Lonza Walkersville, Inc.

Pluristem Ltd.

Octane Biotech Inc.

Lonza Cologne Gmbh

Lonza Inc.

Massachusetts Institute of Technology

The Brigham and Women's Hospital, Inc.

Eytan Abraham

Yaling Shi

Timothy Smith

Nuala Trainor

Erika McAfee

Kelly Purpura

Joseph O'Connor

Samatha Bandapalle

Timo Gleissner

Ann Siehoff

Harel Kasuto

Yonatan Levinson

Colin Mark Jaques

Matthew Hewitt

Carrie Mason

Thaddaeus Webster

Nicholas Uth

Ruth Christine Rowland-Jones

Seshu Tummala

Brian Hadley

Pankaj Sinha

Joseph O'connor

Yi Zhang

Natalie Artzi

Rachel Ofir

Zami Aberman

Lior Raviv

Robert J Young

Chase McRobie

Thomas Payne

Kui Wang

Nicholas Ostrout

Inbar Friedrich Ben Nun

Ayelet Chajut

Nadav Eshkol

Maya Wadamany

The monitoring and control of bioprocesses is provided. The present disclosure provides the ability to generate generic calibration models, independent of cell line, using inline Raman probes to monitor changes in glucose, lactate, glutamate, ammonium, viable cell concentration (VCC), total cell concentration (TCC) and product concentration. Calibration models were developed from cell culture using two different CHOK1SV GS-KO™ cell lines producing different monoclonal antibodies (mAbs). Developed predictive models, qualified using an independent CHOK1SV GS-KO™ cell line not used in calibration, measured changes in glucose, lactate, ammonium, VCC, and TCC with minor prediction errors over the course of cell culture with minimal cell line dependence. The development of these generic models allows the application of spectroscopic PAT techniques in a clinical manufacturing environment, where processes are typically run once or twice in GMP manufacturing based on a common platform process.

Automated control of cell culture using Raman spectroscopy

The present disclosure provides cell culture chambers for use in automated cell engineering systems, and in particular, cell culture chambers that include improved cell-contacting surfaces. Improved cell-contacting surfaces can include a surface coating that promotes cell growth, adherence, differentiation, maintenance of phenotype, and/or improves transduction; a cell-contacting surface comprising a non-porous, gas-permeable material; as well as other modifications to the cell-contacting surfaces. Cassettes comprising the cell culture chambers are also provided.

Cell culture chamber with improved cell-contacting surfaces

The present disclosure provides methods for assessing and optimizing cellular quality of a cell-based therapy that is being produced in an automated cell engineering system. The methods suitably include monitoring molecular characteristics of the cells before, during, and after the automated process to provide feedback to the process parameters. In embodiments, the cells being produced are Chimeric Antigen Receptor (CAR) T-cells.

Quality control methods for automated cell processing

The present disclosure provides an automated method of producing genetically modified immune cells, including chimeric antigen receptor T (CAR T) cells, utilizing a fully-enclosed cell engineering system.

End-to-end cell therapy automation

The present disclosure provides cassettes for use in automated cell engineering systems that include cell concentration filters for reducing fluid volume of a cell sample during or following automated processing. The disclosure also provides methods of concentrating a cell population, as well as automated cell engineering systems that can utilize the cassettes and carry out the methods.

Cell concentration methods and devices for use in automated bioreactors

The current disclosure provides methods for reprogramming mammalian somatic cells by regulating the expression of endogenous cellular genes. Cellular reprogramming of somatic cells can be induced by activating the transcription of embryonic stem cell-associated genes (e.g., oct3/4) and suppressing the transcription of somatic cell-specific and/or cell death-associated genes. The endogenous transcription machinery can be modulated using synthetic transcription factors (activators and suppressors), to allow for faster, and more efficient nuclear reprogramming under conditions amenable for clinical and commercial applications. The current disclosure further provides cells obtained from such methods, along with therapeutic methods for using such cells for the treatment of diseases amendable to stem cell therapy, as well as kits for such uses.

Methods for nuclear reprogramming using synthetic transcription factors

The monitoring and control of bioprocesses is provided. The present disclosure provides the ability to generate generic calibration models, independent of cell line, using inline Raman probes to monitor changes in glucose, lactate, glutamate, ammonium, viable cell concentration (VCC), total cell concentration (TCC) and product concentration. Calibration models were developed from cell culture using two different CHOK1SV GS-KO&#x2122; cell lines producing different monoclonal antibodies (mAbs). Developed predictive models, qualified using an independent CHOK1SV GS-KO&#x2122; cell line not used in calibration, measured changes in glucose, lactate, ammonium, VCC, and TCC with minor prediction errors over the course of cell culture with minimal cell line dependence. The development of these generic models allows the application of spectroscopic PAT techniques in a clinical manufacturing environment, where processes are typically run once or twice in GMP manufacturing based on a common platform process.

Provided are methods of controlling disassociation of cells from a carrier, compositions, and methods of collecting cells. The methods of controlling disassociation of cells from a carrier may include contacting a polymeric carrier with one or more digesting agents to disassociate at least a portion of a plurality of cells from the polymeric carrier. The polymeric carrier may be crosslinked with a crosslinker including at least one of a redox sensitive moiety, a UV light sensitive moiety, a pH sensitive moiety, and a temperature sensitive moiety.

Polymeric carriers and methods

Disclosed herein are altered adherent stromal cells and methods of producing and utilizing same.

Altered adherent stromal cells and methods of producing and using same

Adherent stromal cells cultured under three dimensional conditions are provided, characterized, and distinguished from adherent stromal cells cultured under two dimensional conditions.

Gene and protein expression properties of adherent stromal cells cultured in 3D

Methods for treating or preventing preeclampsia or eclampsia by administering adherent stromal cells are described. The adherent stromal cells may be derived from bone marrow, placenta, or adipose tissue. Also described is the use of adherent stromal cells for the manufacture of a medicament, and an article of manufacture comprising a packaging material which comprises a label for use in treating or preventing preeclampsia or eclampsia.

Methods for prevention and treatment of preeclampsia

Carrier for cell culture

Growing community of inventors

Potomac, MD, United States of America

Eytan Abraham