TREATMENT OF EOSINOPHIL OR MAST CELL RELATED DISORDERS
Provided herein are methods and uses involving antibodies that specifically bind to a KIT receptor tyrosine kinase for managing, treating, or preventing an eosinophil or mast cell related disorder and/or one or more symptoms thereof, for example a mast cell related disorder of the nervous system, e.g., central nervous system, for example neuromyelitis optica (NMO), neuromyelitis optica spectrum disorder (NMOSD), multiple sclerosis (MS), and neurofibromatosis (NF).
1 . A method of protecting against, treating, or managing neurofibromatosis (NF) in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of an antibody which specifically binds to a human KIT receptor (SEQ ID NO: 1), or an antigen binding fragment thereof.
2 . A method of inhibiting growth of neurofibromas in a subject, comprising administering to a subject diagnosed with NF a therapeutically effective amount of an antibody which specifically binds to a human KIT receptor (SEQ ID NO: 1), or an antigen binding fragment thereof.
3 . A method of protecting against, treating, or managing an eosinophil or mast cell related disorder of the nervous system in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of an antibody which specifically binds to a human KIT receptor (SEQ ID NO: 1), or an antigen binding fragment thereof.
4 . A method of treating an eosinophil or mast cell related disorder of the nervous system or nervous system in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of an antibody which specifically binds to a human KIT receptor (SEQ ID NO: 1), or an antigen binding fragment thereof.
5 . A method of managing an eosinophil or mast cell related disorder of the nervous system or nervous system in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of an antibody which specifically binds to a human KIT receptor (SEQ ID NO: 1), or an antigen binding fragment thereof.
6 . A method of protecting against, treating, or managing neuromyelitis optica (NMO) in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of an antibody which specifically binds to a human KIT receptor (SEQ ID NO:
1), or an antigen binding fragment thereof.
7 . A method of protecting against, treating, or managing a NMO spectrum disorder (NMOSD) in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of an antibody which specifically binds to a human KIT receptor (SEQ ID NO: 1), or an antigen binding fragment thereof.
8 . A method of reducing inflammation in a subject, comprising administering to a subject diagnosed with a mast cell related disorder of the central nervous system or nervous system a therapeutically effective amount of an antibody which specifically binds to a human KIT receptor (SEQ ID NO: 1), or an antigen binding fragment thereof.
9 . A method of inhibiting mast cell activation in a subject, comprising administering to a subject diagnosed with a mast cell related disorder of the central nervous system or nervous system a therapeutically effective amount of an antibody which specifically binds to a human KIT receptor (SEQ ID NO: 1), or an antigen binding fragment thereof.
10 . The method of claim 3, 8 or 9 , wherein the mast cell related disorder of the central nervous system or nervous system is NMO, NMOSD, multiple sclerosis (MS), or NF.
11 . The method of claim 1 or 2 , wherein the NF is NF1.
12 . The method of claim 1 or 2 , wherein the NF is NF2.
13 . The method of claim 1 or 2 , wherein the NF is Schwannomatosis.
14 . The method of any one of claims 1-13 , wherein the antibody is a bivalent monospecific antibody.
15 . The method of any one of claims 1-14 , herein the antibody is a humanized antibody.
16 . The method of any one of claims 1-15 , wherein the antibody is a naked antibody.
17 . The method of claim 1 , wherein the antibody comprises a light chain variable region (“VL”) comprising VL CDRs 1-3 comprising SEQ ID NOs: 2-4, respectively, and a heavy chain variable region (“VH”) comprising VH CDRs 1-3 comprising SEQ ID NOs: 5-7, respectively.
18 . The method of claim 17 , wherein the antibody comprises a VL comprising a VL sequence selected from the group consisting of SEQ ID NOs: 13, 14, 15, and 16; and a VH comprising a VH sequence selected from the group consisting of SEQ ID NOs: 8, 9, 10, 11, and 12.
19 . The method of claim 18 , wherein the antibody comprises a VH comprising SEQ ID NO: 8.
20 . The method of claim 18 , wherein the antibody comprises a VH comprising SEQ ID NO: 9.
21 . The method of claim 18 , wherein the antibody comprises a VH comprising SEQ ID NO: 10.
22 . The method of claim 18 , wherein the antibody comprises a VH comprising SEQ ID NO: 11.
23 . The method of claim 18 , wherein the antibody comprises a VH comprising SEQ ID NO: 12.
24 . The method of any one of claims 18-23 , wherein the antibody comprises a VL comprising SEQ ID NO: 13.
25 . The method of any one of claims 18-23 , wherein the antibody comprises a VL comprising SEQ ID NO: 14.
26 . The method of any one of claims 18-23 , wherein the antibody comprises a VL comprising SEQ ID NO: 15.
27 . The method of any one of claims 18-23 , wherein the antibody comprises a VL comprising SEQ ID NO: 16.
28 . The method of claim 2 , wherein the antibody comprises a light chain variable region (“VL”) comprising VL CDRs 1-3 comprising SEQ ID NOs: 2-4, respectively, and a heavy chain variable region (“VH”) comprising VH CDRs 1-3 comprising SEQ ID NOs: 5-7, respectively.
29 . The method of claim 28 , wherein the antibody comprises a VL comprising a VL sequence selected from the group consisting of SEQ ID NOs: 13, 14, 15, and 16; and a VH comprising a VH sequence selected from the group consisting of SEQ ID NOs: 8, 9, 10, 11, and 12.
30 . The method of claim 29 , wherein the antibody comprises a VH comprising SEQ ID NO: 8.
31 . The method of claim 29 , wherein the antibody comprises a VH comprising SEQ ID NO: 9.
32 . The method of claim 29 , wherein the antibody comprises a VH comprising SEQ ID NO: 10.
33 . The method of claim 29 , wherein the antibody comprises a VH comprising SEQ ID NO: 11.
34 . The method of claim 29 , wherein the antibody comprises a VH comprising SEQ ID NO: 12.
35 . The method of any one of claims 29-34 , wherein the antibody comprises a VL comprising SEQ ID NO: 13.
36 . The method of any one of claims 29-34 , wherein the antibody comprises a VL comprising SEQ ID NO: 14.
37 . The method of any one of claims 29-34 , wherein the antibody comprises a VL comprising SEQ ID NO: 15.
38 . The method of any one of claims 29-34 , wherein the antibody comprises a VL comprising SEQ ID NO: 16.
39 . The method of any one of claims 3-16 , wherein the antibody comprises a light chain variable region (“VL”) comprising VL CDRs 1-3 comprising SEQ ID NOs: 2-4, respectively, and a heavy chain variable region (“VH”) comprising VH CDRs 1-3 comprising SEQ ID NOs: 5-7, respectively.
40 . The method of claim 39 , wherein the antibody comprises a VL comprising a VL sequence selected from the group consisting of SEQ ID NOs: 13, 14, 15, and 16; and a VH comprising a VH sequence selected from the group consisting of SEQ ID NOs: 8, 9, 10, 11, and 12.
41 . The method of claim 40 , wherein the antibody comprises a VH comprising SEQ ID NO: 8.
42 . The method of claim 40 , wherein the antibody comprises a VH comprising SEQ ID NO: 9.
43 . The method of claim 40 , wherein the antibody comprises a VH comprising SEQ ID NO: 10.
44 . The method of claim 40 , wherein the antibody comprises a VH comprising SEQ ID NO: 11.
45 . The method of claim 40 , wherein the antibody comprises a VH comprising SEQ ID NO: 12.
46 . The method of any one of claims 40-45 , wherein the antibody comprises a VL comprising SEQ ID NO: 13.
47 . The method of any one of claims 40-45 , wherein the antibody comprises a VL comprising SEQ ID NO: 14.
48 . The method of any one of claims 40-45 , wherein the antibody comprises a VL comprising SEQ ID NO: 15.
49 . The method of any one of claims 40-45 , wherein the antibody comprises a VL comprising SEQ ID NO: 16.
50 . The method of any one of claims 1-49 , wherein the antibody is not a bispecific antibody.
51 . The method of any one of claims 1-50 , wherein the subject is a human adult.
52 . The method of any one of claims 1-51 , wherein the subject is a child.
53 . The method of any one of claims 1-52 , comprising administering a therapeutically effective amount of an antibody which specifically binds to a human KIT receptor (SEQ ID NO: 1).