Anti-mIgE antibodies that bind to the junction between CH4 and CεmX domains
Antibodies binding to junction regions between the CH4 and CεmX domains of membrane-bound IgE and uses thereof in treating IgE-mediated diseases such as allergic diseases.
1. An isolated anti-IgE antibody, which binds to the amino acid sequence SVNPGLAGGSAQS (SEQ ID NO:11).
2. The isolated anti-IgE antibody of claim 1 , wherein the antibody comprises:
(i) a heavy chain variable region (V H ) that contains a V H complementarity determining region (CDR) 1 of GYTFTNYNVH (SEQ ID NO:8), a V H CDR2 of GMYPGNDDILYNQNFKD (SEQ ID NO:9), and a V H CDR3 of SGLQGPWFDY (SEQ ID NO:10); and
(ii) a light chain variable region (V L ) that contains a V L CDR1 of RASDHINNWLA (SEQ ID NO:5), a V L CDR2 of SATSLET (SEQ ID NO:6), and a V L CDR3 of QQCWITPFT (SEQ ID NO:7).
3. The isolated anti-IgE antibody of claim 1 , wherein the antibody comprises:
(i) a heavy chain variable region (V H ) that contains a V H complementary determining region (CDR) 1 of GFSLTDYGVN (SEQ ID NO:19), a V H CDR2 of MIWGDGSTDYNSTL (SEQ ID NO:20), and a V H CDR3 of NWFAY (SEQ ID NO:21); and
(ii) a light chain variable region (V L ) that contains a V L CDR1 of SSSVNYMH (SEQ ID NO:22), a V L CDR2 of DTSKLAS (SEQ ID NO:23), and a V L CDR3 of QQWSSNPW (SEQ ID NO:24).
4. The isolated anti-IgE antibody of claim 1 , wherein the antibody comprises:
a heavy chain variable region set forth as SEQ ID NO:3 and a light chain variable region set forth as SEQ ID NO:4; or
a heavy chain variable region set forth as SEQ ID NO:17 and a light chain variable region set forth as SEQ ID NO:18.
5. The isolated anti-IgE antibody of claim 1 , wherein the antibody binds to the same epitope as an antibody comprising:
a heavy chain variable region set forth as SEQ ID NO:3 and a light chain variable region set forth as SEQ ID NO:4; or
a heavy chain variable region set forth as SEQ ID NO:17 and a light chain variable region set forth as SEQ ID NO:18.
6. The isolated anti-IgE antibody of claim 1 , wherein the antibody is a full length antibody or an antigen-binding fragment thereof.
7. The isolated anti-IgE antibody of claim 1 , wherein the antibody is a human antibody or a humanized antibody.
8. A pharmaceutical composition comprising an anti-IgE antibody of claim 1 , and a pharmaceutically acceptable carrier.
9. An isolated nucleic acid or a nucleic acid set, which encodes or collectively encodes:
(i) a heavy chain variable region (V H ) that contains a V H complementarity determining region (CDR) 1 of GYTFTNYNVH (SEQ ID NO:8), a V H CDR2 of GMYPGNDDILYNQNFKD (SEQ ID NO:9), and a V H CDR3 of SGLQGPWFDY (SEQ ID NO:10); and
(ii) a light chain variable region (V L ) that contains a V L CDR1 of RASDHINNWLA (SEQ ID NO:5), a V L CDR2 of SATSLET (SEQ ID NO:6), and a V L CDR3 of QQCWITPFT (SEQ ID NO:7).
10. The isolated nucleic acid or nucleic acid set of claim 9 , wherein the nucleic acid or nucleic acid set encodes the antibody heavy chain variable region of SEQ ID NO:3 and the antibody light chain variable region of SEQ ID NO: 4.
11. The isolated nucleic acid or nucleic acid set of claim 10 , which comprises the nucleotide sequence of SEQ ID NO:1, and the nucleotide sequence of SEQ ID NO: 2.
12. An isolated nucleic acid or a nucleic acid set, which encodes or collectively encodes:
(i) a heavy chain variable region (V H ) that contains a V H complementarity determining region (CDR1) of GFSLTDYGVN (SEQ ID NO:19), a V H CDR2 of MIWGDGSTDYNSTL (SEQ ID NO:20), and a V H CDR3 of NWFAY (SEQ ID NO:21); and
(ii) a light chain variable region (VL) that contains a V L CDR1 of SSSVNYMH (SEQ ID NO:22), a V L CDR2 of DTSKLAS (SEQ ID NO:23), and a V L CDR3 of QQWSSNPW (SEQ ID NO:24).
13. The isolated nucleic acid or nucleic acid set of claim 12 , wherein the nucleic acid or nucleic acid set encodes the antibody heavy chain variable region of SEQ ID NO: 17 and the antibody light chain variable region of SEQ ID NO:18.
14. A vector or vector set comprising a nucleic acid or nucleic acid set of claim 9 .
15. The vector or vector set of claim 14 , wherein the vector or vector set is an expression vector or expression vector set.
16. A host cell comprising a vector or vector set of claim 14 .
17. A vector or vector set comprising a nucleic acid or nucleic acid set of claim 12 .
18. The vector or vector set of claim 17 , wherein the vector or vector set is an expression vector or expression vector set.
19. A host cell comprising a vector or vector set of claim 17 .
20. A method for treating an IgE-associated disease, comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition of claim 8 .
21. The method of claim 20 , wherein the subject is diagnosed with, suspected of having, or at risk for the IgE-mediated disease.
22. The method of claim 21 , wherein the IgE-mediated disease is an allergic disease.
23. The method of claim 22 , wherein the allergic disease is selected from the group consisting of anaphylaxis, allergic asthma, allergic rhinitis, atopic dermatitis (eczema), dust allergy, insect or reptile venom allergy, food allergy, pollen allergy, and latex allergy.