Government-Owned Inventions; Availability for Licensing, 44665-44667 [05-15347]
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Federal Register / Vol. 70, No. 148 / Wednesday, August 3, 2005 / Notices
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NIH-Funded Behavioral Researchers.
Post-doctoral Fellows .......................
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Comments Due Date: Comments
regarding this information collection are
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Dated: July 27, 2005.
LaVerne Stringfield,
Acting Executive Officer, Office of the
Director, National Institutes of Health.
[FR Doc. 05–15239 Filed 8–2–05; 8:45 am]
BILLING CODE 4140–01–M
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing
National Institutes of Health,
Public Health Service, HHS.
ACTION: Notice.
AGENCY:
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/
PO 00000
Frm 00113
Fmt 4703
Sfmt 4703
496–7057; fax: 301/402–0220. A signed
Confidential Disclosure Agreement will
be required to receive copies of the
patent applications.
A Method With Increased Yield for
Production of Polysaccharide-Protein
Conjugate Vaccines Using Hydrazide
Chemistry
Che-Hung Robert Lee and Carl Frasch
(FDA).
U.S. Provisional Application No. 60/
493,389 filed 06 Aug 2003 (HHS
Reference No. E–301–2003/0–US–01);
PCT Application No. PCT/US04/25477
filed 06 Aug 2004 (HHS Reference No.
E–301–2003/0–PCT–02);
PCT Application No. PCT/US04/26431
filed 06 Aug 2004 (HHS Reference No.
E–301–2003/1–PCT–01).
Licensing Contact: Peter Soukas; 301/
435–4646; soukasp@mail.nih.gov.
Current methods for synthesis and
manufacturing of polysaccharideprotein conjugate vaccines employ
conjugation reactions with low
efficiency (about twenty percent). This
means that up to eighty percent of the
added activated polysaccharide (PS) is
lost. In addition, inclusion of a
chromatographic process for
purification of the conjugates from
unconjugated PS is required.
The present invention utilizes the
characteristic chemical property of
hydrazide groups on one reactant to
react with aldehyde groups or cyanate
esters on the other reactant with an
improved conjugate yield of at least
sixty percent. With this conjugation
efficiency the leftover unconjugated
protein and polysaccharide would not
need to be removed and thus the
purification process of the conjugate
product can be limited to diafiltration to
E:\FR\FM\03AUN1.SGM
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Federal Register / Vol. 70, No. 148 / Wednesday, August 3, 2005 / Notices
remove the by-products of small
molecules. The new conjugation
reaction can be carried out within one
or two days with reactant
concentrations between 1 and 25 mg/mL
at PS/protein ratios from 1:2 to 3:1, at
temperatures between 4 and 40 degrees
Centigrade, and in a pH range of 5.5 to
7.4, optimal conditions varying from PS
to PS.
Therefore, this invention can reduce
the cost of conjugate vaccine
manufacture.
Modulators of Nuclear Hormone
Receptor Activity: Novel Compounds,
Diverse Applications for Infectious
Diseases, Including Anthrax (B.
anthracis)
E.M. Sternberg (NIMH), J.I. Webster
(NIMH), L. H. Tonelli (NIMH), S. H.
Leppla (NIAID), and M. Maoyeri
(NIAID).
U.S. Provisional Application No. 60/
416,222 filed 04 Oct 2002 (HHS
Reference No. E–247–2002/0–US–01);
U.S. Provisional Application No. 60/
419,454 filed 18 Oct 2002 (HHS
Reference No. E–348–2003/0–US–01);
PCT Application No. PCT/US03/31406
filed 03 Oct 2003 (HHS Reference No.
E–247–2002/1–PCT–01);
U.S. Patent Application No. 10/530,254
filed 04 Apr 2005 (HHS Reference No.
E–247–2002/1–US–02).
Licensing Contact: Peter Soukas; 301/
435–4646; soukasp@mail.nih.gov.
Technology summary and benefits:
Nuclear hormones such as
glucocorticoids dampen inflammatory
responses, and thus provide protection
to mammals against inflammatory
disease and septic shock. The Anthrax
lethal factor represses nuclear hormone
receptor activity, and thus may
contribute to the infectious agent
causing even more damage to the host.
This observation can be exploited to
find new means of studying and
interfering with the normal function of
nuclear hormone receptors. Scientists at
NIH have shown that under the
appropriate conditions, these molecules
can be used to modulate the activity of
various nuclear hormone receptors.
Identifying useful agents that modify
these important receptors can provide
relief in several human disorders such
as inflammation, autoimmune disorders,
arthritis, malignancies, shock and
hypertension.
Long-term potential applications: This
invention provides novel agents that can
interfere with the action of nuclear
hormone receptors. It is well known that
malfunction or overdrive of these
receptors can lead to a number of
diseases such as enhanced
inflammation; worse sequelae of
VerDate jul<14>2003
15:22 Aug 02, 2005
Jkt 205001
infection including shock; diabetes;
hypertension and steroid resistance.
Hence a means of controlling or finetuning the activity of these receptors can
be of great benefit. Current means of
affecting steroid receptor activity are
accompanied by undesirable sideeffects. Since the conditions for which
these treatments are sought tend to be
chronic, there is a critical need for safer
drugs that will have manageable sideeffects.
Uniqueness or innovativeness of
technology: The observation that the
lethal factor from Anthrax has a striking
effect on the activity of nuclear hormone
receptors opens up new routes to
controlling their activity. The means of
action of this repressor is sufficiently
different from known modulators of
hormone receptors (i.e. the classical
antagonists). For instance, the
repression of receptor activity is noncompetitive, and does not affect
hormone binding or DNA binding. Also,
the efficacy of nuclear hormone receptor
repression by Anthrax lethal factor is
sufficiently high that the
pharmacological effect of this molecule
is seen at vanishingly small
concentrations. Taken together, these
attributes may satisfy some of the
golden rules of drug development such
as the uniqueness or novelty of the
agent’s structure, a low threshold for
activity, high level of sophistication and
knowledge in the field of enquiry, and
the leeway to further refine the
molecule by rational means.
Stage of Development: In vitro studies
have been completed, and a limited
number of animal studies have been
carried out.
Methods and Compositions for
Production and Purification of
Recombinant Staphylococcal
Enterotoxin B (rSEB)
Daniel Coffman, Steven Giardina,
Jianwei Zhu (NCI).
U.S. Provisional Application No. 60/
328,017 filed 09 Oct 2001 (HHS
Reference No. E–075–2001/0–US–01);
PCT Application No. PCT/US02/31114
filed 27 Sep 2002 (HHS Reference No.
E–075–2001/0–PCT–01);
U.S. Patent Application No. 10/492,105
filed 08 Apr 2004 (HHS Reference No.
E–075–2001/0–US–02).
Licensing Contact: Peter Soukas; 301/
435–4646; soukasp@mail.nih.gov.
This invention claims processes and
compositions for fermentation, recovery,
and purification of recombinant
bacterial superantigens (rSAgs),
exemplified by a recombinant
staphylococcal enterotoxin B SEB
(rSEB) protein mutated for use in
administration to a mammalian
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recipient. This process generates an
economically viable quantity of rSEB
vaccine protein meeting FDA parenteral
drug specifications. The purification
methods generally involve multiple
steps including hydrophobic interaction
chromatography (HIC), buffer exchange
(desalting), and cation exchange. The
final product of the purification is a
highly purified rSAg composition
satisfying clinical safety criteria and is
immunogenic and protective against
lethal aerosol challenge in a murine
model. The methods and compositions
claimed in the patent application
provide possible therapeutics and
prophylactics for diseases caused by
bacterial SAgs, such as food poisoning,
bacterial arthritis and other autoimmune
disorders, toxic shock syndrome, and
the potential use of SAg biowarfare
agents.
Method for Determining Sensitivity to a
Bacteriophage
Carl R. Merril (NIMH), Sankar Adhya
(NCI), Dean M. Scholl (NIMH).
U.S. Provisional Application No. 60/
351,458 filed 23 Jan 2002 (HHS
Reference No. E–318–2000/0–US–01);
PCT Application No. PCT/US03/02179
filed 23 Jan 2003 (HHS Reference No.
E–318–2000/0–PCT–02);
U.S. Patent Application No. 10/498,428
filed 10 Jun 2004 (HHS Reference No.
E–318–2000/0–US–03).
Licensing Contact: Peter Soukas; 301/
435–4646; soukasp@mail.nih.gov.
Traditionally, chemical antibiotics
have been used to treat a variety of
bacterial infections. However, bacterial
resistance to current antibiotics is an
increasingly serious problem in human
and veterinary health as well as
agriculture. Many experts believe that
strains of disease-causing bacteria
resistant to all common antibiotics will
arise in the next ten to twenty years.
Bacteriophages offer a promising
therapeutic alternative to antibiotics for
these antibiotic resistant bacteria. There
are also situations in which
bacteriophage may be more suitable
than antibiotics to treat infections
caused by against antibiotic-sensitive
bacteria. Bacteriophages are highly hostspecific, thus determining whether a
phage would be therapeutically useful
against a particular bacterium or strain
of bacteria is very important but can be
a time-consuming and labor-intensive
process.
The current invention claims a
method for selecting a therapeutic
bacteriophage that would be effective
against a particular disease-causing
bacteria, comprising a number of
bacteriophages containing reporter
nucleic acids capable of being expressed
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Federal Register / Vol. 70, No. 148 / Wednesday, August 3, 2005 / Notices
when the bacteriophage infects a
bacterial cell. These bacteriophages are
separately contacted with a sample
contaminated by a bacterium.
Expression of the reporter is then
detected, indicating which
bacteriophage has infected a bacterial
cell and is thus a potential therapeutic
phage against the particular bacteria.
Also claimed in the application are kits
allowing for the rapid identification of
potentially therapeutic bacteriophages.
Bacteriophage Having Multiple Host
Range
Carl Merril (NIMH), Sankar Adhya
(NCI), Dean Scholl (NIMH).
U.S. Provisional Application No. 60/
220,987 filed 25 Jul 2000 (HHS
Reference No. E–257–2000/0–US–01);
PCT Application No. PCT/US01/22390
filed 25 Jul 2001 (HHS Reference No.
E–257–2000/0–PCT–02);
U.S. Patent Application No. 10/350,256
filed 21 Jan 2003 (HHS Reference No.
E–257–2000/0–US–03).
Licensing Contact: Peter Soukas; 301/
435–4646; soukasp@mail.nih.gov.
Recently, there has been a renewed
interest in the use of phages to treat
bacterial infections. The inventors have
discovered FK1–5, a highly lytic, nonlysogenic, stable bacteriophage with the
ability to kill bacteria rapidly, making it
a good candidate for phage therapy. The
designation FK1–5 denotes the phage’s
ability to infect E. coli strains that
contain the K1 polysaccharide in their
outer capsule as well as E. coli strains
that contain the K5 polysaccharide in
their outer capsule. Sequence analysis
of the tail proteins of phage FK1–5 by
the inventors has shown that they are
arranged in a cassette structure,
suggesting that the host range of phages
can be broadened to other K antigens,
and even possibly other species of
bacteria by recombinant techniques.
FK1–5 has a particular advantage
because it recognizes and attaches to the
structures that confer virulence to
bacteria. The inventors’ demonstration
that a phage can contain multiple tail
proteins that expand its host range is
useful for generating phage with broadspectrum antibacterial properties for the
treatment of infectious diseases. The
inventors have completed in vitro
studies on this phage. Furthermore,
because of the possibility of engineering
the expression of recombinant tail
proteins, gene transfer to organisms that
are not normally infected by phages is
also contemplated by the invention.
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15:22 Aug 02, 2005
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CC Chemokine Receptor 5 DNA, New
Animal Models and Therapeutic Agents
for HIV Infection
C. Combadiere, Y. Feng, E.A. Berger, G.
Alkahatib, P.M. Murphy, C.C. Broder,
P.E. Kennedy (NIAID).
U.S. Provisional Application No. 60/
018,508 filed 28 May 1996 (HHS
Reference No. E–090–1996/0–US–01);
U.S. Patent Application No. 08/864,458
filed 28 May 1997 (HHS Reference
No. E–090–1996/0–US–04);
U.S. Patent Application No. 10/439,845
filed 15 May 2003 (HHS Reference
No. E–090–1996/0–US–05);
U.S. Patent Application No. 10/700,313
filed 31 Oct 2003 (HHS Reference No.
E–090–1996/0–US–06);
U.S. Patent Application No. 10/846,185
filed 14 May 2004 (HHS Reference
No. E–090–1996/0–US–07);
PCT Application No. PCT/US97/09586
filed 28 May 1997 (HHS Reference
No. E–090–1996/0–PCT–02);
European Patent Application No.
97929777.7 filed 28 May 1997 (HHS
Reference No. E–090–1996/0–EP–03).
Licensing Contact: Peter Soukas; 301/
435–4646; soukasp@mail.nih.gov.
Chemokine receptors are expressed by
many cells, including lymphoid cells,
and function to mediate cell trafficking
and localization. CC chemokine receptor
5 (CCR5) is a seven-transmembrane, G
protein-coupled receptor (GPCR) which
regulates trafficking and effector
functions of memory/effector Tlymphocytes, macrophages, and
immature dendritic cells. Chemokine
binding to CCR5 leads to cellular
activation through pertussis toxinsensitive heterotrimeric G proteins as
well as G protein-independent
signalling pathways. Like many other
GPCR, CCR5 is regulated by agonistdependent processes which involve G
protein coupled receptor kinase (GRK)dependent phosphorylation, betaarrestin-mediated desensitization and
internalization.
Human CCR5 also functions as the
main coreceptor for the fusion and entry
of many strains of human
immunodeficiency virus (HIV–1, HIV–
2). HIV–1 transmission almost
invariably involves such CCR5-specific
variants (designated R5); individuals
lacking functional CCR5 (by virtue of
homozygosity for a defective CCR5
allele) are almost completely resistant to
HIV–1 infection. Specific blocking of
CCR5 (e.g. with chemokine ligands,
anti-CCR5 antibodies, CCR5-blocking
low MW inhibitors, etc.) inhibits entry/
infection of target cells by R5 HIV
strains. Cells expressing CCR5 and CD4
are useful for screening for agents that
inhibit HIV by binding to CCR5. Such
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44667
agents represent potential new
approaches to block HIV transmission
and to treat infected people. A small
animal expressing both human CCR5
along with human CD4 supports entry
of HIV into target cells, a necessary
hurdle that must be overcome for
development of a small animal model
(e.g. transgenic mouse, rat, rabbit, mink)
to study HIV infection and its
inhibition.
The invention embodies the CCR5
genetic sequence, cell lines and
transgenic mice, the cells of which
coexpress human CD4 and CCR5, and
which may represent valuable tools for
the study of HIV infection and for
screening anti-HIV agents. The
invention also embodies anti-CCR5
agents that block HIV env-mediated
membrane fusion associated with HIV
entry into human CD4-positive target
cells or between HIV-infected cells and
uninfected human CD4-positive target
cells.
This technology was reported in
Alkhatib et al., ‘‘CC CKR5: a RANTES,
MIP–1alpha, MIP–1beta receptor as a
fusion cofactor for macrophage-tropic
HIV–1,’’ Science 272:1955–1958 (1996).
The technology is available for
exclusive or nonexclusive licensing.
Dated: July 19, 2005.
Steven M. Ferguson,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 05–15347 Filed 8–2–05; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing
National Institutes of Health,
Public Health Service, DHHS.
ACTION: Notice.
AGENCY:
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
E:\FR\FM\03AUN1.SGM
03AUN1
]]>Agencies
[Federal Register Volume 70, Number 148 (Wednesday, August 3, 2005)]
[Notices]
[Pages 44665-44667]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-15347]
-----------------------------------------------------------------------
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 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.
A Method With Increased Yield for Production of Polysaccharide-Protein
Conjugate Vaccines Using Hydrazide Chemistry
Che-Hung Robert Lee and Carl Frasch (FDA).
U.S. Provisional Application No. 60/493,389 filed 06 Aug 2003 (HHS
Reference No. E-301-2003/0-US-01);
PCT Application No. PCT/US04/25477 filed 06 Aug 2004 (HHS Reference No.
E-301-2003/0-PCT-02);
PCT Application No. PCT/US04/26431 filed 06 Aug 2004 (HHS Reference No.
E-301-2003/1-PCT-01).
Licensing Contact: Peter Soukas; 301/435-4646; soukasp@mail.nih.gov.
Current methods for synthesis and manufacturing of polysaccharide-
protein conjugate vaccines employ conjugation reactions with low
efficiency (about twenty percent). This means that up to eighty percent
of the added activated polysaccharide (PS) is lost. In addition,
inclusion of a chromatographic process for purification of the
conjugates from unconjugated PS is required.
The present invention utilizes the characteristic chemical property
of hydrazide groups on one reactant to react with aldehyde groups or
cyanate esters on the other reactant with an improved conjugate yield
of at least sixty percent. With this conjugation efficiency the
leftover unconjugated protein and polysaccharide would not need to be
removed and thus the purification process of the conjugate product can
be limited to diafiltration to
[[Page 44666]]
remove the by-products of small molecules. The new conjugation reaction
can be carried out within one or two days with reactant concentrations
between 1 and 25 mg/mL at PS/protein ratios from 1:2 to 3:1, at
temperatures between 4 and 40 degrees Centigrade, and in a pH range of
5.5 to 7.4, optimal conditions varying from PS to PS.
Therefore, this invention can reduce the cost of conjugate vaccine
manufacture.
Modulators of Nuclear Hormone Receptor Activity: Novel Compounds,
Diverse Applications for Infectious Diseases, Including Anthrax (B.
anthracis)
E.M. Sternberg (NIMH), J.I. Webster (NIMH), L. H. Tonelli (NIMH), S. H.
Leppla (NIAID), and M. Maoyeri (NIAID).
U.S. Provisional Application No. 60/416,222 filed 04 Oct 2002 (HHS
Reference No. E-247-2002/0-US-01);
U.S. Provisional Application No. 60/419,454 filed 18 Oct 2002 (HHS
Reference No. E-348-2003/0-US-01);
PCT Application No. PCT/US03/31406 filed 03 Oct 2003 (HHS Reference No.
E-247-2002/1-PCT-01);
U.S. Patent Application No. 10/530,254 filed 04 Apr 2005 (HHS Reference
No. E-247-2002/1-US-02).
Licensing Contact: Peter Soukas; 301/435-4646; soukasp@mail.nih.gov.
Technology summary and benefits: Nuclear hormones such as
glucocorticoids dampen inflammatory responses, and thus provide
protection to mammals against inflammatory disease and septic shock.
The Anthrax lethal factor represses nuclear hormone receptor activity,
and thus may contribute to the infectious agent causing even more
damage to the host. This observation can be exploited to find new means
of studying and interfering with the normal function of nuclear hormone
receptors. Scientists at NIH have shown that under the appropriate
conditions, these molecules can be used to modulate the activity of
various nuclear hormone receptors. Identifying useful agents that
modify these important receptors can provide relief in several human
disorders such as inflammation, autoimmune disorders, arthritis,
malignancies, shock and hypertension.
Long-term potential applications: This invention provides novel
agents that can interfere with the action of nuclear hormone receptors.
It is well known that malfunction or overdrive of these receptors can
lead to a number of diseases such as enhanced inflammation; worse
sequelae of infection including shock; diabetes; hypertension and
steroid resistance. Hence a means of controlling or fine-tuning the
activity of these receptors can be of great benefit. Current means of
affecting steroid receptor activity are accompanied by undesirable
side-effects. Since the conditions for which these treatments are
sought tend to be chronic, there is a critical need for safer drugs
that will have manageable side-effects.
Uniqueness or innovativeness of technology: The observation that
the lethal factor from Anthrax has a striking effect on the activity of
nuclear hormone receptors opens up new routes to controlling their
activity. The means of action of this repressor is sufficiently
different from known modulators of hormone receptors (i.e. the
classical antagonists). For instance, the repression of receptor
activity is non-competitive, and does not affect hormone binding or DNA
binding. Also, the efficacy of nuclear hormone receptor repression by
Anthrax lethal factor is sufficiently high that the pharmacological
effect of this molecule is seen at vanishingly small concentrations.
Taken together, these attributes may satisfy some of the golden rules
of drug development such as the uniqueness or novelty of the agent's
structure, a low threshold for activity, high level of sophistication
and knowledge in the field of enquiry, and the leeway to further refine
the molecule by rational means.
Stage of Development: In vitro studies have been completed, and a
limited number of animal studies have been carried out.
Methods and Compositions for Production and Purification of Recombinant
Staphylococcal Enterotoxin B (rSEB)
Daniel Coffman, Steven Giardina, Jianwei Zhu (NCI).
U.S. Provisional Application No. 60/328,017 filed 09 Oct 2001 (HHS
Reference No. E-075-2001/0-US-01);
PCT Application No. PCT/US02/31114 filed 27 Sep 2002 (HHS Reference No.
E-075-2001/0-PCT-01);
U.S. Patent Application No. 10/492,105 filed 08 Apr 2004 (HHS Reference
No. E-075-2001/0-US-02).
Licensing Contact: Peter Soukas; 301/435-4646; soukasp@mail.nih.gov.
This invention claims processes and compositions for fermentation,
recovery, and purification of recombinant bacterial superantigens
(rSAgs), exemplified by a recombinant staphylococcal enterotoxin B SEB
(rSEB) protein mutated for use in administration to a mammalian
recipient. This process generates an economically viable quantity of
rSEB vaccine protein meeting FDA parenteral drug specifications. The
purification methods generally involve multiple steps including
hydrophobic interaction chromatography (HIC), buffer exchange
(desalting), and cation exchange. The final product of the purification
is a highly purified rSAg composition satisfying clinical safety
criteria and is immunogenic and protective against lethal aerosol
challenge in a murine model. The methods and compositions claimed in
the patent application provide possible therapeutics and prophylactics
for diseases caused by bacterial SAgs, such as food poisoning,
bacterial arthritis and other autoimmune disorders, toxic shock
syndrome, and the potential use of SAg biowarfare agents.
Method for Determining Sensitivity to a Bacteriophage
Carl R. Merril (NIMH), Sankar Adhya (NCI), Dean M. Scholl (NIMH).
U.S. Provisional Application No. 60/351,458 filed 23 Jan 2002 (HHS
Reference No. E-318-2000/0-US-01);
PCT Application No. PCT/US03/02179 filed 23 Jan 2003 (HHS Reference No.
E-318-2000/0-PCT-02);
U.S. Patent Application No. 10/498,428 filed 10 Jun 2004 (HHS Reference
No. E-318-2000/0-US-03).
Licensing Contact: Peter Soukas; 301/435-4646; soukasp@mail.nih.gov.
Traditionally, chemical antibiotics have been used to treat a
variety of bacterial infections. However, bacterial resistance to
current antibiotics is an increasingly serious problem in human and
veterinary health as well as agriculture. Many experts believe that
strains of disease-causing bacteria resistant to all common antibiotics
will arise in the next ten to twenty years. Bacteriophages offer a
promising therapeutic alternative to antibiotics for these antibiotic
resistant bacteria. There are also situations in which bacteriophage
may be more suitable than antibiotics to treat infections caused by
against antibiotic-sensitive bacteria. Bacteriophages are highly host-
specific, thus determining whether a phage would be therapeutically
useful against a particular bacterium or strain of bacteria is very
important but can be a time-consuming and labor-intensive process.
The current invention claims a method for selecting a therapeutic
bacteriophage that would be effective against a particular disease-
causing bacteria, comprising a number of bacteriophages containing
reporter nucleic acids capable of being expressed
[[Page 44667]]
when the bacteriophage infects a bacterial cell. These bacteriophages
are separately contacted with a sample contaminated by a bacterium.
Expression of the reporter is then detected, indicating which
bacteriophage has infected a bacterial cell and is thus a potential
therapeutic phage against the particular bacteria. Also claimed in the
application are kits allowing for the rapid identification of
potentially therapeutic bacteriophages.
Bacteriophage Having Multiple Host Range
Carl Merril (NIMH), Sankar Adhya (NCI), Dean Scholl (NIMH).
U.S. Provisional Application No. 60/220,987 filed 25 Jul 2000 (HHS
Reference No. E-257-2000/0-US-01);
PCT Application No. PCT/US01/22390 filed 25 Jul 2001 (HHS Reference No.
E-257-2000/0-PCT-02);
U.S. Patent Application No. 10/350,256 filed 21 Jan 2003 (HHS Reference
No. E-257-2000/0-US-03).
Licensing Contact: Peter Soukas; 301/435-4646; soukasp@mail.nih.gov.
Recently, there has been a renewed interest in the use of phages to
treat bacterial infections. The inventors have discovered FK1-5, a
highly lytic, non-lysogenic, stable bacteriophage with the ability to
kill bacteria rapidly, making it a good candidate for phage therapy.
The designation FK1-5 denotes the phage's ability to infect E. coli
strains that contain the K1 polysaccharide in their outer capsule as
well as E. coli strains that contain the K5 polysaccharide in their
outer capsule. Sequence analysis of the tail proteins of phage FK1-5 by
the inventors has shown that they are arranged in a cassette structure,
suggesting that the host range of phages can be broadened to other K
antigens, and even possibly other species of bacteria by recombinant
techniques. FK1-5 has a particular advantage because it recognizes and
attaches to the structures that confer virulence to bacteria. The
inventors' demonstration that a phage can contain multiple tail
proteins that expand its host range is useful for generating phage with
broad-spectrum antibacterial properties for the treatment of infectious
diseases. The inventors have completed in vitro studies on this phage.
Furthermore, because of the possibility of engineering the expression
of recombinant tail proteins, gene transfer to organisms that are not
normally infected by phages is also contemplated by the invention.
CC Chemokine Receptor 5 DNA, New Animal Models and Therapeutic Agents
for HIV Infection
C. Combadiere, Y. Feng, E.A. Berger, G. Alkahatib, P.M. Murphy, C.C.
Broder, P.E. Kennedy (NIAID).
U.S. Provisional Application No. 60/018,508 filed 28 May 1996 (HHS
Reference No. E-090-1996/0-US-01);
U.S. Patent Application No. 08/864,458 filed 28 May 1997 (HHS Reference
No. E-090-1996/0-US-04);
U.S. Patent Application No. 10/439,845 filed 15 May 2003 (HHS Reference
No. E-090-1996/0-US-05);
U.S. Patent Application No. 10/700,313 filed 31 Oct 2003 (HHS Reference
No. E-090-1996/0-US-06);
U.S. Patent Application No. 10/846,185 filed 14 May 2004 (HHS Reference
No. E-090-1996/0-US-07);
PCT Application No. PCT/US97/09586 filed 28 May 1997 (HHS Reference No.
E-090-1996/0-PCT-02);
European Patent Application No. 97929777.7 filed 28 May 1997 (HHS
Reference No. E-090-1996/0-EP-03).
Licensing Contact: Peter Soukas; 301/435-4646; soukasp@mail.nih.gov.
Chemokine receptors are expressed by many cells, including lymphoid
cells, and function to mediate cell trafficking and localization. CC
chemokine receptor 5 (CCR5) is a seven-transmembrane, G protein-coupled
receptor (GPCR) which regulates trafficking and effector functions of
memory/effector T-lymphocytes, macrophages, and immature dendritic
cells. Chemokine binding to CCR5 leads to cellular activation through
pertussis toxin-sensitive heterotrimeric G proteins as well as G
protein-independent signalling pathways. Like many other GPCR, CCR5 is
regulated by agonist-dependent processes which involve G protein
coupled receptor kinase (GRK)-dependent phosphorylation, beta-arrestin-
mediated desensitization and internalization.
Human CCR5 also functions as the main coreceptor for the fusion and
entry of many strains of human immunodeficiency virus (HIV-1, HIV-2).
HIV-1 transmission almost invariably involves such CCR5-specific
variants (designated R5); individuals lacking functional CCR5 (by
virtue of homozygosity for a defective CCR5 allele) are almost
completely resistant to HIV-1 infection. Specific blocking of CCR5
(e.g. with chemokine ligands, anti-CCR5 antibodies, CCR5-blocking low
MW inhibitors, etc.) inhibits entry/infection of target cells by R5 HIV
strains. Cells expressing CCR5 and CD4 are useful for screening for
agents that inhibit HIV by binding to CCR5. Such agents represent
potential new approaches to block HIV transmission and to treat
infected people. A small animal expressing both human CCR5 along with
human CD4 supports entry of HIV into target cells, a necessary hurdle
that must be overcome for development of a small animal model (e.g.
transgenic mouse, rat, rabbit, mink) to study HIV infection and its
inhibition.
The invention embodies the CCR5 genetic sequence, cell lines and
transgenic mice, the cells of which coexpress human CD4 and CCR5, and
which may represent valuable tools for the study of HIV infection and
for screening anti-HIV agents. The invention also embodies anti-CCR5
agents that block HIV env-mediated membrane fusion associated with HIV
entry into human CD4-positive target cells or between HIV-infected
cells and uninfected human CD4-positive target cells.
This technology was reported in Alkhatib et al., ``CC CKR5: a
RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for
macrophage-tropic HIV-1,'' Science 272:1955-1958 (1996). The technology
is available for exclusive or nonexclusive licensing.
Dated: July 19, 2005.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 05-15347 Filed 8-2-05; 8:45 am]
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