Biological products
AssigneeUCB Celltech
InventorsDiljeet Singh Athwal, Derek Thomas Brown, Andrew Neil Charles Weir, Andrew George Popplewell, Andrew Paul Chapman, David John King
Life of this patent
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Abstract
There is disclosed antibody molecules containing at least one CDR derived from a mouse monoclonal antibody having specificity for human TNFα. There is also disclosed a CDR grafted antibody wherein at least one of the CDRs is a hybrid CDR. Further disclosed are DNA sequences encoding the chains of the antibody molecules, vectors, transformed host cells and uses of the antibody molecules in the treatment of diseases mediated by TNFα.
Claims67
An antibody molecule having specificity for human TNFα, comprising a heavy chain wherein the variable domain comprises a complementarity determining region (CDR) having the sequence given as Hi in FIG. 3 (SEQ ID NO:1) for CDRH1, as H2′ in FIG. 3 (SEQ ID NO:2) or as H2 in FIG. 3 (SEQ ID NO:7) for CDRH2 or as H3 in FIG. 3 (SEQ ID NO:3) for CDRH3.
An antibody molecule having specificity for human TNFα, comprising a light chain wherein the variable domain comprises a CDR having the sequence given as L1 in FIG. 3 (SEQ ID NO:4) for CDRL1, as L2 in FIG. 3 (SEQ ID NO:5) for CDRL2 or as L3 in FIG. 3 (SEQ ID NO:6) for CDRL3.
An antibody molecule having specificity for human TNFα, comprising a heavy chain wherein the variable domain comprises a CDR having the sequence given in SEQ ID NO:1 for CDRH1, SEQ ID NO:2 or SEQ ID NO:7, for CDRH2 or SEQ ID NO:3 for CDRH3 and a light chain wherein the variable domain comprises a CDR having the sequence given in SEQ ID NO:4 for CDRL1, SEQ ID NO:5 for CDRL2 or SEQ ID NO:6 for CDRL3.
The antibody molecule of any one of claims 13 which is a Fab fragment.
An antibody molecule having specificity for human TNFα, having a light chain comprising the sequence given in SEQ ID NO:113.
An antibody molecule having specificity for human TNFα, having a light chain consisting of the sequence given in SEQ ID NO:113.
An antibody molecule having specificity for human TNFα, having a heavy chain comprising the sequence given in SEQ ID NO:115.
An antibody molecule having specificity for human TNFα, having a heavy chain consisting of the sequence given in SEQ ID NO:115.
An antibody molecule having specificity for human TNFα, having a light chain comprising the sequence given in SEQ ID NO:113 and a heavy chain comprising the sequence given in SEQ ID NO:115.
An antibody molecule having specificity for human TNFα, having a light chain consisting of the sequence given in SEQ ID NO:113 and a heavy chain consisting of the sequence given in SEQ ID NO:115.
A compound comprising an antibody molecule having specificity for human TNFα, having a light chain comprising the sequence given in SEQ ID NO:113 and a heavy chain comprising the sequence given in SEQ ID NO:115, having attached to one of the cysteine residues at the C-terminal end of the heavy chain one or more synthetic or naturally-occurring polymers.
A compound comprising an antibody molecule having specificity for human TNFα, having a light chain consisting of the sequence given in SEQ ID NO:113 and a heavy chain consisting of the sequence given in SEQ ID NO:115, having attached to one of the cysteine residues at the C-terminal end of the heavy chain one or more synthetic or naturally-occurring polymers.
A compound comprising an antibody molecule having specificity for human TNFα, having a light chain comprising the sequence given in SEQ ID NO:113, having attached to one of the cysteine residues at the C-terminal end of the heavy chain a lysyl-maleimide group wherein each amino group of the lysyl residue has covalently linked to it a methoxypoly(ethyleneglycol) residue having a molecular weight of about 20,000 Da.
A compound comprising an antibody molecule having specificity for human TNFα, having a light chain consisting of the sequence given in SEQ ID NO:113, having attached to one of the cysteine residues at the C-terminal end of the heavy chain a lysyl-maleimide group wherein each amino group of the lysyl residue has covalently linked to it a methoxypoly(ethyleneglycol) residue having a molecular weight of about 20,000 Da.
A compound comprising an antibody molecule having specificity for human TNFα, having a heavy chain comprising the sequence given in SEQ ID NO:115, having attached to one of the cysteine residues at the C-terminal end of the heavy chain a lysyl-maleimide group wherein each amino group of the lysyl residue has covalently linked to it a methoxypoly(ethyleneglycol) residue having a molecular weight of about 20,000 Da.
A compound comprising an antibody molecule having specificity for human TNFα, having a heavy chain consisting of the sequence given in SEQ ID NO:115, having attached to one of the cysteine residues at the C-terminal end of the heavy chain a lysyl-maleimide group wherein each amino group of the lysyl residue has covalently linked to it a methoxy poly(ethyleneglycol) residue having a molecular weight of about 20,000 Da.
A compound comprising an antibody molecule having specificity for human TNFα, having a light chain comprising the sequence given in SEQ ID NO:113 and a heavy chain comprising the sequence given in SEQ ID NO:115, having attached to one of the cysteine residues at the C-terminal end of the heavy chain a lysyl-maleimide group wherein each amino group of the lysyl residue has covalently linked to it a methoxypoly(ethyleneglycol) residue having a molecular weight of about 20,000 Da.
A compound comprising an antibody molecule having specificity for human TNFα, having a light chain consisting of the sequence given in SEQ ID NO:113 and a heavy chain consisting of the sequence given in SEQ ID NO:115, having attached to one of the cysteine residues at the C-terminal end of the heavy chain a lysyl-maleimide group wherein each amino group of the lysyl residue has covalently linked to it a methoxypoly(ethyleneglycol) residue having a molecular weight of about 20,000 Da.
An antibody molecule comprising a hybrid CDR comprising a truncated donor CDR sequence wherein the missing portion of the donor CDR is replaced by a different sequence and forms a functional CDR.
The method of claim 68, wherein the pathology is rheumatoid- or osteo-arthritis.
The vector pDNAbEng-G1 as shown in FIG. 19.
The vector pTTO(CDP870) as shown in FIG. 22.
A polypeptide having the amino acid sequence given in any one of SEQ ID NOS:1 to 7.
Dependencies are inferred from the claim text.