Posaconazole – USA

On Sep 29, 2017, District court of New Jersey issued a ruling in Noxafil® case and found Merck’s compound patent valid.

This patent infringement action was brought by Merck against Actavis for filing an Abbreviated New Drug Application (“ANDA”) with the Food & Drug Administration (“FDA”) for approval to engage in the commercial manufacture, use or sale of a generic version of Merck’s Noxafil® (posaconazole) before expiration of U.S. Patent No. 5,661,151.

In this action, a seven-day bench trial was held in July 2017. During trial, Actavis set forth the defense that filing of the ANDA application does not infringe the ’151 patent because the asserted claims 11 and 12 of the ’151 patent are invalid. In particular, Actavis asserted that—(i) claim 11 of the ’151 patent is invalid because it is inherently anticipated by the European Patent Application EP 0 539 938 A1 (“EP ’938”); and (ii) claim 12 is invalid because it is obvious to a person of ordinary skill in the art (“POSA”) in view of the EP ’938 reference.

In contrast, Merck argued that claims 11 and 12 of the ’151 patent are valid because Actavis has not shown by a clear and convincing evidence that the asserted claims are rendered inherently anticipated or inherently obvious in view of the EP ’938 reference. Further, Merck argued that the EP ’938 reference is not a prior art reference under 35 U.S.C. §§ 102(a) and 103(a) because the inventive concepts recited in claims 11 and 12 of the ’151 patent were invented on April 14, 1993, and diligently reduced to practice prior to or soon thereafter. As such, antedating the EP ’938 reference, published on May 5, 1993.

The parties agree that the earliest priority date of the ’151 patent is December 21, 1993.The issues litigated before the Court were whether Merck can antedate the EP ’938 reference by showing that the claimed subject matter of claims 11 and 12 were conceived before the publication date of the EP ’938 reference, and diligently reduced to practice soon thereafter.

On April 14, 1993, Dr. Pramanik configured the chemical structure in his notebook of Metabolite A after reviewing the mass spectra provided by mass spectrometrist Dr. Heimark. In his configuration of the chemical structure (SCH 51048 Metabolite), Dr. Pramanik provided substantial detail and specificity of the SCH 51048 metabolite. That is, Dr. Pramanik drew out—(i) all the components of the azole core, (ii) all the components of the piperazine linker, (iii) all the components of a side chain; and (iv) where the side chain is attached to the piperazine linker.

Dr. Pramanik discussed his findings with Drs. Giri and Saksena the very same day, April 14, 1993. In this meeting, it was determined that there are seven possibilities for the chemical structure, which included two primary alcohols, four secondary alcohols, and one tertiary alcohol. During this meeting on April 14, 1993, Drs. Giri and Saksena (inventors of the ’151 patent) had conceived of the chemical structure or formula of a potential antifungal drug that would result in posaconazole. Moreover, Actavis agrees that the structure of posaconazole was conceived on April 14, 1993.

With respect to actual reduction to practice court determined that the reduction to practice took place on April 14, 1993, when inventors of the ’151 patent discovered the hydroxyl or OH group on the side chain of metabolite A. This hydroxyl group was missing from the parent compound, Compound IIc or SCH 51048. The Court finds that the reduction to practice of posaconazole was envisioned on April 14, 1993, but some further testing and analysis was required on part of Schering’s scientists to determine and confirm which one of the six alcohols had adequate antifungal activity such that it could be commercially used.  Although such further testing and analysis is not a requirement for showing actual reduction to practice. (Scott, 34 F.3d at 1061-62).

After careful review and consideration of the evidence presented at the bench trial, the Court found that Merck has provided that the subject matter recited in claims 11 and 12 of the ’151 patent was conceived on April 14, 1993, which was diligently reduced to practice thereafter. Thereby, rendering the EP ’938 reference not a prior art reference to the ’151 patent. As such, the Court found that claim 11 of the ’151 patent is not invalid under 35 U.S.C. § 102(a); and claim 12 of the ’151 patent is not invalid under 35 U.S.C. § 103(a).