IP Law Daily, PATENT—D. Mass.: Centocor Ortho may have infringed Abbot’s antibody patents for treatment of rheumatoid arthritis, (Apr 17, 2014)

By Mark Engstrom, J.D.

Abbott Biotechnology could proceed to trial on its patent infringement claims against Centocor Ortho Biotech (now Janssen Biotech), a company that allegedly infringed two Abbott patents that described the use of human antibodies to treat rheumatoid arthritis, the federal district court in Boston has ruled (Abbott Biotechnology Ltd. v. Centocor Ortho Biotech, Inc., April 16, 2014, Saylor IV, F.). The court denied Centocor’s motions for summary judgment of invalidity based on prior art, lack of a written description, lack of enablement, and failure to identify all of the inventors, and it also denied summary judgment based on a lack of willful infringement. In addition, the court denied summary judgment to Abbot to the extent that the company sought a determination that eight references did not constitute invalidating prior art. However, it granted partial summary judgment to Abbott on two other issues: whether the “4SE3” antibody was prior art and whether the asserted patents were invalid for failing to identify a purported inventor.

Background. The patents in suit—U.S. Patent Nos. 7,223,394 and 7,541,031—used human antibodies that were designed to attach to the human protein hTNFα (human tumor necrosis factor alpha) to prevent the over-production of that protein. Because hTNFα produced inflammation in response to pathogens, its over-production could lead to excessive inflammation and tissue damage, a response that occurred in cases of rheumatoid arthritis and other autoimmune diseases.

The court noted that the development of “chimeric” antibodies (antibodies with mouse and human DNA) had furthered the treatment options for autoimmune diseases. In 1999, the FDA approved Remicade—a Centocor drug that was based on chimeric antibodies—for the treatment of rheumatoid arthritis. In 2001 Centocor and the Kennedy Institute obtained a patent that disclosed a method for treating arthritis by administering chimeric anti-hTNFα antibodies in combination with a pre-existing drug called methotrexate.

During the same time period, Abbott sought to develop effective antibodies. In 1993, BASF Bioresearch Corporation (a company that was subsequently acquired by Abbott) and Cambridge Antibody Technology (CAT) were collaborating on the development of antibodies. By July of 1993, three CAT scientists, all of whom were inventors of the patents in suit, succeeded in isolating a human antibody called 4SE3. That antibody did not have the sought-after qualities, however, and it did not fall within the scope of the claims of the patents in suit. By April of 1995, BASF and CAT scientists isolated a high affinity, neutralizing anti-hTNFα antibody called D2E7. BASF engaged in preclinical and clinical testing of that antibody. The patents in suit were issued in 2007 and 2009. Both treated rheumatoid arthritis by administering an anti-hTNFα antibody with methotrexate.

Centocor researchers also developed a fully-human, high-affinity, neutralizing anti-hTNFα antibody that met the functional limitations of the patent in suit. In 2009, Centocor obtained approval from the FDA to manufacture and sell Simponi, a drug that contained the antibody that Centcor had developed. Centocor combined Simponi and methotrexate to treat rheumatoid arthritis.

Licensing agreement. In late 2002, Abbott and Centocor agreed to cross-license a series of patents that were directed to anti-hTNFα antibodies. Centocor extended to Abbott its rights under the 2001 Centocor patent and Abbott extended to Centocor its rights under: (1) the parent patent (No. 6,090,382) of the patents in suit and (2) other patents in that family, including one (No. 6,509,015) that covered a method for treating rheumatoid arthritis and other diseases by co-administering human anti-hTNFα antibodies with a therapeutic agent.

In May of 2009, Abbott sued Centocor for patent infringement. Both Abbott and Centocor sought summary judgment. Centocor argued that Abbot’s claims were invalid based on: (1) prior art; (2) failure to list an inventor; (3) lack of a written description; and (4) lack of enablement. In addition, Centocor argued that it had not willfully infringed the asserted patents. Abbott argued that: (1) eight post-invention references were not prior art; (2) the 4SE3 antibody was not prior art; and (3) the asserted patents were not invalid for failure to list a purported inventor.

Validity based on claimed inventors. The parties filed cross-motions for a declaration that the patents-in-suit were valid (Abbott) or invalid (Centocor) in light of Abbott’s alleged failure to identify a rheumatologist (Dr. Weinblatt) as one of the patents’ inventors. Centocor argued that: (1) Dr. Weinblatt both conceived of the idea of combining the anti-hTNFα antibody and the methotrexate drug into a single administration and (2) communicated that idea to the named inventors. Abbott argued that Dr, Weinblatt did not qualify as an inventor because his contribution to the invention was merely an explanation of known concepts.

According to the court, Centocor could not show that the patents were invalid for failure to identify an inventor. Significantly, Dr. Weinblatt disclaimed being the source of the idea about co-administration. In fact, his testimony that methotrexate was the prevalent, existing treatment for rheumatoid arthritis in the United States, in conjunction with an Abbott memorandum about a “combination treatment of TNF antibodies with current treatments,” supported the opposite inference: that Abbott scientists had considered co-administration prior to Dr. Weinblatt’s visit with Abbott.

Ultimately, Centocor failed to provide clear and convincing evidence that Abbott had omitted an inventor from its patents. Moreover, Abbott offered substantial evidence to rebut each of Centocor’s contentions. According to the court, Centocor did not overcome the presumption of patent validity, and for that reason, Centocor’s motion for summary judgment was denied to the extent that Centocor had argued that the patents in suit were invalid based on Abbott’s failure to identify an inventor. Abbott’s motion for summary judgment on that issue was granted.

Validity based on eight prior art references. The parties filed cross-motions for summary judgment regarding the priority of eight references that fell between the date of the claimed invention (April 14, 1995) and the date of its filing (February 10, 1997).

The court noted that patent law presumed that a patent’s filing date reflected the date of the invention. Nevertheless, an applicant could establish an earlier date, and thereby antedate prior references, by showing either an earlier reduction to practice of the claimed invention or an earlier conception followed by diligence in reducing the invention to practice.

In this case, Abbott argued that: (1) it had conceived of the patented invention by April 14, 1995, “by which point it had created D2E7,” and (2) co-administration with methotrexate to treat rheumatoid arthritis was obvious. Abbott also argued that, up to the 1997 filing date, it had worked diligently to reduce the invention to practice. Alternatively, Abbott argued that it had memorialized the invention by March of 1996, a date that preceded all but one purported reference.

Centocor conceded that Abbott had produced D2E7 by May 1995, but it alleged that: (1) Abbott had not conceived of the whole invention by March of 1996 and (2) Abbott had not been diligent in reducing the invention to practice.

The court concluded that a genuine issue of material fact existed regarding when the inventors had a permanent and settled conception of the entire invention. Abbott’s contemporaneous records, for example, demonstrated that: (1) Abbott had developed an antibody that met the patent claims and (2) its purpose was the treatment of chronic diseases like rheumatoid arthritis.

Nevertheless, an Abbott scientist had stated in the company’s 1996 memorialization that: (1) “[i]t has been proposed to consider an additional toxicology and safety pharmacology program to investigate the effect of drug combinations, especially the interaction of LU200134 [D2E7] and Methotrexate” and (2) “[a] potential Phase I combination study of LU200134 [D2E7] and Methotrexate (MTX) has been suggested to commence in the US” (emphases added by the court). Those statements did not indicate a “specific, settled idea” in the mind of the inventors, the court explained; they indicated a “continuing course of research.”

On the other hand, Dr. Weinblatt had spoken with Abbott scientists about a combination treatment in January of 1995, a date that could corroborate the testimony of the Abbott scientists that they had conceived of the entire invention.

In addition, the parties genuinely disputed whether co-administration was obvious, and the jump from treating patients with the antibody alone to treating them with an antibody and methotrexate combination was “not so small as to render co-administration obvious as a matter of law,” in the court’s view.

For those reasons, the court denied the parties’ cross motions for summary judgment with respect to the eight prior art references.

Validity based on 4SE3 as prior art. Abbott sought a determination that the 4SE3 antibody was not prior art under 35 U.S.C. §102(a), which stated that a person could not receive a patent for something that was already known to others. According to the court, Abbott convincingly argued that 4SE3 was not available to the public, and Centocor failed to raise a question of material fact regarding that argument.

Evidence that the antibody was known to, or used by, anyone other than the CAT or BASF inventors was completely lacking, the court explained. In addition, there was no evidence that the antibody had been disclosed or published before the filing of the patents in suit. For those reasons, 4SE3 was not prior art under §102(a).

Validity based on written description. Centocor argued that the specifications of the patents in suit did not satisfy the written-description requirement because persons of ordinary skill in the art would not clearly recognize that the inventors had invented the genus of antibodies that were described by the asserted claims.

The record did not clearly resolve the complex questions of fact regarding the adequacy of the written description of the patents in suit, the court concluded. The breadth of the variation within the genus of antibodies that were described by the relevant patent claims, the representative nature of D2E7 antibody, and the similarity of the structural features of the antibodies all presented genuine issues of material fact. Because this case was not one of those “rare instances” in which the facts firmly established that a party had met or failed to meet the written-description requirement, the court denied Centocor’s request for summary judgment based on a lack of written description.

Validity based on enablement. To meet the enablement requirement, a patent specification had to teach a person who was skilled in the art “how to make and use the full scope of the claimed invention without undue experimentation.” Centocor argued that the patents in suit did not enable the full scope of the claimed invention. It also argued that the asserted patents enabled the creation of antibodies by only one method.

With respect to enabling the full scope of the claimed invention, Centocor noted that the testing of an antibody could take up to a week, and a person skilled in the art, following the inventors’ instructions on how to alter D2E7, would not uncover the other members of the genus (such as the antibody in Simponi) without undue experimentation. Centocor argued that there could be millions or billions of antibodies within the genus.

Abbott agreed that the number of members was unknown and possibly very large. Nevertheless, it argued that: (1) the required experimentation was routine and (2) the specification provided a clear path for finding other members of the genus. In addition, Abbott disagreed with Centocor’s assertion that D2E7 and Simponi were dissimilar. According to Abbot, genuine issues of material fact precluded summary judgment.

The court agreed with Abbott. Summary judgment was inappropriate because factual disputes existed regarding how much direction the patents provided, how routine the required testing was, and how predictable the art was. Because the parties’ experts disagreed on those and other key factors, Centocor failed to show that no genuine dispute existed as to any material fact.

With respect to Centocor’s argument that the asserted patents enabled the creation of antibodies by only one method, the decision of Federal Circuit in Johns Hopkins University v. CellPro, Inc., 152 F.3d 1342 (1998), rendered that argument legally irrelevant because a patent did not need to teach how to make the claimed invention using every alternate method that was disclosed in the patent.

In this case, the parties did not dispute that non-recombinant (not engineered using recombinant DNA technology) methods could be used to produce the claimed invention. Because that appeared to enable the full scope of the patent, Centocor was not entitled to judgment as a matter of law as to enablement.

Willful infringement. Centocor argued that, if it did infringe the patents-in-suit, it did not do so willfully. According to Centocor, Abbott could not prove by clear and convincing evidence that Centocor was objectively reckless because Centocor had plausible defenses with respect to Abbot’s failure to meet the written-description and enablement requirements.

The court acknowledged that some courts had granted summary judgment of no willful infringement. Nevertheless, many others had waited until the record was further developed at trial. In this case, the court favored a more developed record.

Centocor’s motion was based on claims of non-infringement for failure to meet the written-description and enablement requirements, and the court denied summary judgment on those issues because issues of disputed fact remained. Because the reasonableness of those invalidity defenses had not been determined, the court denied Centocor’s motion for summary judgment based on a lack of willful infringement.

The case is Civil Action No. 09-40089-FDS.

Attorneys: David P. Frazier (Finnean, Henderson, Farabow, Garrett & Dunner, LLP) for Abbott Biotechnology Ltd. and AbbVie Inc. Dianne B. Elderkin (Akin Gump Strauss Hauer & Feld LLP) for Centocor Ortho Biotech, Inc.

Companies: Abbott Biotechnology Ltd; AbbVie Inc.; Centocor Ortho Biotech, Inc.

Cases: Patent MassachusettsNews