AMINO ACID SEQUENCES DIRECTED AGAINST ENVELOPE PROTEINS OF A VIRUS AND POLYPEPTIDES COMPRISING THE SAME FOR THE TREATMENT OF VIRAL DISEASES

• US 20110182897A1
• Filed: 06/05/2009
• Published: 07/28/2011
• Est. Priority Date: 06/05/2008
• Status: Active Grant

• Current Assignee: Ablynx NV (Sanofi )
• Original Assignee: Ablynx NV (Sanofi )
• Inventors: Verrips, Cornelis Theodorus, Hultberg, Anna, Harmsen, Michael Marie, Schepens, Bert, Saelens, Xavier, Maassen, Bram, Weiss, Robert Anthony, Temperton, Nigel J., Van Gucht, Steven, Szyroki, Alexander, De Haard, Johannes Joseph Wilhelmus, Melero, Jose, Saunders, Michael John Scott, Vanlandschoot, Peter, Stortelers, Catelijne, Depla, Erik
• Granted Patent: US 9,193,780 B2
• Time in Patent Office: Days
• US Class Current: 424/134.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: C07K 16/10 from RNA viruses
• CPC Class Codes: C07K 16/1009 Picornaviridae, e.g. hepatitis A virus
• CPC Class Codes: C07K 16/1018 Orthomyxoviridae, e.g. influenza virus
• CPC Class Codes: C07K 16/1027 Paramyxoviridae, e.g. respiratory syncytial virus
• CPC Class Codes: C07K 2317/22 from camelids, e.g. camel, llama or dromedary
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/35 Valency
• CPC Class Codes: C07K 2317/53 Hinge
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/567 Framework region [FR]
• CPC Class Codes: C07K 2317/569 Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/64 comprising a combination of variable region and constant region components
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2317/94 : Stability, e.g. half-life, pH, temperature or enzyme-resistance
• CPC Class Codes: C07K 2319/00 : Fusion polypeptide

Abstract

The present invention relates in part to amino acid sequences that are directed against and/or that can specifically bind to an envelope protein of a virus, as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences.

Claims

1. Amino acid sequence that is directed against and/or that can specifically bind to an envelope protein of a virus.

3. Amino acid sequence according to any of the preceding claims, wherein said amino acid sequence competes with said at least one binding partner for binding to said envelope protein.

4. Amino acid sequence according to claim 3, wherein said at least one binding partner is a viral receptor for an envelope protein of a virus.

5. Amino acid sequence according to claim 4, wherein said viral receptor is sialic acid.

6. Amino acid sequence according to claim 3, wherein said at least one binding partner is a monoclonal antibody or an antigen binding part thereof that is directed against and/or specifically binds to said envelope protein of a virus.

7. Amino acid sequence according to claim 6, wherein said monoclonal antibody or an antigen binding part thereof is selected from Synagis®

, 101F Fab, VN04-2, MAb C179 and MAb 8-2.

8. Amino acid sequence according to any of claims 1 to 7, wherein said amino acid sequence neutralizes said virus.

9. Amino acid sequence directed against an envelope protein of a virus according to any of claims 1 to 8, that comprises one or more stretches of amino acid residues chosen from the group consisting of:

a. the amino acid sequences of SEQ ID NO'"'"'s;

690 to 971, 2467 to 2484, 2590 to 2597, 2754 to 2789 and 3194 to 3258;

b. amino acid sequences that have at least 80% amino acid identity with at least one of the amino acid sequences of SEQ ID NO'"'"'s;

690 to 971, 2467 to 2484, 2590 to 2597, 2754 to 2789 and 3194 to 3258;

c. amino acid sequences that have 3, 2, or 1 amino acid difference with at least one of the amino acid sequences of SEQ ID NO'"'"'s;

690 to 971, 2467 to 2484, 2590 to 2597, 2754 to 2789 and 3194 to 3258;

d. the amino acid sequences of SEQ ID NO'"'"'s;

1254 to 1535, 2503 to 2520, 2606 to 2613, 2826 to 2861 and 3324 to 3388;

e. amino acid sequences that have at least 80% amino acid identity with at least one of the amino acid sequences of SEQ ID NO'"'"'s;

1254 to 1535, 2503 to 2520, 2606 to 2613, 2826 to 2861 and 3324 to 3388;

f. amino acid sequences that have 3, 2, or 1 amino acid difference with at least one of the amino acid sequences of SEQ ID NO'"'"'s;

1254 to 1535, 2503 to 2520, 2606 to 2613, 2826 to 2861 and 3324 to 3388;

g. the amino acid sequences of SEQ ID NO'"'"'s;

1818 to 2099, 2539 to 2556, 2622 to 2629, 2898 to 2933 and 3454 to 3518;

h. amino acid sequences that have at least 80% amino acid identity with at least one of the amino acid sequences of SEQ ID NO'"'"'s;

1818 to 2099, 2539 to 2556, 2622 to 2629, 2898 to 2933 and 3454 to 3518;

i. amino acid sequences that have 3, 2, or 1 amino acid difference with at least one of the amino acid sequences of SEQ ID NO'"'"'s;

1818 to 2099, 2539 to 2556, 2622 to 2629, 2898 to 2933 and 3454 to 3518;

or any suitable combination thereof.

10. Amino acid sequence according to any of claims 1 to 9, that essentially consists of a domain antibody (or an amino acid sequence that is suitable for use as a domain antibody), of a single domain antibody (or an amino acid sequence that is suitable for use as a single domain antibody), of a “

dAb”

(or an amino acid sequence that is suitable for use as a dAb) or of a Nanobody (including but not limited to a Vim sequence).

11. Amino acid sequence according to any of claims 1 to 10, that essentially consists of a Nanobody that

a. has at least 80% amino acid identity with at least one of the amino acid sequences of SEQ ID NO'"'"'s:

1 to 22, 126 to 407, 2431 to 2448, 2574 to 2581, 2682 to 2717 and 3064 to 3128 in which for the purposes of determining the degree of amino acid identity, the amino acid residues that form the CDR sequences are disregarded;

and in which;

b. preferably one or more of the amino acid residues at positions 11, 37, 44, 45, 47, 83, 84, 103, 104 and 108 according to the Kabat numbering are chosen from the Hallmark residues mentioned in Table B-2.

12. Amino acid sequence according to any of claims 1 to 11 that essentially consists of 4 framework regions (FR1 to FR4, respectively) and 3 complementarity determining regions (CDR1 to CDR3, respectively), in which:

CDR1 is chosen from the group consisting of;

a. the amino acid sequences of SEQ ID NO'"'"'s;

690 to 971, 2467 to 2484, 2590 to 2597, 2754 to 2789 and 3194 to 3258;

b. amino acid sequences that have at least 80% amino acid identity with at least one of the amino acid sequences of SEQ ID NO'"'"'s;

690 to 971, 2467 to 2484, 2590 to 2597, 2754 to 2789 and 3194 to 3258;

c. amino acid sequences that have 3, 2, or 1 amino acid difference with at least one of the amino acid sequences of SEQ ID NO'"'"'s;

690 to 971, 2467 to 2484, 2590 to 2597, 2754 to 2789 and 3194 to 3258;

and/or

CDR2 is chosen from the group consisting of;

d. the amino acid sequences of SEQ ID NO'"'"'s;

1254 to 1535, 2503 to 2520, 2606 to 2613, 2826 to 2861 and 3324 to 3388;

e. amino acid sequences that have at least 80% amino acid identity with at least one of the amino acid sequences of SEQ ID NO'"'"'s;

1254 to 1535, 2503 to 2520, 2606 to 2613, 2826 to 2861 and 3324 to 3388;

f. amino acid sequences that have 3, 2, or 1 amino acid difference with at least one of the amino acid sequences of SEQ ID NO'"'"'s;

1254 to 1535, 2503 to 2520, 2606 to 2613, 2826 to 2861 and 3324 to 3388;

and/or

CDR3 is chosen from the group consisting of;

g. the amino acid sequences of SEQ ID NO'"'"'s;

1818 to 2099, 2539 to 2556, 2622 to 2629, 2898 to 2933 and 3454 to 3518;

h. amino acid sequences that have at least 80% amino acid identity with at least one of the amino acid sequences of SEQ ID NO'"'"'s;

1818 to 2099, 2539 to 2556, 2622 to 2629, 2898 to 2933 and 3454 to 3518;

i. amino acid sequences that have 3, 2, or 1 amino acid difference with at least one of the amino acid sequences of SEQ ID NO'"'"'s;

1818 to 2099, 2539 to 2556, 2622 to 2629, 2898 to 2933 and 3454 to 3518.

13. Amino acid sequence according to any of claims 1 to 12, in which the CDR sequences of said amino acid sequence have at least 70% amino acid identity, preferably at least 80% amino acid identity, more preferably at least 90% amino acid identity, such as 95% amino acid identity or more or even essentially 100% amino acid identity with the CDR sequences of at least one of the amino acid sequences of SEQ ID NO'"'"'s:

126 to 407, 2431 to 2448, 2574 to 2581, 2682 to 2717 and 3064 to 3128.

14. Amino acid sequence according to any of claims 1 to 13, essentially consists of one of the amino acid sequences of SEQ ID NO'"'"'s:

126 to 407, 2431 to 2448, 2574 to 2581, 2682 to 2717 and 3064 to 3128 or of an amino acid sequence which has at least 70% amino acid identity, preferably at least 80% amino acid identity, more preferably at least 90% amino acid identity, such as 95% amino acid identity, 99% amino acid identity or more or even essentially 100% amino acid identity with the at least one of the amino acid sequences of SEQ ID NO'"'"'s;

126 to 407, 2431 to 2448, 2574 to 2581, 2682 to 2717 and 3064 to 3128.

15. Amino acid sequence according to any of claims 1 to 14, directed against an envelope protein of a virus that cross-blocks the binding of at least one of the amino acid sequences of SEQ ID NO'"'"'s:

126 to 407, 2431 to 2448, 2574 to 2581, 2682 to 2717 and 3064 to 3128 to an envelope protein of a virus.

16. Amino acid sequence according to any of claims 1 to 15, directed against an envelope protein of a virus that is cross-blocked from binding to an envelope protein of a virus by at least one of the amino acid sequences of SEQ ID NO'"'"'s:

126 to 407, 2431 to 2448, 2574 to 2581, 2682 to 2717 and 3064 to 3128.

17. Amino acid sequence according to any of claims according to any of claims 1 to 16, that essentially consists of a humanized Nanobody.

18. Polypeptide, compound or construct, that comprises or essentially consists of one or more amino acid sequences according to any of claims 1 to 17, and optionally further comprises one or more other groups, residues, moieties or binding units, optionally linked via one or more linkers.

19. Polypeptide, compound or construct according to claim 18, in which said one or more other groups, residues, moieties or binding units are chosen from the group consisting of domain antibodies, amino acid sequences that are suitable for use as a domain antibody, single domain antibodies, amino acid sequences that are suitable for use as a single domain antibody, “

dAb”

'"'"'s, amino acid sequences that are suitable for use as a dAb, or Nanobodies.

20. Polypeptide, compound or construct according to any of claims 18 to 19, in which said one or more amino acid sequences of the invention are chosen from the group consisting of domain antibodies, amino acid sequences that are suitable for use as a domain antibody, single domain antibodies, amino acid sequences that are suitable for use as a single domain antibody, “

dAb”

'"'"'s, amino acid sequences that are suitable for use as a dAb, or Nanobodies.

21. Polypeptide, compound or construct according to any of claims 18 to 20, which is a multivalent construct.

22. Polypeptide, compound or construct according to claim 21, which is a bivalent construct.

23. Polypeptide, compound or construct according to claim 22, which comprises two amino acid sequences that are directed against and/or capable of binding to the Synagis®

binding site on the F protein of RSV and/or that are capable of competing with Synagis®

for binding to the F protein of RSV.

24. Polypeptide, compound or construct according to claim 22, which comprises two amino acid sequences that are directed against and/or capable of binding to the 101F binding site on the F protein of RSV and/or that are capable of competing with 101F for binding to the F protein of RSV.

25. Polypeptide, compound or construct according to claim 22, which comprises two amino acid sequences that are directed against and/or capable of binding to the sialic acid binding site on the hemagglutinin H5 envelope protein of influenza virus and/or that are capable of competing with sialic acid for binding to the hemagglutinin H5 envelope protein of influenza virus.

26. Polypeptide, compound or construct according to claim 22, which comprises two amino acid sequences that are directed against and/or capable of binding to the VN04-2 binding site on the hemagglutinin H5 envelope protein of influenza virus and/or that are capable of competing with VN04-2 for binding to the hemagglutinin H5 envelope protein of influenza virus.

27. Polypeptide, compound or construct according to claim 22, which comprises two amino acid sequences that are directed against and/or capable of binding to the MAb C179 binding site on the hemagglutinin H5 envelope protein of influenza virus and/or that are capable of competing with MAb C179 for binding to the hemagglutinin H5 envelope protein of influenza virus.

28. Polypeptide, compound or construct according to claim 22, which comprises two amino acid sequences that are directed against and/or capable of binding to the MAb 8-2 binding site on the G envelope protein of rabies virus and/or that are capable of competing with the MAb 8-2 for binding to the G envelope protein of rabies virus.

29. Polypeptide, compound or construct according to claim 21, which is a biparatopic construct comprising at least one amino acid sequence directed against a first antigenic determinant, epitope, part or domain of an envelope protein of a virus and at least one amino acid sequence directed against a second antigenic determinant, epitope, part or domain of the envelope protein of a virus different from the first antigenic determinant, epitope, part or domain.

30. Polypeptide, compound or construct according to claim 29, which comprises at least one amino acid sequence directed against a first antigenic determinant, epitope, part or domain of the F protein of RSV virus and at least one amino acid sequence directed against a second antigenic determinant, epitope, part or domain of the F protein of RSV virus different from the first antigenic determinant, epitope, part or domain.

31. Polypeptide, compound or construct according to any of claims 29 to 30, which comprises at least one amino acid sequence that is directed against and/or capable of binding to the Synagis®

binding site on the F protein of RSV and/or which competes with Synagis®

for binding to the F protein of RSV and at least one further amino acid sequence that is capable of binding to at least one other antigenic determinant, epitope, part or domain of the F protein of RSV.

32. Polypeptide, compound or construct according to any of claims 29 to 30, which comprises at least one amino acid sequence that is directed against and/or capable of binding to the 101F binding site on the F protein of RSV and/or which competes with 101F for binding to the F protein of RSV and at least one further amino acid sequence that is capable of binding to at least one other antigenic determinant, epitope, part or domain of the F protein of RSV.

33. Polypeptide, compound or construct according to any of claims 29 to 30, which comprises at least one amino acid sequence that is directed against and/or capable of binding to the Synagis®

binding site on the F protein of RSV and/or which competes with Synagis®

for binding to the F protein of RSV and at least one further amino acid sequence that is directed against and/or capable of binding to the 101F binding site on the F protein of RSV and/or which competes with 101F for binding to the F protein of RSV.

34. Polypeptide, compound or construct according to claim 29, which comprises at least one amino acid sequence directed against a first antigenic determinant, epitope, part or domain of the hemagglutinin H5 envelope protein of influenza virus and at least one amino acid sequence directed against a second antigenic determinant, epitope, part or domain of the hemagglutinin H5 envelope protein of influenza virus different from the first antigenic determinant, epitope, part or domain.

35. Polypeptide, compound or construct according to claim 34, which comprises at least one amino acid sequence that is directed against and/or capable of binding to the sialic acid binding site on the hemagglutinin H5 envelope protein of influenza virus and/or which competes with sialic acid for binding to the hemagglutinin H5 envelope protein of influenza virus and at least one further amino acid sequence that is capable of binding to at least one other antigenic determinant, epitope, part or domain of the hemagglutinin H5 envelope protein of influenza virus.

36. Polypeptide, compound or construct according to claim 34, which comprises at least one amino acid sequence that is directed against and/or capable of binding to the VN04-2 binding site on the hemagglutinin H5 envelope protein of influenza virus and/or which competes with VN04-2 for binding to the hemagglutinin H5 envelope protein of influenza virus and at least one further amino acid sequence that is capable of binding to at least one other antigenic determinant, epitope, part or domain of the hemagglutinin H5 envelope protein of influenza virus.

37. Polypeptide, compound or construct according to claim 34, which comprises at least one amino acid sequence that is directed against and/or capable of binding to the MAb C179 binding site on the hemagglutinin H5 envelope protein of influenza virus and/or which competes with MAb C179 for binding to the hemagglutinin H5 envelope protein of influenza virus and at least one further amino acid sequence that is capable of binding to at least one other antigenic determinant, epitope, part or domain of the hemagglutinin H5 envelope protein of influenza virus.

38. Polypeptide, compound or construct according to claim 29, which comprises at least one amino acid sequence directed against a first antigenic determinant, epitope, part or domain of the G protein of rabies virus and at least one amino acid sequence directed against a second antigenic determinant, epitope, part or domain of the G protein of rabies virus different from the first antigenic determinant, epitope, part or domain.

39. Polypeptide, compound or construct according to claim 38, which comprises at least one amino acid sequence that is directed against and/or capable of binding to the MAb 8-2 binding site on the G protein of rabies virus and/or which competes with MAb 8-2 for binding to the G protein of rabies virus and at least one further amino acid sequence that is capable of binding to at least one other antigenic determinant, epitope, part or domain of the G protein of rabies virus.

40. Polypeptide, compound or construct according to claim 21, which is a trivalent construct.

41. Compound or construct according to claim 40 that comprises three amino acid sequences that are directed against the same antigenic determinant, epitope, part or domain of the viral envelope protein.

42. Polypeptide, compound or construct according to any of claims 40 to 41, that comprises three amino acid sequences that are directed against and/or specifically bind the Synagis®

binding site on the F protein of RSV virus and/or that compete with Synagis®

for binding the F protein of RSV virus.

43. Polypeptide, compound or construct according to any of claims 40 to 41, that comprises three amino acid sequences that are directed against and/or specifically bind the 101F binding site on the F protein of RSV virus and/or that compete with Synagis®

for binding the F protein of RSV virus.

44. Polypeptide, compound or construct according to any of claims 40 to 41, that comprises three amino acid sequences that are directed against and/or specifically bind the sialic acid binding site on the hemagglutinin H5 envelope protein of influenza virus and/or that compete with sialic acid for binding the hemagglutinin H5 envelope protein of influenza virus.

45. Polypeptide, compound or construct according to any of claims 40 to 41, that comprises three amino acid sequences that are directed against and/or specifically bind the VN04-2 binding site on the hemagglutinin H5 envelope protein of influenza virus and/or that compete with VN04-2 for binding the hemagglutinin H5 envelope protein of influenza virus.

46. Polypeptide, compound or construct according to any of claims 40 to 41, that comprises three amino acid sequences that are directed against and/or specifically bind the MAb C179 binding site on the hemagglutinin H5 envelope protein of influenza virus and/or that compete with MAb C179 for binding the hemagglutinin H5 envelope protein of influenza virus.

47. Polypeptide, compound or construct according to any of claims 40 to 41, that comprises three amino acid sequences that are directed against and/or specifically bind the MAb 8-2 binding site on the G envelope protein of rabies virus and/or that compete with MAb 8-2 for binding the G envelope protein of rabies virus.

48. Polypeptide, compound or construct according to claim 40 that comprises two amino acid sequences that are directed against a first antigenic determinant, epitope, part or domain of the viral envelope protein and one amino acid sequence that is directed against a second antigenic determinant, epitope, part or domain of the viral envelope protein.

49. Polypeptide, compound or construct according to claim 48 that comprises two amino acid sequences directed against and or capable of binding the Synagis®

binding site on the F protein of RSV virus and/or that compete with Synagis®

for binding the F protein of RSV virus, and one amino acid sequence directed against another determinant, epitope, part or domain on the F protein of RSV virus.

50. Polypeptide, compound or construct according to claim 40 that comprises two amino acid sequences directed against and or capable of binding the 101F binding site on the F protein of RSV virus and/or that compete with 101F for binding the F protein of RSV virus, and one amino acid sequence directed against another determinant, epitope, part or domain on the F protein of RSV virus.

51. Polypeptide, compound or construct according to claim 40 that comprises two amino acid sequences directed against and or capable of binding the Synagis®

binding site on the F protein of RSV virus and/or that compete with Synagis®

for binding the F protein of RSV virus, and one amino acid sequence directed against and/or capable of binding the 101F binding site on the F protein of RSV virus and/or that competes with 101F for binding the F protein of RSV virus.

52. Polypeptide, compound or construct according to claim 40 that comprises one amino acid sequence directed against and or capable of binding the Synagis®

binding site on the F protein of RSV virus and/or that competes with Synagis®

for binding the F protein of RSV virus, and two amino acid sequences directed against and/or capable of binding the 101F binding site on the F protein of RSV virus and/or that compete with 101F for binding the F protein of RSV virus.

53. Polypeptide, compound or construct according to claim 40 that comprises two amino acid sequences directed against and/or capable of binding the sialic acid binding site on the hemagglutinin H5 envelope protein of influenza virus and/or that compete with sialic acid for binding the hemagglutinin H5 envelope protein of influenza virus, and one amino acid sequence directed against another determinant, epitope, part or domain on the hemagglutinin H5 envelope protein of influenza virus.

54. Polypeptide, compound or construct according to claim 40 that comprises two amino acid sequences directed against and or capable of binding the VN04-2 binding site on the hemagglutinin H5 envelope protein of influenza virus and/or that compete with VN04-2 for binding the hemagglutinin H5 envelope protein of influenza virus, and one amino acid sequence directed against another determinant, epitope, part or domain on the hemagglutinin H5 envelope protein of influenza virus.

55. Polypeptide, compound or construct according to claim 40 that comprises two amino acid sequences directed against and or capable of binding the MAb C179 binding site on the hemagglutinin H5 envelope protein of influenza virus and/or that compete with MAb C179 for binding the hemagglutinin H5 envelope protein of influenza virus, and one amino acid sequence directed against another determinant, epitope, part or domain on the hemagglutinin H5 envelope protein of influenza virus.

56. Polypeptide, compound or construct according to claim 40 that comprises two amino acid sequences directed against and or capable of binding the MAb 8-2 binding site on the G envelope protein of rabies virus and/or that compete with MAb 8-2 for binding the G envelope protein of rabies virus, and one amino acid sequence directed against another determinant, epitope, part or domain on the G envelope protein of rabies virus.

58. Polypeptide, compound or construct according to any of claims 1 to 21, which is a multispecific construct.

59. Polypeptide, compound or construct according to any of claims 1 to 58, which has an increased half-life, compared to the corresponding amino acid sequence according to any of claims 1 to 17 per se, or polypeptide, compound or construct according to any of claims 18 to 58 per se, respectively.

60. Polypeptide, compound or construct according to claim 59, in which one or more other groups, residues, moieties or binding units provide the compound or construct with increased half-life, chosen from the group consisting of serum proteins (such as of human serum albumin) or fragments thereof, binding units (such as domain antibodies, amino acid sequences that are suitable for use as a domain antibody, single domain antibodies, amino acid sequences that are suitable for use as a single domain antibody, “

dAb”

'"'"'s, amino acid sequences that are suitable for use as a dAb, or Nanobodies) that can bind to serum proteins (such as human serum albumin or serum immunoglobulin (such as IgG)), an Fc portion, and small proteins or peptides that can bind to serum proteins.

61. Nucleic acid or nucleotide sequence that encodes an amino acid sequence according to any of claims 1 to 17 or a polypeptide, compound or construct according to any of claims 1 to 60.

62. Host or host cell that expresses, or that under suitable circumstances is capable of expressing, an amino acid sequence according to any of claims 1 to 17, a polypeptide, a compound or construct according to any of claims 18 to 60, that is such that it can be obtained by expression of a nucleic acid or nucleotide sequence encoding the same, and/or that comprises a nucleic acid or nucleotide sequence according to claim 61.

63. Composition, comprising at least one amino acid sequence according to any of claims 1 to 17, polypeptide, compound or construct according to any of claims 18 to 60, or nucleic acid or nucleotide sequence according to claim 61.

64. Composition according to claim 63, which is a pharmaceutical composition, that further comprises at least one pharmaceutically acceptable carrier, diluent or excipient and/or adjuvant, and that optionally comprises one or more further pharmaceutically active polypeptides and/or compounds.

65. Method for producing an amino acid sequence according to any of claims 1 to 17, a polypeptide, a compound or construct according to any of claims 18 to 60, or a composition according to any of claim 63 or 64, said method at least comprising the steps of:

a. expressing, in a suitable host cell or host organism or in another suitable expression system, a nucleic acid or nucleotide sequence according to claim 61,

optionally followed by;

b. isolating and/or purifying the amino acid sequence according to any of claims 1 to 17 or the polypeptide, the compound or construct according to any of claims 18 to 60.

66. Method for producing an amino acid sequence according to any of claims 1 to 17, a polypeptide, a compound or construct according to any of claims 18 to 60, or a composition according to any of claims 63 to 64, said method at least comprising the steps of:

a. cultivating and/or maintaining a host or host cell according to claim 63 under conditions that are such that said host or host cell expresses and/or produces at least one amino acid sequence according to any of claims 1 to 17, polypeptide, compound or construct according to any of claims 18 to 60, or composition according to any of claims 63 to 64,

optionally followed by;

b. isolating and/or purifying the amino acid sequence according to any of claims 1 to 17, the polypeptide, the compound or construct according to any of claims 18 to 60, or the composition according to claims 63 to 64, thus obtained.

67. Method for preparing and/or generating a bivalent or trivalent construct according to any of claims 22 to 57, said method comprising at least the steps of linking two or more monovalent amino acid sequences according to any of claims 1 to 17 and for example one or more linkers.

68. Method according to claim 67, comprising the steps of:

a. linking two or more nucleic acid sequences according to claim 61, encoding an amino acid sequence according to any of claims 1 to 17 (and also for example nucleic acids encoding one or more linkers and further one or more further elements of genetic constructs known per se);

b. expressing, in a suitable host cell or host organism or in another suitable expression system, the genetic construct obtained in a)

optionally followed by;

c. isolating and/or purifying the biparatopic or triparatopic construct according to any of claims 22 to 57 thus obtained.

69. Method for the prevention and/or treatment of at least one disease or disorder that is associated with viral entry and/or viral replication and/or mediated by an envelope protein of a virus and/or its viral receptor, with its biological or pharmacological activity, and/or with the viral-mediated biological pathways in which an envelope protein of a virus and/or its viral receptor is involved, said method comprising administering, to a subject in need thereof, a pharmaceutically active amount of at least one amino acid sequence according to any of claims 1 to 17, polypeptide, compound or construct according to any of claims 18 to 60, and/or composition according to claims 63 to 64.

70. Use of an amino acid sequence according to any of claims 1 to 17, a polypeptide, a compound or construct according to any of claims 18 to 60 and/or a composition according to claims 63 to 64 in the preparation of a pharmaceutical composition for prevention and/or treatment of at least one viral disease.

71. Amino acid sequence according to any of claims 1 to 17, polypeptide, compound or construct according to any of claims 18 to 60 and/or composition according to claims 63 to 64 for use in prevention and/or treatment of at least one disease or disorder that is associated with viral entry and/or viral replication and/or mediated by an envelope protein of a virus and/or its viral receptor, with its biological or pharmacological activity, and/or with the viral-mediated biological pathways in which an envelope protein of a virus and/or its viral receptor is involved.

72. A method for administering an effective amount of an amino acid sequence according to any of claims 1 to 17, a polypeptide, a compound or construct according to any of claims 18 to 60, directed against an envelope protein of a virus (such as an envelope protein of RSV virus, an envelope protein of influenza virus and/or an envelope protein of rabies virus) and/or a composition comprising the same, wherein said method comprises the step of administering the amino acid sequence according to any of claims 1 to 17, the polypeptide, the compound or construct according to any of claims 18 to 60, and/or the composition comprising the same to the pulmonary tissue.

73. The method according to claim 72, wherein the amino acid sequence according to any of claims 1 to 17, the polypeptide, the compound or construct according to any of claims 18 to 60, and/or the composition comprising the same is administered by use of an inhaler, an intranasal delivery device or an aerosol.

74. Pharmaceutical composition comprising an amino acid sequence according to any of claims 1 to 17 and/or a polypeptide, a compound or construct according to any of claims 18 to 60, and a carrier suitable for pulmonary delivery.

75. Pharmaceutical device that is an inhaler for liquids (e.g. a suspension of fine solid particles or droplets), an aerosol or a dry powder inhaler comprising the amino acid sequence according to any of claims 1 to 17 and/or the polypeptide, the compound or construct according to any of claims 18 to 60.

76. Method for the prevention and/or treatment of at least one viral disease, said method comprising administering to the pulmonary tissue of a subject in need thereof, a pharmaceutically active amount of an amino acid sequence according to any of claims 1 to 17, a polypeptide, a compound or construct according to any of claims 18 to 60 and/or of a pharmaceutical composition comprising the same.

2. Amino acid sequence according to claim 2, wherein said amino acid sequence modulates, inhibits and/or prevents the interaction between said envelope protein and at least one binding partner.

57. Polypeptide, compound or construct that comprises or that is chosen from the group consisting of SEQ ID NO'"'"'s:

2382 to 2415, 2423 to 2430, 2641 to 2659, 2663 to 2681, 2978 to 2998 and 3016 to 3056 or from the group consisting of from amino acid sequences that have more than 80%, preferably more than 90%, more preferably more than 95%, such as 99% or more sequence identity (as defined herein) with at least one of the amino acid sequences of SEQ ID NO'"'"'s;

2382 to 2415, 2423 to 2430, 2641 to 2659, 2663 to 2681, 2978 to 2998 and 3016 to 3056.