Kbio Holdings Limited

Kentucky Bioprocessing, Inc.

Mor, Tsafrir

Greg Pogue

Steven D Hume

Barry Bratcher

Joshua D Morton

John W Shepherd

Leigh Burden

Hugh A Haydon

Carrie A Simpson

Nick Partain

Stefan Werner

Tsafrir Mor

Romy Kandzia

Frank Thieme

Michael H Pauly

Youngjun Oh

Ernie Hiatt

Kelsi Swope

Various embodiments disclosed herein include methods and exemplary compositions associated with conjugation of virus and proteins (e.g., antigen) to form vaccines for delivery of immunological and other therapeutic agents, exemplary aspects of which may include harvesting viral and antigenic substances from source organisms; purifying the viral and protein (e.g. antigenic, including influenza hemagglutinin antigens) substances through methodologies described in an exemplary manner, as well as their concentration and collection; and a conjugation platform providing activation of the virus at a pH that increases binding rate and binding propensity between the virus and the protein, wherein embodiments related to the conjugation platform include controlling the ratio of virus to protein.

Virus and antigen conjugation

Disclosed herein are methods of forming compounds and exemplary compounds in the nature of a conjugated compound demonstrating enhanced stability, which in some embodiments comprises a protein and virus particle mixed in a conjugation reaction to form a conjugate mixture, such that the conditions and steps of forming these products allow for unrefrigerated storage for longer time periods than previous approaches, thus making feasible access to such products over a global supply chain.

Virus and antigen purification and conjugation

Disclosed herein are methods of forming compounds and exemplary compounds in the nature of a conjugated compound, which in some embodiments comprises an antigen and virus particle mixed in a conjugation reaction to form a conjugate mixture, such that the conditions and steps of forming these products allow for use of the conjugate mixture as a vaccine, including but not limited to use as a vaccine against various pathogens including for treatment of diseases caused by novel coronaviruses (including SARS-COV 2).

Vaccines formed by virus and antigen conjugation

Disclosed herein are methods of forming compounds and exemplary stable compounds in the nature of a conjugated compound at refrigerated or room temperature, which in some embodiments comprises an antigen and virus particle mixed in a conjugation reaction to form a conjugate mixture, such that the conditions and steps of forming these products allow for use of the conjugate mixture as a vaccine, including but not limited to use as a vaccine against various pathogens including for treatment of diseases caused by novel coronaviruses (including SARS-COV 2).

Disclosed herein are methods and exemplary compositions associated with antigen purification, exemplary aspects of which may include harvesting viral and antigenic substances from source organisms; and a purification platform comprising chemical separation and size-difference separation for the removal of contaminants, debris and impurities from the viral and protein (e.g. antigenic, including influenza hemagglutinin antigens) substances, as well as their concentration and collection.

Antigen purification

Disclosed herein are methods and exemplary compositions associated with virus purification, antigen purification, and conjugation of virus and proteins (e.g., antigen) to form vaccines for delivery of immunological and other therapeutic agents, exemplary aspects of which may include harvesting viral and antigenic substances from source organisms; a purification platform comprising chemical separation and size-difference separation for the removal of contaminants, debris and impurities from the viral and protein (e.g. antigenic, including influenza hemagglutinin antigens) substances, as well as their concentration and collection; and a conjugation platform providing activation of the virus at a pH that increases binding rate and binding propensity between the virus and the protein, wherein embodiments related to the conjugation platform include controlling the ratio of virus to protein.

Disclosed herein are methods and exemplary compositions associated with virus purification, exemplary aspects of which may include harvesting viral and antigenic substances from source organisms; and a purification platform comprising chemical separation and size-difference separation for the removal of contaminants, debris and impurities from the viral and protein (e.g. antigenic, including influenza hemagglutinin antigens) substances, as well as their concentration and collection.

Virus purification

A new, reliable, easily scalable and reproducible method for the production of recombinant butyrylcholinesterase (rBuChE) is provided. Through the utilization of a plant transfection procedure, various plant strains have been shown to generate effective and scalable amounts of rBuChE under acceptable manufacturing processes to permit reliable levels of such enzymes for desired nerve agent protection requirements (including tetrameric products). As well, such methods in engineered plant lines have shown suitable production of these enzymes in tetramer form with glycan formation and sialylation (for terminal groups) to allow for optimal potency against organophosphorus agent exposure as well as proper immunogenic response within the plant sources. The overall production method, including the transfection and production within mammalian cells, as well as the process steps involved for such a reliable sourcing platform from plants is thus encompassed within the invention.

Plant-based recombinant butyrylcholinesterase production methods

A new, reliable, easily scalable and reproducible method for the production of recombinant butyrylcholinesterase (rBuChE) is provided. Through the utilization of a plant transfection procedure, various plant strains have been shown to generate effective and scalable amounts of rBuChE under acceptable manufacturing processes to permit reliable levels of such enzymes for desired nerve agent protection requirements (including tetrameric products). As well, such methods in engineered plant lines have shown suitable production of these enzymes in tetramer form with glycan formation and sialyalation (for terminal groups) to allow for optimal potency against organophosphorus agent exposure as well as proper immunogenic response within the plant sources. The overall production method, including the transfection and production within mammalian cells, as well as the process steps involved for such a reliable sourcing platform from plants is thus encompassed within the invention.

Growing community of inventors

Austin, TX, United States of America

Greg Pogue