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NZ775007B2 - Antibody-mediated neutralization of Chikungunya virus - Google Patents
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NZ775007B2 - Antibody-mediated neutralization of Chikungunya virus - Google Patents

Antibody-mediated neutralization of Chikungunya virus Download PDF

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Publication number
NZ775007B2
NZ775007B2 NZ775007A NZ77500716A NZ775007B2 NZ 775007 B2 NZ775007 B2 NZ 775007B2 NZ 775007 A NZ775007 A NZ 775007A NZ 77500716 A NZ77500716 A NZ 77500716A NZ 775007 B2 NZ775007 B2 NZ 775007B2
Authority
NZ
New Zealand
Prior art keywords
antibody
seq
fragment
antibody fragment
monoclonal antibody
Prior art date
Application number
NZ775007A
Other versions
NZ775007A (en
Inventor
James E Crowe
Terence Dermody
Laurie Silva
Scott A Smith
Original Assignee
Vanderbilt University
Filing date
Publication date
Application filed by Vanderbilt University filed Critical Vanderbilt University
Priority claimed from NZ736445A external-priority patent/NZ736445A/en
Publication of NZ775007A publication Critical patent/NZ775007A/en
Publication of NZ775007B2 publication Critical patent/NZ775007B2/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A61K2039/507—Comprising a combination of two or more separate antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/12—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • C07K16/1081—
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/70—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/005—Assays involving biological materials from specific organisms or of a specific nature from viruses
    • G01N2333/08—RNA viruses
    • G01N2333/18—Togaviridae; Flaviviridae
    • G01N2333/181—Alphaviruses or Group A arboviruses, e.g. sindbis, VEE, EEE, WEE or semliki forest virus
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2469/00—Immunoassays for the detection of microorganisms
    • G01N2469/10—Detection of antigens from microorganism in sample from host
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56983—Viruses
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/577—Immunoassay; Biospecific binding assay; Materials therefor involving monoclonal antibodies binding reaction mechanisms characterised by the use of monoclonal antibodies
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present disclosure is directed to antibodies binding to and neutralizing Chikungunya virus (CHIKV) and methods for use thereof.

Claims (23)

CLAIMS :
1. An isolated and/or recombinant monoclonal antibody, which is an antibody or antibody fragment, wherein said antibody or antibody fragment comprises: ? a CDRH1 consisting of SEQ ID NO: 124; ? a CDRH2 consisting of SEQ ID NO: 125; ? a CDRH3 consisting of SEQ ID NO: 126; ? a CDRL1 consisting of SEQ ID NO: 208; ? a CDRL2 consisting of SEQ ID NO: 209; ? a CDRL3 consisting of SEQ ID NO: 210.
2. The monoclonal antibody of claim 1, wherein said antibody or antibody fragment is encoded by a light chain variable sequence of SEQ ID NO: 17 and a heavy chain variable sequence of SEQ ID NO: 16.
3. The monoclonal antibody of claim 1, wherein said antibody or antibody fragment is encoded by a light chain variable sequence having at least 70%, 80%, or 90% identity to SEQ ID NO: 17 and a heavy chain variable sequence having at least 70%, 80%, or 90% identity to SEQ ID NO: 16.
4. The monoclonal antibody of claim 1, wherein said antibody or antibody fragment is encoded by a light chain variable sequence having at least 95% identity to SEQ ID NO: 17 and a heavy chain variable sequence having at least 95% identity to SEQ ID NO:
5. The monoclonal antibody of claim 1, wherein the variable region of its heavy chain comprises or consists of SEQ ID NO: 67 and the variable region of its light chain comprises or consists of SEQ ID NO: 68.
6. The monoclonal antibody of claim 1, wherein said antibody or antibody fragment comprises a light chain variable sequence having 95% identity to SEQ ID NO: 68 and a heavy chain variable sequence having 95% identity to SEQ ID NO: 67.
7. The monoclonal antibody of any one of claims 1-6, wherein the antibody fragment is a recombinant ScFv (single chain fragment variable) antibody, Fab fragment, F(ab’)2 fragment, or Fv fragment.
8. The monoclonal antibody of any one of claims 1-7, wherein said antibody is a chimeric antibody, or is a bispecific antibody that targets a Chikungunya virus antigen other than glycoprotein.
9. The monoclonal antibody of any one of claims 1-8, wherein said antibody is an IgG. 1005362982
10. The monoclonal antibody of any one of claims 1-9, wherein said antibody or antibody fragment further comprises a cell penetrating peptide and/or is an intrabody.
11. A hybridoma encoding an antibody or antibody fragment according to any one of claims 1-10.
12. A method of detecting a Chikungunya virus infection in a subject, comprising: (a) contacting a sample from said subject with an antibody or antibody fragment of any one of claims 1-10; and (b) detecting Chikungunya virus glycoprotein E2 in said sample by binding of said antibody or antibody fragment to E2 in said sample.
13. The method of claim 12, wherein said sample is a body fluid.
14. The method of claim 12 or 13, further comprising performing steps (a) and (b) a second time and determining a change in the E2 levels as compared to the first assay.
15. A pharmaceutical composition comprising the isolated and/or recombinant monoclonal antibody or antibody fragment according to any one of claims 1-10.
16. Use of an antibody or antibody fragment according to any one of claims 1-10, or the pharmaceutical composition of claim 15, in the manufacture of a medicament for treating or reducing the likelihood of contracting a Chikungunya viral infection in a subject infected with Chikungunya virus or a subject at risk of contracting Chikungunya virus.
17. The use of claim 16, wherein said antibody or antibody fragment is to be administered prior to infection.
18. The use of claim 16, wherein said antibody or antibody fragment is to be administered after infection.
19. The use according to claim 16, wherein the antibody or antibody fragment is to be administered, or an RNA or DNA sequence or vector encoding the antibody or antibody fragment is to be administered.
20. A cell line producing the isolated and/or recombinant monoclonal antibody or antibody fragment according to any one of claims 1-10.
21. A method of producing the isolated and/or recombinant monoclonal antibody or antibody fragment according to any one of claims 1-10, wherein said method comprises the step of: (a) culturing a cell line producing said isolated and/or recombinant monoclonal antibody or antibody fragment; and 1005362982 (b) purifying the produced isolated and/or recombinant monoclonal antibody or antibody fragment.
22. The method of claim 21, wherein the method further comprises step (c) of formulating said isolated and/or recombinant monoclonal antibody or antibody fragment from step (b) into a pharmaceutical composition.
23. A kit comprising an isolated and/or recombinant monoclonal antibody or antibody fragment according to any one of claims 1-10 and optionally packaging material.
NZ775007A 2016-04-14 Antibody-mediated neutralization of Chikungunya virus NZ775007B2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201562147354P 2015-04-14 2015-04-14
NZ736445A NZ736445A (en) 2015-04-14 2016-04-14 Antibody-mediated neutralization of chikungunya virus

Publications (2)

Publication Number Publication Date
NZ775007A NZ775007A (en) 2024-08-30
NZ775007B2 true NZ775007B2 (en) 2024-12-03

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