Recombinant antibodies for treatment of respiratory syncytial virus infections

Abstract

Disclosed are novel polyclonal antibodies, which target respiratory syncytial virus (RSV), as well as novel high affinity antibody molecules reactive with RSV. The polyclonal antibodies may comprise antibody molecules which are reactive with both RSV protein F and RSV protein G, and preferably the polyclonal antibodies target a variety of epitopes on these proteins. The antibody molecules of the invention have shown superior efficacy in vitro and/or in vivo. Also disclosed are methods of producing the antibodies of the invention as well as methods of their use in treatment or prevention of RSV infection.

1 . (canceled) 
     
     
         2 . An anti-RSV antibody comprising a CDRH3 having the general formula: CAX 1 X 2 X 3 X 4 X 5 X 6 PX 7 X 8 X 9 X 10 X 11 W
 where X 1  to X 11  are selected individually from the groups of amino acids listed below   X 1 ═R or K;   X 2 =D, E, N or Q;   X 3 ═S, T, G or A;   X 4 ═S, T, G or A;   X 5 ═N, Q, D or E;   X 6 ═W, Y, F or H;   X 7 =A, G, V, or S;   X 8 =G, A, V, or S;   X 9 ═Y, F, W or H;   X 10 =E or D; and   X 11 =D, E, N or Q;   
       and a CDRL3 described by the following formula: CX 1 X 2 X 3 X 4 X 5 X 6 PX 7 TF
 where X 1  to X 7  are selected individually from the groups of amino acids listed below: 
 X 1 =Q or H; 
 X 2 =Q, E or H; 
 X 3 ═F, Y, W or H; 
 X 4 ═N, Q or H; 
 X 5 =T, S, G or A; 
 X 6 ═Y, F, W or H; and 
 X 7 ═F, Y, W or H. 
 
     
     
         3 . The antibody of  claim 2 , comprising SEQ ID NOs: 232, 317, 487, and 572, wherein up to 2 amino acids have been changed compared to said SEQ ID Nos. 
     
     
         4 . The antibody of  claim 2 , comprising a CDRH3 region having the formula CARDSSNWPAGYEDW (SEQ ID NO 402), and a CDRL3 region having the formula CQQFNTYPFTF (SEQ ID NO 657). 
     
     
         5 . The antibody of  claim 2 , comprising a V H  region encoded by SEQ ID NO: 19. 
     
     
         6 . The antibody of  claim 2 , comprising a V L  region encoded by amino acids 1 to 107 of SEQ ID NO: 107. 
     
     
         7 . The antibody of  claim 2 , comprising a light chain encoded by SEQ ID NO: 107. 
     
     
         8 . The antibody of  claim 2 , comprising a C H  as defined in SEQ ID NO: 178. 
     
     
         9 . The antibody of  claim 2 , having a binding specificity of an antibody comprising CDR1, CDR2 and CDR3 regions of SEQ ID NOs: 232, 317, 402, 487, 572 and 657. 
     
     
         10 . The antibody of  claim 1 , being capable of neutralizing subtypes A and B of RSV in a virus neutralization assay. 
     
     
         11 . The antibody of  claim 2 , being capable of providing a significant reduction of RSV virus load in the lungs of a mammal infected with RSV. 
     
     
         12 . An antibody composition comprising the anti-RSV antibody of  claim 2 , and one or more additional anti-RSV antibodies. 
     
     
         13 . The antibody composition of  claim 12 , wherein the one or more additional anti-RSV antibodies are selected from the group consisting of human antibodies, humanized antibodies, and chimeric human-mouse antibodies. 
     
     
         14 . The antibody composition of  claim 12 , wherein the one or more additional anti-RSV antibodies comprises:
 (i) a CDRH1 selected from the group consisting of SEQ ID NOs: 201-285;   (ii) a CDRH2 selected from the group consisting of SEQ ID NOs: 286-370;   (iii) a CDRH3 selected from the group consisting of SEQ ID NOs: 371-455;   (iv) a CDRL1 selected from the group consisting of SEQ ID NOs: 456-540;   (v) CDRL2 selected from the group consisting of SEQ ID NOs: 541-625; and   (vi) a CDRL3 selected from the group consisting of SEQ ID NOs: 626-710.   
     
     
         15 . A composition comprising an anti-RSV antibody comprising:
 (i) a CDRH1 selected from the group consisting of SEQ ID NOs: 201-285;   (ii) a CDRH2 selected from the group consisting of SEQ ID NOs: 286-370;   (iii) a CDRH3 selected from the group consisting of SEQ ID NOs: 371-455;   (iv) a CDRL1 selected from the group consisting of SEQ ID NOs: 456-540;   (v) a CDRL2 selected from the group consisting of SEQ ID NOs: 541-625; and   (vi) a CDRL3 selected from the group consisting of SEQ ID NOs: 626-710.   
     
     
         16 . The composition of  claim 15 , being capable of neutralizing RSV subtype A in a virus neutralization assay. 
     
     
         17 . The composition of  claim 15 , being capable of neutralizing RSV subtype B in a virus neutralization assay. 
     
     
         18 . The composition of  claim 15 , further comprising one or more additional anti-RSV antibodies. 
     
     
         19 . A method of preventing, treating or ameliorating one or more symptoms associated with a RSV infection in a mammal, comprising administering an effective amount of the anti-RSV antibody according to  claim 2 . 
     
     
         20 . The method according to  claim 19 , wherein the effective amount is between 0.1-50 mg antibody per kg of body weight. 
     
     
         21 . The method according to  claim 19 , wherein the anti-RSV antibody is administered at least 1 time per year. 
     
     
         22 . The method according to  claim 21 , wherein the anti-RSV antibody is administered at regular intervals during a period of the year where there is an increased risk of attracting an RSV infection. 
     
     
         23 . The method according to  claim 22 , wherein the regular intervals are weekly, bi-weekly, monthly, or bi-monthly. 
     
     
         24 . An isolated nucleic acid fragment which encodes the anti-RSV antibody of  claim 2 . 
     
     
         25 - 35 . (canceled)