Same player shoot again

Long time no see! I am sure that readers have noticed that PatentMyFrench has been dormant over the past few months. Hopefully, posting can resume in the near future, so as to perhaps tackle the backlog of interesting decisions that have not been commented on – but let’s face it, we are not there yet.

That said, owing to regular contributor and SPC enthusiast Lionel Vial, the blog at least temporarily comes back to life today, for an update on Halozyme’s mishaps with the French patent office. Many thanks Lionel, the floor is yours.

We had a feeling of déjà-vu with this decision of the Paris Cour d’appel, dated January 18, 2022, concerning the rejection by the French patent office (INPI) of Halozyme Inc.’s SPC application No. FR16C0030. This application pertains to a combination of an anti-CD20 monoclonal antibody, Rituximab, and recombinant human hyaluronidase, which is indicated for the treatment of non-Hodgkin lymphoma.

Indeed, last year we discussed the decision of the Paris Cour d’appel to sustain the decision of the INPI to reject Halozyme Inc.’s SPC application No. FR15C0053 pertaining to a combination of an anti-HER2 monoclonal antibody, Trastuzumab, and recombinant human hyaluronidase (here).

Of note, the panel of judges of the Cour d’appel was the same for both decisions.

In the previous case, the Cour d’appel had decided as follows:

[…] it appears from the “summary of the product characteristics” of the MA [marketing authorisation] that the active ingredient of the medicinal product is Trastuzumab, that hyaluronidase is an excipient, and that no other element contained in the MA justifies that hyaluronidase alone, or associated to Trastuzumab, would produce a pharmacological, immunological or metabolic action of its own which is covered by the therapeutic indications of the MA. […]

It follows that, in the combination of Trastuzumab and recombinant human hyaluronidase, forming the subject-matter of the SPC at stake, only Trastuzumab is the active ingredient, while a MA has already been granted for Trastuzumab alone. Therefore the invoked MA is not the first MA for the product pursuant to article 3(d) of the regulation. Accordingly, the director of the INPI rightly decided that the SPC application did not comply with the requirements of the regulation and that it had to be rejected.” (emphasis added).

In the present case, Halozyme repeated the previously raised arguments that the fact that hyaluronidase was coined an excipient in the MA did not mean that it was deprived of a physiological action of its own. In fact, hyaluronidase makes room in the subcutaneous space by degrading hyaluronan, which increases the dispersion and absorption of Rituximab upon its injection.

In addition, in order to show that hyaluronidase has a therapeutic effect of its own, Halozyme also provided two publications reporting the results of experiments carried out in mouse models of pancreatic cancer and breast cancer, one of the two publications – presumably Shuster et al. (2002) Int J Cancer 102:192-7 –  indicating that hyaluronidase may itself have intrinsic anti-cancer activity.

So, did Halozyme prevail this time?

Moving up to the next level.

This is what the Cour d’appel decided:

[…] the CJEU ruled [in case C-210/13 Glaxosmithkline] that “(…) just as an adjuvant does not fall within the definition of ‘active ingredient’ (…), a combination of two substances, namely an active ingredient having therapeutic effects on its own, and an adjuvant which, while enhancing those therapeutic effects, has no therapeutic effect on its own, does not fall within the definition of ‘combination of active ingredients’ within the meaning of that provision”.

In the present case, the court noted that on page 14 of the assessment report […] a paragraph entitled “New excipient: recombinant human hyaluronidase (rHuPH20)” states that “rHuPH20 degrades hyaluronan under physiological conditions and acts as a propagation factor in vivo. Thus, when combined or co-formulated with certain injectable drugs, rHuPH20 facilitates their absorption and dispersion by temporarily clearing a pathway through the connective tissue in the subcutaneous space […]”.

It follows from these elements that recombinant human hyaluronidase is an excipient that allows to increase the therapeutic effects of the active ingredient by facilitating its absorption and dispersion through the connective tissue of the subcutaneous space. This does not allow, contrary to the allegations of Halozyme, to qualify the combination of Rituximab and recombinant human hyaluronidase as being a combination of active ingredients within the meaning of article 1(b) of the Regulation as interpreted by the CJEU.

It follows from all the foregoing that the combination of Rituximab and recombinant human hyaluronidase for which the contested SPC application was filed is not a product within the meaning of Article 1(b) of Regulation (EC) No 469/2009, that Rituximab has already been the subject of two previous marketing authorizations, so that the MA invoked is not the first for this product within the meaning of article 3(d) of the regulation, and that the Director of the INPI therefore rightly decided that the [SPC] application does not meet the conditions set forth by the Regulation, so that the appeal against the decision of the Director of the INPI must be rejected. (emphasis added).

Same result then.

In this regard, it should be noted that the two above-mentioned publications cited by Halozyme to establish that hyaluronidase has a therapeutic effect of its own were not taken into account by the Cour d’appel because they relate to the treatment of cancers other than non-Hodgkin lymphoma. One can therefore wonder what the outcome would have been, if results of experiments establishing that hyaluronidase has a therapeutic effect of its own in an animal model of non-Hodgkin lymphoma had been presented to the court.

CASE REFERENCE: Cour d’appel de Paris, pôle 5 chambre 1, January 18, 2022, Halozyme Inc. v. Directeur Général de l’INPI, RG No. 20/17731.