Dose

Abstract

The disclosure relates to methods and compositions for the treatment of type I IFN mediated disease. Specifically, the disclosure relates to a subcutaneous dose of a type I IFN receptor inhibitor.

1 .- 89 . (canceled) 
     
     
         90 . A method for treating a type I interferon (IFN)-mediated disease in a subject, the method comprising subcutaneously administering a dose of more than (>)105 mg and less than (<)150 mg of a human monoclonal antibody that specifically binds type I IFN receptor (IFNAR1) to the subject having a type I (IFN)-mediated disease, wherein the antibody comprises:
 (a) a heavy chain variable region complementarity determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO: 3;   (b) a heavy chain variable region complementarity determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO: 4;   (c) a heavy chain variable region complementarity determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO: 5;   (d) a light chain variable region complementarity determining region 1 (LCDR1) comprising the amino acid sequence SEQ ID NO: 6;   (e) a light chain variable region complementarity determining region 2 (LCDR2) comprising the amino acid sequence SEQ ID NO: 7; and   (f) a light chain variable region complementarity determining region 3 (LCDR3) comprising the amino acid sequence SEQ ID NO: 8.   
     
     
         91 . The method of  claim 90 , wherein the human monoclonal antibody that specifically binds IFNAR1 comprises: (a) a human heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 1; and (b) a human light chain variable region comprising the amino acid sequence of SEQ ID NO: 2. 
     
     
         92 . The method of  claim 90 , wherein the human monoclonal antibody that specifically binds IFNAR1 comprises: (a) a human heavy chain comprising the amino acid sequence of SEQ ID NO: 11; and (b) a human light chain comprising the amino acid sequence of SEQ ID NO: 12. 
     
     
         93 . The method of  claim 90 , wherein the human monoclonal antibody that specifically binds IFNAR1 is anifrolumab or a functional variant thereof. 
     
     
         94 . The method of  claim 93 , comprising subcutaneously administering a dose of the human monoclonal antibody that specifically binds IFNAR1, wherein subcutaneously administering the dose every week provides a plasma concentration in the subject that is at least equivalent to the plasma concentration provided by intravenous administration of 300 mg of the human monoclonal antibody that specifically binds IFNAR1 every 4 weeks. 
     
     
         95 . The method of  claim 94 , wherein the dose is 120 mg of the human monoclonal antibody that specifically binds IFNAR1, and the method comprises subcutaneously administering said dose in a single administration step once per week (QW). 
     
     
         96 . The method of  claim 90 , wherein administration of the dose provides a plasma concentration of the human monoclonal antibody that specifically binds IFNAR1 in the subject of ≥10 μg anifrolumab or the functional variant thereof per ml of plasma (≥10 μg/ml). 
     
     
         97 . The method of  claim 90 , wherein the subject is type I interferon stimulated gene signature (IFNGS)-test high. 
     
     
         98 . A method for treating a type I interferon (IFN)-mediated disease in a subject, the method comprising:
 subcutaneously administering a dose of more than (>)105 mg and less than (<)150 mg of a human monoclonal antibody that specifically binds type I IFN receptor (IFNAR1) to the subject having a type I (IFN)-mediated disease, wherein the antibody comprises:   (a) a heavy chain variable region complementarity determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO: 3;   (b) a heavy chain variable region complementarity determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO: 4;   (c) a heavy chain variable region complementarity determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO: 5;   (d) a light chain variable region complementarity determining region 1 (LCDR1) comprising the amino acid sequence SEQ ID NO: 6;   (e) a light chain variable region complementarity determining region 2 (LCDR2) comprising the amino acid sequence SEQ ID NO: 7; and   (f) a light chain variable region complementarity determining region 3 (LCDR3) comprising the amino acid sequence SEQ ID NO: 8;   wherein the subject is identified as type I interferon stimulated gene signature (IFNGS)-test high.   
     
     
         99 . The method of  claim 98 , wherein the dose provides a therapeutic effect in the subject that is at least equivalent to a therapeutic effect provided by administration of an intravenous dose of 300 mg of the human monoclonal antibody that specifically binds IFNAR1 administered once every 4 weeks (Q4W). 
     
     
         100 . The method of  claim 90 , wherein the human monoclonal antibody that specifically binds IFNAR1 is comprised within a pharmaceutical composition comprising 150 mg/mL of the antibody, 50 mM lysine HCl, 130 mM trehalose dihydrate, 0.05% polysorbate 80 and 25 mM histidine/histidine HCl. 
     
     
         101 . The method of  claim 90 , wherein the type I IFN-mediated disease is an autoimmune disease. 
     
     
         102 . The method of  claim 90 , wherein the type I IFN-mediated disease is lupus. 
     
     
         103 . The method of  claim 102 , wherein the type I IFN-mediated disease is systemic lupus erythematosus (SLE), lupus nephritis (LN), or cutaneous lupus erythematosus (CLE). 
     
     
         104 . The method of  claim 90 , wherein the type I IFN-mediated disease is myositis, scleroderma, or Sjogren's syndrome. 
     
     
         105 . The method of  claim 98 , wherein the human monoclonal antibody that specifically binds IFNAR1 neutralizes the elevated IFNGS in the subject. 
     
     
         106 . The method of  claim 93 , wherein the type I IFN-mediated disease is SLE, wherein the human monoclonal antibody that specifically binds IFNAR1 is anifrolumab or a functional variant thereof, wherein the dose is 120 mg, and wherein the method comprises subcutaneously administering the dose weekly. 
     
     
         107 . The method of  claim 93 , wherein the type I IFN-mediated disease is LN, wherein the human monoclonal antibody that specifically binds IFNAR1 is anifrolumab or a functional variant thereof, wherein the dose is 120 mg, and wherein the method comprises subcutaneously administering the dose weekly. 
     
     
         108 . The method of  claim 93 , wherein the type I IFN-mediated disease is CLE, wherein the human monoclonal antibody that specifically binds IFNAR1 is anifrolumab or a functional variant thereof, wherein the dose is 120 mg, and wherein the method comprises subcutaneously administering the dose weekly. 
     
     
         109 . The method of  claim 93 , wherein the type I IFN-mediated disease is myositis, wherein the human monoclonal antibody that specifically binds IFNAR1 is anifrolumab or a functional variant thereof, wherein the dose is 120 mg, and wherein the method comprises subcutaneously administering the dose weekly. 
     
     
         110 . The method of  claim 93 , wherein the type I IFN-mediated disease is scleroderma, wherein the human monoclonal antibody that specifically binds IFNAR1 is anifrolumab or a functional variant thereof, wherein the dose is 120 mg, and wherein the method comprises subcutaneously administering the dose weekly. 
     
     
         111 . The method of  claim 93 , wherein the type I IFN-mediated disease is Sjogren's syndrome, wherein the human monoclonal antibody that specifically binds IFNAR1 is anifrolumab or a functional variant thereof, wherein the dose is 120 mg, and wherein the method comprises subcutaneously administering the dose weekly. 
     
     
         112 . A method for treating a type I interferon (IFN)-mediated disease in a subject, the method comprising:
 (a) subcutaneously administering a dose of more than (>)105 mg and less than (<)150 mg of a human monoclonal antibody that specifically binds type I IFN receptor (IFNAR1), and   (b) a corticosteroid to the subject having a type I IFN-mediated disease, wherein the antibody comprises:   (i) a heavy chain variable region complementarity determining region 1 (HCDR1) comprising the amino acid sequence of SEQ ID NO: 3;   (ii) a heavy chain variable region complementarity determining region 2 (HCDR2) comprising the amino acid sequence of SEQ ID NO: 4;   (iii) a heavy chain variable region complementarity determining region 3 (HCDR3) comprising the amino acid sequence of SEQ ID NO: 5;   (iv) a light chain variable region complementarity determining region 1 (LCDR1) comprising the amino acid sequence SEQ ID NO: 6;   (v) a light chain variable region complementarity determining region 2 (LCDR2) comprising the amino acid sequence SEQ ID NO: 7; and   (vi) a light chain variable region complementarity determining region 3 (LCDR3) comprising the amino acid sequence SEQ ID NO: 8.   
     
     
         113 . The method of  claim 112 , comprising administering a first dose of the corticosteroid and subsequently administering a second dose of the corticosteroid, wherein the second dose of the corticosteroid is lower than the first dose of the corticosteroid. 
     
     
         114 . An injection device comprising the human monoclonal antibody that specifically binds IFNAR1 dose of  claim 90 . 
     
     
         115 . The injection device of  claim 114 , wherein the injection device is a pre-filled syringe (PFS). 
     
     
         116 . The injection device of  claim 115 , wherein the injection device is an accessorized pre-filed syringe (AFPS). 
     
     
         117 . The injection device of  claim 114 , wherein the injection device is an auto-injector. 
     
     
         118 . A kit comprising: (a) the human monoclonal antibody that specifically binds IFNAR1 dose of  claim 90 , and (b) instructions for use, wherein the instructions for use comprise instructions for subcutaneous administration of the antibody dose. 
     
     
         119 . The kit of  claim 118 , wherein the instructions for use comprise instructions for administration of 120 mg anifrolumab or the functional variant thereof.