RU2017117664A - Комбинация - Google Patents
Комбинация Download PDFInfo
- Publication number
- RU2017117664A RU2017117664A RU2017117664A RU2017117664A RU2017117664A RU 2017117664 A RU2017117664 A RU 2017117664A RU 2017117664 A RU2017117664 A RU 2017117664A RU 2017117664 A RU2017117664 A RU 2017117664A RU 2017117664 A RU2017117664 A RU 2017117664A
- Authority
- RU
- Russia
- Prior art keywords
- medi4736
- azd9150
- binding fragment
- antisense compound
- antigen binding
- Prior art date
Links
- 238000000034 method Methods 0.000 claims 24
- 229950009791 durvalumab Drugs 0.000 claims 13
- 108010017324 STAT3 Transcription Factor Proteins 0.000 claims 10
- 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 claims 10
- 230000000692 anti-sense effect Effects 0.000 claims 10
- 239000000427 antigen Substances 0.000 claims 10
- 102000036639 antigens Human genes 0.000 claims 10
- 108091007433 antigens Proteins 0.000 claims 10
- 150000001875 compounds Chemical class 0.000 claims 10
- 239000012634 fragment Substances 0.000 claims 10
- 239000003795 chemical substances by application Substances 0.000 claims 9
- 230000002519 immonomodulatory effect Effects 0.000 claims 8
- 230000008685 targeting Effects 0.000 claims 8
- 239000008194 pharmaceutical composition Substances 0.000 claims 6
- 206010028980 Neoplasm Diseases 0.000 claims 5
- 201000011510 cancer Diseases 0.000 claims 5
- 102000008096 B7-H1 Antigen Human genes 0.000 claims 2
- 108010074708 B7-H1 Antigen Proteins 0.000 claims 2
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 claims 2
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 claims 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims 2
- 239000002955 immunomodulating agent Substances 0.000 claims 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 2
- 230000004083 survival effect Effects 0.000 claims 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 2
- 102000008203 CTLA-4 Antigen Human genes 0.000 claims 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 claims 1
- 229940045513 CTLA4 antagonist Drugs 0.000 claims 1
- 201000009030 Carcinoma Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010025323 Lymphomas Diseases 0.000 claims 1
- 102000004473 OX40 Ligand Human genes 0.000 claims 1
- 108010042215 OX40 Ligand Proteins 0.000 claims 1
- 108091034117 Oligonucleotide Proteins 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 108010044012 STAT1 Transcription Factor Proteins 0.000 claims 1
- 102000006381 STAT1 Transcription Factor Human genes 0.000 claims 1
- 102000005886 STAT4 Transcription Factor Human genes 0.000 claims 1
- 108010019992 STAT4 Transcription Factor Proteins 0.000 claims 1
- 102000013968 STAT6 Transcription Factor Human genes 0.000 claims 1
- 108010011005 STAT6 Transcription Factor Proteins 0.000 claims 1
- 239000000556 agonist Substances 0.000 claims 1
- 239000000074 antisense oligonucleotide Substances 0.000 claims 1
- 238000012230 antisense oligonucleotides Methods 0.000 claims 1
- 210000003719 b-lymphocyte Anatomy 0.000 claims 1
- 210000004027 cell Anatomy 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 201000010536 head and neck cancer Diseases 0.000 claims 1
- 208000014829 head and neck neoplasm Diseases 0.000 claims 1
- 210000002865 immune cell Anatomy 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 229960005386 ipilimumab Drugs 0.000 claims 1
- 201000003445 large cell neuroendocrine carcinoma Diseases 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 229960003301 nivolumab Drugs 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 229960002621 pembrolizumab Drugs 0.000 claims 1
- 229950010773 pidilizumab Drugs 0.000 claims 1
- 229950007217 tremelimumab Drugs 0.000 claims 1
Classifications
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- 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
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/111—General methods applicable to biologically active non-coding nucleic acids
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
- A61K38/1774—Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)
-
- 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
- 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
- A61P35/00—Antineoplastic agents
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- 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
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- 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
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
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- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/323—Chemical structure of the sugar modified ring structure
- C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/341—Gapmers, i.e. of the type ===---===
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- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
-
- 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
- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
- C12N2320/31—Combination therapy
Claims (29)
1. Способ лечения, включающий введение (i) иммуномодулирующего средства и (ii) антисмыслового соединения, нацеленного на STAT3, пациенту, нуждающемуся в этом.
2. Способ по п. 1, где иммуномодулирующее средство является ингибитором иммунных контрольных точек.
3. Способ по п. 1, где иммуномодулирующее средство выбрано из группы, состоящей из антитела к PD-L1 или его антигенсвязывающего фрагмента; антитела к PD1 или его антигенсвязывающего фрагмента; антитела к CTLA-4 или его антигенсвязывающего фрагмента и агониста OX-40.
4. Способ по п. 1, где иммуномодулирующее средство
выбрано из MEDI4736, MPDL3280A, 2.7A4, AMP-714, MDX-1105, ниволумаба, пембролизумаба, пидилизумаба, BMS936559, MPDL3280A, тремелимумаба, ипилимумаба и OX40L FP.
5. Способ по любому из пп. 1-4, где иммуномодулирующее средство представляет собой MEDI4736.
6. Способ по любому из предыдущих пунктов, где антисмысловое соединение, нацеленное на STAT3, не ингибирует STAT1, STAT4 или STAT6.
7. Способ по п. 1, где антисмысловое соединение, нацеленное на STAT3, представляет собой антисмысловой олигонуклеотид.
8. Способ по любому из предыдущих пунктов, где антисмысловое соединение, нацеленное на STAT3, представляет собой AZD9150.
9. Способ по п. 1, где у пациента имеется рак.
10. Способ по п. 9, где рак выбран из рака легкого, в том числе немелкоклеточного рака легкого (NSCLC), рака поджелудочной железы, колоректального рака, гепатоцеллюлярной карциномы (HCC), рака головы и шеи, в том числе плоскоклеточной карциномы головы и шеи (HNSCC), и лимфомы, в том числе диффузной крупноклеточной В-клеточной карциномы (DLBCL).
11. Способ по п. 10, где раковые клетки экспрессируют PD-L1.
12. Способ по п. 1, где у пациента, нуждающегося в этом, было идентифицировано наличие рака, который является положительным по PD-L1.
13. Способ по любому из предыдущих пунктов, где антитело к PD-L1 представляет собой MEDI4736, а антисмысловое соединение, нацеленное на STAT3, представляет собой AZD9150.
14. Способ по п. 13, где пациенту, нуждающемуся в этом, вводят от приблизительно 1 мг/кг до 20 мг/кг MEDI4736 или его антигенсвязывающего фрагмента и от приблизительно 1 мг/кг до 10 мг/кг AZD9150.
15. Способ по п. 14, где средство для лечения вводят каждую неделю, каждые 2 недели, каждые 3 недели или каждые 4 недели.
16. Способ по любому из предыдущих пунктов, где антисмысловое соединение, нацеленное на STAT3, вводят пациенту перед иммуномодулирующим средством.
17. Способ по п. 16, где антисмысловое соединение, нацеленное на STAT3, вводят пациенту по меньшей мере за один день до введения пациенту иммуномодулирующего средства.
18. Способ по любому из пп. 1-17, где вводят приблизительно 10 мг/кг MEDI4736 или его антигенсвязывающего фрагмента и приблизительно 3 мг/кг AZD9150 на дозу.
19. Способ по любому из пп. 1-17, где вводят приблизительно 20 мг/кг MEDI4736 или его антигенсвязывающего фрагмента и приблизительно 3 мг/кг AZD9150 на дозу.
20. Способ по любому из пп. 1-19, где способ обуславливает увеличение выживаемости без прогрессирования и/или общей выживаемости по сравнению с введением MEDI4736 либо AZD9150 в отдельности.
21. Способ по любому из пп. 1-20, где AZD9150 и MEDI4736 или его антигенсвязывающий фрагмент вводят одновременно или в разные моменты времени.
22. Набор для лечения рака, при этом набор содержит иммуномодулирующее средство и антисмысловое соединение, нацеленное на STAT3.
23. Фармацевтическая композиция, которая содержит иммуномодулирующее средство и антисмысловое соединение, нацеленное на STAT3, вместе с фармацевтически приемлемым разбавителем или носителем.
24. Фармацевтическая композиция по п. 23, где иммуномодулирующее средство представляет собой MEDI4736, а антисмысловое соединение, нацеленное на STAT3, представляет собой AZD9150.
25. Фармацевтическая композиция по п. 24, где фармацевтическая композиция составлена для обеспечения дозы от приблизительно 1 мг/кг до приблизительно 20 мг/кг MEDI4736 или его антигенсвязывающего фрагмента и дозы от приблизительно 1 мг/кг до приблизительно 10 мг/кг AZD9150.
26. Фармацевтическая композиция по п. 25, где фармацевтическая композиция составлена для обеспечения дозы приблизительно 10 мг/кг MEDI4736 или его антигенсвязывающего фрагмента и дозы приблизительно 3 мг/кг AZD9150.
27. Способ модуляции инфильтрирующих иммунных клеток у теплокровного животного, такого как человек, который включает введение указанному животному эффективного количества MEDI4736 или его антигенсвязывающего фрагмента перед эффективным количеством AZD9150, после него или одновременно с ним.
28. Способ по любому из пп. 1-21, где пациенту, нуждающемуся в этом, вводят AZD9150, MEDI4736 и тремелимумаб.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201462068141P | 2014-10-24 | 2014-10-24 | |
US62/068141 | 2014-10-24 | ||
PCT/EP2015/074271 WO2016062722A1 (en) | 2014-10-24 | 2015-10-20 | Combination |
Publications (3)
Publication Number | Publication Date |
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RU2017117664A true RU2017117664A (ru) | 2018-11-26 |
RU2017117664A3 RU2017117664A3 (ru) | 2019-05-23 |
RU2744841C2 RU2744841C2 (ru) | 2021-03-16 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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RU2017117664A RU2744841C2 (ru) | 2014-10-24 | 2015-10-20 | Комбинация |
Country Status (16)
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US (2) | US20190194654A1 (ru) |
EP (2) | EP3209778B1 (ru) |
JP (1) | JP6687612B2 (ru) |
KR (2) | KR20230128139A (ru) |
CN (2) | CN107106590B (ru) |
AU (1) | AU2015335029B2 (ru) |
CA (1) | CA2965034C (ru) |
DK (1) | DK3209778T3 (ru) |
ES (1) | ES2727154T3 (ru) |
HU (1) | HUE043227T2 (ru) |
IL (2) | IL251813A0 (ru) |
PL (1) | PL3209778T3 (ru) |
RU (1) | RU2744841C2 (ru) |
SG (2) | SG10202105879XA (ru) |
TR (1) | TR201906415T4 (ru) |
WO (1) | WO2016062722A1 (ru) |
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BRPI1010576A2 (pt) | 2009-05-11 | 2016-03-15 | Berg Biosystems Llc | métodos para tratamento de distúrbios oncológicos usando transferidores epimetabólicos, moléculas intracelulares multidimensionais ou influenciadores ambientais. |
WO2012138765A1 (en) | 2011-04-04 | 2012-10-11 | Berg Pharma Llc | Methods of treating central nervous system tumors |
EP2983654A4 (en) | 2013-04-08 | 2016-11-30 | Berg Llc | TREATMENT OF CANCER USING COENZYME POLYTHERAPIES Q10 |
EP3041496B1 (en) | 2013-09-04 | 2020-04-29 | Berg LLC | Methods of treatment of cancer by continuous infusion of coenzyme q10 |
WO2015183902A1 (en) * | 2014-05-29 | 2015-12-03 | Medimmune, Llc | Ox40l fusion proteins and uses thereof |
CN107106493A (zh) | 2014-11-21 | 2017-08-29 | 西北大学 | 球形核酸纳米颗粒缀合物的序列特异性细胞摄取 |
EP3268392A2 (en) | 2015-03-13 | 2018-01-17 | CytomX Therapeutics, Inc. | Anti-pdl1 antibodies, activatable anti-pdl1 antibodies, and methods of use thereof |
JP6867955B2 (ja) | 2015-05-07 | 2021-05-12 | アジェナス インコーポレイテッド | 抗ox40抗体及びその使用方法 |
JP7014706B2 (ja) | 2015-07-13 | 2022-02-01 | サイトメックス セラピューティクス インコーポレイテッド | 抗pd-1抗体、活性化可能抗pd-1抗体、およびその使用方法 |
EP3371311B1 (en) | 2015-11-06 | 2021-07-21 | Orionis Biosciences BV | Bi-functional chimeric proteins and uses thereof |
MX2018006477A (es) | 2015-12-02 | 2018-09-03 | Agenus Inc | Anticuerpos y metodos de uso de estos. |
CN108883180B (zh) | 2016-02-05 | 2023-07-07 | 奥里尼斯生物科学私人有限公司 | Clec9a结合剂及其用途 |
BR112018071287A2 (pt) * | 2016-04-25 | 2019-02-19 | Medimmune, Llc | composições compreendendo coformulação de anticorpos anti-pd-l1 e anti-ctla-4 |
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EP3550019A1 (en) | 2019-10-09 |
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JP6687612B2 (ja) | 2020-04-22 |
US20190194654A1 (en) | 2019-06-27 |
TR201906415T4 (tr) | 2019-05-21 |
AU2015335029B2 (en) | 2021-09-23 |
EP3209778A1 (en) | 2017-08-30 |
SG10202105879XA (en) | 2021-07-29 |
JP2017537070A (ja) | 2017-12-14 |
CA2965034C (en) | 2023-05-02 |
WO2016062722A8 (en) | 2017-03-09 |
CN115920007A (zh) | 2023-04-07 |
RU2744841C2 (ru) | 2021-03-16 |
HUE043227T2 (hu) | 2019-08-28 |
CN107106590A (zh) | 2017-08-29 |
PL3209778T3 (pl) | 2019-08-30 |
CN107106590B (zh) | 2022-10-18 |
ES2727154T3 (es) | 2019-10-14 |
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