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Methods of Inducing Immune Tolerance Using Immunotoxins

Description of Invention:
The invention concerns immunotoxins and methods of using the immunotoxins for the treatment of rejection response in a patient, including graft-versus-host disease and transplantation of organs, tissues and cells into a host. In a specific embodiment of the invention, the transplant involves pancreatic islet cells. The immunotoxins are targeted via an antibody that is specific to T cells. This allows the specific ablation of resting T cells, resulting in an accentuation of immune tolerizing responses and an increased tolerance to transplants and grafts. The toxin portion of the immunotoxin is genetically engineered to maintain bioactivity when recombinantly produced in Pichia pastoris. Data are available in transgenic animals expressing human CD3epsilon which supports the effects of the immunotoxin against T cells.

Applications:
  • Use of immunotoxins decreases T cell population, allowing greater host immune tolerance of transplants and grafts.
  • Specific method for increasing immune tolerance to pancreatic islet transplants.
Advantages:
  • Specificity of the immunotoxin avoids the killing of other cells, reducing side-effects associated with other mechanisms of treatment (X-ray and cyclophosphamide) such as infection and induced malignancy.
  • A GMP production process for the immunotoxin has already been successfully implemented.
Benefits:
New methods and compositions with limited side-effects have the potential to revolutionize treatment of transplant/graft recipients; provides an opportunity to capture a significant market share for the millions of people who require transplants/grafts.

Inventors:
David Neville et al. (NIMH)

Patent Status:
DHHS Reference No. E-012-1991/4 --
U.S. Patent No. 5,762,927 issued 09 Jun 1998

DHHS Reference No. E-012-1991/0 --
U.S. Patent No. 5,167,956 issued 01 Dec 1992

DHHS Reference No. E-012-1991/7 --
U.S. Patent No. 6,103,235 issued 15 Aug 2000
U.S. Patent No. 7,125,553 issued 24 Oct 2006

DHHS Reference No. E-059-1998/0 --
U.S. Patent Application No. 09/810,999 filed 16 Mar 2001, which published as US 2001/0024645 on 27 Sep 2001, Allowed

DHHS Reference E-168-1999/0 --
International Patent Application No. PCT/US00/10253 filed 14 Apr 2000, which published as WO 00/61132 on 19 Oct 2000

DHHS Reference No. E-044-1997/0 --
U.S. Patent No. 6,632,928 issued 14 Oct 2003
U.S. Patent Application No. 10/435,567 filed 09 May 2003, which published as 2003/0185825 on 02 Oct 2003

DHHS Reference No. E-044-1997/1 --
U.S. Patent Application No. 10/296,085 filed 18 Nov 2002, which published as 2004/0127682 on 01 Jul 2004

Foreign rights are also available.

Licensing Status:
Available for exclusive or non-exclusive licensing.

Collaborative Research Opportunity:
The National Institute of Mental Health, Laboratory of Molecular Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize methods of using the immunotoxins for the treatment of rejection response in a patient. Please contact David Neville at davidn@mail.nih.gov for more information.


Portfolios:
Internal Medicine
Cancer

Cancer -Therapeutics-Immunoconjugates
Internal Medicine-Therapeutics-Anti-Inflammatory (including Autoimmune)
Cancer -Therapeutics
Internal Medicine-Therapeutics

For Additional Information Please Contact:
David A. Lambertson Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-4632
Email: lambertsond@mail.nih.gov
Fax: (301) 402-0220


Web Ref: 1571

Updated: 6/07

 

 
 
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