[Federal Register Volume 85, Number 191 (Thursday, October 1, 2020)]
[Notices]
[Page 61961]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-21708]



[[Page 61961]]

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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 invention listed below is owned by an agency of the U.S. 
Government and is available for licensing 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.

FOR FURTHER INFORMATION CONTACT: Amy F. Petrik, Ph.D., 240-627-3721; 
[email protected]. Licensing information and copies of the U.S. patent 
application listed below may be obtained by communicating with the 
indicated licensing contact at the Technology Transfer and Intellectual 
Property Office, National Institute of Allergy and Infectious Diseases, 
5601 Fishers Lane, Rockville, MD, 20852; tel. 301-496-2644. A signed 
Confidential Disclosure Agreement will be required to receive copies of 
unpublished patent applications.

SUPPLEMENTARY INFORMATION: Technology description follows.

Structure-Based Design of SARS2-CoV-2 Spike Immunogens Stabilized in 
the RBD-All Down Conformation

Description of Technology:

    SARS-CoV-2 has emerged as a global pathogen, sparking urgent 
vaccine development efforts. The trimeric SARS-CoV-2 spike appears to 
be a leading vaccine antigen. However, the inability of antibodies such 
as CR3022, which binds tightly to a cryptic spike epitope, to 
neutralize SARS-CoV-2 suggests a spike-based means of neutralization 
escape.
    Researchers at the Vaccine Research Center (VRC) of the National 
Institute of Allergy and Infectious Diseases (NIAID) sought to 
understand how antibodies with high affinity fail to neutralize the 
SARS-CoV-2. To that end, the researchers characterized the SARS-CoV-2 
spike protein conformational changes as a function of pH and observed 
that at endosomal pH the spike protein has a conformation in which all 
of the receptor binding domains (RBD) are in a down conformation which 
could explain the virus' ability to escape neutralization in the 
endosome.
    Hypothesizing that SARS-CoV-2 escapes neutralization through pH-
dependent conformational masking, the researchers designed spike 
proteins with mutations to stabilize the spike in the RBD-all down 
conformation. Such designs include cavity-filling mutations, 
disulfides, aspartic acid to asparagine mutations, proline mutations, 
and other sequence modifications to fix the spike protein in its RBD-
all down conformation so that immunization at a physiological pH will 
elicit antibodies that can recognize the low pH-stabilized all RBD-down 
conformation of the spike protein and no longer be susceptible to pH-
induced neutralization escape.
    Immunogenicity studies are underway to determine which of the 
designs will yield a neutralizing immune response in mice. Pending 
results in mice, a lead candidate will be selected for studies in 
nonhuman primates.
    This technology is available for licensing for commercial 
development in accordance with 35 U.S.C. 209 and 37 CFR part 404.

Potential Commercial Applications

     An improved stabilized spike immunogen for the development 
of protective SARS-CoV-2 vaccine.

Competitive Advantages

     Stabilized SARS-CoV-2 spike variants with potential to 
elicit higher levels of neutralizing antibodies than current related 
vaccine development.
     Identification of a methodology to screen for improved 
spike variants (by assessing binding by neutralizing versus non-
neutralizing antibodies).
    Development Stage: Preclinical Research.
    Inventors: Peter Dak-Pin Kwong (NIAID); Tongqing Zhou (NIAID); 
Yaroslav Tsybovsky (NCI); Adam Shabbir Olia (NIAID); John R. Mascola 
(NIAID).
    Publications: Zhou, T et al., (2020). Cryo-EM Structures Delineate 
a pH-Dependent Switch that Mediates Endosomal Positioning of SARS-CoV-2 
Spike Receptor-Binding Domains. BioRxiv.
    Intellectual Property: HHS Reference Number E-187-2020 includes 
U.S. Provisional Patent Application Number 63/046,603, filed 06/30/
2020.
    Licensing Contact: To license this technology, please contact Amy 
F. Petrik, Ph.D., 240-627-3721; [email protected].

    Dated: September 17, 2020.
Surekha Vathyam,
Deputy Director, Technology Transfer and Intellectual Property Office, 
National Institute of Allergy and Infectious Diseases.
[FR Doc. 2020-21708 Filed 9-30-20; 8:45 am]
BILLING CODE 4140-01-P