 688 NHQSASRNGEVYIAQAQTQPVQNQG 650 NHQSASRNGEVYIAQAQTAA VQNQG 689 NHQSSTKNGEVFIAQAQTGWQHNQG 651 NHQSASRNGEVYIAQAQTISVQNQG 690 NHQSNTKNGEVnAQAQTGWVQNQG 652 NHQSAVKDGHVLIAMAQTNTVQNQG 691 NHQSSTKNGEVFIAQAQTMTVQNQG 653 NHQSATKNGEIF1AQAQTGWVQNQG 692 NHQSASRNGEVY1AQAQTGWVYSQG 654 NHQSASRNGEVYIAQAQTMWVQNQG 693 NHQSSTKNGE VF1AQAQTKN VQNQG 655 NHQSATRNGEVF1AQAQTSWVQNQG 694 NHQSSTKNGEVFIAQAQRGDVQNQG 656 NI-IQSAVKDGHVLIAMAQTQPVQNQG 695 NHQSASRNGEVYIAQAQTDRVQNQG 657 NHQSSTKNGEVFIAQAQTHPVQNQG 696 NHQSAVKDGHVLIAMAQTLAVQNQG 658 NHQSATRNGEVHIAMAQTYSVQNQG 697 NHQSASRNGEVYIAQAQTAL VQNQG 659 NHQSASRNGEVYIAQAQTGNNQNQG 698 NHQSSTKNGEVFIAQASTAWVQNQG 660 NHQSSTKNGEVFIAQAQTHWVQNQG 699 NHQGSTRN GE VF1AQ AQTQWVQNQG 661 NHQSAVKDGHVLIAMAQTLGVQNQG 700 NHQGATRNGEVY1AQAQTTWVQNQG 662 NHQSSTKNGEVF1AQAQTGTSQNQG 701 NHQSAVKDGHVL1AMAQTGQLQNQG 663 NHQSSTKNGEVFIAQAQNGKVQNQG 702 NHQSASRNGEVYIAQAQTVRVQNQG 664 NHQSATRNGEVHIAMAQTATVQNQG 703 NHQGATRNGEVYIAQAQTGWA'SNQG

[0098]

[0099]

[0100] Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0101] ID ID NO NO

[0102] 704 NHQSATRNGEVFIAQAQTGMVQNQG 743 NFIQSATKNGEVFIAQAQTNW'VQNQG 705 NHQSSTKNGEVFIAQAQTNLVQNQG 744 NHQSSTKNGEVFIAQASTGWVQNQG 706 N HQS ATRN GE VH1 AMAQTGV AQNQG 745 NHQSSTKNGEVF1AQAQTGTVQNQG 707 NHQSAVKDGHVL1AMAQTMGVQNQG 746 NHQSATRNGEVHIAMAQTANVQNQG 708 NHQSSTKNGEVFIAQAQTHMVQNQG 747 NHQSAVKDGHVLIAMAQTGWMHNQG 709 NFIQSASRNGEVYIAQAQTGWVNVQG 748 NHQSASRNGEVYIAQAQTGNAQNQG 710 NHQSSTKNGEVFIAQASTGQVQNQG 749 NHQSSTKNGEVFIAQAQTMVVQNQG 711 NHQSATKNGEVFIAQAQTGMVQNQG 750 NHQSATRNGEVHIAMAQTMYVQNQG 712 NHQSSTKNGEVFIAQANTGFVQNQG 751 NHQSAVKDGHVL1AMAQTGHAQNQG 713 NHQSATRNGEVHIAMAQTGPTQNQG 752 NHQSATRNGEVH1AMAQTGWCHNQG 714 NHQSATRNGEVHIAMAQRGDVQNQG 753 NHQSAVKDGHVL1AMAQTGWGNNQG 715 NHQSATKNGEVFIAQAQTGKVQNQG 754 NHQMNTRNGEVFIAQAQTGWVHNQG 716 NHQS AVKDGI IVLIAMAQTMNVQNQG 755 NHQSSTKNGEVFIAQAQQGQVQNQG 717 NHQSAVKDGHVLIAMAQTGNMQNQG 756 NHQSATRNGEVHIAMAQTGANQNQG 718 NHQSASRNGEVYIAQAQTGPVQNQG 757 NHQSSTKNGEVFIAQAQTGANQNQG 719 NHQSSTKNGEVFIAQAQRGEVQNQG 758 NHQSATRNGEVHIAMAQTGWVNYQG 720 NHQSSTKNGEVFIAQAQTGFVQNQG 759 NHQSSTKNGEVF1AQAQTGNSQNQG 721 NHQSASRNGEVYIAQAQTGWVNIQG 760 NHQSATRNGEVHIAMAQTGFCQNQG 722 NHQSSTKNGEVFIAQAATGKVQNQG 761 NHQGATRNGEVYIAQAQTSWVQNQG 723 NHQSATRNGEVHIAMAQTGFIQNQG 762 NHQSASRNGEVYIAQAQTYMVQNQG 724 NHQSSTKNGEVF1AQAQTGWLNNQG 763 NHQSATRNGEVH1AMAQTGAQQNQG 725 NHQSASRNGEVYIAQAQTGWVFNQG 764 NHQSATKNGEVFIAQAQTGWVQNMG 726 NHQSASRNGEVYIAQAQTTFVQNQG 765 NHQSAVKDGHVL1AMAQTGAQQNQG 727 NHQSATRNGEVHIAIAQTGMVQNQG 766 NHQSASRNGEVYIAQAQTGWNHNQG 728 NHQSASRNGEVYIAQAQTGWSQNQG 767 NHQSSTKNGEVFIAQAQTGVAQNQG 729 NHQSATRNGEVHIAMAQTGWVHAQG 768 NHQSATRNGEVHIAMAQTGFCQNQG 730 NHQSATRNGEVHIAMAQTGGVQNQG 769 NHQSASRNGEVYIAQAQTMTVQNQG 731 NHQSASRNGEVYTAQAQTFQVQNQG 770 NHQSATRNGEVH1AMAQTMTVQNQG 732 N HQS ATRN GE VF1 AN SQTGT VQNQG 771 NHQSSTKNGEVF1AQAQTGPCQNQG 733 NHQSATRNGEVHIAMAQTLSVQNQG 772 NHQSATRNGEVHIAMSQTGSVQNQG 734 NFIQSAVKDGHVLIAMAQTGWANNQG 773 NHQSASRNGEVYIAQAQTGWA'QNCG 735 NHQSSTKNGEVFIAQAQVGGVQNQG 774 NFIQSSTKNGEVFIAQSQTGNVQNQG 736 NHQSASRNGEVYIAQAQTAVVQNQG 775 NHQSSTKNGEVFIAQAQTGWVGSQG 737 NHQSASRNGEVYIAQAQTYKVQNQG 776 NHQSSTKNGEVFIAQAQQSWVQNQG 738 NHQSAVKDGHVLIAMAQTGMCQNQG 777 NHQSATKNGEVFIAQAQTGWVQQQG 739 NHQSASRNGEVYIAQAQTGMCQNQG 778 NHQSSTKNGEVFIAQAQTGWVNVQG 740 NHQSATRNGEVHIAMAQTVSVQNQG 779 NHQS ATRN GE VH1AMAQTGN SQN QG 741 NHQSAVKDGHVLIAMAQTTNVQNQG 780 NHQSATRNGEVHIAMAQTGACQNQG 742 NHQSASRNGEVYIAQAQTGYAQNQG 781

[0103]

[0104]

[0105] NHQSAVKDGHVLIALAQTGWVQNQG Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0106] ID ID NO NO

[0107] 782 NHQSAVKDGHVLIAMAQTGISQNQG 801 NHQSSTKNGEVFIAQAQTGKVQNQG 783 NHQSATRNGEVHIAMAQTVPVQNQG 802 NHQSATRNGEVHIAMAQTGQAQNQG 784 NHQSSTKNGEVF1AQAQVGSVQNQG 803 NHQSAVKDGHVLIAMAQTALVQNQG 785 NHQSATRNGEVH1AMAQTDKVQNQG 804 NHQSATRNGEVHIAMAQTGWINNQG 786 NHQSSTKNGEVFIAQAQTYWVQNQG 805 NHQSASRNGEVYIAQAQTGYSQNQG 787 NHQSSTKNGEVFIAQAQTGIAQNQG 806 NHQSATRNGEVHIAMAQTQTVQNQG 788 NHQSATRNGEVFIAQAQTGNVQNQG 807 NHQSAVKDGHVLIAMAQTYSVQNQG 789 NHQSASRNGEVYIAQAQTQYVQNQG 808 NHQSATRNGEVHIAMAQTFAVQNQG 790 NHQSATRNGEVFIANAQTGSVQNQG 809 NHQS ATRN GE VHIAMAQTQFVQN QG 791 NHQS ATRNGEVHIA MAQTGPAQNQG 810 NHQSATRNGEVHIAMAQTGWVNGQG 792 NHQSAVKDGHVLIAMAQTQMVQNQG 811 NHQSASRNGEVYIAQAQTLKVQNQG 793 NHQSASRNGEVYIAQAQTGASQNQG 812 NHQSSTKNGEVFIAQAQTGWVTGQG 794 NHQSSTKNGEVFIAQAQVAWVQNQG 813 NHQSSTKNGEVFIAQAQTGQAQNQG 795 NHQSASRNGEVYIAQAQTGYIQNQG 814 NHQSSTKNGEVFIAQAQTVMVQNQG 796 NHQGATRNGEVYIAQAQTGMVQNQG 815 NHQSATRNGEVHIAMAQTVPVQNQG 797 NHQSAVKJ9GHVLIAMAQTGWNNNQG 816 NHQSSTKNGEVF1AQAQTEKVQNQG 798 NHQSSTKNGEVFIAQAQTIHVQNQG 817 NHQSSTKNGEVF1AQAQTGMTQNQG 799 NHQSSTKNGEVFIAQAQTTIIVQNQG

[0108]

[0109] 818 NHQSATRNGEVHIAMAQTGWVQFQG

[0110]

[0111] 800 NHQSAVKDGHVLIAMAQTGWVHGQG

[0112] Formula II

[0113] Aspects of the present invention provide an adeno -associated virus (AA V) capsid protein comprising an amino acid sequence having at least 80% identity to a sequence of Formula II:

[0114] X1B-X2B-Q-X4B-X5B-X6B- X7B-X8B- X9B-X1OB-X11B-X12B-X13B"

[0115]

[0116] X14B-X15B-X16B-X17B (II)

[0117] wherein,

[0118] XIB is an amino acid selected from N or S;

[0119] X2B is an amino acid selected from H, N, S, Q, L, V, or W;

[0120] X4B is an amino acid selected from S, T, G, A, M, or C;

[0121] X5B is an amino acid selected from A, Q, S, N, M, E, H, T, D, G, or Y;

[0122] X6B is an amino acid selected from T, M, S, V, L, I, K, Q, ¥, A, N, or E; Patent Application CAPS-041 / 01 WO 35847 / 197 X? B is an amino acid selected from R, K, L, M, S, or A:

[0123] Xgp, is an amino acid selected from N, D, G, A, T, Q, or S,

[0124] XOB is an amino acid selected from G, S, T, E, Q, D, A, K, or N;

[0125] XIOB is an amino acid selected from E, H, Q, A, S, G, N, K, T, D,T, or R;

[0126] Xi IB is an amino acid selected from T, V, I, L, orM;

[0127] X12B is an amino acid selected from Y, L, F, R, M, or H;

[0128] XBB is an amino acid selected from I, V, L, M, S, or Q;

[0129] Xi4B is an amino acid selected from A or S;

[0130] Xt5B is an amino acid selected from S, G, Q, M, A, T, I, N, V, H, or L;

[0131] Xi6B is an amino acid selected from A, P, S, T, F, or I; and

[0132] X17B is an amino acid selected from Q, S, N, A, or T.

[0133] In preferred aspects of the invention,

[0134] X? Bmay be selected from among H, N, or S;

[0135] X-inmay be selected from among S, T, or G;

[0136] XsBmay be selected from among A, Q, or S;

[0137] X6B may be selected from among T, M, or S;

[0138] XyBmay be selected from among R, K, or L;

[0139] XSB may be selected from among N, D, or G;

[0140] XyBinay be selected from among G, S, or T.

[0141] XIOB may be selected from among E, H, or Q;

[0142] XnBmay be selected from among T, V, or I;

[0143] XnBmay be selected from among Y, L, or E;

[0144] XnBmay be selected from among I, V, or L;

[0145] XMB may be selected from among A or S;

[0146] XuBinay be selected from among S, G, or Q;

[0147] XnBmay be selected from among A, P, or S; and / or

[0148] X17B may be selected from among Q, S, or N.

[0149] In aspects of the invention, XIB is located at parental residue 583 and X™ is located at Patent Application CAPS-041 / 01 WO 35847 / 197 parental residue 592 in reference to a parental AAV9 capsid or equivalent residue position in another AAV capsid, wherein in Formula II:

[0150] XIB and X? B are parental or substituted amino acid;

[0151] Q is a parental amino acid;

[0152] X4B and XSB are parental or substituted amino acids;

[0153] XS is a parental or substituted amino acid located at parental residue 588,

[0154] X? B, XSB, XQB. XIOB, XIIB. X12B, Xi3B are an insertion between parental or substituted residues in positions 588 and 589;

[0155] Xi4B, Xi5B, and X16B, are parental or substituted amino acids; and

[0156] Xi7B is a parental or substituted amino acid located at parental residue 592, now residue 599.

[0157] For example, as described above, residues 583-584 may be substituted or remain the parental amino acid, residue 584 remains the parental amino acid, residues 585-587 may be substituted or remain the parental amino acids. A 7-mer amino acid is inserted between parental amino acid residues 588 and 589.

[0158] Residue 589 (now 596) to residue 592 (now 596-599) may be substituted or remain the parental amino acid.

[0159] Capsids of the present invention comprising a sequence of Formula II may comprise the following sequences, with parental residues 593-600 (600-607) remaining the parental amino acids (TGWVQNQG - SEQ ID NO: 4984):

[0160] Table 2: Formula II sequences SEQ VR-VIII amino acid sequence

[0161] ID SEQ VR-VIII amino acid sequence NO

[0162] ID 826 NHQSSVKNGEVYIAQAQTGWVQNQG NO

[0163] 819 827 NHQSATKNGEVYVAGAQTGWVQNQG NHQSQTRNGGTLIAVAQTGWVQNQG

[0164] 820 828 NHQSQTKNGETY1AQAQTGWVQNQG NHQGSKRNGETY1AAAQTGWVQNQG 821 829 NHQMQTRNGETYIAQAQTGWVQNQG NHQSASRNGEVYVAGANTGWVQNQG

[0165] 830

[0166] 822 NHQSQMKNGETYIAGAQTGWVQNQG NHQTQTKN GE V Y I AQAQTGW VQNQG

[0167] 823 831 NHQSQAKNGEVYJAQAQTGWVQNQG NHQTSVRNGEVYIAQAQTGWVQNQG

[0168] 824 832 NHQAATKNGEVY1AQAQTGWVQNQG NHQA QTRNGETY 1 AQAQTGWV QN QG 825 833 NHQSQTRDGQTLIAMAQTGWVQNQG NHQMSSRNGEVY1AQAQTGWVQNQG

[0169]

[0170]

[0171] Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0172] ID ID NO NO

[0173] 834 NHQASTKNGEVYIAQAQTGWVQNQG 873 NHQTQTKNGE VFTA QAQTGWVQNQG 835 NHQGSTRNGETYIAGAQTGWVQNQG 874 NHQSAMRNGETYIAGAQTGWVQNQG 836 NHQSATKNGETY1AGAQTGWVQNQG 875 NHQSASRNGETYIAAANTGWVQNQG 837 NHQSQTRNGATLIAAAQTGWVQNQG 876 NHQMQSKNGEVYIAQAQTGWVQNQG 838 NHQSESRNGQTYIAGAQTGWVQNQG 877 NHQGSTKNGEVYIAQAQTGWVQNQG 839 NHQGSTRNGETYIASAQTGWVQNQG 878 NHQGSMRNGFYYIATAQTGWVQNQG 840 NHQSATKNGEVYVAAANTGWVQNQG 879 NHQGSVRNGETY1ASAQTGWVQNQG 841 NHQMGTRNGETYIATAQTGWVQNQG 880 NHQAQTKNGEVFIAQAQTGWVQNQG 842 NHQTQTRNGETYIAGAQTGWVQNQG 881 NHQSQIKNGETYIAGAQTGWVQNQG 843 NHQMQTKNGETYIAQAQTGWVQNQG 882 NHQTSVKNGEVYIAQAQTGWVQNQG 844 NHQSSTKNGETY1AGAQTGWVQNQG 883 NHQMQTKNGEVF1AQAQTGWVQNQG 845 NHQSQTRNGETYIAQAQTGWVQNQG 884 NHQSQVRNGETLLYMAQTGWVQNQG 846 NHQSASRNGETYIAGASTGWVQNQG 885 NHQMNTKNGEVYIAQAQTGWVQNQG 847 NHQSQIRNGETYLASAQTGWVQNQG 886 NHQSASRNGETYIAGANTGWVQNQG 848 NHQSASRNGETYIASFQTGWVQNQG 887 NHQMQSRNGETYIAQAQTGWVQNQG 849 NHQSETKNGGTYIASAQTGWVQNQG 888 NHQSATKNGEVYSAIAQTGWVQNQG 850 NHQTQYK. NGEVYIAQAQTGWVQNQG 889 NQQS AMRNGET Y1 A AAQTGWV QNQG 851 NHQSQTSNGHTL1AMAQTGWVQNQG 890 NHQS ATRN GET YIAQAQTGW VQNQG 852 NHQSAVRNGETYIAGAQTGWVQNQG 891 NHQSATKNGETYIASANTGWVQNQG 853 NHQSQSRNGETYIAQAQTGWVQNQG 892 NHQMSLKNGEVYIAQAQTGWVQNQG 854 NHQSQTKNGE VH1AM AQTGW VQN QG 893 NHQSQTKNGETFIAGAQTGWVQNQG 855 NHQSQSKNGEVYIAQAQTGWVQNQG 894 NHQSAVLNGEIRIAMAQTGWVQNQG 856 NHQTAVRNGEVYIAQAQTGWVQNQG 895 NHQSQSRNGETYISGAQTGWVQNQG 857 NHQSQNKNGETYIAGAQTGWVQNQG 896 NHQSAKRNGETYIAGAQTGWVQNQG 858 NHQSETKNGGTYIAGAQTGWVQNQG 897 NHQSATKNGEVYVASAQTGWVQNQG 859 NHQGSVRNGETYIAGAQTGWVQNQG 898 NHQSETKNGGVYIAQAQTGWVQNQG 860 NHQSAVRNGETYIASANTGWVQNQG 899 NHQSQIKNGEVYLASAQTGWVQNQG 861 NHQTQVKNGEVYIAQAQTGWVQNQG 900 NHQMATKNGEVYIAQAQTGWVQNQG 862 NHQSATRNGETYISGAQTGWVQNQG 901 NHQTQSRNGEVYIAQAQTGWVQNQG 863 NHQTSTKNGEVYIAQAQTGWVQNQG 902 NHQGSMKNGEVYIAGAQTGWVQNQG 864 NHQSQQKNGETYIAGAQTGWVQNQG 903 NHQSQMKNGETYIASAQTGWVQNQG 865 NHQTQVRNGETYIAGAQTGWVQNQG 904 NHQMSTKNGEVYIAQAQTGWVQNQG 866 NHQGSKKNGEVYIAGAQTGWVQNQG 905 NHQSASRNGETYIAGAQTGWVQNQG 867 NHQSATRNGATLIAVAQTGWVQNQG 906 NHQTQVRNGEVYIAQAQTGWVQNQG 868 NHQGSTRN GEI Y1AQAQTGW VQN QG 907 NHQSQ1KNGEVY1AQAQTGWVQNQG 869 NHQSQTRNGSTLIAVAQTGWVQNQG 908 NHQSATRE> GHTMIAIAQTGWVQNQG 870 NHQTQLKNGEVYIAQAQTGWVQNQG 909 NHQSAMKNGEVYIAGAQTGWVQNQG 871 NHQSQTRDGATLIAMAQTGWVQNQG 910 NHQGSTKNGEVFIAGAQTGWVQNQG 872 911 NHQTQTKNGETYIAHAQTGWVQNQG

[0174]

[0175] NI-IQSAMKNGEVY1ASAQTGWVQNQG

[0176]

[0177] Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0178] ID ID NO NO

[0179] 912 NHQSATRDGHTLIAIAQTGWVQNQG 951 NHQGSTRNGETYIAAAQTGWVQNQG 913 NHQAQSKNGEVYIAQAQTGWVQNQG 952 NHQTQTRNGEVYIANAQTGWVQNQG 914 NHQSQVLDGHTRIAMAQTGWVQNQG 953 NHQTQKRNGETYIAGAQTGWVQNQG 915 NHQSATRNGETFIAGAQTGWVQNQG 954 NHQSQKKNGETYIAGAQTGWVQNQG 916 NHQSESRNGQTYTASAQTGWVQNQG 955 NHQTQTRNGEVHIAMAQTGWVQNQG 917 NHQSAMRNGETYIAAAQTGWVQNQG 956 NHQSQYKNGEVYIAQAQTGWVQNQG 918 NHQAQSKNGEVYIAQAQTGWVQNQG 957 NHQAQLKNGEVY1AQAQTGWVQNQG 919 NHQSQTKNGEVFLASAQTGWVQNQG 958 NHQASMKNGEVFIAGAQTGWVQNQG 920 NHQSQTKNGETFIASAQTGWVQNQG 959 NHQGSLRNGETYIAAAQTGWVQNQG 921 NHQSQLKNGETY1AGAQTGWVQNQG 960 NHQSQMRGTETYIAQAQTGWVQNQG 922 NHQMSTRNGETYIAQAQTGWVQNQG 961 NHQMSKKNGEVYIAQAQTGWVQNQG 923 NHQTQTRNGETYIAQAQTGWVQNQG 962 NHQSATKNGETYIASAQTGWVQNQG 924 NHQMSSRNGETYIAGAQTGWVQNQG 963 NHQSAMKNGEVFIAGAQTGWVQNQG 925 NHQSAIKNGEVYIAQAQTGWVQNQG 964 NHQGSMRNGETYIAAAQTGWVQNQG 926 NHQSQTKNGETYISGAQTGWVQNQG 965 NHQGSKRNGETYIASAQTGWVQNQG 927 NHQSATRNGETYIAGAQTGWVQNQG 966 NHQSATKNGEVYVAAAQTGWVQNQG 928 NHQSATKNGH1LIATAQTGWVQNQG 967 NHQSQTRDGNIHIAMAQTG W VQNQG 929 NHQTQIRNGETYIAGAQTGWVQNQG 968 NHQSAMKNGETYIAAAQTGWVQNQG 930 NHQSQLRAGETYIASAQTGWVQNQG 969 NHQMSSKNGEVYIAQAQTGWVQNQG 931 NHQSQTRNGATLIAVAQTGWVQNQG 970 NHQMSSRNGET YIA S AQTGWVQNQG 932 NHQSAMRNGETYIAGASTGWVQNQG 971 NHQTSTRNGEVY1ANAQTGWVQNQG 933 NHQSQKKNGETYIASAQTGWVQNQG 972 NHQSATRNGQTLIAMAQTGWVQNQG 934 NHQASMRNGETYIASAQTGWVQNQG 973 NHQSQTRNGSTLIAAAQTGWVQNQG 935 NHQSQLKNGEVYIAQAQTGWVQNQG 974 NHQTSTKNGEVYLASAQTGWVQNQG 936 NHQTQTRNGETF1AGAQTGWVQNQG 975 NHQSAIKNGETYIAAAQTGWVQNQG 937 NHQMAKRNGETY1AGAQTGWVQNQG 976 NHQTQTRNGEVYIAQAQTGWVQNQG 938 NHQTQTKNGETYIAGAQTGWVQNQG 977 NHQSATRNGHTLIAVAQTGWVQNQG 939 NHQSATLDGHVRIAMAQTGWVQNQG 978 NHQSAMRGGETYIAGAQTCAWQNQG 940 NHQSSTRNGETYIAGAQTGWVQNQG 979 NHQASLKNGEVYIAQAQTGWWQNQG 941 NHQSETKNGGVF1AQAQTGWVQNQG 980 NHQTQLRNGEVYIAQAQTGWVQNQG 942 NHQTQTKNGELYIAQAQTGWVQNQG 981 NHQAQTKNGEVHIAMAQTGWVQNQG 943 NHQSATRNGETYIASAQTGWVQNQG 982 NHQTQLRNGETYIASAQTGWVQNQG 944 NHQSAMRNEQTYIASAQTGWVQNQG 983 NHQSATRNGETYISSAQTGWVQNQG 945 NHQSATRNGETFIASANTGWVQNQG 984 NHQSQVRDGHTIJAIAQTGWVQNQG 946 NHQSSIKNGEVY1AQAQTGWVQNQG 985 NHQSATRDGHVL1AVPQTGWVQNQG 947 NHQSQTANGHTLIAMAQTGWVQNQG 986 NHQSATKNGETYIAGASTGWVQNQG 948 NHQSQVRNGEIHIAMAQTGWVQNQG 987 NHQSQERNGH1TIAMAQTGWVQNQG 949 NHQGSTKNGEVYIAGAQTGWVQNQG 988 NHQGSTRNGQTYIANAQTGWVQNQG 950 NHQSASRNGEVYLASASTGWVQNQG 989 NHQASMRNGETYIAGAQTGWVQNQG

[0180]

[0181]

[0182] Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0183] ID ID NO NO

[0184] 990 NHQTQTRNGEVFIAQA QTGWVQNQG 1029 NHQSAVRNGQTLIAMAQTGWVQNQG 991 NHQSQTKNGETYLASAQTGWVQNQG 1030 NHQSMSRNGET Y1 AGAQTGWVQN QG 992 NHQSSTKNGETY1ASAQTGWVQNQG 1031 NHQGAMRNGEVYIAGAQTGWVQNQG 993 NHQSQTKNGEVFISGAQTGWVQNQG 1032 NHQSAIKIDGHIMIAMAQTGWVQNQG 994 NHQSNMRNGET YIAS AQTGWVQNQG 1033 NQQSAIRNGETYLA GA QTGWVQNQG 995 NHQSATRNGATLIAMAQTGWVQNQG 1034 NHQMQTKNGETF1AGAQTGWVQNQG 996 NHQSQYKNGETY1AGAQTGWVQNQG 1035 NHQSQTKNGETYMAAAQTGWVQNQG 997 NIIQSNSRNGETYIAGAQTGWVQNQG 1036 NHQSAVRNGELYIAQAQTGWVQNQG 998 NHQSAMRNGETYIAAPQTGWVQNQG 1037 NHQMSTKNGETYIAGAQTGWVQNQG 999 NHQTATRNGEVYIAQAQTGWVQNQG 1038 NHQSATKNGEVYISGAQTGWVQNQG 1000 NHQMSTKNGEVYVAGAQTGWVQNQG 1039 NHQSQSKN GE V YVAAAQTGWVQNQG 1001 NHQSASRNGEVYIANASTGWVQNQG 1040 NHQGSMRNGEVYIAGA QTGWVQNQG 1002 NHQSAVRNGETYIASAQTGWVQNQG 1041 NHQASTRNGEVY1ANA QTGWVQNQG 1003 NHQSAKRNGETYIASAQTGWVQNQG 1042 NHQMQTKNGEVHTAMAQTGWVQNQG 1004 NHQAQTKNGETYIAQ AQTGWVQNQG 1043 NHQGSTRNGDVY1AQAQTGWVQNQG 1005 NHQSASRNGQVYIANAQTGWVQNQG 1044 NWQSASRNGETYIAGAQTGWVQNQG 1006 NHQSQTKAGF. TYIAGAQTGWVQNQG 1045 NNQSQSRNGET YIAS AQTGWVQNQG 1007 NHQSATKNGETY1ASASTGWVQNQG 1046 NHQAQTKNGETYIAGAQTGWVQNQG 1008 NHQAAMKNGEVYIAGAQTGWVQNQG 1047 NHQSAMRDGHTLIAIAQTGWVQNQG 1009 NHQTQVKNGEVFIAQ AQTGWVQNQG 1048 NHQSAKKNGEVYVAAA QTGWVQNQG 1010 NHQSQTRNDGTLIAMAQTGWVQNQG 1049 NHQASLRNGEVYIAQA QTGWVQNQG 1011 NHQSAKRNGEVYVAGAQTGWVQNQG 1050 NHQSAMRNEQTYIAGAQTGWVQNQG 1012 NIIQSQTRDGGIHIAMAQTGWVQNQG 1051 NHQSQSKNGETYIAGAQTGWVQNQG 1013 NHQSAIRNGETYIAAANTGWVQNQG 1052 NHQSSTRNGETFIAGAQTGWVQNQG 1014 NHQSASRNGETYIAAAQTGWVQNQG 1053 NHQSHTRNGETYIASAQTGWVQNQG 1015 NHQGATRNGETYIAGAQTGWVQNQG 1054 NHQTQ1KN GE V Y1AQAQTGWVQNQG 1016 NHQSALKNGETYIAAAQTGWVQNQG 1055 NHQSQTRASETYIASAQTGWVQNQG 1017 NHQSATKNGETYIAGSQTGWVQNQG 1056 NHQSQSRAGETYIAGAQTGWVQNQG 1018 NHQTQTRNGETYISSAQTGWVQNQG 1057 NHQSATRNGETYISAAQTGWVQNQG 1019 NHQSESRNGSTY1ASAQTGWVQNQG 1058 NHQSATRDGQVLIAMAQTGWVQNQG 1020 NIIQSAQKNGEVYIAGAQTGWVQNQG 1059 NHQSQVRGGETLIAMAQTGWQNQG 1021 NHQMNSRNGEVYIAQAQTGWVQNQG 1060 NHQSHTRNGETYIAGAQTGXWQNQG 1022 NHQSASRNGETYIAASQTGWVQNQG 1061 NHQSALRNGETYIAAAQTGWVQNQG 1023 NHQSQSKNGETYIAQAQTGWVQNQG 1062 NHQASMRNGETYI AAA QTGWVQNQG 1024 NHQAS1RNGEVY1AQAQTGWVQNQG 1063 NHQSQTRNGETH1AMAQTGWVQNQG 1025 NHQAQTKNGETFIAGAQTGWVQNQG 1064 NHQTQTRGGETYIASAQTGWWQNQG 1026 NHQTQMRNGETY1AGAQTGWVQNQG 1065 NHQSNSRGGETYIAAAQTGWVQNQG 1027 NHQSATRNGQILIATAQTGWVQNQG 1066 NHQSAMRGKETYIASAQTGWVQNQG 1028 NSQSQTKNGETYIAGAQTGWVQNQG 1067 NHQSASRNGTVYIASAQTGWVQNQG

[0185]

[0186]

[0187] Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0188] ID ID NO NO

[0189] 1068 NHQSAKKNGETYIAAAQTGWVQNQG 1107 NHQSASRNEQTYIAAAQTGWVQNQG 1069 NHQSSIKNGETYJAAAQTGWVQNQG 1108 NHQGQSRNGET Y1AA AQTGWVQN QG 1070 NHQSAIRNGETYIAAAQTGWVQNQG 1109 NHQANSRNGETY1AAAQTGWVQNQG 1071 NHQSASRNGETYIAAASTGWVQNQG 1110 NHQGSTRNGEVYIANAQTGWVQNQG 1072 NHQMQTKNGEVRIAMAQTGWVQNQG m i NHQSATRGGETYIASANTGWVQNQG 1073 NHQASIKNGEVYIAQAQTGWVQNQG 1112 NHQS A SRNGEVYVA A AQTGWVQNQG 1074 NHQSA1RNGEVL1AMAQTGWVQNQG 1113 NHQSQVLDGNIR1AMAQTGWVQNQG 1075 NHQMGSRNGEVYIATAQTGWVQNQG 1114 NHQANTRNGETYIAGAQTGWVQNQG 1076 NHQAQYKNGEVYIAQAQTGWVQNQG 1115 NHQSAIRNGETYIAGAQTGWVQNQG 1077 NHQTQTKNGGVFIAQAQTGWVQNQG 1116 NHQS ATLDGHIRIAV AQTGWVQN QG 1078 NHQSAMRNGETYIASAQTGWVQNQG 1117 NHQSAKRNGEVYVAAAQTGWVQNQG 1079 NHQANMRNGEVFIAQAQTGWVQNQG 1118 NHQSAKRNGEVYIANAATGWVQNQG 1080 NQQSASRNGETYIAAAQTGWVQNQG 1119 NHQGATRNGQVYIANAQTGWVQNQG 1081 NHQMNKRNGETYIAGAQTGWVQNQG 1120 NHQSAMRGSETYIASAQTGWVQNQG 1082 NHQSMTKNGETYIAGAQTGWVQNQG 1121 NHQSQMLDGHTRIAMAQTGWVQNQG 1083 NHQGSVRNGEVYIAQAQTGWVQNQG 1122 NHQGSMKNGEVFIAGAQTGWVQNQG 1084 NHQSAMKNGEVFIAAAQTGWVQNQG 1123 NHQGSTKNGEIY1AQ AQTGWVQNQG 1085 NHQMSTRNGEVHIAMAQTGWVQNQG 1124 NHQTQQKNGEVYIAGAQTGWVQNQG 1086 NHQSQVSNGHTLIAMAQTGWVQNQG 1125 NSQSQSRNGETYIASAQTGWVQNQG 1087 NHQSAVRNGETYIASASTGWVQNQG 1126 NHQSNMRGGETFIA S AQTGWVQNQG 1088 NHQTQKRNGETY1ASAQTGWVQNQG 1127 NHQMSMRNGETYIASAQTGWVQNQG 1089 NHQSSTKNGEVYVAGAQTGWVQNQG 1128 NHQMAQKNGEVYIAGAQTGWVQNQG 1090 NHQGSMRNGEVFIAS AQTGWVQNQG 1129 NHQSATRNGAILIATAQTGWVQNQG 1091 NNQSQTKNGETYIAS AQTGWVQNQG 1130 NHQGNTRNGETYIASAQTGXWQNQG 1092 NHQSAMRGSEVYIAQAQTGWVQNQG 1131 NHQGATKNGEVFIAGAQTGWVQNQG 1093 NHQSQTRDNHTLIAMAQTGWVQNQG 1132 NHQSASRNGETY1AGIQTGWVQNQG 1094 NHQSQTRNAETYIAQAQTGWVQNQG 1133 NHQSSTRNGETYIAQAQTGWVQNQG 1095 NLQSAMRNGETYIAAAQTGWVQNQG 1134 NHQSAIRNGETYLASAQTGWVQNQG 1096 NHQSHTRNGETYIASANTGWVQNQG 1135 NHQAAMRNGETYIAAAQTGWVQNQG 1097 NHQGATKNGEVY1AGAQTGWVQNQG 1136 NHQTQSKNGEVYIAGAQTGWVQNQG 1098 NIIQGSLRNGETYIATAQTGWVQNQG 1137 NHQSMTRNSETYIASAQTGWVQNQG 1099 NHQSMTRNGETYVAGAQTGWVQNQG 1138 NHQSATRDGKILIAIPQTGWVQNQG 1100 NHQSSTRNGEVFIAQAQTGWVQNQG 1139 NHQSQVANGHTLIAMAQTGWVQNQG 1101 NHQSNMRNGETFIAAANTGWVQNQG 1140 NHQMQTKAGEVYIAQAQTGWVQNQG 1102 NHQSNSRNGETYIASAQTGWVQNQG 1141 NHQMNTRN GET YIASAQTGWVQN QG 1103 NHQMSIKNGEVYIAQAQTGWVQNQG 1142 NHQMQSRNGEVYIAQAQTGWVQNQG 1104 NHQMAKRNGETYIAAAQTGWVQNQG 1143 NHQSAMRNGETYIAASQTGWVQNQG 1105 NHQSNTRNGETYLASAQTGWVQNQG 1144 NHQSATRNGETF1ASAQTGWWQNQG 1106 NIIQSATRNGNILIATAQTGWVQNQG 1145 NHQSQMRNDGTLIAMAQTGWVQNQG

[0190]

[0191]

[0192] Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0193] ID ID NO NO

[0194] 1146 NHQSSMKNGEVFIAGAQTGWVQNQG 1185 NHQSNMRNGELYIAQAQTGWVQNQG 1147 NHQSATRNGQTYIANAQTGWVQNQG 1186 NHQSQLKNGETYIASAQTGWVQNQG 1148 NLQSASRNGETY1AAAQTGWVQNQG 1187 NHQGAMKNGEVYIAGAQTGWVQNQG 1149 NHQSNMRGSETFIASAQTGWVQNQG 1188 NHQSAVRNGEVYVAGAQTGWVQNQG 1150 NHQSATRDGHVLVAIAQTGWVQNQG 1189 NHQSQSRNSETYIASAQTGWVQNQG 1151 NHQMSMRNGETYTAGAQTGWVQNQG 1190 NHQSALKNGEVYIAQAQTGWVQNQG 1152 NHQSASRNGEVYVAATQTGWVQNQG 1191 NHQTAVKNGEVY1AQAQTGWVQNQG 1153 NHQSATRNGETYVAAAQTGWVQNQG 1192 NHQSQVRDGQTLIAMAQTGWVQNQG 1154 NHQAAMRNGETYIASAQTGWWQNQG 1193 NHQTQTRNGEVRIAMAQTGWVQNQG 1155 NHQMQARNGEVYIAQAQTGWVQNQG 1194 NHQGSTRN GETFIAS AQTGWVQNQG 1156 NHQSAVRNGETYIAGASTGWVQNQG 1195 NHQSAKRNGETY1AAAQTGWVQNQG 1157 NHQSAVRNGNTLIAIAQTGWVQNQG 1196 NHQSALRNGETYIAGAQTGWVQNQG 1158 NHQSAQRNGETYIAAAQTGWVQNQG 1197 NHQSQTRDGVTLIAMAQTGWVQNQG 1159 NHQSATMDGHIRIAMAQTGWVQNQG 1198 NHQSESRNGATYIASAQTGWVQNQG 1160 NHQSATRNGETYLASAQTGWVQNQG 1199 NHQMAIRNGEVYLASAQTGWVQNQG 1161 NHQSATRNGETYLASANTGWVQNQG 1200 NHQSATRNGETYMATAQTGWVQNQG 1162 NHQA SMKNGE V Y1AGAQTG WVQNQG 1201 NHQSQSKN GE V YLA SA QTGWV QNQG 1163 NSQSQTKNGEVFIAGAQTGWVQNQG 1202 NHQSAVRNGHTL1AV AQTGWVQNQG 1164 NHQANLRNGEVYIAQAQTGWVQNQG 1203 NHQSAVMNGEIRIAMAQTGWVQNQG 1165 NHQTQTRNGETFIASAQTGWVQNQG 1204 NHQSAMRNDQTYIAAAQTGWVQNQG 1166 NHQAAMKNGEVYIASAQTGWVQNQG 1205 NHQSNLRNGET Y1 AS AQTGW VQN QG 1167 NHQSATRNGETYMASASTGWVQNQG 1206 NHQTQSRNGETY1AGAQTGWVQNQG 1168 NHQTQVKNGELYIAQAQTGWVQNQG 1207 NHQSAMRGSETYIATAQTGWVQNQG 1169 NHQA AIRNGE V YIAQA QTGWV QNQG 1208 NHQSQTKDGHMLIAMAQTGWVQNQG 1170 NHQSATRNGETYLASASTGWVQNQG 1209 NHQSAMRNGETY1AAANTGWVQNQG 1171 NHQCQTKN GE V YIAQAQTGW VQNQG 1210 NHQTQTKQGEVYIASAQTGWVQNQG 1172 NHQSAVRDGKIMIAIPQTGWVQNQG 1211 NHQTQNKNGEVYIAGAQTGWVQNQG 1173 NHQSQMRNGETLIAMAQTGWVQNQG 1212 NHQSNSRNGELYIAQAQTGWVQNQG 1174 N HQGSMKNGE V YTAS A QTGWV QNQG 1213 NHQGQTRNGEIWIAQAQTGWVQNQG 1175 NHQSQTRNGTTLIAMAQTGWVQNQG 1214 NHQSQSRNGETYL AS AQTGWVQNQG 1176 NHQN4AIRNGEVYIAQAQTGWVQNQG 1215 NHQSQTKNGETYVAAAQTGWVQNQG 1177 NHQGNTRNGETYIAGAQTGWVQNQG 1216 NHQSSMKNGEVFIAAASTGWWQNQG 1178 NHQTQKKNGEVYIAGAQTGWVQNQG 1217 NHQSQTKTGEVYTAQAQTGWVQNQG 1179 NHQSQVKNGETYIAGAQTGWVQNQG 1218 NHQGASRNGEVYIAGAQTGWVQNQG 1180 NHQANMRNGEVY1AQAQTGWVQNQG 1219 NHQSANKNGHVLIAMAQTGWVQNQG 1181 NHQTQTKNGEVYISGAQTGWVQNQG 1220 NHQSAVKNGETYIAGAQTGWVQNQG 1182 NHQTQ VRNGET Y1AQ AQTGWVQNQG 1221 NHQSNIRGGETYIASAQTGWVQNQG 1183 NHQSAKRNGEVYIANSQTGWVQNQG 1222 NHQSQMRDGQTLIAMAQTGWVQNQG 1184 NHQCQTKNGEVFIAQAQTGWVQNQG 1223 NHQSAKRNGEVYIANAQTGWVQNQG

[0195]

[0196]

[0197] Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0198] ID ID NO NO

[0199] 1224 NHQSATRAGETYIAAAQTCAWQNQG 1263 NHQSQVRNGSTLIAV AQTGWVQNQG 1225 NHQSQTRNGGTLTAMAQTGWVQNQG 1264 NHQGSMKNGEVYIATAQTGWVQNQG 1226 NHQGSLKNGEVYIAGAQTGWVQNQG 1265 NHQTQ1RNGEVYLASAQTGWVQNQG 1227 NHQSAIRNGEVYLASAQTGWVQNQG 1266 NHQMAKRNGEVYIAQAQTGWVQNQG 1228 NHQSQSRNSETYIAGAQTGWVQNQG 1267 NHQSAIRNGETYIAGASTGWVQNQG 1229 NHQSQVMDGHTRTAMAQTGWVQNQG 1268 NHQSASRDGHVLIAVPQTGWVQNQG 1230 NHQTQTKNGETYIASAQTGWVQNQG 1269 NHQMQTRNGETYIANAQTGWVQNQG 1231 NFIQSQVRDGHTMIAIAQTGWVQNQG 1270 NHQSNMRGTEVFIAQAQTGWVQNQG 1232 NHQGSTRNGEVYVAAAQTGWVQNQG 1271 NHQSQSRNEQTYIAQAQTGWVQNQG 1233 NHQSAIKNGETYIAGAQTGWVQNQG 1272 NHQGSTKNGEVYISSAQTGWVQNQG 1234 NHQSATRNGETYLASSQTGWVQNQG 1273 NHQSNTRDGHTLIAMAQTGWVQNQG 1235 NHQAQTRNGETYVAAAQTGWVQNQG 1274 NHQSATRNGEVYIAQAQTGWVQNQG 1236 SHQSATKNGEVYIATAQTGWVQNQG 1275 NHQTQTKNGEVFIAGAQTGWVQNQG 1237 NHQSQTRDGHTHLAMAQTGWVQNQG 1276 NHQTQLRNGEVYLASAQTGWVQNQG 1238 NHQMQTKNGEVY1AQAQTGWVQNQG 1277 NHQSYKKNGEVYIAQAQTGWVQNQG 1239 NHQTQLRNGETYIAGAQTGWVQNQG 1278 NHQSASRNGETYIASASTGWVQNQG 1240 NHQSASRNGETYIASAQTGWVQNQG 1279 NHQSQTRNGGTLIAAAQTGWVQNQG 1241 NHQSATRGGETYIAGAQTGWVQNQG 1280 NHQSATRNGEVFSAISQTGWVQNQG 1242 NHQSSMRNGETYIAAAQTGWVQNQG 1281 NHQAQMRNGETYIAGAQTGWVQNQG 1243 NHQSQTRDGTTMIAMAQTGWVQNQG 1282 NHQSQTRDGHTLIAVAQTGWVQNQG 1244 NHQAMTKNGEVYIAQAQTGWVQNQG 1283 NHQS ATRGGET Y IAS AQTGWVQNQG 1245 NHQSQTRDGAIHIAMAQTGWVQNQG 1284 NHQSQTRDGTTLIAMAQTGWVQNQG 1246 NIIQSQTRDGSIHIAMAQTGWVQNQG 1285 NHQSASRNGEVYLASAQTGXWQNQG 1247 NHQTQSRNGQVYIANAQTGWVQNQG 1286 NHQTQIRNGEVYIAQAQTGWX'QNQG 1248 NHQTQTKN GE V Y LAS AQTGWVQNQG 1287 NHQANSRNGEVYIAQAQTGWVQNQG 1249 NHQSQSRNGETYISSAQTGWVQNQG 1288 NHQMQTKN GE V YVAGAQTGWVQNQG 1250 NHQSESRAGQVYIASAQTGWVQNQG 1289 NHQSAVRNGETYISAAQTGWVQNQG 1251 NHQSATRNGETFIASASTGWVQNQG 1290 NHQGAMRNGEVYIASAQTGWVQNQG 1252 NHQSNSRNGETYIATAQTGWVQNQG 1291 NHQSAMRGSEVYVAGAQTGWVQNQG 1253 NHQSASRNGELY1AGAQTGWVQNQG 1292 NHQSATRNGELYMASAQTGWVQNQG 1254 NHQTQKRNGETYIAAAQTGWVQNQG 1293 NHQTQVRNGEVHIAMAQTGWVQNQG 1255 NHQSATRNGELYMAAAQTGWVQNQG 1294 NHQSQMRDGATMIAMAQTGWVQNQG 1256 NHQSAMRGGETYIASAQTGWVQNQG 1295 NHQSSTRDGQILl AM AQTGWVQNQG 1257 NHQSNMRGTETFI AS AQTGWVQNQG 1296 NHQSAMRGQETYIASAQTGWVQNQG 1258 NHQTQQRNGETYIAAAQTGWVQNQG 1297 NHQSATKDGHILMAIAQTGWVQNQG 1259 NHQSAMRNGETYIAGSQTGWVQNQG 1298 NHQMNTRNGELYIAQAQTGWVQNQG 1260 NHQSQQRDGHTLIAMAQTGWVQNQG 1299 NHQS ATRNGEVRIAM ASTG WVQNQG 1261 NHQSAMRGQEVYIAQAQTGWVQNQG 1300 NSQSQTKNGETYIASAQTGWVQNQG 1262 1301

[0200]

[0201] NHQMNSRNGEVYIANAQTGWVQNQG

[0202]

[0203] NHQSQTKNTEVYIAQAQTGWVQNQG Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0204] ID ID NO NO

[0205] 1302 NHQSNLRNGETYISAAQTGWVQNQG 1341 NHQTQMRGTEVYIAQ AQTGWVQNQG 1303 NHQSATRNGAILVAMAQTGWVQNQG 1342 NHQ AMTKN GE VF1 AQ AQTGWVQNQG 1304 NHQMQLKNGEVYIAQAQTGWVQNQG 1343 NHQS AQRNGHTL1AIAQTGWVQN QG 1305 NHQSQMRNGGTLIAMAQTGWVQNQG 1344 NHQSDKRGGETYIAGAQTGWVQNQG 1306 NHQSASRNGETYIASANTGWVQNQG 1345 NHQSQTKNTEVFIAQAQTGWVQNQG 1307 NHQSAVRNGEVYVAAAQTGWVQNQG 1346 NHQSATRNGELYLASAQTGWVQNQG 1308 NHQAAMRNGEVY1AAA. NTGWVQNQG 1347 NHQSTMKNGEVYIAGAQTGWVQNQG 1309 NIIQSATKDGHILIALAQTGWVQNQG 1348 NHQMQYKNGEVYIAQAQTGWVQNQG 1310 NIIQSAMKNGETYIAGAQTGWVQNQG 1349 NHQSATKNGEVFLASAQTGWVQNQG 1311 NSQSQSKNGEVYIAGAQTGWVQNQG 1350 NHQTQTKSGEVYTAQAQTGWVQNQG 1312 NHQSQVKNGEVYIAQAQTGWVQNQG 1351 NHQMAMRNGETYIAGAQTGWVQNQG 1313 NHQSAVKNGEIMIAMAQTGWVQNQG 1352 NHQSQNRNGATLIAN4AQTGWVQNQG 1314 NHQSAMRNDQTYIASAQTGWVQNQG 1353 NHQSQMRDGATLIAMAQTGWVQNQG 1315 NHQSALRNGETYIASANTGWVQNQG 1354 NHQTQTRGGETYIAGAQTGWVQNQG 1316 NHQSASRNGETYIASPQTGWVQNQG 1355 NHQMNSRN GET YIAS AQTGWVQNQG 1317 NHQTQSRNGTVYIASAQTGWVQNQG 1356 NHQSASRNGETYIATAQTGWVQNQG 1318 NHQSAVKDGHIHTAIAQTGWVQNQG 1357 NHQSNVRNGELY1AQAQTGWVQNQG 1319 NHQMSTKNGETY1ASAQTGWVQNQG 1358 NHQS ATRN GEVRIAMSQTGWVQNQG 1320 NHQGSTKNGETYIAAAQTGWVQNQG 1359 NHQSQERNGAILIAMAQTGWVQNQG 1321 NHQSASRNGETYIAGSQTGWVQNQG 1360 NHQSAKKNGEVYIAQAQTGWVQNQG 1322 NHQMNSRNGETYIAGAQTGWVQNQG 1361 NHQTQMRNGETYIASAQTGWVQNQG 1323 NHQSHTRNGETYIASASTGWVQNQG 1362 NHQTATRNGEVYIASAQTGWVQNQG 1324 NHQSAMRGSETYIAGAQTGWVQNQG 1363 NHQTQIRNGETYIASAQTGWVQNQG 1325 NHQMNMKNGEVYIAQAQTGWVQNQG 1364 NHQANTRNGELYIAQAQTGWVQNQG 1326 NHQGSMKNGEVFIAS AQTGWVQNQG 1365 NHQSNSRNGELY1SSAQTGWVQNQG 1327 NHQSATRNSETY1ASANTGWVQNQG 1366 NHQSQERN GGILIAMAQTGWV QNQG 1328 NHQSQTRNGETLIAMAQTGWVQNQG 1367 NHQGQTRNAETYIASAQTGWVQNQG 1329 NHQSATRDGAVLIAMAQTGWVQNQG 1368 NNQSATRNGEVYMASAQTGWVQNQG 1330 NHQSASRNSEVYIASANTGWVQNQG 1369 NHQSNLRNGETFIASAQTGWVQNQG 1331 NHQGSK. RNGETY1AGAQTGWVQNQG 1370 NHQSAVRNSEVY1AQAQTGWVQNQG 1332 NIIQSTTKNGETYIAAAQTGWVQNQG 1371 NHQSQTKAGETYIASAQTGWVQNQG 1333 NHQSAMRGTETYIASAQTGWVQNQG 1372 NHQSATRNGSTLIAIAQTGWVQNQG 1334 NHQSQTRNSETYLASAQTGWVQNQG 1373 NHQSAKRNGEVYMAAAQTGWVQNQG 1335 NHQSQTRNGETFIAQAQTGWVQNQG 1374 NHQSQSRGTEVYIAQAQTGWVQNQG 1336 NHQSAMRNGEVL1AMAQTGWVQNQG 1375 NHQSQSRTGEVY1AQAQTGWVQNQG 1337 NHQSQVRNGSTLIAMAQTGWVQNQG 1376 NHQSALRGSETYIASAQTGWVQNQG 1338 NHQSQMKDGNILIAMAQTGWVQNQG 1377 NHQGSMRN GE VF1 AG AQTGWVQNQG 1339 NHQSATRDGKIMIAVAQTGWVQNQG 1378 NHQSATKNGEVYLASAQTGWVQNQG 1340 NIIQTQYRNGEVYIAQAQTGWVQNQG 1379 NHQAQTKNGEVYLASAQTGWVQNQG

[0206]

[0207]

[0208] Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0209] ID ID NO NO

[0210] 1380 NHQSQSKNGETYIASAQTGWVQNQG 1419 NHQSATKNGEIRIAMAQTGWVQNQG 1381 NHQGSTKNGEVYISAAQTGWVQNQG 1420 NHQAQIKNGEVYIAQAQTGWVQNQG 1382 NHQSSMKNGEVFIAGASTGWVQNQG 1421 NHQSQSRNGSTLIAMAQTGWVQNQG 1383 NHQSASRNGETYIAGFQTGWVQNQG 1422 NHQSASRNGSVYIANAQTGWVQNQG 1384 NHQSATRNGETYMAAAQTGWVQNQG 1423 NHQSQTRDGATMIAMAQTGWVQNQG 1385 NHQSHTRNGEVYLASAQTGWVQNQG 1424 NHQSATRNGHTEVAIAQTGWVQNQG 1386 NHQS ALRGQE V YIAQ AQTGW VQN QG 1425 NHQSASRNGETY1ASSQTGWVQNQG 1387 NHQS AIRNDQTYIAS AQTGWVQNQG 1426 NHQSHTKNGETYIAAAQTGWVQNQG 1388 NHQTQTRNGQTYIANAQTGWVQNQG 1427 NHQTQKKNGEVYIAQ AQTGWVQNQG 1389 NHQMATRNGEVYVAGAQTGWVQNQG 1428 NHQSALRGGETYIASAQTGWVQNQG 1390 NHQSSVKNGETYIAGAQTGWVQNQG 1429 NHQMAMKNGEVYIASAQTGWVQNQG 1391 NHQSAKKNGEIYIAQAQTGWVQNQG 1430 NHQANLKNGEVYIAQAQTGWVQNQG 1392 NHQGQTRNSETYIAGAQTGWVQNQG 1431 NHQSASRDGHVLIAV AQTGWVQNQG 1393 NHQSTSRNGEAAT AG AQTGWVQNQG 1432 NHQMATKNGEVYSATAQTGWVQNQG 1394 NHQSAIRNEQTYIASAQTGWVQNQG 1433 NHQSQMRN SET YEAS AQTGWVQNQG 1395 NHQAQIKNGEVYIAQAQTGWVQNQG 1434 NHQSATRDGHVLIAV AQTGWVQNQG 1396 NHQSATRNDGILIAMAQTGWVQNQG 1435 NHQS AKKN GET YIAGAQTGWVQNQG 1397 NHQMQTRAGETYIASAQTGWVQNQG 1436 NHQTSMKNGEVYIAAAQTGWVQNQG 1398 NHQSQQRDGHTMIAMAQTGWVQNQG 1437 NHQSATKAGEVYIASAQTGWVQNQG 1399 NHQSETRNGHTLIAMAQTGWVQNQG 1438 NHQS A SRNG AVYI ANA QTGWVQNQG 1400 NHQSASRNGEVFIASAQTGWVQNQG 1439 NHQAATRNGETYIAGAQTGWVQNQG 1401 NHQSQTKQGETYIAGAQTGWVQNQG 1440 NHQTQKRNGEVYIAQAQTGWVQNQG 1402 NHQAMTRNGEVYVAQAQTGWVQNQG 1441 NHQSQIKNGETYIASAQTGWVQNQG 1403 NHQSQSRNGTTYIASAQTGWQNQG 1442 NHQSQVRDGQMMIAMAQTGWVQNQG 1404 NHQSNSRNGETYIAHAQTGWVQNQG 1443 NHQGSMRNGETY1ASAQTGWVQNQG 1405 NHQSNMRNGETYIAGAQTGWVQNQG 1444 NHQS ASKN GE1 YIAQAQTG3VVQN QG 1406 NHQAQSRNGETYIASAQTGWWQNQG 1445 NHQAQKKNGEVYIAQAQTGWVQNQG 1407 NHQSQSRNDEVYIAQAQTGWVQNQG 1446 NHQGSVKNGEVYIAQAQTGWVQNQG 1408 NHQSQTKDGSILIAMAQTGWVQNQG 1447 NHQSNIRNGETYIASAQTGWVQNQG 1409 NHQSATRDGHIMVA1AQTGWVQNQG 1448 NHQSATKNEQTY1AGAQTGWVQNQG 1410 NHQSQTRDSHTLIAMAQTGV / WQNQG 1449 NHQSMSRNGETYIASAQTGWVQNQG 1411 NHQSSMKNGEVFIAAANTGWVQNQG 1450 NHQSAVRNGEVMIAMAQTGWVQNQG 1412 NHQSALRGGETYIAGAQTGWVQNQG 1451 NHQSASRNGETY1ATPQTGWVQNQG 1413 NHQAMKRNGETYIAGAQTGWVQNQG 1452 NHQSASRNGEVYMAAASTGWVQNQG 1414 NHQTQLRAGEVYIASAQTGWVQNQG 1453 NHQAQTKAGEVYIAQAQTGWVQNQG 1415 NHQTQYRNGETYIAGAQTGWVQNQG 1454 NHQSTTRNGETYIAGAQTGWVQNQG 1416 NHQ ASLRN GET YIAS AQTGWVQNQG 1455 NHQGAMKNGEVYIASAQTGWVQNQG 1417 NHQGATRNGAVYIANAQTGWVQNQG 1456 NHQSATRNGSTL1AV AQTGWVQNQG 1418 NHQTQTRNGETYISAAQTGWVQNQG 1457 NHQSNSRNGEVYVAAAQTGWVQNQG

[0211]

[0212]

[0213] Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0214] ID ID NO NO

[0215] 1458 NHQSASRNGEVYVAASQTGWVQNQG 1497 NHQSAVRDGKVLIAIPQTGWVQNQG 1459 NHQSNLRNGETYIAGAQTGWVQNQG 1498 NHQSAQKNGEVFIAGAQTGWVQNQG 1460 NHQS A VKN GH1L1ATAQTGWVQNQG 1499 NHQSSVRNGELY1AQAQTGWVQNQG 1461 NHQGNSRNGETYIAAAQTGWVQNQG 1500 NHQSTTRNGETYIAGASTGWVQNQG 1462 NHQSQTKNGEVRIAMAQTGWVQNQG 1501 NHQSNMRNGETFIA S AQTGWVQNQG 1463 NHQSQVRNGHTL1AAAQTGWVQNQG 1502 NHQSATRDGHTLIAIPQTGWVQNQG 1464 NHQSAMRDGAVL1AMAQTGWVQNQG 1503 NHQSQTKAGEVY1AQAQTGWVQNQG 1465 NHQSQARNAEVYIAQAQTGWVQNQG 1504 NHQGQKRNGETYIASAQTGWVQNQG 1466 NHQSESRNGATYIAGAQTGWVQNQG 1505 NHQSASRNGELYIASAQTGWVQNQG 1467 NHQSMSRNGEVYVAGAQTGWVQNQG 1506 NHQSASRNEQVYTAQAQTGWVQNQG 1468 NHQSASRDGKILIAIPQTGWVQNQG 1507 NHQASQKNGEVF1AGAQTGWVQNQG 1469 NHQSAIRNGETYIAGSQTGWVQNQG 1508 NHQSQTKAGEVYLASAQTGWVQNQG 1470 NHQAAMRNGEVYIASAQTGWVQNQG 1509 NHQSATKNGEVFVAAAQTGWVQNQG 1471 NHQGAMRNGETYIAAAQTGWVQNQG 1510 NHQMAMRNGETYIAAAQTGWVQNQG 1472 NHQSQVLNGSTRIAMAQTGWVQNQG 1511 NHQSQMSNGHTLIAMAQTGWVQNQG 1473 NHQSETRAGGTYIASAQTGWVQNQG 1512 NHQSAVRNGEVYLASAQTGWVQNQG 1474 NHQGAMRGTEVY1ASAQTGWVQNQG 1513 NHQSAVRNGHTLIAIPQTGWVQNQG 1475 NHQSAMRGTEVYVAGAQTGWVQNQG 1514 NHQSATRNGVTLIAMAQTGWVQNQG 1476 NHQMNKRNGETYIASAQTGWVQNQG 1515 NHQSSMKNGEVFIASANTGWVQNQG 1477 NHQANLRNGETYIATAQTGWVQNQG 1516 NHQSAVLNGHTRIAMAQTCAWQNQG 1478 NHQSAILDGHVR1AMAQTGWVQNQG 1517 NHQSQTRDGNTL1AJAQTGWVQNQG 1479 NVQSAMRNGETYIAAAQTGWVQNQG 1518 NHQMQTRNGETYVAAAQTGWVQNQG 1480 NHQSATRDGRVLIAVAQTGWVQNQG 1519 NHQSNMRGGETYIASAQTGWVQNQG 1481 NHQSAVRDGHVMIAVPQTGWVQNQG 1520 NHQNINQRNGETYIAAAQTGWVQNQG 1482 NHQSQTRDGATLIAIAQTGWVQNQG 1521 NHQSQTKNEQTYIAQAQTGWVQNQG 1483 NHQAAKRNGETYIAAAQTGWVQNQG 1522 NHQGSTRAGEVY1ASAQTGWVQNQG 1484 NHQGSMKNGEVFIAAAQTGWVQNQG 1523 NHQSATRNGETYVAASQTGWVQNQG 1485 NHQSDKKNGETYIAGAQTGWVQNQG 1524 NHQGSMRNGEVYIASAQTGWVQNQG 1486 NHQANTRNGETFIAGAQTGWVQNQG 1525 NHQS A MRN GDT Y1 A AAQTGWVQN QG 1487 NHQSATRDGHTMIAMAQTGWVQNQG 1526 NHQSSTKNGEVFVAAAQTGWVQNQG 1488 NI-IQSNSRNGETFIASANTGWVQNQG 1527 NHQSALRGTETYIASAQTGWVQNQG 1489 NHQSQTRNGATHIAMAQTGWVQNQG 1528 NHQSTTRNGETYIASASTGWVQNQG 1490 NHQAQTKNQEVYIAQAQTGWVQNQG 1529 NHQSALRNGETYIASAQTGWVQNQG 1491 NHQSATRDGKILIAVAQTGWVQNQG 1530 NHQGATRNGETY1ATAQTGWVQNQG 1492 NHQAQSRNGETYIAGAQTGWVQNQG 1531 NHQSQTMNGSTL1AMAQTGWVQNQG 1493 NHQSATRNEQTYIANAQTGWVQNQG 1532 NHQTQMRGQEVYIAQAQTGWVQNQG 1494 NHQSQSRDGHTL1AMAQTGWVQNQG 1533 NHQSQTRDGGTLIAMAQTGWVQNQG 1495 NHQMNTRNGETY1AQAQTGWVQNQG 1534 NHQGATRNGETYIASAQTGWVQNQG 1496 NQQSATKNGETYIAGAQTGWVQNQG 1535 NHQSQSRNGETFIASAQTGWVQNQG

[0216]

[0217]

[0218] Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0219] ID ID NO NO

[0220] 1536 NHQMATRNGEVYSAIAQTGWVQNQG 1575 NHQSATKDGHILIAVAQTGWVQNQG 1537 NHQSDKRN GE V Y1AN AQTGW VQN QG 1576 NHQSQKKNGE V Y VAGAQTGWVQN QG 1538 NHQSAMKDGH1LMA1AQTGWVQNQG 1577 NHQSNLRNGETFIAGAQTGWVQNQG 1539 NNQSASRNGEVYIASAQTGWVQNQG 1578 NHQSAVKNGEVLIAMAQTGWVQNQG 1540 NHQAQTKNAEVYIAQAQTGWVQNQG 1579 NHQSASRNGEVYVATSQTGWVQNQG 1541 NHQMATKNGEVYLASAQTGWVQNQG 1580 NHQMNTRNGEVHIA1AQTGWVQNQG 1542 NHQSAVRNGEVLIAMAQTGWVQNQG 1581 NHQMSTRGGEVYIAQAQTGWVQNQG 1543 NHQSASRNGEVFIAQAQTGWVQNQG 1582 NHQSASRDGHIMIAVAQTGWVQNQG 1544 NHQANMRNGETYIASAQTGWVQNQG 1583 NHQAQTKNGEVYVAGAQTGWVQNQG 1545 NHQSQLRDGATLIAMAQTGWVQNQG 1584 NHQTSMKNGEVYIAGAQTGWVQNQG 1546 NHQSQQKNGETYIATAQTGWVQNQG 1585 NHQSATLDGQIRIAMAQTGWVQNQG 1547 NHQSAVRNGETYIAQAQTGWVQNQG 1586 NHQSNSRNGELYIAGAQTGWVQNQG 1548 NHQSNSRAGETYIAAAQTGWVQNQG 1587 NHQSALRGSETYIAGAQTGWVQNQG 1549 NHQSASRNGEVYMATSQTGWVQNQG 1588 NHQGSTKNGEVYISTAQTGWVQNQG 1550 NHQTQSRNGELYIAQAQTGWVQNQG 1589 NHQSASRNGEVYLATAQTGWVQNQG 1551 NHQSQQRDGTIMIAMAQTGWVQNQG 1590 NHQSNMRNGETYISAAQTGWVQNQG 1552 NHQS A VRN GHTLMA1AQTGW VQNQG 1591 NHQTATKNGEVYIAQAQTGWVQNQG 1553 NHQMNTRN GQT YIANAQTGWVQNQG 1592 NHQMQTRNGETYVAGAQTGWVQNQG 1554 NHQGATRNGETYIAAAQTGWVQNQG 1593 NHQTQSRNGEVFIASAQTGWVQNQG 1555 NHQASMKNGEVFIASAQTGWVQNQG 1594 NHQSATKNGETYIAAAQTGWVQNQG 1556 NHQSQSRTGETYIAAAQTGWVQNQG 1595 NHQSATKNGETFIAGAQTGWVQNQG 1557 NHQAAMRGGETYIAAAQTGWVQNQG 1596 NHQTQLRGTEVY1AQAQTGWVQNQG 1558 NHQSQSKNGEWISGAQTGWVQNQG 1597 NHQSSMKNGEVYIAGAQTGWVQNQG 1559 NHQSNIRNGELYIAQAQTGWVQNQG 1598 NHQASIRNGETYIAGAQTGWVQNQG 1560 NHQTQTRSGEVYIAQAQTGWVQNQG 1599 NHQGSSRNGETY1AAAQTGWVQNQG 1561 NHQGQMRNGETY1AAAQTGWVQNQG 1600 NHQTQTKNGQTYIAQAQTGWVQNQG 1562 NHQTQKRNGEVYIANAQTGWVQNQG 1601 NHQSNIKNGETYIAGAQTGWVQNQG 1563 NHQGQTRNQETYIASAQTGWVQNQG 1602 NHQGQTRNSETYIASAQTGWVQNQG 1564 NHQANMRNGETYTAT AQTGW VQNQG 1603 NHQSQNRN GSTLIA MAQTGWVQNQG 1565 NHQSAKKNGETY1ASAQTGWVQNQG 1604 NHQTQSRNGETY1AAAQTGWVQNQG 1566 NHQMNTRNGETYIAGAQTGWVQNQG 1605 NHQTQTRNGELYIAQAQTGWVQNQG 1567 NHQSQSRNAETYIASAQTGWVQNQG 1606 NHQMNTRNGEVRIAMAQTGWVQNQG 1568 NHQSAMRGSETFIASAQTGWVQNQG 1607 NHQSASRNGQTYVAAAQTGVvWQNQG 1569 NHQTQIKNGEVYIAGAQTGWVQNQG 1608 NHQSQAKNGEVFIAQAQTGWVQNQG 1570 NHQGSKRNGEVY1ANAQTGWVQNQG 1609 NHQGSLRNSEVY1ASAQTGWVQNQG 1571 NHQAATRNGETYIASAQTGWVQNQG 1610 NHQSNMRGGETYIAGAQTGWVQNQG 1572 NHQGSTRNGETFIAGAQTGWVQNQG 1611 NHQAMTRNGETYTAGAQTGWVQNQG 1573 NHQMATRNGEVYIANAQTGWVQNQG 1612 NHQSATKNGEVFISGAQTGWVQNQG 1574 1613 NHQSAMLDGHVRIAMAQTGWVQNQG

[0221]

[0222] NHQSQTRNGSTHIAMAQTGWVQNQG

[0223]

[0224] Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0225] ID ID NO NO

[0226] 1614 NHQTQTRNGETYLASAQTGWVQNQG 1653 NHQTQTKNGEVYLATAQTGWVQNQG 1615 NHQAALRGSEVYIAQAQTGWVQNQG 1654 NHQSQTSNGATLIAMAQTGWVQNQG 1616 NHQSQVRNGETHIAMAQTGWVQNQG 1655 NHQSSVRNGEVL1AMAQTGWVQNQG 1617 NHQGAMRNSEVYIASAQTGXWQNQG 1656 NHQSASKNGETYIAAAQTGWVQNQG 1618 NHQTQTRAGETYIAAAQTGWVQNQG 1657 NHQAQMRNGETYIASAQTGWVQNQG 1619 NHQGATRNDQVYIANAQTGWVQNQG 1658 NHQASMKNGEVYIASAQTGWVQNQG 1620 NHQAAMRNGETY1AGAQTGWVQNQG 1659 NHQSAMRGTETY1AAAQTGWVQNQG 1621 NHQAQTKNGELYIAQAQTGWVQNQG 1660 NHQSAVLNGHIRVAMAQTGWVQNQG 1622 NHQSAMKNGEILIAMAQTGWVQNQG 1661 NHQSQVRNGATLIAMAQTGWVQNQG 1623 NHQSATMDGHIRIAVAQTGWVQNQG 1662 NHQGATRNGEVYVAAAQTGWVQNQG 1624 NHQSNMRNGELYLASAQTGWVQNQG 1663 NHQGSTRGGETYIAAAQTGWVQNQG 1625 NHQSAIRGGETYIAGAQTGWVQNQG 1664 NHQSATRNGQILVAMAQTGWVQNQG 1626 NHQGATRNGSVYIANAQTGWVQNQG 1665 NHQSATKNQEVYIAQAQTGWVQNQG 1627 NHQGATRNGEVFIAGAQTGWVQNQG 1666 NHQTATRNGEVYIANAQTGWQNQG 1628 NHQMQTKNGETYIAHAQTGWVQNQG 1667 NHQMQTRNGETYMASAQTGWVQNQG 1629 NHQSATRNGETYVAAASTGWVQNQG 1668 NHQSSTKNGEVFLASAQTGWVQNQG 1630 NHQSATRNGETYMASANTGWVQNQG 1669 NHQAQTRNDEVY1AQAQTGWVQNQG 1631 NHQSQTKNGEVYIAQAQTGWVQNQG 1670 NHQSQARGGETY1ASAQTGWVQNQG 1632 SHQSATRNGEVFIATASTGWVQNQG 1671 NHQTQTKNGNTYIAQAQTGWVQNQG 1633 NHQSQVRNEATLIAMAQTGWVQNQG 1672 NHQSAMRGQETYIATAQTGWVQNQG 1634 NHQSNSRAGEVYIASAQTGWVQNQG 1673 NHQSAIRNGEVYMAAAQTGWVQNQG 1635 NHQTQNRNGEVYIAQAQTGWVQNQG 1674 NHQAATRNGEVYVAAAQTGWVQNQG 1636 NHQSHTKNGEVYIAQAQTGWVQNQG 1675 NHQAQARNGEVYIAQAQTGWVQNQG 1637 NHQGAMRGSEVYIASAQTGWVQNQG 1676 NHQSQVSGGHTLIAMAQTGWVQNQG 1638 NHQSQLRDGG1HJA MA QTGWV QNQG 1677 NHQSQTRN GETFIA S AQTGWVQNQG 1639 NHQGNSRNGELYIASAQTGWVQNQG 1678 NHQSSQKNGEVF1AGAQTGWVQNQG 1640 NHQASKRNGEVYIANAQTGXWQNQG 1679 NHQANSRNGELYIASAQTGWVQNQG 1641 NHQSAMRGKETYIAGAQTGWVQNQG 1680 NHQSATKNGEVFQAIAQTGWVQNQG 1642 NHQSAVRDGHVMMAIAQTGWVQNQG 1681 NHQSTTRNGETYIASPQTGWVQNQG 1643 NNQSSTKNGEVFIASAQTGWVQNQG 1682 NHQMNMRNGETYIASAQTGWVQNQG 1644 NIIQSQVRDGHTLIAAATTGYWQNQG 1683 NHQANKRNGETYIAGAQTGWVQNQG 1645 NHQSQMANGHTLIAMAQTGWVQNQG 1684 NHQSQTRNEGTLIAMAQTGWVQNQG 1646 NHQSATRNGETYMASAQTGWVQNQG 1685 NHQSAMKNGEVYIAAAQTGVvA'QNQG 1647 NHQSNMRNGETFIAGAQTGWVQNQG 1686 NHQMNMRNGEVYIAQAQTGWVQNQG 1648 NHQSATRNEQTYVAAAQTGWVQNQG 1687 NHQGSQKNGEVY1AGAQTGWVQNQG 1649 NHQSAIKNGEILIAMAQTGWVQNQG 1688 NHQSQQRNGHTL1AMAQTGWVQNQG 1650 NHQSASRNGEVYVAGPQTGWVQNQG 1689 NHQANMRNGETYIAGAQTGWVQNQG 1651 NHQSALRGTETYIAGAQTGWVQNQG 1690 NHQMALRNGEVYIAQAQTGWVQNQG 1652 NHQSQLKDGNILIAMAQTGWVQNQG 1691 NHQSQMRNSETYIAGAQTGWVQNQG

[0227]

[0228]

[0229] Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0230] ID ID NO NO

[0231] 1692 NHQMNLKNGEVYIAQAQTGWVQNQG 1731 NHQSAVKNGEILIAMAQTGWVQNQG 1693 NHQSAVRDGKJMIAIAQTGWVQNQG 1732 NHQSAVRDGQIMMAIAQTGWVQNQG 1694 NHQSASRNGETYIAGPQTGWVQNQG 1733 NHQSSVRNGETY1AQAQTGWVQNQG 1695 NHQGSMRNSEVYIASAQTGVWQNQG 1734 NHQAQIRNGETYIASAQTGWVQNQG 1696 NHQASIRNGETYIASAQTGWQNQG 1735 NHQSQNRNGHTLIAMAQTCAWQNQG 1697 NHQSHSRNGEVYIASAQTGWVQNQG 1736 NHQSSMKNGEVFIASAQTGWVQNQG 1698 NHQTSMKNGEVY1ASAQTGWVQNQG 1737 NHQSSLKNGEVY1AQAQTGWVQNQG 1699 NHQGNTRNGEVYLANAQTGWVQNQG 1738 NHQSQARNGHTLIAMAQTGWVQNQG 1700 NHQSAQRDGHVLIAIPQTGWVQNQG 1739 NHQSATRDGHTMIAVAQTGWVQNQG 1701 NHQSQTRNEATL1AMAQTGWVQNQG 1740 NHQSASRNGETYIATSQTGWVQNQG 1702 NHQMAMRNGETY1ASAQTGWVQNQG 1741 NHQANKRNGETY1ASAQTGWVQNQG 1703 NHQSASRNEQVYVAAAQTGWVQNQG 1742 NHQMQTRNTEVYIAQAQTGWVQNQG 1704 NHQSASRNGEVYMAAAQTGWVQNQG 1743 NHQTNMRNGETYIAAAQTGWVQNQG 1705 NHQSQLRDGHTHIAMAQTGWVQNQG 1744 NHQGSTKNGETYIATAQTGWVQNQG 1706 NHQSSMRNGETYLAGAQTGWVQNQG 1745 NHQTATRNGEVFIASAQTGWVQNQG 1707 NHQSQTRAAETYIASAQTGWVQNQG 1746 NHQGSMKNGEVYIAAAQTGWVQNQG 1708 NHQTQTRNGETY1ASAQTGWVQNQG 1747 NHQSASRNGETYIAHAQTGWVQNQG 1709 NHQMNQRNGETYIAGAQTGWVQNQG 1748 NHQSQTKQGETYIASAQTGWVQNQG 1710 NHQSAVRDGHVLIAVPQTGVWQNQG 1749 NHQMSYKNGEVYIAQAQTGWVQNQG 1711 NHQSAVRNGETFIAGAQTGWVQNQG 1750 NHQSAMKNGHILIATAQTGWVQNQG 1712 NHQSASRNGETYIASTQTGWVQNQG 1751 NHQGSMRNGETYIAGAQTGWVQNQG 1713 NHQSQMLDGAIR1AMAQTGWVQNQG 1752 NHQSQ VRN GSTM1A MAQTGWVQN QG 1714 NHQSAIKNGETYIASAQTGWVQNQG 1753 NHQSNMRNGETYISSAQTGWVQNQG 1715 NHQGSTKNGEVYIANAQTGWVQNQG 1754 NHQSHTRNGEVYMAAAQTGWVQNQG 1716 NHQSALRGQETYIASAQTGWVQNQG 1755 NHQSASRNGEVYIANAATGWVQNQG 1717 NHQSQLKDGSILIAMAQTGWVQNQG 1756 NHQSASRNGETY1ATASTGWVQNQG 1718 NHQSNIRNGETYIAGAQTGWVQNQG 1757 NHQANMRGSEVYIAQAQTGWVQNQG 1719 NHQGSLKNGEVYIATAQTGWVQNQG 1758 NHQSASRNGETYIAGTQTGWVQNQG 1720 NHQSAMRGSEVYVAAAQTGWVQNQG 1759 NHQSAMRASEVY1ASAQTGWVQNQG 1721 NHQSNLRGGETY1ASAQTGWVQNQG 1760 NHQMAMKNGEVY1AGAQTGWVQNQG 1722 NHQSQSRNGETYLATAQTGWVQNQG 1761 NHQSALRGSEVYIAQAQTGWVQNQG 1723 NHQGSMRNSEVYIAGAQTGWVQNQG 1762 NHQSAMRGQEVYISGAQTGWVQNQG 1724 NHQMSTKNGEL Y1 AQ AQTGWVQN QG 1763 NHQ'T'QMRGSEVYIAQAQTGWVQNQG 1725 NHQSQLRNGGTLIAMAQTGWVQNQG 1764 NHQS ESRN GST Y1 AGAQTGWVQNQG 1726 NHQSQTRNAETYLASAQTGWVQNQG 1765 NHQSQTRDGNTLIAMAQTGWVQNQG 1727 NHQSHTRNGEVYMASAQTGWVQNQG 1766 NHQSAVRNGEIMIAMAQTGWVQNQG 1728 NHQAATRNGEVY1ANAQTGWVQNQG 1767 NHQSAMRGGETYIAAAQTGWVQNQG 1729 NHQTQMKNGEVY1AGAQTGWVQNQG 1768 SHQSATKNGEVFIATAQTGWVQNQG 1730 NIIQSMSRNGETYVAAAQTGWVQNQG 1769 NHQSASRSGEVYIASAQTGWVQNQG

[0232]

[0233]

[0234] Patent Application CAPS-041 / 01 WO 35847 / 197 SEQ VR-VIII amino acid sequence SEQ VR-VIII amino acid sequence

[0235] ID ID NO NO

[0236] 1770 NHQSAMRNGETYIAAASTGWVQNQG 1809 NHQMQARNGETYIAGAQTGWVQNQG 1771 NHQSNVRDGQLLIAMAQTGWVQNQG 1810 NHQGQVRDGHTHIAMAQTGWVQNQG 1772 NHQTQTKNGEVRIAMAQTGWVQNQG 1811 NHQSQMKDGSILIAMAQTGAWQNQG 1773 NHQSAMRGTETYIAGAQTGWVQNQG 1812 NHQSATMNGHTLIAMAQTGWVQNQG 1774 NHQTQSKNGEVYIASAQTGWVQNQG 1813 NHQSTMRNGEVYIAGAQTGWVQNQG 1775 NHQSAQKNGETYIAAAQTGWVQNQG 1814 NHQSMTRNGET Y V AS AQTGWVQN QG 1776 NHQSNTRNGETYVAAAQTGWVQNQG 1815 NHQTQTRNGATY1ANAQTGWVQNQG 1777 NHQSAIKNGEVYVAAAQTGWVQNQG 1816 NHQSAMRGSEVYLASAQTGWVQNQG 1778 NHQSQTKTGEVFIAQAQTGWVQNQG 1817 NHQSSYKNGEVYIAQAQTGWVQNQG 1779 NHQSNMRNGEVYMA A AQTGWVQN QG 1818 NHQSSTKNGEVHIA1AQTGWVQNQG

[0237]

[0238] 1780 NHQAAKRNGETYIAGAQTGWVQNQG

[0239] 1781 NHQSATRNGEILVAMAQTGWVQNQG

[0240] 1782 NHQGNLRNGEVYLASAQTGWVQNQG

[0241] 1783 NHQTQTRNGETYISGAQTGWVQNQG

[0242] 1784 NHQTQQRNGELYIAGAQTGWVQNQG

[0243] 1785 NHQSMTRNGETYVAAAQTGWVQNQG

[0244] 1786 NHQTQSRNGEVYISSAQTGWVQNQG

[0245] 1787 NHQGAMKNGEVY1AAAQTGWVQNQG

[0246] 1788 NHQSAMRGSEVYVASAQTGWVQNQG

[0247] 1789 NHQCQTRNGETYIAQAQTGWVQNQG

[0248] 1790 NHQTQIKNGGVYIAQAQTGWVQNQG

[0249] 1791 NHQSSMKNGETYIAAAQTGWVQNQG

[0250] 1792 NHQAAKRNGEVYIAQAQTGWVQNQG

[0251] 1793 NHQSQSRATEVYIASAQTGWVQNQG

[0252] 1794 NHQSNMRGSELYIAQAQTGWVQNQG

[0253] 1795 NHQSNSRNGEVY1SGAQTGWVQNQG

[0254] 1796 NHQTQSKNGEVYIAQAQTGWVQNQG

[0255] 1797 NHQAQTRNAETYIASAQTGWVQNQG

[0256] 1798 NHQGALRNSEVYIASAQTGWVQNQG

[0257] 1799 NHQSQTRDTHTLIAMAQTGWVQNQG

[0258] 1800 NHQTQMKNQEVYIAQAQTGWVQNQG

[0259] 1801 NHQSQSRNGETYIAGAQTGWVQNQG

[0260] 1802 NHQSALKNGETY1AGAQTGWVQNQG

[0261] 1803 NHQGQTRGGETYI A SA QTGWVQNQG

[0262] 1804 NHQSQVLDGS1R1AMAQTGWVQNQG

[0263] 1805 NHQANTRNGETFIASAQTGWVQNQG

[0264] 1806 NHQSQVRDGHTLIALAQTGWVQNQG

[0265] 1807 NHQSASRNGETYIASIQTGWVQNQG

[0266] 1808 NHQSQLRDGATMIAMAQTGWVQNQG

[0267]

[0268] Patent Application CAPS -041 / 01 WO 35847 / 197 Formula III

[0269] Aspects of the present invention provide an adeno-associated virus (AAV) capsid protein comprising an amino acid sequence having at least 80% identity to a sequence of Formula III:

[0270] Xic-X2c- X3C-X4C-X5C-X6C-G-F-T-

[0271]

[0272] X10C-XllC-X12C-X13C-X14C-X15C-X]6C-Xl7C-X18C-X19C (HI)

[0273] wherein,

[0274] Xie is an amino acid selected from A, N, V, H, Y, F, S, D, W, I, P, Q, R, K, M, E, T, C, L, or G;

[0275] XJC is an amino acid selected from Q, M, L, A, T, V, I, E, H, S, N, R, K, F, D, or Y; X;,c is an amino acid selected from S, G, or H;

[0276] X4C is an amino acid selected from T, I, V, L, M, F, Y, H, A, K, Q, or S;

[0277] Xsc is an amino acid selected from G or Q;

[0278] X,c is an amino acid selected from Q, D, N, H, G, E, S, A, L, M, or R;

[0279] Xioc is an amino acid selected from A, M, Q, E, N, L, V, T, S, I, D, K, H, C, or R; Xnc is an amino acid selected from Q, M, or Y;

[0280] X12C is an amino acid selected from A, P, G, S, T, V, Y, C, W, I, H, F, or Q;

[0281] Xue is an amino acid selected from Q, T, M, V, E, L, S, A, D, G, I, N, K, R, H, F, or Y;

[0282] Xue is an amino acid selected from T, N, S, Q, I, G, A, L, V, C, D, Y, M, F, E, or W; Xisc is an amino acid selected from G, D, E, A, S, N, T, Q, F, Y, K, M, L, II, I, V, W, or R;

[0283] Xi6c is an amino acid selected from W, D, E, F, L, V, I, P, A, S, T, Y, H, Q, M, N, or G;

[0284] Xnc is an amino acid selected from V, I, N, A, T, S, C, L, Q, P, M, G, D, H, E, or F; Xisc is an amino acid selected from Q, D, N, S, E, H, G, T, A, C, or P; and X19C is an amino acid selected from N, Y, G, S, D, A, Q, E, V, C, F, I, L, M, R, T, or Patent Application CAPS -041 / 01 WO 35847 / 197 W.

[0285] In preferred aspects of the invention,

[0286] Xicmay be selected from among A, N, or V;

[0287] X2C may be selected from among Q, M, or L;

[0288] X4cmay be selected from among T, I, or V;

[0289] Xgcmay be selected from among Q, D, or N;

[0290] Xiocmay be selected from among A, M, or Q;

[0291] 12c may be selected from among A, P, or G;

[0292] Xicmay be selected from among Q, T, or M;

[0293] Xue may be selected from among T, N, or S;

[0294] Xue may be selected from among G, D, or E;

[0295] Xue may be selected from among W, D, or E;

[0296] Xicmay be selected from among V, I, or N;

[0297] Xiscmay be selected from among Q, D, orN;

[0298] Xmcmay be selected from among N, Y, or G

[0299] In aspects of the invention, Xie is located at parental residue 587 and Xi$>c is located at parental residue 598 in reference to a parental AAV9 capsid or equivalent residue position in another AAV capsid, wherein in Formula II:

[0300] Xie is a parental or substituted amino acid;

[0301] X c is a parental or substituted amino acid located at parental residue 588;

[0302] X;,c, X4c. Xsc, X6c. G, F, T, are an insertion between parental or substituted residues 588 and 589;

[0303] Xioc, Xue, Xi2c. Xi3c. Xi4c. Xue. Xi6c, Xi7c, Xi8c are parental or substituted amino acids; and

[0304] Xi9c is a parental or substituted amino acid located at parental residue 598, now residue 605.

[0305] For example, as described above, residues 587-588 may be substituted or remain the Patent Application CAPS -041 / 01 WO 35847 / 197 parental amino acid. A 7-mer amino acid is inserted between parental amino acid residues 588 and 589. Residue 589 to residue 598 (now residue 596 to 605, accommodating the 7-mer insertion) may be substituted or remain the parental amino acid.

[0306] Capsids of the present invention comprising a sequence of Formula III may comprise the following sequences:

[0307] Table 3: Formula III sequences SEQ

[0308] ID SEQ NO VR-VIII amino acid sequence ID 1848 NQSTGQGFTAQAQTGWVQN NO VR-VIII amino acid sequence

[0309] 1849 AQSTGGGFTAQPQTGWVQN 1819 AQSTGQGFTAQTQTGWVQN

[0310] 1850 ASSTGQGFTAQPQTGWVQN 1820 AQSTGQGFTAQGQTGWVQN

[0311] 1851 AQSTGQGFTAQATNGWVQN 1821 AQSTGQGFTAQATTGWVQN

[0312] 1852 AQSTGQGFTTQPQTGWVQN 1822 AQSTGQGFTAQYQTGWVQN

[0313] 1853 AQSTGQGFTAMPQTGWVQN 1823 AQSTGNGFTAQPQTGWVQN

[0314] 1854 AQSTGDGFTAQAQTGWVQN 1824 VQSTGQGFTAQAQTGWVQN

[0315] 1855 AQSTGQGFTAQAQNNWVQN 1825 AQSTGQGFTAQPATGWVQN

[0316] 1856 AQSTGQGFTAQATTGWVQN 1826 AQSTGQGFTNQPQTGWVQN

[0317] 1857 AQSTGQGFTAQATAGWVQN 1827 AQSTGQGFTSQPQTGWVQN

[0318] 1858 AQSTGQGFTAQHQTGWVQN 1828 AQSTGQGFTAQPGTGWVQN

[0319] 1859 AQSTGQGFTAQAQIGWVQN 1829 AQSTGQGFTAQSQTGWVQN

[0320] 1860 AQSTGQGFTAQAQQEWVQN 1830 AQSIGQGFTAQAQTGWVQN

[0321] 1861 AQSTGQGFTAQATIGWVQN 1831 AQSTGQGFTAQVQTGWVQN

[0322] 1862 AQSTGQGFTAQAQSGWVQN 1832 AQSTGQGFTAQAVTGWVQN

[0323] 1863 AISTGQGFTAQPQTGWVQN 1833 AQSTGQGFTAQGTTGWVQN

[0324] 1864 DQSTGQGFTAQAQTGWVQN 1834 ANSTGQGFTAQPQTGWVQN

[0325] 1865 AQSTGQGFTAQAQNGWVQN 1835 AQSTGQGFTAQWQTGWVQN

[0326] 1866 SQSTGQGFTAQTQTGWVQN 1836 AVSTGQGFTAQGQTGWVQN

[0327] 1867 NQSTGQGFTAQASTGWVQN 1837 AQSTGQGFTAQPQTGWVQN

[0328] 1868 AQSTGQGFTAQASTGWWQN 1838 AQSTGQGFTMQAQTGWVQN

[0329] 1869 AHSTGQGFTAQPQTGWVQN 1839 AQSTGSGFTAQPQTGWVQN

[0330] 1870 AVSTGQGFTAQPQTGWVQN 1840 AMSTGQGFTAQTQTGWVQN

[0331] 1871 AASIGQGFTAQAQTGWVQN 1841 MQSTGQGFTAQPQTGWVQN

[0332] 1872 AQSMGQGFTAQATTGWVQN 1842 AQSTGQGFTAQATSGWVQN

[0333] 1873 AQSTGGGFT A QGQTGWV QN 1843 NQSTGQGFTAQTQTGWVQN

[0334] 1874 AQSTGQGFTAQAVNGWVQN 1844 TQSTGQGFTAQPQTGWVQN

[0335] 1875 TQSTGQGFTAQPQTGWVQN 1845 AQSTGQGFTAQAMTGWVQN

[0336] 1876 AQSTGQGFTAQSTTGWVQN 1846 PQSTGQGFTAQPQTGWVQN

[0337] 1877 NQSTGQGFTMQAQTGWVQN

[0338]

[0339] 1847 AQSTGQGFTAQGQTGWVQN

[0340]

[0341] 1878 YQSTGQGFTAQATTGWVQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 1879 YQSTGQGFTAQAQTGWVQN 1920 HQSTGQGFTAQAQTGWVQN 1880 AQSTGQGFTAQAQSEWVQN 1921 AQSTGQGFTMQATTGWVQN 1881 AQSTGQGFTAQIQTGWVQN 1922 AASTGQGFTAQGQTGWVQN 1882 AQSTGQGFTAQAVIGWVQN 1923 NQSTGQGFTAQGQTGWVQN 1883 NQSTGQGFTAQVQTGWVQN 1924 AQSTGQGFTAQAETGWVQN 1884 AQHTGQGFTAQPQTGWVQN 1925 AQSIGQGFTAQASTGWVQN 1885 AQSTGQGFTAQAQSIWVQN 1926 VQSTGQGFTAQATTGWVQN 1886 FQSTGQGFTAQATTGWVQN 1927 AQSIGNGFTAQAQTGWVQN 1887 FQSTGQGFTA Q AQTGWVQN 1928 AVSLGQGFTAQAQTGWVQN 1888 AQSTGQGFTAQAETGWVQN 1929 YQSTGQGFTAQAETGWVQN 1889 AQSTGQGFTAQAQDEWVQN 1930 AQSIGQGFTAQATTGWVQN 1890 ATSTGQGFTAQPQTGWVQN 1931 AQSTGQGFTAQAQNEWVQN 1891 AQSTGQGFTAQTETGWVQN 1932 AQSTGQGFTAQAQNYWVQN 1892 AQSTGQGFTQQGQTGWVQN 1933 AQSLGQGFTSQAQTGWVQN 1893 AQSTGQGFTAQAQNQWVQN 1934 AQSTGQGFTAQAQSVWVQN 1894 AQSIGQGFTAQSQTGWVQN 1935 AQSTGQGFTAQAQTHWVQN 1895 AQSTGQGFTAQAQQDWVQN 1936 AASTGQGFTAQTQTGWVQN 1896 AQSTGQGFTAQAQSEWVQN 1937 VQSTGNGFTAQAQTGWVQN 1897 AQSTGQGFTAQAQQNWVQN 1938 AQSTGQGFTAQAQTGWVDQ 1898 AASTGQGFTAQPQTGWVQN 1939 AQSTGQGFTMQTQTGWVQN 1899 AQSTGQGFTAQAQNDWVQN 1940 AQSIGQGFTAQAGTGWVQN 1900 SQSTGQGFTAQGQTGWVQN 1941 AQSTGQGFTAQAQTDDVQN 1901 AQSTGQGFTMQALTGWVQN 1942 NQSTGQGFTAQSQTGWVQN 1902 AQSTGQGFTAQAQQGWVQN 1943 AQSVGQGFTAQAQTGWVQN 1903 AQSTGQGFTAQAQDDWVQN 1944 AQSTGQGFTAMAQTGWVQN 1904 AQSTGQGFTNQGQTGWVQN 1945 AQSTGQGFTAQASSGWVQN 1905 ATSTGQGFTAQGQTGWVQN 1946 NLSTGQGFTAQATTGWVQN 1906 AQSTGQGFTAQWETGWVQN 1947 AQSTGQGFTAQAQNEWVQN 1907 AQSTGQGFTAQAQNSWVQN 1948 AQSTGQGFTAQAQIAWVQN 1908 AQSTGQGFTAQPSTGWVQN 1949 AMSTGQGFTAQVQTGWVQN 1909 ADSTGQGFTAQPQTGWVQN 1950 AQSTGQGFTAQAQIEWVQN 1910 NQSTGQGFTAQAMTGWVQN 1951 VQSTGQGFTAQATTGWVQN 1911 AQSTGQGFTAQAQTNWVQN 1952 VLSTGQGFTAQAQTGWVQN 1912 VQSTGQGFTAQAVTGWVQN 1953 AQSTGQGFTAQANNGWVQN 1913 NQSTGQGFTAQATTGWVQN 1954 NQSTGQGFTQQAQTGWVQN 1914 AQSTGQGFTAQAQQTWVQN 1955 AQSTGQGFTAQAQTTDVQN 1915 AQSTGQGFTAQAQSNWVQN 1956 AQSTGQGFTAQAQQVWVQN 1916 VMSTGQGFTAQAQTGWVQN 1957 VQSVGQGFTAQAQTGWVQN 1917 AQSTGQGFTAQGETGWVQN 1958 AQSTGQGFTNQTQTGWVQN 1918 YQSTGQGFTAQAETGWVQN 1959 AQSTGQGFTAQAQQIWVQN

[0342]

[0343] 1919 NQSTGDGFTAQAQTGWVQN

[0344]

[0345] 1960 AQSTGQGFTAQAQTEDVQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 1961 VQSTGQGFTAQAMTGWVQN 2002 AQSMGQGFTAQVQTGWVQN 1962 AQSTGNGFTAQATTGWVQN 2003 FQSTGQGFTAQAMTGWVQN 1963 HQSTGQGFTEQAQTGWVQN 2004 HQSTGQGFTAQAQTNWVQN 1964 AQSTGQGFTAQAQIQWVQN 2005 AQSTGQGFTAQAQTRDVQN 1965 AQSVGQGFTAQTQTGWVQN 2006 VQSTGDGFTAQAQTGWVQN 1966 AQSTGQGFTAQAQQYWVQN 2007 AQSTGQGFTAQAQAGWVQN 1967 FQSTGDGFTAQAQTGWVQN 2008 RQSTGDGFTAQAQTGWVQN 1968 AQSTGDGFTAQSQTGWVQN 2009 AQSTGQGFTVQPQTGWVQN 1969 HQSTGQGFTAQATTGWVQN 2010 AQSTGQGFTAQAQNWWVQN 1970 AQSTGQGFTAQAQNTWVQN 2011 NQSTGQGFTAQYQTGWVQN 1971 AMSTGQGFTAQATTGWVQN 2012 NQSTGQGFTNQAQTGWVQN 1972 AQSLGNGFTAQAQTGWVQN 2013 AQSTGQGFTAQANIGWVQN 1973 YQSTGQGFTAQAMTGWVQN 2014 AHSTGQGFTAQTQTGWVQN 1974 AMSTGQGFTAQAQTGWVQN 2015 ATSIGQGFTAQ AQTGWVQN 1975 AQSTGQGFTAQAQINWVQN 2016 AQSTGQGFTNQSQTGWVQN 1976 SQSTGQGFTMQAQTGWVQN 2017 YQSVGQGFTAQAQTGWVQN 1977 AQSTGDGFTNQAQTGWVQN 2018 AQSMGQGFTAQTQTGWVQN 1978 AQSTGQGFTAQATQGWVQN 2019 HQSTGQGFTAQSQTGWVQN 1979 AASTGDGFTAQAQTGWVQN 2020 AQSTGQGFTAQAEQGWVQN 1980 AQSTGQGFTAQAQTKEVQN 2021 AQSLGQGFTAMAQTGWVQN 1981 VASTGQGFTAQAQTGWVQN 2022 AQSTGQGFTAQAQNVWVQN 1982 AASTGQGFTAQAVTGWVQN 2023 AQSTGQGFTAQAQTGWVDL 1983 AQSTGQGFTAQAQNFWVQN 2024 AQSTGQGFTAQAGTGWVQN 1984 AQSTGQGFTAQAESGWVQN 2025 VTSTGQGFTAQAQTGWVQN 1985 AQSTGQGFTAQPHTGWVQN 2026 AQSTGQGFTQQAMTGWVQN 1986 RQSTGDGFTAQAQTGWVQN 2027 WQSTGQGFTAQAQTGWVQN 1987 ALSTGQGFTAQAQTGWVQN 2028 AQSTGQGFTAQAQTGESQN 1988 AV SIGQGFT AQ AQTGWVQN 2029 AQSIGQGFTAQAETGWVQN 1989 AQSTGHGFTAQTQTGWVQN 2030 AQSTGQGFTAQAQQSWWQN 1990 AQSTGQGFTQQAQTGWVQN 2031 AQSTGQGFTAQAQLDXWQN 1991 HQSTGQGFTAQTQTGWVQN 2032 AQSTGQGFTQQTQTGWVQN 1992 AQSTGQGFTAQAQTGWVQD 2033 AQSTGQGFTAQALNGWVQN 1993 AQSTGQGFTMQGQTGWVQN 2034 AQSTGQGFTAQAQSMWVQN 1994 NQSTGQGFTAQALTGWVQN 2035 AQSTGQGFTAQAQNAWVQN 1995 VQSTGDGFTAQAQTGWVQN 2036 DQSTGQGFTAQATTGWVQN 1996 ASSIGQGFTAQAQTGWVQN 2037 AQSTGHGFTAQGQTGWVQN 1997 AQSTGQGFTAQAMNGWVQN 2038 AQSTGQGFTAQAQTGIVQN 1998 SQSTGQGFTAQATTGWVQN 2039 N QSTGQGFT AQWQTGW VQN 1999 PQSIGQGFTAQAQTGWVQN 2040 AQSLGQGFTVQAQTGWVQN 2000 ALSTGQGFTAQWQTGWVQN 2041 AQSTGQGFTAQAQSSAWQN

[0346]

[0347] 2001 HMSTGQGFTAQAQTGWVQN

[0348]

[0349] 2042 AQSTGQGFTAQADTGWVQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 2043 AQSTGQGFTLQPQTGWVQN 2084 AASTGQGFTAQATTGWVQN 2044 AISTGQGFTAQGQTGWVQN 2085 NQSIGQGFTAQAQTGWVQN 2045 ALSTGQGFTAQTQTGVWQN 2086 AESTGQGFTAQPQTGWVQN 2046 AQSMGQGFTAQAQTGWVQN 2087 AQSTGQGFTAQAGAGWVQN 2047 AQSTGQGFTAQASIGWVQN 2088 AQSTGQGFTAQAQTGWLNN 2048 AQSTGQGFTAQAQYDWVQN 2089 AQSLGQGFTTQAQTGWVQN 2049 AMSTGQGFTAQSQTGWVQN 2090 AQSTGQGFTAQAQQFWVQN 2050 YMSTGQGFTAQAQTGWVQN 2091 AQSMGQGFTAQSQTGWVQN 2051 AQSTGQGFTAQAQTGWIAN 2092 AQSTGQGFTAQAAIGWVQN 2052 AQSTGNGFTAQALTGWVQN 2093 AQSTGQGFTAQAQTAWVQN 2053 AQSTGQGFTAQAQTGFPQN 2094 AQSTGQGFTAQAQTTEVQN 2054 ALSTGQGFTAQATTGWVQN 2095 AQSTGDGFTAQAITGWVQN 2055 AQSTGQGFTNQATTGWVQN 2096 AQSTGQGFTAQATLGWVQN 2056 AQSTGQGFTAQAQTGENQN 2097 AQSTGQGFTAQASQGWVQN 2057 AQSTGQGFTAQATGGWVQN 2098 AQSTGQGFTAQAQSHWVQN 2058 AQSTGQGFTQQYQTGWVQN 2099 AQSTGQGFTAQAQTGWPSN 2059 AQSTGQGFTAQASNGWVQN 2100 AQSIGQGFTTQAQTGWVQN 2060 AMSIGQGFTAQAQTGWVQN 2101 AQSTGQGFTQQALTGWVQN 2061 HQSTGQGFTAQALTGWVQN 2102 AQSTGQGFTAQAENGWVQN 2062 AQSTGQGFTAQAVSGWVQN 2103 AQSTGQGFTAQAQNKWVQN 2063 AQSTGMGFTAQATTGWVQN 2104 AQSTGQGFTEQPQTGWVQN 2064 AQSVGQGFTAQSQTGWVQN 2105 AQSTGQGFTAQAQTKDVQN 2065 AQSTGQGFTAQAQTVWVQN 2106 NQSTGQGFTAQAVTGWVQN 2066 AQSIGQGFTAQAMTGWVQN 2107 FQSTGQGFTAQAQTAWVQN 2067 AQSTGQGFTAQAQTQDVQN 2108 AQSMGQGFTAQAMTGWVQN 2068 AQSTGQGFTAQAQSYWVQN 2109 VQSTGQGFTAQTQTGWVQN 2069 AQSTGQGFTMQSQTGWVQN 2110 AQSTGQGFTAQAQNHWVQN 2070 AQSTGQGFTAQAQTGWLSN 2111 AQSTGQGFTEQATTGWVQN 2071 AQSTGQGFTAQAQTVDVQN 2112 AQSTGQGFTAQAQQAWVQN 2072 AQSTGQGFTAQAQNMWVQN 2113 AQSSGQGFTAQPQTGWVQN 2073 AQSTGQGFTAQAQTGWCEN 2114 AQSTGQGFTAQAQYNWVQN 2074 AQSTGQGFTAQAQTMWVQN 2115 AQSTGQGFTAQAQTEWVQN 2075 AQSTGQGFTAQAQGDWVQN 2116 YQSTGQGFTAQAVTGWVQN 2076 AQSTGQGFTAQAQNIWVQN 2117 ALSIGQGFTAQAQTGWVQN 2077 AQSTGQGFTAQAQTDWVQN 2118 AQSTGQGFTMQANTGVWQN 2078 AESTGQGFTAQGQTGWVQN 2119 AQSTGQGFTAQAQTGWVEN 2079 AQSIGQGFTAQANTGWVQN 2120 AQSTGQGFTAQAQSDWVQN 2080 AQSIGQGFTAQAQTGSVQN 2121 AQSTGQGFTAQALGGWVQN 2081 SQSTGQGFTAQALTGWVQN 2122 AQSTGQGFTAQAQTGWGDN 2082 AQSTGQGFTAQAMSGWVQN 2123 LQSTGQGFTAQPQTGWVQN

[0350]

[0351] 2083 TQSLGQGFTAQAQTGWVQN

[0352]

[0353] 2124 AQSTGQGFTAQAQTGWQSN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 2125 AQSTGEGFTVQAQTGWVQN 2166 ALSMGQGFTAQAQTGWVQN 2126 AQSVGQGFTNQAQTGWVQN 2167 AQSHGQGFTAQPQTGWVQN 2127 FQSTGQGFTAQAETGWVQN 2168 AQSIGQGFTIQAQTGWVQN 2128 AQSTGSGFTAQGQTGWVQN 2169 SQSTGQGFTAQHQTGWVQN 2129 WQSTGQGFTAQATTGWVQN 2170 AQSTGQGFTAQADLGWVQN 2130 AQSTGQGFTAQAQTNFVQN 2171 HQSTGQGFTMQAQTGWVQN 2131 AQSTGQGFTAQAQEAWVQN 2172 AQSTGQGFTAQAQGIWVQN 2132 AQSTGQGFTAQAQSTWVQN 2173 VQSTGQGFTAQSQTGWVQN 2133 AQSTGQGFTAQTTTGWVQN 2174 WQSTGDGFTAQAQTGWVQN 2134 AQSTGQGFTAQALQGWVQN 2175 AQSTGQGFTNQAQTGWVQN 2135 AQSTGQGFTAQGSTGWVQN 2176 SQSTGQGFTAQSQTGWVQN 2136 AQSTGQGFTMQAMTGWVQN 2177 AQSTGQGFTAQAQTGWVSN 2137 AQSTGQGFTAQAQWDWVQN 2178 AQSIGQGFTAQAATGWVQN 2138 AQSMGQGFTAQAWGWVQN 2179 VQSTGQGFTQQAQTGWVQN 2139 AQSIGQGFTAQAHTGWVQN 2180 SQSTGQGFTAQAQTGWVQN 2140 AQSIGQGFTAQTQTGWVQN 2181 NQSTGQGFTAQAGTGWVQN 2141 AHSTGDGFTAQAQTGWVQN 2182 AQSTGQGFTAQAQTMEVQN 2142 AQSTGQGFTAQAQTGWVNS 2183 AQSTGQGFTAQAQSAWVQN 2143 SQSTGQGFTAQAMTGWVQN 2184 AQSTGQGFTAQAQTGWVNE 2144 AQSTGQGFTAQAQTGWNEN 2185 FQSTGQGFTAQAVTGWVQN 2145 NISTGQGFTAQAQTGWVQN 2186 AQSTGQGFTAQAQTHEVQN 2146 FQSTGQGFTAQAATGWVQN 2187 AQSTGQGFTAQAGIGWVQN 2147 QQSTGQGFTAQAQTGWVQN 2188 AQSTGQGFTAQAEIGWVQN 2148 VQSTGQGFTMQAQTGWVQN 2189 AQSVGQGFTAQATTGWVQN 2149 AQSTGQGFTAQAQQLWVQN 2190 AQSTGQGFTAQAVQGWVQN 2150 AQSTGQGFTAQAQSQWVQN 2191 AQSTGQGFTMQASTGWVQN 2151 AQSIGGGFTAQAQTGWVQN 2192 AMSTGQGFTAQGQTGVWQN 2152 AQSTGQGFTQQAVTGWVQN 2193 AQSTGQGFTEQAMTGWVQN 2153 RESTGQGFTAQAQNGWVQN 2194 AQSTGQGFTAQAQTGWVDD 2154 AQSTGQGFTAQAEAGWVQN 2195 YLSTGQGFTAQAQTGWVQN 2155 AQSTGQGFTAQAQIKWVQN 2196 NLSTGQGFTAQAQTGWVQN 2156 AQSTGQGFTAQAQSFWVQN 2197 AQGVGQGFTAQPQTGWVQN 2157 AMSTGDGFTAQAQTGWVQN 2198 AQSTGQGFTAQAQTGWVTG 2158 AQSTGQGFTAQPDTGWVQN 2199 AQSIGQGFTAQALTGWVQN 2159 AQSTGQGFTAQSETGWVQN 2200 HISTGQGFTAQAQTGWVQN 2160 AQSTGQGFTAQAQVDWVQN 2201 AMSVGQGFTAQAQTGWVQN 2161 HQSVGQGFTAQAQTGWVQN 2202 AQSIGQGFTAQARTGWVQN 2162 AQSTGQGFTAQAQTGETQN 2203 VQSTGQGFTAQASTGWVQN 2163 AQSMGQGFTAQASTGWVQN 2204 SQSTGQGFTAQQQTGWVQN 2164 AQSTGQGFTAQAQTGWNDN 2205 AISLGQGFTAQAQTGWVQN

[0354]

[0355] 2165 AQSVGQGFTAQAMTGWVQN

[0356]

[0357] 2206 AQSTGQGFTAQAQALWVQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 2207 AQSTGQGFTAQAQGSWVQN 2248 AQSTGDGFTAQAVTGWVQN 2208 VHSTGQGFTAQAQTGWVQN 2249 AQSYGQGFTAQGQTGWVQN 2209 AQSTGQGFTAQPNTGWVQN 2250 AQSTGQGFTAQAQTDEVQN 2210 EQSTGQGFTAQAVTGWVQN 2251 AQSTGQGFTAQAQQHWVQN 2211 AQSTGDGFTAQAMTGWVQN 2252 AQSTGQGFTAQAQTGDVQN 2212 VQSTGQGFTAQGQTGWVQN 2253 AQSTGHGFTAQAQTGWVQN 2213 AQSTGQGFTAQAATGWVQN 2254 AQSTGQGFTAQAQTGWLQN 2214 ATSTGQGFTAQTQTGWVQN 2255 AQSYGQGFTAQATTGWVQN 2215 AQSTGQGFTAQAQTGYVQN 2256 AQSTGQGFTAQAELGWVQN 2216 FQSTGQGFTAQALTGWVQN 2257 AQSTGQGFTNQHQTGWVQN 2217 AQSVGQGFTAQVQTGWVQN 2258 SQSTGQGFTAQIQTGWVQN 2218 AQSTGNGFTAQAQTGWVQN 2259 AQSTGQGFTAQAQTGWVGN 2219 SQSTGQGFTAQVQTGWVQN 2260 AQSTGQGFTNQCQTGWVQN 2220 AQSTGQGFTAQAAQGWVQN 2261 AQSTGQGFTSQGQTGWVQN 2221 AQSTGQGFTAQADNGWVQN 2262 AQSTGDGFTAQASTGWVQN 2222 AQSTGQGFTAQAQTDSVQN 2263 AQSTGQGFTAQAQEQWVQN 2223 AQSMGQGFTAQALTGWVQN 2264 AQSTGQGFTAQADIGWVQN 2224 AQSTGQGFTAQANSGWVQN 2265 AQSTGQGFTAQAQASWVQN 2225 AQSIGQGFTAQAVTGWVQN 2266 AQSLGQGFTAQAQTGWVQN 2226 AMSTGQGFTAQYQTGWVQN 2267 AQSTGQGFTAQAQCDWVQN 2227 AQSTGQGFTAQAQTGWMDN 2268 VQSIGQGFTAQAQTGWVQN 2228 AQSLGGGFTAQAQTGWVQN 2269 AQSTGQGFTAQAQTGWTGN 2229 AQSTGQGFTAQAQQQWVQN 2270 VHSTGQGFTAQALTGWVQN 2230 AQSTGQGFTAQAQTSEVQN 2271 AQSTGQGFTAQAQTGFMQN 2231 AQSTGQGFTAQSLTGWVQN 2272 AQSTGQGFTAQAQTGDTQN 2232 AISTGQGFTAQTQTGWVQN 2273 AQSTGQGFTAQAQTGWVDS 2233 AQSTGHGFTAQATTGWVQN 2274 FLSTGQGFTAQAQTGWVQN 2234 AQSTGQGFTEQAQTGWVQN 2275 AQSTGQGFTAQAQFDWVQN 2235 ALSTGQGFTAQGQTGWVQN 2276 AQSTGQGFTAQAQTNDVQN 2236 AQSTGQGFTAQAVAGWVQN 2277 AQSTGQGFTAQSSTGWVQN 2237 GQSTGQGFTAQPQTGWVQN 2278 AQSMGQGFTNQAQTGWVQN 2238 AQSTGQGFTAQAQMNWVQN 2279 FQSTGQGFTMQAQTGWVQN 2239 AQSFGQGFTAQAQTGWVQN 2280 AQSTGHGFTAQPQTGWVQN 2240 AQSTGQGFTAQAQTGWVTN 2281 AQSTGQGFTAQAQTGWAEN 2241 AQSTGQGFTAQAQTDMVQN 2282 AQSTGQGFTAQAQTGFIQN 2242 AQSTGQGFTQQATTGWVQN 2283 AQSTGQGFTAQYTTGWVQN 2243 NQSTGQGFTEQAQTGWVQN 2284 AQSIGQGFTAQVQTGWVQN 2244 AQSLGQGFTAQAATGWVQN 2285 AQSTGQGFTAQAGNGWVQN 2245 NMSTGQGFTAQAQTGWVQN 2286 AQSTGQGFTAQAQTSWVQN 2246 AQSTGQGFTAQYETGWVQN 2287 AQSTGQGFTAQAQTGDNQN

[0358]

[0359] 2247 AQSTGQGFTAQAVVGWVQN

[0360]

[0361] 2288 AQSTGQGFTAQAQTTWQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 2289 AQSTGQGFTAQAQTGWVDI 2330 AQSTGQGFTAQAQTGWNHN 2290 AQSTGQGFTAQAQTALVQN 2331 AQSTGQGFTMQAITGWVQN 2291 HQSTGDGFTAQAQTGWVQN 2332 AQSTGQGFTAQAASGWVQN 2292 YQSTGQGFTAQASTGWVQN 2333 IQSLGQGFTAQAQTGWVQN 2293 AQSTGDGFTAQAGTGWVQN 2334 AQSTGQGFTAQAQTSAVQN 2294 VQSTGQGFTAQAATGWVQN 2335 AQSTGQGFTAQAQAEWVQN 2295 VQSTGQGFTAQPQTGWVQN 2336 AQSTGQGFTQQAATGWVQN 2296 AQSTGQGFTAQAQTDFVQN 2337 AQSTGQGFTAQAQTEIVQN 2297 VVSTGQGFTAQAQTGWVQN 2338 AQSIGQGFTSQAQTGWVQN 2298 DQSTGQGFTAQALTGWVQN 2339 AQSTGQGFTAQAQQWWVQN 2299 AQSTGQGFTAQAQGNWVQN 2340 AMSTGQGFTAQAMTGWVQN 2300 AQSTGQGFTAQAQTAFVQN 2341 QQSTGQGFTMQAQTGWVQN 2301 AQSTGQGFTMQVQTGWVQN 2342 AQSTGQGFTAQAQTGWTNN 2302 NQSTGQGFTAQAATGWVQN 2343 AQSTGQGFTAQAVLGWVQN 2303 AQSTGQGFTAQAQTGWISN 2344 AQSTGQGFTAQAQTMDVQN 2304 AQSLQQGFTAQPQTGWVQN 2345 AQSTGEGFTTQAQTGWVQN 2305 AQSTGQGFTAQPITGWVQN 2346 AQSTGQGFTAQADFGWVQN 2306 AQSTGQGFTAQAQGTWVQN 2347 AQSTGEGFTLQAQTGWVQN 2307 AQSTGQGFTAQAQTGWSCN 2348 AQSTGQGFTAQAQTGWIQN 2308 AQSTGQGFTAQCETGWVQN 2349 AQSTGQGFTAQAQATWVQN 2309 AHSIGQGFTAQAQTGWVQN 2350 AQSTGQGFTAQAQISWVQN 2310 AQSTGQGFTMQAVTGWVQN 2351 AQSTGQGFTAQAQTGDSQN 2311 AQSTGQGFTAQAQTGWVSY 2352 AQSTGQGFTAQAQTYPVQN 2312 FQSVGQGFTAQAQTGWVQN 2353 AQSTGQGFTDQPQTGWVQN 2313 AQSTGQGFTNQAVTGWVQN 2354 VQSMGQGFTAQAQTGWVQN 2314 HQSIGQGFTAQAQTGWVQN 2355 ASSTGQGFTAQGQTGWVQN 2315 AQSTGQGFTEQGQTGWVQN 2356 VQSTGQGFTIQAQTGWVQN 2316 AQSIGQGFTNQAQTGWVQN 2357 AQSTGAGFTAQPQTGWVQN 2317 AASTGQGFTAQAQTGWVQN 2358 AQSTGDGFTCQAQTGWWQN 2318 ALSTGQGFTEQAQTGWVQN 2359 AQSTGQGFTAQGKTGWWQN 2319 AQSTGQGFTAQAQTGWQDN 2360 AQSIGQGFTAQAKTGWVQN 2320 AQSTGQGFTAQTKTGWVQN 2361 AQSTGQGFTAQAMGGWVQN 2321 AQSTGQGFTAQAQTGYAQN 2362 AQSTGNGFTAQAMTGWVQN 2322 CQSTGQGFTAQAQTGWVQN 2363 MQSIGQGFTAQAQTGWVQN 2323 ALSTGQGFTQQAQTGWVQN 2364 AQSTGQGFTAQAQTGWQNN 2324 ALSTGDGFTAQAQTGWVQN 2365 AYSTGQGFTAQPQTGWVQN 2325 WQSTGQGFTAQAETGWVQN 2366 AQSTGQGFTLQAQTGWVQN 2326 PQSTGQGFTLQAQTGWVQN 2367 AQSTGQGFTAQAQGLWVQN 2327 AQSTGQGFTEQTQTGWVQN 2368 AQSTGQGFTAQAMQGWVQN 2328 NQSTGQGFTAQCQTGWVQN 2369 YMSTGQGFTAQAQTGVVQN

[0362]

[0363] 2329 AHSTGQGFTAQGQTGWVQN

[0364]

[0365] 2370 AQSTGQGFTAQANQGWVQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 2371 AQSTGQGFTAQAQTGWVND 2412 AQSTGQGFTAQAQTGWVHQ 2372 AMSMGQGFTAQAQTGWVQN 2413 AQSTGQGFTAQAQGAWVQN 2373 AQSTGQGFTAQAQTGWVDR 2414 AQSTGEGFTNQAQTGWVQN 2374 AQSTGQGFTAQAQTGSVQN 2415 AASLGQGFTAQAQTGWVQN 2375 AQSTGQGFTNQAMTGWVQN 2416 AQSTGQGFTAQAQTEEVQN 2376 WQSTGNGFTAQAQTGWVQN 2417 NQSTGQGFTAQIQTGWVQN 2377 AQSMGQGFTAQIQTGWVQN 2418 AASTGQGFTAQSQTGWVQN 2378 AQSTGQGFTAQSVTGWVQN 2419 AQSTGDGFTAQGQTGWVQN 2379 AQSTGQGFTAQAQTSFVQN 2420 AQSTGQGFTAQAQTYLVQN 2380 YQSTGHGFTAQAQTGWVQN 2421 AESTGQGFTAQYQTGWVQN 2381 AQSTGQGFTAQAQTGFNQN 2422 AQSTGQGFTNQALTGWVQN 2382 KESTGQGFTAQAQTGWVQN 2423 AQSTGQGFTAQAQTNLVQN 2383 AQSTGQGFTAQAQTSLVQN 2424 AESLGQGFTAQAQTGWVQN 2384 YQSTGQGFTAQAATGWVQN 2425 AQSMGHGFTAQAQTGWVQN 2385 AQSTGQGFTAQAQTKWVQN 2426 AQSTGQGFTEQSQTGWVQN 2386 AQSTGQGFTAQADSGWVQN 2427 AQSTGQGFTAQAQTQVVQN 2387 A VS VGQGFTA QAQTGWVQN 2428 YQSTGQGFTAQALTGWVQN 2388 AQSTGQGFTAQAQTIGVQN 2429 FMSTGQGFTA QAQTGWVQN 2389 HESTGQGFTAQATTGWVQN 2430 FQSTGQGFTAQPQTGWVQN 2390 AQSTGQGFTAQAQTGEVQN 2431 AQSTGQGFTEQCQTGWVQN 2391 AQSTGQGFTVQAQTGWVQN 2432 AQSTGQGFTAQAQTTVVQN 2392 FQSTGNGFTA QAQTGWVQN 2433 AQSTGQGFTAQAQLTWVQN 2393 AQSTGQGFTKQGQTGWVQN 2434 AQSTGQGFTAQAQTNYVQN 2394 AQSYGQGFTA QAQTGWVQN 2435 AQSTGQGFTAQANTGWVQN 2395 HASTGQGFTAQTQTGWVQN 2436 AQSIGQGFTAMAQTGWVQN 2396 AQSTGQGFTAQAQTGWMNN 2437 AQSVGNGFTAQAQTGWVQN 2397 YQSMGQGFTAQAQTGWVQN 2438 HQSTGQGFTAQAITGWVQN 2398 AQSTGQGFTAQAQTAEVQN 2439 AQSTGQGFTAQAQTGWVDE 2399 AQSTGDGFTAQATTGWVQN 2440 ANSIGQGFTAQAQTGWVQN 2400 AQSTGQGFTAQALSGWVQN 2441 AMSTGQGFTNQAQTGWVQN 2401 YQSTGNGFTAQAQTGWVQN 2442 AQSKGQGFTAQPQTGWVQN 2402 VQSTGGGFTAQAQTGWVQN 2443 AMSTGQGFTAQAVTGWVQN 2403 HQSTGQGFTAQVQTGWVQN 2444 AQSTGQGFTAQAQTDNVQN 2404 AQSTGQGFTAQAMVGWVQN 2445 AQSTGQGFTAMYQTGWVQN 2405 FQSTGQGFTQQAQTGWVQN 2446 AQSTGQGFTAQAQTGWIDN 2406 SQSTGQGFTEQAQTGWVQN 2447 NTSTGQGFTAQAQTGWVQN 2407 AMSTGQGFTAQALTGWVQN 2448 AQSTGQGFTAQAQTQIVQN 2408 RQSTGQGFTAQAQTGWVQN 2449 AQSTGQGFTAQAQTGWCSN 2409 DQSTGQGFTAQASTGWWQN 2450 AQSTGHGFTAQSQTGWVQN 2410 AQSTGQGFTAQAQTYDVQN 2451 AQSTGQGFTAQAQAAWVQN

[0366]

[0367] 2411 AQSTGQGFTKQGQTGWVQN

[0368]

[0369] 2452 AQSTGQGFTAQPYTGWVQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 2453 AQSTGQGFTAQAQTGWVNV 2494 AQSTGQGFTAQAQTGWVDT 2454 AQSTGQGFTAQAQTGECQN 2495 DQSTGQGFTAQAMTGWVQN 2455 AQSTGQGFTAQAQTGWVEY 2496 AQSTGQGFTAQAQTGWLDN 2456 AQSTGQGFTAQAQTGWVEG 2497 AQSVGQGFTAQYQTGWVQN 2457 AQSTGQGFTQQSQTGWVQN 2498 DQSTGQGFTAQPQTGWVQN 2458 AQSTGQGFTAQAQLEWVQN 2499 AQSTGDGFTLQAQTGWVQN 2459 RESTGQGFTAQAQTGWVQN 2500 HISTGQGFTAQAQVGWVQN 2460 AQSTGQGFTAQAMAGWVQN 2501 AQSTGQGFTAQAQTGWDDN 2461 DQSTGQGFTAQAVTGWVQN 2502 AQSTGQGFTAQAQTQEVQN 2462 HVSTGQGFTAQAQTGWVQN 2503 AASTGQGFTAQVQTGWVQN 2463 AQSTGQGFTAQAQTGEGQN 2504 AQSTGQGFTAQAQCNWVQN 2464 AQSTGQGFTAQAANGWVQN 2505 AQSTGQGFTAQAQTGWVTD 2465 AQSTGQGFTAQAQADWVQN 2506 AQSTGQGFTAQAQTGEAQN 2466 VQSTGHGFTAQAQTGWVQN 2507 AQSTGQGFTAQAQDAWVQN 2467 NQSVGQGFTAQAQTGWVQN 2508 AQSIGQGFTAQCQTGWVQN 2468 AQSTGQGFTAQAQTFTVQN 2509 ATSLGQGFTAQAQTGWVQN 2469 AQSTGQGFTAQFQTGWVQN 2510 SQSIGQGFTAQAQTGWVQN 2470 RQSTGQGFTAQPQTGWVQN 2511 AQSTGQGFTAQAQTGPVQN 2471 AQSVGQGFTAQAVTGWVQN 2512 AQSTGQGFTAQAQSKWVQN 2472 AHSLGQGFTAQAQTGWVQN 2513 AQSTGQGFTAQAQTGWVNN 2473 AQSTGQGFTEQAITGWVQN 2514 WQSTGQGFTAQASTGWVQN 2474 HQSTGQGFTAQAATGWVQN 2515 AQSTGQGFTAQAQTGTVQN 2475 AASTGQGFTAQAMTGWVQN 2516 VSSTGQGFTAQAQTEWVQN 2476 HQSTGQGFTAQAVTGWVQN 2517 AQSTGQGFTAQAQTNIVQN 2477 AQSTGQGFTAQAQTREVQN 2518 AQSTGQGFTAQAQTFTVQN 2478 AQSTGLGFTAQPQTGWVQN 2519 IQSTGDGFTAQAQTGWVQN 2479 AQSTGQGFTAQAQTGWSEN 2520 NQSTGQGFTAQAETGVWQN 2480 AQSTGQGFTAQAQCTWVQN 2521 AQSTGQGFTAQAQTHDVQN 2481 ALSVGQGFTAQAQTGWVQN 2522 AQSTGQGFTAQAQGEWVQN 2482 AQSTGHGFTAQAVTGWVQN 2523 AQSTGQGFTAQAQTGDIQN 2483 AQSTGQGFTAQAQTGWAAN 2524 AQSTGQGFTAQAQTAYVQN 2484 AQSTGQGFTAQAQTGLIQN 2525 AQSTGQGFTAQTATGWVQN 2485 AQSTGQGFTAQAQTGWPNN 2526 AQSTGQGFTAQAQTTFVQN 2486 ATSMGQGFTAQAQTGWVQN 2527 AMSTGQGFTAQAATGWVQN 2487 AQSTGQGFTAQAQTLGVQN 2528 AQSTGQGFTAQPFTGWVQN 2488 AISTGQGFTAQAVTGWVQN 2529 RESTGQGFTAQAQTGWVQN 2489 AQSTGQGFTAQAQNRWVQN 2530 AQSTGQGFTAQAQCVWVQN 2490 AQSTGQGFTAQAQTWIVQN 2531 WQSTGQGFTNQAQTGWVQN 2491 HQSTGNGFTAQAQTGWVQN 2532 AQSTGQGFTAQAQTGWTTN 2492 AQSTGQGFTAYPQTGWVQN 2533 AQSTGQGFTAQAQTGWTQN

[0370]

[0371] 2493 ATSTGQGFTAQATTGWVQN

[0372]

[0373] 2534 MQSLGQGFTAQAQTGVWQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 2535 AQSTGQGFTAQAQVNWVQN 2576 PQSTGQGFTAQATTGWVQN 2536 FQSTGQGFTAQASTGWVQN 2577 AQSTGQGFTNQVQTGWVQN 2537 AQSTGQGFTAQAQTGWVEF 2578 AQSTGQGFTAQAQGYWVQN 2538 AQSIGHGFTAQAQTGWVQN 2579 AQSTGQGFTAQAQTGWSSN 2539 AQSTGQGFTAQAQANWVQN 2580 AQSTGQGFTAQAQTSPVQN 2540 AQSTGQGFTAQAQYEWVQN 2581 AQSTGQGFTAQAQTSDVQN 2541 AQSMGQGFTMQAQTGWVQN 2582 AQSVGQGFTAQALTGWVQN 2542 DQSTGQGFTAQGQTGWVQN 2583 AQSTGQGFTAQSMTGWVQN 2543 AISIGQGFTAQAQTGWVQN 2584 AQSTGNGFTAQAETGWVQN 2544 AQSTGQGFTAQAQMTWVQN 2585 FQSIGQGFTAQAQTGWVQN 2545 HQSTGQGFTAQAQTSWVQN 2586 AQSTGQGFTAQAQTGVNQN 2546 HQSTGQGFTAQASTGWVQN 2587 AQSTGQGFTAQADYGWVQN 2547 AQSTGQGFTAQAQTSMVQN 2588 AQSTGQGFTAQAQTGWAHN 2548 VQSTGQGFTAQAITGWVQN 2589 DQSTGQGFTAQTQTGWVQN 2549 AQGTGQGFTAQPQTGWVQN 2590 AQSTGQGFTAQHETGWVQN 2550 AISTGQGFTAQATTGWVQN 2591 AQSTGQGFTAQAQGHWVQN 2551 AQSTGQGFTAQAQTGWCHN 2592 AQSTGQGFTAQAQLAWVQN 2552 AQSMGQGFTAQYQTGWVQN 2593 AQSTGQGFTAQAQTGWVNY 2553 AISTGDGFTAQAQTGWVQN 2594 NQSTGQGFTAQAITGWVQN 2554 AQSTGQGFTAQATVGWVQN 2595 AQSTGQGFTAQAQTGWMQN 2555 WQSTGQGFTAQADTGWVQN 2596 ATSTGQGFTAQAQTGWVQN 2556 FQSTGQGFTAQSQTGWVQN 2597 AVSTGQGFTAQAMTGWVQN 2557 ALSTGQGFTAQALTGWVQN 2598 AQSTGQGFTAQAQTGQLQN 2558 AMSTGQGFTAQAITGWVQN 2599 YESTGQGFTAQAQTGFVQN 2559 ASSLGQGF’T A Q AQTGWVQN 2600 AQSTGQGFTAQAQTQFVQN 2560 AQSLGQGFTAQAGTGWVQN 2601 AQSTGQGFTEQASTGWVQN 2561 AQSTGQGFTAQAQTGICQN 2602 AQSTGQGFTAQAQTNVVQN 2562 FQSMGQGFTAQAQTGWVQN 2603 HQSTGGGFTAQAQTGWVQN 2563 AQSTGQGFTAQAQTGWAQN 2604 AQSTGQGFTAQAQTGDGQN 2564 AQSTGQGFTAQAQTKQVQN 2605 ANSTGQGFTEQAQTGWVQN 2565 AQSVGQGFTAQWQTGWVQN 2606 AQSAGQGFTAQPQTGWVQN 2566 AQSTGQGFTAQAQTKLVQN 2607 AQSTGQGFTAQATMGWVQN 2567 AQSTGQGFTAQAQTGWVEM 2608 KQSTGQGFTAQPQTGWVQN 2568 AQSTGQGFTAQAQTGDEQN 2609 AQSTGHGFTAQVQTGWVQN 2569 SQSTGQGFTAQCQTGWVQN 2610 HLSTGQGFTAQAQTGWVQN 2570 NQSTGQGFTLQAQTGWVQN 2611 AASTGQGFTAQYQTGWVQN 2571 AQSTGQGFTAQAQTGWTEN 2612 AQSTGQGFTAQGRTGWVQN 2572 AQSTGQGFTAQAQTGWVSQ 2613 AQSTGN GFT AQGQTGW V QN 2573 AQSTGQGFTAQAQTDIVQN 2614 AQSTGQGFTQQAETGWVQN 2574 AQSTGQGFTAQAQTFPVQN 2615 AQSTGQGFTAQAQTDVVQN

[0374]

[0375] 2575 YQSTGQGFTAQVQTGWVQN

[0376]

[0377] 2616 AQSIGSGFTAQAQTGWVQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 2617 AQSTGQGFTMQAGTGWVQN 2658 AQSTGQGFTAQAQTGVVQN 2618 AQSTGQGFTAQAVGGWVQN 2659 DQSTGQGFTAQAQTKWVQN 2619 AQSTGQGFTAQAQTADVQN 2660 AQSTGQGFTAQAQTGLVQN 2620 AQSTGQGFTAQAQIDWVQN 2661 AQSTGQGFTAQAQTGWVAN 2621 AQSTGQGFTAQAQTGWVDA 2662 QQSTGQGFTAQTQTGWVQN 2622 AVSTGQGFTAQTQTGWVQN 2663 AQSTGQGFTAQAQLFWVQN 2623 AESTGQGFTAQCQTGWVQN 2664 AQSTGQGFTAQAQTYAVQN 2624 AQSTGQGFTAQAQTGWVGG 2665 AQSTGQGFTAQAQTGFQQN 2625 AQSTGQGFTAQAQTDTVQN 2666 AQSTGQGFTAQAQTGWVNC 2626 AQSTGQGFTAQAQTTYVQN 2667 AQSTGQGFTAQAQTGWTSN 2627 AQSTGQGFTAQAQTGWIHN 2668 AQSTGQGFTAQPETGWVQN 2628 SQSTGQGFTAQASTGWVQN 2669 A1STGQGFTAQAQTGWVQN 2629 ALSTGQGFTAQPQTGWVQN 2670 AQSTGQGFTAQAQTGWQHN 2630 AQSQGEGFTAQAQTGWVQN 2671 AQSTGQGFTAQAQTGWIEN 2631 AQSTGQGFTAQVETGWVQN 2672 AQSTGQGFTQQPQTGWVQN 2632 RMSTGQGFTAQAQTGWVQN 2673 AQSTGQGFTAQAQTGWVSA 2633 PQSLGQGFTAQAQTGWVQN 2674 ALSTGQGFTAQAMTGWVQN 2634 AQSTGQGFTAQAQTFSVQN 2675 NQSTGHGFTAQAQTGWVQN 2635 ALSTGQGFTAQAETGWVQN 2676 IQSIGQGFTAQAQTGWVQN 2636 AQSTGQGFTAQAQLYWVQN 2677 AQSLGQGFTAQSQTGWVQN 2637 AQSTGQGFTAQAQTAIVQN 2678 AQSTGQGFTAQAQTGWQQN 2638 PQSTGQGFTAQAQTGWVQN 2679 AQSTGQGFTMQAETGWVQN 2639 IQSTGQGFTAQAMTGWVQN 2680 AQSTGQGFTAQARTGWVQN 2640 AQSVGQGFTEQAQTGWVQN 2681 AQSTGQGFTAQAQTDHVQN 2641 HMSTGQGFTAQAQTQWVQN 2682 AQSTGQGFTAQAQTGEIQN 2642 AVSTGQGFTAQVQTGWVQN 2683 AQSTGQGFTAQAQVGWVQN 2643 AQSTGQGFTAQAQTDAVQN 2684 AQSTGQGFTAQAQTFDVQN 2644 WQSTGQGFTQQAQTGWVQN 2685 AQSTGQGFTAQAQTGWVGY 2645 QQSTGQGFTEQAQTGWVQN 2686 HQSTGQGFTQQAQTGWVQN 2646 AQSTGQGFTAQAQTGWVQY 2687 ATSVGQGFTAQAQTGXWQN 2647 ALSTGQGFTAQSQTGWVQN 2688 AQSTGQGFTAQAQTGWVSG 2648 AQSTGQGFTAQAQTFIVQN 2689 QQSIGQGFTAQAQTGWVQN 2649 AQSTGQGFTAQAQTTNVQN 2690 AQSTGQGFTAQAQSWWVQN 2650 AQSTGQGFTAQAQAMAWQN 2691 AQSTGQGFTAQAQCSWVQN 2651 AQSTGGGFTAQTQTGWVQN 2692 AQSTGQGFTAQSATGWVQN 2652 AQSTGQGFTAQAQTGDPQN 2693 AQSTGQGFTAQAQTGWSHN 2653 AQSTGQGFTAQAQTGPLQN 2694 AQSTGRGFTAQTQTGWVQN 2654 ATSTGQGFTAQAVTGWVQN 2695 AQSFGQGFTAQSQTGWVQN 2655 AQSTGQGFTAQAQTGWVGS 2696 YISTGQGFTAQAQTGFVQN 2656 AQSTGQGFTAQAQTGWVGV 2697 AQSTGQGFTAQAQLSWVQN

[0378]

[0379] 2657 ALSTGQGFTAQAVTGWVQN

[0380]

[0381] 2698 A SSTGQGFT AQ AMTGWVQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 2699 AQSLGQGFTAQAKTGWVQN 2740 AMSTGQGFTQQAQTGWVQN 2700 AQSTGQGFTAQSNTGWVQN 2741 AQSTGQGFTAQAQGWWVQN 2701 KQSTGQGFTAQAETGWVQN 2742 AQSTGQGFTAQAQTFEVQN 2702 AQSTGQGFTAQAQTGQVQN 2743 NVSTGQGFTAQAQTGWVQN 2703 AFSTGQGFTAQPQTGWVQN 2744 AQSTGQGFTAQAQTRFVQN 2704 ALSTGQGFTAQAGTGWVQN 2745 AQSTGDGFTAQAATGWVQN 2705 AQSTGQGFTAQAQTRMVQN 2746 IQSTGQGFTAQAVTGWVQN 2706 DQSTGQGFTAQSQTGWVQN 2747 VISTGQGFTAQAQTGWVQN 2707 AQSVGQGFTAQIQTGWVQN 2748 AQSTGQGFTAQAQTIFVQN 2708 SQSTGDGFTAQAQTGWVQN 2749 SQSTGQGFTNQAQTGWVQN 2709 AQSTGQGFTAQAQTRFVQN 2750 AQSLGQGFTAQAETGWVQN 2710 YHSTGQGFTAQAQTGWVQN 2751 ARSTGQGFT A QTQTGWV QN 2711 AQSTGQGFTAQAQTELVQN 2752 DRSTGQGFTAQATTGWVQN 2712 AQSTGQGFTAQAQTEAVQN 2753 AQSTGQGFTAQAQTLTVQN 2713 AQSTGQGFTAQAQTEVVQN 2754 HQSTGQGFTAQADTGWVQN 2714 AQSTGQGFTAQAQVAWVQN 2755 AQSTGQGFTAQAQTGDCQN 2715 AQSTGQGFTAQQQTGWVQN 2756 FQSTGQGFTAQAITGWVQN 2716 AVSTGQGFTAQATTGWVQN 2757 IQSTGQGFTMQAQTGWVQN 2717 VQSTGQGFTAQADTGWVQN 2758 EQ SIGQGFTAQ AQTGWVQN 2718 AQSTGQGFTAQAQTGEDQN 2759 AHSTGQGFTAQAQTGWVQN 2719 YQSTGQGFTQQAQTGWVQN 2760 KQSVGQGFTAQAQTGWVQN 2720 AQSFGQGFTAQVQTGWVQN 2761 AQSTGQGFTAQAQTGWVSE 2721 AQSFGQGFTAQPQTGWVQN 2762 AASTGQGFTAQCQTGWVQN 2722 AQSTGQGFTAQAQTGWVDV 2763 AQSTGQGFTAQAQTGWVHN 2723 QQSTGDGFTAQAQTGWVQN 2764 AQSTGQGFTAQAQTGWNNN 2724 AQSTGQGFTEQARTGWVQN 2765 AQSTGQGFTAQAQTGPAQN 2725 AQSTGQGFTQQVQTGWVQN 2766 AQSTGQGFTAQAQTGEMQN 2726 AQSTGGGFTAQSQTGWVQN 2767 AQSTGQGFTAQAQFEWVQN 2727 AQSTGQGFTAQFTTGWVQN 2768 AQSTGQGFTAQAQTLSVQN 2728 AQSTGQGFTAQAQTGWSQN 2769 AQSIGQGFTAQAITGWVQN 2729 AQSTGQGFTAQAQTQWVQN 2770 FMSTGQGFTAQAQTGVVQN 2730 AQSTGQGFTAQAQTGWVHF 2771 ATSTGQGFTAQALTGWVQN 2731 AQSTGQGFTQQWQTGWVQN 2772 YVSTGQGFTAQAQTGWVQN 2732 AQSTGQGFTAQAQTGWVGA 2773 AQSIGQGFTVQAQTGWVQN 2733 AHSTGQGFTAQSQTGWVQN 2774 AQSTGQGFTAQAQTGWASN 2734 AQSTGQGFTAQPKTGWVQN 2775 AQSTGQGFTAQAQTWPVQN 2735 AQSTGQGFTAQAQTGWIPN 2776 AQSTGQGFTAQAQTGWPAN 2736 AQSTGQGFTAQAQTDLVQN 2777 AQSTGQGFTAQGATGWVQN 2737 AQSTGQGFTAQAQTGWFNN 2778 ATSTGQGFTAQAMTGWVQN 2738 AQSTGQGFTAQAQTVPVQN 2779 YQSTGQGFTAQPQTGWVQN

[0382]

[0383] 2739 VHSTGQGFTAQSQTGWVQN

[0384]

[0385] 2780 AQSTGQGFTAQAQTIAVQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 2781 AQSTGQGFTAQVATGWVQN 2801 AQSTGQGFTAQAQTSNVQN 2782 AQSTGQGFTAQAQTGWVDW 2802 FQSTGQGFTAQADTGWVQN 2783 PQSTGQGFTAQAMTGWVQN 2803 DLSTGQGFTAQAQTGWVQN 2784 AESTGQGFTMQAQTGWVQN 2804 AQSMGQGFTAQAGTGWVQN 2785 AQSTGQGFTAQADVGWVQN 2805 EKSTGQGFTAQAQQGWVQN 2786 AQSHGEGFTAQAQTGWVQN 2806 AVSTGQGFTAQSQTGWVQN 2787 AQSTGQGFTAQAQTMFVQN 2807 WQSTGQGFTAQAVTGWVQN 2788 AQSTGQGFTAQAQTTSVQN 2808 AQSTGQGFTEQALTGWVQN 2789 AES1GQGFTAQAQTGWVQN 2809 AQSTGQGFTAQAQTGWCDN 2790 AQSTGQGFTAQAQDMWVQN 2810 AQSTGQGFTAQAMIGWVQN 2791 AQSTGQGFTAQAQTYHVQN 2811 AQSTGQGFTRQGQTGWVQN 2792 AQSTGDGFTAQTQTGWVQN 2812 AQSTGQGFTLQATTGWVQN 2793 AQSTGQGFTAQAQTGHIQN 2813 AQSMGQGFTEQAQTGWVQN 2794 AQSTGQGFTAQAQTGWHNN 2814 AQSTGQGFTEQAGTGWVQN 2795 AQSTGQGFTAQAQTYTVQN 2815 NQSTGQGFTAQANTGWVQN 2796 AQSTGQGFTAQSDTGWVQN 2816 AQSTGQGFTAQAQTTLVQN 2797 AQSTGQGFTAQAQTFAVQN 2817 AQSTGQGFTAQAQTGWVQG 2798 AQSTGQGFTAQAQTGWVQS

[0386]

[0387] 2818 AQSTGDGFTAQALTGWVQN 2799 AQSTGQGFTAQAQTHVVQN

[0388]

[0389] 2800 AQSTGQGFTAQAQTGWVDC

[0390] Formula IV

[0391] Aspects of the present invention provide an adeno-associated virus (AAV) capsid protein comprising an amino acid sequence having at least 80% identity to a sequence of Formula IV:

[0392] X1D-X2D- X3D-X4D-X5D-X6D-X7D-XSD-X9D- X

[0393]

[0394] 10D-X11D-X12D-X13D-X14D-X15D-X16D-X17D-X18D-X19D (IV) wherein,

[0395] Xm is an amino acid selected from A, H, Y, F, N, G, Q, W, V, T, D, E, M, S, K, I, P, L, C, or R;

[0396] X2D is an amino acid selected from Q, W, V, T, P, N, A, S, L, H, I, G, D, M, Y, R, K, or F; Patent Application CAPS -041 / 01 WO 35847 / 197 X3D is an amino acid selected from S, I, M, P, G, A, N, V, T, Q, E, D, H, L, Y, K, R, or F;

[0397] X4D is an amino acid selected from T, G, S, N, Q, A, L, I, V, P, E, II, D, M, R, Y, C, K, or F;

[0398] XSD is an amino acid selected from G, S, N. Q, T, A, H, V, M, I, L, D, K, P, or Y; XSD is an amino acid selected from Q, M, A, N, G, S, T, E, V, Y, II, K, P, I, or D and preferably from Q, M, or A;

[0399] X? D is an amino acid selected from G, N, E, T, S, D, A, P, L, Q, I, M, V, H, K, or Y; XSD is an amino acid selected from F, E, L, T, S, Q, N, H, G, D, I, A, V, K, Y, R, M, or P;

[0400] X9Dis an amino acid selected from T, K, R, I, H, Q, A, N, V, M, S, Y, D, E, F, G, P, or L;

[0401] XIOD is an amino acid selected from A, Q, N, S, M, T, I, V, Y, L, E, P, H, F, K, G, R, C, D, or W;

[0402] XIID is an amino acid selected from Q, P, I, N, S, T, M, G, L, D, H, A, R, V, W, or Y; X12D is an amino acid selected from A, P, C, T, G, S, V, I, F, M, Q, E, or L;

[0403] XBD is an amino acid selected from Q, A, S, T, M, G„ D, V, L, E, F, I, N, Y, H, K, or W;

[0404] Xi4D is an amino acid selected from T, S, G, A, V, Q, N, I, M, C, D, E, P, R, or W; XuD is an amino acid selected from G, E, A, D, S, Q, T, N, I, M, V, L, F, W, Y, K, or C;

[0405] Xi6D is an amino acid selected from W, R, N, K, P, V, M, E, Q, T, A, D, Y, S, L, H, I, G, C, or F;

[0406] Xi7D is an amino acid selected from V, N, C, A, I, T, L, Q, or P;

[0407] Xi8D is an amino acid selected from Q, H, E, S, A, D, G, N, L, T, or V; and Xi9D is an amino acid selected from N, V, F, D, S, or T.

[0408] In preferred aspects of the invention,

[0409] Xiomay be selected from among A, H, or Y;

[0410] XjDmay be selected from among Q, W, or V; Patent Application CAPS -041 / 01 WO 35847 / 197 X3Dmay be selected from among S, I, or M;

[0411] X4Dmay be selected from among T, G, or S;

[0412] Xsnmay be selected from among G, S, or N;

[0413] XeDinay be selected from among Q, M, or A;

[0414] Xvomay be selected from among G, N, or E;

[0415] Xsomay be selected from among F, E, or L;

[0416] X D may be selected from among T, K, or R;

[0417] Xionmay be selected from among A, Q, orN;

[0418] Ximmay be selected from among Q, P, or L;

[0419] Xi2D ay be selected from among A, P, or C;

[0420] Xi3Dmay be selected from among Q, A, or S;

[0421] Xi4D may be selected from among T, S or G;

[0422] Xi5omay be selected from among G, E, or A;

[0423] Xi6Di ay be selected from among W, R or N,

[0424] Xi7Dinay be selected from among V, N, or C;

[0425] XisDmay be selected from among Q, IL or E; and / or

[0426] Xi9omay be selected from among N, V, or F.

[0427] In aspects of the invention, XID is located at parental residue 587 and Xi9D is located at parental residue 598 in reference to a parental AAV9 capsid or equivalent residue position in another AAV capsid, wherein in Formula IV:

[0428] XID is a parental or substituted amino acid;

[0429] X2D is a parental or substituted amino acid located at parental residue 588;

[0430] X3D, X4D, XJD, X6D, X? D, XXD, X9D are an insertion between parental or substituted residues 588 and 589;

[0431] XIOD, XIID, X12D, X13D, Xi4D, XuD, Xi6D, Xi7D, XisD are parental or substituted amino acids; and

[0432] X19D is a parental or substituted amino acid located at parental residue 598, now residue 605. Patent Application CAPS -041 / 01 WO 35847 / 197 For example, as described above, residues 587-588 may be substituted or remain the parental amino acid. A 7-mer amino acid is inserted between parental amino acid residues 588 and 589. Residue 589 io residue 598 (now residue 596 to 602, accommodating the 7-mer insertion) may be substituted or remain the parental amino acid.

[0433] Capsids of the present invention comprising a sequence of Formula IV may comprise the following sequences, with parental residues 593-600 (now residues 600 to 605, accommodating the 7-mer insertion) remaining the parental amino acids (TGWVQN - SEQ ID NO: 4985):

[0434] Table 4: Formula IV sequences SEQ

[0435] ID SEQ NO VR-VIII amino acid sequence

[0436] ID 2847 WWSTGQGFTAQAQTGMVQN

[0437] NO VR-VIII amino acid sequence

[0438] 2848 A WSTGQGFS AQA QTGWVQN

[0439] 2819 AQSTGQGFTYPAQ TGWVQN

[0440] 2849 AQSIGQGFTAPAQTGWVQN

[0441] 2820 AQSTGQGFTRPAQTGWVQN

[0442] 2850 AWSTGQGFDAQAQTGWVQN

[0443] 2821 GQSTGQGFTAPAQTGWVQN

[0444] 2851 AQSTGQGFTFPAQTGWVQN

[0445] 2822 AVLTGQGFTAQAFTGWVQN

[0446] 2852 WWSTGQGFTAQAQTGWVQN

[0447] 2823 A WSTGQGFNAQAQTGWV QN

[0448] 2853 AWSTGQGYTAQAQTGWVQN

[0449] 2824 AQSTGQGFPYQAQTGWVQN

[0450] 2854 QQSTGQGFTAPAQTGWVQN

[0451] 2825 AWSVGQGFTAQAQTGWVQN

[0452] 2855 AWSLGQGFTAQAQTGWVQN

[0453] 2826 AQSTGQGFTKPAQTGWVQN

[0454] 2856 AQSTGYGFTAPAQTGWVQN

[0455] 2827 AWSTGQGFI-IAQAQTGWVQN

[0456] 2857 AQPNSMNEKAQA QTGWVQN

[0457] 2828 AQSTGQGFTWPAQTGWVQN

[0458] 2858 1WSTGQGFTAQAQTGWVQN

[0459] 2829 AWSMGQGFTAQAQTGWVQN

[0460] 2859 AQSTTQGFTAQAQTGWVQN

[0461] 2830 AQSTGQGFPYQAQAGWVQN

[0462] 2860 AQLTGQGTTAQAQTGWVQN

[0463] 2831 FWSTGQGFTAQAQTGLVQN

[0464] 2861 AQSTGQGFTHPAQTGWVQN

[0465] 2832 YWSTGQGFTAQAQTGWVQN

[0466] 2862 AWSTGQGFTAIAQTGWVQN

[0467] 2833 AQSTGQGFMAPA QTGWVQN

[0468] 2863 AQIGSMNEKAQAQTKPVQN

[0469] 2834 AWSTTQGFTAQAQTGWVQN

[0470] 2864 AQMSGAELRYWAQTGWVQN

[0471] 2835 AQSTGQGFQAPAQTGWVQN

[0472] 2865 AQIGNHNEKAQAQTGWVQN

[0473] 2836 FWSTGQGFTAQAQTGWVQN

[0474] 2866 APSTGQPFTAQAQTGWVQN

[0475] 2837 AQSTGQGFT1PAQTGWVQN

[0476] 2867 AWSTGQGFTAIAQTGWVQN

[0477] 2838 AWSTSQGFTAQAQTGWVQN

[0478] 2868 AWSTGQGFTAGAQTGWVQN

[0479] 2839 AQMSGAELRRPAQTGWVQN

[0480] 2869 AQSTGQGLTAQA QTGWVQN

[0481] 2840 AWSIGQGFTAQAQTGWVQN

[0482] 2870 AQ1GSMNEKAQAQTIEVQN

[0483] 2841 AQSTTQGFTAPAQTGWVQN

[0484] 2871 AQSTGQGFTAQAQTNMVQN

[0485] 2842 YWSTGQGFTAQAQSGWVQN

[0486] 2872 AQPTGQGTTAQA QTGWVQN

[0487] 2843 VWSTGQGFTAQAQTGWVQN

[0488] 2873 AQSTGQGFHAQPQTGWVQN

[0489] 2844 AQSTGQGFTLPAQTGWVQN

[0490] 2874 AQSTNQGFTAPAQTGWVQN

[0491] 2845 VWSTGQGFTAQAQTAWVQN

[0492] 2875 FQSTGQGNTAQAQTGWVQN

[0493]

[0494] 2846 AQSLGQGFTAQPQTGWVQN

[0495]

[0496] Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 2876 AQSTGQGNTQQAQTGWVQN 2917 AQMSGAENRAQAQTGWVQN 2877 AQGTGQGMTAQAQTGWVQN 2918 AQSTGQGFTAQAQVGWVQN 2878 AQIGSMNEKAQAQTGWVVN 2919 AQSTGNGLTAQAQTGWVQN 2879 AQIGSMNEKQQAQTGWVQN 2920 AQNTGQQFTAQAQTGWVQN 2880 AQIGSESEKAQAQTGWVQN 2921 AQIGSMNEKAQADSGWVQN 2881 AQIVQMNEKAQAQTGWVQN 2922 FQSTGAGFTAQAQTGWVQN 2882 AQNDSMNEKAQAQTGWVQN 2923 AQIGSMNEKAQAQTEAVQN 2883 AQSTGQGTTAQAHTGWVQN 2924 IQSQGQGFTAQAQTGWVQN 2884 AQSTGQNFTSQAQTGWVQN 2925 AQIGSPNEKAQAQTGWVQN 2885 AQSTGQGFHLQAQTGWVQN 2926 ANSTGQGITAQAQTGWVQN 2886 AQSTGQGFTAQAQTGWVQD 2927 AQSTGQGFTNQPQTGWVQN 2887 AWSTAQGFTAQAQTGWVQN 2928 GTMSGAELRAQAQTGWVQN 2888 AQSTGQGQHAQAATGWVQN 2929 AQSTGQGSKAQAQTGWVQN 2889 AQSTNPGFTAQAQTGVVQN 2930 AQSTGQGHTAQALTGWVQN 2890 AQSTGQGNTMQAQTGWVQN 2931 AQSTGQG1TTQAQTGWVQN 2891 AQMSGASDRAQAQTGWVQN 2932 AQSTTQGFTAQGQTGWVQN 2892 AWSTHQGFTAQAQTGWVQN 2933 AQSTGQGDIAQAQTGWVQN 2893 HQNTGQGFTAQAQTGWVQN 2934 AMSSGQGFTAQAQTGWVQN 2894 AQIGSGNEKAQAQTGWVQN 2935 AQSTGQGSIAQAQTNWVQN 2895 KPIGSMNEKAQAQTGWVQN 2936 AVSTGGGFTAQAQTGWVQN 2896 AQSTGQPQTAQAQSGWVQN 2937 AQIGTANEKAQAQTGWVQN 2897 AQSAGNGFTAQAQTGWVQN 2938 AQ1GSMNEKAQAQSSWVQN 2898 AQIGSMNEKAQAQTAQVQN 2939 AQIGGSNEKAQAQTGWVQN 2899 HQSTGQGTTAQAQTGWVQN 2940 AQSTGSGFTAQPQTGWVQN 2900 GQSNGQGFTAQAQTGWVQN 2941 YWSTGQGFTAQFQTGWVQN 2901 AQSTGAELRAQAQTGWVQN 2942 AQSVGQGFTAPAQTGWVQN 2902 AQSTGQGFTAQAQSGWVQN 2943 AQSTGVGFTAQATTGWVQN 2903 QQIGSMNEKAQAQTGWVQN 2944 ALYGSMNEKAQAQTGWVQN 2904 AQIGSMDEKAQAQTGWVQN 2945 AVSTGQGETAQAQTGWVQN 2905 AQYGSMNEKAQAQTGWVQN 2946 AQIGSKTEKAQAQTGWVQN 2906 AQSTKQGFTASAQTGWVQN 2947 AQIGSMNEKAQAQTASVQN 2907 AQMSGAEAMAQAQTGWVQN 2948 AQSTGKGFTAPAQTGWVQN 2908 AQ1GSMNEKAQAQTGWVEN 2949 AQPTGQGSTAQAQTGWVQN 2909 AQSNSMNEKAQAQTGXWQN 2950 ATSTGQGITAQAQTGWVQN 2910 AQMCGAELRAQAQTGWVQN 2951 AQIGVSNEKAQAQTGWVQN 2911 AWSTQQGFTAQAQTGWVQN 2952 AQPTGAGFTAQAQTGWVQN 2912 AQIGSMNEKAQAQTDEVQN 2953 AQSTGQGFTSPAQTGTVQN 2913 AQSTGQG1TAQMQTGWVQN 2954 AQG V GAEL RAQAQTGW VQN 2914 GQSTGQGFTAQAMTGWVQN 2955 VQSTGQGTTAQAQTGWVQN 2915 AQSTGQGFTMPAQTGWVQN 2956 MWSTGQGFTAQAQTGWVQN

[0497]

[0498] 2916 AQVTGQGLTAQAQTGWVQN

[0499]

[0500] 2957 AQITGQGFIAQAQTGWVQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 2958 AQ1GSMNEKAQADAGWVQN 2999 AQSTGAAFTAQAQTGWVQN 2959 AQIGSMNEKAQAEVGWVQN 3000 ANSTGAGFTAQAQTGWVQN 2960 AQYDSMNEKAQAQTGWVQN 3001 AQSAGQAFTAQAQTGWVQN 2961 AQIGSMNEKAQAQTTGVQN 3002 AQIGSMNEKAQAQTEPVQN 2962 AASTGQGLTAQAQTGWVQN 3003 AQSTSMNEKAQAQTGWVQN 2963 AQSSGQGLTAQAQTGWVQN 3004 AQSTGQGFQVQAQTGWVQN 2964 AQIGSMNEKAQAQTAFVQN 3005 AQSAGQGFTAQCQTGWVQN 2965 AQMSGAERAAQAQTGWVQN 3006 AQSTAQGFTAQQQTGWVQN 2966 AQIGSMNEKAQGETGWVQN 3007 AASTGQGQTAQAQTGWVQN 2967 ANSTNQGFTAQAQTGWVQN 3008 AQSTGQNETAQAQTGWVQN 2968 AQSTGQGHTAQSQTGWVQN 3009 AQIGSMNEKAQAQSTWVQN 2969 NQSTGQNFTAQAQTGWVQN 3010 AQSTGQGFTAQAQTGWVHN 2970 AQIGSMNEKAQAQAGWVQN 3011 NQSTGQGGTAQAQTGWVQN 2971 AQSTGQGSTMQAQTGWVQN 3012 AQSTGQGITEQAQTGWVQN 2972 AQIGSMNEKAQAQTGWVTN 3013 AQ1GSMNEKAQAQMTWVQN 2973 AQIGSMNEKAQAQTFNVQN 3014 AQSTGQGTTLQAQTGWVQN 2974 AQIGSMNEKAQAQAMWVQN 3015 EQ STGQGKTAQA QTGWVQN 2975 AQSTGQGGTAPAQTGWVQN 3016 AQSTGQGEHAQAQTGWVQN 2976 AQTAGQGFTAQAQTGWVQN 3017 AQIGSYTEKAQAQTGWVQN 2977 AQSTGQGTTAQ1QTGWVQN 3018 AQIGSHAEKAQAQTGWVQN 2978 AQMSGAEAKAQAQTGWVQN 3019 AQIGSNNEKAQAQTGWV QN 2979 HQSTGQTFTAQAQTGWVQN 3020 AQIGSMNEKAQAQPGWVQN 2980 AQIGSMNEKAQAQSEWVQN 3021 KQSTGQGATAQAQTGWVQN 2981 AQSTQQGATAQAQTGWVQN 3022 AQSTGQGSTAQGQTGWVQN 2982 AQIGSMNEKAQAQTSMVQN 3023 AQMSGAEHHAQAQTGWVQN 2983 AQSTGQGRTEQAQTGWVQN 3024 AQSTGQGFTAQAQTGWVSN 2984 AVSTGQGFSAQAQTGWVQN 3025 AQIGSMNEKAQAQTFRVQN 2985 AQIGSTGEKAQAQTGWVQN 3026 AQ1GSMNEGN QAQTGWVQN 2986 AQSTGAGNTAQAQTGWVQN 3027 AQSTGQGSTAQAFTGWVQN 2987 AQSTGQGDKAQAQTGWVQN 3028 AQSTGQGFTAQAVGGV-WQN 2988 AQSTGQGSTAMAQTGWVQN 3029 AYSLGQGFTAQAQTGWVQN 2989 AASTGNGFTAQAQTGWVQN 3030 AQSTGQGNTAQALTGWVQN 2990 AQSTGQGSTAQAMTGWVQN 3031 AQSTGQGFSMQAQNGWVQN 2991 AQSTGQGSTAQAITGWVQN 3032 AQVSGAELRAQAQTGWVQN 2992 ANETGQGFTAQSQTGWVQN 3033 HQSTGQGFTTQAQTGWVQN 2993 AQSTGIGETAQAQTGWVQN 3034 AQIGSMNEKAQADNGWVQN 2994 AQSTGQGSTAQTQTGWVQN 3035 AQTLSMNEKAQAQTGV'WQN 2995 AQIGVANEKAQAQTGWVQN 3036 AQVTGQGFMAQAQTGWVQN 2996 AQSTGQGGTYQAQTGWVQN 3037 TQPTGQGFTAQAQTGWVQN 2997 AQSTGQGLTAQAHTGWVQN 3038 AQSTGQNFTASAQTGWVQN

[0501]

[0502] 2998 AQIGSMNEKAQAQTMVVQN

[0503]

[0504] 3039 AQATGQGFQAQAQTGWVQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 3040 AQMSGAELRAQAQTIEVQN 3081 AQSTGQGTTAQFQTGWVQN 3041 AQSTNQGFKAQAQTGWVQN 3082 AQSTGQGTTAQTQTGWVQN 3042 AQNSGQGFTAQAQTGWVQN 3083 GQSTGQSFTAQAQTGWVQN 3043 AQIGSMNEKAQAETGWVQN 3084 AQSRGQGFTAPAQTGWVQN 3044 AQSIGQGFHAQAQTGWVQN 3085 AQMSGAERDAQAQTGWVQN 3045 AQSTGVGFTSQAQTGWVQN 3086 AQSTGQGTTAQALTGWVQN 3046 AQIGSMMEKAQAQTNCVQN 3087 AQSTGQGFTAQAQTGECQN 3047 AQSTGQGVQAQAQTGWVQN 3088 ASSTGQGPTAQAQTGWVQN 3048 EQKTGQGFT AQA QTGWV QN 3089 TQSTGQGFTAQAVTGWVQN 3049 AQIGANNEKAQAQTGWVQN 3090 AQIGAYNEKAQAQTGWVQN 3050 AQWSMNEKAQAQTGWVQN 3091 ATSTGSGFTAQAQTGWVQN 3051 AQIGSMNEKAQAQTERVQN 3092 AQ1GSMNEKAQAQTFQVQN 3052 AQIGSMNEKAQAQTGWVGN 3093 AQSTTQGFTAQCQTGWVQN 3053 AQIGSMNEKAQASVGWVQN 3094 AQIGSMNESSQAQTGWQN 3054 AQSTGQGTTQQAQTGWVQN 3095 ALSTGQGTTAQAQTGWVQN 3055 AQSTGQGSTIQAQTGWVQN 3096 AQIGGVNEKAQAQTGWVQN 3056 AQSTAQGTTAQAQTGWVQN 3097 YYSTGQGFTAQAQTGTVQN 3057 AQIGSALEKAQAQTGWVQN 3098 AQSMGQGNTAQAQTGWVQN 3058 AQSTGQGFRAQADTGWVQN 3099 AQIGSMNEKAQAQTESVQN 3059 AQIGSMNEKAQAQTLMVQN 3100 AQIGSMNEKAQAQTGAVQN 3060 AQSTGQGATARAQTGWVQN 3101 AQSTGQGSYAQAQTGWVQN 3061 AGDTGQGFTAQAATGWVQN 3102 AQ1GSMNEKAQAQTLHVQN 3062 AQSTGQGFTAQAQTMRVQN 3103 SGIGSMNEKAQAQTGWVQN 3063 ARSTGQGFTANAQTGWVQN 3104 AQSTGQGFTAAADTGXWQN 3064 AQKEGQGFTAQAQTGWVQN 3105 HQSTNQGFTAQAQTGWVQN 3065 AQQEGQGFTAQAQTGWVQN 3106 ADISGAELRAQAQTGWVQN 3066 AQSHDQGFTAQVQTGWVQN 3107 AQSTGQGNFAQAQTGWVQN 3067 AQSTNQGTTAQAQTGWVQN 3108 AQ1LSMNEKAQAQTGWVQN 3068 ANVGSMNEKAQAQTGWVQN 3109 AQSTQVGFTAQAQTGWVQN 3069 AQIGSMNEKAQAQGSWVQN 3110 AQSTGQGRMAQAQTGWVQN 3070 AQSTGQGFTSQAATGWVQN 3111 AQMSGAELIKQAQTGWVQN 3071 AQMSGAEHQAQAQTGWVQN 3112 AQSTIQGLTAQAQTGWVQN 3072 AQMSGATERAQAQTGWVQN 3113 AQSTGQGNTAQPQTGWVQN 3073 AQSTGQGFQAIAQTGWVQN 3114 WQSTGQGGTAQAQTGWVQN 3074 FQSTGQNFTAQAQTGWVQN 3115 AQSPGQGFTAPAQTGWVQN 3075 YQSTGQGMTAQAQTGWVQN 3116 AQSTGQGLTNQAQTGWVQN 3076 AQIGLNNEKAQAQTGWVQN 3117 AQIGSMNEKAQAQTDNVQN 3077 AQSTGQSFHAQAQTGW'VQN 3118 AQ1GSMNEKAQAQTKWVQN 3078 AQGNGQGFTAQAQTGWVQN 3119 AQSTGQSFIG4QAQTGWVQN 3079 AQSTGQGFTAQAQTQKVQN 3120 DQSSGQGFTAQAQTGWVQN

[0505]

[0506] 3080 AQSTGQGKTDQAQTGWVQN

[0507]

[0508] 3121 AQMTTAELRAQAQTGWVQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 3122 AQSTAQGFTAQAGTGWVQN 3163 AQIGSMNEEVQAQTGWVQN 3123 YQSTGSGFTAQAQTGWVQN 3164 AQSLDQGFTAQAQTGWVQN 3124 AQSTWGFTAQAQTGWVQN 3165 RQSTGQGDTAQAQTGWVQN 3125 AQIGSMNEKAQAQTEYVQN 3166 ATSTGQGFTHQAQTGWVQN 3126 AFPSGAELRAQAQTGWVQN 3167 AQIGSMNEKAQAQTMRVQN 3127 AQIGSMNEKAQAQMDWVQN 3168 AQATGQGFTAQAQTGWVQN 3128 AQIGSYAEKAQAQTGWVQN 3169 AQIGSMNEKAQAAWGWVQN 3129 AQSTGQGLDAQAQTGWVQN 3170 VKIG SMNEKAQAQTGWVQN 3130 ATSPGQGFTAQAQTGWVQN 3171 AQIGSMNEKAQAQTVDVQN 3131 AQSVGQGFTAQALTGWVQN 3172 AQIGSMNEKAQAQTVPVQN 3132 AQSTNQGFTAQATTGWVQN 3173 AQSTGQGFTAQAQTGWLQN 3133 AQIGGQNEKAQA QTGWV QN 3174 AQSTGQEFTAQIQTGWVQN 3134 PNMSGAELRAQAQTGWVQN 3175 EQ STGQGGTAQAQTGWVQN 3135 AQSTGQPLTAQAQTGWVQN 3176 AQSTGQGFQHQAQTGPVQN 3136 AQNTGQSFTAQAQTGWVQN 3177 AQSTGQGFTAQAQGAWVQN 3137 AQIGSMNEKAQAQDMWVQN 3178 AQMSGAELRQQAQTGWVQN 3138 AQSQGQAFTAQAQTGWVQN 3179 SQSTGQGFIAQATTGWVQN 3139 AQIGSMNEKAQAQTTRVQN 3180 AQIGNSNEKAQAQTGWVQN 3140 TQSTGQGFTAPAQTGWVQN 3181 AQIGSMNEKAQAQTAWQN 3141 AQIGSTLEKAQAQTGWVQN 3182 AQIGTHNEKAQAQTGWVQN 3142 AQIGSMNEKAQAQTFEVQN 3183 AQIGSMNEKAQAQTWQVQN 3143 AQSTGQPHTAQAQTGWVQN 3184 AQSTGQGATAQGQTGWVQN 3144 AQIGSMNQAAQAQTGWVQN 3185 AQMSGAELKNQAQTGWVQN 3145 AQSTGQVFTNQAQTGWVQN 3186 AQMSGAELRAQAQTNQVQN 3146 AQSTGQGFTAQAQTGANQN 3187 AQ1GSMNEKAQAQAEWVQN 3147 AQSTGQGLTAQCQTGWVQN 3188 WQSTGQGVTAQAQTGWVQN 3148 AQIGSMNEKAQAERGWVQN 3189 AQIGSMNEKAQAQTEKVQN 3149 HQSTGQGATAQAQTGWVQN 3190 AQSTGQGFTAQAQTGWVHF 3150 QQGTGQGFTAQAQTGWVQN 3191 AQSTIQGNTAQAQTGWVQN 3151 AQSAGQGGTAQAQTGWVQN 3192 AQIGSMNEKAQAQTVQVQN 3152 AQSTQQGTTAQAQTGWVQN 3193 AQSTGQGHTAPAQTGWVQN 3153 NQSTGQGRTAQAQTGWVQN 3194 AQIGSNfNEKAQAQTDRVQN 3154 AQIGSMNDRAQAQTGWVQN 3195 AQSTGKGETAQAQTGWVQN 3155 AQSRGQGETAQAQTGWVQN 3196 ADSTGQGKTAQAQTGWVQN 3156 AQIGVNNEKA. QAQTGWVQN 3197 AQSTGQGGTAQASTGWVQN 3157 KQSTGQGQTAQAQTGWVQN 3198 APSTGQGGTAQAQTGWVQN 3158 AQSTGQYDTAQAQTGWVQN 3199 AQTTGQGFTAIAQTGWVQN 3159 AHSTGQGFTAQATTGWVQN 3200 AQMSGAELRAQAQTGWTQN 3160 AQDLGAELRAQAQTGWVQN 3201 AQPTGQGFIAQAQTGWVQN 3161 VQSTGQGFTAQAVTGWVQN 3202 AQSTGQGSTAQAWTGWVQN

[0509]

[0510] 3162 AQSTGQGNTIQAQTGWVQN

[0511]

[0512] 3203 AQIGSMNEKAQAQTDTVQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 3204 ALSTGQGGTAQAQTGWVQN 3245 AQIGSMNEKAQAQTVAVQN 3205 AQIGQNNEKAQAQTGWVQN 3246 AQMSGAENHAQAQTGWVQN 3206 AQSQGQGITAQAQTGWVQN 3247 EQSTGQGFTSQAQTGWVQN 3207 YQSTGQGNTAQAQTGWVQN 3248 AQMSGAENSAQAQTGWVQN 3208 AQSTGQGFTAQAQCEWVQN 3249 AQSTGQGFTAQAQADWVQN 3209 AVHGSMNEKAQAQTGWVQN 3250 AQSTGQGFTTQASTGWVQN 3210 ATSTGQGFIAQAQTGWVQN 3251 AQIGSMNEKAQAQSVWVQN 3211 AISTAQGFTAQAQTGWVQN 3252 AQSTGQGDAAQTQTGWVQN 3212 AQSTGQGQTAQAQDGWVQN 3253 AQSQGQGITAQAQTGWVQN 3213 AQSTGQGFSAPAQTGWVQN 3254 AQIGSGPEKAQAQTGWVQN 3214 AQSTGQGNTAQGQTGWVQN 3255 AQSTGQGQTQQAQTGWVQN 3215 AQSTGNGQTAQAQTGWVQN 3256 AQSTGQPVTAQAQTGWVQN 3216 AQMSGAELIIQAQTGWVQN 3257 AQSTGTGETAQAQTGWVQN 3217 AQMTSMNEKAQAQTGWVQN 3258 AQSTTQGFTLQAQTGWVQN 3218 ATSTGQGFTAQVQTGWVQN 3259 AQMSGAELRAQAQTGYVQN 3219 AQSTLQGVTAQAQTGWVQN 3260 NQSTGQGATAQAQTGWVQN 3220 AQSTGQGDYAQAKTGWVQN 3261 AQSTGQGPHAQAQTGWVQN 3221 AISGSMNEKAQAQTGWVQN 3262 AQIGSMNEKAQAQTL YVQN 3222 AQIGSMNEKAQAQTIYVQN 3263 AQIGSMNEKAQAQTTLVQN 3223 AQMSGAELRAQAQTWMVQN 3264 AQQTTQGFTAQAQTGWVQN 3224 APSTGQNFTAQAQTGWVQN 3265 AQIGSMNEKAQAQVYWVQN 3225 AQ1GSMNEYSQAQTGWVQN 3266 AQSTGNGFVAQAQTGWVQN 3226 AHSTGQGETAQAQTGWVQN 3267 AQSTGQNFTEQAQTGWVQN 3227 AQMSGAEQRAQAQTGWVQN 3268 AQSTGDGKTAQAQTGWVQN 3228 AQSTMQGQTAQAQTGWVQN 3269 AQ1GSMNEKAQAFVGWVQN 3229 AQSTGQGFTAQAQSQWVQN 3270 AQIGSMNEKAQAQTQWQN 3230 AQSTGQGDAAQAQTGWVQN 3271 AQSTGQGTFAQAMTGWVQN 3231 AQPTGQDFTAQAQTGWVQN 3272 AQ1GHTNEKAQAQTGWVQN 3232 AQIGSMNEKAQAQTEVVQN 3273 AQIGSMNEKAQAQTQFVQN 3233 MQSTGQGHTAQAQTGWVQN 3274 AQSTGQDTTAQAMTGWVQN 3234 A1STGQGQTAQAQTGWVQN 3275 AQSTGQGQDAQAQTGWVQN 3235 AQITGQGFTAQAVTGWVQN 3276 AQIGSMNEKAQAQTSWVQN 3236 AGSTGQGFTNQAQTGWVQN 3277 AQIGSMNEKAQAQTWEVQN 3237 ADSTGGGFTAQAQTGWVQN 3278 AQSTGAGFTAQCQTGWVQN 3238 WQSTGQGLTAQAQTGWVQN 3279 AQIGSMNEKAQAQEEWVQN 3239 AQSTGAGFTAQAATGWVQN 3280 AQSTGQGYTQQAQTGWVQN 3240 AQIGSMNEKAQAQTCTVQN 3281 ATSTGQGFTAQCQTGWVQN 3241 AQTTGAELRAQAQTGWVQN 3282 AQ1GSMNEKAQAQTTVVQN 3242 GQSTGQGFTAQVQTGWVQN 3283 AQSTGQIFTGQAQTGWVQN 3243 MQIGSMNEKAQAQTGWVQN 3284 AQSTGQGITAQQQTGAWQN

[0513]

[0514] 3244 AQSTGQGFTTIAQTGWVQN

[0515]

[0516] 3285 AQMSGAELRAQAQTSRVQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 3286 ANHGSMNEKAQAQTGWVQN 3327 AQNTGQGQTAQAQTGWVQN 3287 AWSTGQGFTANAQTGWVQN 3328 ANSTDQGFTAQAQTGWVQN 3288 AQPTKQGFTAQAQTGWVQN 3329 AQSTGQGFTAQAQTDQVQN 3289 AQSTGQGNIAQTQTGWVQN 3330 ASHTGQGFTAQAQTGWVQN 3290 AQIGSMNEKAQAQTDDVQN 3331 AQSTGAGFTLQAQTGWVQN 3291 AQSTGQGTTGQAQTGWVQN 3332 AQSTGQGPTAQGQTGWVQN 3292 AQSTGQASTAQAQTGWVQN 3333 AQSTGQGDTQQAQTGWVQN 3293 AQSTGQGFTAQAQTGNIQN 3334 AQIG SHEEKAQAQTGWVQN 3294 AQMSGAELRAQAQTSIVQN 3335 AQSTGQGFTAQAQTGWCAN 3295 AQIGSMNEKAQAQTGRVQN 3336 AQIGSANEKAQAQTGWVQN 3296 AQIGSMNEKAQAQTLQVQN 3337 AQSTTQGFHAQAQTGWVQN 3297 AQSTGQGNTAQCQTGWVQN 3338 AQIGSMNEKAQAQTLNVQN 3298 AQSTGQGHTAQGQTGWVQN 3339 LQSQGQGFTAQAQTGWVQN 3299 HQSTGQGNTAQAQTGWVQN 3340 AQSTGQGFTAHATTGWVQN 3300 AQIGSMNEKAQAQQQWVQN 3341 AQMSGAEHAAQAQTGWVQN 3301 AQEKSMNEKAQAQTGWVQN 3342 AMSTGQGSTAQAQTGWVQN 3302 AQSTGQTFTAQSQTGWVQN 3343 YQSTQQGFTAQAQTGWVQN 3303 AQSTGQGTTAQPQTGWVQN 3344 AQSTGQGMIAQAQTGWVQN 3304 ATSTGQGFTKQAQTGWVQN 3345 AQRTGQGFTAQASTGWVQN 3305 AQGYSMNEKAQAQTGWVQN 3346 FQSTGQGFTAQAKTGWVQN 3306 AQSTGQGFTADGQTGWVQN 3347 AQSNGQGFTLQAQTGWVQN 3307 AQSTGQGAVAQAQTGWVQN 3348 AQSTGATFTAQAQTGAVQN 3308 AQIGSQQEKAQAQTGWVQN 3349 AQIGSYNEKAQAQTGWVQN 3309 AQQQGQGFTAQAQTGKVQN 3350 GPMSGAELRAQAQTGWVQN 3310 AQAAGAELRAQAQTGWVON 3351 ALVTGQGFTAQAQTGWVQN 3311 AQSTGQGDTAQQQTGWVQN 3352 AQVTGQGHTAQAQTGWVQN 3312 AQIGNGNEKAQAQTGWVQN 3353 AQSTGQGFTAQAQTLKVQN 3313 AQIGSMNEKAQIATGWVQN 3354 AQ1GSMNEAEQAQTGWVQN 3314 AQMSGADIRAQAQTGWVQN 3355 HQSTGQGFTAQAATGWVQN 3315 AQIGSMDSKAQAQTGWVQN 3356 AQSTGQGSTQQAQTGXWQN 3316 AQSTGQGTT A QVQTGWVQN 3357 AQIGSMGDKAQAQTGWVQN 3317 ALSTGQDFTAQAQTGWVQN 3358 AQIGTGNEKAQAQTGWVQN 3318 SISTGQGFTAQAQTGWVQN 3359 AQIGSMNEKAQA QTWHVQN 3319 AQSEKQGFTAQAQTNWVQN 3360 AQSTGQSFQAQAQTGWVQN 3320 AQSTQQGFTAQTQTGWVQN 3361 AQSTGQGFTAQAQTGWVHV 3321 AQSTGQGTTAQMQTGWVQN 3362 AQSTGQGFTAQAQTMKVQN 3322 AQSTGQGFTVQPQTGWVQN 3363 AQIGSMNEKAQAQTADVQN 3323 A V AGS MNEKAQ AQTGW V QN 3364 AQSTGQNFTAQCQTGWVQN 3324 AQIAAMNEKAQAQTGWVQN 3365 AQSTGQGRTAQMQTGWVQN 3325 AVSSGQGFTAQAQTGWVQN 3366 AQIG SMNEKAQAQTTAVQN

[0517]

[0518] 3326 AQMSGAELARQAQTGWVQN

[0519]

[0520] 3367 AQSIGQGFTNQAQTGWVQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 3368 AQIGSMNEKAQSQTGWVQN 3409 AQSTGAGYTAQ AQTGWVQN 3369 QQSTGQGLTAQAQTGWVQN 3410 AQMSGAELRAQAQTYNVQN 3370 AQSTGQGLNAQAQTGWVQN 3411 AQIGSMNEKAQAQTGWVLN 3371 TPIGSMNEKAQAQTGWVQN 3412 AQGTGQGFTAQGQTGWVQN 3372 AQSGGQGLTAQAQTGWVQN 3413 AVSTGQGQTAQAQTGWVQN 3373 AQIGSMNEKAQAQTGWPQN 3414 AQSTQQGHTAQAQTGWVQN 3374 FQSTNQGFTAQAQTGWVQN 3415 AQGQGQGFTAQAQTGWVQN 3375 AQSTNQGGTAQAQTGWVQN 3416 DQSTGQGFTAQAATGWVQN 3376 AQIGSMNEKAQA QGA WVQN 3417 AQSTGQGl'I A QA ITGW VQN 3377 AQIGSMNEKAQAQTYKVQN 3418 AQSAGQGFTHQAQTGWVQN 3378 A SSTGQGQT AQ AQTGWVQN 3419 AQSTGSGDTAQAQTGWVQN 3379 HQSAGQGFTAQAQTGWVQN 3420 AQSTLQGITAQAQTGWVQN 3380 AQMSGAETYAQAQTGWVQN 3421 AQMSGAEGKAQAQTGWVQN 3381 AQSTGQGFTAQAQTGNAQN 3422 AQSTGQGFNANAQTGWVQN 3382 AQSTGQGFTTLAQTGWVQN 3423 GQSTGQGFTNQAQTGWVQN 3383 AQSEGQGHTAQAQTGWVQN 3424 AQQLSMNEKAQAQTGWVQN 3384 AQSPGQGFTAQCQTGWVQN 3425 AQIGSTNEKAQ AQTGWVQN 3385 AQSTGTGFTAQASTGWVQN 3426 AQSTGQIQTAQAQTGWVQN 3386 AQMSGAELRAQAQTYSVQN 3427 ATSTGQGFTAQASTGWVQN 3387 AQPISMNEKAQAQTGWVQN 3428 AQSTGQGFTPQPQTGWVQN 3388 AQSTGQGQTAQAITGWVQN 3429 AQSTGQGHEAQAQTGWVQN 3389 AQIGSMNEKAQAQTARVQN 3430 AQMSGAELRAQAQTGWVHN 3390 AGSTGQGFTPQAQTGWVQN 3431 HQSGGQGFTAQAQTGWVQN 3391 ASSNGQGFTAQAQTGWVQN 3432 AQIGSMNEKAQAQTVGVQN 3392 AQRTGQGFTAQAGTGWVQN 3433 AQDTGQGHTAQAQTGWVQN 3393 AASTGQGTTAQAQTGWVQN 3434 AAATGQGFTAQAGTGWVQN 3394 AQIGSMNEKAQPATGWVQN 3435 AQIGSMNEKAQAQTNKVQN 3395 AASTQQGFTAQAQTGWVQN 3436 APSTGQGFTAQAQTGWVQN 3396 AQTMSMNEKAQAQTGWVQN 3437 AQSTGQVDTAQAQTNWVQN 3397 AQIGSMNRIAQAQTGWVQN 3438 AQIGSMNEKAQSGTGWVQN 3398 AQSTGQGRNAQAQTAWVQN 3439 AQMSGAELGQQAQTGWVQN 3399 LPSTGQGFTAQAQTGWVQN 3440 AQSTQQGFTAIAQTGWVQN 3400 AQSTGQGGTAQAMTGWVQN 3441 AQIGSMNEKAQA QTIM VQN 3401 AQSTGQGHTAGAQTGWVQN 3442 AQSTGQGFTFQPQTGWVQN 3402 FQSTGQGFTVQAQTGWVQN 3443 DQSNGQGFTAQAQTGWVQN 3403 AQSTGQGFTAQAQTGWQQN 3444 AQIGSMNEKAQA QTGWVQV 3404 APSTGQGFTQQ AQTGWVQN 3445 AQSTGQGFQAQCQTGWVQN 3405 AQSTGNGFTATAQTGWVQN 3446 AQSTGQGQRAQAQTGWVQN 3406 AQIGASNEKAQAQTGWVQN 3447 AQSTGQGGTAIAQTGWVQN 3407 AQIGSMNEKAQL STGWVQN 3448 AQSTGQGTTFQAQTGWVQN

[0521]

[0522] 3408 AQIGSMNEKAQAQTAEVQN

[0523]

[0524] 3449 AQIGSMNEKAQPSTGWVQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 3450 AQSTGQGVMAQAQGGWVQN 3491 AQVTGQGYTAQAQTGWVQN 3451 AQEPSMNEKAQAQTGWVQN 3492 AQIGSMNEKAQAQTENV QN 3452 AQSTGQGFTAQAQTGWVDT 3493 AQIGSGAEKAQAQTGWVQN 3453 AQIGSMNEKAQAQTLWVQN 3494 AQSTGQGDMAQAQTGWVQN 3454 AQMSGATVRAQAQTGWVQN 3495 AQIGSMNEKAQAGGGWVQN 3455 AQIGSMNETAQAQTGWVQN 3496 AQDTGQGGTAQAQTGWVQN 3456 AQSHGTGFTAQAQTGWVQN 3497 AGQTGQGFTAQAQAGWVQN 3457 AQIGSMNEKAQAQTDCVQN 3498 AQSNGQGFIAQAQTGWVQN 3458 APSTGQGDTAQAQTGWVQN 3499 AQSTGQGFTAQAQTMDVQN 3459 AVLTGQGFTAQAQTGWVQN 3500 AQIGSMMQKAQAQTGWVQN 3460 AQIGSATEKAQAQTGWVQN 3501 AHQGSMNEKAQAQTGWVQN 3461 AQIGSMNEKAQSSTGWVQN 3502 AQSTGNGFTAQAVTGWVQN 3462 AQMSGAELRAQAQTSNVQN 3503 AQSTGQGVTAQGQTGWVQN 3463 AQSTGQGFTAQAQTGWCEN 3504 AHPGSMNEKAQAQTGWVQN 3464 AQIGSMNEKAQAQAQWVQN 3505 AQSTGQGHTAMAQTGWVQN 3465 AQSTGQNFTHQAQTGWVQN 3506 AQSTGQGFTAQCATGWVQN 3466 AQSTGQGFTAQAQTGNNQN 3507 AQSVGQGLTAQAQTGWVQN 3467 YMSTGQGFTAQAQTGWVQN 3508 AQIGSMNEKAQAVPGWVQN 3468 AQSEGQGFTASAQTGWVQN 3509 AQMSGAELRAQAATGWVQN 3469 AQMTGQNFTAQAQTGWVQN 3510 AQMSGAELQTQAQTGWVQN 3470 AQIGSMNEKAQAQIVWVQN 3511 AQPTGQGQTAQAQTGWVQN 3471 AQSLGQGFTAQADTGWVQN 3512 AQIGSMNEKAQAQGFWVQN 3472 WQSTGQGYTAQAQTGWVQN 3513 ATSTGQGFTNQAQTGWVQN 3473 FQSTQQGFTAQAQTGWVQN 3514 ES STGQGFTAQAQTGWVQN 3474 AQIGSMNEKAQAQTTMVQN 3515 AQISAMNEKAQAQTGWVQN 3475 AQIGSMNEKAQAQNIWVQN 3516 AQSTI-ITGFTAQAQTGWVQN 3476 AQIGSMNEKAQAQIEWVQN 3517 AQIVNMNEKAQAQTGWVQN 3477 LQSTGQGFVAQAQTGWVQN 3518 AQSTGVGFTMQAQTGWVQN 3478 AQSTGQSNTAQAQTGWVQN 3519 AQSTGQGFTYQAATGWVQN 3479 AQMSGAEDIAQAQTGWVQN 3520 AQINAMNEKAQAQTGWWQN 3480 AQSTGAGFTAQAQTGSVQN 3521 A LSTGQGETA QAQTGWVQN 3481 AQSLGQGLTAQAQTGWVQN 3522 AQSTGQKFTATAQTGWVQN 3482 AQIGSMNEKAQAQTCKVQN 3523 AQSTGQGFTAQAQNIWVQN 3483 AQSTGQGPTEQAQTGWVQN 3524 AHSTGQDFTAQAQTGWVQN 3484 PISTGQGFTAQAQTGWVQN 3525 AMSGSMNEKAQAQTGWVQN 3485 YQSGGQGFTAQAQTGWVQN 3526 AQMSGAELRAQAQTYPVQN 3486 AQSTQQGFTPQAQTGWVQN 3527 AQSTDQGHTAQAQTGWVQN 3487 AQGFSMN EKAQ AQTGW VQN 3528 AGNTGQGFTAQAQTGWVQN 3488 AQSTGQGFTASPQTGWVQN 3529 AQMSGAELRAQAQTTGVQN 3489 AQFTGQGSTAQAQTGWVQN 3530 AQVTGQGFTAIAQTGAWQN

[0525]

[0526] 3490 AQSTGGGFAAQAQTGWVQN

[0527]

[0528] 3531 SQIGSMNEKAQAQTGWVQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 3532 AQSTGQGQLAQAQTGVVQN 3573 AQIG VQNEKA QA QTGWVQN 3533 AQIGSMNEKAQAQAIWVQN 3574 SYSTGQGFTAQAQTGWVQN 3534 AQSTVQGFTAQVQTGWVQN 3575 AQVQSMNEKAQAQTGWVQN 3535 AQDTGQGKTAQAQTGWVQN 3576 AQSTIQGFTIQAQTGWVQN 3536 AQSTGQGTTAQAMTGWVQN 3577 AQSTNQGFTASAQTGWVQN 3537 AQIGSMNEKAQAQTGTVQN 3578 AQSTGQGSTYQAQTGWVQN 3538 AQSTIQGSTAQAQTGWVQN 3579 AQSSGQGFTAQAETGWVQN 3539 AQIGSMNEKAQAQTGHVQN 3580 AQSPGQGFTKQAQTGWVQN 3540 AQSTGGGGTAQAQTGWVQN 3581 AQANSMNEKAQAQTGWVQN 3541 YQSPGQGFTAQAQTGWVQN 3582 AQSTGQGNTWQAQTGWVQN 3542 AQSTGQGLTAQAYTGWVQN 3583 ATSQGQGFTAQAQTGWVQN 3543 ASSTGQGFTGQAQTGWVQN 3584 AQMSGAEQAAQAQTGWVQN 3544 FQSTGQGFTDQAQTGWVQN 3585 YQSTGQGGTAQAQTGWVQN 3545 AQMNHAELRAQAQTGWVQN 3586 HQPTGQGFTAQAQTGWVQN 3546 AQIGSMTAKAQAQTGWVQN 3587 AQSNGQGFTAQAVTGWVQN 3547 AQLTGQGFTAQATTGWVQN 3588 AGSTGQGFTVQAQTGWVQN 3548 ASSTGQGTTAQAQTGWVQN 3589 AQMSGAELRAQAQTDRVQN 3549 AGSTGQGTTAQAQTGWVQN 3590 AQSSGQGFTAQATTGWVQN 3550 AQIGSMNEKAQAQTVIVQN 3591 AQMSGAMTRAQAQTGWVQN 3551 ANTTGQGFTAQAQTGWVQN 3592 AQSTGQGDIAQAMTGWVQN 3552 AVSTGQGFTAQALTGWVQN 3593 AQIGSMNEKAQAQTSHVQN 3553 AQSTGQGFTAQPATGWVQN 3594 AQ1GSMNEKAQAQTGYVQN 3554 DPSTGQGFTAQAQTGWVQN 3595 AQTTGQGFTAPAQTGWVQN 3555 AQESSMNEKAQAQTGWVQN 3596 AQIGSMNEKAQAQTSPVQN 3556 AQSTGQGETAMAQTGWVQN 3597 AQA1SMNEKAQAQTGWVQN 3557 AIAGSMNEKAQAQTGWVQN 3598 ADSTNQGFTAQAQTGWVQN 3558 ALSTGQGFTAQATTGWVQN 3599 AQIGMGNEKAQAQTGVA'QN 3559 AQQTGQGTTAQAQTGWVQN 3600 MQSTGQGKTAQAQTGWVQN 3560 AQSIGQGFTAQSQTGWVQN 3601 AQSTGQTFTAQAGTGVWQN 3561 AQISQMNEKAQAQTGWVQN 3602 ALIGSMNEKAQAQTGWVQN 3562 AQSGGVGFTAQAQTGWVQN 3603 AQSTGQGFTAQAQTGSTQN 3563 AQGLGAELRAQAQTGWVQN 3604 AQSTGNGFTQQAQTGWVQN 3564 AQSTGQGHTAQPQTGWVQN 3605 AQSTGQGGTGQAQTGWVQN 3565 AV STGQGYTAQAQTGW VQN 3606 A1STGQGFTAQASTGWVQN 3566 AQSTQQGVTAQAQTGWVQN 3607 AQSTGQGLTAQASTGWVQN 3567 AQSTGQGFTAQAQTGWVQS 3608 AQSTGQGMTAQCQTGWVQN 3568 AQIGSMNEKAQAQTIWVQN 3609 AQSLGQGFTAQTQTGWVQN 3569 AQIGSMNEKAQAQTWYVQN 3610 AQ1GQANEKAQAQTGWVQN 3570 AQIGSMNEKMQAQTGWVQN 3611 AQIGSMNEKAQASGGWVQN 3571 CQSTGQGTTAQAQTGWVQN 3612 AQIG SMNEKAQAQSDWVQN

[0529]

[0530] 3572 AQSTGQGRTAQPQTGWVQN

[0531]

[0532] 3613 AQSTGQGATTQAQTGWVQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 3614 AQSGGQGDTAQAQTGWVQN 3655 AQSEGQGNTAQAQTGWVQN 3615 AQSTGQGPTAQEQTGWVQN 3656 AQSTGQGNTFQAQTGWVQN 3616 AQIGSMNEKAQAQTGWX^NN 3657 WQSTGQGSTAQAQTGWVQN 3617 AQSSGEGFTAQAQTGWVQN 3658 AQSTGQGATANAQTGWVQN 3618 AQIGSMNEVIQAQTGWVQN 3659 AQIGSMNEKAQAQRS WVQN 3619 AQSTGQGFTQQAMTGWVQN 3660 AQTYSMNEKAQAQTGWVQN 3620 AQIGSMNEKAQAQTDLVQN 3661 AQSTTQGFTAQATTGWVQN 3621 NQSQGQGFTAQAQTGWVQN 3662 AQIGSSSEKAQAQTGWVQN 3622 AQSSGQGGTAQAQTGWVQN 3663 AQSTGQGFTAQAAQGWVQN 3623 AQSTGQGNTAQAFTGWVQN 3664 ANSTGEGFTAQAQTGWVQN 3624 AQSTGQGSTSQAQTGWVQN 3665 AQGTGQGYTAQAQTGWVQN 3625 AQIGS MNEK AQA QT Al. A QN 3666 AQSTGQGSHAQAQTGWVQN 3626 AQHTGQGFTAQAATGWVQN 3667 AQIGSMNEKAQGSTGWVQN 3627 NAMSGAELRAQAQTGWVQN 3668 AQIGSMTVKAQAQTGWVQN 3628 AQSSGGGFTAQAQTGWVQN 3669 AASTGQGGTAQAQTGWVQN 3629 AQSTGQGSTAQAYTGWVQN 3670 AQSTGQGFTAQAQTGTNQN 3630 AQ1THMNEKAQAQTGWVQN 3671 AQIGSMNERQQAQTGWVQN 3631 AQSTGQGFTAQAQSSWVQN 3672 AQIGSEHEKAQAQTGWVQN 3632 AQTTGQGFTAQTQTGWVQN 3673 AQSTGQGFTAQAQTGWISN 3633 AQMANAELRAQAQTGWVQN 3674 AQSTGQGQTAQALTGWVQN 3634 AQSQGQGFTAQMQTGWVQN 3675 AQIG SMNEKAQAQTQNVQN 3635 AQSTGQNFEAQAQTGWVQN 3676 AQSTGQGKTAQAWTGWVQN 3636 AQMSGAELRAQAQSIWVQN 3677 AQNTGAELRAQAQTGWVQN 3637 AQIGSMNEVLQAQTGWVQN 3678 AQIGSMNEKAQAQTWRVQN 3638 AQIGLGNEKAQAQTGWVQN 3679 AQVTGQGNTAQAQTGWVQN 3639 AISTGQGITAQAQTGWVQN 3680 AQMSGAELRAQAQTMRVQN 3640 AQIGSMNEYQQAQTGWVQN 3681 AQSTGQGDTAQMQTGWVQN 3641 NQSTGQGSTAQAQTGWVQN 3682 AQSLGQGFTMQAQTGWVQN 3642 AQMSGAELRAQAQTSHVQN 3683 AQIGSNfNEKAQAQTGNVQN 3643 AQSTVQGYTAQAQTGWVQN 3684 AQIGSSTEKAQAQTGWVQN 3644 AQSTTQGFTQQAQTGWVQN 3685 NQSTGQGFTVQAQTGWVQN 3645 AQIGSMNEKAQAQTIDVQN 3686 AQSTGQGGTAQIQTGWVQN 3646 AQSTGQGFASQAQTGPVQN 3687 AQSTGQGFTA1ADTGWVQN 3647 AQSTGQGFNMQAQTGWVQN 3688 AQSTGQGFNALAQTGWVQN 3648 DQATGQGFTAQAQTGWVQN 3689 AQIGSMNEKAQAQTDIVQN 3649 AQ1GSMNEKAQAQTNLVQN 3690 AQIGPQNEKAQAQTGWVQN 3650 AQIGSMNEKAQAQTNGVQN 3691 AQMSGAELRAQAQTQVVQN 3651 PNIGSMNEKAQAQTGWVQN 3692 AQSTGQGLAAQFQTGWVQN 3652 AQSTGAGFVAQAQTGWVQN 3693 AQPQGAELRAQAQTGWVQN 3653 AQSTGQQSTAQAQVGWVQN 3694 ANSPGQGFTAQAQTGWVQN

[0533]

[0534] 3654 AQSTAQGFTANAQTGWVQN

[0535]

[0536] 3695 AQIGSMNEKAQAQTQWVQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 3696 AQ1GSMNEKAQAQTYNVQN 3737 AQIQSMNEKAQAQTGWVQN 3697 AQSTIQGQTAQAQTGWVQN 3738 AQSTGQGFKIQAQTGWVQN 3698 AQSTGGGFTCQAQTGWVQN 3739 AQMSGAELRAQAQSQWVQN 3699 AQPTGQGFTAQIQTGWVQN 3740 MPIGSMNEKAQAQTGWVQN 3700 AQSTGQGFTTQPQTGWVQN 3741 AQIGSMNEKAQAQTSCVQN 3701 AREGSMNEKAQAQTGWVQN 3742 ARSTGEGFTAQAQTGWVQN 3702 AQQTGQGPTAQAQTGWVQN 3743 TTIGSMNEKAQAQTGWVQN 3703 AVVGSMNEKAQAQTGWVQN 3744 AQMSGAELRAQPSTGWVQN 3704 AQIGSMNEKAQAQTISVQN 3745 AQSTGQPATAQAQTGWVQN 3705 AQIGSMNEKAQAQTA1VQN 3746 AQSTGEAFTAQAQTQWVQN 3706 AQSTGQGQTAQTQTGWVQN 3747 AQSTGQGSTAQPQTGWVQN 3707 AQSTGQGFTAMANTGWVQN 3748 AQNTGQGLTAQAQTGWVQN 3708 QVIGSMNEKAQAQTGWVQN 3749 AQSVGQGFQAQAQTGWVQN 3709 AQATGQNFTAQAQTGWVQN 3750 AQAIGQGFTAQAQTGWVQN 3710 YQSTGQGTTAQAQTGWVQN 3751 AQSAGQGSTAQAQTGWVQN 3711 AQIGSMNEKAQTATGWVQN 3752 GQSTGQGFTAQPQTGWVQN 3712 VQSTGQGITAQAQTGWVQN 3753 AQIGSMNEKAQAQGTWVQN 3713 AQSTGQGFTAQAQTQPVQN 3754 AQSTGNSFTAQAQTGWVQN 3714 AQNTGQGFTAQASTGWVQN 3755 AHGSGAELRAQAQTGWVQN 3715 AQSTGQGNTAQFQTGWVQN 3756 AQSTGQGFTAQVTTGWVQN 3716 HQSTGQGSTAQAQTGWVQN 3757 QI-nGSMNEKAQAQTGWVQN 3717 AQMSGAF. T1AQAQTGWVQN 3758 AQSTGQGFTAQPNTGWVQN 3718 AQATGQGFTATAQTGWVQN 3759 AVSTGQGFTAQTQTGWVQN 3719 NQSTGQGQTAQAQTGWVQN 3760 AQSTGQGHTAQFQTGWVQN 3720 AQIGSMDGKAQAQTGWVQN 3761 AQSNGQGITAQAQTGWVQN 3721 AHISGAELRAQAQTGWVQN 3762 AQIGSRfNEKAQAQEAWVQN 3722 AQSTNQGSTAQAQTGWVQN 3763 AQSTYQGETAQAQTGWVQN 3723 AQIGHNNEKAQAQTGWVQN 3764 AQSTGQGTQAQAYTGWVQN 3724 AQSAGQGFTAQAGTGWVQN 3765 AQNIGAELRAQAQTGWVQN 3725 AQIGSMNEKAWQTGWVQN 3766 AQSTGQGKTAYAQTGWVQN 3726 HQSTSQGFTAQAQTGWVQN 3767 AQIGSMNEKAQAQTFKVQN 3727 AQIGSMNERPQAQTGWVQN 3768 AQSTGQGTIAQAQTGV7VQN 3728 AQ1GSMNEKAQAQTEWVQN 3769 TS STGQGFTAQAQTGWV QN 3729 AQNTGQLFTAQAQTGWVQN 3770 AAPTGQGFTAQAQTGWVQN 3730 AQIGSMNEKAQAFTGWVQN 3771 RQSTGQGMTAQAQTGWVQN 3731 AQ1NSMNEKAQAQTGWVQN 3772 AQMSGADARAQAQTGWVQN 3732 AQIGSMNEKAQAQITWVQN 3773 QQSTGQLFTAQAQTGWVQN 3733 ALATGQGFTAQAQMGWVQN 3774 AQSTGQGHHAQAQTGWVQN 3734 AQPIGQGFTAQAQQGWVQN 3775 AQSGGQGFTAQAATGWVQN 3735 AQSTGQGPNAQAQTGWVQN 3776 AQSTGQGTTAQASTGWVQN

[0537]

[0538] 3736 QQSTGQGFTQQAQTGWVQN

[0539]

[0540] 3777 AQSTGQGFAAPAQTGWVQN Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ ID ID NO VR-VIII amino acid sequence NO VR-VIII amino acid sequence 3778 AQSTAQGFNAQAQTGWVQN 3799 AQSTGQGGTEQAQTGWVQN 3779 IQSTGQGMTAQAQTGWVQN 3800 AQSTGQGFTAQAQTGTAQN 3780 AQSDGQGITAQAQTGWVQN 3801 AQSIGQGFTSQAQTGWVQN 3781 AQIGMNNEKAQAQTGWVQN 3802 AQMSQNELRAQAQTGWVQN 3782 HQSTLQGFTAQAQTGWVQN 3803 AQIGSMNEKAQAQCNWVQN 3783 AASTGQGFTNQAQTGWVQN 3804 AQGHSMNEKAQAQTGWVQN 3784 AQSAGQGFTIQAQTGWVQN 3805 AYSTGEGFTAQAQTGWVQN 3785 AQSTMQGYTAQAQTGWVQN 3806 AQETGQGETAQAQTGWVQN 3786 CQIGSMNEKAQAQTGWVQN 3807 AQQTGQGFNAQAQTGWVQN 3787 AQSTGQEHTAQAGTGWVQN 3808 AQSSGQGHTAQAQTGWVQN 3788 AQSTGQGFTAQAQQTWVQN 3809 EKSTGQGFTAQAQQGWVQN 3789 AQMSGAEKV AQ AQTGWV QN 3810 AQIGSMNEKAQAQTKDVQN 3790 AHSTGQGFTAQTQTGWVQN 3811 AQMSGAELMQQAQTGWVQN 3791 AQIGSMNEHCQAQTGWVQN 3812 APSTGQGMTAQAQTGWVQN 3792 AQSTGQGDTVQAQTGWVQN 3813 AQMSGAELRAP1QTGWVQN 3793 AQTTGQGFTAQAMTGWVQN 3814 ASSTGQGFQAQAQTGWVQN 3794 DQSTGQGFTPQAQTGWVQN 3815 AQIGSMNEKAQAQGEWVQN 3795 AQIGSMNEKAQAQTNRVQN 3816 VQGTGQGFTAQAQTGWVQN 3796 ATSTGQGFTAQANTGWVQN 3817 AQMSAGELRAQAQTGWVQN 3797 AQIGMTNEKAQAQTGWVQN

[0541]

[0542] 3818 AQETHQGFTAQAQTGWVQN

[0543]

[0544] 3798 AQIGSMNHNAQAQTGWVQN

[0545] Formula V

[0546] Aspects of the present invention provide an adeno-associated virus (AAV) capsid protein comprising an amino acid sequence having at least 85% identity to a sequence of Formula V:

[0547] Xi E-X2E-X3E-X4E-X5E-X6E-X7E (V)

[0548] wherein,

[0549] XIE is an amino acid selected from N, G, Q, L, V, A, M, S, H, D, T, I, Y, or E; X? E is an amino acid selected from G, K, H, N, R, S, T, Q, E, or M;

[0550] XSE is an amino acid selected from G, T, A, D, S, V, P, N, H, or Q;

[0551] X4E is an amino acid selected from G, T, S, Q, P, or A;

[0552] XSE is an amino acid selected from S, Q, N, A, T, M, G, K, H, or R; Patent Application CAPS -041 / 01 WO 35847 / 197 XeE is an amino acid selected from N, S, K. T, Q, G, A, or R: and

[0553] X? E is an amino acid selected from Q, K, S. T, N, M, G, E, H, or I.

[0554] In preferred aspects of the invention,

[0555] XIE may be selected from among N, G, or Q;

[0556] X? Emav be selected from among G, K, or H;

[0557] Xarmay be selected from among G, T, or A;

[0558] X4Emay be selected from among G, T, or S;

[0559] XsEinay be selected from among S, Q, or N;

[0560] iEmay be selected from amon N, S, or K,

[0561] X? Emay be selected from among Q, K, or S.

[0562] In aspects of the invention, XIE is located at parental residue 452 and X? E is located at parental residue 458 in reference to a parental AAV9 capsid or equivalent residue position in another AAV capsid, wherein in Formula V any or XIE through X? E (corresponding to residues 452-458) may independently be a parental or substituted amino acid.

[0563] Capsids of the present invention comprising a sequence of Formula V may comprise the following sequences with the initial amino acids RTI corresponding to amino acids at the location relative to parental residues 449-451 and the final amino acids QT representing the amino acids at the location relative to parental residues 459-460.

[0564] Table 5: Formula V sequences

[0565] SEQ SEQ SEQ ID VR-IV amino acid ID VR-IV amino acid ID VR-IV amino acid NO sequence NO sequence NO sequence

[0566] 3819 RTINGSGQNQQT 3825 RT1SGTGQNQQT 3831 RTINKGTSSQQT 3820 RTIQGTGQNQQT 3826 RTIGGTGQNQQT 3832 RTILGTGQNQQT 3821 RTIHGAGQNQQT 3827 RTINGTGQNQQT 3833 RTINQTGQNQQT 3822 RTIAGTGQNQQT 3828 RTILGAGQNQQT 3834 RTINQAGQNQQT 3823 RTINGAGQNQQT 3829 RT1DRGTSSQQT 3835 RTIQGAGQNQQT 3824 RTIVGTGQNQQT 3830 RTIGGAGQNQQT 3836 RTINGGGQNQQT

[0567]

[0568]

[0569]

[0570] Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ SEQ SEQ ID VR-IV amino acid ID VR-IV amino acid ID VR-IV amino acid NO sequence NO sequence NO sequence

[0571] 3837 RTINKGTSQQQT 3876 RTIMGAGQNQQT 3915 RTINKGTSTQQT 3838 R'TTNKTTSQQQT 3877 RTINGHGQNQQT 3916 RTINKGTSSMQT 3839 RTIHGTGQNQQT 3878 RTIGGDSSKQQT 3917 RTIVKGTSSQQT 3840 RTINKGTSSNQT 3879 RTINKGTSSTQT 3918 RTIQKSTSSQQT 3841 RTINGAGQNKQT 3880 RTIQKGSSSQQT 3919 RTINHGTTSQQT 3842 RTINKGSSSQQT 3881 RTINKSTSSQQT 3920 RTINHGTSSQQT 3843 RTIGGDSSRQQT 3882 RT1NKGQSNQQT 3921 RTINKGSSNQQT 3844 RTINKATTSQQT 3883 RTINKGTSSIQT 3929 RTINKGSSTQQT 3845 RTINNTGQNQQT 3884 RTINSAGQNQQT 3923 RTINGVGQNQQT 3846 RTINKGTSSSQT 3885 RTTNKGTSQTQT 3924 RTIAKTTSSQQT 3847 RTIGGDSSKHQT 3886 RTITKTTSSQQT 3925 RTINGAGQKQQT 3848 RTIGGSSSKQQT 3887 RTINKGTSSGQT 3926 RTINKGTNTQQT 3849 RTIIGTGQNQQT 3888 RTIYGAGQNQQT 3927 RTINGAGQNMQT 3850 RTIVGAGQNQQT 3889 RTINGTGQSQQT 3928 RTINNGTSSKQT 3851 RTINKGQSSQQT 3890 RTIQKGTSSQQT 3929 RT1NTAGQNQQT 3852 RTINNAGQNQQT 3891 RTINKGSSSNQT 3930 RTINGTGMNQQT 3853 RTIQKGTSSSQT 3892 RTINTTGQNQQT 3931 RTIQGDSSKQQT 3854 RT1NKGTQSQQT 3893 RTILKGQSSQQT 3932 RTINKGASSQQT 3855 RTIGGQSSKQQT 3894 RTINMTGQNQQT 3933 RTINKGTSAQQT 3856 RTIDKGTSSKQT 3895 RTIVKNTSSQQT 3934 RTIGGVSSKQQT 3857 RTIAGAGQNQQT 3896 RTINKGTQSSQT 3935 RTINKTTASQQT 3858 RTINKGPSTQQT 3897 RT1NKGGSSTQT 3936 RTINKGTSTSQT 3859 RTINGTGQGQQT 3898 RTIGGGSSKQQT 3937 RTINKGTSTNQT 3860 RTIIGAGQNQQT 3899 RTTNKGQSQQQT 3938 RTINKGTNSQQT 3861 RTINKGTSTQQT 3900 RT1NSTGQNQQT 3939 RTIGHDSSKQQT 3862 RT1SGAGQNQQT 3901 RT1YGTGQNQQT 3940 RTINEGTRSQQT 3863 RTINKGTQNQQT 3902 RTINGTGQNKQT 3941 RTINKATSSQQT 3864 RTINKGTSNQQT 3903 RTIGRDSSKQQT 3942 RTIVKGQSSQQT

[0572]

[0573] 3865 RTINGGTKSQQT 3904 RTINKGTQQQQT

[0574] 3866 RTIGGDSHKQQT 3905 RT1GGDSMKQQT

[0575] 3867 RTINRGTSSEQT 3906 RTIQKATSSQQT

[0576] 3868 RTIGGDSSKKQT 3907 RTINKGTSQSQT

[0577] 3869 RTINKGTASQQT 3908 RTTNKGTGTQQT

[0578] 3870 RTIMGTGQNQQT 3909 RTINKSPSSQQT

[0579] 3871 RT1NKGTATQQT 3910 RT1NGTGTNQQT

[0580] 3872 RTIIGAGQNQQT 3911 RTINGAGNNQQT

[0581] 3873 RTIERGTSSQQT 3912 RTINGTGQNMQT

[0582] 3874 RTINKGTSNSQT 3913 RT1NGPGQNQQT

[0583] 3875 RTIQHGTSSQQT 3914 RTIQKGQSSQQT

[0584]

[0585]

[0586] Patent Application CAPS -041 / 01 WO 35847 / 197

[0587] Formula VI

[0588] Aspects of the present invention provide an adeno-associated vims (AAV) capsid protein comprising an amino acid sequence having at least 85% identity to a sequence of Formula VI:

[0589] XIF-X2F-G-X1F-X5F-A-X7F-N-Q (VI)

[0590] wherein,

[0591] XIF is an amino acid selected from N or V;

[0592] X2F is an amino acid selected from K or L;

[0593] XFF is an amino acid selected from G, Q, T, or V;

[0594] XSF is an amino acid selected from S or G; and

[0595] X7p is an amino acid selected from G, A, N, Q, or T.

[0596] In preferred aspects of the invention,

[0597] X4F may be selected from G, Q, or I;

[0598] X7F may be selected from G, A, or N.

[0599] In aspects of the invention, IF is located at parental residue 452 in reference to a parental AAV9 capsid or equivalent residue position in another AAV capsid, wherein in Formula VI:

[0600] XIF is a parental or substituted amino acid,

[0601] six amino acids X7F, G, X4F, SF, A, X7Fare inserted, with four residues substituting positions 453 and 456 relative to the parental capsid; and

[0602] N-Q are parental amino acids located at parental residues 457-458, now residues 459-460.

[0603] Capsids of the present invention comprising a sequence of Formula VI may comprise the following sequences with the initial amino acids RTI corresponding to amino acids at the location relative to parental residues 449-451 and the final amino acids NQQT representing the amino acids at the location relative to parental residues 457-460 (now residue 459 to 462, Patent Application CAPS -041 / 01 WO 35847 / 197 accommodating the inserted amino acids)

[0604] Table 6: Formula VI sequences

[0605] SEQ ID VR-IV amino acid

[0606] NO sequence

[0607] 3943 RTINKGGGAGNQQT

[0608] 3944 RTINKGQSAGNQQT

[0609] 3945 RTINKGGSAANQQT

[0610] 3946 RTINKGGSAQNQQT

[0611] 3947 R'TTNKGGSAGNQQT

[0612] 3948 RT1NKGGSATNQQT

[0613] 3949 RT1NKGVSAGNQQT

[0614] 3950 RTIVKGGSAGNQQT

[0615] 3951 RTINLGGSAGNQQT

[0616] 3952 RTINKGGSANNQQT

[0617]

[0618] 3953 RTINKGTSAGNQQT

[0619] Formula VII

[0620] Aspects of the present invention provide an adeno-associated vims (AAV) capsid protein comprising an amino acid sequence having at least 80% identity to a sequence of Formula VII:

[0621] X1G-G-X3G-X4G-X5G-X6G-X7G-X8G-X9G-X{0G-XJIG(VII) wherein

[0622] XIG is an amino acid selected from N, L, E, M, Q, S, or V;

[0623] X3G is an amino acid selected from P or G;

[0624] X4G is an amino acid selected from V, S, M, or A;

[0625] XSG is an amino acid selected from S, A, G, or Q;

[0626] XeG is an amino acid selected from S, T, G, or A;

[0627] X?ois an amino acid selected from G or N;

[0628] XSG is an amino acid selected from K or II;

[0629] X9G is an amino acid selected from Q, A or P;

[0630] Xioois an amino acid selected from N, A, S, or T; and Patent Application CAPS -041 / 01 WO 35847 / 197 XIIG is an amino acid selected from Q, M, A, N, S, T, or V.

[0631] In preferred aspects of the invention,

[0632] XIG may be selected from N, L, or E;

[0633] X4G may be selected from V, S, or M;

[0634] XSG may be selected from S, A, or G,

[0635] XgG may be selected from S, T, or G;

[0636] XIOG may be selected from N, A, or S;

[0637] Xi IG may be selected from Q, M, or A

[0638] In aspects of the invention, XIG is located at parental residue 452, wherein in Formula VII,

[0639] XIG is a parental or substituted amino acid;

[0640] G is a parental amino acid located at parental residue 453;

[0641] six amino acids XSG, X4G, XSG, XgG, X? G, XXG, are inserted, with two residues substituting positions 454 and 455 of the parental capsid; and

[0642] X9G, XIOG, and Xi JG are parental or substituted amino acids located at parental residues 456-458, now residues 460-462.

[0643] Capsids of the present invention comprising a sequence of and Formula VII may comprise the following sequences, with the initial amino acids RTI corresponding to amino acids at the location relative to parental residues 449-451 and the final amino acids QT representing the amino acids at the location rel tive to parental residues 459 and460 (now residue 463 and 464, accommodating the inserted amino acids).

[0644] Table 7: Formula VII sequences

[0645] SEQ ID VR-IV amino acid

[0646] NO sequence

[0647] 3954 RTTNGPVSTGKQNQQT

[0648] 3955 RTINGPVSSGKQSQQT

[0649] 3956 RTINGPVSSGKQNTQT

[0650] 3957 RTINGPS S S GKQNQQT

[0651]

[0652] 3958 RTINGPVS SNKQNQQT Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ ID VR-IV amino acid

[0653] NO sequence

[0654] 3959 RTINGPVSSGKQTQQT

[0655] 3960 RTINGPVSSGKQNVQT

[0656] 3961 RTINGPVSSGKQAQQT

[0657] 3962 RTINGPVSSGKQNQQT

[0658] 3963 RT1EGPVSSGKQNQQT

[0659] 3964 RTINGPVSAGKQNQQT

[0660] 3965 RTIVGPVSSGKQNQQT

[0661] 3966 RTINGPV S S GKQN SQT

[0662] 3967 RTINGPVGSGKQNQQT

[0663] 3968 RTINGPV A SGKQNQQT

[0664] 3969 RTINGPVSGGKQNQQT

[0665] 3970 RTILGPVSSGKQNQQT

[0666] 3971 RTINGPVS S GKQNA QT

[0667] 3972 RT1NGPVSSGKQNMQT

[0668] 3973 RTINGPMSSGKQNQQT

[0669] 3974 RTINGGVSSGKQNQQT

[0670] 3975 RT1NGPVQSGKQNQQT

[0671] 3976 RTINGPV S S GKQNN QT

[0672] 3977 RTIQGPVSSGKQNQQT

[0673] 3978 RTISGPVSSGKQNQQT

[0674] 3979 RTINGPV S S GHQN QQT

[0675] 3980 RTINGPASSGKQNQQT

[0676] 3981 RTINGPVS SGKPNQQT

[0677] 3982 RTINGPV S S GK AN QQT

[0678]

[0679] 3983 RTIMGPVSSGKQNQQT

[0680] Aspects of the present invention comprise AA V capsid protein comprising an amino acid sequence having at least 80% identity to either: (i) the 7-mer insertion, KPPGYLL (SEQ ID NO: 4994), included between substitutions of G, S, and A in positions 587, 589, and 590 of the parental capsid, or (ii) the resulting capsid sequence NHQSGQKPPGYLLSAAQ (SEQ ID NO: 4995) at positions 583-592 (now 599 with the 7-mer insertion) of parental capsid.

[0681] Aspects of the present invention comprise an AAV capsid protein comprising: (i) an amino acid substitution and / or insertion sequence at positions 583-607 (including the 7-mer amino acid insertion) having at least 80% identity to a sequence provided in Table 1 or Table 2; and (ii) an amino acid substitution and / or insertion sequence at position 452-458 having at least 80% identity to a sequence as provided in Tables 5, Table 6, and / or Table 7.

[0682] Aspects disclosed herein provide AAV capsids comprising an AAV capsid protein comprising a 583-607 sequence and a corresponding substitution and / or insertion between Patent Application CAPS -041 / 01 WO 35847 / 197 positions 452-458, as set forth in Table 8.

[0683] Table 8: Combined VR-IV and VR-VII1 sequences

[0684] SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[0685] ID sequence ID

[0686] NO NO

[0687] 3819 RTINGSGQNQQT 3984 NHQSAVKDGHVLIAMAQTAGVQNQG

[0688] 3819 RTINGSGQNQQT 3985 NIIQSAVKDGHVLIAMAQTSNVQNQG

[0689] 3819 RTINGSGQNQQT 3986 NHQSAVKDGHVLIAMAQTNAVQNQG

[0690] 3819 RTINGSGQNQQT 3987 NHQSASRNGEVYIAQAQTAQVQNQG

[0691] 3819 RTINGSGQNQQT 3988 NIIQSAVKDGHVLIAMAQTSPVQNQG

[0692] 3819 RTINGSGQNQQT 3989 NHQSAVKDGHVLIAMAQTGSAQNQG

[0693] 3819 RTINGSGQNQQT 3990 NHQSAVKDGHVLIAMAQTGTAQNQG

[0694] 3819 RTINGSGQNQQT 3991 NHQSAVKDGHVLIAMAQTGNAQNQG

[0695] 3819 RTINGSGQNQQT 3992 NHQS ASRNGEV YTA Q A QTS AVQNQG

[0696] 3819 RTINGSGQNQQT 3993 NHQSASRNGEVYIAQAQTSQVQNQG

[0697] 3819 RTINGSGQNQQT 3994 NHQSASRNGEVYIAQAQTDKVQNQG

[0698] 3819 RTINGSGQNQQT 3995 NHQS ASRNGEV YIAQAQTEKVQN QG

[0699] 3819 RTINGSGQNQQT 3996 NHQSAVKDGHVL1AMAQTTGVQNQG

[0700] 3819 RTINGSGQNQQT 3997 NHQSAVKDGHVLIAMAQTGSNQNQG

[0701] 3819 RTINGSGQNQQT 3998 NI-IQSAVKDGHVLIAMAQTAQVQNQG

[0702] 3819 RTINGSGQNQQT 3999 NHQSATRNGEVHIAMAQTSGVQNQG

[0703] 3819 RTINGSGQNQQT 4000 NHQSAVfCDGHVLIAMAQTQSVQNQG

[0704] 3819 RTINGSGQNQQT 4001 NHQSASRNGEVYIAQAQTTAVQNQG

[0705] 3819 RTINGSGQNQQT 4002 NHQSAVKDGHVLIAMAQTGSCQNQG

[0706] 3819 RTINGSGQNQQT 4003 NHQSSTKNGEVF1AQAQTSNVQNQG

[0707] 3819 RTINGSGQNQQT 4004 NHQSAVKDGHVLIAMAQTSAVQNQG

[0708] 3819 RTINGSGQNQQT 4005 NHQSAVKDGHVLIAMAQTGGIQNQG

[0709] 3819 RTINGSGQNQQT 4006 NHQSASRNGEVYIAQAQTGQVQNQG

[0710] 3819 RTINGSGQNQQT 4007 NHQSASRNGEVYIAQAQTGWCHNQG

[0711] 3819 RTINGSGQNQQT 4008 NHQSAVKDGHVLIAMAQTSSVQNQG

[0712] 3819 RTINGSGQNQQT 4009 NHQSATRNGEVHIAMAQTSMVQNQG

[0713] 3819 RTINGSGQNQQT 4010 NHQSASRNGEVYIAQAQTTKVQNQG

[0714] 3819 RTINGSGQNQQT 4011 NHQSAVKDGHVLIAMAQTGNTQNQG

[0715] 3819 RTINGSGQNQQT 4012 NHQSAVKDGHVLIAMAQTQNVQNQG

[0716] 3819 RTINGSGQNQQT 4013 NHQS A SRNGE V Y1AQ AQTAG VQN QG

[0717] 3819 RTINGSGQNQQT 4014 NHQSASRNGEVYIAQAQTTQVQNQG

[0718] 3819 RTINGSGQNQQT 4015 NHQSAVKDGHVLIAMAQTGTVQNQG

[0719] 3819 RTINGSGQNQQT 4016 NHQSASRNGEVYIAQAQTGWVNSQG

[0720] 3819 RTINGSGQNQQT 4017 NHQSASRNGEVYIAQAQTSGVQNQG

[0721] 3819 RTINGSGQNQQT 4018 NHQSAVKDGHVLIAMAQTGGAQNQG

[0722]

[0723] 3819 RTINGSGQNQQT 4019 NHQSSTKNGEVFIAQAQTGSVQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-TV amino acid SEQ VR-VIII amino acid sequence

[0724] ID sequence ID

[0725] NO NO

[0726] 3819 RTINGSGQNQQT 4020 NHQSATRNGEVHIAMAQTSYVQNQG

[0727] 3819 RTINGSGQNQQT 4021 NHQSAVKDGHVLIAMAQTGPAQNQG

[0728] 3820 RTIQGTGQNQQT 4022 NHQSSTKNGEVFIAQAQTGWVQNQG

[0729] 3819 RTINGSGQNQQT 4023 NHQSATRNGEVHIAMAQTMAVQNQG

[0730] 3819 RTINGSGQNQQT 4024 NHQSAVKDGHVLIAMAQTGQVQNQG

[0731] 3819 RTINGSGQNQQT 4025 NHQSAVKDGHVLIAMAQTNQVQNQG

[0732] 3819 RTINGSGQNQQT 4026 NHQSASRNGEVYIAQAQTNQVQNQG

[0733] 3819 RTINGSGQNQQT 4027 NHQSATKNGEVFIAQAQTGGVQNQG

[0734] 3819 RTINGSGQNQQT 4028 NHQSSTKNGEVFIAQASTGYVQNQG

[0735] 3819 RTINGSGQNQQT 4029 NHQSAVKDGHVLIAMAQTGGTQNQG

[0736] 3819 RTINGSGQNQQT 4030 NI-IQSAVKDGHVLIAMAQTATVQNQG

[0737] 3819 RTINGSGQNQQT 4031 N HQS ASRNGEV YTA QA QTQQ VQNQG

[0738] 3819 RTINGSGQNQQT 4032 NHQSASRNGEVYIAQAQTIQVQNQG

[0739] 3819 RTINGSGQNQQT 4033 NHQSASRNGEVYIAQAQTGQCQNQG

[0740] 3819 RTINGSGQNQQT 4034 NI-IQSAVKDGHVLIAMAQTGATQNQG

[0741] 3819 RTINGSGQNQQT 4035 NHQSASRNGEVYTAQAQTVQVQNQG

[0742] 3819 RTINGSGQNQQT 4036 NHQSAVKDGHVLIAMAQTGGVQNQG

[0743] 3819 RTINGSGQNQQT 4037 NHQSAVKDGHVLIAMAQTGSVQNQG

[0744] 3819 RTINGSGQNQQT 4038 NHQSASRNGEVYIAQAQTAWVQNQG

[0745] 3819 RTINGSGQNQQT 4039 NHQSSTKNGEVFIAQAQTGWVQNCG

[0746] 3821 RTIHGAGQNQQT 4040 NHQSSTKNGEVFIAQAQTGWVQNQG

[0747] 3819 RTINGSGQNQQT 4041 NHQSATRNGEVHIAMAQTMGVQNQG

[0748] 3819 RTINGSGQNQQT 4042 NHQSAVKDGHVL1AMAQTGMIQNQG

[0749] 3819 RTINGSGQNQQT 4043 NI-IQSAVKDGHVLIAMAQTSTVQNQG

[0750] 3819 RTINGSGQNQQT 4044 NHQS ASRNGEV YIA Q A QTNMVQNQG

[0751] 3819 RTINGSGQNQQT 4045 NHQSASRNGEVYIAQAQTAYVQNQG

[0752] 3819 RTINGSGQNQQT 4046 NHQSASRNGEVY1AQAQTLQVQNQG

[0753] 3819 RTINGSGQNQQT 4047 NI-IQSAVKDGHVLIAMAQTGAIQNQG

[0754] 3819 RTINGSGQNQQT 4048 NHQSAVKDGHVLIAMAQTQQVQNQG

[0755] 3819 RTINGSGQNQQT 4049 NHQSAVKDGHVLIAMAQTGQCQNQG

[0756] 3819 RTINGSGQNQQT 4050 NHQSAVKDGHVLIAMAQTGVAQNQG

[0757] 3819 RTINGSGQNQQT 4051 NHQSSTKNGEVFIAQAQTGNVQNQG

[0758] 3819 RTINGSGQNQQT 4052 NHQSASRNGEVYTAQAQTGWVQNQA

[0759] 3819 RTINGSGQNQQT 4053 NHQSAVKDGHVLIAMAQTTQVQNQG

[0760] 3819 RTINGSGQNQQT 4054 NHQSASRNGEVYIAQAQTSMVQNQG

[0761] 3819 RTINGSGQNQQT 4055 NHQSATKNGEVFIAQAQTGWVQNQG

[0762] 3819 RTINGSGQNQQT 4056 NHQSAVKDGHVLIAMAQTASVQNQG

[0763] 3819 RTINGSGQNQQT 4057 NHQSASRNGEVYIAQAQTGWVNQQG

[0764] 3819 RTINGSGQNQQT 4058 NHQSSTKNGEVF1AQAQTAWVQNQG

[0765]

[0766] 3819 RTINGSGQNQQT 4059 NHQSAVKDGHVLIAMAQTGQMQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-TV amino acid SEQ VR-VIII amino acid sequence

[0767] ID sequence ID

[0768] NO NO

[0769] 3819 RTINGSGQNQQT 4060 NHQSATRNGEVHIAMAQTNAVQNQG

[0770] 3822 RTIAGTGQNQQT 4061 NHQSSTKNGEVFIAQAQTGWVQNQG

[0771] 3819 RTINGSGQNQQT 4062 NHQSAVKDGHVLIAMAQTGPTQNQG

[0772] 3819 RTINGSGQNQQT 4063 NHQSASRNGEVYIAQAQTQKVQNQG

[0773] 3823 RTINGAGQNQQT 4064 NHQSSTKNGEVFIAQAQTGWVQNQG

[0774] 3819 RTINGSGQNQQT 4065 NHQSASRNGEVYIAQAQTGWVNNQG

[0775] 3819 RTINGSGQNQQT 4066 NHQSAVKDGHVLIAMAQTGMAQNQG

[0776] 3819 RTINGSGQNQQT 4067 NHQSAVKDGHVLIAMAQTGAAQNQG

[0777] 3819 RTINGSGQNQQT 4068 NHQSASRNGEVYIAQAQTMGVQNQG

[0778] 3819 RTINGSGQNQQT 4069 NHQSASRNGEVY1AQAQTGWVYNQG

[0779] 3819 RTINGSGQNQQT 4070 NI-IQSAVKDGHVLIAMAQTSQVQNQG

[0780] 3819 RTINGSGQNQQT 4071 N HQS ASRNGEV YTA QA QTNKVQNQG

[0781] 3819 RTINGSGQNQQT 4072 NHQSSTKNGEVFIAQAQTYQVQNQG

[0782] 3819 RTINGSGQNQQT 4073 NHQSATKNGEVFIAQAQTGWVTNQG

[0783] 3819 RTINGSGQNQQT 4074 NI-IQSAVKDGHVLIAMAQTGPSQNQG

[0784] 3819 RTINGSGQNQQT 4075 NHQSAVKDGHVLIAMAQTGSIQNQG

[0785] 3824 RTIVGTGQNQQT 4076 NHQSSTKNGEVFIAQAQTGWVQNQG

[0786] 3819 RTINGSGQNQQT 4077 NHQSASRNGEVYIAQAQTNSVQNQG

[0787] 3819 RTINGSGQNQQT 4078 NHQSSTKNGEVFIAQAQTAGVQNQG

[0788] 3819 RTINGSGQNQQT 4079 NHQSAVKDGHVLIAMAQTGAVQNQG

[0789] 3819 RTINGSGQNQQT 4080 NHQSAVKDGHVLIAMAQTSGVQNQG

[0790] 3819 RTINGSGQNQQT 4081 NHQSATRNGEVHIAMAQTAYVQNQG

[0791] 3819 RTINGSGQNQQT 4082 N H QS A VKDGH VL I AMAQTGANQN QG

[0792] 3819 RTINGSGQNQQT 4083 NHQSAVKDGHVLIAMAQTNSVQNQG

[0793] 3819 RTINGSGQNQQT 4084 NHQSAVKDGHVLIAMAQTGNIQNQG

[0794] 3819 RTINGSGQNQQT 4085 NHQSSTKNGEVFIAQAQTNHVQNQG

[0795] 3819 RTINGSGQNQQT 4086 NHQSAVKDGHVLIAMAQTSMVQNQG

[0796] 3819 RTINGSGQNQQT 4087 NHQSASRNGEVYIAQAQTGWANNQG

[0797] 3819 RTINGSGQNQQT 4088 NHQSAVKDGHVLIAMAQTGSTQNQG

[0798] 3819 RTINGSGQNQQT 4089 NHQSSTKNGEVFIAQAQTKQVQNQG

[0799] 3819 RTINGSGQNQQT 4090 NHQS ASRNGEV YIAQAQTQFVQNQG

[0800] 3819 RTINGSGQNQQT 4091 NI-IQSASRNGEVYIAQAQTASVQNQG

[0801] 3819 RTINGSGQNQQT 4092 N HQS ATRN GE VHI AMAQ'FN S VQN QG

[0802] 3819 RTINGSGQNQQT 4093 NHQSSTKNGEVFIAQAQTQLVQNQG

[0803] 3819 RTINGSGQNQQT 4094 NHQSASRNGEVYIAQAQTGWNNNQG

[0804] 3819 RTINGSGQNQQT 4095 NHQSATRNGEVHIAIAQTGWVSNQG

[0805] 3819 RTINGSGQNQQT 4096 NHQSAVKDGHVLIAMAQTAPVQNQG

[0806] 3819 RTINGSGQNQQT 4097 NHQSSTKNGEVFIAQAQTGWVNYQG

[0807] 3819 RTINGSGQNQQT 4098 NHQSAVKDGHVLIAMAQTGSMQNQG

[0808]

[0809] 3819 RTINGSGQNQQT 4099 NHQSATRNGEVHIAMAQTASVQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[0810] ID sequence ID

[0811] NO NO

[0812] 3819 RTINGSGQNQQT 4100 NHQSATRNGEVHIAMAQTNGVQNQG

[0813] 3819 RTINGSGQNQQT 4101 NHQSAVKDGHVLIAMAQTGLVQNQG

[0814] 3825 RTISGTGQNQQT 4102 NHQSSTKNGEVFIAQAQTGWVQNQG

[0815] 3819 RTINGSGQNQQT 4103 NHQSSTKNGEVFIAQAQTNMVQNQG

[0816] 3819 RTINGSGQNQQT 4104 NHQSSTKNGEVF1AQAQTGWVYNQG

[0817] 3819 RTINGSGQNQQT 4105 NHQSASRNGEVYIAQAQTNWVQNQG

[0818] 3819 RTINGSGQNQQT 4106 NHQS AVKDGHVLIAMAQTGLAQN QG

[0819] 3819 RTINGSGQNQQT 4107 NHQSSTKNGEVFIAQSQTGSVQNQG

[0820] 3819 RTINGSGQNQQT 4108 NHQSSTKNGEVFIAQAQTNQVQNQG

[0821] 3819 RTINGSGQNQQT 4109 NHQSSTKNGEVFIAQAQTGAAQNQG

[0822] 3819 RTINGSGQNQQT 4110 NHQSSTKNGEVFIAQAQTTGVQNQG

[0823] 3819 RTINGSGQNQQT 4111 N HQS ASRNGEV YTA QA QTGWCNNQG

[0824] 3819 RTINGSGQNQQT 4112 NHQSATRNGEVHIAMAQTIGVQNQG

[0825] 3819 RTINGSGQNQQT 4113 NHQSATRNGEVHIAMAQTMSVQNQG

[0826] 3819 RTINGSGQNQQT 4114 NI-IQSASRNGEVYIAQAQTNFVQNQG

[0827] 3819 RTINGSGQNQQT 4115 NHQSAVKDGHVLIAMAQTGQAQNQG

[0828] 3819 RTINGSGQNQQT 4116 NHQSAVKDGHVLIAMAQTGQTQNQG

[0829] 3819 RTINGSGQNQQT 4117 NHQSATRNGEVHIAMAQTGYVQNQG

[0830] 3819 RTINGSGQNQQT 4118 NHQSSTKNGEVFIAQAQTGMVQNQG

[0831] 3819 RTINGSGQNQQT 4119 NHQSASRNGEVYIAQAQTVKVQNQG

[0832] 3819 RTINGSGQNQQT 4120 NHQSAVKDGHVLIAMAQTGQSQNQG

[0833] 3819 RTINGSGQNQQT 4121 NHQSAVKDGHVLIAMAQTGMVQNQG

[0834] 3819 RTINGSGQNQQT 4122 NHQSSTKNGEVFIAQAQTQAVQNQG

[0835] 3819 RTINGSGQNQQT 4123 NI-IQSATRNGEVHIAMAQTSAVQNQG

[0836] 3819 RTINGSGQNQQT 4124 NHOSASRNGEVY1AQAQTSWVQNQG

[0837] 3819 RTINGSGQNQQT 4125 NHQSASRNGEVYIAQAQTGWINNQG

[0838] 3826 RTIGGTGQNQQT 4126 NHQSSTKNGEVFIAQAQTGWVQNQG

[0839] 3819 RTINGSGQNQQT 4127 NHQGSTRNGEVFIAQAQTGWVNNQG

[0840] 3819 RTINGSGQNQQT 4128 NHQSSTKNGEVFIAQAQTTQVQNQG

[0841] 3819 RTINGSGQNQQT 4129 NHQSATRNGEVHIAIAQTGYVQNQG

[0842] 3819 RTINGSGQNQQT 4130 NHQSATKNGEVFIAQAQTGWVHNQG

[0843] 3819 RTINGSGQNQQT 4131 NI-IQSASRNGEVYIAQAQTGWVNDQG

[0844] 3819 RTINGSGQNQQT 4132 NHQSASRNGEVYTAQAQTVSVQNQG

[0845] 3819 RTINGSGQNQQT 4133 NHQSASRNGEVYIAQAQTGANQNQG

[0846] 3819 RTINGSGQNQQT 4134 NHQSASRNGEVYIAQAQTKMVQNQG

[0847] 3819 RTINGSGQNQQT 4135 NHQSASRNGEVYIAQAQTNGVQNQG

[0848] 3819 RTINGSGQNQQT 4136 NHQSSTKNGEVFIAQAQTVNVQNQG

[0849] 3827 RTINGTGQNQQT 4137 NHQSASRNGEVYIAQAQTGWVQNQG

[0850] 3828 RTILGAGQNQQT 4138 NHQSSTKNGEVFIAQAQTGWVQNQG

[0851]

[0852] 3819 RTINGSGQNQQT 4139 THQSAVKDGHVTIAMAQTGWVQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[0853] ID sequence ID

[0854] NO NO

[0855] 3819 RTINGSGQNQQT 4140 NHQSASRNGEVYIAQAQTGPSQNQG

[0856] 3819 RTINGSGQNQQT 4141 NHQSAVKDGHVLIAMAQTGMSQNQG

[0857] 3819 RTINGSGQNQQT 4142 NHQSAVKDGHVLIAMAQTGSSQNQG

[0858] 3819 RTINGSGQNQQT 4143 NHQSATKNGEVFIAQAQTGQVQNQG

[0859] 3819 RTINGSGQNQQT 4144 NHQSASRNGEVY1AQAQTGYVQNQG

[0860] 3819 RTINGSGQNQQT 4145 NHQSSTKNGEVFIAQAQTAQVQNQG

[0861] 3819 RTINGSGQNQQT 4146 NHQSAVKDGHVLIAMAQTGNVQNQG

[0862] 3819 RTINGSGQNQQT 4147 NHQSATRNGEVHIAMAQTAQVQNQG

[0863] 3819 RTINGSGQNQQT 4148 NHQSASRNGEVY1AQAQTGWAHNQG

[0864] 3819 RTINGSGQNQQT 4149 NHQS ASRNGE V Y1AQ AQTMQ V QNQG

[0865] 3819 RTINGSGQNQQT 4150 NHQSATRNGEVHLAMAQTGLSQNQG

[0866] 3819 RTINGSGQNQQT 4151 NHQSAVKDGHVLIAMAQTGQIQNQG

[0867] 3829 RTIDRGTSSQQT 4152 NHQSSTKNGEVFIAQAQTGWVQNQG

[0868] 3819 RTINGSGQNQQT 4153 NHQSSTKNGEVFIAQAQTGWVNNQG

[0869] 3819 RTINGSGQNQQT 4154 NHQSASRNGEVYIAQAQTMMVQNQG

[0870] 3830 RTIGGAGQNQQT 4155 NHQSSTKNGEVFIAQAQTGWVQNQG

[0871] 3819 RTINGSGQNQQT 4156 NHQSASRNGEVYIAQAQTGWSYNQG

[0872] 3819 RTINGSGQNQQT 4157 NHQSSTKNGEVFIAQAQVGAVQNQG

[0873] 3819 RTINGSGQNQQT 4158 NHQSASRNGEVYIAQAQTVPVQNQG

[0874] 3819 RTINGSGQNQQT 4159 NHQS ASRNGE VYIAQAQTGGAQNQG

[0875] 3819 RTINGSGQNQQT 4160 NHQSASRNGEVYIAQAQTGKVQNQG

[0876] 3826 RTIGGTGQNQQT 4161 NHQSASRNGEVYIAQAQTGWVQNQG

[0877] 3819 RTINGSGQNQQT 4162 NHQSATRNGEVHIAMAQTQQVQNQG

[0878] 3819 RTINGSGQNQQT 4163 NHQSSTKNGEVFIAQSQTGGVQNQG

[0879] 3819 RTINGSGQNQQT 4164 NHQS ASRNGEV YIA Q A QTLSVQNQG

[0880] 3819 RTINGSGQNQQT 4165 NHQSSTKNGEVFIAQAQTVHVQNQG

[0881] 3819 RTINGSGQNQQT 4166 NHQSSTKNGEVFIAQAQTGWVNMQG

[0882] 3819 RTINGSGQNQQT 4167 NHQSSTKNGEVFIAQAQTSWVQNQG

[0883] 3819 RTINGSGQNQQT 4168 NHQSASRNGEVYTAQAQTNNVQNQG

[0884] 3819 RTINGSGQNQQT 4169 NHQSASRNGEVYIAQAQVGWVQNQG

[0885] 3819 RTINGSGQNQQT 4170 NHQS ASRNGE VYIAQAQTGAAQNQG

[0886] 3819 RTINGSGQNQQT 4171 NHQSSTKNGEVFIAQAQTIQVQNQG

[0887] 3819 RTINGSGQNQQT 4172 NHQSAVKDGHVLIAMAQTGQNQNQG

[0888] 3819 RTINGSGQNQQT 4173 NHQSASRNGEVYIAQAQTGGNQNQG

[0889] 3819 RTINGSGQNQQT 4174 NHQSASRNGEVYIAQAQTGWQHNQG

[0890] 3819 RTINGSGQNQQT 4175 THQSSTKNGEVFIAQAQTGWVQNQG

[0891] 3819 RTINGSGQNQQT 4176 NHQS ASRNGE VYIAQAQTVAVQNQG

[0892] 3819 RTINGSGQNQQT 4177 NHQSAVKDGHVLIAMAQTGTIQNQG

[0893] 3819 RTINGSGQNQQT 4178 NHQSSTKNGEVF1AQAQTSGVQNQG

[0894]

[0895] 3819 RTINGSGQNQQT 4179 NHQSASRNGEVYIAQAQTGWGNNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[0896] ID sequence ID

[0897] NO NO

[0898] 3819 RTINGSGQNQQT 4180 NHQSASRNGEVYIAQAQTGQIQNQG

[0899] 3819 RTINGSGQNQQT 4181 NHQSSTKNGEVFIAQAQTQNVQNQG

[0900] 3819 RTINGSGQNQQT 4182 NHQSAVKDGHVLIAMAQTGWINNQG

[0901] 3819 RTINGSGQNQQT 4183 NHQSASRNGEVYIAQAQTSLVQNQG

[0902] 3819 RTINGSGQNQQT 4184 NHQSASRNGEVY1AQAQTGWVTSQG

[0903] 3819 RTINGSGQNQQT 4185 NHQSASRNGEVYIAQAQTGWVNFQG

[0904] 3819 RTINGSGQNQQT 4186 NHQSAVKDGHVL1AMAQTGGNQNQG

[0905] 3819 RTINGSGQNQQT 4187 NHQSSTKNGEVFIAQAQTGSTQNQG

[0906] 3819 RTINGSGQNQQT 4188 NHQSATRNGEVHIAMAQTSNVQNQG

[0907] 3819 RTINGSGQNQQT 4189 NHQSASRNGEVY1AQAQTAPVQNQG

[0908] 3819 RTINGSGQNQQT 4190 NHQSSTKNGEVFIAQAQTTAVQNQG

[0909] 3819 RTINGSGQNQQT 4191 NHQSAVKDGHVLIAMAQTGVVQNQG

[0910] 3819 RTINGSGQNQQT 4192 NHQSATRNGEVHIAMAQTTSVQNQG

[0911] 3819 RTINGSGQNQQT 4193 NHQS ASRNGE V YIAQ AQTAK VQN QG

[0912] 3819 RTINGSGQNQQT 4194 NI-IQSASRNGEVYIAQAQTGWVNGQG

[0913] 3819 RTINGSGQNQQT 4195 NHQSATRNGEVHIAMAQRGPVQNQG

[0914] 3831 RTINKGTSSQQT 4196 NHQSSTKNGEVFIAQAQTGWVQNQG

[0915] 3819 RTINGSGQNQQT 4197 NHQSASRNGEVYIAQAQTGWVNMQG

[0916] 3819 RTINGSGQNQQT 4198 NHQSSTKNGEVFIAQAQTFQVQNQG

[0917] 3819 RTINGSGQNQQT 4199 NHQSSTKNGEVFIAQAQTGWVNSQG

[0918] 3819 RTINGSGQNQQT 4200 NHQSSTKNGEVFIAQAQTAWQNQG

[0919] 3819 RTINGSGQNQQT 4201 NHQSATRNGEVHIAMAQTSQVQNQG

[0920] 3819 RTINGSGQNQQT 4202 NHQSASRNGEVY1AQAQTGQAQNQG

[0921] 3832 RTILGTGQNQQT 4203 NFIQSASRNGEVYIAQAQTGWVQNQG

[0922] 3819 RTINGSGQNQQT 4204 NHQS ASRNGEV YTA QA QTQGVQNQG

[0923] 3819 RTINGSGQNQQT 4205 NHQSSTKNGEVFIAQAQTGAVQNQG

[0924] 3819 RTINGSGQNQQT 4206 NHQSATKNGEVFIAQAQTMWVQNQG

[0925] 3819 RTINGSGQNQQT 4207 NI-IQSAVKDGHVLIAMAQTGPIQNQG

[0926] 3819 RTINGSGQNQQT 4208 N HQS ASRNGEV YTA Q A QTLNVQN QG

[0927] 3833 RTINQTGQNQQT 4209 NHQSSTKNGEVFIAQAQTGWVQNQG

[0928] 3819 RTINGSGQNQQT 4210 NHQSSTKNGEVFIAQASTNWVQNQG

[0929] 3819 RTINGSGQNQQT 4211 NHQSSTKNGEVFIAQAQVGQVQNQG

[0930] 3819 RTINGSGQNQQT 4212 N HQS ATRN GE VHI AMAQTGS VQN QG

[0931] 3819 RTINGSGQNQQT 4213 NHQSATRNGEVHIAIAQTGWVHNQG

[0932] 3834 RTINQAGQNQQT 4214 NHQSSTKNGEVFIAQAQTGWVQNQG

[0933] 3819 RTINGSGQNQQT 4215 NHQSASRNGEVYIAQAQTSNVQNQG

[0934] 3819 RTINGSGQNQQT 4216 NHQSAVKDGHVLIAMAQTTSVQNQG

[0935] 3835 RTIQGAGQNQQT 4217 NHQSSTKNGEVFIAQAQTGWVQNQG

[0936] 3819 RTINGSGQNQQT 4218 NHQSATRNGEVHIAMAQTGWVNSQG

[0937]

[0938] 3819 RTINGSGQNQQT 4219 NHQSSTKNGEVFIAQAQTNTVQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[0939] ID sequence ID

[0940] NO NO

[0941] 3819 RTINGSGQNQQT 4220 NHQSSTKNGEVFIAQAQTVSVQNQG

[0942] 3819 RTINGSGQNQQT 4221 NHQSSTKNGEVFIAQSQTGAVQNQG

[0943] 3819 RTINGSGQNQQT 4222 NHQSSTKNGEVFIAQAQTGNNQNQG

[0944] 3819 RTINGSGQNQQT 4223 NHQSSTKNGEVFIAQAQTKWQNQG

[0945] 3819 RTINGSGQNQQT 4224 NHQSSTKNGEVF1AQAQTQMVQNQG

[0946] 3819 RTINGSGQNQQT 4225 NHQSATRNGEVHIAMAQTGWVNFQG

[0947] 3819 RTINGSGQNQQT 4226 NHQSSTKNGEVFIAQAQTGQVQNQG

[0948] 3819 RTINGSGQNQQT 4227 NHQSAVKDGHVLIAMAQTQGVQNQG

[0949] 3819 RTINGSGQNQQT 4228 NHQSASRNGEVYIAQAQTMAVQNQG

[0950] 3819 RTINGSGQNQQT 4229 NHQSATRNGEVHIAMAQTQSVQNQG

[0951] 3819 RTINGSGQNQQT 4230 NI-IQSASRNGEVYIAQAQTAMVQNQG

[0952] 3819 RTINGSGQNQQT 4231 NHQSSTKNGEVFIAQAQTSTVQNQG

[0953] 3819 RTINGSGQNQQT 4232 NHQSATKNGEVFIAQAQTSWWQNQG

[0954] 3819 RTINGSGQNQQT 4233 NHQS ASRNGEV YIAQ AQTKQ VQN QG

[0955] 3819 RTINGSGQNQQT 4234 NI-IQSASRNGEVYIAQAQTYAVQNQG

[0956] 3819 RTINGSGQNQQT 4235 N HQGSTRN GE V YIAQ AQTGWVQN QG

[0957] 3819 RTINGSGQNQQT 4236 NHQSATRNGEVHIAIAQTGGVQNQG

[0958] 3819 RTINGSGQNQQT 4237 NHQSATRNGEVHIAMAQTAAVQNQG

[0959] 3836 RTINGGGQNQQT 4238 NHQSSTKNGEVFIAQAQTGWVQNQG

[0960] 3819 RTINGSGQNQQT 4239 NHQS ASRNGEV YIAQAQTSFVQNQG

[0961] 3832 RTILGTGQNQQT 4240 NHQSSTKNGEVFIAQAQTGWVQNQG

[0962] 3819 RTINGSGQNQQT 4241 NHQSSTKNGEVFIAQAQTNGVQNQG

[0963] 3819 RTINGSGQNQQT 4242 N H QS A S RN GE V YIAQ AQTG WMN N QG

[0964] 3819 RTINGSGQNQQT 4243 NHQSSTKNGEVFIAQAQTGVVQNQG

[0965] 3819 RTINGSGQNQQT 4244 N HQGSTRN GE VFI AQ AQTAWVQNQG

[0966] 3819 RTINGSGQNQQT 4245 NHQSASRNGEVYIAQAQTNHVQNQG

[0967] 3819 RTINGSGQNQQT 4246 NHQSSTKNGEVFIAQAQTLAVQNQG

[0968] 3819 RTINGSGQNQQT 4247 NHQSAVKDGHVLIAMAQTNPVQNQG

[0969] 3819 RTINGSGQNQQT 4248 N H QS A V KDGH VLI AM AQTT A VQN QG

[0970] 3819 RTINGSGQNQQT 4249 NHQSSTKNGEVFIAQAQTMGVQNQG

[0971] 3819 RTINGSGQNQQT 4250 NHQSATRNGEVHIAMAQTGSAQNQG

[0972] 3819 RTINGSGQNQQT 4251 NI-IQSAVKDGHVLIAMAQTGPVQNQG

[0973] 3819 RTINGSGQNQQT 4252 NHQSAVKDGHVLIAMAQTAAVQNQG

[0974] 3819 RTINGSGQNQQT 4253 NHQSATKNGEVFIAQAQTGAVQNQG

[0975] 3819 RTINGSGQNQQT 4254 NHQSSTKNGEVFIAQAQRGNVQNQG

[0976] 3819 RTINGSGQNQQT 4255 NHQSASRNGEVYIAQAQTGFVQNQG

[0977] 3819 RTINGSGQNQQT 4256 N HQS ATRN GE VHIAMAQTGAVQNQG

[0978] 3819 RTINGSGQNQQT 4257 NHQSSTKNGEVFIAQAQTGWVNDQG

[0979] 3819 RTINGSGQNQQT 4258 NHQSASRNGEVY1AQAQTTGVQNQG

[0980]

[0981] 3819 RTINGSGQNQQT 4259 NHQSSTKNGEVFIAQAQTGPVQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[0982] ID sequence ID

[0983] NO NO

[0984] 3819 RTINGSGQNQQT 4260 NHQSASRNGEVYIAQAQTGWVNAQG

[0985] 3819 RTINGSGQNQQT 4261 NHQSSTKNGEVFIAQAQRGPVQNQG

[0986] 3819 RTINGSGQNQQT 4262 NHQSASRNGEVYIAQAQTGWDNNQG

[0987] 3819 RTINGSGQNQQT 4263 NHQSATRNGEVHIAMAQTMQVQNQG

[0988] 3819 RTINGSGQNQQT 4264 NHQSSTKNGEVF1AQAQTGWVNHQG

[0989] 3827 RTINGTGQNQQT 4265 NHQSSTKNGEVFIAQAQTGWVQNQG

[0990] 3819 RTINGSGQNQQT 4266 NHQSAVKDGHVLIAMAQTGLTQNQG

[0991] 3819 RTINGSGQNQQT 4267 NHQSAVKDGHVLIAMAQTAMVQNQG

[0992] 3819 RTINGSGQNQQT 4268 NHQSSTKNGEVF1AQAQTGWVQNQA

[0993] 3819 RTINGSGQNQQT 4269 NHQSSTKNGEVFIAQAQTGNTQNQG

[0994] 3837 RTINKGTSQQQT 4270 NHQSSTKNGEVFIAQAQTGWVQNQG

[0995] 3819 RTINGSGQNQQT 4271 NHQSSTKNGEVFIAQSQTGPVQNQG

[0996] 3819 RTINGSGQNQQT 4272 NHQSASRNGEVYIAQAQTSPVQNQG

[0997] 3819 RTINGSGQNQQT 4273 NHQSSTKNGEVFIAQAQTSWQNQG

[0998] 3819 RTINGSGQNQQT 4274 NHQSSTKNGEVFIAQAQTGWVNQQG

[0999] 3819 RTINGSGQNQQT 4275 NHQSSTKNGEVFIAQAQTGWVSNQG

[1000] 3819 RTINGSGQNQQT 4276 NHQSSTKNGEVFIAQANTGKVQNQG

[1001] 3819 RTINGSGQNQQT 4277 NHQSASRNGEVYIAQAQTTYVQNQG

[1002] 3819 RTINGSGQNQQT 4278 NHQSASRNGEVYIAQAQTERVQNQG

[1003] 3819 RTINGSGQNQQT 4279 NHQSAVKDGHVLIAMAQTGFVQNQG

[1004] 3819 RTINGSGQNQQT 4280 NHQSAVKDGHVLIAMAQTGNSQNQG

[1005] 3838 RTINKTTSQQQT 4281 NHQSSTKNGEVFIAQAQTGWVQNQG

[1006] 3822 RT1AGTGQNQQT 4282 NHQSASRNGEVY1AQAQTGWVQNQG

[1007] 3819 RTINGSGQNQQT 4283 NHQSAVKDGHVLIAMAQTQAVQNQG

[1008] 3819 RTINGSGQNQQT 4284 NHQSATKNGEVFIAQAQTGSVQNQG

[1009] 3819 RTINGSGQNQQT 4285 NHQSATRNGEVHIAMAQTGNAQNQG

[1010] 3819 RTINGSGQNQQT 4286 NHQSSTKNGEVFIAQAQTANVQNQG

[1011] 3819 RTINGSGQNQQT 4287 NHQSASRNGEVYIAQAQTGWVHSQG

[1012] 3819 RTINGSGQNQQT 4288 NHQSASRNGEVYTAQAQTGAVQNQG

[1013] 3954 RTINGPVSTGKQNQQT 4289 NHQSASRNGEVYIAQAQTGWVQNQG

[1014] 3819 RTINGSGQNQQT 4290 NHQSAVKDGHVLIAMAQTGWVSNQG

[1015] 3819 RTINGSGQNQQT 4291 NHQSATRNGEVHIAMAQTNNVQNQG

[1016] 3819 RTINGSGQNQQT 4292 NHQSSTKNGEVFIAQAQTKWVQNQG

[1017] 3819 RTINGSGQNQQT 4293 NHQSSTKNGEVFIAQAQTVPVQNQG

[1018] 3819 RTINGSGQNQQT 4294 NHQSSTKNGEVFIAQAQTGWVNFQG

[1019] 3819 RTINGSGQNQQT 4295 NHQSSTKNGEVFIAQAQTAPVQNQG

[1020] 3819 RTINGSGQNQQT 4296 NHQSASRNGEVYIAQAQTSKVQNQG

[1021] 3839 RTIHGTGQNQQT 4297 NHQSSTKNGEVFIAQAQTGWVQNQG

[1022] 3819 RTINGSGQNQQT 4298 NHQSASRNGEVY1AQAQTGWVHAQG

[1023]

[1024] 3819 RTINGSGQNQQT 4299 NHQSASRNGEVYIAQAQTGACQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[1025] ID sequence ID

[1026] NO NO

[1027] 3840 RTINKGTSSNQT 4300 NHQSSTKNGEVFIAQAQTGWVQNQG

[1028] 3819 RTINGSGQNQQT 4301 NHQSASRNGEVYIAQAQTKAVQNQG

[1029] 3841 RTINGAGQNKQT 4302 N HQS ATRN GE VHIAMAQTGWVQN QG

[1030] 3819 RTINGSGQNQQT 4303 NHQSAVKDGHVLIAMAQTNNVQNQG

[1031] 3819 RTINGSGQNQQT 4304 NHQSATRNGEVHIAMAQTYAVQNQG

[1032] 3819 RTINGSGQNQQT 4305 NHQSASRNGEVYIAQAQTVGVQNQG

[1033] 3819 RTINGSGQNQQT 4306 NHQSAVKDGHVLIAMAQTGASQNQG

[1034] 3955 RTINGPVSSGKQSQQT 4307 NHQSSTKNGEVFIAQAQTGWVQNQG

[1035] 3819 RTINGSGQNQQT 4308 NHQSSTKNGEVFIAQAQTGHVQNQG

[1036] 3842 RTINKGSSSQQT 4309 NHQSSTKNGEVFIAQAQTGWVQNQG

[1037] 3843 RTIGGDSSRQQT 4310 NHQSASRNGEVYIAQAQTGWVQNQG

[1038] 3819 RTINGSGQNQQT 4311 NHQSAVKDGHVLIAMAQTTPVQNQG

[1039] 3819 RTINGSGQNQQT 4312 NHQSAVKDGHVLIAMAQTGQQQNQG

[1040] 3819 RTINGSGQNQQT 4313 NHQSASRNGEVYIAQAQTGPCQNQG

[1041] 3819 RTINGSGQNQQT 4314 NI-IQSASRNGEVYIAQAQTANVQNQG

[1042] 3819 RTINGSGQNQQT 4315 NHQSSTKNGEVFIAQAQTNWVQNQG

[1043] 3819 RTINGSGQNQQT 4316 NHQSSTKNGEVFIAQAQTGWVNEQG

[1044] 3819 RTINGSGQNQQT 4317 NHQSATRNGEVHIAMAQTSSVQNQG

[1045] 3819 RTINGSGQNQQT 4318 NHQSSTKNGEVFIAQAQTTNVQNQG

[1046] 3819 RTINGSGQNQQT 4319 NHQSAVKDGHVLIAMAQTGGSQNQG

[1047] 3819 RTINGSGQNQQT 4320 NHQSAVKDGHVLIAMAQTGAMQNQG

[1048] 3819 RTINGSGQNQQT 4321 NHQSAVKDGHVLIAMAQTANVQNQG

[1049] 3819 RTINGSGQNQQT 4322 NHQSSTKNGEVFIAQAQVGLVQNQG

[1050] 3819 RTINGSGQNQQT 4323 NHQSSTKNGEVFIAQAQVGNVQNQG

[1051] 3819 RTINGSGQNQQT 4324 NHQSSTKNGEVFIAQAQTKLVQNQG

[1052] 3819 RTINGSGQNQQT 4325 NHQSSTKNGEVFIAQAQTQSVQNQG

[1053] 3819 RTINGSGQNQQT 4326 NHQSASRNGEVY1AQAQTGWMHNQG

[1054] 3819 RTINGSGQNQQT 4327 NI-IQSASRNGEVYIAQAQTGHCQNQG

[1055] 3819 RTiNGSGQNQQT 4328 NHQSAVKDGHVLiAMAQTAVVQNQG

[1056] 3819 RTINGSGQNQQT 4329 NHQSSTKNGEVFIAQAQTGWWHNQG

[1057] 3819 RTINGSGQNQQT 4330 NHQSATKNGEVFIAQSQTGWVQNQG

[1058] 3819 RTINGSGQNQQT 4331 NHQSSTKNGEVFIAQAQTVQVQNQG

[1059] 38! 9 RTINGSGQNQQT 4332 NHQSSTKNGEVFIAQSQTNWVQNQG

[1060] 3819 RTINGSGQNQQT 4333 NHQSASRNGEVYIAQAQTQAVQNQG

[1061] 3819 RTINGSGQNQQT 4334 NHQSASRNGEVYIAQAQQGWVQNQG

[1062] 3844 RTINKATTSQQT 4335 NHQSSTKNGEVFIAQAQTGWVQNQG

[1063] 3819 RTINGSGQNQQT 4336 NHQSSTKNGEVFIAQAQTMLVQNQG

[1064] 3819 RTINGSGQNQQT 4337 NHQSSTKNGEVFIAQAQTKPVQNQG

[1065] 3819 RTINGSGQNQQT 4338 NHQSSTKNGEVFIAQAQTNNVQNQG

[1066]

[1067] 3819 RTINGSGQNQQT 4339 NHQSSTKNGEVFIAQAQTYAVQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[1068] ID sequence ID

[1069] NO NO

[1070] 3845 RTINNTGQNQQT 4340 NHQSSTKNGEVFIAQAQTGWVQNQG

[1071] 3819 RTINGSGQNQQT 4341 NHQSSTKNGEVFIAQAQTGSCQNQG

[1072] 3819 RTINGSGQNQQT 4342 NHQSASRNGEVYIAQAQTNPVQNQG

[1073] 3819 RTINGSGQNQQT 4343 NHQSASRNGEVYIAQAQTGFIQNQG

[1074] 3819 RTINGSGQNQQT 4344 NHQSASRNGEVY1AQAQTTSVQNQG

[1075] 3819 RTINGSGQNQQT 4345 NHQSASRNGEVYIAQAQTGSSQNQG

[1076] 3819 RTINGSGQNQQT 4346 NHQSAVKDGHVLIAMAQTGVNQNQG

[1077] 3819 RTINGSGQNQQT 4347 NHQSSTKNGEVFIAQAQTQTVQNQG

[1078] 3819 RTINGSGQNQQT 4348 NHQSSTKNGEVFIAQAQTQQVQNQG

[1079] 3956 RTINGPVSSGKQNTQT 4349 NHQSSTKNGEVFIAQAQTGWVQNQG

[1080] 3819 RTINGSGQNQQT 4350 NHQSSTKNGEVFIAQAQTGLVQNQG

[1081] 3819 RTINGSGQNQQT 4351 NHQSATRNGEVHIAMAQTQYVQNQG

[1082] 3819 RTINGSGQNQQT 4352 NHQSATRNGEVHIAIAQTGWVQNQG

[1083] 3846 RTINKGTSSSQT 4353 NHQSSTKNGEVFIAQAQTGWVQNQG

[1084] 3819 RTINGSGQNQQT 4354 NHQSATKNGEVFIAQAQTGLVQNQG

[1085] 3819 RTINGSGQNQQT 4355 NHQSASRNGEVYTAQAQTGPAQNQG

[1086] 3819 RTINGSGQNQQT 4356 NHQSSTKNGEVFIAQAQTIAVQNQG

[1087] 3819 RTINGSGQNQQT 4357 NHQSSTKNGEVFIAQAQTGASQNQG

[1088] 3819 RTINGSGQNQQT 4358 NHQSSTKNGEVFIAQAQTVAVQNQG

[1089] 3819 RTINGSGQNQQT 4359 N HQS ATKNGEVFIAQAQTA WVQNQG

[1090] 3819 RTINGSGQNQQT 4360 NHQSSTKNGEVFIAQSQTGTVQNQG

[1091] 3847 RTIGGDSSKHQT 4361 NHQSASRNGEVYIAQAQTGWVQNQG

[1092] 3819 RTINGSGQNQQT 4362 NHQSSTKNGEVFIAQAQTKVVQNQG

[1093] 3819 RTINGSGQNQQT 4363 NHQSSTKNGEVFIAQAQTLSVQNQG

[1094] 3819 RTINGSGQNQQT 4364 N HQS ASRNGEV YIA Q A QT AHVQNQG

[1095] 3819 RTINGSGQNQQT 4365 NHQSSTKNGEVFIAQAQTVGVQNQG

[1096] 3819 RTINGSGQNQQT 4366 NHQSSTKNGEVFIAQAQTNSVQNQG

[1097] 3819 RTINGSGQNQQT 4367 NHQSSTKNGEVFIAQAQTGNAQNQG

[1098] 3819 RTiNGSGQNQQT 4368 NHQSATRNGEVH1AMAQTVGVQNQG

[1099] 3819 RTINGSGQNQQT 4369 NHQSSTKNGEVFIAQAQTGWVNAQG

[1100] 3819 RTINGSGQNQQT 4370 NHQS ASRNGEV YIAQAQTGQNQNQG

[1101] 3819 RTINGSGQNQQT 4371 NHQSSTKNGEVFIAQAQTGLSQNQG

[1102] 38! 9 RTINGSGQNQQT 4372 NHQSSTKNGEVF1AQAQTMQVQNQG

[1103] 3819 RTINGSGQNQQT 4373 NHQSATRNGEVHIAMAQTAFVQNQG

[1104] 3848 RTIGGSSSKQQT 4374 NHQSASRNGEVYIAQAQTGWVQNQG

[1105] 3819 RTINGSGQNQQT 4375 NHQSASRNGEVYIAQAQTGWVNLQG

[1106] 3819 RTINGSGQNQQT 4376 NHQSASRNGEVYIAQAQTHMVQNQG

[1107] 3819 RTINGSGQNQQT 4377 NHQSASRNGEVYIAQAQTGWLHNQG

[1108] 3849 RTIIGTGQNQQT 4378 NHQSSTKNGEVFIAQAQTGWVQNQG

[1109]

[1110] 3819 RTINGSGQNQQT 4379 NHQSASRNGEVYIAQAQTGSCQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-TV amino acid SEQ VR-VIII amino acid sequence

[1111] ID sequence ID

[1112] NO NO

[1113] 3819 RTINGSGQNQQT 4380 NHQSSTKNGEVFIAQAQTAAVQNQG

[1114] 3819 RTINGSGQNQQT 4381 NHQSATKNGEVFIAQAQTTWVQNQG

[1115] 3850 RTIVGAGQNQQT 4382 NHQSSTKNGEVFIAQAQTGWVQNQG

[1116] 3819 RTINGSGQNQQT 4383 NHQSASRNGEVYIAQAQTYQVQNQG

[1117] 3851 RTINKGQSSQQT 4384 NHQSSTKNGEVFIAQAQTGWVQNQG

[1118] 3819 RTINGSGQNQQT 4385 NHQSASRNGEVYIAQAQTNA VQNQG

[1119] 3819 RTINGSGQNQQT 4386 NHQSSTKNGEVFIAQAQTQWVQNQG

[1120] 3819 RTINGSGQNQQT 4387 NHQSSTKNGEVFIAQAQTKGVQNQG

[1121] 3819 RTINGSGQNQQT 4388 NHQSSTKNGEVFIAQAQTMWVQNQG

[1122] 3819 RTINGSGQNQQT 4389 NHQS ASRN GE V Y1AQ AQTNL VQNQG

[1123] 3819 RTINGSGQNQQT 4390 NHQSSTKNGEVFIAQSQTGQVQNQG

[1124] 3819 RTINGSGQNQQT 4391 N HQS ATRN GE VHI AMAQTGWVHN QG

[1125] 3819 RTINGSGQNQQT 4392 NHQSASRNGEVYIAQAQTSSVQNQG

[1126] 3823 RTINGAGQNQQT 4393 NHQSATRNGEVFIAQAQTGWVQNQG

[1127] 3852 RTINNAGQNQQT 4394 NHQSSTKNGEVFIAQAQTGWVQNQG

[1128] 3853 RTIQKGTSSSQT 4395 NHQSSTKNGEVFIAQAQTGWVQNQG

[1129] 3819 RTINGSGQNQQT 4396 NHQSAVKDGHVLIAMAQTGFAQNQG

[1130] 3819 RTINGSGQNQQT 4397 NHQSSTKNGEVFIAQAQTMPVQNQG

[1131] 3819 RTINGSGQNQQT 4398 NHQSASRNGEVYIAQAQTMNVQNQG

[1132] 3819 RTINGSGQNQQT 4399 NHQSASRNGEVYIAQAQTGWVGSQG

[1133] 3819 RTINGSGQNQQT 4400 NHQSATRNGEVFIAQAQTGSVQNQG

[1134] 3957 RTINGPS S S GKQNQQT 4401 NHQSASRNGEVYIAQAQTGWVQNQG

[1135] 3819 RTINGSGQNQQT 4402 NHQSSTKNGEVFIAQAQTLMVQNQG

[1136] 3819 RTINGSGQNQQT 4403 NHQSATRNGEVHIAMAQTTAVQNQG

[1137] 3819 RTINGSGQNQQT 4404 NHQSSTKNGEVFIAQAQTNA VQNQG

[1138] 3819 RTINGSGQNQQT 4405 THQSASRNGEVYIAQAQTGWVQNQG

[1139] 3854 RTINKGTQSQQT 4406 NHQSSTKNGEVFIAQAQTGWVQNQG

[1140] 3819 RTINGSGQNQQT 4407 NHQSATRNGEVHIAMAQTAGVQNQG

[1141] 3855 RTIGGQSSKQQT 4408 N HQS ASRNGEV YTA Q A QTGWVQNQG

[1142] 3958 RTINGPVS SNKQNQQT 4409 NHQSSTKNGEVFIAQAQTGWVQNQG

[1143] 3819 RTINGSGQNQQT 4410 NHQSSTKNGEVFIAQAQTGSIQNQG

[1144] 3819 RTINGSGQNQQT 4411 NHQSSTKNGEVFIAQAQTGGVQNQG

[1145] 3819 RTINGSGQNQQT 4412 NHQSSTKNGEVFIAQAQTLGVQNQG

[1146] 3819 RTINGSGQNQQT 4413 NHQSSTKNGEVFIAQAQIGQVQNQG

[1147] 3819 RTINGSGQNQQT 4414 NHQSSTKNGEVFIAQAQVGHVQNQG

[1148] 3819 RTINGSGQNQQT 4415 NHQSASRNGEVYIAQAQTQWVQNQG

[1149] 3819 RTINGSGQNQQT 4416 NHQSSTKNGEVFIAQAQTIGVQNQG

[1150] 3856 RTIDKGTSSKQT 4417 NHQSSTKNGEVFIAQAQTGWVQNQG

[1151] 3819 RTINGSGQNQQT 4418 NHQSASRNGEVYIAQSQTGWVQNQG

[1152]

[1153] 3819 RTINGSGQNQQT 4419 NHQSAVKDGHVLIAMAQTGTNQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[1154] ID sequence ID

[1155] NO NO

[1156] 3819 RTINGSGQNQQT 4420 NHQSATRNGEVHIAMAQTNWVQNQG

[1157] 3819 RTINGSGQNQQT 4421 NHQSSTKNGEVFIAQAQTMSVQNQG

[1158] 3819 RTINGSGQNQQT 4422 N HQS ATKNGEVFIAQAQTGN VQNQG

[1159] 3819 RTINGSGQNQQT 4423 NHQSAVKDGHVLIAMAQTGALQNQG

[1160] 3857 RTIAGAGQNQQT 4424 NHQSSTKNGEVFIAQAQTGWVQNQG

[1161] 3819 RTINGSGQNQQT 4425 NHQSASRNGEVYIAQAQTGWCYNQG

[1162] 3819 RTINGSGQNQQT 4426 NHQSSTKNGEVFIAQAQTSLVQNQG

[1163] 3819 RTINGSGQNQQT 4427 NHQGSTRNGEVFIAQAQTSWVQNQG

[1164] 3819 RTINGSGQNQQT 4428 NHQSAVKDGHVLIAMAQTGACQNQG

[1165] 3819 RTINGSGQNQQT 4429 NHQSATRNGEVHIAMAQTQA VQNQG

[1166] 3819 RTINGSGQNQQT 4430 NHQSSTKNGEVFIAQAQTGWVTNQG

[1167] 3959 RTINGPVSSGKQTQQT 4431 NHQSSTKNGEVFIAQAQTGWVQNQG

[1168] 3819 RTINGSGQNQQT 4432 NHQSSTKNGEVFIAQAQTGWVQNMG

[1169] 3819 RTINGSGQNQQT 4433 NHQSATRNGEVHIAMAQTQGVQNQG

[1170] 3819 RTINGSGQNQQT 4434 NI-IQSASRNGEVYIAQAQTTRVQNQG

[1171] 3819 RTINGSGQNQQT 4435 NHQSSTKNGEVFIAQAQTKA VQNQG

[1172] 3819 RTINGSGQNQQT 4436 NHQSAVKDGHVLIAMAQTNGVQNQG

[1173] 3819 RTINGSGQNQQT 4437 NHQSAVKDGHVLIAMAQTMQVQNQG

[1174] 3819 RTINGSGQNQQT 4438 NHQSASRNGEVYIAQAQTMYVQNQG

[1175] 3858 RTINKGPSTQQT 4439 NHQSSTKNGEVFIAQAQTGWVQNQG

[1176] 3819 RTINGSGQNQQT 4440 NHQSAVKDGHVLIAMAQTGWMNNQG

[1177] 3819 RTINGSGQNQQT 4441 NHQSSTKNGEVFIAQAQTGWTNNQG

[1178] 3819 RTINGSGQNQQT 4442 NHQSSTKNGEVFIAQAQTISVQNQG

[1179] 3819 RTINGSGQNQQT 4443 NHQSASRNGEVYIAQAQTGWSNNQG

[1180] 3819 RTINGSGQNQQT 4444 N HQS A'T'RN GE VH1 AMAQTGWANN QG

[1181] 3819 RTINGSGQNQQT 4445 NHQSAVKDGHVLIAMAQTGVIQNQG

[1182] 3859 RTINGTGQGQQT 4446 NHQSSTKNGEVFIAQAQTGWVQNQG

[1183] 3819 RTINGSGQNQQT 4447 NHQSSTKNGEVFIAQAQTGPAQNQG

[1184] 3860 RTITGAGQNQQT 4448 NHQSSTKNGEVFIAQAQTGWVQNQG

[1185] 3819 RTINGSGQNQQT 4449 NHQSSTKNGEVFIAQAQTGQTQNQG

[1186] 3819 RTINGSGQNQQT 4450 NHQS ASRN GE V YIAQ AQTGWVTGQG

[1187] 3819 RTINGSGQNQQT 4451 NHQSASRNGEVYIAQAQTGWVQGQG

[1188] 3861 RTINKGTSTQQT 4452 NHQSSTKNGEVFIAQAQTGWVQNQG

[1189] 3819 RTINGSGQNQQT 4453 NHQSASRNGEVYIAQAQTQNVQNQG

[1190] 3819 RTINGSGQNQQT 4454 NHQSSTKNGEVFIAQAQTGWVQYQG

[1191] 3819 RTINGSGQNQQT 4455 NHQSATRNGEVHIAIAQTGQVQNQG

[1192] 3819 RTINGSGQNQQT 4456 NHQSSTKNGEVFIAQAQSGYVQNQG

[1193] 3819 RTINGSGQNQQT 4457 NHQSSTKNGEVFIAQAQTKTVQNQG

[1194] 3862 RTISGAGQNQQT 4458 NHQSATRNGEVFIAQAQTGWVQNQG

[1195]

[1196] 3819 RTINGSGQNQQT 4459 NHQSATRNGEVHIAMAQTSWVQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[1197] ID sequence ID

[1198] NO NO

[1199] 3960 RTINGPVS SG KQN VOT 4460 NHQSSTKNGEVFIAQAQTGWVQNQG

[1200] 3819 RTINGSGQNQQT 4461 NHQSATRNGEVHIAMAQTNPVQNQG

[1201] 3819 RTINGSGQNQQT 4462 NHQSSTKNGEVFIAQAQIGAVQNQG

[1202] 3819 RTINGSGQNQQT 4463 NHQSSTKNGEVFIAQAQTGFIQNQG

[1203] 3819 RTINGSGQNQQT 4464 NHQSSTKNGEVFIAQAQTTMVQNQG

[1204] 3819 RTINGSGQNQQT 4465 NHQSATRNGEVHIAMAQTGTAQNQG

[1205] 3819 RTINGSGQNQQT 4466 NHQSSTKNGEVFIAQASTGFVQNQG

[1206] 3819 RTINGSGQNQQT 4467 NHQSNSRNGEVYIAQAQTGWVQNQG

[1207] 3819 RTINGSGQNQQT 4468 NHQSASRNGEVY1AQAQTQSVQNQG

[1208] 3819 RTINGSGQNQQT 4469 NHQSSTKNGEVFIAQASTQWVQNQG

[1209] 3819 RTINGSGQNQQT 4470 NHQSAVKDGHVLIAMAQTGWTNNQG

[1210] 3961 RTINGPVSSGKQAQQT 4471 NHQSSTKNGEVFIAQAQTGWVQNQG

[1211] 3819 RTINGSGQNQQT 4472 NHQSSTKNGEVFIAQAQTGMIQNQG

[1212] 3863 RTINKGTQNQQT 4473 NHQSSTKNGEVFIAQAQTGWVQNQG

[1213] 3864 RTINKGTSNQQT 4474 NHQSSTKNGEVFIAQAQTGWVQNQG

[1214] 3826 RTIGGTGQNQQT 4475 NHQSATRNGEVFIAQAQTGWVQNQG

[1215] 3819 RTINGSGQNQQT 4476 NHQSASRNGEVYIAQAQTGMNQNQG

[1216] 3819 RTINGSGQNQQT 4477 NHQSSTKNGEVFIAQAQTSMVQNQG

[1217] 3865 RTINGGTKSQQT 4478 NHQSSTKNGEVFIAQAQTGWVQNQG

[1218] 3819 RTINGSGQNQQT 4479 NHQSASRNGEVYIAQAQTYGVQNQG

[1219] 3819 RTINGSGQNQQT 4480 NHQSSTKNGEVnAQAQTMNVQNQG

[1220] 3819 RTINGSGQNQQT 4481 NHQSSTKNGEVFIAQAQTGWCNNQG

[1221] 3819 RTINGSGQNQQT 4482 NHQSSTKNGEVFIAQAQSSWVQNQG

[1222] 3819 RTINGSGQNQQT 4483 NHQSSTKNGEVFIAQAQTGATQNQG

[1223] 3819 RTINGSGQNQQT 4484 NHQS ASRNGEV YIA Q A QTTPVQNQG

[1224] 3819 RTINGSGQNQQT 4485 NHQSATRNGEVHIAMAQTGFVQNQG

[1225] 3819 RTINGSGQNQQT 4486 NHQSASRNGEVY1AQAQTIPVQNQG

[1226] 3819 RTINGSGQNQQT 4487 NHQSASRNGEVYIAQAQTGSAQNQG

[1227] 3862 RTiSGAGQNQQT 4488 NHQSSTKNGEVFIAQAQTGWVQNQG

[1228] 3819 RTINGSGQNQQT 4489 NHQSATRNGEVHIAMAQRGNVQNQG

[1229] 3819 RTINGSGQNQQT 4490 NHQSATRNGEVHIAIAQTGSVQNQG

[1230] 3819 RTINGSGQNQQT 4491 NHQSAVKDGHVLIAMAQTGPCQNQG

[1231] 38! 9 RTINGSGQNQQT 4492 NHQSASRNGEVYTAQAQTGWVNYQG

[1232] 3825 RTISGTGQNQQT 4493 NHQSASRNGEVYIAQAQTGWVQNQG

[1233] 3819 RTINGSGQNQQT 4494 NHQS ASRNGE VYIAQAQTS YVQNQG

[1234] 3819 RTINGSGQNQQT 4495 NHQSATKNGEVFIAQAQTGWAQNQG

[1235] 3819 RTINGSGQNQQT 4496 NHQSAVKDGHVLIAMAQTSLVQNQG

[1236] 3962 RTINGPVS SGKQNQQT 4497 NHQSSTKNGEVFIAQAQTGWVQNQG

[1237] 3819 RTINGSGQNQQT 4498 NHQSATRNGEVHIAMAQTSPVQNQG

[1238]

[1239] 3819 RTINGSGQNQQT 4499 NHQSASRNGEVYIAQAQTGLAQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[1240] ID sequence ID

[1241] NO NO

[1242] 3819 RTINGSGQNQQT 4500 NHQSASRNGEVYIAQAQTKFVQNQG

[1243] 3866 RTIGGDSHKQQT 4501 NHQSASRNGEVYIAQAQTGWVQNQG

[1244] 3819 RTINGSGQNQQT 4502 NHQSSTKNGEVFIAQAQTGVIQNQG

[1245] 3819 RTINGSGQNQQT 4503 NHQSSTKNGEVFIAQAQTGWVQNIG

[1246] 3819 RTINGSGQNQQT 4504 NHQSATKNGEVFIAQAQTGWVSNQG

[1247] 3867 RTINRGTSSEQT 4505 NHQSSTKNGEVFIAQAQTGWVQNQG

[1248] 3868 RTIGGDSSKKQT 4506 NHQSASRNGEVYIAQAQTGWVQNQG

[1249] 3962 RTINGPVS SGKQNQQT 4507 NHQSASRNGEVYIAQAQTGWVQNQG

[1250] 3819 RTINGSGQNQQT 4508 NHQGSTRNGEVFIAQATTGWVQNQG

[1251] 3819 RTINGSGQNQQT 4509 NHQSSTKNGEVFIAQAQTGSAQNQG

[1252] 3819 RTINGSGQNQQT 4510 NHQSATKNGEVFIAQAQTGWTQNQG

[1253] 3819 RTINGSGQNQQT 4511 N HQS ASRNGE V YTA QA QQN WVQNQG

[1254] 3819 RTINGSGQNQQT 4512 NHQSSTKNGEVFIAQAQTSSVQNQG

[1255] 3819 RTINGSGQNQQT 4513 NHQSSTKNGEVFIAQAQTSPVQNQG

[1256] 3819 RTINGSGQNQQT 4514 NHQGSTRNGEVFIAQAQTGWVHNQG

[1257] 3819 RTINGSGQNQQT 4515 N HQMSTKNGE VFIAQ AQTGW VQNQG

[1258] 3819 RTINGSGQNQQT 4516 NHQSSTKNGEVFIAQAQTLNVQNQG

[1259] 3869 RTINKGTASQQT 4517 NHQSSTKNGEVFIAQAQTGWVQNQG

[1260] 3819 RTINGSGQNQQT 4518 NHQSATKNGEVFIAQAQTGWVNNQG

[1261] 3819 RTINGSGQNQQT 4519 NHQSSTKNGEVFIAQAQTALVQNQG

[1262] 3861 RTINKGTSTQQT 4520 NHQSASRNGEVYIAQAQTGWVQNQG

[1263] 3819 RTINGSGQNQQT 4521 NHQSATRNGEVHIAMAQTAMVQNQG

[1264] 3819 RTINGSGQNQQT 4522 N HQSASRN GEV Y1AQAQTGN VQNQG

[1265] 3819 RTINGSGQNQQT 4523 NHQSATRNGEVHIAMAQTTGVQNQG

[1266] 3819 RTINGSGQNQQT 4524 N HQS ASRNGEV YIA QA QTN YVQNQG

[1267] 3819 RTINGSGQNQQT 4525 NHQSSTKNGEVFIAQSQTGWVQNQG

[1268] 3819 RTINGSGQNQQT 4526 NHQSASRNGEVY1AQAQTSTVQNQG

[1269] 3943 RTINKGGGAGNQQT 4527 NHQSSTKNGEVFIAQAQTGWVQNQG

[1270] 3819 RTINGSGQNQQT 4528 N HQS ASRNGEV YTA Q A QTGWV YGQG

[1271] 3819 RTINGSGQNQQT 4529 NHQSATRNGEVHIAMAQTLGVQNQG

[1272] 3819 RTINGSGQNQQT 4530 NHQSASRNGEVYIAQAQSMWVQNQG

[1273] 3819 RTINGSGQNQQT 4531 NHQSASRNGEVYIAQAQTTMVQNQG

[1274] 3819 RTINGSGQNQQT 4532 N HQS AVKDGHVLI AMAQTQT VQN QG

[1275] 3819 RTINGSGQNQQT 4533 NHQSSVKNGEVFIAQAQTGWVQNQG

[1276] 3819 RTINGSGQNQQT 4534 NHQSATRNGEVHIAMAQTGMVQNQG

[1277] 3819 RTINGSGQNQQT 4535 NHQSASRNGEVYIAQAQTYNVQNQG

[1278] 3819 RTINGSGQNQQT 4536 N HQSSTKNGE VFIAQAQTGWLHN QG

[1279] 3819 RTINGSGQNQQT 4537 NHQSSTKNGEVFIAQAQTGWTTNQG

[1280] 3819 RTINGSGQNQQT 4538 NHQSSTKNGEVF1AQAQTMAVQNQG

[1281]

[1282] 3819 RTINGSGQNQQT 4539 NHQSATRNGEVHIAMAQTTMVQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[1283] ID sequence ID

[1284] NO NO

[1285] 3820 RTIQGTGQNQQT 4540 NHQSASRNGEVYIAQAQTGWVQNQG

[1286] 3819 RTINGSGQNQQT 4541 NHQSAVKDGHVLIAMAQTGVTQNQG

[1287] 3870 RTIMGTGQNQQT 4542 NHQSSTKNGEVFIAQAQTGWVQNQG

[1288] 3819 RTINGSGQNQQT 4543 NHQSSTKNGEVFIAQAQTGWVYGQG

[1289] 3819 RTINGSGQNQQT 4544 NHQSAVKDGHVLIAMAQTGPMQNQG

[1290] 3819 RTINGSGQNQQT 4545 NHQSASRNGEVYIAQAQTGWAQNQG

[1291] 3819 RTINGSGQNQQT 4546 NHQSATRNGEVH1AMAQTNYVQNQG

[1292] 3845 RTINNTGQNQQT 4547 NHQSASRNGEVYIAQAQTGWVQNQG

[1293] 3819 RTINGSGQNQQT 4548 NHQSATRNGEVHIAMAQTSFVQNQG

[1294] 3819 RTINGSGQNQQT 4549 NHQSSTKNGEVFIAQAQTSAVQNQG

[1295] 3819 RTINGSGQNQQT 4550 NHQGSTRNGEVFIAQAQTGWVQNQG

[1296] 3819 RTINGSGQNQQT 4551 N HQS ASRNGE V YIA QA QTSHVQNQG

[1297] 3819 RTINGSGQNQQT 4552 NHQSASRNGEVYIAQAQTGWVHGQG

[1298] 3819 RTINGSGQNQQT 4553 NHQSASRNGE VYIAQAQTMP VQN QG

[1299] 3819 RTINGSGQNQQT 4554 NHQSSTKNGEVFIAQAQTKSVQNQG

[1300] 3819 RTINGSGQNQQT 4555 NHQSSTKNGEVFIAQAQTGAIQNQG

[1301] 3819 RTINGSGQNQQT 4556 NHQSSTKNGEVFIAQAQTGLNQNQG

[1302] 3819 RTINGSGQNQQT 4557 NHQSATRNGEVHIAMAQRGSVQNQG

[1303] 3819 RTINGSGQNQQT 4558 NHQSSTKNGEVFIAQAQTGTAQNQG

[1304] 3963 RTIEGPVSSGKQNQQT 4559 NHQSSTKNGEVFIAQAQTGWVQNQG

[1305] 3819 RTINGSGQNQQT 4560 NHQSASRNGEVYIAQAQTTWVQNQG

[1306] 3819 RTINGSGQNQQT 4561 NHQSAVKDGHVLIAMAQTGTTQNQG

[1307] 3819 RTINGSGQNQQT 4562 NHQSASRNGEVY1AQAQTGSVQNQG

[1308] 3819 RTINGSGQNQQT 4563 NHQSSTKNGEVFIAQAQTGGNQNQG

[1309] 3871 RTINKGTATQQT 4564 NHQSSTKNGEVFIAQAQTGWVQNQG

[1310] 3819 RTINGSGQNQQT 4565 NHQSSTKNGEVFIAQAQTGMAQNQG

[1311] 3819 RTINGSGQNQQT 4566 NHQSATRNGEVHIAIAQTGAVQNQG

[1312] 3819 RTINGSGQNQQT 4567 NHQSSTKNGEVFIAQAQTGNIQNQG

[1313] 3819 RTINGSGQNQQT 4568 NHQSSTKNGEVFIAQAQTGGTQNQG

[1314] 3819 RTINGSGQNQQT 4569 NHQSASRNGEVYIAQAQTGGSQNQG

[1315] 3819 RTINGSGQNQQT 4570 NHQSSTKNGEVFIAQAQTGWVHSQG

[1316] 3819 RTINGSGQNQQT 4571 NHQSASRNGEVYIAQAQTGWAYNQG

[1317] 3819 RTINGSGQNQQT 4572 NHQSSTKNGEVFIAQAQTHLVQNQG

[1318] 3819 RTINGSGQNQQT 4573 NHQSSTKNGEVFIAQAQVGWVQNQG

[1319] 3819 RTINGSGQNQQT 4574 NHQSATRNGEVHIAMAQTGSIQNQG

[1320] 3819 RTINGSGQNQQT 4575 NHQSSTKNGEVFIAQAQTGTAQNQG

[1321] 3819 RTINGSGQNQQT 4576 N HQS ASRNGE VYIAQAQTGWVTNQG

[1322] 3819 RTINGSGQNQQT 4577 NHQSASRNGEVYIAQAQTYSVQNQG

[1323] 3819 RTINGSGQNQQT 4578 NHQSASRNGEVYIAQAQTLGVQNQG

[1324]

[1325] 3872 RTITGAGQNQQT 4579 NHQSSTKNGEVFIAQAQTGWVQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[1326] ID sequence ID

[1327] NO NO

[1328] 3873 RTIERGTSSQQT 4580 NHQSSTKNGEVFIAQAQTGWVQNQG

[1329] 3819 RTINGSGQNQQT 4581 NHQSSTKNGEVFIAQSQTGMVQNQG

[1330] 3819 RTINGSGQNQQT 4582 N HQS ATRN GE VHIAMAQTMN VQNQG

[1331] 3819 RTINGSGQNQQT 4583 NHQSATRNGEVHIAMAQTGWVNNQG

[1332] 3819 RTINGSGQNQQT 4584 NHQSATRNGEVHIAMAQTQNVQNQG

[1333] 3964 RTINGPVSAGKQNQQT 4585 NHQSASRNGEVYIAQAQTGWVQNQG

[1334] 3819 RTINGSGQNQQT 4586 NHQSASRNGEVYIAQASTGWVQNQG

[1335] 3819 RTINGSGQNQQT 4587 NHQSSTKNGEVFIAQAQTAHVQNQG

[1336] 3819 RTINGSGQNQQT 4588 NHQSAVKDGHVLIAMAQTGLCQNQG

[1337] 3965 RTIVGPVSSGKQNQQT 4589 NHQSSTKNGEVFIAQAQTGWVQNQG

[1338] 3819 RTINGSGQNQQT 4590 NHQSASRNGEVYIAQAQTGWTNNQG

[1339] 3819 RTINGSGQNQQT 4591 NHQSSTKNGEVFIAQAQTMMVQNQG

[1340] 3819 RTINGSGQNQQT 4592 NHQSSTKNGEVFIAQAQTGPSQNQG

[1341] 3819 RTINGSGQNQQT 4593 NHQSAVKDGHVLIAMAQTGPNQNQG

[1342] 3819 RTINGSGQNQQT 4594 NI-IQSAVKDGHVLIAMAQTMSVQNQG

[1343] 3819 RTINGSGQNQQT 4595 N HQS ATKNGEVYIAQAQTGW VQNQG

[1344] 3819 RTINGSGQNQQT 4596 NHQSSTKNGEVFIAQAQVSWVQNQG

[1345] 3966 RTINGPVS SGKQNSQT 4597 NHQSSTKNGEVFIAQAQTGWVQNQG

[1346] 3819 RTINGSGQNQQT 4598 NHQSAVKDGHVLIAMAQTGNLQNQG

[1347] 3819 RTINGSGQNQQT 4599 NHQSSTKNGEVFIAQAQQAWVQNQG

[1348] 3819 RTINGSGQNQQT 4600 NHQSATRNGEVHIAMAQTTQVQNQG

[1349] 3819 RTINGSGQNQQT 4601 NHQSSTKNGEVFIAQAQTTSVQNQG

[1350] 3874 RTLNKGTSNSQT 4602 NHQSSTKNGEVFIAQAQTGWVQNQG

[1351] 3819 RTINGSGQNQQT 4603 NHQSATRNGEVFIAQAQTGGVQNQG

[1352] 3819 RTINGSGQNQQT 4604 NHQSSTKNGEVFIAQAQTFNVQNQG

[1353] 3875 RTIQHGTSSQQT 4605 NHQSSTKNGEVFIAQAQTGWVQNQG

[1354] 3876 RTIMGAGQNQQT 4606 NHQSSTKNGEVFIAQAQTGWVQNQG

[1355] 3819 RTINGSGQNQQT 4607 NHQSATRNGEVHIAMAQTGQVQNQG

[1356] 3819 RTiNGSGQNQQT 4608 NHQSASRNGEVYTAQAQTQTVQNQG

[1357] 3819 RTINGSGQNQQT 4609 NHQSSTKNGEVFIAQAQTGYVQNQG

[1358] 3819 RTINGSGQNQQT 4610 NHQSSTKNGEVFIAQSQTSWVQNQG

[1359] 3819 RTINGSGQNQQT 4611 NHQSAVKDGHVLIAMAQTGSLQNQG

[1360] 3819 RTINGSGQNQQT 4612 NHQSATRNGEVHIAMAQTGQCQNQG

[1361] 3819 RTINGSGQNQQT 4613 NHQSATRNGEVHIAMAQTGWVNMQG

[1362] 3819 RTINGSGQNQQT 4614 NHQSSTKNGEVFIAQAQTGWMNNQG

[1363] 3819 RTINGSGQNQQT 4615 NHQGSTRNGEVFIAQAQTGWVSNQG

[1364] 3819 RTINGSGQNQQT 4616 NHQSSTKNGEVFIAQAQTGWVSQQG

[1365] 3819 RTINGSGQNQQT 4617 NHQSSTKNGEVFIAQAQTAWQNQG

[1366] 3819 RTINGSGQNQQT 4618 NHQSSTKNGEVFIAQAQTGWVNWQG

[1367]

[1368] 3819 RTINGSGQNQQT 4619 NHQSSTKNGEVFIAQAQAGFVQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[1369] ID sequence ID

[1370] NO NO

[1371] 3967 RTINGPVGSGKQNQQT 4620 NHQSSTKNGEVFIAQAQTGWVQNQG

[1372] 3819 RTINGSGQNQQT 4621 NHQSSTKNGEVFIAQAQSGWVQNQG

[1373] 3819 RTINGSGQNQQT 4622 NHQSASRNGEVYIAQAQTGMSQNQG

[1374] 3819 RTINGSGQNQQT 4623 NHQSASRNGEVYIAQAQTGSIQNQG

[1375] 3819 RTINGSGQNQQT 4624 NHQSATRNGEVHIAMAQTGAAQNQG

[1376] 3819 RTINGSGQNQQT 4625 NHQSSTKNGEVFIAQAQTATVQNQG

[1377] 3819 RTINGSGQNQQT 4626 NHQSASRNGEVYIAQAQTGHSQNQG

[1378] 3819 RTINGSGQNQQT 4627 NHQSAVKDGHVLIAMAQTGYIQNQG

[1379] 3819 RTINGSGQNQQT 4628 NHQSASRNGEVY1AQAQTTLVQNQG

[1380] 3819 RTINGSGQNQQT 4629 NHQSATRNGEVFIAQAQTGPVQNQG

[1381] 3819 RTINGSGQNQQT 4630 NHQSSTKNGEVFIAQAQTHNVQNQG

[1382] 3819 RTINGSGQNQQT 4631 NHQSATRNGEVHIAMAQTYGVQNQG

[1383] 3819 RTINGSGQNQQT 4632 NHQSAVKDGHVLIAMAQTGYTQNQG

[1384] 3819 RTINGSGQNQQT 4633 NHQSASRNGEVYIAQAQTGWSHNQG

[1385] 3877 RTINGHGQNQQT 4634 NHQSSTKNGEVFIAQAQTGWVQNQG

[1386] 3819 RTINGSGQNQQT 4635 N HQS A'T'RN GE VHI AMAQ'FN MVQNQG

[1387] 3819 RTINGSGQNQQT 4636 NHQSSTKNGEVFIAQAQTNPVQNQG

[1388] 3870 RTIMGTGQNQQT 4637 NHQSASRNGEVYIAQAQTGWVQNQG

[1389] 3819 RTINGSGQNQQT 4638 NHQSSTKNGEVFIAQAQSNWVQNQG

[1390] 3878 RTIGGDSSKQQT 4639 NHQSASRNGEVYIAQAQTGWVQNQG

[1391] 3819 RTINGSGQNQQT 4640 NHQSATRNGEVHIAMAQTVQVQNQG

[1392] 3819 RTINGSGQNQQT 4641 NHQSSTKNGEVFIAQAQTGMSQNQG

[1393] 3819 RTINGSGQNQQT 4642 NHQSSTKNGEIFLAQAQTGWVQNQG

[1394] 3879 RTINKGTSSTQT 4643 NHQSSTKNGEVFIAQAQTGWVQNQG

[1395] 3819 RTINGSGQNQQT 4644 NHQSSTKNGEVFIAQAQTGPIQNQG

[1396] 3819 RTINGSGQNQQT 4645 NHQSSTKNGEVFIAQAQIGTVQNQG

[1397] 3819 RTINGSGQNQQT 4646 NHQSATRNGEVHIAMAQTNTVQNQG

[1398] 3819 RTINGSGQNQQT 4647 NHQSSTKNGEVFIAQAQTGWVQGQG

[1399] 3819 RTiNGSGQNQQT 4648 NHQSATKNGEVFIAQAQTGFVQNQG

[1400] 3880 RTIQKGSSSQQT 4649 NHQSSTKNGEVFIAQAQTGWVQNQG

[1401] 3819 RTINGSGQNQQT 4650 NHQSATRNGEVHIAMAQTSTVQNQG

[1402] 3819 RTINGSGQNQQT 4651 NHQSASRNGEVYIAQAQTMLVQNQG

[1403] 3819 RTINGSGQNQQT 4652 NHQSASRNGEVYTAQAQTYPVQNQG

[1404] 3819 RTINGSGQNQQT 4653 NHQSASRNGEVYIAQAQTGGVQNQG

[1405] 3881 RTINKSTSSQQT 4654 NHQSSTKNGEVFIAQAQTGWVQNQG

[1406] 3968 RT1NGPVASGKQNQQT 4655 NHQSSTKNGEVFIAQAQTGWVQNQG

[1407] 3819 RTINGSGQNQQT 4656 NHQSASRNGEVYIAQAQTIGVQNQG

[1408] 3819 RTINGSGQNQQT 4657 NHQSAVKDGHVLIAMAQTGMMQNQG

[1409] 3819 RTINGSGQNQQT 4658 NHQSASRNGEVYIAQAQTGQTQNQG

[1410]

[1411] 3957 RTINGPS S SGKQNQQT 4659 NHQSSTKNGEVFIAQAQTGWVQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[1412] ID sequence ID

[1413] NO NO

[1414] 3819 RTINGSGQNQQT 4660 NHQSASRNGEVYIAQAQTGWTHNQG

[1415] 3819 RTINGSGQNQQT 4661 NHQSATRNGEVHIAMAQTAWVQNQG

[1416] 3819 RTINGSGQNQQT 4662 N HQS ATRN GE VHIAMAQTGGAQNQG

[1417] 3828 RTILGAGQNQQT 4663 NHQSATRNGEVFIAQAQTGWVQNQG

[1418] 3819 RTINGSGQNQQT 4664 NHQSSTKNGEVFIAQAQTQPVQNQG

[1419] 3819 RTINGSGQNQQT 4665 NHQSATRNGEVHIAMAQVGQVQNQG

[1420] 3819 RTINGSGQNQQT 4666 NHQSASRNGEVYIAQAQTSVVQNQG

[1421] 3819 RTINGSGQNQQT 4667 NHQSASRNGEVYIAQAQTQMVQNQG

[1422] 3819 RTINGSGQNQQT 4668 NHQSSTKNGEVFIAQAQTGWAYNQG

[1423] 3819 RTINGSGQNQQT 4669 NHQSATRNGEVFIAQAQTGA VQNQG

[1424] 3819 RTINGSGQNQQT 4670 NHQSAVKDGHVLIAMAQTGFSQNQG

[1425] 3819 RTINGSGQNQQT 4671 NHQSSTKNGEVFIAQAQTGWVTQQG

[1426] 3819 RTINGSGQNQQT 4672 NHQSSTKNGEVFIAQASTSWVQNQG

[1427] 3819 RTINGSGQNQQT 4673 NHQSSTKNGEVFIAQAQTTTVQNQG

[1428] 3819 RTINGSGQNQQT 4674 NHQSATKNGEVFIAQAQTGWVYNQG

[1429] 3819 RTINGSGQNQQT 4675 N HQS ATRN GE VHI AMAQTTP VQNQG

[1430] 3819 RTINGSGQNQQT 4676 NHQSSTKNGEVFIAQAQTGWVTSQG

[1431] 3819 RTINGSGQNQQT 4677 NHQSASRNGEVYIAQAQTIAVQNQG

[1432] 3819 RTINGSGQNQQT 4678 NHQSSTKNGEVFIAQAQTSHVQNQG

[1433] 3819 RTINGSGQNQQT 4679 N HQS ATRN GE VHIAMAQTAPVQN QG

[1434] 3819 RTINGSGQNQQT 4680 NHQSAVKDGHVLIAMAQTGMTQNQG

[1435] 3819 RTINGSGQNQQT 4681 NHQSASRNGEVYIAQAQTGWIHNQG

[1436] 3882 RTINKGQSNQQT 4682 NHQSSTKNGEVFIAQAQTGWVQNQG

[1437] 3819 RTINGSGQNQQT 4683 NHQSASRNGEVYIAQAQTHQVQNQG

[1438] 3819 RTINGSGQNQQT 4684 NHQSSTKNGEVFIAQSQTGLVQNQG

[1439] 3819 RTINGSGQNQQT 4685 NHQSATKNGEVFIAQAQTGWVQNQA

[1440] 3883 RTINKGTSSIQT 4686 NHQSSTKNGEVFIAQAQTGWVQNQG

[1441] 3819 RTINGSGQNQQT 4687 NHQSASRNGEVYIAQAQTGWVQSQG

[1442] 3819 RTINGSGQNQQT 4688 NHQSSTKNGEVFIAQAQTIP VQNQG

[1443] 3819 RTINGSGQNQQT 4689 NHQMNTRNGEVFLXQAQTGWVNNQG

[1444] 3944 RTINKGQSAGNQQT 4690 NHQSSTKNGEVFIAQAQTGWVQNQG

[1445] 3819 RTINGSGQNQQT 4691 NI-IQSATRNGEVFIAQAQTGQVQNQG

[1446] 3819 RTINGSGQNQQT 4692 N HQS ASRNGE V YIA QAQTLMVQNQG

[1447] 3819 RTINGSGQNQQT 4693 NHQSATRNGEVFIAQASTGWVQNQG

[1448] 3884 RTINSAGQNQQT 4694 NHQSSTKNGEVFEAQAQTGWVQNQG

[1449] 3819 RTINGSGQNQQT 4695 NHQSATRNGEVHIAMAQTGQQQNQG

[1450] 3819 RTINGSGQNQQT 4696 NHQSSTKNGEVFIAQAQRGL VQNQG

[1451] 3885 RTINKGTSQTQT 4697 NHQSSTKNGEVFIAQAQTGWVQNQG

[1452] 3819 RTINGSGQNQQT 4698 NHQSSTKNGEVYIAQAQTGWVQNQG

[1453]

[1454] 3819 RTINGSGQNQQT 4699 NHQSSTKNGEVFIAQAQTLHVQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[1455] ID sequence ID

[1456] NO NO

[1457] 3886 RTITKTTSSQQT 4700 NHQSSTKNGEVFIAQAQTGWV'QNQG

[1458] 3819 RTINGSGQNQQT 4701 NHQSASRNGEVYIAQAQTGMVQNQG

[1459] 3819 RTINGSGQNQQT 4702 NHQSSTKNGEVFIAQSQTAWVQNQG

[1460] 3819 RTINGSGQNQQT 4703 NHQSAVKDGHVLIAMAQTGLSQNQG

[1461] 3887 RTINKGTSSGQT 4704 NHQSSTKNGEVFIAQAQTGWV'QNQG

[1462] 3819 RTINGSGQNQQT 4705 NHQSATRNGEVHIAMATTGDVQNQG

[1463] 3819 RTINGSGQNQQT 4706 NHQSATRNGEVHIAMAQTERVQNQG

[1464] 3969 RTINGPVSGGKQNQQT 4707 NHQSSTKNGEVFIAQAQTGWVQNQG

[1465] 3819 RTINGSGQNQQT 4708 NHQSSTKNGEVFIAQAQTGLCQNQG

[1466] 3819 RTINGSGQNQQT 4709 NHQS ASRN GE V Y1AQ AQRD WVQNQG

[1467] 3819 RTINGSGQNQQT 4710 NHQSSTKNGEVFIAQAQVGMVQNQG

[1468] 3954 RTINGPVSTGKQNQQT 4711 NHQSSTKNGEVFIAQAQTGWVQNQG

[1469] 3819 RTINGSGQNQQT 4712 NHQASTKNGEVFIAQAQTGWVQNQG

[1470] 3819 RTINGSGQNQQT 4713 NHQS ASRN GE V YIAQ AQTGWVHNQG

[1471] 3888 RTIYGAGQNQQT 4714 NHQSSTKNGEVFIAQAQTGWVQNQG

[1472] 3819 RTINGSGQNQQT 4715 NHQSATRNGEVHIAIAQTGNVQNQG

[1473] 3819 RTINGSGQNQQT 4716 NHQSASRNGEVYIAQAQQQWVQNQG

[1474] 3889 RTINGTGQSQQT 4717 NHQSSTKNGEVFIAQAQTGWVQNQG

[1475] 3819 RTINGSGQNQQT 4718 NHQSAVKDGHVLIAMAQTMPVQNQG

[1476] 3945 RTINKGGSAANQQT 4719 NHQSSTKNGEVFIAQAQTGWVQNQG

[1477] 3819 RTINGSGQNQQT 4720 NHQSAVKDGHVLIAMAQTGWIHNQG

[1478] 3819 RTINGSGQNQQT 4721 NHQSATKNGEVFIAQAQTGYVQNQG

[1479] 3819 RTINGSGQNQQT 4722 NHQSSTKNGEVFIAQAQTLTVQNQG

[1480] 3819 RTINGSGQNQQT 4723 NHQSSTKNGEVFIAQAQNGYVQNQG

[1481] 3819 RTINGSGQNQQT 4724 NHQS ATRN GE VHI AMAQTGN CQNQG

[1482] 3819 RTINGSGQNQQT 4725 NHQSATKNGEVFIAQAQTQWVQNQG

[1483] 3890 RTIQKGTSSQQT 4726 NHQSATRNGEVFIAQAQTGWVQNQG

[1484] 3819 RTINGSGQNQQT 4727 NHQSSTKNGEVFIAQAQTQGVQNQG

[1485] 3819 RTiNGSGQNQQT 4728 N HQS ASRNGEV YTA Q A QTGWI YNQG

[1486] 3819 RTINGSGQNQQT 4729 NHQSSTKNGEVFIAQAQIGSVQNQG

[1487] 3819 RTINGSGQNQQT 4730 NHQSATRNGEVHIAMAQTSLVQNQG

[1488] 3819 RTINGSGQNQQT 4731 NHQSSTKNGEVFIAQAQTGWVHEQG

[1489] 3819 RTINGSGQNQQT 4732 NHQSSTKNGEVFIAQASTGSVQNQG

[1490] 3891 RTINKGSSSNQT 4733 NHQSSTKNGEVFIAQAQTGWVQNQG

[1491] 3819 RTINGSGQNQQT 4734 NHQSASRNGEVYIAQAQTQRVQNQG

[1492] 3819 RTINGSGQNQQT 4735 NHQSASRNGEVYIAQAQTAAVQNQG

[1493] 3819 RTINGSGQNQQT 4736 NHQS ASRNGEV YIAQAQTISVQNQG

[1494] 3819 RTINGSGQNQQT 4737 NHQSAVKDGHVLIAMAQTNTVQNQG

[1495] 3892 RTINTTGQNQQT 4738 NHQSSTKNGEVFIAQAQTGWV'QNQG

[1496]

[1497] 3893 RT1LKGQSSQQT 4739 NHQSSTKNGEVFIAQAQTGWVQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[1498] ID sequence ID

[1499] NO NO

[1500] 3819 RTINGSGQNQQT 4740 NHQSATKNGEIFIAQAQTGWVQNQG

[1501] 3819 RTINGSGQNQQT 4741 NHQSASRNGEVYIAQAQTMWVQNQG

[1502] 3819 RTINGSGQNQQT 4742 N HQS ATRN GE VF1AQAQTS WVQNQG

[1503] 3819 RTINGSGQNQQT 4743 NHQSAVKDGHVLIAMAQTQPVQNQG

[1504] 3946 RTINKGGSAQNQQT 4744 NHQSSTKNGEVFIAQAQTGWVQNQG

[1505] 3819 RTINGSGQNQQT 4745 NHQSSTKNGEVFIAQAQTHPVQNQG

[1506] 3819 RTINGSGQNQQT 4746 NHQSATRNGEVHIAMAQTYSVQNQG

[1507] 3819 RTINGSGQNQQT 4747 NHQSASRNGEVYIAQAQTGNNQNQG

[1508] 3970 RTILGPVSSGKQNQQT 4748 NHQSSTKNGEVFIAQAQTGWVQNQG

[1509] 3819 RTINGSGQNQQT 4749 NHQSSTKNGEVFIAQAQTHWVQNQG

[1510] 3819 RTINGSGQNQQT 4750 NI-IQSAVKDGHVLIAMAQTLGVQNQG

[1511] 3819 RTINGSGQNQQT 4751 NHQSSTKNGEVFIAQAQTGTSQNQG

[1512] 3819 RTINGSGQNQQT 4752 NHQSSTKNGEVFIAQAQNGKVQNQG

[1513] 3819 RTINGSGQNQQT 4753 NHQSATRNGEVHIAMAQTATVQNQG

[1514] 3819 RTINGSGQNQQT 4754 NI-IQSASRNGEVYIAQAQTATVQNQG

[1515] 3819 RTINGSGQNQQT 4755 NHQSSTKNGEVFIAQSQTGVVQNQG

[1516] 3819 RTINGSGQNQQT 4756 NHQSSTKNGEVFIAQAQTYNVQNQG

[1517] 3819 RTINGSGQNQQT 4757 NHQSSTKNGEVFIAQAQIGGVQNQG

[1518] 3819 RTINGSGQNQQT 4758 NHQSAVKDGHVLIAMAQTGTLQNQG

[1519] 3819 RTINGSGQNQQT 4759 NHQSAVKDGHVLIAMAQTGMNQNQG

[1520] 3947 RTINKGGSAGNQQT 4760 NHQSSTKNGEVFIAQAQTGWVQNQG

[1521] 3819 RTINGSGQNQQT 4761 NHQSSTKNGEVFIAQASTGKVQNQG

[1522] 3819 RTINGSGQNQQT 4762 N H QS A VKDGH VL I AMAQT Y A VQN QG

[1523] 3819 RTINGSGQNQQT 4763 NHQGATRNGEVYIAQAQTGAVQNQG

[1524] 3819 RTINGSGQNQQT 4764 N HQS ATRN GE VH1 AMAQTGM AQNQG

[1525] 3819 RTINGSGQNQQT 4765 NHQSSTKNGEVFIAQAQTTPVQNQG

[1526] 3819 RTINGSGQNQQT 4766 NHQSASRNGEVY1AQAQTFAVQNQG

[1527] 3819 RTINGSGQNQQT 4767 NHQSSTKNGEVFIAQAQSGFVQNQG

[1528] 3894 RTINMTGQNQQT 4768 NHQSSTKNGEVFIAQAQTGWVQNQG

[1529] 3819 RTINGSGQNQQT 4769 NHQSSTKNGEVFIAQAQTGWVNCQG

[1530] 3819 RTINGSGQNQQT 4770 NHQSSTKNGEVFIAQAQTGW1QNQG

[1531] 3819 RTINGSGQNQQT 4771 NHQSSTKNGEVFIAQAQTHGVQNQG

[1532] 3895 RTIVKNTSSQQT 4772 NHQSSTKNGEVFIAQAQTGWVQNQG

[1533] 3819 RTINGSGQNQQT 4773 NHQSASRNGEVYIAQAQTGSNQNQG

[1534] 3971 RTINGPVS SGKQNAQT 4774 NHQSSTKNGEVFIAQAQTGWVQNQG

[1535] 3819 RTINGSGQNQQT 4775 NHQSSTKNGEVFIAQAQSAWVQNQG

[1536] 3819 RTINGSGQNQQT 4776 N HQS ATRN GE VHIAMAQTGWAHN QG

[1537] 3819 RTINGSGQNQQT 4777 NHQSSTKNGEVFIAQAQTGWVHQQG

[1538] 3896 RTINKGTQSSQT 4778 NHQSSTKNGEVFIAQAQTGWVQNQG

[1539]

[1540] 3819 RTINGSGQNQQT 4779 NHQSSTKNGEVFIAQAQTGIVQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[1541] ID sequence ID

[1542] NO NO

[1543] 3870 RTIMGTGQNQQT 4780 NHQSATRNGEVFIAQAQTGWVQNQG

[1544] 3897 RTINKGGSSTQT 4781 NHQSSTKNGEVFIAQAQTGWVQNQG

[1545] 3819 RTINGSGQNQQT 4782 NHQSASRNGEVYIAQAQTGWVHQQG

[1546] 3819 RTINGSGQNQQT 4783 NHQSAVKDGHVLIAMAQTMAVQNQG

[1547] 3898 RTIGGGSSKQQT 4784 NHQSASRNGEVY1AQAQTGWVQNQG

[1548] 3819 RTINGSGQNQQT 4785 NHQSASRNGEVYIAQAQTQPVQNQG

[1549] 3972 RTINGPVSSGKQNMQT 4786 NHQSSTKNGEVFIAQAQTGWVQNQG

[1550] 3819 RTINGSGQNQQT 4787 NHQSSTKNGEVFIAQAQTGWQHNQG

[1551] 3819 RTINGSGQNQQT 4788 NHQSNTKNGEVFIAQAQTGWVQNQG

[1552] 3899 RTINKGQSQQQT 4789 NHQSSTKNGEVFIAQAQTGWVQNQG

[1553] 3819 RTINGSGQNQQT 4790 NHQSSTKNGEVFIAQAQTMTVQNQG

[1554] 3973 RTINGPMSSGKQNQQT 4791 N HQS ASRNGEV YTA QA QTGWVQNQG

[1555] 3819 RTINGSGQNQQT 4792 NHQSASRNGEVYIAQAQTGWVYSQG

[1556] 3819 RTINGSGQNQQT 4793 NHQSSTKNGEVFIAQAQTKNVQNQG

[1557] 3890 RTIQKGTSSQQT 4794 NHQSSTKNGEVFIAQAQTGWVQNQG

[1558] 3819 RTINGSGQNQQT 4795 NHQSSTKNGEVFIAQAQRGDVQNQG

[1559] 3819 RTINGSGQNQQT 4796 NHQSASRNGEVYIAQAQTDRVQNQG

[1560] 3819 RTINGSGQNQQT 4797 NHQSAVKDGHVLIAMAQTLAVQNQG

[1561] 3819 RTINGSGQNQQT 4798 NHQSASRNGEVYIAQAQTALVQNQG

[1562] 3948 RTINKGGSATNQQT 4799 NHQSSTKNGEVFIAQAQTGWVQNQG

[1563] 3900 RTINSTGQNQQT 4800 NHQSSTKNGEVFIAQAQTGWVQNQG

[1564] 3968 RTINGPVASGKQNQQT 4801 NHQSATRNGEVHIAMAQTGWVQNQG

[1565] 3819 RTINGSGQNQQT 4802 NHQSSTKNGEVFIAQASTAWVQNQG

[1566] 3819 RTINGSGQNQQT 4803 NHQGSTRNGEVFIAQAQTQWVQNQG

[1567] 3819 RTINGSGQNQQT 4804 NHQGATRNGEVYIAQAQTTWVQNQG

[1568] 3819 RTINGSGQNQQT 4805 NHQSAVKDGHVLIAMAQTGQLQNQG

[1569] 3819 RTINGSGQNQQT 4806 NHQSASRNGEVY1AQAQTVRVQNQG

[1570] 3901 RTIYGTGQNQQT 4807 NHQSSTKNGEVFIAQAQTGWVQNQG

[1571] 3819 RTINGSGQNQQT 4808 N HQGATRNGEV Y I AQ AQTGWVSNQG

[1572] 3902 RTINGTGQNKQT 4809 NHQSSTKNGEVFIAQAQTGWVQNQG

[1573] 3819 RTINGSGQNQQT 4810 NHQSATRNGEVFIAQAQTGMVQNQG

[1574] 3841 RTINGAGQNKQT 4811 NHQSSTKNGEVFIAQAQTGWVQNQG

[1575] 3819 RTINGSGQNQQT 4812 NHQSSTKNGEVFIAQAQTNLVQNQG

[1576] 3903 RTIGRDSSKQQT 4813 NHQSASRNGEVYIAQAQTGWVQNQG

[1577] 3819 RTINGSGQNQQT 4814 NHQSATRNGEVHIAMAQTGVAQNQG

[1578] 3822 RTIAGTGQNQQT 4815 NHQSATRNGEVFIAQAQTGWVQNQG

[1579] 3904 RTINKGTQQQQT 4816 NHQSSTKNGEVFIAQAQTGWVQNQG

[1580] 3819 RTINGSGQNQQT 4817 NHQSAVKDGHVLIAMAQTMGVQNQG

[1581] 3905 RTIGGDSMKQQT 4818 NHQSSTKNGEVFIAQAQTGWVQNQG

[1582]

[1583] 3819 RTINGSGQNQQT 4819 NHQSSTKNGEVFIAQAQTHMVQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[1584] ID sequence ID

[1585] NO NO

[1586] 3819 RTINGSGQNQQT 4820 NHQSASRNGEVYIAQAQTGWVNVQG

[1587] 3819 RTINGSGQNQQT 4821 NHQSSTKNGEVFIAQASTGQVQNQG

[1588] 3819 RTINGSGQNQQT 4822 NHQSATKNGEVFIAQAQTGMVQNQG

[1589] 3819 RTINGSGQNQQT 4823 NHQSSTKNGEVFIAQANTGFVQNQG

[1590] 3819 RTINGSGQNQQT 4824 NHQSATRNGEVHIAMAQTGPTQNQG

[1591] 3819 RTINGSGQNQQT 4825 NHQSATRNGEVHIAMAQRGDVQNQG

[1592] 3819 RTINGSGQNQQT 4826 NHQSATKNGEVFIAQAQTGKVQNQG

[1593] 3819 RTINGSGQNQQT 4827 NHQSAVKDGHVLIAMAQTMNVQNQG

[1594] 3974 RTINGGVSSGKQNQQT 4828 NHQSASRNGEVY1AQAQTGWVQNQG

[1595] 3906 RTIQKATSSQQT 4829 NHQSSTKNGEVFIAQAQTGWVQNQG

[1596] 3819 RTINGSGQNQQT 4830 NHQSAVKDGHVLIAMAQTGNMQNQG

[1597] 3907 RTINKGTSQSQT 4831 NHQSSTKNGEVFIAQAQTGWVQNQG

[1598] 3908 RTINKGTGTQQT 4832 NHQSSTKNGEVFIAQAQTGWVQNQG

[1599] 3975 RTINGPVQSGKQNQQT 4833 NHQSSTKNGEVFIAQAQTGWVQNQG

[1600] 3909 RTINKSPSSQQT 4834 NHQSSTKNGEVFIAQAQTGWVQNQG

[1601] 3819 RTINGSGQNQQT 4835 NHQSASRNGEVYTAQAQTGPVQNQG

[1602] 3819 RTINGSGQNQQT 4836 NHQSSTKNGEVFIAQAQRGEVQNQG

[1603] 3819 RTINGSGQNQQT 4837 NHQSSTKNGEVFIAQAQTGFVQNQG

[1604] 3819 RTINGSGQNQQT 4838 NHQSASRNGEVYIAQAQTGWVNIQG

[1605] 3819 RTINGSGQNQQT 4839 NHQSSTKNGEVFIAQAATGKVQNQG

[1606] 3819 RTINGSGQNQQT 4840 NHQSATRNGEVHIAMAQTGFIQNQG

[1607] 3819 RTINGSGQNQQT 4841 NHQSSTKNGEVFIAQAQTGWLNNQG

[1608] 3819 RTINGSGQNQQT 4842 N H QS A S RN GE V Y1AQ AQTG W VFN QG

[1609] 3819 RTINGSGQNQQT 4843 NHQSASRNGEVYIAQAQTTFVQNQG

[1610] 3910 RTINGTGTNQQT 4844 NHQSSTKNGEVFIAQAQTGWVQNQG

[1611] 3819 RTINGSGQNQQT 4845 NHQSATRNGEVHIAIAQTGMVQNQG

[1612] 3819 RTINGSGQNQQT 4846 NHQSASRNGEVY1AQAQTGWSQNQG

[1613] 3819 RTINGSGQNQQT 4847 NHQSATRNGEVHIAMAQTGWVHAQG

[1614] 3819 RTINGSGQNQQT 4848 NHQSATRNGEVH1AMAQTGGVQNQG

[1615] 3911 RTINGAGNNQQT 4849 NHQSSTKNGEVFIAQAQTGWVQNQG

[1616] 3912 RTINGTGQNMQT 4850 NHQSSTKNGEVFIAQAQTGWVQNQG

[1617] 3819 RTINGSGQNQQT 4851 NHQSASRNGEVYIAQAQTFQVQNQG

[1618] 3819 RTINGSGQNQQT 4852 N HQS AT'RN GE VFI AN SQ'T'GT VQNQG

[1619] 3913 RTINGPGQNQQT 4853 NHQSSTKNGEVFIAQAQTGWVQNQG

[1620] 3819 RTINGSGQNQQT 4854 NHQSATRNGEVHIAMAQTLSVQNQG

[1621] 3819 RTINGSGQNQQT 4855 NHQSAVKDGHVLIAMAQTGWANNQG

[1622] 3914 RTIQKGQSSQQT 4856 NHQSSTKNGEVFIAQAQTGWVQNQG

[1623] 3819 RTINGSGQNQQT 4857 NHQSSTKNGEVFIAQAQVGGVQNQG

[1624] 3915 RTINHGTSTQQT 4858 NHQSSTKNGEVFIAQAQTGWVQNQG

[1625]

[1626] 3819 RTINGSGQNQQT 4859 NHQSASRNGEVYIAQAQTAVVQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[1627] ID sequence ID

[1628] NO NO

[1629] 3819 RTINGSGQNQQT 4860 NHQSASRNGEVYIAQAQTYKVQNQG

[1630] 3819 RTINGSGQNQQT 4861 NHQSAVKDGHVLIAMAQTGMCQNQG

[1631] 3819 RTINGSGQNQQT 4862 NHQSASRNGEVYIAQAQTGMCQNQG

[1632] 3819 RTINGSGQNQQT 4863 NHQSATRNGEVHIAMAQTVSVQNQG

[1633] 3819 RTINGSGQNQQT 4864 NHQSAVKDGHVLIAMAQTTNVQNQG

[1634] 3916 RTINKGTSSMQT 4865 NHQSSTKNGEVFIAQAQTGWVQNQG

[1635] 3819 RTINGSGQNQQT 4866 NHQSASRNGEVYIAQAQTGYAQNQG

[1636] 3819 RTINGSGQNQQT 4867 NHQSATKNGEVFIAQAQTNWVQNQG

[1637] 3917 RTIVKGTSSQQT 4868 NHQSSTKNGEVFIAQAQTGWVQNQG

[1638] 3918 RTIQKSTSSQQT 4869 NHQSSTKNGEVFIAQAQTGWVQNQG

[1639] 3819 RTINGSGQNQQT 4870 NHQSSTKNGEVFIAQASTGWVQNQG

[1640] 3819 RTINGSGQNQQT 4871 NHQSSTKNGEVFIAQAQTGTVQNQG

[1641] 3819 RTINGSGQNQQT 4872 NHQSATRNGEVHIAMAQTANVQNQG

[1642] 3819 RTINGSGQNQQT 4873 NHQSAVKDGHVLIAMAQTGWMHNQG

[1643] 3819 RTINGSGQNQQT 4874 NI-IQSASRNGEVYIAQAQTGNAQNQG

[1644] 3819 RTINGSGQNQQT 4875 NHQSSTKNGEVFIAQAQTMVVQNQG

[1645] 3819 RTINGSGQNQQT 4876 NHQSATRNGEVHIAMAQTMYVQNQG

[1646] 3819 RTINGSGQNQQT 4877 NHQSAVKDGHVLIAMAQTGHAQNQG

[1647] 3962 RTINGPVSSGKQNQQT 4878 NHQSATRNGEVHIAMAQTGWVQNQG

[1648] 3819 RTINGSGQNQQT 4879 N HQS ATRN GE VHIAMAQTGWCHNQG

[1649] 3819 RTINGSGQNQQT 4880 NHQSAVKDGHVLIAMAQTGWGNNQG

[1650] 3819 RTINGSGQNQQT 4881 NHQMNTRNGEVFIAQAQTGWVHNQG

[1651] 3919 RTINHGTTSQQT 4882 NHQSSTKNGEVFIAQAQTGWVQNQG

[1652] 3819 RTINGSGQNQQT 4883 NHQSSTKNGEVFIAQAQQGQVQNQG

[1653] 3920 RTINHGTSSQQT 4884 NHQSSTKNGEVFIAQAQTGWVQNQG

[1654] 3819 RTINGSGQNQQT 4885 NHQSATRNGEVHIAMAQTGANQNQG

[1655] 3921 RTINKGSSNQQT 4886 NHQSSTKNGEVFIAQAQTGWVQNQG

[1656] 3819 RTINGSGQNQQT 4887 NHQSSTKNGEVFIAQAQTGANQNQG

[1657] 3819 RTINGSGQNQQT 4888 NHQSATRNGEVH1AMAQTGWVNYQG

[1658] 3819 RTINGSGQNQQT 4889 NHQSSTKNGEVFIAQAQTGNSQNQG

[1659] 3819 RTINGSGQNQQT 4890 NHQSATRNGEVHIAMAQTGFCQNQG

[1660] 3819 RTINGSGQNQQT 4891 NHQGATRNGEVYIAQAQTSWVQNQG

[1661] 3922 RTINKGSSTQQT 4892 NHQSSTKNGEVFIAQAQTGWVQNQG

[1662] 3819 RTINGSGQNQQT 4893 NHQSASRNGEVYIAQAQTYMVQNQG

[1663] 3819 RTINGSGQNQQT 4894 NHQSATRNGEVHIAMAQTGAQQNQG

[1664] 3923 RTINGVGQNQQT 4895 NHQSSTKNGEVFIAQAQTGWVQNQG

[1665] 3819 RTINGSGQNQQT 4896 N HQS ATKNGEVFIAQAQTGWVQNMG

[1666] 3819 RTINGSGQNQQT 4897 NHQSAVKDGHVLIAMAQTGAQQNQG

[1667] 3924 RTIAKTTSSQQT 4898 NHQSSTKNGEVFIAQAQTGWVQNQG

[1668]

[1669] 3819 RTINGSGQNQQT 4899 NHQSASRNGEVYIAQAQTGWNHNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[1670] ID sequence ID

[1671] NO NO

[1672] 3925 RTINGAGQKQQT 4900 NHQSATRNGEVHIAMAQTGWVQNQG

[1673] 3819 RTINGSGQNQQT 4901 NHQSSTKNGEVFIAQAQTGVAQNQG

[1674] 3819 RTINGSGQNQQT 4902 N HQS ATRN GE VH1AMAQTGPCQNQG

[1675] 3926 RTINKGTNTQQT 4903 NHQSSTKNGEVFIAQAQTGWVQNQG

[1676] 3927 RTINGAGQNMQT 4904 NHQSSTKNGEVFIAQAQTGWVQNQG

[1677] 3928 RTINNGTSSKQT 4905 NHQSSTKNGEVFIAQAQTGWVQNQG

[1678] 3819 RTINGSGQNQQT 4906 NHQSASRNGEVYIAQAQTMTVQNQG

[1679] 3819 RTINGSGQNQQT 4907 NHQSATRNGEVHIAMAQTMTVQNQG

[1680] 3819 RTINGSGQNQQT 4908 NHQSSTKNGEVFIAQAQTGPCQNQG

[1681] 3819 RTINGSGQNQQT 4909 NHQSATRNGEVHIAMSQTGSVQNQG

[1682] 3819 RTINGSGQNQQT 4910 NHQSASRNGEVYIAQAQTGWVQNCG

[1683] 3976 RTINGPVSSGKQNNQT 4911 NHQSSTKNGEVFIAQAQTGWVQNQG

[1684] 3929 RTINTAGQNQQT 4912 NHQSSTKNGEVFIAQAQTGWVQNQG

[1685] 3819 RTINGSGQNQQT 4913 NHQSSTKNGEVF1AQSQTGNVQNQG

[1686] 3819 RTINGSGQNQQT 4914 NHQSSTKNGEVFIAQAQTGWVGSQG

[1687] 3819 RTINGSGQNQQT 4915 NHQSSTKNGEVFIAQAQQSWVQNQG

[1688] 3949 RTINKGVSAGNQQT 4916 NHQSASRNGEVYIAQAQTGWVQNQG

[1689] 3819 RTINGSGQNQQT 4917 NHQSATKNGEVFIAQAQTGWVQQQG

[1690] 3819 RTINGSGQNQQT 4918 NHQSSTKNGEVFIAQAQTGWVNVQG

[1691] 3819 RTINGSGQNQQT 4919 N HQS ATRN GE VHIAMAQTGN SQN QG

[1692] 3930 RTINGTGMNQQT 4920 NHQSASRNGEVYIAQAQTGWVQNQG

[1693] 3819 RTINGSGQNQQT 4921 NHQSATRNGEVHIAMAQTGACQNQG

[1694] 3950 RTiVKGGSAGNQQT 4922 NHQSSTKNGEVFIAQAQTGWVQNQG

[1695] 3819 RTINGSGQNQQT 4923 NHQSAVKDGHVLIAIAQTGWVQNQG

[1696] 3951 RTINLGGSAGNQQT 4924 NHQSSTKNGEVFIAQAQTGWVQNQG

[1697] 3819 RTINGSGQNQQT 4925 NHQSAVKDGHVLIAMAQTGISQNQG

[1698] 3819 RTINGSGQNQQT 4926 NHQSATRNGEVHIAMAQTVPVQNQG

[1699] 3931 RTIQGDSSKQQT 4927 NHQSASRNGEVYIAQAQTGWVQNQG

[1700] 3932 RTiNKGASSQQT 4928 NHQSSTKNGEVFIAQAQTGWVQNQG

[1701] 3819 RTINGSGQNQQT 4929 NHQSSTKNGEVFIAQAQVGSVQNQG

[1702] 3819 RTINGSGQNQQT 4930 NHQSATRNGEVHIAMAQTDKVQNQG

[1703] 3819 RTINGSGQNQQT 4931 NHQSSTKNGEVFIAQAQTYWVQNQG

[1704] 3819 RTINGSGQNQQT 4932 NHQSSTKNGEVFIAQAQTGIAQNQG

[1705] 3819 RTINGSGQNQQT 4933 NHQSATRNGEVFIAQAQTGNVQNQG

[1706] 3851 RTINKGQSSQQT 4934 NHQSASRNGEVYIAQAQTGWVQNQG

[1707] 3977 RT1QGPVSSGKQNQQT 4935 NHQSSTKNGEVFIAQAQTGWVQNQG

[1708] 3933 RTINKGTSAQQT 4936 N HQS ATRN GE VF1AQAQTGWVQNQG

[1709] 3934 RTIGGVSSKQQT 4937 NHQSASRNGEVYIAQAQTGWVQNQG

[1710] 3935 RTINKTTASQQT 4938 NHQSSTKNGEVFIAQAQTGWVQNQG

[1711]

[1712] 3819 RTINGSGQNQQT 4939 NHQSASRNGEVYIAQAQTQYVQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[1713] ID sequence ID

[1714] NO NO

[1715] 3819 RTINGSGQNQQT 4940 NHQSATRNGEVFIANAQTGSVQNQG

[1716] 3819 RTINGSGQNQQT 4941 NHQSATRNGEVHIAMAQTGPAQNQG

[1717] 3936 RTINKGTSTSQT 4942 NHQSSTKNGEVFIAQAQTGWVQNQG

[1718] 3978 RTISGPVSSGKQNQQT 4943 NHQSSTKNGEVFIAQAQTGWVQNQG

[1719] 3937 RTINKGTSTNQT 4944 NHQSSTKNGEVFIAQAQTGWVQNQG

[1720] 3819 RTINGSGQNQQT 4945 NHQSAVKDGHVLIAMAQTQMVQNQG

[1721] 3819 RTINGSGQNQQT 4946 NHQSASRNGEVYIAQAQTGASQNQG

[1722] 3819 RTINGSGQNQQT 4947 NHQSSTKNGEVFIAQAQVAWVQNQG

[1723] 3819 RTINGSGQNQQT 4948 NHQSASRNGEVYIAQAQTGY1QNQG

[1724] 3979 RTINGPVSSGHQNQQT 4949 NHQSSTKNGEVFIAQAQTGWVQNQG

[1725] 3980 RTINGPAS SGKQNQQT 4950 NHQSASRNGEVYIAQAQTGWVQNQG

[1726] 3981 RTINGPVSSGKPNQQT 4951 NHQSSTKNGEVFIAQAQTGWVQNQG

[1727] 3819 RTINGSGQNQQT 4952 NHQGATRNGEVYIAQAQTGMVQNQG

[1728] 3982 RTINGPVS SGKANQQT 4953 NHQSSTKNGEVFIAQAQTGWVQNQG

[1729] 3819 RTINGSGQNQQT 4954 NHQSAVKDGHVLIAMAQTGWNNNQG

[1730] 3938 RTINKGTNSQQT 4955 NHQSSTKNGEVFIAQAQTGWVQNQG

[1731] 3819 RTINGSGQNQQT 4956 NHQSSTKNGEVFIAQAQTIHVQNQG

[1732] 3819 RTINGSGQNQQT 4957 NHQSSTKNGEVFIAQAQTTHVQNQG

[1733] 3952 RTINKGGSANNQQT 4958 NHQSSTKNGEVFIAQAQTGWVQNQG

[1734] 3819 RTINGSGQNQQT 4959 NHQSAVKDGHVLIAMAQTGWVHGQG

[1735] 3819 RTINGSGQNQQT 4960 NHQSSTKNGEVFIAQAQTGKVQNQG

[1736] 3819 RTINGSGQNQQT 4961 NHQSATRNGEVHIAMAQTGQAQNQG

[1737] 3819 RTINGSGQNQQT 4962 NHQSAVKDGHVL1AMAQTALVQNQG

[1738] 3819 RTINGSGQNQQT 4963 NHQSATRNGEVHIAMAQTGWINNQG

[1739] 3819 RTINGSGQNQQT 4964 N HQS ASRNGEV YIA Q A QTGYSQNQG

[1740] 3939 RTIGHDSSKQQT 4965 NHQSASRNGEVYIAQAQTGWVQNQG

[1741] 3819 RTINGSGQNQQT 4966 NHQSATRNGEVHIAMAQTQTVQNQG

[1742] 3819 RTINGSGQNQQT 4967 NHQSAVKDGHVLIAMAQTYSVQNQG

[1743] 3819 RTINGSGQNQQT 4968 NHQSATRNGEVH1AMAQTFAVQNQG

[1744] 3983 RTIMGPVSSGKQNQQT 4969 NHQSSTKNGEVFIAQAQTGWVQNQG

[1745] 3819 RTINGSGQNQQT 4970 NHQSATRNGEVHIAMAQTQFVQNQG

[1746] 3819 RTINGSGQNQQT 4971 NHQSATRNGEVHIAMAQTGWVNGQG

[1747] 3819 RTINGSGQNQQT 4972 N HQS ASRNGEV YIA QAQTLK VQN QG

[1748] 3940 RTINEGTRSQQT 4973 NHQSSTKNGEVFIAQAQTGWVQNQG

[1749] 3819 RTINGSGQNQQT 4974 NHQSSTKNGEVFIAQAQTGWVTGQG

[1750] 3941 RTINKATSSQQT 4975 NHQSSTKNGEVFIAQAQTGWVQNQG

[1751] 3742 RTIVKGQSSQQT 4976 NHQSSTKNGEVFIAQAQTGWVQNQG

[1752] 3819 RTINGSGQNQQT 4977 NHQSSTKNGEVFIAQAQTGQAQNQG

[1753] 3819 RTINGSGQNQQT 4978 NHQSSTKNGEVF1AQAQTVMVQNQG

[1754]

[1755] 3819 RTINGSGQNQQT 4979 NHQSATRNGEVHIAMAQTYPVQNQG Patent Application CAPS -041 / 01 WO 35847 / 197 SEQ VR-IV amino acid SEQ VR-VIII amino acid sequence

[1756] ID sequence ID

[1757] NO NO

[1758] 3819 RTINGSGQNQQT 4980 NHQSSTKNGEVFIAQAQTEKVQNQG

[1759] 3953 RTINKGTSAGNQQT 4981 NHQSASRNGEVYIAQAQTGWVQNQG

[1760] 3819 RTINGSGQNQQT 4982 NHQSSTKNGEVFIAQAQTGMTQNQG

[1761] 3819

[1762]

[1763] RTINGSGQNQQT 4983 NHQSATRNGEVHIAMAQTGWVQFQG

[1764] Further aspects of the invention

[1765] Aspects disclosed throughout this disclosure provide methods of treating a disease or condition in a subject comprising administering a therapeutically effective amount of a pharmaceutical formulation comprising the AAV capsid protein or the AAV capsid of the present disclosure, as described throughout the present specification. In some embodiments, the disease or the condition is a disease or a condition of the brain or CNS of the subject. Relatedly, the invention includes use of the rAAVs of the invention for the treatment of a disease or medical condition or for use in the manufacture of a medicament for treating or preventing the disease or medical condition.

[1766] In certain aspects, the invention provides an the AAV capsid protein, wherein the AAV capsid protein comprises an amino acid sequence selected from the group consisting of:

[1767] AQSTGQGFTAQAQTGWVQN (SEQ ID NO: 4991);

[1768] AQSTGQGFTAQPATGWVQN (SEQ ID NO: 1825);

[1769] AQSTGQGFTYPAQTGWVQN (SEQ ID NO: 2819), NHQSASRNGEVYIAQAQTAQVQNQG (SEQ ID NO: 3987);

[1770] NHQSSTKNGEVFIAQAQTSNVQNQG(SEQ ID NO: 4003);

[1771] NHQSSTKNGEVFIAQAQTGWVQNQG (SEQ ID NO: 40), NHQSASRNGEVYIAQAQTGWVQNQG (SEQ ID NO: 4137);

[1772] NHQSQTRNGGTLIAVAQTGWVQNQG (SEQ ID NO: 819);

[1773] NHQSATRNGEVFIAQAQTGWVQNQG (SEQ ID NO: 4936); and NHQSAVKDGHVLI AMAQTGSAQNQG (SEQ ID NO: 3989). Patent Application CAPS -041 / 01 WO 35847 / 197 In certain embodiments, the invention provides an the AAV capsid protein, wherein the AAV capsid protein comprises an amino acid sequence selected from the group consisting of:

[1774] RTINGAGQNQQT (SEQ ID NO: 3823);

[1775] RTINGSGQNQQT (SEQ ID NO: 3819);

[1776] RTIQGTGQNQQT (SEQ ID NO: 3820); and

[1777] RTINGTGQNQQT (SEQ ID NO: 3827).

[1778] In certain embodiments, the invention provides an AAV capsid comprising an AAV capsid provided herein. The present disclosure provides AAV capsids comprising AAV capsid protein comprising an amino acid substitution and / or insertion in a template AAV9 capsid protein. In certain embodiments, the template AAV9 capsid protein is provided in SEQ ID NO: 1.

[1779] In certain embodiments, 60 copies of the AAV capsid protein are assembled into the AAV capsid. In certain embodiments, the AAV capsid protein is present in VP1, VP2, and VP3 of the AAV capsid. In certain embodiments, the AAV capsid protein is characterized by at least one of an increased transduction enrichment when measured in a brain, spinal cord, and / or CNS in a subject when delivered to the subject systemically.

[1780] In certain embodiments, wherein the AAV capsid comprising AAV capsid protein of the invention is characterized by an increased transduction enrichment when measured in a brain in a subject when delivered to the subject systemically

[1781] In certain aspects, the invention provides pharmaceutical formulations comprising the AAV capsids of the invention. In certain aspects, the pharmaceutical formulations are for systemic administration to treat a disease or a condition of the brain, spinal cord, and / or central nervous system. In certain embodiments, the pharmaceutical formulations of the invention further comprise a pharmaceutically acceptable carrier.

[1782] In certain aspects, the invention provides for nucleic acid sequences encoding the capsid proteins of the invention. In certain embodiments, the invention provides a nucleic acid sequence encoding a capsid protein comprising the peptide sequence, wherein the peptide sequence is selected from the group consisting of peptide sequences provided in Tables 1-8.

[1783] In certain aspects, the invention provides a recombinant AAV comprising AAV capsid protein of the invention. In certain aspects, the invention provides a kit comprising: Patent Application CAPS -041 / 01 WO 35847 / 197 a) a first vector comprising the recombinant vector of the invention;

[1784] b) a second vector encoding a helper virus protein; and

[1785] c) a third vector comprising a therapeutic nucleic acid encoding a therapeutic gene expression product.

[1786] Aspects disclosed herein provide methods of treating a disease or condition in a subject comprising administering a therapeutically effective amount of a pharmaceutical formulation comprising the AAV capsid protein or the AAV capsid of the present disclosure. In some embodiments, the disease or the condition is a disease or a condition of the brain, and brain of the subject. Relatedly, the invention includes use of the rAAVs in the manufacture of a medicament for treating or preventing the disease or medical condition.

[1787] Advantageously, the AAVs of the invention rely on interaction of the AAV capsid protein with transmembrane proteins. Without being bound by the theory, the invention provides that this interaction with transmembrane proteins promotes transcytosis. In certain embodiments, the transmembrane proteins are disintegrin and metalloproteinase domain 15 (ADAMIS) or reversion inducing cysteine rich protein with Kazal motifs (RECK). ADAMI 5 is a metalloprotease-disintegrin implicated in ectodomain shedding and cell adhesion. ADAMI 5 has been implicated in numerous physiological and pathological processes through their proteolytic or adhesive activities, including ectodomain shedding and cell-cell interactions. ADAMI 5 is also known to impact the permeability of blood brain barrier, and is a target of interest for transcytosis. RECK is a dimeric multi-domain glycosylphosphatidylinositol (GPI)-anchored protein isolated as a tumor suppressor whose overexpressi on normalizes the aberrant morphology of transformed fibroblasts RECK is an inhibitor for metalloproteinases (MPs) of the MMP (matrix metalloproteinase). MPs promote cell migration by weakening the mechanical barrier properties of the extracellular matrix (ECM) and reducing cell-cell adhesion by destruction of intercellular junctions, which play a critical role in maintenance of blood-brain barrier. Accordingly, the invention recognizes that RECK is a target of interest to promote transcytosis.

[1788] Accordingly, in certain aspects, the present invention provides engineered AAV vectors, and methods of using vectors, comprising capsid proteins that comprise a sequence that binds to either a disintegrin and metalloproteinase domain 15 (ADAMI 5) or reversion inducing cysteine rich protein with Kazal motifs (RECK), membrane proteins expressed in several cell populations and tissues in the body, including brain microvascular endothelial cells in humans. By the present Patent Application CAPS -041 / 01 WO 35847 / 197 invention, it was discovered that engineered novel AAV vectors comprising a capsid protein having a sequence that allows the vector to bind to ADAMI 5 or RECK may have an increased ability to provide a gene therapy which crosses the blood brain barrier.

[1789] Without being limited by a mechanism of action, this increased ability to cross the plasma membrane of the target cells may be provided by ADAMI 5 or RECK mediated transcytosis (i.e. receptor mediated transport of extracellular cargo across the cytoplasm of a cell to a different plasma membrane surface).

[1790] In certain aspects, the invention provides an engineered AAV vector comprising an engineered capsid protein comprising an amino acid sequence that allows the capsid protein to bind to ADAMI 5 or RECK. The engineered AAV may further comprise a nucleic acid encoding a transgene, with the nucleic acid encapsidated by the engineered capsid protein.

[1791] In certain embodiments, the engineered AAV vector may be derived from an AAV9 vector. Advantageously, the AAV vector may be modified from the AAV9 vector to exhibit tissue specificity and to comprise the sequence that binds to the AD AMI 5 or RECK protein.

[1792] For example, the amino acid sequence that allows the capsid protein to bind to ADAMI 5 or RECK comprises an amino acid sequence selected from the amino acid sequences provided in Tables 1-8. Advantageously, the AAV vector may be characterized by at least one of an increased specificity and / or increased transduction efficiency in the central nervous system (CNS) tissue. Notably, when provided to a cell expressing ADAM 15 or RECK as a surface protein, binding of the capsid protein to the binding protein, ADAMI 5 and / or RECK, may mediate delivery of the transgene across the BBB, for example via transcytosis.

[1793] Accordingly, in certain aspects, the invention provides an engineered adeno-associated virus (AAV) vector comprising an engineered capsid protein comprising an amino acid sequence that allows the capsid protein to bind disintegrin and metalloproteinase domain 15 (ADAM15). In certain aspects, when the capsid protein is in presence of a cell expressing ADAMI 5, then the capsid protein binds to ADAM 15. In certain aspects, the invention provides an AAV vector comprising a nucleic acid encoding a transgene, wherein the nucleic acid encapsidated by the engineered capsid protein. In certain embodiments, the AAV capsid comprises an engineered capsid protein comprises amino acid sequence selected from the amino acid sequences provided in Tables 1-8. In certain embodiments, the AAV capsid comprises an engineered capsid protein comprises amino acid sequence selected from the group consisting of: Patent Application CAPS -041 / 01 WO 35847 / 197 NHQSASRNGEVYIAQAQTAQVQNQG (SEQ ID NO: 3987);

[1794] NHQSSTKNGEVFIAQAQTSNVQNQG (SEQ ID NO: 4003);

[1795] NHQSSTKNGEVFIAQAQTGWVQNQG (SEQ ID NO: 40);

[1796] NHQSASRNGEVYIAQAQTGWVQNQG (SEQ ID NO: 4137);

[1797] NHQSQTRNGGTLIAVAQTGWVQNQG (SEQ ID NO: 819); and NHQSATRNGEVFIAQAQTGWVQNQG (SEQ ID NO: 4936).

[1798] In certain aspects, the invention provides a method of delivering a transgene across the BBB, the method comprising providing a subject an engineered AAV vector comprising: a) an engineered capsid protein comprising an amino acid sequence that allows the A AV vector to bind the ADAMI 5 protein; and

[1799] b) a transgene encapsidated by the capsid protein;

[1800] binding the AAV vector to the ADAMI 5 protein in cells expressing the ADAM 15 protein, thereby delivering the transgene to the cell. In certain embodiments, the AAV capsid comprises an engineered capsid protein comprises amino acid sequence selected from the amino acid sequences provided in Tables 1-8. In certain embodiments, the AAV capsid comprises an engineered capsid protein comprises amino acid sequence selected from the group consisting of:

[1801] NHQSASRNGEVYIAQAQTAQVQNQG (SEQ ID NO: 3987);

[1802] NHQSSTKNGEVFIAQAQTSNVQNQG (SEQ ID NO: 4003);

[1803] NHQSSTKNGEVFIAQAQTGWVQNQG (SEQ ID NO: 40);

[1804] NHQSASRNGEVYIAQAQTGWVQNQG (SEQ ID NO: 4137);

[1805] NHQSQTRNGGTLIAVAQTGWVQNQG (SEQ ID NO: 819); and NHQSATRNGEVFIAQAQTGWVQNQG (SEQ ID NO: 4936).

[1806] In certain aspects, the invention provides an engineered adeno-associated virus (AAV) vector comprising an engineered capsid protein comprising an amino acid sequence that allows the capsid protein to bind reversion-inducing cysteine-rich protein with kazal motifs (RECK), wherein when the capsid protein is in presence of a cell expressing RECK, then the capsid protein binds to RECK. In certain aspects, when the capsid protein is in presence of a cell expressing RECK, then the capsid protein binds to RECK. In certain aspects, the invention provides an AAV vector comprising a nucleic acid encoding a transgene, wherein the nucleic acid encapsidated by the engineered capsid protein. In certain embodiments, the AAV capsid further comprises a nucleic acid encoding a transgene, wherein the nucleic acid encapsidated by the engineered capsid protein. Patent Application CAPS -041 / 01 WO 35847 / 197 In certain embodiments, the AAV capsid comprises an engineered capsid protein comprises amino acid sequence selected from the amino acid sequences provided in Tables 1-8. In certain embodiments, the AAV capsid comprises an engineered capsid protein comprises amino acid sequence selected from the group consisting of:

[1807] AQSTGQGFTAQAQTGWVQN (SEQ ID NO: 4991);

[1808] AQSTGQGFTAQPATGWVQN (SEQ ID NO: 1825); and AQSTGQGFTYPAQTGWVQN (SEQ ID NO: 2819).

[1809] In certain aspects, the invention provides a method of delivering a transgene across the BBB, the method comprising providing a subject an engineered A AV vector comprising:

[1810] a) an engineered capsid protein comprising an amino acid sequence that allows the AAV vector to bind the RECK protein, and

[1811] b) a transgene encapsidated by the capsid protein;

[1812] binding the AAV vector to the RECK protein in cells expressing the RECK protein, thereby delivering the transgene across the BBB. In certain embodiments, the AAV capsid comprises an engineered capsid protein comprises amino acid sequence selected from the amino acid sequences provided in Tables 1-8. In certain embodiments, the AAV capsid comprises an engineered capsid protein comprises amino acid sequence selected from the group consisting of:

[1813] AQSTGQGFTAQAQTGWVQN (SEQ ID NO: 4991);

[1814] AQSTGQGFTAQPATGWVQN (SEQ ID NO: 1825), and AQSTGQGFTYPAQTGWVQN (SEQ ID NO: 2819)

[1815] In certain aspects, the invention beneficially relies on enhanced transcytosis of AAV capsids of the invention in cells expressing certain proteins. Without being bound by the theory, the engineered AAV capsids of the invention rely on interaction with the proteins expressed on the surface for delivering AAV capsids inside the cell. In certain embodiments, the engineered AAV capsids of the invention are delivered to the cells expressing ADAM15 In certain embodiments, the engineered AAV capsids of the invention are delivered to the cells expressing RECK.

[1816] In certain aspects, the invention provides a method for delivery of the engineered AAV capsids in the cells in brain by direct systemic administration of the capsids in the invention. In certain embodiments, the engineered AAV capsids of the invention are delivered to the cells in the brain expressing ADAMI 5. In certain embodiments, the engineered AAV capsids of the invention Patent Application CAPS -041 / 01 WO 35847 / 197 are delivered to the cells in the brain expressing ADAMI 5. Accordingly, the methods of the invention provide targeted delivery to cells in the brain expressing certain proteins.

[1817] In certain aspects, the invention provides a method of delivering a transgene to a cell in the brain, the method comprising providing a subject an engineered AAV vector comprising:

[1818] a) an engineered capsid protein comprising an amino acid sequence that allows the AAV vector to bind ADAM 15 protein; and

[1819] b) a transgene encapsi dated by the capsid protein;

[1820] binding the AAV vector to the ADAMI 5 protein in cells expressing the ADAMI 5 protein, thereby delivering the transgene in the cell.

[1821] In certain embodiments, the engineered capsid protein is any capsid protein provided herein. In certain embodiments, the engineered capsid protein comprises amino acid sequence selected from the amino acid sequences provided in Tables 1-8, and preferably engineered capsid protein comprise amino acid sequence selected from the group consisting of:

[1822] NHQSASRNGEVYIAQAQTAQVQNQG (SEQ ID NO: 3987);

[1823] NHQSSTKNGEVFIAQAQTSNVQNQG (SEQ ID NO: 4003), NHQSSTKNGEVFIAQAQTGWVQNQG (SEQ ID NO: 40);

[1824] NHQSASRNGEVYIAQAQTGWVQNQG (SEQ ID NO: 4137);

[1825] NHQSQTRNGGTLIAVAQTGWVQNQG (SEQ ID NO: 819); and NHQSATRNGEVFIAQAQTGWVQNQG (SEQ ID NO: 4936)

[1826] In certain embodiments, the AAV vector exhibits increased specificity toward the cells expressing ADAM15 as compared to cells not expressing ADAM15. In certain embodiments, said engineered AAV vector is administered directly to brain of said subject. In certain embodiments, said engineered AAV vector is administered via systemic administration. In certain embodiments, said engineered AAV vector exhibits increased specificity and / or increased transcytosis in cells expressing ADAMI 5 as compared to cells that do not express ADAMIS.

[1827] In certain aspects, the invention provides a method of delivering a transgene to a cell in the brain, the method comprising providing a subject an engineered AAV vector comprising:

[1828] a) an engineered capsid protein comprising an amino acid sequence that allows the AAV vector to bind RECK protein; and

[1829] b) a transgene encapsidated by the capsid protein; Patent Application CAPS -041 / 01 WO 35847 / 197 binding the AAV vector to the RECK protein in cells expressing the RECK protein, thereby delivering the transgene in the cell. In certain embodiments, the engineered capsid protein is any capsid protein provided herein. In certain embodiments, the engineered capsid protein comprises amino acid sequence selected from the amino acid sequences provided in Tables 1-8, and preferably engineered capsid protein comprise amino acid sequence selected from the group consisting of:

[1830] AQSTGQGFTAQAQTGWVQN (SEQ ID NO: 4991);

[1831] AQSTGQGFTAQPATGWVQN (SEQ ID NO: 1825); and AQSTGQGFTYPAQTGWVQN (SEQ ID NO: 2819).

[1832] In certain embodiments, the AAV vector exhibits increased specificity toward the cells expressing RECK as compared to cells not expressing RECK. In certain embodiments, said engineered AAV vector is administered to brain of said subject. In certain embodiments, said engineered AAV vector is administered directly to brain of said subject. In certain embodiments, said engineered AAV vector is administered via systemic administration. In certain embodiments, said engineered AAV vector exhibits increased specificity and / or increased transcytosis in cells expressing RECK as compared to cells that do not express RECK.

[1833] Aspects of capsid proteins are described in further detail below. For sequences disclosed throughout this application, it is understood that nucleic acid molecules and peptides may comprise one or more substitutions, for example conservative substitutions, that allow sequences to continue to function. Accordingly, sequences may have at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence disclosed.

[1834] A conservative substitution refers to amino acid substitutions that do not significantly affect or alter binding characteristics of a particular protein. Generally, conservative substitutions are ones in which a substituted amino acid residue is replaced with an amino acid residue having a similar side chain. For example, conservative substitutions may include a substitution found in one of the following groups: Group 1: Alanine (Ala or A), Glycine (Gly or G), Serine (Ser or S), Threonine (Thr or T); Group 2: Aspartic acid (Asp or D), Glutamic acid (Glu or E); Group 3: Asparagine (Asn or N), Glutamine (Gin or Q); Group 4: Arginine (Arg or R), Lysine (Lys or K), Histidine (His or H); Group 5: Isoleucine (He or I), Leucine (Leu or L), Methionine (Met or M), Valine (Vai or V); and Group 6: Phenylalanine (Phe or F), Tyrosine (Tyr or Y), Tryptophan (Trp Patent Application CAPS -041 / 01 WO 35847 / 197 or W). Additionally, or alternatively, amino acids can be grouped into conservative substitution groups by similar function, chemical structure, or composition (e.g., acidic, basic, aliphatic, aromatic, or sulfur-containing). For example, an aliphatic grouping may include, for purposes of substitution, Gly, Ala, Vai, Leu, and He. Other conservative substitutions groups include sulfur-containing: Met and Cysteine (Cys or C); acidic: Asp, Glu, Asn, and Gin; small aliphatic, nonpolar, or slightly polar residues: Ala, Ser, Thr, Pro, and Gly; polar, negatively charged residues and their amides: Asp, Asn, Glu, and Gin; polar, positively charged residues: His, Arg, and Lys; large aliphatic, nonpolar residues: Met, Leu, He, Vai, and Cys; and large aromatic residues: Phe, Tyr, a d Trp.

[1835] Other aspects of the invention will be apparent from the detailed description and claims that follow.

[1836] BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1A and FIG. IB provide the data from library screening for identification of ADAMI 5 and RECK as the binding partners for the capsids.

[1837] FIG. 2 provides siRNA knockdown data with engineered capsids.

[1838] FIG. 3 provides the data related to the overexpression of homologs of ADAM 15 in modulating transduction.

[1839] FIG. 4 provides the data related to overexpression screening in CHO-K1 cells.

[1840] FIG. 5A, FIG. 5B, and FIG. 5C provide data for species-specific RECK for the novel engineered capsids.

[1841] DETAILED DESCRIPTION OF THE DISCLOSURE

[1842] Disclosed herein are AAV capsids engineered with increased viral transduction in the brain. The AAV capsids can encapsidate a viral vector with a heterologous nucleic acid encoding, for example, a therapeutic gene expression product. Transduction of the heterologous nucleic acid in the brain can be achieved upon systemic delivery' to a subject of the AAV capsid of the present disclosure encapsidating a heterologous nucleic acid. The AAV capsids disclosed herein are advantageous for many applications of gene therapy to treat human disease, including, but not limited to, disorders of the central nervous system.

[1843] The recombinant AAV vectors comprising a nucleic acid sequence encoding the AAV Patent Application CAPS -041 / 01 WO 35847 / 197 capsid proteins of the present disclosure as also provided herein. For example, the viral vectors of the present disclosure comprise a nucleic acid sequence comprising the AAV viral Cap (Capsid) encoding VP1, VP2, and VP3, at least one of which is modified to produce the AAV capsid proteins of the present disclosure. The recombinant AAV vector provided can be derived from an AAV serotype (e.g, AAV9) or a variant AAV serotype including an insertion of the present invention.

[1844] AAV Capsids

[1845] Provided herein are modified adeno-associated (AAV) virus capsid compositions useful for integrating a transgene into a target cell or environment (in a subject when they are administered systemically).

[1846] An rAAV comprises an AAV capsid that can be engineered to encapsidate a heterologous nucleic acid (e.g., therapeutic nucleic acid, gene editing machinery). The AAV capsid is made up of three AAV capsid protein monomers, VP1, VP2, and VP3. Sixty copies of these three VP proteins interact in a 1:1:10 ratio to form the viral capsid. VP1 covers the whole of VP2 protein in addition to a -137 amino acid N-terminal region (VPlu), VP2 covers the whole of VP3 in addition to -65 amino acid N-terminal region (VP 1 / 2 common region). The three capsid proteins share a conserved amino acid sequence of VP3, which in some cases is the region beginning at amino acid position 138 e.g., AA139-736).

[1847] While not wishing to be bound by theory, it is understood that a parent AAV capsid sequence comprises a VP1 region. In certain embodiments, a parent AAV capsid sequence comprises a VP1, VP2, and / or VP3 region, or any combination thereof. A parent VP1 sequence may be considered synonymous with a parent AAV capsid sequence.

[1848] The AAV VP3 structure contains highly conserved regions that are common to all serotypes, a core eight-stranded P-barrel motif ( B- i) and a small a-helix (aA). The loop regions inserted between the P-strands consist of the distinctive HI loop between p-strands H and I, the DE loop between P-strands D and E, and nine variable regions (VRs), which form the top of the loops. These VRs, such as the VR-VIII, which contains AA588 in AAV9, are found on the capsid surface and can be associated with specific functional roles in the AAV life cycle including receptor binding, transduction, and antigenic specificity. Patent Application CAPS -041 / 01 WO 35847 / 197 In some embodiments, the w-mer motif can be inserted between two amino acids in a variable amino acid region in an AAV capsid protein. The core of each wild-type AAV viral protein contains an eight-stranded beta-barrel motif (betaB to betal) and an alpha-helix (alphaA) that are conserved in autonomous parvovirus capsids (see e.g., DiMattia et al. 2012. J. Virol.

[1849] 86(12):6947-6958). Structural variable regions (VRs) occur in the surface loops that connect the beta-strands, which cluster to produce local variations in the capsid surface. AAVs have 12 variable regions (also referred to as hypervariable regions) (see e.g., Weitzman and Linden. 2011. “Adeno-Associated Virus Biology.” In Snyder, R. O., Moullier, P. (eds.) Totowa, NJ: Humana Press). In some embodiments, one or more w-mer motifs can be inserted between two amino acids in one or more of the 12 variable regions in the wild-type AAV capsid proteins. In some embodiments, the one or more w-mer motifs can be each be inserted between two amino acids in VR-I, VR-II, VR-III, VR-IV, VR-V, VR-VI, VR-VII, VR-III, VR-IX, VR-X, VR-XI, VR-XII, or a combination thereof. In some embodiments, the w-mer can be inserted between two amino acids in the VR-III of a capsid protein.

[1850] In some aspects, the rAAV variant of the present invention comprises an AAV capsid protein having a peptide insertion at the residues corresponding to amino acids 588-589 (VR-VI II) of the AAV9 native sequence of SEQ ID NO: 1

[1851] The AAV capsids comprise AAV capsid proteins (e.g., VP1, VP2, and VP3), each with an insertion, such as in the VR-VIII containing AA588 of a parental AAV capsid protein structure (AAV9 VP1 numbering). VR-VIII contains the site of heparan sulfate binding of AAV2 and is amenable to peptide display. The only known receptors for AAV9 are N-linked terminal galactose and AAV receptor (AAVR), but many indications point toward there being others. Modifications to AAV9 within VR-VIII are shown herein to confer an increased transgene transduction in target in vivo environments.

[1852] Disclosed herein are AAV capsids comprising AAV capsid proteins with an insertion in VR-VIII that confer a higher transduction in brain cell types (e.g., brain endothelial cells, neurons, astrocytes). In particular, the AAV capsid proteins disclosed herein enable rAAV-mediated transduction of a heterologous nucleic acid (e.g., transgene) in the brain of a subject. The AAV capsids of the present disclosure may be formulated as a pharmaceutical composition. In addition, the AAV capsids can be isolated and purified to be used for a variety of applications. Patent Application CAPS -041 / 01 WO 35847 / 197 The rAAV capsid proteins of the present disclosure may also have an insertion and / or substitution of an amino acid sequence in the VR-IV region, for example at amino acid position 452-458 in a parental AAV9 capsid protein, or variant thereof, for example in the manner described in W02020 / 068990.

[1853] In some embodiments, the rAAV capsid of the present disclosure are generated using the methods disclosed herein. In some instances, the rAAV capsid is chimeric. In some instances, the rAAV, or variant AAV protein comprises therein, confer an increase in a localization of the rAAV within the target tissue, as compared to the parental AAV capsid or capsid protein.

[1854] AAV Capsid Proteins

[1855] Disclosed herein are recombinant AAV (rAAV) capsids which comprise AAV capsid proteins that are engineered with a modified capsid protein (e.g., VP1, VP2, VP3). In some embodiments, the rAAV capsid proteins of the present disclosure are generated using the methods disclosed herein. In some embodiments, the AAV capsid proteins are used in the methods of delivering a therapeutic nucleic acid (e.g, a transgene) to a subject. In some instances, the rAAV capsid proteins have desired AAV expression rendering them particularly suitable for certain therapeutic applications, e.g., the treatment of a disease or disorder in a subject such as those disclosed herein.

[1856] The rAAV capsid proteins are engineered for optimized expression in the brain, for example the brain, of a subject upon systemic administration of the rAAV to the subject. The rAAV capsid proteins are engineered to include the insertions / substitutions provided above. The rAAV capsid proteins are engineered to achieve efficient transduction of an encapsidated transgene. In particular, the rAAV capsid proteins have increased expression in the brain of a subject.

[1857] The engineered AAV capsid proteins described herein have, in some cases, an insertion of an amino acid that is heterologous to the parental AAV capsid protein at amino acid positions in the VR-VIII region of the capsid. In some embodiments, the amino acid is not endogenous to the parental AAV capsid protein at the amino acid position of the insertion. The amino acid may be a naturally occurring amino acid in the same or equivalent amino acid position as the insertion of the substitution in a different AAV capsid protein. Patent Application CAPS -041 / 01 WO 35847 / 197 The rAAV capsid proteins of the present disclosure comprise an insertion of an amino acid in an amino acid sequence of an AAV capsid protein. The AAV capsid, from which an engineered AAV capsid protein of the present disclosure is produced, is referred to as a “parental” AAV capsid. The complete genome of AAV1 is provided in GenBank Accession No. NC__002077; the complete genome of AAV2 is provided in GenBank Accession No. NC 001401 and Srivastava et al., J. Virol,, 45: 555-564 (1983), the complete genome of AAV3 is provided in GenBank Accession No. NC_1829; the complete genome of AAV4 is provided in GenBank Accession No. NC 001829; the AAV 5 genome is provided in GenBank Accession No. AF085716; the complete genome of AAV6 is provided in GenBank Accession No. NC_001862; at least portions of AAV7 and AAV8 genomes are provided in GenBank Accession Nos. AX753246 and AX753249, respectively; the AAV9 genome is provided in Gao et al., J. Virol., 78: 6381-6388 (2004); the AAV10 genome is provided in Mol. Then, 13(1): 67-76 (2006); the AAV11 genome is provided in Virology, 330(2): 375-383 (2004); portions of the AAV12 genome are provided in Genbank Accession No. DQ813647; portions of the AAV13 genome are provided in Genbank Accession No. EU285562.

[1858] In some cases, the parental AAV is derived from an AAV with a serotype selected from AAV1, AAV2, AAV3, AAV4, AAV5, A V6, AAV7, AAV8, AAV9, AAV 10, A AV 11 and AAV12. The AAV capsid protein that is “derived” from another may be a variant AAV capsid protein. A variant may include, for example, a heterologous amino acid in an amino acid sequence of the AAV capsid protein. The heterologous amino acid may be non-naturally occurring in the AAV capsid protein. The heterologous amino acid may be naturally occurring in a different AAV capsid protein. In some instances, the parental AAV capsid is described in US Pat Publication 2020 / 0165576 and US. Pat App, Ser. No. 62 / 832,826 and PCT / US20 / 20778; the content of each of which is incorporated herein.

[1859] In some instances, the parental AAV is AAV9. In some instances, the amino acid sequence of the AAV9 capsid protein comprises SEQ ID NO: 1. The amino acid sequence of AAV9 VP1 capsid protein is provided in SEQ ID NO: 1: (MAADGYLPDWLEDNLSEGIREWWALKPGAPQPKANQQHQDNARGLVLPGYKYLGPG NGLDKGEPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGG NLGRAVFQAKKRLLEPLGLVEEAAKTAPGKKRPVEQSPQEPDSSAGIGKSGAQPAKKRL Patent Application CAPS -041 / 01 WO 35847 / 197 NFGQTGDTES VPDPQPIGEPP A APSGVGSLTMA SGGGAPVADNNEGADGVGS S SGNWH CDSQWLGDRVITTSTRTWALPTYNNHLTTCQISNSTSGGSSNDNAYFGYSTPWGYFDFN RFFICHFSPRDWQRLINNNWGFRPKRLNFKLFNIQVKEVTDNNGVKTIANNLTSTVQVFT D SD YQLPYVLG S AHEGCLPPFP AD VFMIPQ YG YLTLNDG SQ AVGRS SF YCLE YFP SQML RTGNNFQFSYEFENVPFHSSYAHSQSLDRLMNPLIDQYLYYLSKTINGSGQNQQTLKFSV AGPSNMAVQGRNYIPGPSYRQQRVSTTVTQNNNSEFAWPGASSWALNGRNSLMNPGP AMASHKEGEDRFFPLSGSLIFGKQGTGRDNVDADKVMITNEEEIKTTNPVATESYGQVA TNHQ S AQ AQ AQTGWVQNQGILPGMVWQDRD VYLQGPIWAKIPHTDGNFHP SPLMGGF GMKFIPPPQIL1KNTPVPADPPTAFNKDKLNSFITQYSTGQVSVTIEWELQKENSKRWNPE IQYINNYYKSNNVEFAVNTEGVYSEPRPIGTRYLTRNL).

[1860] In some instances, the parental AAV capsid protein sequence is 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% homologous to SEQ ID NO: 1.

[1861] AAV capsid proteins from naturally occurring AAV serotypes, such as / XAV9, display peripheral organ tropism (including the liver) and activate the innate immune response. In some cases, transduction of peripheral organs can cause a severe inflammatory response in a subject, which can lead to multi-organ failure. By improving transduction of a native AAV serotype for a target in vivo tissue e.g., brain), the r. AAV particles of the present disclosure reduce the immunogenic properties of AAV-mediated transgene delivery and prevent activation of the innate immune response.

[1862] In some instances, the parental AAV capsid protein comprises the entire VP1 region provided in SEQ ID NO: 1 (e.g., amino acids 1-736). In some instances, the parental AAV capsid protein comprises amino acids 217-736 in SEQ ID NO: 1, which is the common region found in VP1, VP2, and VP3 AAV9 capsid proteins. In some instances, the AAV capsid protein comprises amino acids 64-736 in SEQ ID NO: 1, which is the common region found in VP1 and VP2. The parental AAV capsid protein sequence may comprise amino acids selected from 1-736, 10-736. 20-736, 30-736, 40-736, 50-736, 60-736, 70-736, 80-736, 90-736, 100-736, 110-736, 120-736, 130-736, 140-736, 150-736, 160-736, 170-736, 180-736, 190-736, 200-736, 210-736, 220-736, 230-736, 240-736, 250-736, 260-736, 270-736, 280-736, 290-736, 300-736, 310-736, 320-736, 330-736, 340-736, 350-736, 360-736, 370- Patent Application CAPS -041 / 01 WO 35847 / 197 736, 380-736, 390-736, 400-736, 410-736, 420-736, 430-736, 440-736, and 450-736, from SEQ ID NO: 1. In some aspects, the rAAV variant comprises an AAV capsid protein comprising an amino acid sequence that is at least 98% identical to amino acid 217 to amino acid 736 of SEQ ID NO: 1. In some instances, the amino acid insertion is at a three (3)-fold axis of symmetry' of a corresponding parental AAV capsid protein.

[1863] Disclosed herein are insertions of an amino acid sequence in an AAV capsid protein. Where the sequence numbering designation “’588-589” is noted for AAV9, for example AAV VP1, the invention also includes insertions in similar locations in the other AAV serotypes. As used herein, “AA588-589” indicates that the insertion and / or substitution of the amino acid (or amino acid sequence) is immediately after an amino acid (AA) at position 588 and immediately before an AA at position 589 within an amino acid sequence of a parental AAV VP capsid protein (VP1 numbering). Itis envisioned that the sequences disclosed herein (Tables 1-4, Table 8, andFormulas I-IV) may be inserted at AA583-600 (replacing amino acids AA583-600) and / or AA452-458 (replacing amino acids AA452-458) in an amino acid sequence of a parental AAV9, a variant thereof, or equivalent amino acid position of a parental AAV of a different serotype (e.g., AAV1, AAV2, AAV3, and the like).

[1864] The insertions described herein may, in some cases, comprise a 7-mer insertion between AA588 and AA589. It is envisioned that a 7-mer insertion included within the sequence lists disclosed herein, in addition to a substitution with any amino acid at amino acid positions 587-597 of SEQ ID NO: 1, may comprise an 11-mer.

[1865] Disclosed herein are AAV capsid proteins with an insertion described above in a parental AAV capsid protein that confers an increased transduction in the brain in a subject, even when delivered systemically. One of the many advantages of the AAV capsid proteins described herein is their ability to target tissue and cells within the brain. The tissue can be the brain. Non -limiting examples of brain cells include a neuron and a glial cell. Glial cells can be selected from an oligodendrocyte, an ependymal cell, an astrocyte, and a microglia.

[1866] The rAAV capsid proteins of the present disclosure may also have an insertion and / or substitution of an amino acid sequence at amino acid position 452-458 in a parental AAV9 capsid protein, or variant thereof, as described in W02020 / 068990.

[1867] The rAAV capsid proteins described herein may be isolated and purified. The AAV may Patent Application CAPS -041 / 01 WO 35847 / 197 be isolated and purified by methods standard in the art such as by column chromatography, iodixanol gradients, or cesium chloride gradients. Methods for purifying AAV from helper virus are known in the art and may include methods disclosed in, for example, Clark et al., Hum. Gene Then, 10(6): 1031-1039 (1999); Schenpp and Clark, Methods Mol. Med., 69: 427-443 (2002); U. S. Patent No. 6,566,118 and WO 98 / 09657.

[1868] In addition, the AAV capsid proteins disclosed herein, either isolated and purified, or not, may be formulated into a pharmaceutical formulation, which in some cases, further comprises a pharmaceutically acceptable carrier.

[1869] The rAAV capsid protein can be conjugated to a nanoparticle, a second molecule, or a viral capsid protein. In some cases, the nanoparticle or viral capsid protein would encapsidate the therapeutic nucleic acid described herein. In some instances, the second molecule is a therapeutic agent, e.g., a small molecule, antibody, antigen-binding fragment, peptide, or protein, such as those described herein

[1870] ■‘Percent Identity” is the percent of the symbols that actually match. Percent Similarity is the percent of the symbols that are similar. Symbols that are across from gaps are ignored. A similarity is scored when the scoring matrix value for a pair of symbols is greater than or equal to 0.50, the similarity threshold. The scoring matrix used in Version 10 of the Wisconsin Genetics Software Package is BLOSUM62 (see: Henikoff and Henikoff, (1989) Proc. Natl. Acad. Sci. USA 89: 10915).

[1871] Sequence identity / similarity values provided herein can refer to the value obtained using the BLAST-r 2.5.0 suite of programs using default settings (blast.ncbi.nlm.nih.gov) (Camacho, C., et al. (2009) BLAST+: architecture and applications. BMC Bioinformatics 10:421).

[1872] As those of ordinary skill in the art will understand, BLAST searches assume that proteins can be modeled as random sequences. However, many real proteins comprise regions of nonrandom sequences, which may be homopolymeric tracts, short-period repeats, or regions enriched in one or more amino acids. Such low-complexity regions may be aligned between unrelated proteins even though other regions of the protein are entirely dissimilar. A number of low-complexity filter programs can be employed to reduce such low-complexity alignments. For example, the SEG (Wooten and Federhen, (1993) Comput. Chem. 17: 149-63) and XNU (Ci-ayerie and States (1993) Comput. Chem. 17: 191-201) low-complexity filters can be employed alone or Patent Application CAPS -041 / 01 WO 35847 / 197 in combination

[1873] The terms “substantial identity” and “substantially identical” indicate that a polypeptide or nucleic acid comprises a sequence with between 55-100% sequence identity to a reference sequence, with at least 55% sequence identity, or at least 60%, or at least 65%, or at least 70%, or at least 75%, or at least 80%, or at least 85%, or at least 90%, or at least 95%, or at least 99% sequence identity or any percentage of value within the range of 55-100% sequence identity relative to the reference sequence. The percent sequence identity may occur over a specified comparison window. Optimal alignment may be ascertained or conducted using the homology alignment algorithm of Needleman and Wunsch, supra

[1874] For example, the insertion sequences may include, but are not limited to, sequences that are not exactly the same as the sequences disclosed herein, but which have, in addition to the substitutions explicitly described for various sequences listed herein, additional substitutions of amino acid residues which substantially do not impair the activity or properties of the sequences described herein, such as those predicted by homology software e.g. BLOSUM62 matrices.

[1875] AAV Particles

[1876] The rAAV particles with the insertion sequences described herein have an increased transduction enrichment in the brain. In some instances, the increased transduction enrichment comprises a 1-fold, 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold, 8-fold, 9-fold or 10-fold increase, or more. In some instances, the increased transduction enrichment is at least 1-fold. In some instances, the increased transduction enrichment is at least 2-fold. In some instances, the increased transduction enrichment is at least 4-fold.

[1877] The rAAV particles with the insertion sequences described herein have an increased expression enrichment in the brain. Detecting whether a rAAV possesses more or less specificity for a target in vivo environment, includes measuring a level of gene expression product (e.g., RNA or protein) expressed from the heterologous nucleic acid encapsidated by the rAAV in a tissue sample obtained from a subject. Suitable methods for measuring expression of a gene expression product include next-generation sequencing (NGS) and quantitative polymerase chain reaction (qPCR). Patent Application CAPS -041 / 01 WO 35847 / 197 Heterologous Nucleic Acids

[1878] Disclosed herein are therapeutic nucleic acids useful for the treatment or prevention of a disease or condition, or symptom of the disease or condition. In some embodiments, the therapeutic nucleic acids encode a therapeutic gene expression product. Non-limiting examples of gene expression products include proteins, polypeptides, peptides, enzymes, antibodies, antigen binding fragments, nucleic acid (RNA, DNA, antisense oligonucleotide, siRNA, and the like), and gene editing components, for use in the treatment, prophylaxis, and / or amelioration of the disease or disorder, or symptoms of the disease or disorder. In some instances, the therapeutic nucleic acids are placed in an organism, cell, tissue or organ of a subject by way of a rAAV, such as those disclosed herein.

[1879] Disclosed herein are rAAVs, each comprising a viral vector (e.g., a single stranded DNA molecule (ssDNA)) In some instances, the viral vector comprises two inverted terminal repeat (ITR) sequences that are about 145 bases each, flanking a transgene. In some embodiments, the transgene comprises a therapeutic nucleic acid, and in some cases, a promoter in cis with the therapeutic nucleic acid in an open reading frame (ORF). The promoter is capable of initiating transcription of therapeutic nucleic acid in the nucleus of the target cell. The ITR sequences can be from any AAV serotype. Non-limiting examples of AAV serotypes include AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, and AAV12. In some cases, an ITR is from AAV2. In some cases, an ITR is from AAV9.

[1880] Disclosed herein are transgenes that can comprise any number of nucleotides. In some cases, a transgene can comprise less than about 100 nucleotides. In some cases, a transgene can comprise at least about 100 nucleotides In some cases, a transgene can comprise at least about 200 nucleotides. In some cases, a transgene can comprise at least about 300 nucleotides. In some cases, a transgene can comprise at least about 400 nucleotides In some cases, a transgene can comprise at least about 500 nucleotides. In some cases, a transgene can comprise at least about 1000 nucleotides. In some cases, a transgene can comprise at least about 5000 nucleotides. In some cases, a transgene can comprise over 5,000 nucleotides. In some cases, a transgene can comprise between about 500 and about 5000 nucleotides. In some cases, a transgene comprises about 5000 nucleotides. In any of the cases disclosed herein, the transgene can comprise DNA, RNA, or a Patent Application CAPS -041 / 01 WO 35847 / 197 hybrid of DNA and RNA In some cases, the transgene can be single stranded In some cases, the transgene can be double stranded.

[1881] Disclosed herein are transgenes useful for modulating the expression or activity of a target gene or gene expression product thereof. In some instances, the transgene is encapsidated by an rAAV capsid protein of an rAAV particle described herein. In some instances, the rAAV particle is delivered to a subject to treat a disease or condition disclosed herein in the subject. In some instances, the delivery is systemic.

[1882] The transgenes disclosed herein are useful for expressing an endogenous gene at a level similar to that of a healthy or normal individual. This is particularly useful in the treatment of a disease or condition related to the under-expression, or lack of expression, of a gene expression product. In some embodiments, the transgenes disclosed herein are useful for overexpressing an endogenous gene, such that an expression level of the endogenous gene is above the expression level of a healthy or normal individual Additionally, transgenes can be used to express exogenous genes (e.., active agent such as an antibody, peptide, nucleic acid, or gene editing components). In some embodiments, the therapeutic gene expression product is capable of altering, enhancing, increasing, or inducing the activity of one or more endogenous biological processes in the cell. In some embodiments, the transgenes disclosed herein are useful for reducing expression of an endogenous gene, for example, a dominant negative gene. In some embodiments, the therapeutic gene expression product is capable of altering, inhibiting, reducing, preventing, eliminating, or impairing the activity of one or more endogenous biological processes in the cell. In some aspects, the increase of gene expression refers to an increase by at least about 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95% and 100%. In one aspect, the protein product of the targeted gene may be increased by at least about 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%. 90%, 95% and 100%. In some aspects, the decrease of gene expression refers to an increase by at least about 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95% and 100%. In one aspect, the protein product of the targeted gene may be decreased by at least about 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%. 95% and 100%.

[1883] When endogenous sequences (endogenous or part of a transgene) are expressed with a transgene, the endogenous sequences can be full-length sequences (wild-type or mutant) or partial sequences. The endogenous sequences can be functional. Non-limiting examples of the function Patent Application CAPS -041 / 01 WO 35847 / 197 of these full length or partial sequences include increasing the serum half-life of the polypeptide expressed by a transgene (e.g., therapeutic gene) and / or acting as a carrier.

[1884] A transgene can be inserted into an endogenous gene such that all, some or none of the endogenous gene is expressed. For example, a transgene as described herein can be inserted into an endogenous locus such that some (N-terminal and / or C-terminal to a transgene) or none of the endogenous sequences are expressed, for example as a fusion with a transgene. In other cases, a transgene (e.g., with or without additional coding sequences of the endogenous gene) is integrated into any endogenous locus, for example a safe-harbor locus. For example, a Frataxin (FXN) transgene can be inserted into an endogenous FXN gene. A transgene can be inserted into any gene, e.g., the genes as described herein.

[1885] At least one advantage of the present disclosure is that virtually any therapeutic nucleic acid may be used to express any therapeutic gene expression product. In some instances, the therapeutic gene expression product is a therapeutic protein or a peptide (e.g., antibody, antigenbinding fragment, peptide, or protein). In one embodiment the protein encoded by the therapeutic nucleic acid is between 50-5000 amino acids in length. In some embodiments the protein encoded is between 50-2000 amino acids in length. In some embodiments the protein encoded is between 50-1000 amino acids in length. In some embodiments the protein encoded is between 50-1500 amino acids in length. In some embodiments the protein encoded is between 50-800 amino acids in length. In some embodiments the protein encoded is between 50-600 amino acids in length. In some embodiments the protein encoded is between 50-400 amino acids in length. In some embodiments the protein encoded is between 50-200 amino acids in length. In some embodiments the protein encoded is between 50-100 amino acids in length. In some embodiments the peptide encoded is between 4-50 amino acids in length In some embodiments, the protein encoded is a tetrapeptide, a pentapeptide, a hexapeptide, a heptapeptide, an octapeptide, a nonapeptide, or a decapeptide. In some embodiments, the protein encoded comprises a peptide of 2-30 amino acids, such as for example 5-30, 10-30, 2-25, 5-25, 10-25, or 10-20 amino acids. In some embodiments, the protein encoded comprises a peptide of at least 11, 12, 13, 14, 15, 17, 20, 25 or 30 amino acids, or a peptide that is no longer than 50 amino acids, e.g., no longer than 35, 30, 25, 20, 17, 15, 14, 13, 12, 11 or 10 amino acids.

[1886] Non-limiting examples of therapeutic protein or peptides include an adrenergic agonist, an Patent Application CAPS -041 / 01 WO 35847 / 197 anti -apoptosis factor, an apoptosis inhibitor, a cytokine receptor, a cytokine, a cytotoxin, an erythropoietic agent, a glutamic acid decarboxylase, a glycoprotein, a growth factor, a growth factor receptor, a hormone, a hormone receptor, an interferon, an interleukin, an interleukin receptor, a kinase, a kinase inhibitor, a nerve growth factor, a netrin, a neuroactive peptide, a neuroactive peptide receptor, a neurogenic factor, a neurogenic factor receptor, a neuropilin, a neurotrophic factor, a neurotrophin, a neurotrophin receptor, an N-methyl-D-aspartate antagonist, a plexin, a protease, a protease inhibitor, a protein decarboxylase, a protein kinase, a protein kinsase inhibitor, a proteolytic protein, a proteolytic protein inhibitor, a semaphoring, a semaphorin receptor, a serotonin transport protein, a serotonin uptake inhibitor, a serotonin receptor, a serpin, a serpin receptor, and a tumor suppressor. In certain embodiments, the therapeutic protein or peptide is selected from brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), macrophage colony-stimulating factor (CSF), epidermal growth factor (EGF), fibroblast growth factor (FGF), gonadotropin, interferon-gamma (IFN), insulin-like growth factor 1 (IFG-1), nerve growth factor (NGF), platelet-derived growth factor (PDGF), pigment epithelium-derived factor (PEDF), transforming growth factor (TGF), transforming growth factor-beta (TGF-B), tumor necrosis factor (TNF), vascular endothelial growth factor (VEGF), prolactin, somatotropin, X-linked inhibitor of apoptosis protein 1 (XI API), interleukin 1 (IL-1), IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-10, viral IL-10, IL-11, IL-12, IL- 13, IL-14, IL-15, IL-16, IL-17, and IL-18.

[1887] A therapeutic gene expression product can comprise gene editing components. Nonlimiting examples of gene editing components include those required for CRISPR / Cas, artificial site-specific RNA endonuclease (ASRE), zinc finger endonuclease (ZFN), and transcription factor like effector nuclease (TALEN). In a non-limiting example, a subject having Huntington's disease is identified. The subject is then systemically administered a first amount of a rAAV encapsidating a viral vector encoding ZFN engineered to represses the transcription of the Huntingtin (HTT) gene. The rAAV will include a modified AAV capsid protein that includes an amino acid sequence, as described above in Tables 1-8 and / or Formula I-VII, so as to allow proper targeting of the ZFN to the nervous system, while reducing expression in off-target organs, such as the liver. If needed, the subject is administered a second or third dose of the rAAV, until a therapeutically effective amount of the ZFN is expressed in the subject’s nervous system. Patent Application CAPS -041 / 01 WO 35847 / 197 A therapeutic nucleic acid can comprise a non-protein coding gene e.g., sequences encoding antisense RNAs, RNAi, shRNAs and micro RNAs (miRNAs), miRNA sponges or decoys, recombinase delivery for conditional gene deletion, conditional (recombinase-dependent) expression, includes those required for the gene editing components described herein. The nonprotein coding gene may also encode a tRNA, rRNA, tmRNA, piRNA, double stranded RNA, snRNA, snoRNA, and / or long non-coding RNA (IncRNA). In some cases, the non-protein coding gene can modulate the expression or the activity of a target gene or gene expression product. For example, the RNAs described herein may be used to inhibit gene expression in the brain. In some cases, inhibition of gene expression refers to an inhibition by at least about 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95% and 100%. In some cases, the protein product of the targeted gene may be inhibited by at least about 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95% and 100%. The gene can be either a wild type gene or a gene with at least one mutation. The targeted protein may be either a wild type protein or a protein with at least one mutation.

[1888] A therapeutic nucleic acid can modulate the expression or activity of a gene or gene expression product expressed from the gene that is implicated in a disease or disorder of the brain. For example, the therapeutic nucleic acid, in some cases is a gene or a modified version of the gene described herein. In some instances, the gene or gene expression product is inhibited. In some instances, the gene or gene expression product is enhanced.

[1889] In another example, the therapeutic nucleic acid comprises an effector gene expression product such as a gene editing component specific to target a gene therein. Non-limited examples of genes include target gene or gene expression product selected from ATPIA2, C / XCNAIA, SETD5, SHANK3, NF2, DNMT1, TCF4, RAI1, PEX1, ARSA, EIF2B5, EIF2B1, EIF2B2, NPC1, ADAR, MFSD8, STXBP1, PRICKLE2, PRRT2, IDUA, STX1B, Sarcoglycan Alpha (SGCA), glutamic acid decarboxylase 65 (GAD65), glutamic acid decarboxylase 67 (GAD67), CLN2, Nerve Growth Factor (NGF ), glial cell derived neurotrophic factor (GDNF), Survival Of Motor Neuron 1, STXBP1, Telomeric (SMN1), Factor X (FIX), Retinoid Isomerohydrolase (RPE65), sarco / endoplasmic reticulum Ca2+-ATPase (SERCA2a), Glucocerebrosidase (GCase), galactocerebrosidase (GALC), CDKL5, Frataxin (FXN), Huntingtin (HTT), methyl-CpG binding protein 2 (MECP2), a peroxisomal biogenesis factor (PEX), progranulin (GRN), an antitubulin agent, copper-zinc superoxide dismutase (SOD1), iduronate 2 sulfatase (hIDS), Patent Application CAPS -041 / 01 WO 35847 / 197 Glucosylceramidase Beta (GBA), fragile X mental retardation 1 (FMR1), NPC Intracellular Cholesterol Transporter 1 (NPC1), SCN1A, C9orf72, NPS3 and a NLRP3 inflammasome. In some embodiments, the peroxisomal biogenesis factor (PEX) is selected from PEX1, PEX2, PEX3, PEX4, PEX5, PEX6, PEX7, PEX10, PEX110, PEX12, PEX13, PEX14, PEX16, PEX19, and PEX26. In some instances, the gene or gene expression product is inhibited. In some instances, the gene or gene expression product is enhanced.

[1890] AAV Vectors

[1891] Aspects disclosed herein comprise plasmid vectors comprising a nucleic acid sequence encoding the AAV capsids and AAV capsid proteins described herein. AAV vectors described herein are useful for the assembly of a rAAV and viral packaging of a heterologous nucleic acid. In addition, an AA V vector may encode a transgene comprising the heterologous nucleic acid.

[1892] An AAV vector can comprise a transgene, which in some cases encodes a heterologous gene expression product (e.g., therapeutic gene expression product, recombinant capsid protein, and the like). The transgene is in cis with two inverted terminal repeats (ITRs) flanking the transgene. The transgene may comprise a therapeutic nucleic acid encoding a therapeutic gene expression product. Due to the limited packaging capacity of the rAAV (~5kB), in some cases, a longer transgene may be split between two AAV vectors, the first with 3’ splice donor and the second with a 5’ splice acceptor. Upon co-infection of a cell, concatemers form, which are spliced together to express a full-length transgene.

[1893] A transgene is generally inserted so that its expression is driven by the endogenous promoter at the integration site, namely the promoter that drives expression of the endogenous gene into which a transgene is inserted. In some instances, a transgene comprises a promoter and / or enhancer, for example a constitutive promoter or an inducible or tissue / cell specific promoter. As a non-limiting example, the promoter may be CMV promoter, a CMV-|3-Actin-intron-p-Globin hybrid promoter (CAG), CBA promoter, FRDA or FXN promoter, UBC promoter, GUSB promoter, NSE promoter, Synapsin promoter, MeCP2 promoter, GFAP promoter, Hl promoter, U6 promoter, NFL promoter, NFH promoter, SCN8A promoter, or PGK promoter As a non-limiting example, promoters can be tissue-specific expression elements include, but are not limited to, human elongation factor la-subunit (EFla), immediate-early Patent Application CAPS -041 / 01 WO 35847 / 197 cytomegalovirus (CMV), chicken P-actin (CBA) and its derivative CAG, the P glucuronidase (GUSB), and ubiquitin C (UBC). The transgene may include a tissue-specific expression elements for neurons such as, but not limited to, neuron -specific enolase (NSE), platelet-derived growth factor (PDGF), platelet-derived growth factor B-chain (PDGF-P), the synapsin (Syn), the methyl -CpG binding protein 2 (MeCP2), Ca2+ / calmodulin-dependent protein kinase II (CaMKII), metabotropic glutamate receptor 2 (mGluR2), NFL, NFH, np32, PPE, Enk and EAAT2 promoters The transgene may comprise a tissue-specific expression element for astrocytes such as, but not limited to, the glial fibrillary acidic protein (GFAP) and EAAT2 promoters. The transgene may comprise tissue-specific expression elements for oligodendrocytes such as, but not limited to, the myelin basic protein (MBP) promoter.

[1894] In some embodiments, the promoter is less than 1 kb. The promoter may have a length of 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, 530, 540, 550, 560, 570, 580, 590, 600, 610, 620, 630, 640, 650, 660, 670, 680, 690, 700, 710, 720, 730, 740, 750, 760, 770, 780, 790, 800 or more than 800. The promoter may have a length between 200-300, 200-400, 200-500, 200-600, 200-700, 200-800, 300-400, 300-500, 300-600, 300-700, 300-800, 400-500, 400-600, 400-700, 400-800, 500-600, 500-700, 500-800, 600-700, 600-800 or 700-800. The promoter may provide expression of the therapeutic gene expression product for a period of time in targeted tissues such as, but not limited to, the brain. Expression of the therapeutic gene expression product may be for a period of 1 hour, 2, hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 2 weeks, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 3 weeks, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, 31 days, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, 11 years, 12 years, 13 years, 14 years, 15 years, 16 years, 17 years, 18 years, 19 years, 20 years, 21 years, 22 years, 23 years, 24 years, 25 years, 26 years, 27 years, 28 years, 29 years, 30 years, 31 years, 32 Patent Application CAPS -041 / 01 WO 35847 / 197 years, 33 years, 34 years, 35 years, 36 years, 37 years, 38 years, 39 years, 40 years, 41 years, 42 years, 43 years, 44 years, 45 years, 46 years, 47 years, 48 years, 49 years, 50 years, 55 years, 60 years, 65 years, or more than 65 years. Expression of the payload may be for 1 -5 hours, 1-12 hours, 1-2 days, 1-5 days, 1-2 weeks, 1-3 weeks, 1-4 weeks, 1-2 months, 1-4 months, 1-6 months, 2-6 months, 3-6 months, 3-9 months, 4-8 months, 6-12 months, 1-2 years, 1-5 years, 2-5 years, 3-6 years, 3-8 years, 4-8 years or 5-10 years or 10-15 years, or 15-20 years, or 20-25 years, or 25-30 years, or 30-35 years, or 35-40 years, or 40-45 years, or 45-50 years, or 50-55 years, or 55-60 years, or 60-65 years.

[1895] An A V vector can compri se a genome of a helper virus. Helper virus proteins are required for the assembly of a recombinant AAV (rAAV), and packaging of a transgene containing a heterologous nucleic acid into the rAAV. The helper virus genes are adenovirus genes E4, E2a and VA, that when expressed in the cell, assist with AAV replication. In some embodiments, an AAV vector comprises E2. In some embodiments, an AAV vector comprises E4. In some embodiments, an AAV vector comprises VA. In some instances, the AAV vector comprises one of helper vims proteins, or any combination.

[1896] The target gene or gene expression product for use in a transgene can be selected from ATP1A2, CACNAIA, SETD5, SHANK3, NF2, DNMT1, TCF4, RAH, PEX1, ARSA, EIF2B5, EIF2BI, EIF2B2, NPC1, ADAR, MFSD8, STXBP1, PRICKLE2, PRRT2, IDUA, STX1B, Sarcoglycan Alpha (SGCA), glutamic acid decarboxylase 65 (GAD65), glutamic acid decarboxylase 67 (GAD67), CLN2, Nerve Growth Factor (NGF), glial cell derived neurotrophic factor (GDNF), Survival Of Motor Neuron 1, STXBPI, Telomeric (SMN1), Factor X (FIX), Retinoid Isomerohydrolase (RPE65), sarco / endoplasmic reticulum Ca2+-ATPase (SERCA2a), Glucocerebrosidase (GCase), galactocerebrosidase (GALC), CDKL5, Frataxin (FXN), Huntingtin (HTT), methyl-CpG binding protein 2 (MECP2), a peroxisomal biogenesis factor (PEX), progranulin (GRN), an antitubulin agent, copper -zinc superoxide dismutase (SOD1), iduronate 2 sulfatase (hIDS), Glucosylceramidase Beta (GBA), fragile X mental retardation 1 (FMR1), NPC Intracellular Cholesterol Transporter 1 (NPC1), SCN1A, C9orf72, NPS3 and aNLRP3 inflammasome. In some embodiments, the peroxisomal biogenesis factor (PEX) is selected from PEX1, PEX2, PEX3, PEX4, PEX5, PEX6, PEX7, PEX10, PEX110, PEX12, PEX13, PEX14, PEX16, PEX19, and PEX26. Patent Application CAPS -041 / 01 WO 35847 / 197 An AAV vector can comprise a viral genome comprising a nucleic acid encoding the recombinant AAV (rAAV) capsid protein described herein. The viral genome can comprise a Replication (Rep) gene encoding a Rep protein, and Capsid (Cap) gene encoding an AAP protein in the first open reading frame (ORF1) or a Cap protein in the second open reading frame (ORF2). The Rep protein is selected from Rep78, Rep68, Rep52, and Rep40. In some instances, the Cap gene is modified encoding a modified AAV capsid protein described herein, A wild-type Cap gene encodes three proteins, VP1, VP2, and VP3. In some cases, VP1 is modified. In some cases, VP2 is modified. In some cases, VP3 is modified. In some cases, all three VP1-VP3 are modified. The AAV vector can comprise nucleic acids encoding wild-type Rep78, Rep68, Rep52, Rep40 and AAP proteins.

[1897] Methods of Producing rAAVs

[1898] Disclosed herein are methods of producing the AAV capsids comprising the AAV capsid proteins and viral vector encoding a therapeutic nucleic acid. The AAV capsid proteins are produced by introduction into a cell (e.g., immortalized stem cell) a first vector containing a transgene cassette flanked by inverted terminal repeat (ITR) sequences from a parental AA V virus (the transgene cassette has a promoter sequence that drives transcription of a heterologous nucleic acid in the nucleus of the target cell), a second vector encoding the AAV genome with a AAV capsid protein (encoding the AAV Rep gene as well as the modified Cap gene for the variant being produced), and a third vector encoding helper virus proteins, required for assembly of the AAV capsid structure and packaging of the transgene in the modified AAV capsid structure. The assembled AAV capsid can be isolated and purified from the cell using suitable methods known in the art.

[1899] The transgenes contained in a recombinant AAV (rAAV) vector and encapsidated by the AAV capsid proteins of the present disclosure are also provided herein. The transgenes disclosed herein are delivered to a subject for a variety of purposes, such as to treat a disease or condition in the subject. The transgene can be gene editing components that modulate the activity or expression of a target gene or gene expression product. Alternatively, the transgene is a gene encoding a therapeutic gene expression product that is effective to modulate the activity or expression of itself, or another target gene or gene expression product. Patent Application CAPS -041 / 01 WO 35847 / 197 Aspects disclosed herein provide methods of manufacturing rAAV virus or virus particles comprising: (a) introducing into a cell a nucleic acid comprising: (i) first vector containing a transgene cassette flanked by inverted terminal repeat (ITR) sequences from a parental AAV virus (the transgene cassette has a promoter sequence that drives transcription of a heterologous nucleic acid in the nucleus of the target cell); (ii) a second vector encoding the AAV genome with a AAV capsid protein of the present invention; and (iii) a vector encoding helper virus proteins, required for assembly of the AAV capsid structure and packaging of the transgene in the modified AAV capsid structure; (b) expressing in the cell the AAV capsid protein described herein; (c) assembling an AAV particle comprising the AAV capsid proteins disclosed herein; and (d) packaging the AAV particle. In some instances, the cell is mammalian. In some instances, the cell is immortalized. In some instances, the immortalized cell is an embryonic stem cell. In some instances, the embryonic stem cell is a human embryonic stem cell. In some instances, the human embryonic stem cell is a human embryonic kidney 293 (HEK-293) cell In some instances, the Cap gene is derived from the deoxyribose nucleic acid (DNA). In some instances, the 5’ ITR and the 3’ ITR are derived from an AAV2 serotype. In some instances, the 5’ ITR and the 3’ ITR are derived from an AAV5 serotype. In some instances, the 5’ ITR and the 3’ ITR are derived from an AAV9 serotype. In some instances, the 5’ ITR and / or the 3’ ITR originate from another natural serotype or have been engineered for improved transduction or transgene expression efficiency. In some instances, the first nucleic acid sequence and the second nucleic acid sequence are in trans. In some instances, the first nucleic acid sequence and the second nucleic acid sequence are in cis. In some instances, the first nucleic acid sequence, the second nucleic acid sequence and the third nucleic acid sequence, are in trans.

[1900] In some instances, the methods comprise packing the first nucleic acid sequence encoding the therapeutic gene expression product such that it becomes encapsidated by the modified AAV capsid protein. In some embodiments, the rAAV particles are isolated, concentrated, and purified using suitable viral purification methods, such as those described herein.

[1901] In some cases, rAAVs of the present disclosure are generated using the methods described in Challis, R. C. et al. Nat. Protoc. 14, 379 (2019). Briefly, triple transfection of HEK293T cells (ATCC) using polyethylenimine (PEI) is performed, viruses are collected after 120 hours from both cell lysates and media and purified over iodixanol. In a non-limiting example, the rAAVs are Patent Application CAPS -041 / 01 WO 35847 / 197 generated by triple transfection of precursor cells (e.g., HEK293T) cells using a standard transfection protocol (e.g., PEI). Viral particles are harvested from the media after a period of time (e.g., 72 h post transfection) and from the cells and media at a later point in time e.g., 1 0 h post transfection). Virus present in the media is concentrated by precipitation with 8% polyethylene glycol (PEG) and 500 mM sodium chloride and the precipitated virus is added to the lysates prepared from the collected cells. The viruses are purified over iodixanol (Optiprep, Sigma) step gradients (15%, 25%, 40% and 60%). Viruses are concentrated and formulated in PBS. Virus titers are determined by measuring the number of DNasel -resistant vector genome copies (VGs) using qPCR and the linearized genome plasmid as a control.

[1902] The cell can be selected from a human, a primate, a murine, a feline, a canine, a porcine, an ovine, a bovine, an equine, an epine, a caprine and a lupine host cell. In some instances, the cell is a progenitor or precursor cell, such as a stem cell. In some instances, the stem cell is a mesenchymal cell, embryonic stem cell, induced pluripotent stem cell (iPSC), fibroblast or other tissue specific stem cell. The cell can be immortalized. In some cases, the immortalized cell is a HEK293 cell. In some instances, the cell is a differentiated cell. Based on the disclosure provided, it is expected that this system can be used in conjunction with any transgenic line expressing a recombinase in the target cell type of interest to develop AAV capsids that more efficiently transduce that target cell population.

[1903] Methods of Treatment

[1904] Disclosed herein are methods of treating a disease or condition, or a symptom of the disease or condition, in a subject, comprising administrating of therapeutically effective amount of one or more compositions (e.g., rAAV particle, AAV vector, pharmaceutical composition) disclosed herein to the subject. In some embodiments, the composition is a rAAV capsid protein described herein. In some embodiments, the composition is an isolated and purified rAAV capsid protein described herein. In some embodiments, the rAAV particle encapsidates an AAV vector comprising a transgene (e.g., therapeutic nucleic acid). In some embodiments, the composition is a rAAV capsid protein described herein conjugated with a therapeutic agent disclosed herein. In some embodiments, the composition is a pharmaceutical composition comprising the rAAV particle and a pharmaceutically acceptable carrier. In some embodiments, the one or more Patent Application CAPS -041 / 01 WO 35847 / 197 compositions are administered to the subject alone (e.g., stand-alone therapy). In some embodiments, the composition is a first-line therapy for the disease or condition. In some embodiments, the composition is a second-line, third-line, or fourth -line therapy, for the disease or condition.

[1905] Recombinant adeno-associated virus (rAAV) mediated gene delivery' leverages the AAV mechanism of viral transduction for nuclear expression of an episomal heterologous nucleic acid (e.g., a transgene, therapeutic nucleic acid) For example, upon delivery to a host in vivo environment, a rAAV may (1) bind or attach to cellular surface receptors on the target cell, (2) endocytose, (3) traffic to the nucleus, (4) uncoat the virus to release the encapsi dated heterologous nucleic acid, (5 ) convert of the heterologous nucleic acid from single-stranded to double-stranded DNA as a template for transcription in the nucleus, and (6) transcribe of the episomal heterologous nucleic acid in the nucleus of the host cell. rAAVs engineered to have an increased specificity (binding to cellular surface receptors on the target cell), transduction efficiency (the effectiveness of a virus, engineered or naturally occurring, at delivering its DNA component to a host cell), and transgene expression (transcription of the episomal heterologous nucleic acid in the host cell) are desirable for gene therapy applications.

[1906] Aspects disclosed herein provide methods of treating a disease or condition in a subject, the method comprising administering to the subject a therapeutically effective amount of the rAAV of the present disclosure, or the pharmaceutical formulation of the present disclosure, wherein the gene product is a therapeutic gene product. In some embodiments, the administering is by intracranial, intraventricular, intracerebroventricular, intravenous, intraarterial, intranasal, intrathecal, intracisternae magna, or subcutaneous.

[1907] Provided here, are methods of treating a disease or a condition associated with an aberrant expression or activity of a target gene or gene expression product thereof, the method comprising modulating the expression or the activity of a target gene or gene expression product in a subject by administering a rAAV encapsidating a heterologous nucleic acid of the present disclosure. In some instances, the expression or the activity of the target gene or gene expression product is decreased, relative to that in a normal (non-diseased) individual; and administering the rAAV to the subject is sufficient to increase the expression of the activity of the target gene or gene expression product. In some instances, the expression or the activity of the gene or gene expression Patent Application CAPS -041 / 01 WO 35847 / 197 product is increased, relative to that in a normal individual; and administering the rAAV to the subject is sufficient to decrease the expression or the activity of the target gene or gene expression product. Tn a non-limiting example, a subject diagnosed with Alzheimer’s disease, which is caused, in some cases, by a gain-of-function of a Presenilin 1 and / or Presenilin 2 (encoded by the gene PSEN1 and PSEN2, respectively) is administered a rAAV disclosed herein encapsidating a therapeutic nucleic acid that is a silencing RNA (siRNA), or other RNAi with a loss-of-function effect on PSEN1 mRNA.

[1908] Also provided are methods of preventing a disease or condition disclosed herein in a subject comprising administering to the subject a therapeutically effective amount of an rAAV vector comprising a nucleic acid sequence encoding a therapeutic gene expression product described herein. The rAAV vector may be encapsidated in the modified capsid protein or rAAV viral particle described herein. In some instances, the therapeutic gene expression product is effective to modulate the activity or expression of a target gene or gene expression product.

[1909] Disclosed herein are methods of treating a disease or condition in a subject by administering a composition comprising a rAAV disclosed herein. An advantage of the rAAVs disclosed herein, is that the rAAV may be used to treat virtually any disease or condition that would benefit from a transgene therapy, including but not limited to spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), Parkinson's disease, Pompe disease, mucopolysaccharidosis type II, fragile X syndrome, STXBP1 encephalopathy, Krabbe disease. Huntington's disease, Alzheimer's disease, Battens disease, lysosomal storage disorders, glioblastoma multiforme, Rett syndrome, Leber's congenital amaurosis. Late infantile neuronal ceroid lipofuscinosis (LINCL), chronic pain, stroke, spinal cord injury, traumatic brain injury and lysosomal storage disorders.

[1910] In some cases, the disease or condition is localized to a particular in vivo environment in the subject, e.g., the brain. The compositions of the present disclosure are particularly useful for the treatment of the diseases or conditions described herein because they specifically or more efficiently target the in vivo environment and deliver a therapeutic nucleic acid engineered to modulate the activity or the expression of a target gene expression product involved with the pathogenesis or pathology of the disease or condition.

[1911] Provided herein are methods of treating a disease or a condition, or a symptom of the Patent Application CAPS -041 / 01 WO 35847 / 197 disease or condition, in a subject, comprising: (a) diagnosing a subject with a disease or a condition affecting a target in vivo environment; and (b) treating the disease or the condition by administering to the subject a therapeutically effective amount of a composition disclosed herein (e.g., rAAV particle, AAV vector, pharmaceutical composition), wherein the composition is engineered with an increased specificity for the target in vivo environment.

[1912] Disclosed herein are methods of treating a disease or a condition, or a symptom of the disease or the condition, afflicting a target in a subject comprising: (a) administering to the subject a composition (e.g., rAAV particle, AAV vector, pharmaceutical composition); and (b) expressing the therapeutic nucleic acid into a target in vivo environment in the subject with an increased transduction enrichment.

[1913] In some embodiments, methods further comprise reducing or ablating delivery of the heterologous nucleic acid in an off-target in vivo environment, such as the liver. In some embodiments, delivery is characterized by an increase in enrichment of transduction (e.g., of the heterologous nucleic acid) in the brain.

[1914] In some embodiments, methods of treating a disease or condition affecting the brain comprise administering a rAAV particle to a brain in a subject, the rAAV particle comprising an rAAV capsid protein comprising an insertion at an amino acid position of AA588-589 in a parental AAV capsid protein. In some embodiments, methods of treating a disease or condition affecting the brain comprise administering a rAAV particle to a brain in a subject, the rAAV particle comprising an rAAV capsid protein comprising an insertion of about, five, six, or seven amino acids of an amino acid sequence as well as one or more substitutions as described throughout the present application. In some embodiments, the parental AAV capsid protein is AAV9 capsid protein (for e.g., provided in SEQ ID NO: 1).

[1915] Also provided are methods of modulating a target gene expression product, the methods comprising administering to a subject in need thereof a composition (e.g., rAAV particle, AAV vector, pharmaceutical composition) disclosed herein. For example, methods provided herein comprise administering to a subject a rAAV with a rAAV capsid protein encapsidating a viral vector comprising a heterologous nucleic acid that modulates the expression or the activity of the target gene expression product.

[1916] The term “normal individual” refers to an individual that is not afflicted with the disease Patent Application CAPS -041 / 01 WO 35847 / 197 or the condition characterized by the variation in expression or activity of the gene or gene expression product thereof.

[1917] In some embodiments, the disease or condition of the brain selected from Absence of the Septum Pellucidum, Acid Lipase Disease, Acid Maltase Deficiency, Acquired Epileptiform Aphasia, Acute Disseminated Encephalomyelitis, Attention Deficit-Hyperactivity Disorder (ADHD), Adie's Pupil, Adie's Syndrome, Adrenoleukodystrophy, Agenesis of the Corpus Callosum, Agnosia, Aicardi Syndrome, Aicardi-Goutieres Syndrome Disorder, AIDS - Neurological Complications, Alexander Disease, Alpers' Disease, Alternating Hemiplegia, Alzheimer's Disease, Amyotrophic Lateral Sclerosis (ALS), Anencephaly, Aneurysm, Angelman Syndrome, Angiomatosis, Anoxia, Antiphospholipid Syndrome, Aphasia, Apraxia, Arachnoid Cysts, Arachnoiditis, Arnold-Chiari Malformation, Arteriovenous Malformation, Asperger Syndrome, Ataxia, Ataxia Telangiectasia, Ataxias and Cerebellar or Spinocerebellar Degeneration, Atrial Fibrillation and Stroke, Attention Deficit-Hyperactivity Disorder, Autism Spectrum Disorder, Autonomic Dysfunction, Back Pain, Barth Syndrome, Batten Disease, Becker's Myotonia, Behcet's Disease, Bell's Palsy, Benign Essential Blepharospasm, Benign Focal Amyotrophy, Benign Intracranial Hypertension, Bernhardt-Roth Syndrome, Binswanger's Disease, Blepharospasm, Bloch-Sulzberger Syndrome, Brachial Plexus Birth Injuries, Brachial Plexus Injuries, Bradbury-Eggleston Syndrome, Brain and Spinal Tumors, Brain Aneurysm, Brain Injury’, Brown-Sequard Syndrome, Bulbospinal Muscular Atrophy, Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), Canavan Disease, Carpal Tunnel Syndrome, Causalgia, Cavernomas, Cavernous Angioma, Cavernous Malformation, Central Cervical Cord Syndrome, Central Cord Syndrome, Central Pain Syndrome, Central Pontine Myelinolysis, Cephalic Disorders, Ceramidase Deficiency, Cerebellar Degeneration, Cerebellar Hypoplasia, Cerebral Aneurysms, Cerebral Arteriosclerosis, Cerebral Atrophy, Cerebral Beriberi, Cerebral Cavernous Malformation, Cerebral Gigantism, Cerebral Hypoxia, Cerebral Palsy, Cerebro-Oculo-Facio-Skeletal Syndrome (COFS), Charcot-Marie-Tooth Disease, Charcot-Marie-Tooth syndrome, classical rhizomelic chondrodysplasia punctata (RCDP), Chiari Malformation, Cholesterol Ester Storage Disease, Chorea, Choreoacanthocytosis, Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Chronic Orthostatic Intolerance, Chronic Pain, Cockayne Syndrome, Cockayne Syndrome Type II, Coffin Lowry Syndrome, Patent Application CAPS -041 / 01 WO 35847 / 197 Colpocephaly, Coma, Complex Regional Pain Syndrome, Congenital Facial Diplegia, Congenital Myasthenia, Congenital Myopathy, Congenital Vascular Cavernous Malformations, Corticobasal Degeneration, Cranial Arteritis, Craniosynostosis, Cree encephalitis, Creutzfeldt- Jakob Disease, Cumulative Trauma Disorders, Cushing's Syndrome, Cytomegalic Inclusion Body Disease, Cytomegalovirus Infection, Dancing Eyes-Dancing Feet Syndrome, Dandy-Walker Syndrome, Dawson Disease, Deafness, De Morsier's Syndrome, Dejerine-Klumpke Palsy, Dementia, Dementia -Multi -Infarct, Dementia-Semantic, Dementia-Subcortical, Dementia With Lewy Bodies, Dentate Cerebellar Ataxia, Dentatorubral Atrophy, Dermatomyositis, Developmental Dyspraxia, Devic's Syndrome, Diabetic Neuropathy, Diffuse Sclerosis, Dravet Syndrome, Duchenne muscular dystrophy, Dysautonomia, Dysgraphia, Dyslexia, Dysphagia, Dyspraxia, Dyssynergia Cerebellaris Myoclonica, Dyssynergia Cerebellaris Progressiva, Dystonias, Early Infantile Epileptic Encephalopathy, Empty Sella Syndrome, Encephalitis, Encephalitis Lethargica, Encephaloceles, Encephalopathy, Encephalopathy (familial infantile), Encephalotrigeminal Angiomatosis, Epilepsy, Epileptic Hemiplegia, Erb's Palsy, Erb-Duchenne and Dejerine-Klumpke Palsies, Essential Tremor, Extrapontine Myelinolysis, Fabry Disease, Fahr's Syndrome, Fainting, Familial Dysautonomia, Familial Hemangioma, Familial Idiopathic Basal Ganglia Calcification, Familial Periodic Paralyses, Familial Spastic Paralysis, Farber's Disease, Febrile Seizures, Fibromuscular Dysplasia, Fisher Syndrome, Floppy Infant Syndrome, Foot Drop, Fragile X syndrome, Friedreich's Ataxia, Frontotemporal Dementia (FTD), Gaucher Disease, Generalized Gangliosidoses, Gerstmann's Syndrome, Gerstmann-Straussler-Scheinker Disease, Giant Axonal Neuropathy, Giant Cell Arteritis, Giant Cell Inclusion Disease, glioblastoma. Globoid Cell Leukodystrophy, Glossopharyngeal Neuralgia, Glycogen Storage Disease, Guillain-Barre Syndrome, Hallervorden-Spatz Disease, Head Injury, Headache, Hemicrania Continua, Hemifacial Spasm, Hemiplegia Alterans, Hereditary Neuropathies, Hereditary Spastic Paraplegia, Heredopathia Atactica Polyneuritiformis, Herpes Zoster, Herpes Zoster Oticus, Hirayama Syndrome, Holmes-Adie syndrome, Holoprosencephaly, HTLV-1 Associated Myelopathy, Hughes Syndrome, Huntington's Disease, Hydranencephaly, Hydrocephalus, Hydrocephalus -Normal Pressure, Hydromyelia, Hypercortisolism, Hypersomnia, Hypertonia, Hypotonia, Hypoxia, Immune-Mediated Encephalomyelitis, Inclusion Body Myositis, Incontinentia Pigmenti, Infantile Hypotonia, Infantile Neuroaxonal Dystrophy, Infantile Phytanic Acid Storage Disease, Patent Application CAPS -041 / 01 WO 35847 / 197 Infantile Refsum Disease (IRD), Infantile Spasms. Inflammatory Myopathies, Iniencephaly, Intestinal Lipodystrophy, Intracranial Cysts, Intracranial Hypertension, Isaacs' Syndrome, Joubert Syndrome, Kearns-Sayre Syndrome, Kennedy's Disease, Kinsboume syndrome, Kleine-Levin Syndrome, Klippel-Feil Syndrome, Klippel-Trenaunay Syndrome (KTS), Klüver-Bucy Syndrome, Korsakoff's Amnesic Syndrome, Krabbe Disease, Kugelberg-Welander Disease, Kuril, Lambert-Eaton Myasthenic Syndrome, Landau-Kleffner Syndrome, Lateral Femoral Cutaneous Nerve Entrapment, Lateral Medullary Syndrome, Learning Disabilities, Leigh's Disease, Lennox -Gastaut Syndrome, Lesch-Nyhan Syndrome, Leukodystrophy, Levine-Critchley Syndrome, Lewy Body Dementia, Lipid Storage Diseases, Lipoid Proteinosis, Lissencephaly, Locked-In Syndrome, Lou Gehrig's Disease, Lupus-Neurological Sequelae, Lyme Disease - Neurological Complications, Machado-Joseph Disease, Macrencephaly, Maple syrup urine disease, Megalencephaly, Melkersson-Rosenthal Syndrome, Meningitis, Meningitis and Encephalitis, Menkes Disease, Menkes syndrome, Meralgia Paresthetica, Metachromatic Leukodystrophy, Microcephaly, Migraine, Miller Fisher Syndrome, Mini Stroke, Mitochondrial Myopathy, Moebius Syndrome, Monomelic Amyotrophy, Motor Neuron Diseases, Moyamoya Disease, Mucolipidoses, Mucopolysaccharidosis, Mucopolysaccharidosis II, Multi-Infarct Dementia, Multifocal Motor Neuropathy, Multiple Sclerosis, Multiple System Atrophy, Multiple System Atrophy with Orthostatic Hypotension, Muscular Dystrophy, Myasthenia -Congenital, Myasthenia Gravis, Myelinoclastic Diffuse Sclerosis, Myoclonic Encephalopathy of Infants, Myoclonus, Myopathy, Myopathy-Congenital, Myopathy-Thyrotoxic, Myotonia, Myotonia Congenita, Myotonic dystrophy, Narcolepsy, Neuroacanthocytosis, Neurodegeneration with Brain Iron Accumulation, Neurofibromatosis, Neuroleptic Malignant Syndrome, Neurological Complications of AIDS, Neurological Complications of Lyme Disease, Neurological Consequences of Cytomegalovirus Infection, Neurological Manifestations of Pompe Disease, Neurological Sequelae Of Lupus, Neuromyelitis Optica, Neuromyotonia, Neuronal Ceroid Lipofuscinosis, Neuronal Migration Disorders, Neuropathy- Hereditary, Neurosarcoidosis, Neurosyphilis, Neurotoxicity, Nevus Cavernosus, Niemann-Pick Disease, O'Sullivan-McLeod Syndrome, Occipital Neuralgia, Ohtahara Syndrome, Olivopontocerebellar Atrophy, Opsoclonus Myoclonus, Orthostatic Hypotension, Overuse Syndrome, Pain -Chronic, Pantothenate Kinase-Associated Neurodegeneration, Paraneoplastic Syndromes, Paresthesia, Parkinson's Disease, Paroxysmal

[1918] 12.4 Patent Application CAPS -041 / 01 WO 35847 / 197 Choreoathetosis, Paroxysmal Hemicrania, Parry -Romberg, Pelizaeus-Merzbacher Disease, Pena Shokeir II Syndrome, Perineural Cysts, Periodic Paralyses, Peripheral Neuropathy, Periventricular Leukomalacia, Persistent Vegetative State, Pervasive Developmental Disorders, Phenylketonuria, Phytanic Acid Storage Disease, Pick’s Disease, Pinched Nerve, Piriformis Syndrome, Pituitary Tumors, Polymyositis, Pompe Disease, Porencephaly, Post-Polio Syndrome, Postherpetic Neuralgia, Postinfectious Encephalomyelitis, Postural Hypotension, Postural Orthostatic Tachycardia Syndrome, Postural Tachycardia Syndrome, Prader-Willi syndrome, Primary Dentatum Atrophy, Primary Lateral Sclerosis, Primary Progressive Aphasia, Prion Diseases, Progressive Hemifacial Atrophy, Progressive Locomotor Ataxia, Progressive Multifocal Leukoencephalopathy, Progressive Sclerosing Poliodystrophy, Progressive Supranuclear Palsy, Prosopagnosia, Pseudo-Torch syndrome, Pseudotoxoplasmosis syndrome, Pseudotumor Cerebri, Psychogenic Movement, Ramsay Hunt Syndrome I, Ramsay Hunt Syndrome II, Rasmussen's Encephalitis, Reflex Sympathetic Dystrophy Syndrome, Refsum Disease, Refsum Disease -Infantile, Repetitive Motion Disorders, Repetitive Stress Injuries, Restless Legs Syndrome, Retrovirus-Associated Myelopathy, Rett Syndrome, Reye's Syndrome, Rheumatic Encephalitis, Riley-Day Syndrome, Sacral Nerve Root Cysts, Saint Vitus Dance, Salivary Gland Disease, Sandhoff Disease, Schilder's Disease, Schizencephaly, Seitelberger Disease, Seizure Disorder, Semantic Dementia, Septo-Optic Dysplasia, Severe Myoclonic Epilepsy of Infancy (SMEI), Shaken Baby Syndrome, Shingles, Shy -Drager Syndrome, Sjogren's Syndrome, Sleep Apnea, Sleeping Sickness, Sotos Syndrome, Spasticity, Spina Bifida, Spinal Cord Infarction, Spinal Cord Injury, Spinal Cord Tumors, Spinal Muscular Atrophy, Spinocerebellar ataxia, Spinocerebellar Atrophy, Spinocerebellar Degeneration, Steele-Richardson-Olszewski Syndrome, Stiff-Person Syndrome, Striatonigral Degeneration, Stroke, Sturge-Weber Syndrome, STXBP1 encephalopathy, Subacute Sclerosing Panencephalitis, Subcortical Arteriosclerotic Encephalopathy, Short-lasting, Unilateral, Neuralgiform (SUNCT) Headache, Swallowing Disorders, Sydenham Chorea, Syncope, Syphilitic Spinal Sclerosis, Syringohydromyelia, Syringomyelia, Systemic Lupus Erythematosus, Tabes Dorsalis, Tangier disease. Tardive Dyskinesia, Tarlov Cysts, Tay-Sachs Disease, Temporal Arteritis, Tethered Spinal Cord Syndrome, Thomsen's Myotonia, Thoracic Outlet Syndrome, Thyrotoxic Myopathy, Tic Douloureux, Todd's Paralysis, Tourette Syndrome, Transient Ischemic Attack, Transmissible Patent Application CAPS -041 / 01 WO 35847 / 197 Spongiform Encephalopathies, Transverse Myelitis, Traumatic Brain Injury, Tremor, Trigeminal Neuralgia, Tropical Spastic Paraparesis, Troyer Syndrome, Tuberous Sclerosis, Vascular Erectile Tumor, Vasculitis Syndromes of the Central Nervous Systems, Von Economo's Disease, Von Hippel-Lindau Disease (VHL), Von Hippel-Lindau syndrome, Von Recklinghausen's Disease, Wallenberg's Syndrome, Werdnig-Hoffman Disease, Wernicke-Korsakoff Syndrome, West Syndrome, Whiplash, Whipple's Disease, Williams Syndrome, Wilson Disease, Wolman's Disease, X-Linked Spinal and Bulbar Muscular Atrophy and Zellweger syndrome.

[1919] In some embodiments, the pharmaceutical formulation comprises a therapeutic nucleic acid encoding a therapeutic gene expression product. In some instances, the therapeutic gene expression product is effective to modulate an activity or an expression of a target gene or gene expression product selected from ATP1A2, CACNAIA, SETD5, SHANK3, NF2, DNMT1, TCF4, RAI1, PEX1, ARSA, EIF2B5, EIF2B1, EIF2B2, NPC1, ADAR, MFSD8, STXBP1, PRICKLE2, PRRT2, IDUA, STX1B, Sarcoglycan Alpha (SGCA), glutamic acid decarboxylase 65 (GAD65), glutamic acid decarboxylase 67 (GAD67), CLN2, Nerve Growth Factor (NGF), glial cell derived neurotrophic factor (GDNF), Survival Of Motor Neuron 1, STXBP1, Telomeric (SMN1), Factor X (FIX), Retinoid Isomerohydrolase (RPE65), sarco / endoplasmic reticulum Ca2+-ATPase (SERCA2a), Glucocerebrosidase (GCase), galactocerebrosidase (GALC), CDKL5, Frataxin (FXN), Huntingtin (HTT), methyl-CpG binding protein 2 (MECP2), a peroxisomal biogenesis factor (PEX), progranulin (GRN), an antitubulin agent, copper-zinc superoxide dismutase (SOD1), iduronate 2 sulfatase (hIDS), Glucosylceramidase Beta (GBA), fragile X mental retardation 1 (FMR1), NPC Intracellular Cholesterol Transporter 1 (NPC1), SCN1A, C9orf72, NPS3 and a NLRP3 inflammasome. In some embodiments, the peroxisomal biogenesis factor (PEX) is selected from PEX1, PEX2, PEX3, PEX4, PEX5, PEX6, PEX7, PEX 10, PEX11p, PEX12, PEX13, PEX14, PEX16, PEX 19, and PEX26.

[1920] In some aspects, other examples of genes involved in neurologic or brain diseases or disorders include MAPI, IDUA, SNCA, ATXN2, Ube3a, GNS, HGSNAT, NAGLU, SGSH, CLN1, CLN3, CLN4, CLN5, CLN6, CLN7, CLN8, CTSD, ABCD1, HEXA, HEXB, ASM, ASP A, GLB1, AADC, MFN2, GNAO1, SYNGAP1, GRIN2A, GRIN2B, KCNQ2, EPM2A, NHLRC1, SLC6A1, SLC13A5, SURF1, GBE1, ATXN1, ATXN3, and ATXN7. Patent Application CAPS -041 / 01 WO 35847 / 197 In some instances, the therapeutic gene expression product comprises gene editing components. In some instances, the gene editing components are selected from an artificial site-specific RNA endonuclease (ASRE), a zinc finger endonuclease (ZFN), a transcription factor like effector nuclease (TALEN), a clustered regularly interspaced short palindromic repeats (CRISPR) / Cas enzyme, and a CRISPR / Cas guide RNA.

[1921] In some instances, the expression of a gene or expression or activity of a gene expression product is inhibited by the administration of the composition to the subject. In some instances, the expression of a gene or the expression or the activity of a gene expression product is enhanced by the administration of the composition to the subject.

[1922] Formulations, Dosages, and Routes of Admini stration

[1923] Disclosed herein are methods comprising delivering a rAAV particle encapsidating a heterologous nucleic acid to the brain in a subject, the rAAV particle comprising (i) an increased transduction of the heterologous nucleic acid in the brain.

[1924] In general, methods disclosed herein comprise administering a therapeutic rAAV composition by systemic administration. In some instances, methods comprise administering a therapeutic rAAV composition by intravenous (“i.v.”) administration. One may administer therapeutic rAAV compositions by additional routes, such as subcutaneous injection, intramuscular injection, intradermal injection, transdermal injection, percutaneous administration, intranasal administration, intralymphatic injection, rectal administration intragastric administration, intraocular administration, intracerebroventricular administration, intrathecally, intraci stem al, or any other suitable parenteral administration. Routes, dosage, time points, and duration of administrating therapeutics may be adjusted. In some embodiments, administration of therapeutics is prior to, or after, onset of either, or both, acute and chronic symptoms of the disease or condition. Other routes of delivery to the brain include, but are not limited to intracranial administration, lateral cerebroventricular administration, and endovascular administration.

[1925] An effective dose and dosage of pharmaceutical compositions to prevent or treat the disease or condition disclosed herein is defined by an observed beneficial response related to the disease or condition, or symptom of the disease or condition. Beneficial response comprises preventing, alleviating, arresting, or curing the disease or condition, or symptom of the disease or condition. Patent Application CAPS -041 / 01 WO 35847 / 197 In some embodiments, the beneficial response may be measured by detecting a measurable improvement in the presence, level, or activity, of biomarkers, transcriptomic risk profile, or intestinal microbiome in the subject. An “improvement,” as used herein refers to shift in the presence, level, or activity towards a presence, level, or activity, observed in normal individuals (e.g. individuals who do not suffer from the disease or condition). In instances wherein the therapeutic rAAV composition is not therapeutically effective or is not providing a sufficient alleviation of the disease or condition, or symptom of the disease or condition, then the dosage amount and / or route of administration may be changed, or an additional agent may be administered to the subject, along with the therapeutic rAAV composition. In some embodiments, as a patient is started on a regimen of a therapeutic rAAV composition, the patient is also weaned off (e.g., step-wise decrease in dose) a second treatment regimen.

[1926] In some cases, a dose of the pharmaceutical composition may comprise a concentration of infectious particles of at least or about 107, 108, 109, 1010, 1011, 1012, 1013, 1014, 1015, 1016, or 1017In some cases, the concentration of infectious particles is 2x107, 2x108, 2x109, 2x1010, 2x1011, 2x1012, 2x1013, 2x1014, 2x1015, 2x1016, or 2x1017. In some cases, the concentration of the infectious particles is 3x107, 3x108, 3x109, 3x1010, 3x1011, 3x1012, 3x1013, 3x1014, 3x1015, 3x1016, or 3x1017In some cases, the concentration of the infectious particles is 4x107, 4x108, 4x109, 4x1010, 4x1011, 4x1012, 4x1013, 4x1014, 4x1015, 4x1016, or 4x1017. In some cases, the concentration of the infectious particles is 5x107, 5x108, 5x109, 5x1010, 5x1011, 5x1012, 5x1013, 5x1014, 5x1015, 5x1016, or 5x1017In some cases, the concentration of the infectious particles is 6xl07, 6x10s, 6x109, 6xlO30, 6xlO13, 6xl012, 6xl013, 6xl034, 6xlO3’, 6xl016, or 6xlO37In some cases, the concentration of the infectious particles is 7x107, 7x108, 7x109, 7x1010, 7x1011, 7x1012, 7x1013, 7x1014, 7x1015, 7x1016, or 7x1017In some cases, the concentration of the infectious particles is 8x107, 8x108, 8x109, 8x1010, 8x1011, 8x1012, 8x1013, 8x1014, 8x1015, 8x1016, or 8x1017. In some cases, the concentration of the infectious particles is 9x107, 9x108, 9x109, 9x1010, 9x1011, 9x1012, 9x1013, 9x1014, 9x1015, 9x1016, or 9x1017Disclosed herein, in some embodiments are formulations of pharmaceutically-acceptable excipients and carrier solutions suitable for delivery of the rAAV compositions described herein, as well as suitable dosing and treatment regimens for using the particular compositions described herein in a variety of treatment regimens. In some embodiments, the amount of therapeutic gene expression product in each therapeutically-useful composition may be prepared in such a way that Patent Application CAPS -041 / 01 WO 35847 / 197 a suitable dosage will be obtained in any given unit dose of the compound. Factors such as solubility, bioavailability, biological half-life, route of administration, product shelf life, as well as other pharmacological considerations will be contemplated by one skilled in the art of preparing such pharmaceutical formulations, and as such, a variety of dosages and treatment regimens may be desirable.

[1927] In some embodiments, the pharmaceutical forms of the rAAV-based viral compositions suitable for injectable use include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), suitable mixtures thereof, and / or vegetable oils. Proper fluidity may be maintained, for example, by the use of a coating, such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. The prevention of the action of microorganisms can be brought about by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars or sodium chloride.

[1928] In some cases, for administration of an injectable aqueous solution, the solution may be suitably buffered, if necessary, and the liquid diluent first rendered isotonic with sufficient saline or glucose. These particular aqueous solutions are especially suitable for intravenous, intramuscular, subcutaneous and intraperitoneal administration. Some variation in dosage will necessarily occur depending on the condition of the subject being treated. The person responsible for administration will, in any event, determine the appropriate dose for the individual subject. Moreover, for human administration, preparations should meet sterility, pyrogenicity, and the general safety and purity standards as required by FDA Office of Biologies standards.

[1929] Disclosed herein are sterile injectable solutions comprising the rAAV compositions disclosed herein, which are prepared by incorporating the rAAV compositions disclosed herein in the required amount in the appropriate solvent with several of the other ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the various sterilized active ingredients into a sterile vehicle which contains the basic dispersion medium and the required other ingredients from those enumerated above. In the case of Patent Application CAPS -041 / 01 WO 35847 / 197 sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum-drying and freeze-drying techniques which yield a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof. Injectable solutions may be advantageous for systemic administration, for example by intravenous or intrathecal administration.

[1930] Suitable do...

Claims

Patent Application CAPS -041 / 01 WO 35847 / 197 CLAIMS1. An adeno-associated virus (AAV) capsid protein comprising an amino acid sequence having at least 80% identity to a sequence of Formula I:X1A-H-Q-X4A-X5A-X6A-X7A-X8A-G-X10A-X11A-X12A-I-A-X15A-X16A-X17A-X18A-X19A-X20A-X21A-X22A-X23A-X24A-X25A (I)wherein,XIA is an amino acid selected from N or T;X4A is an amino acid selected from S, G, M, or A;X5A is an amino acid selected from A, S, or N;X6A is an amino acid selected from T, S, or V;X7A is an amino acid selected from K or R;X8A is an amino acid selected from N or D;X9A is amino acid G;X10A is an amino acid selected from E or H;X11A is an amino acid selected from V or I;X12A is an amino acid selected from F, Y, L, or H;X15A is an amino acid selected from Q, M, I, or N;X16A is an amino acid selected from A or S;X17A is an amino acid selected from Q, S, N, T, or A;X18A is an amino acid selected from T, V, R, S, Q, I, N, or A;X19A is an amino acid from G, S, A, N, Q, M, T, V, Y, L, K, I, H, F, D, or E;X20A is an amino acid selected from W, A, Q, S, G, N, P, M, T, L, Y, F, K, V, H, R, D, I, or E;X21A is an amino acid selected from V, A, I, S, C, T, N, M, L, Q, G, or D,X22A is an amino acid selected from Q, N, H, Y, T, S, G, or F;X23A is an amino acid selected from N, S, G, Q, Y, A, F, M, D, V, E, C, I, H, L, or W; X24A is an amino acid selected from Q, C, M, or I; andPatent Application CAPS -041 / 01 WO 35847 / 197 X25A is an amino acid selected from G or A.

2. The AAV capsid protein of claim 1, wherein XIA is located at parental residue 583 and X?5A is located at parental residue 600 in reference to a parental AAV9 capsid or equivalent residue position in another AAV capsid, wherein in Formula I:XIA is a parental or substituted amino acid;H and Q are parental amino acids,X4A and X5A are parental or substituted amino acids;X6A is a substituted amino acid located at parental residue 588;, X7A, X8A, G, X10A, X11A, X12A, and I are an insertion between parental residues 588 and 589, now residue 596;A is a parental amino acid located at parental residue 589, now residue 596;X15A, X16A, X17A, X18A, X19A, X20A, X21A, X22A, X23A, X24A are parental or substituted amino acids; andX25A is a parental or substituted amino acid located at parental residue 600, now residue 607.

3. The AAV capsid protein of claim 1, wherein X4A is selected from among S, G, or M.

4. The AAV capsid protein of claim 1, wherein X12A is selected from among F, Y, or L.

5. The AAV capsid protein of claim 1, wherein X15A is selected from among Q, M, or I.

6. The AAV capsid protein of claim 1, wherein X17A is selected from among Q, S, or N.

7. The AAV capsid protein of claim 1, wherein X18A is selected from among T, V, or R.

8. The AAV capsid protein of claim 1, wherein X19A is selected from among G, S, or A.

9. The AAV capsid protein of claim 1, wherein X20A is selected from among W, A, or Q.Patent Application CAPS -041 / 01 WO 35847 / 197 10 The AAV capsid protein of claim 1, wherein X21A is selected from among V, A, or I.

11. The AAV capsid protein of claim 1, wherein X22A is selected from among Q, N, or H.

12. The AAV capsid protein of claim 1, wherein X23 is selected from among N, S, or G.

13. The AAV capsid protein of claim 1, wherein X24A is selected from among Q, C, or M.

14. The AAV capsid of claim 1, wherein the capsid protein comprises an amino acid sequence selected from Table 1 or 8.

15. An AAV capsid protein comprising an amino acid sequence having at least 80% identity to a sequence of Formula II:X1B-X2B-Q-X4B-X5B-X6B-X7B-X8B-X9B-X10B-X11B-X12B-X13B-X14B-X15B-X16B-X17B (II)wherein,XIB is an amino acid selected from N or S;X2B is an amino acid selected from H, N, S, Q, L, V, or W;X4B is an amino acid selected from S, T, G, A, M, or C;XSB is an amino acid selected from A, Q, S, N, M, E, H, T, D, G, or Y;X6B is an amino acid selected from T, M, S, V, L, I, K, Q, Y, A, N, or E;X7B is an amino acid selected from R, K, L, M, S, or A;X8B is an amino acid selected from N, D, G, A, T, Q, or S,X9B is an amino acid selected from G, S, T, E, Q, D, A, K, or N;X10B is an amino acid selected from E, H, Q, A, S, G, N, K, T, D, V, or R;X11B is an amino acid selected from T, V, I, L, or M;X12B is an amino acid selected from Y, L, F, R, M, or H;X13B is an amino acid selected from I, V, L, M, S, or Q:X14B is an amino acid selected from A or S,Patent Application CAPS -041 / 01 WO 35847 / 197 XISB is an amino acid selected from S, G, Q, M, A, T, I, N, V, H, or L;Xi6B is an amino acid selected from A, P, S, T, F, or I, andX17B is an amino acid selected from Q, S, N, A, or T16 The AAV capsid protein of claim 15, wherein XIB is located at parental residue 583 and XI? B is located at parental residue 592 in reference to a parental AAV9 capsid or equivalent residue position in another AA V capsid, wherein in Formula II:XIB and X213 may be parental or substituted amino acid;Q is a parental amino acid;X4B and XSB are parental or substituted amino acids;XeB is a parental or substituted amino acid located at parental residue 588;X7B, XSB, X9B. XIOB, XnB, X12B, XHB are an insertion between parental or substituted residues in positions 588 and 589;X14B, Xi5B, and XISB, are parental or substituted amino acids; andX17 is a parental or substituted amino acid located at parental residue 592, now residue 599.

17. The AAV capsid protein of claim 15, wherein X2B is selected from among H, N, or S.

18. The AAV capsid protein of claim 15, wherein XXsis selected from among S, T, or G.

19. The AAV capsid protein of claim 15, wherein XSB is selected from among A, Q. or S20. The AAV capsid protein of claim 15, wherein XSB is selected from among T, M, or S.

21. The AAV capsid protein of claim 15, wherein X-nis selected from among R, K, or L.

22. The AAV capsid protein of claim 15, wherein XSB is selected from among N, D, or G.

23. The AAV capsid protein of claim 15, wherein X9BIS selected from among G, S, or T.Patent Application CAPS -041 / 01 WO 35847 / 197 24 The AAV capsid protein of claim 15, wherein Xiosis selected from among E, H, or Q.

25. The AAV capsid protein of claim 15, wherein Ximis selected from among T, V, or I.

26. The AAV capsid protein of claim 15, wherein Xnnis selected from among Y, L, or E.

27. The AAV capsid protein of claim 15, wherein Xonis selected from among I, V, or L.

28. The AAV capsid protein of claim 15, wherein Xunis selected from among A or S.

29. The AAV capsid protein of claim 15, wherein Xunis selected from among S, G, or Q.

30. The AAV capsid protein of claim 15, wherein Xi6B is selected from among A, P, or S.

31. The AAV capsid protein of claim 15, wherein Xivsis selected from among Q, S, or N.

32. The AAV capsid of claim 15, wherein the capsid protein comprises an amino acid sequence selected from Table 2.33 An AAV capsid protein comprising an amino acid sequence having at least 80% identity to a sequence of Formul a III.X1C-X2C- X3C-X, C-X5C-X6C-G-F-T- Xioc-X] 10-Xl2C-X13C-Xl4C-X15C-Xi6C-X17C-X] 8C-Xl9C (111)wherein,Xie is an amino acid selected from A, N, V, H, Y, F, S, D, W, I, P, Q, R, K, M, E, T, C, L, or G;X3c is an amino acid selected from Q, M, L, A, T, V, I, E, H, S, N, R, K, F, D, or Y; X?,c is an amino acid selected from S, G, or FI;X4C is an amino acid selected from T, I, V, L, M, F, Y, H, A, K, Q, or S;Patent Application CAPS -041 / 01 WO 35847 / 197 Xsc is an amino acid selected from G or Q;Xec is an amino acid selected from Q, D, N, H, G, E, S, A, L, M, or R,Xtoc is an amino acid selected from A, M, Q, E, N, L, V, T, S, I, D, K, H, C, or R;Xnc is an amino acid selected from Q, M, or Y;Xnc is an amino acid selected from A, P, G, S, T, V, Y, C, W, I, H, F, or Q;XBC is an amino acid selected from Q, T, M, V, E, L, S, A, D, G, I, N, K, R, H, F, or Y; Xue is an amino acid selected from T, N, S, Q, I, G, A, L, V, C, D, Y, M, F, E, or W; Xisc is an amino acid selected from G, D, E, A, S, N, T, Q, F, Y, K, M, L, H, I, V, W, or R;Xi6c is an amino acid selected from W, D, E, F, L, V, ], P, A, S, T, Y, H, Q, M, N, or G; Xi7c is an amino acid selected from V, I, N, A, T, S, C, L, Q, P, M, G, D, FL E, or F; Xisc is an amino acid selected from Q, D, N, S, E, 11. G, T, A, C, or P; andXi9c is an amino acid selected from N, Y, G, S, D, A, Q, E, V, C, F, 1, L, M, R, T, or W.

34. The AAV capsid protein of claim 33, wherein Xie is located at parental residue 587 and Xj9c is located at parental residue 598 in reference to a parental AAV9 capsid or equivalent residue position in another AAV capsid, wherein in Formula III:Xie is a parental or substituted amino acid;X2C is a parental or substituted amino acid located at parental residue 588,Xac, X4C, Xsc. Xec. G, F, T, are an insertion between parental or substituted residues 588 and 589;Xtoc, Xue, Xi2c. XBC, Xue, Xisc, Xi6c, Xnc, Xisc are parental or substituted amino acids; andXue is a parental or substituted amino acid located at parental residue 598, now residue 605.

35. The AAV capsid protein of claim 33, wherein Xicis selected from among A, N, or V.

36. The AAV capsid protein of claim 33, wdierein X2C is selected from among Q, M, or L.Patent Application CAPS -041 / 01 WO 35847 / 197 37 The AAV capsid protein of claim 33, wherein X,icis selected from among T, I, or V.

38. The AAV capsid protein of claim 33, wherein Xec is selected from among Q, D, or N.

39. The AAV capsid protein of claim 33, wherein Xioc is selected from among A, M, or Q.

40. The AA V capsid protein of claim 33, wherein Xue is selected from among A, P, or G.

41. The AAV capsid protein of claim 33, wherein Xjscis selected from among Q, T, orM.

42. The AAV capsid protein of claim 33, wherein Xue is selected from among T, N, or S.

43. The AAV capsid protein of claim 33, wherein Xisc is selected from among G, D, or E.

44. The AAV capsid protein of claim 33, wherein Xue is selected from among W, D, or E.

45. The A / XV capsid protein of claim 33, wherein Xucis selected from among V, I, or N.

46. The AAV capsid protein of claim 33, wherein Xisc is selected from among Q, D, or N,47. The AAV capsid protein of claim 33, wherein Xi9c is selected from among N, Y, or G.

48. The AAV capsid of claim 33, wherein the capsid protein comprises an amino acid sequence selected from Table 3.

49. An AAV capsid protein comprising an amino acid sequence having at least 80% identity to a sequence of Formula IV:X1D-X2D- X3D-X4D-X5D-X6D-X7D-X8D-X9D- X10D-X11D-X12D-X13D-X14D-X15D-X16D-X17D-X18D-X19D (IV)wherein.Patent Application CAPS -041 / 01 WO 35847 / 197 XID is an amino acid selected from A, H, Y, F, N, G, Q, W, V, T, D, E, M, S, K, I, P, L, C, or R;XZD is an amino acid selected from Q, W, V, T, P, N, A, S, L, H, I, G, D, M, Y, R, K, or F; X3D is an amino acid selected from S, I, M, P, G, A, N, V, T, Q, E, D, H, L, Y, K, R, or F; X4D is an amino acid selected from T. G, S. N, Q, A, L, I, V, P, E, II D, M, R, Y, C, K, or F;XSD is an amino acid selected from G, S, N, Q, T, A, H, V, M, I, L, D, K, P, or Y;X6D is an amino acid from Q, M, A, N, G, S, T, E, V, Y, H, K, P, I, or D and preferably from Q, M, or A,X? D is an amino acid selected from G, N, E, T, S, D, A, P, L, Q, I, M, V, H, K, or Y; XSD is an amino acid selected from F, E, L, T, S, Q, N, H, G, D, I, A, V, K, Y, R, M, or P; Xsois an amino acid selected from T, K, R, I, FI, Q, A, N, V, M, S, Y, D, E, F, G, P, or L; XIOD is an amino acid selected from A, Q, N, S, M, T, I, V, Y, L, E, P, H, F, K, G, R, C, D, or W;XIID is an amino acid selected from Q, P, I, N, S, T, M, G, L, D, H, A, R, V, W, or Y; X12D is an amino acid selected from A, P, C, T, G, S, V, I, F, M, Q, E, or L;XBD is an amino acid selected from Q, A, S, T, M, G, D, V, L, E, F, I, N, Y, H, K, or W; Xi4D is an amino acid selected from T, S, G, A, V, Q, N, I, M, C, D, E, P, R, or W;Xi so is an amino acid selected from G, E, A, D, S, Q, T, N, I, M. V, L, F, W, Y, K, or C; Xt6D is an amino acid selected from W, R, N, K, P, V, M, E, Q, T, A, D, Y, S, L, FL I, G, (. or F;Xi7D is an amino acid selected from V, N, C, A, I, T, L, Q, or P;XISD is an amino acid selected from Q, FI, E, S, A, D, G, N, L, T, or V; andXi9D is an amino acid selected from N, V, F, D, S, or T.

50. The AAV capsid protein of claim 49, wherein XID is located at parental residue 587 and Xi9D is located at parental residue 598 in reference to a parental AAV9 capsid or equivalent residue position in another AAV capsid, wherein in Formula IV:XID is a parental or substituted amino acid;? D is a parental or substituted amino acid located at parental residue 588;Patent Application CAPS -041 / 01 WO 35847 / 197 X3D, X4D, XSD, X6D. X? D, XSD, X9D are an insertion between parental or substituted residues 588 and 589;XIOD, XUD, Xt2D, Xt3D, Xt4D, XUD, XUD, Xi7D;Xi8D are parental or substituted amino acids; andXi9D is a parental or substituted amino acid located at parental residue 598, now residue 605.

51. The AAV capsid protein of claim 49, wherein X is selected from among A, H, or Y.

52. The AAV capsid protein of claim 49, wherein X2D is selected from among Q, W, or V.

53. The AAV capsid protein of claim 49, wherein Xaois selected from among S, I, or M,54. The AAV capsid protein of claim 49, wherein X< ID is selected from among T, G, or S.

55. The AA V capsid protein of claim 49, wherein XJD IS selected from among G, S, or N.

56. The AAV capsid protein of claim 49, wherein Xsois selected from among Q, M, or A.

57. The AAV capsid protein of claim 49, wherein XTD IS selected from among G, N, or E.58 The AAV capsid protein of claim 49, wherein XXD is selected from among F, E, or L.

59. The AAV capsid protein of claim 49, wherein Xgois selected from among T, K, or R.

60. The AAV capsid protein of claim 49, wherein XIOD is selected from among A, Q, or N.61 The AAV capsid protein of claim 49, wherein XUD is selected from among Q, P, or L.

62. The AAV capsid protein of claim 49, wlierein XUD is selected from among A, P, or C.Patent Application CAPS -041 / 01 WO 35847 / 19763. The AAV capsid protein of claim 49, wherein XBDIS selected from among Q, A, or S.

64. The AAV capsid protein of claim 49, wherein XMD IS selected from among T, S or G.

65. The AAV capsid protein of claim 49, wherein Xisnis selected from among G, E, or A.

66. The AAV capsid protein of claim 49, wherein Xi6D is selected from among W, R or N.

67. The AAV capsid protein of claim 49, wherein Xnois selected from among V, N, or C;68. The AAV capsid protein of claim 49, wherein XISD is selected from among Q, II, or E.

69. The AAV capsid protein of claim 49, wherein Xi9D is selected from among N, V, or F.

70. The AAV capsid of claim 49, wherein the capsid protein comprises an amino acid sequence selected from Table 4.

71. An AAV capsid protein comprising an amino acid sequence having at least 85% identity to a sequence of Formula V:X1E-X2E-X3E-X4E-X5E-X6E-X7E ( V)wherein,XIE is an amino acid selected from N, G, Q, L, V, A, M, S, FI, D, T, I, Y, or E, X? E is an amino acid selected from G, K, H, N, R, S, T, Q, E, or M;X3E is an amino acid selected from G, T, A, D, S, V, P, N, H, or Q;X4E is an amino acid selected from G, T, S, Q, P, or A;X5E is an amino acid selected from S, Q, N, A, T, M, G, K, H, or R;X6E is an amino acid selected from N, S, K, T, Q, G, A, or R; andX7E is an amino acid selected from Q, K, S, T, N, M, G, E, H, or I.Patent Application CAPS -041 / 01 WO 35847 / 19772. The AAV capsid protein of claim 71, wherein XIE is located at parental residue 452 and X?i is located at parental residue 458 in reference to a parental AAV9 capsid or equivalent residue position in another AAV capsid, wherein in Formula V any or XIE through X? E, corresponding to residues 452-458, may independently be a parental or substituted amino acid.

73. The AAV capsid protein of claim 71, wherein XIE is selected from among N, G, or Q.

74. The AAV capsid protein of claim 71, wherein X2E is selected from among G, K, or H.

75. The AAV capsid protein of claim 71, wherein XSE IS selected from among G, T, or A.

76. The AAV capsid protein of claim 71, wherein X.n is selected from among G, T, or S.

77. The AAV capsid protein of claim 71, wherein XJE IS selected from among S, Q, orN.

78. The AAV capsid protein of claim 71, wherein XeE is selected from among N, S, or K.

79. The AAV capsid protein of claim 71, wherein X71. is selected from among Q, K, or S.

80. The AAV capsid protein of claim 71, wherein the capsid protein comprises a 12-mer amino acid sequence selected from Table 5 or 8.

81. An AAV capsid protein comprising an amino acid sequence having at least 85% identity to a sequence of Formula VI:X1F-X2F-G-X4F-X5F-A-X7F-N-Q (VI)wherein,XJF is an amino acid selected from N or V;X2F is an amino acid selected from K or L;Patent Application CAPS -041 / 01 WO 35847 / 197 X4F is an amino acid selected from G, Q, T, or V;XSF is an amino acid selected from S or G; andX? F is an amino acid selected from G, A, N, Q, or T.82 The AAV capsid protein of claim 81, wherein XIF is located at parental residue 452 in reference to a parental AAV9 capsid or equivalent residue position in another AAV capsid, wherein in Formula VI:XIF is a parental or substituted amino acid;six amino acids XZF, G, X4F, XSF, A, and X? F are inserted, with four residues substituting positions 453 and 456 relative to the parental capsid; andN and Q are parental amino acids located at parental residues 457-458, now residues 459- 460.

83. The AAV capsid protein of claim 81, wherein +F is selected from G, Q, or T.

84. The AAV capsid protein of claim 81, wherein X? F is selected from G, A, or N.

85. The AAV capsid protein of claim 81, wherein the capsid protein comprises a 14-mer amino acid sequence selected from Table 6 or 8.

86. An AAV capsid protein comprising an amino acid sequence having at least 80% identity to a sequence of Formula VII:XlG-G-XsG^-XjG-XeG-X G-XsG-XsG-X G-XnG / VII)whereinXIG is an amino acid selected from N, L, E, M, Q, S, or V;X. G is an amino acid selected from P or G;X4G is an amino acid selected from V, S, M, or A;X? G is an amino acid selected from S, A, G, or Q;XgG is an amino acid selected from S, T, G, or A;X? G is an amino acid selected from G or N;Patent Application CAPS -041 / 01 WO 35847 / 197 XgG is an amino acid selected from K or H;X9G is an amino acid selected from Q, A or P,Xioois an amino acid selected from N, A, S, or T; andXIIG is an amino acid selected from Q, M, A, N, S, T, or V.

87. The AAV capsid protein of claim 86, wherein XJG is located at parental residue 452, wherein in Formula VII,XIG is a parental or substituted amino acid;G is a parental amino acid located at parental residue 453;six amino acids XJG, X4G, XSG, XSG, X? G, and XSG are inserted, with two residues substituting positions 454 and 455 of the parental capsid; andXSG, XIOG, and XHG are parental or substituted amino acids located at parental residues 456-458, now residues 460-462.

88. The AAV capsid protein of claim 86, wherein XIG is selected from N, L, or E.

89. The AAV capsid protein of claim 86, X4G is selected from V, S, or M;90. The AAV capsid protein of claim 86, XSG is selected from S, A, or G;91 The AAV capsid protein of claim 86, XgG is selected from S, T, or G;92. The AAV capsid protein of claim 86, XIOG is selected from N, A, or S;93. The AAV capsid protein of claim 86, XHG is selected from Q, M, or A.

94. The AAV capsid protein of claim 86, wherein the capsid protein comprises a 16-mer amino acid sequence selected from Table 7 or 8.

95. An AAV capsid protein comprising an amino acid sequence having at least 80% identity toPatent Application CAPS -041 / 01 WO 35847 / 197 capsid sequence NHQSGQKPPGYLLSAAQ (SEQ ID NO: 4995) at positions 583-592 (now 599 with the 7-mer insertion) of parental capsid.96 The AAV capsid protein of any of claims 1- 95, wherein the AAV capsid protein comprises an amino acid sequence selected from the group consisting of:AQSTGQGFTAQAQTGWVQN (SEQ ID NO: 4991);AQSTGQGFTAQPATGWVQN (SEQ ID NO: 1825);AQSTGQGFTYPAQTGWVQN (SEQ ID NO: 2819);NHQSASRNGEVYIAQAQTAQVQNQG (SEQ ID NO: 3987);NHQSSTKNGEVFIAQAQTSNVQNQG (SEQ ID NO: 4003);NHQSSTKNGEVFIAQAQTGWVQNQG (SEQ ID NO: 40);NHQSASRNGEVYIAQAQTGWVQNQG (SEQ ID NO: 4137);NHQSQTRNGGTLIAVAQTGWVQNQG (SEQ ID NO: 819);NHQSATRNGEVFIAQAQTGWVQNQG (SEQ ID NO: 4936); and NHQSAVKDGHVLIAMAQTGSAQNQG (SEQ ID NO: 3989).

97. The AAV capsid protein of any of claims 1-95, wherein the AAV capsid protein comprises an amino acid sequence selected from the group consisting of:RTINGAGQNQQT (SEQ ID NO: 3823);RTINGSGQNQQT (SEQ ID NO: 3819);RTIQGTGQNQQT (SEQ ID NO: 3820), andRTINGTGQNQQT (SEQ ID NO: 3827).

98. The AAV capsid protein of any of claims 1-97, wherein 60 copies of the AAV capsid proteins are assembled into the AAV capsid.

99. The AAV capsid protein of any of claims 1-97, wherein the AAV capsid protein is characterized by at least one of an increased transduction enrichment when measured in a central nervous system in a subject when delivered to the subject systemically.Patent Application CAPS -041 / 01 WO 35847 / 197 100. The AAV capsid protein of any of claims 1-97, wherein the AAV capsid protein is characterized by at least one of an increased transduction enrichment when measured in a brain in a subject when delivered to the subject systemically.

101. The AAV capsid protein of any of claims 1-97, wherein the AAV capsid protein is characterized by at least one of an increased transduction enrichment when measured in a spinal cord in a subject when delivered to the subject systemically.102 An AAV capsid comprising an AAV capsid protein of any of claims 1-101103. The AAV capsid of claim 102, wherein the AAV capsid is chimeric.

104. The AAV capsid of any of claims 102-103 that is isolated and purified.

105. The AAV capsid of any of claims 102-104 formulated as a pharmaceutical formulation for systemic administration to treat a disease or a condition of the brain, spinal cord, and / or central nervous system the pharmaceutical formulation further comprising a pharmaceutically acceptable carrier.

106. A nucleic acid sequence encoding the capsid protein of any of claims 1-101107. A nucleic acid sequence encoding a peptide sequence as provided in Tables 1-8.

108. A recombinant vector comprising a nucleic acid encoding the AAV capsid protein of any one of claims 1-101.

109. A kit comprising:a) a first vector comprising the recombinant vector of claim 108;b) a second vector encoding a helper virus protein; andc) a third vector comprising a therapeutic nucleic acid encoding a therapeutic gene expression product.Patent Application CAPS -041 / 01 WO 35847 / 197110. A method of treating a disease or condition in a subject comprising administering a therapeutically effective amount of a pharmaceutical formulation comprising the AAV capsid protein of any one of claims 1-101.

111. The method of claim 110, wherein the disease or the condition is a disease or a condition of a central nervous system, brain, and / or spinal cord of the subject.112 An engineered adeno-associated virus (AAV) vector comprising an engineered capsid protein comprising an amino acid sequence that allows the capsid protein to bind Disintegrin And Metalloproteinase domain 15 (ADAMI 5), wherein when the capsid protein is in presence of a cell expressing ADAMI 5, then the capsid protein binds to ADAMI 5.

113. The engineered AAV vector of claim 112, further comprising a nucleic acid encoding a transgene, wherein the nucleic acid is encapsidated by the engineered capsid protein.

114. The engineered AAV vector of claim 112, wherein the engineered capsid protein is any capsid protein provided in claims 1 - 97.

115. The engineered AAV vector of claim 114, wherein the engineered capsid protein comprises amino acid sequence selected from the amino acid sequences provided in Tables 1-8, and preferably engineered capsid protein comprise amino acid sequence selected from the group consisting ofNHQSASRNGEVYIAQAQTAQVQNQG (SEQ ID NO: 3987);NHQSSTKNGEVFIAQAQTSNVQNQG (SEQ ID NO: 4003);NHQSSTKNGEVFIAQAQTGWVQNQG (SEQ ID NO: 40);NHQSASRNGEVYIAQAQTGWVQNQG (SEQ ID NO: 4137);NHQSQTRNGGTLIAVAQTGWVQNQG (SEQ ID NO: 819); and NHQSATRNGEVFIAQAQTGWVQNQG (SEQ ID NO: 4936).Patent Application CAPS -041 / 01 WO 35847 / 197 116. The engineered AAV vector of claim 115, wherein the AAV vector is characterized by at least one of an increased specificity and / or increased transduction efficiency in the central nervous system (CNS) tissue.

117. The engineered AAV vector of claim 116, wherein the AAV capsid protein is characterized by at least one of an increased specificity and / or increased transduction efficiency in the brain.

118. The engineered AAV vector of claim 117, wherein the AAV capsid protein is characterized by delivery of the transgene across the blood brain barrier (BBB).

119. The engineered AAV vector of claim 118, wherein the transgene is a therapeutic transgene for the treatment of a disorder affecting the central nervous system.120 The engineered AAV vector of claim 119, wherein the ADAMI 5 protein is human ADAM 15, wherein when provided to a cell expressing ADAMI 5 as a surface protein, binding of the capsid protein to ADAM15 protein mediates transcytosis of the transgene across the BBB.

121. A method of delivering a transgene across the BBB, the method comprising providing a subject an engineered AAV vector comprising:a) an engineered capsid protein comprising an amino acid sequence that allows the AAV vector to bind the ADAMI 5 protein; andb) a transgene encapsidated by the capsid protein;binding the AAV vector to the ADAMI 5 protein in cells expressing the ADAMI 5 protein, thereby delivering the transgene across the BBB.

122. The method of claim 121, wherein the engineered capsid protein is any capsid protein provided in claims 1 - 97.

123. The method of claim 122, wherein the engineered capsid protein comprises amino acid sequence selected from the amino acid sequences provided in Tables 1-8, and preferably engineered capsid protein comprise amino acid sequence selected from the group consisting of:Patent Application CAPS -041 / 01 WO 35847 / 197 NHQSASRNGEVYIAQAQTAQVQNQG (SEQ ID NO: 3987);NHQSSTKNGEVFIAQAQTSNVQNQG (SEQ ID NO: 4003);NHQSSTKNGEVFIAQAQTGWVQNQG (SEQ ID NO: 40);NHQSASRNGEVYIAQAQTGWVQNQG (SEQ ID NO: 4137);NHQSQTRNGGTLIAVAQTGWVQNQG (SEQ ID NO: 819); and NHQSATRNGEVFIAQAQTGWVQNQG (SEQ ID NO: 4936).

124. The method of claim 123, wherein the AAV vector exhibits increased specificity and / or increased transduction efficiency in the CNS tissue.

125. The method of claim 124, wherein the AAV capsid protein exhibits increased specificity and / or increased transduction efficiency in the brain.126 The method of claim 125, wherein the transgene is a therapeutic transgene for the treatment of a disorder affecting the central nervous system.

127. The method of claim 126, wherein the subject is human128. The method of claim 127, wherein binding of the capsid protein to ADAM 15 protein mediates deliver}' of the transgene across the BBB via transcytosis129. An engineered adeno-associated virus (AAV) vector comprising an engineered capsid protein comprising an amino acid sequence that allows the capsid protein to bind reversioninducing cysteine-rich protein with kazal motifs (RECK), wherein when the capsid protein is in presence of a cell expressing RECK, then the capsid protein binds to RECK.

130. The engineered AAV vector of claim 129, further comprising a nucleic acid encoding a transgene, wherein the nucleic acid is encapsidated by the engineered capsid protein.

131. The engineered AAV vector of claim 129, wherein the engineered AAV vector is derived from an AAV9 vector.Patent Application CAPS -041 / 01 WO 35847 / 197132. The engineered AAV vector of claim 131, wherein the engineered capsid protein is any capsid protein provided in claims 1 - 97.

133. The engineered AAV vector of claim 132, wherein the engineered capsid protein comprises amino acid sequence selected from the amino acid sequences provided in Tables 1-8, and preferably engineered capsid protein comprise amino acid sequence selected from the group consisting of:AQSTGQGFTAQAQTGWVQN (SEQ ID NO: 4991);AQSTGQGFTAQPATGWVQN (SEQ ID NO: 1825); and AQSTGQGFTYPAQTGWVQN (SEQ ID NO: 2819).

134. The engineered AAV vector of claim 133, wherein the AAV capsid protein is characterized by at least one of an increased specificity and / or increased transduction efficiency in the brain.

135. The engineered AAV vector of claim 134, wherein the AAV capsid protein is characterized by delivery of the transgene across the blood brain barrier (BBB)136. The engineered AAV vector of claim 135, wherein the transgene is a therapeutic transgene for the treatment of a disorder affecting the central nervous system.

137. The engineered AAV vector of claim 129, wherein the RECK protein is human RECK, wherein when provided to a cell expressing R ECK as a surface protein, binding of the capsid protein to RECK protein mediates transcytosis of the transgene across the BBB, wherein when the capsid protein is in presence of a cell expressing RECK, then the capsid protein binds to RECK.138 A method of delivering a transgene across the BBB, the method comprising providing a subject an engineered AAV vector comprising:a) an engineered capsid protein comprising an amino acid sequence that allows the AAV vector to bind the RECK protein; andPatent Application CAPS -041 / 01 WO 35847 / 197 b) a transgene encapsidated by the capsid protein;binding the AAV vector to the RECK protein in cells expressing the RECK protein, thereby delivering the transgene across the BBB.

139. The method of claim 138, wherein the engineered capsid protein is any capsid protein provided in claims 1 - 97.

140. The method of claim 138, wherein the engineered capsid protein comprises amino acid sequence selected from the amino acid sequences provided in Tables 1-8, and preferably engineered capsid protein comprise amino acid sequence selected from the group consisting of:AQSTGQGFTAQAQTGWVQN (SEQ ID NO: 4991);AQSTGQGFTAQPATGWVQN (SEQ ID NO: 1825); and AQSTGQGFTYPAQTGWVQN (SEQ ID NO: 2819).

141. The method of claim 140, wherein the AAV vector exhibits increased specificity and / or increased transduction efficiency in the CNS tissue.

142. The method of claim 140, wherein the AAV capsid protein exhibits increased specificity and / or increased transduction efficiency in the brain.

143. The method of claim 142, wherein the transgene is a therapeutic transgene for the treatment of a disorder affecting the central nervous system.

144. The method of claim 143, wherein the subject is human.

145. The method of claim 144, wherein binding of the capsid protein to RECK protein mediates delivery of the transgene across the BBB via transcytosis.

146. A method of delivering a transgene to a cell, the method comprising providing a subject an engineered AAV vector comprising:Patent Application CAPS -041 / 01 WO 35847 / 197 c) an engineered capsid protein comprising an amino acid sequence that allows the AAV vector to bind ADAMI 5 protein; andd) a transgene encapsidated by the capsid protein;binding the AAV vector to the ADAMI 5 protein in cells expressing the ADAMI 5 protein, thereby delivering the transgene in the cell.

147. The method of claim 146, wherein the engineered capsid protein is any capsid protein provided in claims 1 - 97.

148. The method of claim 146, wherein the engineered capsid protein comprises amino acid sequence selected from the amino acid sequences provided in Tables 1-8, and preferably engineered capsid protein comprise amino acid sequence selected from the group consisting of:NHQSASRNGEVYIAQAQTAQVQNQG (SEQ ID NO: 3987);NHQSSTKNGEVFIAQAQTSNVQNQG (SEQ ID NO: 4003);NHQSSTKNGEVFIAQAQTGWVQNQG (SEQ ID NO: 40);NHQSASRNGEVYIAQAQTGWVQNQG (SEQ ID NO: 4137);NHQSQTRNGGTLIAVAQTGWVQNQG (SEQ ID NO: 819); and NHQSATRNGEVFIAQAQTGWVQNQG (SEQ ID NO: 4936)149. The method of claim 146, wherein the AAV vector exhibits increased specificity toward the cells expressing ADAMI 5 as compared to cells not expressing ADAMI 5.150 The method of claim 146, wherein said engineered AAV vector is administered directly administered to brain of said subject.

151. The method of claim 145, wherein said engineered AAV vector is administered via systemic administration.

152. The method of claim 146, wherein said engineered AAV vector exhibits increased specificity and / or increased transcytosis in cells expressing ADAM 15 as compared to cells that do not express ADAMI 5.Patent Application CAPS -041 / 01 WO 35847 / 197153. A method of delivering a transgene to a cell, the method comprising providing a subject an engineered AAV vector comprising:c) an engineered capsid protein comprising an amino acid sequence that allows the AAV vector to bind RECK protein; andd) a transgene encapsidated by the capsid protein;binding the AAV vector to the RECK protein in cells expressing the RECK protein, thereby delivering the transgene in the cell.

154. The method of claim 153, wherein the engineered capsid protein is any capsid protein provided in claims 1 - 97.

155. The method of claim 153, wherein the engineered capsid protein comprises amino acid sequence selected from the amino acid sequences provided in Tables 1-8, and preferably engineered capsid protein comprise amino acid sequence selected from the group consisting of:AQSTGQGFTAQAQTGWVQN (SEQ ID NO: 4991);AQSTGQGFTAQPATGWVQN (SEQ ID NO: 1825); and AQSTGQGFTYPAQTGWVQN (SEQ ID NO: 2819).

156. The method of claim 153, wherein the AAV vector exhibits increased specificity toward the cells expressing RECK as compared to cells not expressing RECK.157 The method of claim 153, wherein said engineered AAV vector is administered directly to brain of said subject.

158. The method of claim 153, wherein said engineered AAV vector is administered via systemic administration159. The method of claim 153, wherein said engineered AAV vector exhibits increased specificity and / or increased transcytosis in cells expressing RECK as compared to cells that do not express RECK.

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