China Patent Board Upholds RNAi Therapeutic Patents Despite Broad Claim Challenges

China's Patent Re-examination Board has delivered significant victories for RNAi (搜索)搜索该药品 therapeutic patent holders, upholding multiple patents despite challenges to their broad claim language and sufficiency of experimental support. The decisions, featured in China's 2023 Summaries of 50 Typical Patent Invalidation Cases, provide crucial guidance for the rapidly expanding RNAi pharmaceutical sector.

Landmark Inclisiran Patent Decisions

The Board upheld patents covering inclisiran查看药品详情, a PCSK9查看药品详情-inhibiting RNAi (搜索)搜索该药品 composition designed to reduce LDL cholesterol in adult patients with heterozygous familial hypercholesterolemia (搜索)搜索该疾病 (HeFH) and atherosclerotic cardiovascular disease (搜索)搜索该疾病 (ASCVD). The patents faced invalidation challenges on grounds of insufficient disclosure and lack of inventiveness, but the Board rejected these arguments after detailed technical analysis.

The parent patent primarily claims the double-stranded RNAi (搜索)搜索该药品 agent with specific sequences, modifications and conjugations, while the divisional patent covers broader variations in RNAi design. Both patents successfully defended against challenges to their claim scope covering RNAi compositions conjugated to various ligands.

Sufficiency Standards for Broad Claims

Petitioners argued that the patent specifications only provided experimental data for RNAi (搜索)搜索该药品 compositions linked to one specific GalNAc (搜索)搜索该药品 ligand, L96, but lacked support for compositions linked to other ligands. The Board rejected this challenge, establishing that the amount of support needed should be considered alongside a skilled person's reasonable expectations.

The Board determined that ligand-mediated delivery and gene silencing represent relatively independent technical solutions. Since various ligands for directing RNAi (搜索)搜索该药品 delivery are known in the art, a person having ordinary skill in the art (PHOSITA) could reasonably "mix-and-match" suitable ligands with the claimed siRNA查看药品详情 while expecting similar technical effects.

"The technical solution provided by the ligand is directed delivery of the RNAi (搜索)搜索该药品 composition, which is provided relatively independently from the gene-silencing solution of the effective RNAi sequence," the Board stated, concluding that skilled practitioners could anticipate combining different components to solve the presented technical problem.

Inventiveness Analysis Considers Field Unpredictability

For the divisional patent, challengers contended that prior art CN 102458366A already disclosed highly effective nucleotide regions inhibiting PCSK9查看药品详情 expression, making it obvious to add modifications and ligands to create similar RNAi (搜索)搜索该药品 compositions.

The Board identified several key differences between the prior art and claimed invention:

• Different targeted regions in unmodified antisense strand sequences
• Complete nucleotide modifications throughout the RNAi composition versus partial modifications in prior art
• Novel phosphorothioate modifications not disclosed in prior art
• Sole reliance on ligands for delivery versus lipid formulation-based delivery systems

Critically, the Board noted that the cited prior art "taught away" from the claimed invention by suggesting that additional modifications were not particularly beneficial. The claimed invention demonstrated superior silencing effects through specific combinations of sequence selection and phosphorothioate modifications.

Implications for RNAi Patent Strategy

These decisions build upon China's first RNAi (搜索)搜索该药品 patent invalidation case from 2022, which involved Hepatitis B Virus (搜索)搜索该疾病 RNAi compositions. That landmark case established that identifying effective primary sequences represents inventive activity due to the field's unpredictability, while minor modifications maintaining sequence integrity could be expected to solve similar technical problems.

The Board consistently emphasized that RNAi (搜索)搜索该药品 represents an unpredictable field where minor sequence modifications can significantly impact siRNA查看药品详情 characteristics. This unpredictability supports broader patent protection when applicants can demonstrate that skilled practitioners would recognize the inventive nature of their technical solutions.

Examination Practice Remains Restrictive

Despite these favorable invalidation decisions, patent prosecution experience suggests that China National Intellectual Property Administration (搜索)搜索该词条 (CNIPA) examiners remain reluctant to grant broad "comprising" language for sequence listings without extensive data support. The Board's recognition of broader claim scope possibilities may not immediately translate to more permissive examination practices.

However, these cases provide important precedent by affirming that generic scope around RNAi (搜索)搜索该药品 inventions disclosing limited species can be obtained when specifications provide sufficient information for skilled practitioners to recognize that related species would function similarly.

Technical Complexity Drives Patent Strategy

As RNAi (搜索)搜索该药品 compositions become increasingly sophisticated, incorporating complex modifications to nucleotides and delivery ligands, the predictability of individual features may diminish. This growing complexity could impact the ability of skilled practitioners to confidently predict functionality across broad patent claims without supporting data.

The invalidation proceedings underscore the importance of addressing specific technical problems while acknowledging the unpredictable nature of RNAi (搜索)搜索该药品 technology when assessing both inventiveness and sufficient disclosure requirements. These principles will likely influence future RNAi patent examination and litigation strategies in China's expanding biotechnology market.