Methods of treating amyloidosis with humanized anti-beta-amyloid antibodies
First Claim
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1. A method for treating or alleviating the effects of a disease or disorder associated with amyloid plaque formation, said method comprising administering to an animal or a human in need thereof an antibody or a fragment thereof capable of specifically binding beta-amyloid peptide, wherein said antibody or fragment thereof comprises:
- (i) human- or primate-derived framework regions,(ii) a Heavy Chain Variable Region (HCVR) CDR1 having the amino acid sequence of SEQ ID NO;
1,(iii) an HCVR CDR2 having the amino acid sequence of SEQ ID NO;
2,(iv) an HCVR CDR3 having the amino acid sequence of SEQ ID NO;
3, and(v) a Light Chain Variable Region (LCVR) comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
12, wherein the LCVR comprises an LCVR CDR2 having the amino acid sequence of SEQ ID NO;
5 or the amino acid sequence of SEQ ID NO;
5 with one amino acid substitution; and
wherein at least one of the effects of the disease or disorder associated with amyloid plaque formation is treated or alleviated.
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Abstract
The present invention is related to chimeric and humanized antibody and to methods and compositions for the therapeutic and diagnostic use in the treatment of amyloidosis, a group of disorders and abnormalities associated with amyloid protein such as Alzheimer'"'"'s disease.
191 Citations
57 Claims
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1. A method for treating or alleviating the effects of a disease or disorder associated with amyloid plaque formation, said method comprising administering to an animal or a human in need thereof an antibody or a fragment thereof capable of specifically binding beta-amyloid peptide, wherein said antibody or fragment thereof comprises:
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(i) human- or primate-derived framework regions, (ii) a Heavy Chain Variable Region (HCVR) CDR1 having the amino acid sequence of SEQ ID NO;
1,(iii) an HCVR CDR2 having the amino acid sequence of SEQ ID NO;
2,(iv) an HCVR CDR3 having the amino acid sequence of SEQ ID NO;
3, and(v) a Light Chain Variable Region (LCVR) comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
12, wherein the LCVR comprises an LCVR CDR2 having the amino acid sequence of SEQ ID NO;
5 or the amino acid sequence of SEQ ID NO;
5 with one amino acid substitution; andwherein at least one of the effects of the disease or disorder associated with amyloid plaque formation is treated or alleviated. - View Dependent Claims (3, 4, 21, 22, 23, 24, 25, 26)
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2. A method for treating or alleviating the effects of a disease or disorder associated with amyloid plaque formation, said method comprising administering a composition to an animal or a human in need thereof, wherein said composition comprises a therapeutically effective amount of an antibody or fragment thereof capable of specifically binding beta-amyloid peptide, and wherein said antibody or fragment thereof comprises:
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(i) human- or primate-derived framework regions, (ii) an HCVR CDR1 having the amino acid sequence of SEQ ID NO;
1,(iii) an HCVR CDR2 having the amino acid sequence of SEQ ID NO;
2,(iv) an HCVR CDR3 having the amino acid sequence of SEQ ID NO;
3, and(v) a Light Chain Variable Region (LCVR) comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
12, wherein the LCVR comprises an LCVR CDR2 having the amino acid sequence of SEQ ID NO;
5 or the amino acid sequence of SEQ ID NO;
5 with one amino acid substitution in a therapeutically effective amount. - View Dependent Claims (9, 10)
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5. A method for treating or alleviating the effects of a disease or disorder associated with amyloid plaque formation, said method comprising administering to an animal or a human in need thereof an antibody or a fragment thereof capable of specifically binding beta-amyloid peptide, wherein said antibody or fragment thereof comprises:
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(i) human- or primate-derived framework regions, (ii) a Light Chain Variable Region (LCVR) CDR1 having the amino acid sequence of SEQ ID NO;
4,(iii) an LCVR CDR2 having the amino acid sequence of SEQ ID NO;
5 or the amino acid sequence of SEQ ID NO;
5 with one amino acid substitution,(iv) an LCVR CDR3 having the amino acid sequence of SEQ ID NO;
6, and(v) an HCVR comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
15; andwherein at least one of the effects of the disease or disorder associated with amyloid plaque formation is treated or alleviated. - View Dependent Claims (7, 8)
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6. A method for treating or alleviating the effects of a disease or disorder associated with amyloid plaque formation, said method comprising administering to an animal or a human in need thereof a composition comprising a therapeutically effective amount of an antibody or fragment thereof capable of specifically binding beta-amyloid peptide, wherein said antibody or fragment thereof comprises:
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(i) human- or primate-derived framework regions, (ii) a Light Chain Variable Region (LCVR) CDR1 having the amino acid sequence of SEQ ID NO;
4,(iii) an LCVR CDR2 having the amino acid sequence of SEQ ID NO;
5 or the amino acid sequence of SEQ ID NO;
5 with one amino acid substitution,(iv) an LCVR CDR3 having the amino acid sequence of SEQ ID NO;
6, and(v) an HCVR comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
15.
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11. A method for treating or alleviating the effects of a disease or disorder associated with amyloid plaque formation, said method comprising administering to an animal or a human in need thereof an antibody or a fragment thereof capable of specifically binding beta-amyloid peptide, wherein said antibody or fragment thereof comprises:
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(i) human- or primate-derived framework regions; (ii) an HCVR comprising an HCVR CDR1 having the amino acid sequence of SEQ ID NO;
1,an HCVR CDR2 having the amino acid sequence of SEQ ID NO;
2, andan HCVR CDR3 having the amino acid sequence of SEQ ID NO;
3, wherein said HCVR comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
15; and(iii) an LCVR comprising an LCVR CDR1 having the amino acid sequence of SEQ ID NO;
4,an LCVR CDR2 having the amino acid sequence of SEQ ID NO;
5 or the amino acid sequence of SEQ ID NO;
5 with one amino acid substitution, andan LCVR CDR3 having the amino acid sequence of SEQ ID NO;
6, wherein said LCVR comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
12; andwherein at least one of the effects of the disease or disorder associated with amyloid plaque formation is treated or alleviated. - View Dependent Claims (13, 14, 15, 16, 17, 18, 19, 20)
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12. A method for treating or alleviating the effects of a disease or disorder associated with amyloid plaque formation, said method comprising administering to an animal or a human in need thereof a composition comprising a therapeutically effective amount of an antibody or fragment thereof capable of specifically binding beta-amyloid peptide, wherein said antibody or fragment thereof comprises:
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(i) human- or primate-derived framework regions; (ii) an HCVR comprising an HCVR CDR1 having the amino acid sequence of SEQ ID NO;
1,an HCVR CDR2 having the amino acid sequence of SEQ ID NO;
2, andan HCVR CDR3 having the amino acid sequence of SEQ ID NO;
3, wherein said HCVR comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
15; and(iii) an LCVR comprising an LCVR CDR1 having the amino acid sequence of SEQ ID NO;
4,an LCVR CDR2 having the amino acid sequence of SEQ ID NO;
5 or the amino acid sequence of SEQ ID NO;
5 with one amino acid substitution, andan LCVR CDR3 having the amino acid sequence of SEQ ID NO;
6, wherein said LCVR comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
12 .
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27. A method for the preparation of a composition for use in treating or alleviating the effects of a disease or disorder associated with amyloid plaque formation, comprising formulating an antibody or a fragment thereof in a pharmaceutically acceptable form, wherein said antibody or fragment thereof is capable of specifically binding beta-amyloid peptide, and wherein said antibody or fragment thereof comprises:
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(i) human- or primate-derived framework regions, (ii) an HCVR CDR1 having the amino acid sequence of SEQ ID NO;
1,(iii) an HCVR CDR2 having the amino acid sequence of SEQ ID NO;
2,(iv) an HCVR CDR3 having the amino acid sequence of SEQ ID NO;
3, and(v) a Light Chain Variable Region (LCVR) comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
12, wherein the LCVR comprises an LCVR CDR2 having the amino acid sequence of SEQ ID NO;
5 or the amino acid sequence of SEQ ID NO;
5 with one amino acid substitution.
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28. A method for the preparation of a composition for use in treating or alleviating the effects of a disease or disorder associated with amyloid plaque formation, comprising formulating an antibody or a fragment thereof in a pharmaceutically acceptable form, wherein said antibody or fragment thereof comprises:
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(i) an HCVR having the amino acid sequence of SEQ ID NO;
15, and(ii) an LCVR having the amino acid sequence of SEQ ID NO;
12.
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29. A method for disaggregating preformed beta-amyloid fibers, comprising interacting an antibody or fragment thereof with preformed beta-amyloid fibers, wherein said antibody or fragment thereof is capable of specifically binding beta-amyloid peptide, and wherein said antibody or fragment thereof comprises:
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(i) human- or primate-derived framework regions, (ii) an HCVR CDR1 having the amino acid sequence of SEQ ID NO;
1,(iii) an HCVR CDR2 having the amino acid sequence of SEQ ID NO;
2,(iv) an HCVR CDR3 having the amino acid sequence of SEQ ID NO;
3, and(v) a Light Chain Variable Region (LCVR) comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
12, wherein the LCVR comprises an LCVR CDR2 having the amino acid sequence of SEQ ID NO;
5 or the amino acid sequence of SEQ ID NO;
5 with one amino acid substitution.
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30. A method for disaggregating preformed beta-amyloid fibers, comprising interacting an antibody or fragment thereof with preformed beta-amyloid fibers, wherein said antibody or fragment thereof is capable of specifically binding beta-amyloid peptide, and wherein said antibody or fragment thereof comprises:
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(i) an HCVR having the amino acid sequence of SEQ ID NO;
15, and(ii) an LCVR having the amino acid sequence of SEQ ID NO;
12.
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- 31. A method for treating or alleviating the effects of a disease or disorder associated with amyloid plaque formation, said method comprising administering to an animal or a human in need thereof a therapeutically effective amount of an antibody or a fragment thereof capable of specifically binding beta-amyloid peptide, wherein said antibody or fragment thereof comprises an HCVR having the amino acid sequence of SEQ ID NO:
- 34. A method for treating or alleviating the effects of a disease or disorder associated with amyloid plaque formation, said method comprising administering to an animal or a human in need thereof a therapeutically effective amount of an antibody or a fragment thereof capable of specifically binding beta-amyloid peptide, wherein said antibody or fragment thereof comprises an LCVR having the amino acid sequence of SEQ ID NO:
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37. A method for treating or alleviating the effects of a disease or disorder associated with amyloid plaque formation, said method comprising administering to an animal or a human in need thereof a therapeutically effective amount of an antibody or a fragment thereof capable of specifically binding beta-amyloid peptide, wherein said antibody or a fragment thereof comprises:
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(i) an HCVR having the amino acid sequence of SEQ ID NO;
15, and(ii) an LCVR having the amino acid sequence of SEQ ID NO;
12. - View Dependent Claims (38, 39, 49)
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40. A method for treating or alleviating the effects of a disease or disorder associated with amyloid plaque formation in the brain, said method comprising administering to an animal or a human in need thereof an antibody or a fragment thereof capable of specifically binding beta-amyloid peptide, wherein said antibody or fragment thereof comprises:
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(i) human- or primate-derived framework regions, (ii) an HCVR CDR1 having the amino acid sequence of SEQ ID NO;
1,(iii) an HCVR CDR2 having the amino acid sequence of SEQ ID NO;
2,(iv) an HCVR CDR3 having the amino acid sequence of SEQ ID NO;
3, and(v) an LCVR comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
12, wherein the LCVR comprises an LCVR CDR2 having the amino acid sequence of SEQ ID NO;
5 or the amino acid sequence of SEQ ID NO;
5 with one amino acid substitution; andwherein at least one of the effects of the disease or disorder associated with amyloid plaque formation in the brain is treated or alleviated. - View Dependent Claims (42, 43, 44, 45, 46, 47, 48)
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41. A method for treating or alleviating the effects of a disease or disorder associated with amyloid plaque formation in the brain, said method comprising administering to an animal or a human in need thereof an antibody or a fragment thereof capable of specifically binding beta-amyloid peptide, wherein said antibody or fragment thereof comprises:
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(i) human- or primate-derived framework regions, (ii) an LCVR CDR1 having the amino acid sequence of SEQ ID NO;
4,(iii) an LCVR CDR2 having the amino acid sequence of SEQ ID NO;
5 or the amino acid sequence of SEQ ID NO;
5 with one amino acid substitution,(iv) an LCVR CDR3 having the amino acid sequence of SEQ ID NO;
6, and(v) an HCVR comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
15; andwherein at least one of the effects of the disease or disorder associated with amyloid plaque formation in the brain is treated or alleviated.
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50. A method for retaining or increasing cognitive memory capacity of an animal or a human suffering from memory impairment associated with a disease or disorder associated with brain amyloid plaque formation by administering to the animal or the human, a pharmaceutical composition comprising an antibody or a fragment thereof which is capable of specifically binding beta-amyloid peptide, and wherein said antibody or fragment thereof comprises:
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(i) an HCVR comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
15, or(ii) an LCVR comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
12, or(iii) an HCVR comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
15 and an LCVR comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
12.
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51. A method for retaining or increasing cognitive memory capacity of an animal or a human suffering from memory impairment associated with a disease or disorder associated with brain amyloid plaque formation by administering to the animal or the human, a pharmaceutical composition comprising an antibody or a fragment thereof which is capable of specifically binding beta-amyloid peptide, and wherein said antibody or fragment thereof comprises:
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(i) an HCVR comprising the amino acid sequence of SEQ ID NO;
15, or(ii) an LCVR comprising the amino acid sequence of SEQ ID NO;
12 or(iii) an HCVR comprising the amino acid sequence of SEQ ID NO;
15 and an LCVR comprising the amino acid sequence of SEQ ID NO;
12.
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52. A method for retaining or increasing cognitive memory capacity of an animal or a human suffering from memory impairment associated with a disease or disorder associated with brain amyloid plaque formation by administering to the animal or the human, a pharmaceutical composition comprising an antibody or a fragment thereof which is capable of specifically binding beta-amyloid peptide, and wherein said antibody or fragment thereof comprises:
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(i) an HCVR comprising the amino acid sequence of SEQ ID NO;
15, and(ii) an LCVR comprising the amino acid sequence of SEQ ID NO;
12.
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53. A method for restoring the cognitive memory capacity of an animal or a human suffering from memory impairment associated with a disease or disorder associated with brain amyloid plaque formation by administering to the animal or the human, a pharmaceutical composition comprising an antibody or a fragment thereof which is capable of specifically binding beta-amyloid peptide, and wherein said antibody or fragment thereof comprises:
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(i) an HCVR comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
15, or(ii) an LCVR comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
12, or(iii) an HCVR comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
15 and an LCVR comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
12.
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54. A method for restoring the cognitive memory capacity of an animal or a human suffering from memory impairment associated with a disease or disorder associated with brain amyloid plaque formation by administering to the animal or the human, a pharmaceutical composition comprising an antibody or a fragment thereof which is capable of specifically binding beta-amyloid peptide, and wherein said antibody or fragment thereof comprises:
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(i) an HCVR comprising the amino acid sequence of SEQ ID NO;
15, or(ii) an LCVR comprising the amino acid sequence of SEQ ID NO;
12 or(iii) an HCVR comprising the amino acid sequence of SEQ ID NO;
15 and an LCVR comprising the amino acid sequence of SEQ ID NO;
12.
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55. A method for restoring the cognitive memory capacity of an animal or a human suffering from memory impairment associated with a disease or disorder associated with brain amyloid plaque formation by administering to the animal or the human, a pharmaceutical composition comprising an antibody or a fragment thereof which is capable of specifically binding beta-amyloid peptide, and wherein said antibody or fragment thereof comprises:
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(i) an HCVR comprising the amino acid sequence of SEQ ID NO;
15, and(ii) an LCVR comprising the amino acid sequence of SEQ ID NO;
12.
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56. A method of protecting neurons from beta-amyloid induced neuron degradation comprising treating neurons with an effective amount of a humanized antibody or a fragment thereof which is capable of specifically binding beta-amyloid peptide, and wherein said humanized antibody or fragment thereof comprises:
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(i) an HCVR comprising the amino acid sequence of SEQ ID NO;
15 or an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
15, or(ii) an LCVR comprising the amino acid sequence of SEQ ID NO;
12 or an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
12, or(iii) an HCVR comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
15 and an LCVR comprising an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO;
12, or(iv) an HCVR comprising the amino acid sequence of SEQ ID NO;
15 and an LCVR comprising the amino acid sequence of SEQ ID NO;
12.
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57. A method of protecting neurons from beta-amyloid induced neuron degradation comprising treating neurons with an effective amount of a humanized antibody or a fragment thereof which is capable of specifically binding beta-amyloid peptide, and wherein said humanized antibody or fragment thereof comprises:
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(i) an HCVR comprising the amino acid sequence of SEQ ID NO;
15, and(ii) an LCVR comprising the amino acid sequence of SEQ ID NO;
12.
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Specification