Antibodies associated with alterations in bone density
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C07K-016/00
A61K-039/395
C12N-015/00
출원번호
UP-0788606
(2004-02-27)
등록번호
US-7758858
(2010-08-09)
발명자
/ 주소
Brunkow, Mary E
Galas, David J
Kovacevich, Brian
Mulligan, John T
Paeper, Bryan W
Van Ness, Jeffrey
Winkler, David G
출원인 / 주소
Darwin Discovery Ltd.
대리인 / 주소
Marshall, Gerstein & Borun LLP
인용정보
피인용 횟수 :
24인용 특허 :
44
초록▼
Compositions and methods for increasing bone density using antibodies directed to a novel class or family of TGF-β binding proteins are provided. The disclosed compositions are useful, for example, in the diagnosis, prevention and/or treatment of diseases associated with a loss of bone density
Compositions and methods for increasing bone density using antibodies directed to a novel class or family of TGF-β binding proteins are provided. The disclosed compositions are useful, for example, in the diagnosis, prevention and/or treatment of diseases associated with a loss of bone density, for example osteoporosis.
대표청구항▼
We claim: 1. An isolated antibody or antigen binding fragment thereof which specifically binds to a polypeptide at least 90% identical to the secreted protein encoded by a polynucleotide sequence selected from the group consisting of SEQ ID NOS: 1, 5, 9, 11, 13 and 15, wherein said polypeptide reta
We claim: 1. An isolated antibody or antigen binding fragment thereof which specifically binds to a polypeptide at least 90% identical to the secreted protein encoded by a polynucleotide sequence selected from the group consisting of SEQ ID NOS: 1, 5, 9, 11, 13 and 15, wherein said polypeptide retains a cysteine backbone comprising eight cysteines and retains the ability to decrease bone mineral content. 2. The antibody or antigen binding fragment thereof of claim 1 wherein the isolated antibody or binding fragment thereof is a polyclonal antibody. 3. The antibody or antigen binding fragment thereof of claim 1 wherein the isolated antibody or binding fragment thereof is a monoclonal antibody. 4. The antibody or antigen binding fragment thereof of claim 1 wherein the isolated antibody or binding fragment thereof is a humanized antibody. 5. The antibody or antigen binding fragment thereof of claim 1 wherein the antibody or antigen binding fragment binds to said secreted protein with an affinity Ka of at least 107 M−1. 6. The antibody or antigen binding fragment thereof of claim 1 wherein the antibody or antigen binding fragment binds to said secreted protein with an affinity Ka of at least 108 M−1. 7. A hybridoma that produces an antibody according to claim 1. 8. A method of producing the antibody of claim 1, comprising immunizing an animal with a protein comprising a polypeptide that is encoded by a polynucleotide that comprises a nucleotide sequence selected from SEQ ID NOs:1, 5, 9, 11, 13, and 15, wherein said polypeptide retains a cysteine backbone comprising eight cysteines and retains the ability to decrease bone mineral content. 9. A method for production of an antibody according to claim 1 comprising culturing hybridoma cells under conditions that permit the production of said antibody. 10. A method for production of an antibody or binding fragment thereof of claim 1, comprising: (a) providing a recombinant host cell capable of producing said antibody or binding fragment thereof; and (b) culturing said cell under conditions that permit the production of said antibody or binding fragment. 11. A method for immunizing an animal to produce a cell capable of expressing the antibody of claim 1, comprising injecting into an animal: a polypeptide encoded by a polynucleotide that comprises a nucleotide sequence selected from SEQ ID NOs: 1, 5, 9, 11, 13, and 15, wherein said polypeptide retains a cysteine backbone comprising eight cysteines and retains the ability to decrease bone mineral content. 12. An isolated conjugate or fusion protein comprising the antibody, or antibody fragment of claim 1. 13. An isolated antibody or antibody fragment that binds to the secreted protein encoded by SEQ ID NO: 1, wherein the antibody or antibody fragment binds said secreted protein with an affinity Ka of greater than or equal to 107 M−1. 14. An isolated conjugate or fusion protein comprising an antibody, or an antibody fragment that binds to the secreted protein encoded by SEQ ID NO: 1, wherein the conjugate or fusion protein binds said protein with an affinity Ka of greater than or equal to 107 M−1. 15. The conjugate or fusion protein of claim 14, further comprising an effector or reporter molecule. 16. The conjugate or fusion protein of claim 15, wherein the effector or reporter molecule is selected from the group consisting of antineoplastic agents, toxins, enzymes and fragments thereof, naturally occurring and synthetic polymers and derivatives thereof, radionuclides, chelated metals, fluorescent compounds and compounds which may be detected by NMR or ESR spectroscopy. 17. The conjugate or fusion protein of claim 14, wherein the antibody fragment is selected from the group consisting of F(ab′)2, F(ab)2, Fab′, Fab, and Fv. 18. The conjugate or fusion protein of claim 14, wherein the antibody is selected from the group consisting of murine monoclonal antibodies, human monoclonal antibodies, humanized monoclonal antibodies, and antibody fragments thereof. 19. A method of increasing bone mineral content in a human comprising administering to the human (a) the conjugate or fusion protein of claim 14 in an amount effective to increase bone mineral content and (b) an inhibitor of bone resorption. 20. The method of claim 19, wherein the inhibitor of bone resorption is selected from the group consisting of calcitonin, estrogen, a bisphosphonate, a growth factor having anti-resorptive activity and tamoxifen. 21. The method of claim 19, wherein the inhibitor of bone resorption is a bisphosphonate.
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이 특허에 인용된 특허 (44)
Btzow Ralf (Helsinki CA FIX) Ruoslahti Erkki (Rancho Santa Fe CA), 60 kDa transforming growth factor-b
상세보기
Brunkow, Mary E.; Galas, David J.; Kovacevich, Brian; Mulligan, John T.; Paeper, Bryan W.; Van Ness, Jeffrey; Winkler, David G., Antibodies associated with alterations in bone density.
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Mary E. Brunkow ; David J. Galas ; Brian Kovacevich ; John T. Mulligan ; Bryan W. Paeper ; Jeffrey Van Ness ; David G. Winkler, Compositions and methods for increasing bone mineralization.
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Stemmer Willem P. C. ; Crameri Andreas, Methods for generating polynucleotides having desired characteristics by iterative selection and recombination.
Margolis David J. (Philadelphia PA), Methods of treating osteoporosis, increasing bone mineral content and preventing the occurrence of compression fractures.
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Mary E. Brunkow ; David J. Galas ; Brian Kovacevich ; John T. Mulligan ; Bryan W. Paeper ; Jeffrey Van Ness ; David G. Winkler, Polypeptides associated with alterations in bone density.
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Goldenberg Milton D. (11837 Gainsborough Rd. Potomac MD 20854), Tumor localization and therapy with labeled antibody fragments specific to tumor-associated markers.
Brunkow, Mary E.; Galas, David J.; Kovacevich, Brian; Mulligan, John T.; Paeper, Bryan W.; Van Ness, Jeffrey; Winkler, David G., Compositions and methods for increasing bone mineralization.
Brunkow, Mary E.; Galas, David J.; Kovacevich, Brian; Mulligan, John T.; Paeper, Bryan W.; Van Ness, Jeffrey; Winkler, David G., Compositions and methods for increasing bone mineralization.
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