August 27, 2012

Appeals Court OKs Funding of Embryonic Stem Cell Research

The current legal challenge to federal funding of human embryonic stem cell (hESC) research continues (hESC litigation has been in the courts for several years), and a new appellate ruling on the merits of the challenge has been issued by the Court of Appeals for the D.C. Circuit. Embryonic stem cells are derived from embryos that may already exist (from, e.g., in vitro fertilization) or be newly created. The funding challenge was brought by several adult stem cell scientists who argue that NIH (National Institutes of Health) funding for hESC research violates existing federal law which prohibits the use of federal monies for any research in which embryos are destroyed (see here). The prohibition is found in the Dickey-Wicker amendment, first enacted in 1996. Now, the D.C. Circuit has reviewed a lower court’s ruling that the NIH funding did not violate the law, and it has upheld that decision. This ruling allows those engaged in hESC research to continue, and anticipate future funding opportunities from NIH. However, an appeal of this decision is likely, but beyond that, the politics of hESC research are still volatile and subject to the views of the governing executive branch. In the shift from the Bush to the Obama administration in 2009, the federal funding ban on hESC research was reversed by Executive Order 13503, and NIH is free to make grants for hESC research. Although stem cell policy issues are not  prominent in this year’s presidential campaign, there are pronounced differences between President Obama and Mitt Romney’s positions on stem cell research (Obama supporting embryonic stem cell research, while Romney focusing only on adult stem cell research), such that a GOP victory would likely ensure a return to the Bush-era restrictions on federal funding, while a Democratic win will keep the current policy. A recent article in the New England Journal of Medicine that examined the political climate for stem cell policies reported that 62% of those in a 2011 Gallup poll supported hESC research, suggesting that national support for such research could legitimize a more stable funding policy that reflected existing political consensus. However, federal funding for hESC research, generally interpreted ideologically as related to views on abortion, is likely to remain a political football in the U.S., with consequences for the stability of research plans and general optimism about the future of such research in American science. That volatility is costly.

August 24, 2012

FDA Approval of Companion Diagnostics in Pharmacogenomics

Pharmacogenomics (abbreviated PGx) is the use of genetic information in tailoring or predicting drug response – examples include whether a patient has a particularly favorable genetic profile that indicates that a drug will likely work, or whether the tumor from a cancer patient appears to be genetically vulnerable to chemotherapeutic drugs. In general, the FDA does not regulate the vast field of genetic testing (see here for more background). However, the FDA has been involved in regulating some coupling of genetic testing with the use of FDA-approved drugs (resulting in a companion diagnostic). This paradigm of approving drugs for specific genetically typed populations began with the approval of Herceptin and an accompanying genetic test in 1998. Herceptin is a monoclonal antibody that targets a particular protein on breast cancer cells. The subset of cancer patients who tested for HER-2 positive cancer cells became the target group for the use of this drug. This drug was developed through the detailed molecular study of cancer cells and so the genetic profile for the drug was known at the start. The trend toward the approval of companion diagnostic continues. The FDA definition: "An in vitro companion diagnostic device is an in vitro diagnostic device that provides information that is essential for the safe and effective use of a corresponding therapeutic product. The use of an IVD companion diagnostic device with a particular therapeutic product is stipulated in the instructions for use in the labeling of both the diagnostic device and the corresponding therapeutic product, as well as in the labeling of any generic equivalents and biosimilar equivalents of the therapeutic product." Here is the current FDA list of approvals. The FDA has approved another companion diagnostic for use in the treatment of colon cancer. In this case, the TheraScreen test for mutations in the K-ras gene will be used to evaluate the likelihood that the already approved Erbitux will be effective in the treatment of colon cancer. The infilitration of PGx into drug prescribing does not stop there. Fast forward and we now have dozens of drugs (not all of which are newly developed) which include PGx information on their FDA-approved labels. This reflects the FDA’s increasing embrace of genomic information as a component of the therapeutic information climate, and it continues to advise drug companies who wish to include such information by issuing guidance on how to incorporate a genomic dimension into clinical trials. A number of PGx correlates for drug use have come to light after drug approval, as researchers attempt to identify successes and failures as the drug is used in the general population (see here for earlier story on Plavix and PGx). The PGx field is distinctive in genetic testing as the FDA is taking affirmative steps to manage the use of genetic information in drug prescribing, while it continues to exercise what it describes as “enforcement discretion” with respect to other applications of genetic testing.

August 16, 2012

Genetics or Chemistry? Federal Circuit Again Upholds Gene Patents

The Federal Circuit has just issued its newest opinion in the gene patent case, Association for Molecular Pathology v. Myriad Genetics (AMP v. USPTO). This case was reargued before the court in late July, so this is a quick turnaround (see here). This case is a challenge from a coalition of patients, researchers and medical organizations to the validity of granting patents on isolated genes; specifically, the BRCA1 and BRCA2 breast cancer genes. The Federal Circuit had previously issued a ruling in 2011 which upheld patent claims to genes and DNA primers, while it invalidated method claims that relied on comparing DNA sequences to identify mutations.This latest appeal was directed to the decision on the genes (compositions of matter in patent terms) – and followed a petition to the Supreme Court, which remanded back in view of the Mayo v. Prometheus decision this year. In an opinion again authored by Judge Lourie, the court has returned to much of its reasoning in 2011, holding that isolated genes are not “products of nature” and also do not bear on a law of nature. The court rejects the arguments that the native coding sequences of the isolated genes are identical to natural DNA sequences (and make them products of nature), and finds that the laboratory manipulations that produce the extracted gene are enough to qualify as inventive work. Judge Moore, while concurring, was more receptive to considering how Mayo, although directed to method claims, provides analytic help in evaluating the patentability of genes. She dissected the various patent claim types (primers, cDNAs, genes) to find that the patenting of genes is most problematic because the isolated gene has most of the natural character, and continues to find them valid. There is a hint that she might have ruled against the gene claims ("on a blank slate"), but is constrained by the awareness of the long-standing PTO practice and “settled expectations;” she declares an implicit approval of gene patenting by Congress after its failure to carve out any special legislative treatment for genes, despite a number of bills that have been introduced to do so. Judge Bryson dissented and would have invalidated the patent claims to isolated genes and DNA fragments that mimic natural molecules. He suggests a focus on genetics, not chemistry, in evaluating function, not just structure, and because function is retained, he concludes that the isolated gene is a natural compound ineligible for patenting (that is also my analysis of these patent claims, as I argued here). Bryson also rejects any deference to the PTO or undue concern for any settled practices, noting that there can be no adverse possession claim for patent rights. The ACLU (lead attorneys for plaintiffs) was disappointed in the ruling, calling it a "devastating decision for a woman's health" (PubPat is co-counsel on the case). What’s next? A likely appeal for an en banc review by the full Federal Circuit or another petition for certiorari to the Supreme Court. The Supreme Court will take a more expansive view of the similar policy underpinnings between its Mayo decision and the AMP case, and could take the opportunity to clarify broad principles of patent eligibility that transcend claim categorization.