Reshaped human anti-HM 1.24 antibody
The invention provides a reshaped human anti-HM 1.24 antibody having: (A) an L chain having (1) the C region of a human L chain, and (2) the V region of an L chain having the FR of a human L chain and the CDR of the L chain of a mouse anti-HM 1.24 monoclonal antibody; and (B) an H chain having (1) the C region of a human H chain, and (2) the V region of an H chain having the FR of a human H chain and the CDR of the H chain of a mouse anti-HM 1.24 monoclonal antibody. This reshaped human antibody is derived from human antibody and the CDR has a low antigenicity, and the reshaped human antibody of the present invention has a low antigenicity and can be used for medical treatment.
1. An isolated or recombinant nucleic acid encoding an L chain and an H chain of an antibody, comprising a nucleotide sequence encoding a V region of the L chain
comprising the amino acid sequence of SEQ ID NO:104, and
a nucleotide sequence encoding a V region of the H chain comprising the amino acid sequence of SEQ ID NO:105.
2. The isolated or recombinant nucleic acid of claim 1 wherein the nucleotide sequence encoding said V region of the L chain comprises the nucleotide sequence of SEQ ID NO:1, and the nucleotide sequence encoding said V region of the H chain comprises the nucleotide sequence of SEQ ID NO:2.
3. The isolated or recombinant nucleic acid of claim 1 , further comprising a nucleotide sequence encoding a C region of a human L chain and/or the C region of a human H chain.
4. An isolated or recombinant nucleic acid comprising:
(A) a nucleotide sequence encoding a V region of a reshaped human L chain of an anti-HM 1.24 antibody comprising the amino acid sequence of SEQ ID NO:106 from position 1 to 107; and
(B) a nucleotide sequence encoding a V region of a reshaped human H chain of an anti-HM 1.24 antibody comprising the amino acid sequence of SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125 or SEQ ID NO:128, from position 1 to position 120.
5. The isolated or recombinant nucleic acid of claim 4 , wherein the nucleotide sequence encoding the V region of the reshaped human L chain comprises the nucleotide sequence of SEQ ID NO:9 from position 58 to 378.
6. The isolated or recombinant nucleic acid of claim 4 , wherein the nucleotide sequence encoding the V region of the reshaped human H chain comprises the nucleotide sequence of SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:28 or SEQ ID NO:102, from position 58 to position 417.
7. The isolated or recombinant nucleic acid of claim 4 further comprising a nucleotide sequence encoding the C region of a human L chain; and/or the C region of a human H chain.
8. An isolated or recombinant nucleic acid, comprising:
(A) a nucleotide sequence encoding a V region of a reshaped human L chain of an anti-HM 1.24 antibody comprising the amino acid sequence of SEQ ID NO:106; and
(B) a nucleotide sequence encoding a V region of a reshaped human H chain on an anti-HM 1.24 antibody comprising the amino acid sequence of SEQ ID NO:113, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125 or SEQ ID NO:128.
9. An isolated vector comprising the nucleic acid of claim 3 .
10. An isolated vector comprising the nucleic acid of claim 4 .
11. An isolated vector comprising the nucleic acid of claim 7 .
12. An isolated cell modified with the vector of claim 9 .
13. An isolated cell modified with the vector of claim 10 .
14. An isolated cell modified with the vector of claim 11 .
15. A method for preparing an antibody, comprising:
a cell modified with the vector of claim 9 under conditions wherein the antibody-encoding nucleic acid is expressed, and
recovering said antibody from the culture.
16. A method for preparing an antibody, comprising:
culturing a cell modified with the vector of claim 10 under conditions wherein the antibody-encoding nucleic acid is expressed, and
recovering said antibody from the culture.
17. A method for preparing an antibody, comprising:
culturing a cell modified with the vector of claim 11 under conditions wherein the antibody-encoding nucleic acid is expressed, and
recovering said antibody from the culture.
18. An isolated or recombinant nucleic acid encoding an L chain and an H chain of an antibody, comprising:
a nucleotide sequence encoding a V region of the L chain, wherein the nucleotide sequence comprises the amino acid sequence from position 1 to position 107 of SEQ ID NO:104, and
a nucleotide sequence encoding a V region of the H chain, wherein the nucleotide sequence comprises the amino acid sequence from position 1 to position 120 of SEQ ID NO:105.
19. The isolated or recombinant nucleic acid of claim 18 wherein the nucleotide sequence encoding said V region of the L chain comprises the nucleotide sequence of position 73 to position 393 of SEQ ID NO:1, and the nucleotide sequence encoding said V region of the H chain comprises the nucleotide sequence of position 58 to position 417 of SEQ ID NO:2.
20. The isolated or recombinant nucleic acid of claim 19 , further comprising a nucleotide sequence encoding a C region of a human L chain and/or the C region of a human H chain.
21. The isolated or recombinant nucleic acid of claim 8 , wherein the nucleotide sequence encoding the V region of the reshaped human L chain comprises the nucleotide sequence of SEQ ID NO:9.
22. The isolated or recombinant nucleic acid of claim 8 , wherein the nucleotide sequence encoding the V region of the reshaped human H chain comprises the nucleotide sequence of SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:28, or SEQ ID NO:102.
23. The isolated or recombinant nucleic acid of claim 8 further comprising a nucleotide sequence encoding the C region of a human L chain; and/or the C region of a human H chain.
24. An isolated vector comprising the nucleic acid of claim 1 .
25. An isolated vector comprising the nucleic acid of claim 18 .
26. An isolated vector comprising the nucleic acid of claim 20 .
27. An isolated vector comprising the nucleic acid of claim 8 .
28. An isolated vector comprising the nucleic acid of claim 23 .
29. An isolated cell modified with the vector of claim 24 .
30. An isolated cell modified with the vector of claim 25 .
31. An isolated cell modified with the vector of claim 26 .
32. An isolated cell modified with the vector of claim 27 .
33. An isolated cell modified with the vector of claim 28 .
34. The isolated cell of claim 29 , where said cell is a mammalian cell.
35. The isolated cell of claim 12 , where said cell is a mammalian cell.
36. The isolated cell of claim 30 , where said cell is a mammalian cell.
37. The isolated cell of claim 31 , where said cell is a mammalian cell.
38. The isolated cell of claim 13 , where said cell is a mammalian cell.
39. The isolated cell of claim 14 , where said cell is a mammalian cell.
40. The isolated cell of claim 32 , where said cell is a mammalian cell.
41. The isolated cell of claim 33 , where said cell is a mammalian cell.
42. A method for preparing an antibody which has the nucleotide sequence of claim 1 , wherein the method comprises culturing the cells which are modified with a vector comprising said nucleotide sequence under conditions wherein said nucleic acid is expressed, and
recovering said antibody from the culture.
43. A method for preparing an antibody which is encoded by the nucleotide sequence of claim 18 , wherein the method comprises culturing the cells which are modified with a vector comprising said nucleotide sequence under conditions wherein said nucleic acid is expressed, and
recovering said antibody from the culture.
44. A method for preparing an antibody which is encoded by the nucleotide sequence of claim 20 , wherein the method comprises culturing the cells which are modified with a vector comprising said nucleotide sequence under conditions wherein said nucleic acid is expressed, and
recovering said antibody from the culture.
45. A method for preparing an antibody which has the nucleotide sequence of claim 8 , wherein the method comprises culturing the cells which are modified with a vector comprising said nucleotide sequence under conditions wherein said nucleic acid is expressed, and
recovering said antibody from the culture.
46. A method for preparing an antibody which has the nucleotide sequence of claim 23 , wherein the method comprises culturing the cells which are modified with a vector comprising said nucleotide sequence under conditions wherein said nucleic acid is expressed, and
recovering said antibody from the culture.