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Title:
ANTI-GHRELIN FAB ANTIBODIES
Document Type and Number:
WIPO Patent Application WO2005016951
Kind Code:
A3
Abstract:
Monoclonal antibodies, including humanized antibodies, which preferentially bind acetylated human ghrelin with respect to unacylated human ghrelin are disclosed. These antibodies have high affinity for acylated human ghrelin, a slow off rate for acylated human ghrelin dissociation and neutralize an acylated human ghrelin activity. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antigen-binding portions, of the invention are useful for neutralizing ghrelin activity, e.g., in a human subject suffering from a disorder in which ghrelin activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant anti-ghrelin antibodies are also encompassed by the invention.

Inventors:
HEIMAN MARK LOUIS (US)
KIKLY KRISTINE KAY (US)
MANETTA JOSEPH VINCENT (US)
WITCHER DERRICK RYAN (US)
Application Number:
PCT/US2004/014537
Publication Date:
May 26, 2005
Filing Date:
May 28, 2004
Export Citation:
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Assignee:
LILLY CO ELI (US)
HEIMAN MARK LOUIS (US)
KIKLY KRISTINE KAY (US)
MANETTA JOSEPH VINCENT (US)
WITCHER DERRICK RYAN (US)
International Classes:
C07K16/26; (IPC1-7): A61K39/395; A61P3/06
Foreign References:
EP1197496A12002-04-17
Other References:
HOSODA H ET AL: "STRUCTURAL DIVERGENCE OF HUMAN GHRELIN IDENTIFICATION OF MULTIPLE GHRELIN-DERIVED MOLECULES PRODUCED BY POST-TRANSLATIONAL PROCESSING", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY OF BIOLOGICAL CHEMISTS, BALTIMORE, MD, US, vol. 278, no. 1, 3 January 2003 (2003-01-03), pages 64 - 70, XP001205462, ISSN: 0021-9258
MURAKAMI N ET AL: "Role for central ghrelin in food intake and secretion profile of stomach ghrelin in rats", JOURNAL OF ENDOCRINOLOGY, BRISTOL, GB, vol. 174, no. 2, August 2002 (2002-08-01), pages 283 - 288, XP009022559, ISSN: 0022-0795
DAVIES J ET AL: "Affinity improvement of single antibody VH domains: residues in all three hypervariable regions affect antigen binding", IMMUNOTECHNOLOGY, ELSEVIER SCIENCE PUBLISHERS BV, NL, vol. 2, no. 3, September 1996 (1996-09-01), pages 169 - 179, XP004070292, ISSN: 1380-2933
HOLT L J ET AL: "Domain antibodies: proteins for therapy", TRENDS IN BIOTECHNOLOGY, ELSEVIER PUBLICATIONS, CAMBRIDGE, GB, vol. 21, no. 11, November 2003 (2003-11-01), pages 484 - 490, XP004467495, ISSN: 0167-7799
See also references of EP 1633397A2
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