Anti-IL13 antibodies and uses thereof
View Patent ↗The present invention relates to anti-IL13 antibodies that bind specifically and with high affinity to both glycosylated and non-glycosylated human IL13, does not bind mouse IL13, and neutralize human IL13 activity at an approximate molar ratio of 1:2 (MAb:IL13). The invention also relates to the use of these antibodies in the treatment of IL13-mediated diseases, such as allergic disease, including asthma, allergic asthma, non-allergic (intrinsic) asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, eczema, urticaria, food allergies, chronic obstructive pulmonary disease, ulcerative colitis, RSV infection, uveitis, scleroderma, and osteoporosis.
1. A polynucleotide encoding a heavy chain or a variable heavy chain region of a monoclonal antibody that specifically binds human IL-13, wherein said monoclonal antibody comprises a heavy and light chain variable region comprising the complementarity determining regions of the anti-IL-13 antibody produced by a hybridoma designated with American Type Culture Collection (“ATCC”) accession number PTA-5657.
2. A polynucleotide encoding a light chain or a variable light chain region of a monoclonal antibody that specifically binds human IL-13, wherein said monoclonal antibody comprises a heavy and light chain variable region comprising the complementarity determining regions of the anti-IL-13 antibody produced by a hybridoma designated with American Type Culture Collection (“ATCC”) accession number PTA-5657.
3. The polynucleotide of claim 1 , wherein said monoclonal antibody that specifically binds human IL-13 comprises (i) complementarity determining regions CDRH1, CDRH2 and CDRH3 having the sequences of SEQ ID NO: 117, SEQ ID NO: 123, and SEQ ID NO: 135, respectively; and (ii) complementarity determining regions CDRL 1, CDRL2 and CDRL3 having the sequences of SEQ ID NO: 99, SEQ ID NO: 104, and SEQ ID NO: 115, respectively.
4. The polynucleotide of claim 2 , wherein said monoclonal antibody that specifically binds human IL-13 comprises (i) complementarity determining regions CDRH1, CDRH2 and CDRH3 having the sequences of SEQ ID NO: 117, SEQ ID NO: 123, and SEQ ID NO: 135, respectively; and (ii) complementarity determining regions CDRL 1, CDRL2 and CDRL3 having the sequences of SEQ ID NO: 99, SEQ ID NO: 104, and SEQ ID NO: 115, respectively.
5. The polynucleotide of claim 1 , wherein said monoclonal antibody that specifically binds human IL-13 comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 143.
6. The polynucleotide of claim 2 , wherein said monoclonal antibody that specifically binds human IL-13 comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO: 142.
7. The polynucleotide of claim 1 , wherein said monoclonal antibody that specifically binds human IL-13 comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 4, 143, 145, 146, 147, 148 or 149.
8. The polynucleotide of claim 2 , wherein said monoclonal antibody that specifically binds human IL-13 comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO: 3, 142, 144 or 150.
9. The polynucleotide of claim 1 or 3 , wherein said monoclonal antibody that specifically binds human IL-13 is a monovalent antibody, a multispecific antibody, a chimeric antibody, a humanized antibody, a single chain antibody, a Fab fragment or a F(ab′) fragment.
10. The polynucleotide of claim 2 or 4 , wherein said monoclonal antibody that specifically binds human IL-13 is a monovalent antibody, a multispecific antibody, a chimeric antibody, a humanized antibody, a single chain antibody, a Fab fragment or a F(ab′) fragment.
11. The polynucleotide of claim 1 , wherein said monoclonal antibody that specifically binds human IL-13 comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 4.
12. The polynucleotide of claim 2 , wherein said monoclonal antibody that specifically binds human IL-13 comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO: 3.
13. The polynucleotide of claim 9 , wherein the multispecific antibody is a bispecific antibody.
14. The polynucleotide of claim 10 , wherein the multispecific antibody is a bispecific antibody.
15. The polynucleotide of claim 1 or 3 , wherein the monoclonal antibody is a humanized antibody.
16. The polynucleotide of claim 2 or 4 , wherein the monoclonal antibody is a humanized antibody.
17. A polynucleotide encoding a heavy chain or a variable heavy chain region of a monoclonal antibody that specifically binds human IL-13, wherein said monoclonal antibody is a humanized antibody of an antibody produced by a hybridoma designated with ATCC accession number PTA-5657, wherein said humanized antibody comprises (i) complementarity determining regions CDRH1, CDRH2 and CDRH3 having the sequences of SEQ ID NO: 117, SEQ ID NO: 123, and SEQ ID NO: 135, respectively; and (ii) complementarity determining regions CDRL 1, CDRL2 and CDRL3 having the sequences of SEQ ID NO: 99, SEQ ID NO: 104, and SEQ ID NO: 115, respectively.
18. A polynucleotide encoding a light chain or a variable light chain region of a monoclonal antibody that specifically binds human IL-13, wherein said monoclonal antibody is a humanized antibody of an antibody produced by a hybridoma designated with ATCC accession number PTA-5657, wherein said humanized antibody comprises (i) complementarity determining regions CDRH1, CDRH2 and CDRH3 having the sequences of SEQ ID NO: 117, SEQ ID NO: 123, and SEQ ID NO: 135, respectively; and (ii) complementarity determining regions CDRL 1, CDRL2 and CDRL3 having the sequences of SEQ ID NO: 99, SEQ ID NO: 104, and SEQ ID NO: 115, respectively.
19. A polynucleotide encoding a heavy chain or a variable heavy chain region of an antibody that binds human IL-13, wherein said antibody comprises a variable heavy chain region comprising complementarity determining regions CDRH 1, CDRH2 and CDRH3 having the sequences of SEQ ID NO: 117, SEQ ID NO: 123, and SEQ ID NO: 135, respectively; and wherein said antibody comprises a variable light chain region comprising complementarity determining regions CDRL1, CDRL2 and CDRL3 having the sequences of SEQ ID NO: 99, SEQ ID NO: 104, and SEQ ID NO: 115, respectively.
20. A polynucleotide encoding a light chain or a variable light chain region of an antibody that binds human IL-13, wherein said antibody comprises a variable heavy chain region comprising complementarity determining regions CDRH1, CDRH2 and CDRH3 having the sequences of SEQ ID NO: 117, SEQ ID NO: 123, and SEQ ID NO: 135, respectively; and wherein said antibody comprises a variable light chain region comprising complementarity determining regions CDRL 1, CDRL2 and CDRL3 having the sequences of SEQ ID NO: 99, SEQ ID NO: 104, and SEQ ID NO: 115, respectively.
21. The polynucleotide of claim 17 , wherein the monoclonal antibody that specifically binds human IL-13 comprises a heavy chain and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 143 and SEQ ID NO: 142, respectively.
22. The polynucleotide of claim 18 , wherein the monoclonal antibody that specifically binds human IL-13 comprises a heavy chain and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 143 and SEQ ID NO: 142, respectively.
23. The polynucleotide of claim 19 , wherein the antibody that binds human IL-13 comprises the amino acid sequence of SEQ ID NO: 143 and SEQ ID NO: 142.
24. The polynucleotide of claim 20 , wherein the antibody that binds human IL-13 comprises the amino acid sequence of SEQ ID NO: 143 and SEQ ID NO: 142.
25. The polynucleotide of claim 17 or 18 , wherein said monoclonal antibody that specifically binds human IL-13 is selected from the group consisting of: a monovalent antibody, a multispecific antibody, a single chain antibody, a Fab fragment, and a F(ab′) fragment.
26. The polynucleotide of claim 25 , wherein said a multispecific antibody is a bispecific antibody.
27. The polynucleotide of claim 19 or 20 , wherein said antibody that binds human IL-13 is a monovalent antibody, a multispecific antibody, a chimeric antibody, a humanized antibody, a single chain antibody, a Fab fragment, or a F(ab′) fragment.
28. The polynucleotide of claim 27 , wherein said multispecific antibody is a bispecific antibody.
29. The polynucleotide of claim 19 or 20 , wherein said antibody is a monoclonal antibody.
30. The polynucleotide of claim 17 or 18 , wherein the monoclonal antibody is an IgG antibody.
31. The polynucleotide of claim 19 or 20 , wherein the antibody is an IgG antibody.
32. The polynucleotide of claim 30 , wherein the antibody is an IgG1, an IgG2, an IgG3 or an IgG4 antibody.
33. The polynucleotide of claim 31 , wherein the antibody is an IgG1, an IgG2, an IgG3 or an IgG4 antibody.
34. The polynucleotide of claim 1 , 2 , 3 , or 4 , wherein the monoclonal antibody is an IgG1, an IgG2, an IgG3 or an IgG4 antibody.
35. A vector comprising one or more of the polynucleotides of claims 17 , 18 , 19 , and 20 .
36. The vector of claim 35 , wherein said vector comprises a polynucleotide encoding (i) a heavy chain or a variable heavy chain region, and (ii) a light chain or a variable light chain region of the antibody that binds human IL-13.
37. A host cell comprising one or more polynucleotides of claims 17 , 18 , 19 , and 20 .
38. The host cell of claim 37 comprising a polynucleotide encoding a variable heavy chain region and a polynucleotide encoding a variable light chain region of the antibody that binds human IL-13.
39. The host cell of claim 37 , wherein the host cell is a mammalian cell.
40. The host cell of claim 38 , wherein the host cell is a mammalian cell.
41. The host cell of claim 39 , wherein the mammalian cell is a Chinese hamster ovary (CHO) cell.
42. The host cell of claim 40 , wherein the mammalian cell is a Chinese hamster ovary (CHO) cell.
43. The host cell of claim 37 , wherein the host cell is a bacteria.
44. The host cell of claim 38 , wherein the host cell is a bacteria.
45. A method of producing an antibody that binds human IL-13, wherein said method comprises culturing a host cell of claim 38 .
46. A method of producing an antibody that binds human IL-13, wherein said method comprises culturing a host cell of claim 40 that expresses a heavy chain or a variable heavy chain region and a light chain or a variable light chain region of the antibody that binds human IL-13.
47. A method of producing an antibody that binds human IL-13, wherein said method comprises culturing a host cell of claim 40 .
48. The method of claim 45 , further comprising the step of obtaining the antibody expressed by the host cell.
49. The method of claim 46 , further comprising the step of obtaining the antibody expressed by the host cell.
50. The method of claim 47 , further comprising the step of obtaining the antibody expressed by the host cell.