HUMANIZED ANTIBODIES THAT SEQUESTER AMYLOID BETA PEPTIDE

• US 20090238821A1
• Filed: 02/08/2008
• Published: 09/24/2009
• Est. Priority Date: 02/24/2000
• Status: Active Grant

• Current Assignee: Eli Lilly and Company, Washington University In St Louis
• Original Assignee: Eli Lilly and Company
• Inventors: Vasquez, Maximiliano, Tsurushita, Naoya, Paul, Steven M., Holtzman, David M., Bales, Kelly R., DeMattos, Ronald
• Granted Patent: US 7,892,545 B2
• Time in Patent Office: Days
• US Class Current: 424/133.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/34 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 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/567 Framework region [FR]
• 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

Abstract

A method to treat conditions characterized by formation of amyloid plaques both prophylactically and therapeutically is described. The method employs humanized antibodies which sequester soluble Aβ peptide from human biological fluids or which preferably specifically bind an epitope contained within position 13-28 of the amyloid beta peptide Aβ.

Claims

1-65. -65. (canceled)

66. A method to inhibit the formation of amyloid plaques or to inhibit the formation of toxic soluble Aβ

species in humans, comprising administering to a human subject in need of such inhibition an effective amount of a humanized antibody, wherein said antibody comprises;

a. a light chain comprising a light chain variable region comprising the following sequence;

67. The method of claim 66 wherein said light chain variable region comprises the sequence given by SEQ ID NO:

9 and said heavy chain variable region comprises the sequence given by SEQ ID NO;

10.

68. The method of claim 67 wherein said light chain comprises the sequence given by SEQ ID NO:

11 and said heavy chain comprises the sequence given by SEQ ID NO;

12.

69. A method to reduce the formation of amyloid plaques or to reduce the formation of toxic soluble Aβ

species in a human, comprising administering to a human subject in need of such reduction an effective amount of a humanized antibody, wherein said antibody comprises;

a. a light chain comprising a light chain variable region comprising the following sequence;

70. The method of claim 69 wherein said light chain variable region comprises the sequence given by SEQ ID NO:

9 and said heavy chain variable region comprises the sequence given by SEQ ID NO;

10.

71. The method of claim 70 wherein said light chain comprises the sequence given by SEQ ID NO:

11 and said heavy chain comprises the sequence given by SEQ ID NO;

12.

72. A method of treating, preventing, or reversing cognitive decline in a subject, comprising administering to the subject an effective amount of a humanized antibody, wherein said antibody comprises:

a. a light chain comprising a light chain variable region comprising the following sequence;

73. The method of claim 72 wherein said light chain variable region comprises the sequence given by SEQ ID NO:

9 and said heavy chain variable region comprises the sequence given by SEQ ID NO;

10.

74. The method of claim 73 wherein said light chain comprises the sequence given by SEQ ID NO:

11 and said heavy chain comprises the sequence given by SEQ ID NO;

12.

81. The method of any one of claims 72 to 80, wherein said subject has clinical or pre-clinical Alzheimer'"'"'s disease, Down'"'"'s syndrome, or clinical or pre-clinical cerebral amyloid angiopathy.

75. A method of treating, preventing, or reversing cognitive decline in a human subject, comprising expressing recombinant sequences of a humanized antibody in human tissue, wherein said antibody comprises:

a. a light chain comprising a light chain variable region comprising the following sequence;

76. The method of claim 75 wherein said light chain variable region comprises the sequence given by SEQ ID NO:

9 and said heavy chain variable region comprises the sequence given by SEQ ID NO;

10.

77. The method of claim 76 wherein said light chain comprises the sequence given by SEQ ID NO:

11 and said heavy chain comprises the sequence given by SEQ ID NO;

12.

78. A method of improving cognition in a human subject, comprising administering to the subject an effective amount of a humanized antibody, wherein said antibody comprises:

a. a light chain comprising a light chain variable region comprising the following sequence;

79. The method of claim 78 wherein said light chain variable region comprises the sequence given by SEQ ID NO:

9 and said heavy chain variable region comprises the sequence given by SEQ ID NO;

10.

80. The method of claim 79 wherein said light chain comprises the sequence given by SEQ ID NO:

11 and said heavy chain comprises the sequence given by SEQ ID NO;

12.

82. A method of treating Alzheimer'"'"'s disease, comprising administering to a patient in need thereof an effective amount of a humanized antibody, wherein said antibody comprises:

a. a light chain comprising a light chain variable region comprising the following sequence;

83. The method of claim 82 wherein said Alzheimer'"'"'s disease is pre-clinical Alzheimer'"'"'s disease.

84. The method of claim 82 wherein said Alzheimer'"'"'s disease is clinical Alzheimer'"'"'s disease.

85. The method of claim 82 wherein said light chain variable region comprises the sequence given by SEQ ID NO:

9 and said heavy chain variable region comprises the sequence given by SEQ ID NO;

10.

86. The method of claim 85 wherein said Alzheimer'"'"'s disease is pre-clinical Alzheimer'"'"'s disease.

87. The method of claim 85 wherein said Alzheimer'"'"'s disease is clinical Alzheimer'"'"'s disease.

88. The method of claim 83 wherein said light chain comprises the sequence given by SEQ ID NO:

11 and said heavy chain comprises the sequence given by SEQ ID NO;

12.

89. The method of claim 88 wherein said Alzheimer'"'"'s disease is pre-clinical Alzheimer'"'"'s disease.

90. The method of claim 88 wherein said Alzheimer'"'"'s disease is clinical Alzheimer'"'"'s disease.