By Kevin E. Noonan --
The U.S. Patent and Trademark Office rendered its final decision on Monday in one of the re-examinations of the Thomson stem cell patents provoked 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 Patent Office decision comes in the inter partes (35 U.S.C. § 311-318) re-examination of U.S. Patent No. 7,029,913.
The inter partes requesters had asserted four grounds of unpatentability against the claims of the '913 patent:
• That the claims are unpatentable under 35 U.S.C. § 103(a) for being obvious in light of the Robertson '83 reference (Cold Spring Harbor 10: 647-63) in view of the Loring Declaration (see "It's Time to Stop the Hypocrisy over Stem Cell Patents - Part I").
• That the claims are unpatentable under 35 U.S.C. § 103(a) for being obvious in light of the Piedrahita 1990 reference (Theriogenology 34: 879-901) in view of the Loring Declaration.
• That the claims are unpatentable under 35 U.S.C. § 103(a) for being obvious in light of the Robertson '83 reference, the Robertson '87 reference (Teratocarcinomas and Embryonic Stem Cells: A Practical Approach, IRL Press) and the Piedrahita 1990 reference in view of the Loring Declaration.
As set forth in the decision, the Examiner refused to adopt any of these grounds of unpatentability, since they improperly relied on the Loring declaration (which does not properly form a basis for re-examination). The Examiner instead raised the following grounds of unpatentability:
• That the claims were unpatentable under 35 U.S.C. § 102(b) for being anticipated by U.S. Patent No. 5,166,065 to Williams, either alone or based on evidence of inherency.
• That the claims were unpatentable under 35 U.S.C. § 103(a) for being obvious in light of the '065 patent, either alone or based on evidence of inherency.
• That the claims were unpatentable under 35 U.S.C. § 102(b) for being anticipated by U.S. Patent No. 5,690,926 to Hogan, either alone or based on evidence of inherency.
• That the claims were unpatentable under 35 U.S.C. § 103(a) for being obvious in light of the '926 patent, either alone or based on evidence of inherency.
• That the claims were unpatentable under 35 U.S.C. § 103(a) for being obvious in light of Robertson '83 reference, the Robertson '87 reference, the '065 patent, and the '926 patent.
However, in Monday's decision, the Examiner withdrew all these grounds of rejection, finding that the claims were patentable over the combinations of the cited references and under 35 U.S.C. §§ 102 and 103. The Examiner did not merely withdraw these rejections, however, but rather set forth the basis for these determinations for all of the art and all of the arguments raised by the requestor. Specifically, the Examiner made these determinations:
U.S. Patent No. 5,166,056 to Williams does not anticipate the '913 patent claims; the Williams patent disclosed only mouse ES cells and did not inherently enable the human ES cells claimed in the '913 patent. Moreover, any implied teaching with regard to human ES cells was contradicted by a later paper (Cherny, 1994, Reprod. Fert. Develop. 6: 569-75; Williams co-authored), stating that isolation of human pluripotent ES cells had "remained elusive." Moreover, the Examiner considered the "precise impetus" for Cherny, 1994 was to find alternative methods for producing ES cells from non-mouse species, because the methods used for mouse ES cells had not been "applicable to other domestic animals." Indeed, the Examiner agreed with WARF's position that Cherny, 1994 contradicted any interpretation that the Williams patent enabled human ES cell preparation. Finally, the Examiner believed that undue experimentation would be required to practice the methods of the Williams patent to produce human ES cells, since there could be no reasonable expectation of success in view of all of the evidence of record.
This belief was supported by evidence from the art, specifically the Gardener and Brook reference (1997, Proc. Natl. Acad. Sci. U.S.A. 94: 5709-12) and the Brook et al. reference (2003, Diabetes 52: 205-08), of the failure of others to produce human ES cells using prior art methods such as those set forth in the Williams patent. The Examiner's undue experimentation determination was also supported by the Iannacone et al. (1994, Develop. Biol. 163: 288-92) and Ouhibi et al. (1995, Molec. Reprod. Devel. 40: 311-24) references, showing the unpredictability of producing rat ES cells. On the other hand, Doetschman (1988, Develop. Biol. 127: 224-27) isolated hamster ES cells, but Piedrahita (1990, Theriogenology 34: 879-901) failed to isolate ES cells from pigs or sheep, and while unable to determine whether Talbot (1995, Molec. Reprod. & Develop. 42: 35-52) isolated bovine ES cells, the evidence supported the Examiner's position that the art evidence showed that ES cells were sufficiently unpredictable to amount to undue experimentation absent evidence that ES cells from a particular species had in fact been made.
The most directly applicable reference to the human ES cells of the '913 patent was the Bongso reference (1994, Human Reprod. 9: 2010-17) (see "WARF Responds to the Patent Office on Its Re-examined Stem Cell Patents"). However, although the Examiner believed that Bongso may have in fact isolated human ES cells, he was unable to maintain them in culture as recited in the claims.
With regard to obviousness under 35 U.S.C. § 103(a), the Examiner determined that the Williams patent did not support a prima facie obviousness determination, expressly considering the matter under the Supreme Court's recent KSR Int'l Co. v Teleflex Inc. decision. Specifically, the Examiner determined that the art failed to provide a reasonable expectation of success in achieving the claimed invention, in view of the previously-determined unpredictability in producing ES cells from a variety of mammalian species (including human). The Examiner also determined that evidence of "public acclaim" submitted by WARF would be properly considered as one of the "secondary indicia" of non-obviousness if WARF had established the source of the acclaim as being from those of at least ordinary skill in the art. Since the Examiner concluded that the evidence did not support a prima facie obviousness determination, he did not need to consider the secondary indicia in this case.
Importantly, the Examiner also determined that the declaration evidence submitted by the third party requestor to the effect that Dr. Thomson succeeded in isolating human ES cells where others failed merely due to access to resources (human embryos) and funding others did not have, was merely hindsight reasoning and thus impermissible for consideration in an obviousness determination. The Examiner also noted for the record that at least two of the declarants were not disinterested parties.
Turning to the Hogan patent, the Examiner determined that the EG cells disclosed by Hogan are distinct from the ES cells claimed in the '913 patent, and thus that the Hogan patent neither anticipates nor renders obvious the claims of the '913 patent. The Examiner's conclusions were based on comparisons between characteristic properties of the two cell types, including the presence or absence of certain cell surface markers (such as SSEA-1).
Finally, the Examiner considered whether the combination of the '065 patent and the '926 patent, in view of the Robertson '83 reference or the Robertson '87 reference rendered obvious the invention claimed in the '913 patent. He found that while the two Robertson references disclosing mouse ES cells provided strong motivation in the art to produce human ES cells, the unpredictability in the art noted above made the claimed invention non-obvious. The Examiner came to the same conclusion with regard to the combination of the '065 patent and the '926 patent with the Piedrahita 1990 reference discussed above. The Examiner came to the same conclusions when considering the obviousness question in view of the teachings of all these references combined.
The Patent Office decision issued Monday was not a Notice of Allowance or other final determination. Rather, it was a (non-final) Action Closing Prosecution. According to the paper itself, no appeal could be taken from this Action; the patentee has one month to file a "submission," and if one is filed the Third Party Requester has the right to file responsive comments within 30 days. Thereafter, the Office will issue a Right of Appeal Notice pursuant to 37 C.F.R. § 1.953(a), giving the parties one month to file an appeal to the Board of Patent Appeals and Interferences.
One final note: the patentee submitted amendments to the claims that the Examiner states are not necessary for patentability but that "provide further clarity to the claims." Presumably, a re-examination certificate will include the amendments to the claims, which are as follows:
1. A replicating in vitro cell culture of pluripotent human embryonic stem cells derived from a pre-implantation embryo, the culture comprising cells which (i) [[are capable of proliferation]] will proliferate in an undifferentiated state 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.
2. The in vitro cell culture [[preparation]] of claim 1, wherein the stem cells will spontaneously differentiate to trophoblast and produce chorionic gonadotropin when cultured to high density.
3. The in vitro cell culture [[preparation]] of claim 1 wherein the cells are negative for the SSEA-1 marker, positive for the SSEA-4 marker, and express alkaline phosphatase.
Two ex parte re-examinations (35 U.S.C. § 302-307) remain: Control No. 90/008102 for U.S. Patent No. 5,843,780 (claiming primate embryonic stem (pES) cells) and Control No. 90/008139 for U.S. Patent No. 6,200,806 (claiming human embryonic stem cell (hES) cells). Since the progress of these re-examinations have paralleled the inter partes re-examination, and in view of the "special dispatch" provisions of the re-examination rules, we should expect a decision in these re-examinations shortly.
For information regarding this and other related topics, please see:
• "WARF Licenses Stem Cell Patent Portfolio to BioTime," January 23, 2008
• "It's Time to Stop the Hypocrisy over Stem Cell Patents - Part III," July 4, 2007
• "WARF Responds to the Patent Office on Its Re-examined Stem Cell Patents," June 26, 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
As It Turns Out, It Doesn't Have to Be a Rose to Smell as Sweet
By Kevin E. Noonan --
The return on investment is high, with individual scents (used as components for popular perfumes and other fragrances) so dear, their producers decline to specify their cost (other than saying they were "not cheap). These new scent molecules provide the raw material for the up to 600 new fragrances introduced each year. They also have advantages over naturally-occurring scents, such as lacking allergenicity present in natural products such as rose ketones, the amount of which is restricted due to their propensity to provoke allergic reactions. Other advantages include the capacity to cling to fabrics, to be used in scented laundry products and soaps, while at the same time being more potent so that less scent must be used (and less water used to wash the scent away).
Importantly, there are also ecological advantages: for example, the article cites the price of natural sandalwood as reaching $1,700 per kilogram, due to severe over-foresting of Indian sandalwood that forced the Indian government to ban further harvesting. Additionally, using synthetic rather than naturally-occurring scents avoids the ancillary economic and ecological costs of fertilizers, soil erosion, and diverting cropland to non-agricultural uses.
Some of the most expensive of the scents, described as "captives" in the industry, are those that are under patent, the most potent analogy made by the article to the pharmaceutical industry. In addition to the analogies noted above to the high development costs and low probability of success, the article also notes the importance of toxicology and the effects of the scope of available patent protection in different countries (while getting the current extent of U.S. patent term wrong, citing a figure not used for the past thirteen years).
But the analogies to patenting and its importance to the industry are where an otherwise informative article goes a little wrong. Maybe it's because the Times published it, or maybe it's the title ("Ahh, the Seductive Fragrance of Molecules under Patent") (something that could be the product of a copy editor well aware of the Times patent animus). Whatever the reason, rather than being enlightening, the patent angle seems gratuitous. The antiparallels to pharmaceuticals are never mentioned: the much higher regulatory costs and barriers for drugs, the factors other than toxicity that can make even fewer potential drug leads suitable for commercialization, and of course the unstated difference between "luxury" items like perfumes and life-saving drugs. And the overall effect is insidious: another Times article where patents are not described as helping companies protect hard-earned investment but rather just make things cost too much. The unspoken assumptions have substantive consequences: in discussing Takasago's patent strategy for it synthetic must product, l-muscone (the company patented the synthetic methods rather than the scent itself), the effect, that these methods will be dedicated to the public when Takasago's patents expire goes unmentioned. It seems a shame that such important considerations are left to innuendo or discussed obliquely, even by the Times. You might even say it stinks.
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