It's Time to Stop the Hypocrisy over Stem Cell Patents - Part III

    By Kevin E. Noonan --

Although it is well past time to stop the hypocrisy over stem cell patents (see Part I and Part II of this series), the forces aligned against the Thomson human embryonic stem cell patents refuse to do so.  This was made evident again this week, when additional voices, none without significant conflicts of interest, joined the fray.

The stem cell patents, owned by the Wisconsin Alumni Research Foundation, have been involved in re-examination proceedings in the U.S. Patent and Trademark Office prompted by two groups:  the Public Patent Foundation (PUBPAT), headed by Dan Ravicher, and The Foundation for Taxpayer and Consumer Rights (FTCR), a California taxpayer group.  The patents in re-examination are U.S. Patent Nos. 5,843,780 (claiming primate embryonic stem (pES) cells); 6,200,806 (claiming human embryonic stem cell (hES) cells); and 7,029,913 (hES); '708 and '806 patents are undergoing re-examination under the conventional ex parte re-examination proceedings (35 U.S.C. § 302-307) under Serial Nos. 90/008102 and 90/008139, respectively, while the '913 patent is being re-examined inter partes (35 U.S.C. § 311-318) under Serial No. 95/000154.

The Patent and Trademark Office initially rejected all the claims of all the patents, based on novelty (35 U.S.C. § 102) and obviousness (35 U.S.C § 103) grounds (see "WARF Stem Cell Patent Claims Rejected in Re-examination").  WARF responded to these rejections, providing amendments, arguments, and expert testimony in a declaration from Dr. Colin Stewart, a mouse embryologist from the Institute of Medical Biology in Singapore (see "WARF Responds to the Patent Office on Its Re-examined Stem Cell Patents").  The response is being considered by the patent examiner.

In the ex parte re-examinations, the third party re-examination requestors cannot comment on WARF's response or evidence.  This is not the case in the inter partes re-examination, and the opponents have taken advantage of their opportunity to provide affidavit evidence of their own.  Specifically, the opponents have submitted declarations from four individuals:  Dr. Doug Melton, a co-director of the Harvard Stem Cell Institute, Harvard University; Dr. Chad Cowan, also at Harvard; Dr. Jeanne Loring, from the Burnham Institute for Medical Research in San Diego; and Dr. Alan Trounson, of Monash University in Australia.  In their declarations, these affiants provide a new, previously unasserted basis for finding the claims of the Thompson patent obvious.  For the first time, the opponents assert that Dr. Thomson was able to make human embryonic stem cells not because the prior art made them obvious, but because he had "unique access" to an Israeli scientist who provided him with human embryos.  In addition, they cite funding from the San Francisco biotech company Geron, an exclusive licensee in some fields of use of the Thomson patents in re-examination.

Substantively, of course, the fact that Dr. Thomson (lower left) had sufficient financial support for his work is an irrelevancy; it is nonsensical that this factor could raise the bar of non-obviousness, which would put well-financed companies and industries at a competitive disadvantage.  It also appears that the other factor cited, access to previously unavailable starting materials, should not be dispositive of novelty or non-obviousness, for several reasons.  First, 35 U.S.C § 103 explicitly recites that "patentability shall not be negatived by the manner in which the invention is made."  In addition, the absence of the appropriate starting materials in the prior art would by itself render any prior art teachings non-enabled, and this would prevent the art from anticipating Thomson's invention.  Indeed, these affidavits provide admissions by the challengers that the art did not anticipate, since their position is that the necessary starting materials were not available.

This lack of availability would not appear to support their obviousness argument, either.  Their affidavits (if believed) establish that the art prior to Dr. Thomson's invention was incapable of producing human embryonic stem cells.  Under these circumstances, the best the art could provide is a suggestion about how human stem cells might be produced were the necessary starting materials (human embryos) available.  If the subject matter was a simple mechanical device, this argument may have had some force.  However, in view of the inherently high degree of unpredictability in producing embryonic stem cells from any source, these affidavits do not support the other prong of the non-obviousness test:  that the skilled worker would have had a reasonable expectation of success in achieving the claimed invention based on the teachings of the prior art.

The requirement for such a reasonable expectation of success was not overturned by the Supreme Court's recent decision in KSR International Co. v. Teleflex Inc. (see "Implications of the Supreme Court's KSR v. Teleflex Decision for Biotechnology").  Indeed, as recently as last Thursday, the Court of Appeals for the Federal Circuit affirmed the necessity for an obviousness determination that a reasonable expectation of success exist, in Takeda Chem. Indus., Ltd. v. Alphapharm (see "Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd. (Fed. Cir. 2007)").  In this case, WARF has presented evidence (unrefuted by these affidavits) from Dr. Stewart that even among mouse strains there was variability in the facility with which ES cells could be isolated (i.e., some strains reliably produced ES cells, and some strains did not, and success was not predictable a priori).  In addition, Dr. Stewart averred that attempts to isolate rat or ovine ES cells had been unsuccessful.  Human embryonic stem cells would appear to be sufficiently unpredictable that their invention by Dr. Thomson was non-obvious.

Thus, on the merits, the recently-submitted affidavits do not overcome WARF's arguments of unpredictability made in its response to the Patent Office rejections of the Thomson patents, and in some respects bolsters WARF's arguments that the cited art fails either to anticipate or render obvious the Thomson claims to human embryonic stem cells.

But it is the hypocrisy that stands out, as it has throughout the re-examinations.  Dr. Loring's culpability in this regard has been the subject of a previous post:  the patent examiner excoriated her affidavit submitted in support of the original inter partes re-examination request (see "WARF Stem Cell Patent Claims Rejected in Re-examination").  In that declaration, Dr. Loring (at right) opined not only on the prior art but on the legal conclusions regarding the art (i.e., that it rendered the claims obvious) as well as the "public injury" occasioned by the Thomson patents.  The Examiner handling the inter partes re-examination explicitly condemned this declaration as being improper in a re-examination as being outside the scope of the statutory limits.  And Dr. Loring is not beyond shaping her opinions on the availability of stem cell patents depending on her own self-interest:  in 2002, Dr. Loring submitted her own U.S. patent application on stem cells, published as U.S. Publication No. 2002/0188963.  Although ultimately rejected by the Patent Office, in her application Dr. Loring claimed "an isolated population of non-mouse embryonic stem cells," a claim much broader than any of Dr. Thomson's claims.  The capacity for "public injury" would appear to have been much higher for Dr. Loring's claims than Dr. Thomson's (see Part I of this series).  And recently Millipore announced plans for training workshops on human stem cells developed at the Burnham Institute. These workshops are intended to be comprehensive and frequent, being 4-5 days long and offered quarterly. The workshops are to be held at the Burnham Institute at a cost of $1,500 per student.

Any mention of Dr. Melton's self-interest must be tempered by the recognition that he has a personal stake in the outcome of stem cell research.  As he has made clear in opposing the Bush administration's unnecessary limits on federal funding for stem cell research, his own son is a juvenile diabetic whose life might be immeasurably improved by stem cell replacement of his pancreatic islet cells.  However, this does not change the fact that Dr. Melton (at left) is not a disinterested observer without a financial stake in the outcome of the re-examination.  Besides his own interest in funding for his laboratory, the decision of the Massachusetts state government to provide one billion dollars for biotechnology research (see "Massachusetts to Invest $1 Billion on Medical and Science Research"), with a hefty dose earmarked for stem cell research, may be expected to motivate his participation if not his opinions on the Thomson re-examinations.  Dr. Melton's colleague, Dr. Cowan, suffers from the same financial conflict of interest.

Like Dr. Loring, Dr. Trounson also has a number (five) of published U.S. patent applications directed to stem cells, including U.S. Publication No. 2002/0160509 reciting the following claim:

Claim 1.  A purified preparation of human undifferentiated embryonic stem cells capable of proliferation in vitro.

The relative overbreadth of this claim, compared with Dr. Thomson's claims in re-examination, make it hard to give credence to Dr. Trounson's testimony.  This is particularly true since Dr. Trounson (at right) was required to supply a declaration/power of attorney in his U.S. application attesting to the fact that he was an inventor of this claim.  If the art available when Dr. Thomson filed his earliest application rendered human embryonic stem cells obvious, the question arises as to whether Dr Trounson was mistaken when he signed his application declaration or when he signed the declaration submitted in the Thomson patent re-examinations.

The challengers have also tried to raise the political and public relations pressure on WARF by releasing these affidavits to the press, which lacks the capacity (scientific or political) to properly evaluate their claims or provide an unbiased review of the self-interest of the challengers (while trumpeting the self-interests of the patentee as being contrary to the public interest).  The sad thing is that neither the press nor the public seems to have any interest in dispassionately assessing the motivations of the parties, and appear content in reporting the largely unsubstantiated charges against WARF made by the patent challengers (see Part II of this series).

The Patent Office is now considering WARF's responses and, in the inter partes re-examinations, the challengers' affidavits and the arguments accompanying them.  Under the "special dispatch" rules for patent re-examinations, it can be expected that any further Action should issue from the Patent Office by autumn, and that a final (appealable) determination should issue by the end of this year.

For additional information on this and related topics, please see:

• "The Potential Usefulness of Adult Stem Cells Reaffirmed," June 25, 2007
• "Can Fibroblasts Solve The Problems with Human Embryonic Stem Cells?" June 15, 2007
• "Massachusetts to Invest $1 Billion on Medical and Science Research," May 10, 2007
• "It's Time to Stop the Hypocrisy over Stem Cell Patents - Part II," April 26, 2007
• "It's Time to Stop the Hypocrisy over Stem Cell Patents - Part I," April 17, 2007
• "WARF Stem Cell Patent Claims Rejected in Re-examination," April 3, 2007
• "NIH Chief Dissents on Federal Stem Cell Funding Ban," March 20, 2007
• "Stem Cells a Go! in California," February 28, 2007
• "Limitations on the Usefulness of Adult Stem Cells," February, 28, 2007

Comments

[Channamma.S.Shanbhag]

it is really great work and i learnt lot from this article and now i am able make differentiate between adult stem cell and embryonic stem cell and really i am thankful to u all.

[Channamma.S.Shanbhag]

I am doing my research work on stem cell patenting so i need your help please help in understanding more about stem cells