[Federal Register Volume 70, Number 66 (Thursday, April 7, 2005)]
[Notices]
[Pages 17699-17702]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-6895]


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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.

Methods for High-Efficiency Single Genome Sequencing of HIV

Drs. John Coffin, Mary Kearney, Frank Maldarelli and Sarah E. Palmer 
(NCI), et al.
U.S. Provisional Application filed 25 Jan 2005 (DHHS Reference No. E-
022-2005/0-US-01).
Licensing Contact: Sally Hu; 301/435-5606; [email protected].

    The invention is directed to a method for efficiently obtaining 
single genome sequences (SGS) of HIV from a biological sample. The 
invention has the following advantages over the current commercial 
genotyping in use: (1) It might improve the sensitivity of diagnosis of 
drug resistant HIV in newly infected HIV patients; (2) It might provide 
a more affordable diagnostic tool for early detection of drug 
resistance since the invention is adaptable to an automated approach 
for the high-throughput processing of a large number of patient sample; 
(3) It might improve patient outcome since SGS has the ability to 
identify low level mutation and will permit a more comprehensive 
evaluation of resistance in patients and might potentially change the 
clinical approach to treating resistant virus. In summary, this

[[Page 17700]]

invention might be a new important diagnostic tool for AIDS patients.
    Reference: Sarah Palmer et al., ``Multiple, Linked Human 
Immunodeficiency Virus Type 1 Drug Resistance Mutations in Treatment-
Experienced Patients are Missed by Standard Genotype Analysis,'' J. 
Clin. Microbiol. (Jan 2005) 43(1):406-413.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

HIV Neutralization by Structure-Based Enhancements of CD4-Molecular 
Mimicry

Peter D. Kwong, Chih-chin Huang, and Tongqing Zhou (NIAID), et al.
U.S. Provisional Patent Application No. 60/623,762 filed 29 Oct 2004 
(DHHS Reference No. E-333-2004/0-US-01).
Licensing Contact: Michael Shmilovich; 301/435-5019; 
[email protected].

    Available for licensing are compositions and methods for inhibiting 
CD4-gp120 interactions. HIV infectivity is mediated by interactions 
between the lymphocyte cellular protein CD4 and HIV exterior gp120 
envelope glycoprotein. The invention presents crystal structures of a 
number of co-complexes between CD4 mimics, CD4M33, F23, and others 
disclosed herein, with gp120, as well as other mimics and molecules, 
which interact with gp120. CD4M33 has greater affinity than F23 for 
HIV-1 primary isolates, whereas F23 is a better mimic of CD4 and showed 
greater neutralization breadth than CD4M33 against diverse isolates 
from HIV-1, HIV-2, and SIVcpz. These results provide a basis for the 
development of anti-HIV antagonists with increased breadth of 
neutralization. Moreover, methods are disclosed for the identification 
of a mimic of CD4 with possible broad-spectrum activity. These methods 
can be used for drug screening and variant CD4 mimic production. Also, 
methods are provided for characterizing and evaluating protein 
structure, for designing candidate ligands, and for constructing CD4 
mimetic antagonist or the interfacial cavity binding compounds.
    Finally, provided are methods for producing mono- and polyclonal 
antibodies for use in vaccines. Mimics binding to gp120 cause 
conformational change in the protein, thus exposing epitope regions for 
antibody recognition. The uses of the mimetics and also of a mimetic-
based immunogen in inhibiting, reducing, or preventing HIV infection 
are also discussed. Suggestions are presented for therapeutic uses of 
the antibodies in preventing a decline in CD4 T cell levels in HIV-
positive patients.

Candidate DNA HIV Vaccine

Gary J. Nabel et al. (NIAID).
U.S. Provisional Application No. 60/588,378 filed 16 Jul 2004 (DHHS 
Reference No. E-267-2004/0-US-01).
Licensing Contact: Susan Ano; 301/435-5515; [email protected].

    NIH is pleased to announce as available for licensing technology 
related to HIV vaccines, which involves a vaccine candidate that is in 
phase I clinical trials. The subject technology is from a broad 
scientific program directed toward development of an HIV vaccine that 
will generate cellular and humoral immunity to HIV from different 
clades, which vary in regions throughout the world and which is a 
critical aspect to be addressed by an HIV vaccine to be administered 
worldwide. The vaccine candidate described herein is one of the first 
multiclade-component HIV vaccines to enter into clinical trials. This 
technology describes a candidate HIV vaccine comprising six DNA 
constructs, each expressing different HIV proteins, HIV Env from clades 
A, B, and C, and the Gag, Pol, and Nef proteins from clade B. Phase I 
clinical trials for this vaccine combination are currently underway. 
The DNA expression vectors described herein were designed to maximize 
protein expression levels. This technology offers a promising approach 
in the HIV vaccine field.

HIV Vaccine Immunogens and Immunization Strategies

Gilad Ofek et al. (NIAID).
U.S. Provisional Application No. 60/570,883 filed 14 May 2004 (DHHS 
Reference No. E-218-2004/0-US-01).
Licensing Contact: Susan Ano; 301/435-5515; [email protected].

    This invention relates to novel immunogens that generate an immune 
response against HIV-1 gp41 in mammals. The immunogens bind to the 
broadly neutralizing 2F5 monoclonal antibody as well as to antibodies 
4E10 and Z13. The immunogens were designed based on structural 
considerations from peptide-2F5 complexes. These complexes were 
characterized and found to have specific features, necessary to elicit 
an antibody response. It has been difficult to elicit broadly 
neutralizing antibodies against HIV-1, and this technology offers a 
potential solution.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Template Methods and Devices for Preparing Sample Arrays

Stephen Hewitt (NCI).
U.S. Patent Application No. 10/928,656 filed 26 Aug 2004 (DHHS Ref. E-
098-2004-0-US-01).
Licensing Contact: Cristina Thalhammer-Reyero; 301/435-4507; 
[email protected].

    Available for licensing and commercial development is a simple and 
inexpensive device and method for preparing tissue microarrays. The 
method includes placing a template defining an array of openings over a 
surface of the recipient block with receptacle holes, such that a 
needle or punch that contains a sample can be inserted through the 
openings of the template and the sample is then inserted into the 
receptacle hole in the recipient block. Tissue microarrays can include 
hundreds or even thousands of about 1mm discs of tissue specimens, 
fixed and arranged on a single microscope slide. Currently available 
tools provide means to generate hundreds of copies of this kind of 
slide. However, the equipment currently available can be quite complex 
and expensive, and thus it is often beyond the resources of many 
researchers.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Chimeric HIV/SIV Polypeptide Trimers as HIV/AIDS Vaccine Candidates

Bernard Moss (NIAID).
U.S. Provisional Application No. 60/510,952 filed 10 Oct 2003 (DHHS 
Reference No. E-356-2003/0-US-01); PCT Application filed 12 Oct 2004 
(DHHS Reference No. E-356-2003/0-PCT-02).
Licensing Contact: Susan Ano; 301/435-5515; [email protected].

    The technology describes recombinant chimeric polypeptides of HIV 
Env in which all or part of the N-terminal portion (85 amino acids) of 
gp41 is replaced with the corresponding region of SIV. These chimeric 
polypeptides may be potential HIV/AIDS vaccine candidates. The 
substitution described above promotes efficient trimerization of the 
Env protein, which has been found in functional virions to have almost 
exclusively a trimeric structure. Therefore, by mimicking native HIV 
structure, the chimeric polypeptides

[[Page 17701]]

described in this technology could be used as immunogens for the 
generation of neutralizing antibodies that would bind to native HIV. 
The chimeric polypeptide that contains only the N-terminal portion of 
SIV in an HIV-1 background is particularly interesting, because several 
broadly neutralizing HIV-1 epitopes are present in the C-terminal 
segment of gp41.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Antibodies Against the Amino Terminus Region of Circumsporozoite 
Protein Prevent the Onset of Malaria

Dharmendar Rathore, Thomas McCutchan (NIAID).
U.S. Provisional Application No. 60/532,676 filed 23 Dec 2003 (DHHS 
Reference No. E-176-2003/0-US-01); PCT filed.
Licensing Contact: Robert Joynes; 301/594-6565; [email protected].
    Malaria is one of the 5 major diseases of the world and a leading 
cause of childhood death in sub-Saharan Africa. Furthermore, the 
economic devastation of the disease is measured in the billions of 
dollars of lost wages and lowered productivity for the endemic areas of 
the world. In the U.S., it is a concern of travelers as well the 
military having to serve in those parts of the world. To date, there is 
no vaccine and one is not expected for another decade.
    The invention presented here focuses on the ability of the malarial 
sporozoite to infect liver cells. Previous vaccines have focused on the 
carboxyl end of the circumsporozoite (CSP) protein and have few 
successes to show. This invention utilizes the finding that the amino 
terminal portion of the CSP protein is required for hepatic entry. The 
invention includes several CSP polypeptides and constructs encoding 
such polypeptides that have been shown to be required for hepatic entry 
for vaccine development, prevention and treatment are also claimed. 
Methods and kit claims are included for the detection of the CSP 
protein in biological samples as well as for the detection of 
circulating antibodies of the CSP protein are also included.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Determining Kinase Specificity

J.S. Shaw and Y. Liu (NCI).
U.S. Patent Application No. 10/660,370 filed 11 Sep 2003 (DHHS 
Reference No. E-054-2003/0-US-01) and International Application Number 
PCT/US04/029397 filed 10 Sep 2004 (DHHS Reference No. E-054-2003/1-PCT-
01).
Licensing Contact: Cristina Thalhammer-Reyero; 301/435-4507; 
[email protected].

    Available for licensing and commercial development are methods, 
articles, software and kits for determining the spectrum of peptidyl 
sequences that are recognized and phosphorylated by a kinase, such as 
those sites on proteins involved in signal transduction pathways. More 
specifically, the following is disclosed:
    (a) Methods involving a degenerate library approaches to identify 
kinase specificity by identifying peptide sequences around such 
phosphorylation sites and ranking the peptides in preferential order 
after calculating a predictive score, such as the widely used position-
specific scoring matrix (PSSM). The method also provides an informative 
graphical format for visually representing that information and 
software to output data in that format. The method provides significant 
improvements over other methods currently used for such purpose;
    (b) Peptide sequences identified by the method of the invention, 
such as: (i) The spectrum of peptidyl sequences that are recognized and 
phosphorylated by a kinase, (ii) peptides that include kinase 
recognition sites and (iii) binding entities that specifically 
distinguish phosphorylated versus non-phosphorylated peptidyl 
sequences; and
    (c) Kits for identifying kinase substrates including anti-peptide 
antibodies for research and diagnostic uses.
    The technology is further described in: Fujii K, Zhu G, Liu Y, 
Hallam J, Chen L, Herrero J, Shaw S. 2004. Kinase peptide specificity: 
Improved determination and relevance to protein phosphorylation. Proc 
Natl Acad Sci USA 101:13744-9 (PMID: 15356339) and Zhu G, Fujii K, 
Belkina N, Liu Y, James M, Herrero J, Shaw S. 2005. Exceptional 
disfavor for proline at the P+1 position amongst AGC and CAMK kinases 
establishes reciprocal specificity between them and the proline-
directed kinases. J Biol Chem 280:10743-8: (PMID: 15647260).
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

MVA Expressing Modified HIV Envelope, Gag, and Pol Genes

Bernard Moss (NIAID), Patricia Earl (NIAID), Linda Wyatt (NIAID), Leigh 
Anne Steinmeyer (EM), Thomas VanCott (EM), Matthew Harris (EM).
U.S. Provisional Application No. 60/459,175 filed 28 Mar 2003 (DHHS 
Reference No. E-023-2003/0-US-01); PCT Application filed 28 Mar 2004, 
which published as WO 2004/087201 on 14 Oct 2004 (DHHS Reference No. E-
023-2003/0-PCT-02).
Licensing Contact: Peter Soukas; 301/435-4646; [email protected].

    This invention claims Modified Vaccinia Ankara (MVA), a 
replication-deficient strain of vaccinia virus, expressing Human 
Immunodeficiency Virus (HIV) env, gag, and pol genes, where the genes 
are isolated from Ugandan Clade D isolates, Kenyan Clade A isolates, 
and Tanzanian Clade C isolates. In a rhesus macaque SHIV model, DNA 
priming followed by a recombinant MVA (rMVA) booster controlled a 
highly pathogenic immunodeficiency challenge. Both the DNA and the rMVA 
components of the vaccine expressed multiple immunodeficiency virus 
proteins. Two DNA inoculations at zero (0) and eight (8) weeks and a 
single rMVA booster at twenty-four (24) weeks effectively controlled an 
intrarectal challenge administered seven (7) months after the booster. 
Additionally, the inventors have generated data showing that 
inoculations of rMVA induce good immune responses even without DNA 
priming.
    The inventors are continuing preclinical work on the vaccine, and 
have generated further data on the vaccine. Furthermore, the inventors 
are continuing to optimize the vaccine by genetically modifying the 
genes. This vaccine will be the subject of an upcoming Phase I clinical 
trial. These findings provide hope that a relatively simple 
multiprotein DNA/MVA vaccine can help to control the Acquired Immune 
Deficiency Syndrome (AIDS) epidemic.

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 (DHHS 
Reference No. E-090-1996/0-US-01);
U.S. Patent Application No. 08/864,458 filed 28 May 1997 (DHHS 
Reference No. E-090-1996/0-US-04);

[[Page 17702]]

U.S. Patent Application No. 10/439,845 filed 15 May 2003 (DHHS 
Reference No. E-090-1996/0-US-05);
U.S. Patent Application No. 10/700,313 filed 31 Oct 2003 (DHHS 
Reference No. E-090-1996/0-US-06);
U.S. Patent Application No. 10/846,185 filed 14 May 2004 (DHHS 
Reference No. E-090-1996/0-US-07);
PCT Application No. PCT/US97/09586 filed 28 May 1997 (DHHS Reference 
No. E-090-1996/0-PCT-02);
European Patent Application No. 97929777.7 filed 28 May 1997 (DHHS 
Reference No. E-090-1996/0-EP-03).
Licensing Contact: Peter Soukas; 301/435-4646; [email protected].

    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: March 25, 2005.
Steven M. Ferguson, Director, Division of Technology Development and 
Transfer, Office of Technology Transfer, National Institutes of Health.
[FR Doc. 05-6895 Filed 4-6-05; 8:45 am]
BILLING CODE 4140-01-P