Peptides antibodies directed thereagainst and methods using same for diagnosing and treating amyloid-associated diseases

1 . A peptide comprising amino acid sequence X-Y or Y-X, wherein X is an aromatic amino acid and Y is any amino acid other than glycine, the peptide being at least 2 and no more than 15 amino acid residues in length.

2 . The peptide of claim 1 , wherein Y is a polar uncharged amino acid selected from the group consisting of serine, threonine, asparagine, glutamine and natural derivatives thereof.

3 . The peptide of claim 1 , wherein Y is a β-sheet breaker amino acid.

4 . The peptide of claim 3 , wherein said β-sheet breaker amino acid is a naturally occurring amino acid.

5 . The peptide of claim 4 , wherein said naturally occurring amino acid is selected from the group consisting of proline, aspartic acid, glutamine acid, glycine, lysine and serine.

6 . The peptide of claim 3 , wherein said β-sheet breaker amino acid is a synthetic amino acid.

7 . The peptide of claim 6 , wherein said synthetic amino acid is a Ca-methylated amino acid.

8 . The peptide of claim 7 , wherein said Ca-methylated amino acid is a-aminoisobutyric acid.

9 . The peptide of claim 1 , wherein the peptide is a linear or cyclic peptide.

10 . The peptide of claim 1 , wherein the peptide is selected from the group consisting of SEQ ID NOs. 4, 12-19, 27-45, 112-123, 125 and 127.

11 . The peptide of claim 1 , wherein the peptide is at least 4 amino acids in length and includes at least two serine residues at a C-terminus thereof.

12 . The peptide of claim 1 , wherein the peptide is at least 3 amino acid residues in length and whereas at least one of said amino acid residues of the peptide other than X-Y is a polar uncharged amino acid selected from the group consisting of serine, threonine, asparagine, glutamine and natural derivatives thereof.

13 . The peptide of claim 1 , wherein the peptide is at least 3 amino acid residues in length and whereas at least one of said amino acid residues of the peptide other than X-Y is a β-sheet breaker amino acid.

14 . The peptide of claim 13 , wherein said β-sheet breaker amino acid is a naturally occurring amino acid.

15 . The peptide of claim 14 , wherein said naturally occurring amino acid is selected from the group consisting of proline, aspartic acid, glutamic acid, glycine, lysine and serine.

16 . The peptide of claim 13 , wherein said β-sheet breaker amino acid is a synthetic amino acid.

17 . The peptide of claim 16 , wherein said synthetic amino acid is a Ca-methylated amino acid.

18 . The peptide of claim 17 , wherein said Ca-methylated amino acid is a-aminoisobutyric acid.

19 . The peptide of claim 13 , wherein said β-sheet breaker amino acid is located downstream to said X-Y in the peptide.

20 . The peptide of claim 13 , wherein said β-sheet breaker amino acid is located upstream to said X-Y in the peptide.

21 . The peptide of claim 1 , wherein the peptide is at least 3 amino acid residues in length and whereas at least one of said amino acid residues of the peptide is a positively charged amino acid and at least one of said amino acid residues of the peptide is a negatively charged amino acid.

22 . The peptide of claim 21 , wherein said positively charged amino acid is selected from the group consisting of lysine, arginine, and natural and synthetic derivatives thereof.

23 . The peptide of claim 21 , wherein said negatively charged amino acid is selected from the group consisting of aspartic acid, glutamic acid and natural and synthetic derivatives thereof.

24 . A peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs. 4, 12-19, 27-45, 112-123, 125 and 127, the peptide being at least 2 and no more than 15 amino acid residues in length.

25 . The peptide of claim 24 , wherein the peptide is capable of self-aggregating under physiological conditions.

26 . The peptide of claim 24 , wherein the peptide is at least 4 amino acids in length and includes at least two serine residues at a C-terminus thereof.

27 . The peptide of claim 24 , wherein the peptide is a linear or cyclic peptide.

28 . A peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs. 4, 12-19, 27-45, 112-123, 125 and 127, the peptide being at least 2 and no more than 15 amino acid residues in length.

29 . The peptide of claim 28 , wherein the peptide is capable of self-aggregating under physiological conditions.

30 . The peptide of claim 28 , wherein the peptide is at least 4 amino acids in length and includes at least two serine residues at a C-terminus thereof.

31 . The peptide of claim 28 , wherein the peptide is a linear or cyclic peptide.

32 . A peptide selected from the group consisting of SEQ ID NOs. 4, 12-19, 27-45, 112-123, 125 and 127.

33 . The peptide of claim 32 , wherein the peptide is a linear or cyclic peptide.

34 . A method of treating or preventing an amyloid-associated disease in an individual, the method comprising providing to the individual a therapeutically effective amount of a peptide including the amino acid sequence X-Y or Y-X, wherein X is an aromatic amino acid and Y is any amino acid other than glycine, said peptide being at least 2 and no more than 15 amino acid residues in length.

35 . The method of claim 34 , wherein Y is a polar uncharged amino acid selected from the group consisting of serine, threonine, asparagine, glutamine and natural derivatives thereof.

36 . The method of claim 34 , wherein Y is a β-sheet breaker amino acid.

37 . The method of claim 36 , wherein said β-sheet breaker amino acid is a naturally occurring amino acid.

38 . The method of claim 37 , wherein said naturally occurring amino acid is selected from the group consisting of proline, aspartic acid, glutamic acid, glycine, lysine and serine.

39 . The method of claim 36 , wherein said β-sheet breaker amino acid is a synthetic amino acid.

40 . The method of claim 39 , wherein said synthetic amino acid is a Ca-methylated amino acid.

41 . The method of claim 40 , wherein said Ca-methylated amino acid is a-aminoisobutyric acid.

42 . The method of claim 34 , wherein said peptide is a linear or cyclic peptide.

43 . The method of claim 34 , wherein said peptide is selected from the group consisting of SEQ ID NOs. 4, 12-19, 27-45, 112-123, 125 and 127.

44 . The method of claim 34 , wherein said peptide is at least 4 amino acids in length and includes at least two serine residues at a C-terminus thereof.

45 . The method of claim 34 , wherein said peptide is at least 3 amino acid residues in length and whereas at least one of said amino acid residues of said peptide other than X-Y is a polar uncharged amino acid selected from the group consisting of serine, threonine, asparagine, glutamine and natural derivatives thereof.

46 . The method of claim 34 , wherein said peptide is at least 3 amino acid residues in length and whereas at least one of said amino acid residues of said peptide other than X-Y is a β-sheet breaker amino acid.

47 . The method of claim 46 , wherein said β-sheet breaker amino acid is a naturally occurring amino acid.

48 . The method of claim 47 , wherein said naturally occurring amino acid is selected from the group consisting of proline, aspartic acid, glutamic acid, glycine, lysine and serine.

49 . The method of claim 46 , wherein said β-sheet breaker amino acid is a synthetic amino acid.

50 . The method of claim 49 , wherein said synthetic amino acid is a Ca-methylated amino acid.

51 . The method of claim 50 , wherein said Ca-methylated amino acid is a-aminoisobutyric acid.

52 . The method of claim 46 , wherein said β-sheet breaker amino acid is located downstream to said X-Y in said peptide.

53 . The method of claim 46 , wherein said β-sheet breaker amino acid is located upstream to said X-Y in said peptide.

54 . The method of claim 34 , wherein said peptide is at least 3 amino acid residues in length and whereas at least one of said amino acid residues of said peptide is a positively charged amino acid and at least one of said amino acid residues of said peptide is a negatively charged amino acid.

55 . The method of claim 54 , wherein said positively charged amino acid is selected from the group consisting of lysine, arginine, and natural and synthetic derivatives thereof.

56 . The method of claim 54 , wherein said negatively charged amino acid is selected from the group consisting of aspartic acid, glutamic acid and natural and synthetic derivatives thereof.

57 . The method of claim 34 , wherein said peptide is an active ingredient of a pharmaceutical composition which also includes a physiologically acceptable carrier.

58 . The method of claim 34 , wherein said peptide is expressed from a nucleic acid construct.

59 . A pharmaceutical composition for treating or preventing an amyloid-associated disease comprising as an active ingredient a peptide including the amino acid sequence X-Y or Y-X, wherein X is an aromatic amino acid and Y is any amino acid other than glycine, said peptide being at least 2 and no more than 15 amino acid residues in length and a pharmaceutically acceptable carrier or diluent.

60 . The pharmaceutical composition of claim 59 , wherein Y is a polar uncharged amino acid selected from the group consisting of serine, threonine, asparagine, glutamine and natural derivatives thereof.

61 . The pharmaceutical composition of claim 59 , wherein Y is a β-sheet breaker amino acid.

62 . The pharmaceutical composition of claim 61 , wherein said β-sheet breaker amino acid is a naturally occurring amino acid.

63 . The pharmaceutical composition of claim 62 , wherein said naturally occurring amino acid is selected from the group consisting of proline, aspartic acid, glutamic acid, glycine, lysine and serine.

64 . The pharmaceutical composition of claim 61 , wherein said β-sheet breaker amino acid is a synthetic amino acid.

65 . The pharmaceutical composition of claim 64 , wherein said synthetic amino acid is a Ca-methylated amino acid.

66 . The pharmaceutical composition of claim 65 , wherein said Ca-methylated amino acid is a-aminoisobutyric acid.

67 . The pharmaceutical composition of claim 59 , wherein said peptide is a linear or cyclic peptide.

68 . The pharmaceutical composition of claim 59 , wherein said peptide is selected from the group consisting of SEQ ID NOs. 4, 12-19, 27-45, 112-123, 125 and 127.

69 . The pharmaceutical composition of claim 59 , wherein said peptide is at least 4 amino acids in length and includes at least two serine residues at a C-terminus thereof.

70 . The pharmaceutical composition of claim 59 , wherein said peptide is at least 3 amino acid residues in length and whereas at least one of said amino acid residues of said peptide other than X-Y is a polar uncharged amino acid selected from the group consisting of serine, threonine, asparagine, glutamine and natural derivatives thereof.

71 . The pharmaceutical composition of claim 59 , wherein said peptide is at least 3 amino acid residues in length and whereas at least one of said amino acid residues of said peptide other than X-Y is a β-sheet breaker amino acid.

72 . The pharmaceutical composition of claim 71 , wherein said β-sheet breaker amino acid is a naturally occurring amino acid.

73 . The pharmaceutical composition of claim 72 , wherein said naturally occurring amino acid is selected from the group consisting of proline, aspartic acid, glutamic acid, glycine, lysine and serine.

74 . The pharmaceutical composition of claim 71 , wherein said β-sheet breaker amino acid is a synthetic amino acid.

75 . The pharmaceutical composition of claim 74 , wherein said synthetic amino acid is a Ca-methylated amino acid.

76 . The pharmaceutical composition of claim 75 , wherein said Ca-methylated amino acid is a-aminoisobutyric acid.

77 . The pharmaceutical composition of claim 71 , wherein said β-sheet breaker amino acid is located downstream to said X-Y in said peptide.

78 . The pharmaceutical composition of claim 71 , wherein said β-sheet breaker amino acid is located upstream to said X-Y in said peptide.

79 . The pharmaceutical composition of claim 59 , wherein said peptide is at least 3 amino acid residues in length and whereas at least one of said amino acid residues of said peptide is a positively charged amino acid and at least one of said amino acid residues of said peptide is a negatively charged amino acid.

80 . The pharmaceutical composition of claim 79 , wherein said positively charged amino acid is selected from the group consisting of lysine, arginine, and natural and synthetic derivatives thereof.

81 . The pharmaceutical composition of claim 79 , wherein said negatively charged amino acid is selected from the group consisting of aspartic acid, glutamic acid and natural and synthetic derivatives thereof.

82 . A nucleic acid construct comprising a polynucleotide segment encoding a peptide including the amino acid sequence X-Y or Y-X, wherein X is an aromatic amino acid and Y is any amino acid other than glycine, said peptide being at least 2 and no more than 15 amino acid residues in length.

83 . The nucleic acid construct of claim 82 , wherein Y is a polar uncharged amino acid selected from the group consisting of serine, threonine, asparagine, glutamine.

84 . The nucleic acid construct of claim 82 , wherein Y is a β-sheet breaker amino acid.

85 . The nucleic acid construct of claim 84 , wherein said β-sheet breaker amino acid is selected from the group consisting of proline, aspartic acid, glutamic acid, glycine, lysine and serine.

86 . The nucleic acid construct of claim 82 , wherein said peptide is selected from the group consisting of SEQ ID NOs. 4, 12-19, 27-45, 112-123, 125 and 127.

87 . The nucleic acid construct of claim 82 , wherein said peptide is at least 4 amino acids in length and includes at least two serine residues at a C-terminus thereof.

88 . The nucleic acid construct of claim 82 , wherein said peptide is at least 3 amino acid residues in length and whereas at least one of said amino acid residues of said peptide other than X-Y is a polar uncharged amino acid selected from the group consisting of serine, threonine, asparagine and glutamine.

89 . The nucleic acid construct of claim 82 , wherein said peptide is at least 3 amino acid residues in length and whereas at least one of said amino acid residues of said peptide other than X-Y is a β-sheet breaker amino acid.

90 . The nucleic acid construct of claim 89 , wherein said β-sheet breaker amino acid is selected from the group consisting of proline, aspartic acid, glutamic acid, glycine, lysine and serine.

91 . The nucleic acid construct of claim 89 , wherein said β-sheet breaker amino acid is located downstream to said X-Y in said peptide.

92 . The nucleic acid construct of claim 89 , wherein said β-sheet breaker amino acid is located upstream to said X-Y in said peptide.

93 . The nucleic acid construct of claim 82 , wherein said peptide is at least 3 amino acid residues in length and whereas at least one of said amino acid residues of said peptide is a positively charged amino acid and at least one of said amino acid residues of said peptide is a negatively charged amino acid.

94 . The nucleic acid construct of claim 93 , wherein said positively charged amino acid is selected from the group consisting of lysine and arginine.

95 . The nucleic acid construct of claim 93 , wherein said negatively charged amino acid is selected from the group consisting of aspartic acid and glutamic acid.

96 . The nucleic acid construct of claim 82 , further comprising a promoter.

97 . An antibody or an antibody fragment comprising an antigen recognition region capable of binding a peptide including the amino acid sequence X-Y or Y-X, wherein X is an aromatic amino acid and Y is any amino acid other than glycine, said peptide being at least 2 and no more than 15 amino acid residues in length.

98 . The antibody of claim 97 , wherein Y is a polar uncharged amino acid selected from the group consisting of serine, threonine, asparagine, glutamine and natural derivatives thereof.

99 . The antibody of claim 97 , wherein Y is a β-sheet breaker amino acid.

100 . The antibody of claim 99 , wherein said β-sheet breaker amino acid is a naturally occurring amino acid.

101 . The antibody of claim 100 , wherein said naturally occurring amino acid is selected from the group consisting of proline, aspartic acid, glutamic acid, glycine, lysine and serine.

102 . The antibody of claim 99 , wherein said β-sheet breaker amino acid is a synthetic amino acid.

103 . The antibody of claim 102 , wherein said synthetic amino acid is a Ca-methylated amino acid.

104 . The antibody of claim 103 , wherein said Ca-methylated amino acid is a-aminoisobutyric acid.

105 . The antibody of claim 97 , wherein said peptide is a linear or cyclic peptide.

106 . The antibody of claim 97 , wherein said peptide is selected from the group consisting of SEQ ID NOs. 4, 12-19, 27-45, 112-123, 125 and 127.

107 . The antibody of claim 97 , wherein said peptide is at least 4 amino acids in length and includes at least two serine residues at a C-terminus thereof.

108 . The antibody of claim 97 , wherein said peptide is at least 3 amino acid residues in length and whereas at least one of said amino acid residues of said peptide other than X-Y is a polar uncharged amino acid selected from the group consisting of serine, threonine, asparagine, glutamine and natural derivatives thereof.

109 . The antibody of claim 97 , wherein said peptide is at least 3 amino acid residues in length and whereas at least one of said amino acid residues of said peptide other than X-Y is a β-sheet breaker amino acid.

110 . The antibody of claim 109 , wherein said β-sheet breaker amino acid is a naturally occurring amino acid.

111 . The antibody of claim 110 , wherein said naturally occurring amino acid is selected from the group consisting of proline, aspartic acid, glutamic acid, glycine, lysine and serine.

112 . The antibody of claim 109 , wherein said β-sheet breaker amino acid is a synthetic amino acid.

113 . The antibody of claim 112 , wherein said synthetic amino acid is a Ca-methylated amino acid.

114 . The antibody of claim 113 , wherein said Ca-methylated amino acid is a-aminoisobutyric acid.

115 . The antibody of claim 109 , wherein said β-sheet breaker amino acid is located downstream to said X-Y in said peptide.

116 . The antibody of claim 109 , wherein said β-sheet breaker amino acid is located upstream to said X-Y in said peptide.

117 . The antibody of claim 97 , wherein said peptide is at least 3 amino acid residues in length and whereas at least one of said amino acid residues of said peptide is a positively charged amino acid and at least one of said amino acid residues of said peptide is a negatively charged amino acid.

118 . The antibody of claim 117 , wherein said positively charged amino acid is selected from the group consisting of lysine, arginine, and natural and synthetic derivatives thereof.

119 . The antibody of claim 117 , wherein said negatively charged amino acid is selected from the group consisting of aspartic acid, glutamic acid and natural and synthetic derivatives thereof.

120 . A pharmaceutical composition for treating or preventing an amyloid-associated disease comprising as an active ingredient an antibody or an antibody fragment having an antigen recognition region capable of binding a peptide including the amino acid sequence X-Y or Y-X, wherein X is an aromatic amino acid and Y is any amino acid other than glycine, said peptide being at least 2 and no more than 15 amino acid residues in length and a pharmaceutical acceptable carrier or diluent.

121 . The pharmaceutical composition of claim 120 , wherein Y is a polar uncharged amino acid selected from the group consisting of serine, threonine, asparagine, glutamine and natural derivatives thereof.

122 . The pharmaceutical composition of claim 120 , wherein said peptide is selected from the group consisting of SEQ ID NOs. 4, 12-19 and 27-44.

123 . The pharmaceutical composition of claim 120 , wherein said peptide is at least 3 amino acid residues in length and whereas at least one of said amino acid residues of said peptide other than X-Y is a polar uncharged amino acid selected from the group consisting of serine, threonine, asparagine, glutamine and natural derivatives thereof.

124 . The pharmaceutical composition of claim 120 , wherein said peptide is at least 3 amino acid residues in length and whereas at least one of said amino acid residues of said peptide is a positively charged amino acid and at least one of said amino acid residues of said peptide is a negatively charged amino acid.

125 . The pharmaceutic al composition of claim 124 , wherein said positively charged amino acid is selected from the group consisting of lysine, arginine, and natural and synthetic derivatives thereof.

126 . The pharmaceutical composition of claim 124 , wherein said negatively charged amino acid is selected from the group consisting of aspartic acid, glutamic acid and natural and synthetic derivatives thereof.

127 . A method of treating or preventing an amyloid-associated disease in an individual, the method comprising providing to the individual therapeutically effective amount of an antibody or an antibody fragment having an antigen recognition region capable of binding a peptide including the amino acid sequence X-Y or Y-X wherein X is an aromatic amino acid and Y is any amino acid other than glycine, said peptide being at least 2 and no more than 15 amino acid residues in length.

128 . The method of claim 127 , wherein Y is a polar uncharged amino acid selected from the group consisting of serine, threonine, asparagine, glutamine and natural derivatives thereof.

129 . The method of claim 127 , wherein said peptide is selected from the group consisting of SEQ ID NOs. 4, 12-19 and 27-44.

130 . The method of claim 127 , wherein said peptide is at least 3 amino acid residues in length and whereas at least one of said amino acid residues of said peptide other than X-Y is a polar uncharged amino acid selected from the group consisting of serine, threonine, asparagine, glutamine and natural derivatives thereof.

131 . The method of claim 127 , wherein said peptide is at least 3 amino acid residues in length and whereas at least one of said amino acid residues of said peptide is a positively charged amino acid and at least one of said amino acid residues of said peptide is a negatively charged amino acid.

132 . The method of claim 131 , wherein said positively charged amino acid is selected from the group consisting of lysine, arginine, and natural and synthetic derivatives thereof.

133 . The method of claim 131 , wherein said negatively charged amino acid is selected from the group consisting of aspartic acid, glutamic acid and natural and synthetic derivatives thereof.