Eli Lilly and Company

The United States Government As Represented by the Department of Veterans Affairs

Indiana University

Radmila Micanovic

Christopher Carl Frye

Lihua Huang

Radhakrishnan Rathnachalam

David A Driver

Derrick Ryan Witcher

Craig Duane Dickinson

Wolfgang Glaesner

Ryan James Darling

Sheng-Hung Rainbow Tschang

Beth Ann Strifler

John Michael Beals

Gerald W Becker

John Edward Hale

Shun Li

Malgorzata Donata Gonciarz

Fredric Jay Cohen

Timothy Wayne Noblitt

Maigorzata Donata Gonciarz

Tarek Maurice Ashkar

Jing Shang

Patricia Ann Gonzalez-DeWhitt

Christy Michelle Newton

Victor John Wroblewski

Embodiments of the present disclosure provide polypeptides, related materials and compositions, and methods for their use. In certain embodiments, the present disclosure provides a monomeric Tamm-Horsfall Protein polypeptide, or a biologically active truncation thereof. Other embodiments provide polynucleotides encoding a polypeptide described herein, nucleic acid expression vectors including the polynucleotides, and recombinant host cells including the expression vector. Yet other embodiments provide pharmaceutical compositions including a polypeptide described herein. Also provided are methods for treating a renal disease, disorder, or condition in a subject and/or modulating an immune response in a subject.

Modified Tamm-Horsfall protein and related compositions and methods of use

This present invention relates to pharmacologically potent and/or stable variants of human fibroblast growth factor 21 (FGF21), pharmaceutical compositions comprising FGF21 variants, and methods for treating type 2 diabetes, obesity, dyslipidemia, or metabolic syndrome, or any combination thereof, using such variants.

Fibroblast growth factor 21 variants

Fibroblast growth factor 21 variants having improved pharmacological potency and/or improved pharmaceutical stability

The present invention relates to novel muteins of human fibroblast growth factor 21 with reduced deamidation compared to wild-type human FGF-21. Both protein and the respective encoding nucleic acid species are disclosed. The invention also embodies vectors and host cells for the propagation of said nucleic acid sequences and the production of said muteins. Also disclosed are methods for treating type 2 diabetes, obesity, or metabolic syndrome.

Muteins of fibroblast growth factor 21

The present invention relates to novel muteins of human fibroblast growth factor-21 with reduced susceptibility for proteolytic degradation when expressed in yeast. Both protein and the respective encoding nucleic acid species are disclosed. The invention also embodies vectors and host cells for the propagation of said nucleic acid sequences and the production of said muteins. Also disclosed are methods for treating type 2 diabetes, obesity, or metabolic syndrome.

The present invention relates to novel muteins of human fibroblast growth factor 21 with reduced capacity of O-glycosylation when expressed in yeast compared to wild-type human FGF-21. Both protein and the respective encoding nucleic acid species are disclosed. The invention also embodies vectors and host cells for the propagation of said nucleic acid sequences and the production of said muteins. Also disclosed are methods for treating type 2 diabetes, obesity, or metabolic syndrome.

The present invention relates to novel muteins of human fibroblast growth factor 21 with improved pharmaceutical properties. Both protein and the respective encoding nucleic acid species are disclosed. The invention also embodies vectors and host cells for the propagation of said nucleic acid sequences and the production of said muteins. Also disclosed are methods for treating type 2 diabetes, obesity, metabolic syndrome, and in reducing the mortality and morbidity of critically ill patients.

The present invention relates to glucagon-like-1 compounds fused to proteins that have the effect of extending the in vivo half-life of the peptides. These fusion proteins can be used to treat non-insulin dependent diabetes mellitus as well as a variety of other conditions.

GLP-1 fusion proteins

Disclosed are polypeptide analogs of FLINT, polydeoxynucleotides encoding FLINT analogs, and methods of using FLINT analogs and polydeoxynucleotides. The FLINT analogs of the invention include polypeptides having the amino acid sequence of FLINT, modified at one or more positions with amino acid substitutions, and include fragments thereof, as well as Fc fusions comprising FLINT and FLINT analogs.

Flint polypeptide analogs

The invention relates to FLINT analogs that are to proteolysis in vivo and in vitro at amino acid position 218 of mature FLINT, clinical and therapeutic uses thereof, and pharmaceutical formulations comprising said analogs.

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Indianapolis, IN, United States of America

Radmila Micanovic