Recombinant tumor specific antibody and use thereof
First Claim
Patent Images
1. A recombinant anti-EpCAM antibody, wherein the antibody comprises an amino acid sequence defining an immunoglobulin light chain framework region selected from the group consisting of:
- (i) amino acid residues 1-23 of SEQ ID NO;
5, wherein Xaa1 is Q or E, Xaa3 is L or V, Xaa10 is I or T, Xaa11 is M or L, Xaa13 is A or L, Xaa18 is K or R, or Xaa21is M or L, provided that at least one of the amino acid residues at positions Xaa1, Xaa3, Xaa10, Xaa11, Xaa13, Xaa18, or Xaa21 is not the same as the amino acid at the corresponding position in SEQ ID NO;
1;
(ii) amino acid residues 34-48 of SEQ ID NO;
5, wherein Xaa41 is S or Q, Xaa42 is S or A, Xaa45 is P or L, or Xaa46 is W or L, provided that at least one of the amino acid residues at positions Xaa41, Xaa42, Xaa45, or Xaa46 is not the same as the amino acid at the corresponding position in SEQ ID NO;
1; and
(iii) amino acid residues 56-87 of SEQ ID NO;
5, wherein Xaa57 is F or I, Xaa69 is S or D, Xaa71 is S or T, Xaa73 is I or T, Xaa77 is M or L, Xaa79 is A or P, Xaa82 is A or F, or Xaa84 is T or V, provided that at least one of the amino acid residues at positions Xaa57, Xaa69, Xaa71, Xaa73, Xaa77, Xaa79, Xaa82, or Xaa84 is not the same as the amino acid at the corresponding position in SEQ ID NO;
1.
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Accused Products
Abstract
The invention provides a family of antibodies that specifically bind the human epithelial cell adhesion molecule. The antibodies comprise modified variable regions, more specially, modified framework regions, which reduce their immunogenicity when administered to a human. The antibodies, when coupled to the appropriate moiety, may be used in the diagnosis, prognosis and treatment of cancer.
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Citations
18 Claims
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1. A recombinant anti-EpCAM antibody, wherein the antibody comprises an amino acid sequence defining an immunoglobulin light chain framework region selected from the group consisting of:
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(i) amino acid residues 1-23 of SEQ ID NO;
5, wherein Xaa1 is Q or E, Xaa3 is L or V, Xaa10 is I or T, Xaa11 is M or L, Xaa13 is A or L, Xaa18 is K or R, or Xaa21is M or L, provided that at least one of the amino acid residues at positions Xaa1, Xaa3, Xaa10, Xaa11, Xaa13, Xaa18, or Xaa21 is not the same as the amino acid at the corresponding position in SEQ ID NO;
1;
(ii) amino acid residues 34-48 of SEQ ID NO;
5, wherein Xaa41 is S or Q, Xaa42 is S or A, Xaa45 is P or L, or Xaa46 is W or L, provided that at least one of the amino acid residues at positions Xaa41, Xaa42, Xaa45, or Xaa46 is not the same as the amino acid at the corresponding position in SEQ ID NO;
1; and
(iii) amino acid residues 56-87 of SEQ ID NO;
5, wherein Xaa57 is F or I, Xaa69 is S or D, Xaa71 is S or T, Xaa73 is I or T, Xaa77 is M or L, Xaa79 is A or P, Xaa82 is A or F, or Xaa84 is T or V, provided that at least one of the amino acid residues at positions Xaa57, Xaa69, Xaa71, Xaa73, Xaa77, Xaa79, Xaa82, or Xaa84 is not the same as the amino acid at the corresponding position in SEQ ID NO;
1. - View Dependent Claims (3, 4, 8, 9, 10, 11, 13, 16, 17, 18)
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2. A recombinant anti-EpCAM antibody, wherein the antibody comprises an amino acid sequence defining an immunoglobulin heavy chain framework region selected from the group consisting of:
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(i) amino acid residues 1-25 of SEQ ID NO;
6, wherein Xaa2 is I or V, Xaa9 is P or A, Xaa11 is L or V, or Xaa17 is T or S, provided that at least one of the amino acid residues at positions Xaa2, Xaa9, Xaa11 or Xaa17 is not the same as the amino acid at the corresponding position in SEQ ID NO;
2;
(ii) amino acid residues 36-49 of SEQ ID NO;
6, wherein Xaa38 is K or R, Xaa40 is T or A, or Xaa46 is K or E, provided that at least one of the amino acid residues at positions Xaa38, Xaa40, Xaa46 is not the same as the amino acid at the corresponding position in SEQ ID NO;
2;
(iii) amino acid residues 67-98 of SEQ ID NO;
6, wherein Xaa68 is F or V, Xaa69 is A or T, Xaa70 is F or I, Xaa73 is E or D, Xaa76 is A or T, Xaa80 is F or Y, Xaa83 is I or L, Xaa84 is N or S, Xaa85 is N or S, Xaa88 is N, A or S, Xaa91 is M or T, or Xaa93 is T or V, provided that at least one of the amino acid residues at positions Xaa68, Xaa69, Xaa70, Xaa73, Xaa76, Xaa80, Xaa83, Xaa84, Xaa85, Xaa88, Xaa91 or Xaa93 is not the same as the amino acid at the corresponding position in SEQ ID NO;
2; and
(iv) amino acid residues 106-116 of SEQ ID NO;
6, wherein Xaa108 is Q or T. - View Dependent Claims (5, 6, 12)
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7. A recombinant anti-EpCAM antibody comprising light chain amino acid residues 1-106 of SEQ ID NO:
- 9 and heavy chain amino acid residues of SEQ ID NO;
18. - View Dependent Claims (14)
- 9 and heavy chain amino acid residues of SEQ ID NO;
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15. An expression vector having a nucleotide sequence set forth in SEQ ID NO:
- 32.
Specification