USE OF AN ANTI-CD19 ANTIBODY TO TREAT AUTOIMMUNE DISEASE

1 . A method of treating neuromyelitis optica spectrum disorder (NMOSD), the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient had been previously treated with an anti-CD20 antibody.

2 . A method of treating NMOSD, the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient had been previously treated with an anti-CD20 antibody, wherein the patient had an NMOSD attack while being treated with or within 6 months of the last dose of the anti-CD20 antibody.

3 . The method of claim 1 or claim 2 , wherein VIB551 is administered intravenously at a dose of 300 mg every 6 months.

4 . A method of treating NMOSD, the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient is an astrocyte water channel aquaporin-4 (AQP4)-Immunoglobulin (Ig)G + patient,

wherein the VIB551 is administered intravenously at a dose of 300 mg every 6 months,

wherein the patient had been previously treated with an anti-CD20 antibody, and wherein the patient had an NMOSD attack while being treated with the anti-CD20 antibody.

5 . A method of treating NMOSD, the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient is an AQP4-IgG + patient,

wherein the VIB551 is administered intravenously at a dose of 300 mg every 6 months,

wherein the patient had been previously treated with an anti-CD20 antibody; and, wherein the patient had an NMOSD attack within 6 months of the last dose of the anti-CD20 antibody.

6 . The method of any one of claims 3 - 5 , wherein the patient receives at least one initial dose of VIB551.

7 . The method of any one of claims 3 - 6 , wherein the VIB551 is administered intravenously with a first initial dose of 300 mg, a second initial dose of 300 mg two weeks after the first initial dose, and subsequent doses of 300 mg every 6 months following the first initial dose.

8 . The method of claim 6 or claim 7 , wherein oral corticosteroids are co-administered to the patient with the initial VIB551 dose.

9 . The method of claim 8 , wherein the oral corticosteroids are administered daily for at least 2 weeks.

10 . The method of any one of claims 1 - 9 , wherein the anti-CD20 antibody is rituximab.

11 . The method of any one of claims 1 - 10 , wherein the treating is a reduction in worsening of Kurtzke Expanded Disability Severity Scale (EDSS) in the patient.

12 . The method of claim 11 , wherein the reduction in worsening of EDSS in the patient is:

a worsening of fewer than 2 points in EDSS score if the patient has a baseline score of 0;

a worsening of fewer than 1 point if the patient has a baseline score of 1 to 5: or

a worsening of less than 0.5 point if the patient has a baseline score of 5.5 or more.

13 . The method of any one of claims 1 - 10 , wherein the treating is a reduction in number of active magnetic resonance imaging (MRI) lesions.

14 . The method of claim 13 wherein the active MRI lesions are enlarging T2 MRI lesions.

15 . The method of any one of claims 1 - 10 , wherein the treating is a reduction in number of new MRI lesions.

16 . The method of any one of claims 1 - 10 , wherein the treating is a reduction in worsening of modified Rankin Score in the patient.

17 . The method of any one of claims 1 - 10 , wherein the treating is a reduction in frequency of in-patient hospitalizations of the patient related to NMOSD.

18 . The method of any one of claims 1 - 10 , wherein the treating is a reduction of risk of an NMOSD-related attack of the patient.

19 . The method of claim 18 , wherein the NMOSD-related attack is characterized by appearance of a new symptom or worsening of an existing symptom related to NMOSD.

20 . The method of claim 19 , wherein the symptom is an eye symptom.

21 . The method of claim 20 , wherein the eye symptom is eye pain, blurred vision, loss of vision, or appearance of an optic nerve lesion detected by MRI.

22 . The method of claim 19 , wherein the symptom is a spinal cord symptom.

23 . The method of claim 22 , wherein the spinal cord symptom is deep or radicular pain, extremity paraesthesia, weakness, sphincter dysfunction, Lhermitte's sign, or a spinal cord lesion detectable by MRI.

24 . The method of claim 19 , wherein the symptom is a brain or brain stem symptom.

25 . The method of claim 24 , wherein the brain or brainstem symptom is nausea, double vision, oculomotor palsy, vertigo, intractable vomiting, intractable hiccups, dysarthria, dysphagia, weakness, encephalopathy, hypothalamic dysfunction, or a brain or brain stem lesion detectable by MRI.

26 . The method of claim 18 , wherein the reduction of risk of the NMOSD-related attack is between 60 and 85%.

27 . The method of any one of claims 1 - 10 , wherein the treating is a reduction in optic neuritis.

28 . The method of any one of claims 1 - 10 , wherein the treating is a reduction of severity of NMOSD-related attacks.

29 . The method of claim 28 , wherein the reduction of severity of NMOSD-related attacks is the reduction in NMOSD-related attacks graded as major.

30 . The method of claim 28 , wherein the reduction of severity of NMOSD-related attacks is the reduction in NMOSD attacks requiring in-patient hospitalization.

31 . The method of any one of claims 1 - 10 , wherein the treating is a decrease in NMOSD-related pain in the patient.

32 . The method of claim 31 , wherein the decrease in NMOSD-related pain is determined by measuring pain in legs of the patient.

33 . The method of any one of claims 1 - 5 , wherein two weeks prior to the first administering the 300 mg VIB551 every 6 months, an initial 300 mg VIB551 dose is administered to the subject.

34 . The method of claim 33 , wherein oral corticosteroids are co-administered to the patient with the initial 300 mg VIB551 dose.

35 . The method of claim 1 or claim 2 , wherein the patient is AQP4-IgG seropositive.

36 . A method of reducing active MRI lesions in a patient diagnosed with NMOSD, the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient had been previously treated with an anti-CD20 antibody, wherein the patient had an NMOSD attack while being treated with the anti-CD20 antibody.

37 . A method of reducing active MRI lesions in a patient diagnosed with NMOSD, the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient had been previously treated with an anti-CD20 antibody, wherein the patient had an NMOSD attack within 6 months of the last dose of the anti-CD20 antibody.

38 . The method of claim 36 or 37 , wherein the VIB551 is administered intravenously at a dose of 300 mg every 6 months.

39 . A method of reducing active MRI lesions in a patient diagnosed with NMOSD, the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient had been previously treated with an anti-CD20 antibody, wherein the patient had an NMOSD attack while being treated with the anti-CD20 antibody, and,

wherein the VIB551 is administered intravenously at a dose of 300 mg every 6 months.

40 . A method of reducing active MRI lesions in a patient diagnosed with NMOSD, the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient had been previously treated with an anti-CD20 antibody, wherein the patient had an NMOSD attack within 6 months of the last dose of the anti-CD20 antibody; and,

wherein the VIB551 is administered intravenously at a dose of 300 mg every 6 months.

41 . A method of reducing AQP4-IgG titers in a AQP4-IgG + patient in need of treatment for NMOSD, the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient had been previously treated with an anti-CD20 antibody, wherein the patient had an NMOSD attack while being treated with the anti-CD20 antibody.

42 . A method of reducing AQP4-IgG titers in a AQP4-IgG + patient in need of treatment for NMOSD, the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient had been previously treated with an anti-CD20 antibody, wherein the patient had an NMOSD attack within 6 months of the last dose of the anti-CD20 antibody.

43 . The method of claim 41 or 42 , wherein the VIB551 is administered intravenously at a dose of 300 mg every 6 months.

44 . A method of reducing AQP4-IgG titers in a AQP4-IgG + patient in need of treatment for NMOSD, the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient had been previously treated with an anti-CD20 antibody, wherein the patient had an NMOSD attack while being treated with the anti-CD20 antibody; and,

wherein the VIB551 is administered intravenously at a dose of 300 mg every 6 months.

45 . A method of reducing AQP4-IgG titers in a AQP4-IgG + patient in need of treatment for NMOSD, the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient had been previously treated with an anti-CD20 antibody, wherein the patient had an NMOSD attack within 6 months of the last dose of the anti-CD20 antibody; and,

wherein the VIB551 is administered intravenously at a dose of 300 mg every 6 months.

46 . The method of any one of claims 1 - 45 , wherein the administration depletes at least 90% of circulating CD20+ B cells for at least six months.

47 . The method of any one of claims 1 - 46 , wherein the administration does not increase risk of infections in the patient.

48 . The method of any one of claims 1 - 47 , wherein the VIB551 depletes peripheral blood CD20 − plasmablasts and plasma cells within 8 days following the administering.

49 . A method of reducing NMOSD-related disability in a patient diagnosed with NMOSD, the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient had been previously treated with an anti-CD20 antibody, wherein the patient had an NMOSD attack while being treated with the anti-CD20 antibody.

50 . A method of reducing NMOSD-related disability in a patient diagnosed with NMOSD, the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient had been previously treated with an anti-CD20 antibody, wherein the patient had an NMOSD attack within 6 months of the last dose of the anti-CD20 antibody.

51 . The method of claim 49 or 50 , wherein the VIB551 is administered intravenously at a dose of 300 mg every 6 months.

52 . A method of reducing NMOSD-related disability in a patient diagnosed with NMOSD, the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient had been previously treated with an anti-CD20 antibody, wherein the patient had an NMOSD attack while being treated with the anti-CD20 antibody; and,

wherein the VIB551 is administered intravenously at a dose of 300 mg every 6 months.

53 . A method of reducing NMOSD-related disability in a patient diagnosed with NMOSD, the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient had been previously treated with an anti-CD20 antibody, wherein the patient had an NMOSD attack within 6 months of the last dose of the anti-CD20 antibody; and,

wherein the VIB551 is administered intravenously at a dose of 300 mg every 6 months.

54 . The method of any one of claims 49 - 53 , wherein the reducing the NMOSD-related disability in the patient is a reduction in a rate of worsening of NMOSD-related disability in the patient.

55 . The method of any one of claims 49 - 54 , wherein the reducing the NMOSD-related disability in the patient is a lessening of NMOSD-related disability in the patient.

56 . The method of any one of claims 49 - 55 , wherein the NMOSD-related disability is neurological disability.

57 . The method of any one of claims 49 - 56 , wherein the reducing the NMOSD-related disability is determined using EDSS.

58 . A method of reducing NMOSD-related attacks in a patient in need of treatment for NMOSD, the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient had been previously treated with an anti-CD20 antibody, wherein the patient had an NMOSD attack while being treated with the anti-CD20 antibody.

59 . A method of reducing NMOSD-related attacks in a patient in need of treatment for NMOSD, the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient had been previously treated with an anti-CD20 antibody, wherein the patient had an NMOSD attack within 6 months of the last dose of the anti-CD20 antibody.

60 . The method of claim 58 or 59 , wherein the VIB551 is administered intravenously at a dose of 300 mg every 6 months.

61 . A method of reducing NMOSD-related attacks in a patient in need of treatment for NMOSD, the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient had been previously treated with an anti-CD20 antibody, wherein the patient had an NMOSD attack while being treated with the anti-CD20 antibody, and,

wherein the VIB551 is administered intravenously at a dose of 300 mg every 6 months.

62 . A method of reducing NMOSD-related attacks in a patient in need of treatment for NMOSD, the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient had been previously treated with an anti-CD20 antibody, wherein the patient had an NMOSD attack within 6 months of the last dose of the anti-CD20 antibody; and,

wherein the VIB551 is administered intravenously at a dose of 300 mg every 6 months.

63 . The method of claim 61 or claim 62 , wherein the NMOSD-related attacks suffered by the patient comprise any one or more of an optic neuritis, a myelitis, or a brainstem attack.

64 . The method of claim 63 , wherein the NMOSD-related attacks suffered by the patient are clinically asymptomatic.

65 . The method of any one of claims 36 - 64 , wherein the patient receives at least one initial dose of VIB551.

66 . The method of claim 65 , wherein the VIB551 is administered intravenously with a first initial dose of 300 mg, a second initial dose of 300 mg two weeks after the first initial dose, and subsequent doses of 300 mg every 6 months following the first initial dose.

67 . The method of claim 66 , wherein oral corticosteroids are co-administered to the patient with the initial 300 mg VIB551 dose.

68 . The method of claim 67 , wherein the oral corticosteroids are administered daily for at least 2 weeks.

69 . The method of any one of claims 36 - 68 , wherein the anti-CD20 antibody is rituximab.

70 . The method of any one of claims 1 - 69 , wherein the VIB551 comprises a heavy chain variable region (VH) comprising the amino acid of SEQ ID NO:1 and a light chain variable region (VL) comprising the amino acid of SEQ ID NO: 2.

71 . A method of treating NMOSD, the method comprising:

administering an anti-CD19 antibody to a patient in need of treatment for NMOSD,

wherein the patient had been previously treated with an anti-CD20 antibody, wherein the patient had an NMOSD attack while being treated with the anti-CD20 antibody.

72 . A method of treating NMOSD, the method comprising:

administering an anti-CD19 antibody to a patient in need of treatment for NMOSD,

wherein the patient had been previously treated with an anti-CD20 antibody, wherein the patient had an NMOSD attack within 6 months of the last dose of the anti-CD20 antibody.

73 . A method of treating NMOSD, the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient is an AQP4-IgG + patient,

wherein the VIB551 is administered intravenously with a first initial dose of 300 mg, a second initial dose of 300 mg two weeks after the first initial dose, and subsequent doses of 300 mg every 6 months following the first initial dose,

wherein patient had been previously treated with an anti-CD20 antibody, and wherein the patient had an NMOSD attack while being treated with the anti-CD20 antibody.

74 . A method of treating NMOSD, the method comprising:

administering the anti-CD19 antibody VIB551 to a patient in need of treatment for NMOSD,

wherein the patient is an AQP4-IgG + patient,

wherein the VIB551 is administered intravenously with a first initial dose of 300 mg, a second initial dose of 300 mg two weeks after the first initial dose, and subsequent doses of 300 mg every 6 months following the first initial dose,

wherein the patient had been previously treated with an anti-CD20 antibody; and, wherein the patient had an NMOSD attack within 6 months of the last dose of the anti-CD20 antibody.

75 . The method of any one of claims 1 - 74 , further comprising, prior to the administering:

identifying the patient as having previously been treated with the anti-CD20 antibody;

determining that the patient:

(i) suffered at least one NMOSD attack while being treated with the anti-CD20 antibody; or

(ii) had suffered at least one NMOSD attack within 6 months of the last dose of the anti-CD20 antibody; and

selecting the patient for the administering the anti-CD19 antibody as a result of the determining (i) or (ii).