NZ755339B2 - Inhibition of platelet aggregation using anti-human gpvi antibodies - Google Patents
Inhibition of platelet aggregation using anti-human gpvi antibodies Download PDFInfo
- Publication number
- NZ755339B2 NZ755339B2 NZ755339A NZ75533918A NZ755339B2 NZ 755339 B2 NZ755339 B2 NZ 755339B2 NZ 755339 A NZ755339 A NZ 755339A NZ 75533918 A NZ75533918 A NZ 75533918A NZ 755339 B2 NZ755339 B2 NZ 755339B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- use according
- administered
- protein
- seq
- humanized protein
- Prior art date
Links
- 230000005764 inhibitory process Effects 0.000 title 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 title 1
- 108090000623 proteins and genes Proteins 0.000 claims abstract 21
- 102000004169 proteins and genes Human genes 0.000 claims abstract 21
- 102100038394 Platelet glycoprotein VI Human genes 0.000 claims abstract 6
- 101710194982 Platelet glycoprotein VI Proteins 0.000 claims abstract 6
- 108010064773 platelet membrane glycoprotein VI Proteins 0.000 claims abstract 2
- 208000007536 Thrombosis Diseases 0.000 claims 4
- 230000001154 acute effect Effects 0.000 claims 4
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims 3
- 206010003178 Arterial thrombosis Diseases 0.000 claims 2
- 208000006011 Stroke Diseases 0.000 claims 2
- 206010047249 Venous thrombosis Diseases 0.000 claims 2
- 210000004351 coronary vessel Anatomy 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 238000001802 infusion Methods 0.000 claims 2
- 208000028867 ischemia Diseases 0.000 claims 2
- 230000000302 ischemic effect Effects 0.000 claims 2
- 208000037803 restenosis Diseases 0.000 claims 2
- 208000011580 syndromic disease Diseases 0.000 claims 2
- KRQUFUKTQHISJB-YYADALCUSA-N 2-[(E)-N-[2-(4-chlorophenoxy)propoxy]-C-propylcarbonimidoyl]-3-hydroxy-5-(thian-3-yl)cyclohex-2-en-1-one Chemical compound CCC\C(=N/OCC(C)OC1=CC=C(Cl)C=C1)C1=C(O)CC(CC1=O)C1CCCSC1 KRQUFUKTQHISJB-YYADALCUSA-N 0.000 claims 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 1
- 201000001320 Atherosclerosis Diseases 0.000 claims 1
- 208000021910 Cerebral Arterial disease Diseases 0.000 claims 1
- 208000032064 Chronic Limb-Threatening Ischemia Diseases 0.000 claims 1
- 101100215344 Dictyostelium discoideum act17 gene Proteins 0.000 claims 1
- 206010014522 Embolism venous Diseases 0.000 claims 1
- 238000012276 Endovascular treatment Methods 0.000 claims 1
- 208000032382 Ischaemic stroke Diseases 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 206010034576 Peripheral ischaemia Diseases 0.000 claims 1
- 208000010378 Pulmonary Embolism Diseases 0.000 claims 1
- 241000613130 Tima Species 0.000 claims 1
- 206010047097 Vascular purpura Diseases 0.000 claims 1
- 238000004220 aggregation Methods 0.000 claims 1
- 230000002776 aggregation Effects 0.000 claims 1
- 210000000709 aorta Anatomy 0.000 claims 1
- 210000001367 artery Anatomy 0.000 claims 1
- 230000007214 atherothrombosis Effects 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 230000002490 cerebral effect Effects 0.000 claims 1
- 230000001684 chronic effect Effects 0.000 claims 1
- 208000029078 coronary artery disease Diseases 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 238000001727 in vivo Methods 0.000 claims 1
- 230000002757 inflammatory effect Effects 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 206010062198 microangiopathy Diseases 0.000 claims 1
- 208000010125 myocardial infarction Diseases 0.000 claims 1
- 238000013146 percutaneous coronary intervention Methods 0.000 claims 1
- 230000002093 peripheral effect Effects 0.000 claims 1
- 208000001297 phlebitis Diseases 0.000 claims 1
- 239000012146 running buffer Substances 0.000 claims 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 claims 1
- 238000013151 thrombectomy Methods 0.000 claims 1
- 238000011282 treatment Methods 0.000 claims 1
- 230000002792 vascular Effects 0.000 claims 1
- 208000004043 venous thromboembolism Diseases 0.000 claims 1
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
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
-
- 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
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- 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
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39541—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against normal tissues, cells
-
- 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
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
-
- 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
-
- 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
- C07K2317/55—Fab or Fab'
-
- 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
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6456—Plasminogen activators
- C12N9/6459—Plasminogen activators t-plasminogen activator (3.4.21.68), i.e. tPA
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21068—Tissue plasminogen activator (3.4.21.68), i.e. tPA
Abstract
The present invention relates to an isolated humanized protein binding to human Glycoprotein VI (hGPVI ) for treating a GPVI-related condition in a subject in need thereof, wherein said isolated humanized protein is to be administered during at least 2 hours to the subject, preferably during at least 4 to 6 hours.
Claims (21)
1. Use of an isolated humanized protein binding to human rotein VI (hGPVI) in the manufacture of a medicament for the treatment of a GPVI-related condition 5 in a subject in need f, wherein said isolated humanized protein is to be stered during at least 2 hours to the t, wherein said isolated humanized protein is an antibody le or an antibody fragment, and wherein: - the variable region of the heavy chain comprises the following CDRs: 10 VH-CDR1: GYTFTSYNMH (SEQ ID NO: 1); VH-CDR2: GIYPGNGDTSYNQKFQG (SEQ ID NO: 2); and VH-CDR3: GTVVGDWYFDV (SEQ ID NO: 3); and - the variable region of the light chain comprises the following CDRs: VL-CDR1: RSSQSLENSNGNTYLN (SEQ ID NO: 4); 15 VL-CDR2: RVSNRFS (SEQ ID NO: 5); and VL-CDR3: LQLTHVPWT (SEQ ID NO: 6).
2. The use according to claim 1, wherein the isolated humanized protein is to be administered during at least 4 to 6 hours.
3. The use according to claim 1 or 2, wherein the isolated humanized protein is to be 20 injected.
4. The use according to claim 3, wherein the isolated humanized protein is to be injected by intravenous infusion.
5. The use ing to any one of claims 1 to 4, wherein a dose of humanized protein ranging from about 0.5 mg/kg to about 50 mg/kg is to be administered to the subject. 25
6. The use according to claim 5, wherein a dose of zed protein ranging from about 1 mg/kg to about 32 mg/kg is to be administered to the subject.
7. The use according to claim 5 or 6, n a dose of humanized protein of about 8 mg/kg is to be administered to the subject. 1005280383
8. The use according to any one of claims 1 to 4, wherein a dose of humanized n ranging from about 125 mg to about 2000 mg is to be administered to the subject.
9. The use according to claim 8, wherein a dose of zed protein ranging from about 250 mg to about 1000 mg is to be administered to the subject. 5
10. The use according to claim 8 or 9, wherein a dose of humanized protein ranging from about 500 mg to about 1000 mg is to be administered to the t.
11. The use according to any one of claims 1 to 10, wherein a first bolus of the ed humanized protein is to be administered.
12. The use according to claim 11, wherein said first bolus administration comprises 10 about 10 to 50% of the total dosage of the isolated humanized protein to be administered, and wherein said first bolus is to be administered in about 5 to 30 minutes.
13. The use according to claim 11 or 12, wherein said first bolus administration comprises about 20% of the total dosage of the isolated humanized protein to be 15 administered, and wherein said first bolus is to be administered in about 15 s.
14. The use according to any one of claims 1 to 13, wherein said protein has a KD for binding to hGPVI less than 15 nM, wherein said KD is measured by surface plasmon resonance using 960 to 1071 RU of soluble human GPVI and using PBS pH 7.4 as running buffer and wherein said isolated humanized protein does not induce a GPVI 20 depletion phenotype in vivo.
15. The use according to any one of claims 1 to 14, wherein said isolated humanized protein is an antibody molecule or an antibody fragment selected from the group consisting of a whole antibody, a humanized dy, a single chain antibody, a
16.Fv, a Fab and a unibody. 25 16. The use ing to any one of claims 1 to 15, wherein said ed humanized protein is monovalent.
17. The use according to any one of claims 1 to 16, wherein said protein is an antibody molecule or an antibody fragment, and wherein the amino acid sequence encoding 1005280383 the heavy chain le region is SEQ ID NO: 7 and the amino acid sequence encoding the light variable region is SEQ ID NO: 8, or any sequence having an amino acid sequence that shares at least 60% identity with said SEQ ID NO: 7 or 8.
18. The use according to any one of claims 1 to 17, wherein said GPVI-related 5 condition is selected from arterial and venous thrombosis, restenosis, acute ry syndrome, cerebrovascular accidents due to atherosclerosis, cerebral vascular es including ischemic stroke, venous thromboembolism diseases, otic microangiopathies, vascular purpura and critical limb ischemia.
19. The use according to any one of claims 1 to 17, wherein said GPVI-related 10 condition is ed from coronary artery and cerebral artery diseases.
20. The use according to any one of claims 1 to 17, wherein said GPVI-related condition is selected from atherothrombosis, ischemic events, acute coronary artery syndrome, myocardial infarction, stroke, percutaneous coronary intervention, ng thrombosis, ischemic restenosis, acute ischemia, chronic ischemia, 15 diseases of the aorta and its branches, peripheral artery e, venous thrombosis, acute phlebitis, pulmonary embolism, cancer-associated thrombosis, inflammatory thrombosis and thrombosis associated to ion.
21. The use according to any one of claims 1 to 20, wherein said subject was previously treated or is to be d by endovascular treatment and/or thrombectomy. 1005280383 (A) 32 g Aura? mglkg E” an 1 ..... 2 3’ + 4 3 4.. a 0.9 as 1.0 m 253 .3: 150 5 gI g 3’ +1 E 50 “a + 4 :59. vi— 8 a. 0 7 0.0 9.5 m 135 20 Time (H) PIa$eeletcoun£G.i“ as; :7; 3 3 E; E E ,E '9 a; g E M W «E .E ”a ? ii 3% m m 0,0 ([5 L0 125 30 2.3 0.0 (3.5 L0 L5 2.0 2.6 Time (Mum) Time (hams) 301 l) é & E“ g1 "3 ‘53 ,3 .125 m as; (W (15 If! L5 213 15 EM} 6,5 131 L59 31) 3:3 Time (Mum) Tim: (Mum) Which: wwwww ROW} 7 lmgjkg ACTGH 2mgfkg ~— -—- w ACTG! I? 4mgfkg .. . - ~— AC‘TO} 3’ ?mgfkg g» 100‘ E * 4 6 8 Time (H) + ACT17 2 mglkg -I- ACT 17 8 mg/kg g9 100 E ‘ Q 50 0 7771‘77 J G 2 4 6 8 Time (H) «I- ACT 17 2 mglkg «I- ACT 17' 8 mglkg ~o— WMOF -l- AMBQUF + MSSOJ «Iv-- AK‘EZH E da- GATUZF "3-“ 3125’? ~a~ BY4791 20H!) wan G????‘t 0 2 4 Ei 3 Tima (H) A 80 y a: : a? ...E . E --—ACT017 8mg/kg / 15-minute bolus + 5,75 hour-Enfusmn g 60 -I—ACT017 Smg/kg/ 1—hour infusion E «- ACTON Smg/kg / 25-minute bolus g ------ Vehicle ’57: 40 0 2 4 6 8 10 ‘12 GPV! R: my mi} +WT Mutant 9 O 100 200 300 400 500 600 700 800 900 ACTGW (mg/ mi) 100,00 , 00,00 _ 30,00 Aggregation 70,00 60,00 50,00 , t 1 of 40,00 , +subject 2 30,00 * 29,09 10,00 5 D(00 lW._,_—‘______"WW—“Tnnnnnnnn.—.r_._..w__...w(nnnnnnnnnnnnnnnnnnnnnnnnn'—§‘—"""""T...._._._._._._._.T"""""""""""""T"—— r—""""""""""t é?o 2: ‘9 ”v, E 7G ‘b 0 ‘3‘ ‘b V ‘b has (2:3, '0 x “x m 0 36° 597 *6 99 ‘3’ Time {hours}. FIG. 9
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP17154658 | 2017-02-03 | ||
| PCT/EP2018/052664 WO2018141909A1 (en) | 2017-02-03 | 2018-02-02 | Inhibition of platelet aggregation using anti-human gpvi antibodies |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ755339A NZ755339A (en) | 2024-07-05 |
| NZ755339B2 true NZ755339B2 (en) | 2024-10-08 |
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