Monoclonal antibody

• US 20070166311A1
• Filed: 12/11/2006
• Published: 07/19/2007
• Est. Priority Date: 12/12/2005
• Status: Active Grant

• Current Assignee: Andrea Pfeifer, Andreas Muhs, Claude Nicolau, David Hickman, Ruth Greferath
• Original Assignee: AC Immune SA
• Inventors: Muhs, Andreas, Pfeifer, Andrea, Greferath, Ruth, Hickman, David, Nicolau, Claude
• Granted Patent: US 7,772,375 B2
• Time in Patent Office: Days
• US Class Current: 424/146.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• 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: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: G01N 2333/4709 Amyloid plaque core protein

Abstract

The present invention is related to methods and compositions for the therapeutic and diagnostic use in the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of disorders and abnormalities associated with amyloid protein such as Alzheimer'"'"'s disease. The present invention provides novel methods and compositions comprising highly specific and highly effective antibodies having the ability to specifically recognize and bind to specific epitopes from a range of β-amyloid proteins. The antibodies enabled by the teaching of the present invention are particularly useful for the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of diseases and disorders associated with amyloid plaque formation including secondary amyloidosis and age-related amyloidosis including, but not limited to, neurological disorders such as Alzheimer'"'"'s Disease (AD).

Claims

1. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof, which antibody, upon co-incubation with amyloid monomeric peptides, particularly β

-amyloid monomeric peptides such as, for example, Aβ

monomeric peptides 1-39;

1-40, 1-41, 1-42, or 1-43, but especially Aβ

_1-42 monomeric peptides inhibits the aggregation of the Aβ

monomers to high molecular polymeric fibrils.

2. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof according to claim 1, which antibody inhibits the aggregation of the Aβ

monomers to high molecular polymeric fibrils by at least 50%, particularly by at least 60%, particularly by at least 65%, more particularly by at least 75%, even more particularly by at least 80%, but especially by at least 85%-90%, or more as compared to the respective amyloid peptide monomers incubated in buffer (control).

3. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof according to claims 1 or 2, which antibody is co-incubated with amyloid monomeric peptides at a molar concentration ratio of up to 1:

100.

4. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof according to claim 3, which antibody exhibits its aggregation inhibition property upon co-incubation with amyloid monomeric peptides at a molar concentration ratio of between 1:

30 and 1;

100.

5. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof according to claim 3 or 4, which antibody exhibits its aggregation inhibition property upon co-incubation with amyloid monomeric peptides for 48 hours at a temperature of 37°

C.

6. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof according to claim 5, which antibody, upon co-incubation at a molar concentration ratio of between 1:

30 and 1;

100, particularly at a ratio of 1;

100 with preformed high molecular polymeric amyloid fibrils or filaments formed by the aggregation of amyloid monomeric peptides, particularly β

-amyloid monomeric peptides such as, for example, Aβ

monomeric peptides 1-39;

1-40, 1-41, 1-42, or 1-43, but especially Aβ

_1-42 monomeric peptides, is capable of disaggregating the preformed polymeric fibrils or filaments by at least 35%, particularly by at least 40%, more particularly by at least 50%, even more particularly by at least 60%, but especially by at least 70% or more.

7. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof according to any one of claims 1-6, wherein the aggregation inhibition and the disaggregation potential of the antibody, respectively, is determined by density-gradient ultracentrifugation followed by a SDS-PAGE sedimentation analysis on a preformed gradient.

8. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof according to any one of claims 1 to 6, wherein the aggregation inhibition and the disaggregation potential of the antibody, respectively, is determined by thioflavin T (Th-T) fluorescent assay.

20. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof, which antibody incorporates the aggregation inhibition property according to any one of claims 1-5 and 14-19 and the disaggregation property according to any one of claims 6-8, 12 and 14-19- as well as the β

-sheet breaking property according to any one of claims 9-13.

22. A monoclonal antibody, including any functionally equivalent antibody or functional parts thereof according to any of the preceding claims, which recognized the native conformation of amyloid in that it specifically binds to amyloid oligomers and fibers, but not to not linearized amyloid species.

23. A monoclonal antibody, including any functionally equivalent antibody or functional parts thereof according to any of the preceding claims, which antibody or fragment binds to an Aβ

monomer with a binding affinity of at least about 1×

10<sup>−

6</sup> to at least about 1×

10<sup>−

8</sup>, particularly of at least about 1×

10<sup>−

6</sup> to at least about 1×

10<sup>−

7</sup>, more particularly of at least about 1×

10<sup>−

7</sup> to at least about 1×

10<sup>−

8</sup>, even more particularly of at least about 1×

10<sup>−

7</sup> to at least about 4×

10<sup>−

7</sup>, but, preferably, does not show any significant cross-reactivity with amyloid precursor protein (APP).

24. A monoclonal antibody, including any functionally equivalent antibody or functional parts thereof according to any of the preceding claims, which antibody or fragment binds to an Aβ

fiber, fibril or filament with a binding affinity of at least about 1×

10<sup>−

7</sup> to at least about 1×

10<sup>−

9</sup>, particularly of at least about 1×

10<sup>−

7</sup> to at least about 1×

10<sup>−

8</sup>, more particularly of at least about 1×

10<sup>−

8</sup> to at least about 1×

10<sup>−

9</sup>, even more particularly of at least about 1×

10<sup>−

8</sup> to at least about 5×

10−

8, but, preferably does not show any significant cross-reactivity with amyloid precursor protein (APP).

25. A monoclonal antibody, including any functionally equivalent antibody or functional parts thereof according to of the preceding claims, which antibody or fragment exhibits an binding affinity to an Aβ

fiber, fibril or filament which is at least 5 times, particularly at least 10 times, more particularly at least 15 times, higher than the binding affinity to an Aβ

monomer.

26. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof, which antibody incorporates at least one of the properties according to any one of claims 1 to 25, that is aggregation inhibition, disaggregation, induction of conformational transition, recognition of and direct binding to an epitopic region of the Aβ

polypeptide, but especially a combination of two or more of said properties.

27. A monoclonal antibody according to any of the preceding claims including any functionally equivalent antibody or functional parts thereof, which antibody exhibits high specificity to Aβ

_1-42 monomeric peptides but shows essentially no cross-reactivity to Aβ

_1-38, Aβ

_1-39, Aβ

_1-40, and/or Aβ

_1-41 monomeric peptides.

28. A monoclonal antibody according to claim 27 including any functionally equivalent antibody or functional parts thereof, which antibody is up to 100 fold, particularly 50 to 100 fold, more particularly 80 to 100 fold, but especially 100 fold more sensitive to amyloid peptide Aβ

_1-42 as compared to Aβ

_1-38, Aβ

_1-39, Aβ

_1-40, Aβ

_1-41 and capable of inhibiting, in vitro and in vivo, the aggregation of amyloidogenic monomeric peptides.

29. A monoclonal antibody according to claims 27 or 28 including any functionally equivalent antibody or functional parts thereof, which antibody has a high binding sensitivity to amyloid peptide Aβ

_1-42 and is capable of detecting Aβ

_1-42 fibers in a concentration of up to 0.01 μ

g, but particularly in a concentration range of between 0.5 μ

g and 0.01 μ

g, more particularly between 0.1 μ

g and 0.01 μ

g, but especially in a concentration of 0.01 μ

g.

30. A monoclonal antibody according to any of the preceding claims including any functionally equivalent antibody or functional parts thereof which antibody is capable of decreasing the total amount of soluble Aβ

in the brain of an animal, particularly a mammal, but especially a human suffering from a disease or condition leading to increased concentrations of soluble Aβ

in the brain.

31. A monoclonal antibody according to any of the preceding claims including any functionally equivalent antibody or functional parts thereof which antibody is capable of disrupting plaques thus decreasing the plaque load in the brain of an animal, particularly a mammal, but especially a human suffering from a disease or condition leading to an increased plaque load in the brain.

32. The antibody according to claim 31 including any functionally equivalent antibody or functional parts thereof, which antibody decreases the plaque load in the brain by at least 20%, particularly by at least 25%, more particularly by at least 30%, even more particularly by more than 30%.

33. A monoclonal antibody according to claim 31 including any functionally equivalent antibody or functional parts thereof, which antibody is capable of solubilizing plaques leading to a reduction of the amount of plaques in the brain of an animal, particularly a mammal, but especially a human suffering from a disease or condition leading to an increased plaque load in the brain.

34. The antibody according to claim 31 including any functionally equivalent antibody or functional parts thereof, which antibody reduces the amount of plaques in the brain by at least 10%, particularly by at least 15%, more particularly by at least 20%.

46. A monoclonal antibody according to any one of claims 1-36 including any functionally equivalent antibody or functional parts thereof, which antibody recognizes and binds to a conformational discontinuous epitope as defined in any one of claims 37 to 45.

54. A monoclonal antibody according to any one of claims 4753 including any functionally equivalent antibody or functional parts thereof, which antibody recognizes and binds to a conformational discontinuous epitope as defined in any one of claims 37 to 45 and exhibits the specific properties of an antibody according to any one of claims 1-36.

76. A composition comprising the monoclonal antibody including any functionally equivalent antibody or functional parts thereof according to any one of claims 1 to 65 in a therapeutically effective amount.

77. A composition according to claim 76 which is a pharmaceutical composition optionally further comprising a pharmaceutically acceptable carrier.

78. A composition according to claim 77 comprising the monoclonal antibody in a therapeutically effective amount.

79. A composition according to any one of claims 76 to 78 for use in the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of diseases and disorders associated with amyloid or amyloid-like protein such as the Aβ

protein involved in Alzheimer'"'"'s disease.

80. A mixture comprising a monoclonal antibody including any functionally equivalent antibody or functional parts thereof according to any one of claims 1 to 65 in a therapeutically effective amount and, optionally, a further biologically active substance and/or a pharmaceutically acceptable carrier and/or a diluent and/or an excipient.

81. A mixture according to claim 80, wherein the further biologically active substance is a compound used in the medication of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of diseases and disorders associated with amyloid or amyloid-like protein such as the Aβ

protein involved in Alzheimer'"'"'s disease.

82. A mixture according to claims 80 or 81 comprising in addition to the monoclonal antibody including any functionally equivalent antibody or functional parts thereof according to any one of claims 1 to 65 at least one compound selected from the group consisting of compounds against oxidative stress, anti-apoptotic compounds, metal chelators, inhibitors of DNA repair such as pirenzepin and metabolites, 3-amino-1-propanesulfonic acid (3APS), 1,3-propanedisulfonate (1,3PDS), secretase activators, β

- and γ

-secretase inhibitors, tau proteins, neurotransmitter, β

-sheet breakers, anti-inflammatory molecules, or cholinesterase inhibitors (ChEIs) such as tacrine, rivastigmine, donepezil, and/or galantamine and other drugs and nutritive supplements, together with an antibody according to the present invention and, optionally, a pharmaceutically acceptable carrier and/or a diluent and/or an excipient.

83. A mixture according to claim 82, wherein the compound is a cholinesterase inhibitor (ChEIs).

84. A mixture according to claim 82, wherein the compound is one selected from the group consisting of tacrine, rivastigmine, donepezil, galantamine, niacin and memantine.

85. A mixture according to any one of claims 80 to 84 comprising the monoclonal antibody and/or the biologically active substance in a therapeutically effective amount.

86. A method for producing an antibody including any functionally equivalent antibody or functional parts thereof according to any one of claims 1 to 65, which method comprises raising in a suitable host organism antibodies but particularly monoclonal antibodies against a supramolecular antigenic construct comprising an antigenic peptide corresponding to the amino acid sequence of the β

-amyloid peptide, particularly of β

-amyloid peptide Aβ

_1-15, Aβ

_1-16 and Aβ

<sub>1-16(Δ

14)</sub>, modified with hydrophobic moieties such as, for example, palmitic acid or a hydrophilic moiety such as, for example, polyethylene glycol (PEG) or a combination of both, wherein said hydrophobic and hydrophilic moiety, respectively, is covalently bound to each terminus through an amino acid such as, for example, lysine or any other suitable amino acid or amino acid analogue capable of serving as a linker molecule; and

isolating the antibody.

87. Use of a monoclonal antibody and/or a functional part thereof according to any one of claims 1 to 65 and/or a pharmaceutical composition according to any one of claims 76 to 79, or a mixture according to any one of claims 80 to 85 for the preparation of a medicament for treating or alleviating the effects of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of diseases and disorders associated with amyloid plaque formation including secondary amyloidosis and age-related amyloidosis such as diseases including, but not limited to, neurological disorders such as Alzheimer'"'"'s Disease (AD and diseases or conditions characterized by a loss of cognitive memory capacity such as, for example, mild cognitive impairment (MCI), Lewy body dementia, Down'"'"'s syndrome, hereditary cerebral hemorrhage with amyloidosis (Dutch type);

the Guam Parkinson-Dementia complex;

as well as other diseases which are based on or associated with amyloid-like proteins such as progressive supranuclear palsy, multiple sclerosis;

Creutzfeld Jacob disease, Parkinson'"'"'s disease, HIV-related dementia, ALS (amyotropic lateral sclerosis), inclusion-body myositis (IBM), Adult Onset Diabetis;

senile cardiac amyloidosis;

endocrine tumors, and others, including macular degeneration.

88. A method for the preparation of a pharmaceutical composition according to any one of claims 76 to 79, or a mixture according to any one of claims 80 to 85 using a monoclonal antibody and/or a functional part thereof according to any one of claims 1 to 65 for use in treating or alleviating the effects of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of diseases and disorders associated with amyloid plaque formation including secondary amyloidosis and age-related amyloidosis such as diseases including, but not limited to, neurological disorders such as Alzheimer'"'"'s Disease (AD) and diseases or conditions characterized by a loss of cognitive memory capacity such as, for example, mild cognitive impairment (MCI), Lewy body dementia, Down'"'"'s syndrome, hereditary cerebral hemorrhage with amyloidosis (Dutch type);

the Guam Parkinson-Dementia complex;

as well as other diseases which are based on or associated with amyloid-like proteins such as progressive supranuclear palsy, multiple sclerosis;

Creutzfeld Jacob disease, Parkinson'"'"'s disease, HIV-related dementia, ALS (amyotropic lateral sclerosis), Adult Onset Diabetis;

senile cardiac amyloidosis;

endocrine tumors, and others, including macular degeneration.

89. A method for the preparation of a medicament using a monoclonal antibody and/or a functional part thereof or a functionally equivalent antibody according to any one of claims 1 to 65 a pharmaceutical composition according to any one of claims 76 to 79, or a mixture according to any one of claims 80 to 85 for preventing, treating or alleviating the effects of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of diseases and disorders associated with amyloid plaque formation including secondary amyloidosis and age-related amyloidosis such as diseases including, but not limited to, neurological disorders such as Alzheimer'"'"'s Disease (AD) and diseases or conditions characterized by a loss of cognitive memory capacity such as, for example, mild cognitive impairment (MCI), Lewy body dementia, Down'"'"'s syndrome, hereditary cerebral hemorrhage with amyloidosis (Dutch type);

the Guam Parkinson-Dementia complex;

as well as other diseases which are based on or associated with amyloid-like proteins such as progressive supranuclear palsy, multiple sclerosis;

Creutzfeld Jacob disease, Parkinson'"'"'s disease, HIV-related dementia, ALS (amyotropic lateral sclerosis), inclusion-body myositis (IBM), Adult Onset Diabetis;

senile cardiac amyloidosis;

endocrine tumors, and others, including macular degeneration.

90. A method for the preparation of a pharmaceutical composition according to any one of claims 76 to 79 using a monoclonal antibody and/or a functional part thereof or a functionally equivalent antibody according to any one of claims 1 to 65, comprising formulating said antibody in a pharmaceutically acceptable form.

91. A method according to claim 90, wherein the antibody is comprised in the composition in a therapeutically effective amount.

92. A method for reducing the plaque load in the brain of an animal, particularly a mammal, but especially a human suffering from a disease or condition leading to an increased plaque load in the brain comprising administering to an animal, particularly a mammal, more particularly a human in need of such a treatment, a therapeutically effective amount of a monoclonal antibody any one of claims 1 to 65, or a composition according to any one of claims 76 to 79, or a mixture according to any one of claims 80 to 85.

93. A method according to claim 92, wherein the plaque load in the brain is decreased by at least 20%, particularly by at least 25%, more particularly by at least 30%, even more particularly by more than 30%.

94. A method for reducing the amount of plaques in the brain of an animal, particularly a mammal, but especially a human suffering from a disease or condition leading to an increased plaque load in the brain comprising administering to an animal, particularly a mammal, more particularly a human in need of such a treatment, a therapeutically effective amount of a monoclonal antibody any one of claims 1 to 65, or a composition according to any one of claims 76 to 79, or a mixture according to any one of claims 80 to 85.

95. A method according to claim 94, wherein the amount of plaques in the brain is reduced by at least 10%, particularly by at least 15%, more particularly by at least 20%.

96. A method for decreasing the total amount of soluble Aβ

in the brain of an animal, particularly a mammal, but especially a human suffering from a disease or condition leading to increased concentrations of soluble Aβ

in the brain comprising administering to an animal, particularly a mammal, more particularly a human in need of such a treatment, a therapeutically effective amount of a monoclonal antibody any one of claims 1 to 65, or a composition according to any one of claims 76 to 79, or a mixture according to any one of claims 80 to 85.

97. A method for preventing, treating or alleviating the effects of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of diseases and disorders associated with amyloid plaque formation including secondary amyloidosis and age-related amyloidosis such as diseases including, but not limited to, neurological disorders such as Alzheimer'"'"'s Disease (AD) and diseases or conditions characterized by a loss of cognitive memory capacity such as, for example, mild cognitive impairment (MCI), Lewy body dementia, Down'"'"'s syndrome, hereditary cerebral hemorrhage with amyloidosis (Dutch type);

the Guam Parkinson-Dementia complex;

as well as other diseases which are based on or associated with amyloid-like proteins such as progressive supranuclear palsy, multiple sclerosis;

Creutzfeld Jacob disease, Parkinson'"'"'s disease, HIV-related dementia, ALS (amyotropic lateral sclerosis), inclusion-body myositis (IBM), Adult Onset Diabetis;

senile cardiac amyloidosis;

endocrine tumors, and others, including macular degeneration by administering an antibody, but particularly a monoclonal antibody or a composition or mixture comprising such an antibody according to any one of claims 1 to 39 to a an animal or a human affected by such a disorder comprising administering to an animal, particularly a mammal, more particularly a human in need of such a treatment, a therapeutically effective amount of a monoclonal antibody any one of claims 1 to 65, or a composition according to any one of claims 76 to 79, or a mixture according to any one of claims 80 to 85.

98. A methods for retaining or increasing cognitive memory capacity in a mammal exhibiting an amyloid-associated disease or condition comprising administering to an animal, particularly a mammal, more particularly a human in need of such a treatment, a therapeutically effective amount of a monoclonal antibody any one of claims 1 to 65, or a composition according to any one of claims 76 to 79, or a mixture according to any one of claims 80 to 85.

99. A method according to claim 98, wherein the monoclonal antibody or the composition comprising the monoclonal antibody is administered in a therapeutically effective amount.

100. A hybridoma cell line characterized in that it produces a monoclonal antibody according to any one of claims 1 to 65.

112. Method of determining the extent of amyloidogenic plaque burden in a tissue comprising

(a) obtaining a sample representative of the tissue under investigation;

(b) testing said sample for the presence of amyloid antigen with an antibody according to any one of claims 1-65;

(c) determining the amount of antibody bound to the antigen; and

(d) calculating the plaque burden in the tissue.

113. A method according to claim 112, wherein the formation of the immunological complex in step c) is determined such that presence or absence of the immunological complex correlates with presence or absence of amyloid antigen.

115. A method for monitoring minimal residual disease in a patient following treatment with an antibody or a vaccine composition according to any one of the preceding claims, wherein said method comprises:

(a) bringing the sample or a specific body part or body area suspected to contain the amyloid antigen into contact with an antibody according to the invention and as described herein before, which antibody binds an epitope of the amyloid protein;

(b) allowing the antibody to bind to the amyloid antigen to form an immunological complex;

(c) detecting the formation of the immunological complex; and

(d) correlating the presence or absence of the immunological complex with the presence or absence of amyloid antigen in the sample or specific body part or area,

(e) comparing the amount of said immunological complex to a normal control value,

wherein an increase in the amount of said aggregate compared to a normal control value indicates that said patient still suffers from a minimal residual disease.

116. A method for predicting responsiveness of a patient being treated with an antibody or a vaccine composition according to any one of the preceding claims comprising:

(a) bringing the sample or a specific body part or body area suspected to contain the amyloid antigen into contact with an antibody according to the invention and as described herein before, which antibody binds an epitope of the amyloid protein;

(b) allowing the antibody to bind to the amyloid antigen to form an immunological complex;

(c) detecting the formation of the immunological complex; and

(d) correlating the presence or absence of the immunological complex with the presence or absence of amyloid antigen in the sample or specific body part or area,

(e) comparing the amount of said immunological complex before and after onset of the treatment,

wherein a decrease in the amount of said aggregate indicates that said patient has a high potential of being responsive to the treatment.

117. Test kits for detection and diagnosis of amyloid-associated diseases and conditions comprising antibodies according to any one of claims 1-65.

9. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof, which antibody, upon co-incubation with preformed high molecular polymeric amyloid fibrils or filaments formed by the aggregation of amyloid monomeric peptides, particularly β

-amyloid monomeric peptides such as, for example, Aβ

monomeric peptides 1-39;

1-40, 1-41, 1-42, or 1-43, but especially Aβ

_1-42 monomeric peptides is capable of inducing a transition of the β

-sheet conformation towards a random coil conformation at a given location in the molecule, which leads to an increase of the random coil conformation at the expense of the β

-sheet conformation and an improved solubilization of the preformed high molecular polymeric amyloid fibrils or filaments.

10. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof according to claim 9, which antibody is capable of inducing an increase of the random coil conformation at the expense of the β

-sheet conformation with the latter being reduced by at least 30%, particularly by at least 35%, and more particularly by at least 40% and more as compared to the respective preformed amyloid polymeric fibrils or filaments incubated in buffer (control).

11. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof according to any one of claims 9 and 10, wherein the transition in the secondary conformation takes place in the environment of Val12 of the Aβ

protein.

12. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof according to any one of claims 6-11, wherein co-incubation with preformed high molecular polymeric amyloid fibrils or filaments was done for 24 hours at a temperature of 37°

C.

13. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof according to claim 9-12, wherein the antibody'"'"'s potential in inducing a transition in the secondary structure is determined by solid state NMR spectroscopy.

14. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof, which antibody, upon co-incubation with amyloid monomeric peptides, particularly β

-amyloid monomeric peptides such as, for example, Aβ

monomeric peptides 1-39;

1-40, 1-41, 1-42, or 1-43, but especially Aβ

_1-42 monomeric peptides inhibits the aggregation of the Aβ

monomers into high molecular polymeric fibrils or filaments and, in addition, upon co-incubation with preformed high molecular polymeric amyloid fibrils or filaments formed by the aggregation of amyloid monomeric peptides, particularly β

-amyloid monomeric peptides such as, for example, Aβ

monomeric peptides 1-39;

1-40, 1-41, 1-42, or 1-43, but especially Aβ

_1-42 monomeric peptides, is capable of disaggregating the preformed polymeric fibrils or filaments.

15. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof according to claim 14, wherein co-incubation with amyloid monomeric peptides and preformed high molecular polymeric amyloid fibrils or filaments, respectively, takes place at a molar concentration ratio of up to 1:

100.

16. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof according to claim 15, wherein co-incubation with amyloid monomeric peptides and preformed high molecular polymeric amyloid fibrils or filaments, respectively, takes place at a molar concentration ratio of between 1:

30 and 1;

100, particularly at a molar concentration ratio of 1;

100.

17. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof according to any one of claims 14-16, wherein co-incubation with amyloid monomeric peptides and preformed high molecular polymeric amyloid fibrils or filaments is done for 48 hours and 24 hours, respectively, at a temperature of 37°

C.

18. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof according to any one of claims 14-17, which antibody is capable of disaggregating the preformed polymeric fibrils or filaments by at least 10%, particularly by at least 25%, more particularly by at least 35%, even more particularly by at least 50%, but especially by at least 60-70% or more.

19. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof according to any one of claims 14-17, which antibody inhibits the aggregation of amyloid monomeric peptides, particularly β

-amyloid monomeric peptides such as, for example, Aβ

monomeric peptides 1-39;

1-40, 1-41, 1-42, or 1-43, but especially Aβ

_1-42 monomeric peptides by at least 50%, particularly by at least 65%, more particularly by at least 75%, even more particularly by at least 80%, but especially by at least 85-90%, or more as compared to the respective amyloid peptide monomers incubated in buffer (control).

21. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof, which antibody directly and specifically binds to Aβ

fibers by targeting an epitopic region of the Aβ

polypeptide confined by amino acid residues aa_n-aa_m with n being an integer between 13 and 15, but especially 14 and m being an integer between 22 and 24, but especially 23, wherein n and m cannot be identical numbers and n must always be a smaller number than m, with the difference between n and m≧

2.

35. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof, which antibody incorporates at least one of the properties selected from the group consisting of aggregation inhibition, disaggregation, induction of conformational transition, recognition of and direct binding to an epitope, particularly a conformational discontinuous epitope in the 14-23, particularly in the 14-20 region, preventing or slowing down the formation of amyloid plaques, decreasing the total amount of soluble Aβ

in the brain, decreasing the plaque load in the brain, reducing the amount of plaques in the brain, retaining or increasing cognitive memory capacity, but especially a combination of two or more of said properties.

36. A monoclonal antibody according to claim 35 including any functionally equivalent antibody or functional parts thereof, which antibody incorporates at least 2, particularly at least 3, more particularly at least 4, even more particularly at least 5, 6, 7 or 8, but especially all of the above mentioned properties.

37. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof, which antibody recognizes and binds to at least one distinct binding site, particularly to a least two distinct binding sites on the β

-amyloid protein wherein the said at least one or said at least two distinct binding sites comprise at least one amino acid residue and at least two consecutive amino acid residues, respectively, predominantly involved in the binding of the antibody, wherein, in a specific embodiment of the invention, the at least one residue constituting the first distinct binding site is Leu and the at least two consecutive amino acid residues, constituting the second distinct binding site, are -Phe-Phe- embedded within the following core sequence;

Xaa₁-Xaa₂-Xaa₃-Leu -Xaa₄-Phe-Phe-Xaa₅-Xaa₆-Xaa₇-

wherein

Xaa₁ is an amino acid residue selected from the group comprising His, Asn, Gln Lys, and Arg;

Xaa₂ is an amino acid residue selected from the group comprising Asn and Gln;

Xaa₃ is an amino acid residue selected from the group comprising Lys, His, Asn, Gln and Arg

Xaa₄ is an amino acid residue selected from the group comprising Ala, Val, Leu, norleucine, Met, Phe, and Ile;

Xaa₅ is an amino acid residue selected from the group comprising Ala, Val, Leu, Ser and Ile;

Xaa₆ is an amino acid residue selected from the group comprising Glu and Asp,

Xaa₇ is an amino acid residue selected from the group comprising Glu and Asp.

45. A monoclonal antibody according to any one of claims 37-44 including any functionally equivalent antibody or functional parts thereof, wherein said consecutive amino acid residues, particularly -Lys-Leu- at position 16 and 17 and -Phe- Phe- at position 19 and 20, which are predominantly involved in the binding of the β

-amyloid protein, are embedded into the following core region of the amyloid β

peptide;

38. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof, which antibody recognizes and binds to at least one distinct binding site, particularly to a least two distinct binding sites, more particularly to at least three distinct binding sites on the β

-amyloid protein wherein said distinct binding sites comprise at least one and at least two consecutive amino acid residues, respectively, predominantly involved in the binding of the antibody, wherein the at least one and the at least two consecutive amino acids, which are separated by at least one amino acid residue not involved in antibody binding or to a significantly smaller extent as compared to the amino acid residues predominantly involved in the binding of the antibody, are -His- and -Lys-Leu-, respectively, embedded within the following core sequence;

-His-Xaa₂-Lys-Leu-Xaa₃-Xaa₄-Xaa₅-Xaa₆-Xaa₇-Xaa₈-

wherein

Xaa₂ is an amino acid residue selected from the group comprising Asn and Gln;

Xaa₃ is an amino acid residue selected from the group comprising Ala, Val, Leu, norleucine, Met, Phe, and Ile;

Xaa₄ is an amino acid residue selected from the group comprising Ala, Val, Leu, norleucine, Met, Phe, and Ile

Xaa₅ is an amino acid residue selected from the group comprising Ala, Val, Leu, norleucine, Met, Phe, and Ile

Xaa₆ is an amino acid residue selected from the group comprising Ala, Val, Leu, Ser and Ile;

Xaa₇ is an amino acid residue selected from the group comprising Glu and Asp,

Xaa₈ is an amino acid residue selected from the group comprising Glu and Asp and wherein said amino acid residues Xaa₂, Xaa₃ Xaa₆, Xaa₇, Xaa₈, are not involved in antibody binding or to a significantly smaller extent as compared to the -His- and the -Lys-Leu- binding site.

39. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof, which antibody recognizes and binds to at least one distinct binding site, particularly to a least two distinct binding sites, more particularly to at least three distinct binding sites on the β

-amyloid protein wherein said distinct binding sites comprise at least one and at least two consecutive amino acid residues, respectively, predominantly involved in the binding of the antibody, wherein the at least two consecutive amino acid residues representing a first binding site are -Phe-Phe- and the at least one amino acid residue is -His- embedded within the following core sequence;

-Xaa₁-His-Xaa₃-Xaa₄-Xaa₅-Xaa₆-Phe-Phe-Xaa₇-Xaa₈-Xaa₉-, wherein

Xaa₁ is an amino acid residue selected from the group comprising His, Asn, Gln, Lys and Arg

Xaa₃ is an amino acid residue selected from the group comprising Asn and Gln

Xaa₄ is an amino acid residue selected from the group comprising His, Asn, Gln, Lys and Arg

Xaa₅ is an amino acid residue selected from the group comprising Ala, Val, Leu, Ser and Ile;

Xaa₆ is an amino acid residue selected from the group comprising Ala, Val, Leu and Ile

Xaa₇ is an amino acid residue selected from the group comprising Ala, Val, Leu and Ile

Xaa₈ is an amino acid residue selected from the group comprising Glu and Asp,

Xaa₉ is an amino acid residue selected from the group comprising Glu and Asp, and wherein said amino acid residues Xaa₁, Xaa₃, Xaa₆, Xaa₇, Xaa₈ and Xaa₉, are not involved in antibody binding or to a significantly smaller extent as compared to the His and the -Phe-Phe- binding site.

40. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof, which antibody recognizes and binds to at least one distinct binding site, particularly to a least two distinct binding sites, more particularly to at least three distinct binding sites on the β

-amyloid protein wherein said distinct binding sites comprise at least one and at least two consecutive amino acid residues, respectively, predominantly involved in the binding of the antibody, wherein the first of the at least two consecutive amino acid residues predominantly involved in the binding of the antibody are -Lys- and -Leu-, and the second of the at least two consecutive amino acid residues are -Phe-Phe- embedded within the following core sequence;

Xaa₁-Xaa₂-Lys-Leu-Xaa₄-Phe-Phe-Xaa₅-Xaa₆-Xaa₇-

wherein

Xaa₁ is an amino acid residue selected from the group comprising His, Asn, Gln Lys, and Arg;

Xaa₂ is an amino acid residue selected from the group comprising Asn and Gln;

Xaa₄ is an amino acid residue selected from the group comprising Ala, Val, Leu, norleucine, Met, Phe, and Ile;

Xaa₅ is an amino acid residue selected from the group comprising Ala, Val, Leu, Ser and Ile;

Xaa₆ is an amino acid residue selected from the group comprising Glu and Asp,

Xaa₇ is an amino acid residue selected from the group comprising Glu and Asp, and wherein said amino acid residues Xaa₂, Xaa₃, Xaa₄, Xaa₅, Xaa₆, Xaa₇ are not involved in antibody binding or to a significantly smaller extent as compared to the -Lys-Leu and the -Phe-Phe- binding site.

41. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof, which antibody recognizes and binds to at least one distinct binding site, particularly to a least two distinct binding sites, more particularly to at least three distinct binding sites on the β

-amyloid protein wherein said distinct binding sites comprise at least one and at least two consecutive amino acid residues, respectively, predominantly involved in the binding of the antibody, wherein the first of the at least two consecutive amino acid residues predominantly involved in the binding of the antibody are -Lys-Leu-, and the second of the at least two consecutive amino acid residues are-Phe-Phe-, and the third at least one amino residue is -His- embedded within the following core sequence;

-His-Xaa₂-Lys-Leu-Xaa₄-Phe-Phe-Xaa₅-Xaa₆-Xaa₇-

wherein

Xaa₂ is an amino acid residue selected from the group comprising Asn and Gln;

Xaa₄ is an amino acid residue selected from the group comprising Ala, Val, Leu, norleucine, Met, Phe, and Ile;

Xaa₅ is an amino acid residue selected from the group comprising Ala, Val, Leu, Ser and Ile;

Xaa₆ is an amino acid residue selected from the group comprising Glu and Asp,

Xaa₇ is an amino acid residue selected from the group comprising Glu and Asp, and wherein said amino acid residues Xaa₂, Xaa₃, Xaa₄, Xaa₅, Xaa₆, Xaa₇ are not involved in antibody binding or to a significantly smaller extent as compared to the -His-, the -Lys-Leu, and the -Phe-Phe- binding site.

42. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof, which antibody recognizes and binds to at least one distinct binding site, particularly to a least two distinct binding sites, more particularly to at least three distinct binding sites on the β

-amyloid protein wherein said distinct binding sites comprise at least one and at least two consecutive amino acid residues, respectively, predominantly involved in the binding of the antibody, wherein the first of the at least two consecutive amino acid residues predominantly involved in the binding of the antibody are -Lys-Leu-, and the second of the at least two consecutive amino acid residues are -Phe-Phe-, and the third at least one amino residue is -Asp- embedded within the following core sequence;

Xaa₁-Xaa₂-Lys-Leu-Xaa₄-Phe-Phe-Xaa₅-Xaa₆-Asp-

wherein

Xaa₁ is an amino acid residue selected from the group comprising His, Asn, Gln Lys, and Arg;

Xaa₂ is an amino acid residue selected from the group comprising Asn and Gln;

Xaa₄ is an amino acid residue selected from the group comprising Ala, Val, Leu, norleucine, Met, Phe, and Ile;

Xaa₅ is an amino acid residue selected from the group comprising Ala, Val, Leu, Ser and Ile;

Xaa₆ is an amino acid residue selected from the group comprising Glu and Asp, and wherein said amino acid residues Xaa₂, Xaa₃, Xaa₄, Xaa₅, Xaa₆, Xaa₇ are not involved in antibody binding or to a significantly smaller extent as compared to the -Asp-, the -Lys-Leu, and the -Phe-Phe- binding site.

43. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof, which antibody binds to 4 distinct binding sites on the β

-amyloid protein wherein said 4 distinct binding sites comprise one amino acid residue and two consecutive amino acid residues, respectively, which residues are predominantly involved in the binding of the antibody, wherein said 4 distinct binding sites are located in close proximity to each other on the antigen, separated by at least one amino acid residue not involved in antibody binding or to a significantly smaller extent as compared to said one amino acid residue and said two consecutive amino acid residues of the 4 distinct binding sites thus forming a conformational discontinuous epitope.

44. The monoclonal antibody according to claim 43 including any functionally equivalent antibody or functional parts thereof, wherein the first of the two consecutive amino acid residues predominantly involved in the binding of the antibody are -Lys-Leu-, and the second of the at least two consecutive amino acid residues are -Phe-Phe-, the first of the single amino residues is -His- and the second of the single amino residues is -Asp-embedded within the following core sequence:

His-Xaa₂-Lys-Leu -Xaa₄-Phe-Phe-Xaa₅-Xaa₆- Asp-

wherein

Xaa₂ is an amino acid residue selected from the group comprising Asn and Gln;

Xaa₄ is an amino acid residue selected from the group comprising Ala, Val, Leu, norleucine, Met, Phe, and Ile;

Xaa₅ is an amino acid residue selected from the group comprising Ala, Val, Leu, Ser and Ile;

Xaa₆ is an amino acid residue selected from the group comprising Glu and Asp, and wherein said amino acid residues Xaa₂, Xaa₃, Xaa₄, Xaa₅, Xaa₆, Xaa₇ are not involved in antibody binding or to a significantly smaller extent as compared to the -His-, -Asp-, the -Lys-Leu, and the -Phe-Phe- binding site.

47. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof, which comprises the Light Chain Variable Region (LCVR) of SEQ ID NO:

7

48. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof, which comprises the Heavy Chain Variable Region (HCVR) of SEQ ID NO:

8.

49. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof, which comprises both the Heavy Chain Variable Region (HCVR) of SEQ ID NO:

8 and the Light Chain Variable Region (LCVR) of SEQ ID NO;

7.

50. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof comprising a Light Chain Variable Region (LCVR) or Heavy Chain Variable Region (HCVR) or both, a Light Chain Variable Region (LCVR) and a Heavy Chain Variable Region (HCVR) that is homolgous to any of the peptides provided in SEQ ID NO:

7 and 8, respectively.

51. A monoclonal antibody according to claim 50 including any functionally equivalent antibody or functional parts thereof wherein the Light Chain Variable Region (LCVR) has an amino acid sequence that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the sequence given in SEQ ID NO:

7.

52. A monoclonal antibody according to claim 50 including any functionally equivalent antibody or functional parts thereof wherein the Heavy Chain Variable Region (HCVR) has an amino acid sequence that is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the sequence given in SEQ ID NO:

8.

53. A monoclonal antibody according to claim 50 including any functionally equivalent antibody or functional parts thereof wherein the Light Chain Variable Region (LCVR) and the Heavy Chain Variable Region (HCVR) together have an amino acid sequence that is 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical to the sequence given in SEQ ID NOS:

7 and 8.

55. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof which antibody has the characteristic properties of an antibody produced by hybridoma cell line FP 12H3, deposited on Dec. 1, 2005 and Dec. 9, 2005, respectively as DSM ACC2752.

56. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof which antibody has the characteristic properties of an antibody produced by hybridoma cell line FP 12H3-C2, deposited on Dec. 1, 2005 and Dec. 9, 2005, respectively as DSM ACC2750.

57. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof which antibody has the characteristic properties of an antibody produced by hybridoma cell line FP 12H3-G2, deposited on Dec. 1, 2005 and Dec. 9, 2005, respectively as DSM ACC2751.

58. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof which antibody has the characteristic properties of an antibody produced by hybridoma cell line ET 7E3, deposited on Dec. 8, 2005 as DSM ACC2755.

59. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof which antibody has the characteristic properties of an antibody produced by hybridoma cell line EJ 7H3, deposited on Dec. 8, 2005 as DSM ACC2756.

60. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof produced by hybridoma cell line FP 12H3, deposited on Dec. 1, 2005 and Dec. 9, 2005, respectively as DSM ACC2752 including functional equivalents thereof.

61. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof produced by hybridoma cell line FP 12H3-C2, deposited on Dec. 1, 2005 and Dec. 9, 2005, respectively as DSM ACC2750 including functional equivalents thereof.

62. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof produced by hybridoma cell line FP 12H3-G2, deposited on Dec. 1, 2005 and Dec. 9, 2005, respectively as DSM ACC2751 including functional equivalents thereof.

63. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof produced by hybridoma cell line ET 7E3, deposited on Dec. 8, 2005 as DSM ACC2755 including functional equivalents thereof.

64. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof produced by hybridoma cell line EJ 7H3, deposited on Dec. 8, 2005 as DSM ACC2756 including functional equivalents thereof.

65. A monoclonal antibody including any functionally equivalent antibody or functional parts thereof, which antibody has been raised against a supramolecular antigenic construct comprising an antigenic peptide corresponding to the amino acid sequence of the β

-amyloid peptide, particularly of β

-amyloid peptide Aβ

_1-15, Aβ

_1-16 and Aβ

<sub>1-16(Δ

14)</sub>, modified with hydrophobic moieties such as, for example, palmitic acid or a hydrophilic moiety such as, for example, polyethylene glycol (PEG) or a combination of both, wherein said hydrophobic and hydrophilic moiety, respectively, is covalently bound to each terminus through an amino acid such as, for example, lysine or any other suitable amino acid or amino acid analogue capable of serving as a linker molecule.

66. A polynucleotide comprising a nucleotide sequence encoding a monoclonal antibody including any functionally equivalent antibody or functional parts thereof, comprising

(a) at least the nucleotide sequence of the light chain variable region of SEQ ID NO:

9

(b) a nucleotide sequence that differ from the nucleotide sequence of (a) in codon sequence due to the degeneracy of the genetic code

(c) a nucleotide sequence with the complementary sequence to (a) and (b) or

(d) a fragment of a nucleotide sequence of (a), (b) or (c) comprising a contiguous stretch of nucleotides selected from the group consisting of at least 20 contiguous nucleotides, at least 25 contiguous nucleotides, at least 30 contiguous nucleotides, at least 35 contiguous nucleotides, at least 40 contiguous nucleotides, at least 45 contiguous nucleotides, and at least 50 contiguous nucleotides.

70. A polynucleotide comprising a nucleotide sequence which hybridizes to a nucleotide sequence of any one of claims 66-69.

71. A polynucleotide according to claim 70, wherein said nucleotide sequence hybridizes under conventional hybridization conditions, particularly under stringent hybridization conditions, to a nucleotide sequence according to any one of claims 66-69.

67. A polynucleotide comprising a nucleotide sequence encoding a monoclonal antibody including any functionally equivalent antibody or functional parts thereof, comprising

(a) at least the nucleotide sequence of the light chain of SEQ ID NO:

10

(b) a nucleotide sequence that differ from the nucleotide sequence of (a) in codon sequence due to the degeneracy of the genetic code

(c) a nucleotide sequence with the complementary sequence to (a) and (b) or

(d) a fragment of a nucleotide sequence of (a), (b) or (c) comprising a contiguous stretch of nucleotides selected from the group consisting of at least 20 contiguous nucleotides, at least 25 contiguous nucleotides, at least 30 contiguous nucleotides, at least 35 contiguous nucleotides, at least 40 contiguous nucleotides, at least 45 contiguous nucleotides, and at least 50 contiguous nucleotides.

68. A polynucleotide comprising a nucleotide sequence encoding a monoclonal antibody including any functionally equivalent antibody or functional parts thereof, comprising

(a) at least the nucleotide sequence of the heavy chain variable region of SEQ ID NO:

11

(b) a nucleotide sequence that differ from the nucleotide sequence of (a) in codon sequence due to the degeneracy of the genetic code

(c) a nucleotide sequence with the complementary sequence to (a) and (b) or

(d) a fragment of a nucleotide sequence of (a), (b) or (c) comprising a contiguous stretch of nucleotides selected from the group consisting of at least 20 contiguous nucleotides, at least 25 contiguous nucleotides, at least 30 contiguous nucleotides, at least 35 contiguous nucleotides, at least 40 contiguous nucleotides, at least 45 contiguous nucleotides, and at least 50 contiguous nucleotides.

69. A polynucleotide comprising a nucleotide sequence encoding a monoclonal antibody including any functionally equivalent antibody or functional parts thereof, comprising

(a) at least the nucleotide sequence of the heavy chain of SEQ ID NO:

12

(b) a nucleotide sequence that differ from the nucleotide sequence of (a) in codon sequence due to the degeneracy of the genetic code

(c) a nucleotide sequence with the complementary sequence to (a) and (b) or

(e) a fragment of a nucleotide sequence of (a), (b) or (c) comprising a contiguous stretch of nucleotides selected from the group consisting of at least 20 contiguous nucleotides, at least 25 contiguous nucleotides, at least 30 contiguous nucleotides, at least 35 contiguous nucleotides, at least 40 contiguous nucleotides, at least 45 contiguous nucleotides, and at least 50 contiguous nucleotides.

72. The Light Chain Variable Region (LCVR) of SEQ ID NO:

7.

73. The Heavy Chain Variable Region (HCVR) of SEQ ID NO:

8.

74. A polynucleotide encoding the Light Chain Variable Region (LCVR) of SEQ ID NO:

7.

75. A polynucleotide encoding the Heavy Chain Variable Region (HCVR) of SEQ ID NO:

8.

101. A hybridoma cell line characterized in that it produces a monoclonal antibody including any functionally equivalent antibody or functional parts thereof which antibody has the characteristic properties of an antibody produced by hybridoma cell line FP 12H3, deposited on Dec. 1, 2005 as DSM ACC2752.

102. A hybridoma cell line characterized in that it produces a monoclonal antibody including any functionally equivalent antibody or functional parts thereof which antibody has the characteristic properties of an antibody produced hybridoma cell line FP 12H3-C2, deposited on Dec. 1, 2005 as DSM ACC2750.

103. A hybridoma cell line characterized in that it produces a monoclonal antibody including any functionally equivalent antibody or functional parts thereof which antibody has the characteristic properties of an antibody produced hybridoma cell line FP 12H3-C2, deposited on Dec. 1, 2005 as DSM ACC2751.

104. A hybridoma cell line characterized in that it produces a monoclonal antibody including any functionally equivalent antibody or functional parts thereof which antibody has the characteristic properties of an antibody produced hybridoma cell line ET 7E3, deposited on Dec. 8, 2005 as DSM ACC2755.

105. A hybridoma cell line characterized in that it produces a monoclonal antibody including any functionally equivalent antibody or functional parts thereof which antibody has the characteristic properties of an antibody produced hybridoma cell line EJ 7H3, deposited on Dec. 8, 2005 as DSM ACC2756.

106. Hybridoma cell line hybridoma cell line FP 12H3, deposited on Dec. 1, 2005 as DSM ACC2752.

107. Hybridoma cell line hybridoma cell line FP 12H3-C2, deposited on Dec. 1, 2005 as DSM ACC2750.

108. Hybridoma cell line hybridoma cell line FP 12H3-G2, deposited on Dec. 1, 2005 as DSM ACC2751.

109. Hybridoma cell line hybridoma cell line ET 7E3, deposited on Dec. 8, 2005 as DSM ACC2755.

110. Hybridoma cell line hybridoma cell line EJ 7H3, deposited on Dec. 8, 2005 as DSM ACC2756.

111. Method of diagnosis of an amyloid-associated disease or condition in a patient comprising detecting the immunospecific binding of a monoclonal antibody or an active fragment thereof to an epitope of the amyloid protein in a sample or in situ which includes the steps of

(a) bringing the sample or a specific body part or body area suspected to contain the amyloid antigen into contact with an antibody according to the invention and as described herein before, which antibody binds an epitope of the amyloid protein;

(b) allowing the antibody to bind to the amyloid antigen to form an immunological complex;

(c) detecting the formation of the immunological complex; and

(d) correlating the presence or absence of the immunological complex with the presence or absence of amyloid antigen in the sample or specific body part or area.

114. A method for diagnosing a predisposition to an amyloid-associated disease or condition in a patient comprising detecting the immunospecific binding of a monoclonal antibody or an active fragment thereof to an epitope of the amyloid protein in a sample or in situ which includes the steps of

(a) bringing the sample or a specific body part or body area suspected to contain the amyloid antigen into contact with an antibody according to the invention and as described herein before, which antibody binds an epitope of the amyloid protein;

(b) allowing the antibody to bind to the amyloid antigen to form an immunological complex;

(c) detecting the formation of the immunological complex; and

(d) correlating the presence or absence of the immunological complex with the presence or absence of amyloid antigen in the sample or specific body part or area,

(e) comparing the amount of said immunological complex to a normal control value,

wherein an increase in the amount of said aggregate compared to a normal control value indicates that said patient is suffering from or is at risk of developing an amyloid-associated disease or condition.

118. Test kit according to claim 114 comprising a container holding one or more antibodies according to the present invention and instructions for using the antibodies for the purpose of binding to amyloid antigen to form an immunological complex and detecting the formation of the immunological complex such that presence or absence of the immunological complex correlates with presence or absence of amyloid antigen.