Parathyroid hormone antagonists and uses thereof
First Claim
1. A pharmaceutical composition, which pharmaceutical composition comprises an effective amount of a parathyroid hormone (PTH) antagonist and a pharmaceutically acceptable carrier or excipient, wherein said PTH antagonist comprises a contiguous portion of human PTH having an amino acid sequence set forth in SEQ ID NO:
- 1 (PTH184), or a nucleic acid encoding said portion of human PTH, and said PTH antagonist has the following characteristics;
a) the N-terminal amino acid residue of said PTH antagonist starts at any position spanning position 2 through position 33 of said PTH1-84;
b) the C-terminal amino acid residue of said PTH antagonist ends at any position spanning position 35 through position 84 of said PTH1-84; and
c) said PTH antagonist has a minimal length of three amino acid residues.
1 Assignment
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Accused Products
Abstract
The present invention relates to parathyroid hormone (PTH) antagonists. More particularly, the present invention provides for pharmaceutical compositions, kits and combinations comprising the PTH antagonist. The present invention also provides for methods for preventing, treating or delaying a disease or disorder associated with excessive bone mineral, e.g., calcium, loss or for preventing, treating or delaying the effect of a PTH agonist using the PTH antagonist. The present invention further provides for methods for identifying a subject having or at risk of having osteoporosis or decreased bone density, or for identifying a subject in need of PTH antagonist treatment, or for monitoring a subject undergoing treatment for osteoporosis or decreased bone density, by determining and/or monitoring PTH antagonist level or a comparative value between PTH agonist and PTH antagonist. The present invention further provides for methods for identifying an agent suitable for preventing, treating or delaying osteoporosis by identifying a compound that enhances the PTH antagonist activity.
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Citations
87 Claims
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1. A pharmaceutical composition, which pharmaceutical composition comprises an effective amount of a parathyroid hormone (PTH) antagonist and a pharmaceutically acceptable carrier or excipient, wherein said PTH antagonist comprises a contiguous portion of human PTH having an amino acid sequence set forth in SEQ ID NO:
- 1 (PTH184), or a nucleic acid encoding said portion of human PTH, and said PTH antagonist has the following characteristics;
a) the N-terminal amino acid residue of said PTH antagonist starts at any position spanning position 2 through position 33 of said PTH1-84;
b) the C-terminal amino acid residue of said PTH antagonist ends at any position spanning position 35 through position 84 of said PTH1-84; and
c) said PTH antagonist has a minimal length of three amino acid residues. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 87)
- 1 (PTH184), or a nucleic acid encoding said portion of human PTH, and said PTH antagonist has the following characteristics;
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18. A combination, which combination comprises an effective amount of a parathyroid hormone (PTH) antagonist and an effective amount of an agent suitable for preventing, treating or delaying a disease or disorder associated with excessive bone mineral loss, wherein said PTH antagonist comprises a contiguous portion of human PTH having an amino acid sequence set forth in SEQ ID NO:
- 1 (PTH1-84), or a nucleic acid encoding said portion of human PTH, and said PTH antagonist has the following characteristics;
a) the N-terminal amino acid residue of said PTH antagonist starts at any position spanning position 2 through position 33 of said PTH1-84;
b) the C-terminal amino acid residue of said PTH antagonist ends at any position spanning position 35 through position 84 of said PTH1-84; and
c) said PTH antagonist has a minimal length of three amino acid residues.
- 1 (PTH1-84), or a nucleic acid encoding said portion of human PTH, and said PTH antagonist has the following characteristics;
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19. A method for preventing, treating or delaying a disease or disorder associated with excessive bone mineral loss in a mammal, which method comprises administering to a mammal, to which such prevention, treatment or delay is needed or desirable, an effective amount of a parathyroid hormone (PTH) antagonist or an agent that enhances production and/or antagonizing function of said PTH antagonist,
wherein said PTH antagonist comprises a contiguous portion of human PTH having an amino acid sequence set forth in SEQ ID NO: - 1 (PTH1-84), or a nucleic acid encoding said portion of human PTH, and said PTH antagonist has the following characteristics;
a) the N-terminal amino acid residue of said PTH antagonist starts at any position spanning position 2 through position 33 of said PTH1-84;
b) the C-terminal amino acid residue of said PTH antagonist ends at any position spanning position 35 through position 84 of said PTH1-84; and
c) said PTH antagonist has a minimal length of three amino acid residues, whereby said disease or disorder associated with excessive bone mineral loss is prevented, treated or delayed. - View Dependent Claims (20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49)
- 1 (PTH1-84), or a nucleic acid encoding said portion of human PTH, and said PTH antagonist has the following characteristics;
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50. A method for preventing, treating or delaying the effect of a PTH agonist in a mammal, which method comprises administering to a mammal, to which such prevention, treatment or delay is needed or desirable, an effective amount of a parathyroid hormone (PTH) antagonist or an agent that enhances production and/or antagonizing function of said PTH antagonist wherein said PTH antagonist comprises a contiguous portion of human PTH having an amino acid sequence set forth in SEQ ID NO:
- 1 (PTH1-84), or a nucleic acid encoding said portion of human PTH, and said PTH antagonist has the following characteristics;
a) the N-terminal amino acid residue of said PTH antagonist starts at any position spanning position 2 through position 33 of said PTH1-84;
b) the C-terminal amino acid residue of said PTH antagonist ends at any position spanning position 35 through position 84 of said PTH1-84; and
c) said PTH antagonist has a minimal length of three amino acid residues, whereby the effect of said PTH agonist is prevented, treated or delayed. - View Dependent Claims (51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64)
- 1 (PTH1-84), or a nucleic acid encoding said portion of human PTH, and said PTH antagonist has the following characteristics;
- 65. A method for identifying a subject having or at risk of having osteoporosis or decreased bone density, which method comprises determining PTH antagonist level or a comparative value between PTH agonist and PTH antagonist and identifying a subject having an abnormal PTH antagonist level or an abnormal comparative value between PTH agonist and PTH antagonist as having or at risk of having osteoporosis or decreased bone density.
- 67. A method for identifying a subject in need of parathyroid hormone (PTH) antagonist treatment, which method comprises determining PTH antagonist level or a comparative value between PTH agonist and PTH antagonist and identifying a subject having an abnormal PTH antagonist level or an abnormal comparative value between PTH agonist and PTH antagonist as in need of parathyroid hormone (PTH) antagonist treatment.
- 71. A method for monitoring a subject undergoing treatment for osteoporosis or decreased bone density, which method comprises determining PTH antagonist level or a comparative value between PTH agonist and PTH antagonist and identifying a subject having an abnormal PTH antagonist level or an abnormal comparative value between PTH agonist and PTH antagonist.
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76. A method for identifying an agent suitable for preventing, treating or delaying osteoporosis, which method comprises:
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a) measuring PTH antagonist activity in the presence and absence of a candidate compound; and
b) identifying a compound that enhances said PTH antagonist activity as an agent suitable for preventing, treating or delaying osteoporosis. - View Dependent Claims (77)
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78. A pharmaceutical composition, which pharmaceutical composition comprises an effective amount of a parathyroid hormone (PTH) antagonist and a pharmaceutically acceptable carrier or excipient, wherein said PTH antagonist comprises a contiguous portion of pig PTH having an amino acid sequence set forth in SEQ ID NO:
- 2, dog PTH having an amino acid sequence set forth in SEQ ID NO;
3, bovine PTH having an amino acid sequence set forth in SEQ ID NO;
4, rat PTH having an amino acid sequence set forth in SEQ ID NO;
5, or chicken PTH having an amino acid sequence set forth in SEQ ID NO;
6, or a nucleic acid encoding said portion of pig, dog, bovine, rat or chicken PTH, and said PTH antagonist has the following characteristics;
a) the N-terminal amino acid residue of said PTH antagonist starts at any position spanning position 2 through position 33 of said PTH1-84;
b) the C-terminal amino acid residue of said PTH antagonist ends at any position spanning position 35 through position 84 of said PTH1-84; and
c) said PTH antagonist has a minimal length of three amino acid residues.
- 2, dog PTH having an amino acid sequence set forth in SEQ ID NO;
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79. A method for preventing, treating or delaying a disease or disorder associated with excessive bone mineral loss in a mammal, which method comprises administering to a mammal, to which such prevention, treatment or delay is needed or desirable, an effective amount of a parathyroid hormone (PTH) antagonist or an agent that enhances production and/or antagonizing function of said PTH antagonist, wherein said PTH antagonist comprises a contiguous portion of pig PTH having an amino acid sequence set forth in SEQ ID NO:
- 2, dog PTH having an amino acid sequence set forth in SEQ ID NO;
3, bovine PTH having an amino acid sequence set forth in SEQ ID NO;
4, rat PTH having an amino acid sequence set forth in SEQ ID NO;
5 or chicken PTH having an amino acid sequence set forth in SEQ ID NO;
6, or a nucleic acid encoding said portion of pig, dog, bovine, rat or chicken PTH, and said PTH antagonist has the following characteristics;
a) the N-terminal amino acid residue of said PTH antagonist starts at any position spanning position 2 through position 33 of said PTH1-84;
b) the C-terminal amino acid residue of said PTH antagonist ends at any position spanning position 35 through position 84 of said PTH1-84; and
c) said PTH antagonist has a minimal length of three amino acid residues, whereby said disease or disorder associated with excessive bone mineral loss is prevented, treated or delayed.
- 2, dog PTH having an amino acid sequence set forth in SEQ ID NO;
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80. A method for preventing, treating or delaying the effect of a PTH agonist in a mammal, which method comprises administering to a mammal, to which such prevention, treatment or delay is needed or desirable, an effective amount of a parathyroid hormone (PTH) antagonist or an agent that enhances production and/or antagonizing function of said PTH antagonist, wherein said PTH antagonist comprises a contiguous portion of pig PTH having an amino acid sequence set forth in SEQ ID NO:
- 2, dog PTH having an amino acid sequence set forth in SEQ ID NO;
3, bovine PTH having an amino acid sequence set forth in SEQ ID NO;
4, rat PTH having an amino acid sequence set forth in SEQ ID NO;
5 (PTH1-84), or chicken PTH having an amino acid sequence set forth in SEQ ID NO;
6, or a nucleic acid encoding said portion of pig, dog, bovine, rat or chicken PTH, and said PTH antagonist has the following characteristics;
a) the N-terminal amino acid residue of said PTH antagonist starts at any position spanning position 2 through position 33 of said PTH1-84;
b) the C-terminal amino acid residue of said PTH antagonist ends at any position spanning position 35 through position 84 of said PTH1-84; and
c) said PTH antagonist has a minimal length of three amino acid residues, whereby the effect of said PTH agonist is prevented, treated or delayed.
- 2, dog PTH having an amino acid sequence set forth in SEQ ID NO;
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81. A method for preventing, treating or delaying bone metastasis in a human, which method comprises administering to a human, to which such prevention, treatment or delay is needed or desirable, an effective amount of a parathyroid hormone (PTH) antagonist or an agent that enhances production and/or antagonizing function of said PTH antagonist, wherein said PTH antagonist comprises a contiguous portion of human PTH having an amino acid sequence set forth in SEQ ID NO:
- 1 (PTH1-84), or a nucleic acid encoding said portion of human PTH, and said PTH antagonist has the following characteristics;
a) the N-terminal amino acid residue of said PTH antagonist starts at any position spanning position 2 through position 33 of said PTH1-84;
b) the C-terminal amino acid residue of said PTH antagonist ends at any position spanning position 35 through position 84 of said PTH1-84; and
c) said PTH antagonist has a minimal length of three amino acid residues, whereby said bone metastasis is prevented, treated or delayed. - View Dependent Claims (82, 83, 84, 85, 86)
- 1 (PTH1-84), or a nucleic acid encoding said portion of human PTH, and said PTH antagonist has the following characteristics;
Specification