CD1a antibodies and uses thereof
Antibodies, and antigen-binding fragments thereof, that specifically bind to Cluster of Differentiation 1a (CD1a) are provided. Embodiments include uses, and associated methods of using the antibodies, and antigen-binding fragments thereof.
1. An antibody, or antigen binding fragment thereof, that specifically binds to human Cluster of Differentiation 1a (CD1a), comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 30, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 41, a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 17, a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 25, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 27.
2. The antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody, or antigen-binding fragment thereof, comprises at least one of the following:
(i) a heavy chain variable region (VH) framework sequence obtained from a human germline VH sequence selected from the group consisting of IGHV1-2*02, IGHV1-3*01, IGHV1-46*01, IGHV1-69*01, IGHV1-69*02, IGHV1-8*01, IGHV3-7*01, IGHV3-13*01, IGHV3-23*01, IGHV3-23*04, IGHV3-30*01, IGHV3-30*18, IGHV5-10-1*01, IGHV5-10-1*04, and IGHV5-51*01;
(ii) a light chain variable region (VL) framework sequence obtained from a human germline VL sequence selected from the group consisting of IGKV1-12*01, IGKV1-13*02, IGKV1-33*01, IGKV1-39*01, IGKV1-5*01, IGKV3-11*01, IGKV3-15*01, IGKV3-20*01, IGKV3D-20*02, and IGKV4-1*01;
(iii) a heavy chain constant domain comprising an IgA, IgD, IgE, IgM, or IgG; and/or
(iv) a human V K or V λ light chain constant domain.
3. The antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody, or antigen-binding fragment thereof, comprises:
(i)
a VH comprising the amino acid sequence of SEQ ID NO: 55 and a VL comprising the amino acid sequence of SEQ ID NO: 28;
(ii) a HC comprising, or consisting of, the amino acid sequence of SEQ ID NO: 54 and a LC comprising, or consisting of, the amino acid sequence of SEQ ID NO: 24; or
(iii) the amino acid sequence encoded by the insert in the plasmid deposited at the ATCC and having ATCC Accession No. PTA-126810 and comprising the amino acid sequence encoded by the insert in the plasmid deposited at the ATCC and having ATCC Accession No. PTA-126811.
4. The antibody, or antigen binding fragment thereof, of claim 1 , comprising a VL comprising the sequence of SEQ ID NO:28 and a VH comprising the sequence of SEQ ID NO: 55.
5. The antibody, or antigen binding fragment thereof, of claim 1 , comprising a light chain comprising the amino acid sequence of SEQ ID NO: 24 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 54.
6. The antibody, or antigen-binding fragment thereof, of claim 1 that binds an epitope on Cluster of Differentiation 1a (CD1a), wherein the epitope comprises Glu82 and/or His170, according to the numbering of SEQ ID NO: 1, and where the epitope:
(i) optionally further comprises Ile92 and/or Arg93, according to the numbering of SEQ ID NO: 1, and
(ii) optionally comprises at least one of the following amino acid residues: Glu78, Lys81, Thr85, Ile89, Arg93, Asp173, and Asn177, according to the numbering of SEQ ID NO: 1; and
(iii) optionally comprises at least one of the following residues: Leu86, Asn168, Ile174, His176, Asp181, and Arg185, according to the numbering of SEQ ID NO: 1; and
(iv) optionally comprises at least one of the following residues: Glu79, Leu83, Glu84, Arg88, Ile92, Gln169, Leu178, Ser180, and Thr182 according to the numbering of SEQ ID NO: 1; and
(v) optionally does not comprise Asn146 and/or Asn168 according to the numbering of SEQ ID NO: 1.
7. An isolated nucleic acid molecule comprising a nucleic acid sequence encoding the antibody, or antigen binding fragment thereof, of claim 1 , and optionally wherein said nucleic acid molecule comprises one or more nucleic acid sequences selected from the group consisting of:
(i) the nucleic acid sequence of SEQ ID NO: 80,
(ii) the nucleic acid sequence of SEQ ID NO: 81,
(iii) the nucleic acid sequence of SEQ ID NO: 82,
(iv) the nucleic acid sequence of SEQ ID NO: 83, or
(v)
the nucleic acid sequence of the insert of the vector deposited as Ab571-VH under ATCC Accession No. PTA-126810, and the nucleic acid sequence of the insert of the vector deposited as Ab571-VL under ATCC Accession No. PTA-126811.
8. A vector comprising the nucleic acid molecule of claim 7 .
9. A host cell comprising the vector of claim 8 .
10. A method of making an antibody or antigen-binding fragment thereof, comprising culturing the host cell of claim 9 , under a condition wherein said antibody, or antigen-binding fragment, is expressed by said host cell.
11. A pharmaceutical composition comprising the antibody, or antigen-binding fragment thereof, of claim 1 , and a pharmaceutically acceptable carrier or excipient.
12. A method of treating atopic dermatitis, comprising administering to a subject in need thereof a therapeutically effective amount of the antibody, or antigen-binding fragment thereof, of claim 1 .
13. A method of manufacturing a medicament for treating atopic dermatitis comprising the antibody, or antigen-binding fragment thereof, the method comprising culturing the host cell of claim 9 under a condition wherein said antibody, or antigen-binding fragment, is expressed by said host cell.
14. The antibody, or antigen binding fragment thereof, of claim 1 , for use in the treatment of at least one sign and/or symptom of atopic dermatitis.
15. A kit for the treatment of atopic dermatitis (AD), comprising a therapeutically effective amount of the antibody, or antigen binding fragment thereof, of claim 1 .
16. The antibody, or antigen binding fragment thereof, of claim 1 , comprising the amino acid sequence encoded by the insert in the plasmid deposited at the ATCC and having ATCC Accession No. PTA-126810 and comprising the amino acid sequence encoded by the insert in the plasmid deposited at the ATCC and having ATCC Accession No. PTA-126811.
17. The antibody, or antigen binding fragment thereof, of claim 1 , wherein the antibody, or antigen binding fragment thereof is a humanized or chimeric antibody, or antigen binding fragment thereof.
18. An antibody, or antigen binding fragment thereof, that specifically binds to human Cluster of Differentiation 1a (CD1a), comprising a VH comprising the amino acid sequence of SEQ ID NO: 55 and a VL comprising the amino acid sequence of SEQ ID NO: 28.
19. The antibody, or antigen-binding fragment thereof, of claim 18 , wherein the antibody, or antigen-binding fragment thereof, comprises at least one of the following:
a heavy chain variable region (VH) framework sequence obtained from a human germline VH sequence selected from the group consisting of IGHV1-2*02, IGHV1-3*01, IGHV1-46*01, IGHV1-69*01, IGHV1-69*02, IGHV1-8*01, IGHV3-7*01, IGHV3-13*01, IGHV3-23*01, IGHV3-23*04, IGHV3-30*01, IGHV3-30*18, IGHV5-10-1*01, IGHV5-10-1*04, and IGHV5-51*01;
(ii) a light chain variable region (VL) framework sequence obtained from a human germline VL sequence selected from the group consisting of IGKV1-12*01, IGKV1-13*02, IGKV1-33*01, IGKV1-39*01, IGKV1-5*01, IGKV3-11*01, IGKV3-15*01, IGKV3-20*01, IGKV3D-20*02, and IGKV4-1*01;
(iii) a heavy chain constant domain comprising an IgA, IgD, IgE, IgM, or IgG; and/or
(iv) a human V K or V), light chain constant domain.
20. The antibody, or antigen-binding fragment thereof, of claim 18 , wherein the antibody, or antigen-binding fragment thereof, comprises:
(i) the CDR-H1, CDR-H2, and CDR-H3 sequences as set forth in SEQ ID NO: 55 and the CDR-L1, CDR-L2, and CDR-L3 sequences as set forth in SEQ ID NO: 28;
(ii) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 30, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 41, a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 17, a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 25, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 27;
(iii) a HC comprising, or consisting of, the amino acid sequence of SEQ ID NO: 54 and a LC comprising, or consisting of, the amino acid sequence of SEQ ID NO: 24; or
(iv) the amino acid sequence encoded by the insert in the plasmid deposited at the ATCC and having ATCC Accession No. PTA-126810 and comprising the amino acid sequence encoded by the insert in the plasmid deposited at the ATCC and having ATCC Accession No. PTA-126811.
21. The antibody, or antigen binding fragment thereof, of claim 18 , comprising the CDR-H1, CDR-H2, and CDR-H3 sequences as set forth in SEQ ID NO: 55 and the CDR-L1, CDR-L2, and CDR-L3 sequences as set forth in SEQ ID NO: 28.
22. The antibody, or antigen binding fragment thereof, of claim 18 , comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 30, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 41, a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 17, a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 25, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 27.
23. The antibody, or antigen binding fragment thereof, of claim 18 , comprising a light chain comprising the amino acid sequence of SEQ ID NO: 24 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 54.
24. The antibody, or antigen binding fragment thereof, of claim 18 , comprising the amino acid sequence encoded by the insert in the plasmid deposited at the ATCC and having ATCC Accession No. PTA-126810 and comprising the amino acid sequence encoded by the insert in the plasmid deposited at the ATCC and having ATCC Accession No. PTA-126811.
25. The antibody, or antigen-binding fragment thereof, of claim 18 that binds an epitope on Cluster of Differentiation 1a (CD1a), wherein the epitope comprises Glu82 and/or His170, according to the numbering of SEQ ID NO: 1, and where the epitope:
(i) optionally further comprises Ile92 and/or Arg93, according to the numbering of SEQ ID NO: 1, and
(ii) optionally comprises at least one of the following amino acid residues: Glu78, Lys81, Thr85, Ile89, Arg93, Asp173, and Asn177, according to the numbering of SEQ ID NO: 1; and
(iii) optionally comprises at least one of the following residues: Leu86, Asn168, Ile174, His176, Asp181, and Arg185, according to the numbering of SEQ ID NO: 1; and
(iv) optionally comprises at least one of the following residues: Glu79, Leu83, Glu84, Arg88, Ile92, Gln169, Leu178, Ser180, and Thr182 according to the numbering of SEQ ID NO: 1; and
(v) optionally does not comprise Asn146 and/or Asn168 according to the numbering of SEQ ID NO: 1.
26. An isolated nucleic acid molecule comprising a nucleic acid sequence encoding the antibody, or antigen binding fragment thereof, of claim 18 , and optionally wherein said nucleic acid molecule comprises one or more nucleic acid sequences selected from the group consisting of:
(i) the nucleic acid sequence of SEQ ID NO: 80,
(ii) the nucleic acid sequence of SEQ ID NO: 81,
(iii) the nucleic acid sequence of SEQ ID NO: 82,
(iv) the nucleic acid sequence of SEQ ID NO: 83, or
(v) the nucleic acid sequence of the insert of the vector deposited as Ab571-VH under ATCC Accession No. PTA-126810, and the nucleic acid sequence of the insert of the vector deposited as Ab571-VL under ATCC Accession No. PTA-126811.
27. A vector comprising the nucleic acid molecule of claim 26 .
28. A host cell comprising the vector of claim 27 .
29. A method of making an antibody or antigen-binding fragment thereof, comprising culturing the host cell of claim 28 , under a condition wherein said antibody, or antigen-binding fragment, is expressed by said host cell.
30. A pharmaceutical composition comprising the antibody, or antigen-binding fragment thereof, of claim 18 , and a pharmaceutically acceptable carrier or excipient.
31. The antibody, or antigen binding fragment thereof, of claim 18 , for use in the treatment of at least one sign and/or symptom of atopic dermatitis.
32. A method of manufacturing a medicament for treating atopic dermatitis comprising the antibody, or antigen-binding fragment thereof, the method comprising culturing the host cell of claim 27 under a condition wherein said antibody, or antigen-binding fragment, is expressed by said host cell.
33. A method of treating atopic dermatitis, comprising administering to a subject in need thereof a therapeutically effective amount of the antibody, or antigen-binding fragment thereof, of claim 18 .
34. A kit for the treatment of atopic dermatitis (AD), comprising a therapeutically effective amount of the antibody, or antigen binding fragment thereof, of claim 18 .
35. The antibody, or antigen binding fragment thereof, of claim 18 , wherein the antibody, or antigen binding fragment thereof, is a humanized or chimeric antibody, or antigen binding fragment thereof.
36. An antibody, or antigen binding fragment thereof, that specifically binds to human Cluster of Differentiation 1a (CD1a), comprising the CDR-H1, CDR-H2, and CDR-H3 sequences as set forth in SEQ ID NO: 55 and the CDR-L1, CDR-L2, and CDR-L3 sequences as set forth in SEQ ID NO: 28.
37. The antibody, or antigen-binding fragment thereof, of claim 36 , wherein the antibody, or antigen-binding fragment thereof, comprises at least one of the following:
a heavy chain variable region (VH) framework sequence obtained from a human germline VH sequence selected from the group consisting of IGHV1-2*02, IGHV1-3*01, IGHV1-46*01, IGHV1-69*01, IGHV1-69*02, IGHV1-8*01, IGHV3-7*01, IGHV3-13*01, IGHV3-23*01, IGHV3-23*04, IGHV3-30*01, IGHV3-30*18, IGHV5-10-1*01, IGHV5-10-1*04, and IGHV5-51*01;
(ii) a light chain variable region (VL) framework sequence obtained from a human germline VL sequence selected from the group consisting of IGKV1-12*01, IGKV1-13*02, IGKV1-33*01, IGKV1-39*01, IGKV1-5*01, IGKV3-11*01, IGKV3-15*01, IGKV3-20*01, IGKV3D-20*02, and IGKV4-1*01;
(iii) a heavy chain constant domain comprising an IgA, IgD, IgE, IgM, or IgG; and/or
(iv) a human V K or V), light chain constant domain.
38. The antibody, or antigen-binding fragment thereof, of claim 36 , wherein the antibody, or antigen-binding fragment thereof, comprises:
(i) a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 30, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 41, a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 17, a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 25, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 27;
(ii) a VH comprising the amino acid sequence of SEQ ID NO: 55 and a VL comprising the amino acid sequence of SEQ ID NO: 28;
(iii) a HC comprising, or consisting of, the amino acid sequence of SEQ ID NO: 54 and a LC comprising, or consisting of, the amino acid sequence of SEQ ID NO: 24; or
(iv) the amino acid sequence encoded by the insert in the plasmid deposited at the ATCC and having ATCC Accession No. PTA-126810 and comprising the amino acid sequence encoded by the insert in the plasmid deposited at the ATCC and having ATCC Accession No. PTA-126811.
39. The antibody, or antigen binding fragment thereof, of claim 36 , comprising a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 30, a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 41, a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 17, a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 25, a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 26, and a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 27.
40. The antibody, or antigen binding fragment thereof, of claim 36 , comprising a VH comprising the amino acid sequence of SEQ ID NO: 55 and a VL comprising the amino acid sequence of SEQ ID NO: 28.
41. The antibody, or antigen binding fragment thereof, of claim 36 , comprising a HC comprising, or consisting of, the amino acid sequence of SEQ ID NO: 54 and a LC comprising, or consisting of, the amino acid sequence of SEQ ID NO: 24.
42. The antibody, or antigen binding fragment thereof, of claim 36 , comprising the amino acid sequence encoded by the insert in the plasmid deposited at the ATCC and having ATCC Accession No. PTA-126810 and comprising the amino acid sequence encoded by the insert in the plasmid deposited at the ATCC and having ATCC Accession No. PTA-126811.
43. The antibody, or antigen-binding fragment thereof, of claim 36 that binds an epitope on Cluster of Differentiation 1a (CD1a), wherein the epitope comprises Glu82 and/or His170, according to the numbering of SEQ ID NO: 1, and where the epitope:
(i) optionally further comprises Ile92 and/or Arg93, according to the numbering of SEQ ID NO: 1, and
(ii) optionally comprises at least one of the following amino acid residues: Glu78, Lys81, Thr85, Ile89, Arg93, Asp173, and Asn177, according to the numbering of SEQ ID NO: 1; and
(iii) optionally comprises at least one of the following residues: Leu86, Asn168, Ile174, His176, Asp181, and Arg185, according to the numbering of SEQ ID NO: 1; and
(iv) optionally comprises at least one of the following residues: Glu79, Leu83, Glu84, Arg88, Ile92, Gln169, Leu178, Ser180, and Thr182 according to the numbering of SEQ ID NO: 1; and
(v) optionally does not comprise Asn146 and/or Asn168 according to the numbering of SEQ ID NO: 1.
44. An isolated nucleic acid molecule comprising a nucleic acid sequence encoding the antibody, or antigen binding fragment thereof, of claim 36 , and optionally wherein said nucleic acid molecule comprises one or more nucleic acid sequences selected from the group consisting of:
(i) the nucleic acid sequence of SEQ ID NO: 80,
(ii) the nucleic acid sequence of SEQ ID NO: 81,
(iii) the nucleic acid sequence of SEQ ID NO: 82,
(iv) the nucleic acid sequence of SEQ ID NO: 83, or
(v) the nucleic acid sequence of the insert of the vector deposited as Ab571-VH under ATCC Accession No. PTA-126810, and the nucleic acid sequence of the insert of the vector deposited as Ab571-VL under ATCC Accession No. PTA-126811.
45. A vector comprising the nucleic acid molecule of claim 44 .
46. A host cell comprising the vector of claim 45 .
47. A method of making an antibody or antigen-binding fragment thereof, comprising culturing the host cell of claim 46 , under a condition wherein said antibody, or antigen-binding fragment, is expressed by said host cell.
48. A pharmaceutical composition comprising the antibody, or antigen-binding fragment thereof, of claim 36 , and a pharmaceutically acceptable carrier or excipient.
49. The antibody, or antigen binding fragment thereof, of claim 36 , for use in the treatment of at least one sign and/or symptom of atopic dermatitis.
50. A method of manufacturing a medicament for treating atopic dermatitis comprising the antibody, or antigen-binding fragment thereof, the method comprising culturing the host cell of claim 46 under a condition wherein said antibody, or antigen-binding fragment, is expressed by said host cell.
51. A method of treating atopic dermatitis, comprising administering to a subject in need thereof a therapeutically effective amount of the antibody, or antigen-binding fragment thereof, of claim 36 .
52. A kit for the treatment of atopic dermatitis (AD), comprising a therapeutically effective amount of the antibody, or antigen binding fragment thereof, of claim 36 .
53. The antibody, or antigen binding fragment thereof, of claim 36 , wherein the antibody, or antigen binding fragment thereof, is a humanized or chimeric antibody, or antigen binding fragment thereof.