Hepcidin, hepcidin antagonists and methods of use
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C07K-016/00
A61K-039/395
C07K-016/28
출원번호
US-0022515
(2008-01-30)
등록번호
US-8629250
(2014-01-14)
발명자
/ 주소
Sasu, Barbra
Haniu, Mitsuru
Boone, Thomas Charles
Bi, Xiao-juan
Lee, Grace Ki Jeong
Arvedson, Tara
Winters, Aaron George
Cooke, Keegan
Sheng, Jackie Z.
출원인 / 주소
Amgen Inc.
대리인 / 주소
Bugaisky, Lawrence B.
인용정보
피인용 횟수 :
0인용 특허 :
85
초록
The invention relates to purified, correctly folded hepcidin, antibodies that bind hepcidin, and methods of making and using such materials. Also provide are methods of treated hepcidin-related disorders.
대표청구항▼
1. An isolated monoclonal antibody which specifically binds to human hepcidin, wherein said human hepcidin consists of the amino acid sequence set forth in SEQ ID NO: 9 and has a conformation comprising four disulfide-bond loops formed between residues 7 and 23, 10 and 13, 11 and 19, and 14 to 22 as
1. An isolated monoclonal antibody which specifically binds to human hepcidin, wherein said human hepcidin consists of the amino acid sequence set forth in SEQ ID NO: 9 and has a conformation comprising four disulfide-bond loops formed between residues 7 and 23, 10 and 13, 11 and 19, and 14 to 22 as located in SEQ ID NO: 9 and the isolated monoclonal antibody inhibits the iron-regulating activity of hepcidin. 2. The isolated monoclonal antibody of claim 1 that binds to human hepcidin of SEQ ID NO: 9 and increases circulating iron concentration or Tsat. 3. An isolated monoclonal antibody that competes with another antibody for binding to hepcidin (SEQ ID NO: 9) by at least about 75% said monoclonal antibody comprising the amino acid sequences having SEQ ID NOs: 164, 165, 166, 225, 226 and 227 or the monoclonal antibody comprising SEQ ID NO: 224 or the monoclonal antibody comprising SEQ ID NO: 229. 4. An isolated monoclonal antibody, wherein the antibody comprises the amino acid sequence of SEQ ID NO: 225, the amino acid sequence of SEQ ID NO: 226, the amino acid sequence of SEQ ID NO: 227, the amino acid sequence SEQ ID NO: 164, the amino acid sequence SEQ ID NO: 165 and the amino acid sequence SEQ ID NO: 166. 5. An isolated monoclonal antibody that competes with an antibody for binding to hepcidin (SEQ ID NO: 9) by at least about 75% said monoclonal antibody comprising the amino acid sequence of SEQ ID NO: 224 or SEQ ID NO:229. 6. An isolated monoclonal antibody comprising the amino acid sequence of SEQ ID NO: 229 or SEQ ID NO:224. 7. An isolated monoclonal antibody comprising the amino acid sequence of SEQ ID NO: 160 or SEQ ID NO:255. 8. An isolated monoclonal antibody comprising the amino acid sequence of SEQ ID NO: 255 and SEQ ID NO:229. 9. An isolated monoclonal antibody comprising the amino acid sequence of SEQ ID NO: 160 and SEQ ID NO:224. 10. The isolated monoclonal antibody of any one of claims 1, 2, 3, 4, 5, 6, 7, 8 or 9 wherein said antibody is selected from the group consisting of a chimerized antibody, a humanized antibody, a fully human antibody, a single chain Fv fragment, a (Fab')2 fragment, a domain antibody (dAb), a diabody, and a maxibody. 11. The isolated monoclonal antibody of any one of claims 1, 2, 3, 4, 5, 6, 7, 8 or 9, wherein the antibody is a human antibody. 12. The isolated monoclonal antibody of any one of claims 1, 2, 3, 4, 5, 6, 7, 8 or 9, that binds both human hepcidin (SEQ ID NO: 9) and cynomologous monkey hepcidin (SEQ ID NO: 6). 13. The isolated monoclonal antibody of any one of claims 1, 2, 3, 4, 5, 6, 7, 8 or 9 that binds both human hepcidin (SEQ ID NO: 9) and murine hepcidin (SEQ ID NO: 80). 14. A composition comprising the antibody of any one of claims 1, 2, 3, 4, 5, 6, 7, 8 or 9 and pharmaceutically acceptable carrier, diluent or excipient. 15. A vial or prefilled syringe comprising the composition of claim 14.
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