Sutro Biopharma, Inc.

Catalyst Biosciences, Inc.

Actym Therapeutics, Inc.

Vertex Pharmaceuticals, Inc.

Brown University

Halozyme, Inc.

Neurotrophincell Pty, Limited

Gc Biopharma Corp.

Christopher D Thanos

Edwin L Madison

Ryan Stafford

Kalyani Penta

Avinash Gill

Ramesh Baliga

Gang Yin

Laura Hix Glickman

Wenjin Yang

Justin Skoble

Leslie McEvoy

Sunil Bajad

Sonia Pollitt

Chris Murray

Alex Steiner

Alexandre Charles Michel Iannello

Erik Zimmerman

Edith Mathiowitz

Zhi Liu

Christopher James Murray

Alice Yam

Heather Stephenson

Junhao Yang

Grant Ellsworth Blouse

H Michael Shepard

Eric Steven Furfine

Jeffrey Charles Way

Mikhail Popkov

Vanessa Soros

Dan Groff

Matthew John Traylor

Patrick Rivers

Lin Wang

Kimberly Tipton

Megan Billings

John Mills

Alexandre Charles Iannello

Christopher J Murray

Aaron Sato

Sandra Waugh Ruggles

Xiaofan Li

George Harb

Robert Bartlett Elliott

Jack Nguyen

Chunhui Xie

Moses Sandrof

Divya Bhatnagar

Wendy L Webber

Moses Goddard

Danya M Lavin

Yang Qiu

Haixing Kehoe

Briannan E Bintz

Aleksander Szymaniak

Rebecca Chinn

Evrett Thompson

Bryce W Carey

Suyash Raj

Yang Qui

Livia Del Carmen Escobar Orellana

Stephen John Martin Skinner

Shaun Coughlin

Sandra Ruggles

Erik S Zimmerman

Provided herein are devices, systems, and methods for subcutaneous membrane, encapsulation chamber, or reservoir implantation comprising or employing an implantation device configured to insert a membrane, encapsulation chamber, or reservoir into a subject.

Implantation devices, system, and methods

Provided are delivery immunostimulatory bacteria that have enhanced colonization of tumors, the tumor microenvironment and/or tumor-resident immune cells, and enhanced anti-tumor activity. The immunostimulatory bacteria are modified by deletion of genes encoding the flagella, or by modification of the genes so that functional flagella are not produced, and/or are modified by deletion of pagP or modification of pagP to produce inactive PagP product. As a result, the immunostimulatory bacteria are flagellinand/or pagP. The immunostimulatory bacteria optionally have additional genomic modifications so that the bacteria are adenosine or purine auxotrophs. The bacteria optionally are one or more of asd, purI, and msbB. The immunostimulatory bacteria, such asspecies, are modified to encode immunostimulatory proteins that confer anti-tumor activity in the tumor microenvironment, and/or are modified so that the bacteria preferentially infect immune cells in the tumor microenvironment, or tumor-resident immune cells, and/or are modified to induce less cell death in immune cells than in other cells. Also provided are methods of inhibiting the growth or reducing the volume of a solid tumor by administering the immunostimulatory bacteria.

Engineered immunostimulatory bacterial strains and uses thereof

Provided are nucleic acid molecules, including vectors and plasmids, encoding modified u-PA polypeptides and fusion proteins containing the modified u-PA polypeptides. The u-PA polypeptides are modified to have altered activity and/or specificity so that they cleave a complement protein, such as complement protein C3, to thereby inhibit complement activation. The nucleic acids and encoded modified u-PA polypeptides and fusion proteins that inhibit complement activation can be used for treatment of diseases and conditions that are mediated by complement activation, or in which complement activation plays a role. These disorders include ischemic and reperfusion disorders, including myocardial infarction and stroke, sepsis, autoimmune diseases, diabetic retinopathies, age-related macular degeneration, transplanted organ rejection, inflammatory diseases and diseases with an inflammatory component.

Modified urokinase-type plasminogen activator polypeptides and methods of use

Provided herein are modified amino acids comprising an azido group, polypeptides, antibodies and conjugates comprising the modified amino acids, and methods of producing the polypeptides, antibodies and conjugates comprising the modified amino acids. The polypeptides, antibodies and conjugates are useful in methods of treatment and prevention, methods of detection and methods of diagnosis.

Modified amino acids

Provided herein are modified Fc proteins comprising non-natural amino acid residues at site-specific positions, conjugates of the modified Fc proteins for therapy or diagnosis, compositions comprising the modified Fc proteins and conjugates thereof, methods of their production and methods of their use. The modified Fc proteins and conjugates are useful for methods of treatment and prevention, methods of detection and methods of diagnosis.

Modified Fc proteins comprising site-specific non-natural amino acid residues, conjugates of the same, methods of their preparation and methods of their use

The present invention provides devices and methods for delivering a population of cells or a therapeutic agent to a subject in need thereof.

Devices and methods for delivering therapeutics

Provided are delivery immunostimulatory bacteria that have enhanced colonization of tumors, the tumor microenvironment and/or tumor-resident immune cells, and enhanced anti-tumor activity. The immunostimulatory bacteria are modified by deletion of genes encoding the flagella or by modification of the genes so that functional flagella are not produced, and/or are modified by deletion of pagP or modification of pagP to produce inactive PagP product. As a result, the immunostimulatory bacteria are flagellinand/or pagP. The immunostimulatory bacteria optionally have additional genomic modifications so that the bacteria are adenosine and/or purine auxotrophs. The bacteria optionally are one or more of asd, purIand msbB. The immunostimulatory bacteria, such asspecies, are modified to encode proteins that induce type I interferon (IFN) expression, or that are variants thereof that have increased activity to induce type I IFN expression, or that are variants thereof that result in constitutive expression of type I IFN. The bacteria can encode a modified Stimulator of Interferon Genes (STING) protein from a non-human species, that has lower NF-κB signaling activity, and, optionally, higher type I IFN pathway signaling activity, compared to human STING. The bacteria preferentially infect immune cells in the tumor microenvironment, or tumor-resident immune cells, and/or induce less cell death in immune cells than in other cells. Also provided are methods of inhibiting the growth or reducing the volume of a solid tumor by administering the immunostimulatory bacteria.

Immunostimulatory bacteria engineered to colonize tumors, tumor-resident immune cells, and the tumor microenvironment

Provided are immunostimulatory bacteria and oncolytic viruses, and pharmaceutical compositions containing the bacteria and/or viruses, that act as three prime repair exonuclease 1 (TREX1) antagonists. The bacteria and viruses are for treating tumors that are human papillomavirus (HPV) positive or that have a high tumor mutational burden (TMB). The immunostimulatory bacteria and oncolytic viruses encode therapeutic products such RNAi, such as shRNA and microRNA, that mediate gene disruption and/or inhibit expression of TREX1, or that inhibit TREX1. The bacteria contain additional modifications to enhance their anti-tumor activity. The bacteria and viruses are used for treatment of tumors in which TREX1 expression correlates with the presence of the tumor or properties of the tumor, such that inhibition of TREX1 advantageously treats the tumor.

Disclosed herein are compositions and methods related to differentiation of stem cells into pancreatic islet cells. In some aspects, the methods provided herein relate to generation of pancreatic β cell, α cell, δ cells, and EC cells in vitro. In some aspects, the disclosure provides pharmaceutical compositions including the cells generated according to the methods disclosed herein, as well as methods of treatment making use thereof.

Stem cell derived pancreatic islet differentiation

Provided herein are antibodies comprising non-natural amino acid residues at site-specific positions, compositions comprising the antibodies, methods of their production and methods of their use. The antibodies are useful for methods of treatment and prevention, methods of detection and methods of diagnosis.

Antibodies comprising site-specific non-natural amino acid residues, methods of their preparation and methods of their use

The present disclosure provides a cell housing device and a method of manufacturing such a device that has an array of channels to increase the ratio of surface area to volume.

Cell housing device

Provided are delivery immunostimulatory bacteria that have enhanced colonization of tumors, the tumor microenvironment and/or tumor-resident immune cells, and enhanced anti-tumor activity. The immunostimulatory bacteria are modified by deletion of genes encoding the flagella or modification of the genes so that functional flagella are not produced, and/or are modified by deletion of pagP or modification of pagP to produce inactive PagP product. As a result, the immunostimulatory bacteria are flagellinand/or pagP. The immunostimulatory bacteria optionally have additional genomic modifications so that the bacteria are adenosine or purine auxotrophs. The bacteria optionally are one or more of asd, purIand msbB. The immunostimulatory bacteria, such asspecies, are modified to encode immunostimulatory proteins that confer anti-tumor activity in the tumor microenvironment, and/or are modified so that the bacteria preferentially infect immune cells in the tumor microenvironment or tumor-resident immune cells and/or induce less cell death in immune cells than in other cells. Also provided are methods of inhibiting the growth or reducing the volume of a solid tumor by administering the immunostimulatory bacteria.

Provided are u-PA polypeptides and fusion proteins containing the u-PA polypeptides. The u-PA polypeptides are modified to have altered activity and/or specificity so that they cleave a complement protein, such as complement protein C3, to thereby inhibit complement activation. The modified u-PA polypeptides and fusion proteins that inhibit complement activation can be used for treatment of diseases and conditions that are mediated by complement activation, or in which complement activation plays a role. These disorders include ischemic and reperfusion disorders, including myocardial infarction and stroke, sepsis, autoimmune diseases, diabetic retinopathies, age-related macular degeneration, transplanted organ rejection, inflammatory diseases and diseases with an inflammatory component.

Growing community of inventors

Tiburon, CA, United States of America

Christopher D Thanos