by Arthur P. Gershman
In March of 1995 IP Today's predecessor, "The Law Works," published my article "The Ethics of Biotechnology: The Kosher Goldfish." In this article, I reported about the "Harvard Mouse," and the ethical questions it raised from the viewpoint of the Reform Jewish movement.
In October, 1997, "The Golem of Pook's Hill" discussed the application of these principles to human genetic material, namely the Human Genome Project.
In July of 2002 I reported on new developments in the field, including a similar viewpoint by the United Methodist Church. That article was entitled "The Kosher Goldfish Redux."
In this issue of IP Today, October of 2009, I report on more new developments and look forward to the future. You can see why I call this a pentathlon.
II. NEW DEVELOPMENTS
Since those first three named articles, the USPTO has been issuing patents directed not only to the methods of making gene sequences, but also patents whose claims may be construed to cover human genes. A typical example is U.S.P.N. 7,544,859, issued June 9, 2009 for "Elongase gene and method for producing multiple-unsaturated fatty acids." The patent includes the following claims:
1. An isolated nucleic acid sequence which encodes a polypeptide which elongates C.sub.18-fatty acids with at least two double bonds in the fatty acid molecule, said isolated nucleic acid sequence selected from the group consisting of: a) the nucleic acid sequence of SEQ ID NO:1, and, b) a nucleic acid sequence derived from SEQ ID NO:1 according to the degeneracy of the genetic code.
3. A gene construct comprising the isolated nucleic acid sequence as claimed in claim 1, wherein the isolated nucleic acid sequence is functionally linked to one or more regulatory signals.
4. The gene construct as claimed in claim 3 further comprising a nucleic acid sequence which encodes a fatty acid biosynthesis gene.
6. The amino acid sequence which is encoded by the isolated nucleic acid sequence as claimed in claim 1
8. A non-human recombinant organism comprising the isolated nucleic acid sequence of claim 1, said non-human organism comprising one of yeast or a transgenic plant.
9. The non-human recombinant organism as claimed in claim 8, wherein the organism is yeast.
Note that there are four types of claims shown above: Claim 1 is directed to an isolated nucleic acid sequence, Claims 3 and 4 to a gene construct, Claim 6 to an
amino acid sequence, and Claims 8 and 9 to a non-human recombinant organism. In particular, note that Claims 8 and 9 are limited to non-human organisms, while no such limitation is present in the other claims cited.
In another development, the International Center for Technology Assessment (CTA) successfully battled the University of Texas over USPN 6,444,872, in which the university claimed a beagle whose immune system was compromised to facilitate the dog's use in medical experiments.? The patent, issued September 3, 2002 to Andersson et al., was titled "Large animal model of invasive pulmonary aspergillosis in an immunocompromised host. According to an excerpt from the patent abstract, the invention comprised:
"A model of systemic mold/Aspergillus
infection in a profoundly immunocom-
promised host has been established in the
beagle dog. The beagle was rendered immunosuppressed using a combination
of total body irradiation and daily steroids,
which provided a window of time where
the mold could be successfully inoculated
through a bronchoscope. This created a
localized infection in one lung lobe, which subsequently spread diffusely throughout
the lung parenchyma, and uniformly
resulted in the animal's death."
On December 11, 2007 the CTA. together with the American Anti-Vivisection Society and the Alternatives Research & Development Foundation, filed a Request for Reexamination of the patent, accompanied by an extensive brief. The brief argued that the patent was invalid as lacking novelty under 35 U.S.C. Section 102(b), as obvious under Section 103(a) due to various combinations of cited prior art, as lacking statutory subject matter under Section 101 for failing to fall in one of the enumerated statutory classes, and for something called a "lack utility/moral utility under 35 U.S.C. §101," this latter argument based on animal welfare concerns.
The USPTO granted CTA's Request on May 19, 2004.
On May 24, 2004. The University of Texas filed a disclaimer of all claims in the patent for the remainder of the term of the patent.
In LabCorp v Metabolite, 548 U.S.__ (2006) the US Supreme Court once again danced around the Section 101 issues involving genetic material, as it had done in ALDC v Quigg, 932 F.2d 920, 937-39 (Fed. Cir. 1991). The suit considered a single claim, claim 13, of USPN 4,490,658 to to Allen et al.
Claim 13 reads:
"13. A method for detecting a deficiency of cobalamin or folate in warm-blooded animals comprising the steps of:
assaying a body fluid for an elevated level of total homocysteine; and
correlating an elevated level of total homocysteine in said body fluid with a deficiency of cobalamin or folate. "
This method tests for a deficiency in B vitamins.
A jury found LabCorp guilty of patent infringement and breach of contract and awarded damages to Metabolite. In an appeal to the Circuit Court of Appeals for the Federal Circuit, LabCorp argued that the patent was invalid under 35 USC Section 101. Natural phenomena themselves are not patentable, but new applications of them normally are. LabCorp argued that Metabolite had impermissibly patented a relationship that already existed in nature. The Federal Circuit rejected that argument, however, ruling that Metabolite could patent its discovery of the correlation and that any association of homocysteine levels with B vitamin deficiency could constitute patent infringement. LabCorp appealed its case to the Supreme Court. The case was granted certiorori.
However, in a per curium opinion by a vote of 5-3 (The Chief Justice not participating), the Court dismissed the writ of certiorari as improvidently granted. The decision of the Federal Circuit was left in place. Justice Stephen Breyer, joined by Justices Stevens and Souter, dissented from the order. The dissent argued that the Court should have taken the case in order to lend necessary clarity to an important issue in patent law. In the dissenters' view, a natural correlation between two substances in the body is a "natural phenomenon" that cannot be patented.
Justice Breyer argued:
"Even were I to assume (purely for argument's sake) that claim 13 meets certain general definitions of process patentability, however, it still fails the one at issue here: the requirement that it not amount to a simple natural correlation, i.e., a 'natural phenomenon.' See Flook, supra, at 588, n. 9 (even assuming patent for improved catalytic converter system meets broad statutory definition of patentable 'process,' it is invalid under natural phenomenon doctrine); Diehr, 450 U. S., at 184-185 (explaining that, even if patent meets all other requirements, it must meet the natural phenomena requirement as well). At most, respondents have simply described the natural law at issue in the abstract patent language of a 'process.' But they cannot avoid the fact that the process is no more than an instruction to read some numbers in light of medical knowledge. Cf. id., at 192 (warning against 'allow[ing] a competent draftsman to evade the recognized limitations on the type of subject matter eligible for patent protection'). One might, of course, reduce the 'process' to a series of steps, e.g., Step 1: gather data; Step 2: read a number; Step 3: compare the number with the norm; Step 4: act accordingly. But one can reduce any process to a series of steps. The question is what those steps embody. And here, aside from the unpatented test, they embody only the correlation between homocysteine and vitamin deficiency that the researchers uncovered. In my view, that correlation is an unpatentable 'natural phenomenon,'and I can find nothing in claim 13 that adds anything more of significance. "
What is most significant about this case is that the Supreme Court refused to decide the Section 101 issue with respect to patents on organisms of a higher order than microorganisms.
An amicus brief filed on behalf of AAPR strenuously supported the petitioner's position.
(An interesting perspective on LabCorp v Metabolite is offered by Mark Davies in his article at IP Today, June 2007, at page 28.)
In breaking news, on May 12, 2009 four learned medical societies, seven medical researchers, two women's cancer societies, and six women patients, headed by the Association of Molecular Pathology (AMP) sued the USPTO, Myriad Corp., and the trustees of the University of Utah Research Foundation to declare invalid or unenforceable selected claims of seven patents which cover the BRACA1 and BRACA2 genes, relevant for the detection of breast cancer in women.
The complaint was filed in the US District Court for the Southern District of New York. attacking the patents primarily under 35 USC Section 101 as a product of nature and thus constituting non-statutory subject matter.
Selected claims of seven patents are in contention:
USPNs 5,747,282; 5,837,492; 5,693,473; 5,709,999; 5,710,001; 5,753,441; and 6,033,857.
Typical is claim 1 of the first named patent:
1. An isolated DNA coding for a BRCA1 polypeptide, said polypeptide having the amino acid sequence set forth in SEQ ID NO:2.
The plaintiffs were represented by the ACLU and the Public Patent Foundation at the Cardozo School of Law (PUBPAT). The ACLU position is that genes and the relationship between genes and disease are products and laws of nature that should never have been considered as patentable subject matter. The ACLU and PUBPAT are challenging gene patenting because they believe that the USPTO has violated patent law by granting patents over an area of intellectual activity that should not be covered by patents, and in doing so, is unreasonably restraining free speech and scientific research.
They contend that the USPTO has granted thousands of patents covering human genes - an estimated 20 percent of human genes are patented. According to the ACLU the USPTO should never have granted these patents in the first place, because patenting human genes is unconstitutional and unlawful. In order to invalidate gene patents, they challenge at least one specific gene patent. Since the patents on the genes that correlate with an increased risk of breast and/or ovarian cancer are among the most offensive, they are also suing Myriad Genetics because it controls the BRCA patents and aggressively enforces them. Myriad does not allow anyone else to conduct clinical full sequencing testing. In addition, these patents have particularly broad claims on the BRCA genes, covering mutations that had not yet even been identified.
More information is available on the ACLU website at aclu.org.
As of the writing of this article, a pretrial motion and settlement conference was scheduled for September 30, 2009. I do not expect either settlement or dismissal of the case.
I look forward to reporting furthur developments on this case.
According to an article in the Journal of Philosophy and Law by Dr. Annabelle Lever, entitled "Ethics and the Patenting of Human Genes," The USPTO has issued thousands of patents on human genetic material and "...it is generally believed that their legality is well-established, although no court has yet ruled on the matter directly." This article challenges the assumption of their legality.
III. THE CONSTITUTIONALITY OF PATENTS
ON HUMAN GENETIC MATERIAL
THE ETHICS OF PATENTS ON HUMAN GENETIC MATERIAL
As Earl Warren put it, “In civilized life, law floats in a sea of ethics.” In “Questions and Reform Jewish Answers,” Dr. Walter Jacob, then Rabbi, Rodeph Shalom Temple, Pittsburgh, PA and Chairman of the Responsa Committee, Central Conference of American Rabbis, answered the question: May genetically engineered changes in a mouse designed for medical experiments be patented? The members of the Responsa Committee who discussed this question felt a high degree of discomfort with patenting changes in a living creature. According to the Reform Rabbis: “The animal itself should not be patented, ...Social policy has led to plant patents. This has protected the livelihood of individuals and made a more abundant human existence possible. However, patenting an animal leads us in a direction not conducive to respect for life. The Holocaust has made us aware of the dangers of dehumanization. The process, i.e., the genetic change may be patented, but the mouse itself should not be patented.”
For further details of the methodology of the Responsa, see my paper, “The Kosher Goldfish,”and for a similar position by the United Methodist Church, see my paper “The Kosher Goldfish Redux.”
I am making the assumption that the Reform Rabbis and the Methodists would take a similar position with regard to patents claiming human genetic material.
In Muller v Oregon, 208 U.S. 412 (1908), Louis Brandeis, acting as lawyer, submitted a brief in which the Supreme Court accepted external source material as a basis for the decision, rather than relying exclusively on case law in accordance with the principal of stare decisis. This became known as the Brandeis Brief, and became the model for future Supreme Court briefs in cases affecting the health or welfare of classes of individuals. This model was later successfully used in Brown v Board of Education, 347 U. S. 483 (1954), to demonstrate the harmful psychological effects of segregated education on African-American children. It is suggested that similar tactics may be used in an attack on the constitutionality of patents on human genetic material, using the CCAR Responsa, the UMC Resolutions, and other similar external source material.
THE CONSTITUTIONALITY OF PATENTS ON HUMAN GENETIC MATERIAL
The CTA v U. of Texas (immunocompromised beagle) and AMP v USPTO (BRACA breast cancer) are nightmare scenarios which illustrate how far the ethics of the biotechnology industry have been stretched. These cases put my previosly posited Horrible Hypotheticals to shame. Apparently unable to exercise self-restraint, industry leaders have been lured by excessive possibilities for profit without regard to moral standards. The patents illustrate examples which appear to be challengeable under fourteenth Amendment right to privacy and fifth Amendment substantive due process grounds.
The question of statutory subject matter under 35 USC Section 101 challenges are under way and have ben so since ALDF v Quigg. We can expect more challenges on other grounds.
Patents on human genetic material are unethical. The Supreme Court has never ruled on this issue. In deciding this issue the Court may take into account the literature on this subject to declare patents on human genetic material invalid and unenforceable.
The author gratefully acknowledges the generous contribution of Prof. Joshua Sarnoff, RN 36,913.