Sunday, October 3, 2010

Yeda Appeals Board Decision Favoring Abbott in TBP-II Interference

Abbott and the Yeda Research and Development Co. have been involved in a patent interference since 1996 over the right to patent TNF-alpha Binding Protein II (TBP-II, also known as TNF receptor 2). This is a therapeutically and commercially relevant protein. ENBREL (etanercept), a biologic drug developed and marketed by Immunex (now Amgen) for the treatment of autoimmune disease, is a fusion protein comprising the Fc component of human immunoglobulin G1 and TBP-II. I don't know what the specific commercial implications of the patent interference are, but clearly the parties view the patent as sufficiently valuable to justify the cost of a prolonged interference contest. A corresponding patent application claiming the genetic sequence encoding TBP-II was the subject of an important 2004 Federal Circuit decision relating to the written description requirement (In re Wallach).

The interference involves a patent issued to Abbott (5,344,915) and Yeda’s US patent application. The inventor on the Yeda application is Wallach (claiming common priority to the application at issue in In re Wallach). The interference was declared by the patent office in 1996, and resulted in a "Final Decision" by the Board of Patent Appeals and Interferences (the Board). In this decision, the Board invalidated Abbott's patent as anticipated by a prior art reference. Abbott claimed priority to two German applications that would have predated the invalidating prior art reference, but the Board denied Abbott the benefit of these two earlier filing dates. The Board essentially held that the German applications did not satisfy the written description requirement of section 112 with respect to the claimed invention.

The German applications disclosed an isolated protein, defined in terms of its approximate molecular weight and an incomplete N-terminal sequence. The applications also disclosed the source of the protein (the urine of patients with fever) and the method used to purify the protein. Abbott's US patent claims the protein as a "purified and isolated TNF-alpha binding protein which has a molecular weight of about 42,000 daltons and has at the end terminus the amino acid sequence [the specific amino acid sequence of the N-terminus of TBP-II]” The critical difference between the patent claims and the disclosure in the German applications is the N-terminal amino acid sequence. In the German applications, there was some uncertainty about the exact N-terminal sequence, and some amino acids in the sequence were not disclosed. These ambiguities were addressed and resolved in the subsequent filed US patent.

The Board’s decision was based on its determination that the earlier incomplete disclosure failed to adequately describe the more complete amino acid sequence provided in the ultimately issued claims. Abbott argued that the proteins described in the US patent claims and the German applications are the same, as demonstrated by the fact that they have the same molecular weight, bind specifically to TNF-alpha, are isolated from the same source (urine from patients with fever), and isolated and purified using the same methods. In essence, Abbott argued that the German applications inherently disclosed the later claimed protein. However, the Board rejected this argument, finding that the record failed to establish to the necessary degree of certainty that TBP-II was inherently disclosed in the German applications, and noting that "inherency may not be established by probabilities or possibilities."

Abbott appealed the Board decision under 35 USC 146 to the District Court for the District of Columbia. In 2008 the District Court granted Abbott's motion for summary judgment, vacated the Board's final decision and remanded to the Board for further proceedings. The District Court was obliged to review the Board's decision under the "clearly erroneous" standard, but even under this deferential standard of review the court reversed the Board, holding that the German applications inherently disclosed the later claimed protein to a degree of certainty sufficient to satisfy the written description requirement. The court rejected alleged ambiguities raised by Yeda (and accepted by the Board) with respect to the identity of the protein disclosed in the German applications.

Yeda appealed the district court decision to the Federal Circuit, but in 2009 the court dismissed the appeal, holding that they did not have jurisdiction to hear the case prior to a final decision in the interference.

On remand, the Board granted Abbott priority benefit of the German applications, and in May 2010 awarded judgment in the interference to Abbott.

On September 9, 2010, Yeda filed its appeal under 35 USC 146, again in the District of Columbia, challenging the Board's decision. It seems likely the case will continue on for at least several more years, since the District Court's decision will begin be subject to appeal to the Federal Circuit (which should have jurisdiction to hear the case since a final decision will have been rendered in interference).

It interesting to compare this case with Goeddel v. Sugano, a September 7 Federal Circuit decision regarding a patent interference over mature human fibroblast interferon (beta interferon). At issue were claims directed to the mature form of the protein, and the DNA encoding the mature form of the protein.

The mature form of fibroblast interferon is produced by cleaving a 21 amino acid presequence from the N-terminal of precursor fibroblast interferon. Sugano attempted to claim priority to a Japanese application that disclosed the full length precursor protein, and also disclosed the N-terminal sequence of the mature protein. Based on this disclosure, clearly anyone that knows anything about molecular biology would know the sequence of the mature protein - it is simply the portion of the disclosed precursor protein sequence that begins with the N-terminal sequence of mature protein.

However, whoever drafted Sugano’s Japanese patent application (filed more than 30 years ago) apparently did not see the need to point out the obvious, and thus there is no explicit disclosure in the application specifically pointing out the sequence of the mature protein. Because the Japanese application failed to connect the dots, the Federal Circuit held that the Japanese patent application did not satisfy the requirements of section 112 first paragraph (enablement and/or written description), and as a result awarded priority to Goedell.

It seems to me a good argument could be made that the Sugano Japanese application inherently but unambiguously disclosed the sequence of the mature protein. This strict application of the written description requirement is arguably inconsistent with the relatively lenient standard applied by the District Court in reversing the first Board decision in the interference involving Abbott and Yeda.

I say arguably, because even though both interferences involve claims directed to proteins, the facts are quite distinct. In Yeda v. Abbott, the court found that the claimed protein was the same protein disclosed in the priority applications, even though the earlier disclosure provided less detail with respect to the amino acid sequence of the protein. In Goeddel v. Sugano, on the other hand, the priority document provided the full amino acid sequence of the later claimed protein, but failed to explicitly point out the distinction between the mature protein and the precursor protein from which it is derived.

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