Pacific Biosciences of California, Inc.

Amgen Inc.

Lei Jia

Erik Miller

Satwik Kamtekar

Robin A Emig

Jeremiah Hanes

Walter H Lee

Keith P Bjornson

Fred C Christians

Arek Bibillo

Molly Min He

Pranav Patel

John Lyle

Insil Park

Stephen Wilson Turner

Jonas Korlach

Colleen Cutcliffe

Harold Ray Lee

Kevin Travers

Lubomir Sebo

Jon M Sorenson

Benjamin A Flusberg

Dale R Webster

Sonya Clark

Jessica Lee

Qingyian Liu

Liping H Pettus

Michael J Frohn

Jian Jeffrey Chen

Thomas T Nguyen

Nobuko Nishimura

Qiufen May Xue

Cheryl Heiner

Nuria A Tamayo

Jonathan Dante Low

Kexue Li

Tyson A Clark

Austin B Tomaney

Ana Elena Minatti

John Gordon Allen

Jeffrey Wegener

Paul S Peluso

Matthew Paul Bourbeau

Patrick Marks

Igor D Vilfan

Abhisek Banerjee

Joseph Puglisi

Andrey Kislyuk

Vu Van Ma

Andrei Fedorov

James A Brown

Mary Walton

Mark Chaisson

Christopher Silk

John M Lyle

Matthew Richard Kaller

James Alexander Brown

Compounds of formula (I): as defined herein, and synthetic intermediates thereof, which are capable of modulating KIF18A protein thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of KIF18A.

KIF18A inhibitors

Provided are compositions comprising recombinant DNA polymerases that include amino acid substitutions, insertions, deletions, and/or exogenous features that confer modified properties upon the polymerase for enhanced single molecule sequencing. Such properties can include enhanced metal ion coordination, reduced exonuclease activity, reduced reaction rates at one or more steps of the polymerase kinetic cycle, decreased branching fraction, altered cofactor selectivity, increased yield, increased thermostability, increased accuracy, increased speed, increased readlength, and the like. Also provided are nucleic acids which encode the polymerases with the aforementioned phenotypes, as well as methods of using such polymerases to make a DNA or to sequence a DNA template.

Recombinant polymerases for improved single molecule sequencing

Provided are compositions comprising recombinant DNA polymerases that include amino acid substitutions, insertions, deletions, and/or exogenous features that confer modified properties upon the polymerase for enhanced single molecule sequencing. Such properties include increased resistance to photodamage, and can also include enhanced metal ion coordination, reduced exonuclease activity, reduced reaction rates at one or more steps of the polymerase kinetic cycle, decreased branching fraction, altered cofactor selectivity, increased yield, increased thermostability, increased accuracy, increased speed, increased readlength, and the like. Also provided are nucleic acids which encode the polymerases with the aforementioned phenotypes, as well as methods of using such polymerases to make a DNA or to sequence a DNA template.

Recombinant polymerases with increased phototolerance

Methods, compositions, and systems are provided for characterization of modified nucleic acids. In certain preferred embodiments, single molecule sequencing methods are provided for identification of modified nucleotides within nucleic acid sequences. Modifications detectable by the methods provided herein include chemically modified bases, enzymatically modified bases, abasic sites, non-natural bases, secondary structures, and agents bound to a template nucleic acid.

Identification of nucleic acid template-linked barcodes comprising nucleic acid modifications

Methods, Compositions, and Systems are provided for nucleic acid sequencing where the sequential incorporation of nucleotides uses two distinct chemical steps. A plurality of nucleotide analogs, each having a labeled leaving group at its 3' hydroxyl can be sequentially added to a growing strand in the presence of a selective cleaving activity that cleaves the 3&#x2032; hydroxyl leaving group preferentially after it has been incorporated. The selective cleaving agent can comprise an exonuclease activity, and the exonuclease activity can be a polymerase-associated exonuclease activity. Nucleotide analogs having labels on both a cleavable polyphosphate portion and on a 3&#x2032; hydroxyl leaving group can provide signals characteristic of nucleotide analog incorporation. Systems having illumination optics, collection optics, and substrates observe signals from the labels as they are being incorporated into a growing nucleic acid strand, allowing for the sequencing of template nucleic acids.

Single molecule sequencing with two distinct chemistry steps

Methods for identifying nucleic acid modifications

Growing community of inventors

Newbury Park, CA, United States of America

Lei Jia