Mutated fibroblast growth factor (FGF) 1 and methods of use

Abstract

The invention discloses a mutated fibroblast growth factor (FGF) 1 and methods of use. The present disclosure provides FGF1 mutant proteins, such as those having an N-terminal deletion, point mutation(s), or combinations thereof, which can reduce blood glucose in a mammal. Such mutant FGF1 proteins can be part of a chimeric protein that includes a [Beta]-Klotho-binding protein, an FGFRlc-binding protein, a [Beta]-Klotho-binding protein and a FGFRlc-binding protein, a C-terminal region from FGF 19 or FGF21. In some examples, 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. Methods of using the disclosed molecules to reduce blood glucose levels are also provided.

Description

[0001] Cross References to Related Applications

[0002] This application claims U.S. Provisional Application No. 61 / 893,766, filed October 21, 2013, U.S. Provisional Application No. 61 / 949,945, filed March 7, 2014, U.S. Provisional Application No. 61 / 949,945, filed April 4, 2014 Priority to Application No. 61 / 975,530, U.S. Provisional Application No. 62 / 019,185, filed June 30, 2014, U.S. Provisional Application No. 62 / 046,038, filed September 4, 2014, all of which Incorporated herein by reference.

[0003] Statement of Government Funding

[0004] This invention was made with government support under grant numbers DK057978, DK090962, HL088093, HL105278, and ES010337 awarded by the National Institutes of Health, National Human Genome Research Institute. The government has certain rights in this invention. technical field

[0005] The present application provides mutated FGF1 proteins, FGFR1c-binding protein multimers, nucleic acids encoding the proteins, and methods of their...

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