HRP20210152T1 - Bispecifična antitijela za uporabu u imunoterapiji raka - Google Patents
Bispecifična antitijela za uporabu u imunoterapiji raka Download PDFInfo
- Publication number
- HRP20210152T1 HRP20210152T1 HRP20210152TT HRP20210152T HRP20210152T1 HR P20210152 T1 HRP20210152 T1 HR P20210152T1 HR P20210152T T HRP20210152T T HR P20210152TT HR P20210152 T HRP20210152 T HR P20210152T HR P20210152 T1 HRP20210152 T1 HR P20210152T1
- Authority
- HR
- Croatia
- Prior art keywords
- amino acid
- bispecific antibody
- specificity
- chain bispecific
- variable domain
- Prior art date
Links
- 238000002619 cancer immunotherapy Methods 0.000 title 1
- 150000001413 amino acids Chemical group 0.000 claims 5
- 108090000765 processed proteins & peptides Proteins 0.000 claims 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims 2
- 239000004471 Glycine Substances 0.000 claims 2
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims 2
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims 2
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 claims 2
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims 2
- 210000001744 T-lymphocyte Anatomy 0.000 claims 2
- 239000002246 antineoplastic agent Substances 0.000 claims 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 2
- 210000004881 tumor cell Anatomy 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 239000000427 antigen Substances 0.000 claims 1
- 102000036639 antigens Human genes 0.000 claims 1
- 108091007433 antigens Proteins 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- 231100000433 cytotoxic Toxicity 0.000 claims 1
- 230000001472 cytotoxic effect Effects 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 238000001802 infusion Methods 0.000 claims 1
- 238000007918 intramuscular administration Methods 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- 238000002372 labelling Methods 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 239000003550 marker Substances 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 239000002105 nanoparticle Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 230000000069 prophylactic effect Effects 0.000 claims 1
- 238000007920 subcutaneous administration Methods 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
Classifications
-
- 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
- C07K16/2809—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 against the T-cell receptor (TcR)-CD3 complex
-
- 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
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- 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
- C07K16/2878—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 NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- 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
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/626—Diabody or triabody
-
- 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
-
- 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
- C07K2317/75—Agonist effect on antigen
-
- 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
- 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)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Oncology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Claims (12)
1. Jednolančano bispecifično dijatijelo koje sadrži:
a. varijabilnu domenu teškog lanca imunoglobulina (VH) s prvom specifičnošću (A), pri čemu navedena varijabilna domena teškog lanca (VHA) ima aminokiselinsku sekvencu prema SEQ ID NO: 1, pri čemu je prva specifičnost (A) usmjerena protiv antigena TRAIL-R2;
b. varijabilnu domenu lakog lanca imunoglobulina (VL) s drugom specifičnošću (B), pri čemu navedena varijabilna domena lakog lanca (VLB) ima aminokiselinsku sekvencu prema SEQ ID NO: 3, pri čemu je druga specifičnost (B) usmjerena protiv CD3 limfocita T;
c. varijabilnu domenu teškog lanca imunoglobulina (VH) sa specifičnošću (B), pri čemu navedena varijabilna domena teškog lanca (VHB) ima aminokiselinsku sekvencu prema SEQ ID NO: 5; i
d. varijabilnu domenu lakog lanca imunoglobulina (VL) sa specifičnošću (A), pri čemu navedena varijabilna domena lakog lanca (VLA) ima aminokiselinsku sekvencu prema SEQ ID NO: 7;
pri čemu su VH i VL domene jednolančanog bispecifičnog antitijela povezane redom VHA-VLB-VHB-VLA, pri čemu je svaka VH i VL domena povezana peptidnim veznikom, pri čemu se navedeni peptidni veznik između VHA i VLB domena i između VHB i VLA domena sastoji od četiri glicinska aminokiselinska ostatka i jednog serinskog aminokiselinskog ostatka (GGGGS), i peptidni veznik između VLB i VHB domena sastoji od tri sekvence veznika koje se sastoje od četiri glicinska aminokiselinska ostatka i jednog serinskog aminokiselinskog ostatka od kojih je svaki (GGGGS)3.
2. Jednolančano bispecifično antitijelo prema zahtjevu 1, ima aminokiselinsku sekvencu prema SEQ ID NO: 13.
3. Pripravak koji sadrži jednolančano bispecifično antitijelo prema bilo kojem od zahtjeva 1 ili 2 i sredstvo za obilježavanje.
4. Pripravak prema zahtjevu 3, naznačen time što je navedeno sredstvo za obilježavanje odabrano iz skupine koja se sastoji od radionuklida ili fluorescentnih nanočestica.
5. Farmaceutski pripravak koji sadrži jednolančano bispecifično antitijelo prema bilo kojem od zahtjeva 1 ili 2 i farmaceutski prihvatljiv nosač.
6. Farmaceutski pripravak prema zahtjevu 5, za intramuskularnu, intravensku infuziju, potkožno ili puteve inhalacijskog davanja.
7. Farmaceutski pripravak prema bilo kojem od zahtjeva 5 ili 6, koristi se u kombinaciji s najmanje jednim daljnjim spojem, koji može povećati ili smanjiti njegovu učinkovitost.
8. In vitro metoda za preusmjeravanje citotoksičnog djelovanja T-limfocita na tumorsku stanicu, naznačena time što obuhvaća korak kontakta navedene tumorske stanice s jednolančanim bispecifičnim antitijelom prema bilo kojem od zahtjeva 1 ili 2.
9. Jednolančano bispecifično antitijelo, prema bilo kojem od zahtjeva 1 ili 2, za uporabu u liječenju tumora.
10. Jednolančano bispecifično antitijelo za uporabu prema zahtjevu 9, naznačeno time što je navedeni tumor odabran iz skupine koja se sastoji od melanoma, karcinoma jajnika, karcinoma dojke, karcinoma prostate, kolorektalnih adenokarcinoma, hepatocelularnog karcinoma i karcinoma pluća.
11. Jednolančano bispecifično antitijelo za uporabu prema zahtjevu 9, naznačeno time što se navedeno liječenje odnosi na pacijente koji su otporni ili netolerantni na prethodno liječenje s najmanje jednim antitumorskim sredstvom ili u kojem treba izbjegavati liječenje antitumorskim sredstvom.
12. Jednolančano bispecifično antitijelo za uporabu prema bilo kojem zahtjevu 10 do 11, naznačeno time što je navedeni tretman profilaktički ili terapijski.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP15174741.7A EP3112381A1 (en) | 2015-07-01 | 2015-07-01 | Bispecific antibodies for use in cancer immunotherapy |
| EP16744669.9A EP3317300B1 (en) | 2015-07-01 | 2016-07-01 | Bispecific antibodies for use in cancer immunotherapy |
| PCT/EP2016/065577 WO2017001681A1 (en) | 2015-07-01 | 2016-07-01 | Bispecific antibodies for use in cancer immunotherapy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20210152T1 true HRP20210152T1 (hr) | 2021-03-19 |
Family
ID=53498900
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20210152TT HRP20210152T1 (hr) | 2015-07-01 | 2021-01-29 | Bispecifična antitijela za uporabu u imunoterapiji raka |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US10813995B2 (hr) |
| EP (2) | EP3112381A1 (hr) |
| JP (1) | JP6876006B2 (hr) |
| KR (1) | KR20180053639A (hr) |
| CN (1) | CN108602886B (hr) |
| AU (1) | AU2016285118B2 (hr) |
| CA (1) | CA2990517C (hr) |
| CY (1) | CY1123839T1 (hr) |
| DK (1) | DK3317300T3 (hr) |
| ES (1) | ES2848391T3 (hr) |
| HR (1) | HRP20210152T1 (hr) |
| HU (1) | HUE053128T2 (hr) |
| LT (1) | LT3317300T (hr) |
| PL (1) | PL3317300T3 (hr) |
| PT (1) | PT3317300T (hr) |
| RS (1) | RS61444B1 (hr) |
| SI (1) | SI3317300T1 (hr) |
| WO (1) | WO2017001681A1 (hr) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107417792B (zh) * | 2017-08-29 | 2020-07-03 | 天津医科大学总医院 | 抗cd40-her2双特异性单链抗体及其在制备抗肿瘤药物中的应用 |
| WO2019098563A1 (ko) | 2017-11-20 | 2019-05-23 | 주식회사 엘지화학 | 회전식 디스크 시스템을 활용한 중금속 정성 및 정량 분석 디바이스 및 분석 방법 |
| AU2019266042A1 (en) | 2018-05-10 | 2021-01-14 | Mirabiologics Inc. | Artificial protein containing an antibody antigen-binding region, fused with bioactive peptides |
| CN114573705B (zh) * | 2022-03-17 | 2024-05-14 | 杭州师范大学 | 特异性启动抗乙型肝炎病毒t细胞免疫的双特异性抗体及其应用 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6342369B1 (en) * | 1997-05-15 | 2002-01-29 | Genentech, Inc. | Apo-2-receptor |
| NZ521540A (en) * | 2000-04-11 | 2004-09-24 | Genentech Inc | Multivalent antibodies and uses therefor |
| JP3803790B2 (ja) * | 2003-02-17 | 2006-08-02 | 株式会社東北テクノアーチ | 新規なダイアボディ型二重特異性抗体 |
| EP3239178A1 (en) * | 2007-12-14 | 2017-11-01 | Bristol-Myers Squibb Company | Binding molecules to the human ox40 receptor |
| EP2684896A1 (en) * | 2012-07-09 | 2014-01-15 | International-Drug-Development-Biotech | Anti-DR5 family antibodies, bispecific or multivalent anti-DR5 family antibodies and methods of use thereof |
| UA118028C2 (uk) * | 2013-04-03 | 2018-11-12 | Рош Глікарт Аг | Біспецифічне антитіло, специфічне щодо fap і dr5, антитіло, специфічне щодо dr5, і спосіб їх застосування |
| TWI707872B (zh) * | 2014-05-29 | 2020-10-21 | 美商宏觀基因股份有限公司 | 特異性結合多種癌症抗原的三特異性結合分子和其使用方法 |
| JP6602875B2 (ja) * | 2015-01-26 | 2019-11-06 | マクロジェニクス，インコーポレーテッド | Ｄｒ５結合ドメインを含む多価分子 |
-
2015
- 2015-07-01 EP EP15174741.7A patent/EP3112381A1/en not_active Withdrawn
-
2016
- 2016-07-01 PL PL16744669T patent/PL3317300T3/pl unknown
- 2016-07-01 SI SI201631071T patent/SI3317300T1/sl unknown
- 2016-07-01 ES ES16744669T patent/ES2848391T3/es active Active
- 2016-07-01 WO PCT/EP2016/065577 patent/WO2017001681A1/en active Application Filing
- 2016-07-01 CA CA2990517A patent/CA2990517C/en active Active
- 2016-07-01 EP EP16744669.9A patent/EP3317300B1/en active Active
- 2016-07-01 US US15/740,560 patent/US10813995B2/en active Active
- 2016-07-01 KR KR1020187003075A patent/KR20180053639A/ko not_active Application Discontinuation
- 2016-07-01 PT PT167446699T patent/PT3317300T/pt unknown
- 2016-07-01 AU AU2016285118A patent/AU2016285118B2/en active Active
- 2016-07-01 DK DK16744669.9T patent/DK3317300T3/da active
- 2016-07-01 CN CN201680048299.5A patent/CN108602886B/zh active Active
- 2016-07-01 HU HUE16744669A patent/HUE053128T2/hu unknown
- 2016-07-01 LT LTEP16744669.9T patent/LT3317300T/lt unknown
- 2016-07-01 RS RS20210080A patent/RS61444B1/sr unknown
- 2016-07-01 JP JP2017568240A patent/JP6876006B2/ja active Active
-
2021
- 2021-01-28 CY CY20211100075T patent/CY1123839T1/el unknown
- 2021-01-29 HR HRP20210152TT patent/HRP20210152T1/hr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL3317300T3 (pl) | 2021-05-31 |
| LT3317300T (lt) | 2021-05-10 |
| KR20180053639A (ko) | 2018-05-23 |
| CA2990517C (en) | 2023-08-29 |
| WO2017001681A8 (en) | 2018-03-29 |
| CA2990517A1 (en) | 2017-01-05 |
| SI3317300T1 (sl) | 2021-04-30 |
| CN108602886A (zh) | 2018-09-28 |
| AU2016285118A9 (en) | 2019-08-01 |
| US10813995B2 (en) | 2020-10-27 |
| HUE053128T2 (hu) | 2021-06-28 |
| DK3317300T3 (da) | 2021-02-01 |
| ES2848391T3 (es) | 2021-08-09 |
| AU2016285118A1 (en) | 2018-02-22 |
| AU2016285118B2 (en) | 2021-12-16 |
| US20180250396A1 (en) | 2018-09-06 |
| JP2018525347A (ja) | 2018-09-06 |
| WO2017001681A1 (en) | 2017-01-05 |
| EP3112381A1 (en) | 2017-01-04 |
| PT3317300T (pt) | 2021-02-04 |
| JP6876006B2 (ja) | 2021-05-26 |
| CN108602886B (zh) | 2021-10-15 |
| EP3317300A1 (en) | 2018-05-09 |
| CY1123839T1 (el) | 2022-05-27 |
| RS61444B1 (sr) | 2021-03-31 |
| EP3317300B1 (en) | 2020-11-18 |
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