METHODS FOR TREATING AND/OR PREVENTING IDIOPATHIC PNEUMONIA SYNDROME (IPS) AND/OR CAPILLARY LEAK SYNDROME (CLS) AND/OR ENGRAFTMENT SYNDROME (ES) AND/OR FLUID OVERLOAD (FO) ASSOCIATED WITH HEMATOPOIETIC STEM CELL TRANSPLANT
In one aspect, the invention provides methods of inhibiting the effects of MASP-2-dependent complement activation in a human subject suffering from, or at risk for developing HSCT-IPS and/or suffering from, or at risk for developing HSCT-CLS and/or suffering from, or at risk for developing HSCT-FO and/or suffering from, or at risk for developing HSCT-ES. The methods comprise the step of administering, to a subject in need thereof, an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation.
1 . A method of treating a human subject suffering from idiopathic pneumonia syndrome following hematopoietic stem cell transplant (HSCT-IPS) comprising administering to the subject a composition comprising an amount of a MASP-2 inhibitory antibody, or antigen-binding fragment thereof, effective to inhibit MASP-2-dependent complement activation.
2 . The method of claim 1 , wherein the MASP-2 inhibitory antibody is a monoclonal antibody, or fragment thereof that specifically binds to human MASP-2.
3 . (canceled)
4 . The method of claim 1 , wherein the MASP-2 inhibitory antibody does not substantially inhibit the classical pathway.
5 . (canceled)
6 . (canceled)
7 . The method of claim 1 , wherein the method further comprises identifying a human subject suffering from idiopathic pneumonia syndrome following hematopoietic stem cell transplant (HSCT-IPS) prior to the step of administering to the subject a composition comprising an amount of a MASP-2 inhibitory antibody, or antigen-binding fragment thereof, effective to inhibit MASP-2-dependent complement activation.
8 . The method of claim 1 , wherein the subject has previously undergone an allogeneic hematopoietic stem cell transplant.
9 . (canceled)
10 . (canceled)
11 . The method of claim 1 , wherein the MASP-2 inhibitory antibody or antigen-binding fragment thereof, comprises 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.
12 . (canceled)
13 . The method of claim 1 , wherein the method comprises administering to the subject a composition comprising said MASP-2 inhibitory antibody having a dosage of about 4 mg/kg at least once weekly for a treatment period of at least 4 weeks.
14 . (canceled)
15 . (canceled)
16 . (canceled)
17 . A method of treating a human subject suffering from capillary leak syndrome following hematopoietic stem cell transplant (HSCT-CLS) comprising administering to the subject a composition comprising an amount of a MASP-2 inhibitory antibody, or antigen-binding fragment thereof, effective to inhibit MASP-2-dependent complement activation.
18 . The method of claim 17 , wherein the MASP-2 inhibitory antibody is a monoclonal antibody, or fragment thereof that specifically binds to human MASP-2.
19 . (canceled)
20 . The method of claim 17 , wherein the MASP-2 inhibitory antibody does not substantially inhibit the classical pathway.
21 . (canceled)
22 . (canceled)
23 . The method of claim 17 , wherein the method further comprises identifying a human subject suffering from capillary leak syndrome following hematopoietic stem cell transplant (HSCT-CLS) prior to the step of administering to the subject a composition comprising an amount of a MASP-2 inhibitory antibody, or antigen-binding fragment thereof, effective to inhibit MASP-2-dependent complement activation.
24 . The method of claim 17 , wherein the subject has previously undergone an allogeneic hematopoietic stem cell transplant.
25 . (canceled)
26 . (canceled)
27 . The method of claim 17 , wherein the MASP-2 inhibitory antibody or antigen-binding fragment thereof, comprises 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.
28 . (canceled)
29 . The method of claim 17 , wherein the method comprises administering to the subject a composition comprising said MASP-2 inhibitory antibody having a dosage of about 4 mg/kg at least once weekly for a treatment period of at least 4 weeks.
30 . (canceled)
31 . (canceled)
32 . (canceled)
33 . A method of treating a human subject suffering from fluid overload following hematopoietic stem cell transplant (HSCT-FO) comprising administering to the subject a composition comprising an amount of a MASP-2 inhibitory antibody, or antigen-binding fragment thereof, effective to inhibit MASP-2-dependent complement activation.
34 . The method of claim 33 , wherein the MASP-2 inhibitory antibody is a monoclonal antibody, or fragment thereof that specifically binds to human MASP-2.
35 . (canceled)
36 . The method of claim 33 , wherein the MASP-2 inhibitory antibody does not substantially inhibit the classical pathway.
37 . (canceled)
38 . (canceled)
39 . The method of claim 33 , wherein the method further comprises identifying a human subject suffering from fluid overload following hematopoietic stem cell transplant (HSCT-FO) prior to the step of administering to the subject a composition comprising an amount of a MASP-2 inhibitory antibody, or antigen-binding fragment thereof, effective to inhibit MASP-2-dependent complement activation.
40 . The method of claim 33 , wherein the subject has previously undergone an allogeneic hematopoietic stem cell transplant.
41 . (canceled)
42 . The method of claim 33 , wherein the MASP-2 inhibitory antibody or antigen-binding fragment thereof, comprises 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.
43 . (canceled)
44 . The method of claim 33 , wherein the method comprises administering to the subject a composition comprising said MASP-2 inhibitory antibody having a dosage of about 4 mg/kg at least once weekly for a treatment period of at least 4 weeks.
45 . (canceled)
46 . (canceled)
47 . (canceled)
48 . A method of treating a human subject suffering from engraftment syndrome following hematopoietic stem cell transplant (HSCT-ES) comprising administering to the subject a composition comprising an amount of a MASP-2 inhibitory antibody, or antigen-binding fragment thereof, effective to inhibit MASP-2-dependent complement activation.
49 . The method of claim 48 , wherein the MASP-2 inhibitory antibody is a monoclonal antibody, or fragment thereof that specifically binds to human MASP-2.
50 . (canceled)
51 . The method of claim 48 , wherein the MASP-2 inhibitory antibody does not substantially inhibit the classical pathway.
52 . (canceled)
53 . (canceled)
54 . The method of claim 48 , wherein the method further comprises identifying a human subject suffering from engraftment syndrome following hematopoietic stem cell transplant (HSCT-ES) prior to the step of administering to the subject a composition comprising an amount of a MASP-2 inhibitory antibody, or antigen-binding fragment thereof, effective to inhibit MASP-2-dependent complement activation.
55 . The method of claim 48 , wherein the subject has previously undergone an allogeneic hematopoietic stem cell transplant.
56 . (canceled)
57 . The method of claim 48 , wherein the MASP-2 inhibitory antibody or antigen-binding fragment thereof, comprises 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.
58 . (canceled)
59 . The method of claim 48 , wherein the method comprises administering to the subject a composition comprising said MASP-2 inhibitory antibody having a dosage of about 4 mg/kg at least once weekly for a treatment period of at least 4 weeks.
60 . (canceled)
61 . (canceled)
62 . (canceled)