METHODS FOR REDUCING PROTEINURIA IN A HUMAN SUBJECT SUFFERING FROM IMMUNOGLOBULIN A NEPHROPATHY

1 . A method of reducing proteinuria in a human subject suffering from IgAN comprising administering to the subject a MASP-2 inhibitory antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising CDR-H1, CDR-H2 and CDR-H3 of the amino acid sequence set forth as SEQ ID NO:67 and a light chain variable region comprising CDR-L1, CDR-L2 and CDR-L3 of the amino acid sequence set forth as SEQ ID NO:70 according to a dosage regimen as follows:

a. administering about 4 mg/kg (i.e., from 3.6 mg/kg to 4.4 mg/kg) of said antibody to a subject suffering from IgAN once weekly intravenously for a treatment period of at least 12 weeks; or

b. administering from about 180 mg to about 725 mg (i.e., from 162 mg to 797 mg) of said antibody to a subject suffering from IgAN once weekly intravenously for a treatment period of at least 12 weeks,

wherein the method reduces proteinuria in said human subject.

2 . The method of claim 1 , wherein the treatment period is 12 weeks.

3 . The method of claim 1 or 2 , wherein the treatment period is followed by a rest period (i.e., no administration of a MASP-2 inhibitor) of at least 2 months.

4 . The method of claim 1 or 2 , wherein the treatment period is followed by a rest period (i.e., no administration of a MASP-2 inhibitor) of at least 3 months.

5 . The method of claim 1 or 2 , wherein the treatment period is followed by a rest period (i.e., no administration of a MASP-2 inhibitor) of at least 4 months.

6 . The method of claim 1 or 2 , wherein the treatment period is followed by a rest period (i.e., no administration of a MASP-2 inhibitor) of at least 5 months.

7 . The method of claim 1 or 2 , wherein the treatment period is followed by a rest period (i.e., no administration of a MASP-2 inhibitor) of at least 6 months.

8 . The method of any of claims 1 to 7 , wherein proteinuria in the subject is reduced by at least 20% from baseline (prior to treatment) at the end of the treatment period and/or at the end of the rest period (i.e., a decrease in uACR and/or a decrease in 24-hour urine protein concentration).

9 . The method of any of claims 1 to 7 , wherein proteinuria in the subject is reduced by at least 30% from baseline (prior to treatment) at the end of the treatment period and/or at the end of the rest period (i.e., a decrease in uACR and/or a decrease in 24-hour urine protein concentration).

10 . The method of any of claims 1 to 7 , wherein proteinuria in the subject is reduced by at least 40% from baseline (prior to treatment) at the end of the treatment period and/or at the end of the rest period (i.e., a decrease in uACR and/or a decrease in 24-hour urine protein concentration).

11 . The method of any of claims 1 to 7 , wherein proteinuria in the subject is reduced by at least 50% from baseline (prior to treatment) at the end of the treatment period and/or at the end of the rest period (i.e., a decrease in uACR and/or a decrease in 24-hour urine protein concentration).

12 . The method of any of claims 1 to 7 , wherein proteinuria in the subject is reduced by greater than 50% from baseline (prior to treatment) at the end of the treatment period and/or at the end of the rest period (i.e., a decrease in uACR and/or a decrease in 24-hour urine protein concentration).

13 . The method of any of claims 1 to 7 , where the method further comprises periodically monitoring the urinary protein levels in the subject during the treatment period and/or rest period.

14 . The method of any of claims 1 to 7 , wherein the estimated glomerular filtration rate (eGFR) increases in the subject.

15 . The method of any of claims 1 to 7 , wherein the subject has discontinued or substantially reduced corticosteroid dosage at the end of the treatment period and/or at the end of the rest period as compared to corticosteroid dosage taken prior to the start of treatment with the MASP-2 inhibitory antibody.

16 . The method of claim 1 , wherein the MASP-2 inhibitory antibody or fragment thereof is selected from the group consisting of a recombinant antibody, an antibody having reduced effector function, a chimeric antibody, a humanized antibody and a human antibody.

17 . The method of claim 1 , wherein MASP-2 inhibitory antibody, or fragment thereof, comprises:

(a) a heavy-chain variable region comprising: i) a heavy chain CDR-H1 comprising the amino acid sequence from 31-35 of SEQ ID NO:67; and ii) a heavy-chain CDR-H2 comprising the amino acid sequence from 50-65 of SEQ ID NO:67; and iii) a heavy-chain CDR-H3 comprising the amino acid sequence from 95-107 of SEQ ID NO:67 and

(b) a light-chain variable region comprising: i) a light-chain CDR-L1 comprising the amino acid sequence from 24-34 of SEQ ID NO:70; and ii) a light-chain CDR-L2 comprising the amino acid sequence from 50-56 of SEQ ID NO:70; and iii) a light-chain CDR-L3 comprising the amino acid sequence from 89-97 of SEQ ID NO:70.

18 . The method of claim 1 , wherein the MASP-2 inhibitory antibody or fragment thereof comprises a heavy-chain variable region comprising an amino acid sequence having at least 95% identity to the amino acid sequence set forth as SEQ ID NO:67 and a light-chain variable region comprising an amino acid sequence having at least 95% identity to the amino acid sequence set forth as SEQ ID NO:70.

19 . The method of claim 1 , wherein the MASP-2 inhibitory antibody or fragment thereof comprises a heavy-chain variable region comprising an amino acid sequence forth as SEQ ID NO:67 and comprises a light-chain variable region set forth as SEQ ID NO:70.

20 . The method of claim 1 , wherein the subject suffering from IgAN has proteinuria of greater than 1 gram protein/24 hour urine protein excretion prior to treatment and the method is effective to reduce proteinuria in the subject in the subject by at least 30%.