JP2020510075A - 乳癌の治療のための組合せ療法 - Google Patents
乳癌の治療のための組合せ療法 Download PDFInfo
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- JP2020510075A JP2020510075A JP2019550800A JP2019550800A JP2020510075A JP 2020510075 A JP2020510075 A JP 2020510075A JP 2019550800 A JP2019550800 A JP 2019550800A JP 2019550800 A JP2019550800 A JP 2019550800A JP 2020510075 A JP2020510075 A JP 2020510075A
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- 230000008719 thickening Effects 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 231100000747 viability assay Toxicity 0.000 description 1
- 238000003026 viability measurement method Methods 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
Classifications
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/453—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- 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
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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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Abstract
Description
mm3でのTVを、以下の式に従って算出した。
TV=長さ×幅2×0.5
長さ:腫瘍の最大直径(mm)
幅:長さに対して直角の直径(mm)
腫瘍増殖阻害率%(TGI)を、次式:
(式中、DAY Xは、測定の任意の日である)
に従って算出した。
Claims (37)
- 治療を必要とする患者において乳癌を治療する方法であって、(E)−N,N−ジメチル−4−((2−((5−((Z)−4,4,4−トリフルオロ−1−(3−フルオロ−1H−インダゾール−5−イル)−2−フェニルブタ−1−エン−1−イル)ピリジン−2−イル)オキシ)エチル)アミノ)ブタ−2−エンアミド、(E)−4−((2−(4−((E)−1−(1H−インダゾール−5−イル)−2−フェニルブタ−1−エン−1−イル)フェノキシ)エチル)アミノ)−N,N−ジメチルブタ−2−エンアミド、及び(E)−N,N−ジメチル−4−((2−(4−((E)−4,4,4−トリフルオロ−1−(3−フルオロ−1H−インダゾール−5−イル)−2−フェニルブタ−1−エン−1−イル)フェノキシ)エチル)アミノ)ブタ−2−エンアミド、又はそれらの薬学的に許容される塩からなる群から選択されるERα阻害剤と、CDK4/6阻害剤又はその薬学的に許容される塩との組合せを前記患者に投与することを含む、方法。
- 前記ERα阻害剤が、(E)−N,N−ジメチル−4−((2−((5−((Z)−4,4,4−トリフルオロ−1−(3−フルオロ−1H−インダゾール−5−イル)−2−フェニルブタ−1−エン−1−イル)ピリジン−2−イル)オキシ)エチル)アミノ)ブタ−2−エンアミド又はその薬学的に許容される塩である、請求項1に記載の方法。
- 前記ERα阻害剤又はその薬学的に許容される塩が、50mgから1000mgの間の1日用量で投与される、請求項1又は2に記載の方法。
- 前記ERα阻害剤又はその薬学的に許容される塩が、300mgの1日用量で投与される、請求項3に記載の方法。
- 前記CDK4/6阻害剤が、6−アセチル−8−シクロペンチル−5−メチル−2−{[5−(ピペラジン−1−イル)ピリジン−2イル]アミノ}ピリド[2,3−d]ピリミジン−7(8H)−オン(パルボシクリブ)及びその薬学的に許容される塩、N−(5−((4−エチルピペラジン−1−イル)メチル)ピリジン−2−イル)−5−フルオロ−4−(4−フルオロ−1−イソプロピル−2−メチル−1H−ベンゾ[d]イミダゾール−6−イル)ピリミジン−2−アミン(アベマシクリブ)及びその薬学的に許容される塩、及び7−シクロペンチル−2−(5−ピペラジン−1−イル−ピリジン−2−イルアミノ)−7H−ピロロ[2,3−d]ピリミジン−6−カルボン酸ジメチルアミド(リボシクリブ)、2’−((5−(4−イソプロピルピペラジン−1−イル)ピリジン−2−イル)アミノ)−7’,8’ジヒドロ−6’H−スピロ[シクロヘキサネル,9’ピラジノ[1’,2’:1,5]ピロロ[2,3−d]ピリミジン]−6’−オン二塩酸塩、2’−((5−(4−メチルピペラジン−1−イル)ピリジン−2−イル)アミノ)−7’,8’−ジヒドロ−6’H−スピロ[シクロヘキサン−1,9’−ピラジノ[1’,2’:1,5]ピロロ[2,3−d]ピリミジン]−6’−オン(GIT−28)、N−(4−ピペリジニル)−4−(2,6−ジクロロベンゾイルアミノ)−1H−ピラゾール−3−カルボキサミド(AT−7519)、2−ヒドロキシ−1−[2−[[9−(trans−4−メチルシクロヘキシル)−9H−ピリド[4’,3’:4,5]ピロロ[2,3−d]ピリミジン−2−イル]アミノ]−7,8−ジヒドロ−1,6−ナフチリジン−6(5H)−イル]エタノン(FLX−925)、2−(2−クロロフェニル)−5,7−ジヒドロキシ−8−((3S,4R)−3−ヒドロキシ−1−メチルピペリジン−4−イル)−4H−クロメン−4−オン(アルボシジブ)、及びそれらの薬学的に許容される塩からなる群から選択される、請求項1〜4のいずれか一項に記載の方法。
- 前記CDK4/6阻害剤が、パルボシクリブである、請求項5に記載の方法。
- 前記パルボシクリブが、75mgの1日用量で投与される、請求項6に記載の方法。
- 前記パルボシクリブが、100mgの1日用量で投与される、請求項6に記載の方法。
- 前記パルボシクリブが、125mgの1日用量で投与される、請求項6に記載の方法。
- 前記CDK4/6阻害剤が、リボシクリブである、請求項5に記載の方法。
- 前記リボシクリブが、200mg/日の1日用量で投与される、請求項10に記載の方法。
- 前記リボシクリブが、400mg/日の1日用量で投与される、請求項10に記載の方法。
- 前記リボシクリブが、600mg/日の1日用量で投与される、請求項10に記載の方法。
- 前記CDK4/6阻害剤が、アベマシクリブである、請求項5に記載の方法。
- 前記アベマシクリブが、200mg/日の1日用量で投与される、請求項14に記載の方法。
- 前記アベマシクリブが、300mg/日の1日用量で投与される、請求項14に記載の方法。
- 前記アベマシクリブが、400mg/日の1日用量で投与される、請求項14に記載の方法。
- 前記CDK4/6阻害剤が、2’−((5−(4−イソプロピルピペラジン−1−イル)ピリジン−2−イル)アミノ)−7’,8’ジヒドロ−6’H−スピロ[シクロヘキサネル,9’ピラジノ[1’,2’:1,5]ピロロ[2,3−d]ピリミジン]−6’−オン二塩酸塩である、請求項5に記載の方法。
- 前記CDK4/6阻害剤が、2’−((5−(4−メチルピペラジン−1−イル)ピリジン−2−イル)アミノ)−7’,8’−ジヒドロ−6’H−スピロ[シクロヘキサン−1,9’−ピラジノ[1’,2’:1,5]ピロロ[2,3−d]ピリミジン−6’−オン又はその薬学的に許容される塩である、請求項5に記載の方法。
- 2’−((5−(4−メチルピペラジン−1−イル)ピリジン−2−イル)アミノ)−7’,8’−ジヒドロ−6’H−スピロ[シクロヘキサン−1,9’−ピラジノ[1’,2’:1,5]ピロロ[2,3−d]ピリミジン−6’−オン又はその薬学的に許容される塩が、190から200mg/m2の間の投与量で投与される、請求項19に記載の方法。
- 前記CDK4/6阻害剤が、AT−7519である、請求項5に記載の方法。
- 前記AT−7519が、3週間にわたり投与され、前記AT−7519が、第1日、第4日、第8日及び第11日に、各投与時、27mg/m2の量で投与される、請求項21に記載の方法。
- 前記CDK4/6阻害剤が、FLX−925である、請求項5に記載の方法。
- 前記CDK4/6阻害剤が、アルボシジブである、請求項5に記載の方法。
- 前記アルボシジブが、約72時間にわたり、8〜122mg/m2の間の投与量で投与される、請求項24に記載の方法。
- 前記ERα阻害剤又はその薬学的に許容される塩と、前記CDK4/6阻害剤又はその薬学的に許容される塩とが、別々の製剤として投与される、請求項1〜25のいずれか一項に記載の方法。
- 前記ERα阻害剤又はその薬学的に許容される塩と、前記CDK4/6阻害剤又はその薬学的に許容される塩とが、単一の製剤として投与される、請求項1〜25のいずれか一項に記載の方法。
- 前記ERα阻害剤又はその薬学的に許容される塩と、前記CDK4/6阻害剤又はその薬学的に許容される塩とが、順次投与される、請求項1〜25のいずれか一項に記載の方法。
- 前記ERα阻害剤又はその薬学的に許容される塩と、前記CDK4/6阻害剤又はその薬学的に許容される塩とが、同時に投与される、請求項1〜25のいずれか一項に記載の方法。
- 前記ERα阻害剤が、前記ERα阻害剤の遊離塩基の形態である、請求項1〜29のいずれか一項に記載の方法。
- 前記ERα阻害剤の薬学的に許容される塩が、塩酸塩である、請求項1〜29のいずれか一項に記載の方法。
- (E)−N,N−ジメチル−4−((2−((5−((Z)−4,4,4−トリフルオロ−1−(3−フルオロ−1H−インダゾール−5−イル)−2−フェニルブタ−1−エン−1−イル)ピリジン−2−イル)オキシ)エチル)アミノ)ブタ−2−エンアミド、(E)−4−((2−(4−((E)−1−(1H−インダゾール−5−イル)−2−フェニルブタ−1−エン−1−イル)フェノキシ)エチル)アミノ)−N,N−ジメチルブタ−2−エンアミド、及び(E)−N,N−ジメチル−4−((2−(4−((E)−4,4,4−トリフルオロ−1−(3−フルオロ−1H−インダゾール−5−イル)−2−フェニルブタ−1−エン−1−イル)フェノキシ)エチル)アミノ)ブタ−2−エンアミド、又はそれらの薬学的に許容される塩からなる群から選択されるERα阻害剤、及びCDK4/6阻害剤又はその薬学的に許容される塩を含む、医薬製剤。
- (E)−N,N−ジメチル−4−((2−((5−((Z)−4,4,4−トリフルオロ−1−(3−フルオロ−1H−インダゾール−5−イル)−2−フェニルブタ−1−エン−1−イル)ピリジン−2−イル)オキシ)エチル)アミノ)ブタ−2−エンアミドの遊離塩基の形態を含む、請求項32に記載の医薬製剤。
- 前記ERα阻害剤が、(E)−N,N−ジメチル−4−((2−((5−((Z)−4,4,4−トリフルオロ−1−(3−フルオロ−1H−インダゾール−5−イル)−2−フェニルブタ−1−エン−1−イル)ピリジン−2−イル)オキシ)エチル)アミノ)ブタ−2−エンアミドの薬学的に許容される塩である、請求項32に記載の医薬製剤。
- (E)−N,N−ジメチル−4−((2−((5−((Z)−4,4,4−トリフルオロ−1−(3−フルオロ−1H−インダゾール−5−イル)−2−フェニルブタ−1−エン−1−イル)ピリジン−2−イル)オキシ)エチル)アミノ)ブタ−2−エンアミドの薬学的に許容される塩が、(E)−N,N−ジメチル−4−((2−((5−((Z)−4,4,4−トリフルオロ−1−(3−フルオロ−1H−インダゾール−5−イル)−2−フェニルブタ−1−エン−1−イル)ピリジン−2−イル)オキシ)エチル)アミノ)ブタ−2−エンアミドの塩酸塩の形態である、請求項34に記載の医薬製剤。
- 乳癌の治療における、(E)−N,N−ジメチル−4−((2−((5−((Z)−4,4,4−トリフルオロ−1−(3−フルオロ−1H−インダゾール−5−イル)−2−フェニルブタ−1−エン−1−イル)ピリジン−2−イル)オキシ)エチル)アミノ)ブタ−2−エンアミド、(E)−4−((2−(4−((E)−1−(1H−インダゾール−5−イル)−2−フェニルブタ−1−エン−1−イル)フェノキシ)エチル)アミノ)−N,N−ジメチルブタ−2−エンアミド、及び(E)−N,N−ジメチル−4−((2−(4−((E)−4,4,4−トリフルオロ−1−(3−フルオロ−1H−インダゾール−5−イル)−2−フェニルブタ−1−エン−1−イル)フェノキシ)エチル)アミノ)ブタ−2−エンアミド、又はそれらの薬学的に許容される塩からなる群から選択されるERα阻害剤と、CDK4/6阻害剤又はその薬学的に許容される塩との組合せの使用。
- 乳癌の治療のための医薬の調製における、(E)−N,N−ジメチル−4−((2−((5−((Z)−4,4,4−トリフルオロ−1−(3−フルオロ−1H−インダゾール−5−イル)−2−フェニルブタ−1−エン−1−イル)ピリジン−2−イル)オキシ)エチル)アミノ)ブタ−2−エンアミド、(E)−4−((2−(4−((E)−1−(1H−インダゾール−5−イル)−2−フェニルブタ−1−エン−1−イル)フェノキシ)エチル)アミノ)−N,N−ジメチルブタ−2−エンアミド、及び(E)−N,N−ジメチル−4−((2−(4−((E)−4,4,4−トリフルオロ−1−(3−フルオロ−1H−インダゾール−5−イル)−2−フェニルブタ−1−エン−1−イル)フェノキシ)エチル)アミノ)ブタ−2−エンアミド、又はそれらの薬学的に許容される塩からなる群から選択されるERα阻害剤と、CDK4/6阻害剤又はその薬学的に許容される塩との組合せの使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US201762472345P | 2017-03-16 | 2017-03-16 | |
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KR102425785B1 (ko) * | 2016-11-28 | 2022-07-28 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 인다졸 유도체의 염 및 이의 결정 |
RU2020123665A (ru) | 2018-01-08 | 2022-02-10 | Г1 Терапьютикс, Инк. | Преимущественные режимы дозирования g1т38 |
KR20230104158A (ko) * | 2020-11-06 | 2023-07-07 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 유방암의 치료 방법 |
CN113018357A (zh) * | 2021-02-08 | 2021-06-25 | 湖南农业大学 | 茶多酚和帕博西尼联合在制备治疗乳腺癌的制剂中的用途 |
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EP3595725B1 (en) | 2023-05-03 |
MX2019010981A (es) | 2020-09-07 |
CN110636862A (zh) | 2019-12-31 |
JP7219224B2 (ja) | 2023-02-07 |
WO2018170447A1 (en) | 2018-09-20 |
RU2019132893A3 (ja) | 2021-06-24 |
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IL269357A (en) | 2019-11-28 |
SG11201908531WA (en) | 2019-10-30 |
MA47776A (fr) | 2020-01-22 |
BR112019019261A2 (pt) | 2020-06-16 |
KR20190125448A (ko) | 2019-11-06 |
EP4218820A3 (en) | 2023-09-20 |
KR102517650B1 (ko) | 2023-04-05 |
RU2019132893A (ru) | 2021-04-16 |
EP4218820A2 (en) | 2023-08-02 |
AU2018234903B2 (en) | 2024-02-08 |
AU2018234903A1 (en) | 2019-10-10 |
US11083722B2 (en) | 2021-08-10 |
EP3595725A1 (en) | 2020-01-22 |
CA3056701A1 (en) | 2018-09-20 |
RU2764724C2 (ru) | 2022-01-19 |
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