Antibody preparation
AssigneeBTG International Limited
InventorsHerman Waldmann, Mark Frewin
Life of this patent
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AssigneeBTG International Limited
InventorsHerman Waldmann, Mark Frewin
Estimating the term…
An IgG antibody is provided having a binding affinity for the CD3 antigen complex in which in the heavy chain has a variable region framework together with at least one CDR selected from the amino acid sequences of SEQ ID No 2, 4 and 6 and respective conservatively modified variants thereof and the light chain has a variable region framework together with at least one CDR selected from the amino acid sequences of SEQ ID No 8, 10 and 12 and respective conservatively modified variants thereof characterised in that the heavy chain variable region framework corresponds in sequence to the human type sequence and the light chain variable region framework includes one or more of the specific amino acids characteristic of the rodent type sequence. The novel antibody is capable of being expressed by mammalian cell expression systems at enhanced yields.
An IgG antibody having a binding affinity for the CD3 antigen complex in which in the heavy chain has a variable region framework together with at least one CDR selected from the amino acid sequences of SEQ ID No 2, 4 and 6 and respective conservatively modified variants thereof and the light chain has a variable region framework together with at least one CDR selected from the amino acid sequences of SEQ ID No 8, 10 and 12 and respective conservatively modified variants thereof
An antibody as claimed in any one of the preceding claims characterised in that the light chain variable region corresponds to that of SEQ ID No 14 or that sequence altered such that one or more, but not all, of the amino acids Gln-1, Ala-2, Val-3, Val-4, Ala-7, Asn-8, Thr-12, Leu-14, Ser-16, Lys-19, Leu-20, Leu-39, Tyr-40, Glu-41, Ser-44, Met-48, Tyr-50, Phe-75, His-79, Asn-80, Val-81, Ala-82, Ile-83, Ile-88 and Phe-90 arc substituted by corresponding human amino acids selected from Asp-1, Phe-2, Met-3, Leu-4, Pro-7, His-8, Glu-12, Pro-14, Lys-15, Ile-19, Ile-20, Gln-39, Arg-40, Pro-41, Ala-44, Val-48, Phe-50, Ser-75, Ser-79, Gly-80, Leu-81, Gln-82, Thr-83, Asp-88 and Tyr-90.
An antibody as claimed in any one of the preceding claims characterised in that the heavy chain and/or light chain each have all three of their respective CDRs of SEQ ID No 2, 4 and 6 and SEQ. ID. No 8, 10 and 12.
An antibody as claimed in any one of the preceding claims characterised in that the antibody is aglycosylated.
An antibody as claimed in any one of the preceding claims characterised in that the CDRs are arranged in the heavy chain in the sequence in the order:
An antibody as claimed in any one of the preceding claims characterised in that the human framework regions comprise amino acid sequences SEQ ID No 21, 22, 23 and/or 24
An antibody as claimed in any one of the preceding claims characterised in that the one or more preferred CDRs of the heavy chain of the rat anti-CD3 antibody are present in a human variable domain framework which has the amino acid sequence reading in the leader to constant region direction comprising SEQ ID No 21/CDR/SEQ ID No 22/CDR/SEQ ID No 23/CDR/SEQ ID No 24.
An antibody as claimed in any one of the preceding claims characterised in that the antibody constant region is of human type.
An antibody as claimed in any one of the preceding claims characterised in that the antibody constant region comprises the human type lambda constant region.
An antibody as claimed in any one of the preceding claims characterised in that the rodent light chain variable region is attached to human type lambda constant region.
An antibody as claimed in any one of the preceding claims characterised in that it comprises a rat light chain variable domain framework region of SEQ ID No 14.
An antibody as claimed in any one of the preceding claims characterised in that it comprises a rat human chimeric light chain and lambda constant region amino acid sequence SEQ ID No 18.
An aglycosylated antibody according any one of the preceding claims in which asparagine residue at position 297 of the constant region heavy chain is replaced by an alternative amino acid residue.
An aglycosylated antibody according to any of the preceding claims, in which only one of the arms thereof has an affinity for the CD3 antigen.
An aglycosylated antibody according to any one of the preceding claims characterised in that it is in the form of a pharmaceutical composition comprising a physiologically acceptable diluent or carrier.
Recombinant nucleic acid encoding for an antibody as claimed in any one of the preceding claims.
Recombinant nucleic acid characterised in that it encodes for a protein comprising an amino acid sequence SEQ ID No 18
Recombinant DNA of SEQ ID No 17.
Dependencies are inferred from the claim text.