CPC C07K 16/28 (2013.01) [A61K 47/6803 (2017.08); A61K 47/6849 (2017.08); A61P 1/18 (2018.01); A61P 35/00 (2018.01); C07K 16/2809 (2013.01); G01N 33/57492 (2013.01); G01N 33/68 (2013.01); A61K 2039/505 (2013.01); C07K 2317/24 (2013.01); C07K 2317/31 (2013.01); C07K 2317/56 (2013.01); C07K 2317/77 (2013.01); C07K 2317/92 (2013.01)] | 99 Claims |
1. An antigen-binding protein that binds to a human Claudin 18.2 (CLDN 18.2) protein (SEQ ID NO: 1) comprising any of:
a. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGN AMDYWGQGTLVTVSS (SEQ ID NO: 42); and-CDR1-3 derived from a light chain variable region comprising the amino acid sequence: DIVMTQSPDSLAVSLGERVTMNCKSSQSLLNSGNQKNYLSWYQQ KPGQPPKLLFYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQN DYSYPFTFGQGTKLEIK (SEQ ID NO: 45);
b. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGN AMDYWGQGTLVTVSS (SEQ ID NO: 42), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNQKNYLSWYQQKPGQPPKL LIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQNDYSYPFTFG QGTKLEIK (SEQ ID NO: 43);
c. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGN AMDYWGQGTLVTVSS (SEQ ID NO: 42), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNQKNYLSWYQQKPGQPPKL LFYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQNDYSYPFTF GQGTKLEIK (SEQ ID NO: 44);
d. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGN AMDYWGQGTLVTVSS (SEQ ID NO: 42), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLLQSGNQKNYLSWYQQKPGQPPK LLFYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNDYSYPFT FGQGTKLEIK (SEQ ID NO: 140);
e. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGN AMDYWGQGTLVTVSS (SEQ ID NO: 42), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLLSSGNQKNYLSWYQQKPGQPPK LLFYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNDYSYPFT FGQGTKLEIK (SEQ ID NO: 130);
f. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGQ AMDYWGQGTLVTVSS (SEQ ID NO: 138), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLLNSGNQKNYLSWYQQKPGQPPK LLFYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNDYSYPFT FGQGTKLEIK (SEQ ID NO: 142);
g. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGQ AMDYWGQGTLVTVSS (SEQ ID NO: 138), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLLQSGNQKNYLSWYQQKPGQPPK LLFYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNDYSYPFT FGQGTKLEIK (SEQ ID NO: 140);
h. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGQ AMDYWGQGTLVTVSS (SEQ ID NO: 138), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLLSSGNQKNYLSWYQQKPGQPPK LLFYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNDYSYPFT FGQGTKLEIK (SEQ ID NO: 141);
i. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGS AMDYWGQGTLVTVSS (SEQ ID NO: 139), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLLNSGNQKNYLSWYQQKPGQPPK LLFYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNDYSYPFT FGQGTKLEIK (SEQ ID NO: 142);
j. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGS AMDYWGQGTLVTVSS (SEQ ID NO: 139), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLLQSGNQKNYLSWYQQKPGQPPK LLFYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNDYSYPFT FGQGTKLEIK (SEQ ID NO: 140);
k. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATII IGGSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLVKGS AMDYWGQGTLVTVSS (SEQ ID NO: 139), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLLSSGNQKNYLSWYQQKPGQPPK LLFYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNDYSYPFT FGQGTKLEIK (SEQ ID NO: 141);
l. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLQQSGPELVKPGASVKISCKASGYSFTVYYMNWVKQSPEKSLEWIGEIN PSTGGTTYNPKFKAKATLTVDKSSSTAYMQLKSLTSEDSAIYFCVRWADYW GQGTTLTVSS (SEQ ID NO: 40), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVITQDELSNPVTSGESVSISCRSSKSLLYKDGKTYLNWFLQRPGQSPQLLV YWMSTRASGVSDRFSGSGSGTDFTLEISRVKAEDVGVYYCQQVVYYPYTFG SGTKLEIK (SEQ ID NO: 41);
m. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATI SSGVSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLTKG NAMDYWGQGTLVTVSS (SEQ ID NO: 46), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNQKNYLTWYQQKPGQPPKL LIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQNDYSYPFTFG QGTKLEIK (SEQ ID NO: 47);
n. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYTMSWVRQAPGKGLEWVATI SSGVSYTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCTRLTKG NAMDYWGQGTLVTVSS (SEQ ID NO: 46), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNDYSYPFTF GQGTKLEIK (SEQ ID NO: 48);
o. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSFGMHWVRQAPGKGLEWVAYI SSGTTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GNSLDYWGQGTLVTVSS (SEQ ID NO: 131), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERATINCKSSQSLFNSGNQRNYLTWYQQKPGQPPKL LIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQNVYIYPLTFG QGTKLEIK (SEQ ID NO: 149);
p. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSFGMHWVRQAPGKGLEWVAYI SSGTTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GNSLDYWGQGTLVTVSS (SEQ ID NO: 131), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLFNSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNVYIYPLTF GQGTKLEIK (SEQ ID NO: 150);
q. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSFGMHWVRQAPGKGLEWVAYI SSGTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GNSLDYWGQGTLVTVSS (SEQ ID NO: 131), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLFNSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNVYIYPLTF GQGTKLEIK (SEQ ID NO: 147);
r. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSFGMHWVRQAPGKGLEWVAYI SSGTTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GNSLDYWGQGTLVTVSS (SEQ ID NO: 131), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLFQSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNVYIYPLTF GQGTKLEIK (SEQ ID NO: 135);
s. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSFGMHWVRQAPGKGLEWVAYI SSGTTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GNSLDYWGQGTLVTVSS (SEQ ID NO: 131), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLFSSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNVYIYPLTF GQGTKLEIK (SEQ ID NO: 136);
t. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSFGMHWVRQAPGKGLEWVAYI SSGTTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GQSLDYWGQGTLVTVSS (SEQ ID NO: 133), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLFNSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNVYIYPLTF GQGTKLEIK (SEQ ID NO: 137);
u. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSFGMHWVRQAPGKGLEWVAYI SSGTTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GSSLDYWGQGTLVTVSS (SEQ ID NO: 134), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLFNSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNVYIYPLTF GQGTKLEIK (SEQ ID NO: 137);
v. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSFGMHWVRQAPGKGLEWVAYI SSGTTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GQSLDYWGQGTLVTVSS (SEQ ID NO: 133), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLFQSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNVYIYPLTF GQGTKLEIK (SEQ ID NO: 135);
w. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSFGMHWVRQAPGKGLEWVAYI SSGTTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GQSLDYWGQGTLVTVSS (SEQ ID NO: 133), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLFSSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNVYIYPLTF GQGTKLEIK (SEQ ID NO: 136);
x. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSFGMHWVRQAPGKGLEWVAYI SSGTTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GSSLDYWGQGTLVTVSS (SEQ ID NO: 134), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLFQSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNVYIYPLTF GQGTKLEIK (SEQ ID NO: 135);
y. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLVESGGGLVQPGGSLRLSCAVSGFTFSSFGMHWVRQAPGKGLEWVAYI SSGTTNIYYADSVKGRFTVSRDNAKNSLYLQMNSLRAEDTAVYYCVRSGYY GSSLDYWGQGTLVTVSS (SEQ ID NO: 134), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLFSSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNVYIYPLTF GQGTKLEIK (SEQ ID NO: 136);
z. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYLMHWVRQAPGQGLEWIGY INPYNDGTNYAQKFQGRVTMTSDTSTSTVYMELSSLRSEDTAVYYCTRGDY WGQGTLVTVSS (SEQ ID NO: 52), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNQKNYLTWYQQKPGQPPKL LIYWASIRQSGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCLNDYGFPLTFG QGTKLEIK (SEQ ID NO: 53);
aa. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYLMHWVRQAPGQGLEWIGY INPYNDGTNYAQKFQGRVTMTSDTSTSTVYMELSSLRSEDTAVYYCTRGDY WGQGTLVTVSS (SEQ ID NO: 52), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASIRQSGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCLNDYGFPLTF GQGTKLEIK (SEQ ID NO: 54);
ab. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
QVQLVQSGAEVKKPGASVKMSCKASGYTFTSYLMHWVRQAPGQGLEWIG YINPYNDGTNYAQKFQGRATLTSDTSTSTAYMELSSLRSEDTAVYYCTRGD YWGQGTLVTVSS (SEQ ID NO: 55), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNQKNYLTWYQQKPGQPPKL LIYWASIRQSGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCLNDYGFPLTFG QGTKLEIK (SEQ ID NO: 53);
ac. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
QVQLVQSGAEVKKPGASVKMSCKASGYTFTSYLMHWVRQAPGQGLEWIG YINPYNDGTNYAQKFQGRATLTSDTSTSTAYMELSSLRSEDTAVYYCTRGD YWGQGTLVTVSS (SEQ ID NO: 55), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASIRQSGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCLNDYGFPLTF GQGTKLEIK (SEQ ID NO: 54);
ad. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
QVQLVQSGAEVKKPGASVKMSCKASGYTFTSYLMHWVRQAPGQGLEWIG YINPYNDGTNYAQKFQGRATLTSDKSTSTAYMELSSLRSEDTAVYYCTRGD YWGQGTLVTVSS (SEQ ID NO: 56), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERATINCKSSQSLLNSGNQKNYLTWYQQKPGQPPKL LIYWASIRQSGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCLNDYGFPLTFG QGTKLEIK (SEQ ID NO: 53);
ae CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
QVQLVQSGAEVKKPGASVKMSCKASGYTFTSYLMHWVRQAPGQGLEWIG YINPYNDGTNYAQKFQGRATLTSDKSTSTAYMELSSLRSEDTAVYYCTRGD YWGQGTLVTVSS (SEQ ID NO: 56), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSSQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASIRQSGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCLNDYGFPLTF GQGTKLEIK (SEQ ID NO: 54);
af. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSDVISWVRQAPGQGLEWMGE SYLRNGNTYYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCARSYY GNSFAYWGQGTLVTVSS (SEQ ID NO: 57), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERATINCKSTQSLLNSGNQKNYLTWYQQKPGQPPKL LIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQNAYYYPFTF GQGTKLEIK (SEQ ID NO: 50);
ag. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSDVISWVRQAPGQGLEWMGE SYLRNGNTYYAQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCARSYY GNSFAYWGQGTLVTVSS (SEQ ID NO: 57), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSTQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNAYYYPFT FGQGTKLEIK (SEQ ID NO: 51);
ah. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
QVQLVQSGAEVKKPGSSVKLSCKASGYTFTSDVISWVRQAPGQGLEWIGES YLRNGNTYYAQKFQGRATLTADKSTSTAYMELSSLRSEDTAVYYCARSYYG NSFAYWGQGTLVTVSS (SEQ ID NO: 49), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERATINCKSTQSLLNSGNQKNYLTWYQQKPGQPPKL LIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQNAYYYPFTF GQGTKLEIK (SEQ ID NO: 50); or
ai. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
QVQLVQSGAEVKKPGSSVKLSCKASGYTFTSDVISWVRQAPGQGLEWIGES YLRNGNTYYAQKFQGRATLTADKSTSTAYMELSSLRSEDTAVYYCARSYYG NSFAYWGQGTLVTVSS (SEQ ID NO: 49), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPDSLAVSLGERVTMNCKSTQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFSGSGSGTDFTLTISSVQAEDVAVYYCQNAYYYPFT FGQGTKLEIK (SEQ ID NO: 51);
aj. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
DVKLVESGGGLVKPGGSLKLSCAASGFTFSSYTMSWVRQTPEKRLEWVATII IGGSYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCTRLVKGN AMDYWGQGTSVAVSS (SEQ ID NO: 10), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPSSLTVTTGEKVTMSCKSSQSLLNSGNQKNYLSWYQQIPGQPPKL LFYWASTRESGVPDRFTGSGSGTDFTLTISNVQAEDLAVYYCQNDYSYPFTF GAGTKLELR (SEQ ID NO: 11);
ak. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
DVKLVESGGGLVKPGGSLKLSCAASGFTFTSYTMSWVRQTPEKRLEWVATII IGGSYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCTRLVKGN AMDYWGQGTSVTVSS (SEQ ID NO: 12), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DILMTQSPSSLTVTAGEKVTMTCKSSQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASSRESGVPDRFTGSGSGTDFTLTISSVQAEDLAVYYCQNDYSYPFTF GAGTKLELK (SEQ ID NO: 13);
al. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
DVKLVESGGGLVKPGGSLKLSCAASGFTFSSYTMSWVRQTPEKRLYWVATI SSGVSYTYYPDSVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCTRLTKG NAMDYWGQGTSVTVSS (SEQ ID NO: 14), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPSSLTVTAGEKVTMSCKSSQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFTGSGSGTGFTLTISSVQAEDLAVYYCQNDYSYPFTF GAGTKLELK (SEQ ID NO: 15);
am. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
VVQLVESGGDFVQPGGSRKLSCAVSGFTFSSFGMHWVRQAPEKGLEWVAYI SSGTTNIYYADTVKGRFTVSRDNPKNSLFLHMTSLRSEDTAMYYCVRSGYY GNSLDYWGQGTPLTVSS (SEQ ID NO: 16), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPSSLTVTAGEKVTMSCKSSQSLFNSGNQRNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFTGSGSGTGFTLTISSVQAEDLAFYYCQNVYIYPLTF GLGTKLELR (SEQ ID NO: 17);
an. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
QVQLQQSGAELARPGASVKLSCKASDYTFTSYVISWVKQRTGQGLEWIGEIY PRNGNTYYNEKFKGKATLTADKSSSTAYMELRSLTSEDSAVYFCARSYYGN SFAYWGQGTLVTVSA (SEQ ID NO: 18), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPSSLTVTAGEKVTMSCKSSQSLLNSGNQKNYLTWYQQRPGQPPK LLIYWASTRESGVPDRFTGSGSGTDFTLTISSVQAEDLAVYCCQNNYYYPFTF GGGTKLGIK (SEQ ID NO: 19);
ao. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
VVQLQQSGPELVKPGASVKMSCKASGYTFTSYLMHWVRQKPGLGLDWIGY INPYNDGTNYNAKFIDKATLTSDKTSSTAYMELSSLTSEDSAIYYCTRGDYW GQGTSVTVSS (SEQ ID NO: 20), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPSSLAVTAGEQVTMSCKSSQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASIRQSGVPDRFTGSGSGTDFTLTISSVQAEDLAVYYCLNDYGFPLTF GAGTKLELK (SEQ ID NO: 21);
ap. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
QIQLQQSGAELARPRASVKLSCKASGYTFTSDVISWVKQRPGQGLEWIGESY LRNGNTYYNENFKGKATLTADKSSSTAYMELRSLTSEDSAVYFCARSYYGN SFAYWGQGTLVTVSA (SEQ ID NO: 22), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPSSLTVTAREKVTMNCKSTQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASTRESGVPDRFTGSGSGTDFTLTISSVQAEDLAVYYCQNAYYYPFTF GGGTKLEIK (SEQ ID NO: 23);
aq. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
QVQLKESGPGLVAPSQSLSITCTVSGFSLNSYGVSWVRQPPGKGLEWLGVIW GDGSTNYHSALKSRLNINKDKSKSQVFLKLNSLQTDDTATYYCARPTRGNA MDYWGQGTSVTVSS (SEQ ID NO: 24), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DVVMTQSPSSLTVTAGEKVTMNCKSSQSLLNSGNQRSYLTWYQQKPGQPPK LLIYWASTRESGAPDRFTGSGSGADFTLTISSVQAEDLAIYYCQNNYNYPFTF GSGTKLEIK (SEQ ID NO: 25);
ar. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLQQSGPELVKPGASVRMSCKASGYTFTSYIMHWVKQKPGQGPEWMGY INPYNDGTNYNEKFKDKATLTSDKSSSTAYMDLSSLTSEDSAVYYCTRGDY WGQGTSVTVSS (SEQ ID NO: 26), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPSSLTVTAGEKVTMSCKSSQSLLNSGNQKNYLTWYQQKPGQPPK LLFYWASTKKSGVPDRFTGSGSRTDFTLTISSVQAEDLAVYYCLNDYSFPLTF GAGTKLELK (SEQ ID NO: 27);
as. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLQQSGPELVKPGASVKMSCKASGYTFTSYLIHWVKQKPGQGLEWIGYI NPYNDATYYNEKFKAKATLTSDKSSSTAYMELSSLTSEDTAIYYCTRGDYW SQGTSVTVSS (SEQ ID NO: 28), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPSSLTVTAGEKVTMSCKSSQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASTRQSGVPDRFTGSGSGTDFTLTISSVQAEDLTVYYCLNDYSFPLTF GAGTKLELK (SEQ ID NO: 29);
at. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLQQSGPELVKPGASVKMSCKASGYTFTSYVMHWVKQKPGQGLEWIGY FNPYNDDTKYNEKFKGKATLTSDKSSSTAYMDLSSLTSEDSAVYXCTRGDY WGQGTSVTVSS (SEQ ID NO: 30), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPSSLTVTAGEKVTMTCKSSQSLLNSGNQKNYLTWYQQKPGQPPK LLIYWASTGASGVPDRFTGSGSGTDFTLTISSAQAADLAVYYCLNDYSFPLTF GAGTKLELK (SEQ ID NO: 31);
au. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
VVQLQQSGPELVKPGASVKMSCKASGYTFTSFLIHWVRQKPGLGLEWIGYIN PYDYGINYNVKFMDKVTLTSDKTSSTAYMELSSLTSADSAIYYCTRGDYWG QGTSVIVSS (SEQ ID NO: 32), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPSSLAVTTGEQVTMNCKSSQSLLNSGNQKNYLTWYQQKTGQSPK LLIYWASTRQSGVPDRFTGSGSGTDFTLTISSVQAEDLAVYYCLNDYGFPLTF GAGTKLELK (SEQ ID NO: 33);
av. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EVQLQQSGPELVKPGASVKMSCKASGFTFTSYVMHWVKQKSGQGLEWIGYI NPYNDDIKYNAKFEDKATLTSDRSSSTAYMELSSLTSDDSAVYFCTRGDYW GQGTTLTVSS (SEQ ID NO: 34), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIVMTQSPSSLTVTTGEKVTMDCKSSQSLLNSGNQKNYLTWYQQKSGQPPK LLIYWASIRKSGVPDRFTGSGSGTDFTLTISSVQAEDLAVYYCLNDYSFPLTF GAGTKLELK (SEQ ID NO: 35);
aw. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
EFQLQQSGPELVKPGASVKISCKASVYSFTGYNMNWVKQSNGKSLEWIGVI NPNYGNTNYNQRFKGKATLTVDQSSSTAYMQLNSLTSEDSAVYYCARSEDY YNIRGASWGQGTLVTVSA (SEQ ID NO: 36), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
QIVLTQSPAIMSASPGQKVTITCSASSTINYMHWYQQKLGSSPKLWIYDTSKL APGVPARFSGSGSGTSYSLTISSMEAEDAASYFCHQWSSYPPTFGSGTKLELK (SEQ ID NO: 37); and
ax. CDR1-3 derived from a heavy chain variable region comprising the amino acid sequence:
QVQLQQSGAELARPGASVKLSCKASGYTFTSYGISWVKQRTGQGLEWIGEIS PRSGNTYYNEKFKGKATLTADKSSSTAYMELRSLTSEDSAVYFCATGVITTV IPTDWYFDVWGTGTTVTVSS (SEQ ID NO: 38), and CDR1-3 derived from a light chain variable region comprising the amino acid sequence:
DIQMTQTTSSLSASLGDRVTISCRASQDISNYLNWYQQKPDGTVKLLIYYTSR LHSGVPSRFSGSGSGTDYSLTISNLEPEDIATYYCQHYSKLPPTFGSGTKLEIK (SEQ ID NO: 39).
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