前沿专利观察 / Patent Frontier Watch
第007期：制药前沿：LNP、核酸递送与蛋白降解
本期重写为逐件研读版，重点看生命科学专利怎样把靶点、递送、组合物、制剂、给药路径和稳定性条件落成可制造的技术方案。
为什么选这些专利
本期选择标准不是随机编号，也不是标题看起来热门，而是每件专利都对应一个可被拆解的工程问题：它必须能说明一个具体痛点，并且在公开文本中给出结构、流程、材料组合、数据处理或控制策略。下面按逐件研读方式展开。
1. Lipid nanoparticles and preparation methods and use thereof
代表专利：US-2025213496-A1。申请人/权利人：INST CHEMISTRY CAS (CN) PROXYBIO THERAPEUTICS CO LTD (CN)。优先权日：2022/10/11；公开日：2025/07/03。
它真正发现的问题
这件专利的问题落在“Lipid nanoparticles and preparation methods and use thereof”对应的药物转化环节：A lipid nanoparticle and a preparation method and use thereof are provided. The lipid nanoparticle (LNP) includes a carrier and an encapsulated nucleic acid, the carrier includes an ionizable lipid, a helper phospholipid, a PEGylated lipid, cholesterol and its derivatives, and a retinoid compound; and the nucleic acid is one or more of mRNA, circRNA, siRNA,... 研读重点是成分、载体、给药或制备条件如何解决稳定性、递送效率或药效路径问题。
它的技术方案
公开摘要显示，方案的具体构成是：A lipid nanoparticle and a preparation method and use thereof are provided. The lipid nanoparticle (LNP) includes a carrier and an encapsulated nucleic acid, the carrier includes an ionizable lipid, a helper phospholipid, a PEGylated lipid, cholesterol and its derivatives, and a retinoid compound; and the nucleic acid is one or more of mRNA, circRNA, siRNA, microRNA, antisense nucleic acid, and plasmid.
给我们的启示
启示是，递送平台布局要覆盖配方比例、制备方法、载荷类型、稳定性指标和用途，而不是只保护一种载荷。
2. [Translated] A protein degradation agent capable of self-assembly in cells and its preparation method and application
代表专利：CN-115385859-A。申请人/权利人：UNIV XI AN JIAOTONG。优先权日：2022/08/22；公开日：2022/11/25。
它真正发现的问题
这件专利的问题落在“[Translated] A protein degradation agent capable of self-assembly in cells and its preparation method and application”对应的药物转化环节：[Translated] The invention discloses a protein degrading agent capable of being self-assembled in cells, a preparation method and application thereof. 研读重点是成分、载体、给药或制备条件如何解决稳定性、递送效率或药效路径问题。
它的技术方案
公开摘要显示，方案的具体构成是：[Translated] The invention discloses a protein degrading agent capable of being self-assembled in cells, a preparation method and application thereof.A linker is used for connecting a target protein ligand Linifanib with one of target protein ligands S5 and a bioorthogonal group norbornene to obtain a target protein ligand with the bioorthogonal group norbornene; modifying a tetrazine group on an E3 ubiquitin ligase ligand through a connecting chain to obtain the E3 ubiquitin ligase ligand with bio-orthogonal grou...
给我们的启示
启示是，蛋白降解专利要把靶点、E3配体、连接子、细胞内组装和药效结果串起来，形成组合保护。
3. [Translated] Pharmaceutical composition containing clarithromycin and Shu Da pyridine
代表专利：CN-116763807-B。申请人/权利人：公开页面未列明。优先权日：2023/08/08；公开日：2025/04/11；授权日：2025/04/11。
它真正发现的问题
这件专利的问题落在“[Translated] Pharmaceutical composition containing clarithromycin and Shu Da pyridine”对应的药物转化环节：[Translated] The invention belongs to the technical field of medicines, and particularly relates to a pharmaceutical composition containing clarithromycin and Shu Da pyridine, which solves the technical problems that the selection of medicines for inhibiting mycobacterium abscesses is limited, the treatment period is long, the medicines are easy to repeat a. 研读重点是成分、载体、给药或制备条件如何解决稳定性、递送效率或药效路径问题。
它的技术方案
公开摘要显示，方案的具体构成是：[Translated] The invention belongs to the technical field of medicines, and particularly relates to a pharmaceutical composition containing clarithromycin and Shu Da pyridine, which solves the technical problems that the selection of medicines for inhibiting mycobacterium abscesses is limited, the treatment period is long, the medicines are easy to repeat and resistant to common clinical antibiotics, the pharmaceutical composition inhibits the mycobacterium abscesses by combining clarithromycin and Shu Da pyridine...
给我们的启示
启示是，药物组合物专利的价值在可重复产品条件：配比、剂型、给药路径、稳定性数据和适应症选择需要相互支撑。
4. Ionizable cationic lipids and lipid nanoparticles
代表专利：US-2024299311-A1。申请人/权利人：KARMALI PRIYA PRAKASH (US) TANIS STEVEN (US) CAPSTAN THERAPEUTICS INC (US)。优先权日：2022/04/05；公开日：2024/09/12。
它真正发现的问题
这件专利的问题落在“Ionizable cationic lipids and lipid nanoparticles”对应的药物转化环节：Ionizable cationic lipids, methods for synthesizing them, as well as intermediates useful in synthesis of these lipids and methods of synthesizing the intermediates are disclosed. 研读重点是成分、载体、给药或制备条件如何解决稳定性、递送效率或药效路径问题。
它的技术方案
公开摘要显示，方案的具体构成是：Ionizable cationic lipids, methods for synthesizing them, as well as intermediates useful in synthesis of these lipids and methods of synthesizing the intermediates are disclosed. The ionizable cationic lipids are useful as a component of lipid nanoparticles (LNP), which in turn can be used for the delivery of nucleic acids into cells in vivo or ex vivo. LNP compositions are also disclosed, including LNP comprising a functionalized lipid to enable conjugation of a binding moiety, and targeted LNP (tLNP), that is a...
给我们的启示
启示是，递送平台布局要覆盖配方比例、制备方法、载荷类型、稳定性指标和用途，而不是只保护一种载荷。
5. Heterobifunctional compositions for targeted protein degradation and methods for their use
代表专利：WO-2022187650-A1。申请人/权利人：SCRIPPS RESEARCH INST (US)。优先权日：2021/03/04；公开日：2022/09/09。
它真正发现的问题
这件专利的问题落在“Heterobifunctional compositions for targeted protein degradation and methods for their use”对应的药物转化环节：Compositions and methods for control and/or modification of endogenous protein degradation are described. 研读重点是成分、载体、给药或制备条件如何解决稳定性、递送效率或药效路径问题。
它的技术方案
公开摘要显示，方案的具体构成是：Compositions and methods for control and/or modification of endogenous protein degradation are described. The compositions are directed to heterobifunctional molecules having protein and enzyme system binding moieties linked together by an organic linker group. The compositions are selective for binding to certain endogenous proteins and function to recruit endogenous decomposition systems such as the polyubiquitin system for peptide cleavage and reassimilation.
给我们的启示
启示是，蛋白降解专利要把靶点、E3配体、连接子、细胞内组装和药效结果串起来，形成组合保护。
6. Pharmaceutical composition
代表专利：US-12364684-B2。申请人/权利人：ASTRAZENECA AB (SE) ARRAY BIOPHARMA INC (US)。优先权日：2008/03/28；公开日：2025/07/22；授权日：2025/07/22。
它真正发现的问题
这件专利的问题落在“Pharmaceutical composition”对应的药物转化环节：The invention concerns pharmaceutical compositions containing a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide and solvates, crystalline forms and amorphous forms thereof, to the use of said compositions as a medicament, and to processes for the preparation of said co. 研读重点是成分、载体、给药或制备条件如何解决稳定性、递送效率或药效路径问题。
它的技术方案
公开摘要显示，方案的具体构成是：The invention concerns pharmaceutical compositions containing a hydrogen sulphate salt of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3-methyl-3H-benzoimidazole-5-carboxylic acid (2-hydroxy-ethoxy)-amide and solvates, crystalline forms and amorphous forms thereof, to the use of said compositions as a medicament, and to processes for the preparation of said compositions.
给我们的启示
启示是，药物组合物专利的价值在可重复产品条件：配比、剂型、给药路径、稳定性数据和适应症选择需要相互支撑。
7. [Translated] lipid nanoparticles
代表专利：CN-114174522-A。申请人/权利人：LEGAL PERSON NORKAIDO UNIV OF NATIONAL UNIV。优先权日：2019/05/30；公开日：2022/03/11。
它真正发现的问题
这件专利的问题落在“[Translated] lipid nanoparticles”对应的药物转化环节：[Translated] The present invention addresses the problem of providing lipid nanoparticles that contain nucleic acids and the like required for genome editing, can be produced by an alcohol dilution method using a flow channel, and have excellent genome editing efficiency. 研读重点是成分、载体、给药或制备条件如何解决稳定性、递送效率或药效路径问题。
它的技术方案
公开摘要显示，方案的具体构成是：[Translated] The present invention addresses the problem of providing lipid nanoparticles that contain nucleic acids and the like required for genome editing, can be produced by an alcohol dilution method using a flow channel, and have excellent genome editing efficiency. The present invention is a lipid nanoparticle comprising a lipid component, a DNA nuclease, a guide RNA, and a single-stranded oligonucleotide, wherein the lipid component comprises a pH-sensitive cationic lipid, a neutral phospholipid, and a pol...
给我们的启示
启示是，递送平台布局要覆盖配方比例、制备方法、载荷类型、稳定性指标和用途，而不是只保护一种载荷。
8. Glycan-mediated protein degradation
代表专利：WO-2022200390-A3。申请人/权利人：GLYCOERA AG (CH)。优先权日：2021/03/23；公开日：2022/11/10。
它真正发现的问题
这件专利的问题落在“Glycan-mediated protein degradation”对应的药物转化环节：The present disclosure provides glycoengineered bifunctional binding proteins for glycan-mediated degradation. 研读重点是成分、载体、给药或制备条件如何解决稳定性、递送效率或药效路径问题。
它的技术方案
公开摘要显示，方案的具体构成是：The present disclosure provides glycoengineered bifunctional binding proteins for glycan-mediated degradation. Such glycan modifications will improve current treatments and allow a better quality of life for patients. Accordingly, such glycoengineered bifunctional binding proteins are useful for treating and preventing various diseases.
给我们的启示
启示是，蛋白降解专利要把靶点、E3配体、连接子、细胞内组装和药效结果串起来，形成组合保护。
9. Pharmaceutical composition, methods for treating and uses thereof
代表专利：US-12263153-B2。申请人/权利人：BOEHRINGER INGELHEIM INT (DE)。优先权日：2016/11/10；公开日：2025/04/01；授权日：2025/04/01。
它真正发现的问题
这件专利的问题落在“Pharmaceutical composition, methods for treating and uses thereof”对应的药物转化环节：The present invention relates to methods for treating or preventing chronic kidney disease and cardiovascular disease in patients with chronic kidney disease comprising administering empagliflozin to the patient. 研读重点是成分、载体、给药或制备条件如何解决稳定性、递送效率或药效路径问题。
它的技术方案
公开摘要显示，方案的具体构成是：The present invention relates to methods for treating or preventing chronic kidney disease and cardiovascular disease in patients with chronic kidney disease comprising administering empagliflozin to the patient.
给我们的启示
启示是，药物组合物专利的价值在可重复产品条件：配比、剂型、给药路径、稳定性数据和适应症选择需要相互支撑。
10. [Translated] Transfection reagent based on blank lipid nanoparticles, preparation method and application thereof
代表专利：CN-117925729-A。申请人/权利人：SHENGDI BIOLOGICAL MEDICINE SUZHOU CO LTD。优先权日：2024/01/19；公开日：2024/04/26。
它真正发现的问题
这件专利的问题落在“[Translated] Transfection reagent based on blank lipid nanoparticles, preparation method and application thereof”对应的药物转化环节：[Translated] The present invention provides a transfection reagent based on blank lipid nanoparticles, a preparation method and application thereof, and belongs to the field of biomedical technology. 研读重点是成分、载体、给药或制备条件如何解决稳定性、递送效率或药效路径问题。
它的技术方案
公开摘要显示，方案的具体构成是：[Translated] The present invention provides a transfection reagent based on blank lipid nanoparticles, a preparation method and application thereof, and belongs to the field of biomedical technology. The transfection reagent based on blank lipid nanoparticles of the present invention comprises: (1) blank lipid nanoparticles; (2) biologically active ingredients; the blank lipid nanoparticles are composed of: ionizable lipids, phospholipids, cholesterol and polyethylene glycol-conjugated lipids. The preparation proc...
给我们的启示
启示是，递送平台布局要覆盖配方比例、制备方法、载荷类型、稳定性指标和用途，而不是只保护一种载荷。
11. miRNA profiling compositions and methods of use
代表专利：US-10086093-B2。申请人/权利人：MASSACHUSETTS GEN HOSPITAL (US)。优先权日：2013/02/28；公开日：2018/10/02；授权日：2018/10/02。
它真正发现的问题
这件专利的问题落在“miRNA profiling compositions and methods of use”对应的药物转化环节：Disclosed herein is a nanosensor of miRNA activity in a target cell, and methods of use, for detection and diagnostic applications. 研读重点是成分、载体、给药或制备条件如何解决稳定性、递送效率或药效路径问题。
它的技术方案
公开摘要显示，方案的具体构成是：Disclosed herein is a nanosensor of miRNA activity in a target cell, and methods of use, for detection and diagnostic applications. The nanosensor comprises a delivery particle comprising an iron oxide crystal coated with a polymer; and a sensor oligonucleotide covalently attached to the polymer. The sensor oligonucleotide comprises a seed region, comprising a nucleic acid sequence that is completely complementary to the target miRNA and comprises a cleavage site which can be engaged and cleaved by the target miRN...
给我们的启示
启示是，递送平台布局要覆盖配方比例、制备方法、载荷类型、稳定性指标和用途，而不是只保护一种载荷。
12. Novel bifunctional molecules for targeted protein degradation
代表专利：WO-2022129925-A1。申请人/权利人：AMPHISTA THERAPEUTICS LTD (GB)。优先权日：2020/12/18；公开日：2022/06/23。
它真正发现的问题
这件专利的问题落在“Novel bifunctional molecules for targeted protein degradation”对应的药物转化环节：The present disclosure relates to a novel class of bifunctional molecules that are useful in a targeted or selective degradation of a protein. 研读重点是成分、载体、给药或制备条件如何解决稳定性、递送效率或药效路径问题。
它的技术方案
公开摘要显示，方案的具体构成是：The present disclosure relates to a novel class of bifunctional molecules that are useful in a targeted or selective degradation of a protein.
给我们的启示
启示是，蛋白降解专利要把靶点、E3配体、连接子、细胞内组装和药效结果串起来，形成组合保护。
13. [Translated] Pharmaceutical composition containing anti-CCR 8 antibody and application thereof
代表专利：CN-119909167-A。申请人/权利人：JIANGSU HENGRUI MEDICINE CO Shanghai hengrui pharmaceutical co ltd。优先权日：2023/10/31；公开日：2025/05/02。
它真正发现的问题
这件专利的问题落在“[Translated] Pharmaceutical composition containing anti-CCR 8 antibody and application thereof”对应的药物转化环节：[Translated] The present disclosure relates to a pharmaceutical composition comprising an anti-CCR 8 antibody and uses thereof. 研读重点是成分、载体、给药或制备条件如何解决稳定性、递送效率或药效路径问题。
它的技术方案
公开摘要显示，方案的具体构成是：[Translated] The present disclosure relates to a pharmaceutical composition comprising an anti-CCR 8 antibody and uses thereof. In particular, the disclosure relates to a pharmaceutical composition comprising an anti-CCR 8 antibody and a buffer, the buffer being an acetate buffer, a histidine buffer or a phosphate buffer. The pharmaceutical composition has therapeutic activity. In addition, the pharmaceutical composition has the advantages of good stability and the like.
给我们的启示
启示是，药物组合物专利的价值在可重复产品条件：配比、剂型、给药路径、稳定性数据和适应症选择需要相互支撑。
14. Therapeutic Targeting of Lipid Nanoparticles
代表专利：US-2020093936-A1。申请人/权利人：UNIV PENNSYLVANIA (US)。优先权日：2018/09/21；公开日：2020/03/26。
它真正发现的问题
这件专利的问题落在“Therapeutic Targeting of Lipid Nanoparticles”对应的药物转化环节：The present invention relates to compositions comprising a delivery vehicle conjugated to a targeting domain, wherein the delivery vehicle comprises at least one agent, and wherein the targeting domain specifically binds to an endothelial marker. 研读重点是成分、载体、给药或制备条件如何解决稳定性、递送效率或药效路径问题。
它的技术方案
公开摘要显示，方案的具体构成是：The present invention relates to compositions comprising a delivery vehicle conjugated to a targeting domain, wherein the delivery vehicle comprises at least one agent, and wherein the targeting domain specifically binds to an endothelial marker. The invention also relates to methods of treating or preventing neurological or pulmonary conditions using the described compositions.
给我们的启示
启示是，递送平台布局要覆盖配方比例、制备方法、载荷类型、稳定性指标和用途，而不是只保护一种载荷。
15. Glycan-mediated protein degradation
代表专利：US-2025282886-A1。申请人/权利人：GLYCOERA AG (CH)。优先权日：2021/03/23；公开日：2025/09/11。
它真正发现的问题
这件专利的问题落在“Glycan-mediated protein degradation”对应的药物转化环节：The present disclosure provides glycoengineered bifunctional binding proteins for glycan-mediated degradation. 研读重点是成分、载体、给药或制备条件如何解决稳定性、递送效率或药效路径问题。
它的技术方案
公开摘要显示，方案的具体构成是：The present disclosure provides glycoengineered bifunctional binding proteins for glycan-mediated degradation. Such glycan modifications will improve current treatments and allow a better quality of life for patients. Accordingly, such glycoengineered bifunctional binding proteins are useful for treating and preventing various diseases.
给我们的启示
启示是，蛋白降解专利要把靶点、E3配体、连接子、细胞内组装和药效结果串起来，形成组合保护。
16. [Translated] Intra-articular injection formulation containing colchicine and an anesthetic for the treatment of acute inflammatory arthritis associated with crystals and amorphous cysts
代表专利：KR-20250091283-A。申请人/权利人：PK MED (FR)。优先权日：2022/10/25；公开日：2025/06/20。
它真正发现的问题
这件专利的问题落在“[Translated] Intra-articular injection formulation containing colchicine and an anesthetic for the treatment of acute inflammatory arthritis associated with crystals and amorphous cysts”对应的药物转化环节：[Translated] The present invention relates to a pharmaceutical composition suitable for intra-articular injection comprising an immediate or controlled release formulation comprising an anesthetic and colchicine. 研读重点是成分、载体、给药或制备条件如何解决稳定性、递送效率或药效路径问题。
它的技术方案
公开摘要显示，方案的具体构成是：[Translated] The present invention relates to a pharmaceutical composition suitable for intra-articular injection comprising an immediate or controlled release formulation comprising an anesthetic and colchicine. The present invention further relates to a pharmaceutical composition in powder form comprising an immediate or controlled release formulation comprising an anesthetic and colchicine, wherein said controlled release formulation comprising colchicine is in the form of microparticles. The present invention ...
给我们的启示
启示是，药物组合物专利的价值在可重复产品条件：配比、剂型、给药路径、稳定性数据和适应症选择需要相互支撑。
本期结论
这些制药专利共同说明，药物专利的价值常在转化细节：递送载体、组合比例、制备条件、给药方式和稳定性指标决定了发明能否从机理走向产品。
资料来源 / Sources
本期依据 PubChem patent JSON、Google Patents 公开页面和原公开链接研读整理。正式FTO或授权稳定性判断仍需进一步核对官方登记簿、审查历史、同族和权利要求全文。
- US-2025213496-A1 - Lipid nanoparticles and preparation methods and use thereof
- CN-115385859-A - [Translated] A protein degradation agent capable of self-assembly in cells and its preparation method and application
- CN-116763807-B - [Translated] Pharmaceutical composition containing clarithromycin and Shu Da pyridine
- US-2024299311-A1 - Ionizable cationic lipids and lipid nanoparticles
- WO-2022187650-A1 - Heterobifunctional compositions for targeted protein degradation and methods for their use
- US-12364684-B2 - Pharmaceutical composition
- CN-114174522-A - [Translated] lipid nanoparticles
- WO-2022200390-A3 - Glycan-mediated protein degradation
- US-12263153-B2 - Pharmaceutical composition, methods for treating and uses thereof
- CN-117925729-A - [Translated] Transfection reagent based on blank lipid nanoparticles, preparation method and application thereof
- US-10086093-B2 - miRNA profiling compositions and methods of use
- WO-2022129925-A1 - Novel bifunctional molecules for targeted protein degradation
- CN-119909167-A - [Translated] Pharmaceutical composition containing anti-CCR 8 antibody and application thereof
- US-2020093936-A1 - Therapeutic Targeting of Lipid Nanoparticles
- US-2025282886-A1 - Glycan-mediated protein degradation
- KR-20250091283-A - [Translated] Intra-articular injection formulation containing colchicine and an anesthetic for the treatment of acute inflammatory arthritis associated with crystals and amorphous cysts