[Federal Register Volume 63, Number 216 (Monday, November 9, 1998)]
[Notices]
[Pages 60361-60362]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-29989]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Licensing Opportunity and/or Cooperative Research and Development 
Agreement (``CRADA'') Opportunity: Drug and Method for the Therapeutic 
Treatment of Leukemia, Lymphoma, Hairy Cell Leukemia, Hodgkin's 
Disease, and Other Hematologic Malignancies

AGENCY: National Institutes of Health, PHS, DHHS.

ACTION: Notice.

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SUMMARY: The NIH is seeking Licensees to further develop, evaluate, and 
commercialize anti-Tac (Fv)-PE38, also known as LMB2, immunotoxin for 
the therapeutic treatment of refractory Leukemia, Lymphoma, Hairy Cell 
Leukemia, Hodgkin's disease and other hematologic malignancies. Anti-
Tac (Fv)-PE38 (LMB2) is a recombinant immunotoxin composed of a single-
chain Fv form of the anti-Tac (anti-CD25) monoclonal antibody, which 
binds to the  subunit of the IL2 receptor (also called P55, 
Tac, or CD25), fused to PE38, a mutant form of Pseudomonas Exotoxin A. 
Anti-TAC (Fv)-PE38 (LMB2) is very cytotoxic to normal or malignant 
cells expressing IL2 receptors and is being developed for the therapy 
of chronic lymphocytic leukemia, lymphoma, Hodgkin's disease and Hairy 
Cell Leukemia. The goal is to move the Anti-Tac (FV)-PE38 (LMB2) 
immunotoxin into Phase II and III clinical trials. The inventions 
claimed in USPN 4,892,827, entitled: ``Recombinant Pseudomonas 
Exotoxins: Construction of an Active Immunotoxin with Low Side 
Effects''; USSN 07/865,722, entitled: ``Recombinant Antibody-Toxin 
Fusion Protein''; USPN 5,696,237, entitled: ``Recombinant Antibody-
Toxin Fusion Protein''; and USSN 08/461,825, entitled: ``Recombinant 
Antibody-Toxin Fusion Protein''; are available for either exclusive or 
non-exclusive licensing for these aforementioned applications only (in 
accordance with 35 U.S.C. 207 and 37 CFR Part 404).

ADDRESSES: Questions about licensing opportunities may be addressed to 
J.R. Dixon, Ph.D., Technology Licensing Specialist, Office of 
Technology Transfer, National Institutes of Health, 6011 Executive 
Boulevard, Suite 325, Rockville, Maryland 20852-3804; Telephone: (301)-
496-7056 ext. 206; Facsimile: (301)-402-0220; E-Mail: 
``[email protected]''. Information about Patent Applications and 
pertinent information not yet publicly described can be obtained under 
the terms of a Confidential Disclosure Agreement. Respondees interested 
in licensing the invention(s) will be required to submit an 
``Application for License to Public Health Service Inventions''.
    Depending upon the mutual interests of the Licensee(s) and the NCI, 
a Cooperative Research and Development Agreement (CRADA) to collaborate 
to improve the properties of the Anti-Tac (Fv)-PE38 may also be 
negotiated. Proposals and questions about this CRADA opportunity may be 
addressed to Dr. Patrick Twomey, Technology Development Specialist, 
Technology Development & Commercialization Branch, National Cancer 
Institute, 6120 Executive Plaza South-Room 450, Rockville, Maryland 
20852; Telephone: (301)-496-0477; Facsimile: (301)-402-2117; email: 
[email protected]. Respondees interested in submitting a CRADA 
Proposal should be aware that it may be necessary to secure a license 
to the above-mentioned patent rights in order to commercialize products 
arising from a CRADA.

EFFECTIVE DATE: Respondees interested in licensing the invention(s) 
will be required to submit an ``Application for License to Public 
Health Service Inventions'' on or before January 8, 1999 for priority 
consideration.
    Interested CRADA collaborators must submit a confidential proposal 
summary to the NCI [attention Dr. Patrick Twomey at the aforementioned 
address] on or before January 8, 1999,

[[Page 60362]]

for consideration. Guidelines for preparing full CRADA proposals will 
be communicated shortly thereafter to all respondents with whom initial 
confidential discussions will have established sufficient mutual 
interest. CRADA proposals submitted thereafter may be considered if a 
suitable CRADA Collaborator has not been selected.

SUPPLEMENTARY INFORMATION: In a Phase I trial, patients with 
hematologic malignancies and CD25 expression on malignant cells based 
on pre-screening immunocytochemistry and radiolabeled binding studies 
were given anti-Tac(Fv)-PE38 (LMB2) immunotoxin intravenously qod x 3. 
Thirty-two (32) patients received a total of fifty-three (53) cycles. 
Grade III non-hematologic toxicity was considered dose-limiting. Only 5 
of the 32 patients developed significant neutralizing antibodies after 
the first cycle. The T1/2 was 3-7 hours. Partial responses 
occurred in 5 patients including cutaneous T-cell Lymphoma, hairy cell 
leukemia, and chronic lymphocytic leukemia. Marginal responses were 
observed in two patient with Hodgkin's disease and in one patient with 
mantle cell lymphoma. Thus LMB-2 has activity in several forms of 
CD25+hematologic malignancies and is relatively non-immunogenic in this 
patient population.
    A Cooperative Research and Development Agreement or CRADA means the 
anticipated joint agreement to be entered into by NCI pursuant to the 
Federal Technology Transfer Act of 1986 and Executive Order 12591 of 
April 10, 1987 as amended by the National Technology Transfer 
Advancement Act of 1995 to collaborate to improve the properties of 
Anti-Tac(Fv)-PE38. The expected duration of the CRADA would be from one 
(1) to five (5) years.
    The role of the NCI in the CRADA may include, but not be limited 
to:
    1. Providing sufficient amounts of anti-Tac (Fv)-PE38 (LMB2) for 
clinical trails.
    2. Conducting Phase 2 and Phase 3 clinical trials.
    3. Providing significant intellectual, scientific, and technical 
expertise or experience to the research project.
    4. Planning research studies and interpreting research results.
    5. Providing technical and/or financial support to facilitate 
scientific goals and for further design of applications of the 
technology outlined in the agreement.
    6. Incorporating the immunotoxin into formulations in order to 
increase the therapeutic efficacy and decrease immunogenicity.
    7. Providing immunotoxin for laboratory and animal studies.
    8. Publishing research results.
    The role of the CRADA Collaborator may include, but not be limited 
to:
    1. Providing sufficient amounts of anti-Tac (Fv)-PE38 (LMB2) for 
clinical trials.
    2. Conducting Phase 2 and Phase 3 clinical trials.
    3. Providing significant intellectual, scientific, and technical 
expertise or experience to the research project.
    4. Planning research studies and interpreting research results.
    5. Providing samples of the subject compounds to create, optimize, 
test and develop targeted drugs for clinical studies.
    6. Providing technical and/or financial support to facilitate 
scientific goals and for further design of applications of the 
technology outlined in the agreement.
    7. Incorporating the immunotoxin into formulations in order to 
increase the therapeutic efficacy and decrease immunogenicity.
    8. Providing immunotoxin for laboratory and animal studies.
    9. Publishing research results.
    Selection criteria for choosing the CRADA Collaborator may include, 
but not be limited to:
    1. The ability to collaborate with NCI on further research and 
development of this technology. This ability can be demonstrated 
through experience and expertise in this or related areas of technology 
indicating the ability to contribute intellectually to ongoing research 
and development.
    2. The demonstration of adequate resources to perform the research 
and development of this technology (e.g., facilities, personnel and 
expertise) and accomplish objectives according to an appropriate 
timetable to be outlined in the CRADA Collaborator's proposal.
    3. The willingness to commit best effort and demonstrated resources 
to the research and development of this technology, as outlined in the 
CRADA Collaborator's proposal.
    4. The demonstration of expertise in the commercial development and 
production of products related to this area of technology.
    5. The level of financial support the CRADA Collaborator will 
provide for CRADA-related Government activities.
    6. The demonstration of expertise pertinent to the development of 
models to evaluate and improve the efficacy of the anti-Tac (Fv)-PE38 
(LMB2) immunotoxin for the treatment of leukemias and lymphomas.
    7. The demonstration of expertise in the formulation of drugs.
    8. The willingness to cooperate with the NCI in the timely 
publication of research results.
    9. The agreement to be bound by the appropriate DHHS regulations 
relating to human subjects, and all PHS policies relating to the use 
and care of laboratory animals.
    10. The willingness to accept the legal provisions and language of 
the CRADA with only minor modifications, if any. These provisions 
govern the distribution of patent rights to CRADA inventions. 
Generally, the rights of ownership are retained by the organization 
that is the employer of the inventor, with (1) the grant of a license 
for research and other Government purposes to the Government when the 
CRADA Collaborator's employee is the sole inventor, or (2) the grant of 
an option to elect an exclusive or nonexclusive license to the CRADA 
Collaborator when the Government employee is the sole inventor.

    Dated: October 31, 1998.
Kathleen Sybert,
Acting Director, Technology Development and Commercialization Branch, 
National Cancer Institute, National Institutes of Health.

    Dated: October 6, 1998.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 98-29989 Filed 11-6-98; 8:45 am]
BILLING CODE 4140-01-M