[Federal Register: October 26, 2007 (Volume 72, Number 207)]
[Notices]
[Page 60865-60866]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr26oc07-79]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Public Teleconference Regarding Licensing and Collaborative
Research Opportunities for: Treatment of Autoimmune and Allergic
Disorders (NIAID)
AGENCY: National Institutes of Health, Public Health Service, HHS.
ACTION: Notice.
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Technology Summary
These technologies relate to compositions and methods useful in
treating autoimmune diseases generally, and Multiple Sclerosis
specifically.
Technology Description
Scientists at the NIH have discovered a method for the treatment or
prevention of autoimmune diseases, allergic or atopic disorders, and
graft rejections. This method selectively induces apoptosis of disease
causing T lymphocytes, while sparing the majority of T-cells. Cell
death is achieved by the cyclical administration of disease specific
antigens and IL-2.
Further, the NIH scientists have developed compositions and methods
for clinical assessment, diagnosis and treatment of Multiple Sclerosis
(MS). The compositions are molecules related to the human proteolipid
protein (PLP), and the 21.5 kDA fetal isoform of human myelin basic
protein (MBP), including nucleic acids and polypeptides. The
polypeptides can be used to assay T-cells for responsiveness to MBP and
PLP epitopes. They are further useful as therapeutic agents for
treating MS by inducing T-cell apoptosis. The inventors have
demonstrated that treatment with MP4, a protein chimera of MBP, and a
modified form of PLP, termed PLP4, prevented clinical symptoms of MS in
both rodent and non-human primates. They have also completed primate
toxicity tests demonstrating the compounds are non-toxic.
Novel application of these methods described in these technologies
include:
Infusion of autoimmune disease antigen peptides reduces the
severity of allergic diseases.
[[Page 60866]]
Pre-immunization prior to engraftment with foreign tissues prolongs
graft survival time.
With molecular identification of allergy-evoking antigens, it will
be possible to immunize in cycle with IL-4 to induce apoptosis of T
cells involved in allergic disorders.
It is envisioned that autoimmune diseases such as multiple
sclerosis, rheumatic fever, lupus and others can be treated using IL-2
and the relevant peptide to cause apoptosis of the T cells responsible
for the disease.
The fact that interleukin-2 and 4 participates in the death of a
subpopulation of T lymphocytes cells capable of causing diseases while
leaving the majority of T lymphocyte cells substantially unaffected
enhances the therapeutic value of these inventions.
The use of a novel therapeutic agent, i.e., MP4, in the treatment
of MS.
Competitive Advantage of Our Technology
Autoimmune diseases result from a dysfunction of the immune system
in which the body attacks its own organs, tissues and cells. More than
80 clinically distinct autoimmune diseases have been identified,
including: type-1 diabetes (300,000-500,000 cases in the U.S.);
systemic lupus erythematosus (240,000 cases in the U.S.); multiple
sclerosis (250,000 to 350,000); rheumatoid arthritis (2.1 million cases
in the U.S.); inflammatory bowel diseases, including both Crohn's
disease and ulcerative colitis (800,000 in the U.S.); hemolytic anemia;
Graves' disease; scleroderma; psoriasis (2% to 4% of the U.S.
population); Sj[ouml]rgen's syndrome, Immune Thrombocytopenic Purpura
(ITP). Collectively, autoimmune diseases afflict 14-22 million
Americans or 5% to 8% of the United States population.
Treatment of autoimmune diseases generally involves suppressing the
immune system, and depending on the particular disease, different
treatments are used. To demonstrate the diversity among these
treatments consider the following: immunosuppressants such as
azathioprine, chlorambucil, cyclophosphamide, cyclosporine or
methostrexate are among the category of therapeutic agents employed in
treating some autoimmune diseases. Corticosteroids such as prednisone
are also used for both their immunosuppressive effect and anti-
inflammatory activities. Tumor Necrosis Factor Antagonists, such as
Etanercept and Infliximab are also used in treating some autoimmune
disorders. Finally, Platelet transfusion and Plasmapheresis are used to
treat a few autoimmune disorders.
MS is an autoimmune disease affecting the central nervous system,
characterized by disseminated patches of demyelination in the brain and
spinal cord, resulting in multiple and varied neurologic symptoms and
signs, usually with remissions and exacerbations. The currently
approved drugs for MS are different recombinant forms of interferons
and are primarily used for the treatment of RRMS. Antegren, which
blocks cellular adhesion, is currently in the pipeline and will be
useful in treating SPMS patients.
There is a current theoretical patient population of approx 368,000
patients with MS in the U.S. and approx. 450,000 in Western Europe.
Considering an estimated yearly growth rate of this market of 0.9%,
this number will increase to approximately 390,000 by 2010 and
approximately 400,000 by 2013 in the U.S. alone.
The total U.S. sales in 2003 for the top MS drugs, i.e., Rebif,
Avonex, Betaseron, and Copaxone, was about $1.7 billion. However,
within a six-month period, 6-10% of the patients have to discontinue
interferon therapy. These patients are likely to switch to new
therapies as they become available. Thus, this is the patient
population that will benefit from the compositions discovered at the
NIH, i.e., MP4 therapy.
Patent Estate
This technology consists of the following patents and patent
applications:
1. U.S. Patent No. 6,083,503, entitled ``Interleukin-2 stimulated T
lymphocyte cell death for the treatment of autoimmune diseases,
allergic responses, and graft rejection'' (E-137-1991/0-US-03);
2. U.S. Patent No. 5,989,546, entitled ``Interleukin-2 stimulated T
lymphocyte cell death for the treatment of allergic responses'' (E-137-
1991/0-US-04);
3. U.S. Patent No. 5,935,575, entitled ``Interleukin-4 stimulated T
lymphocyte cell death for the treatment of allergic disorders'' (E-151-
1992/0-US-11);
4. U.S. Patent Application No. 08/431,644 entitled ``Modified
Myelin Basic Protein Molecules'' (E-033-1996/0-US-01); and
5. U.S. Patent Application No. 08/482,114 entitled ``Modified
Proteolipid Protein Molecules'' (E-128-1996/1-US-01).
Next Step: Teleconference
There will be a teleconference where the principal investigator
will explain this technology. Licensing and collaborative research
opportunities will also be discussed. If you are interested in
participating in this teleconference please call or e-mail Mojdeh
Bahar; (301) 435-2950; baharm@mail.nih.gov. OTT will then e-mail you
the date, time and number for the teleconference.
Dated: October 22, 2007.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E7-21104 Filed 10-25-07; 8:45 am]
BILLING CODE 4140-01-P