Title:
FIBROBLAST GROWTH FACTOR (FGF) 1 WITH MUTATION IN THE HEPARIN BINDING DOMAIN AND METHODS OF USE TO REDUCE BLOOD GLUCOSE
Document Type and Number:
WIPO Patent Application WO/2016/172153
Kind Code:
A3
Abstract:
The present disclosure provides FGF1 mutant proteins having one or more mutations in the heparin binding domain. Such mutants may also have an N-terminal deletion, point mutation(s), or combinations thereof. In some examples, the mutant FGF1 proteins have reduced mitogenic activity. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. The disclosed FGF1 mutants can reduce blood glucose in a mammal, and in some examples are used to treat a metabolic disorder.
Inventors:
EVANS RONALD M (US)
DOWNES MICHAEL (US)
ATKINS ANNETTE (US)
YU RUTH T (US)
BLABER MICHAEL (US)
XIA XUE (US)
DOWNES MICHAEL (US)
ATKINS ANNETTE (US)
YU RUTH T (US)
BLABER MICHAEL (US)
XIA XUE (US)
Application Number:
PCT/US2016/028365
Publication Date:
January 12, 2017
Filing Date:
April 20, 2016
Export Citation:
Assignee:
SALK INST FOR BIOLOGICAL STUDI (US)
FLORIDA STATE UNIV RES FOUND INCORPORATED (US)
FLORIDA STATE UNIV RES FOUND INCORPORATED (US)
International Classes:
A61K38/18; C07K14/50
Domestic Patent References:
| WO2013184962A1 | 2013-12-12 | |||
| WO2011130729A2 | 2011-10-20 | |||
| WO2010135491A2 | 2010-11-25 | |||
| WO2016089945A1 | 2016-06-09 |
Other References:
KLINGENBERG, O ET AL.: "Effects of Mutations of a Phosphorylation Site in an Exposed Loop in Acidic Fibroblast Growth Factor", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 274, no. 25, 1999, pages 18081 - 18086, XP002627206
SHIREMAN, P.K. ET AL.: "The S130K fibroblast growth factor- mutant induces heparin- independent proliferation and is resistant to thrombin degradation in fibrin glue", JOURNAL OF VASCULAR SURGERY, vol. 31, no. 2, 2000, pages 382 - 390, XP002350859
BREWSTER, L.P. ET AL.: "Heparin-independent mitogenicity in an endothelial and smooth muscle cell chimeric growth factor (S130K-HBGAM", THE AMERICAN JOURNAL OF SURGERY, vol. 188, 2004, pages 575 - 579, XP004641818
BREWSTER, L.P. ET AL.: "Improving endothelial healing with novel chimeric mitogens", THE AMERICAN JOURNAL OF SURGERY, vol. 192, 2006, pages 589 - 593, XP027911836
SHIREMAN, P.K. ET AL.: "The S130K fibroblast growth factor- mutant induces heparin- independent proliferation and is resistant to thrombin degradation in fibrin glue", JOURNAL OF VASCULAR SURGERY, vol. 31, no. 2, 2000, pages 382 - 390, XP002350859
BREWSTER, L.P. ET AL.: "Heparin-independent mitogenicity in an endothelial and smooth muscle cell chimeric growth factor (S130K-HBGAM", THE AMERICAN JOURNAL OF SURGERY, vol. 188, 2004, pages 575 - 579, XP004641818
BREWSTER, L.P. ET AL.: "Improving endothelial healing with novel chimeric mitogens", THE AMERICAN JOURNAL OF SURGERY, vol. 192, 2006, pages 589 - 593, XP027911836
Attorney, Agent or Firm:
RYBAK, Sheree, Lynn (US)
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