In a recent decision, the Patent Court held that the novelty and inventiveness of a medicinal use invention may not be negated solely by the publication of a clinical trial protocol disclosing the medicinal use of the invention (Patent Court Case No. 2019 Heo 4147 dated February 7, 2020; final and conclusive). 

▶Background of the Case

A. Subject Invention

Korean Patent Application No. 2014-7009738 relates to a pharmaceutical composition for neoadjuvant therapy use (i.e., systemic therapy given prior to surgery) in patients with early HER2-positive breast cancer, comprising four (4) known antitumor agents of Pertuzumab, Trastuzumab, Docetaxel and Carboplatin. 

B. Prior Art Reference and Clinical Trial

The prior art reference is a protocol for a phase 2 clinical trial of the use of Pertuzumab in combination with Trastuzumab and chemotherapy medication such as Docetaxel and Carboplatin, published on the website of the U.S. Food and Drug Administration, which provides a database for clinical studies. The prior art reference describes the purpose of the study as assessing the tolerability, safety and efficacy of neoadjuvant treatment regimens in patients with early HER2-positive breast cancer. 

Generally, a phase 1 clinical trial evaluates the safety of a drug by administering the drug to a small group of healthy people based on data obtained from a preclinical animal trial. Further, a phase 2 clinical trial is conducted with a larger treatment group to establish the efficacy and safety of a drug. However, in case of a combination therapy of antitumor agents whose safety and efficacy have already been identified, the results of a phase 2 clinical trial, without any data of a preclinical or a phase 1 clinical trial, can be sufficient as safety and efficacy data for obtaining market approval. For the combination therapy of the subject invention, neither the preclinical trial nor the phase 1 clinical trial was conducted before the phase 2 clinical trial of the prior art reference. 

C. Trial Board Decision 

During the prosecution stage, the subject application was rejected for lack of novelty and inventiveness over the prior art reference. While affirming the Examiner’s final rejection, the Trial Board noted that there was no difference between the subject invention and the prior art reference since both treated the same disease by administering the same composition. The Trial Board stated that the medicinal use disclosed in the prior art reference, i.e., neoadjuvant therapy for the patients with early HER-2 positive breast cancer, was identical to the subject invention, and the effects were nothing but a limitation of intrinsic properties of the pharmaceutical composition. 

▶The Patent Court Decision

On appeal, however, the Patent Court overturned the Trial Board’s decision.

The Patent Court found that the description of the prior art reference merely indicated plans to assess the safety and efficacy of neoadjuvant therapy using the four drugs in patients with early HER2-positive breast cancer and to identify, in the future, whether the medicinal use effects existed; and thus failed to specifically disclose the pharmacological effects related to the medicinal use to the extent that a person skilled in the art could objectively confirm such effects. Based on the above reasoning, the Patent Court determined that the prior art reference failed to defeat the novelty of the subject invention. 

With regard to inventiveness, the Patent Court noted that a person skilled in the art could not have easily expected the remarkable pharmacological effects of the subject invention from the prior art reference, for the reasons that:  (i) the prior art reference did not disclose pharmacological effects confirmed from the clinical trial and no experiments were conducted before the clinical trial of the prior art reference in order to identify the effects of the subject invention, (ii) a person skilled in the art could not have easily predicted whether the combined administration of four antitumor agents showed synergistic pharmacological effects as compared to the single administration thereof, although each agent was already known to have antitumor effects in the art, (iii) the subject invention was recognized to achieve remarkable effects over other combination therapies based on its specification.

Accordingly, the Patent Court concluded that the subject invention was novel and inventive over the prior art reference, which merely mentioned the medicinal use of the invention without providing concrete pharmacological effects, and revoked the Trial Board’s decision. 

The Patent Court decision was not appealed to the Supreme Court; thus became final and irrevocable.

▶Significance of the Decision

The above decision clarifies that, even though the medicinal use of an invention is disclosed in a prior art reference such as a clinical trial protocol, a medicinal use invention meets the novelty and inventiveness requirements as long as the pharmacological effects to confirm the medicinal use are not specifically disclosed in the prior art reference.