With the rapid expansion of siRNA research and application worldwide, the number of patent applications has also surged. An analysis of prosecution history of various siRNA patent applications in China shows there has been a shift in patent examination practice for siRNA drugs to a more case-specific assessment.

Small interfering RNA (siRNA), also known as short interfering RNA or silencing RNA, is a class of double-stranded non-coding RNA molecules, typically 20-24 base pairs in length. It knocks down expression of specific genes by binding and degrading messenger RNA(mRNA).

As a result, siRNA-based therapies have emerged as potent therapeutic approach to treat human diseases by reducing or inhibiting the abnormal expression of disease-causing genes.

In recent years, several siRNA-based drugs have gained regulatory approval, including Onpattro(Patisiran), Givlaari (Givosiran), Oxlumo (Lumasiran), Leqvio(Inclisiran), Amvuttra (Vutrisiran)‌, and Rivfloza(Nedosiran).

Shift in CNIPA’s examination

China National Intellectual Property Administration (CNIPA) has previously considered common technical means in the art with regard to design of a siRNA, and the examiners required to limit the claims to the exemplified siRNAs in the application.

However, CNIPA has moved its position to acknowledge that there are no recognised design standards and rules for siRNAs, as these vary depend on the target disease.

Experimental data are most important for an application

Experimental data provided in the patent application – particularly in vivo data – plays an important role in assessing the inventiveness of siRNA inventions or the breadth of the claims that can be allowed.

For example, long in vivo stability and inhibitory effects on a target DNA are often regarded as unexpected technical effects, given the known challenges of siRNA, such as low transfection efficiency, poor stability and high degradability in vivo.

Further, comparative experimental data demonstrating superior or unexpected technical effects over prior art siRNAs is generally helpful for the prosecution.

Novelty and inventiveness assessment

The novelty/inventiveness of a siRNA is determined by the primary sequence of its core dsRNA. Generally, if the target gene is newly discovered and links to a specific disease, an siRNA targeting this gene is likely to be considered as novel and inventive, provided the application includes supporting data.

However, if the target gene has been disclosed by prior art, the assessment depends on the siRNA’s sequence and effect:  

• A claimed siRNA comprising the same primary sequence as a prior art siRNA and achieving similar technical effect will be denied as lacking novelty;
• A claimed siRNA with partially overlapping sequence or minor variations (e.g., a few nucleotide changes) may be considered inventive if it achieves significantly superior or unexpected technical effect over the prior art;
• A claimed siRNA targeting the same target gene but at a different position from the prior art siRNA will be considered as inventive only if it achieves superior or unexpected technical effect, or it aims to treat a different indication.

Modifications to improve stability

In order to address the inherent stability of siRNAs in vivo, modifications to both the strands of the dsRNA are generally employed.

CNIPA generally allows such modifications, as long as they do not introduce non-natural amino acids and do not impair the antisense strand’s ability to bind to the target mRNA.

CNIPA may allow a broader scope of modifications if the primary sequence of a claimed siRNA differs substantially from the prior art siRNAs, and there is sufficient data in the description to verify that the modifications, in various combinations, achieve unexpected technical effects. These modifications would be generally required to be specified in the claims if a claimed siRNA is similar in the primary sequence to the prior art siRNA.

While the above trends provide a general framework, it’s important to note that the examination of siRNA inventions is highly case-specific.

If you have any questions or need assistance with an siRNA-related patent application, our team is here to help. Feel free to reach out to discuss how we can support you.