[Federal Register Volume 73, Number 164 (Friday, August 22, 2008)]
[Notices]
[Pages 49686-49688]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-19462]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Licensing and/or Cooperative Research and Development Agreement 
(CRADA) Opportunities--Enhanced T-cell Activation by Costimulation: A 
Potentially Novel Approach for the Prevention and/or Therapy of Cancer 
(Excluding Prostate Diseases and Melanoma) and for Infectious Diseases

AGENCY: National Institutes of Health, Public Health Service, HHS.

ACTION: Notice.

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SUMMARY: The inventions listed below are owned by an agency of the U.S. 
Government and are available for licensing in the U.S. in accordance 
with 35 U.S.C. 207 to achieve expeditious commercialization of results 
of federally-funded research and development. Foreign patent 
applications are filed on selected inventions to extend market coverage 
for companies and may also be available for licensing. Cooperative 
Research and Development Agreement (CRADA) opportunities are also 
available.

FOR FURTHER INFORMATION CONTACT: Licensing information and copies of 
the U.S. patent applications listed below may be obtained by contacting 
Mojdeh Bahar, J.D., Office of Technology Transfer, National Institutes 
of Health, 6011 Executive Boulevard, Suite 325, Rockville MD 20852; 
telephone: 301/435-2950; e-mail: <a href="/cdn-cgi/l/email-protection#0c6e6d646d7e614c616d656022626564226b637a"><span class="__cf_email__" data-cfemail="4527242d2437280528242c296b2b2c2d6b222a33">[email protected]</span></a>. A signed 
Confidential Disclosure Agreement will be required to receive copies of 
the patent applications. If interested in a Cooperative Research and 
Development Agreement (CRADA) Opportunity, please submit a statement of 
interest and capability to Kevin Brand, J.D., in the NCI Technology 
Transfer Center, 6120 Executive Boulevard, Suite 450, Rockville MD 
20852; telephone: 301/451-4566; e-mail: <a href="/cdn-cgi/l/email-protection#52393060606b26123c3b3a7c353d24"><span class="__cf_email__" data-cfemail="68030a5a5a511c28060100460f071e">[email protected]</span></a>.

SUPPLEMENTARY INFORMATION: 

Description of Technology

    Cancer immunotherapy is a recent approach where tumor associated 
antigens (TAAs), which are primarily expressed in human tumor cells and 
not expressed or minimally expressed in normal tissues, are employed to 
generate a tumor specific immune response. Specifically, these antigens 
serve as targets for the host immune system and elicit responses that 
results in tumor destruction. The initiation of an effective T-cell 
immune response to antigens requires two signals. The first one is 
antigen specific via the peptide/major histocompatibility complex and 
the second or ``costimulatory'' signal is required for cytokine 
production, proliferation, and other aspects of T-cell activation.
    The present technology describes recombinant poxvirus vectors 
encoding at least three or more costimulatory molecules and tumor 
associated antigens (TAAs). The use of three costimulatory molecules 
such as B7.1, ICAM-1 and LFA-3 (TRICOM<SUP>[reg]</SUP>) has been shown 
to act in synergy with several tumor antigens and antigen epitopes to 
activate T cells. The effects with TRICOM<SUP>[reg]</SUP> were 
significantly greater than with one or two costimulatory molecules. 
Laboratory results support the greater effect of TRICOM<SUP>[reg]</SUP> 
to activate both CD4<SUP>+</SUP> and CD8<SUP>+</SUP> T cells. The 
invention also describes the use of at least one target antigen or 
immunological epitope as an immunogen or vaccine in conjunction with 
TRICOM<SUP>[reg]</SUP>. The antigens include but are not limited to 
carcinoembryonic antigen (CEA) and MUC-1. The combination of CEA, MUC-
1, and TRICOM<SUP>[reg]</SUP> is referred to as PANVAC<SUP>[reg]</SUP>.

Availability

    The technology is available for exclusive and non-exclusive license 
in combinations and fields of use. Some potential licensing 
opportunities involving recombinant poxviral vectors containing 
transgenes are as follows:
    (1) TRICOM<SUP>[reg]</SUP> (alone or with a transgene for a tumor 
antigen and/or an immunostimulatory molecule);

[[Page 49687]]

    (2) The antigens only, including but not limited to CEA and MUC-1;
    PANVAC<SUP>[reg]</SUP>; and
    (3) Recombinant fowlpox-GM-CSF.

Applications and Modality

    Vector-based TRICOM<SUP>[reg]</SUP> (alone or with a transgene(s) 
for a tumor antigen and/or an immunostimulatory molecule(s)), 
PANVAC<SUP>[reg]</SUP> and combinations thereof can be a potential 
novel approach for the prevention or treatment of cancer (with the 
exclusion of prostate cancer, prostatic diseases, and melanoma) and 
infectious diseases.

Advantages

    <bullet> The technology is beyond proof-of-concept, supported by 
laboratory results and publications.
    <bullet> Phase I and Phase II clinical data available (to qualified 
licensees).
    <bullet> Fewer validation studies are required compared to other 
immunotherapy related technologies.

Development Status

    Phase I and Phase II results available (to qualified licensees) for 
poxvirus recombinants containing transgenes for TRICOM<SUP>[reg]</SUP>, 
CEA-TRICOM<SUP>[reg]</SUP>, and PANVAC<SUP>[reg]</SUP>. Further 
clinical studies are ongoing.

Inventors

    Jeffrey Schlom (NCI) et al. (Inventor Web page: http://ccr.cancer.gov/Staff/staff.asp?profileid=5444).

Publications

    1. Kudo-Saito C, Wansley EK, Gruys ME, Wiltrout R, Schlom J and 
Hodge JW. Combination therapy of an orthotopic renal cell carcinoma 
model employing intratumoral vector-mediated costimulation and systemic 
IL-2. Clin Cancer Res. 13:1936-1946, 2007.
    2. Chakraborty M, Schlom J, and Hodge JW. The combined activation 
of positive costimulatory signals with modulation of a negative 
costimulatory signal for the enhancement of vaccine mediated T-cell 
responses. Cancer Immunol Immunother. 56:1471-1484, 2007.
    3. Kudo-Saito C, Garnett CT, Wansley EK, Schlom J, and Hodge JW. 
Intratumoral delivery of vector mediated IL-2 in combination with 
vaccine results in enhanced T-cell avidity and anti-tumor activity. 
Cancer Immunol Immunother. 56:1897-1910, 2007.
    4. Garnett CT, Schlom J, and Hodge JW. Combination of docetaxel and 
recombinant vaccine enhances T-cell responses and antitumor activity: 
Effects of docetaxel on immune enhancement. Clin Cancer Res. (in 
press).
    5. Chakraborty M, Gelbard A, Carrasquillo JA, Yu S, Mamede M, Park 
CH, Camphuasen K, Schlom J, and Hodge JW. Use of radiolabeled 
monoclonal antibody to enhance vaccine-mediated antitumor effects. 
Cancer Immunol Immunother. 56:1471-1484, 2007.
    6. Litzinger MT, Fernando R, Curiel TJ, Grosenbach DW, Schlom J, 
and Palena C. The IL-2 immunotoxin denileukin diftitox reduces 
regulatory T-cells and enhances vaccine-mediated T-cell immunity. Blood 
110:3192-3201, 2007.
    7. Gelbard A, Garnett CT, Abrams SI, Patel V, Gutkind JS, Palena C, 
Tsang KY, Schlom J, and Hodge JW. Combination chemotherapy and 
radiation of human squamous cell carcinoma of the head and neck 
augments CTL-mediated lysis. Clin Cancer Res. 12:1897-1905, 2006.
    8. Kaufman HL, Cohen S, Cheung K, DeRaffele, Mitcham J, Moroziewicz 
D, Schlom J, and Hesdorffer C. Local delivery of vaccinia virus 
expressing multiple costimulatory molecules for the treatment of 
established tumors. Human Gene Ther. 17:239-244, 2006.
    9. Marshall J, Gulley JL, Arlen PM, Beetham PK, Tsang KY, Slack R, 
Hodge JW, Doren S, Grosenbach DW, Hwang J, Fox E, Odogwa L, Park S, 
Panicali D, Schlom J. A phase I study of sequential vaccinations with 
fowlpox-CEA(6D)-TRICOM (B7-1/ICAM-1/LFA-3) alone and sequentially with 
vaccinia-CEA(6D)-TRICOM, with and without GM-CSF, in patients with CEA-
expressing carcinomas. J Clin Oncol. 23:720-731, 2005.
    10. Palena C, Foon KA, Panicali D, Yafal AG, Chinsangaram J, Hodge 
JW, Schlom J, and Tsang KY. A potential approach to immunotherapy of 
chronic lymphocytic leukemia (CLL): enhanced immunogenicity of CLL 
cells via infection with vectors encoding for multiple costimulatory 
molecules. Blood 106:3515-3523, 2005.
    11. Yang S, Hodge JW, Grosenbach DW, and Schlom J. Vaccines with 
enhanced costimulation maintain high avidity memory CTL. J. Immunol. 
175:3715-3723, 2005.
    12. Yang S, Tsang KY, and Schlom J. Induction of higher avidity 
human CTL by vector-mediated enhanced costimulation of antigen-
presenting cells. Clin Cancer Res. 11:5603-5615, 2005.
    13. Hodge JW, Chakraborty M, Kudo-Saito C, Garnett CT, Schlom J. 
Multiple costimulatory modalities enhance CTL avidity. J Immunol 
174:5994-6004, 2005.
    14. Tsang K-Y, Palena C, Yokokawa J, Arlen PM, Gulley JL, Mazzara 
GP, Gritz L, G[oacute]mez Yafal A, Ogueta S, Greenhalgh P, Manson K, 
Panicali D, and Schlom J. Analyses of recombinant vaccinia and fowlpox 
vaccine vectors expressing transgenes for two human tumor antigens and 
three human costimulatory molecules. Clin Cancer Res. 11:1597-1607, 
2005.
    15. Chakraborty M, Abrams SI, Coleman CN, Camphausen K, Schlom J, 
Hodge JW. External beam radiation of tumors alters phenotype of tumor 
cells to render them susceptible to vaccine-mediated T-cell killing. 
Cancer Res. 64:4328-4337, 2004.
    16. Zeytin HE, Patel AC, Rogers CJ, et al. Combination of a 
poxvirus-based vaccine with a cyclooxygenase-2 inhibitor (celecoxib) 
elicits antitumor immunity and long-term survival in CEA.Tg/MIN mice. 
Cancer Res. 64:3668-3678, 2004.
    17. Palena C, Zhu M-Z, Schlom J, and Tsang K-Y. Human B cells that 
hyperexpress a triad of costimulatory molecules via avipoxvector 
infection: An alternative source of efficient antigen-presenting cells. 
Blood 104:192-199, 2004.
    18. Kudo-Saito C, Schlom J, and Hodge JW. Intratumoral vaccination 
and diversified subcutaneous/intratumoral vaccination with recombinant 
poxviruses encoding a tumor antigen and multiple costimulatory 
molecules. Clin Cancer Res. 10:1090-1099, 2004.
    19. Hodge JW, Poole DJ, Aarts WM, G[oacute]mez Yafal A, Gritz L, 
and Schlom J. Modified vaccinia virus ankara recombinants are as potent 
as vaccinia recombinants in diversified prime and boost vaccine 
regimens to elicit therapeutic antitumor responses. Cancer Res. 
63:7942-7949, 2003.
    20. Hodge JW, Grosenbach DW, Aarts WM, Poole DJ, and Schlom J. 
Vaccine therapy of established tumors in the absence of autoimmunity. 
Clin Cancer Res. 9:1837-1849, 2003.
    21. Aarts WM, Schlom J, and Hodge JW. Vector-based vaccine/cytokine 
combination therapy to enhance induction of immune responses to a self-
antigen and anti-tumor activity. Cancer Res. 62:5770-5777, 2002.
    22. Hodge JW, Sabzevari H, Yafal AG, Gritz L, Lorenz MG, Schlom J. 
A triad of costimulatory molecules synergize to amplify T-cell 
activation. Cancer Res. 59: 5800-5807, 1999.

Patent Status

    1. U.S. Patent No. 6,969,609 issued November 29, 2005 as well as 
issued and pending foreign counterparts [HHS Ref. No. E-256-1998/0];
    2. U.S. Patent Application No. 11/321,868 filed December 30, 2005 
[HHS Ref. No. E-256-1998/1]; and
    3. U.S. Patent No. 6,756,038 issued June 29, 2004 as well as issued 
and

[[Page 49688]]

pending foreign counterparts [HHS Ref. No. E-099-1996/0];
    4. U.S. Patent No. 6,001,349 issued December 14, 1999 as well as 
issued and pending foreign counterparts [HHS Ref. No E-200-1990/3-US-
01];
    5. U.S. Patent No.6,165,460 issued December 26, 2000; as well as 
issued and pending foreign counterparts [HHS Ref. No E-200-1990/4-US-
01];
    6. U.S. Patent No. 7,118,738 issued October 10, 2006 as well as 
issued and pending foreign counterparts [HHS Ref. No E-154-1998/0-US-
07];
    7. PCT Application No. PCT/US97/12203 filed July 15, 1997 [HHS Ref. 
No E-259-1994/3-PCT-02];
    8. U.S. Patent Application Nos. 10/197,127. and 08/686,280 filed 
July 17, 2002 and July 25, 1996 [HHS Ref. No E-259-1994/3-US-08 and /4-
US-01];
    9. U.S. Patent No. 6,946,133 issued September 20, 2005 as well as 
issued and pending foreign counterparts [HHS Ref. No E-062-1996/0-US-
01];
    10. U.S. Patent Application No. 11/606,929 filed December 1, 2006 
[E-062-1996/0-US-11];
    11. U.S. Patent Nos. 6,893,869, 6,548,068 and 6,045,802 issued May 
17, 2005, April 15, 2003 and April 4, 2000 respectively, as well as 
issued and pending foreign counterparts [HHS Ref. Nos. E-260-1994/1-US-
03, US-02, US-01]; and
    12. U.S. Patent. Application No. 11/090,686 filed March 8, 2005 
[HHS Ref. No E-260-1994/1-US-04].

Cooperative Research and Development Agreement (CRADA) Opportunities

    A CRADA partner for the further co-development of this technology 
is currently being sought by the Laboratory of Tumor Immunology and 
Biology, Center for Cancer Research, NCI. The CRADA partner will (a) 
generate and characterize recombinant poxviruses expressing specific 
tumor-associated antigens, cytokines, and/or T-cell costimulatory 
factors, (b) analyze the recombinant poxviruses containing these genes 
with respect to appropriate expression of the encoded gene product(s), 
(c) supply adequate amounts of recombinant virus stocks for preclinical 
testing, (d) manufacture and test selected recombinant viruses for use 
in human clinical trials (with the exception of trials for prostatic 
diseases and melanoma), (e) submit Drug Master Files detailing the 
development, manufacture, and testing of live recombinant vaccines to 
support the NCI-sponsored IND and/or company-sponsored IND, (f) supply 
adequate amounts of clinical grade recombinant poxvirus vaccines for 
clinical trials conducted at the NCI Center for Cancer Research (CCR), 
and (g) provide adequate amounts of vaccines for extramural clinical 
trials, if agreed upon by the parties, and conduct clinical trials 
under company-sponsored or NCI-sponsored INDs. NCI will (a) provide 
genes of tumor-associated antigens, cytokines and other 
immunostimulatory molecules for incorporation into poxvirus vectors, 
(b) evaluate recombinant vectors in preclinical models alone and in 
combination therapies, and (c) conduct clinical trials (with the 
exception of trials for prostatic diseases and melanoma) of recombinant 
vaccines alone and in combination therapies.

     Dated: August 14, 2008
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E8-19462 Filed 8-21-08; 8:45 am]
BILLING CODE 4140-01-P


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