Methods of administering / dosing anti-rsv antibodies for prophylaxis and treatment

Abstract

The present invention encompasses novel antibodies and fragments thereof which immunospecifically bind to one or more RSV antigens and compositions comprising said antibodies and antibody fragments. The present invention encompasses methods preventing respiratory syncytial virus (RSV) infection in a human, comprising administering to said human a prophylactically effective amount of one or more antibodies or fragments thereof that immunospecifically bind to one or more RSV antigens, wherein a certain serum titer of said antibodies or antibody fragments is achieved in said human subject. The present invention also encompasses methods for treating or ameliorating symptoms associated with a RSV infection in a human, comprising administering to said human a therapeutically effective amount of one or more antibodies or fragments thereof that immunospecifically bind to one or more RSV antigens, wherein a certain serum titer of said antibodies or antibody fragments is achieved in said human subject. The present invention further encompasses compositions comprising antibodies or fragments thereof that immunospecifically bind to a RSV antigen, and methods using said compositions for detection or diagnosis a RSV infection

1 . An antibody that immunospecifically binds to a respiratory syncytial virus (RSV) antigen, wherein the antibody comprises:
 (a) variable heavy (VH) domain having an amino acid sequence of the VH domain of AFFF, P12f2, P12f4, P11d4, A1e9, A12a6, A17d4, A4B4, A8c7, H3-3F4, M3H9, 6H8, or A13:   (b) a variable light (VL) domain having the amino acid sequence of the VL domain of AFFF, P12f2, P12f4, P11d4, A1e9, A12a6, A13c4, A17d4, A4B4, A8c7, IX-493L1FR, H3-F4, Y10H6, AFFF(1), 6h8, L1-7E5, L2-15B10, A13a11, A1h5, A4B4(1), A4B4L1 FR-S28R, or A4B4-F52S;   (c) a VH domain having the amino acid sequence of the VH domain of AFFF, P12f2, P12f4, P11d4, A1e9, A12a6, A13c4, A17d4, A4B4, A8c7, IX-493L1FR, H3-F4, Y10H6, AFFF(1), 6h8, L1-7E5, L2-15B10, A13a11, A1h5, A4B4(1), A4B4L1 FR-S28R, or A4B4-F52S, and
 a VL domain having the amino acid sequence of the VL domain of AFFF, P12f2, P12f4, P11d4, A1e9, A12a6, A13c4, A17d4, A4B4, A8c7, IX-493L1FR, H3-F4, Y10H6, AFFF(1), 6h8, L1-7E5, L2-15B10, A13a11, A1h5, A4B4(1), A4B4L1 FR-S28R, or A4B4-F52S; 
   (d) a VL chain having the amino acid sequence of the VL chain of AFFF, P12f2, P12f4, P11d4, A1e9, A12a6, A13c4, A17d4, A4B4, A8c7, IX-493L1FR, H3-F4, Y10H6, AFFF(1), 6h8, L1-7E5, L2-15B10, A13a11, A1h5, A4B4(1), A4B4L1 FR-S28R, or A4B4-F52S;   (e) a VH chain having an amino acid sequence of the VH chain of AFFF, P12f2, P12f4, P11d4, A1e9, A12a6, A17d4, A4B4, A8c7, H3-3F4, M3H9, 6H8, or A13a11; or   (f) a VH chain having the amino acid sequence of the VH chain of AFFF, P12f2, P12f4, P11d4, A1e9, A12a6, A13c4, A17d4, A4B4, A8c7, IX-493L1FR, H3-F4, Y10H6, AFFF(1), 6h8, L1-7E5, L2-15B10, A13a11, A1h5, A4B4(1), A4B4L1 FR-S28R, or A4B4-F52S, and
 a VL chain having the amino acid sequence of the VL chain of AFFF, P12f2, P12f4, P11d4, A1e9, A12a6, A13c4, A17d4, A4B4, A8c7, IX-493L1FR, H3-F4, Y10H6, AFFF(1), 6h8, L1-7E5, L2-15B10, A13a11, A1h5, A4B4(1), A4B4L1 FR-S28R, or A4B4-F52S; or 
   (g) a VH domain comprising a VH complementarity determining region (CDR)1, a VH CDR2, and a VH CDR3 having the amino acid sequences of the VH CDR1, the VH CDR2 and the VH CDR3 of AFFF, P12f2, P12f4, P11d4, A1e9, A12a6, A13c4, A17d4, A4B4, A8c7, IX-493L1FR, H3-F4, Y10H6, AFFF(1), 6h8, L1-7E5, L2-15B10, A13a11, A1h5, A4B4(1), A4B4L1 FR-S28R, or A4B4-F52S, and
 a VL domain comprising a VL CDR1, a VLCDR2, and a VL CDR3 having the amino acid sequence of the VL CDR1, the VL CDR2 and the VL CDR3 of AFFF, P12f2, P12f4, P11d4, A1e9, A12a6, A13c4, A17d4, A4B4, A8c7, IX-493L1FR, H3-F4, Y10H6, AFFF(1), 6h8, L1-7E5, L2-15B10, A13a11, A1h5, A4B4(1), A4B4L1 FR-S28R, or A4B4-F52S. 
   
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . (canceled) 
     
     
         12 . An isolated nucleic acid molecule comprising a nucleotide sequence encoding the antibody of  claim 1 . 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . A vector comprising the nucleic acid molecule of  claim 12 . 
     
     
         17 . The vector of  claim 16  further comprising a nucleotide sequence which regulates the expression of said antibody. 
     
     
         18 . A host cell genetically engineered to express the nucleic acid molecule of  claim 12 . 
     
     
         19 . A host cell comprising the vector of  claim 16 . 
     
     
         20 . A method of producing an antibody comprising culturing the host cell of  claim 18  under conditions in which the nucleic acid molecule is expressed. 
     
     
         21 . A pharmaceutical composition comprising the antibody of  claim 1 , and a carrier or excipient. 
     
     
         22 . (canceled) 
     
     
         23 . A method of preventing, treating or ameliorating a RSV infection or a symptom thereof, comprising administering to a mammal in need thereof the pharmaceutical composition of  claim 21  in an amount effective to treat, prevent or ameliorate the RSV infection. 
     
     
         24 . The method of  claim 23 , wherein the pharmaceutical composition is administered once or every two months a month prior to or during the RSV season. 
     
     
         25 . (canceled) 
     
     
         26 . The method of  claim 23 , wherein the pharmaceutical composition is administered intramusclarly, intravaneously or subcutaneously. 
     
     
         27 . (canceled) 
     
     
         28 . The method of  claim 23 , wherein the mammal is a human. 
     
     
         29 . A method for detecting a RSV infection, comprising:
 (a) assaying the level of a RSV antigen in cells or a tissue sample of a subject using an antibody of  claim 1 ; and   (b) comparing the assayed level of the RSV antigen with a control level, whereby an increase in the assayed level of RSV antigen compared to the control level of the RSV antigen is indicative of a RSV infection.   
     
     
         30 . A fusion protein comprising a CDR having the amino acid sequence of a CDR listed in Table 2 or Table 3 and a heterologous amino acid sequence. 
     
     
         31 . (canceled) 
     
     
         32 . A method for preventing one or more symptoms of a RSV infection in a human subject, comprising administering to the subject a first dose of a prophylactically effective amount of an antibody that immunospecifically binds to a RSV antigen, wherein the prophylactically effective amount is a dose of less than 15 mg/kg of the antibody, and wherein the prophylactically effective amount of the antibody results in a prophylactically effective serum titer of at least 75 μg/ml at least 30 days after the administration of the first dose and to prior to the administration of a subsequent dose. 
     
     
         33 . A method for treating or ameliorating one or more symptoms of a RSV infection in a human subject, comprising administering to the subject a first dose of a therapeutically effective amount of an antibody that immunospecifically binds to a RSV antigen, wherein the therapeutically effective amount is a dose of less than 15 mg/kg of the antibody, and wherein the therapeutically effective amount of the antibody results in a therapeutically effective serum titer of at least 75 μg/ml at least 30 days after the administration of the first dose and to prior to the administration of a subsequent dose.