Prevention and treatment of amyloidogenic disease

• US 20050019328A1
• Filed: 04/12/2004
• Published: 01/27/2005
• Est. Priority Date: 12/02/1997
• Status: Abandoned Application

• Current Assignee: Janssen Alzheimer Immunotherapy (Johnson & Johnson)
• Original Assignee: Neuralab Ltd. (Perrigo Company PLC)
• Inventors: Schenk, Dale B.
• Application Number:
  US10/823,463
• Publication Number:
  US 20050019328A1
• Time in Patent Office: Days
• US Class Current: 424/146.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/55505 Inorganic adjuvants
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 2039/55572 Lipopolysaccharides; Lipid A; Monophosphoryl lipid A
• CPC Class Codes: A61K 2039/55577 Saponins; Quil A; QS21; ISCOMS
• CPC Class Codes: A61K 2039/6037 Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]
• CPC Class Codes: A61K 2039/605 MHC molecules or ligands thereof
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/193 Colony stimulating factors [CSF]
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/0007 Nervous system antigens; Prions
• CPC Class Codes: C07K 14/4711 Alzheimer's disease; Amyloid plaque core protein
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/77 Internalization into the cell
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

The invention provides improved agents and methods for treatment of diseases associated with amyloid deposits of Aβ in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the amyloid deposit. The methods are useful for prophylactic and therapeutic treatment of Alzheimer'"'"'s disease. Preferred agents including N-terminal fragments of Aβ and antibodies binding to the same.

Claims

1-68. -68. (Canceled)

69. A composition comprising one or more antibodies that binds soluble aggregated amyloid β

protein.

72. The composition of claim 69, wherein the aggregated amyloid β

proteins are full length amyloid β

.

103. The composition of any of claims 69, 70, 72, 74-77, 83, 85-88, 96, or 97, wherein the aggregated amyloid β

protein binding site is incorporated into a human antibody framework.

70. A composition comprising one or more antibodies that binds soluble, non-fibrillar aggregated amyloid β

protein.

71. A composition comprising one or more antibodies that interacts preferentially with soluble, non-fibrillar oligomeric assemblies of amyloid β

protein.

73. A composition as in claim 71, wherein the assemblies are ADDLs.

74. A composition comprising one or more antibodies that binds soluble aggregated amyloid β

_1-42.

75. The composition of claim 74 wherein the aggregated soluble amyloid β

_1-42 is identified as AN1792.

83. A composition as in claim 74, wherein the assemblies are ADDLs.

76. A composition comprising one or more antibodies that binds soluble non-fibrillar aggregated amyloid β

_1-42.

77. The composition of claim 76 wherein the soluble non-fibrillar aggregated amyloid β

_1-42 is identified as AN1792.

81. The composition of claim 76 wherein the soluble non-fibrillar aggregated amyloid β

_1-42 is identified as AN1792.

78. A composition comprising one or more antibodies that specifically binds soluble aggregated amyloid β

_1-42.

79. The composition of claim 78 wherein the aggregated soluble amyloid β

_1-42 is identified as AN1792.

80. A composition comprising one or more antibodies that specifically binds soluble non-fibrillar aggregated amyloid β

_1-42.

82. A composition comprising one or more antibodies that bind preferentially to soluble, globular, non-fibrillar protein assemblies of amyloid β

_1-42.

84. A composition as in claim 82, wherein the assemblies are ADDLs.

85. A composition comprising antibodies that binds soluble aggregated amyloid β

protein.

86. The composition of claim 85 wherein the aggregated soluble amyloid β

_1-42 is identified as AN1792.

87. A composition comprising antibodies that binds soluble non-fibrillar aggregated amyloid β

protein.

88. The composition of claim 87 wherein the soluble non-fibrillar aggregated amyloid β

protein is AN1792.

89. A composition comprising antibodies that specifically binds soluble aggregated amyloid β

protein.

90. The composition of claim 89 wherein the aggregated soluble amyloid β

_1-42 is identified as AN1792.

91. A composition comprising antibodies that specifically binds soluble non-fibrillar aggregated amyloid β

protein.

92. The composition of claim 91 wherein the soluble non-fibrillar aggregated amyloid β

protein is AN1792.

93. A composition comprising antibodies that bind preferentially to amyloid β

-derived diffusible ligands (ADDLs).

94. A composition comprising one or more antibody binding sites that specifically binds soluble amyloid β

protein.

95. A composition comprising one or more antibody binding sites that bind preferentially to ADDLs.

96. A composition comprising one or more modified antibody binding sites that bind soluble aggregated amyloid β

protein.

97. A composition comprising one or more antibody binding sites that bind soluble amyloid β

protein, wherein said antibody sites are derived from genetically engineered antibodies or fragments thereof.

98. A composition comprising one or more modified antibody binding sites that specifically bind soluble aggregated amyloid β

protein.

99. A composition comprising one or more antibody binding sites that specifically bind soluble amyloid β

protein, wherein said antibody sites are derived from genetically engineered antibodies or fragments thereof.

100. A composition comprising one or more modified antibody binding sites that bind preferentially to ADDLs.

105. Any composition of any of claims 71, 73, 82, 84, 93, 95, 100 or 102, wherein the ADDL binding site is incorporated into a human antibody framework.

108. A method for detecting, in fluid taken from a patient, the presence of soluble, non-fibrillar assemblies of amyloid β

protein, the method comprising contacting the fluid with the composition as in any one of claims 71, 73, 82, 84, 93, 95, 100, 102, 105 or 108 and determining the presence of the assemblies.

110. A method for counteracting the effects of soluble, non-fibrillar assemblies of amyloid β

protein, the method comprising administering the composition as in any one of claims 71, 73, 82, 84, 93, 95, 100, 102, 105, or 108 to a patient in need of such treatment.

101. A composition consisting of one or more binding sites that specifically bind soluble amyloid β

protein, wherein said antibody sites are derived from genetically engineered antibodies or fragments thereof.

104. The composition of any of claims 78-81, 89-92, 94, 98, 99 or 101, wherein the aggregated amyloid β

protein binding site is incorporated into a human antibody framework.

106. A method for detecting, in a tissue sample taken from a patient, the presence of soluble aggregated amyloid β

protein, the method comprising contacting the sample with the composition of any of claims 69-70, 72, 74-81, 83, 85-92, 94, 96-99, 101, 103, 104, 106 or 107.

107. A method for detecting, in a tissue sample taken from a patient, the presence of soluble non-fibrillar aggregated amyloid β

protein, the method comprising contacting the sample with the composition of any of claims 69-70, 72, 74-81, 83, 85-92, 94, 96-99, 101, 103, 104, 106 or 107.

109. A method for reducing or terminating the progression of amyloidogenic disease in a patient, comprising administering an effective dosage of the composition of any one of claims 69-70, 72, 74-81, 83, 85-92, 94, 96-99, 101, 103, 104, 106, or 107 to the patient.

102. A composition consisting of one or more binding sites that preferentially bind to ADDLs.