[Federal Register: October 24, 2005 (Volume 70, Number 204)]
[Notices]               
[Page 61458-61460]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr24oc05-58]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health

 
Government-Owned Inventions; Availability for Licensing

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

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 writing to the indicated 
licensing contact at the Office of Technology Transfer, National 
Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, 
Maryland 20852-3804; telephone: 301/496-7057; fax: 301/402-0220. A 
signed Confidential Disclosure Agreement will be required to receive 
copies of the patent applications.

NIH3T3 Cell Lines Carrying c-Met Mutations Including G3906A, G3522A, 
G3810T, T3936C, T3936G, T3997C, C3528T, C3564G, C3831G, A3529T, and 
T3640C

Laura S. Schmidt (NCI).
HHS Reference No. E-327-2005/0--Research Tool.
Licensing Contact: John Stansberry; 301/435-5236: 
stansbej@mail.nih.gov.

    MET is over expressed in a variety of cancers including hereditary 
papillary renal cell carcinoma and non-small cell lung cancer. These 
cell lines carry naturally-occurring Met mutations and were derived 
from the germline of patients with hereditary papillary renal cell 
carcinoma. These cell lines can be used as drug discovery research 
reagents.
    These cell lines were described in part in Schmidt et al., ``Novel 
mutations of the MET proto-oncogene in papillary renal carcinomas. 
Oncogene. (1999) 18:2343-2350 and Jeffers et al., ``Activating 
mutations for the met tyrosine kinase receptor in human cancer.'' PNAS 
(1997) 94:11445-11450.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

[[Page 61459]]

Mouse Fibroblasts Stably Expressing C-Type Lectin Receptors DC-SIGN and 
L-SIGN

Vineet N. KewelRamani and Thomas Martin (NCI).
HHS Reference Nos. E-321-2005/0 and E-322-2005/0--Research Tools.
Licensing Contact: Susan Ano; 301/435-5515; anos@mail.nih.gov.

    The NIH is pleased to offer for licensing mouse fibroblasts that 
stably express the C-type lectin receptors DC-SIGN and L-SIGN (CD209 
and CD209L, respectively). L-SIGN and DC-SIGN both exhibit selectivity 
for highly mannosylated glycoproteins. DC-SIGN is also selective for 
certain Lewis X sugar groups. These types of interactions allow L-SIGN 
and DC-SIGN to interact with a wide spectrum of pathogens including 
HIV, hepatitis C virus, and SARS coronavirus, which appear to use L-
SIGN and DC-SIGN to facilitate their replication. In addition to HIV, 
HCV, and SARS, pathogens such as Ebola virus, some herpes viruses, and 
tuberculosis interact with DC-SIGN. In contrast to primary cells 
expressing L-SIGN and DC-SIGN, the subject fibroblasts are resilient, 
adhere to coated tissue culture plates, grow rapidly and continually 
express high levels of their respective receptor. The subject materials 
could be used to study the interaction of pathogens with L-SIGN or DC-
SIGN and to screen for compounds that block these interactions. 
Additionally, the materials could be used for the development of 
antibodies or compounds through rational design that interacted with L-
SIGN or DC-SIGN. The NIH3T3/DC-SIGN and NIH3T3/L-SIGN cells are further 
described in Journal of Virology, 2002, vol. 26(12), pages 5905-5914. 
The subject technologies are available for licensing from the NIH 
through biological materials license agreements.

Murine Mast Cell Line Useful for Toxicity and Immunopotency Screens

Michael Potter (NCI).
HHS Reference No. E-274-2005/0--Research Tool.
Licensing Contact: John Stansberry; 301/435-5236; 
stansbej@mail.nih.gov.


    The technology is a mouse cell line (P815) that could be useful for 
screening biological and chemical agents for toxicity and 
immunopotency. Specifically, the cell line is useful for screening for 
toxic effects of immunopotentiators including Mycobacterium bovis, 
Bacillus Calmette-Gurerin strain, zymosan, lipopolysaccharide and 
dextran sulfate. The cell line may also have application in screening 
other compounds.
    The cell line may also prove useful for studies of cancer and tumor 
immunology as injection of mice with P815 leads to progressive tumors. 
The P815 tumors express cell surface antigens that could provide a 
model for cancer vaccine development.

Mutated Pseudomonas Exotoxins with Reduced Antigenicity

Ira H. Pastan et al. (NCI).
U.S. Provisional Patent Application filed 29 Jul 2005 (HHS Reference 
No. E-262-2005/0-US-01).
Licensing Contact: Jesse S. Kindra; 301-435-5559; kindraj@mail.nih.gov.

    The use of Pseudomonas exotoxins (PE) for treatment of solid 
tumors, in particular, has been limited because of the development of 
neutralizing antibodies to the immunotoxin after the first 
administration. These antibodies develop before most protocols would 
call for a second administration of the immunotoxin, and therefore 
render further use of the immunotoxins ineffective against solid tumors 
in previously exposed patients.
    The studies underlying this novel invention reveal that the 
predominant immune response of patients to PE-immunotoxins is the PE 
portion of the immunotoxin. This finding indicates that reducing the 
antigenicity of the PE molecules used for immunotoxins would reduce the 
overall antigenicity of the immunotoxin, and increase their utility.
    Therefore, this invention relates to mutated Pseudomonas exotoxins 
(PE) that have reduced antigenicity compared to PEs containing the 
native sequence. The PEs of this invention have one or more individual 
mutations that reduce antibody binding to one or more epitopes of PE.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Methods and Materials for Identifying Polymorphic Variants, Diagnosing 
Susceptibilities, and Treating Disease

Lawrence C. Brody (NHGRI) et al.
PCT Application No. PCT/US05/21288 filed 16 Jun 2005 (HHS Reference No. 
E-149-2005/0-PCT-01).
Licensing Contact: Marlene Shinn-Astor; 301/435-4426; 
shinnm@mail.nih.gov.


    This invention relates to materials and methods associated with 
polymorphic variants in two enzymes involved in folate-dependent and 
one-carbon metabolic pathways important in pregnancy-related 
complications and neural tube birth defects: MTHFD1 (5,10-
methylenetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate 
cyclohydrolase, 10-formyltetrahydrofolate synthase) and 
methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like 
(MTHFD1L). These enzymes are extremely important in the promotion of 
DNA synthesis, a process that is critical for normal placental and 
fetal development.
    Recently, the inventors have discovered that a MTHFD1 polymorphism 
is also a strong maternal genetic risk factor for placental abruption, 
premature separation of a normally implanted placenta. This 
polymorphism may also be a risk factor for first and second trimester 
miscarriages. Diagnostic and therapeutic methods are provided in this 
invention involving the correlation of polymorphic variants in MTHFD1 
and other genes with relative susceptibility for various pregnancy-
related and other complications such as cancer, cardiovascular disease, 
and developmental anomalies. Both nutrient status and genetic 
background are independent yet interacting risk factors for impaired 
folate metabolism. However, the mechanisms that lead to pathology or 
the mechanisms whereby folate prevents these disorders are unknown. 
Therefore, a diagnostic and therapeutic invention of this kind would 
significantly improve the detection and treatment of disorders 
associated with folate metabolism.
    For further information, see Brody et al., July 28, 2005, ``A 
polymorphism in the MTHFD1 gene increases a mother's risk of having an 
unexplained second trimester pregnancy loss,'' Mol. Hum. Reprod. 
10.1093/molehr/gah204.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

AAV5 Vector and Uses Thereof

John A. Chiorini, Robert M. Kotin (NHLBI).
U.S. Provisional Application No. 60/087,029 filed 28 May 1998 (HHS 
Reference No. E-127-1998/0-US-01).
U.S. Patent Application No. 09/717,789 filed 21 Nov 2000 (HHS Reference 
No. E-127-1998/0-US-07).
U.S. Patent Application Serial No. 11/184,380 filed 19 Jul 2005 (HHS 
Reference No. E-127-1998/0-US-08).
Licensing Contact: Jesse S. Kindra; 301/435-5559; kindraj@mail.nih.gov.

    The invention described and claimed in this patent application 
provides for novel vectors and viral particles which

[[Page 61460]]

comprise adeno-associated virus serotype 5 (AAV5). AAV5 is a single-
stranded DNA virus of either plus or minus polarity which, like other 
AAV serotypes (e.g., AAV4, AAV2) requires a helper virus for 
replication. AAV type 2 has the interesting and potentially useful 
ability to integrate into human chromosome 19 q 13.3-q ter. This 
activity is dependent on the non-structural, Rep, proteins of AAV2. The 
Rep proteins of AAV types 2 and 5 are dissimilar and are not able to 
substitute in DNA replication of the heterologous serotype.
    AAV5 offers several advantages which make it attractive for use in 
gene therapy: 1. Increased production (10-50 fold greater than AAV2); 
2. distinct integration locus when compared to AAV2; 3. Rep protein and 
ITR regions do not complement other AAV serotypes; and 4. appears to 
utilize different cell surface attachment molecules than those of AAV 
type 2.
    In addition to licensing, the technology may be available for 
further development through collaborative research opportunities with 
the inventors.

The Use of Nitroxides in the Prophylactic and Therapeutic Treatment of 
Cancer Due to Genetic Defects

James Mitchell, Angelo Russo, Anne Deluca and Murali Cherukuri (NCI).
U.S. Patent Application No. 09/424,519 filed 03 Mar 2000, claiming 
priority to 27 May 1997 (HHS Reference No. E-167-1997/0-US-07).
Licensing Contact: George Pipia; 301/435-5560; pipiag@mail.nih.gov.

    The invention is a method for preventing or treating cancer, 
especially cancers associated with defects in the p53 gene. This gene 
is generally considered to be a tumor-suppressor gene, and in a large 
percentage of malignancies including pancreatic, colon, lung, and 
breast, the gene is found to be inactive in the cancer. It is believed 
that many individuals have genetic defects in p53 predisposing them to 
cancer.
    The invention involves the use of certain nitroxides as agents to 
slow the appearance or progression of tumors associated with p53 
knockout. Thus, these compounds could serve as preventative agents for 
people predisposed to cancer, or as therapeutic agents for certain 
cancers. As nitroxides have already been identified as antioxidants, 
such agents could become part of a cancer prevention and anti-aging 
regimen. A new method of use for these compounds now include their use 
in imaging, which correlates functional information about the tumor 
with magnetic resonance imaging data.

    Dated: October 13, 2005.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 05-21118 Filed 10-21-05; 8:45 am]

BILLING CODE 4140-01-P