[Federal Register Volume 83, Number 199 (Monday, October 15, 2018)]
[Notices]
[Page 51967]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-22316]


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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, HHS.

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. to achieve 
expeditious commercialization of results of federally-funded research 
and development.

FOR FURTHER INFORMATION CONTACT: Licensing information may be obtained 
by emailing the indicated licensing contact at the National Heart, 
Lung, and Blood, Office of Technology Transfer and Development Office 
of Technology Transfer, 31 Center Drive Room 4A29, MSC2479, Bethesda, 
MD 20892-2479; telephone: 301-402-5579. A signed Confidential 
Disclosure Agreement may be required to receive any unpublished 
information.

SUPPLEMENTARY INFORMATION: Technology description follows.

High Density Lipoprotein (HDL) Targeting Protease Inhibitor

    Available for licensing and commercial development is intellectual 
property covering a class of lipoproteins targeting protease inhibitors 
and methods of their use for treating a protease-mediated disease. 
Alpha-1-antitrypsin (A1AT) deficiency occurs in about 1 in 2500 
individuals in the United States and Europe. Persons with this 
condition develop severe liver disease and emphysema/chronic 
obstructive pulmonary disease (COPD). The current treatment for A1AT 
deficiency includes intravenous infusion of purified human A1AT 
protein. This treatment strategy is expensive and only moderately 
effective. A recent study demonstrated improvement in the treatment of 
A1AT deficiency in a mouse model of emphysema by pre-incubating A1AT 
with high density lipoprotein (HDL) particles prior to infusion. This 
resulted in improvements in lung morphology and inflammatory markers in 
the lung compared to A1AT treatment alone. The mechanism for this 
improvement in function of A1AT when bound to HDL is believed to be 
increased trafficking of A1AT to the lung. The lipoprotein targeting 
protease inhibitory peptide of the present invention represents 
provides advances upon these existing methods. First, it replaces the 
need for full length A1AT protein with a known small peptide inhibitor 
of elastase (the natural target protease of A1AT; a small tetra-peptide 
with the sequence Ala-Ala-Pro-Val-chloromethylketone). Second, the 
peptide can be conjugated by amine reactive chemistry to a lipoprotein 
targeting motif. The inventors have data linking the peptide to a 
Vitamin E with a polyethylene glycol spacer arm to distance the 
functional AAPV peptide from the targeting moiety and to provide 
improved solubility. Third, the approach promises improved efficacy 
over the current standard of care (A1AT infusion) because the overall 
molecule is small molecule, 2.5 kDa versus 52 kDa for the the full 
length A1AT protein. An HDL particle can generally accommodate only one 
molecule of A1AT, whereas many copies of our VitE-PEG-AAPV peptide can 
reside on an HDL particle providing a significant increase in potency.

Potential Commercial Applications

 Alpha-1-antitrypsin deficiency
 severe liver disease
 emphysema/chronic obstructive pulmonary disease

Development Stage

 Early stage

    Inventors: Alan Remaley and Scott Maxwell Gordon (both of NHLBI)
    Relevant Publications: Gordon, et al. Molecular & Cellular 
Proteomics 14: 10.1074/mcp.M115.054031, 3247-3257, 2015.
    Intellectual Property: HHS Reference No. E-155-2016; U.S Patent 
Application 15/297,054 filed October 18, 2016.
    Licensing Contact: Michael Shmilovich, Esq, CLP; 301-435-5019; 
[email protected].

     Dated: September 24, 2018.
Michael A. Shmilovich,
Senior Licensing and Patenting Manager, National Heart, Lung, and Blood 
Institute, Office of Technology Transfer and Development.
[FR Doc. 2018-22316 Filed 10-12-18; 8:45 am]
 BILLING CODE 4140-01-P