Pharma IP / English Article
Patent Layout Strategy for Generic Drugs
A structured reading of how generic pharmaceutical players can understand and respond to patent barriers.
Generic Drug Competition Is Also Patent Competition
Generic-drug strategy is not only a matter of formulation, approval, and manufacturing. It is also a matter of patent layout. Originator companies often build dense patent fences around compounds, crystal forms, formulations, dosage regimens, manufacturing methods, indications, delivery devices, and combinations.
A generic company must understand this fence before deciding where to enter. The question is not simply whether the core compound patent has expired. The question is whether later patents still control commercially important routes.
Generic Drug Competition Is Also Patent Competition: practical detail
For generic-drug companies, pharmaceutical IP teams, and technical decision makers, this point should be treated as a working step rather than a slogan. The practical work is to connect the article's idea with layer-by-layer patent mapping, formulation and process comparison, barrier classification, design-around planning, and invalidation-risk review. That is what turns a general insight into a repeatable professional service.
The team should record concrete evidence: compound patents, crystal-form patents, formulation claims, process claims, stability data, bioequivalence constraints, and regulatory timing. Without this evidence layer, the method remains only an opinion. With it, the article becomes useful for client communication, internal decision-making, patent drafting, prosecution strategy, and later portfolio review.
A complete application of this section normally ends with a decision: whether to avoid, challenge, license, wait, or build an independent improvement portfolio around the generic product. Ma Su's examiner background matters here because the decision is not based only on enthusiasm; it is tested against technical contribution, support in the disclosure, likely examination reasoning, and business value.
Map the Patent Barrier Layer by Layer
The first task is to build a patent map. Identify the basic compound patents, then examine secondary patents covering salts, polymorphs, particle size, sustained-release structures, excipients, manufacturing processes, packaging, medical use, patient groups, and dosage schedules.
Each layer should be connected to product reality. Some patents may look broad but be easy to design around. Others may cover a small feature that is essential to stability, bioavailability, or regulatory equivalence.
Map the Patent Barrier Layer by Layer: practical detail
For generic-drug companies, pharmaceutical IP teams, and technical decision makers, this point should be treated as a working step rather than a slogan. The practical work is to connect the article's idea with layer-by-layer patent mapping, formulation and process comparison, barrier classification, design-around planning, and invalidation-risk review. That is what turns a general insight into a repeatable professional service.
The team should record concrete evidence: compound patents, crystal-form patents, formulation claims, process claims, stability data, bioequivalence constraints, and regulatory timing. Without this evidence layer, the method remains only an opinion. With it, the article becomes useful for client communication, internal decision-making, patent drafting, prosecution strategy, and later portfolio review.
A complete application of this section normally ends with a decision: whether to avoid, challenge, license, wait, or build an independent improvement portfolio around the generic product. Ma Su's examiner background matters here because the decision is not based only on enthusiasm; it is tested against technical contribution, support in the disclosure, likely examination reasoning, and business value.
Choose Between Avoidance, Challenge, and Improvement
After mapping, the company has three strategic routes. The first is avoidance: design a formulation or process that does not fall into the patent scope. The second is challenge: attack weak patents through invalidation or other legal routes. The third is improvement: develop a new technical solution that creates the company's own patent position.
The best route depends on technical feasibility, regulatory timing, cost, market size, and evidence strength. A patent strategy that ignores pharmaceutical development reality is just paper. A development strategy that ignores patent barriers is dangerous.
Choose Between Avoidance, Challenge, and Improvement: practical detail
For generic-drug companies, pharmaceutical IP teams, and technical decision makers, this point should be treated as a working step rather than a slogan. The practical work is to connect the article's idea with layer-by-layer patent mapping, formulation and process comparison, barrier classification, design-around planning, and invalidation-risk review. That is what turns a general insight into a repeatable professional service.
The team should record concrete evidence: compound patents, crystal-form patents, formulation claims, process claims, stability data, bioequivalence constraints, and regulatory timing. Without this evidence layer, the method remains only an opinion. With it, the article becomes useful for client communication, internal decision-making, patent drafting, prosecution strategy, and later portfolio review.
A complete application of this section normally ends with a decision: whether to avoid, challenge, license, wait, or build an independent improvement portfolio around the generic product. Ma Su's examiner background matters here because the decision is not based only on enthusiasm; it is tested against technical contribution, support in the disclosure, likely examination reasoning, and business value.
Build Your Own Defensive Portfolio
Generic companies should not only avoid others' patents. They should also protect their own improvements. Manufacturing stability, impurity control, dissolution performance, excipient selection, packaging, storage, and patient-compliance improvements can all become patentable when they solve real technical problems.
In pharmaceutical IP, the winner is often the party that understands both the regulatory route and the patent map.
Build Your Own Defensive Portfolio: practical detail
For generic-drug companies, pharmaceutical IP teams, and technical decision makers, this point should be treated as a working step rather than a slogan. The practical work is to connect the article's idea with layer-by-layer patent mapping, formulation and process comparison, barrier classification, design-around planning, and invalidation-risk review. That is what turns a general insight into a repeatable professional service.
The team should record concrete evidence: compound patents, crystal-form patents, formulation claims, process claims, stability data, bioequivalence constraints, and regulatory timing. Without this evidence layer, the method remains only an opinion. With it, the article becomes useful for client communication, internal decision-making, patent drafting, prosecution strategy, and later portfolio review.
A complete application of this section normally ends with a decision: whether to avoid, challenge, license, wait, or build an independent improvement portfolio around the generic product. Ma Su's examiner background matters here because the decision is not based only on enthusiasm; it is tested against technical contribution, support in the disclosure, likely examination reasoning, and business value.
Original Chinese Essay
权威解读仿制药如何玩转专利布局
制药行业如何玩转专利布局：从司美格鲁肽看GLP-1赛道的“组合锁”攻防
2025年12月31日，诺和诺德中国官网发布公告：最高人民法院作出终审判决，支持北京知识产权法院关于维持司美格鲁肽化合物专利有效的决定。这场历时四年半的专利挑战“拉锯战”，最终以专利权利人诺和诺德胜诉落下帷幕。
但胜诉并不意味着高枕无忧。按照专利布局，司美格鲁肽的化合物专利在中国将在2026年3月到期，截至目前，国家药监局已受理了至少10款国产司美格鲁肽的上市申请——九源基因、丽珠集团、中美华东、齐鲁制药、石药集团、联邦制药、惠升生物……每一个都虎视眈眈。
诺和诺德自己也很清楚这一点。2025年底，公司罕见地提前把司美格鲁肽“诺和盈”价格腰斩47%，以应对即将到来的仿制药强攻。
这场GLP-1赛道的大战，为我们提供了观察制药行业专利布局的绝佳样本。本文将围绕司美格鲁肽及相关GLP-1药物的专利攻防，解析制药企业如何玩转专利布局。
一、核心化合物专利：定海神针的“生死时速”
在药品专利体系中，核心化合物专利是最重要的一环——它保护的是药物活性成分本身，是所有后续专利的基础。一旦化合物专利被无效或被绕过，整个“专利城堡”就可能土崩瓦解。
司美格鲁肽的化合物专利保卫战
这场历时四年半的专利挑战，始于2021年华东医药子公司中美华东向国家知识产权局提起的无效宣告请求。中美华东以“说明书公开不充分、部分权利要求不具备创造性”为由，对诺和诺德“酰化的GLP-1化合物”专利发起挑战。
2022年9月，国家知识产权局宣告该化合物专利权全部无效，理由是诺和诺德在申请专利时没能证明司美格鲁肽具体化合物所具有的技术效果。
诺和诺德随即向北京知识产权法院提起行政诉讼。案件的核心争议在于：诺和诺德主张的司美格鲁肽技术效果，是否可以从说明书公开的内容中“得到”？
北京知识产权法院法官芮松艳分析指出，说明书中诺和诺德虽然没有给出司美格鲁肽在临床前试验中的具体实验数据，但后续补充的数据证明司美格鲁肽比利拉鲁肽具有更长的作用持续时间（约48小时）。这可以证明司美格鲁肽在内的通式化合物均具有“至少24小时的作用持续时间”这一技术效果。
2024年10月，北京知识产权法院一审判决要求国家知识产权局重新审查该专利有效性。2025年12月31日，最高法作出终审判决，维持专利有效。
这一案例的关键启示在于：在撰写化合物专利申请时，应当包含“宽泛但合理”的效果描述，为后续补交实验数据预留空间。正如DrugPatentWatch的分析所指出的，说明书中“延长持续时间”的概括性描述，为后来接受补充数据奠定了基础。
二、利用结构通式进行前瞻布局
通过已知药物的特性，推演其他可能有效的结构并进行提前布局，这正是制药行业“快速跟进”（fast follow）策略的核心逻辑。
从Orforglipron看结构优化布局
礼来的Orforglipron是由日本中外制药发现的口服小分子GLP-1R激动剂，其核心专利WO2018056453A1于2018年3月公开。
在这份专利中，权利人通过马库什通式覆盖了包含吲哚环和吡唑并吡啶结构的一大类化合物。这意味着，任何试图开发类似结构的药企，都可能落入这一专利的保护范围。
但众多中国药企并未就此止步。通过对Orforglipron结构的深入分析，他们找到了优化的空间：
· 翰森制药（Hansoh Pharma） 于2023年7月提交了PCT专利申请WO2025026270A1，其化合物结构与Orforglipron高度相似，主要区别在于吲唑环氮原子上的取代基。其中化合物143的EC50低至0.013nM，显示出极高的受体激活效力。
· 诚益生物（CYSW） 开发的ECC5004，通过对苯环上取代基、吲哚环N原子位置及C3环烷取代基的优化，成功突破了Orforglipron的专利屏障，并于2020年7月提交优先权专利申请。
2023年11月，诚益生物与阿斯利康就ECC5004达成价值超20亿美元的独家许可协议。这充分说明：基于已知药物的结构特征进行差异化优化，不仅可以绕开专利壁垒，还能创造巨大的商业价值。
操作要点：如何做好结构优化布局
1. 深度解析核心专利的权利要求范围：不仅要看独立权利要求，还要分析从属权利要求限定的具体取代基范围。
2. 识别可优化的结构位点：通常在保持核心药效团的前提下，寻找可以替换的取代基。
3. 评估差异化程度：优化的目的是“不同且更好”——既要确保不落入原研专利保护范围，又要在药效、药代或安全性方面有所提升。
4. 尽早提交专利申请：从翰森的案例看，其优先权日（2023年7月）距Orforglipron核心专利公开（2018年3月）仅5年多；诚益生物的跟进时间（2020年7月）更是缩短到2年4个月。
三、构筑“专利组合锁”：不止于化合物
核心化合物专利终将到期，但原研药企可以通过构筑外围专利网，将仿制药阻挡多年。这正是业内所称的“专利常青”策略。
诺和诺德围绕GLP-1的53件专利
国家知识产权局专利审查信息平台显示，诺和诺德围绕“GLP-1”共申请相关专利53件。这些专利覆盖了哪些领域？
· 晶型专利：保护药物特定晶体形态，不同晶型可能影响溶解度、稳定性
· 制剂专利：如缓释注射剂、口服制剂的特定配方
· 用途专利：覆盖糖尿病、肥胖症、心血管保护、MASH（代谢功能障碍相关性脂肪性肝炎）等多种适应症
· 制备方法专利：保护药物的合成工艺
· 组合物专利：与其他活性成分的联用
这套“组合锁”的效果是：即便最核心的化合物专利到期，仿制药企业仍可能被其他配套专利阻挡多年。
以修美乐（阿达木单抗）为例，其化合物专利早在2016年到期，但艾伯维通过与多家仿制药企达成诉讼和解，成功将生物类似药在美国的上市时间推迟到2023年。
外围专利布局的策略要点
1. 时间错峰申请：外围专利可以在化合物专利之后陆续申请，使各专利到期时间错开，延长整体保护期。
2. 覆盖所有商业应用：不仅保护最初的适应症，还要为后续拓展的新适应症申请用途专利。
3. 布局不同晶型：在化合物专利公开后、发现稳定晶型时及时申请晶型专利。
4. 制剂创新专利化：开发口服制剂、缓释制剂等改良剂型并申请专利。
四、快速跟进与差异化创新的平衡
GLP-1赛道的竞争格局，清晰地展示了快速跟进策略的优势与风险。
优势：缩短研发周期、降低验证风险
当先发药企已经验证了靶点的安全性和有效性，跟进者可以大大降低研发风险。正如环球律师事务所的分析所指出的：QLRG在Danuglipron专利公开仅5个月后就提交了RGT-075的优先权申请，并在2021年将该项目许可给礼来，获得最高15亿美元的里程碑付款。
风险：过快跟进可能踩坑
快速跟进也有代价。辉瑞的Danuglipron因IIb期试验中胃肠道反应发生率过高（停药率超过50%）而终止开发；另一款Lotiglipron也因转氨酶升高被叫停。
这意味着：以Danuglipron为蓝图的快速跟进药物，如果未能提前识别先导化合物的安全性问题，可能面临同样的研发失败风险。
差异化不足的知识产权风险
如果在快速跟进过程中仅在结构或工艺上做微小调整，极可能落入先导药企布局的专利覆盖范围。
歌礼制药与石药集团的海外专利战即为典型案例。石药集团正在申请的GLP-1小分子化合物，被歌礼指控与后者已获授权的化合物1分子结构完全一致。尽管石药向USPTO提交复审申请，但歌礼的专利申请比石药早了三个多月，这一时间差可能成为裁决的关键因素。
启示：差异化不能只是“换汤不换药”。真正的差异化应当是功能层面的优化，而不仅仅是结构上的微小变动。
五、专利布局与商业化的协同
利用专利组合促成BD交易
强大的专利布局本身就是商业价值的体现。翰森制药与默沙东就HS-10535达成的超20亿美元合作，很大程度上得益于其专利WO2025026270A1中化合物143和282展现出的优异数据。
同样，诚益生物的ECC5004在专利公开后不久便与阿斯利康达成20亿美元级合作。
应对仿制药竞争的双重准备
面对即将到来的专利悬崖，诺和诺德采取了双重策略：
· 法律层面：全力维护化合物专利有效性，赢得四年半的专利战
· 商业层面：提前降价47%，为仿制药涌入后的价格战做准备
这种“法律+商业”的双重准备，值得所有原研药企借鉴。
把握专利悬崖前的窗口期
中国上市药品专利信息登记平台显示，截至2025年底，专利四类声明累计提交量已超过500个。这意味着越来越多仿制药企业在争夺提前上市的机会。
对于仿制药企而言，关键在于找准挑战方向。闫春辉律师建议：如果目标市场集中于特定疾病领域，而原研专利保护范围覆盖多个适应症，那么集中质疑直接阻碍产品上市的部分，比发起全面挑战更高效。
结语：专利布局是一场“组合锁”攻防战
回看司美格鲁肽的专利历程，我们可以清晰地看到制药行业专利布局的核心逻辑：
以核心化合物专利为“定海神针”，通过精细的权利要求撰写和充分的说明书支持，为后续确权留足空间。
以结构通式为“防御阵地”，通过马库什权利要求覆盖尽可能多的结构变体，压缩竞争对手的绕行空间。
以晶型、制剂、用途专利为“外围护城河”，构筑层层递进的“组合锁”，将仿制药阻挡多年。
以差异化创新为“进攻武器”，在识别先导化合物可优化位点的基础上，开发“不同且更好”的分子，既绕开专利壁垒，又创造新的商业价值。
正如业内专家所言：原研药企的专利如同一套环环相扣的“组合锁”，即便最核心的锁芯被打开，其他锁扣仍能将仿制药阻挡多年。
在这场“组合锁”的攻防战中，胜出的永远是准备更充分、布局更系统、策略更精准的一方。GLP-1赛道的竞争才刚刚开始，后续的专利博弈仍将精彩纷呈。
· 核心化合物专利是根基：撰写时需预留补交实验数据的空间
· 结构通式可覆盖广泛变体：深度解析权利要求，寻找可优化的位点
· 外围专利构筑“组合锁”：晶型、制剂、用途、方法专利缺一不可
· 快速跟进需平衡速度与差异化：微小创新可能引发侵权风险
· 专利布局与商业协同：强大的专利组合可促成重磅BD交易