Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Human monoclonal antibodies broadly protective against influenza b virus and methods of using the same

a technology of monoclonal antibodies and influenza b, applied in the field of influenza b viral infection treatment materials and methods, can solve the problems of limited efficacy and continuous public health threat, and achieve the effect of showing therapeutic efficacy

Inactive Publication Date: 2014-12-25
OSAKA UNIV +3
View PDF0 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent is about three monoclonal antibodies that can neutralize influenza B viruses. These antibodies recognize different regions in the virus's hemagglutinin protein and have been tested in the lab and in mice. The results show that these antibodies can be used as therapeutics against influenza B viruses. The main technical effect of the patent is that it provides a way to develop drugs that can treat a wide range of influenza B viral strains.

Problems solved by technology

The ability of influenza virus to evade immune surveillance through rapid genetic drift and reassortment means that it remains a continuous public health threat.
However, they have limited efficacy when administered more than 48 hours after the onset of illness (Aoki et al., The Journal of Antimicrobial Chemotherapy 51: 123-129), and widespread use has resulted in the emergence of resistant viral strains (Kiso et al, Lancet 364:759-765; Lowen et al., Infectious Disorders Drug Targets 7:318-328; Reece, Journal of Medical Virology 79:1577-1586).

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Human monoclonal antibodies broadly protective against influenza b virus and methods of using the same
  • Human monoclonal antibodies broadly protective against influenza b virus and methods of using the same
  • Human monoclonal antibodies broadly protective against influenza b virus and methods of using the same

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0115]Human monoclonal antibodies (HuMAbs) were prepared in accordance with the procedure described in Kubota-Koketsu et al., Biochemical and Biophysical Research Communications 387:180-185 (2009). Healthy volunteers were vaccinated with the HA split vaccine including A / Brisbane / 59 / 2007 (H1N1), A / Uruguay / 716 / 2007 (H3N2), and B / Florida / 4 / 2006 strains. One to two weeks later, the vaccine-derived PBMCs were fused with SPYMEG cells and after screening and cloning, three hybridoma clones producing HuMAbs, designated 5A7, 3A2, and 10C4, were established. The reactivity of the HuMAbs was tested by IFA and Western blotting.

[0116]Briefly, 10 ml blood was drawn from a healthy volunteer vaccinated in the 2008 / 2009 winter season with trivalent HA split vaccine, which included A / Brisbane / 59 / 2007, A / Uruguay / 716 / 2007, and B / Florida / 4 / 2006 (The Research Foundation for Microbial Diseases of Osaka University, Kagawa, Japan), and then the PBMCs were collected by density gradient centrifugation through...

example 2

[0125]To determine the epitope regions of B / Florida / 4 / 2006 recognized by the three HuMAbs, escape mutants were selected. The escape mutants were selected by the incubation of B / Florida / 4 / 2006 with HuMAbs. Escape mutants were selected by culturing B / Florida / 4 / 2006 in the presence of MAb as described previously (Gulati et al., Journal of Virology 76:12274-12280), with minor modification. Viruses were incubated with MAb serially diluted 10-fold (to give final concentrations of 0.0025 to 2.5 mcg / ml) at 37 C. for 1 hour. Then MDCK cells were inoculated with the mixtures and cultured in DMEM / F-12+GlutaMAX™-I supplemented with 0.4% BSA, antibiotics, and 2 mcg / ml acetylated trypsin. After culturing for 72 hours, the supernatants were collected and subjected to VN and HI assays. Those viral samples that showed a reduced VN50 and HI titer were subjected to direct sequencing analysis of the entire HA gene.

[0126]Direct sequencing analysis was performed as follows. Viral RNA extracted with QIAam...

example 3

[0129]HuMAb 3A2 showed low reactivity against B / Shanghai / 361 / 2002 and was therefore examined for an additional distinct epitope region. To do this, various chimeric sequences of HA were constructed from B / Florida / 4 / 2006 and B / Shanghai / 361 / 2002, which differ at seven residues (positions 37, 40, 88, 131, 227, 249, 456), expressed in plasmids, and transfected into 293T cells. IFA of the chimeric HA proteins expressed in 293T cells showed that 131P and 227S were essential for the reaction with 3A2 (FIG. 3). These results indicate that the epitope of 3A2 is dependent on residues at positions 131, 194, 196, and 227, and the epitope of 10C4 is dependent on residues at positions 194 and 196. The epitope regions to which the three HuMAbs map are shown in a HA trimer three-dimensional model in FIG. 4. HuMAbs 3A2 and 10C4 recognized the top of the globular head including the 190-helix antigenic site, whereas 5A7 reacted with the stalk region distant from the viral membrane.

[0130]HuMAb, 5A7 rec...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
pHaaaaaaaaaa
temperatureaaaaaaaaaa
pHaaaaaaaaaa
Login to View More

Abstract

Materials and methods are provided for treating influenza B infections in humans. Anti-human influenza virus monoclonal antibodies and antigen-binding fragments thereof having a neutralization activity against a human influenza B virus are provided. Methods for producing anti-human influenza B virus monoclonal antibodies are also provided. The antibodies and antigen-binding fragments thereof can be effective against a wide range of influenza B viral strains. Methods of inhibiting or treating a human influenza B infection are provided. The anti-influenza B therapeutics can also be used to manufacture medicaments effective against influenza B infections, to detect human influenza B in a human subject, for use in pharmaceutical compositions, and for use in kits for at least one of the prevention, the treatment, and the detection of human influenza B in a human subject.

Description

RELATED APPLICATIONS[0001]The present application claims the benefit of U.S. Provisional Patent Application No. 61 / 592,657, filed on Jan. 31, 2012, which is incorporated herein by reference in its entirety.GOVERNMENT FUNDING[0002]The subject matter described herein was supported, at least in part, by the Japan Science and Technology Agency / Japan International Cooperation Agency, Science and Technology Research Partnership for Sustainable Development (JST / JICA, SATREPS); and a Grant-in-Aid for Young Scientists (B) from the Japan Society for the Promotion of Science to Mayo Yasugi.TECHNICAL FIELD[0003]The present invention relates to materials and methods for the treatment of influenza B viral infections in humans.BACKGROUND ART[0004]The ability of influenza virus to evade immune surveillance through rapid genetic drift and reassortment means that it remains a continuous public health threat. During annual epidemics five to fifteen percent of the worldwide population are typically inf...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): C07K16/10G01N33/569
CPCC07K16/1018G01N33/56983C07K2317/76C07K2317/21G01N2333/11C07K2317/54C07K2317/565A61K2039/505C07K2317/24A61P31/16C07K2317/34C07K2317/92
Inventor YASUGI, MAYOKUHARA, MOTOKIBOON-LONG, JOTIKAFUJIYAMA, KAZUHITOKOKETSU, RITSUKOIKUTA, KAZUYOSHI
Owner OSAKA UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com