[Federal Register Volume 68, Number 19 (Wednesday, January 29, 2003)]
[Notices]
[Pages 4497-4498]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-1988]


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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 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.

Minimally Immunogenic Variant of Humanized COL-1 Antibody Against 
Carcinoembryonic Antigen (CEA)

Syed V.S. Kashmiri (NCI), Jeffrey Schlom (NCI), Eduardo A. Padlan 
(NIDDK)
DHHS Reference No. E-239-2002/0-US-01 filed 05 Sep 2002
Licensing Contact: Jonathan Dixon; 301/435-5559; [email protected]

    Monoclonal antibodies (mAbs) show promise for the diagnosis and 
treatment of human cancers. COL-1 has a high affinity for 
carcinoembryonic antigen (CEA), and it reacts specifically to CEA. The 
present invention discloses humanized COL-1 (HuCOL-1) mAbs that are 
potentially minimally immunogenic and retain CEA binding affinity. 
Humanization of the antibody by ``abbreviated'' CDR grafting has 
reduced the risk of human anti-murine antibody response associated with 
the clinical use of murine mAbs for diagnosis and treatment of CEA 
expressing tumors. This invention also provides further methods of 
detecting and treating CEA expressing tumors.

Novel Broadly Cross-Reactive HIV Neutralizing Human Monoclonal 
Antibodies Selected From Fab Phage Display Libraries Using a Novel 
Strategy Based on Alternative Antigen Panning

Dimiter S. Dimitrov (NCI) and Mei-Yun Zhang (SAIC)
DHHS Reference No. E-144-2002/0-US-01 filed 05 May 2002 and

Novel Broadly Cross-Reactive HIV-1 Neutralizing Human Single-Chain 
Antibodies Derived From X5 by DNA Shuffling and Alternating Antigen 
Panning

Dimiter S. Dimitrov (NCI) and Mei-Yun Zhang (SAIC)
DHHS Reference No. E-144-2002/1-US-01 filed 05 May 2002
Licensing Contact: Sally Hu; 301/435-5606; [email protected]

    This invention (E-144-2002/0-US-01) identifies four antibodies, 
designed m12, m14, m16, and m18. These four antibodies were isolated 
from a human Fab phage display library using alternating antigen 
panning (AAP). All four antibodies bind to recombinant HIV envelope 
glycoproteins (Env) gp12089.6, gp120JR-FL and 
gp120IIIB with high affinity. Moreover, m12 binding to gp 
120 or gp 140 is significantly enhanced in the presence of the receptor 
CD4. The second invention (E-144-2002/1-US-01) describes two scFv 
clones, designated M6 and M9 that were selected form phage-displayed X5 
scFv mutants library by panning the library against 
gp12089.6/IIIB-CD4 complex using

[[Page 4498]]

the same strategy, alternating antigen panning strategy (AAP). M6 and 
M9 are more stable than previously reported HIV-1 antibody named X5 and 
have significant improved binding activities to gp120IIIB. 
Both scFvs inhibit more efficiently membrane fusion mediated by 
envelope glycoproteins of primary HIV isolates with a broader spectrum 
compared to X5, indicating that scFv format may be a more proper format 
compared to Fab for HIV-1 neutralizing antibodies to inhibit virus 
infection and transmission. Furthermore, scFv is a single molecule with 
almost half size of Fab, which makes scFv more suitable for 
constructing bivalent and multivalent antibodies and antibody fusion 
proteins. Thus, since all six antibodies from the above two inventions 
cross-react with different HIV-1 isolates, these antibodies could be 
directly used for therapy of HIV-1 infected individuals. In addition, 
these antibodies can be also used for screening of peptide phage 
display libraries, libraries of Envs, and in general as tools for 
development of HIV vaccines.

A Mouse Model for Human Osteoarthritis

Laurent G. Ameye (NIDCR), Marian F. Young (NIDCR), Ake Oldberg (EM), 
Tianshun Xu (NIDCR)
DHHS Reference No. E-081-2002/0
Licensing Contact: Susan Carson; 301/435-5020; [email protected]

    Osteoarthritis (OA) is the most common form of arthritis and 
affects more than 20 million Americans, costing billions of dollars in 
health care annually. Osteoarthritis is caused by the breakdown of 
joint cartilage, leading to a loss of the cartilage ``cushion'' between 
the bones of the joints. Risk factors associated with OA include age, 
obesity, traumatic injury and overuse due to sports or occupational 
stresses. There is no cure for OA and current treatments are directed 
at the symptomatic relief of pain, and at improving and maintaining 
joint function. There remains, however, a critical need both to develop 
OA treatments that focus on slowing down the degenerative process of 
the disease and for validated animal models to test these new 
treatments. NIH scientists at the NIDCR have generated a mouse model 
for osteoarthritis (FASEB J. (2002) 16, 673-680) that fills one part of 
this important gap.
    The mouse model is a double knockout mouse that lacks biglycan and 
fibromodulin, two members of the small leucine-rich proteoglycan 
family, and that spontaneously develops OA. All the hallmarks of human 
osteoarthritis are present, including: progressive degeneration of the 
articular cartilage from early fibrillation to complete erosion, 
subchondral sclerosis, an absence of inflammation and development of 
osteophytes and cysts. Advantages over the existing models for 
osteoarthritis include: high phenotypic penetrance, early onset (at 1-2 
months) and a rapid disease progression (between 3-6 months) which can 
be accelerated by moderate levels of exercise, such as treadmill 
running. These properties, combined with a normal life span, make the 
biglycan/fibromodulin-deficient mouse an ideal animal model for 
evaluating new drugs and treatments for osteoarthritis.

Ligands for FPR Class Receptors That Induce a Host Immune Response to a 
Pathogen or Inhibit HIV Infection

Ji Ming Wang et al. (NCI)
DHHS Reference Nos. E-267-1999/0-PCT-04 filed 04 Feb 2000 (PCT/US00/
02842) and E-267-1999/0-US-05 filed 17 Jul 2002
Licensing Contact: Marlene Shinn-Astor; 301/435-4426; [email protected]

    The NIH announces a technology that relates a synthetic amino acid 
peptide that has been discovered to have chemotactic activity and the 
ability to activate both the FPR and FPRL1 receptors. This peptide has 
been found by NIH investigators to be a potent inhibitor of cellular 
response to chemokines including those chemokines that use the CCR5 
receptor. It has been found that the activation of the FPRL1 by the 
peptide will in fact inhibit HIV-1 fusion to a cell and its infection 
through the CCR5 receptor. The peptide can potentially be used as a 
topical drug in the anal-vaginal tract to prevent or reduce the mucosal 
transmission of HIV-1. It also has the potential to be used as a 
vaccine adjuvant to prime a host response from a patient to a microbial 
infection. In addition, because of its interaction with the FPR and 
FPRL1 receptor it could be used to design drugs which interfere with 
responses due to the presence of excess quantities of chemokines. The 
peptide is short and contains a D-amino acid so that it is economical 
and easy to synthesize. Also, it may be more resistant to proteolytic 
degradation in vivo, which will prolong its half-life and therefore 
make it more effective as a treatment. It is available for immediate 
licensing and research collaborations via a Cooperative Research and 
Development Agreement (CRADA).

    Dated: January 10, 2003.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 03-1988 Filed 1-28-03; 8:45 am]
BILLING CODE 4140-01-P