APPA

专利舞蹈的相关规定和程序，主要体现在以下三个法案里： BPCIA 2010年，Biologics Price Competition and Innovation Act（BPCIA，生物制品价格竞争与创新法案）作为《患者保护与平价医疗法案》（ACA）的一部分正式通过，成为法律，旨在为生物类似药的研发和审批提供清晰的法规框架。BPCIA通过简化审批程序促进生物类似药的市场准入，同时保护创新药物的专利权，设立了“专利舞蹈(Patent Dance)”机制解决专利争议，确保在促进市场竞争，降低生物制品价格的同时，推动生物制药领域的创新。专利舞蹈流程可简要概括如下表。 BPCIA中关于专利舞蹈的部分主要体现在42 U.S. Code § 262(I)，稍后我们会逐条详细解读。 BPTA 2020年，Biologic Patent Transparency Act（BPTA，生物制剂专利透明度法案）通过，该法案强制要求原研药企（Reference Product Sponsor）把它在 patent dance中给 biosimilar 公司的专利清单提交给 FDA，FDA则必须把这些清单公开发布在 “Purple Book” 上。这里所说的专利清单，包括(l)(3)(A)初始清单（“3A list”）以及(l)(7) 补充清单（a supplement to 3A list）。FDA需至少每30天更新 Purple Book 上的内容。 APPA 2024年，Cornyn–Blumenthal Affordable Prescriptions for Patients Act（APPA，患者可负担处方药法案）通过，鉴于原研药企日益增多的manufacturing platform patents，且专利诉讼中出现冗长的专利清单，给生物类似药申请人带来的巨大的负担，该方案要求针对那些“have an actual filing date of more than 4 years after the date on which the reference product is approved” or “include a claim to a method in a manufacturing process that is not used by the reference product sponsor”，原研可在诉讼中主张的专利总数不得超过20项，且这些专利必须列在§351(l)(3)(A)的专利清单中（包括根据§351(l)(7) 提供的补充专利），其中在§351(l)(7)(A)日期后获得的专利不超过10项。 42 U.S. Code § 262(I)逐条解读 (I) (2) Subsection (k) application information Not later than 20 days after the Secretary notifies the subsection (k) applicant that the application has been accepted for review, the subsection (k) applicant— (A)shall provide to the reference product sponsor a copy of the application submitted to the Secretary under subsection (k), and such other information that describes the process or processes used to manufacture the biological product that is the subject of such application; and (B)may provide to the reference product sponsor additional information requested by or on behalf of the reference product sponsor. 在FDA受理生物类似药20天内，生物类似药申请人需向原研药企提供申请副本，以及生产工艺描述。 (I) (3) (A) List by reference product sponsor Not later than 60 days after the receipt of the application and information under paragraph (2), the reference product sponsor shall provide to the subsection (k) applicant— (i)a list of patents for which the reference product sponsor believes a claim of patent infringement could reasonably be asserted by the reference product sponsor, or by a patent owner that has granted an exclusive license to the reference product sponsor with respect to the reference product, if a person not licensed by the reference product sponsor engaged in the making, using, offering to sell, selling, or importing into the United States of the biological product that is the subject of the subsection (k) application; and (ii)an identification of the patents on such list that the reference product sponsor would be prepared to license to the subsection (k) applicant. 原研药企收到上述资料的60天内，需向生物类似药申请人提供一份可合理主张专利侵权的专利清单，并标出原研药企愿意向生物类似药申请人许可的专利。 (I)(3) (B) List and description by subsection (k) applicant Not later than 60 days after receipt of the list under subparagraph (A), the subsection (k) applicant— (i)may provide to the reference product sponsor a list of patents to which the subsection (k) applicant believes a claim of patent infringement could reasonably be asserted by the reference product sponsor ... (ii)shall provide to the reference product sponsor,...(I)a detailed statement that describes, on a claim by claim basis, the factual and legal basis of the opinion of the subsection (k) applicant that such patent is invalid, unenforceable, or will not be infringed by the commercial marketing of the biological product that is the subject of the subsection (k) application; or(II)a statement that the subsection (k) applicant does not intend to begin commercial marketing of the biological product before the date that such patent expires; and (iii)shall provide to the reference product sponsor a response regarding each patent identified by the reference product sponsor under subparagraph (A)(ii). 生物类似药企在收到上述专利清单的60天内，向原研药企提供一份对方可合理主张专利侵权的专利清单，并就该份清单提供：基于事实和法律基础逐项说明该份清单中的专利应当被无效、不可执行或不侵权的详细声明；或专利过期前不上市的声明。并就3(A)(ii)中原研药企提出愿意向生物类似药申请人许可的专利逐件回复。 (I) (3) (C) Description by reference product sponsor Not later than 60 days after receipt of the list and statement under subparagraph (B), the reference product sponsor shall provide to the subsection (k) applicant a detailed statement that describes, with respect to each patent described in subparagraph (B)(ii)(I), on a claim by claim basis, the factual and legal basis of the opinion of the reference product sponsor that such patent will be infringed by the commercial marketing of the biological product that is the subject of the subsection (k) application and a response to the statement concerning validity and enforceability provided under subparagraph (B)(ii)(I). 原研药企收到上述专利清单和声明的60天内，应当向生物类似药申请人提供详细的反驳声明（逐项的，基于事实和法律基础的）。 (I) (4) Patent resolution negotiations (A)After receipt by the subsection (k) applicant of the statement under paragraph (3)(C),the reference product sponsor and the subsection (k) applicant shall engage in good faith negotiations to agree on which, if any, patents listed under paragraph (3) by the subsection (k) applicant or the reference product sponsor shall be the subject of an action for patent infringement under paragraph (6). (B)If, within 15 days of beginning negotiations under subparagraph (A), the subsection (k) applicant and the reference product sponsor fail to agree on a final and complete list of which, if any, patents listed under paragraph (3) by the subsection (k) applicant or the reference product sponsor shall be the subject of an action for patent infringement under paragraph (6), the provisions of paragraph (5) shall apply to the parties. 在生物类似药申请人收到上述反驳声明后的15天内，双方协商确定诉讼中的涉案专利有哪些。 (I) (5) Patent resolution if no agreement (A)Number of patents: The subsection (k) applicant shall notify the reference product sponsor of the number of patents that such applicant will provide to the reference product sponsor under subparagraph (B)(i)(I). (B)Exchange of patent lists (i)In general: On a date agreed to by the subsection (k) applicant and the reference product sponsor, but in no case later than 5 days after the subsection (k) applicant notifies the reference product sponsor under subparagraph (A), the subsection (k) applicant and the reference product sponsor shall simultaneously exchange— (I)the list of patents that the subsection (k) applicant believes should be the subject of an action for patent infringement under paragraph (6); and (II)the list of patents, in accordance with clause (ii), that the reference product sponsor believes should be the subject of an action for patent infringement under paragraph (6). (ii)Number of patents listed by reference product sponsor (I)In general: Subject to subclause (II), the number of patents listed by the reference product sponsor under clause (i)(II) may not exceed the number of patents listed by the subsection (k) applicant under clause (i)(I). (II)Exception: If a subsection (k) applicant does not list any patent under clause (i)(I), the reference product sponsor may list 1 patent under clause (i)(II). 如果双方无法协商一致，则由生物类似药企业确定一个数量，然后在数量给出的5天内双方同时列出并交换专利清单，原研药企列出的专利数量不能多于生物类似药企业列出的专利数量;如果生物类似药企业没有列出任何专利，则原研药企只能列出一个专利。 (I) (6) Immediate patent infringement action (A)Action if agreement on patent list If the subsection (k) applicant and the reference product sponsor agree on patents as described in paragraph (4), not later than 30 days after such agreement, the reference product sponsor shall bring an action for patent infringement with respect to each such patent. (B)Action if no agreement on patent list If the provisions of paragraph (5) apply to the parties as described in paragraph (4)(B), not later than 30 days after the exchange of lists under paragraph (5)(B), the reference product sponsor shall bring an action for patent infringement with respect to each patent that is included on such lists. (C)(i)Notification to Secretary: Not later than 30 days after a complaint is served to a subsection (k) applicant in an action for patent infringement described under this paragraph, the subsection (k) applicant shall provide the Secretary with notice and a copy of such complaint. 在确定诉讼专利清单后的30天内，由原研药企发起针对每一项专利的侵权诉讼。生物类似药企在收到诉状的30天内应向FDA提供相应副本。 (I) (7) Newly issued or licensed patents In the case of a patent that is issued to, or exclusively licensed by, the reference product sponsor after the date that the reference product sponsor provided the list to the subsection (k) applicant under paragraph (3)(A); and...not later than 30 days after such issuance or licensing, the reference product sponsor shall provide to the subsection (k) applicant a supplement to the list provided by the reference product sponsor under paragraph (3)(A) that includes such patent, not later than 30 days after such supplement is provided, the subsection (k) applicant shall provide a statement to the reference product sponsor in accordance with paragraph (3)(B), and such patent shall be subject to paragraph (8). 如果原研在提交3A 专利列表之后又获得新专利（授予或独占许可），那么需要在该专利授权或获得license后的30天内向生物类似药企业提供补充3A清单，生物类似药企在收到该补充清单的30天内需向原研药企提供一份3B声明；这些新专利将适用(l)(8) 的第二阶段诉讼规则（即上市通知后才可诉）。 (I) (8)(A) Notice of commercial marketing The subsection (k) applicant shall provide notice to the reference product sponsor not later than 180 days before the date of the first commercial marketing of the biological product licensed under subsection (k). 生物类似药申请人须在 计划商业上市前至少180天向原研药企发出书面通知。 (I) (8)(B) Preliminary injunction After receiving the notice under subparagraph (A) and before such date of the first commercial marketing of such biological product, the reference product sponsor may seek a preliminary injunction prohibiting the subsection (k) applicant from engaging in the commercial manufacture or sale of such biological product until the court decides the issue of patent validity, enforcement, and infringement with respect to any patent that is— (i)included in the list provided by the reference product sponsor under paragraph (3)(A) or in the list provided by the subsection (k) applicant under paragraph (3)(B); and (ii)not included, as applicable, on(I)the list of patents described in paragraph(4); or(II)the lists of patents described in paragraph (5)(B). 在收到上述通知后，原研药企可以就某些尚未在第一批诉讼中处理的专利，申请初步禁令阻止生物类似药的商业化生产或销售。这些专利必须来自早期的交换列表（3A 或 3B），但不能是双方已经同意要在第一阶段诉讼的专利（4 list 或 5B list）。 (I) (9)(A) Subsection (k) application provided If a subsection (k) applicant provides the application and information required under paragraph (2)(A), neither the reference product sponsor nor the subsection (k) applicant may, prior to the date notice is received under paragraph (8)(A), bring any action under section 2201 of title 28 for a declaration of infringement, validity, or enforceability of any patent that is described in clauses (i) and (ii) of paragraph (8)(B). 如果生物类似药申请人按规则提供了申请与制造信息，则双方都不能在原研收到上市通知前对“第二阶段专利”提 declaratory judgment。 (I) (9)(B) Subsequent failure to act by subsection (k) applicant If a subsection (k) applicant fails to complete an action required of the subsection (k) applicant under paragraph (3)(B)(ii), paragraph (5), paragraph (6)(C)(i), paragraph (7), or paragraph (8)(A), the reference product sponsor, but not the subsection (k) applicant, may bring an action under section 2201 of title 28 for a declaration of infringement, validity, or enforceability of any patent included in the list described in paragraph (3)(A), including as provided under paragraph (7). 如果生物类似药申请人不遵守 patent dance 某些步骤（跳舞跳了一半跑路不合作了），原研可以对所有 3A 专利（包括(I) (7)新增）直接提declaratory judgment；生物仿制药申请人则完全失去 declaratory judgment 权利。 (I) (9)(C) Subsection (k) application not provided If a subsection (k) applicant fails to provide the application and information required under paragraph (2)(A), the reference product sponsor, but not the subsection (k) applicant, may bring an action under section 2201 of title 28 for a declaration of infringement, validity, or enforceability of any patent that claims the biological product or a use of the biological product. 如果生物类似药申请人根本不提供申请与制造信息（完全不跳舞），原研可以对任何产品专利（包括使用专利）提前提 declaratory judgment；生物类似药申请人完全不能提。 往期精彩： GLP-1赛道的BIC之争 KRAS竞争格局整理 如何证明1+1>2？ 如何查找已披露BD Deal的合同原文？ 国内可以考美国专利代理人证书并执业吗？ 在已知CDR上改一个氨基酸，可以申请专利吗？ 关于manufacturing process patents的论战 用已知单抗拼双抗，可以申请专利吗？ 联合用药专利，何去何从？ 专利申请可以挑数据吗？ 没做过的实施例可以写入专利吗？ 美国专利实践中的Double Patenting 如何计算美国专利到期日？ 临床试验方案公开对专利申请的影响（欧洲篇） 临床试验方案公开对专利申请的影响（美国篇） 临床试验方案公开对专利申请的影响（中国篇） 临床试验是否构成“使用公开”？（美国篇） 聊聊专利保密审查 PTE法规要求和计算公式（中国篇） PTE法规要求和计算公式（美国篇） SPC法规要求和计算公式（欧洲篇） PTE案例解析（中国篇） PTE案例解析（美国篇） SPC案例解析（欧洲篇） 如何准确认定专利发明人？ 药品集采中的专利问题 补充实验数据的接受标准和案例分析（中国篇） 补充实验数据的接受标准和案例分析（欧洲篇） 补充实验数据的接受标准和案例分析（美国篇） 化合物结构的非显而易见性判例学习 Skinny Label的运用及挑战 开放式和封闭式权利要求