WARF Reexamination Takes Another Bite Out of Biotech Patents

Two months ago, the Myriad gene patent litigation generated a slew of national and international coverage. We said, “Pigs Fly: Federal Court Invalidates Myriad’s Patent Claims.”  “Is the DNA patent dead?” asked CNN. Wired (apparently answering CNN) declared the “End of Gene Patents Will Help Patients, Force Companies to Change.” Everyone, it seemed, either had an opinion on what the Myriad decision meant for the future of biotechnology or was looking for somebody who did.

It’s not surprising that the Myriad litigation has dominated the headlines. The ACLU’s challenge to Myriad Genetics was a first-of-its-kind frontal attack on gene patents. But with Myriad now on appeal to the Federal Circuit, and a final resolution to that particular piece of litigation likely several years away, a variety of other legal developments are slowly but surely reshaping the biotechnology patent landscape. In the next few years, while frontal attacks such as Myriad are likely to occupy the press and policymakers, those interested in forecasting the future of biotechnology patents will be paying equally close attention to the various collateral attacks on gene, protein, association, diagnostic, and other biotechnology patents and claims.

The WARF Reexamination. A perfect example of this is the recent decision to invalidate a Wisconsin Alumni Research Foundation (WARF) patent on stem cell cultures. On April 28, 2010, Board of Patent Appeals and Interferences (the Board) of the U.S. Patent and Trademark Office (USPTO) invalidated one of WARF’s patents on stem cell cultures. The decision is Foundation for Taxpayer and Consumer Rights v. WARF (B.P.A.I. No. 2010-001854, 4/28/10) (pdf), and in it the Board ruled that the WARF claims were anticipated by a 1992 patent and were obvious in light of “significant guideposts” in the prior art. After some additional USPTO proceedings, there may be an appeal to the Federal Circuit.

The ruling was made in an “inter partes reexamination” requested by public domain advocacy organizations, including one—the Public Patent Foundation—that is, so far, a successful plaintiff in the ongoing Myriad case. Pursuant to § 301 and § 302 of the Patent Act, anyone can initiate a reexamination by identifying to the USPTO “prior art consisting of patents or printed publications which that person believes to have a bearing on the patentability of any claim of a particular patent.” Pursuant to § 303, if the USPTO finds that the request raises “a substantial new question of patentability,” it conducts an adversarial proceeding in which both the requester and the patentee can state their positions.

If the reexamination proceeds to an adversarial proceeding, the case is then decided according to the usual standards of patentability—whether the invention comprises patentable subject matter and is new, useful, and non-obvious. Outsiders rarely request inter partes reexamination because, on the one hand, the requester has limited procedural rights, but on the other, a ruling upholding the patent will bind the requester in future patent litigation.

Last month, the USPTO Board invalidated patent number 7,029,913 (the ‘913 Patent), issued to James A. Thomson on April 26, 2006, assigned to WARF thereafter and currently licensed to Geron Corp. The broadest of the ‘913 Patent’s three short and straightforward claims covers:

A replicating in vitro cell culture of human embryonic stem cells comprising cells which (i) are capable of proliferation in in vitro culture for over one year without the application of exogenous leukemia inhibitory factor, (ii) maintain a karyotype in which the chromosomes are euploid through prolonged culture, (iii) maintain the potential to differentiate to derivatives of endoderm, mesoderm, and ectoderm tissues throughout the culture, and (iv) are inhibited from differentiation when cultured on a fibroblast feeder layer.

The claim is stunning in its breadth. With the exception of “without the application of exogenous leukemia inhibitory factor” (LIF) in item (i), the remainder of the limiting language in items (i)-(iv) of the ‘913 Patent is the patentee’s definition of a stable human embryonic cell line. Thus, any similar cell line maintained without applying LIF would infringe.

Anticipation and Obviousness. The Board held that the WARF patent was anticipated by a 1992 patent issued to an Australian named Williams. To be anticipated, the claimed invention must be fully disclosed by a reference in the prior art—here, the Williams patent. (There is an old saying in patent law: “That which infringes, if later, anticipates, if earlier.”) The Williams patent disclosed “animal” embryonic stem cell cultures, giving the single example of mouse cells as a source. But the Williams patent did include human embryos on a list of possible animal sources, which led to the Board’s finding of anticipation. Williams’ abstract also described “the use of . . . LIF in the maintenance and derivation of embryonic stem (ES) cells in culture,” which might have distinguished it from the WARF claim. The Board found, however, that Williams’ mention of LIF-aided derivation of ES cells was irrelevant to WARF’s claim to LIF-free proliferation of the same cells.

In analyzing the ‘913 Patent, the Board did not seem to acknowledge the distinction between primary ES cells and a stable ES cell line. The opinion repeatedly discussed support in the prior art for “the derivation of human ES cells.” Primary cultures of human ES cells were indeed known in the art, but earlier attempts to create stable cell lines from ES cells had been unsuccessful. Thomson’s invention was, by his account, the first stable primate/human ES cell line. The administration of LIF had kept mouse ES cells from differentiating, but attempts to use LIF on primates had failed. According to the specification, which is the (often lengthy) written description that describes the patented invention, “There are no reports of the derivation of any primate ES cell line.” The most important contribution of the ‘913 Patent, and Thomson’s invention, was thus the maintenance of primate ES cells in prolonged stable cultures without LIF.

The Board also found the WARF patent obvious. The standard here is a fairly subjective one. Section 103 of the Patent Act explains that a proposed invention is obvious if at the time of invention

…the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious . . . to a person having ordinary skill in the art to which said subject matter pertains.

Although anticipation usually requires full disclosure by a single item of prior art, multiple such items can be combined to find an invention obvious. Moreover, under the Supreme Court’s 2007 decision in KSR International Co. v. Teleflex, and the Federal Circuit’s 2009 decision in In re Kubin, an invention can be held obvious if the prior art made it “obvious to try” to invent it.

Applying these standards to the WARF patent, the Board found that “the path to deriving human ES cells had a definite starting point with explicit landmarks along the way.” That is, it was obvious to try to derive human ES cells, and the person of ordinary skill in the art would have had “significant guideposts” as to how to do it. Accordingly, the invention was obvious.

This WARF Patent is Not Like the Others? As a practical matter, it would have been difficult to assert infringement of the now-invalidated ‘913 Patent. Proof of infringement would take a year of continuous culture before the difficult karyotyping and pluripotentiality tests could begin.

It is also interesting to note that two related WARF patents have previously survived reexamination at the patent examiner level: patent number 5,843,780 (1998) and patent number 6,200,806 (2001). While there are some specific differences in the wording of the claims in the three WARF patents—for example, primate versus human and the presence or absence of the LIF limitation—the three are very close in their structure and scope. It is not immediately clear why only one them has failed thus far.

WARF’s Reexamination is Obviously Significant. So what, exactly, is the significance of the WARF reexamination ruling for biotechnology patent law? First, we would not read too much into the anticipation ruling. Such rulings are case-by-case and very fact-specific. Nonetheless, the Board did tilt against patentability in resolving some close questions about just what the prior art of the Williams patent disclosed.

However, the obviousness finding is probably of much greater general significance. This is the type of collateral attack on biotechnology patents that may have a lasting effect. Myriad is the exception that proves the rule: a rare and, for the moment, anyway, successful frontal attack on gene patents. Even if Myriad ultimately impairs the patentability of identified DNA sequences (genes), a higher threshold for overcoming obviousness—one of the fundamental requirements for patentability—could have a much more lasting impact on the biotechnology patent landscape.

Nor does WARF stand alone in its challenge to obviousness. Last year there was In re Kubin (pdf), in which the Federal Circuit held that it would have been “obvious to try” to isolate polynucleotides that encode natural killer cell activation proteins. Also an important part of this trend was the Federal Circuit’s en banc (all of the judges on the entire Federal Circuit sitting together, instead of the typical three judge panel) ruling on March 22nd of this year in Ariad v. Eli Lilly (pdf), which invalidated a Harvard patent on a method to treat disease by reducing activity of a messenger protein that regulates gene expression in cells. The court got to that result by a very demanding reading of the Patent Act’s § 112 “written description” requirement, holding that a patent applicant must both demonstrate possession of the specific claimed invention (as opposed to the broad category of things into which it falls) and teach others how to make it. The Ariad court expressed special concern about the “vast scope of generic claims” and saw the written description requirement as a way to limit them. Finally, depending on what it says about the allowable scope of method claims, the Supreme Court’s imminent decision in the Bilski commodities hedging case could well take another significant bite out of biotech claims.

At any rate, the finding of obviousness for WARF’s ‘913 Patent carries negative implications across the biotechnology patent landscape and represents another important piece in the shifting patent landscape puzzle. So the next time you are reading about Myriad and the death of gene patents, remember that, over time, the more significant developments for biotechnology patent law are more likely to be the collateral attacks represented by WARF and other similar examples of patent litigation, even if they do not lead to special features on 60 Minutes.

Allison Williams Dobson

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