Monoclonal antibody to CEA, conjugates comprising said antibody and their therapeutic use
View Patent ↗An anti-CEA monoclonal antibody, designated 806.077, of murine origin is useful for the diagnosis and therapy of cancer. The antibody complementarity determining regions have the following sequences: heavy chain CDR1 DBYMH CDR2 WIDPENGDTE YAPKFRG, CDR3 LIYAGYLAMD Y; and light chain CDR1 SASSSVTYMH, CDR2 STSNLAS, CDR3 QQRSTYPLT. The antibody optionally is humanized and can be in the form of a conjugate with either an enzyme, such as carboxypeptidase, or a co-stimulatory molecule such as the extracellular domain of human B7.1.
1. An isolated polynucleotide sequence encoding a polypeptide comprising an anti-carcinoembryonic antigen (anti-CEA) antibody (“806.077 Ab”) comprising complementarity determining regions (CDRs) in which the CDRs comprise the following sequences:
a)
heavy chain
CDRI DNYMH (SEQ ID NO: 29)
CDR2 WIDPENGDTE YAPKFRG (SEQ ID NO: 31)
CDR3 LIYAGYLAMD Y(SEQ ID NO: 32); and
b)
light chain
CDRI SASSSVTYMH (SEQ ID NO: 26)
CDR2 STSNLAS (SEQ ID NO: 27)
CDR3 QQRSTYPLT (SEQ ID NO: 28).
2. A host cell transformed with a polynucleotide sequence as defined in claim 1 .
3. A polynucleotide sequence encoding a polypeptide comprising an antibody conjugate comprising an antibody as defined in claim 1 and an effector moiety.
4. A vector comprising a polynucleotide sequence as defined in claim 3 .
5. A host cell transformed with a polynucleotide sequence as defined in claim 3 .
6. A method of making a conjugate as defined in claim 3 which comprises:
subjecting a host cell to conditions conducive to expression of the antibody conjugate.
7. A polynucleotide sequence encoding a polypeptide comprising an antibody as defined in claim 1 , wherein the heavy chain CDRs 1 and 3 are further defined as:
CDR1 FNIKDNYMH (SEQ ID NO: 30); and
CDR3 HVLIYAGYLA MDY (SEQ ID NO: 33).
8. A polynucleotide sequence encoding a polypeptide comprising an antibody as defined in claim 1 , said antibody comprising the following structure:
a heavy chain variable region sequence (SEQ
ID NO: 11)
EVQLQQSGAE LVRSGASVKL SCTASGFNIK DNYMHWVKQR
40
PEQGLEWIAW IDPENGDTEY APKFRGKATL TADSSSNTAY
80
LHLSSLTSED TAVYYCHVLI YAGYLAMDYW GQGTSVAVSS
120
and;
a light chain variable region sequence (SEQ
ID NO: 9)
DIELTQSPAI MSASPGEKVT ITCSASSSVT YMHWFQQKPG
40
TSPKLWIYST SNLASGVPAR FSGSGSGTSY SLTISRMEAE
80
DAATYYCQQR STYPLTFGAG TKLELKRA
108.
9. The polynucleotides sequence of claim 8 , wherein said antibody is a humanized antibody.
10. A polynucleotide sequence encoding a polypeptide comprising a humanized antibody as defined in claim 9 said antibody comprising at least one of the following sequences:
a heavy chain variable region sequence which is VH1 (SEQ ID NO:55);
a light chain variable region sequence which is VK4 (SEQ ID NO: 71);
a human CH1 heavy chain IgG3 constant region;
a human kappa light chain CL region; and
a human IgG3 hinge region.
11. The polynucleotide sequence of claim 10 , wherein said antibody is in the form of an f(ab′) 2 fragment.
12. A vector comprising a polynucleotide as defined in claim 1 , 7 , 8 , 9 , 10 or 11 .