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

• US 20070196916A1
• Filed: 12/20/2006
• Published: 08/23/2007
• Est. Priority Date: 11/28/2000
• Status: Active Grant

• Current Assignee: Medimmune LLC (Astrazeneca PLC)
• Original Assignee: Medimmune Incorporated (Astrazeneca PLC)
• Inventors: Wu, Herren, Koenig, Scott, Huse, William, Johnson, Leslie, Young, James, Watkins, Jeffrey
• Granted Patent: US 7,553,489 B2
• Time in Patent Office: Days
• US Class Current: 435/345
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: C07K 16/1027 Paramyxoviridae, e.g. respiratory syncytial virus
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]

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 of a RSV infection.

Claims

1. An antibody comprising a variable heavy (VH) domain having the amino acid sequence of the VH domain of AFFF, P12f2, P12f4, P11d4, A1e9, A12a6, A17d4, A4B4, A8c7, H3-3F4, M3H9, 6H8, or A13a11 and/or 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), A4B4L1FR-S28R, or A4B4-F52S, wherein said antibody immunospecifically binds to a respiratory syncytial virus (RSV) F antigen.

7. The antibody of claim 1, wherein the antibody is AFFF, P12f2, P12f4, P11d4, A1e9, A12a6, A13c4, A17d4, A4B4, A8c7, IX-493LER, H3-3F4, M3H9, Y10H6, DG, AFFF(1), 6H8, L1-7E5, L2-15B10, A13a11, A1h5, A4B4(1), A4B4L1FR-S28R, or A4B4-F52S.

11. A composition comprising one or more antibodies of claim 7.

15. An isolated nucleic acid molecule comprising a nucleotide sequence encoding the antibody of claim 7.

21. A pharmaceutical composition comprising the antibody of claim 1 or 3 and a carrier or excipient.

23. A method of preventing, treating or ameliorating a RSV infection, 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.

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 or 7; 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.

2. (canceled)

3. An antibody comprising a VH complementarity determining region (CDR) having the amino acid sequence of a CDR of AFFF, P12f2, P12f4, P11d4, A1e9, A12a6, A13c4, A17d4, A4B4, A8c7, IX-493L1FR, H3-3F4, M3H9, Y10H6, DG, AFFF(1), 6H8, L1-7E5, L2-15B10, A13a11, A1h5, A4B4(1), A4B4L1FR-S28R, or A4B4-F52S, and/or a VL CDR having the amino acid sequence of a CDR of AFFF, P12f2, P12f4, P11d4, A1e9, A12a6, A13c4, A17d4, A4B4, A8c7, IX-493L1FR, H3-3F4, M3H9, Y10H6, DG, AFFF(1), 6H8, L1-7E5, L2-15B10, A13a11, A1h5, A4B4(1), A4B4L1FR-S28R, or A4B4-F52S, wherein said antibody immunospecifically binds to a RSV F antigen and said antibody is not palivizumab.

4-6. -6. (canceled)

8. A composition comprising one or more species of antibodies, each species of antibody comprising a VH domain having the amino acid sequence of the VH domain of AFFF, P12f2, P12f4, P11d4, A1e9, A12a6, A17d4, A4B4, A8c7, H3-3F4, M3H9, 6H8, or A13a11 and/or 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), A4B4L1FR-S28R, or A4B4-F52S antigen.

9. (canceled)

10. A composition comprising one or more species of antibodies, each species of antibody comprising a CDR having the amino acid sequence of a CDR of AFFF, P12f2, P12f4, P11d4, A1e9, A12a6, A13c4, A17d4, A4B4, A8c7, IX-493L1FR, H3-3F4, M3H9, Y10H6, DG, AFFF(1), 6H8, L1-7E5, L2-15B10, A13a11, A1h5, A4B4(1), A4B4L1FR-S28R, or A4B4-F52S, wherein each species of antibody immunospecifically binds to a RSV F antigen and none of the species of antibodies is palivizumab.

12. An isolated nucleic acid molecule comprising a nucleotide sequence encoding an antibody comprising a 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 A13a11, and/or a VL domain having an 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), A4B4L1FR-S28R, or A4B4-F52S, wherein said antibody immunospecifically binds to a RSV F antigen.

16. A vector comprising the nucleic acid molecule of claim 12 or 14.

18. A host cell genetically engineered to express the nucleic acid molecule of claim 12 or 14.

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.

13. (canceled)

14. An isolated nucleic acid molecule comprising a nucleotide sequence encoding an antibody comprising a CDR having the amino acid sequence of a CDR of AFFF, P12f2, P12f4, P11d4, A1e9, A12a6, A13c4, A17d4, A4B4, A8c7, IX-493L1FR, H3-3F4, M3H9, Y10H6, DG, AFFF(1), 6H8, L1-7E5, L2-15B10, A13a11, A1h5, A4B4(1), A4B4L1FR-S28R, or A4B4-F52S, wherein said antibody immunospecifically binds to a RSV F antigen and said antibody is not palivizumab.

17. (canceled)

19. (canceled)

22. (canceled)

24-27. -27. (canceled)

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. A composition comprising 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.