Sorafenib Tosylate: Germany

With effect in Germany, European patent EP2305255B1 was provisionally found invalid to the extent of patent claim 12. It's about a cancer medicine with a patent claim on the active ingredient Sorafenib Tosylate, which is a salt of Sorfenib for oral administration.

Nexavar® is the brand name for the cancer medicine whose patent was challenged in the Federal Patent Court (BPatG). It's approved for the treatment of inoperable hepatocellular carcinoma and advanced renal cell carcinoma. The active substance Sorafenib Tosylate is covered by European patent EP2305255B1. Here below is claims summary of EP2305255B1.

• Claim 1: Method of Use Claim
• Claim 2 to 11: These are Dependent claims which are Directly or indirectly have dependency on Claim 1
• Claim 12: Claim to the active substance Sorafenib Tosylate (as a single agent)

The BPatG concluded on the invalidity action against this substance claim 12 in September 2021 (3 Ni 12/20 (EP) plus 3 Ni 13/21 (EP)). The provision of the Tosylate Salt of the active component Sorafenib, according to the applicant, could not be considered an independent innovation. The solubility of the active ingredient or its salt was not addressed, and the active substance sorafenib's bioavailability could not be regarded an issue.

The plaintiff mostly used NiK2 (J.F. LYONS et al., Endocrine-Related Cancer 2001, 8, 219-225) as a counter-argument. This was due to the fact that Sorafenib free base had already been proven to be an orally accessible efficient Raf kinase inhibitor with high action against a variety of human tumour types.

Point to Ponder: The BPatG's determination of whether providing the active ingredient as the salt Sorafenib Tosylate was a “inventive step” was therefore important to the current case.

• The BPatG did not see any inventive step in the provision of the active substance as a salt in the present case. However, the court’s comments are interesting with regard to the patentability of pharmacological salts.
• The Federal Patent Court explained that Sorafenib showed poor solubility according to counterpart NiK2. And in principle, the search for an improved therapy and also for an improved oral form of a medicine can justify a patent claim. But NiK2 also proves a good gastrointestinal permeability of the active substance Sorafenib, so that a good efficacy is given with oral administration of the active substance despite poor solubility.
• But even if the active ingredient did not have good efficacy, salt formation would have been a common and, according to NiK11 (R. J. Bastin, Organic Process Research & Development 2000, 4, 427-435), even the preferred way to improve the solubility of a poorly soluble active ingredient, the German Federal patent court explained. The skilled person would also not disregard the Tosylate salt because no active ingredient formulated as a Tosylate salt and to be administered orally had been approved up to the priority date.
• According to the court, the physico-chemical analysis of an active substance was part of the pharmacologist’s daily routine in the preformulation phase. And there was no prejudice or reservation against the use of Tosylate salts in professional circles.
• Effort of Salt Screening: The BPatG also commented on the costs of salt screening. According to the BPatG, the time and financial effort of a salt screening played a subordinate role in the assessment of inventive step. In this context, the court also referred to the BGH decision Dreinahtschlauchfolienbeutel (BGH GRUR 2010), according to which evidence such as the time and financial expenditure in an individual case can at most give rise to an examination as to whether they provide sufficient indications (against the background of general technical knowledge) that the subject-matter of the dispute is obvious and do not only contain a suggestion leading to the invention from an ex-post point of view.

In view of the foregoing, the court held that the person skilled in the art arrived at Sorafenib Tosylate as a suitable oral form of administration of the active ingredient Sorafenib in an obvious manner based on NiK2 and in combination with his expertise (documented, inter alia, by NiK5 or NIB5, NiK11 and NIB15).

Therefore, the provision of the active ingredient as a salt and thus patent claim 12 from the present case is not to be regarded as an inventive step. European patent EP2305255B1 was therefore declared invalid for the time being to the extent of patent claim 12 with effect for Germany.

In anyway, the decision is not final because the parties to the appeal proceedings have the right to appeal it.