KR20220014316A - 항-lilrb1 항체 및 그의 용도 - Google Patents
항-lilrb1 항체 및 그의 용도 Download PDFInfo
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- KR20220014316A KR20220014316A KR1020210098593A KR20210098593A KR20220014316A KR 20220014316 A KR20220014316 A KR 20220014316A KR 1020210098593 A KR1020210098593 A KR 1020210098593A KR 20210098593 A KR20210098593 A KR 20210098593A KR 20220014316 A KR20220014316 A KR 20220014316A
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- 239000012634 fragment Substances 0.000 claims abstract description 59
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- 201000011510 cancer Diseases 0.000 claims abstract description 50
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 156
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 21
- 230000017188 evasion or tolerance of host immune response Effects 0.000 claims description 14
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Abstract
LILRB1에 대한 특이성이 증진된 항-LILRB1 항체 및 이의 용도와 관련된 것으로, 구체적으로, 항-LILRB1 항체 또는 이의 항원 결합 단편, 및 이의 암 치료 용도가 제공된다.
Description
항-LILRB1 항체 및 이의 용도와 관련된 것으로, 구체적으로, 항-LILRB1 항체 또는 이의 항원 결합 단편, 및 이의 암 치료 용도에 관한 것이다.
Leukocyte immunoglobulin-like receptor subfamily B member 1(LILRB1, 또는 ILT2, CD85j, LIR-1)은 B 세포, T 세포, NK 세포, 수지상 세포, 대식 세포 및 기타 면역 세포 등에 발현되는 활성억제 수용체(inhibitory receptor)이다. LILRB1은 classical 및 non-classical MHC class I과 결합하여, 면역세포의 활성을 억제시키는 신호 전달 기작을 가진다.
따라서, LILRB1를 표적으로 하는 물질의 개발이 요구된다.
일 예는 LILRB1에 결합하는 항-LILRB1 항체 또는 이의 항원 결합 단편을 제공한다. 상기 항-LILRB1 항체 또는 이의 항원 결합 단편은 암세포들의 면역 회피를 저해하는 활성을 갖는 것일 수 있다. 또한, 상기 항-LILRB1 항체 또는 이의 항원 결합 단편은 우수한 항암 활성을 갖는 것일 수 있다. 상기 암은 표면에 MHC Class I을 발현 또는 과발현하는 것일 수 있다.
다른 예는 상기 항-LILRB1 항체 또는 이의 항원 결합 단편을 포함하는 약학 암의 치료 및/또는 예방용 약학 조성물을 제공한다. 다른 예는 상기 항-LILRB1 항체 또는 이의 항원 결합 단편의 약학적 유효량을 암의 치료 및/또는 예방을 필요로 하는 대상에게 투여하는 단계를 포함하는, 암의 치료 및/또는 예방 방법을 제공한다. 다른 예는 상기 항-LILRB1 항체 또는 이의 항원 결합 단편의 암의 치료 및/또는 예방에 사용하기 위한 용도 또는 암의 치료 및/또는 예방용 약학 조성물의 제조에 사용하기 위한 용도를 제공한다.
다른 예는 상기 항-LILRB1 항체 또는 이의 항원 결합 단편을 포함하는 암세포의 면역 회피 저해용 약학 조성물을 제공한다. 다른 예는 상기 항-LILRB1 항체 또는 이의 항원 결합 단편의 약학적 유효량을 암세포의 면역 회피 저해를 필요로 하는 대상에게 투여하는 단계를 포함하는, 암세포의 면역 회피 저해 방법을 제공한다. 다른 예는 상기 항-LILRB1 항체 또는 이의 항원 결합 단편의 암세포의 면역 회피 저해에 사용하기 위한 용도 또는 암세포의 면역 회피 저해용 약학 조성물의 제조에 사용하기 위한 용도를 제공한다.
일 예는 LILRB1에 결합하는 항-LILRB1 항체 또는 이의 항원 결합 단편을 제공한다. 상기 항-LILRB1 항체 또는 이의 항원 결합 단편은 암세포들의 면역 회피를 저해하는 활성을 갖는 것일 수 있다. 또한, 상기 항-LILRB1 항체 또는 이의 항원 결합 단편은 우수한 항암 활성을 갖는 것일 수 있다.
상기 항-LILRB1 항체 또는 이의 항원 결합 단편은 다음의 상보성결정영역(CDR)을 포함하는 것일 수 있다:
Kabat numbering에 따른 CDR 정의(Kabat, E.A., Wu, T.T., Perry, H., Gottesman, K. and Foeller, C. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition. NIH Publication No. 91-3242; http://www.abysis.org/)를 기준으로,
서열번호 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181, 193, 205, 또는 217의 아미노산 서열을 포함하는 CDR-L1,
서열번호 2, 14, 26, 38, 50, 62, 74, 86, 98, 110, 122, 134, 146, 158, 170, 182, 194, 206, 또는 218의 아미노산 서열을 포함하는 CDR-L2,
서열번호 3, 15, 27, 39, 51, 63, 75, 87, 99, 111, 123, 135, 147, 159, 171, 183, 195, 207, 또는 219의 아미노산 서열을 포함하는 CDR-L3,
서열번호 4, 16, 28, 40, 52, 64, 76, 88, 100, 112, 124, 136, 148, 160, 172, 184, 196, 208, 또는 220의 아미노산 서열을 포함하는 CDR-H1,
서열번호 5, 17, 29, 41, 53, 65, 77, 89, 101, 113, 125, 137, 149, 161, 173, 185, 197, 209, 또는 221의 아미노산 서열을 포함하는 CDR-H2, 및
서열번호 6, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 또는 222의 아미노산 서열을 포함하는 CDR-H3 를 포함하는 것일 수 있다.
일 구체예에서, 본 명세서에서 제공되는 항-LILRB1 항체 또는 이의 항원 결합 단편에 포함 가능한 6개 CDR(CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2, 및 CDR-H3)의 조합을 아래의 표 1에 예시하였다:
클론 | CDR | 아미노산 서열(N>C)(Kabat) | 서열번호 |
5 | CDR-L1 | RASQSIANYLN | 1 |
CDR-L2 | ATSTLQS | 2 | |
CDR-L3 | QQSYSFPWT | 3 | |
CDR-H1 | AYGIH | 4 | |
CDR-H2 | WIIPLSGGAHYAQKFQG | 5 | |
CDR-H3 | LYGWAEYFDV | 6 | |
6 | CDR-L1 | RASQSISNYLN | 13 |
CDR-L2 | AASTLQS | 14 | |
CDR-L3 | QQSYSFPWT | 15 | |
CDR-H1 | SYTIS | 16 | |
CDR-H2 | WISPELGTSNYAQKFQG | 17 | |
CDR-H3 | LRYGQTLYGFDI | 18 | |
7 | CDR-L1 | RASQSISNWLN | 25 |
CDR-L2 | GTSSLQS | 26 | |
CDR-L3 | QQSYSFPFT | 27 | |
CDR-H1 | SYGMH | 28 | |
CDR-H2 | WIIPVSGGATYAQKFQG | 29 | |
CDR-H3 | GSWAYYAEFDY | 30 | |
8 | CDR-L1 | RASQSISSYLN | 37 |
CDR-L2 | AASTLQS | 38 | |
CDR-L3 | QQSYSFPYT | 39 | |
CDR-H1 | SYGIH | 40 | |
CDR-H2 | WIIPISGTTNYAQKFQG | 41 | |
CDR-H3 | VGGVGLYVFDV | 42 | |
9 | CDR-L1 | RASQSISNYLN | 49 |
CDR-L2 | AASSLQS | 50 | |
CDR-L3 | QQSYSFPWT | 51 | |
CDR-H1 | SYAIH | 52 | |
CDR-H2 | WIVPGLGVTNYAQKFQG | 53 | |
CDR-H3 | QATLYQTEYMDV | 54 | |
10 | CDR-L1 | RASQSISNYLN | 61 |
CDR-L2 | AASNLQS | 62 | |
CDR-L3 | QQSYSFPFT | 63 | |
CDR-H1 | SHYMH | 64 | |
CDR-H2 | WISPYLGSTNYAQKFQG | 65 | |
CDR-H3 | DETGSTYGAFDY | 66 | |
11 | CDR-L1 | RASQSISNYLN | 73 |
CDR-L2 | DASTLQS | 74 | |
CDR-L3 | QQSYSFPWT | 75 | |
CDR-H1 | SYYVH | 76 | |
CDR-H2 | WISPYSGGTNYAQKFQG | 77 | |
CDR-H3 | DYYVSAYGAFDY | 78 | |
12 | CDR-L1 | RASQDISNYLN | 85 |
CDR-L2 | ATSSLQS | 86 | |
CDR-L3 | QQSYSFPWT | 87 | |
CDR-H1 | SYDIH | 88 | |
CDR-H2 | RIVPYLGVTNYAQKFQG | 89 | |
CDR-H3 | RQSQSSVYAFDI | 90 | |
13 | CDR-L1 | RASQSISNYLN | 97 |
CDR-L2 | AASRLQS | 98 | |
CDR-L3 | QQSYSFPFT | 99 | |
CDR-H1 | GYYIH | 100 | |
CDR-H2 | WISPSSGGTIYAQKFQG | 101 | |
CDR-H3 | DISVRVVQAFDY | 102 | |
14 | CDR-L1 | RASQSISNYLN | 109 |
CDR-L2 | ATSNLQS | 110 | |
CDR-L3 | QQSYSFPWT | 111 | |
CDR-H1 | SYYMH | 112 | |
CDR-H2 | WISPYLGITNYAQKFQG | 113 | |
CDR-H3 | AGYQQAQYWFDY | 114 | |
15 | CDR-L1 | RASQSISNYLN | 121 |
CDR-L2 | ATSSLQS | 122 | |
CDR-L3 | QQSYSFPYT | 123 | |
CDR-H1 | SYAMS | 124 | |
CDR-H2 | WIIPISGTTNYAQKFQG | 125 | |
CDR-H3 | QHSVGSVFDY | 126 | |
16 | CDR-L1 | RASQDISSWLN | 133 |
CDR-L2 | AASSLQS | 134 | |
CDR-L3 | QQSYSFPWT | 135 | |
CDR-H1 | SYYMT | 136 | |
CDR-H2 | GISPILGVTNYAQKFQG | 137 | |
CDR-H3 | LLVGVSETYFDY | 138 | |
17 | CDR-L1 | RASQSISNYLN | 145 |
CDR-L2 | AASNMHS | 146 | |
CDR-L3 | QQSHSFPWT | 147 | |
CDR-H1 | TYAMS | 148 | |
CDR-H2 | GISPTLGIANYAQKFQG | 149 | |
CDR-H3 | VRYAGWTGYFDL | 150 | |
18 | CDR-L1 | RASQSISRWLN | 157 |
CDR-L2 | AASRLQS | 158 | |
CDR-L3 | QQSESFPWT | 159 | |
CDR-H1 | SYDIN | 160 | |
CDR-H2 | WIIPTSGSTNYAQKFQG | 161 | |
CDR-H3 | DSQSSYIGYFDV | 162 | |
19 | CDR-L1 | RASQSISNYLN | 169 |
CDR-L2 | DTSSLQS | 170 | |
CDR-L3 | QQSYSTPYT | 171 | |
CDR-H1 | AYGIS | 172 | |
CDR-H2 | RIIPYLGTANYAQKFQG | 173 | |
CDR-H3 | LSYGIGYESFDV | 174 | |
20 | CDR-L1 | RASQSISSYLN | 181 |
CDR-L2 | DTSTLQS | 182 | |
CDR-L3 | QQSYSFPWT | 183 | |
CDR-H1 | SYAMS | 184 | |
CDR-H2 | SISSSGGSTYYADSVKG | 185 | |
CDR-H3 | ELGGYGFSYFDY | 186 | |
21 | CDR-L1 | RASQSIRNYLN | 193 |
CDR-L2 | ATSSLQS | 194 | |
CDR-L3 | QQSYSFPWT | 195 | |
CDR-H1 | DYAMS | 196 | |
CDR-H2 | GISGSDIYYADSVKG | 197 | |
CDR-H3 | AVSYWSYTFDY | 198 | |
22 | CDR-L1 | RASQSIGSYLN | 205 |
CDR-L2 | DASTLQS | 206 | |
CDR-L3 | QQSYSFPWT | 207 | |
CDR-H1 | SYAMH | 208 | |
CDR-H2 | GISSSGGTTYYADSVKG | 209 | |
CDR-H3 | ALGVVGGTWFDY | 210 | |
23 | CDR-L1 | RASQSISNYLN | 217 |
CDR-L2 | DTSTLQS | 218 | |
CDR-L3 | QQSYSFPWT | 219 | |
CDR-H1 | DYAMH | 220 | |
CDR-H2 | AISGSGGYTHYADSVKG | 221 | |
CDR-H3 | SATFGVWETFDV | 222 |
일 예에서, 상기 항-LILRB1 항체 또는 이의 항원 결합 단편은, 상기한 바와 같은,
CDR-L1, CDR-L2, 및 CDR-L3를 포함하는 경쇄가변영역, 및
CDR-H1, CDR-H2, 및 CDR-H3를 포함하는 중쇄가변영역
을 포함하는 것일 수 있다.
구체예에서, 상기 항-LILRB1 항체 또는 이의 항원 결합 단편은,
서열번호 7, 19, 31, 43, 55, 67, 79, 91, 103, 115, 127, 139, 151, 163, 175, 187, 199, 211, 또는 223의 아미노산 서열을 포함하는 경쇄 가변영역, 및
서열번호 9, 21, 33, 45, 57, 69, 81, 93, 105, 117, 129, 141, 153, 165, 177, 189, 201, 213, 또는 225의 아미노산 서열을 포함하는 중쇄 가변영역
을 포함하는 것일 수 있다.
본 명세서에서 제공되는 항-LILRB1 항체 또는 이의 항원 결합 단편에 포함 가능한 경쇄가변영역 및 중쇄가변영역의 조합을 아래의 표 2에 예시하였다:
클론 | 가변 영역 | 아미노산 서열(N→C) | 서열번호 |
5 | 경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSIANYLNWYQQKPGKAPKLLIYATSTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 7 |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSAYGIHWVRQAPGQGLEWMGWIIPLSGGAHYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARLYGWAEYFDVWGQGTLVTVSS | 9 | |
6 | 경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 19 |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYTISWVRQAPGQGLEWMGWISPELGTSNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARLRYGQTLYGFDIWGQGTLVTVSS | 21 | |
7 | 경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNWLNWYQQKPGKAPKLLIYGTSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPFTFGQGTKVEIK | 31 |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYGMHWVRQAPGQGLEWMGWIIPVSGGATYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGSWAYYAEFDYWGQGTLVTVSS | 33 | |
8 | 경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPYTFGQGTKVEIK | 43 |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYGIHWVRQAPGQGLEWMGWIIPISGTTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARVGGVGLYVFDVWGQGTLVTVSS | 45 | |
9 | 경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 55 |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAIHWVRQAPGQGLEWMGWIVPGLGVTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARQATLYQTEYMDVWGQGTLVTVSS | 57 | |
10 | 경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPFTFGQGTKVEIK | 67 |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSHYMHWVRQAPGQGLEWMGWISPYLGSTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDETGSTYGAFDYWGQGTLVTVSS | 69 | |
11 | 경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYDASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 79 |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYVHWVRQAPGQGLEWMGWISPYSGGTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDYYVSAYGAFDYWGQGTLVTVSS | 81 | |
12 | 경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYATSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 91 |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYDIHWVRQAPGQGLEWMGRIVPYLGVTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARRQSQSSVYAFDIWGQGTLVTVSS | 93 | |
13 | 경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPFTFGQGTKVEIK | 103 |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSGYYIHWVRQAPGQGLEWMGWISPSSGGTIYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDISVRVVQAFDYWGQGTLVTVSS | 105 | |
14 | 경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYATSNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 115 |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYMHWVRQAPGQGLEWMGWISPYLGITNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGYQQAQYWFDYWGQGTLVTVSS | 117 | |
15 | 경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYATSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPYTFGQGTKVEIK | 127 |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAMSWVRQAPGQGLEWMGWIIPISGTTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARQHSVGSVFDYWGQGTLVTVSS | 129 | |
16 | 경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQDISSWLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 139 |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYMTWVRQAPGQGLEWMGGISPILGVTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARLLVGVSETYFDYWGQGTLVTVSS | 141 | |
17 | 경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASNMHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSHSFPWTFGQGTKVEIK | 151 |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSTYAMSWVRQAPGQGLEWMGGISPTLGIANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARVRYAGWTGYFDLWGQGTLVTVSS | 153 | |
18 | 경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISRWLNWYQQKPGKAPKLLIYAASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSESFPWTFGQGTKVEIK | 163 |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYDINWVRQAPGQGLEWMGWIIPTSGSTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDSQSSYIGYFDVWGQGTLVTVSS | 165 | |
19 | 경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYDTSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIK | 175 |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSAYGISWVRQAPGQGLEWMGRIIPYLGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARLSYGIGYESFDVWGQGTLVTVSS | 177 | |
20 | 경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYDTSTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 187 |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAMSWVRQAPGQGLEWMGSISSSGGSTYYADSVKGRVTITADESTSTAYMELSSLRSEDTAVYYCARELGGYGFSYFDYWGQGTLVTVSS | 189 | |
21 | 경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSIRNYLNWYQQKPGKAPKLLIYATSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 199 |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSDYAMSWVRQAPGQGLEWMGGISGSDIYYADSVKGRVTITADESTSTAYMELSSLRSEDTAVYYCARAVSYWSYTFDYWGQGTLVTVSS | 201 | |
22 | 경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSIGSYLNWYQQKPGKAPKLLIYDASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 211 |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAMHWVRQAPGQGLEWMGGISSSGGTTYYADSVKGRVTITADESTSTAYMELSSLRSEDTAVYYCARALGVVGGTWFDYWGQGTLVTVSS | 213 | |
23 | 경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYDTSTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 223 |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSDYAMHWVRQAPGQGLEWMGAISGSGGYTHYADSVKGRVTITADESTSTAYMELSSLRSEDTAVYYCARSATFGVWETFDVWGQGTLVTVSS | 225 |
본 명세서에서, 항체(예컨대, CDR, 가변영역, 또는 중쇄/경쇄)가 "특정 아미노산 서열을 포함한다 또는 특정 아미노산 서열로 이루어진다" 함은 상기 아미노산 서열을 필수적으로 포함하는 경우, 및/또는 상기 아미노산 서열에 항체 활성에 영향이 없는 무의미한 변이(예컨대, 아미노산 잔기의 치환, 결실, 및/또는 추가)가 도입된 경우를 모두 의미하는 것일 수 있다.
본 명세서에서 제공되는 항-LILRB1 항체 또는 이의 항원 결합 단편은 LILRB1(예컨대, 인간 LILRB1)에 대한 결합 친화도(KD)는, 예를 들어, 표면 플라스몬 공명(Surface plasmon resonance, SPR)으로 측정된 경우를 기준으로, 10mM 이하, 5mM 이하, 1mM 이하, 0.5mM 이하, 0.2mM, 또는 0.15mM 이하일 수 있으며, 예를 들어 0.001nM 내지 10mM, 0.005nM 내지 10mM, 0.01nM 내지 10mM, 0.05nM 내지 10mM, 0.1nM 내지 10mM, 0.5nM 내지 10mM, 1nM 내지 10mM, 0.001nM 내지 5mM, 0.005nM 내지 5mM, 0.01nM 내지 5mM, 0.05nM 내지 5mM, 0.1nM 내지 5mM, 0.5nM 내지 5mM, 1nM 내지 5mM, 0.001nM 내지 1mM, 0.005nM 내지 1mM, 0.01nM 내지 1mM, 0.05nM 내지 1mM, 0.1nM 내지 1mM, 0.5nM 내지 1mM, 1nM 내지 1mM, 0.001nM 내지 0.5mM, 0.005nM 내지 0.5mM, 0.01nM 내지 0.5mM, 0.05nM 내지 0.5mM, 0.1nM 내지 0.5mM, 0.5nM 내지 0.5mM, 1nM 내지 0.5mM, 0.001nM 내지 0.2mM, 0.005nM 내지 0.2mM, 0.01nM 내지 0.2mM, 0.05nM 내지 0.2mM, 0.1nM 내지 0.2mM, 0.5nM 내지 0.2mM, 1nM 내지 0.2mM, 0.001nM 내지 0.15mM, 0.005nM 내지 0.15mM, 0.01nM 내지 0.15mM, 0.05nM 내지 0.15mM, 0.1nM 내지 0.15mM, 0.5nM 내지 0.15mM, 또는 1nM 내지 0.15mM일 수 있다.
다른 예는 상기 항-LILRB1 항체 또는 이의 항원 결합 단편을 포함하는 약학 조성물을 제공한다. 예를 들어, 상기 약학 조성물은 암의 치료 및/또는 예방을 위한 약학 조성물일 수 있다. 일 예에서, 상기 약학 조성물은 암세포들의 면역 회피를 저해하는 활성을 갖는 것일 수 있다. 상기 암세포는 표면에 MHC Class I를 발현 또는 과발현하는 것일 수 있다.
다른 예는 상기 항-LILRB1 항체 또는 이의 항원 결합 단편의 약학적 유효량을 암의 치료 및/또는 예방을 필요로 하는 대상(예컨대, 인간을 포함하는 포유류)에게 투여(경구 또는 비경구 투여)하는 단계를 포함하는, 암을 치료 및/또는 예방하는 방법을 제공한다.
본 명세서에서 제공되는 방법은, 상기 투여하는 단계 이전에, 암의 치료 및/또는 예방을 필요로 하는 대상, 및/또는 암세포의 면역 회피 저해를 필요로 하는 대상을 확인하는 단계를 추가로 포함할 수 있다.
다른 예는 상기 항-LILRB1 항체 또는 이의 항원 결합 단편의 암의 치료 및/또는 예방에 사용하기 위한 용도 또는 암의 치료 및/또는 예방용 약학 조성물의 제조에 사용하기 위한 용도를 제공한다. 또 다른 예는 상기 항-LILRB1 항체 또는 이의 항원 결합 단편의 암세포의 면역 회피 저해에 사용하기 위한 용도 또는 암세포의 면역 회피 저해용 약학 조성물의 제조에 사용하기 위한 용도를 제공한다.
다른 예는 상기한 항-LILRB1 항체의 CDR(CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2, CDR-H3, 또는 CDR-L1, CDR-L2, 및 CDR-L3의 조합, 또는 CDR-H1, CDR-H2, 및 CDR-H3의 조합); CDR-L1, CDR-L2, 및 CDR-L3를 포함하는 경쇄 가변영역; CDR-H1, CDR-H2, 및 CDR-H3를 포함하는 중쇄 가변영역; 상기 경쇄가변영역을 포함하는 경쇄; 및 상기 중쇄가변영역을 포함하는 중쇄로 이루어진 군에서 선택된 하나 이상의 폴리펩타이드를 암호화하는 핵산 분자를 제공한다.
다른 예는 상기 핵산 분자를 포함하는 재조합 벡터를 제공한다. 일 예에서, 상기 재조합 벡터는 상기 경쇄 가변영역 또는 경쇄, 및 상기 중쇄 가변영역 또는 중쇄를(예컨대, 두 개의 벡터에) 각각 포함하거나, (예컨대, 하나의 벡터에) 함께 포함하는 것일 수 있다. 상기 재조합 벡터는 상기 경쇄 가변영역 또는 경쇄, 및 상기 중쇄 가변영역 또는 중쇄를 적절한 세포에서 발현시키기 위한 발현 벡터일 수 있다.
다른 예는 상기 재조합 벡터를 포함하는 재조합 세포를 제공한다.
다른 예는 상기 재조합 세포를 발현시키는 단계를 포함하는, 항-LILRB1 항체 또는 이의 항원 결합 단편의 제조 방법을 제공한다.
본 명세서에 기재된 바로서, 항-LILRB1 항체의 항원 결합 단편은 상기 항-LILRB1 항체에서 유래하고 항원(LILRB1)에 대한 결합력을 보유하는 단편을 의미하는 것으로, 상기한 항-LILRB1 항체의 6개의 CDR을 포함하는 임의의 폴리펩타이드, 예를 들어 scFv, scFv-Fc, scFv-Cκ(카파 불변영역), scFv-Cλ(람다 불변영역), (scFv)2, Fab, Fab' 또는 F(ab')2일 수 있으나, 이에 한정되는 것은 아니다.
상기 항-LILRB1 항체 또는 이의 항원 결합 단편은 LILRB1 단백질에 대하여 조절 작용, 예컨대, 길항작용(antagonism) 또는 작용(agonism)을 하는 것일 수 있다. 또한, 상기 항-LILRB1 항체 또는 이의 항원 결합 단편은 암세포들의 면역 회피를 저해하는 활성을 갖는 것일 수 있다. 또한, 상기 항-LILRB1 항체 또는 이의 항원 결합 단편은 우수한 항암 활성을 갖는 것일 수 있다.
본 명세서에서 제공되는 항체 또는 항원 결합 단편의 항원으로 작용하는 LILRB1은 포유류 유래의 것일 수 있으며, 예컨대 인간 유래 LILRB1(예컨대, GenBank accession numbers NP_001265328.2, NP_001265327.2, NP_001075108.2, NP_001075107.2, NP_001075106.2, NP_006660.4, NM_001081637.2, NM_001081638.3, NM_001081639.3, NM_001278398.2, NM_001278399.2 등)일 수 있으나, 이에 제한되는 것은 아니다.
본 명세서에 기재된 MHC Class I는 major histocompatibility complex(MHC) 분자의 한 분류이다. 일 예에서, 상기 MHC Class I는 인간 유래의 것일 수 있고, HLA(human leukocyte antigen)-A, HLA-B, HLA-C, HLA-E, HLA-F, 및 HLA-G로 이루어진 군에서 선택된 1종 이상일 수 있으나, 이에 제한되는 것은 아니다.
본 명세서에서 "항체"라 함은, 특정 항원에 특이적으로 결합하는 단백질을 총칭하는 것으로서, 면역계 내에서 항원의 자극에 의하여 만들어지는 단백질 또는 이를 화학적 합성 또는 재조합적으로 제조한 단백질일 수 있으며, 그 종류는 특별히 제한되지 않는다. 상기 항체는 비자연적으로 생성된 것, 예컨대, 재조합적 또는 합성적으로 생성된 것일 수 있다. 상기 항체는 동물 항체(예컨대, 마우스 항체 등), 키메릭 항체, 인간화 항체, 또는 인간 항체일 수 있다. 상기 항체는 단클론 항체 또는 다클론 항체일 수 있다.
본 명세서에서 제공되는 항-LILRB1 항체 또는 이의 항원 결합 단편에서 앞서 정의한 중쇄 CDR 및 경쇄 CDR 부위, 또는 중쇄 가변 영역 및 경쇄 가변 영역을 제외한 나머지 부위는 모든 서브타입의 면역글로불린(예컨대, IgA, IgD, IgE, IgG(IgG1, IgG2, IgG3, 또는 IgG4), IgM, 등)으로부터 유래한 것일 수 있고, 예컨대, 상기 모든 서브타입의 면역글로불린의 프레임워크 부위, 및/또는 경쇄 불변 영역 및/또는 중쇄 불변 영역으로부터 유래한 것일 수 있다. 일 예에서, 본 명세서에서 제공되는 항-LILRB1 항체는 인간 IgG형 항체, 예컨대, IgG1, IgG2, IgG3, 또는 IgG4 형태의 항체일 수 있으나, 이에 제한되는 것은 아니다.
완전한 항체(예컨대, IgG형)는 2개의 전장(full length) 경쇄 및 2개의 전장 중쇄를 가지는 구조이며 각각의 경쇄는 중쇄와 이황화 결합으로 연결되어 있다. 항체의 불변 영역은 중쇄 불변 영역과 경쇄 불변 영역으로 나뉘어지며, 중쇄 불변 영역은 감마(γ), 뮤(μ), 알파(α), 델타(δ) 및 엡실론(ε) 타입을 포함하고, 서브클래스로 감마1(γ1), 감마2(γ2), 감마3(γ3), 감마4(γ4), 알파1(α1) 및 알파2(α2)를 포함한다. 경쇄의 불변 영역은 카파(κ) 및 람다(λ) 타입을 포함한다.
용어, "중쇄(heavy chain)"는 항원에 특이성을 부여하기 위해 충분한 가변영역 서열을 갖는 아미노산 서열을 포함하는 가변영역 도메인 VH 및 3개의 불변 영역 도메인 CH1, CH2 및 CH3과 힌지(hinge)를 포함하는 전장 중쇄 및 이의 단편을 모두 포함하는 의미로 해석된다. 또한, 용어 "경쇄(light chain)"는 항원에 특이성을 부여하기 위한 충분한 가변영역 서열을 갖는 아미노산 서열을 포함하는 가변영역 도메인 VL 및 불변 영역 도메인 CL을 포함하는 전장 경쇄 및 이의 단편을 모두 포함하는 의미로 해석된다.
용어, "CDR(complementarity determining region)"은 항체의 가변 부위 중에서 항원과의 결합 특이성을 부여하는 부위를 의미하는 것으로, 면역글로불린의 중쇄 및 경쇄의 고가변영역(hypervariable region)의 아미노산 서열을 의미한다. 중쇄 및 경쇄는 각각 3개의 CDR을 포함할 수 있다(CDR-H1, CDR-H2, CDR-H3 및 CDR-L1, CDR-L2, CDR-L3). 상기 CDR은 항체가 항원 또는 에피토프에 결합하는 데 있어서 주요한 접촉 잔기를 제공할 수 있다. 한편, 본 명세서에 있어서, 용어, "특이적으로 결합" 또는 "특이적으로 인식"은 당업자에게 통상적으로 공지되어 있는 의미와 동일한 것으로서, 항원 및 항체가 특이적으로 상호작용하여 면역학적 반응을 하는 것을 의미한다.
본 명세서에서 항체는, 특별한 언급이 없는 한, 항원 결합능을 보유하는 항체의 항원 결합 단편을 포함하는 것으로 이해될 수 있다.
용어, "항원 결합 단편"은 항원이 결합할 수 있는 부분(예컨대, 본 명세서에서 정의된 6개의 CDR)을 포함하는 모든 형태의 폴리펩타이드를 의미한다. 예를 들어, 항체의 scFv, (scFv)2, Fab, Fab' 또는 F(ab')2일 수 있으나, 이에 한정되지 않는다. 또한, 앞서 설명한 바와 같이, 상기 항원 결합 단편은 scFv, 또는 scFv가 면역글로불린(예컨대, IgA, IgD, IgE, IgG(IgG1, IgG2, IgG3, IgG4), IgM, 등)의 Fc 부위 또는 경쇄의 불변 영역(예컨대, 카파 또는 람다)와 융합된 융합 폴리펩타이드일 수 있다.
상기 항원 결합 단편 중 Fab는 경쇄 및 중쇄의 가변영역과 경쇄의 불변 영역 및 중쇄의 첫 번째 불변 영역(CH1)을 가지는 구조로 1개의 항원 결합 부위를 가진다.
Fab'는 중쇄 CH1 도메인의 C-말단에 하나 이상의 시스테인 잔기를 포함하는 힌지 영역(hinge region)을 가진다는 점에서 Fab와 차이가 있다.
F(ab')2 항체는 Fab'의 힌지 영역의 시스테인 잔기가 이황화 결합을 이루면서 생성된다. Fv는 중쇄 가변부위 및 경쇄 가변부위만을 가지고 있는 최소의 항체조각으로 Fv 단편을 생성하는 재조합 기술은 당업계에 널리 공지되어 있다.
이중쇄 Fv(two-chain Fv)는 비공유 결합으로 중쇄 가변부위와 경쇄 가변부위가 연결되어 있고 단쇄 Fv(single-chain Fv)는 일반적으로 펩타이드 링커를 통하여 중쇄의 가변영역과 단쇄의 가변영역이 공유 결합으로 연결되거나 또는 C-말단에서 바로 연결되어 있어서 이중쇄 Fv와 같이 다이머와 같은 구조를 이룰 수 있다.
상기 항원 결합 단편은 단백질 가수분해 효소를 이용해서 얻을 수 있고(예를 들어, 전체 항체를 파파인으로 제한 절단하면 Fab를 얻을 수 있고 펩신으로 절단하면 F(ab')2 단편을 얻을 수 있다), 유전자 재조합 기술을 통하여 제작할 수 있다.
용어 "힌지 영역(hinge region)"은 항체의 중쇄에 포함되어 있는 영역으로서, CH1 및 CH2 영역 사이에 존재하며, 항체 내 항원 결합 부위의 유연성(flexibility)를 제공하는 기능을 하는 영역을 의미한다.
상기 항-LILRB1 항체는 단클론 항체일 수 있다. 단클론 항체는 당 업계에 널리 알려진 방법대로 제조될 수 있다. 예컨대, phage display 기법을 이용해서 제조될 수 있다. 또는, 항-LILRB1 항체는 통상의 방법에 의하여 마우스 유래의 단클론 항체로 제조될 수 있다.
한편, 전형적인 ELISA(Enzyme-Linked ImmunoSorbent Assay) 포맷을 이용하여 LILRB1와의 결합능에 기초하여 개별 단클론 항체들을 스크리닝할 수 있다. 결합체들에 대해 분자적 상호작용을 검정하기 위한 경쟁적 ELISA(Competitive ELISA)와 같은 기능성 분석 또는 세포-기반 분석(cell-based assay)과 같은 기능성 분석을 통해 저해 활성에 대해 검정할 수 있다. 그런 다음 강한 저해 활성에 기초하여 선택된 단클론항체 멤버들에 대해 LILRB1에 대한 각각의 친화도(Kd values)를 검정할 수 있다.
최종 선택된 항체들은 항원결합부를 제외한 나머지 부분이 인간의 면역글로블린 항체화된 항체뿐만 아니라, 인간화 항체로서 제조하여 사용할 수 있다. 인간화 항체의 제조방법은 당 업계에 잘 알려져 있다.
본 명세서에서 제공되는 약학 조성물은 약학적으로 허용 가능한 담체를 추가로 포함할 수 있다. 상기 약학적으로 허용 가능한 담체는 약물의 제제화에 통상적으로 이용되는 것으로서, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 전분, 아카시아 고무, 인산 칼슘, 알기네이트, 젤라틴, 규산 칼슘, 미세결정성 셀룰로스, 폴리비닐피롤리돈, 셀룰로스, 물, 시럽, 메틸 셀룰로스, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 활석, 스테아르산 마그네슘, 미네랄 오일 등으로 이루어진 군에서 선택된 1종 이상일 수 있으나, 이에 한정되는 것은 아니다. 상기 약학 조성물은 또한 약학 조성물 제조에 통상적으로 사용되는 희석제, 부형제, 윤활제, 습윤제, 감미제, 향미제, 유화제, 현탁제, 보존제 등으로 이루어진 군에서 선택된 1종 이상을 추가로 포함할 수 있다.
상기 약학 조성물, 또는 상기 항체 또는 이의 항원 결합 단편의 유효량은 경구 또는 비경구로 투여할 수 있다. 비경구 투여인 경우에는 정맥내 주입, 피하 주입, 근육 주입, 복강 주입, 내피 투여, 비내 투여, 폐내 투여, 직장내 투여, 또는 병변부위 국소 투여 등으로 투여할 수 있다. 경구 투여시, 단백질 또는 펩타이드는 소화가 되기 때문에 경구용 조성물은 활성 약제를 코팅하거나 위에서의 분해로부터 보호되도록 제형화될 수 있다. 또한, 상기 조성물은 활성 물질이 표적 세포로 이동할 수 있는 임의의 장치에 의해 투여될 수 있다.
상기 약학 조성물 내의 항-LILRB1 항체 또는 이의 항원 결합 단편의 함유량 또는 항-LILRB1 항체 또는 이의 항원 결합 단편의 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성별, 병적 상태, 음식, 투여 시간, 투여 간격, 투여 경로, 배설 속도, 반응 감응성 등의 요인들에 의해 다양하게 처방될 수 있다. 예컨대, 상기 항-LILRB1 항체 또는 이의 항원 결합 단편의 1일 투여량은 0.005μg/kg 내지 1000mg/kg, 0.005μg/kg 내지 500mg/kg, 0.005μg/kg 내지 250mg/kg, 0.005μg/kg 내지 100mg/kg, 0.005μg/kg 내지 75mg/kg, 0.005μg/kg 내지 50mg/kg, 0.01μg/kg 내지 1000mg/kg, 0.01μg/kg 내지 500mg/kg, 0.01μg/kg 내지 250mg/kg, 0.01μg/kg 내지 100mg/kg, 0.01μg/kg 내지 75mg/kg, 0.01μg/kg 내지 50mg/kg, 0.05μg/kg 내지 1000mg/kg, 0.05μg/kg 내지 500mg/kg, 0.05μg/kg 내지 250mg/kg, 0.05μg/kg 내지 100mg/kg, 0.05μg/kg 내지 75mg/kg, 또는 0.05μg/kg 내지 50mg/kg 범위일 수 있으나 이에 제한되는 것은 아니다. 상기 1일 투여량은 단위 용량 형태로 하나의 제제로 제제화되거나, 적절하게 분량하여 제제화되거나, 다용량 용기 내에 내입시켜 제조될 수 있다.
상기 약학 조성물은 오일 또는 수성 매질중의 용액, 현탁액, 시럽제 또는 유화액 형태이거나 엑스제, 산제, 분말제, 과립제, 정제 또는 캅셀제 등의 형태로 제형화될 수 있으며, 제형화를 위하여 분산제 또는 안정화제를 추가적으로 포함할 수 있다.
본 발명의 적용 대상 환자는 인간, 원숭이 등을 포함하는 영장류, 마우스, 래트 등을 포함하는 설치류 등을 포함하는 포유류일 수 있다.
상기 암은 고형암 또는 혈액암일 수 있으며, 이에 제한되지 않지만, 폐암(예컨대, 소세포폐암, 비소세포폐암, 폐선암, 폐편평상피암 등), 복막암, 피부암, 피부 또는 안구내 흑색종, 직장암, 항문부근암, 식도암, 소장암, 내분비선암, 부갑상선암, 부신암, 연조직 육종, 요도암, 백혈병(예컨대, 만성 또는 급성 백혈병), 림프종, 간세포암, 위암, 췌장암, 교아종, 경부암, 난소암, 간암, 방광암, 간종양, 유방암, 결장암, 대장암, 자궁내막 또는 자궁암, 침샘암, 신세포암, 신장암, 간암, 전립선암, 음문암, 갑상선암, 간암, 두경부암, 뇌암, 골육종 등으로 이루어진 군에서 선택된 1종 이상일 수 있다. 상기 암은 원발성 암 또는 전이성 암일 수 있다. 상기 암은 표면에 MHC Class I이 발현 또는 과발현된 것일 수 있으며, 예컨대, 대장암(colon adenocarcinoma), 소세포폐암(small cell lung carcinoma), 비소세포폐암(Non-small-cell lung carcinoma), 유방암(breast cancer), 췌장암(pancreatic cancer), 피부암(maligmant melanoma), 골육종(bone osteosarcoma), 신세포암(renal cell carcinoma), 위암(gastric cancer)일 수 있다. 상기 MHC Class I의 과발현은, 정상 세포와 비교하여, 상기 항체 적용 대상 암세포에서 과발현된 것을 의미할 수 있다. 일 예에서, 상기 암은 T-세포 매개 면역 치료에 항암 효과가 나타나지 않는(저항성이 있는) 암종일 수 있다.
본 명세서에서 암의 치료는 암세포의 증식 저해, 암세포 사멸, 전이 억제 등과 같이 암의 증상의 악화를 방지하거나 완화 또는 호전시키거나, 암을 부분적 또는 전부 소멸시키는 모든 항암 작용을 의미하는 것일 수 있다.
본 명세서에서 제공되는 항-LILRB1 항체 또는 이의 항원 결합 단편은 다른 약물, 예컨대, 통상적으로 사용 가능한 면역치료제, 항암제, 세포독성 제제 등으로 이루어진 군에서 선택된 1종 이상과 병용될 수 있다. 따라서, 일 예는(1) 항-LILRB1 항체 또는 이의 항원 결합 단편, 및 (2) 면역치료제, 항암제, 세포독성 제제 등으로 이루어진 군에서 선택되는 1종 이상의 약물을 포함하는, 암의 예방 및/또는 치료를 위한 병용 투여용 약학 조성물을 제공한다. 다른 예는 암의 예방 및/또는 치료를 필요로 하는 환자에게 (1) 항-LILRB1 항체 또는 이의 항원 결합 단편, 및 (2) 면역치료제, 항암제, 세포독성 제제 등으로 이루어진 군에서 선택되는 1종 이상의 약물을 투여하는 단계를 포함하는, 암의 예방 및/또는 치료 방법이 제공된다. 상기 면역치료제, 항암제 및 세포독성 제제는 통상적으로 암 치료, 및/또는 세포 독성 활성을 갖는 모든 약물을 포괄하는 것으로, 세포치료제, 항체 등의 단백질, siRNA 등의 핵산 분자, 및/또는 파클리탁셀, 도세탁셀 등의 소분자 화합물 중에서 1종 이상 선택될 수 있으나, 이에 제한되는 것은 아니다.
다른 예에서, 앞서 설명한 항-LILRB1 항체의 중쇄 상보성 결정 부위(CDR-H1, CDR-H2, CDR-H3, 또는 이들의 조합), 경쇄 상보성 결정 부위(CDR-L1, CDR-L2, CDR-L3, 또는 이들의 조합), 또는 이들의 조합; 또는 중쇄 가변영역, 경쇄 가변영역, 또는 이들의 조합을 포함하는 폴리펩타이드 분자가 제공된다. 상기 폴리펩타이드 분자는 항체의 전구체로서 항체 제작에 사용될 수 있을 뿐 아니라 항체와 유사한 구조를 갖는 단백질 골격체(protein scaffold; 예컨대 펩티바디), 이중 특이 항체, 다중 특이 항체의 구성 성분으로 포함될 수 있다. 또 다른 예에서, 상기 항-LILRB1 항체의 중쇄 상보성 결정 부위(CDR-H1, CDR-H2, CDR-H3, 또는 이들의 조합), 경쇄 상보성 결정 부위(CDR-L1, CDR-L2, CDR-L3, 또는 이들의 조합), 또는 이들의 조합; 또는 중쇄 가변영역, 경쇄 가변영역, 또는 이들의 조합을 포함하는 폴리펩타이드 분자는 CAR-T 등의 표적 세포치료제에서 표적(항원) 인지부, 분비되는 항체, 상기 항-LILRB1 항체를 분비하도록 제작된 세포 치료제 등으로서 사용 가능하다.
다른 예는 항-LILRB1 항체의 중쇄 상보성 결정 부위(CDR-H1, CDR-H2, CDR-H3, 또는 이들의 조합), 중쇄 가변영역 또는 중쇄를 암호화하는 핵산 분자를 제공한다.
다른 예는 항-LILRB1 항체의 경쇄 상보성 결정 부위(CDR-L1, CDR-L2, CDR-L3, 또는 이들의 조합), 경쇄 가변영역 또는 경쇄를 암호화하는 핵산 분자를 제공한다.
다른 예는 상기 항-LILRB1 항체의 중쇄 상보성 결정 부위, 중쇄 가변영역 또는 중쇄를 암호화하는 핵산 분자 및 항-LILRB1 항체의 경쇄 상보성 결정 부위, 경쇄 가변영역 또는 경쇄를 암호화하는 핵산 분자를 하나의 벡터에 함께 포함하거나 각각 별개의 벡터에 포함하는 재조합 벡터를 제공한다.
다른 예는 상기 재조합 벡터를 포함하는 재조합 세포를 제공한다.
용어 "벡터(vector)"는 숙주 세포에서 목적 유전자를 발현시키기 위한 수단을 의미한다. 예를 들어, 플라스미드 벡터, 코즈미드 벡터 및 박테리오파아지 벡터, 렌티바이러스 벡터, 아데노바이러스 벡터, 레트로바이러스 벡터 및 아데노-연관 바이러스 벡터와 같은 바이러스 벡터를 포함한다. 상기 재조합 벡터로 사용될 수 있는 벡터는 당업계에서 종종 사용되는 플라스미드(예를 들면, pSC101, pGV1106, pACYC177, ColE1, pKT230, pME290, pBR322, pUC8/9, pUC6, pBD9, pHC79, pIJ61, pLAFR1, pHV14, pGEX 시리즈, pET 시리즈 및 pUC19 등), 파지(예를 들면, λgt4λB, λ-Charon, λΔz1 및 M13 등) 또는 바이러스(예를 들면, SV40 등)를 조작하여 제작될 수 있다.
상기 재조합 벡터에서 상기 핵산 분자는 프로모터에 작동적으로 연결될 수 있다. 용어 "작동 가능하게 연결된(operatively linked)"은 뉴클레오타이드 발현 조절 서열(예를 들어, 프로모터 서열)과 다른 뉴클레오타이드 서열 사이의 기능적인 결합을 의미한다. 상기 조절 서열은 "작동 가능하게 연결(operatively linked)"됨으로써 다른 뉴클레오타이드 서열의 전사 및/또는 해독을 조절할 수 있다.
상기 재조합 벡터는, 전형적으로 클로닝을 위한 벡터 또는 발현을 위한 벡터로서 구축될 수 있다. 상기 발현용 벡터는 당업계에서 식물, 동물 또는 미생물에서 외래의 단백질을 발현하는 데 사용되는 통상의 것을 사용할 수 있다. 상기 재조합 벡터는 당업계에 공지된 다양한 방법을 통해 구축될 수 있다.
상기 재조합 벡터는 원핵 세포 또는 진핵 세포를 숙주로 하여 구축될 수 있다. 예를 들어, 사용되는 벡터가 발현 벡터이고, 원핵 세포를 숙주로 하는 경우에는, 전사를 진행시킬 수 있는 강력한 프로모터(예를 들어, pLλ 프로모터, trp 프로모터, lac 프로모터, tac 프로모터, T7 프로모터 등), 해독의 개시를 위한 라이보좀 결합 자리 및 전사/해독 종결 서열을 포함하는 것이 일반적이다. 진핵 세포를 숙주로 하는 경우에는, 벡터에 포함되는 진핵 세포에서 작동하는 복제원점은 f1 복제원점, SV40 복제원점, pMB1 복제원점, 아데노 복제원점, AAV 복제원점 및 BBV 복제원점 등을 포함하나, 이에 한정되는 것은 아니다. 또한, 포유동물 세포의 게놈으로부터 유래된 프로모터(예를 들어, 메탈로티오닌 프로모터) 또는 포유동물 바이러스로부터 유래된 프로모터(예를 들어, 아데노바이러스 후기 프로모터, 백시니아 바이러스 7.5K 프로모터, SV40 프로모터, 사이토메갈로바이러스 프로모터 및 HSV의 tk 프로모터)가 이용될 수 있으며, 전사 종결 서열로서 폴리아데닐화 서열을 일반적으로 갖는다.
다른 예는 상기 재조합 벡터를 포함하는 재조합 세포를 제공한다.
상기 재조합 세포는 상기 재조합 벡터를 적절한 숙주 세포에 도입시킴으로써 얻어진 것일 수 있다. 상기 숙주세포는 상기 재조합 벡터를 안정되면서 연속적으로 클로닝 또는 발현시킬 수 있는 세포로서 당업계에 공지된 어떠한 숙주 세포도 이용할 수 있으며, 원핵 세포로는, 예를 들어, E. coli JM109, E. coli BL21, E. coli RR1, E. coli LE392, E. coli B, E. coli X 1776, E. coli W3110, 바실러스 서브틸리스, 바실러스 츄린겐시스와 같은 바실러스 속 균주, 그리고 살모넬라 티피무리움, 세라티아 마르세슨스 및 다양한 슈도모나스 종과 같은 장내균과 균주 등이 있으며, 진핵 세포에 형질 전환시키는 경우에는 숙주 세포로서, 효모(Saccharomyce cerevisiae), 곤충 세포, 식물 세포 및 동물 세포, 예를 들어, Sp2/0, CHO(Chinese hamster ovary) K1, CHO DG44, CHO S, CHO DXB11, CHO GS-KO, PER.C6, W138, BHK, COS-7, 293, HepG2, Huh7, 3T3, RIN, MDCK 세포주 등이 이용될 수 있으나, 이에 제한되는 것은 아니다.
상기 핵산 분자 또는 이를 포함하는 재조합 벡터의 숙주 세포 내로의 운반(도입)은, 당업계에 널리 알려진 운반 방법을 사용할 수 있다. 상기 운반 방법은 예를 들어, 숙주 세포가 원핵 세포인 경우, CaCl2 방법 또는 전기 천공 방법 등을 사용할 수 있고, 숙주 세포가 진핵 세포인 경우에는, 미세 주입법, 칼슘 포스페이트 침전법, 전기 천공법, 리포좀-매개 형질감염법 및 유전자 밤바드먼트 등을 사용할 수 있으나, 이에 한정하지는 않는다.
상기 형질 전환된 숙주 세포를 선별하는 방법은 선택 표지에 의해 발현되는 표현형을 이용하여, 당업계에 널리 알려진 방법에 따라 용이하게 실시할 수 있다. 예를 들어, 상기 선택 표지가 특정 항생제 내성 유전자인 경우에는, 상기 항생제가 함유된 배지에서 형질전환체를 배양함으로써 형질전환체를 용이하게 선별할 수 있다.
다른 예는 상기 핵산 분자 또는 이를 포함하는 재조합 벡터를 숙주 세포에서 발현시키는 단계를 포함하는 항-LILRB1 항체 또는 이의 항원 결합 단편의 제조 방법을 제공한다. 상기 제조 방법은 상기 재조합 벡터를 포함하는 재조합 세포를 배양하는 단계, 및 임의로 배양 배지로부터 항체 또는 항원 결합 단편을 분리 및/또는 정제하는 단계를 포함하는 것일 수 있다.
본 명세서에서 제공되는 항-LILRB1 항체 또는 이의 항원 결합 단편은 암세포의 면역회피기전을 저해하여 면역세포의 항암 효능이 저해되지 않고 잘 발휘될 수 있도록 함으로써, 우수한 항암활성을 나타낼 수 있다.
도 1은 일 실시예에서 정제된 항-LILRB1 항체의 SDS-PAGE 젤 분석 결과를 보여주는 전기영동 사진이다.
도 2는 일 실시예에 따른 항-LILRB1 13번 항체에 대한 SPR(surface plasmon resonance) sensorgram 결과를 보여준다.
도 3은 일 실시예에 따른 항-LILRB1 8번, 10번, 11번, 13번, 및 18번 항체의 LILRB1 과발현 CHO 세포에 대한 결합력을 보여주는 그래프이다.
도 4는 일 실시예에 따른 항-LILRB1 항체(10번, 11번 및 13번 항체) 또는 human IgG4 isotype control 항체(음성 대조군) 처리시의 자연살해세포 KHYG-1에 의한 HLA-G 과발현 HEK293 세포 사멸능을 IncuCyte S3로 분석한 결과를 보여주는 그래프이다.
도 5는 일 실시예에 따른 항-LILRB1 10번, 11번 및 13번 항체의 in vivo 항종양 효과를 보여주는 그래프이다.
도 2는 일 실시예에 따른 항-LILRB1 13번 항체에 대한 SPR(surface plasmon resonance) sensorgram 결과를 보여준다.
도 3은 일 실시예에 따른 항-LILRB1 8번, 10번, 11번, 13번, 및 18번 항체의 LILRB1 과발현 CHO 세포에 대한 결합력을 보여주는 그래프이다.
도 4는 일 실시예에 따른 항-LILRB1 항체(10번, 11번 및 13번 항체) 또는 human IgG4 isotype control 항체(음성 대조군) 처리시의 자연살해세포 KHYG-1에 의한 HLA-G 과발현 HEK293 세포 사멸능을 IncuCyte S3로 분석한 결과를 보여주는 그래프이다.
도 5는 일 실시예에 따른 항-LILRB1 10번, 11번 및 13번 항체의 in vivo 항종양 효과를 보여주는 그래프이다.
이하에서는 실시예를 들어 본 발명을 더욱 구체적으로 설명하고자 하나, 이는 예시적인 것에 불과할 뿐 본 발명의 범위를 제한하고자 함이 아니다. 아래 기재된 실시예들은 발명의 본질적인 요지를 벗어나지 않는 범위에서 변형될 수 있음은 당 업자들에게 있어 자명하다.
실시예 1. LILRB1에 대한 인간 항체의 생산
1.1. 파지디스플레이(phage display)를 이용한 LILRB1에 대한 인간 항체의 선별
인간 LILRB1을 특이적으로 인식하는 항체를 선별하기 위해 인간 합성 Fab 항체로 이루어진 라이브러리를 이용하여 파지디스플레이 선별법을 수행하였다. 항원은 RnD systems 사의 human LILRB1-Fc(Cat. No. 2017-T2)를 사용하여 파지 패닝을 4 라운드까지 수행하였다. 추가적으로 항원이 Fc fusion 형태이므로, 패닝 단계에서 Fc binder를 제거하는 Fc control 패닝도 병행하였다. 선별된 산출물은 파지 ELISA를 통하여 항원에 대한 결합을 확인하였다.
1.2. 단클론 파지 ELISA
상기 실시예 1.1에서 패닝을 통해 얻어진 파지들 가운데 항원에 특이적으로 결합하는 클론을 선별하기 위해 단클론 파지 ELISA를 수행하였다. 상기 실시예 1.1의 항원에 대해 흡광도(A450nm) cut-off 0.4 이상을 정하여 양성인 클론을 확인하고 해당 유전자의 서열을 분석하였다. 항원의 특이성을 확인하기 위하여 항원에 대한 unique Fab 클론의 purified phage ELISA를 실시하여 EC50(pfu) 값을 구하였다.
1.3. 단클론 soluble Fab 분석
상기 실시예 1.2에서 패닝을 통해 얻어진 항원에 결합하는 47 종의 특이적 클론(unique clone) 가운데, phage specificity ELISA에서의 EC50 기준 상위 19 종의 클론의 Fab를 코딩하는 유전자를 PCR로 증폭하여 발현 벡터를 제작하였다. TB media를 이용하여 항체를 발현 후, periplasmic extraction을 통해 soluble 단백질을 확보하였다. Affinity chromatography를 통해 정제 후, ELISA를 수행하여 항원에 대한 결합을 확인하였다.
실시예 2. 선별된 항체의 IgG로의 변환
상기 실시예 1.3에서 선별된 Fab 형태의 파지디스플레이 라이브러리에서 선별된 유전자에 대해 각각의 중쇄가변영역(VH)과 경쇄가변영역(VL)에 해당하는 서열을 PCR로 증폭하였다. 일부 발현량이 낮은 클론의 경우, 경쇄가변영역(VL)은 동일하게 PCR로 증폭하고, 중쇄가변영역(VH)에 해당하는 유전자 서열은 발현량이 높았던 클론의 구조형성부위(FR)에 해당하는 서열에 CDR을 이식하여 제작하였다. 제작된 중쇄가변영역(VH)와 경쇄가변영역(VL) 유전자 서열은 IgG4 형태의 인간 항체(IgG4 Fc: 서열번호 229, Kappa 불변영역: 서열번호 230)를 코딩하도록 제작된 발현벡터(pCB-LIR-mAB, 이 외에도 CMV promoter, 또는 CMV/CHO beta-actin 융합 프로모터(KR10-1038126B1)를 가지고 human IgG4의 heavy chain constant region과 kappa light chain의 constant region 서열을 포함하는 벡터 중 어느 것을 사용하여도 무방함)에 삽입하였다. 제작된 발현벡터는 sequencing을 통해 그의 DNA 서열을 확인하였다.
하기 표 3 내지 21에 선별된 항체 19종의 CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2, CDR-H3, 경쇄가변영역, 중쇄가변영역, 경쇄, 및 중쇄의 아미노산 서열과, 경쇄가변영역 유전자와 중쇄가변영역 유전자의 핵산 서열을 나타내었다. 각 클론에 대해 클론 번호를 부여하였다. 이하에서는 단순 클론 번호만으로 표기하였다.
클론 | 부위 | 아미노산 서열(N>C) 또는 핵산 서열(5’>3') | 서열번호 |
5 | CDR-L1 | RASQSIANYLN | 1 |
CDR-L2 | ATSTLQS | 2 | |
CDR-L3 | QQSYSFPWT | 3 | |
CDR-H1 | AYGIH | 4 | |
CDR-H2 | WIIPLSGGAHYAQKFQG | 5 | |
CDR-H3 | LYGWAEYFDV | 6 | |
경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSIANYLNWYQQKPGKAPKLLIYATSTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 7 | |
경쇄가변영역유전자 | GACATTCAAATGACGCAGAGTCCCTCCTCACTGAGTGCTAGCGTGGGCGATCGTGTGACAATTACTTGTCGCGCTAGCCAGTCTATCGCAAATTACCTGAACTGGTATCAGCAGAAACCGGGCAAGGCGCCAAAATTGCTGATTTACGCAACTTCCACTCTGCAGTCTGGTGTACCGTCCCGTTTCTCTGGCAGCGGTTCTGGTACGGATTTTACCCTGACCATCTCAAGCCTCCAGCCTGAAGATTTTGCCACCTATTATTGTCAGCAATCTTACTCTTTTCCGTGGACGTTCGGGCAGGGAACTAAAGTGGAAATTAAA | 8 | |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSAYGIHWVRQAPGQGLEWMGWIIPLSGGAHYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARLYGWAEYFDVWGQGTLVTVSS | 9 | |
중쇄가변영역유전자 | CAAGTTCAGCTGGTCCAGAGCGGCGCAGAGGTGAAGAAGCCCGGCAGTTCTGTTAAGGTTTCCTGCAAAGCCTCAGGCGGGACTTTTAGTGCATACGGTATCCATTGGGTGCGGCAGGCGCCCGGCCAGGGTCTCGAATGGATGGGGTGGATTATCCCACTGTCTGGTGGTGCACATTATGCACAAAAATTCCAAGGCCGCGTAACTATTACCGCCGACGAATCAACCTCCACCGCCTACATGGAACTCAGCTCTCTGAGGTCAGAAGACACGGCCGTCTATTATTGCGCCAGACTGTACGGTTGGGCAGAATACTTCGATGTTTGGGGTCAGGGTACTCTGGTTACCGTCTCATCG | 10 | |
경쇄(Kappa) | DIQMTQSPSSLSASVGDRVTITCRASQSIANYLNWYQQKPGKAPKLLIYATSTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC | 11 | |
중쇄 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSAYGIHWVRQAPGQGLEWMGWIIPLSGGAHYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARLYGWAEYFDVWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 12 |
클론 | 부위 | 아미노산 서열(N>C) 또는 핵산 서열(5’>3') | 서열번호 |
6 | CDR-L1 | RASQSISNYLN | 13 |
CDR-L2 | AASTLQS | 14 | |
CDR-L3 | QQSYSFPWT | 15 | |
CDR-H1 | SYTIS | 16 | |
CDR-H2 | WISPELGTSNYAQKFQG | 17 | |
CDR-H3 | LRYGQTLYGFDI | 18 | |
경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 19 | |
경쇄가변영역유전자 | GACATTCAAATGACGCAGAGTCCCTCCTCACTGAGTGCTAGCGTGGGCGATCGTGTGACAATTACTTGTCGCGCTAGCCAGTCTATCTCTAATTACCTGAACTGGTATCAGCAGAAACCGGGCAAGGCGCCAAAATTGCTGATTTACGCAGCATCCACTCTGCAGTCTGGTGTACCGTCCCGTTTCTCTGGCAGCGGTTCTGGTACGGATTTTACCCTGACCATCTCAAGCCTCCAGCCTGAAGATTTTGCCACCTATTATTGTCAGCAATCTTACTCTTTTCCGTGGACGTTCGGGCAGGGAACTAAAGTGGAAATTAAA | 20 | |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYTISWVRQAPGQGLEWMGWISPELGTSNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARLRYGQTLYGFDIWGQGTLVTVSS | 21 | |
중쇄가변영역유전자 | CAAGTTCAGCTGGTCCAGAGCGGCGCAGAGGTGAAGAAGCCCGGCAGTTCTGTTAAGGTTTCCTGCAAAGCCTCAGGCGGGACTTTTAGTTCTTACACCATTTCTTGGGTGCGGCAGGCGCCCGGCCAGGGTCTCGAATGGATGGGGTGGATTTCTCCAGAACTGGGTACCTCTAACTATGCACAAAAATTCCAAGGCCGCGTAACTATTACCGCCGACGAATCAACCTCCACCGCCTACATGGAACTCAGCTCTCTGAGGTCAGAAGACACGGCCGTCTATTATTGCGCCAGACTGCGTTACGGTCAGACTCTGTACGGTTTCGATATCTGGGGTCAGGGTACTCTGGTTACCGTCTCATCG | 22 | |
경쇄(Kappa) | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC | 23 | |
중쇄 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYTISWVRQAPGQGLEWMGWISPELGTSNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARLRYGQTLYGFDIWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 24 |
클론 | 부위 | 아미노산 서열(N>C) 또는 핵산 서열(5’>3') | 서열번호 |
7 | CDR-L1 | RASQSISNWLN | 25 |
CDR-L2 | GTSSLQS | 26 | |
CDR-L3 | QQSYSFPFT | 27 | |
CDR-H1 | SYGMH | 28 | |
CDR-H2 | WIIPVSGGATYAQKFQG | 29 | |
CDR-H3 | GSWAYYAEFDY | 30 | |
경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNWLNWYQQKPGKAPKLLIYGTSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPFTFGQGTKVEIK | 31 | |
경쇄가변영역유전자 | GACATTCAAATGACGCAGAGTCCCTCCTCACTGAGTGCTAGCGTGGGCGATCGTGTGACAATTACTTGTCGCGCTAGCCAGTCTATCTCTAATTGGCTGAACTGGTATCAGCAGAAACCGGGCAAGGCGCCAAAATTGCTGATTTACGGTACTTCCTCTCTGCAGTCTGGTGTACCGTCCCGTTTCTCTGGCAGCGGTTCTGGTACGGATTTTACCCTGACCATCTCAAGCCTCCAGCCTGAAGATTTTGCCACCTATTATTGTCAGCAATCTTACTCTTTTCCGTTTACGTTCGGGCAGGGAACTAAAGTGGAAATTAAA | 32 | |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYGMHWVRQAPGQGLEWMGWIIPVSGGATYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGSWAYYAEFDYWGQGTLVTVSS | 33 | |
중쇄가변영역유전자 | CAAGTTCAGCTGGTCCAGAGCGGCGCAGAGGTGAAGAAGCCCGGCAGTTCTGTTAAGGTTTCCTGCAAAGCCTCAGGCGGGACTTTTAGTTCTTACGGTATGCATTGGGTGCGGCAGGCGCCCGGCCAGGGTCTCGAATGGATGGGGTGGATTATCCCAGTTTCTGGTGGTGCAACCTATGCACAAAAATTCCAAGGCCGCGTAACTATTACCGCCGACGAATCAACCTCCACCGCCTACATGGAACTCAGCTCTCTGAGGTCAGAAGACACGGCCGTCTATTATTGCGCCAGAGGTTCTTGGGCATACTACGCTGAATTCGATTACTGGGGTCAGGGCACTTTAGTGACCGTCTCATCG | 34 | |
경쇄(Kappa) | DIQMTQSPSSLSASVGDRVTITCRASQSISNWLNWYQQKPGKAPKLLIYGTSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPFTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC | 35 | |
중쇄 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYGMHWVRQAPGQGLEWMGWIIPVSGGATYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGSWAYYAEFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 36 |
클론 | 부위 | 아미노산 서열(N>C) 또는 핵산 서열(5’>3') | 서열번호 |
8 | CDR-L1 | RASQSISSYLN | 37 |
CDR-L2 | AASTLQS | 38 | |
CDR-L3 | QQSYSFPYT | 39 | |
CDR-H1 | SYGIH | 40 | |
CDR-H2 | WIIPISGTTNYAQKFQG | 41 | |
CDR-H3 | VGGVGLYVFDV | 42 | |
경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPYTFGQGTKVEIK | 43 | |
경쇄가변영역유전자 | GACATTCAAATGACGCAGAGTCCCTCCTCACTGAGTGCTAGCGTGGGCGATCGTGTGACAATTACTTGTCGCGCTAGCCAGTCTATCTCTTCTTACCTGAACTGGTATCAGCAGAAACCGGGCAAGGCGCCAAAATTGCTGATTTACGCAGCATCCACTCTGCAGTCTGGTGTACCGTCCCGTTTCTCTGGCAGCGGTTCTGGTACGGATTTTACCCTGACCATCTCAAGCCTCCAGCCTGAAGATTTTGCCACCTATTATTGTCAGCAATCTTACTCTTTTCCGTACACGTTCGGGCAGGGAACTAAAGTGGAAATTAAA | 44 | |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYGIHWVRQAPGQGLEWMGWIIPISGTTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARVGGVGLYVFDVWGQGTLVTVSS | 45 | |
중쇄가변영역유전자 | CAAGTTCAGCTGGTCCAGAGCGGCGCAGAGGTGAAGAAGCCCGGCAGTTCTGTTAAGGTTTCCTGCAAAGCCTCAGGCGGGACTTTTAGTTCTTACGGTATCCATTGGGTGCGGCAGGCGCCCGGCCAGGGTCTCGAATGGATGGGGTGGATTATCCCAATCTCTGGTACCACCAACTATGCACAAAAATTCCAAGGCCGCGTAACTATTACCGCCGACGAATCAACCTCCACCGCCTACATGGAACTCAGCTCTCTGAGGTCAGAAGACACGGCCGTCTATTATTGCGCCAGAGTTGGTGGTGTTGGTCTGTACGTTTTCGATGTTTGGGGTCAGGGTACTCTGGTTACCGTCTCATCG | 46 | |
경쇄(Kappa) | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC | 47 | |
중쇄 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYGIHWVRQAPGQGLEWMGWIIPISGTTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARVGGVGLYVFDVWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 48 |
클론 | 부위 | 아미노산 서열(N>C) 또는 핵산 서열(5’>3') | 서열번호 |
9 | CDR-L1 | RASQSISNYLN | 49 |
CDR-L2 | AASSLQS | 50 | |
CDR-L3 | QQSYSFPWT | 51 | |
CDR-H1 | SYAIH | 52 | |
CDR-H2 | WIVPGLGVTNYAQKFQG | 53 | |
CDR-H3 | QATLYQTEYMDV | 54 | |
경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 55 | |
경쇄가변영역유전자 | GACATTCAAATGACGCAGAGTCCCTCCTCACTGAGTGCTAGCGTGGGCGATCGTGTGACAATTACTTGTCGCGCTAGCCAGTCTATCTCTAATTACCTGAACTGGTATCAGCAGAAACCGGGCAAGGCGCCAAAATTGCTGATTTACGCAGCATCCTCTCTGCAGTCTGGTGTACCGTCCCGTTTCTCTGGCAGCGGTTCTGGTACGGATTTTACCCTGACCATCTCAAGCCTCCAGCCTGAAGATTTTGCCACCTATTATTGTCAGCAATCTTACTCTTTTCCGTGGACGTTCGGGCAGGGAACTAAAGTGGAAATTAAA | 56 | |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAIHWVRQAPGQGLEWMGWIVPGLGVTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARQATLYQTEYMDVWGQGTLVTVSS | 57 | |
중쇄가변영역유전자 | CAAGTTCAGCTGGTCCAGAGCGGCGCAGAGGTGAAGAAGCCCGGCAGTTCTGTTAAGGTTTCCTGCAAAGCCTCAGGCGGGACTTTTAGTTCTTACGCAATCCATTGGGTGCGGCAGGCGCCCGGCCAGGGTCTCGAATGGATGGGGTGGATTGTTCCAGGTCTGGGTGTTACCAACTATGCACAAAAATTCCAAGGCCGCGTAACTATTACCGCCGACGAATCAACCTCCACCGCCTACATGGAACTCAGCTCTCTGAGGTCAGAAGACACGGCCGTCTATTATTGCGCCAGACAGGCAACTCTGTACCAGACTGAATACATGGATGTTTGGGGTCAGGGTACTCTGGTTACCGTCTCATCG | 58 | |
경쇄(Kappa) | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC | 59 | |
중쇄 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAIHWVRQAPGQGLEWMGWIVPGLGVTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARQATLYQTEYMDVWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 60 |
클론 | 부위 | 아미노산 서열(N>C) 또는 핵산 서열(5’>3') | 서열번호 |
10 | CDR-L1 | RASQSISNYLN | 61 |
CDR-L2 | AASNLQS | 62 | |
CDR-L3 | QQSYSFPFT | 63 | |
CDR-H1 | SHYMH | 64 | |
CDR-H2 | WISPYLGSTNYAQKFQG | 65 | |
CDR-H3 | DETGSTYGAFDY | 66 | |
경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPFTFGQGTKVEIK | 67 | |
경쇄가변영역유전자 | GACATTCAAATGACGCAGAGTCCCTCCTCACTGAGTGCTAGCGTGGGCGATCGTGTGACAATTACTTGTCGCGCTAGCCAGTCTATCTCTAATTACCTGAACTGGTATCAGCAGAAACCGGGCAAGGCGCCAAAATTGCTGATTTACGCAGCATCCAATCTGCAGTCTGGTGTACCGTCCCGTTTCTCTGGCAGCGGTTCTGGTACGGATTTTACCCTGACCATCTCAAGCCTCCAGCCTGAAGATTTTGCCACCTATTATTGTCAGCAATCTTACTCTTTTCCGTTTACGTTCGGGCAGGGAACTAAAGTGGAAATTAAA | 68 | |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSHYMHWVRQAPGQGLEWMGWISPYLGSTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDETGSTYGAFDYWGQGTLVTVSS | 69 | |
중쇄가변영역유전자 | CAAGTTCAGCTGGTCCAGAGCGGCGCAGAGGTGAAGAAGCCCGGCAGTTCTGTTAAGGTTTCCTGCAAAGCCTCAGGCGGGACTTTTAGTTCTCATTACATGCATTGGGTGCGGCAGGCGCCCGGCCAGGGTCTCGAATGGATGGGGTGGATTTCTCCATACCTGGGTTCTACCAACTATGCACAAAAATTCCAAGGCCGCGTAACTATTACCGCCGACGAATCAACCTCCACCGCCTACATGGAACTCAGCTCTCTGAGGTCAGAAGACACGGCCGTCTATTATTGCGCCAGAGATGAAACTGGTTCTACTTACGGTGCATTCGATTACTGGGGTCAGGGTACTCTGGTTACCGTCTCATCG | 70 | |
경쇄(Kappa) | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPFTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC | 71 | |
중쇄 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSHYMHWVRQAPGQGLEWMGWISPYLGSTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDETGSTYGAFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 72 |
클론 | 부위 | 아미노산 서열(N>C) 또는 핵산 서열(5’>3') | 서열번호 |
11 | CDR-L1 | RASQSISNYLN | 73 |
CDR-L2 | DASTLQS | 74 | |
CDR-L3 | QQSYSFPWT | 75 | |
CDR-H1 | SYYVH | 76 | |
CDR-H2 | WISPYSGGTNYAQKFQG | 77 | |
CDR-H3 | DYYVSAYGAFDY | 78 | |
경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYDASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 79 | |
경쇄가변영역유전자 | GACATTCAAATGACGCAGAGTCCCTCCTCACTGAGTGCTAGCGTGGGCGATCGTGTGACAATTACTTGTCGCGCTAGCCAGTCTATCTCTAATTACCTGAACTGGTATCAGCAGAAACCGGGCAAGGCGCCAAAATTGCTGATTTACGATGCATCCACTCTGCAGTCTGGTGTACCGTCCCGTTTCTCTGGCAGCGGTTCTGGTACGGATTTTACCCTGACCATCTCAAGCCTCCAGCCTGAAGATTTTGCCACCTATTATTGTCAGCAATCTTACTCTTTTCCGTGGACGTTCGGGCAGGGAACTAAAGTGGAAATTAAA | 80 | |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYVHWVRQAPGQGLEWMGWISPYSGGTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDYYVSAYGAFDYWGQGTLVTVSS | 81 | |
중쇄가변영역유전자 | CAAGTTCAGCTGGTCCAGAGCGGCGCAGAGGTGAAGAAGCCCGGCAGTTCTGTTAAGGTTTCCTGCAAAGCCTCAGGCGGGACTTTTAGTTCTTACTACGTTCATTGGGTGCGGCAGGCGCCCGGCCAGGGTCTCGAATGGATGGGGTGGATTTCTCCATACTCTGGTGGTACCAACTATGCACAAAAATTCCAAGGCCGCGTAACTATTACCGCCGACGAATCAACCTCCACCGCCTACATGGAACTCAGCTCTCTGAGGTCAGAAGACACGGCCGTCTATTATTGCGCCAGAGATTACTACGTTTCTGCATACGGTGCATTCGATTACTGGGGTCAGGGTACTCTGGTTACCGTCTCATCG | 82 | |
경쇄(Kappa) | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYDASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC | 83 | |
중쇄 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYVHWVRQAPGQGLEWMGWISPYSGGTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDYYVSAYGAFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 84 |
클론 | 부위 | 아미노산 서열(N>C) 또는 핵산 서열(5’>3') | 서열번호 |
12 | CDR-L1 | RASQDISNYLN | 85 |
CDR-L2 | ATSSLQS | 86 | |
CDR-L3 | QQSYSFPWT | 87 | |
CDR-H1 | SYDIH | 88 | |
CDR-H2 | RIVPYLGVTNYAQKFQG | 89 | |
CDR-H3 | RQSQSSVYAFDI | 90 | |
경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYATSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 91 | |
경쇄가변영역유전자 | GACATTCAAATGACGCAGAGTCCCTCCTCACTGAGTGCTAGCGTGGGCGATCGTGTGACAATTACTTGTCGCGCTAGCCAGGATATCTCTAATTACCTGAACTGGTATCAGCAGAAACCGGGCAAGGCGCCAAAATTGCTGATTTACGCAACTTCCTCTCTGCAGTCTGGTGTACCGTCCCGTTTCTCTGGCAGCGGTTCTGGTACGGATTTTACCCTGACCATCTCAAGCCTCCAGCCTGAAGATTTTGCCACCTATTATTGTCAGCAATCTTACTCTTTTCCGTGGACGTTCGGGCAGGGAACTAAAGTGGAAATTAAA | 92 | |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYDIHWVRQAPGQGLEWMGRIVPYLGVTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARRQSQSSVYAFDIWGQGTLVTVSS | 93 | |
중쇄가변영역유전자 | CAAGTTCAGCTGGTCCAGAGCGGCGCAGAGGTGAAGAAGCCCGGCAGTTCTGTTAAGGTTTCCTGCAAAGCCTCAGGCGGGACTTTTAGTTCTTACGATATCCATTGGGTGCGGCAGGCGCCCGGCCAGGGTCTCGAATGGATGGGGCGTATTGTTCCATACCTGGGTGTTACCAACTATGCACAAAAATTCCAAGGCCGCGTAACTATTACCGCCGACGAATCAACCTCCACCGCCTACATGGAACTCAGCTCTCTGAGGTCAGAAGACACGGCCGTCTATTATTGCGCCAGACGTCAGTCTCAGTCTTCTGTTTACGCATTCGATATCTGGGGTCAGGGCACTTTAGTGACCGTCTCATCG | 94 | |
경쇄(Kappa) | DIQMTQSPSSLSASVGDRVTITCRASQDISNYLNWYQQKPGKAPKLLIYATSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC | 95 | |
중쇄 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYDIHWVRQAPGQGLEWMGRIVPYLGVTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARRQSQSSVYAFDIWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 96 |
클론 | 부위 | 아미노산 서열(N>C) 또는 핵산 서열(5’>3') | 서열번호 |
13 | CDR-L1 | RASQSISNYLN | 97 |
CDR-L2 | AASRLQS | 98 | |
CDR-L3 | QQSYSFPFT | 99 | |
CDR-H1 | GYYIH | 100 | |
CDR-H2 | WISPSSGGTIYAQKFQG | 101 | |
CDR-H3 | DISVRVVQAFDY | 102 | |
경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPFTFGQGTKVEIK | 103 | |
경쇄가변영역유전자 | GACATTCAAATGACGCAGAGTCCCTCCTCACTGAGTGCTAGCGTGGGCGATCGTGTGACAATTACTTGTCGCGCTAGCCAGTCTATCTCTAATTACCTGAACTGGTATCAGCAGAAACCGGGCAAGGCGCCAAAATTGCTGATTTACGCAGCATCCCGTCTGCAGTCTGGTGTACCGTCCCGTTTCTCTGGCAGCGGTTCTGGTACGGATTTTACCCTGACCATCTCAAGCCTCCAGCCTGAAGATTTTGCCACCTATTATTGTCAGCAATCTTACTCTTTTCCGTTTACGTTCGGGCAGGGAACTAAAGTGGAAATTAAA | 104 | |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSGYYIHWVRQAPGQGLEWMGWISPSSGGTIYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDISVRVVQAFDYWGQGTLVTVSS | 105 | |
중쇄가변영역유전자 | CAAGTTCAGCTGGTCCAGAGCGGCGCAGAGGTGAAGAAGCCCGGCAGTTCTGTTAAGGTTTCCTGCAAAGCCTCAGGCGGGACTTTTAGTGGTTACTACATCCATTGGGTGCGGCAGGCGCCCGGCCAGGGTCTCGAATGGATGGGGTGGATTTCTCCATCTTCTGGTGGTACCATCTATGCACAAAAATTCCAAGGCCGCGTAACTATTACCGCCGACGAATCAACCTCCACCGCCTACATGGAACTCAGCTCTCTGAGGTCAGAAGACACGGCCGTCTATTATTGCGCCAGAGATATCTCTGTTCGTGTTGTTCAGGCATTCGATTACTGGGGTCAGGGTACTCTGGTTACCGTCTCATCG | 106 | |
경쇄(Kappa) | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPFTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC | 107 | |
중쇄 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSGYYIHWVRQAPGQGLEWMGWISPSSGGTIYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDISVRVVQAFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 108 |
클론 | 부위 | 아미노산 서열(N>C) 또는 핵산 서열(5’>3') | 서열번호 |
14 | CDR-L1 | RASQSISNYLN | 109 |
CDR-L2 | ATSNLQS | 110 | |
CDR-L3 | QQSYSFPWT | 111 | |
CDR-H1 | SYYMH | 112 | |
CDR-H2 | WISPYLGITNYAQKFQG | 113 | |
CDR-H3 | AGYQQAQYWFDY | 114 | |
경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYATSNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 115 | |
경쇄가변영역유전자 | GACATTCAAATGACGCAGAGTCCCTCCTCACTGAGTGCTAGCGTGGGCGATCGTGTGACAATTACTTGTCGCGCTAGCCAGTCTATCTCTAATTACCTGAACTGGTATCAGCAGAAACCGGGCAAGGCGCCAAAATTGCTGATTTACGCAACTTCCAATCTGCAGTCTGGTGTACCGTCCCGTTTCTCTGGCAGCGGTTCTGGTACGGATTTTACCCTGACCATCTCAAGCCTCCAGCCTGAAGATTTTGCCACCTATTATTGTCAGCAATCTTACTCTTTTCCGTGGACGTTCGGGCAGGGAACTAAAGTGGAAATTAAA | 116 | |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYMHWVRQAPGQGLEWMGWISPYLGITNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGYQQAQYWFDYWGQGTLVTVSS | 117 | |
중쇄가변영역유전자 | CAAGTTCAGCTGGTCCAGAGCGGCGCAGAGGTGAAGAAGCCCGGCAGTTCTGTTAAGGTTTCCTGCAAAGCCTCAGGCGGGACTTTTAGTTCTTACTACATGCATTGGGTGCGGCAGGCGCCCGGCCAGGGTCTCGAATGGATGGGGTGGATTTCTCCATACCTGGGTATCACCAACTATGCACAAAAATTCCAAGGCCGCGTAACTATTACCGCCGACGAATCAACCTCCACCGCCTACATGGAACTCAGCTCTCTGAGGTCAGAAGACACGGCCGTCTATTATTGCGCCAGAGCAGGTTACCAGCAGGCACAGTACTGGTTCGATTACTGGGGTCAGGGCACTTTAGTGACCGTCTCATCG | 118 | |
경쇄(Kappa) | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYATSNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC | 119 | |
중쇄 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYMHWVRQAPGQGLEWMGWISPYLGITNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARAGYQQAQYWFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 120 |
클론 | 부위 | 아미노산 서열(N>C) 또는 핵산 서열(5’>3') | 서열번호 |
15 | CDR-L1 | RASQSISNYLN | 121 |
CDR-L2 | ATSSLQS | 122 | |
CDR-L3 | QQSYSFPYT | 123 | |
CDR-H1 | SYAMS | 124 | |
CDR-H2 | WIIPISGTTNYAQKFQG | 125 | |
CDR-H3 | QHSVGSVFDY | 126 | |
경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYATSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPYTFGQGTKVEIK | 127 | |
경쇄가변영역유전자 | GACATTCAAATGACGCAGAGTCCCTCCTCACTGAGTGCTAGCGTGGGCGATCGTGTGACAATTACTTGTCGCGCTAGCCAGTCTATCTCTAATTACCTGAACTGGTATCAGCAGAAACCGGGCAAGGCGCCAAAATTGCTGATTTACGCAACTTCCTCTCTGCAGTCTGGTGTACCGTCCCGTTTCTCTGGCAGCGGTTCTGGTACGGATTTTACCCTGACCATCTCAAGCCTCCAGCCTGAAGATTTTGCCACCTATTATTGTCAGCAATCTTACTCTTTTCCGTACACGTTCGGGCAGGGAACTAAAGTGGAAATTAAA | 128 | |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAMSWVRQAPGQGLEWMGWIIPISGTTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARQHSVGSVFDYWGQGTLVTVSS | 129 | |
중쇄가변영역유전자 | CAAGTTCAGCTGGTCCAGAGCGGCGCAGAGGTGAAGAAGCCCGGCAGTTCTGTTAAGGTTTCCTGCAAAGCCTCAGGCGGGACTTTTAGTTCTTACGCAATGTCTTGGGTGCGGCAGGCGCCCGGCCAGGGTCTCGAATGGATGGGGTGGATTATCCCAATCTCTGGTACCACCAACTATGCACAAAAATTCCAAGGCCGCGTAACTATTACCGCCGACGAATCAACCTCCACCGCCTACATGGAACTCAGCTCTCTGAGGTCAGAAGACACGGCCGTCTATTATTGCGCCAGACAGCATTCTGTTGGTTCTGTTTTCGATTACTGGGGTCAGGGTACTCTGGTTACCGTCTCATCG | 130 | |
경쇄(Kappa) | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYATSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC | 131 | |
중쇄 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAMSWVRQAPGQGLEWMGWIIPISGTTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARQHSVGSVFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 132 |
클론 | 부위 | 아미노산 서열(N>C) 또는 핵산 서열(5’>3') | 서열번호 |
16 | CDR-L1 | RASQDISSWLN | 133 |
CDR-L2 | AASSLQS | 134 | |
CDR-L3 | QQSYSFPWT | 135 | |
CDR-H1 | SYYMT | 136 | |
CDR-H2 | GISPILGVTNYAQKFQG | 137 | |
CDR-H3 | LLVGVSETYFDY | 138 | |
경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQDISSWLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 139 | |
경쇄가변영역유전자 | GACATTCAAATGACGCAGAGTCCCTCCTCACTGAGTGCTAGCGTGGGCGATCGTGTGACAATTACTTGTCGCGCTAGCCAGGATATCTCTTCTTGGCTGAACTGGTATCAGCAGAAACCGGGCAAGGCGCCAAAATTGCTGATTTACGCAGCATCCTCTCTGCAGTCTGGTGTACCGTCCCGTTTCTCTGGCAGCGGTTCTGGTACGGATTTTACCCTGACCATCTCAAGCCTCCAGCCTGAAGATTTTGCCACCTATTATTGTCAGCAATCTTACTCTTTTCCGTGGACGTTCGGGCAGGGAACTAAAGTGGAAATTAAA | 140 | |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYMTWVRQAPGQGLEWMGGISPILGVTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARLLVGVSETYFDYWGQGTLVTVSS | 141 | |
중쇄가변영역유전자 | CAAGTTCAGCTGGTCCAGAGCGGCGCAGAGGTGAAGAAGCCCGGCAGTTCTGTTAAGGTTTCCTGCAAAGCCTCAGGCGGGACTTTTAGTTCTTACTACATGACCTGGGTGCGGCAGGCGCCCGGCCAGGGTCTCGAATGGATGGGGGGTATTTCTCCAATCCTGGGTGTTACCAACTATGCACAAAAATTCCAAGGCCGCGTAACTATTACCGCCGACGAATCAACCTCCACCGCCTACATGGAACTCAGCTCTCTGAGGTCAGAAGACACGGCCGTCTATTATTGCGCCAGACTGCTGGTTGGTGTTTCTGAAACTTACTTCGATTACTGGGGTCAGGGTACTCTGGTTACCGTCTCATCG | 142 | |
경쇄(Kappa) | DIQMTQSPSSLSASVGDRVTITCRASQDISSWLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC | 143 | |
중쇄 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYYMTWVRQAPGQGLEWMGGISPILGVTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARLLVGVSETYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 144 |
클론 | 부위 | 아미노산 서열(N>C) 또는 핵산 서열(5’>3') | 서열번호 |
17 | CDR-L1 | RASQSISNYLN | 145 |
CDR-L2 | AASNMHS | 146 | |
CDR-L3 | QQSHSFPWT | 147 | |
CDR-H1 | TYAMS | 148 | |
CDR-H2 | GISPTLGIANYAQKFQG | 149 | |
CDR-H3 | VRYAGWTGYFDL | 150 | |
경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASNMHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSHSFPWTFGQGTKVEIK | 151 | |
경쇄가변영역유전자 | GACATTCAAATGACGCAGAGTCCCTCCTCACTGAGTGCTAGCGTGGGCGATCGTGTGACAATTACTTGTCGCGCTAGCCAGTCTATCTCTAATTACCTGAACTGGTATCAGCAGAAACCGGGCAAGGCGCCAAAATTGCTGATTTACGCAGCATCCAATATGCACTCTGGTGTACCGTCCCGTTTCTCTGGCAGCGGTTCTGGTACGGATTTTACCCTGACCATCTCAAGCCTCCAGCCTGAAGATTTTGCCACCTATTATTGTCAGCAATCTCACTCTTTTCCGTGGACGTTCGGGCAGGGAACTAAAGTGGAAATTAAA | 152 | |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSTYAMSWVRQAPGQGLEWMGGISPTLGIANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARVRYAGWTGYFDLWGQGTLVTVSS | 153 | |
중쇄가변영역유전자 | CAAGTTCAGCTGGTCCAGAGCGGCGCAGAGGTGAAGAAGCCCGGCAGTTCTGTTAAGGTTTCCTGCAAAGCCTCAGGCGGGACTTTTAGTACCTACGCAATGTCTTGGGTGCGGCAGGCGCCCGGCCAGGGTCTCGAATGGATGGGGGGTATTTCTCCAACCCTGGGTATCGCAAACTATGCACAAAAATTCCAAGGCCGCGTAACTATTACCGCCGACGAATCAACCTCCACCGCCTACATGGAACTCAGCTCTCTGAGGTCAGAAGACACGGCCGTCTATTATTGCGCCAGAGTTCGTTACGCAGGTTGGACTGGTTACTTCGATCTGTGGGGTCAGGGTACTCTGGTTACCGTCTCATCG | 154 | |
경쇄(Kappa) | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASNMHSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSHSFPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC | 155 | |
중쇄 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSTYAMSWVRQAPGQGLEWMGGISPTLGIANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARVRYAGWTGYFDLWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 156 |
클론 | 부위 | 아미노산 서열(N>C) 또는 핵산 서열(5’>3') | 서열번호 |
18 | CDR-L1 | RASQSISRWLN | 157 |
CDR-L2 | AASRLQS | 158 | |
CDR-L3 | QQSESFPWT | 159 | |
CDR-H1 | SYDIN | 160 | |
CDR-H2 | WIIPTSGSTNYAQKFQG | 161 | |
CDR-H3 | DSQSSYIGYFDV | 162 | |
경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISRWLNWYQQKPGKAPKLLIYAASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSESFPWTFGQGTKVEIK | 163 | |
경쇄가변영역유전자 | GACATTCAAATGACGCAGAGTCCCTCCTCACTGAGTGCTAGCGTGGGCGATCGTGTGACAATTACTTGTCGCGCTAGCCAGTCTATCTCTCGTTGGCTGAACTGGTATCAGCAGAAACCGGGCAAGGCGCCAAAATTGCTGATTTACGCAGCATCCCGTCTGCAGTCTGGTGTACCGTCCCGTTTCTCTGGCAGCGGTTCTGGTACGGATTTTACCCTGACCATCTCAAGCCTCCAGCCTGAAGATTTTGCCACCTATTATTGTCAGCAATCTGAATCTTTTCCGTGGACGTTCGGGCAGGGAACTAAAGTGGAAATTAAA | 164 | |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYDINWVRQAPGQGLEWMGWIIPTSGSTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDSQSSYIGYFDVWGQGTLVTVSS | 165 | |
중쇄가변영역유전자 | CAAGTTCAGCTGGTCCAGAGCGGCGCAGAGGTGAAGAAGCCCGGCAGTTCTGTTAAGGTTTCCTGCAAAGCCTCAGGCGGGACTTTTAGTTCTTACGATATCAACTGGGTGCGGCAGGCGCCCGGCCAGGGTCTCGAATGGATGGGGTGGATTATCCCAACCTCTGGTTCTACCAACTATGCACAAAAATTCCAAGGCCGCGTAACTATTACCGCCGACGAATCAACCTCCACCGCCTACATGGAACTCAGCTCTCTGAGGTCAGAAGACACGGCCGTCTATTATTGCGCCAGAGATTCTCAGTCTTCTTACATCGGTTACTTCGATGTTTGGGGTCAGGGTACTCTGGTTACCGTCTCATCG | 166 | |
경쇄(Kappa) | DIQMTQSPSSLSASVGDRVTITCRASQSISRWLNWYQQKPGKAPKLLIYAASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSESFPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC | 167 | |
중쇄 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYDINWVRQAPGQGLEWMGWIIPTSGSTNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDSQSSYIGYFDVWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 168 |
클론 | 부위 | 아미노산 서열(N>C) 또는 핵산 서열(5’>3') | 서열번호 |
19 | CDR-L1 | RASQSISNYLN | 169 |
CDR-L2 | DTSSLQS | 170 | |
CDR-L3 | QQSYSTPYT | 171 | |
CDR-H1 | AYGIS | 172 | |
CDR-H2 | RIIPYLGTANYAQKFQG | 173 | |
CDR-H3 | LSYGIGYESFDV | 174 | |
경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYDTSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIK | 175 | |
경쇄가변영역유전자 | GACATTCAAATGACGCAGAGTCCCTCCTCACTGAGTGCTAGCGTGGGCGATCGTGTGACAATTACTTGTCGCGCTAGCCAGTCTATCTCTAATTACCTGAACTGGTATCAGCAGAAACCGGGCAAGGCGCCAAAATTGCTGATTTACGATACTTCCTCTCTGCAGTCTGGTGTACCGTCCCGTTTCTCTGGCAGCGGTTCTGGTACGGATTTTACCCTGACCATCTCAAGCCTCCAGCCTGAAGATTTTGCCACCTATTATTGTCAGCAATCTTACTCTACTCCGTACACGTTCGGGCAGGGAACTAAAGTGGAAATTAAA | 176 | |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSAYGISWVRQAPGQGLEWMGRIIPYLGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARLSYGIGYESFDVWGQGTLVTVSS | 177 | |
중쇄가변영역유전자 | CAAGTTCAGCTGGTCCAGAGCGGCGCAGAGGTGAAGAAGCCCGGCAGTTCTGTTAAGGTTTCCTGCAAAGCCTCAGGCGGGACTTTTAGTGCATACGGTATCTCTTGGGTGCGGCAGGCGCCCGGCCAGGGTCTCGAATGGATGGGGCGTATTATCCCATACCTGGGTACCGCAAACTATGCACAAAAATTCCAAGGCCGCGTAACTATTACCGCCGACGAATCAACCTCCACCGCCTACATGGAACTCAGCTCTCTGAGGTCAGAAGACACGGCCGTCTATTATTGCGCCAGACTGTCTTACGGTATCGGTTACGAATCTTTCGATGTTTGGGGTCAGGGCACTTTAGTGACCGTCTCATCG | 178 | |
경쇄(Kappa) | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYDTSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC | 179 | |
중쇄 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSAYGISWVRQAPGQGLEWMGRIIPYLGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARLSYGIGYESFDVWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 180 |
클론 | 부위 | 아미노산 서열(N>C) 또는 핵산 서열(5’>3') | 서열번호 |
20 | CDR-L1 | RASQSISSYLN | 181 |
CDR-L2 | DTSTLQS | 182 | |
CDR-L3 | QQSYSFPWT | 183 | |
CDR-H1 | SYAMS | 184 | |
CDR-H2 | SISSSGGSTYYADSVKG | 185 | |
CDR-H3 | ELGGYGFSYFDY | 186 | |
경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYDTSTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 187 | |
경쇄가변영역유전자 | GACATTCAAATGACGCAGAGTCCCTCCTCACTGAGTGCTAGCGTGGGCGATCGTGTGACAATTACTTGTCGCGCTAGCCAGTCTATCTCTTCTTACCTGAACTGGTATCAGCAGAAACCGGGCAAGGCGCCAAAATTGCTGATTTACGATACTTCCACTCTGCAGTCTGGTGTACCGTCCCGTTTCTCTGGCAGCGGTTCTGGTACGGATTTTACCCTGACCATCTCAAGCCTCCAGCCTGAAGATTTTGCCACCTATTATTGTCAGCAATCTTACTCTTTTCCGTGGACGTTCGGGCAGGGAACTAAAGTGGAAATTAAA | 188 | |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAMSWVRQAPGQGLEWMGSISSSGGSTYYADSVKGRVTITADESTSTAYMELSSLRSEDTAVYYCARELGGYGFSYFDYWGQGTLVTVSS | 189 | |
중쇄가변영역유전자 | CAAGTTCAGCTGGTCCAGAGCGGCGCAGAGGTGAAGAAGCCCGGCAGTTCTGTTAAGGTTTCCTGCAAAGCCTCAGGCGGGACTTTTAGTTCTTATGCAATGTCTTGGGTGCGGCAGGCGCCCGGCCAGGGTCTCGAATGGATGGGGTCTATCTCTTCTTCTGGTGGTTCTACTTACTATGCCGATTCAGTGAAGGGTCGCGTAACTATTACCGCCGACGAATCAACCTCCACCGCCTACATGGAACTCAGCTCTCTGAGGTCAGAAGACACGGCCGTCTATTATTGCGCCAGAGAACTGGGTGGTTACGGTTTCTCTTACTTCGATTACTGGGGTCAGGGCACTTTAGTGACCGTCTCATCG | 190 | |
경쇄(Kappa) | DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYDTSTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC | 191 | |
중쇄 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAMSWVRQAPGQGLEWMGSISSSGGSTYYADSVKGRVTITADESTSTAYMELSSLRSEDTAVYYCARELGGYGFSYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 192 |
클론 | 부위 | 아미노산 서열(N>C) 또는 핵산 서열(5’>3') | 서열번호 |
21 | CDR-L1 | RASQSIRNYLN | 193 |
CDR-L2 | ATSSLQS | 194 | |
CDR-L3 | QQSYSFPWT | 195 | |
CDR-H1 | DYAMS | 196 | |
CDR-H2 | GISGSDIYYADSVKG | 197 | |
CDR-H3 | AVSYWSYTFDY | 198 | |
경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSIRNYLNWYQQKPGKAPKLLIYATSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 199 | |
경쇄가변영역유전자 | GACATTCAAATGACGCAGAGTCCCTCCTCACTGAGTGCTAGCGTGGGCGATCGTGTGACAATTACTTGTCGCGCTAGCCAGTCTATCCGTAATTACCTGAACTGGTATCAGCAGAAACCGGGCAAGGCGCCAAAATTGCTGATTTACGCAACTTCCTCTCTGCAGTCTGGTGTACCGTCCCGTTTCTCTGGCAGCGGTTCTGGTACGGATTTTACCCTGACCATCTCAAGCCTCCAGCCTGAAGATTTTGCCACCTATTATTGTCAGCAATCTTACTCTTTTCCGTGGACGTTCGGGCAGGGAACTAAAGTGGAAATTAAA | 200 | |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSDYAMSWVRQAPGQGLEWMGGISGSDIYYADSVKGRVTITADESTSTAYMELSSLRSEDTAVYYCARAVSYWSYTFDYWGQGTLVTVSS | 201 | |
중쇄가변영역유전자 | CAAGTTCAGCTGGTCCAGAGCGGCGCAGAGGTGAAGAAGCCCGGCAGTTCTGTTAAGGTTTCCTGCAAAGCCTCAGGCGGGACTTTTAGTGATTATGCAATGTCTTGGGTGCGGCAGGCGCCCGGCCAGGGTCTCGAATGGATGGGGGGTATCTCTGGTTCTGATATCTACTATGCCGATTCAGTGAAGGGTCGCGTAACTATTACCGCCGACGAATCAACCTCCACCGCCTACATGGAACTCAGCTCTCTGAGGTCAGAAGACACGGCCGTCTATTATTGCGCCAGAGCAGTTTCTTACTGGTCTTACACTTTTGATTACTGGGGTCAGGGCACTTTAGTGACCGTCTCATCG | 202 | |
경쇄(Kappa) | DIQMTQSPSSLSASVGDRVTITCRASQSIRNYLNWYQQKPGKAPKLLIYATSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC | 203 | |
중쇄 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSDYAMSWVRQAPGQGLEWMGGISGSDIYYADSVKGRVTITADESTSTAYMELSSLRSEDTAVYYCARAVSYWSYTFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 204 |
클론 | 부위 | 아미노산 서열(N>C) 또는 핵산 서열(5’>3') | 서열번호 |
22 | CDR-L1 | RASQSIGSYLN | 205 |
CDR-L2 | DASTLQS | 206 | |
CDR-L3 | QQSYSFPWT | 207 | |
CDR-H1 | SYAMH | 208 | |
CDR-H2 | GISSSGGTTYYADSVKG | 209 | |
CDR-H3 | ALGVVGGTWFDY | 210 | |
경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSIGSYLNWYQQKPGKAPKLLIYDASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 211 | |
경쇄가변영역유전자 | GACATTCAAATGACGCAGAGTCCCTCCTCACTGAGTGCTAGCGTGGGCGATCGTGTGACAATTACTTGTCGCGCTAGCCAGTCTATCGGTTCTTACCTGAACTGGTATCAGCAGAAACCGGGCAAGGCGCCAAAATTGCTGATTTACGATGCATCCACTCTGCAGTCTGGTGTACCGTCCCGTTTCTCTGGCAGCGGTTCTGGTACGGATTTTACCCTGACCATCTCAAGCCTCCAGCCTGAAGATTTTGCCACCTATTATTGTCAGCAATCTTACTCTTTTCCGTGGACGTTCGGGCAGGGAACTAAAGTGGAAATTAAA | 212 | |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAMHWVRQAPGQGLEWMGGISSSGGTTYYADSVKGRVTITADESTSTAYMELSSLRSEDTAVYYCARALGVVGGTWFDYWGQGTLVTVSS | 213 | |
중쇄가변영역유전자 | CAAGTTCAGCTGGTCCAGAGCGGCGCAGAGGTGAAGAAGCCCGGCAGTTCTGTTAAGGTTTCCTGCAAAGCCTCAGGCGGGACTTTTAGTTCTTATGCAATGCACTGGGTGCGGCAGGCGCCCGGCCAGGGTCTCGAATGGATGGGGGGTATCTCTTCTTCTGGTGGTACTACTTACTATGCCGATTCAGTGAAGGGTCGCGTAACTATTACCGCCGACGAATCAACCTCCACCGCCTACATGGAACTCAGCTCTCTGAGGTCAGAAGACACGGCCGTCTATTATTGCGCCAGAGCACTGGGTGTTGTTGGTGGTACTTGGTTCGATTACTGGGGTCAGGGCACTTTAGTGACCGTCTCATCG | 214 | |
경쇄(Kappa) | DIQMTQSPSSLSASVGDRVTITCRASQSIGSYLNWYQQKPGKAPKLLIYDASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC | 215 | |
중쇄 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAMHWVRQAPGQGLEWMGGISSSGGTTYYADSVKGRVTITADESTSTAYMELSSLRSEDTAVYYCARALGVVGGTWFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 216 |
클론 | 부위 | 아미노산 서열(N>C) 또는 핵산 서열(5’>3') | 서열번호 |
23 | CDR-L1 | RASQSISNYLN | 217 |
CDR-L2 | DTSTLQS | 218 | |
CDR-L3 | QQSYSFPWT | 219 | |
CDR-H1 | DYAMH | 220 | |
CDR-H2 | AISGSGGYTHYADSVKG | 221 | |
CDR-H3 | SATFGVWETFDV | 222 | |
경쇄가변영역 | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYDTSTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIK | 223 | |
경쇄가변영역유전자 | GACATTCAAATGACGCAGAGTCCCTCCTCACTGAGTGCTAGCGTGGGCGATCGTGTGACAATTACTTGTCGCGCTAGCCAGTCTATCTCTAATTACCTGAACTGGTATCAGCAGAAACCGGGCAAGGCGCCAAAATTGCTGATTTACGATACTTCCACTCTGCAGTCTGGTGTACCGTCCCGTTTCTCTGGCAGCGGTTCTGGTACGGATTTTACCCTGACCATCTCAAGCCTCCAGCCTGAAGATTTTGCCACCTATTATTGTCAGCAATCTTACTCTTTTCCGTGGACGTTCGGGCAGGGAACTAAAGTGGAAATTAAA | 224 | |
중쇄가변영역 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSDYAMHWVRQAPGQGLEWMGAISGSGGYTHYADSVKGRVTITADESTSTAYMELSSLRSEDTAVYYCARSATFGVWETFDVWGQGTLVTVSS | 225 | |
중쇄가변영역유전자 | CAAGTTCAGCTGGTCCAGAGCGGCGCAGAGGTGAAGAAGCCCGGCAGTTCTGTTAAGGTTTCCTGCAAAGCCTCAGGCGGGACTTTTAGTGATTATGCAATGCACTGGGTGCGGCAGGCGCCCGGCCAGGGTCTCGAATGGATGGGGGCAATCTCTGGTTCTGGTGGTTACACTCACTATGCCGATTCAGTGAAGGGTCGCGTAACTATTACCGCCGACGAATCAACCTCCACCGCCTACATGGAACTCAGCTCTCTGAGGTCAGAAGACACGGCCGTCTATTATTGCGCCAGATCTGCAACTTTCGGTGTTTGGGAAACTTTCGATGTTTGGGGTCAGGGCACTTTAGTGACCGTCTCATCG | 226 | |
경쇄(Kappa) | DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYDTSTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPWTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC | 227 | |
중쇄 | QVQLVQSGAEVKKPGSSVKVSCKASGGTFSDYAMHWVRQAPGQGLEWMGAISGSGGYTHYADSVKGRVTITADESTSTAYMELSSLRSEDTAVYYCARSATFGVWETFDVWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG | 228 |
실시예
3. 선별된 항체의 제조
상기 실시예 2에서 구축된 벡터는 Plasmid Plus Maxi kit(Qiagen)을 이용하여 증폭되었다. 이 벡터는 ExpiCHO-STM 세포를 이용하여 항체 발현에 사용되었다. 이 벡터를 ExpiCHO-STM 세포(Gibco)(1.2 x 109 cells/Culture Volume 200mL)에 ExpiFectamineTM CHO reagent(Thermo Fisher)를 640μL 첨가하여 트랜스펙션(transfection)하였다. Transfection 1 일 후, ExpiCHOTM Expression Media(Thermo Fisher)에서 32°C, 5% CO2 조건 하에서 7~11일 동안 배양하였다. Day 1에 ExpiCHOTM Enhancer(Thermo Fisher) 1200μL 와 ExpiCHOTM Feed(Thermo Fisher) 48mL을 첨가하였다.
상기 배양된 세포를 4°C, 3500 rpm에서 20 분간 원심분리 후, 0.22μm의 bottle-top filter system(Corning)을 사용하여 여과하였다. 회수한 배양액을 AKTA Pure L(GE healthcare)를 이용하여 정제하였다. AKTA Pure L에 Hitrap MabSelectSure 5mL 컬럼(GE healthcare)을 장착하고 배양액을 5mL/min의 유속으로 흘려준 후, 1X PBS로 10 column volume(CV) 씻어주었다. 용출 버퍼(0.1 M sodium citrate pH 3.4 buffer)를 흘려주어 목적 단백질을 용출 시켰다. 용출액은 Amicon Ultra Filter Device(MWCO 10K, Merck)와 원심분리기를 이용하여 농축을 수행한 후 1X PBS 완충용액으로 버퍼교환을 실시하였다.
정제한 항체 시료는 1X PBS로 희석하여 약 1mg/mL이 되도록 준비하였다. Reducing Loading Buffer(3X) 또는 Non-reducing Loading Buffer(3X) 10μL와 정제한 항체 시료 20μL를 혼합한 후, 95°C heating bath에 2분간 방치한 후 꺼내어 냉각시켰다. SDS-PAGE Gradient Gel(4-12%)을 전기영동 장치에 장착한 후, well 당 10μg의 시료를 주입하고 gel을 전개하였다. 시료의 분자량 분석을 위해 Precision Plus ProteinTM Dual Color Standards(BIO-RAD)를 별도의 well에 주입하였다. Coomassie staining solution으로 gel을 staining하고 destaining 한 후 gel 사진을 촬영하였다(도 1).
실시예 4. 선별된 항체의 결합 친화도 분석
상기 실시예 3에서 제조된 항체 19 종의 LILRB1 항원에 대한 친화력을 Biacore T200(GE healthcare)를 사용하여 측정하였다. Series S Sensor Chip CM5(GE healthcare, Cat. No. BR-1005-30) 상에 Amine Coupling Kit(GE healthcare, Cat. No. BR-1000-50)을 이용하여 anti-human IgG(Fc) 항체(GE healthcare, Cat. No. BR-1008-39, 최종 농도 25μg/mL)를 5μL/min으로 360초 동안 흘려 약 5000-7000 RU로 고정시켰다. 항원인 인간 LILRB1 단백질(LILRB1-His, RnD systems Cat. No. 8989-T2)을 25nM부터 400nM까지의 농도 범위 내에서 서로 다른 5개의 농도로 30μL/min의 속도로 주입하여, 하기 표와 같이 ka과 kd 값을 구하고, 이로부터 KD값을 계산하였다. 10번 항체는 LILRB1 항원에 대하여 약 24.13nM의 결합력을 보였으며, 13번 항체는 LILRB1 항원에 대하여 약 30.27nM의 결합력을 보였다(표 22). 13번 항체에 대한 sensorgram 결과를 도 2에 나타내었다.
클론 번호 | k a(x 105)(1/Ms) | k d(x 10-4)(1/s) | K D(nM) |
8 | 0.6166 | 46.37 | 75.2 |
10 | 0.1233 | 2.977 | 24.13 |
11 | 0.08662 | 1.061 | 12.25 |
13 | 0.9729 | 2.945 | 30.27 |
14 | 1.621 | 663.1 | 409.1 |
16 | 1.157 | 96.35 | 83.3 |
18 | 1.439 | 6.221 | 4.32 |
22 | 0.6826 | 340.8 | 499.3 |
실시예
5: 선별된 항체의 인 비트로(
in vitro
) 생물학적 활성 분석
5.1. 세포 표면 결합 분석(Cell surface binding assay)
상기 실시예 4에서 선별된 항체들이 세포 표면에 발현된 LILRB1과도 결합하는지 여부를 확인하기 위해 세포 표면 결합 분석(Cell surface binding assay)를 수행하였다. LILRB1을 과발현시킨 CHO 세포를 Chemical Defined Medium에서 배양하였고, 2x105 cells/well이 되도록 U-bottomed 96-well tissue culture plate(BD Falcon)에 분주하였다. 각 well 당 최종 농도가 10μg/mL가 되도록 항체를 가하고, 4°C에서 30분 동안 두었다. LILRB1에 특이적인 결합을 보기 위해, human IgG4 isotype control 항체(Biolegend)도 동일하게 처리하였다. FACS buffer로 washing 한 후, 각 well에 anti-human Fc-biotin 항체(life technologies)를 가하고, 4°C에서 1 시간 동안 두었다. FACS buffer로 washing 한 후, 각 well에 streptavidin PE(BD Pharmigen)를 가하고 4°C에서 30 분 동안 두었다. FACS buffer로 washing한 후, 현탁하여 iQue screener(Sartorius)에서 분석하였다. 도 3에 나타낸 것과 같이 8, 10, 11, 13, 18 번 항체의 경우 human IgG4 isotype control 항체에 비해 더 많은 결합 정도를 보여주었다.
5.2. 자연살해세포에 의한 암세포 사멸능 증가 분석
상기 실시예 4에서 선별된 항체들이 자연살해세포에 의한 암세포 사멸능을 증가시키는지 여부를 확인하기 위해 자연살해세포 KHYG-1에 의한 HLA-G 과발현 HEK293 세포 사멸능 분석을 수행하였다. KHYG-1 세포를 4x105 cells/mL(2x104 cells/well)이 되도록 96-well tissue culture plate(BD Falcon)에 분주하였다. 선별된 항체를 HLA-G 과발현 HEK293 세포 처리 후 최종 농도가 10μg/mL이 되도록 가하고, 37°C에서 1 시간 동안 두었다. (음성 대조군으로서 human IgG4 isotype control 항체(Biolegend)도 동일하게 처리하였다. HLA-G 과발현 HEK293 세포를 IncuCyte CytoLight Rapid Red Reagent(Sartorius)를 이용하여 제조사의 설명서에 따라 염색하였다. 1 시간 후, HLA-G 과발현 HEK293 세포를 4x105 cells/mL(2x104 cells/well)이 되도록 가하였다. 플레이트를 37°C, 5% CO2 배양기에 설치된 IncuCyte S3(Sartorius)에 넣고 72 시간 동안 이미지를 촬영하였다.
각 항체의 효능 비교를 위해서, Isotype control antibody의 Normalized red area confluence 값이 1 일 때의 Relative cell viability(Isotype=1)를 다음 수학식 1과 같이 구하였다.
[수학식 1]
Relative cell viability = [각 항체의 Normalized red area confluence 값]/[Isotype의 Normalized red area confluence 값]
상기 얻어진 결과를 도 4에 나타내었다. 도 4에서 Relative cell viability 가 낮을수록 Anti-LILRB1 mAb 에 의한 NK Cell mediated cytotoxicity 가 높다고 해석될 수 있다. 도 4와 같이, 시험된 모든 항체(10번, 11번, 13번 항체)는 human IgG4 Isotype control 대비 HLA-G 과발현 HEK293 세포의 사멸을 증가시켰다. 이러한 결과는 본원발명에서 제공되는 항체가 암세포에 대하여 높은 Cytotoxicity 를 나타냄을 보여준다.
실시예 6. 시험 항체의 인 비보(
in vivo
) 생물학적 활성 분석
상기 실시예 3에서 항원에 대한 결합력이 확인된 3종의 항체(10번, 11번, 13번)의 항암 효능 개선 여부를 확인하기 위하여, Bioware Bite Cell Line HCT116 Red-Fluc 대장암 세포(PerkinElmer) 및 THP-1 유래 대식세포(THP-1 derived macrophage), 항체를 투여한 이종 이식 대장암 마우스 동물 모델을 대상으로 인 비보(in vivo)에서 3종의 항체 투여에 의하여 종양의 크기가 감소되는지 여부를 확인하였다. 음성 대조군으로서 human IgG1 isotype control 항체(BioXcell, Cat. No. BP0297)를 사용하였다.
6.1. THP-1 유래 대식세포(THP-1 derived macrophage)의 제조
THP-1 유래 대식세포는 THP-1 세포(ATCC)로부터 150nM phorbol 12-myristate 13-acetate(PMA, Sigma) 및 20ng/mL interferon gamma(Peprotech), 10 pg/mL lipopolysaccharide(LPS, Sigma)를 가하여 분화하여 사용하였다.
6.2. 마우스 동물 모델에서 항체의 항암 효능 분석
마우스 동물 모델은 3 x 106 개의 HCT116 Red-Fluc 대장암 세포와 3 x 106 개의 THP-1 유래 대식세포 및 항체(마리 당 20μg)를 5 주령의 웅성 CIEA NOG Mouse(NOG 면역부전 마우스, 일본 실험동물중앙연구소)에 피하주사하여 사용하였다. 또한 각 항체는 세포 이식 후 4일째부터 복강주사에 의해 5mg/kg의 용량으로 주 2회 투여하였다.
항체 투여에 따른 종양 부피 변화를 측정하여 도 5에 나타내었다. 도 5에서와 같이, HCT116 대장암 세포 및 THP-1 유래 대식세포를 이식한 마우스 동물 모델에서, 시험된 모든 항체(10번, 11번, 13번 항체)가 확연한 종양 성장 억제 효능을 보였으며, 음성대조군과 통계적으로 유의한 차이를 보였다.
<110> LG CHEM, LTD.
<120> ANTI-LILRB1 ANTIBODY AND USES THEREOF
<130> DPP20212098KR
<150> KR 10-2020-0094053
<151> 2020-07-28
<160> 230
<170> koPatentIn 3.0
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Arg Ala Ser Gln Ser Ile Ala Asn Tyr Leu Asn
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<210> 2
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Ala Thr Ser Thr Leu Gln Ser
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Ala Tyr Gly Ile His
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Trp Ile Ile Pro Leu Ser Gly Gly Ala His Tyr Ala Gln Lys Phe Gln
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Gly
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Leu Tyr Gly Trp Ala Glu Tyr Phe Asp Val
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Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
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Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ala Asn Tyr
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Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
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Tyr Ala Thr Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
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Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
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Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
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Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
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<211> 321
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<220>
<223> Synthetic (5_LightChain_VariableRegion_gene)
<400> 8
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attacttgtc gcgctagcca gtctatcgca aattacctga actggtatca gcagaaaccg 120
ggcaaggcgc caaaattgct gatttacgca acttccactc tgcagtctgg tgtaccgtcc 180
cgtttctctg gcagcggttc tggtacggat tttaccctga ccatctcaag cctccagcct 240
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ggaactaaag tggaaattaa a 321
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Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ala Tyr
20 25 30
Gly Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ile Pro Leu Ser Gly Gly Ala His Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Tyr Gly Trp Ala Glu Tyr Phe Asp Val Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 10
<211> 357
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<213> Artificial Sequence
<220>
<223> Synthetic (5_HeavyChain_VariableRegion_gene)
<400> 10
caagttcagc tggtccagag cggcgcagag gtgaagaagc ccggcagttc tgttaaggtt 60
tcctgcaaag cctcaggcgg gacttttagt gcatacggta tccattgggt gcggcaggcg 120
cccggccagg gtctcgaatg gatggggtgg attatcccac tgtctggtgg tgcacattat 180
gcacaaaaat tccaaggccg cgtaactatt accgccgacg aatcaacctc caccgcctac 240
atggaactca gctctctgag gtcagaagac acggccgtct attattgcgc cagactgtac 300
ggttgggcag aatacttcga tgtttggggt cagggtactc tggttaccgt ctcatcg 357
<210> 11
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (5_LightChain_Kappa)
<400> 11
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ala Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Thr Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 12
<211> 445
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (5_HeavyChain)
<400> 12
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ala Tyr
20 25 30
Gly Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ile Pro Leu Ser Gly Gly Ala His Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Tyr Gly Trp Ala Glu Tyr Phe Asp Val Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro
210 215 220
Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe
225 230 235 240
Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro
245 250 255
Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val
260 265 270
Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
275 280 285
Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val
290 295 300
Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
305 310 315 320
Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser
325 330 335
Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
340 345 350
Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val
355 360 365
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
370 375 380
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp
385 390 395 400
Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp
405 410 415
Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His
420 425 430
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440 445
<210> 13
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (6_CDR-L1)
<400> 13
Arg Ala Ser Gln Ser Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 14
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (6_CDR-L2)
<400> 14
Ala Ala Ser Thr Leu Gln Ser
1 5
<210> 15
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (6_CDR-L3)
<400> 15
Gln Gln Ser Tyr Ser Phe Pro Trp Thr
1 5
<210> 16
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (6_CDR-H1)
<400> 16
Ser Tyr Thr Ile Ser
1 5
<210> 17
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (6_CDR-H2)
<400> 17
Trp Ile Ser Pro Glu Leu Gly Thr Ser Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 18
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (6_CDR-H3)
<400> 18
Leu Arg Tyr Gly Gln Thr Leu Tyr Gly Phe Asp Ile
1 5 10
<210> 19
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (6_LightChain_VariableRegion)
<400> 19
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 20
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (6_LightChain_VariableRegion_gene)
<400> 20
gacattcaaa tgacgcagag tccctcctca ctgagtgcta gcgtgggcga tcgtgtgaca 60
attacttgtc gcgctagcca gtctatctct aattacctga actggtatca gcagaaaccg 120
ggcaaggcgc caaaattgct gatttacgca gcatccactc tgcagtctgg tgtaccgtcc 180
cgtttctctg gcagcggttc tggtacggat tttaccctga ccatctcaag cctccagcct 240
gaagattttg ccacctatta ttgtcagcaa tcttactctt ttccgtggac gttcgggcag 300
ggaactaaag tggaaattaa a 321
<210> 21
<211> 121
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (6_HeavyChain_VariableRegion)
<400> 21
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Thr Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Pro Glu Leu Gly Thr Ser Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Arg Tyr Gly Gln Thr Leu Tyr Gly Phe Asp Ile Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 22
<211> 363
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (6_HeavyChain_VariableRegion_gene)
<400> 22
caagttcagc tggtccagag cggcgcagag gtgaagaagc ccggcagttc tgttaaggtt 60
tcctgcaaag cctcaggcgg gacttttagt tcttacacca tttcttgggt gcggcaggcg 120
cccggccagg gtctcgaatg gatggggtgg atttctccag aactgggtac ctctaactat 180
gcacaaaaat tccaaggccg cgtaactatt accgccgacg aatcaacctc caccgcctac 240
atggaactca gctctctgag gtcagaagac acggccgtct attattgcgc cagactgcgt 300
tacggtcaga ctctgtacgg tttcgatatc tggggtcagg gtactctggt taccgtctca 360
tcg 363
<210> 23
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (6_LightChain_Kappa)
<400> 23
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 24
<211> 447
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (6_HeavyChain)
<400> 24
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Thr Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Pro Glu Leu Gly Thr Ser Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Arg Tyr Gly Gln Thr Leu Tyr Gly Phe Asp Ile Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly
210 215 220
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
225 230 235 240
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
245 250 255
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
260 265 270
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
275 280 285
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
290 295 300
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
305 310 315 320
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
325 330 335
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
340 345 350
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
355 360 365
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
370 375 380
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
385 390 395 400
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
405 410 415
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
420 425 430
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440 445
<210> 25
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (7_CDR-L1)
<400> 25
Arg Ala Ser Gln Ser Ile Ser Asn Trp Leu Asn
1 5 10
<210> 26
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (7_CDR-L2)
<400> 26
Gly Thr Ser Ser Leu Gln Ser
1 5
<210> 27
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (7_CDR-L3)
<400> 27
Gln Gln Ser Tyr Ser Phe Pro Phe Thr
1 5
<210> 28
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (7_CDR-H1)
<400> 28
Ser Tyr Gly Met His
1 5
<210> 29
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (7_CDR-H2)
<400> 29
Trp Ile Ile Pro Val Ser Gly Gly Ala Thr Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 30
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (7_CDR-H3)
<400> 30
Gly Ser Trp Ala Tyr Tyr Ala Glu Phe Asp Tyr
1 5 10
<210> 31
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (7_LightChain_VariableRegion)
<400> 31
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Trp
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Gly Thr Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Phe
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 32
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (7_LightChain_VariableRegion_gene)
<400> 32
gacattcaaa tgacgcagag tccctcctca ctgagtgcta gcgtgggcga tcgtgtgaca 60
attacttgtc gcgctagcca gtctatctct aattggctga actggtatca gcagaaaccg 120
ggcaaggcgc caaaattgct gatttacggt acttcctctc tgcagtctgg tgtaccgtcc 180
cgtttctctg gcagcggttc tggtacggat tttaccctga ccatctcaag cctccagcct 240
gaagattttg ccacctatta ttgtcagcaa tcttactctt ttccgtttac gttcgggcag 300
ggaactaaag tggaaattaa a 321
<210> 33
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (7_HeavyChain_VariableRegion)
<400> 33
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ile Pro Val Ser Gly Gly Ala Thr Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Ser Trp Ala Tyr Tyr Ala Glu Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 34
<211> 360
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (7_HeavyChain_VariableRegion_gene)
<400> 34
caagttcagc tggtccagag cggcgcagag gtgaagaagc ccggcagttc tgttaaggtt 60
tcctgcaaag cctcaggcgg gacttttagt tcttacggta tgcattgggt gcggcaggcg 120
cccggccagg gtctcgaatg gatggggtgg attatcccag tttctggtgg tgcaacctat 180
gcacaaaaat tccaaggccg cgtaactatt accgccgacg aatcaacctc caccgcctac 240
atggaactca gctctctgag gtcagaagac acggccgtct attattgcgc cagaggttct 300
tgggcatact acgctgaatt cgattactgg ggtcagggca ctttagtgac cgtctcatcg 360
360
<210> 35
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (7_LightChain_Kappa)
<400> 35
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Trp
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Gly Thr Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Phe
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 36
<211> 446
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (7_HeavyChain)
<400> 36
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ile Pro Val Ser Gly Gly Ala Thr Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Ser Trp Ala Tyr Tyr Ala Glu Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro
210 215 220
Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
290 295 300
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
325 330 335
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440 445
<210> 37
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (8_CDR-L1)
<400> 37
Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn
1 5 10
<210> 38
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (8_CDR-L2)
<400> 38
Ala Ala Ser Thr Leu Gln Ser
1 5
<210> 39
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (8_CDR-L3)
<400> 39
Gln Gln Ser Tyr Ser Phe Pro Tyr Thr
1 5
<210> 40
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (8_CDR-H1)
<400> 40
Ser Tyr Gly Ile His
1 5
<210> 41
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (8_CDR-H2)
<400> 41
Trp Ile Ile Pro Ile Ser Gly Thr Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 42
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (8_CDR-H3)
<400> 42
Val Gly Gly Val Gly Leu Tyr Val Phe Asp Val
1 5 10
<210> 43
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (8_LightChain_VariableRegion)
<400> 43
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 44
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (8_LightChain_VariableRegion_gene)
<400> 44
gacattcaaa tgacgcagag tccctcctca ctgagtgcta gcgtgggcga tcgtgtgaca 60
attacttgtc gcgctagcca gtctatctct tcttacctga actggtatca gcagaaaccg 120
ggcaaggcgc caaaattgct gatttacgca gcatccactc tgcagtctgg tgtaccgtcc 180
cgtttctctg gcagcggttc tggtacggat tttaccctga ccatctcaag cctccagcct 240
gaagattttg ccacctatta ttgtcagcaa tcttactctt ttccgtacac gttcgggcag 300
ggaactaaag tggaaattaa a 321
<210> 45
<211> 120
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (8_HeavyChain_VariableRegion)
<400> 45
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Gly Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ile Pro Ile Ser Gly Thr Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Val Gly Gly Val Gly Leu Tyr Val Phe Asp Val Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 46
<211> 360
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (8_HeavyChain_VariableRegion_gene)
<400> 46
caagttcagc tggtccagag cggcgcagag gtgaagaagc ccggcagttc tgttaaggtt 60
tcctgcaaag cctcaggcgg gacttttagt tcttacggta tccattgggt gcggcaggcg 120
cccggccagg gtctcgaatg gatggggtgg attatcccaa tctctggtac caccaactat 180
gcacaaaaat tccaaggccg cgtaactatt accgccgacg aatcaacctc caccgcctac 240
atggaactca gctctctgag gtcagaagac acggccgtct attattgcgc cagagttggt 300
ggtgttggtc tgtacgtttt cgatgtttgg ggtcagggta ctctggttac cgtctcatcg 360
360
<210> 47
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (8_LightChain_Kappa)
<400> 47
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 48
<211> 446
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (8_HeavyChain)
<400> 48
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Gly Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ile Pro Ile Ser Gly Thr Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Val Gly Gly Val Gly Leu Tyr Val Phe Asp Val Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro
210 215 220
Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
290 295 300
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
325 330 335
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440 445
<210> 49
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (9_CDR-L1)
<400> 49
Arg Ala Ser Gln Ser Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 50
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (9_CDR-L2)
<400> 50
Ala Ala Ser Ser Leu Gln Ser
1 5
<210> 51
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (9_CDR-L3)
<400> 51
Gln Gln Ser Tyr Ser Phe Pro Trp Thr
1 5
<210> 52
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (9_CDR-H1)
<400> 52
Ser Tyr Ala Ile His
1 5
<210> 53
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (9_CDR-H2)
<400> 53
Trp Ile Val Pro Gly Leu Gly Val Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 54
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (9_CDR-H3)
<400> 54
Gln Ala Thr Leu Tyr Gln Thr Glu Tyr Met Asp Val
1 5 10
<210> 55
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (9_LightChain_VariableRegion)
<400> 55
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 56
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (9_LightChain_VariableRegion_gene)
<400> 56
gacattcaaa tgacgcagag tccctcctca ctgagtgcta gcgtgggcga tcgtgtgaca 60
attacttgtc gcgctagcca gtctatctct aattacctga actggtatca gcagaaaccg 120
ggcaaggcgc caaaattgct gatttacgca gcatcctctc tgcagtctgg tgtaccgtcc 180
cgtttctctg gcagcggttc tggtacggat tttaccctga ccatctcaag cctccagcct 240
gaagattttg ccacctatta ttgtcagcaa tcttactctt ttccgtggac gttcgggcag 300
ggaactaaag tggaaattaa a 321
<210> 57
<211> 121
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (9_HeavyChain_VariableRegion)
<400> 57
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Ala Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Val Pro Gly Leu Gly Val Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gln Ala Thr Leu Tyr Gln Thr Glu Tyr Met Asp Val Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 58
<211> 363
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (9_HeavyChain_VariableRegion_gene)
<400> 58
caagttcagc tggtccagag cggcgcagag gtgaagaagc ccggcagttc tgttaaggtt 60
tcctgcaaag cctcaggcgg gacttttagt tcttacgcaa tccattgggt gcggcaggcg 120
cccggccagg gtctcgaatg gatggggtgg attgttccag gtctgggtgt taccaactat 180
gcacaaaaat tccaaggccg cgtaactatt accgccgacg aatcaacctc caccgcctac 240
atggaactca gctctctgag gtcagaagac acggccgtct attattgcgc cagacaggca 300
actctgtacc agactgaata catggatgtt tggggtcagg gtactctggt taccgtctca 360
tcg 363
<210> 59
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (9_LightChain_Kappa)
<400> 59
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 60
<211> 447
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (9_HeavyChain)
<400> 60
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Ala Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Val Pro Gly Leu Gly Val Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gln Ala Thr Leu Tyr Gln Thr Glu Tyr Met Asp Val Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly
210 215 220
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
225 230 235 240
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
245 250 255
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
260 265 270
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
275 280 285
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
290 295 300
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
305 310 315 320
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
325 330 335
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
340 345 350
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
355 360 365
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
370 375 380
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
385 390 395 400
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
405 410 415
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
420 425 430
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440 445
<210> 61
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (10_CDR-L1)
<400> 61
Arg Ala Ser Gln Ser Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 62
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (10_CDR-L2)
<400> 62
Ala Ala Ser Asn Leu Gln Ser
1 5
<210> 63
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (10_CDR-L3)
<400> 63
Gln Gln Ser Tyr Ser Phe Pro Phe Thr
1 5
<210> 64
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (10_CDR-H1)
<400> 64
Ser His Tyr Met His
1 5
<210> 65
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (10_CDR-H2)
<400> 65
Trp Ile Ser Pro Tyr Leu Gly Ser Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 66
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (10_CDR-H3)
<400> 66
Asp Glu Thr Gly Ser Thr Tyr Gly Ala Phe Asp Tyr
1 5 10
<210> 67
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (10_LightChain_VariableRegion)
<400> 67
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Asn Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Phe
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 68
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (10_LightChain_VariableRegion_gene)
<400> 68
gacattcaaa tgacgcagag tccctcctca ctgagtgcta gcgtgggcga tcgtgtgaca 60
attacttgtc gcgctagcca gtctatctct aattacctga actggtatca gcagaaaccg 120
ggcaaggcgc caaaattgct gatttacgca gcatccaatc tgcagtctgg tgtaccgtcc 180
cgtttctctg gcagcggttc tggtacggat tttaccctga ccatctcaag cctccagcct 240
gaagattttg ccacctatta ttgtcagcaa tcttactctt ttccgtttac gttcgggcag 300
ggaactaaag tggaaattaa a 321
<210> 69
<211> 121
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (10_HeavyChain_VariableRegion)
<400> 69
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser His
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Pro Tyr Leu Gly Ser Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Glu Thr Gly Ser Thr Tyr Gly Ala Phe Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 70
<211> 363
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (10_HeavyChain_VariableRegion_gene)
<400> 70
caagttcagc tggtccagag cggcgcagag gtgaagaagc ccggcagttc tgttaaggtt 60
tcctgcaaag cctcaggcgg gacttttagt tctcattaca tgcattgggt gcggcaggcg 120
cccggccagg gtctcgaatg gatggggtgg atttctccat acctgggttc taccaactat 180
gcacaaaaat tccaaggccg cgtaactatt accgccgacg aatcaacctc caccgcctac 240
atggaactca gctctctgag gtcagaagac acggccgtct attattgcgc cagagatgaa 300
actggttcta cttacggtgc attcgattac tggggtcagg gtactctggt taccgtctca 360
tcg 363
<210> 71
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (10_LightChain_Kappa)
<400> 71
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Asn Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Phe
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 72
<211> 447
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (10_HeavyChain)
<400> 72
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser His
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Pro Tyr Leu Gly Ser Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Glu Thr Gly Ser Thr Tyr Gly Ala Phe Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly
210 215 220
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
225 230 235 240
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
245 250 255
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
260 265 270
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
275 280 285
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
290 295 300
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
305 310 315 320
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
325 330 335
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
340 345 350
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
355 360 365
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
370 375 380
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
385 390 395 400
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
405 410 415
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
420 425 430
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440 445
<210> 73
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (11_CDR-L1)
<400> 73
Arg Ala Ser Gln Ser Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 74
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (11_CDR-L2)
<400> 74
Asp Ala Ser Thr Leu Gln Ser
1 5
<210> 75
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (11_CDR-L3)
<400> 75
Gln Gln Ser Tyr Ser Phe Pro Trp Thr
1 5
<210> 76
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (11_CDR-H1)
<400> 76
Ser Tyr Tyr Val His
1 5
<210> 77
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (11_CDR-H2)
<400> 77
Trp Ile Ser Pro Tyr Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 78
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (11_CDR-H3)
<400> 78
Asp Tyr Tyr Val Ser Ala Tyr Gly Ala Phe Asp Tyr
1 5 10
<210> 79
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (11_LightChain_VariableRegion)
<400> 79
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Asp Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 80
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (11_LightChain_VariableRegion_gene)
<400> 80
gacattcaaa tgacgcagag tccctcctca ctgagtgcta gcgtgggcga tcgtgtgaca 60
attacttgtc gcgctagcca gtctatctct aattacctga actggtatca gcagaaaccg 120
ggcaaggcgc caaaattgct gatttacgat gcatccactc tgcagtctgg tgtaccgtcc 180
cgtttctctg gcagcggttc tggtacggat tttaccctga ccatctcaag cctccagcct 240
gaagattttg ccacctatta ttgtcagcaa tcttactctt ttccgtggac gttcgggcag 300
ggaactaaag tggaaattaa a 321
<210> 81
<211> 121
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (11_HeavyChain_VariableRegion)
<400> 81
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Pro Tyr Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Val Ser Ala Tyr Gly Ala Phe Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 82
<211> 363
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (11_HeavyChain_VariableRegion_gene)
<400> 82
caagttcagc tggtccagag cggcgcagag gtgaagaagc ccggcagttc tgttaaggtt 60
tcctgcaaag cctcaggcgg gacttttagt tcttactacg ttcattgggt gcggcaggcg 120
cccggccagg gtctcgaatg gatggggtgg atttctccat actctggtgg taccaactat 180
gcacaaaaat tccaaggccg cgtaactatt accgccgacg aatcaacctc caccgcctac 240
atggaactca gctctctgag gtcagaagac acggccgtct attattgcgc cagagattac 300
tacgtttctg catacggtgc attcgattac tggggtcagg gtactctggt taccgtctca 360
tcg 363
<210> 83
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (11_LightChain_Kappa)
<400> 83
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Asp Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 84
<211> 447
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (11_HeavyChain)
<400> 84
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Tyr Val His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Pro Tyr Ser Gly Gly Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Tyr Tyr Val Ser Ala Tyr Gly Ala Phe Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly
210 215 220
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
225 230 235 240
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
245 250 255
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
260 265 270
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
275 280 285
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
290 295 300
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
305 310 315 320
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
325 330 335
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
340 345 350
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
355 360 365
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
370 375 380
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
385 390 395 400
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
405 410 415
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
420 425 430
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440 445
<210> 85
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (12_CDR-L1)
<400> 85
Arg Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 86
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (12_CDR-L2)
<400> 86
Ala Thr Ser Ser Leu Gln Ser
1 5
<210> 87
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (12_CDR-L3)
<400> 87
Gln Gln Ser Tyr Ser Phe Pro Trp Thr
1 5
<210> 88
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (12_CDR-H1)
<400> 88
Ser Tyr Asp Ile His
1 5
<210> 89
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (12_CDR-H2)
<400> 89
Arg Ile Val Pro Tyr Leu Gly Val Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 90
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (12_CDR-H3)
<400> 90
Arg Gln Ser Gln Ser Ser Val Tyr Ala Phe Asp Ile
1 5 10
<210> 91
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (12_LightChain_VariableRegion)
<400> 91
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Thr Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 92
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (12_LightChain_VariableRegion_gene)
<400> 92
gacattcaaa tgacgcagag tccctcctca ctgagtgcta gcgtgggcga tcgtgtgaca 60
attacttgtc gcgctagcca ggatatctct aattacctga actggtatca gcagaaaccg 120
ggcaaggcgc caaaattgct gatttacgca acttcctctc tgcagtctgg tgtaccgtcc 180
cgtttctctg gcagcggttc tggtacggat tttaccctga ccatctcaag cctccagcct 240
gaagattttg ccacctatta ttgtcagcaa tcttactctt ttccgtggac gttcgggcag 300
ggaactaaag tggaaattaa a 321
<210> 93
<211> 121
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (12_HeavyChain_VariableRegion)
<400> 93
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Asp Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Arg Ile Val Pro Tyr Leu Gly Val Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Arg Gln Ser Gln Ser Ser Val Tyr Ala Phe Asp Ile Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 94
<211> 363
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (12_HeavyChain_VariableRegion_gene)
<400> 94
caagttcagc tggtccagag cggcgcagag gtgaagaagc ccggcagttc tgttaaggtt 60
tcctgcaaag cctcaggcgg gacttttagt tcttacgata tccattgggt gcggcaggcg 120
cccggccagg gtctcgaatg gatggggcgt attgttccat acctgggtgt taccaactat 180
gcacaaaaat tccaaggccg cgtaactatt accgccgacg aatcaacctc caccgcctac 240
atggaactca gctctctgag gtcagaagac acggccgtct attattgcgc cagacgtcag 300
tctcagtctt ctgtttacgc attcgatatc tggggtcagg gcactttagt gaccgtctca 360
tcg 363
<210> 95
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (12_LightChain_Kappa)
<400> 95
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Thr Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 96
<211> 447
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (12_HeavyChain)
<400> 96
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Asp Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Arg Ile Val Pro Tyr Leu Gly Val Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Arg Gln Ser Gln Ser Ser Val Tyr Ala Phe Asp Ile Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly
210 215 220
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
225 230 235 240
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
245 250 255
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
260 265 270
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
275 280 285
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
290 295 300
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
305 310 315 320
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
325 330 335
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
340 345 350
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
355 360 365
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
370 375 380
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
385 390 395 400
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
405 410 415
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
420 425 430
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440 445
<210> 97
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (13_CDR-L1)
<400> 97
Arg Ala Ser Gln Ser Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 98
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (13_CDR-L2)
<400> 98
Ala Ala Ser Arg Leu Gln Ser
1 5
<210> 99
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (13_CDR-L3)
<400> 99
Gln Gln Ser Tyr Ser Phe Pro Phe Thr
1 5
<210> 100
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (13_CDR-H1)
<400> 100
Gly Tyr Tyr Ile His
1 5
<210> 101
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (13_CDR-H2)
<400> 101
Trp Ile Ser Pro Ser Ser Gly Gly Thr Ile Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 102
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (13_CDR-H3)
<400> 102
Asp Ile Ser Val Arg Val Val Gln Ala Phe Asp Tyr
1 5 10
<210> 103
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (13_LightChain_VariableRegion)
<400> 103
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Arg Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Phe
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 104
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (13_LightChain_VariableRegion_gene)
<400> 104
gacattcaaa tgacgcagag tccctcctca ctgagtgcta gcgtgggcga tcgtgtgaca 60
attacttgtc gcgctagcca gtctatctct aattacctga actggtatca gcagaaaccg 120
ggcaaggcgc caaaattgct gatttacgca gcatcccgtc tgcagtctgg tgtaccgtcc 180
cgtttctctg gcagcggttc tggtacggat tttaccctga ccatctcaag cctccagcct 240
gaagattttg ccacctatta ttgtcagcaa tcttactctt ttccgtttac gttcgggcag 300
ggaactaaag tggaaattaa a 321
<210> 105
<211> 121
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (13_HeavyChain_VariableRegion)
<400> 105
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Gly Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Pro Ser Ser Gly Gly Thr Ile Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ile Ser Val Arg Val Val Gln Ala Phe Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 106
<211> 363
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (13_HeavyChain_VariableRegion_gene)
<400> 106
caagttcagc tggtccagag cggcgcagag gtgaagaagc ccggcagttc tgttaaggtt 60
tcctgcaaag cctcaggcgg gacttttagt ggttactaca tccattgggt gcggcaggcg 120
cccggccagg gtctcgaatg gatggggtgg atttctccat cttctggtgg taccatctat 180
gcacaaaaat tccaaggccg cgtaactatt accgccgacg aatcaacctc caccgcctac 240
atggaactca gctctctgag gtcagaagac acggccgtct attattgcgc cagagatatc 300
tctgttcgtg ttgttcaggc attcgattac tggggtcagg gtactctggt taccgtctca 360
tcg 363
<210> 107
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (13_LightChain_Kappa)
<400> 107
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Arg Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Phe
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 108
<211> 447
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (13_HeavyChain)
<400> 108
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Gly Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Pro Ser Ser Gly Gly Thr Ile Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ile Ser Val Arg Val Val Gln Ala Phe Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly
210 215 220
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
225 230 235 240
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
245 250 255
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
260 265 270
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
275 280 285
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
290 295 300
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
305 310 315 320
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
325 330 335
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
340 345 350
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
355 360 365
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
370 375 380
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
385 390 395 400
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
405 410 415
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
420 425 430
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440 445
<210> 109
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (14_CDR-L1)
<400> 109
Arg Ala Ser Gln Ser Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 110
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (14_CDR-L2)
<400> 110
Ala Thr Ser Asn Leu Gln Ser
1 5
<210> 111
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (14_CDR-L3)
<400> 111
Gln Gln Ser Tyr Ser Phe Pro Trp Thr
1 5
<210> 112
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (14_CDR-H1)
<400> 112
Ser Tyr Tyr Met His
1 5
<210> 113
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (14_CDR-H2)
<400> 113
Trp Ile Ser Pro Tyr Leu Gly Ile Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 114
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (14_CDR-H3)
<400> 114
Ala Gly Tyr Gln Gln Ala Gln Tyr Trp Phe Asp Tyr
1 5 10
<210> 115
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (14_LightChain_VariableRegion)
<400> 115
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Thr Ser Asn Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 116
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (14_LightChain_VariableRegion_gene)
<400> 116
gacattcaaa tgacgcagag tccctcctca ctgagtgcta gcgtgggcga tcgtgtgaca 60
attacttgtc gcgctagcca gtctatctct aattacctga actggtatca gcagaaaccg 120
ggcaaggcgc caaaattgct gatttacgca acttccaatc tgcagtctgg tgtaccgtcc 180
cgtttctctg gcagcggttc tggtacggat tttaccctga ccatctcaag cctccagcct 240
gaagattttg ccacctatta ttgtcagcaa tcttactctt ttccgtggac gttcgggcag 300
ggaactaaag tggaaattaa a 321
<210> 117
<211> 121
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (14_HeavyChain_VariableRegion)
<400> 117
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Pro Tyr Leu Gly Ile Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ala Gly Tyr Gln Gln Ala Gln Tyr Trp Phe Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 118
<211> 363
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (14_HeavyChain_VariableRegion_gene)
<400> 118
caagttcagc tggtccagag cggcgcagag gtgaagaagc ccggcagttc tgttaaggtt 60
tcctgcaaag cctcaggcgg gacttttagt tcttactaca tgcattgggt gcggcaggcg 120
cccggccagg gtctcgaatg gatggggtgg atttctccat acctgggtat caccaactat 180
gcacaaaaat tccaaggccg cgtaactatt accgccgacg aatcaacctc caccgcctac 240
atggaactca gctctctgag gtcagaagac acggccgtct attattgcgc cagagcaggt 300
taccagcagg cacagtactg gttcgattac tggggtcagg gcactttagt gaccgtctca 360
tcg 363
<210> 119
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (14_LightChain_Kappa)
<400> 119
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Thr Ser Asn Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 120
<211> 447
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (14_HeavyChain)
<400> 120
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Pro Tyr Leu Gly Ile Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ala Gly Tyr Gln Gln Ala Gln Tyr Trp Phe Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly
210 215 220
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
225 230 235 240
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
245 250 255
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
260 265 270
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
275 280 285
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
290 295 300
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
305 310 315 320
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
325 330 335
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
340 345 350
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
355 360 365
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
370 375 380
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
385 390 395 400
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
405 410 415
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
420 425 430
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440 445
<210> 121
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (15_CDR-L1)
<400> 121
Arg Ala Ser Gln Ser Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 122
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (15_CDR-L2)
<400> 122
Ala Thr Ser Ser Leu Gln Ser
1 5
<210> 123
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (15_CDR-L3)
<400> 123
Gln Gln Ser Tyr Ser Phe Pro Tyr Thr
1 5
<210> 124
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (15_CDR-H1)
<400> 124
Ser Tyr Ala Met Ser
1 5
<210> 125
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (15_CDR-H2)
<400> 125
Trp Ile Ile Pro Ile Ser Gly Thr Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 126
<211> 10
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (15_CDR-H3)
<400> 126
Gln His Ser Val Gly Ser Val Phe Asp Tyr
1 5 10
<210> 127
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (15_LightChain_VariableRegion)
<400> 127
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Thr Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 128
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (15_LightChain_VariableRegion_gene)
<400> 128
gacattcaaa tgacgcagag tccctcctca ctgagtgcta gcgtgggcga tcgtgtgaca 60
attacttgtc gcgctagcca gtctatctct aattacctga actggtatca gcagaaaccg 120
ggcaaggcgc caaaattgct gatttacgca acttcctctc tgcagtctgg tgtaccgtcc 180
cgtttctctg gcagcggttc tggtacggat tttaccctga ccatctcaag cctccagcct 240
gaagattttg ccacctatta ttgtcagcaa tcttactctt ttccgtacac gttcgggcag 300
ggaactaaag tggaaattaa a 321
<210> 129
<211> 119
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (15_HeavyChain_VariableRegion)
<400> 129
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ile Pro Ile Ser Gly Thr Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gln His Ser Val Gly Ser Val Phe Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 130
<211> 357
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (15_HeavyChain_VariableRegion_gene)
<400> 130
caagttcagc tggtccagag cggcgcagag gtgaagaagc ccggcagttc tgttaaggtt 60
tcctgcaaag cctcaggcgg gacttttagt tcttacgcaa tgtcttgggt gcggcaggcg 120
cccggccagg gtctcgaatg gatggggtgg attatcccaa tctctggtac caccaactat 180
gcacaaaaat tccaaggccg cgtaactatt accgccgacg aatcaacctc caccgcctac 240
atggaactca gctctctgag gtcagaagac acggccgtct attattgcgc cagacagcat 300
tctgttggtt ctgttttcga ttactggggt cagggtactc tggttaccgt ctcatcg 357
<210> 131
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (15_LightChain_Kappa)
<400> 131
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Thr Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 132
<211> 445
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (15_HeavyChain)
<400> 132
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ile Pro Ile Ser Gly Thr Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gln His Ser Val Gly Ser Val Phe Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro
210 215 220
Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe
225 230 235 240
Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro
245 250 255
Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val
260 265 270
Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
275 280 285
Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val
290 295 300
Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
305 310 315 320
Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser
325 330 335
Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
340 345 350
Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val
355 360 365
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
370 375 380
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp
385 390 395 400
Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp
405 410 415
Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His
420 425 430
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440 445
<210> 133
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (16_CDR-L1)
<400> 133
Arg Ala Ser Gln Asp Ile Ser Ser Trp Leu Asn
1 5 10
<210> 134
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (16_CDR-L2)
<400> 134
Ala Ala Ser Ser Leu Gln Ser
1 5
<210> 135
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (16_CDR-L3)
<400> 135
Gln Gln Ser Tyr Ser Phe Pro Trp Thr
1 5
<210> 136
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (16_CDR-H1)
<400> 136
Ser Tyr Tyr Met Thr
1 5
<210> 137
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (16_CDR-H2)
<400> 137
Gly Ile Ser Pro Ile Leu Gly Val Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 138
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (16_CDR-H3)
<400> 138
Leu Leu Val Gly Val Ser Glu Thr Tyr Phe Asp Tyr
1 5 10
<210> 139
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (16_LightChain_VariableRegion)
<400> 139
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Trp
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 140
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (16_LightChain_VariableRegion_gene)
<400> 140
gacattcaaa tgacgcagag tccctcctca ctgagtgcta gcgtgggcga tcgtgtgaca 60
attacttgtc gcgctagcca ggatatctct tcttggctga actggtatca gcagaaaccg 120
ggcaaggcgc caaaattgct gatttacgca gcatcctctc tgcagtctgg tgtaccgtcc 180
cgtttctctg gcagcggttc tggtacggat tttaccctga ccatctcaag cctccagcct 240
gaagattttg ccacctatta ttgtcagcaa tcttactctt ttccgtggac gttcgggcag 300
ggaactaaag tggaaattaa a 321
<210> 141
<211> 121
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (16_HeavyChain_VariableRegion)
<400> 141
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Tyr Met Thr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Gly Ile Ser Pro Ile Leu Gly Val Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Leu Val Gly Val Ser Glu Thr Tyr Phe Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 142
<211> 363
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (16_HeavyChain_VariableRegion_gene)
<400> 142
caagttcagc tggtccagag cggcgcagag gtgaagaagc ccggcagttc tgttaaggtt 60
tcctgcaaag cctcaggcgg gacttttagt tcttactaca tgacctgggt gcggcaggcg 120
cccggccagg gtctcgaatg gatggggggt atttctccaa tcctgggtgt taccaactat 180
gcacaaaaat tccaaggccg cgtaactatt accgccgacg aatcaacctc caccgcctac 240
atggaactca gctctctgag gtcagaagac acggccgtct attattgcgc cagactgctg 300
gttggtgttt ctgaaactta cttcgattac tggggtcagg gtactctggt taccgtctca 360
tcg 363
<210> 143
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (16_LightChain_Kappa)
<400> 143
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Ser Ser Trp
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 144
<211> 447
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (16_HeavyChain)
<400> 144
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Tyr Met Thr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Gly Ile Ser Pro Ile Leu Gly Val Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Leu Val Gly Val Ser Glu Thr Tyr Phe Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly
210 215 220
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
225 230 235 240
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
245 250 255
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
260 265 270
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
275 280 285
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
290 295 300
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
305 310 315 320
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
325 330 335
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
340 345 350
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
355 360 365
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
370 375 380
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
385 390 395 400
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
405 410 415
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
420 425 430
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440 445
<210> 145
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (17_CDR-L1)
<400> 145
Arg Ala Ser Gln Ser Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 146
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (17_CDR-L2)
<400> 146
Ala Ala Ser Asn Met His Ser
1 5
<210> 147
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (17_CDR-L3)
<400> 147
Gln Gln Ser His Ser Phe Pro Trp Thr
1 5
<210> 148
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (17_CDR-H1)
<400> 148
Thr Tyr Ala Met Ser
1 5
<210> 149
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (17_CDR-H2)
<400> 149
Gly Ile Ser Pro Thr Leu Gly Ile Ala Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 150
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (17_CDR-H3)
<400> 150
Val Arg Tyr Ala Gly Trp Thr Gly Tyr Phe Asp Leu
1 5 10
<210> 151
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (17_LightChain_VariableRegion)
<400> 151
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Asn Met His Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser His Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 152
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (17_LightChain_VariableRegion_gene)
<400> 152
gacattcaaa tgacgcagag tccctcctca ctgagtgcta gcgtgggcga tcgtgtgaca 60
attacttgtc gcgctagcca gtctatctct aattacctga actggtatca gcagaaaccg 120
ggcaaggcgc caaaattgct gatttacgca gcatccaata tgcactctgg tgtaccgtcc 180
cgtttctctg gcagcggttc tggtacggat tttaccctga ccatctcaag cctccagcct 240
gaagattttg ccacctatta ttgtcagcaa tctcactctt ttccgtggac gttcgggcag 300
ggaactaaag tggaaattaa a 321
<210> 153
<211> 121
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (17_HeavyChain_VariableRegion)
<400> 153
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Thr Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Gly Ile Ser Pro Thr Leu Gly Ile Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Val Arg Tyr Ala Gly Trp Thr Gly Tyr Phe Asp Leu Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 154
<211> 363
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (17_HeavyChain_VariableRegion_gene)
<400> 154
caagttcagc tggtccagag cggcgcagag gtgaagaagc ccggcagttc tgttaaggtt 60
tcctgcaaag cctcaggcgg gacttttagt acctacgcaa tgtcttgggt gcggcaggcg 120
cccggccagg gtctcgaatg gatggggggt atttctccaa ccctgggtat cgcaaactat 180
gcacaaaaat tccaaggccg cgtaactatt accgccgacg aatcaacctc caccgcctac 240
atggaactca gctctctgag gtcagaagac acggccgtct attattgcgc cagagttcgt 300
tacgcaggtt ggactggtta cttcgatctg tggggtcagg gtactctggt taccgtctca 360
tcg 363
<210> 155
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (17_LightChain_Kappa)
<400> 155
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Asn Met His Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser His Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 156
<211> 447
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (17_HeavyChain)
<400> 156
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Thr Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Gly Ile Ser Pro Thr Leu Gly Ile Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Val Arg Tyr Ala Gly Trp Thr Gly Tyr Phe Asp Leu Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly
210 215 220
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
225 230 235 240
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
245 250 255
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
260 265 270
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
275 280 285
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
290 295 300
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
305 310 315 320
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
325 330 335
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
340 345 350
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
355 360 365
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
370 375 380
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
385 390 395 400
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
405 410 415
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
420 425 430
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440 445
<210> 157
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (18_CDR-L1)
<400> 157
Arg Ala Ser Gln Ser Ile Ser Arg Trp Leu Asn
1 5 10
<210> 158
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (18_CDR-L2)
<400> 158
Ala Ala Ser Arg Leu Gln Ser
1 5
<210> 159
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (18_CDR-L3)
<400> 159
Gln Gln Ser Glu Ser Phe Pro Trp Thr
1 5
<210> 160
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (18_CDR-H1)
<400> 160
Ser Tyr Asp Ile Asn
1 5
<210> 161
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (18_CDR-H2)
<400> 161
Trp Ile Ile Pro Thr Ser Gly Ser Thr Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 162
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (18_CDR-H3)
<400> 162
Asp Ser Gln Ser Ser Tyr Ile Gly Tyr Phe Asp Val
1 5 10
<210> 163
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (18_LightChain_VariableRegion)
<400> 163
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Arg Trp
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Arg Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Glu Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 164
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (18_LightChain_VariableRegion_gene)
<400> 164
gacattcaaa tgacgcagag tccctcctca ctgagtgcta gcgtgggcga tcgtgtgaca 60
attacttgtc gcgctagcca gtctatctct cgttggctga actggtatca gcagaaaccg 120
ggcaaggcgc caaaattgct gatttacgca gcatcccgtc tgcagtctgg tgtaccgtcc 180
cgtttctctg gcagcggttc tggtacggat tttaccctga ccatctcaag cctccagcct 240
gaagattttg ccacctatta ttgtcagcaa tctgaatctt ttccgtggac gttcgggcag 300
ggaactaaag tggaaattaa a 321
<210> 165
<211> 121
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (18_HeavyChain_VariableRegion)
<400> 165
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ile Pro Thr Ser Gly Ser Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ser Gln Ser Ser Tyr Ile Gly Tyr Phe Asp Val Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 166
<211> 363
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (18_HeavyChain_VariableRegion_gene)
<400> 166
caagttcagc tggtccagag cggcgcagag gtgaagaagc ccggcagttc tgttaaggtt 60
tcctgcaaag cctcaggcgg gacttttagt tcttacgata tcaactgggt gcggcaggcg 120
cccggccagg gtctcgaatg gatggggtgg attatcccaa cctctggttc taccaactat 180
gcacaaaaat tccaaggccg cgtaactatt accgccgacg aatcaacctc caccgcctac 240
atggaactca gctctctgag gtcagaagac acggccgtct attattgcgc cagagattct 300
cagtcttctt acatcggtta cttcgatgtt tggggtcagg gtactctggt taccgtctca 360
tcg 363
<210> 167
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (18_LightChain_Kappa)
<400> 167
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Arg Trp
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Arg Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Glu Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 168
<211> 447
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (18_HeavyChain)
<400> 168
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ile Pro Thr Ser Gly Ser Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ser Gln Ser Ser Tyr Ile Gly Tyr Phe Asp Val Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly
210 215 220
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
225 230 235 240
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
245 250 255
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
260 265 270
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
275 280 285
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
290 295 300
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
305 310 315 320
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
325 330 335
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
340 345 350
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
355 360 365
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
370 375 380
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
385 390 395 400
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
405 410 415
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
420 425 430
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440 445
<210> 169
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (19_CDR-L1)
<400> 169
Arg Ala Ser Gln Ser Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 170
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (19_CDR-L2)
<400> 170
Asp Thr Ser Ser Leu Gln Ser
1 5
<210> 171
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (19_CDR-L3)
<400> 171
Gln Gln Ser Tyr Ser Thr Pro Tyr Thr
1 5
<210> 172
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (19_CDR-H1)
<400> 172
Ala Tyr Gly Ile Ser
1 5
<210> 173
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (19_CDR-H2)
<400> 173
Arg Ile Ile Pro Tyr Leu Gly Thr Ala Asn Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 174
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (19_CDR-H3)
<400> 174
Leu Ser Tyr Gly Ile Gly Tyr Glu Ser Phe Asp Val
1 5 10
<210> 175
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (19_LightChain_VariableRegion)
<400> 175
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Asp Thr Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 176
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (19_LightChain_VariableRegion_gene)
<400> 176
gacattcaaa tgacgcagag tccctcctca ctgagtgcta gcgtgggcga tcgtgtgaca 60
attacttgtc gcgctagcca gtctatctct aattacctga actggtatca gcagaaaccg 120
ggcaaggcgc caaaattgct gatttacgat acttcctctc tgcagtctgg tgtaccgtcc 180
cgtttctctg gcagcggttc tggtacggat tttaccctga ccatctcaag cctccagcct 240
gaagattttg ccacctatta ttgtcagcaa tcttactcta ctccgtacac gttcgggcag 300
ggaactaaag tggaaattaa a 321
<210> 177
<211> 121
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (19_HeavyChain_VariableRegion)
<400> 177
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ala Tyr
20 25 30
Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Arg Ile Ile Pro Tyr Leu Gly Thr Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Ser Tyr Gly Ile Gly Tyr Glu Ser Phe Asp Val Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 178
<211> 363
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (19_HeavyChain_VariableRegion_gene)
<400> 178
caagttcagc tggtccagag cggcgcagag gtgaagaagc ccggcagttc tgttaaggtt 60
tcctgcaaag cctcaggcgg gacttttagt gcatacggta tctcttgggt gcggcaggcg 120
cccggccagg gtctcgaatg gatggggcgt attatcccat acctgggtac cgcaaactat 180
gcacaaaaat tccaaggccg cgtaactatt accgccgacg aatcaacctc caccgcctac 240
atggaactca gctctctgag gtcagaagac acggccgtct attattgcgc cagactgtct 300
tacggtatcg gttacgaatc tttcgatgtt tggggtcagg gcactttagt gaccgtctca 360
tcg 363
<210> 179
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (19_LightChain_Kappa)
<400> 179
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Asp Thr Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 180
<211> 447
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (19_HeavyChain)
<400> 180
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ala Tyr
20 25 30
Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Arg Ile Ile Pro Tyr Leu Gly Thr Ala Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Leu Ser Tyr Gly Ile Gly Tyr Glu Ser Phe Asp Val Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly
210 215 220
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
225 230 235 240
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
245 250 255
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
260 265 270
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
275 280 285
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
290 295 300
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
305 310 315 320
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
325 330 335
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
340 345 350
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
355 360 365
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
370 375 380
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
385 390 395 400
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
405 410 415
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
420 425 430
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440 445
<210> 181
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (20_CDR-L1)
<400> 181
Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn
1 5 10
<210> 182
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (20_CDR-L2)
<400> 182
Asp Thr Ser Thr Leu Gln Ser
1 5
<210> 183
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (20_CDR-L3)
<400> 183
Gln Gln Ser Tyr Ser Phe Pro Trp Thr
1 5
<210> 184
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (20_CDR-H1)
<400> 184
Ser Tyr Ala Met Ser
1 5
<210> 185
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (20_CDR-H2)
<400> 185
Ser Ile Ser Ser Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys
1 5 10 15
Gly
<210> 186
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (20_CDR-H3)
<400> 186
Glu Leu Gly Gly Tyr Gly Phe Ser Tyr Phe Asp Tyr
1 5 10
<210> 187
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (20_LightChain_VariableRegion)
<400> 187
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Asp Thr Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 188
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (20_LightChain_VariableRegion_gene)
<400> 188
gacattcaaa tgacgcagag tccctcctca ctgagtgcta gcgtgggcga tcgtgtgaca 60
attacttgtc gcgctagcca gtctatctct tcttacctga actggtatca gcagaaaccg 120
ggcaaggcgc caaaattgct gatttacgat acttccactc tgcagtctgg tgtaccgtcc 180
cgtttctctg gcagcggttc tggtacggat tttaccctga ccatctcaag cctccagcct 240
gaagattttg ccacctatta ttgtcagcaa tcttactctt ttccgtggac gttcgggcag 300
ggaactaaag tggaaattaa a 321
<210> 189
<211> 121
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (20_HeavyChain_VariableRegion)
<400> 189
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ser Ile Ser Ser Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Leu Gly Gly Tyr Gly Phe Ser Tyr Phe Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 190
<211> 363
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (20_HeavyChain_VariableRegion_gene)
<400> 190
caagttcagc tggtccagag cggcgcagag gtgaagaagc ccggcagttc tgttaaggtt 60
tcctgcaaag cctcaggcgg gacttttagt tcttatgcaa tgtcttgggt gcggcaggcg 120
cccggccagg gtctcgaatg gatggggtct atctcttctt ctggtggttc tacttactat 180
gccgattcag tgaagggtcg cgtaactatt accgccgacg aatcaacctc caccgcctac 240
atggaactca gctctctgag gtcagaagac acggccgtct attattgcgc cagagaactg 300
ggtggttacg gtttctctta cttcgattac tggggtcagg gcactttagt gaccgtctca 360
tcg 363
<210> 191
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (20_LightChain_Kappa)
<400> 191
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Asp Thr Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 192
<211> 447
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (20_HeavyChain)
<400> 192
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ser Ile Ser Ser Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Glu Leu Gly Gly Tyr Gly Phe Ser Tyr Phe Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly
210 215 220
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
225 230 235 240
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
245 250 255
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
260 265 270
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
275 280 285
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
290 295 300
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
305 310 315 320
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
325 330 335
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
340 345 350
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
355 360 365
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
370 375 380
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
385 390 395 400
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
405 410 415
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
420 425 430
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440 445
<210> 193
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (21_CDR-L1)
<400> 193
Arg Ala Ser Gln Ser Ile Arg Asn Tyr Leu Asn
1 5 10
<210> 194
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (21_CDR-L2)
<400> 194
Ala Thr Ser Ser Leu Gln Ser
1 5
<210> 195
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (21_CDR-L3)
<400> 195
Gln Gln Ser Tyr Ser Phe Pro Trp Thr
1 5
<210> 196
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (21_CDR-H1)
<400> 196
Asp Tyr Ala Met Ser
1 5
<210> 197
<211> 15
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (21_CDR-H2)
<400> 197
Gly Ile Ser Gly Ser Asp Ile Tyr Tyr Ala Asp Ser Val Lys Gly
1 5 10 15
<210> 198
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (21_CDR-H3)
<400> 198
Ala Val Ser Tyr Trp Ser Tyr Thr Phe Asp Tyr
1 5 10
<210> 199
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (21_LightChain_VariableRegion)
<400> 199
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Arg Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Thr Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 200
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (21_LightChain_VariableRegion_gene)
<400> 200
gacattcaaa tgacgcagag tccctcctca ctgagtgcta gcgtgggcga tcgtgtgaca 60
attacttgtc gcgctagcca gtctatccgt aattacctga actggtatca gcagaaaccg 120
ggcaaggcgc caaaattgct gatttacgca acttcctctc tgcagtctgg tgtaccgtcc 180
cgtttctctg gcagcggttc tggtacggat tttaccctga ccatctcaag cctccagcct 240
gaagattttg ccacctatta ttgtcagcaa tcttactctt ttccgtggac gttcgggcag 300
ggaactaaag tggaaattaa a 321
<210> 201
<211> 118
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (21_HeavyChain_VariableRegion)
<400> 201
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Asp Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Gly Ile Ser Gly Ser Asp Ile Tyr Tyr Ala Asp Ser Val Lys Gly
50 55 60
Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr Met Glu
65 70 75 80
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg
85 90 95
Ala Val Ser Tyr Trp Ser Tyr Thr Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ser
115
<210> 202
<211> 354
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (21_HeavyChain_VariableRegion_gene)
<400> 202
caagttcagc tggtccagag cggcgcagag gtgaagaagc ccggcagttc tgttaaggtt 60
tcctgcaaag cctcaggcgg gacttttagt gattatgcaa tgtcttgggt gcggcaggcg 120
cccggccagg gtctcgaatg gatggggggt atctctggtt ctgatatcta ctatgccgat 180
tcagtgaagg gtcgcgtaac tattaccgcc gacgaatcaa cctccaccgc ctacatggaa 240
ctcagctctc tgaggtcaga agacacggcc gtctattatt gcgccagagc agtttcttac 300
tggtcttaca cttttgatta ctggggtcag ggcactttag tgaccgtctc atcg 354
<210> 203
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (21_LightChain_Kappa)
<400> 203
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Arg Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Thr Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 204
<211> 444
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (21_HeavyChain)
<400> 204
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Asp Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Gly Ile Ser Gly Ser Asp Ile Tyr Tyr Ala Asp Ser Val Lys Gly
50 55 60
Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr Met Glu
65 70 75 80
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg
85 90 95
Ala Val Ser Tyr Trp Ser Tyr Thr Phe Asp Tyr Trp Gly Gln Gly Thr
100 105 110
Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
115 120 125
Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly
130 135 140
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
145 150 155 160
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
165 170 175
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
180 185 190
Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser
195 200 205
Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys
210 215 220
Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu
225 230 235 240
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
245 250 255
Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln
260 265 270
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
275 280 285
Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu
290 295 300
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
305 310 315 320
Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys
325 330 335
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
340 345 350
Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
355 360 365
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
370 375 380
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
385 390 395 400
Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln
405 410 415
Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
420 425 430
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440
<210> 205
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (22_CDR-L1)
<400> 205
Arg Ala Ser Gln Ser Ile Gly Ser Tyr Leu Asn
1 5 10
<210> 206
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (22_CDR-L2)
<400> 206
Asp Ala Ser Thr Leu Gln Ser
1 5
<210> 207
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (22_CDR-L3)
<400> 207
Gln Gln Ser Tyr Ser Phe Pro Trp Thr
1 5
<210> 208
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (22_CDR-H1)
<400> 208
Ser Tyr Ala Met His
1 5
<210> 209
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (22_CDR-H2)
<400> 209
Gly Ile Ser Ser Ser Gly Gly Thr Thr Tyr Tyr Ala Asp Ser Val Lys
1 5 10 15
Gly
<210> 210
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (22_CDR-H3)
<400> 210
Ala Leu Gly Val Val Gly Gly Thr Trp Phe Asp Tyr
1 5 10
<210> 211
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (22_LightChain_VariableRegion)
<400> 211
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Gly Ser Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Asp Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 212
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (22_LightChain_VariableRegion_gene)
<400> 212
gacattcaaa tgacgcagag tccctcctca ctgagtgcta gcgtgggcga tcgtgtgaca 60
attacttgtc gcgctagcca gtctatcggt tcttacctga actggtatca gcagaaaccg 120
ggcaaggcgc caaaattgct gatttacgat gcatccactc tgcagtctgg tgtaccgtcc 180
cgtttctctg gcagcggttc tggtacggat tttaccctga ccatctcaag cctccagcct 240
gaagattttg ccacctatta ttgtcagcaa tcttactctt ttccgtggac gttcgggcag 300
ggaactaaag tggaaattaa a 321
<210> 213
<211> 121
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (22_HeavyChain_VariableRegion)
<400> 213
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Ala Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Gly Ile Ser Ser Ser Gly Gly Thr Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ala Leu Gly Val Val Gly Gly Thr Trp Phe Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 214
<211> 363
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (22_HeavyChain_VariableRegion_gene)
<400> 214
caagttcagc tggtccagag cggcgcagag gtgaagaagc ccggcagttc tgttaaggtt 60
tcctgcaaag cctcaggcgg gacttttagt tcttatgcaa tgcactgggt gcggcaggcg 120
cccggccagg gtctcgaatg gatggggggt atctcttctt ctggtggtac tacttactat 180
gccgattcag tgaagggtcg cgtaactatt accgccgacg aatcaacctc caccgcctac 240
atggaactca gctctctgag gtcagaagac acggccgtct attattgcgc cagagcactg 300
ggtgttgttg gtggtacttg gttcgattac tggggtcagg gcactttagt gaccgtctca 360
tcg 363
<210> 215
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (22_LightChain_Kappa)
<400> 215
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Gly Ser Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Asp Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 216
<211> 447
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (22_HeavyChain)
<400> 216
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr
20 25 30
Ala Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Gly Ile Ser Ser Ser Gly Gly Thr Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ala Leu Gly Val Val Gly Gly Thr Trp Phe Asp Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly
210 215 220
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
225 230 235 240
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
245 250 255
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
260 265 270
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
275 280 285
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
290 295 300
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
305 310 315 320
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
325 330 335
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
340 345 350
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
355 360 365
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
370 375 380
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
385 390 395 400
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
405 410 415
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
420 425 430
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440 445
<210> 217
<211> 11
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (23_CDR-L1)
<400> 217
Arg Ala Ser Gln Ser Ile Ser Asn Tyr Leu Asn
1 5 10
<210> 218
<211> 7
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (23_CDR-L2)
<400> 218
Asp Thr Ser Thr Leu Gln Ser
1 5
<210> 219
<211> 9
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (23_CDR-L3)
<400> 219
Gln Gln Ser Tyr Ser Phe Pro Trp Thr
1 5
<210> 220
<211> 5
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (23_CDR-H1)
<400> 220
Asp Tyr Ala Met His
1 5
<210> 221
<211> 17
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (23_CDR-H2)
<400> 221
Ala Ile Ser Gly Ser Gly Gly Tyr Thr His Tyr Ala Asp Ser Val Lys
1 5 10 15
Gly
<210> 222
<211> 12
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (23_CDR-H3)
<400> 222
Ser Ala Thr Phe Gly Val Trp Glu Thr Phe Asp Val
1 5 10
<210> 223
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (23_LightChain_VariableRegion)
<400> 223
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Asp Thr Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 224
<211> 321
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (23_LightChain_VariableRegion_gene)
<400> 224
gacattcaaa tgacgcagag tccctcctca ctgagtgcta gcgtgggcga tcgtgtgaca 60
attacttgtc gcgctagcca gtctatctct aattacctga actggtatca gcagaaaccg 120
ggcaaggcgc caaaattgct gatttacgat acttccactc tgcagtctgg tgtaccgtcc 180
cgtttctctg gcagcggttc tggtacggat tttaccctga ccatctcaag cctccagcct 240
gaagattttg ccacctatta ttgtcagcaa tcttactctt ttccgtggac gttcgggcag 300
ggaactaaag tggaaattaa a 321
<210> 225
<211> 121
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (23_HeavyChain_VariableRegion)
<400> 225
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Asp Tyr
20 25 30
Ala Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Ile Ser Gly Ser Gly Gly Tyr Thr His Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ala Thr Phe Gly Val Trp Glu Thr Phe Asp Val Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 226
<211> 363
<212> DNA
<213> Artificial Sequence
<220>
<223> Synthetic (23_HeavyChain_VariableRegion_gene)
<400> 226
caagttcagc tggtccagag cggcgcagag gtgaagaagc ccggcagttc tgttaaggtt 60
tcctgcaaag cctcaggcgg gacttttagt gattatgcaa tgcactgggt gcggcaggcg 120
cccggccagg gtctcgaatg gatgggggca atctctggtt ctggtggtta cactcactat 180
gccgattcag tgaagggtcg cgtaactatt accgccgacg aatcaacctc caccgcctac 240
atggaactca gctctctgag gtcagaagac acggccgtct attattgcgc cagatctgca 300
actttcggtg tttgggaaac tttcgatgtt tggggtcagg gcactttagt gaccgtctca 360
tcg 363
<210> 227
<211> 214
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (23_LightChain_Kappa)
<400> 227
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Asp Thr Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Phe Pro Trp
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 228
<211> 447
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (23_HeavyChain)
<400> 228
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Asp Tyr
20 25 30
Ala Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ala Ile Ser Gly Ser Gly Gly Tyr Thr His Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ala Thr Phe Gly Val Trp Glu Thr Phe Asp Val Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly
210 215 220
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
225 230 235 240
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg
245 250 255
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro
260 265 270
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
275 280 285
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val
290 295 300
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
305 310 315 320
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr
325 330 335
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
340 345 350
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
355 360 365
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
370 375 380
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
385 390 395 400
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser
405 410 415
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
420 425 430
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly
435 440 445
<210> 229
<211> 326
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (IgG4_Fc)
<400> 229
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg
1 5 10 15
Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr
65 70 75 80
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
100 105 110
Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
115 120 125
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
130 135 140
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
145 150 155 160
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
165 170 175
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
180 185 190
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
195 200 205
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
210 215 220
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
225 230 235 240
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
245 250 255
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
260 265 270
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
275 280 285
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
290 295 300
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
305 310 315 320
Leu Ser Leu Ser Leu Gly
325
<210> 230
<211> 107
<212> PRT
<213> Artificial Sequence
<220>
<223> Synthetic (Kappa_ConstatRegion)
<400> 230
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu
1 5 10 15
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe
20 25 30
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln
35 40 45
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser
50 55 60
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu
65 70 75 80
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser
85 90 95
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
100 105
Claims (12)
- 다음의 상보성 결정부위(complementarity determining region; CDRs)를 포함하는, 항-LILRB1 항체 또는 이의 항원 결합 단편:
서열번호 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181, 193, 205, 또는 217의 아미노산 서열을 포함하는 CDR-L1,
서열번호 2, 14, 26, 38, 50, 62, 74, 86, 98, 110, 122, 134, 146, 158, 170, 182, 194, 206, 또는 218의 아미노산 서열을 포함하는 CDR-L2,
서열번호 3, 15, 27, 39, 51, 63, 75, 87, 99, 111, 123, 135, 147, 159, 171, 183, 195, 207, 또는 219의 아미노산 서열을 포함하는 CDR-L3,
서열번호 4, 16, 28, 40, 52, 64, 76, 88, 100, 112, 124, 136, 148, 160, 172, 184, 196, 208, 또는 220의 아미노산 서열을 포함하는 CDR-H1,
서열번호 5, 17, 29, 41, 53, 65, 77, 89, 101, 113, 125, 137, 149, 161, 173, 185, 197, 209, 또는 221의 아미노산 서열을 포함하는 CDR-H2, 및
서열번호 6, 18, 30, 42, 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, 또는 222의 아미노산 서열을 포함하는 CDR-H3
(Kabat numbering을 기준으로 함). - 제1항에 있어서, 다음을 포함하는, 항-LILRB1 항체 또는 이의 항원 결합 단편:
(1) 서열번호 1의 아미노산 서열을 포함하는 CDR-L1, 서열번호 2의 아미노산 서열을 포함하는 CDR-L2, 서열번호 3의 아미노산 서열을 포함하는 CDR-L3, 서열번호 4의 아미노산 서열을 포함하는 CDR-H1, 서열번호 5의 아미노산 서열을 포함하는 CDR-H2, 및 서열번호 6의 아미노산 서열을 포함하는 CDR-H3;
(2) 서열번호 13의 아미노산 서열을 포함하는 CDR-L1, 서열번호 14의 아미노산 서열을 포함하는 CDR-L2, 서열번호 15의 아미노산 서열을 포함하는 CDR-L3, 서열번호 16의 아미노산 서열을 포함하는 CDR-H1, 서열번호 17의 아미노산 서열을 포함하는 CDR-H2, 및 서열번호 18의 아미노산 서열을 포함하는 CDR-H3;
(3) 서열번호 25의 아미노산 서열을 포함하는 CDR-L1, 서열번호 26의 아미노산 서열을 포함하는 CDR-L2, 서열번호 27의 아미노산 서열을 포함하는 CDR-L3, 서열번호 28의 아미노산 서열을 포함하는 CDR-H1, 서열번호 29의 아미노산 서열을 포함하는 CDR-H2, 및 서열번호 30의 아미노산 서열을 포함하는 CDR-H3;
(4) 서열번호 37의 아미노산 서열을 포함하는 CDR-L1, 서열번호 38의 아미노산 서열을 포함하는 CDR-L2, 서열번호 39의 아미노산 서열을 포함하는 CDR-L3, 서열번호 40의 아미노산 서열을 포함하는 CDR-H1, 서열번호 41의 아미노산 서열을 포함하는 CDR-H2, 및 서열번호 42의 아미노산 서열을 포함하는 CDR-H3;
(5) 서열번호 49의 아미노산 서열을 포함하는 CDR-L1, 서열번호 50의 아미노산 서열을 포함하는 CDR-L2, 서열번호 51의 아미노산 서열을 포함하는 CDR-L3, 서열번호 52의 아미노산 서열을 포함하는 CDR-H1, 서열번호 53의 아미노산 서열을 포함하는 CDR-H2, 및 서열번호 54의 아미노산 서열을 포함하는 CDR-H3;
(6) 서열번호 61의 아미노산 서열을 포함하는 CDR-L1, 서열번호 62의 아미노산 서열을 포함하는 CDR-L2, 서열번호 63의 아미노산 서열을 포함하는 CDR-L3, 서열번호 64의 아미노산 서열을 포함하는 CDR-H1, 서열번호 65의 아미노산 서열을 포함하는 CDR-H2, 및 서열번호 66의 아미노산 서열을 포함하는 CDR-H3;
(7) 서열번호 73의 아미노산 서열을 포함하는 CDR-L1, 서열번호 74의 아미노산 서열을 포함하는 CDR-L2, 서열번호 75의 아미노산 서열을 포함하는 CDR-L3, 서열번호 76의 아미노산 서열을 포함하는 CDR-H1, 서열번호 77의 아미노산 서열을 포함하는 CDR-H2, 및 서열번호 78의 아미노산 서열을 포함하는 CDR-H3;
(8) 서열번호 85의 아미노산 서열을 포함하는 CDR-L1, 서열번호 86의 아미노산 서열을 포함하는 CDR-L2, 서열번호 87의 아미노산 서열을 포함하는 CDR-L3, 서열번호 88의 아미노산 서열을 포함하는 CDR-H1, 서열번호 89의 아미노산 서열을 포함하는 CDR-H2, 및 서열번호 90의 아미노산 서열을 포함하는 CDR-H3;
(9) 서열번호 97의 아미노산 서열을 포함하는 CDR-L1, 서열번호 98의 아미노산 서열을 포함하는 CDR-L2, 서열번호 99의 아미노산 서열을 포함하는 CDR-L3, 서열번호 100의 아미노산 서열을 포함하는 CDR-H1, 서열번호 101의 아미노산 서열을 포함하는 CDR-H2, 및 서열번호 102의 아미노산 서열을 포함하는 CDR-H3;
(10) 서열번호 109의 아미노산 서열을 포함하는 CDR-L1, 서열번호 110의 아미노산 서열을 포함하는 CDR-L2, 서열번호 111의 아미노산 서열을 포함하는 CDR-L3, 서열번호 112의 아미노산 서열을 포함하는 CDR-H1, 서열번호 113의 아미노산 서열을 포함하는 CDR-H2, 및 서열번호 114의 아미노산 서열을 포함하는 CDR-H3;
(11) 서열번호 121의 아미노산 서열을 포함하는 CDR-L1, 서열번호 122의 아미노산 서열을 포함하는 CDR-L2, 서열번호 123의 아미노산 서열을 포함하는 CDR-L3, 서열번호 124의 아미노산 서열을 포함하는 CDR-H1, 서열번호 125의 아미노산 서열을 포함하는 CDR-H2, 및 서열번호 126의 아미노산 서열을 포함하는 CDR-H3;
(12) 서열번호 133의 아미노산 서열을 포함하는 CDR-L1, 서열번호 134의 아미노산 서열을 포함하는 CDR-L2, 서열번호 135의 아미노산 서열을 포함하는 CDR-L3, 서열번호 136의 아미노산 서열을 포함하는 CDR-H1, 서열번호 137의 아미노산 서열을 포함하는 CDR-H2, 및 서열번호 138의 아미노산 서열을 포함하는 CDR-H3;
(13) 서열번호 145의 아미노산 서열을 포함하는 CDR-L1, 서열번호 146의 아미노산 서열을 포함하는 CDR-L2, 서열번호 147의 아미노산 서열을 포함하는 CDR-L3, 서열번호 148의 아미노산 서열을 포함하는 CDR-H1, 서열번호 149의 아미노산 서열을 포함하는 CDR-H2, 및 서열번호 150의 아미노산 서열을 포함하는 CDR-H3;
(14) 서열번호 157의 아미노산 서열을 포함하는 CDR-L1, 서열번호 158의 아미노산 서열을 포함하는 CDR-L2, 서열번호 159의 아미노산 서열을 포함하는 CDR-L3, 서열번호 160의 아미노산 서열을 포함하는 CDR-H1, 서열번호 161의 아미노산 서열을 포함하는 CDR-H2, 및 서열번호 162의 아미노산 서열을 포함하는 CDR-H3;
(15) 서열번호 169의 아미노산 서열을 포함하는 CDR-L1, 서열번호 170의 아미노산 서열을 포함하는 CDR-L2, 서열번호 171의 아미노산 서열을 포함하는 CDR-L3, 서열번호 172의 아미노산 서열을 포함하는 CDR-H1, 서열번호 173의 아미노산 서열을 포함하는 CDR-H2, 및 서열번호 174의 아미노산 서열을 포함하는 CDR-H3;
(16) 서열번호 181의 아미노산 서열을 포함하는 CDR-L1, 서열번호 182의 아미노산 서열을 포함하는 CDR-L2, 서열번호 183의 아미노산 서열을 포함하는 CDR-L3, 서열번호 184의 아미노산 서열을 포함하는 CDR-H1, 서열번호 185의 아미노산 서열을 포함하는 CDR-H2, 및 서열번호 186의 아미노산 서열을 포함하는 CDR-H3;
(17) 서열번호 193의 아미노산 서열을 포함하는 CDR-L1, 서열번호 194의 아미노산 서열을 포함하는 CDR-L2, 서열번호 195의 아미노산 서열을 포함하는 CDR-L3, 서열번호 196의 아미노산 서열을 포함하는 CDR-H1, 서열번호 197의 아미노산 서열을 포함하는 CDR-H2, 및 서열번호 198의 아미노산 서열을 포함하는 CDR-H3;
(18) 서열번호 205의 아미노산 서열을 포함하는 CDR-L1, 서열번호 206의 아미노산 서열을 포함하는 CDR-L2, 서열번호 207의 아미노산 서열을 포함하는 CDR-L3, 서열번호 208의 아미노산 서열을 포함하는 CDR-H1, 서열번호 209의 아미노산 서열을 포함하는 CDR-H2, 및 서열번호 210의 아미노산 서열을 포함하는 CDR-H3; 또는
(19) 서열번호 217의 아미노산 서열을 포함하는 CDR-L1, 서열번호 218의 아미노산 서열을 포함하는 CDR-L2, 서열번호 219의 아미노산 서열을 포함하는 CDR-L3, 서열번호 220의 아미노산 서열을 포함하는 CDR-H1, 서열번호 221의 아미노산 서열을 포함하는 CDR-H2, 및 서열번호 222의 아미노산 서열을 포함하는 CDR-H3. - 제1항에 있어서,
서열번호 7, 19, 31, 43, 55, 67, 79, 91, 103, 115, 127, 139, 151, 163, 175, 187, 199, 211, 또는 223의 아미노산 서열을 포함하는 경쇄 가변영역, 및
서열번호 9, 21, 33, 45, 57, 69, 81, 93, 105, 117, 129, 141, 153, 165, 177, 189, 201, 213, 또는 225의 아미노산 서열을 포함하는 중쇄 가변영역
을 포함하는, 항-LILRB1 항체 또는 이의 항원 결합 단편. - 제1항에 있어서, 인간 IgG1 또는 IgG4 항체인, 항-LILRB1 항체 또는 이의 항원 결합 단편.
- 제1항에 있어서, 상기 항원 결합 단편은 상기 항-LILRB1 항체의 scFv,(scFv)2, Fab, Fab', F(ab')2, scFv가 면역글로불린의 Fc와 융합된 융합 폴리펩타이드, 또는 scFv가 경쇄의 불변 영역과 융합된 융합 폴리펩타이드인, 항-LILRB1 항체 또는 이의 항원 결합 단편.
- 제1항 내지 제5항 중 어느 한 항의 항-LILRB1 항체 또는 이의 항원 결합 단편을 포함하는, 암의 예방 또는 치료용 약학 조성물.
- 제6항에 있어서, 상기 암은 MHC Class I이 과발현된 특성을 갖는 것인, 약학 조성물.
- 제6항에 있어서, 상기 조성물은 암세포의 면역 회피를 저해하는 활성 가지는 것인, 약학 조성물.
- 제1항 내지 제5항 중 어느 한 항의 항체 또는 이의 항원 결합 단편을 암호화하는 핵산 분자.
- 제9항의 핵산 분자를 포함하는 재조합 벡터.
- 제9항의 핵산 분자 또는 이를 포함하는 재조합 벡터를 포함하는 재조합 세포.
- 제11항의 재조합 세포를 배양하는 단계를 포함하는, 항-LILRB1 항체 또는 이의 항원 결합 단편의 제조 방법.
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EP3740224A4 (en) * | 2018-01-18 | 2022-05-04 | Adanate, Inc. | ANTI-LILRB ANTIBODIES AND THEIR USES |
AU2019412489A1 (en) * | 2018-12-26 | 2021-06-10 | Innate Pharma | Leucocyte immunoglobulin-like receptor 2 neutralizing antibodies |
CA3150428A1 (en) * | 2019-08-12 | 2021-02-18 | Biond Biologics Ltd. | Antibodies against ilt2 and use thereof |
CA3161827A1 (en) * | 2019-12-23 | 2021-07-01 | Yoon Aa Choi | Anti-lilrb1 antibody and uses thereof |
-
2021
- 2021-07-27 KR KR1020210098593A patent/KR20220014316A/ko active Search and Examination
- 2021-07-27 WO PCT/KR2021/009696 patent/WO2022025585A1/ko unknown
- 2021-07-27 TW TW110127573A patent/TW202208438A/zh unknown
- 2021-07-27 EP EP21851407.3A patent/EP4169950A4/en active Pending
- 2021-07-27 CA CA3186256A patent/CA3186256A1/en active Pending
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- 2021-07-27 BR BR112022026922A patent/BR112022026922A2/pt unknown
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- 2021-07-27 IL IL299942A patent/IL299942A/en unknown
- 2021-07-27 TW TW112122842A patent/TW202340258A/zh unknown
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- 2021-07-27 CN CN202180046031.9A patent/CN115867353A/zh active Pending
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CA3186256A1 (en) | 2022-02-03 |
CN115867353A (zh) | 2023-03-28 |
IL299942A (en) | 2023-03-01 |
AU2021315366A1 (en) | 2023-02-02 |
US20230374127A1 (en) | 2023-11-23 |
EP4169950A4 (en) | 2024-03-20 |
ZA202213434B (en) | 2024-04-24 |
BR112022026922A2 (pt) | 2023-02-07 |
EP4169950A1 (en) | 2023-04-26 |
MX2023001041A (es) | 2023-02-16 |
AU2021315366A9 (en) | 2023-06-29 |
WO2022025585A1 (ko) | 2022-02-03 |
JP2023537225A (ja) | 2023-08-31 |
TW202208438A (zh) | 2022-03-01 |
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