Abbott Biotechnology Ltd. v. Centocor Ortho Biotech, Inc.
Docket: Civil Action No. 09-40089-FDS
Court: District Court, D. Massachusetts; April 16, 2014; Federal District Court
A patent dispute involves plaintiffs Abbott Biotechnology Ltd. and AbbVie Inc. ("Abbott") claiming that the drug Simponi, produced by defendant Centocor Ortho Biotech, Inc. ("Centocor"), infringes Abbott’s patents when used with methotrexate to treat rheumatoid arthritis. Centocor seeks a declaration of non-infringement and invalidity of Abbott’s patents, citing various grounds, including lack of written description, enablement issues, failure to list an inventor, and prior art references that Abbott allegedly did not reduce to practice diligently. Abbott counters with cross-motions for summary judgment, arguing that certain antibodies and references should not be considered prior art and that its patents are valid.
The patents in question include U.S. Patents No. 7,223,394 and No. 7,541,031, stemming from a parent patent filed in 1996. These patents are related to human antibodies targeting tumor necrosis factor alpha (hTNFa), a protein involved in immune regulation. Overproduction of hTNFa can cause tissue damage in autoimmune diseases. Abbott seeks to develop antibodies that neutralize hTNFa by binding to it, with effectiveness depending on the antibody's affinity for hTNFa, measured by Kd and Koff values that indicate binding strength and duration.
The court's decision will partially grant and partially deny the summary judgment motions.
Researchers have aimed to create antibodies that effectively neutralize human tumor necrosis factor alpha (hTNFa) for treating autoimmune diseases. Initial efforts in the 1980s led to the development of a high-affinity, neutralizing anti-hTNFa antibody from mouse DNA, which proved ineffective for humans due to adverse reactions to non-human antibodies. The introduction of chimeric antibodies (comprising both mouse and human DNA) provided better treatment options, leading to a 2001 patent by Centocor and the Kennedy Institute for treating arthritis using chimeric anti-hTNFa antibodies alongside methotrexate (U.S. Patent No. 6,270,766). In 1999, the FDA approved Centocor’s Remicade, based on chimeric antibodies.
Simultaneously, Abbott was developing antibodies through a collaboration between BASF Bioresearch Corporation and Cambridge Antibody Technology (CAT). In July 1993, CAT scientists isolated a human antibody, 4SE8, which lacked desired properties. By April 1995, they isolated a high-affinity neutralizing anti-hTNFa antibody named D2E7 and considered co-administering it with methotrexate for rheumatoid arthritis treatment. Abbott argues that the concept was obvious and predates D2E7's development, though no scientist claims credit for the idea, and Centocor disputes that it was obvious, suggesting it was derived from discussions with Dr. Weinblatt, who denies introducing the concept.
In 1996, Abbott filed the '382 patent, disclosing fully-human, high-affinity anti-hTNFa antibodies without addressing co-administration with methotrexate. Following this, from April 1995 to February 1997, various patents and publications emerged regarding similar inventions. Abbott filed the '394 and '031 patents on February 10, 1997, as continuations of the '382 patent. The '394 patent, issued in 2007, specifically relates to treating rheumatoid arthritis with human anti-hTNFa antibodies and methotrexate, while the '031 patent, issued in 2009, shares its specification. Both patents claim priority to a 1997 Patent Cooperation Treaty application and assert that the invention date is at least as early as April 14, 1995, coinciding with the D2E7 development. The patents define a genus of human anti-hTNFa antibodies characterized by high affinity and neutralizing capability.
Patents reveal potential methods for creating additional antibodies derived from D2E7, though they do not specify the total number of qualifying antibodies. Abbott developed Humira, approved by the FDA in December 2002 for rheumatoid arthritis treatment, typically administered biweekly with methotrexate or weekly when not combined with it. Centocor also created a fully-human anti-hTNFa antibody, leading to the FDA approval of Simponi in 2009 for moderate to severe rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, administered monthly.
In late 2002, Abbott and Centocor entered a cross-licensing agreement for patents related to anti-hTNFa antibodies. Centocor granted Abbott rights under a 2001 patent for treating arthritis with chimeric antibodies, while Abbott granted Centocor rights under the '382 patent and connected patents covering treatments with human anti-hTNFa antibodies.
Abbott initiated legal action against Centocor in May 2009, leading to arbitration over whether the 2002 agreement implied a license under Abbott's '394 and '031 patents. The arbitrator ruled in June 2010 that the agreement did not cover those patents. Following a Markman hearing in August 2011, the Court clarified that "administering to the subject both an antibody and methotrexate" means administering them in combination.
Both parties moved for summary judgment on various grounds. Centocor's motions included claims of invalidity due to lack of written description, enablement, inventor listing, and prior art issues, alongside a defense against willful infringement. Abbott's motions contested the designation of certain post-invention references as prior art and the validity of claims regarding the 4SE3 antibody and inventor listing.
Centocor's sixth motion aligns with part A of Abbott's motion, while Centocor's third motion pertains to part C of Abbott's motion. Summary judgment serves to evaluate whether a trial is necessary by assessing the evidence beyond the pleadings. It is appropriate when there is no genuine dispute regarding material facts, allowing the movant to claim judgment as a matter of law, as outlined in Federal Rule of Civil Procedure 56(a). A genuine issue necessitates trial if evidence, viewed favorably for the nonmovant, could lead a rational fact finder to favor either party. The court favors the non-moving party in drawing reasonable inferences. The non-moving party must present specific facts demonstrating a genuine issue, rather than relying solely on allegations or denials. Cross motions for summary judgment do not change the Rule 56 standard but require assessing whether either party merits judgment based on undisputed facts.
In the analysis section, the parties seek a declaration regarding the validity of the patents based on Abbott's alleged omission of Dr. Weinblatt as an inventor. Under 35 U.S.C. §§ 102(f) and 116, all joint inventors must be listed for a patent to be valid, and failure to include an actual inventor can invalidate a patent. To qualify as an inventor, a person must significantly contribute to the conception or reduction to practice of the invention, with contributions deemed non-insignificant relative to the entire invention. However, merely consulting with others does not automatically confer co-inventor status. Inventorship is a legal question with a presumption favoring the listed inventors. When challenging inventorship, a patent-holder only needs to provide evidence to counter any claims of invalidity.
A party alleging misjoinder or nonjoinder of inventors must provide clear and convincing evidence to support its claim, as established in Eli Lilly Co. v. Aradigm Corp. Centocor argues that Dr. Weinblatt conceived the idea of co-administering an anti-hTNFa antibody with methotrexate and communicated this idea to the development team. They cite Dr. Weinblatt's testimony where he stated he advised the scientists to develop the drug with methotrexate, highlighting his expertise as a rheumatologist involved in relevant clinical trials. Furthermore, none of the listed inventors claimed the idea originated from them, nor could they recall its source.
In opposition, Abbott asserts that Dr. Weinblatt's input was merely a reiteration of already known concepts, and thus he does not qualify as an inventor. Their expert, Dr. Seigel, noted that the combination of anti-TNF-a antibodies with methotrexate was already established knowledge. Dr. Weinblatt himself acknowledged that he did not believe he was the first to suggest using D2E7 in combination with methotrexate. Records from his visit indicate that the main discussion was about clinical trial design, with a brief mention of co-administration focused on patients partially responding to methotrexate. Despite the potential financial implications of inventorship, Dr. Weinblatt did not claim any ownership. Dr. Salfeld, the lead inventor, explicitly stated that the idea of co-administration did not originate from Dr. Weinblatt. Additionally, Abbott had considered combination treatments before Dr. Weinblatt’s involvement, as indicated in a memorandum discussing their anti-TNF-a antibody project.
The scientists involved in the patent dispute do not recall who originally proposed the idea of co-administration, acknowledging it was a collective notion within the team. Dr. Weinblatt, who was implicated as a potential source of the idea, denies being the originator and states that methotrexate was already a widely accepted treatment for rheumatoid arthritis prior to his involvement. A 1994 memorandum indicates that the team was considering combinations with existing treatments, suggesting prior contemplation of co-administration before Dr. Weinblatt's visit. The inability of the scientists to identify the initial proponent of the idea is seen as reasonable due to the time elapsed and the nature of collaborative discussions. Case law supports the dismissal of validity challenges based on such memory lapses, particularly when the omitted inventor's idea is not uniquely novel or obscure. There is no evidence that the claimed inventor or anyone skilled in the art could have provided an alternative mechanism to realize the invention, and the omitted inventor himself characterized his contribution as obvious. Consequently, Centocor has failed to present clear and convincing evidence of a missing inventor, and Abbott has successfully countered Centocor's claims. As a result, Centocor’s motion for summary judgment is denied, while part C of Abbott's motion for summary judgment is granted.
Additionally, the parties have cross-moved for summary judgment regarding the relevance of eight references from April 14, 1995, to February 10, 1997, to determine if they constitute prior art that could invalidate the patents. According to Section 102 of 35 U.S.C., a patent is invalid if it is anticipated by or obvious in light of prior art, which includes inventions known or used by others or described in publications before the applicant's invention date.
The statute assumes that the filing date of a patent application corresponds to the date of invention, but applicants can prove an earlier invention date by demonstrating either an earlier reduction to practice or an earlier conception followed by diligent efforts to reduce the invention to practice. Conception requires a definite and permanent idea of the complete invention, not merely a general research direction. If an inventor's oral testimony is used to prove conception, it must be corroborated by additional evidence. Diligence must be shown from just before a prior reference to the date of reduction to practice, with continuous activity demonstrating efforts to reduce the invention to practice. However, not every single day requires evidence of activity if overall diligent efforts are established, although mere preparations for commercial practice or fundraising do not count as diligence. The determination of priority, conception, and reduction to practice involves legal questions based on factual findings, and undisputed facts may allow for summary judgment on prior art issues.
Abbott claims to have conceived of the invention by April 14, 1995, when it developed D2E7, and asserts it worked diligently to reduce it to practice until its 1997 filing date. Alternatively, Abbott argues that it documented the invention by March 1996, predating most references. Centocor acknowledges Abbott produced D2E7 by May 1995 but contests that Abbott had a complete conception by March 1996 and questions its diligence in reducing the invention to practice. There exists a genuine dispute regarding the timeline of the inventors' complete conception. Abbott's records indicate it developed a suitable antibody for treating chronic diseases, but statements from 1996 suggest ongoing research rather than a definitive conception.
Dr. Weinblatt's discussions in January 1995 about combination treatment may support the scientists' claims of having conceived the entire invention. Abbott argues that co-administration with methotrexate was obvious, implying that the scientists possessed the complete invention before isolating the antibody. However, mere possession does not equate to recognition of the invention as established in Invitrogen Corp. v. Clontech Labs, Inc. and Burroughs Wellcome Co. The parties dispute the obviousness of co-administration, suggesting that the transition from using the antibody alone to in combination with methotrexate is not so slight as to be legally obvious.
Abbott also claims that the Salfeld Presentation cannot be classified as prior art since it stems from the inventors themselves. Under 35 U.S.C. 102(a), prior art refers to inventions known or described by others, whereas an inventor's work is only prior art if disclosed more than a year before a patent application. Centocor argues that Dr. Weinblatt is an unlisted inventor from the 1996 Salfeld presentation, but the Court has granted summary judgment to Abbott regarding inventorship, negating Centocor's claim. Consequently, the Salfeld presentation is not prior art, and Centocor cannot argue otherwise at trial.
Regarding Abbott's Part B motion, Abbott asserts that the 4SE3 antibody is not prior art under 35 U.S.C. 102(a), (f), and (g)(2), which address prior knowledge, inventorship, and prior invention. Abbott convincingly argues that 4SE3 was not publicly available and that Centocor has not provided material evidence to dispute this. The record indicates that no one other than the inventors had knowledge of the antibody, confirming that it does not qualify as prior art under 102(a). Additionally, 4SE3 is not considered prior art since it was developed by joint inventors rather than another inventor.
A subset of named inventors may independently create an invention prior to a larger group that includes them, which could render the earlier work prior art against the later invention. However, the 1984 patent law amendments expanded the concept of joint inventorship to support collaborative efforts. In the case of Abbott GMBH. Co. KG v. Centocor Ortho Biotech, the scientists’ initial contributions were part of a larger collaborative project that resulted in the patented inventions, similar to the current case, thus reinforcing their status as inventors alongside the larger group. Centocor's arguments do not sufficiently differentiate the current case from Abbott, leading to the granting of part B of Abbott's motion for summary judgment.
Regarding the validity of the patents based on the written description, Section 112 mandates a clear and concise written description of the invention, enabling skilled individuals to make and use it. Centocor claims the patents do not meet this requirement, arguing that a person skilled in the art would not recognize the inventors as having created the claimed genus of antibodies. A patent claim is invalid if the specification does not clearly indicate the inventor's possession of the claimed invention. While the adequacy of a written description is typically a factual question, it can be deemed invalid as a matter of law based on the patent's face. Clear and convincing evidence is required to prove non-compliance with the written-description requirement. The claims in question pertain to a genus of antibodies defined both structurally and functionally. Centocor contends that the structural features lack sufficient commonality and that the limited examples provided do not adequately support the genus claims, particularly since functional claims may risk claiming a result without adequately describing the species that achieve it.
The specification must disclose either a representative number of species or common structural features within a genus to meet the written-description requirement. There are no fixed rules for how many species are needed, as this can vary with each invention and the field's progress. In biological patents, a limited number of species may not suffice due to unpredictability in results among unlisted species. However, not every species in a genus needs to be described to satisfy this requirement, as mandating full disclosure could impose an unreasonable burden on the patentee. Courts generally address failures to meet the written-description requirement as a matter of law, but determining the adequacy of representative species often necessitates a fact-intensive analysis not suitable for summary judgment. Rarely, courts have ruled that insufficient species were disclosed to support a genus claim, particularly if no species were identified at all. Nonetheless, even a single representative embodiment can suffice in some cases. In the context of the patents reviewed, Abbott claims that D2E7, as a representative member, shares structural and functional similarities with others in the genus, which comprises human antibodies with specified structural features. Centocor argues that Abbott has not demonstrated common structures that effectively distinguish the claimed genus from others, emphasizing variability in antibody lengths and amino acid differences. The existing record reveals unresolved factual issues regarding the adequacy of the written description, including the representativeness of D2E7 and the overall structural similarities within the genus.
Centocor's first motion for summary judgment is denied as the facts do not clearly establish whether the written-description requirement has been met. In the context of enablement under 35 U.S.C. § 112, a patent must instruct skilled individuals on how to make and use the full scope of the claimed invention without undue experimentation. Enablement is assessed as of the patent application's effective filing date, based on legal standards and factual findings. Not all experimentation is deemed "undue," and this determination is nuanced, considering factors such as the quantity of experimentation needed, guidance provided, presence of working examples, the nature of the invention, prior art, and the skills of those in the field. Centocor argues that the patents do not enable the full scope of the claimed invention, claiming that significant testing is required to identify other antibodies in the genus, suggesting that this constitutes undue experimentation. Abbott counters that the required testing is routine and that the specification offers sufficient guidance. The court identifies genuine disputes over the extent of direction provided by the patents, the routine nature of experimentation, and the predictability of the art, which preclude summary judgment. Thus, it views the evidence favorably for Abbott, concluding that Centocor has not demonstrated any lack of genuine disputes over material facts.
The Federal Circuit upheld a district court's ruling on nonenablement due to undue experimentation regarding patents for treating or preventing restenosis in mammals using rapamycin. The court noted that the specification provided only a starting point for further research in a complex field, indicating that a skilled individual would need to test numerous candidates without guidance on effective substitutions. Consequently, summary judgment on enablement was denied due to unknown factors that could differentiate this case from others.
Centocor additionally argued that certain patent claims failed the enablement requirement under § 112 because they included non-recombinant antibodies, which the specification and prior art did not enable. Specifically, they contested claims related to an "isolated human antibody" that lacked limitations distinguishing between recombinant and non-recombinant methods, while dependent claims specified recombinant methods. Centocor asserted that the lack of enabling methods for non-recombinant antibodies meant the patents did not cover the full scope of the invention.
In response, Abbott argued that enabling one method suffices, and since the patent includes a method for producing recombinant antibodies, summary judgment was not warranted. Abbott further noted that recombinant and non-recombinant antibodies, despite differing production methods, ultimately share the same structure and function. The doctrine of claim differentiation supports Abbott's position, as dependent claims are presumed to encompass narrower scopes than independent claims, implying that the independent claims may include non-recombinant antibodies.
In the case Liebel-Flarsheim Co. v. Medrad, Inc., the Federal Circuit addressed issues surrounding patent enablement and willful infringement. It clarified that even if the challenged claims might be broader than the unchallenged dependent claims—which could include recombinant antibodies—there is no automatic finding of lack of enablement. The terms "recombinant" and "non-recombinant" pertain to the processes rather than the final invention itself, distinguishing this case from ALZA, where the product was not enabled. The court emphasized that enablement requires only that any mode of making and using the invention is sufficiently described, not that every possible implementation be outlined. Centocor’s arguments claiming lack of enablement were deemed insufficient; specifically, the court noted that it is unnecessary for a patent to disclose every method for producing the claimed invention.
Centocor also sought a ruling that any infringement was not willful, arguing Abbott could not show Centocor was objectively reckless due to plausible defenses regarding written-description and enablement. To establish willful infringement, Abbott must demonstrate by clear and convincing evidence both objective recklessness in Centocor's conduct and subjective awareness of the risk of infringing a valid patent. The court highlighted that a ruling of willful infringement permits the awarding of enhanced damages under 35 U.S.C. § 284. Consequently, Centocor's motion for summary judgment on both enablement and willful infringement was denied.
Courts have determined that the objective prong of willfulness is not met when alleged infringers present reasonable defenses against infringement claims, such as challenges related to written description or enablement. Relevant cases include Spine Solutions, Inc. v. Medtronic Sofamor Danek USA, Inc. and DePuy Spine, Inc. v. Medtronic Sofamor Danek, where reasonable reliance on legal counsel's advice is recognized as a valid defense. Some courts have granted summary judgment to find no willful infringement, while others have postponed such determinations until more evidence is available at trial, as demonstrated in cases like Uniloc USA, Inc. v. Microsoft Corp. and Honeywell Int’l Inc. v. Universal Avionics Systems Corp.
Centocor's motion for summary judgment was based on claims of non-infringement due to alleged failures in meeting written-description and enablement requirements, which the Court denied due to existing disputed facts. The reasonableness of these defenses remains to be established. Additionally, when the objective prong involves factual or legal questions, judges retain the authority to assess the reasonableness of defenses, even if fact questions are sent to a jury.
In conclusion, the Court ruled as follows: 1. plaintiffs’ motion regarding prior art references is denied; 2. plaintiffs’ motions regarding the 4SE3 antibody and inventor listings are granted; and 3. defendant’s motions for summary judgment are denied. Abbott Laboratories has since rebranded as AbbVie Inc. Definitions for "IQ" and "Koff" related to antibody-antigen interactions are provided. Methotrexate, originally a chemotherapy drug, is now classified as a disease-modifying anti-rheumatic drug (DMARD).
Methotrexate is recognized as an effective treatment for rheumatoid arthritis, with physicians having the option to prescribe it alone or in combination with an anti-hTNFa antibody drug. The prescribing physician is responsible for determining the dosage and frequency of methotrexate administration. The relevant legal framework, Title 35, U.S.C. 102, has been amended since the start of the litigation, but the earlier version applies for this case. Abbott does not contest the classification of three patents as prior art, which are essential for evaluating the obviousness of the claimed invention: U.S. Patent No. 5,530,101 (Queen et al.), U.S. Patent No. 5,698,195 (Le et al.), and U.S. Patent No. 6,270,766 (Feldman et al.). The presence of a factual dispute regarding conception has led the Court to defer examination of Abbott's diligence in reducing the invention to practice. The Court clarified that the term "isolated human antibody" does not necessitate any specific production method, while "recombinant antibody" is defined as one that is prepared or isolated through recombinant techniques.
