Bayer Healthcare LLC

Boehringer Ingelheim International Gmbh

Jens Holger Vogel

Konstantin Konstantinov

Huong My Nguyen

Jonathan Coffman

Raquel Orozco

Scott Godfrey

Paul Wu

Jeff Goby

Roberto Giovannini

Chi Shung Brian To

Carolina Lucia Bianco

Huong Nguyen

Konstatin B Konstantinov

Konstantin B Konstantinov

Peng Wu

Methods for continuously inactivating virus during manufacture of a biological product are provided. The methods include steps of (1) combining (a) a composition including a biological product, and (b) a composition including a virus-inactivation reagent, to obtain (c) a treatment composition having a predetermined property for inactivation of a virus, (2) confirming that the treatment composition exhibits the predetermined property, (3) transferring the treatment composition to a treatment vessel that includes an inlet, an outlet, and a static mixer, the transferring occurring at the inlet, (4) incubating the treatment composition in the treatment vessel at a predetermined temperature while the treatment composition flows at a predetermined rate and contacts the static mixer, and (5) collecting the treatment composition from the treatment vessel at the outlet, wherein steps (1) to (5) are carried out continuously. Apparatuses and systems including such a treatment vessel are also provided.

Methods, apparatuses, and systems for continuously inactivating a virus during manufacture of a biological product

The present invention is directed to a method for producing a biomolecule conjugate where the method is integrated into a single unit operation.

Method for activation and conjugation of biomolecules

The present invention relates to a process and apparatus for purifying a molecule of interest from a heterogeneous clarified fluid mixture. The apparatus of the invention generally comprises a continuous perfusion fermentation system, a continuous particle removal system integrated with the perfusion fermentation system; and a continuous purification system integrated with the particle removal system, which is maintained under sterile conditions. The process comprises filtering a heterogeneous clarified fluid mixture by continuous ultrafiltration at a specific flow rate below the transition point of the molecule of interest in the pressure-dependent region of the flux versus TMP curve, wherein the specific flow rate is maintained substantially constant throughout the continuous ultrafiltration.

Devices and methods for integrated continuous manufacturing of biological molecules

The invention provides methods for concentrating a macromolecule from a solution comprising the macromolecule and an organic polymer by first subjecting the solution to ultrafiltration to produce a first retentate solution, then adjusting the conductivity of the first retentate solution such that any protein precipitation induced by the organic polymer is essentially prevented to produce a second retentate solution, and then subjecting the second retentate solution to ultrafiltration. In a preferred embodiment, the conductivity is adjusted by diafiltration against water, suitable diluent or buffer. Preferably, the invention pertains to the concentration of solutions of native or recombinant proteins. The invention further pertains preferably to methods for the concentration of cell culture supernatant comprising a product protein and organic polymers of the PLURONIC family of nonionic block co-polymers, and more preferably comprising PLURONIC F-68 nonionic block co-polymer.

Process for concentration of macromolecules

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Richmond, CA, United States of America

Jens Holger Vogel