John Grant Tew

US Patent:

8003385, Aug 23, 2011

Filed:

Feb 17, 2010

Appl. No.:

12/707563

Inventors:

Selva Sukumar - Berkeley CA, US
Mohey Eldin M. El Shikh - Richmond VA, US
John G. Tew - Mechanicsville VA, US
Donald Drake, III - Orlando FL, US
Luis Mosquera - Oviedo FL, US
Conan Li - Los Altos CA, US
Anatoly M. Kachurin - Orlando FL, US
Russell Higbee - Orlando FL, US
Heather Fahlenkamp - Cleveland OK, US
Eric Mishkin - Winter Springs FL, US
William L. Warren - Orlando FL, US

Assignee:

Sanofi Pasteur Vax Design Corp. - Orlando FL

International Classification:

C12N 5/06
C12N 5/02

US Classification:

435326, 435375, 435377

Abstract:

The present invention incorporates germinal centers (GCs) into three-dimensional (3D) engineered tissue constructs (ETCs). In an embodiment, we have incorporated the GC in the design of an artificial immune system (AIS) to examine immune responses to vaccines and other compounds. Development of an in vitro GC adds functionality to an AIS, in that it enables generation of an in vitro human humoral response by human B lymphocytes that is accurate and reproducible, without using human subjects. The invention also permits evaluation of, for example, vaccines, allergens, and immunogens, and activation of human B cells specific for a given antigen, which can then be used to generate human antibodies. In an embodiment of the present invention the function of the in vitro GC is enhanced by placing FDCs and other immune cells in a 3D ETC; FDCs appear more effective over a longer time (antibody production is sustained for up to about 14 days.

US Patent:

8003387, Aug 23, 2011

Filed:

Dec 21, 2006

Appl. No.:

11/642938

Inventors:

Selva Sukumar - Berkeley CA, US
Mohey Eldin M. El Shikh - Richmond VA, US
John G. Tew - Mechanicsville VA, US
Donald Drake, III - Orlando FL, US
Luis Mosquera - Oviedo FL, US
Eric Mishkin - Winter Springs FL, US
Anatoly M. Kachurin - Orlando FL, US
Russell Higbee - Orlando FL, US
Conan Li - Los Altos CA, US
William L. Warren - Orlando FL, US
Heather Fahlenkamp - Cleveland OK, US

Assignee:

Sanofi Pasteur Vaxdesign Corp. - Orlando FL

International Classification:

C12N 5/08
C12N 5/00
C12N 5/02

US Classification:

435373, 435375, 435377

Abstract:

The present invention incorporates germinal centers (GCs) into three-dimensional (3D) engineered tissue constructs (ETCs). In an embodiment, we have incorporated the GC in the design of an artificial immune system (AIS) to examine immune responses to vaccines and other compounds. Development of an in vitro GC adds functionality to an AIS, in that it enables generation of an in vitro human humoral response by human B lymphocytes that is accurate and reproducible, without using human subjects. The invention also permits evaluation of, for example, vaccines, allergens, and immunogens, and activation of human B cells specific for a given antigen, which can then be used to generate human antibodies. In an embodiment of the present invention the function of the in vitro GC is enhanced by placing FDCs and other immune cells in a 3D ETC; FDCs appear more effective over a longer time (antibody production is sustained for up to about 14 days.

US Patent:

8071373, Dec 6, 2011

Filed:

Jun 15, 2006

Appl. No.:

11/453046

Inventors:

William L. Warren - Orlando FL, US
Donald Drake, III - Orlando FL, US
Janice Moser - Orlando FL, US
Inderpal Singh - Oviedo FL, US
Haifeng Song - Germantown MD, US
Eric Mishkin - Winter Springs FL, US
John G. Tew - Mechanicsville VA, US

Assignee:

Sanofi Pasteur Vaxdesign Corp. - Orlando FL
Virginia Commonwealth University - Richmond VA

International Classification:

C12N 5/00
C12N 5/08

US Classification:

435347, 4353722, 4353723, 435372

Abstract:

The present invention relates to methods for preparing an artificial immune system. The artificial immune system comprises a cell culture comprising T cells, B cells and antigen-primed dendritic cells. The artificial immune system of the present invention can be used for in vitro testing of vaccines, adjuvants, immunotherapy candidates, cosmetics, drugs, biologics and other chemicals.

US Patent:

8247226, Aug 21, 2012

Filed:

Jun 23, 2011

Appl. No.:

13/167115

Inventors:

Selva Sukumar - Berkeley CA, US
Mohey Eldin M. El Shikh - Richmond VA, US
John G. Tew - Mechanicsville VA, US
Donald Drake, III - Orlando FL, US
Luis Mosquera - Oviedo FL, US
Conan Li - Los Altos CA, US
Anatoly M. Kachurin - Orlando FL, US
Russell Higbee - Orlando FL, US
Heather Fahlenkamp - Cleveland OK, US
Eric Mishkin - Winter Springs FL, US
William L. Warren - Orlando FL, US

Assignee:

Sanofi Pasteur Vaxdesign Corp. - Orlando FL

International Classification:

C12N 5/00
C12N 5/02

US Classification:

435375, 435382, 435404

Abstract:

The present invention incorporates germinal centers (GCs) into three-dimensional (3D) engineered tissue constructs (ETCs). In an embodiment, we have incorporated the GC in the design of an artificial immune system (AIS) to examine immune responses to vaccines and other compounds. Development of an in vitro GC adds functionality to an AIS, in that it enables generation of an in vitro human humoral response by human B lymphocytes that is accurate and reproducible, without using human subjects. The invention also permits evaluation of, for example, vaccines, allergens, and immunogens, and activation of human B cells specific for a given antigen, which can then be used to generate human antibodies. In an embodiment of the present invention the function of the in vitro GC is enhanced by placing FDCs and other immune cells in a 3D ETC; FDCs appear more effective over a longer time (antibody production is sustained for up to about 14 days.

US Patent:

20060275270, Dec 7, 2006

Filed:

Mar 15, 2006

Appl. No.:

11/375128

Inventors:

William Warren - Orlando FL, US
Russell Higbee - Orlando FL, US
Heather Fahlenkamp - Broken Arrow OK, US
Donald Drake - Orlando FL, US
John Tew - Mechanicsville VA, US

International Classification:

A61K 35/14
A61K 39/00
C12N 5/08
A61K 9/14

US Classification:

424093700, 424184100, 435366000, 435372000, 424486000

Abstract:

The present invention relates to methods of constructing an integrated artificial immune system that comprises appropriate in vitro cellular and tissue constructs or their equivalents to mimic the normal tissues that interact with pathogens and vaccines in mammals. The artificial immune system can be used to test the efficacy of vaccine candidates in vitro and thus, is useful to accelerate vaccine development and testing drug and chemical interactions with the immune system.

US Patent:

20080008653, Jan 10, 2008

Filed:

Jun 27, 2007

Appl. No.:

11/819335

Inventors:

John Tew - Mechanicsville VA, US
Mohey Eldin El Shikh - Richmond VA, US
Inderpal Singh - Orlando FL, US
Eric Mishkin - Winter Springs FL, US
Donald Drake - Orlando FL, US
Haifeng Song - Ellicott City MD, US
William Warren - Orlando FL, US

International Classification:

A61K 39/00
A01K 67/00
A61K 49/00
A61P 43/00
C12N 5/06

US Classification:

424009200, 424184100, 424093700, 435326000, 435375000, 800009000

Abstract:

The present invention is directed to methods for constructing and using in vivo and in vitro models of aspects of human immunity and, in particular, construction of a human immune system model for the testing of, for example, vaccines, adjuvants, immunotherapy candidates, cosmetics, drugs, biologics and other chemicals. The present invention comprises both in vivo and in vitro models of aspects of human immunity that are useful for assessing the interaction of substances with the immune system, and thus can be used to accelerate and improve the accuracy and predictability of, for example, vaccine, drug, biologic, immunotherapy, cosmetic and chemical development. The invention is also useful for the generation of human monoclonal and polyclonal antibodies.

US Patent:

20090104221, Apr 23, 2009

Filed:

Jul 3, 2008

Appl. No.:

12/167689

Inventors:

Mohey Eldin Moustafa El Shikh - Richmond VA, US
Rania El Sayed - Richmond VA, US
Andras K. Szakal - Midlothian VA, US
John G. Tew - Mechanicsville VA, US
Vaughan Wittman - Oviedo FL, US
Jennifer Eatrides - Orlando FL, US
William L. Warren - Orlando FL, US

International Classification:

A61K 39/00
C12Q 1/02
C12P 21/00

US Classification:

4241931, 435 29, 435 704

Abstract:

The present invention comprises the use of follicular dendritic cells (FDCs) or FDC-like cells to generate FDC-dependent, but T cell-independent, B cell responses to T cell-dependent antigens, with antigen-specific and polyclonal antibody production in 48 h. In another embodiment, a germinal center (GC) lymphoid tissue equivalent (LTE) was used to generate antigen-specific IgM, followed by switching to IgG. The GC LTE model can be used in vaccine assessment. Dual forms of immunogen were used in the GC LTE and in vivo. Dual immunogens resulted in rapid, specific IgM responses and enhanced IgG responses. This vaccine design approach can be used, for example, to provide rapid IgM protection (24-48 h) and high-affinity IgG more quickly in people moving to areas with endemic disease, or in people with T cell insufficiencies, who can be immunized to rapidly generate protective IgM.

US Patent:

20100287630, Nov 11, 2010

Filed:

Mar 17, 2010

Appl. No.:

12/726054

Inventors:

John G. TEW - Mechanicsville VA, US
Mohey Eldin M. EL SHIKH - Richmond VA, US
Inderpal SINGH - Oviedo FL, US
Eric MISHKIN - Winter Springs FL, US
Donald DRAKE, III - Orlando FL, US
Haifeng SONG - Ellicott City MD, US
William L. WARREN - Orlando FL, US

Assignee:

VAXDESIGN CORP. - Orlando FL

International Classification:

A01K 67/00
C07K 16/00
C12P 21/08
A61K 39/00
A61K 39/395
A61P 37/00

US Classification:

800 9, 5303871, 435 711, 4241841, 4242771, 4241301

Abstract:

The present invention is directed to methods for constructing and using in vivo and in vitro models of aspects of human immunity and, in particular, construction of a human immune system model for the testing of, for example, vaccines, adjuvants, immunotherapy candidates, cosmetics, drugs, biologics and other chemicals. The present invention comprises both in vivo and in vitro models of aspects of human immunity that are useful for assessing the interaction of substances with the immune system, and thus can be used to accelerate and improve the accuracy and predictability of, for example, vaccine, drug, biologic, immunotherapy, cosmetic and chemical development. The invention is also useful for the generation of human monoclonal and polyclonal antibodies.