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Proof to a Scientific Certainty Not Always Required for Conception

July 23, 2009

Decision icon Decision

Last Month at the Federal Circuit - August 2009

Judges:  Mayer (author), Rader, Bryson

[Appealed from: C.D. Cal., Senior Judge]

In University of Pittsburgh v. Hedrick, No. 08-1468 (Fed. Cir. July 23, 2009), the Federal Circuit affirmed the district court’s ruling that University of Pittsburgh (“Pittsburgh”) researchers Adam J. Katz and Ramon Llull completed conception of the claimed invention before Marc H. Hedrick, Prosper Benhaim, Hermann Peter Lorenz, and Min Zhu contributed their efforts.

Drs. Katz and Llull, researchers at Pittsburgh, began a project in 1996 involving cells from human liposuctioned adipose tissue. They observed that under certain conditions, mature fat cells called adipocytes would transform into a more primitive cell having a fibroblast-like appearance, and under other circumstances, these primitive cells could transform back to mature adipocytes. They referred to these phenomena as de-differentiation and re-differentiation. By late 1996, they had developed a method to isolate these de-differentiated cells from liposuctioned tissue’s stromal vascular fraction.

By 1997, Katz and Llull had explored the idea that these cells could “transdifferentiate” into lineages other than adipocyte cells, including bone, cartilage, and muscle. They recorded their observations, including that their cells appeared to change to the shape and form of nonadipose cells, contemporaneously in laboratory notebooks, a January 1997 invention disclosure for their cell isolator device, and a document titled “What’s So Great About Fat?” in February 1997.

On January 20 and 24, and February 6, 1997, Katz wrote in his laboratory notebook that he had experimented with media to induce his cells to differentiate into muscle. In other entries, Katz described media and protocols that differentiated the cells into bone, muscle, fat, cartilage, and nerve cells. While not scientifically certain, he and Llull believed that they had observed cells changing into cells resembling muscle and fat cells. By April 1997, they had the firm and definite idea that the cells were human, could be genetically modified, secreted hormones, and contained cell-surface bound intracellular signaling moieties, all properties
known at the time to scientists in the field.

In July 1997, Hedrick joined the Pittsburgh laboratory for a yearlong fellowship. During his time in the lab, Katz submitted a grant proposal summarizing his work with Llull. While some researchers other than Katz and Llull were listed in the proposal, Hedrick was not. Hedrick was also not mentioned in Katz’s laboratory notebook in connection with any work on adipose-derived stem cells, though other researchers involved in the work were mentioned. Hedrick, however, wrote his own research proposal setting forth some experiments on Katz’s cells. In April 1998, Katz, Llull, and Hedrick submitted an invention disclosure to Pittsburgh stating that the isolated cells could be induced to transform into fat, bone, cartilage, and muscle tissues, and listed the first date of conception as October 1996.

In March 1999, Pittsburgh filed a provisional patent application, claiming a method of differentiating adipose-derived stem cells into bone, fat, cartilage, and muscle. The application listed Katz, Llull, William Futrell, and Hedrick as inventors. In October 1999, they filed a second provisional patent application listing the same inventors, acknowledging ongoing experimentation to find the cells in human liposuctioned fat tissue and the similarities to bone marrow-derived mesenchymal stem cells. In March 2000, Pittsburgh filed an international patent application listing all seven named inventors: Katz, Llull, Futrell, Hedrick, Benhaim, Lorenz, and Zhu. This application issued as U.S. Patent No. 6,777,231 (“the ’231 patent”).

On October 29, 2004, Pittsburgh filed suit seeking to remove named inventors Futrell, Hedrick, Benhaim, Lorenz, and Zhu. Futrell voluntarily dismissed himself from the suit, leaving the Regenerative Bioengineering and Research (“REBAR”) researchers as the only defendants.

Before the district court, the parties disputed the constructions of several terms, including the term “adipose-derived,” which is present in each claim of the ’231 patent. The REBAR researchers argued that the construction should be limited to a “species of stem cell distinct from the mesenchymal stem cell that is obtainable from bone marrow tissue.” Slip op. at 6. Katz and Llull argued for a plain meaning: cells “derived from fat tissue.” Id. The district court adopted Katz and Llull’s proposed construction after determining that the specification supported the plain meaning and that there was no disavowal of any other meaning during prosecution.

The district court then found that Katz and Llull conceived the claimed invention as construed prior to Hedrick’s arrival at Pittsburgh. The district court also found that Katz’s laboratory notebooks would have enabled a scientist skilled in the field to isolate his adipose-derived cells and differentiate them into each of the lineages claimed in the ’231 patent. The REBAR researchers appealed the construction of “adipose-derived” and the district court’s finding that they were not joint inventors of the claimed invention.

The Federal Circuit affirmed the district court’s decision. First, the Court rejected the REBAR researchers’ arguments attempting to limit the meaning of the claim term “adipose-derived” based on the specification and prosecution history. The Court found that the specification did not say that the cells are a separate species from mesenchymal stem cells collected from bone marrow, as the REBAR researchers argue— just that those derived from bone marrow have different isolation requirements than those derived from adipose tissue. Additionally, the Federal Circuit could not impute a reason for the difference in isolation requirements of cells harvested from bone marrow versus those harvested from adipose tissue by requiring them to be of a separate species. The Court noted that the fact “[t]hat other similar prior art cells are described differently than the inventive cells [did] not rise to an intent to deviate from the meaning of the terms describing the inventive cells.” Id. at 9 (citing Voda v. Cordis Corp., 536 F.3d 1311, 1320 (Fed. Cir. 2008)).

Further, the Court rejected the REBAR researchers’ argument that Katz and Llull clearly and unambiguously disclaimed any construction of “adipose-derived” that could read on prior art mesenchymal stem cells when they overcame an examiner’s rejection by introducing the term “adipose-derived.” Contrary to the REBAR researchers’ argument that the interview summary reflected a disclaimer of claim scope, the Federal Circuit found that the summary did not state why the adipose-derived stem cells in the invention were distinct from mesenchymal stem cells and thus did not explicitly characterize the invention at all, let alone in a specific manner to overcome prior art. Thus, the Court concluded that “[a] wide chasm exists between the weak inference from the summary that adipose-derived stem cells in this invention must be a different species from mesenchymal stem cells and a clear and unmistakable disavowal as required to limit a claim term.” Id. at 10.

Second, the Federal Circuit reviewed de novo the ultimate question of inventorship and the underlying facts for clear error. The Court found that the district court correctly applied the law of inventorship in determining that Katz and Llull conceived of each element of each claim of the invention. Instead of challenging the district court’s specific factual findings on conception, the REBAR researchers argued that Katz and Llull’s research was inconclusive until Hedrick and the other researchers added their efforts. Specifically, they argued that Katz and Llull’s work remained “highly speculative” through the end of Hedrick’s fellowship and that Katz and Llull were required to “know” that the invention contained every limitation of each claim at the time of conception, but that the evidence did not establish that they had this knowledge until the REBAR researchers helped them confirm the claimed properties.

The Court rejected the REBAR researchers’ argument because it was premised upon a misapprehension of what it means to “know” the limitations of the claims. “Knowledge in the context of a possessed, isolated biological construct does not mean proof to a scientific certainty that the construct is exactly what a scientist believes it is.” Id. at 13. “Proof that the invention works to a scientific certainty is reduction to practice.” Id. Therefore, because the district court found evidence that Katz and Llull had formed a definite and permanent idea of the cells’ inventive qualities, and had in fact observed them, the Court found it was immaterial that their knowledge was not scientifically certain and that the REBAR researchers helped them gain such scientific certainty. As the Court stated, “The determinative inquiry is not whether [the inventor’s] disclosure was phrased certainly or tentatively, but whether the idea expressed therein was sufficiently developed to support conception of the subject matter.” Id. at 14 (alteration in original) (quoting In re Jolley, 308 F.3d 1317, 1324 (Fed. Cir. 2002)). Given the district court’s finding that Katz’s laboratory notebooks sufficiently described to those skilled in the art how to isolate the cells from adipose tissue, they had disclosed a “completed thought expressed in such clear terms as to enable those skilled in the art to make the invention.” Id. (quoting Coleman v. Dines, 754 F.2d 353, 359 (Fed. Cir. 1985)).

Finally, the Federal Circuit rejected the REBAR researchers’ argument that the district court improperly supplemented Katz and Llull’s conception with knowledge that a skilled artisan would have had at the time when no corroborating evidence of their own knowledge was produced. The Court explained that evidence need not always expressly show possession of the invention to corroborate conception, and a court may properly weigh evidence that a claimed attribute is merely an obvious property of a greater discovery at issue. The Court then found that it was not improper for the district court to recognize that skilled artisans at the time of the alleged conception would have known the obvious properties.

Summary authored by Bart A. Gerstenblith, Esq.