[Federal Register Volume 70, Number 56 (Thursday, March 24, 2005)]
[Notices]
[Pages 15107-15109]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-5875]


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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.

Minimally Immunogenic Germline Sequence Variants of COL-1 Antibody and 
Their Use

Syed Kashmiri (NCI), Eduardo Padlan (NIDDK), and Jeffrey Schlom (NCI)
U.S. Provisional Application No. 60/562,781 filed 15 Apr 2004 (DHHS 
Reference No. E-105-2004/0-US-01) and U.S. Provisional Application No.

[[Page 15108]]

60/580,839 filed 16 Jun 2004 (DHHS Reference No. E-105-2004/1-US-01)

    Licensing Contact: Jeffrey Walenta; 301/435-4633; 
[email protected].
    This invention relates to humanized monoclonal antibodies that bind 
to the tumor antigen carcinoembryonic antigen (CEA). More specifically, 
the present technology relates to humanized COL-1 antibodies that have 
minimal immunogenicity and retain antigen-binding affinity for CEA. CEA 
is over expressed in 95% of gastrointestinal and pancreatic tumors. 
Because CEA is over expressed consistently, it is anticipated that CEA 
would be an excellent target for an antibody-based therapeutics.
    The invention also discloses a novel method for humanizing 
monoclonal antibodies. This humanization method encompasses grafting 
xenogenic Specificity Determining Regions (SDRs) onto Complementarity 
Determining Regions (CDR) templates derived from several different 
human germline sequences. The use of several different human germline 
sequences greatly reduces the potential for immunogenicity and greatly 
minimizes the number of SDRs required for equivalent or better antigen 
binding of the antibody.
    This humanization method is applicable to development of antibodies 
to any immunogenic epitopes.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Modulating p38 Kinase Activity

Jonathan D. Ashwell et al. (NCI)
PCT Application filed 04 Feb 2005 (DHHS Reference No. E-010-2004/2-PCT-
01)

    Licensing Contact: Marlene Shinn-Astor; 301/435-4426; 
[email protected].
    Protein kinases are involved in various cellular responses to 
extracellular signals. The protein kinase termed p38 is also known as 
cytokine suppressive anti-inflammatory drug binding protein (CSBP) and 
RK. It is believed that p38 has a role in mediating cellular response 
to inflammatory stimuli, such as leukocyte accumulation, macrophage/
monocyte activation, tissue resorption, fever, acute phase responses 
and neutrophilia. In addition, p38 has been implicated in cancer, 
thrombin-induced platelet aggregation, immunodeficiency disorders, 
autoimmune diseases, cell death, allergies, osteoporosis and 
neurodegenerative disorders.
    This invention includes compositions and methods for controlling 
the activity of p38 specifically in T cells through an alternate 
activation pathway. By controlling p38 activity through interference 
with this alternate pathway, the T cells themselves can be controlled 
which in turn can be a treatment for conditions or diseases 
characterized by T cell activation such as autoimmune diseases, 
transplant rejection, graft-versus-host disease, systemic lupus 
erythematosus, and viral infections such as HIV infections. One major 
benefit for this invention is the development of small molecular 
inhibitors of the alternative p38 activation pathway (i.e. Gadd45a-
mimetics). The inventors have found that Gadd45a specifically inhibits 
the activity of p38 phosphorylated on Tyr-323. p38 activated by MKK6 
(which phosphorylates Thr-180/Tyr-182) is found not to be inhibited by 
Gadd45a. This emphasizes the specific nature of the activating 
modification and its regulation by Gadd45a, including its suitability 
as a tissue-specific molecular target.
    References: JM Salvador et al., ``The autoimmune suppressor 
Gadd45alpha inhibits the T cell alternative p38 activation pathway,'' 
Nat. Immunol. advance online publication, 27 Feb 2005 (doi:10.1038/
ni1176); JM Salvador et al., ``Alternative p38 activation pathway 
medicated by T cell receptor-proximal tyrosine kinases,'' Nat. Immunol. 
advance online publication, 27 Feb 2005 (doi:10.1038/ni1177).
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Mu Opiate Receptor Knockout Mouse

George R. Uhl (NIDA)
DHHS Reference No. E-034-2003/0--Research Material

    Licensing Contact: Norbert Pontzer; 301/435-5502; 
[email protected].
    The researchers produced heterozygous and homozygous mu opiate 
receptor knockout mice that displayed 54% and 0% of wild-type levels of 
mu opiate receptor expression, respectively. These knockout mice were 
generated by injecting 15-20 homologous, recombinant ES cells into 
blastocysts harvested from C57BL/6J mice and by implanting the 
blastocysts into the uteri of pseudopregnant CD-1 mice.
    Morphine acts on opiate receptors found on spinal and supraspinal 
neurons in the central nervous system. There are three main subtypes of 
these receptors, mu, kappa, delta. Morphine produces an analgesic 
effect by acting through these receptors, especially the mu receptor. 
However, the roles played by each of these receptors in pain processing 
in either drug-free or morphine-treated states are not clear. A mu 
opiate receptor knockout mouse model can be used to elucidate 
mechanistic and behavioral roles of this receptor subtype.
    Reference: I. Sora et al., ``Opiate receptor knockout mice define 
mu receptor roles in endogenous mociceptive responses and morphine-
induced analgesia,'' Proc. Natl. Acad. Sci. USA 18 Feb 1997 94(4):1544-
1549.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Tryptophan as a Functional Replacement for ADP-ribose-arginine in 
Recombinant Proteins

Joel Moss et al. (NHLBI)
U.S. Patent Application No. 10/517,565 filed 07 Dec 2004 (DHHS Ref. No. 
E-160-2002/0-US-03), claiming priority to 28 Jun 2002; Foreign rights 
available

    Licensing Contact: Marlene Shinn-Astor; 301/435-4426; 
[email protected].
    Bacterial toxins such as cholera toxin and diphtheria toxin 
catalyze the ADP-ribosylation of important cellular target proteins in 
their human hosts, thereby, as in the case of cholera toxin, 
irreversibly activating adenylyl cyclase. In this reaction, the toxin 
transfers the ADP-ribose moiety of Nicotinamide Adenine Dinucleotide 
(NAD) to an acceptor amino acid in a protein or peptide. ADP-
ribosylation leads to a peptide/protein with altered biochemical or 
pharmacological properties. Mammalians proteins catalyze reactions 
similar to the bacterial toxins. The ADP-ribosylated proteins represent 
useful pharmacological agents, however, their use is limited by the 
inherent instability of the ADP-ribose-protein linkage.
    The NIH announces a new technology wherein recombinant proteins are 
created that substitute tryptophan for an arginine, thereby making the 
protein more stable, and better suited as agents for therapeutic 
purposes. The modification creates an effect similar to ADP-
ribosylation of the arginine. An example of a protein that can be 
modified is the defensin molecule, which is a broad-spectrum 
antimicrobial that acts against infectious agents and plays an 
important role in the innate immune defense in vertebrates.
    In addition to licensing, the technology is available for further 
development through collaborative

[[Page 15109]]

research opportunities with the inventors.

Cannula for Pressure Mediated Drug Delivery

Stephen Wiener, Robert Hoyt, John Deleonardis, Randal Clevenger, Robert 
Lutz, Brian Safer (NHLBI)
PCT Application No. PCT/US99/11277 filed 21 May 1999, which published 
as WO 99/59666 on 25 Nov 1999 (DHHS Reference No. E-196-1998/2-PCT-01); 
U.S., Australian, Japanese, and European rights pending

    Licensing Contact: Michael Shmilovich; 301/435-5019; 
[email protected].
    Available for licensing are methods and devices for selective 
delivery of therapeutic substances to specific histologic or 
microanatomic areas of organs (introduction of the therapeutic 
substance into a hollow organ space (such as an hepatobiliary duct or 
the gallbladder lumen) at a controlled pressure, volume or rate allows 
the substance to reach a predetermined cellular layer (such as the 
epithelium or sub-epithelial space). The volume or flow rate of the 
substance can be controlled so that the intralumenal pressure reaches a 
predetermined threshold level beyond which subsequent subepithehal 
delivery of the substance occurs. Alternatively, a lower pressure is 
selected that does not exceed the threshold level, so that delivery 
occurs substantially only to the epithelial layer. Such site-specific 
delivery of therapeutic agents permits localized delivery of substances 
(for example to the interstitial tissue of an organ) in concentrations 
that may otherwise produce systemic toxicity. Occlusion of venous or 
lymphatic drainage from the organ can also help prevent systemic 
administration of therapeutic substances, and increases selective 
delivery to superficial epithelial cellular layers. Delivery of genetic 
vectors can also be better targeted to cells where gene expression is 
desired. The access device comprises a cannula with a wall piercing 
tracar within the lumen. Two axially spaced inflatable balloons engage 
the wall securing the cannula and sealing the puncture site. A catheter 
equipped with an occlusion balloon is guided through the cannula to the 
location where the therapeutic substance is to be delivered.

    Dated: March 17, 2005.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 05-5875 Filed 3-23-05; 8:45 am]
BILLING CODE 4140-01-P