CA3062609A1 - Compositions comprising naphthyridine derivatives and aluminium adjuvant for use in treating solid tumors - Google Patents
Compositions comprising naphthyridine derivatives and aluminium adjuvant for use in treating solid tumors Download PDFInfo
- Publication number
- CA3062609A1 CA3062609A1 CA3062609A CA3062609A CA3062609A1 CA 3062609 A1 CA3062609 A1 CA 3062609A1 CA 3062609 A CA3062609 A CA 3062609A CA 3062609 A CA3062609 A CA 3062609A CA 3062609 A1 CA3062609 A1 CA 3062609A1
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- Prior art keywords
- pharmaceutical composition
- amino
- aluminum
- naphthyridin
- pharmaceutically acceptable
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 title claims abstract description 386
- 239000000203 mixture Substances 0.000 title claims abstract description 244
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 205
- 239000004411 aluminium Substances 0.000 title description 6
- 239000002671 adjuvant Substances 0.000 title description 2
- 150000005054 naphthyridines Chemical class 0.000 title description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 491
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- 150000003839 salts Chemical class 0.000 claims description 390
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 303
- 150000001875 compounds Chemical class 0.000 claims description 289
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- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 111
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- YBFHZUZABVBQKU-UHFFFAOYSA-N 6-[4-[2-(5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl]-3-methylphenoxy]hexylphosphonic acid Chemical compound C=1C(C)=CC=C(C2=C3)C=1N=C(N)C2=NC=C3CCC1=CC=C(OCCCCCCP(O)(O)=O)C=C1C YBFHZUZABVBQKU-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- 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
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Landscapes
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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| US201762508474P | 2017-05-19 | 2017-05-19 | |
| US62/508,474 | 2017-05-19 | ||
| PCT/IB2018/053481 WO2018211453A1 (en) | 2017-05-19 | 2018-05-17 | Compositions comprising naphthyridine derivatives and aluminium adjuvant for use in treating solid tumors |
Publications (1)
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| CA3062609A1 true CA3062609A1 (en) | 2018-11-22 |
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| CA3062609A Pending CA3062609A1 (en) | 2017-05-19 | 2018-05-17 | Compositions comprising naphthyridine derivatives and aluminium adjuvant for use in treating solid tumors |
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| CA3029902A1 (en) | 2016-07-07 | 2018-01-11 | The Board Of Trustees Of The Leland Stanford Junior University | Antibody adjuvant conjugates |
| US11364304B2 (en) | 2016-08-25 | 2022-06-21 | Northwestern University | Crosslinked micellar spherical nucleic acids |
| AR111760A1 (es) * | 2017-05-19 | 2019-08-14 | Novartis Ag | Compuestos y composiciones para el tratamiento de tumores sólidos mediante administración intratumoral |
| JP2022525594A (ja) | 2019-03-15 | 2022-05-18 | ボルト バイオセラピューティクス、インコーポレーテッド | Her2を標的とする免疫結合体 |
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Family Cites Families (46)
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| IL73534A (en) | 1983-11-18 | 1990-12-23 | Riker Laboratories Inc | 1h-imidazo(4,5-c)quinoline-4-amines,their preparation and pharmaceutical compositions containing certain such compounds |
| CZ288182B6 (en) | 1993-07-15 | 2001-05-16 | Minnesota Mining & Mfg | Imidazo[4,5-c]pyridine-4-amines and pharmaceutical preparations based thereon |
| UA67760C2 (uk) | 1997-12-11 | 2004-07-15 | Міннесота Майнінг Енд Мануфакчурінг Компані | Імідазонафтиридин та тетрагідроімідазонафтиридин, фармацевтична композиція, спосіб індукування біосинтезу цитокінів та спосіб лікування вірусної інфекції, проміжні сполуки |
| US6110929A (en) | 1998-07-28 | 2000-08-29 | 3M Innovative Properties Company | Oxazolo, thiazolo and selenazolo [4,5-c]-quinolin-4-amines and analogs thereof |
| IL129299A0 (en) | 1999-03-31 | 2000-02-17 | Mor Research Applic Ltd | Monoclonal antibodies antigens and diagnosis of malignant diseases |
| IL149820A0 (en) | 2002-05-23 | 2002-11-10 | Curetech Ltd | Humanized immunomodulatory monoclonal antibodies for the treatment of neoplastic disease or immunodeficiency |
| WO2004056875A1 (en) | 2002-12-23 | 2004-07-08 | Wyeth | Antibodies against pd-1 and uses therefor |
| US20040265351A1 (en) | 2003-04-10 | 2004-12-30 | Miller Richard L. | Methods and compositions for enhancing immune response |
| GB0321710D0 (en) | 2003-09-16 | 2003-10-15 | Novartis Ag | Organic compounds |
| EP1696912B1 (en) | 2003-10-03 | 2016-05-11 | 3M Innovative Properties Company | Pyrazolopyridines and analogs thereof |
| DK2161336T4 (en) | 2005-05-09 | 2017-04-24 | Ono Pharmaceutical Co | Human monoclonal antibodies for programmed death 1 (PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapies |
| NZ582150A (en) | 2007-06-18 | 2012-08-31 | Msd Oss Bv | Antibodies to human programmed death receptor pd-1 |
| KR101208778B1 (ko) | 2008-03-03 | 2012-12-05 | 노파르티스 아게 | Tlr 활성 조정제로서의 화합물 및 조성물 |
| WO2009114335A2 (en) | 2008-03-12 | 2009-09-17 | Merck & Co., Inc. | Pd-1 binding proteins |
| CN102203125A (zh) | 2008-08-25 | 2011-09-28 | 安普利穆尼股份有限公司 | Pd-1拮抗剂及其使用方法 |
| EP2342229A1 (en) | 2008-09-12 | 2011-07-13 | ISIS Innovation Limited | Pd-1 specific antibodies and uses thereof |
| MX2011003195A (es) | 2008-09-26 | 2011-08-12 | Dana Farber Cancer Inst Inc | Anticuerpos anti-pd-1, pd-l1 y pd-l2 humanos y usos de los mismos. |
| TR201802380T4 (tr) | 2009-06-10 | 2018-03-21 | Glaxosmithkline Biologicals Sa | Benzonaftiridin içeren aşılar. |
| JO3257B1 (ar) | 2009-09-02 | 2018-09-16 | Novartis Ag | مركبات وتركيبات كمعدلات لفاعلية tlr |
| NZ598654A (en) | 2009-09-02 | 2014-05-30 | Novartis Ag | Immunogenic compositions including tlr activity modulators |
| JP2013512251A (ja) | 2009-11-24 | 2013-04-11 | アンプリミューン、インコーポレーテッド | Pd−l1/pd−l2の同時阻害 |
| EP2545078A1 (en) | 2010-03-11 | 2013-01-16 | UCB Pharma, S.A. | Pd-1 antibody |
| JP6023696B2 (ja) * | 2010-03-31 | 2016-11-09 | スタビリテック リミテッド | ミョウバンアジュバントおよびミョウバンアジュバント化ワクチンの保存方法 |
| US9597326B2 (en) | 2010-04-13 | 2017-03-21 | Glaxosmithkline Biologicals Sa | Benzonapthyridine compositions and uses thereof |
| US8907053B2 (en) | 2010-06-25 | 2014-12-09 | Aurigene Discovery Technologies Limited | Immunosuppression modulating compounds |
| CN105999275A (zh) | 2010-09-01 | 2016-10-12 | 诺华有限公司 | 免疫增强剂吸附不溶性金属离子 |
| CA2833636A1 (en) | 2011-04-20 | 2012-10-26 | Amplimmune, Inc. | Antibodies and other molecules that bind b7-h1 and pd-1 |
| EP2532359A1 (en) | 2011-06-10 | 2012-12-12 | Affiris AG | CETP fragments |
| EP2734551B1 (en) | 2011-07-24 | 2018-01-10 | Cure Tech Ltd. | Variants of humanized immunomodulatory monoclonal antibodies |
| KR20140066212A (ko) * | 2011-09-01 | 2014-05-30 | 노파르티스 아게 | 스타필로코쿠스 아우레우스 항원의 보조제 첨가된 조제물 |
| US9827190B2 (en) | 2013-02-01 | 2017-11-28 | Glaxosmithkline Biologicals Sa | Intradermal delivery of immunological compositions comprising toll-like receptor 7 agonists |
| HRP20210122T1 (hr) | 2013-05-02 | 2021-04-16 | Anaptysbio, Inc. | Protutijela usmjerena protiv programirane smrti-1 (pd-1) |
| US9676853B2 (en) | 2013-05-31 | 2017-06-13 | Sorrento Therapeutics, Inc. | Antigen binding proteins that bind PD-1 |
| WO2014209804A1 (en) | 2013-06-24 | 2014-12-31 | Biomed Valley Discoveries, Inc. | Bispecific antibodies |
| SG11201601844TA (en) | 2013-09-13 | 2016-04-28 | Beigene Ltd | Anti-pd1 antibodies and their use as therapeutics and diagnostics |
| SG11201604738TA (en) | 2013-12-12 | 2016-07-28 | Shanghai Hengrui Pharm Co Ltd | Pd-1 antibody, antigen-binding fragment thereof, and medical application thereof |
| TWI681969B (zh) | 2014-01-23 | 2020-01-11 | 美商再生元醫藥公司 | 針對pd-1的人類抗體 |
| JOP20200094A1 (ar) | 2014-01-24 | 2017-06-16 | Dana Farber Cancer Inst Inc | جزيئات جسم مضاد لـ pd-1 واستخداماتها |
| BE1022875B1 (fr) | 2014-03-26 | 2016-09-30 | Glaxosmithkline Biologicals S.A. | Compositions pour une immunisation contre staphylococcus aureus |
| TWI693232B (zh) | 2014-06-26 | 2020-05-11 | 美商宏觀基因股份有限公司 | 與pd-1和lag-3具有免疫反應性的共價結合的雙抗體和其使用方法 |
| WO2016019232A1 (en) | 2014-08-01 | 2016-02-04 | John Vasilakos | Methods and therapeutic combinations for treating tumors |
| CN105296433B (zh) | 2014-08-01 | 2018-02-09 | 中山康方生物医药有限公司 | 一种ctla4抗体、其药物组合物及其用途 |
| EP3206711B1 (en) | 2014-10-14 | 2023-05-31 | Novartis AG | Antibody molecules to pd-l1 and uses thereof |
| TWI595006B (zh) | 2014-12-09 | 2017-08-11 | 禮納特神經系統科學公司 | 抗pd-1抗體類和使用彼等之方法 |
| JP7378931B2 (ja) * | 2015-11-03 | 2023-11-14 | エイシー イミューン ソシエテ アノニム | ヒト患者における自己抗原に対するワクチン接種法 |
| AR111760A1 (es) * | 2017-05-19 | 2019-08-14 | Novartis Ag | Compuestos y composiciones para el tratamiento de tumores sólidos mediante administración intratumoral |
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| RU2019141837A3 (enExample) | 2021-09-10 |
| CN116473981A (zh) | 2023-07-25 |
| TW201900166A (zh) | 2019-01-01 |
| EP3624806A1 (en) | 2020-03-25 |
| MX2023004381A (es) | 2023-05-04 |
| RU2019141837A (ru) | 2021-06-21 |
| AU2018268420B2 (en) | 2021-07-15 |
| AU2021203564B2 (en) | 2023-01-05 |
| US11752162B2 (en) | 2023-09-12 |
| AR111760A1 (es) | 2019-08-14 |
| JP2020520910A (ja) | 2020-07-16 |
| AU2018268420A1 (en) | 2019-11-21 |
| BR112019024260A2 (pt) | 2020-06-09 |
| KR20200007040A (ko) | 2020-01-21 |
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