US 12,577,318 B2Granted

Humanized anti-CA IX antibodies and methods of their use

AssigneeMabpro A.S.

InventorsMiriam Zatovicova, Silvia Pastorekova, Martina Takacova, Monika Barathova, Jaromir Pastorek

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Abstract

A humanized antibody specifically recognizing human CA IX, and to therapeutic and diagnostic methods utilizing this antibody is disclosed. The methods relate in particular to treatment or diagnosis of cancers selected from squamous cell carcinoma, myeloma, small-cell lung cancer, non-small cell lung cancer, glioma, hodgkin's lymphoma, non-hodgkin's lymphoma, acute myeloid leukemia, multiple myeloma, gastrointestinal (tract) cancer, renal cancer, ovarian cancer, liver cancer, lymphoblastic leukemia, lymphocytic leukemia, colorectal cancer, endometrial cancer, kidney cancer, prostate cancer, thyroid cancer, melanoma, chondrosarcoma, neuroblastoma, pancreatic cancer, glioblastoma multiforme, cervical cancer, brain cancer, stomach cancer, bladder cancer, hepatoma, breast cancer, colon carcinoma, mesothelioma, and head and neck cancer.

Claims21

Dependent claims

A humanized antibody, comprising at least one heavy chain variable region selected from the group consisting of:

a heavy chain variable region comprising or having the sequence:
(SEQ ID NO. 33)
X1VX2LVX3SGGGLVQPGX4SLRLSCX5ASGFTFTDYYMHWVRQAPGX6GL
EWX7X8FIRNKASGYTPQYSASVKGRFTISRDX9X10X11X12X13X14YLQM
NSLX15X16EDTAX17YYVRGGHAGSNYWYFDVWGX18GTX19VTVSS
wherein
X1=E or Q
X2=Q or R
X3=E or Q
X4=G or R
X5=A or T
X6=K or R
X7=V or L
X8=A or G
X9=D or N
X10=S or A
X11=K or T or E
X12=N or T
X13=S or I
X14=L or A
X15=K or R
X16=T or A or I
X17=V or I
X18=Q or K
X19=T or L or M;
and
a heavy chain variable region comprising or having the sequence:
(SEQ ID NO. 35)
X32VQLVESGGGX33VQPGX34SLX35LSCAASGFTFNTNAMHWVRQAX36G
X37GLEWVX38RIRSKSNNYTTYYADSVKDRFTISRDX39SKX40TX41YLQ
X42NSLX43X44EDTAVYYCVCGSWFAYWGQGTX45VTVSS
wherein
X32=E or Q
X33=L or V
X34=G or R
X35=K or R
X36=S or P
X37=K or R
X38=A or G
X39=D or N
X40=N or S
X41=A or L
X42=M or V
X43=K or R
X44=T or A
X45=L or T;
and
and further comprising at least one light chain variable region selected from the group consisting of:
a light chain variable region comprising or havinf sequence:
(SEQ IDNO. 34)
DIQMTQSPSX20LSASVGDRVTIX21CHVSQNINVWLSWYQQKPGX22AP
X23LLIYQASNLHTGVPSRFSGSGSGTX24FTX25TIX26SLQPX27DX28X29
TYYCQQGQSYPFTFGX30GTKX31EIK
wherein
X20=S or T
X21=T or N
X22=K or N or E
X23=N or K
X24=H or E or D or G
X25=L or F
X26=S or G or R
X27=E or D
X28=I or F or Y
X29=A or V
X30=Q or G
X31=V or L;
and
a light chain variable region comprising or having sequence:
(SEQ ID NO. 36)
DX46X47MTQSPDSLAVSLGERX48TINCKSSQSLLNSSNQKNYLAWX49QQK
PGQX50PX51X52X53IYFTSTRQSGVPDRFX54GSGSGTDFTLTIX55SLQAE
DVAVYX56CQQHYSIPLTFGQGTX57X58EIK
X46=V or I
X47=V or Q
X48=V or A
X49=Y or F
X50=S or P
X51=K or N
X52=L or V
X53=L or V
X54=S or T
X55=S or N
X56=Y or F
X57=K or Q
X58=L or V.

82 more elements

Dependencies are inferred from the claim text.