[Federal Register: March 18, 2003 (Volume 68, Number 52)]
[Notices]
[Page 12917-12918]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr18mr03-67]
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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 agencies 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.
IL-21 Critically Regulates Immunoglobulin Production
Warren J. Leonard, Katsutoshi Ozaki, and Rosanne Spolski (NHLBI)
U.S. Provisional Patent Application 60/393,215 filed 01 Jul 2002
Licensing Contact: Brenda Hefti; 301/435-4632; heftib@od.nih.gov.
The invention includes a mouse in which the IL-21 receptor gene is
disrupted by homologous recombination, the disruption being sufficient
to prevent expression of the IL-21 receptor and thus to inhibit the
action of IL-21. The invention also includes a mouse in which both the
IL-21 receptor gene and the IL-4 gene are simultaneously disrupted in
fashions being sufficient to inhibit the action of IL-21 and the
production of IL-4. In a homozygous state, these mutations produce a
mouse that has diminished B cell function.
This invention also relates to the use of agents that inhibit the
interaction of IL-21 with the IL-21 receptor to modulate an immune
response. This invention may be used to alter B cell activity, to treat
a subject with Job's disorder, to treat an allergic reaction in a
subject, or prevent an allergic reaction in a subject.
Grafting of a Murine Antibody Onto a Human Framework
S. Rybak, J. Krauss, M. Arndt, and A. Martin (NCI)
U.S. Provisional Patent Application 60/390,033 filed 17 June 2002
Licensing Contact: Brenda Hefti; 301/435-4632; heftib@od.nih.gov.
This invention relates to humanization of antibodies specifically
providing novel biophysically stable human framework sequences that can
be used to humanize antibody single chain Fv (scFv) fragments. An
exemplary RFB4 humanized scFv antibody was constructed using the new
sequences. The novel sequences were obtained after stringent panning of
a human phage display library on (irrelevant) antigen. These antibody
variable domain frameworks were subsequently used as human acceptor
scaffolds for grafting the murine antibody specificity. The general
approach described here differs from other humanization procedures
wherein appropriate human acceptor scaffolds are selected from either
antibodies with solved crystal structures or (germline) sequence
databases. In the current invention, human acceptor frameworks were
first pre-selected for
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stability. Appropriate framework sequences with high sequence
identities to the murine antibody to be humanized were then chosen from
the pre-selected pool of stable scaffolds. As a result, humanized scFv
fragments with low immunogenic potential and high biophysical stability
were generated.
In contrast to other methodologies, unusual human framework
residues were identified by aligning the human variable domain
sequences to several sequence reference templates from antibody
repertoires. The structural role of each identified unusual residue was
further examined on the basis of information of antibodies with known
crystal structures. Several residues were considered critical for
interfering with the structural integrity of the antigen binding site
and were successively back-mutated to the murine donor sequence. As a
result, a panel of three humanized scFv antibodies with nanomolar
affinity constants were generated. Importantly, the introduced back-
mutations did not alter the biophysical properties of the constructs.
Tumor Suppressor Gene Polypeptides and Related Nucleic Acids, Host
Cells, Compositions, and Methods of Use in Inhibition of Cell Growth,
Modulation of Gene Expression, and Enhancement of Immune-Response
Inducing Effect of a Vaccine
Denise Simmons (NCI)
DHHS Reference No. E-052-02/0 filed 03 May 2002
Licensing Contact: Matthew Kiser; 301/435-5236; kiserm@od.nih.gov.
Many cell lines have specific suppressor proteins that can inhibit
the proliferation of cancer cells. These regulatory proteins are
crucial in maintaining the fine line between appropriate proliferation
and over proliferation. It is when these regulatory suppressor proteins
become inactivated or over/under expressed that uncontrolled cell
growth leading to neoplasia can result.
It has been established that certain suppressor proteins can
inhibit cell proliferation: tazarotene-induced gene 3 (H-TIG-3), and
Hras Revertant gene 107 (H-rev107). Modification or over/under
expression of these proteins can cause excessive cellular
proliferation. It is now known that these proteins, as well as a
candidate tumor suppressor protein, lecithin:retinol acyl transferase
(LRAT) share a homologous region. The subject invention pertains to a
group of short polypeptide sequences that are based on this homologous
region. These short polypeptides are effective tumor suppressors.
The scope of this invention includes amino acid sequences and the
corresponding nucleic acid sequences that encode the polypeptides.
Modifications of the polypeptide sequences include both substitution
and additions. The subject invention also applies to the method of
inhibiting cell growth, a method of modulating gene expression, and a
method of enhancing the immune response-inducing effect of a vaccine.
Material and Methods for Inhibiting Wip1
Dimtry V. Bulavin (NCI), Ettore Appella (NCI), Albert Fornace (NCI),
Anne Kallioniemi (NCI)
DHHS Reference No. E-002-02/0 filed 22 Mar 2002
Licensing Contact: Matthew Kiser; 301/435-5236; kiserm@od.nih.gov.
p53 protein is an attractive cancer-therapeutics target since it is
expressed in all normal cells and is important for cancer cell
apoptosis (death). The p53 protein provides a cellular self-destruct
signal when DNA damage has occurred. Under expression of this protein
can cause damaged cells to proliferate causing cancer. A potential
proto-oncogene, wild-type p53-induced phosphatase 1 (Wip1), has been
implicated in the down regulation of p53. Therapeutic strategies that
can block Wip1 will increase the activity of p53 thus preventing cancer
cell proliferation in p53 wt tumors that over-express Wip1. The subject
invention pertains to isolated and purified oligonucleotides or
isolated and purified morpholino oligonucleotides with the ability to
inhibit Wip1 expression. These oligomers can be used for the treatment
of cancer. In addition to practical uses of the oligomers, a
methodology for screening standard and morpholino oligonucleotides for
Wip1 inhibition is included. Finally, a methodology to test the
efficacy of standard and morpholino test oligonucleotides completes
this invention.
Attenuated and Dominant Negative Variant cDNAs of STAT6: STAT6b and
STAT6c
William LaRochelle, Bharvin K.R. Patel, Jacalyn H. Pierce (all of NCI)
Serial No. 09/511,625 filed 23 Feb. 2000, now U.S. Patent 6,368,828
issued 09 Apr. 2002.
Licensing Contact: Susan S. Rucker; 301/435-4478; ruckers@od.nih.gov.
This patent relates to signal transduction pathways. In particular,
the patent relates to transcription factors. The transcription factors
described in the patent are members of the family of transcription
factors known as Signal Transducers and Activators of Transcription
(STATs). More particularly, the patent discloses the identification,
isolation, sequencing and cloning of cDNAs that encode naturally
occurring variants, Stat6b and Stat6c, of the protein STAT6.
The Stat6b variant contains an NH2 terminal deletion of
naturally occurring Stat6. The Stat6c variant contains an internal
deletion, within the SH2 domain, of naturally occurring Stat6. The
naturally occurring variants exhibit different properties. Stat6b acts
as an attenuated variant, with respect to IL-4 induced MHC class II and
Fc receptor cell surface expression, promoter binding and
transcriptional activation when compared to Stat6. Stat6c acts as a
dominant negative variant with respect to IL-4 mediated up-regulation
of the cell surface antigens CD16/CD32 and CD23. The role of both
variants in mediating IL-4 activity suggests that either could be
useful in developing drugs for targeting diseases involving
inflammatory and cell-mediated immune responses such as asthma.
The patent includes claims to the Stat6 variant polypeptides, the
nucleic acids, vectors for expression of the variants, cells into which
the variants have been introduced and methods of producing the Stat6
variant polypeptides.
This work has been published in part at B.K.R. Patel et al., PNAS
USA 95: 175-77 (Jan. 1998).
Dated: March 12, 2003.
Steven M. Ferguson,
Acting Director, Division of Technology Development and Transfer,
Office of Technology Transfer, National Institutes of Health.
[FR Doc. 03-6443 Filed 3-17-03; 8:45 am]
BILLING CODE 4140-01-P