NZ745564B2 - Antibodies specific to human poliovirus receptor (pvr) - Google Patents
Antibodies specific to human poliovirus receptor (pvr) Download PDFInfo
- Publication number
- NZ745564B2 NZ745564B2 NZ745564A NZ74556417A NZ745564B2 NZ 745564 B2 NZ745564 B2 NZ 745564B2 NZ 745564 A NZ745564 A NZ 745564A NZ 74556417 A NZ74556417 A NZ 74556417A NZ 745564 B2 NZ745564 B2 NZ 745564B2
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- NZ
- New Zealand
- Prior art keywords
- seq
- antibody
- monoclonal antibody
- sequence
- antibody fragment
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
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- 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
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- 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
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
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- 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
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- 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
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- 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
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/70596—Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705
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- 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
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
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- 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 invention provides monoclonal antibodies that recognize polio virus receptor (PVR) and inhibit its binding to T cell immunoreceptor with Ig and ITIM domains (TIGIT). The present invention further provides pharmaceutical compositions comprising the antibodies and methods for their use in cancer immunotherapy, treating infections and in diagnosis.
Claims (21)
1. An isolated monoclonal antibody which binds to human poliovirus receptor (PVR), or an antibody fragment thereof comprising at least the antigen binding portion, wherein the isolated antibody or antibody fragment comprises: a CDR set of six CDRs wherein: HC CDR1 is selected from GYTFSNYWIE (SEQ ID NO: 36) and SNYWIE (SEQ ID NO: 84); HC CDR2 is EIFPGSGRINFNEKFKG (SEQ ID NO: 38); HC CDR3 is TKIYGNSFDY (SEQ ID NO: 40); LC CDR1 is selected from KASQDVGTAVV (SEQ ID NO: 44) and KASQDVGTAV (SEQ ID NO: 85); LC CDR2 is selected from the group consisting of: WASSRHN (SEQ ID NO: 46), WASSRHA (SEQ ID NO: 56), WASSRHR (SEQ ID NO: 57), WASSRHD (SEQ ID NO: 58), WASSRHE (SEQ ID NO: 59), WASSRHP (SEQ ID NO: 60), and WASSRHT (SEQ ID NO: 61); and LC CDR3 is QQYSRYPLT (SEQ ID NO: 48).
2. The isolated monoclonal antibody or the antibody fragment according to claim 1, wherein the HC CDR1 sequence is selected from the group consisting of GYTFSNYWIE (SEQ ID NO: 36) and SNYWIE (SEQ ID NO: 84); HC CDR2 sequence consists of the sequence EIFPGSGRINFNEKFKG (SEQ ID NO: 38); HC CDR3 consists of the sequence: TKIYGNSFDY (SEQ ID NO: 40); LC CDR1 sequence is selected from the group consisting of KASQDVGTAVV (SEQ ID NO: 44) and KASQDVGTAV (SEQ ID NO: 85); LC CDR2 consists of the sequence: WASSRHN (SEQ ID NO: 46); and LC CDR3 consists of the sequence: QQYSRYPLT (SEQ ID NO: 48).
3. An isolated monoclonal antibody which binds to human poliovirus receptor (PVR) monoclonal antibody or antibody fragment thereof comprising a heavy-chain (HC) variable region of SEQ ID NO: 77, and a light-chain (LC) variable region selected from the group consisting of SEQ ID NO: 79, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, and SEQ ID NO: 54.
4. The isolated monoclonal antibody or the antibody fragment according to any one of claims 1 to 3, comprising a heavy chain and a light chain, wherein the heavy chain comprises SEQ ID NO: 77 and the light chain comprises SEQ ID NO: 79.
5. The isolated monoclonal antibody or the antibody fragment thereof according to any one of claims 1 to 4, wherein the antibody is a chimeric antibody.
6. The chimeric monoclonal antibody or the antibody fragment thereof according to claim 5, comprising a heavy-chain (HC) variable region of SEQ ID NO: 77, and a light-chain (LC) variable region MARKED-UP COPY selected from the group consisting of SEQ ID NO: 79, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, and SEQ ID NO: 54.
7. The chimeric monoclonal antibody or antibody fragment according to claim 5 or 6, comprising a human constant region.
8. The chimeric monoclonal antibody or antibody fragment according to claim 7, comprising a human IgG1 constant region.
9. The isolated monoclonal antibody according to any one of claims 1 to 8 capable of inhibit binding of PVR to T cell immunoreceptor with Ig and ITIM domains (TIGIT).
10. A polynucleotide sequence encoding at least one region of a HC or a LC sequence of a monoclonal antibody or antibody fragment according to any one of claims 1 to 9.
11. The polynucleotide sequence of claim 10, encoding a monoclonal antibody heavy chain variable region, wherein the polynucleotide sequence comprises SEQ ID NO: 33, or a variant thereof having at least 90% identity to SEQ ID NO: 33.
12. The polynucleotide sequence of claim 10, encoding a monoclonal antibody light chain variable region, wherein the polynucleotide sequence SEQ ID NO: 41, or a variant thereof having at least 90% identity to SEQ ID NO: 41.
13. A plasmid comprising at least one polynucleotide sequence according to any one of claims 10 to 12.
14. A cell line comprising a polynucleotide sequence according to any one of claims 10 to 12.
15. The monoclonal antibody according to any one of claims 1 to 8 attached to a cytotoxic moiety, a radioactive moiety, or an identifiable moiety.
16. A pharmaceutical composition comprising as an active ingredient, at least one isolated antibody or fragment thereof, according to any one of claims 1 to 9 and 15, and a pharmaceutical acceptable excipient, diluent, salt or carrier.
17. The pharmaceutical composition of claim 16 for use in modulating the immune system by inhibiting binding of PVR to TIGIT.
18. The pharmaceutical composition of claim 16 for use in treating cancer.
19. The pharmaceutical composition of claim 16 for use in preventing or treating a viral infection in a subject.
20. A method of diagnosing a cancer in a subject, the method comprising contacting a biological sample with an antibody or antibody fragment according to any one of claims 1 to 8 and 15.
21. A kit for diagnosing a cancer in a subject comprising at least one antibody or antibody fragment according to any one of claims 1 to 8 and 15.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662301727P | 2016-03-01 | 2016-03-01 | |
| US201662364924P | 2016-07-21 | 2016-07-21 | |
| PCT/IL2017/050256 WO2017149538A1 (en) | 2016-03-01 | 2017-02-28 | Antibodies specific to human poliovirus receptor (pvr) |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ745564A NZ745564A (en) | 2024-12-20 |
| NZ745564B2 true NZ745564B2 (en) | 2025-03-21 |
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