[Federal Register Volume 65, Number 143 (Tuesday, July 25, 2000)]
[Notices]
[Pages 45780-45782]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-18724]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES (DHHS)

National Instututes of Health (NIH); National Institute on Drug 
Abuse (NIDA)


Licensing Opportunity and/or Cooperative Research and Development 
Agreement (``CRADA'') Opportunity: Novel Methods and Compositions for 
Diagnosing, Treating and Monitoring Psychiatric Disease

AGENCY: NIDA, NIH, DHHS.

ACTION:  Notice.

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SUMMARY: The National Institute on Drug Abuse (NIDA), Cellular 
Neurobiology Research Branch, is seeking Licensee(s) and/or proposals 
from potential collaborators for a Cooperative Research and Development 
Agreement (CRADA) to participate in the exploration of the clinical 
significance of recent studies in which NIDA has identified variations 
in the isoforms of neural cell adhesion molecule (N-CAM) associated 
with neuropsychiatric disorders. Elevations in certain isoforms are 
associated with specific neuropsychiatric disorders. These specific 
variations in the levels of N-CAM suggest that diagnostic techniques or 
therapeutic interventions could be based on the observed alterations in 
cell adhesion molescules. A provisional patent application relating to 
the N-CAM isoforms associated with neuropsychiatric disorders has been 
filed. Any successful CRADA collaborator may need to negotiate a 
license to the provisional patent application in order to commercialize 
developments under the CRADA. Contact information to apply for a 
license to the provisional patent application appears below.

DATES: Interested CRADA applicants should submit written notice of 
intent to apply within 45 days of the date of this notice. NIDA will 
consider all written proposals received within 60 days of the date of 
publication of this notice. CRADA proposals submitted thereafter may be 
considered if a suitable CRADA collaborator has not been found. There 
is no specific deadline for licensing applications.

ADDRESSES: Scientific questions about this notice may be addressed to 
Dr. Marquis Vawter, National Institute on Drug Abuse, 5500 Nathan Shock 
Drive, Baltimore, Maryland 21224, Tel. 410-550-1405; questions 
concerning the CRADA opportunity may be addressed to Dr. Malka Scher, 
Technology Development and Commercialization Branch, National Cancer 
Institute, 6120 Executive Boulevard, Suite 450, Rockville, Maryland 
20852, Tel: 301-496-0477, Fax: 301-402-2117, e-mail: 
[email protected]; and questions concerning the patent application 
should be addressed to Dr. Norbert Pontzer, Office of Technology 
Transfer, National Institutes of Health, 6011 Executive Boulevard, 
Suite 325, Rockville, Maryland 20852-3804, Tel: 301-496-7057 (ext. 
284), Fax: 301-402-0220, e-mail: [email protected].

SUPPLEMENTARY INFORMATION: Respondees interested in licensing the 
invention will be required to submit an Application for License to 
Public Health Service Inventions. Inventions described in the patent 
application are available for either exclusive or non-exclusive 
licensing in accordance with 35 U.S.C. 207 and 37 CFR Part 404. 
Information about Patent Application(s) and pertinent information not 
yet publicly described can be obtained under the terms of a 
Confidential Disclosure Agreement.
    A ``Cooperative Research and Development Agreement'' or ``CRADA'' 
is the anticipated joint agreement to be entered into by NIDA and a 
collaborator pursuant to the Federal Technology

[[Page 45781]]

Transfer Act of 1986 as amended by the National Technology Transfer and 
Advancement Act of 1995 (Pub. L. 104-113 (Mar. 7, 1996)) and by the 
Executive Order 12591 of October 10, 1987. The CRADA would pertain to 
inventions conceived or reduced to practice after the effective date of 
the CRADA. CRADA applicants should be aware that a license to the above 
mentioned patent rights may be necessary in order to commercialize 
products arising from a CRADA.
    A CRADA is an agreement designed to enable certain collaborations 
between Government laboratories and non-Government laboratories. It is 
not a grant, and is not a contract for the procurement of goods/
services. The NIDA is prohibited from transferring funds to a CRADA 
collaborator. Under a CRADA, NIDA can contribute facilities, staff, 
materials, and expertise to the effort. The collaborator may contribute 
facilities, staff, materials, expertise, and funding to the 
collaboration. The CRADA collaborator receives an exclusive option to 
negotiate an exclusive or non-exclusive license to Government 
intellectual property rights arising under the CRADA in a pre-
determined field of use and may qualify as a co-inventor of new 
technology developed under the CRADA.
    NIDA's principal objectives under a License and/or CRADA would be 
the development and timely commercialization of new diagnostics and/or 
therapeutics for specific neuropsychiatric disorders and rapid 
publication of results related to these research projects.
    Scientists at NIDA have discovered that distinct isoforms of N-CAM 
are elevated in the cerebrospinal fluid (CSF) and brains of patients 
diagnosed with specific neuropsychiatric disorders including 
schizophrenia, bipolar disorder and depression. A distinct isoform with 
molecular weight 105-115 kDa is present in elevated levels in both the 
CSF and brain tissues of patients with schizophrenia. The secreted 
(SEC) N-CAM isoform was elevated in brain tissue from bipolar disorder 
patients. Elevation of at least one isoform, the variable alternative 
spliced exon, or VASE isoform, is correlated significantly with 
behavioral ratings in patients with schizophrenia but not affective 
disorders. Thus, patients with neuropsychiatric disorders exhibit 
variations in N-CAM isoforms which are specific for their particular 
disorder. The specific association of these variations in N-CAM 
isoforms with particular neuropsychiatric disorders suggests the 
potential for development of therapeutic interventions, clinical trials 
for monitoring treatment response, and diagnostic methods of 
schizophrenia, bipolar disorder, depression and related diseases.
    Present treatment of schizophrenia, bipolar disorder, depression 
and related diseases is inadequate. Existing treatments may have 
serious side effects and do not prevent the progression of 
schizophrenia. Development of an effective treatment requires a greater 
understanding of the biological mechanisms underlying the disease 
conditions. Through NIDA's discovery of an association between clinical 
abnormalities and alterations in the level of N-CAM, a greater 
understanding of the disease process is now possible, and this 
discovery suggests possible therapies.
    In addition to inadequate existing treatments, there is presently 
no definitive diagnostic test for schizophrenia. Determination of the 
presence of the various criteria characteristic of schizophrenia is 
made by a trained clinician and is somewhat subjective. NIDA's 
discovery suggests that altered levels of N-CAM isoforms in the CSF may 
be the basis of an objective diagnostic test.
    N-CAM is a cell recognition molecule with four major isoforms 
present in the brain. N-CAM isoforms are membrane-associated 
glycoproteins, either transmembrane glycoproteins or 
glycosylphosphatidyl inositol-anchored glycoproteins. There is also a 
secretory isoform. Membrane-associated N-CAM has several roles in 
cellular organization and development of the central nervous system. An 
important aspect of N-CAM activity is the regulation of adhesion of 
brain cells. Adhesion of neural to glial cells is mediated by N-CAM 
binding. N-CAM is also involved in memory processes, intracellular 
signal cascades, and neurite outgrowth. N-CAM is thought to be a 
neuronal protein and is known to be associated with synaptosomes, 
vesicles recovered from neuronal preparations. Thus, alterations in N-
CAM influence brain structure, learning, and psychiatric systems, as 
shown in the recent research that NIDA is seeking to develop with a 
collaborator.
    The proposed collaboration would include in vivo investigations of 
production of N-CAM isoforms and release of N-CAM isoforms into CSF. 
Measurements on N-CAM production and release would be correlated with 
the clinical status of patients. The possibility of using these 
correlations to develop a diagnostic method will be investigated. 
Potential therapeutic compounds would be tested for effects on the 
biochemical parameters and the clinical status of patients. The 
collaboration would also involve in vitro investigation of N-CAM 
fragment production and release from brain tissue.
    The proposed duration of the CRADA is two (2) years. However, the 
duration could be as long as five (5) years depending on the nature of 
the research plan developed by the parties.
    The role of NIDA under the proposed CRADA may include the 
following, and other relevant scientifically appropriate collaborative 
research projects will be considered:
    (1) Provide further characterization of association between N-CAM 
variations with neuropsychiatric disorders.
    (2) Perform in vitro determinations of N-CAM fragment production 
and release from brain tissue.
    (3) Provide in vitro assessment of possible therapeutic compounds.
    (4) Monitor the efficacy of therapeutic compounds through 
biochemical methodology.
    (5) Jointly publish results.
    (6) Provide project coordination for the overall development and 
testing.
    The role of the Collaborator under the proposed CRADA may include 
the following, and other relevant and scientifically appropriate 
collaborative research projects will be considered:
    (1) Provide significant intellectual, scientific, and technical 
expertise in developing appropriate methods for a diagnostic assay 
based on the level of N-CAM isoforms in cerebrospinal fluid.
    (2) Determine whether the variation in level of N-CAM isoforms in 
cerebrospinal fluid can be used diagnostically.
    (3) Provide compounds which may have therapeutic potential.
    (4) Provide significant intellectual, scientific, and technical 
expertise in developing a therapeutic protocol based on regulating the 
level of N-CAM isoforms.
    (5) Perform clinical studies including assessments of patients and 
collection of samples.
    (6) Monitor the efficacy of therapeutic compounds using clinical 
determinations of efficacy.
    (7) Jointly publish results.
    (8) Jointly provide project coordination for the overall 
development and testing.
    The following factors will be evaluated in selecting a CRADA 
collaborator:
    (1) Corporate expertise in the field of development of diagnostic 
tools.
    (2) Competency in developing and assessing efficacy of therapeutic 
interventions.

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    (3) Number and character of possible therapeutic compounds that 
collaborator may be able to provide.
    (4) Ability to provide for staff to perform in vitro studies.
    (5) Key staff expertise, qualifications and relevant experience.
    (6) Ability to effectively commercialize new technologies.

    Dated: July 6, 2000.
Kathleen Sybert,
Director, Technology Development and Commercialization Branch, National 
Cancer Institute, National Institutes of Health.
    Dated: July 14, 2000.
Jack Spiegel,
Director, Division of Technology Transfer and Development, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 00-18724 Filed 7-24-00; 8:45 am]
BILLING CODE 4140-01-M