Research Corporation Technologies, Inc.

The University of Chicago

University of Rochester

Novartis Ag

Novartis International Pharmaceutical, Ltd.

The State University of New York

Brookhaven Science Associates, Lcc

Shohei Koide

Akiko Koide

Shun-Ichi Tanaka

John J Dunn

Jin Huang

Benjamin J Luft

Catherine L Lawson

Andreas Loew

Brian Edward Vash

Stephen Dewhurst

Joseph Taft

John Bernard Wojcik

Ryan Nicholas Gilbreth

Julie Richards

Takamitsu Hattori

Michelle Miller

The current application describes various compositions and methods for the production of FN3-based binding proteins with improved stability properties. Aspects of the disclosure relate to polypeptides comprising a variant fibronectin type III (FN3) domain fromorcomprising one or more amino acid substitutions or insertions in a loop region of FN3, in a non-loop region of FN3, or in both.

Methods and composition involving thermophilic fibronectin type III (FN3) monobodies

Aspects of the disclosure relate to compositions of enzyme-binding polypeptides (EBPs) that modify the substrate specificity of an enzyme and a method for identifying an EBP that modifies substrate specificity of an enzyme binding at least one substrate, the method comprising: contacting the enzyme with a polypeptide library comprising a plurality of EBPs that bind different epitopes of the enzyme; identifying EBPs that bind to the enzyme to form an EBP-enzyme complex; assaying for the activity level and substrate specificity of the EBP-enzyme complex; and identifying EBPs that modify the substrate specificity of the enzyme by identifying EBPs that, when in an EBP-enzyme complex, have a different substrate specificity than un-complexed EBP; wherein the catalytic rate constant of the EBP-enzyme complex is &#x2265;50% of the un-complexed enzyme for at least one substrate and/or wherein the EBP-enzyme complex retains binding to a substrate.

Methods and composition for modifying enzymes

The present invention provides modified fibronectin type III (Fn3) molecules, and nucleic acid molecules encoding the modified Fn3 molecules. Also provided are methods of preparing these molecules, and kits to perform the methods.

Reconstituted polypeptides

Embodiments concern compositions and methods involving recombinant antibodies to histone post-translational modifications. The invention provides compositions and methods for histone methyltransferase assays. In certain embodiments, the compositions and methods involve a recombinant antibody that binds histone H3 fragment harboring biomarkers such as H3K9me3 mark, H3K4me3 mark, H3K36me3 mark, H3K27me3, H3K9me3 and H3S10phos or a recombinant antibody that binds histone H4 fragment harboring H4K20me3 mark.

Compositions and methods related to recombinant antibodies to histone posttranslational modifications

The invention provides a molecular affinity clamp. The architecture of the affinity clamp is modular with two biorecognition modules, each capable of binding a target motif. The first biorecognition module has a recognition domain that possesses inherent or natural specificity for the target motif. The second biorecognition module also has a recognition domain that binds the motif. The two biorecognition modules are tethered together either directly, e.g., via a peptide bond between the two modules, or indirectly, e.g., via a linker moiety or linker.

Molecular affinity clamp technology and uses thereof

The here described invention discloses a combination of a top and bottom loop binder library using the CD and the FG loops of a number of FnIII domains (FnIII) (e.g., FnIII, FnIIIand FnIII) together with the surface exposed residues of the beta-sheet. The invention also pertains to a method of forming a library of FnIII domain polypeptides useful in screening for the presence of one or more polypeptides having a selected binding or enzymatic activity.

Fibronectin cradle molecules and libraries thereof

A fibronectin type III (Fn3) polypeptide monobody, a nucleic acid molecule encoding said monobody, and a variegated nucleic acid library encoding said monobody, are provided by the invention. Also provided are methods of preparing a Fn3 polypeptide monobody, and kits to perform said methods. Further provided is a method of identifying the amino acid sequence of a polypeptide molecule capable of binding to a specific binding partner (SBP) so as to form a polypeptide:SSP complex, and a method of identifying the amino acid sequence of a polypeptide molecule capable of catalyzing a chemical reaction with a catalyzed rate constant, k, and an uncatalyzed rate constant, k, such that the ratio of k/kis greater than 10.

Artificial antibody polypeptides

Provided herein are OspA polypeptides from Lyme Disease-causinghaving certain alteration(s). In one embodiment, the alteration(s) increase the conformational stability of the OspA polypeptide containing the alteration(s) while maintaining at least some of the antigenicity of the corresponding unaltered OspA polypeptide. In another embodiment, the altered OspA polypeptide has reduced cross-reactivity to hLFA-1, as compared to the corresponding unaltered OspA polypeptide.

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The present invention provides a fibronectin type III (Fn3) molecule, wherein the Fn3 contains a stabilizing mutation. The present invention also provides Fn3 polypeptide monobodies, nucleic acid molecules encoding monobodies, and variegated nucleic acid libraries encoding such monobodies. Also provided are methods of preparing a Fn3 polypeptide monobody, and kits to perform the methods.

The invention provides a molecular affinity clamp. The architecture of the affinity clamp is modular with two biorecognition modules, each capable of binding a target motif. The first biorecognition module has a recognition domain that possesses inherent or natural specificity for the target motif. The second biorecognition module also has a recognition domain that binds the motif. The two biorecognition modules are tethered together either directly, e.g., via a peptide bond between the two modules, or indirectly, e.g., via a linker moiety or linker. The invention further provides a novel affinity ligand which is specifically bound by the molecular affinity clamps of the invention.

Growing community of inventors

Rochester, NY, United States of America

Shohei Koide