US 11,834,499 B1
Claudin18 antibodies and methods of treating cancer
Dylan Conklin, Los Angeles, CA (US); Martina S. McDermott, Los Angeles, CA (US); Neil A. O'Brien, Los Angeles, CA (US); Michael J. Palazzolo, Los Angeles, CA (US); and Dennis Slamon, Los Angeles, CA (US)
Assigned to The Regents of the University of California, Oakland, CA (US)
Filed by The Regents of the University of California, Oakland, CA (US)
Filed on Oct. 3, 2022, as Appl. No. 17/959,104.
Application 17/959,104 is a continuation of application No. 17/627,540, previously published as PCT/US2020/042573, filed on Jul. 17, 2020.
Claims priority of provisional application 62/875,416, filed on Jul. 17, 2019.
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/28 (2006.01); A61K 47/68 (2017.01); G01N 33/68 (2006.01); G01N 33/574 (2006.01); A61P 1/18 (2006.01); A61P 35/00 (2006.01); A61K 39/00 (2006.01)
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).