Harvard College

Wave Life Sciences Ltd.

Dana-farber-cancer Institute Inc.

Revolution Medicines, Inc.

Variagenics, Inc.

Other

Warp Drive Bio, Inc.

Ginkgo Bioworks, Inc.

Fog Pharmaceuticals, Inc.

Lifemine Therapeutics, Inc.

Sandoz Gmbh

Celgene Corporation

Sequenom, Inc.

Aileron Therapeutics, Inc.

Nuvelo, Inc.

Gregory Lawrence Verdine

Meena

Naoki Iwamoto

Vincent P Stanton, Jr

Brian Roger Bowman

Mathew Edward Sowa

Loren D Walensky

Stanley J Korsmeyer

Jia Liu Wolfe

Nenad Svrzikapa

Tomohiko Kawate

Christian E Schafmeister

Dylan Talbot Stiles

Sharon Ann Townson

Ivan Zlatev

Gerard Hilinski

Uddhav Kumar Shigdel

Jay Paul Morgenstern

David Charles Donnell Butler

Keith Earl Robison

John Hanney McGee

Neville J Anthony

David Butler

David M Armistead

Brian Yichiun Chow

David W White

Deborah Palestrant

Chris K Varma

Chandra Vargeese

Seung-Joo Lee

Young-Woo Kim

Christopher J Francis

James P Basilion

Federico Bernal

Ling X Shen

Daniel C Gray

M James Nichols

Joshua Alan Van Dyke Blodgett

Raymond E Moellering

Charles Allerson

Jeffrey Charles Olson

Bryce Alden Harrison

Susan Korsmeyer, Legal Representative

Tiffany Malinky Gierasch

Zhangjie Shi

Joshua A V Blodgett

Lucy Foulston

Vince P Stanton, Jr

Origene Nyanguile

Susovan Mohapatra

Paula Cristina Ortet

John Baxter Biggins

Anna Sokolovska

So Youn Shim

Tom N Grossmann

Tsung-Han Johannes Yeh

Matthew Reiser Patton

Maria Frank-Kamenetsky

Timothy David Cushing

Genliang Lu

James Bradner

Subramanian Marappan

Yoshihiko Norimine

Jason Jingxin Zhang

Ty Matthew Thomson

Sethumadhavan Divakaramenon

Michael Storek

Eileen Jeanne Kennedy

Hailin Yang

Stephan Bertel

Milan Chytil

Mary T Didiuk

Tiffany Malinky

Colin W Dykes

Li Deng

Meena Meena

Sebastian Christof Theodor Wahl

Raheleh Rezaei Araghi

Yue-Mei Zhang

Mark Joseph Mulvihill

Rebecca Yue Liang

Yvonne Alice Nagel

Minyun Zhou

Matthew James Nichols

Kazuhiro Hayashi

Lourdes Gude-Rodriguez

Yue Rebecca Yue Liang

Youbean Oak

Nicholas H Vrolijk

Yue Liang

David Charles Butler

John Hanney Mcgee

Frederico Bernal

Kasuhiro Hayashi

Joshua AV Blodgett

Johannes Tsung-Han Yeh

The present disclosure provides powerful technologies for the development, production, characterization, and/or use of stapled peptide compositions. Among other things, the present disclosure provides strategies for defining amino acid sequences particularly amenable or useful for stapling, as well as technologies, reagents, and systems for developing, producing, characterizing, and/or using stapled peptides having such amino acid sequences.

Collections of peptides, peptide agents, and methods of use thereof

The present invention provides stapled polypeptides of the Formulae (I) and (VI): and salts thereof; wherein the groups; R, R, R, R, R, R, R, R, R, R, R, L, L, L, L, X, v, w, p, m, s, n, t, and q are as defined herein. The present invention further provides methods of preparing the inventive stapled polypeptides from unstapled polypeptide precursors. The present invention further provides pharmaceutical compositions comprising a stapled polypeptide of Formula (I) or (VI), and methods of using the stapled peptides. The present invention also provides modifications of the staples post ring closing metathesis.

Stapled and stitched polypeptides and uses thereof

Among other things, the present disclosure provides technologies for efficient and effective identification of ETaGs, for example, from fungi genomes. In some embodiments, provided technologies are particularly useful for identifying mammalian targets of biosynthetic products of fungi. In some embodiments, provided technologies are particularly useful for identifying and/or prioritizing human targets for drug development. In some embodiments, provided technologies are particularly useful for developing modulators for human targets based on biosynthetic products of fungi.

Human therapeutic targets and modulators thereof

The present invention relates to chirally controlled oligonucleotides of select designs, chirally controlled oligonucleotide compositions, and methods of making and using the same. In some embodiments, a provided chirally controlled oligonucleotide composition provides different cleavage patterns of a nucleic acid polymer than a reference oligonucleotide composition. In some embodiments, a provided chirally controlled oligonucleotide composition provides single site cleavage within a complementary sequence of a nucleic acid polymer.

Chiral design

The invention features compounds (e.g., macrocyclic compounds) capable of modulating biological processes, for example through binding to a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein such as CEP250. These compounds bind endogenous intracellular presenter proteins, such as the FKBPs or cyclophilins, and the resulting binary complexes selectively bind and modulate the activity of the target protein. Formation of a tripartite complex among the presenter protein, the compound, and the target protein is driven by both protein-compound and protein-protein interactions, and both are required for modulation of target protein activity.

Compounds that participate in cooperative binding and uses thereof

Among other things, the present disclosure provides technologies for modulating functions of beta-catenin. In some embodiments, the present disclosure provides stapled peptides that interact with beta-catenin. In some embodiments, provided stapled peptides interact with beta-catenin at an Axin-binding site of beta-catenin. In some embodiments, the present disclosure provides compounds, compositions and methods for preventing and/or treating conditions, disorders and diseases that are associated with beta-catenin.

Agents modulating beta-catenin functions and methods thereof

The present invention relates to chirally controlled oligonucleotides, chirally controlled oligonucleotide compositions, and the method of making and using the same. The invention specifically encompasses the identification of the source of certain problems with prior methodologies for preparing chiral oligonucleotides, including problems that prohibit preparation of fully chirally controlled compositions, particularly compositions comprising a plurality of oligonucleotide types. In some embodiments, the present invention provides chirally controlled oligonucleotide compositions. In some embodiments, the present invention provides methods of making chirally controlled oligonucleotides and chirally controlled oligonucleotide compositions.

Chiral control

Disclosed herein are methods for identifying novel drug candidates.

Identifying new therapeutic agents

The present disclosure provides proteins, nucleic acids, vectors, and host molecules useful for the production of compounds of interest, and methods for their use.

Compositions and methods for the production of compounds

The present disclosure provides nucleic acids encoding a Large ATP-binding regulator of the LuxR family (LAL) of transcription factors, vectors and host cells including such nucleic acids, and methods for producing compounds (e.g., polyketides or &#x3b2;-lactam compounds) with such nucleic acids, vectors, and/or host cells.

The present invention provides peptides comprising a sequence of X-X-X-X-X-X-XPXXPXXPGXXAXXXXLXXXXXXLXXYLXXXX(SEQ ID NO: 13) wherein the amino acids X, X, X, X, X, X, X, X, X, X, X, X, X, X, X, X, X, X, X, X, X, X, X, X, X, X, X, and Xare as defined herein. The present invention further provides pharmaceutical compositions comprising the peptides and methods of using the peptides for treating proliferative diseases such as cancer which are associated with Ras. Also provided are methods of screening a library of peptide dimers using a peptide dimer display technology.

Ras inhibitory peptides and uses thereof

The invention features compounds (e.g., macrocyclic compounds) capable of modulating biological processes, for ex ample through binding to a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein such as CEP250. These compounds bind endogenous intracellular presenter proteins, such as the FKBPs or cyclophilins, and the resulting binary complexes selectively bind and modulate the activity of the target protein. Formation of a tripartite complex among the presenter protein, the compound, and the target protein is driven by both protein-compound and protein-protein interactions, and both are required for modulation of target protein activity.

Growing community of inventors

Boston, MA, United States of America

Gregory Lawrence Verdine