TWI601537B - 抗－ｃｄ１９類美登醇（ｍａｙｔａｎｓｉｎｏｉｄ）免疫結合物抗體於治療ｂ－細胞惡性症狀之用途 - Google Patents
抗－ｃｄ１９類美登醇（ｍａｙｔａｎｓｉｎｏｉｄ）免疫結合物抗體於治療ｂ－細胞惡性症狀之用途 Download PDFInfo
- Publication number
- TWI601537B TWI601537B TW101117628A TW101117628A TWI601537B TW I601537 B TWI601537 B TW I601537B TW 101117628 A TW101117628 A TW 101117628A TW 101117628 A TW101117628 A TW 101117628A TW I601537 B TWI601537 B TW I601537B
- Authority
- TW
- Taiwan
- Prior art keywords
- lymphoma
- seq
- maytansinoid
- hodgkin
- antibody
- Prior art date
Links
- 229940127121 immunoconjugate Drugs 0.000 title claims description 49
- 238000011282 treatment Methods 0.000 title claims description 20
- 210000003719 b-lymphocyte Anatomy 0.000 title claims description 17
- 208000024891 symptom Diseases 0.000 title claims description 17
- 230000003211 malignant effect Effects 0.000 title description 5
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 claims description 25
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 claims description 25
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 19
- 206010028980 Neoplasm Diseases 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 11
- 230000002411 adverse Effects 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 9
- 230000036210 malignancy Effects 0.000 claims description 9
- 201000011510 cancer Diseases 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 7
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims description 7
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims description 7
- 210000004027 cell Anatomy 0.000 claims description 6
- 230000000306 recurrent effect Effects 0.000 claims description 6
- 206010025323 Lymphomas Diseases 0.000 claims description 5
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims description 4
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 claims description 4
- 201000003444 follicular lymphoma Diseases 0.000 claims description 4
- 201000007924 marginal zone B-cell lymphoma Diseases 0.000 claims description 4
- 208000021937 marginal zone lymphoma Diseases 0.000 claims description 4
- 229960004641 rituximab Drugs 0.000 claims description 4
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 3
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 3
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 3
- 208000032839 leukemia Diseases 0.000 claims description 3
- SLMVEZKWNOGJPD-UHFFFAOYSA-N 4-(pyridin-2-yldisulfanyl)butanoic acid Chemical compound OC(=O)CCCSSC1=CC=CC=N1 SLMVEZKWNOGJPD-UHFFFAOYSA-N 0.000 claims description 2
- 229960002317 succinimide Drugs 0.000 claims description 2
- 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
- 230000000735 allogeneic effect Effects 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 230000009870 specific binding Effects 0.000 claims 1
- 238000002054 transplantation Methods 0.000 claims 1
- 238000000034 method Methods 0.000 description 26
- 231100000419 toxicity Toxicity 0.000 description 13
- 230000001988 toxicity Effects 0.000 description 13
- 239000000562 conjugate Substances 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 231100000682 maximum tolerated dose Toxicity 0.000 description 11
- 208000028564 B-cell non-Hodgkin lymphoma Diseases 0.000 description 9
- 239000005022 packaging material Substances 0.000 description 9
- 239000000203 mixture Substances 0.000 description 7
- 241000699660 Mus musculus Species 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 230000003442 weekly effect Effects 0.000 description 5
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 231100000327 ocular toxicity Toxicity 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 206010061137 Ocular toxicity Diseases 0.000 description 3
- 206010044245 Toxic optic neuropathy Diseases 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 229940049595 antibody-drug conjugate Drugs 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 230000008602 contraction Effects 0.000 description 3
- 230000001186 cumulative effect Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 2
- 230000000690 anti-lymphoma Effects 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 206010014801 endophthalmitis Diseases 0.000 description 2
- 208000030533 eye disease Diseases 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 208000035824 paresthesia Diseases 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000004797 therapeutic response Effects 0.000 description 2
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 206010060933 Adverse event Diseases 0.000 description 1
- 206010065553 Bone marrow failure Diseases 0.000 description 1
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
- 208000035126 Facies Diseases 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 208000010428 Muscle Weakness Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 229940122429 Tubulin inhibitor Drugs 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000000611 antibody drug conjugate Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- -1 coatings Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 229960000520 diphenhydramine Drugs 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000003560 epithelium corneal Anatomy 0.000 description 1
- 230000007684 eye toxicity Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 231100001156 grade 3 toxicity Toxicity 0.000 description 1
- 231100000226 haematotoxicity Toxicity 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000001471 micro-filtration Methods 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 239000008299 semisolid dosage form Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 210000001988 somatic stem cell Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 238000011476 stem cell transplantation Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229940043263 traditional drug Drugs 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/537—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines spiro-condensed or forming part of bridged ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/68033—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a maytansine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
-
- 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
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
-
- 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
-
- 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
- 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
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3061—Blood 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- 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
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/515—Complete light chain, i.e. VL + CL
-
- 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
- C07K2317/77—Internalization into the cell
-
- 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
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Cell Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Oncology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11290232A EP2524929A1 (en) | 2011-05-17 | 2011-05-17 | Use of anti-CD19 maytansinoid immunoconjugate antibody for the treatment of CD19+ B-cell malignancies syptoms |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201249460A TW201249460A (en) | 2012-12-16 |
| TWI601537B true TWI601537B (zh) | 2017-10-11 |
Family
ID=46085972
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW101117628A TWI601537B (zh) | 2011-05-17 | 2012-05-17 | 抗－ｃｄ１９類美登醇（ｍａｙｔａｎｓｉｎｏｉｄ）免疫結合物抗體於治療ｂ－細胞惡性症狀之用途 |
| TW107102069A TW201834687A (zh) | 2011-05-17 | 2012-05-17 | 抗-cd19類美登醇(maytansinoid )免疫結合物抗體於治療b-細胞惡性症狀之用途 |
| TW105134320A TW201726167A (zh) | 2011-05-17 | 2012-05-17 | 抗-ｃｄ１９類美登醇（ｍａｙｔａｎｓｉｎｏｉｄ）免疫結合物抗體於治療ｂ-細胞惡性症狀之用途 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW107102069A TW201834687A (zh) | 2011-05-17 | 2012-05-17 | 抗-cd19類美登醇(maytansinoid )免疫結合物抗體於治療b-細胞惡性症狀之用途 |
| TW105134320A TW201726167A (zh) | 2011-05-17 | 2012-05-17 | 抗-ｃｄ１９類美登醇（ｍａｙｔａｎｓｉｎｏｉｄ）免疫結合物抗體於治療ｂ-細胞惡性症狀之用途 |
Country Status (30)
| Country | Link |
|---|---|
| US (2) | US9555126B2 (enExample) |
| EP (2) | EP2524929A1 (enExample) |
| JP (4) | JP6050328B2 (enExample) |
| KR (1) | KR20140043388A (enExample) |
| CN (2) | CN107007840A (enExample) |
| AR (1) | AR086412A1 (enExample) |
| AU (3) | AU2012258254B2 (enExample) |
| BR (1) | BR112013029330A8 (enExample) |
| CA (1) | CA2835738A1 (enExample) |
| CL (1) | CL2013003272A1 (enExample) |
| CO (1) | CO6821893A2 (enExample) |
| CR (1) | CR20130593A (enExample) |
| DO (1) | DOP2013000260A (enExample) |
| EA (1) | EA028574B1 (enExample) |
| EC (1) | ECSP13013084A (enExample) |
| GT (1) | GT201300276A (enExample) |
| IL (3) | IL229380B (enExample) |
| MA (1) | MA35180B1 (enExample) |
| MX (1) | MX347019B (enExample) |
| MY (1) | MY163736A (enExample) |
| NI (1) | NI201300119A (enExample) |
| PE (1) | PE20141018A1 (enExample) |
| PH (2) | PH12013502305A1 (enExample) |
| SG (2) | SG10201609729VA (enExample) |
| TN (1) | TN2013000468A1 (enExample) |
| TW (3) | TWI601537B (enExample) |
| UA (1) | UA114401C2 (enExample) |
| UY (1) | UY34077A (enExample) |
| WO (1) | WO2012156455A1 (enExample) |
| ZA (1) | ZA201309400B (enExample) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2524929A1 (en) * | 2011-05-17 | 2012-11-21 | Sanofi | Use of anti-CD19 maytansinoid immunoconjugate antibody for the treatment of CD19+ B-cell malignancies syptoms |
| EP2777714A1 (en) * | 2013-03-15 | 2014-09-17 | NBE-Therapeutics LLC | Method of producing an immunoligand/payload conjugate by means of a sequence-specific transpeptidase enzyme |
| LT3038650T (lt) | 2013-08-30 | 2021-09-10 | Immunogen, Inc. | Antikūnai ir foliatų receptoriaus 1 nustatymo testai |
| CN105837689B (zh) * | 2015-01-13 | 2020-06-19 | 博生吉安科细胞技术有限公司 | 抗cd19单克隆抗体及其制备方法 |
| WO2016180941A1 (en) * | 2015-05-13 | 2016-11-17 | Sanofi | Liquid compositions for anti-cd19 antibody-drug conjugates |
| HUE046328T2 (hu) | 2015-05-26 | 2020-03-30 | Morphosys Ag | CD19 elleni ellenanyag és Bruton-féle tirozin-kináz gátlójának kombinációja és a kombináció alkalmazásai |
| AU2016311136B2 (en) | 2015-08-21 | 2022-02-17 | Incyte Corporation | Combinations and uses thereof |
| EP3349796A4 (en) | 2015-09-17 | 2019-05-29 | ImmunoGen, Inc. | THERAPEUTIC COMBINATIONS WITH ANTI-FOLR1 IMMUNOCONJUGATES |
| FI3380525T3 (fi) | 2015-11-25 | 2024-01-30 | Immunogen Inc | Lääkeformulaatioita ja niiden käyttömenetelmiä |
| PT3916392T (pt) | 2016-05-30 | 2024-06-04 | Incyte Corp | Métodos para prever o benefício terapêutico da terapia anti-cd19 nos pacientes |
| HRP20210945T1 (hr) | 2016-06-27 | 2021-09-17 | Morphosys Ag | Formulacije protutijela anti-cd19 |
| LT3532098T (lt) | 2016-10-28 | 2021-06-25 | Morphosys Ag | Anti cd19 antikūno derinys su bcl-2 inhibitoriumi, ir jo naudojimas |
| WO2018183494A1 (en) * | 2017-03-31 | 2018-10-04 | Immunogen, Inc. | Cd19-targeting antibody-drug conjugates |
| KR20190137151A (ko) * | 2017-04-20 | 2019-12-10 | 에이디씨 테라퓨틱스 에스에이 | 병용 요법 |
| ES2988683T3 (es) | 2017-06-14 | 2024-11-21 | Adc Therapeutics Sa | Pautas posológicas para la administración de un CAF anti-CD19 |
| SG11202001817PA (en) * | 2017-09-21 | 2020-03-30 | Wuxi Biologics Ireland Ltd | Novel anti-cd19 antibodies |
| IL273424B2 (en) | 2017-09-22 | 2024-09-01 | Wuxi Biologics Ireland Ltd | Novel bispecific cd3/cd19 polypeptide complexes |
| US11274121B2 (en) | 2018-01-12 | 2022-03-15 | Immunogen, Inc. | Methods for antibody drug conjugation, purification, and formulation |
| CN113766954B (zh) | 2019-04-26 | 2024-09-24 | 伊缪诺金公司 | 喜树碱衍生物 |
| MA55794A (fr) | 2019-05-03 | 2022-03-09 | Morphosys Ag | Thérapie anti-cd19 chez des patients ayant un nombre limité de cellules nk |
| NZ786589A (en) * | 2019-10-31 | 2025-03-28 | Forty Seven Llc | Anti-cd47 and anti-cd20 based treatment of blood cancer |
| AU2020372646A1 (en) | 2019-10-31 | 2022-05-12 | Incyte Corporation | Anti-tumor combination therapy comprising anti-CD19 antibody and gamma delta T-cells |
| KR20220103969A (ko) | 2019-10-31 | 2022-07-25 | 모르포시스 아게 | 백혈병 또는 림프종의 치료를 위해 레날리도마이드와 조합된 항-cd19 요법 |
| CN110845617B (zh) * | 2019-12-05 | 2021-07-09 | 常州费洛斯药业科技有限公司 | 针对cd19的全人源抗体或抗体片段、嵌合抗原受体及应用 |
| JP2023530499A (ja) | 2020-06-22 | 2023-07-18 | モルフォシス・アーゲー | 抗ＣＤ１９抗体及びＳＩＲＰα－ＣＤ４７自然免疫チェックポイントを遮断するポリペプチドを含む抗腫瘍組み合わせ療法 |
| TW202229349A (zh) | 2020-10-06 | 2022-08-01 | 美商山可爾股份有限公司 | 用於治療包括全身性紅斑性狼瘡(sle)的自體免疫疾病之生物標記、方法及組合物 |
| BR112023010885A2 (pt) | 2020-12-04 | 2023-10-03 | Incyte Corp | Terapia de combinação de anti-cd19 |
| WO2023073645A1 (en) | 2021-10-29 | 2023-05-04 | Takeda Pharmaceutical Company Limited | Therapy comprising anti-cd19 antibody and sumo-activating enzyme inhibitor |
| EP4572756A1 (en) | 2022-08-17 | 2025-06-25 | Incyte Corporation | Therapy comprising anti-cd19 antibody and ezh2 modulators |
| WO2025087382A1 (zh) * | 2023-10-26 | 2025-05-01 | 上海先博生物科技有限公司 | 靶向cd19的嵌合抗原受体的治疗用途 |
| WO2025157132A1 (en) | 2024-01-23 | 2025-07-31 | Wuxi Biologics (Shanghai) Co., Ltd. | Multispecific antibodies targeting cd3, cd19 and cd20 and uses thereof |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2427858A1 (en) * | 2000-11-03 | 2002-05-10 | University Of Vermont And State Agricultural College | Compositions for inhibiting grb7 |
| AU2004240541B2 (en) * | 2003-05-20 | 2009-08-20 | Immunogen, Inc. | Improved cytotoxic agents comprising new maytansinoids |
| KR101456728B1 (ko) * | 2006-09-08 | 2014-10-31 | 메디뮨 엘엘씨 | 인간화 항-ｃｄ19 항체, 및 이것의 종양학, 이식 및 자가면역 질환의 치료에서의 용도 |
| EP3100745B1 (en) * | 2009-02-05 | 2018-04-18 | Immunogen, Inc. | Novel benzodiazepine derivatives |
| MX2011011684A (es) * | 2009-05-06 | 2012-01-20 | Biotest Ag | Usos de inmunoconjugados dirigidos a cd138. |
| IN2012DN02826A (enExample) * | 2009-10-21 | 2015-07-24 | Immunogen Inc | |
| EP2524929A1 (en) * | 2011-05-17 | 2012-11-21 | Sanofi | Use of anti-CD19 maytansinoid immunoconjugate antibody for the treatment of CD19+ B-cell malignancies syptoms |
| EP2550975A1 (en) * | 2011-07-29 | 2013-01-30 | Sanofi | Combination therapy for the treatment of CD19+ B-cell malignancies symptoms comprising an anti-CD19 maytansinoid immunoconjugate and rituximab |
-
2011
- 2011-05-17 EP EP11290232A patent/EP2524929A1/en not_active Ceased
-
2012
- 2012-05-16 UA UAA201314732A patent/UA114401C2/uk unknown
- 2012-05-16 EP EP12721529.1A patent/EP2710034A1/en not_active Withdrawn
- 2012-05-16 JP JP2014510798A patent/JP6050328B2/ja not_active Expired - Fee Related
- 2012-05-16 KR KR1020137033076A patent/KR20140043388A/ko not_active Abandoned
- 2012-05-16 EA EA201391714A patent/EA028574B1/ru not_active IP Right Cessation
- 2012-05-16 CN CN201611022631.9A patent/CN107007840A/zh active Pending
- 2012-05-16 BR BR112013029330A patent/BR112013029330A8/pt not_active IP Right Cessation
- 2012-05-16 SG SG10201609729VA patent/SG10201609729VA/en unknown
- 2012-05-16 CA CA2835738A patent/CA2835738A1/en not_active Abandoned
- 2012-05-16 US US14/117,806 patent/US9555126B2/en not_active Expired - Fee Related
- 2012-05-16 AU AU2012258254A patent/AU2012258254B2/en not_active Ceased
- 2012-05-16 PE PE2013002503A patent/PE20141018A1/es not_active Application Discontinuation
- 2012-05-16 MY MYPI2013004057A patent/MY163736A/en unknown
- 2012-05-16 PH PH1/2013/502305A patent/PH12013502305A1/en unknown
- 2012-05-16 CN CN201280023918.7A patent/CN103547596A/zh active Pending
- 2012-05-16 SG SG2013083407A patent/SG194894A1/en unknown
- 2012-05-16 MX MX2013013455A patent/MX347019B/es active IP Right Grant
- 2012-05-16 WO PCT/EP2012/059141 patent/WO2012156455A1/en not_active Ceased
- 2012-05-16 AR ARP120101724A patent/AR086412A1/es unknown
- 2012-05-17 UY UY0001034077A patent/UY34077A/es not_active Application Discontinuation
- 2012-05-17 TW TW101117628A patent/TWI601537B/zh not_active IP Right Cessation
- 2012-05-17 TW TW107102069A patent/TW201834687A/zh unknown
- 2012-05-17 TW TW105134320A patent/TW201726167A/zh unknown
-
2013
- 2013-11-11 IL IL229380A patent/IL229380B/en active IP Right Grant
- 2013-11-12 GT GT201300276A patent/GT201300276A/es unknown
- 2013-11-12 NI NI201300119A patent/NI201300119A/es unknown
- 2013-11-12 DO DO2013000260A patent/DOP2013000260A/es unknown
- 2013-11-12 TN TNP2013000468A patent/TN2013000468A1/fr unknown
- 2013-11-13 CR CR20130593A patent/CR20130593A/es unknown
- 2013-11-14 CL CL2013003272A patent/CL2013003272A1/es unknown
- 2013-12-12 MA MA36558A patent/MA35180B1/fr unknown
- 2013-12-12 ZA ZA2013/09400A patent/ZA201309400B/en unknown
- 2013-12-16 EC ECSP13013084 patent/ECSP13013084A/es unknown
- 2013-12-16 CO CO13293559A patent/CO6821893A2/es unknown
-
2016
- 2016-07-21 AU AU2016206317A patent/AU2016206317A1/en not_active Abandoned
- 2016-11-22 JP JP2016226407A patent/JP6181273B2/ja not_active Expired - Fee Related
- 2016-12-16 US US15/381,266 patent/US20170196988A1/en not_active Abandoned
-
2017
- 2017-07-18 JP JP2017138852A patent/JP2018021020A/ja active Pending
- 2017-07-28 PH PH12017501368A patent/PH12017501368A1/en unknown
-
2018
- 2018-02-12 IL IL257475A patent/IL257475A/en unknown
- 2018-03-01 AU AU2018201504A patent/AU2018201504A1/en not_active Abandoned
- 2018-12-16 IL IL263728A patent/IL263728A/en unknown
-
2019
- 2019-05-08 JP JP2019087962A patent/JP2019142961A/ja active Pending
Non-Patent Citations (3)
| Title |
|---|
| Al-Katib AM et al., "Superior antitumor activity of SAR3419 to rituximab in xenograft models for non-Hodgkin's lymphoma". Clin. Cancer Res.,15(12),pp.4038-45,2009. * |
| Malcolm A.Smith. "Update on developmental therapeutics for acute lymphoblastic leukemia. "Current Hematologic Malignancy Reports,Volume 4, Issue 3, pp 175-182,2009. * |
| SAR3419 Phase I Study Results in non-Hodgkin's Lymphoma at ASH.THE FREE LIBRARY. http://www.thefreelibrary.com/SAR3419+Phase+I+Study+Results+in+non-Hodgkin%27s+Lymphoma+at+ASH.-a0213720363,2009/12/07. * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TWI601537B (zh) | 抗－ｃｄ１９類美登醇（ｍａｙｔａｎｓｉｎｏｉｄ）免疫結合物抗體於治療ｂ－細胞惡性症狀之用途 | |
| TWI549690B (zh) | 包含抗－ｃｄ１９類美登素（ｍａｙｔａｎｓｉｎｏｉｄ）免疫結合物及利妥昔單抗（ｒｉｔｕｘｉｍａｂ）之用於治療ｃｄ１９＋ｂ－細胞惡性症狀之組合療法 | |
| JP6426093B2 (ja) | 組み合わせ及びその使用 | |
| US8992915B2 (en) | Combination of CD37 antibodies with ICE | |
| US20130309224A1 (en) | Combination of cd37 antibodies with rituximab | |
| JP2021525735A (ja) | 抗ｃｄ３７免疫コンジュゲート投薬レジメン | |
| TW202346342A (zh) | 抗tim-3抗體與抗pd-1抗體的藥物組合 | |
| JP2019070004A (ja) | ヒトのがんを治療するための特異的抗ｃｄ３８抗体 | |
| KR20200010472A (ko) | 항-cd19 항체 및 베네토클락스 조합 치료에 대한 치료 패러다임 | |
| EP3873524B1 (en) | Methods of treatment using anti-cd123 immunoconjugates | |
| US20160106837A1 (en) | Combination of cd37 antibodies with chlorambucil | |
| JP2019505516A (ja) | インターロイキン−１７（ｉｌ−１７）アンタゴニストを使用してざ瘡を治療する方法 | |
| NZ618012B2 (en) | Use of anti-cd19 maytansinoid immunoconjugate antibody for the treatment of b-cell malignancies symptoms | |
| OA16782A (en) | Use of anti-CD19 maytansinoid immunoconjugate antibody for the treatment of Bcell malignancies symptoms. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Annulment or lapse of patent due to non-payment of fees |