[Federal Register Volume 76, Number 208 (Thursday, October 27, 2011)]
[Notices]
[Pages 66728-66730]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2011-27859]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Licensing and Collaborative Research 
Opportunity for PANVAC--Cancer Vaccine for the Prevention and Treatment 
of Colorectal Cancer

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.

ADDRESSES: Licensing information and copies of the U.S. patent 
applications listed below may be obtained by contacting Sabarni 
Chatterjee at the Office of Technology Transfer, National Institutes of 
Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852; 
telephone: (301) 435-5587; email [email protected]. A signed 
Confidential Disclosure Agreement will be required to receive copies of 
the patent applications.
    Inquiries related to Collaborative Research Opportunities may be 
directed to Michael Pollack at the Technology Transfer Center, National 
Cancer Institute, 6120 Executive Boulevard, Suite 450, Rockville, MD 
20852; telephone: (301) 435-3118; email [email protected].

SUPPLEMENTARY INFORMATION: 

Technology Summary

    PANVAC is a pox-vector-based cancer vaccine in clinical stage 
development with high potential for leading to a new therapeutic 
approach in the prevention and treatment of colorectal cancer. A 
combination of carcinoembryonic antigen (CEA) and pan-carcinoma antigen 
MUC-1, and TRICOM, PANVAC has been used with promising results in 
treating metastatic colorectal cancer.
    In a recent multicenter phase II clinical trial reported at ASCO 
2011, improved survival was observed among patients vaccinated with 
PANVAC following resection of colorectal cancer metastases; at a median 
follow up of forty (40) months, the survival rate of vaccinated 
patients clearly exceeding that of the unvaccinated contemporary 
control population. T-cell responses to CEA were also observed in 
vaccinated patients.

Competitive Advantage of Our Technology

     The technology is in clinical stage, supported by clinical 
results and numerous publications.
     TRICOM, contained in pox vectors have been evaluated in 
prime (V)/boost (F) regimens in preclinical models and in several 
clinical trials in patients with metastatic colorectal cancer.
     Phase I and Phase II clinical data are available (to 
qualified licensees) for poxvirus recombinants containing transgenes 
for TRICOM, CEA-TRICOM, and PANVAC. Further clinical studies are 
ongoing.
     Given the relatively more advanced stage of development of 
this technology, fewer validation studies are required compared to 
other immunotherapy related technologies.

Technology Description

    Cancer immunotherapy is an 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 PANVAC technology employs avirulent poxviruses to present a 
combination of tumor-associated antigens (TAAs) and costimulatory 
molecules to activate T-cells and break the immune systems tolerance 
towards cancer cells. This is performed using recombinant poxvirus DNA 
vectors that encode both T-cell costimulatory molecules and TAAs. The 
combination of the costimulatory molecules B7.1, ICAM-1 and LFA-3, is 
known as TRICOM. Recombinant poxviral vaccines (vaccinia (V) and 
fowlpox (F) containing TRICOM have been evaluated in prime (V)/boost 
(F) regimens in preclinical models and in several clinical trials in 
patients with metastatic colorectal cancer. Additionally, PANVAC has 
shown promising survival results in treating patients with metastatic 
colorectal cancer.
    Furthermore, recombinant poxviral TRICOM based vaccines can also be 
employed for the prevention and/or therapy of colorectal cancer 
containing a range of other TAAs such as the T-box transcription factor 
Brachyury.

Market

    With the identification of molecular targets associated with 
cancer, the focus of drug development has shifted from broadly acting 
cytotoxic drugs to targeted therapeutics in the hope of finding drugs 
that selectively kill cancer cells and do not harm normal cells. 
Historically, because the expertise of pharmaceutical companies has 
been in the domain of small molecule therapeutics, several compounds 
have been developed that inhibit the abnormal biochemical activity of 
cancer cells. This approach has been successful to an extent as 
illustrated by the kinase inhibitors and EGFR inhibitors. However, as 
for chemotherapeutics, cancer cells frequently acquire drug resistance 
to targeted small-molecule therapeutics rendering them ineffective in 
the long run. In addition, these small-molecules produce adverse side 
effects which can prevent the administration of the maximum effective 
dose. An alternative approach to overcome these problems relies on the 
use of biologics such as antibodies and vaccines.

[[Page 66729]]

    The biotechnology industry has principally focused on an 
immunotherapy approach using monoclonal antibodies (mAb) to enlist the 
help of the patient's own immune system. This approach has successfully 
led to several FDA approved and marketed mAbs. Typically, cancer cells 
are less susceptible to acquiring resistance to antibodies; however, as 
seen for trastuzumab, resistance can occur. Another limitation of mAbs 
is that they activate only part of the immune system and do not produce 
future immunity against the cancer. More recently, cancer vaccines are 
being developed as an addition to the immunotherapy approach. It is 
expected that activating the cells of the immune system should be 
effective in killing cancer cells with the added benefit that it would 
lead to a sustained surveillance by the patient's own body that 
prevents the tumor from reemerging in the future.
    Vaccines have been very successful in the prevention of infectious 
diseases, and are now being evaluated for the treatment of cancer. The 
development of cancer vaccines could result in a paradigm shift in the 
treatment and clinical management of cancer. Recently, a cancer vaccine 
PROVENGE[supreg] (Sipuleucel-T) was approved by the FDA for the 
treatment of metastatic prostate cancer. The development of the TRICOM-
based ``off the shelf'' technology using costimulatory vaccines is 
designed to magnify the immune response against cancer cells and lead 
to prolonged cancer immunity.
    PANVAC has much potential for becoming a therapeutically effective 
cancer vaccine for colorectal cancer. It has demonstrated evidence of 
patient benefit in several Phase I and II clinical studies 
demonstrating a high safety profile and is a good candidate for 
initiating pivotal efficacy studies. Recently, very encouraging results 
were announced for PROSTVAC\TM\ (prostate cancer vaccine), based on the 
same TRICOM technology platform as PANVAC, which further validates this 
technology platform. PANVAC is a decidedly mature technology that holds 
promise to transform the treatment of colorectal cancer.

Patent Estate

    The portfolio includes the following issued patents and pending 
patent applications:

1. U.S. Patent No. 6,756,038 issued June, 29 2004 as well as issued and 
pending foreign counterparts [HHS Ref. No. E-099-1996/0-US-07];
2. U.S. Patent No. 7,723,096 issued May 25, 2010 as well as 
continuation and divisional applications, and issued and pending 
foreign counterparts [HHS Ref. No. E-099-1996/0-US-08];
3. Europe Patent No. 1017810 [HHS Ref. No. E-099-1996/0-EP-05], and all 
European contracting states in which this patent is validated,
4. Europe Patent Application No. 04011673.3 (now EP Patent No. 1447414) 
[HHS Ref. No. E-099-1996/0-EP-17], and all European contracting states 
in which this patent is validated, Japan Patent Application No. 2000-
516030 (now JP Patent No. 4291508) [HHS Ref. No. E-099-1996/0-JP-06], 
and all continuations and divisional applications claiming priority to 
this application;
5. Australia Patent No. 745863 [HHS Ref. No. E-099-1996/0-AU-03], and 
all continuations and divisional applications claiming priority to this 
application;
6. Canada Patent No. 2308127 [HHS Ref. No. E-099-1996/0-CA-04], and all 
continuations and divisional applications claiming priority to this 
application;
7. U.S. Patent No. 5,698,530 issued December 6, 1997 as well as issued 
and pending foreign counterparts [HHS Ref. No. E-200-1990/1-US-02];
8. Australian Patent No. 674492 issued April 22, 1997 [HHS Ref. No. E-
200-1990/2-AU-02]; Europe Patent No. 0584266 issued September 3, 2003 
[HHS Ref. No. E-200-1990/2-EP-04]; Japan Patent No. 3399943 issued 
February 21, 2003 [HHS Ref. No. E-200-1990/2-JP-05]; and Canada Patent 
No. 2102623 issued April 22, 2003 [HHS Ref. No. E-200-1990/2-CA-03];
9. 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];
10. U.S. Patent Application No. 10/579,025 filed May 11, 2006 as well 
as all continuation and divisional applications, and issued and pending 
foreign counterparts [HHS Ref. No. E-087-2005/0-US-03];
11. U.S. Patent Application No. 10/579,007 filed May 11, 2006 as well 
as all continuation and divisional applications, and issued and pending 
foreign counterparts [HHS Ref. No. E-088-2005/0-US-03];
12. U.S. Patent No. 7,118,738 issued October 10, 2006 as well as all 
continuations and divisional applications, and issued and pending 
foreign counterparts [HHS Ref. No. E-154-1998/0-US-07];
13. U.S. Patent Application Nos. 08/686,280 filed July 25, 1996 as well 
as all issued and pending foreign counterparts [HHS Ref. No. E-259-
1994/3-US-01];
14. U.S. Patent No. 7,410,644 issued August 12, 2008 as well as all 
continuation and divisional applications, and issued and pending 
foreign counterparts [HHS Ref. No. E-259-1994/3-US-08];
15. 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]; U.S. Patent No. 7,368,116 issued May 6, 2008 and U.S. 
Patent Application No. 12/112,819, as well as all continuation and 
divisional applications [HHS Ref. Nos. E-260-1994/1-US-04 and US-05];
16. Europe Patent Application No. 00102998.2 filed October 2, 1995, 
Europe Patent No. 0784483 issued November 29, 2001, Europe Patent 
Application No. 09013495.8 filed October 26, 2009, as well as all 
continuation, and divisional applications [HHS Ref. Nos. E-260-1994/2-
EP-15, EP-16 and EP-27]; Japan Patent Application No. 512100/96 filed 
October 2, 1995; Japan Patent No. 4078319 issued February 8, 2008 [HHS 
Ref. No. E-260-1994/2-JP-25]; and Japan Patent No. 4160612 issued July 
25, 2008, as well as all continuation and divisional applications; [HHS 
Ref. No. E-260-1994/2-JP-21, JP-25 and JP-26]; Australia Patent No. 
688606 issued July 2, 1998 [HHS Ref. No. E-260-1994/2-AU-11]; Canada 
Patent No. 2201587 issued June 25, 2002 [HHS Ref. No. E-260-1994/2-CA-
12];
17. Canada Patent Application No. 2,412,050 filed June 15, 2001 [HHS 
Ref. No. E-187-2000/0-CA-05]; Australia Patent No. 2001268452 issued 
November 30, 2006 [HHS Ref. No. E-187-2000/0-AU-06]; Japan Patent 
Application No. 2002-510097 filed June 15, 2001 [HHS Ref. No. E-187-
2000/0-JP-07]; Hong Kong Patent Application No. 03105975.5 filed June 
15, 2001 [HHS Ref. No. E-187-2000/0-HK-08];
18. U.S. Patent Application No. 12/280,534 filed February 21, 2007, 
[HHS Ref. No. E-104-2006/0-US-06]; Australia Patent Application No. 
2007221255 filed February 21, 2007 [HHS Ref. No. E-104-2006/0-AU-03]; 
Europe Patent Application No. 07751371.1 filed February 21,

[[Page 66730]]

2007, [HHS Ref. No. E-104-2006/0-EP-05]; Canada Patent Application No. 
2642994 filed February 21, 2007 [HHS Ref. No. E-104-2006/0-CA-04];
19. U.S. Patent Application No. 12/528,796 filed August 26, 2009 [HHS 
Ref. No. E-074-2007/0-US-07]; Australia Patent Application No. 
2008221383 filed February 27, 2008 [HHS Ref. No. E-074-2007/0-AU-03]; 
Europe Patent Application No. 08743578.0 filed February 27, 2008 [HHS 
Ref. No. E-074-2007/0-EP-05]; Canada Patent Application No. 2,678,404 
filed February 27, 2008 [HHS Ref. No. E-074-2007/0-CA-04]; Japan Patent 
Application No. 2009-551830 filed February 27, 2008 [HHS Ref. No. E-
074-2007/0-JP-06];
20. U.S. Patent No. 6,969,609 issued November 29, 2005; U.S. Patent No. 
7,211,432 issued May 1, 2007; U.S. Patent Application No. 11/723,666 
filed March 21, 2007; as well as all continuation and divisional 
applications, and issued and pending foreign counterparts [HHS Ref. No. 
E-256-1998/0, 1];
21. U.S. Patent Application Nos. 60/448,591 and 10/543,944 filed 
February 20, 2003 and February 20, 2004 respectively, as well as all 
continuation and divisional applications, and issued and pending 
foreign counterparts [HHS Ref. No. E-028-2007/0];
22. U.S. Patent No. 6,699,475 issued March 2, 2004, as well as all 
continuation and divisional applications, and issued and pending 
foreign counterparts [HHS Ref. No. E-134-2007/0];
23. U.S. Patent No. 5,093,258 issued March 3, 1992, as well as all 
continuation and divisional applications, and issued and pending 
foreign counterparts [HHS Ref. No. E-135-2007/0];
24. U.S. Patent Application No. 07/205,189 filed June 10, 1988, as well 
as all continuation and divisional applications, and issued and pending 
foreign counterparts [HHS Ref No. E-136-2007/0];
25. U.S. Patent Application No. 60/625,321 filed November 5, 2004, as 
well as all continuation and divisional applications, and issued and 
pending foreign counterparts [HHS Ref. No. E-138-2007/0];
26. U.S. Patent Application No. 60/678,329 filed May 5, 2005, as well 
as all continuation and divisional applications, and issued and pending 
foreign counterparts [HHS Ref. No. E-139-2007/0]; and
27. U.S. Patent Application No. 07/340,052 filed April 18, 1989, as 
well as all continuation and divisional applications, and issued and 
pending foreign counterparts [HHS Ref. No. E-147-2007/0].

    Note that some of the patent estate above is available for non-
exclusive licensing only.

Cooperative Research and Development Agreement (CRADA) Opportunities

    A CRADA partner for the further codevelopment of this technology 
specifically in colorectal cancer 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 
for colorectal cancer, (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 for colorectal 
cancer of recombinant vaccines alone and in combination therapies.

Next Step

Licensing and CRADA

    Licensing and collaborative research opportunities are available. 
If you are interested in licensing and/or CRADA opportunities, please 
contact call Sabarni Chatterjee at (301) 435-5587 or email 
[email protected] (for licensing) and Michael Pollack at (301) 
435-3118 or email [email protected] (for CRADAs).

    Dated: October 21, 2011.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 2011-27859 Filed 10-26-11; 8:45 am]
BILLING CODE 4140-01-P