Biogen, Inc., Plaintiff-Cross v. Berlex Laboratories, Inc., and Schering Ag
Docket: 01-1058
Court: Court of Appeals for the Federal Circuit; January 30, 2003; Federal Appellate Court
Biogen, Inc. brought a declaratory action against Berlex Laboratories regarding the non-infringement of U.S. Patents No. 5,376,567 and No. 5,795,779, which pertain to recombinant DNA technology for producing human interferon. The U.S. Court of Appeals for the Federal Circuit upheld the District Court's summary judgment in favor of Biogen, while Biogen cross-appealed on patent validity.
The patents in question, attributed to inventors from Cetus Corporation and Stanford University, involve the method of using Chinese hamster ovary (CHO) cells to produce human interferon through linked co-transformation. This method requires the use of a single DNA construct that contains both a selectable marker gene and the human interferon gene. The court noted that successful transformation of CHO cells is rare and that detecting transformed cells is crucial for obtaining pure protein products.
Biogen’s method utilizes unlinked co-transformation, where the interferon and DHFR marker genes are introduced into host cells via separate constructs. Berlex contended that its claims would cover this method when properly construed and argued that the doctrine of equivalents applies to the construct claims. The court's decision focused on the interpretation of the claims and the legal definitions surrounding the processes described in the patents.
The court conducts a plenary review of patent claim interpretations and grants summary judgment based on this review, as established in Cybor Corp. v. FAS Technologies. Claim construction occurs de novo on appeal. Claims 42, 66, 68, and 70 of the '567 patent are highlighted, with Berlex arguing that these claims do not necessitate a single DNA construct containing both the human interferon gene and a marker gene. Claim 70 specifically references the dihydrofolate reductase marker gene, but none of the claims explicitly require the use of a single construct.
The district court determined that the '567 patent specification only discusses a method involving a single DNA construct that integrates both the interferon and marker genes, thus limiting all claims. Berlex contends that the single construct is merely a preferred embodiment and that the claims should not be confined to it. Berlex asserts that the patent encompasses a broader discovery related to using Chinese hamster ovary cells for human interferon production, independent of whether a single or multiple constructs are used.
Biogen counters that Berlex’s broader interpretation lacks support in the specification and would render the claims invalid due to inadequate written description if accepted. Biogen also notes that the patent examiner did not recognize the claims as having the breadth Berlex now claims. Both parties cite the specification and prosecution history along with expert testimonies to bolster their positions on how a person skilled in the art would interpret the patent documentation.
Berlex argues for a broad interpretation of its claims based on several statements from the specification, emphasizing that the invention pertains to human interferons produced in Chinese hamster ovary (CHO) cells without specifying a requirement for a single construct or linked genes. Key points include a description of methods for introducing DNA fragments into CHO cells, highlighting the flexibility of approaches and asserting that the invention encompasses any methods for DNA introduction and cell selection. Berlex contends that existing knowledge in the field indicated that selectable markers are not typically employed in viral transformation, thus supporting their claim that the invention is not confined to a single DNA construct.
In contrast, Biogen asserts that the specification predominantly focuses on a specific method involving a single DNA construct that integrates linked genes for interferon and a selectable marker into CHO cells. Biogen references the Summary of the Invention and the Abstract, which detail a DNA construct designed for the expression of human interferon in CHO cells, clearly outlining the operable linkage of a cloning vector sequence, an expression gene, and the human interferon gene.
The Description of the Preferred Embodiments outlines a method for expressing heterologous genes in Chinese hamster ovary (CHO) cells, involving the preparation of DNA constructs linked to a prokaryotic replication sequence, a marker gene, and a human interferon (IFN) gene. These constructs are introduced into CHO cells, but the specification primarily details linked DNA sequences and transformation procedures with single constructs for transfecting CHO cells. Although viral vectors are mentioned, the document stresses that referencing general techniques does not confirm their applicability to specific biological processes. It is noted that previous studies did not resolve technical challenges associated with introducing DNA into animal tissue culture cells or producing host IFN.
Berlex acknowledges that the specification demonstrates only co-transformation with a linked construct but argues that the prosecution history indicates a broader scope for the invention, namely the use of CHO cells for recombinant human interferon production, regardless of the construct. This interpretation was rejected by the district court and not supported by the prosecution record, which shows that the claims were amended to focus on a single construct of linked interferon and marker genes during the prosecution of the '567 patent, which stemmed from a divisional application of the parent '843 patent. The '843 claims explicitly included a single construct, while subsequent claims added by Berlex attempted to correct an oversight regarding unnecessary prokaryotic sequences.
A terminal disclaimer was filed to align the expiration of the '567 claims with the '843 patent, but the examiner raised an obviousness-type double-patenting rejection, stating that the '567 claims were not patentably distinct from the '843 claims and merely reformulated the claims using functional language, effectively limiting them to the original vector construct described in the prior patent. Thus, the DNA construct remains unchanged in description, regardless of whether it is defined by its physical elements or functional language.
On October 5, 1992, Berlex corrected a terminal disclaimer flaw, leading to the allowance of DNA construct claims while other claims related to "muteins" were rejected due to prior art. Following an interview, the applicant removed references to muteins, amended the allowed claims to include the dihydrofolate reductase (dhfr) marker gene, and revised method and cell claims to incorporate the single linked DNA construct. The amendments were described as "clarifying," with the applicant asserting that no adverse prior art existed and that further searching was unnecessary. The applicant also clarified the parent '843 record concerning linked co-transformation, acknowledging an earlier misinterpretation of a reference to Axel et al.
The relevance of the current application record supersedes that of the ancestor prosecution, regardless of whether Axel et al. employed unlinked co-transformed genes. The patentability of the claims is justified by the non-obviousness of expressing human interferon in CHO cells, independent of nucleic acid construct configurations. In subsequent remarks, the applicant indicated that the scope of the amendments aligned with previously allowed subject matter.
A telephonic interview on November 14, 1994, followed by a Notice of Allowability on November 16, confirmed that the claims related to a DNA construct comprising a vector, an interferon gene, and a dhfr marker gene expressed in CHO cells were allowable due to a terminal disclaimer filed over the '843 claims. Although the applicant contended that the current claims did not rely on specific nucleic acid configurations, the examiner's rationale for allowance did not acknowledge this.
Berlex's response to the examiner's Reasons for Allowance was omitted from the certified prosecution record due to a PTO error, leading the district court to disregard it. However, the court recognized the document as part of the official record and reviewed it, noting the applicant's claim that both the current application and the '843 patent contained additional aspects not addressed by the examiner, ultimately concluding that double patenting was not applicable.
The examiner approved the claims without differentiating between the construct, cell, and method claims. Berlex contends that during prosecution, it clarified that its cell and method claims broadly encompassed the use of Chinese hamster ovary cells for producing human interferon; however, the district court interpreted the prosecution record as indicating the examiner did not share this view. Berlex claims the district court misinterpreted the record, asserting that the examiner's Reasons for Allowance pertained solely to the construct claims. The prosecution history suggests that the examiner recognized the claims' supportable scope was limited to the linked construct, which was reflected in the Reasons for Allowance and upheld by the district court.
Berlex argues that the district court incorrectly relied on the prosecution of the parent '843 patent, unjustly restricting the '567 claims to the same scope. During the '843 prosecution, the applicant claimed that a single linked construct of interferon/marker DNA distinguished it from the multiple unlinked constructs in the Axel prior art. Berlex later identified a misunderstanding regarding Axel and corrected it in the '567 prosecution. Although the district court acknowledged this correction, it did not interpret it as supporting a broader claim construction for the '567 claims.
While Berlex is correct that arguments from a related application do not automatically apply to different claims, the applicant's realization of the mischaracterization in the '843 prosecution warranted a change aligned with the accurate content of the Axel reference. In the '567 prosecution, the applicant noted that Axel discusses both linked and unlinked genes, arguing that the distinction was irrelevant. However, this correction did not alter the specification's content or its description of the invention as employing a single construct for linked co-transformation. The applicant’s assertions that the '567 claims "fall within the scope of subject matter already allowable over the prior art" significantly undermine Berlex's proposed broad construction.
The district court determined that the single DNA construct was central to the '567 patent claims, refusing to interpret the claims as excluding this limitation. The court held that when the preferred embodiment is detailed in the specification, the claims cannot be interpreted more broadly. It emphasized that the prosecution history should be viewed as an official record, highlighting the objective understanding of terms as recognized by those skilled in the art, rather than the subjective intent of the inventor. The court correctly focused on the specification and claims to resolve any ambiguities, stating that representations made during prosecution cannot expand the content of the specification.
The district court concluded that the invention is defined as using a single DNA construct to introduce specific genes into host cells, limiting both method and cell claims accordingly. Although claims are not confined to the preferred embodiment, they cannot extend beyond what is described in the specification. It affirmed that features explicitly excluded from the specification are outside the claims, even if the claims' language appears broad. Consequently, the district court's interpretation of claims 42, 66, 68, and 70 of the '567 patent was upheld, leading to an affirmation of the summary judgment of no literal infringement.
The district court granted Biogen summary judgment of non-infringement regarding the '567 patent based on prosecution history estoppel. The court determined that during the prosecution of the parent '843 application, the applicant had disclaimed the use of multiple constructs, arguing the benefits of a single construct over the Axel reference. However, in prosecuting the '567 application, Berlex clarified misunderstandings about the Axel reference that were presented during the '843 prosecution, asserting that those points were not pertinent to the patentability of the '567 claims.
Estoppel from arguments made in a related application is context-sensitive and not automatically applied; not every statement made to distinguish prior art creates estoppel. In related applications, applicants can introduce new arguments or correct prior mistakes. Notably, estoppel generally does not apply to different claims in a divisional application. The court noted that the '567 patentee, having argued the advantages of a single linked construct in the '843 prosecution, was not estopped from claiming infringement by a multiple construct under the doctrine of equivalents, as inefficient infringement could still constitute infringement.
The court found that no estoppel arose from the prior arguments distinguishing the Axel reference. However, the district court did not evaluate the facts regarding equivalency, having made a summary decision solely based on estoppel. Subsequently, the en banc decision in Festo, which occurred after the district court's ruling, indicated that Berlex's claim for equivalency was hindered by an absolute bar, which the Supreme Court later vacated, allowing for the reconsideration of Berlex's equivalency arguments by the district court.
The '779 patent, a continuation of the '567 patent, claims a composition involving Chinese hamster ovary (CHO) cells transformed to secrete human beta-interferon at specific concentrations. Claim 1 outlines a CHO cell culture composition consisting of transformed CHO cells and a medium containing the secreted IFN, with specified concentration parameters.
The district court interpreted the '779 patent claims to require that the specified interferon activity of 150,000-600,000 IU/ml is measured at the end of the production process, after "confluence and superinduction." Biogen's composition, which achieves a final concentration exceeding 1,200,000 IU/ml, was found to pass through the claimed range during production. The court ruled this passage through the range irrelevant to infringement, granting Biogen a summary judgment of non-infringement.
Berlex contended that any composition achieving the claimed concentration at any production stage infringes the claim; however, the court rejected this interpretation as inconsistent with the claim language, specification, and prosecution history. The specification indicates that the relevant measurements are taken at the end of production, and the court deemed the claim limitation meaningless unless it referred to the final product's activity.
Berlex also argued that the district court's interpretation made subordinate claims superfluous, violating the doctrine of claim differentiation. Nonetheless, the court maintained that claims limited to expedite prosecution cannot regain broader scope for infringement purposes, aligning with precedents such as Genentech, Inc. v. Wellcome Foundation Ltd.
The court affirmed the district court’s claim construction for both the '567 and '779 patents, upholding the summary judgment of non-infringement for the '567 patent and the '779 patent. However, it vacated the non-infringement ruling of the '567 patent under the doctrine of equivalents, remanding that issue for further consideration. Biogen's conditional cross-appeal was deemed moot and dismissed, with each party bearing its own costs. The decision was affirmed in part, vacated in part, and remanded, with a concurring opinion from Judge Rader expressing agreement but with different reasoning on the '567 patent's doctrine of equivalents.
In 1985, Berlex added a Summary of the Invention section to its original patent application, leading to the '843 patent. Subsequently, Berlex filed a divisional application which resulted in the '567 patent. The focus is on 80 new claims added in a 1992 preliminary amendment and an additional 39 claims added in 1994. Throughout the '567 patent application, the examiner indicated that these new claims were not patentably distinct from those in the '843 patent. The court acknowledges that arguments from the '843 patent prosecution do not automatically apply to different claims in a separate application, but evidence suggests the '567 claims are not distinct from the '843 claims, as both patents cover the same subject matter. The public would not see a difference between the two sets of claims.
To extend the '567 claims under the doctrine of equivalents, one would have to ignore Berlex's statements distinguishing the linked construct of the '843 claims from prior art. Since Berlex relinquished certain constructs during the '843 prosecution, it cannot reclaim them through claims that are not patentably distinct in a related patent. The prosecution history of the '843 patent could influence the '567 claims. Furthermore, claiming broader interpretations of the '567 patent could violate rules against introducing new matter in amended claims, as these claims were added significantly after the initial filing. The district court rightly concluded that the specification does not support interpretations of the new claims that involve multiple constructs. Ultimately, the '843 and '567 patents cannot simultaneously present claims that are "patentably indistinguishable" yet have substantively different scopes. On remand regarding the Supreme Court's Festo factors, the district court should consider the arguments presented during the '843 patent prosecution when evaluating infringement by equivalents.
