Jonathan A Powell

US Patent:

8551481, Oct 8, 2013

Filed:

Oct 22, 2009

Appl. No.:

12/578887

Inventors:

Drew M Pardoll - Brookeville MD, US
Ching-Tai Huang - Taipei, TW
Jonathan Powell - Baltimore MD, US
Charles Drake - Baltimore MD, US
Dario A Vignali - Germantown TN, US
Creg J Workman - Memphis TN, US

Assignee:

The Johns Hopkins University - Baltimore MD
St. Jude Children's Research Hospital, Inc. - Memphis TN

International Classification:

A61K 39/00
A61K 39/395
A61K 39/38
C12P 21/08

US Classification:

4241391, 4241411, 4241841, 5303881, 53038875

Abstract:

Regulatory T cells (Treg) limit autoimmunity but can also attenuate the magnitude of anti-pathogen and anti-tumor immunity. Understanding the mechanism of Treg function and therapeutic manipulation of Treg in vivo requires identification of Treg selective receptors. A comparative analysis of gene expression arrays from antigen specific CD4+ T cells differentiating to either an effector/memory or a regulatory phenotype revealed Treg selective expression of LAG-3 (CD223), a CD4-related molecule that binds MHC class II. LAG-3 expression on CD4+ T cells correlates with the cells' in vitro suppressor activity, and ectopic expression of LAG-3 on CD4 T cells confers suppressor activity on the T cells. Antibodies to LAG-3 inhibit suppression both in vitro and in vivo. LAG-3 marks regulatory T cell populations and contributes to their suppressor activity.

US Patent:

20060240024, Oct 26, 2006

Filed:

Mar 1, 2004

Appl. No.:

10/547371

Inventors:

Drew Pardoll - Brookeville MD, US
Ching-Tai Huang - Taipei, TW
Dario Vignali - Bartlett TN, US
Creg Workman - Memphis TN, US
Jonathan Powell - Baltimore MD, US
Charles Drake - Baltimore MD, US

Assignee:

The Johns Hopkins University - Baltimore MD
St Jude Children's Research Hospital Inc. - Memphis TN

International Classification:

A61K 39/395

US Classification:

424155100

Abstract:

Regulatory T cells (Treg) limit autoimmunity but can also attenuate the magnitude of anti-pathogen and anti-tumor immunity. Understanding the mechanism of Treg function and therapeutic manipulation of Treg in vivo requires identification of Treg selective receptors. A comparative analysis of gene expression arrays from antigen specific CD4+ T cells differentiating to either an effector/memory or a regulatory phenotype revealed Treg selective expression of LAG-3 (CD223), a CD4-related molecule that binds MHC class II. LAG-3 expression on CD4+ T cells correlates with the cells' in vitro suppressor activity, and ectopic expression of LAG-3 on CD4 T cells confers suppressor activity on the T cells. Antibodies to LAG-3 inhibit suppression both in vitro and in vivo. LAG-3 marks regulatory T cell populations and contributes to their suppressor activity.

US Patent:

20100040636, Feb 18, 2010

Filed:

Sep 11, 2006

Appl. No.:

11/991693

Inventors:

Hong Yu - Baltimore MD, US
Drew Pardoll - Brookeville MD, US
Xiaoya Pan - Baltimore MD, US
Charles George Drake - Baltimore MD, US
Jonathan D. Powell - Baltimore MD, US
Ching-Tai Huang - Taipei, TW

Assignee:

The Johns Hopkins University - Baltimore MD

International Classification:

A61K 39/395
A61K 35/12
A61K 38/16
C07K 16/00
A61P 31/00
C07H 21/00
A61P 35/00
C12N 15/63
A61P 37/06
A01K 67/027
C12Q 1/02

US Classification:

4241721, 424 9371, 424 9321, 514 12, 5303891, 5303873, 536 231, 536 245, 4353201, 536 2353, 800 18, 435 29

Abstract:

We demonstrate herein that neuritin controls the homeostasis of regulatory T cells in an antigen dependent manner. Based on this discovery, we describe herein the application of neuritin as a therapeutic agent to manipulate antigen specific regulatory T cells in various disease settings is described. Thus manipulation of Treg cells and DCs through neuritin can be used to enhance immunotherapy of autoimmune diseases, cancer and infectious diseases, as well as enhance lymphocyte engraftment in settings of donor lymphocyte infusion, bone marrow transplant, as well as other types of transplants, and adoptive transfer.

US Patent:

20110027295, Feb 3, 2011

Filed:

Sep 8, 2008

Appl. No.:

12/676741

Inventors:

Jonathan D Powell - Baltimore MD, US
Charles George Drake - Baltimore MD, US
Paul Zarek - McLean VA, US

Assignee:

THE JOHNS HOPKINS UNIVERSITY - Baltimore MD

International Classification:

A61K 39/395
A61K 39/00
A61P 37/04
A61P 37/06
A61P 35/00
A61P 31/00

US Classification:

4241741, 4241841, 4241301

Abstract:

Described are uses of A2a adenosine receptor antagonists and agonists to provide long term modulation of immune responses. A2a receptor antagonists in particular are provided to enhance immune responses by reducing T-cell mediated tolerance to antigenic stimuli and agonists are provided to enhance effectiveness of immunosuppressive agents. The application provides methods of treatment and prevention based on the long term effects of the compounds on T cell responses.

US Patent:

20110229498, Sep 22, 2011

Filed:

May 8, 2009

Appl. No.:

12/991654

Inventors:

Charles George Drake - Baltimore MD, US
Drew M. Pardoll - Brookeville MD, US
Jonathan Davie Powell - Baltimore MD, US
Derese Getnet - Baltimore MD, US
Edward Luther Hipkiss - Mechanicsburg PA, US
Joseph Frank Grosso - Pennington NJ, US

Assignee:

THE JOHNS HOPKINS UNIVERSITY - Baltimore MD

International Classification:

A61K 39/00
C12N 5/02
C07H 21/04
C12N 15/63
C12Q 1/68
A61P 37/00

US Classification:

4241841, 435375, 536 245, 4353201, 435 613

Abstract:

The invention generally features compositions and methods for modulating an immune response. In particular embodiments, such compositions and methods modulate regulatory T cell suppressive activity.

US Patent:

20130095114, Apr 18, 2013

Filed:

Nov 16, 2012

Appl. No.:

13/679485

Inventors:

The Johns Hopkins University - Baltimore MD, US
Jonathan Powell - Baltimore MD, US
Charles Drake - Baltimore MD, US
Dario A. Vignali - Germantown TN, US
Creg J. Workman - Memphis TN, US

Assignee:

ST. JUDE CHILDREN'S RESEARCH HOSPITAL INC. - Memphis TN
THE JOHNS HOPKINS UNIVERSITY - Baltimore MD

International Classification:

A61K 39/395

US Classification:

4241521, 4241721

Abstract:

Combinations of anti-cancer vaccines and inhibitory antibodies to CD223 overcome immune suppression in cancer patients. The vaccines may be isolated antigens, groups of antigens, or whole tumor cells. The inhibitory antibodies may be generated in an animal by injection of fragments of CD223. Antibodies may be monoclonal antibodies or single chain antibodies or humanized antibodies.

US Patent:

20190240327, Aug 8, 2019

Filed:

Nov 8, 2013

Appl. No.:

14/075566

Inventors:

- BALTIMORE MD, US
Drew M. Pardoll - Brookeville MD, US
Xiaoyu Pan - Cockeysville MD, US
Charles G. Drake - Baltimore MD, US
Jonathan D. Powell - Baltimore MD, US
Ching-Tai Huang - Taipei, TW
Joseph Barbi - East Amherst NY, US
Fan Pan - Baltimore MD, US

International Classification:

A61K 39/395
A61K 35/14
A61K 31/713
A61K 39/00

Abstract:

We demonstrate herein that neuritin controls the homeostasis of regulatory T cells in an antigen dependent manner. Based on this discovery, we describe herein the application of neuritin as a therapeutic agent to manipulate antigen specific regulatory T cells in various disease settings is described. Thus manipulation of Treg cells and DCs through neuritin can be used to enhance immunotherapy of autoimmune diseases, cancer and infectious diseases, as well as enhance lymphocyte engraftment in settings of donor lymphocyte infusion, bone marrow transplant, as well as other types of transplants, and adoptive transfer.

US Patent:

20190216757, Jul 18, 2019

Filed:

Jan 30, 2019

Appl. No.:

16/262476

Inventors:

- Baltimore MD, US
Jonathan POWELL - Baltimore MD, US

International Classification:

A61K 31/198
A61K 35/17
A61K 39/00
A61K 39/395
A61P 35/00

Abstract:

The disclosure provides methods of treating cancer in a subject or preventing a relapse or reducing the incidence of relapse of cancer in a subject in remission, comprising administering to the subject: (a) a therapeutically effective amount of an immunotherapeutic agent, e.g., an immune checkpoint blockade therapy, an adoptive cellular therapy, a marrow-infiltrating lymphocytes, an adenosine A2aR inhibitor, or an antibody; and (b) a compound having formula (1):and the pharmaceutically acceptable salts thereof, wherein R, R, R′, and X are as defined as set forth in the specification. Compounds having formula (I) are prodrugs that release glutamine analogs, e.g., 6-diazo-5-oxo-L-norleucine (DON).