Government-Owned Inventions; Availability for Licensing, 31791-31794 [2010-13480]
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Federal Register / Vol. 75, No. 107 / Friday, June 4, 2010 / Notices
Sponsors of ANDAs do not have to
repeat the extensive clinical testing
otherwise necessary to gain approval of
a new drug application (NDA). The only
clinical data required in an ANDA are
data to show that the drug that is the
subject of the ANDA is bioequivalent to
the listed drug.
The 1984 amendments include what
is now section 505(j)(7) of the Federal
Food, Drug, and Cosmetic Act (21 U.S.C.
355(j)(7)), which requires FDA to
publish a list of all approved drugs.
FDA publishes this list as part of the
‘‘Approved Drug Products With
Therapeutic Equivalence Evaluations,’’
which is known generally as the
‘‘Orange Book.’’ Under FDA regulations,
drugs are removed from the list if the
agency withdraws or suspends approval
of the drug’s NDA or ANDA for reasons
of safety or effectiveness or if FDA
determines that the listed drug was
withdrawn from sale for reasons of
safety or effectiveness (§ 314.162 (21
CFR 314.162)). Under § 314.161(a)(1) (21
CFR 314.161(a)(1)), the agency must
determine whether a listed drug was
withdrawn from sale for reasons of
safety or effectiveness before an ANDA
that refers to that listed drug may be
approved. FDA may not approve an
ANDA that does not refer to a listed
drug.
Cysteine HCl is the subject of NDA
19–523, most recently held by Hospira,
Inc. (Hospira), and initially approved on
October 22, 1986. Cysteine HCl is
indicated for use as an additive to
amino acid solutions to meet the
nutritional requirements of newborn
infants requiring total parenteral
nutrition (TPN) and of adult and
pediatric patients with severe liver
disease who may have impaired
enzymatic processes and require TPN. It
can also be added to amino acid
solutions to provide a more complete
profile of amino acids for protein
synthesis. Hospira notified FDA in a
letter dated May 26, 2005, that it had
not commercially manufactured and
marketed Cysteine HCl, and voluntarily
asked that the NDA be withdrawn. The
drug product was moved to the
‘‘Discontinued Drug Product List’’
section of the Orange Book, and FDA
withdrew approval of NDA 19–523
effective June 16, 2006 (71 FR 34940). In
previous instances (see, e.g., 74 FR
63404, December 3, 2009; 72 FR 9763,
March 5, 2007; 61 FR 25497, May 21,
1996), the agency has determined that,
for purposes of §§ 314.161 and 314.162,
never marketing an approved drug
product is equivalent to withdrawing
the drug from sale. Regulus
Pharmaceutical Consulting, Inc.,
submitted a citizen petition, dated April
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30, 2008 (Docket No. FDA–2008–P–
0278), under 21 CFR 10.30, requesting
that the agency determine whether
Cysteine HCl was withdrawn from sale
for reasons of safety or effectiveness.
FDA has reviewed its records and,
under § 314.161, has determined that
Cysteine Hydrochloride Injection, USP,
7.25%, was not withdrawn for reasons
of safety or effectiveness. We have also
independently evaluated relevant
literature and have found no
information that would indicate that
this product was withheld from sale for
reasons of safety or effectiveness.
Accordingly, the agency will continue
to list Cysteine Hydrochloride Injection,
USP, 7.25%, in the ‘‘Discontinued Drug
Product List’’ section of the Orange
Book. The ‘‘Discontinued Drug Product
List’’ delineates, among other items,
drug products that have been
discontinued from marketing for reasons
other than safety or effectiveness.
ANDAs that refer to Cysteine
Hydrochloride Injection, USP, 7.25%
may be approved by the agency if all
other legal and regulatory requirements
for the approval of ANDAs are met. If
FDA determines that the labeling for
this drug product should be revised to
meet current standards, the agency will
advise ANDA applicants to submit such
labeling.
Dated: May 27, 2010.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2010–13463 Filed 6–3–10; 8:45 am]
BILLING CODE 4160–01–S
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing
AGENCY: National Institutes of Health,
Public Health Service, HHS.
ACTION: Notice.
SUMMARY: The inventions listed below
are owned by an agency of the U.S.
Government and are available for
licensing in the United States 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
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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.
888-mel: A Target for Anti-Tumor
Immune Responses
Description of Invention: Scientists at
the National Institutes of Health (NIH)
have developed a human melanoma cell
line designated 888-mel from the
resected tumor of a 26-year old
Caucasian female (patient 888)
diagnosed with metastatic melanoma, a
frequently terminal cancer. The 888-mel
cell line was derived from three separate
subcutaneous melanoma lesions on the
patient and possesses many
characteristics representative of
melanoma cell lines developed by these
researchers. Most prominently, the 888mel cell line was used to develop a
tumor infiltrating lymphocyte (TIL)
culture with high affinity for the tumor
cells of patient 888. When the TIL 888
culture was provided as an autologous
adoptive immunotherapy treatment to
patient 888 in combination with
interleukin-2 (IL–2), a complete
remission of subcutaneous, lung, and
mucosal metastases was observed in the
patient for over three years.
Since this medical breakthrough, the
888-mel cell line has been well
characterized through various laboratory
procedures and data involving this cell
line has been published as part of
numerous articles. Studies have shown
that the cell line expresses a variety of
tumor associated antigens (TAAs),
including tyrosinase, TRP1, TRP2,
gp100, MART–1, p15, gp75, mutated
beta-catenin, and p53. However, 888mel does not normally express the
MAGE 1, 2, or 3 TAAs. Many melanoma
cell lines are HLA–A2 restricted, but the
888-mel cell line is HLA–A2 negative.
The HLA class I typing for this cell line
is as follows: HLA–A0101, A2402, B55,
B62, Cw5201, Cw55, DRbl*1502,
DRbl*1610, DQbl*0601, DRb5*0102,
DRb5*0203. 888-mel is a validated
source of HLA class I peptides utilized
in screens that test the reactivity of TIL
cultures that are candidates for adoptive
immunotherapy trials. 888-mel is also a
standard cell line for studying immune
responses in cancer, particularly T cell
responses. Other experiments show that
roscovitine, a cyclin-dependent kinase
inhibitor, can induce apoptosis in the
888-mel cell line, so these cells may be
useful in various cell death studies.
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srobinson on DSKHWCL6B1PROD with NOTICES
Applications
• Research tool for investigating the
key immune responses required to
mediate the remission of metastatic
melanoma in order to identify the
immune cell types necessary to produce
an effective immunotherapy.
• Research tool for investigating the
tumor associated antigens that
contribute to the dampening of the
immune response in many melanoma
tumors so that researchers can better
understand how to boost
immunogenicity against these antigens.
• Source material for tumor
associated peptides that could serve as
melanoma vaccine candidates or
utilized to determine the reactivity of
tumor infiltrating lymphocyte (TIL)
cultures being considered for clinical
trials.
• Source material for the
development of TIL cultures for use in
adoptive immunotherapy protocols to
treat melanoma patients.
Advantages
• Cell line is derived from a
melanoma patient that underwent
complete tumor remission: Immune cell
cultures capable of treating melanoma
patients in adoptive immunotherapy
protocols could be derived from the
tumor associated antigen epitopes found
on the 888-mel cell line. This cell line
may be a source of novel antigenic
peptides capable of triggering immune
responses in melanoma patients that
lead to tumor regression or stabilization.
888-mel cells have been shown to retain
many features of primary melanoma
samples, including the expression of
common tumor associated antigens.
• 888-mel is an HLA–A2 negative cell
line: A majority of the cancer vaccines
and immunotherapies developed to date
have focused on utilizing HLA–A2
restricted tumor epitopes since this HLA
allele is largely expressed in the human
population. However, therapies
restricted to HLA–A2 recognition will
not be successful in melanoma patients
that do not express this allele. For these
patients, additional therapies are
needed that are directed against
melanoma tumor epitopes presented by
different HLA alleles.
• The 888-mel cell line has been well
characterized through multiple years of
study and is a fundamental cell line for
melanoma studies: The collection of
tumor associated antigens expressed by
this cell line have been determined
through multiple studies, many of
which were performed by researchers in
the inventors’ laboratory. A significant
amount of data has also been compiled
detailing the immune responses
triggered by 888-mel cells.
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Inventors: Steven A. Rosenberg (NCI)
et al.
Selected Publications
1. J Weber et al. Expression of the
MAGE–1 tumor antigen is up-regulated
by the demethylating agent 5-aza-21deoxycytidine. Cancer Res. 1994 Apr 1;
54(7):1766–1771. [PubMed: 7511051]
2. PF Robbins et al. Recognition of
tyrosinase by tumor-infiltrating
lymphocytes from a patient responding
to immunotherapy. Cancer Res. 1994
Jun 15; 54(12):3124–3126. Erratum in:
Cancer Res. 1994 Jul 15; 54(14):3952.
[PubMed: 8205528]
3. PF Robbins et al. Multiple HLA
class II-restricted melanocyte
differentiation antigens are recognized
by tumor-infiltrating lymphocytes from
a patient with melanoma. J Immunol.
2002 Nov 15; 169(10):6036–6047.
[PubMed: 12421991]
Patent Status: HHS Reference No. E–
070–2010/0—Research Tool. Patent
protection is not being pursued for this
technology.
Licensing Status: Available for
licensing under a Biological Materials
License Agreement.
Licensing Contact: Samuel E. Bish,
PhD; 301–435–5282;
bishse@mail.nih.gov.
Collaborative Research Opportunity:
The Surgery Branch, National Cancer
Institute, is seeking statements of
capability or interest from parties
interested in collaborative research to
carry out genotypic as well as
phenotypic analysis of the 888-mel cell
line in order to better understand the
nature of tumor cells that respond to
therapy. In addition, this cell line can be
used as a target of humoral or cell
mediated immune responses as a part of
studies characterizing the nature of
immune responses directed against
tumor cells. Please contact John Hewes,
PhD at 301–435–3131 or
hewesj@mail.nih.gov for more
information.
UOK171, A Spontaneous Clear Cell
Type Renal Cell Carcinoma (ccRCC)
Human Cell Line Derived From a
Surgically Removed Tumor
Description of Invention: Scientists at
the National Institutes of Health (NIH)
have developed a renal cell carcinoma
(RCC) cell line designated UOK171 from
the resected tumor of a patient
diagnosed with stage IV high nuclear
grade clear cell type renal cell
carcinoma (ccRCC). The UOK171 cell
line was immortalized spontaneously by
mincing the resected tumor into pieces
followed by propagation of the cells
over more than twenty generations. One
of the most prominent characteristics of
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this cell line is its intact, nonmutated
von Hippel-Lindau (VHL) tumor
suppressor gene. In the majority of
sporadic and hereditary ccRCC cases,
the VHL gene is functionally disrupted
due to hypermethylation or the gene is
completely lost. Thus, the UOK171 cell
line is very useful as a positive control
for VHL gene expression in studies of
the genetic and molecular mechanisms
underlying advanced ccRCC, a disease
for which there is no effective treatment.
Specifically, this cell line has been used
as a non-methylated control cell line in
studying the effects of 5–Aza-dCyd and
Zebularine on VHL re-expression from
methylated-VHL cell line models. These
agents do not affect the methylation
status of the VHL gene in UOK171. This
cell line also exhibits decreased
fibroblast growth factor 5 (FGF5)
expression, unbalanced chromosome 3
translocations, translocations involving
chromosome 14, the losses of
chromosome 14 and 22, and
chromosome structural aberration 1(8)
(q10). UOK171 is also one of the 40member cell lines in the National
Cancer Institute (NCI) Urologic
Oncology Branch (UOB) Tumor Cell
Line Repository.
Applications
• Research tool for investigating the
underlying molecular mechanisms
contributing to advanced ccRCC,
including the identification of new RCC
tumor antigens for immunotherapy.
• Research tool for studying the
methylation status of genes involved in
ccRCC to reveal the genetic processes
occurring in ccRCC tissues that may
contribute to advanced disease.
• Positive control cell line for VHL
gene expression and function studies,
including cytogenetics, gene mutation
research, and examination of
chromosomal structural abnormalities
that may contribute to ccRCC.
• Research tools for testing the
activity of potential anti-cancer drugs
against ccRCC, a disease which has no
effective treatment options.
• Possible starting material for
developing a cancer vaccine against
RCC.
Advantages
• Cell line is derived from a ccRCC
patient: These cell lines are anticipated
to retain many features of primary
ccRCC samples and novel ccRCC
antigens identified from this cell line
are likely to correlate with antigens
expressed on human ccRCC tumors.
Studies performed using these cell lines
may have a direct correlation to the
initiation, progression, treatment, and
prevention of ccRCC in humans.
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• Expresses a non-mutated VHL gene:
In the majority of advanced ccRCC
patients the VHL gene has been mutated
or deleted. The UOK171 cell line
represents a tool that can be utilized to
study the impact of this VHL gene and
various mutations on advanced ccRCC.
• Molecular and genetic features are
well characterized: This cell line is part
of NCI Urologic Oncology Branch’s
Tumor Cell Line Repository. The
inventor has elucidated many physical
characteristics of the cell line, including
chromosomal attributes and important
ccRCC genes, under various conditions.
Inventor: W. Marston Linehan (NCI).
srobinson on DSKHWCL6B1PROD with NOTICES
Related Publications
1. WG Alleman et al. The in vitro and
in vivo effects of re-expressing
methylated von Hippel-Lindau tumor
suppressor gene in clear cell renal
carcinoma with 5-Aza-2′-deoxycytidine.
Clin Cancer Res. 2004 Oct 15;
10(20):7011–7021. [PubMed: 15501981]
2. CP Pavlovich et al. Patterns of
aneuploidy in stage IV clear cell renal
carcinoma revealed comparative
genomic hybridization and spectral
karyotyping. Genes Chromosomes
Cancer. 2003 Jul; 37(3):252–260.
[PubMed: 12759923]
3. K Hanada et al. Identification of
fibroblast growth factor-5 as an
overexpressed antigen in multiple
human adenocarcinomas. Cancer Res.
2001 Jul 15; 61(14):5511–5516.
[PubMed: 11454700]
4. C Stolle et al. Improved detection
of germline mutations in the von
Hippel-Lindau disease tumor
suppressor gene. Hum Mutat. 1998;
12(6):417–423. [PubMed: 9829911]
5. P Anglard et al. Molecular and
cellular characterization of human renal
cell carcinoma cell lines. Cancer Res.
1992 Jan 15; 52(2):348–356. [PubMed:
1345811]
Patent Status: HHS Reference No. E–
033–2010/0—Research Tool. Patent
protection is not being pursued for this
technology.
Licensing Status: Available for
licensing under a Biological Materials
License Agreement.
Licensing Contact: Samuel E. Bish,
Ph.D.; 301–435–5282;
bishse@mail.nih.gov.
Collaborative Research Opportunity:
The Urologic Oncology Branch, Center
for Cancer Research, is seeking
statements of capability or interest from
parties interested in collaborative
research to further develop, evaluate, or
commercialize UOK171. Please contact
John Hewes, Ph.D. at 301–435–3131 or
hewesj@mail.nih.gov for more
information.
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Delivery of Transthyretin (TTR) Across
the Blood Brain Barrier as a Treatment
for Alzheimer’s Disease
Description of Invention: The
invention describes products and
methods of treating Alzheimer’s disease.
Alzheimer’s disease is characterized by
the formation of amyloid plaques and
tangles in areas of the brain critical for
learning and memory. The products are
a transthyretin and other blood brain
barrier impermeable proteins
transformed into blood brain barrier
permeable forms by the coupling of an
Inter-Cellular Adhesion Molecule-1
(ICAM-1) targeting agent. Transthyretin
binds to, and inhibits amyloid protein
from forming plaque deposits.
Deposition of amyloid is thought to
underlie the disease pathology of
Alzheimer’s. Thus, this invention treats
Alzheimer’s by inhibiting the formation
of amyloid plaques, which normally
would result in amyloid plaque
formation, inflammation, and neuronal
cell death.
Applications
• Therapeutic for Alzheimer’s
disease.
• Therapeutic for other amyloidrelated diseases.
Development Status: Early stage.
Market: As of 2007 over 5 million
people in America are living with
Alzheimer’s disease.
Inventors: Juan Marugan et al.
(NHGRI)
Patent Status: U.S. Provisional
Application No. 61/286,205 filed 14 Dec
2009 (HHS Reference No. E–268–2009/
0–US–01).
Licensing Status: Available for
licensing.
Licensing Contact: Steve Standley,
Ph.D.; 301–435–4074;
sstand@od.nih.gov.
Collaborative Research Opportunity:
The NIH Chemical Genomics Center
(NCGC) is open to collaborating in order
to further develop this invention. Please
contact Dr. Juan Marugan at
maruganj@mail.nih.gov for more
information about collaborative research
opportunities.
Vaccines Comprising Sand Fly Salivary
Proteins for Control of Leishmania
Infection
Description of Invention: This
invention relates to the use of several
peptides from the salivary glands of
various sand fly species for the control
of leishmania infection. Many of these
peptides were shown to be effective in
eliciting potent immune responses in
animal models and are excellent
candidates for the development of
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vaccines against the disease. A vaccine
comprising one of the peptides was
used to protect mice challenged with
parasites and salivary gland
homogenates. A DNA vaccine
containing the cDNA for this same
peptide also provided protection that
lasted at least 3 months after
immunization and produced both
intense humoral and delayed-type
hypersensitivity reactions. Other
experiments have shown that B celldeficient mice immunized with the
plasmid vaccine also successfully
controlled leishmania infection. Current
in-vivo studies continue to explore the
use of these sand fly salivary peptides
for use as animal vaccines.
Leishmania parasites are transmitted
to their vertebrate hosts by infected sand
fly bites. Sand fly saliva helps to
enhance infection but immunity to the
saliva protects against the infection,
allowing the possibility of vaccine
development. A number of major
salivary proteins from sand fly species
such as Lutzomyia longipalpis,
Phlebotomus ariasi, and Phlebotomus
perniciosus are claimed in the
invention.
Leishmania infection affects as many
as 12 million people worldwide, with
1.5–2 million new cases each year.
Control of this disease will be a major
milestone for public health efforts in
endemic areas of the world. The current
invention provides a potential means to
achieve widespread vaccination that
may lead to significantly control of the
disease in areas such as South America,
South Asia, and the Mediterranean
where it is still a significant health
problem. An effective veterinary vaccine
will be of benefit to veterinary medicine
and may pave the way for human
vaccines against Leishmaniasis. The
vaccination of animals may also have a
positive impact on the epidemiology of
the disease by reducing the number of
animal reservoirs and the possibility of
human infection.
Applications
• Vaccines to control leishmania
infection.
• Use of peptides to elicit potent
immune responses.
Development Status: Early stage.
Inventors: Jesus G. Valenzuela et al.
(NIAID).
Related Publications
1. Oliveira F, Jochim RC, Valenzuela
JG, Kamhawi S. Sand flies, Leishmania,
and transcriptome-borne solutions.
Parasitol Int. 2009 Mar; 58(1):1–5.
[PubMed: 18768167]
2. Valenzuela JG, Garfield M, Rowton
ED, Pham VM. Identification of the most
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abundant secreted proteins from the
salivary glands of the sand fly
Lutzomyia longipalpis, vector of
Leishmania chagasi. J Exp Biol. 2004
Oct; 207(Pt 21):3717–3729. [PubMed:
15371479]
3. Valenzuela JG, Belkaid Y, Garfield
MK, Mendez S, Kamhawi S, Rowton ED,
Sacks DL, Ribeiro JM. Toward a defined
anti-Leishmania vaccine targeting vector
antigens: Characterization of a
protective salivary protein. J Exp Med.
2001 Aug 6; 194(3):331–342. [PubMed:
11489952]
4. Belkaid Y., Valenzuela JG,
Kamhawi S., Rowton E., Sacks DL,
Ribeiro JM. Delayed-type
hypersensitivity to Phlebotomus
papatasi sand fly bite: An adaptive
response induced by the fly? Proc Natl
Acad Sci U S A. 2000 Jun 6;
97(12):6704–6709. [PubMed: 10841567]
srobinson on DSKHWCL6B1PROD with NOTICES
• U.S. Patent Application No. 60/
422,303 filed October 29, 2002 (HHS
Ref. No. E–285–2002/0–US–01).
• PCT Application No. PCT/US2003/
03453 filed October 29, 2003 (HHS Ref.
No E–285–2002/0–PCT–02).
Application filed in the following
countries: the USA, Europe, Brazil,
Japan, Mexico, India and Israel.
• U.S. Patent No. 7,485,386 issued
February 3, 2009 (HHS Reference No. E–
285–2002/0–US–03).
• European Patent Number No.
1572968 issued April 22, 2009 (HHS
Reference No. E–285–2002/0–EP–04).
• PCT Application No. PCT/US2009/
042980 filed May 05, 2009 (HHS
Reference No. E–189–2008/2–PCT–01).
• U.S. Patent Application No. 60/
421,327 filed September 19, 2002 (HHS
Ref. No. E–130–2002/0–US–01).
• PCT Application No. PCT/US03/
29833 filed September 18, 2003 (HHS
Ref. No. E–130–2002/0–PCT–02).
Application filed in the following
countries: USA, Europe, Brazil, Japan,
Mexico, India and Israel.
Licensing Status: Available for
licensing.
Licensing Contact: John Stansberry,
PhD; 301–435–5236;
stansbej@mail.nih.gov.
Collaborative Research Opportunity:
The NIAID, OTD is seeking statements
of capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize ‘‘Vaccines Comprising
Sand Fly Salivary Proteins for Control of
Leishmania Infection’’. Please contact
Dana Hsu at 301–451–3521 for more
information.
16:01 Jun 03, 2010
[FR Doc. 2010–13480 Filed 6–3–10; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2008–D–0406]
Information Sheet Guidance for
Sponsors, Clinical Investigators, and
IRBs; Frequently Asked Questions—
Statement of Investigator (Form FDA
1572); Availability
AGENCY:
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Food and Drug Administration,
HHS.
ACTION:
Patent Status
VerDate Mar<15>2010
Dated: May 26, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
Notice.
SUMMARY: The Food and Drug
Administration (FDA) is announcing the
availability of an information sheet
guidance entitled, ‘‘Information Sheet
Guidance for Sponsors, Clinical
Investigators, and IRBs; Frequently
Asked Questions—Statement of
Investigator (Form FDA 1572).’’ This
guidance is intended to assist sponsors,
clinical investigators, and institutional
review boards (IRBs) involved in
clinical investigations of investigational
drugs and biologics in completing the
Statement of Investigator form (Form
FDA 1572). FDA developed this
information sheet guidance in response
to numerous questions from the
research community regarding Form
FDA 1572. This information sheet
guidance provides FDA’s responses to
the most frequently asked questions.
DATES: Submit either written or
electronic comments on agency
guidances at any time.
ADDRESSES: Submit written requests for
single copies of the guidance to the
Division of Drug Information (HFD–
240), 10903 New Hampshire Ave.,
Silver Spring, MD 20993 or to the Office
of Communication, Training, and
Manufacturers Assistance (HFM–40),
Center for Biologics Evaluation and
Research, Food and Drug
Administration, 1401 Rockville Pike,
Rockville, MD 20852–1448. Send one
self-addressed adhesive label to assist
the office in processing your requests.
Submit electronic comments to https://
www.regulations.gov. See the
SUPPLEMENTARY INFORMATION section for
electronic access to the information
sheet guidance document.
FOR FURTHER INFORMATION CONTACT:
Joseph Salewski, Division of Scientific
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Investigations, Office of Compliance,
Center for Drug Evaluation and
Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Silver Spring MD 20993, 301–
796–3395.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of
an information sheet guidance entitled,
‘‘Information Sheet Guidance for
Sponsors, Clinical Investigators, and
IRBs; Frequently Asked Questions—
Statement of Investigator (Form FDA
1572).’’ This guidance is intended to
assist sponsors, clinical investigators,
and IRBs involved in clinical
investigations of investigational drugs
and biologics in complying with the
requirement that each investigator
complete and sign a Form FDA 1572
before participating in an investigation.
This guidance describes how to
complete the Statement of Investigator
form (Form FDA 1572).
FDA developed this information sheet
guidance in response to numerous
questions from the research community
regarding the Form FDA 1572. In this
guidance, we provide answers to
frequently asked questions concerning
the purpose of this form, when this form
needs to be completed and signed by the
investigator, how to best complete the
various blocks within the form, and
when the form might need to be
updated. In addition, we clarify
questions related to the use of Form
FDA 1572 by clinical investigators
participating in studies conducted
outside the United States that may or
may not be under an investigational
new drug application.
This information sheet guidance is
part of the Information Sheet Guidance
Initiative, announced on February 3,
2006, in the Federal Register (71 FR
5861), which describes FDA’s intention
to update the process for developing,
issuing, and making available guidances
intended for IRBs, clinical investigators,
and sponsors. Known as ‘‘Information
Sheets,’’ these guidances have provided
recommendations to IRBs, clinical
investigators, and sponsors to help them
fulfill their responsibilities to protect
human subjects who participate in
research regulated by the FDA since the
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Guidance Initiative is intended to
ensure that the Information Sheets are
consistent with the FDA’s good
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E:\FR\FM\04JNN1.SGM
04JNN1
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[Federal Register Volume 75, Number 107 (Friday, June 4, 2010)]
[Notices]
[Pages 31791-31794]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2010-13480]
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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, 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 United States 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.
888-mel: A Target for Anti-Tumor Immune Responses
Description of Invention: Scientists at the National Institutes of
Health (NIH) have developed a human melanoma cell line designated 888-
mel from the resected tumor of a 26-year old Caucasian female (patient
888) diagnosed with metastatic melanoma, a frequently terminal cancer.
The 888-mel cell line was derived from three separate subcutaneous
melanoma lesions on the patient and possesses many characteristics
representative of melanoma cell lines developed by these researchers.
Most prominently, the 888-mel cell line was used to develop a tumor
infiltrating lymphocyte (TIL) culture with high affinity for the tumor
cells of patient 888. When the TIL 888 culture was provided as an
autologous adoptive immunotherapy treatment to patient 888 in
combination with interleukin-2 (IL-2), a complete remission of
subcutaneous, lung, and mucosal metastases was observed in the patient
for over three years.
Since this medical breakthrough, the 888-mel cell line has been
well characterized through various laboratory procedures and data
involving this cell line has been published as part of numerous
articles. Studies have shown that the cell line expresses a variety of
tumor associated antigens (TAAs), including tyrosinase, TRP1, TRP2,
gp100, MART-1, p15, gp75, mutated beta-catenin, and p53. However, 888-
mel does not normally express the MAGE 1, 2, or 3 TAAs. Many melanoma
cell lines are HLA-A2 restricted, but the 888-mel cell line is HLA-A2
negative. The HLA class I typing for this cell line is as follows: HLA-
A0101, A2402, B55, B62, Cw5201, Cw55, DRbl*1502, DRbl*1610, DQbl*0601,
DRb5*0102, DRb5*0203. 888-mel is a validated source of HLA class I
peptides utilized in screens that test the reactivity of TIL cultures
that are candidates for adoptive immunotherapy trials. 888-mel is also
a standard cell line for studying immune responses in cancer,
particularly T cell responses. Other experiments show that roscovitine,
a cyclin-dependent kinase inhibitor, can induce apoptosis in the 888-
mel cell line, so these cells may be useful in various cell death
studies.
[[Page 31792]]
Applications
Research tool for investigating the key immune responses
required to mediate the remission of metastatic melanoma in order to
identify the immune cell types necessary to produce an effective
immunotherapy.
Research tool for investigating the tumor associated
antigens that contribute to the dampening of the immune response in
many melanoma tumors so that researchers can better understand how to
boost immunogenicity against these antigens.
Source material for tumor associated peptides that could
serve as melanoma vaccine candidates or utilized to determine the
reactivity of tumor infiltrating lymphocyte (TIL) cultures being
considered for clinical trials.
Source material for the development of TIL cultures for
use in adoptive immunotherapy protocols to treat melanoma patients.
Advantages
Cell line is derived from a melanoma patient that
underwent complete tumor remission: Immune cell cultures capable of
treating melanoma patients in adoptive immunotherapy protocols could be
derived from the tumor associated antigen epitopes found on the 888-mel
cell line. This cell line may be a source of novel antigenic peptides
capable of triggering immune responses in melanoma patients that lead
to tumor regression or stabilization. 888-mel cells have been shown to
retain many features of primary melanoma samples, including the
expression of common tumor associated antigens.
888-mel is an HLA-A2 negative cell line: A majority of the
cancer vaccines and immunotherapies developed to date have focused on
utilizing HLA-A2 restricted tumor epitopes since this HLA allele is
largely expressed in the human population. However, therapies
restricted to HLA-A2 recognition will not be successful in melanoma
patients that do not express this allele. For these patients,
additional therapies are needed that are directed against melanoma
tumor epitopes presented by different HLA alleles.
The 888-mel cell line has been well characterized through
multiple years of study and is a fundamental cell line for melanoma
studies: The collection of tumor associated antigens expressed by this
cell line have been determined through multiple studies, many of which
were performed by researchers in the inventors' laboratory. A
significant amount of data has also been compiled detailing the immune
responses triggered by 888-mel cells.
Inventors: Steven A. Rosenberg (NCI) et al.
Selected Publications
1. J Weber et al. Expression of the MAGE-1 tumor antigen is up-
regulated by the demethylating agent 5-aza-2\1\-deoxycytidine. Cancer
Res. 1994 Apr 1; 54(7):1766-1771. [PubMed: 7511051]
2. PF Robbins et al. Recognition of tyrosinase by tumor-
infiltrating lymphocytes from a patient responding to immunotherapy.
Cancer Res. 1994 Jun 15; 54(12):3124-3126. Erratum in: Cancer Res. 1994
Jul 15; 54(14):3952. [PubMed: 8205528]
3. PF Robbins et al. Multiple HLA class II-restricted melanocyte
differentiation antigens are recognized by tumor-infiltrating
lymphocytes from a patient with melanoma. J Immunol. 2002 Nov 15;
169(10):6036-6047. [PubMed: 12421991]
Patent Status: HHS Reference No. E-070-2010/0--Research Tool.
Patent protection is not being pursued for this technology.
Licensing Status: Available for licensing under a Biological
Materials License Agreement.
Licensing Contact: Samuel E. Bish, PhD; 301-435-5282;
bishse@mail.nih.gov.
Collaborative Research Opportunity: The Surgery Branch, National
Cancer Institute, is seeking statements of capability or interest from
parties interested in collaborative research to carry out genotypic as
well as phenotypic analysis of the 888-mel cell line in order to better
understand the nature of tumor cells that respond to therapy. In
addition, this cell line can be used as a target of humoral or cell
mediated immune responses as a part of studies characterizing the
nature of immune responses directed against tumor cells. Please contact
John Hewes, PhD at 301-435-3131 or hewesj@mail.nih.gov for more
information.
UOK171, A Spontaneous Clear Cell Type Renal Cell Carcinoma (ccRCC)
Human Cell Line Derived From a Surgically Removed Tumor
Description of Invention: Scientists at the National Institutes of
Health (NIH) have developed a renal cell carcinoma (RCC) cell line
designated UOK171 from the resected tumor of a patient diagnosed with
stage IV high nuclear grade clear cell type renal cell carcinoma
(ccRCC). The UOK171 cell line was immortalized spontaneously by mincing
the resected tumor into pieces followed by propagation of the cells
over more than twenty generations. One of the most prominent
characteristics of this cell line is its intact, nonmutated von Hippel-
Lindau (VHL) tumor suppressor gene. In the majority of sporadic and
hereditary ccRCC cases, the VHL gene is functionally disrupted due to
hypermethylation or the gene is completely lost. Thus, the UOK171 cell
line is very useful as a positive control for VHL gene expression in
studies of the genetic and molecular mechanisms underlying advanced
ccRCC, a disease for which there is no effective treatment.
Specifically, this cell line has been used as a non-methylated control
cell line in studying the effects of 5-Aza-dCyd and Zebularine on VHL
re-expression from methylated-VHL cell line models. These agents do not
affect the methylation status of the VHL gene in UOK171. This cell line
also exhibits decreased fibroblast growth factor 5 (FGF5) expression,
unbalanced chromosome 3 translocations, translocations involving
chromosome 14, the losses of chromosome 14 and 22, and chromosome
structural aberration 1(8) (q10). UOK171 is also one of the 40-member
cell lines in the National Cancer Institute (NCI) Urologic Oncology
Branch (UOB) Tumor Cell Line Repository.
Applications
Research tool for investigating the underlying molecular
mechanisms contributing to advanced ccRCC, including the identification
of new RCC tumor antigens for immunotherapy.
Research tool for studying the methylation status of genes
involved in ccRCC to reveal the genetic processes occurring in ccRCC
tissues that may contribute to advanced disease.
Positive control cell line for VHL gene expression and
function studies, including cytogenetics, gene mutation research, and
examination of chromosomal structural abnormalities that may contribute
to ccRCC.
Research tools for testing the activity of potential anti-
cancer drugs against ccRCC, a disease which has no effective treatment
options.
Possible starting material for developing a cancer vaccine
against RCC.
Advantages
Cell line is derived from a ccRCC patient: These cell
lines are anticipated to retain many features of primary ccRCC samples
and novel ccRCC antigens identified from this cell line are likely to
correlate with antigens expressed on human ccRCC tumors. Studies
performed using these cell lines may have a direct correlation to the
initiation, progression, treatment, and prevention of ccRCC in humans.
[[Page 31793]]
Expresses a non-mutated VHL gene: In the majority of
advanced ccRCC patients the VHL gene has been mutated or deleted. The
UOK171 cell line represents a tool that can be utilized to study the
impact of this VHL gene and various mutations on advanced ccRCC.
Molecular and genetic features are well characterized:
This cell line is part of NCI Urologic Oncology Branch's Tumor Cell
Line Repository. The inventor has elucidated many physical
characteristics of the cell line, including chromosomal attributes and
important ccRCC genes, under various conditions.
Inventor: W. Marston Linehan (NCI).
Related Publications
1. WG Alleman et al. The in vitro and in vivo effects of re-
expressing methylated von Hippel-Lindau tumor suppressor gene in clear
cell renal carcinoma with 5-Aza-2'-deoxycytidine. Clin Cancer Res. 2004
Oct 15; 10(20):7011-7021. [PubMed: 15501981]
2. CP Pavlovich et al. Patterns of aneuploidy in stage IV clear
cell renal carcinoma revealed comparative genomic hybridization and
spectral karyotyping. Genes Chromosomes Cancer. 2003 Jul; 37(3):252-
260. [PubMed: 12759923]
3. K Hanada et al. Identification of fibroblast growth factor-5 as
an overexpressed antigen in multiple human adenocarcinomas. Cancer Res.
2001 Jul 15; 61(14):5511-5516. [PubMed: 11454700]
4. C Stolle et al. Improved detection of germline mutations in the
von Hippel-Lindau disease tumor suppressor gene. Hum Mutat. 1998;
12(6):417-423. [PubMed: 9829911]
5. P Anglard et al. Molecular and cellular characterization of
human renal cell carcinoma cell lines. Cancer Res. 1992 Jan 15;
52(2):348-356. [PubMed: 1345811]
Patent Status: HHS Reference No. E-033-2010/0--Research Tool.
Patent protection is not being pursued for this technology.
Licensing Status: Available for licensing under a Biological
Materials License Agreement.
Licensing Contact: Samuel E. Bish, Ph.D.; 301-435-5282;
bishse@mail.nih.gov.
Collaborative Research Opportunity: The Urologic Oncology Branch,
Center for Cancer Research, is seeking statements of capability or
interest from parties interested in collaborative research to further
develop, evaluate, or commercialize UOK171. Please contact John Hewes,
Ph.D. at 301-435-3131 or hewesj@mail.nih.gov for more information.
Delivery of Transthyretin (TTR) Across the Blood Brain Barrier as a
Treatment for Alzheimer's Disease
Description of Invention: The invention describes products and
methods of treating Alzheimer's disease. Alzheimer's disease is
characterized by the formation of amyloid plaques and tangles in areas
of the brain critical for learning and memory. The products are a
transthyretin and other blood brain barrier impermeable proteins
transformed into blood brain barrier permeable forms by the coupling of
an Inter-Cellular Adhesion Molecule-1 (ICAM-1) targeting agent.
Transthyretin binds to, and inhibits amyloid protein from forming
plaque deposits. Deposition of amyloid is thought to underlie the
disease pathology of Alzheimer's. Thus, this invention treats
Alzheimer's by inhibiting the formation of amyloid plaques, which
normally would result in amyloid plaque formation, inflammation, and
neuronal cell death.
Applications
Therapeutic for Alzheimer's disease.
Therapeutic for other amyloid-related diseases.
Development Status: Early stage.
Market: As of 2007 over 5 million people in America are living with
Alzheimer's disease.
Inventors: Juan Marugan et al. (NHGRI)
Patent Status: U.S. Provisional Application No. 61/286,205 filed 14
Dec 2009 (HHS Reference No. E-268-2009/0-US-01).
Licensing Status: Available for licensing.
Licensing Contact: Steve Standley, Ph.D.; 301-435-4074;
sstand@od.nih.gov.
Collaborative Research Opportunity: The NIH Chemical Genomics
Center (NCGC) is open to collaborating in order to further develop this
invention. Please contact Dr. Juan Marugan at maruganj@mail.nih.gov for
more information about collaborative research opportunities.
Vaccines Comprising Sand Fly Salivary Proteins for Control of
Leishmania Infection
Description of Invention: This invention relates to the use of
several peptides from the salivary glands of various sand fly species
for the control of leishmania infection. Many of these peptides were
shown to be effective in eliciting potent immune responses in animal
models and are excellent candidates for the development of vaccines
against the disease. A vaccine comprising one of the peptides was used
to protect mice challenged with parasites and salivary gland
homogenates. A DNA vaccine containing the cDNA for this same peptide
also provided protection that lasted at least 3 months after
immunization and produced both intense humoral and delayed-type
hypersensitivity reactions. Other experiments have shown that B cell-
deficient mice immunized with the plasmid vaccine also successfully
controlled leishmania infection. Current in-vivo studies continue to
explore the use of these sand fly salivary peptides for use as animal
vaccines.
Leishmania parasites are transmitted to their vertebrate hosts by
infected sand fly bites. Sand fly saliva helps to enhance infection but
immunity to the saliva protects against the infection, allowing the
possibility of vaccine development. A number of major salivary proteins
from sand fly species such as Lutzomyia longipalpis, Phlebotomus
ariasi, and Phlebotomus perniciosus are claimed in the invention.
Leishmania infection affects as many as 12 million people
worldwide, with 1.5-2 million new cases each year. Control of this
disease will be a major milestone for public health efforts in endemic
areas of the world. The current invention provides a potential means to
achieve widespread vaccination that may lead to significantly control
of the disease in areas such as South America, South Asia, and the
Mediterranean where it is still a significant health problem. An
effective veterinary vaccine will be of benefit to veterinary medicine
and may pave the way for human vaccines against Leishmaniasis. The
vaccination of animals may also have a positive impact on the
epidemiology of the disease by reducing the number of animal reservoirs
and the possibility of human infection.
Applications
Vaccines to control leishmania infection.
Use of peptides to elicit potent immune responses.
Development Status: Early stage.
Inventors: Jesus G. Valenzuela et al. (NIAID).
Related Publications
1. Oliveira F, Jochim RC, Valenzuela JG, Kamhawi S. Sand flies,
Leishmania, and transcriptome-borne solutions. Parasitol Int. 2009 Mar;
58(1):1-5. [PubMed: 18768167]
2. Valenzuela JG, Garfield M, Rowton ED, Pham VM. Identification of
the most
[[Page 31794]]
abundant secreted proteins from the salivary glands of the sand fly
Lutzomyia longipalpis, vector of Leishmania chagasi. J Exp Biol. 2004
Oct; 207(Pt 21):3717-3729. [PubMed: 15371479]
3. Valenzuela JG, Belkaid Y, Garfield MK, Mendez S, Kamhawi S,
Rowton ED, Sacks DL, Ribeiro JM. Toward a defined anti-Leishmania
vaccine targeting vector antigens: Characterization of a protective
salivary protein. J Exp Med. 2001 Aug 6; 194(3):331-342. [PubMed:
11489952]
4. Belkaid Y., Valenzuela JG, Kamhawi S., Rowton E., Sacks DL,
Ribeiro JM. Delayed-type hypersensitivity to Phlebotomus papatasi sand
fly bite: An adaptive response induced by the fly? Proc Natl Acad Sci U
S A. 2000 Jun 6; 97(12):6704-6709. [PubMed: 10841567]
Patent Status
U.S. Patent Application No. 60/422,303 filed October 29,
2002 (HHS Ref. No. E-285-2002/0-US-01).
PCT Application No. PCT/US2003/03453 filed October 29,
2003 (HHS Ref. No E-285-2002/0-PCT-02). Application filed in the
following countries: the USA, Europe, Brazil, Japan, Mexico, India and
Israel.
U.S. Patent No. 7,485,386 issued February 3, 2009 (HHS
Reference No. E-285-2002/0-US-03).
European Patent Number No. 1572968 issued April 22, 2009
(HHS Reference No. E-285-2002/0-EP-04).
PCT Application No. PCT/US2009/042980 filed May 05, 2009
(HHS Reference No. E-189-2008/2-PCT-01).
U.S. Patent Application No. 60/421,327 filed September 19,
2002 (HHS Ref. No. E-130-2002/0-US-01).
PCT Application No. PCT/US03/29833 filed September 18,
2003 (HHS Ref. No. E-130-2002/0-PCT-02). Application filed in the
following countries: USA, Europe, Brazil, Japan, Mexico, India and
Israel.
Licensing Status: Available for licensing.
Licensing Contact: John Stansberry, PhD; 301-435-5236;
stansbej@mail.nih.gov.
Collaborative Research Opportunity: The NIAID, OTD is seeking
statements of capability or interest from parties interested in
collaborative research to further develop, evaluate, or commercialize
``Vaccines Comprising Sand Fly Salivary Proteins for Control of
Leishmania Infection''. Please contact Dana Hsu at 301-451-3521 for
more information.
Dated: May 26, 2010.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 2010-13480 Filed 6-3-10; 8:45 am]
BILLING CODE 4140-01-P
