June, 2018｜News Letter

1. Stronger Arguments that There is No Reasonable Basis (i.e., No Motivation) for One Skilled in the Art to Apply Common Technical Knowledge to Method Disclosed in Primary Reference, are Needed

Novo Nordisk Healthcare A.G. v. Laboratoire Francais Du Fractionnement Et Des Biotechnologies, Case No. 2017 (Gyo-Ke) 10061 (Decision rendered on June 7, 2018)

The Patentee, Novo Nordisk Healthcare (NNH), obtained a patent relating to a method for removing viruses from a liquid Factor VII composition in 2011. Against the NNH’s patent, Laboratoire Francais Du Fractionnement Et Des Biotechnologies (LFFB) filed an invalidation trial with the JPO in 2015. During the trial proceedings, NNH demanded a correction of claims. The JPO admitted the correction, but rendered a decision of invalidation on the grounds of lacking inventive step and not satisfying the enablement requirement in 2016. NNH filed an appeal against the JPO's decision to the IPHC in 2017.

The corrected Claim 1 of the NNH’s patent at issue claims as follows:
1. A method for removing viruses from a liquid Factor VII composition, said composition comprising one or more Factor VII polypeptides,
wherein at least 50% of the one or more Factor VII polypeptides is in an activated form; and
wherein the concentration of the Factor VII polypeptides in the liquid composition is in the range of 0.01 to 5 mg/ml;
said method comprising the following steps (a) and (b) in an arbitrary order:
(a) inactivating viruses by a method comprising the step of combining said composition with a detergent, and
(b) subjecting a solution of said liquid Factor VII composition to nanofiltration using a nanofilter having a pore size of at the most 80 nm.

Corrected claims 2 to 17 depend from claim 1.

The IPHC only made a decision on inventive step, and denied the inventiveness of the corrected claims 1 and 2.

One of the main issues in this case related to whether those skilled in the art would have had a motivation to combine Exhibit 1 and several exhibits (in particular, Exhibits 3 and 13) that LFFB provided. The IPHC answered to the issue as follows:

The differences between what is claimed in corrected claim 1 (hereinafter referred to as "Corrected Invention 1") and what is disclosed in Exhibit 1 are:
i) Corrected Invention 1 comprises both steps (a) and (b) in an arbitrary order whereas Exhibit 1 explicitly does not disclose that the method comprises the both steps;
ii) Corrected Invention 1 recites that "at least 50% of the one or more Factor VII polypeptides is in an activated form" whereas Exhibit 1 does not have such recitation.
iii) Corrected Invention recites that the concentration of the Factor VII polypeptides for removing the viruses is "in the range of 0.01 to 5 mg/ml" whereas Exhibit 1 does not disclose the range of the concentration; and
iv) Corrected Invention 1 recites that the viruses are removed by conducting "nanofiltration using a nanofilter having a pore size of at the most 80 nm" whereas Exhibit 1 does not have such recitation on a nanofilter to be used in the nanofiltration.

Regarding Difference i), Exhibit 1 recommends incorporating two different steps for inactivation and removal of the viruses into the process of the plasma product. As of the priority date, as disclosed in Exhibit 3, nanofiltration of Factor VII composition was performed. Furthermore, as disclosed in Exhibits 4, 20 and 21, nanofiltration was commonly conducted to remove viruses while preserving the integrity of a wide variety of proteins. Therefore, one skilled in the art, when conducting the method disclosed in Exhibit 1, would have been motivated to perform both steps (a) and (b).

Regarding Difference ii), considering that the product comprises Factor VIIa, i.e., active Factor VII (cf. Exhibits 1 and 2), it was a well-known technical challenge to provide a composition comprising Factor VIIa at a higher concentration. Exhibit 5, for example, teaches that Factor VII composition with an activation rate of 50% or more can be provided through isolation steps. Exhibit 13 teaches that about 50% of single-stranded Factor VII is transformed to double-stranded Factor VII (i.e., active Factor VII) in about 43 minutes. Nanofiltration was commonly conducted to remove viruses while preserving the integrity of a wide variety of proteins. Therefore, those skilled in the art would have easily subjected a solution of the liquid Factor VII composition in which "at least 50% of the one or more Factor VII polypeptides is in an activated form" to nanofiltration.

Regarding Difference iii), according to Exhibit 3, the yield of Factor VII from 22 liters of Factor VII fraction nanofiltrated for removal of viruses is about 4.5 g, which is about 0.20 mg/ml of Factor VII. The concentration of Factor VII before nanofiltration is presumably near 0.20 mg/ml, which falls into "the range of 0.01 to 5 mg/ml". Thus, those skilled in the art would have easily produced a liquid Factor VII composition "wherein the concentration of the Factor VII polypeptides in the liquid composition is in the range of 0.01 to 5 mg/ml".

Regarding Difference iv), Exhibit 3 teaches that nanofilter named BMM-15 for removal of viruses was used, and that the pore size of BMM-15 is 15 nm. Exhibit 4 teaches that nanofiltration is a "manufacturing step that consists in filtering protein solution through membranes of a very small pore size (typically 15–40 nm)" and "a robust and reliable viral reduction technique that can be applied to essentially all plasma products". Thus, those skilled in the art, conducting the method disclosed in Exhibit 1, would have easily used a nanofilter having a pore size of at the most 80 nm, as disclosed in Exhibit 3 or 4.

The Patentee, NNH, argued that the common technical knowledge as of the filing date teaches away from the nanofiltration of Factor VIIa due to the possibility for degradation of the molecule. The Patentee's argument is not persuasive. Commonly-used nanofilters have a pore size through which Factor VII, which is larger protein than Factor VII/VIIa, can pass, and it presumably does not take a long time before Factor VIIa is greatly degraded.

Conclusively, the IPHC dismissed the Patentee, NNH's appeal, and upheld the JPO’s decision.

An appeal to the Supreme Court was NOT filed against this decision, and thus the decision is final and binding.

K&P’s Comments This decision follows the Examination Guidelines and legal precedents. All the differences between the claimed method and the disclosure of Exhibit 1 are disclosed in other Exhibits or belong to common technical knowledge. In such cases, stronger arguments that there is no reasonable basis (i.e., no motivation) for one skilled in the art to apply the common technical knowledge to the method disclosed in primary reference, are needed.

(by Naomi YOSHIDA, Patent Attorney)

In June 2018, the IPHC handed down 9 decisions including the above case on patent, and overturned the previous decision in1 case.

In June 2018, the IPHC handed down 6 decisions on trademark, and overturned the previous decision in 1 case.

In June 2018, the IPHC handed down 2 decisions on industrial design, both of which maintained the previous decisions.