KR102642385B1 - 표적화된 키메라 단백질 및 이의 용도 - Google Patents
표적화된 키메라 단백질 및 이의 용도 Download PDFInfo
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- KR102642385B1 KR102642385B1 KR1020197024342A KR20197024342A KR102642385B1 KR 102642385 B1 KR102642385 B1 KR 102642385B1 KR 1020197024342 A KR1020197024342 A KR 1020197024342A KR 20197024342 A KR20197024342 A KR 20197024342A KR 102642385 B1 KR102642385 B1 KR 102642385B1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2896—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/555—Interferons [IFN]
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- 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
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- 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
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
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- A61P3/00—Drugs for disorders of the metabolism
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
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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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/555—Interferons [IFN]
- C07K14/56—IFN-alpha
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IG], 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IG], 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
- C07K16/2818—Immunoglobulins [IG], 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 CD28 or CD152
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IG], 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
- C07K16/2827—Immunoglobulins [IG], 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 B7 molecules, e.g. CD80, CD86
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2851—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the lectin superfamily, e.g. CD23, CD72
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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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
- A61K2039/507—Comprising a combination of two or more separate antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/22—Immunoglobulins specific features characterized by taxonomic origin from camelids, e.g. camel, llama or dromedary
-
- 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
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- 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
- C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
-
- 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
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- 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
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Virology (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Communicable Diseases (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Neurology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Transplantation (AREA)
- Biomedical Technology (AREA)
- Dermatology (AREA)
- Obesity (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762454993P | 2017-02-06 | 2017-02-06 | |
| US62/454,993 | 2017-02-06 | ||
| PCT/EP2018/052814 WO2018141964A1 (en) | 2017-02-06 | 2018-02-05 | Targeted chimeric proteins and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20190115005A KR20190115005A (ko) | 2019-10-10 |
| KR102642385B1 true KR102642385B1 (ko) | 2024-03-04 |
Family
ID=61274224
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020197024342A Active KR102642385B1 (ko) | 2017-02-06 | 2018-02-05 | 표적화된 키메라 단백질 및 이의 용도 |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US11384154B2 (https=) |
| EP (1) | EP3577133A1 (https=) |
| JP (2) | JP7476467B2 (https=) |
| KR (1) | KR102642385B1 (https=) |
| CN (1) | CN110546160A (https=) |
| AU (1) | AU2018216032B2 (https=) |
| CA (1) | CA3052523A1 (https=) |
| IL (1) | IL268346B2 (https=) |
| MX (1) | MX2019009255A (https=) |
| WO (1) | WO2018141964A1 (https=) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3455245A2 (en) * | 2016-05-13 | 2019-03-20 | Orionis Biosciences NV | Therapeutic targeting of non-cellular structures |
| KR102642385B1 (ko) * | 2017-02-06 | 2024-03-04 | 오리오니스 바이오사이언시스 엔브이 | 표적화된 키메라 단백질 및 이의 용도 |
| AU2018313810B2 (en) | 2017-08-09 | 2025-05-15 | Orionis Biosciences BV | Clec9A binding agents and use thereof |
| CN111511763B (zh) | 2017-08-09 | 2024-05-31 | 奥里尼斯生物科学有限公司 | Cd8结合剂 |
| EP3664829A4 (en) | 2017-08-09 | 2021-05-05 | Orionis Biosciences, Inc. | LIAISON OFFICERS AT PD-1 AND PD-L1 |
| KR102877915B1 (ko) | 2018-02-05 | 2025-10-29 | 오리오니스 바이오사이언시즈 인코포레이티드 | 섬유아세포 결합제 및 이의 용도 |
| WO2020033646A1 (en) | 2018-08-08 | 2020-02-13 | Orionis Biosciences, Inc. | SIRP1α TARGETED CHIMERIC PROTEINS AND USES THEREOF |
| US20220249679A1 (en) * | 2018-10-02 | 2022-08-11 | Mitsubishi Tanabe Pharma Corporation | Bi-specific binding agents targeting syndecan-1 and fibroblast growth factor receptor |
| GB2593632B (en) * | 2018-10-29 | 2023-05-24 | Umc Utrecht Holding Bv | IGA mediated killing of aberrant cells by CD47-Sirpalpha checkpoint inhibition of neutrophils |
| US12410225B2 (en) | 2018-11-08 | 2025-09-09 | Orionis Biosciences, Inc | Modulation of dendritic cell lineages |
| JP2022507295A (ja) | 2018-11-14 | 2022-01-18 | アーチ オンコロジー,インコーポレイテッド | 治療用SIRPα抗体 |
| US11440943B2 (en) | 2019-03-28 | 2022-09-13 | Orionis Biosciences, Inc. | Therapeutic interferon alpha 1 proteins |
| US12351614B2 (en) | 2019-03-28 | 2025-07-08 | Orionis Biosciences, Inc. | CLEC9A-based chimeric protein complexes |
| JP7773372B2 (ja) | 2019-03-28 | 2025-11-19 | オリオニス バイオサイエンシズ,インコーポレイテッド | 線維芽細胞活性化タンパク質結合物質およびその使用 |
| EP4023679A4 (en) * | 2019-08-30 | 2023-10-04 | Nanjing Shunxin Pharmaceuticals Co., Ltd. of Chiatai Tianqing Pharmaceutical Group | FUSION PROTEIN TARGETING PD-L1 AND TGF-BETA AND USE THEREOF |
| US20220378925A1 (en) * | 2019-09-26 | 2022-12-01 | Orionis Biosciences, Inc. | Conjugated chimeric proteins |
| WO2021101796A1 (en) * | 2019-11-18 | 2021-05-27 | The Brigham And Women's Hospital, Inc. | Codon optimized new generation regulatable fusogenic oncolytic herpes simplex virus type 1 virus and methods of use |
| US20230242655A1 (en) | 2019-12-03 | 2023-08-03 | Evotec International Gmbh | Interferon-associated antigen binding proteins and uses thereof |
| CN113354738B (zh) * | 2020-03-05 | 2022-09-09 | 绍兴德方华生物技术有限公司 | 融合毒素VEGF165b/mGEL及其编码基因与应用 |
| BR112022021992A2 (pt) * | 2020-04-30 | 2023-01-03 | Arch Oncology Inc | Método de tratamento de câncer em um sujeito em necessidade do mesmo |
| JP7799638B2 (ja) * | 2020-06-30 | 2026-01-21 | チア タイ ティエンチン ファーマシューティカル グループ カンパニー リミテッド | 腫瘍を治療するための薬物 |
| JP2023539195A (ja) * | 2020-08-27 | 2023-09-13 | ユニバーシティ オブ ピッツバーグ - オブ ザ コモンウェルス システム オブ ハイヤー エデュケイション | 組換えトランスフォーミング増殖因子(tgf)-ベータ単量体をコードする腫瘍溶解性ウイルスおよびその使用 |
| JP2023541601A (ja) | 2020-09-10 | 2023-10-03 | プレシリックス・ナームローゼ・ベンノートシヤープ | Fapに対する抗体フラグメント |
| US20220196651A1 (en) * | 2020-12-06 | 2022-06-23 | ALX Oncology Inc. | Multimers for reducing the interference of drugs that bind cd47 in serological assays |
| CN114349850A (zh) * | 2020-12-18 | 2022-04-15 | 蒋庆华 | 抗体及其制备方法和编码核酸以及工程细胞 |
| WO2023203135A1 (en) | 2022-04-22 | 2023-10-26 | Precirix N.V. | Improved radiolabelled antibody |
| AU2023264245A1 (en) | 2022-05-02 | 2024-12-19 | Precirix N.V. | Pre-targeting |
| EP4619435A1 (en) | 2022-11-16 | 2025-09-24 | Boehringer Ingelheim International GmbH | Predictive efficacy biomarkers for anti-sirpa antibodies |
| CN116732012A (zh) * | 2023-03-13 | 2023-09-12 | 山东舜丰生物科技有限公司 | 碱基编辑器及其应用 |
| EP4480501A1 (en) * | 2023-06-21 | 2024-12-25 | Nmi Naturwissenschaftliches Und Medizinisches Institut An Der Universität Tübingen | Sirp nanobodies |
| AU2024317606A1 (en) * | 2023-07-29 | 2026-02-26 | Chimagen Biosciences, Ltd | Modified type e multi-specific antibodies |
| CN117430716B (zh) * | 2023-10-16 | 2024-05-31 | 珠海臻谱基因科技有限公司 | 靶向保守的HIV gp41亚基近膜端外区的重组干扰素药物及其应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015500796A (ja) * | 2011-10-28 | 2015-01-08 | テバ・ファーマシューティカルズ・オーストラリア・ピーティワイ・リミテッド | ポリペプチド構築物およびその使用 |
| WO2015138600A2 (en) * | 2014-03-11 | 2015-09-17 | The Board Of Trustees Of The Leland Stanford Junior University | Anti sirp-alpha antibodies and bi-specific macrophage enhancing antibodies |
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- 2018-02-05 AU AU2018216032A patent/AU2018216032B2/en active Active
- 2018-02-05 WO PCT/EP2018/052814 patent/WO2018141964A1/en not_active Ceased
- 2018-02-05 CN CN201880023712.1A patent/CN110546160A/zh active Pending
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| JP2015500796A (ja) * | 2011-10-28 | 2015-01-08 | テバ・ファーマシューティカルズ・オーストラリア・ピーティワイ・リミテッド | ポリペプチド構築物およびその使用 |
| WO2015138600A2 (en) * | 2014-03-11 | 2015-09-17 | The Board Of Trustees Of The Leland Stanford Junior University | Anti sirp-alpha antibodies and bi-specific macrophage enhancing antibodies |
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| IL268346B1 (en) | 2024-04-01 |
| MX2019009255A (es) | 2019-11-05 |
| US20220281992A1 (en) | 2022-09-08 |
| CA3052523A1 (en) | 2018-08-09 |
| AU2018216032B2 (en) | 2022-04-07 |
| US11384154B2 (en) | 2022-07-12 |
| IL268346B2 (en) | 2024-08-01 |
| IL268346A (en) | 2019-09-26 |
| JP2020506727A (ja) | 2020-03-05 |
| JP7605800B2 (ja) | 2024-12-24 |
| AU2018216032A1 (en) | 2019-08-08 |
| US20200087411A1 (en) | 2020-03-19 |
| EP3577133A1 (en) | 2019-12-11 |
| WO2018141964A1 (en) | 2018-08-09 |
| JP7476467B2 (ja) | 2024-05-01 |
| JP2023011661A (ja) | 2023-01-24 |
| KR20190115005A (ko) | 2019-10-10 |
| CN110546160A (zh) | 2019-12-06 |
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