The Board of Patent Appeals and Interferences at the Patent and Trademark Office found April 28 that a patent on human embryonic stem cells was invalid as anticipated by an earlier patent and obvious in light of the "significant guideposts" in the literature for deriving the cells at the time of invention (Foundation for Taxpayer and Consumer Rights v. Wisconsin Alumni Research Foundation, B.P.A.I., No. 2010-001854, 4/28/10).

The patent is one of three on stem cell derivation assigned to Wisconsin Alumni Research Foundation and licensed to Geron Corp. It was challenged by consumer advocacy groups in a PTO inter partes reexamination proceeding.

One of the challengers was also successful recently in the Myriad case challenging gene patenting on Section 101 grounds. A stakeholder in the biotechnology industry suggested that both cases represent a "pushback" against the "land rush" for intellectual property in the field.

Challenge by PUBPAT and Consumer Watchdog.

A patent (7,029,913) was issued April 18, 2006, to James A. Thomson titled "Primate embyronic stem cells," with claims drawn to pluripotent human embryonic stem, or ES, cells derived from a pre-implantation embryo. The patent, assigned to WARF, shares ancestry with two others (5,843,780 and 6,200,806) whose patentability was confirmed in separate reexamination proceedings. The application for the '780 patent was filed in 1996.

An inter partes reexamination request for the '913 patent was filed July 17, 2006, by the Public Patent Foundation on behalf of the Foundation for Taxpayer and Consumer Rights, now known as Consumer Watchdog. The request cited three publications as prior art references rendering the claims invalid for obviousness under 35 U.S.C. §103. Withdrawing initial rejections, an examiner found independent Claim 1 and dependent Claims 2 and 3 of the '913 patent allowable on Feb. 28, 2008.

The Foundation appealed, claiming the rejections were improperly withdrawn.

1992 Patent Anticipates WARF Patent.

Claim 1 is directed to "A replicating in vitro cell culture of human embryonic stem cells comprising cells (i) which are capable of proliferation in in vitro culture for over one year without the application of exogenous leukemia inhibitory factor," or LIF, with three other limitations not at issue in the reexamination.

Administrative Patent Judge Richard M. Lebovitz found the claim anticipated by a patent (5,166,065) issued in 1992 to an Australian team headed by Robert L. Williams.

First addressing WARF's argument that the only working example in the '065 patent was to use mouse ES cells, Lebovitz noted that "human embryos are explicitly recited in a list of animal embryos that can be used as a source."

"A species which is specifically disclosed in a prior art reference is anticipatory even though it appears 'without special emphasis in a longer list,' " he said, citing Perricone v. Medicis Pharmaceuticals Corp., 432 F.3d 1368, 1376, 77 USPQ2d 1321 (Fed. Cir. 2005) (71 PTCJ 226, 1/6/06).

Next, the board noted that the anticipatory reference must be enabling. WARF argued that Thomson used a different method than Williams to isolate the ES cells, but the board said no evidence was provided that Williams's method would not work when applied to human embryos.

"ES cells are claimed, not a method of making them," the board explained. "Consequently, differences in the isolation method do not alone distinguish the claimed cells from those produced using the Williams methods nor establish that the claimed subject matter was not enabled by the Williams patent."

The board acknowledged that Williams coauthored a paper two years after his patent was issued, criticizing the applicability of the murine model to other species. But, Lebovitz said, "A reference is no less anticipatory if, after disclosing the invention, the reference then disparages it. Thus, the question whether a reference 'teaches away' from the invention is inapplicable to an anticipation analysis," he quoted from Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516 (Fed. Cir. 1998)

Finally, the abstract of the Williams patent indicates that it "relates generally to the use of leukaemia inhibitory factor (LIF) in the maintenance and derivation of embryonic stem (ES) cells in culture," so ARF argued that the patent did not teach the first limitation of Claim 1 of proliferation without LIF.

But the limitation requires that the cells "proliferate" without LIF and "does not exclude the ES cells from having been derived in the presence of LIF," Lebovitz said, again noting that Claim 1 is a product and not a method claim. WARF's expert's testimony once again was insufficient, the judge contended, in that there was no evidence that cells derived using Williams LIF-based methods, "would not have the claimed property of 'proliferat[ing] in an in vitro culture' " without LIF.

The board thus concluded that Williams's '065 patent anticipated WARF's '913 patent Claim 1, and since Clams 2 and 3 were not separately argued, they fell within the same judgment.

ES Cells From Germ Cells Not Anticipatory.

Another patent (5,690,926), issued to Brigid L. M. Hogan of Vanderbilt University in Tennessee in 1997, with a 1994 application date, described human ES cells derived from germ cells. Since Claim 1 of the '913 patent contained the product-by-process limitation of cells "derived from a pre-implantation embryo," Lebovitz said, "The pivotal question … is whether derivation from a pre-implantation embryo confers some structural or other characteristic on the human stem cell that makes it different from the stem cells described in Hogan derived from germ cells."

"Evidence was provided that human embryonic germ cells express SSEA-1[, stage-specific embryonic antigen-1,] as a cell surface marker, but that human ES cells derived from human preimplantation embryos do not," he said. Thus, Claim 1 included a product-by-process limitation, he concluded.

Invention Obvious in Light of Significant Guideposts.

The BPAI's obviousness judgment was based on 41 findings of facts related to stem cell research derived from 11 different prior art references in addition to the Williams and Hogan patents. The board concluded that "Persons of ordinary skill in the art, as evidenced by [the findings of fact], were familiar with cell culture technology, mouse ES derivation, and able to apply mouse techniques to embryos from other species."

After recapping the techniques employed at the time of Thomson's work, Lebovitz said:

Based on these familiar techniques, the path to deriving human ES cells had a definite starting point with explicit landmarks along the way. A person of ordinary skill in the art, highly skilled in cell culture technology …, was not required to design new protocols or explore new approaches, but rather would follow a path already taken in the mouse. In sum, there were a "finite number of identified" and "predictable" solutions which would have been readily applied by one of ordinary [skill] in the art to produce human embryonic stem cells. [KSR International Co. v. Teleflex Inc., 550 U.S. 398, 421, 82 USPQ2d 1385 (2007) (74 PTCJ 5, 5/4/07)].

The board rejected the argument that Thomson had to "try all possibilities in a field unreduced by direction," saying that "significant guideposts" provided "the right direction to successful isolation of human ES cells."

Lebovitz also rejected WARF's characterization of "a high degree of unpredictability" in the mammalian stem cell field. "[T]here were a small number of known options to make embryonic stem cells," he said. "These options were known to work, albeit not in every species in which they had been tried, and therefore remained 'viable' and 'obvious to try' techniques to derive human embryonic stem cells."

The examiner thus improperly withdrew the rejections based on obviousness, Lebovitz concluded.

Administrative Patent Judges Donald E. Adams and Romulo H. Delmendo joined the opinion.

Drinker Biddle & Reath, Philadelphia, represented WARF. The third-party requestors were represented by Daniel B. Ravicher of the Public Patent Foundation.

Consumer Watchdog Hails Victory.

In an April 30 press statement, licensee Geron's chief patent counsel, David J. Earp, said, "This is not a final rejection of the patent claims. … We are confident that WARF will make a strong case in support of the patentability of these claims in continued examination."

However, John M. Simpson, Consumer Watchdog's stem cell project director in a May 3 statement, called the PTO ruling "a major victory for unfettered scientific research that could lead to cures for some of the most debilitating diseases."

In the same press release, Ravicher--who also serves as PUBPAT's executive director, said, "We've said from the very beginning that WARF's patents on stem cells are undeserved. … Should WARF continue to try to defend their unjustified patents, we will continue to prove them invalid."

"This is great news for medical research," Jeanne Loring, director of the Center for Regenerative Medicine at the Scripps Institute, added. "Human embryonic stem cells hold great promise for advancing human health, and no one has the ethical right to own them."

The release allowed that "Thomson deserved acclaim for his research that isolated human stem cells," but also noted that "one of the main reasons he was able to derive a human stem cell line was because he had access to human embryos and financial support that other researchers did not have."

As to the possibility that WARF will seek continued examination in the PTO, Simpson said, "The best course if WARF truly cares about scientific advancement would be to simply abandon these over-reaching patent claims."

Comparison to Gene Patents Case?

"What strikes me most about this situation is how much it has in common with the human gene patent ruling and what together these may say about the direction of intellectual property in biotech,'' Jesse Reynolds, the Center for Genetics and Society's project director on Biotechnology in the Public Interest, told BNA.

Reynolds's reference was to the decision by the U.S. District Court for the Southern District of New York finding patents on genes linked to hereditary breast cancer unpatentable subject matter under Section 101. Association for Molecular Pathology v. U.S. Patent and Trademark Office, No. 09 Civ. 4515 (S.D.N.Y. March 29, 2010) (79 PTCJ 661, 4/2/10).

In both cases public interest groups, including the Public Patent Foundation, challenged broad patents ''and in both cases they were joined by researchers,'' Reynolds said.

He called the challenges "an important kind of pushback'' in the biotechnology industry. Consumer groups ask whether they are in the public interest, Reynolds said. Universities make patent claims but also pay one another for patents used in research, he noted. ''There's something kind of like a land rush here where all the parties are staking their claims but they would have been better off all along thinking about how they could all benefit from the property and in this case the property is the knowledge.''

"I think that a rethinking of intellectual property in biomedical research is overdue and hopefully these two cases are components of that,'' Reynolds said. He added that WARF has gradually reduced its licensing fees for researchers. ''I would venture that the challenge of these licenses is part of the reason for that,'' he said.

''A lot of these tech transfer offices are at public universities [and] are rabidly defending the patents they obtained on publicly funded research," he said. "And I think to frame the question of the relevance or the benefits of these patents as an issue of the public interest is very justified."