TYSON KO*

Developing a new drug involves extensive costs, typically ranging from hundreds of millions to billions of dollars, and requires considerable time and effort in research and development, about 10 to 15 years on average^{1 2}. Patent protection grants pharmaceutical and biotechnology companies developing new drugs a time period of market exclusivity against competitive threats. Thus, patents are often viewed as the “lifeblood” of pharmaceutical and biotechnology companies^{3 4 5}. In addition to patents directly claiming the active ingredients of new drugs, the following approaches may strengthen patent protection of new drugs in Taiwan.

Secondary Patents

In general, primary patents refer to core patents which directly protect active ingredients, and secondary patents refer to peripheral patents which protect subject-matters other than but related to active ingredients. For example, secondary patents may be derived from improved forms (e.g., salts, esters, hydrates, solvates, polymorphs, prodrugs, and metabolites), improved formulae (e.g., formulations, compositions, and kits), manufacturing processes (e.g., high-yield or high-purity synthesis schemes), and medical uses (e.g., treatments for specific diseases or regimens for specific patients).

According to Article 52, Paragraph 3 of the Patent Act, the term of an invention patent shall expire after a period of twenty years from the filing date of the application. Since applications for secondary patents are normally filed after applications for primary patents, secondary patents may retain a certain degree of market exclusivity after the expiration of the primary patent.

Compared with the claims of primary patents, the claims of secondary patents are usually subject to more limitations (e.g., definitions by specific forms, constituents in formulations, and particular uses) and have narrower scopes. Accordingly, multiple secondary patents are beneficial to expand the coverage of patent protection and thereby prevent competitors from easily avoiding patent infringement by designing around the claimed scopes.

Notably, if an active ingredient of a primary patent has been disclosed prior to the filing of applications for secondary patents, the inventions in the applications for secondary patents may be vulnerable to challenges, particularly inventiveness objections. Specifically, based on the Patent Examination Guidelines, for inventions regarding derivative forms of a known chemical entity (such as structurally similar compounds, enantiomers, hydrates, polymorphs, and the like), if a person ordinarily skilled in the art would be motivated to prepare or isolate the derivative forms through conventional methods, such inventions would be deemed obvious unless the derivative forms exhibit an unexpected effect over the prior art. Further, for a combination invention including two or more known ingredients, should a person ordinarily skilled in the art have a motivation to find an optimal combination of the ingredients or the effects of such combination (e.g., enhancing therapeutic efficacy or reducing side effects) by referring to the prior art, the combination invention does not possess an inventive step.

Patent Term Extension

In order to ensure safety and effectiveness of drugs that can be administered to the human body, Article 39 of the Pharmaceutical Affairs Act stipulates that for the manufacturing and importation of drugs, relevant information shall be filed with the Taiwan Food and Drug Administration (TFDA) for registration and marketing approval (MA), and no manufacturing or importation of a drug shall be allowed until an MA of the drug is approved and issued. Accordingly, a drug patent cannot be exploited before the collection of a corresponding MA. Since it often takes a considerable period of time from the grant of a drug patent to the collection of the MA, patent term extension (PTE) is a form of compensation for the aforesaid period of time.

For PTE, Article 53 of the Patent Act stipulates that where a regulatory approval shall be obtained in accordance with other laws and regulations for the exploitation of an invention patent involving a pharmaceutical or agrichemical, or the manufacturing process thereof, if such regulatory approval is obtained after the publication of the concerned invention patent, the patentee may apply for one and only one extension of the patent term of said invention patent on the basis of the first regulatory approval. The said regulatory approval is allowed to be used only once for seeking PTE. A request for PTE must be submitted within three months after the collection date of the first regulatory approval, and no request for PTE shall be filed within six months prior to the expiration of the original patent term.

Moreover, according to the Patent Examination Guidelines, whether an MA is the “first marketing approval” for PTE is determined on the basis of the active ingredients and uses indicated in the MA. In principle, different MAs for (a) different chemical entities (including different salts/esters/hydrates of the same chemical moiety) or (b) different medical uses of the same chemical entity can all serve as a first MA for PTE applications. Where PTE is requested for a pharmaceutical patent, at least one claim of the patent should cover or correspond to the active ingredient indicated in the first MA. For instance, if the active ingredient indicated in an MA is a salt of a compound while the salt is not covered by the claims of the patent, the MA cannot serve as the first MA for PTE.

Regarding calculation of the time period of PTE, according to Article 4 of the Regulations Governing the Determination of Patent Term Extension, the following time periods, after the publication of the granted patent, can be included in the PTE calculation: (i) the periods of domestic and foreign clinical trials (including bridging studies) for obtaining the first MA; and (ii) the examination period for obtaining the domestic MA. The upper limit of PTE is five years. If the calculated period exceeds five years, PTE that can be granted shall still be restricted to five years.

Additionally, for one patent, only one PTE is available even if the patent covers different pharmaceutical inventions and two or more MAs therefor are secured. Thus, if the subject-matters of the claims of a patent application involve two or more different active ingredients or different medical uses of the same active ingredient, it is suggested to file one or more divisional applications from the patent application to separately claim the subject-matters so that two or more PTE applications for different patents based on different first MAs are feasible.

Furthermore, according to Article 56 of the Patent Act, for a patent of which PTE has been granted, the scope of the patent during the period of PTE shall be limited to only the “active ingredient” and “indication (use)” recorded in the MA on which PTE is based. Hence, as long as the active ingredient and indication recorded in the MA are covered by at least one claim of the patent, the scopes or quantities of the claims to which PTE is applicable do not substantially influence the scope of the patent during the period of PTE.

Patent Linkage System

The patent linkage system in Taiwan has been implemented since August 20, 2019 and contributes to early settlement of disputes on patent invalidity and infringement between brand drug companies and generic (or biosimilar) drug companies.

According to the regulations for the patent linkage system, if the holder of an MA for a new drug (including new small-molecule drugs and new biologics) deems it necessary to submit the information of patents regarding the new drug, the holder shall submit patent information to the patent linkage system within 45 days from the day after collection of the MA (in the case that the collection of the MA is later than the publication of the relevant patents) or within 45 days from the day after publication of the relevant patents (in the case that the collection of the MA is earlier than the publication of the relevant patents).

The invention scope of drug patents for patent linkage registration includes: (i) substances (active ingredients, including polymorphic compounds); (ii) compositions or formulations comprising active ingredients; and (iii) medical uses (which shall be in accordance with all or part of the indications recorded in the MA). Moreover, the manufacturing processes, intermediates, metabolites or packages of medicaments are not eligible inventions for the patent linkage system.

When filing an abbreviated new drug application (ANDA) for a generic drug by referring to the data of a new drug, the ANDA applicant shall make one of the following certifications:

1. No patent information of the new drug has been listed.
2. The patent listed for the new drug has extinguished.
3. The TFDA will issue the MA of the generic drug after the patent listed for the new drug extinguishes.
4. The patent(s) listed for the new drugs shall be revoked, or the patents corresponding to said new drugs will not be infringed by the generic drug subject to the ANDA. (P4 Certification)

When an ANDA applicant makes a P4 Certification with respect to patent(s) listed for the new drug, the patentee or the exclusive licensee of the patent(s) may, upon receipt of the notification of said certification, file a patent litigation against the ANDA applicant to prevent patent infringement. Once the patentee or the exclusive licensee files a patent litigation against the ANDA applicant, the TFDA may stay the issuance of the MA for the ANDA application for a maximum of 12 months. In addition, if the patentee or the exclusive licensee obtains a final and binding judgment confirming the infringement within the time period of the stay of MA issuance for the generic drug, the TFDA will delay the MA issuance for the ANDA application until the extinguishment of the patent(s) listed. Therefore, patent protection directed to a new drug substance, pharmaceutical compositions/formulations and medical uses thereof can be solidified through the Patent Linkage System.

However, it should be noted that if valid patents listed under the MA of a new drug are directed to medical uses only and the ANDA applicant carves out the indications corresponding to the medical uses when filing the ANDA for the generic drug, the provisions related to the stay of MA issuance for the generic drug will not be applicable.

Conclusions

Properly employing secondary patents in combination with the application for patent term extension and/or the patent linkage registration can strengthen patent protection of new drugs, and taking into account some of these considerations may help build a comprehensive patent portfolio. Pharmaceutical and biotechnology companies that strategically maintain and strengthen patent protection can extend the life-cycle of products and recoup investments in drug development.