Novartis Ag

Irm LLC

Shari Lynn Caplan

Brian R Boettcher

Stuart Licht

Norio Hamamatsu

Douglas S Daniels

Stephen Craig Weldon

Andreas Loew

Bernhard Hubert Geierstanger

Fangmin Xu

John A Taraszka

Regis Cebe

Susan E Cellitti

David Langdon Yowe

Guochun Li

John Taraszka

Brian Boettcher

Jun Yuan

Michael Kaleko

Sheila Connelly

Frederic Zecri

Philipp Grosche

Hongjuan Zhao

Katsumasa Nakajima

Changgang Lou

Urvi J Desai

Eric D Slosberg

Eric Peters

Bernhard Hubert Geierstranger

Susan E Litti

Berhard Hubert Geierstanger

The invention relates to the identification of fusion proteins comprising polypeptide and protein variants of fibroblast growth factor 21 (FGF21) with improved pharmaceutical properties. Also disclosed are methods for treating FGF21-associated disorders, including metabolic conditions.

Fibroblast growth factor-21-Fc fusion proteins

The present invention relates to monoclonal antibodies and antigen-binding fragments thereof that bind to human &#x3b2;-klotho, and pharmaceutical compositions and methods of treatment comprising the same.

Methods of treating FGF21-associated disorders

This invention provides messenger RNA (mRNA) molecules comprising an open reading frame that encodes a protein of interest, wherein said modified RNA comprises a modified nucleoside selected from the group consisting of: (I), (II), and (III), gene therapy vectors comprising same, methods of synthesizing same, and methods for gene replacement, gene therapy, gene transcription silencing, and the delivery of therapeutic proteins to tissue in vivo, comprising the molecules. The present invention also provides methods of reducing the immunogenicity of mRNA molecules. 

Chemically modified messenger RNA's

The invention relates to nucleic acids encoding fusion proteins comprising polypeptide and protein variants of fibroblast growth factor 21 (FGF21) with improved pharmaceutical properties. Also disclosed are vectors and host cells comprising the same and methods of producing the fusion proteins.

Nucleic acids encoding FGF21-Fc fusion proteins

The present invention relates to the identification of dual function fusion proteins comprising fibroblast growth factor 21 (FGF21) and Exenatide, Exendin-4, or GLP-1. Also disclosed are methods for treating metabolic, cardiovascular, and endocrine conditions related to glucose and/or lipid homeostasis.

Methods of treating metabolic disorders with dual function fibroblast growth factor 21 proteins

FGF21-FC fusion proteins for treating metabolic disorders

The present invention relates to dual function fusions proteins comprising fibroblast growth factor 21 (FGF21) and Exenatide, Exendin-4, or GLP-1. Also disclosed are methods for treating FGF21-associated disorders, GLP-1-associated disorders, and Exendin-4-associated disorders, including metabolic conditions.

Dual function fibroblast growth factor 21 proteins

The invention provides a bioconjugates comprising a synthetic polypeptide of Formula I' (SEQ ID NO: 1): or an amide, an ester or a salt thereof, wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12 and X13 are defined herein and a half-life extending moiety wherein the peptide and the half-life extending moiety are covalently linked or fuse, optionally via a linker. The polypeptides are agonist of the APJ receptor. The invention also relates to a method for manufacturing the bioconjugates of the invention, and its therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

Bioconjugates of synthetic apelin polypeptides

Methods of treating metabolic disorders with an FGF21 variant

The present invention provides novel polypeptide and protein variants of fibroblast growth factor 21 (FGF21) and pharmaceutical compositions comprising FGF21 polypeptide and protein variants.

Fibroblast growth factor 21 mutations

Disclosed are methods and compositions for treatment of diabetes, obesity and diabetic-related conditions. The methods include gene therapy based administration of a therapeutically effective amount of vectors encoding the following: glucokinase regulatory protein alone or co-administered with glucokinase or with metabolism modifying proteins; glucokinase co-administered with metabolism modifying proteins; or glucokinase regulatory protein co-administered with glucokinase in combination with metabolism modifying proteins, to a diabetic patient. Wherein the metabolism modifying proteins include UCP2, UCP3, PPAR&agr;, OB-Rb, GLP-1 and GLP-1 analogs (administered via vector or directly as a peptide). Preferred examples of GLP-1 analogs include GLP-1-Gly8, Extendin-4 and the &ldquo;Black Widow&rdquo; chimeric GLP-1 analog. Additionally, PPAR&agr; ligands and DPP-IV inhibitors may be co-administered with the above.

Methods and compositions for treatment of diabetes and related conditions via gene therapy

Growing community of inventors

Lunenburg, MA, United States of America

Shari Lynn Caplan