Patrick Allan Rabjohn

US Patent:

20030202980, Oct 30, 2003

Filed:

Mar 18, 2002

Appl. No.:

10/100303

Inventors:

Michael Caplan - Woodbridge CT, US
Howard Sosin - Fairfield CT, US
Hugh Sampson - Larchmont NY, US
Gary Bannon - Wentzville MO, US
A. Burks - Little Rock AR, US
Gael Cockrell - Cabot AR, US
Cesar Compadre - Little Rock AR, US
Cathie Connaughton - Conway AR, US
Ricki Helm - Little Rock AR, US
Nina King - Mason OH, US
Randall Kopper - Conway AR, US
Soheila Maleki - New Orleans LA, US
Patrick Rabjohn - Little Rock AR, US
David Shin - San Diego CA, US
J. Stanley - North Little Rock AR, US

International Classification:

A61K039/00
C07H021/04
C12P021/02
C12N005/06
C07K014/415
C07K014/47

US Classification:

424/185100, 435/069100, 435/320100, 435/325000, 530/350000, 530/370000, 536/023500, 536/023600

Abstract:

It has been determined that allergens, which are characterized by both humoral (IgE) and cellular (T-cell) binding sites, can be modified to be less allergenic by modifying the IgE binding sites. The IgE binding sites can be converted to non-IgE binding sites by altering as little as a single amino acid within the protein, preferably a hydrophobic residue towards the center of the IgE epitope, to eliminate IgE binding. Additionally or alternatively a modified allergen with reduced IgE binding may be prepared by disrupting one or more of the disulfide bonds that are present in the natural allergen. The disulfide bonds may be disrupted chemically, e.g., by reduction and alkylation or by mutating one or more cysteine residues present in the primary amino acid sequence of the natural allergen. In certain embodiments, modified allergens are prepared by both altering one or more linear IgE eitopes and disrupting one or more disulfide bonds of the natural allergen. In certain embodiments, the methods of the present invention allow allergens to be modified while retaining the ability of the protein to activate T-cells, and, in some embodiments by not significantly altering or decreasing IgG binding capacity. The Examples provided herein use peanut allergens to illustrate applications of the invention.

US Patent:

20120283421, Nov 8, 2012

Filed:

Jul 15, 2011

Appl. No.:

13/183892

Inventors:

Michael J. Caplan - Woodbridge CT, US
Howard B. Sosin - Fairfield CT, US
Hugh A. Sampson - Greenwich CT, US
Gary A. Bannon - Wentzville MO, US
Gael Cockrell - Cabot AR, US
Cesar M. Compadre - Little Rock AR, US
Cathie Connaughton - Conway AR, US
Ricki M. Helm - Little Rock AR, US
Nina E. King - Mason OH, US
Randall A. Kopper - Conway AR, US
Soheila J. Maleki - New Orleans LA, US
Patrick A. Rabjohn - Little Rock AR, US
David S. Shin - San Diego CA, US
J. Steven Stanley - North Little Rock AR, US

International Classification:

C07K 14/00

US Classification:

530403, 530350

Abstract:

It has been determined that allergens, which are characterized by both humoral (IgE) and cellular (T-cell) binding sites, can be modified to be less allergenic by modifying the IgE binding sites. The IgE binding sites can be converted to non-IgE binding sites by altering as little as a single amino acid within the protein, preferably a hydrophobic residue towards the center of the IgE epitope, to eliminate IgE binding. Additionally or alternatively a modified allergen with reduced IgE binding may be prepared by disrupting one or more of the disulfide bonds that are present in the natural allergen. The disulfide bonds may be disrupted chemically, e.g., by reduction and alkylation or by mutating one or more cysteine residues present in the primary amino acid sequence of the natural allergen. In certain embodiments, modified allergens are prepared by both altering one or more linear IgE epitopes and disrupting one or more disulfide bonds of the natural allergen. In certain embodiments, the methods of the present invention allow allergens to be modified while retaining the ability of the protein to activate T-cells, and, in some embodiments by not significantly altering or decreasing IgG binding capacity. The Examples provided herein use peanut allergens to illustrate applications of the invention.

US Patent:

7485708, Feb 3, 2009

Filed:

Aug 26, 2002

Appl. No.:

10/228806

Inventors:

Gary A. Bannon - Wentzville MO, US
Hugh A. Sampson - Larchmont NY, US
Ricki M. Helm - Little Rock AR, US
J. Steven Stanley - North Little Rock AR, US
Patrick A. Rabjohn - Little Rock AR, US

Assignee:

University of Arkansas - Little Rock AR

International Classification:

C07H 21/04

US Classification:

536 231, 435325, 530370, 530806, 530868

Abstract:

It has been determined that allergens, which are characterized by both humoral (IgE) and cellular (T cell) binding sites, can be modified to be less allergenic by modifying the IgE binding sites. The IgE binding sites can be converted to non-IgE binding sites by masking the site with a compound that prevents IgE binding or by altering as little as a single amino acid within the protein, most typically a hydrophobic residue towards the center of the IgE binding epitope, to eliminate IgE binding. The method allows the protein to be altered as minimally as possible, other than within the IgE-binding sites, while retaining the ability of the protein to activate T cells, and, in some embodiments by not significantly altering or decreasing IgG binding capacity. The examples use peanut allergens to demonstrate alteration of IgE binding sites. The critical amino acids within each of the IgE binding epitopes of the peanut protein that are important to immunoglobulin binding have been determined.