Description of Invention: Intraocular inflammatory disease (uveitis) is characterized by pain and a decrease in vision that can lead to blindness if not treated appropriately. The incidence and prevalence of the disease are approximately 52/100,000 and 112/100,000, and this translates into an incidence of 151,000 per year and a prevalence of 322,000. The numbers are expected to increase as the population ages. Treatment of severe uveitis often focuses on the control of the inflammatory symptoms using high dose corticosteroids, cytotoxic drugs or other immunosuppressive agents and there is a need for therapies that reduce the major side effects associated with the prolonged use of systemic steroids (e.g. hyperglycemia, osteoporosis and loss of immunocompetence).
Daclizumab is a humanized anti-Tac (HAT) antibody that specifically binds to the alpha subunit (CD25 or Tac subunit) of the human high affinity interleukin-2 (IL-2) receptor expressed on the surface of activated lymphocytes. Dr. Nussenblatt and colleagues at the NEI have previously shown that daclizumab can be used to successfully treat quiescent uveitis. Long term daclizumab therapy at a dose of 1mg/kg can be used instead of standard immunosuppressive agents to treat severe uveitis for more than 4 years with no adverse effects attributable to the medication, and subcutaneously administered daclizumab also appeared to be clinically effective. However, subjects with active uveitis were less likely under this regimen to have their disease controlled (J. Autoimmunity (2003) 21, 283-293).
The present invention targets patients with refractory, active uveitis and consists of a high dose intravenous induction therapy using daclizumab at two different doses and times followed by a longer term maintenance therapy. Positive therapeutic effects have been seen with this protocol in a small group of patients within 4-6 weeks after the initiation of therapy. As previous work indicated that IL-2R receptors have a slow turnover rate on CD4 positive subpopulation of lymphocytes, a possible mechanism of action of this new protocol is saturation of CD25 (TAC) receptors on cells in sequestered sites.
Available for licensing are methods directed to this treatment of active uveitis using a high dose pulsatile induction protocol of an interleukin-2 (Il-2) receptor antagonist. Methods are also provided for the treatment of corneal transplant rejection, limbal stem cell rejection following transplantation, optic neuritis and dry eye.
Inventors: Robert B Nussenblatt (NEI) Thomas A Waldmann (NCI) Ronald Buggage (NEI) Zhuqing Li (NEI)
Patent Status: HHS, Reference No. E-328-2004/0
Portfolios: Internal Medicine Internal Medicine - Therapeutics
For Additional Information Please Contact: Admin. Licensing Spec-GenMed NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325, Rockville, MD 20852 United States Email: rodrigr@mail.nih.gov Phone: 301-496-7057 Fax: 301-402-0220
Description of Invention:
Intraocular inflammatory disease (uveitis) is characterized by pain and a decrease in vision that can lead to blindness if not treated appropriately. The incidence and prevalence of the disease are approximately 52/100,000 and 112/100,000, and this translates into an incidence of 151,000 per year and a prevalence of 322,000. The numbers are expected to increase as the population ages. Treatment of severe uveitis often focuses on the control of the inflammatory symptoms using high dose corticosteroids, cytotoxic drugs or other immunosuppressive agents and there is a need for therapies that reduce the major side effects associated with the prolonged use of systemic steroids (e.g. hyperglycemia, osteoporosis and loss of immunocompetence).
Daclizumab is a humanized anti-Tac (HAT) antibody that specifically binds to the alpha subunit (CD25 or Tac subunit) of the human high affinity interleukin-2 (IL-2) receptor expressed on the surface of activated lymphocytes. Dr. Nussenblatt and colleagues at the NEI have previously shown that daclizumab can be used to successfully treat quiescent uveitis. Long term daclizumab therapy at a dose of 1mg/kg can be used instead of standard immunosuppressive agents to treat severe uveitis for more than 4 years with no adverse effects attributable to the medication, and subcutaneously administered daclizumab also appeared to be clinically effective. However, subjects with active uveitis were less likely under this regimen to have their disease controlled (J. Autoimmunity (2003) 21, 283-293).
The present invention targets patients with refractory, active uveitis and consists of a high dose intravenous induction therapy using daclizumab at two different doses and times followed by a longer term maintenance therapy. Positive therapeutic effects have been seen with this protocol in a small group of patients within 4-6 weeks after the initiation of therapy. As previous work indicated that IL-2R receptors have a slow turnover rate on CD4 positive subpopulation of lymphocytes, a possible mechanism of action of this new protocol is saturation of CD25 (TAC) receptors on cells in sequestered sites.
Available for licensing are methods directed to this treatment of active uveitis using a high dose pulsatile induction protocol of an interleukin-2 (Il-2) receptor antagonist. Methods are also provided for the treatment of corneal transplant rejection, limbal stem cell rejection following transplantation, optic neuritis and dry eye.
Inventors:
Robert B Nussenblatt (NEI)
Thomas A Waldmann (NCI)
Ronald Buggage (NEI)
Zhuqing Li (NEI)
Patent Status:
HHS, Reference No. E-328-2004/0
Portfolios:
Internal Medicine
Internal Medicine - Therapeutics
For Additional Information Please Contact:
Admin. Licensing Spec-GenMed
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: rodrigr@mail.nih.gov
Phone: 301-496-7057
Fax: 301-402-0220
Ref No: 1024
Updated: 06/2010