On December 22, 2011, the Pennsylvania General Assembly adopted two bills (H.B. 332 and H.B. 333) to amend the commonwealth’s Medical Practice Act of 1985 (P.L. 457, No. 112) and the Osteopathic Medical Practice Act of 1978 (P.L. 1109, No. 261) to include provisions that regulate genetic counselors. Pennsylvania Governor Corbett approved the bills and signed them into law the same day.

PA’s GC Law in Context. According to the National Conference of State Legislatures’ survey of state requirements for genetic counselors, in 2008 only six states required licenses to practice genetic counseling (California, Illinois, Massachusetts, Oklahoma, Tennessee, and Utah). Pennsylvania is the latest to join a number of states (including Delaware, Hawaii, Indiana, New Jersey, New Mexico, South Dakota and Washington) that have enacted GC licensing laws since 2008. The National Society of Genetic Counselors reports that additional states (e.g. Florida, Michigan, Minnesota, New York, Rhode Island, Texas, and Wisconsin) are considering similar legislation. While the state licensing requirements are similar, state-by-state variation and nuances in the statutes may exist. The following information pertains to Pennsylvania’s new licensing law only.

Defining the GC Field.  Specifically, the two laws define genetic counseling as “[t]he provision of services to individuals, couples, families and organizations by one or more appropriately trained individuals to address the physical and psychological issues associated with the occurrence or risk of occurrence of a genetic disorder, birth defect or genetically influenced condition or disease in an individual or a family.” They define genetic counselor as “[a]n individual who is licensed to practice genetic counseling by the State Board of Medicine or the State Board of Osteopathic Medicine.” (63 P.S. §422.2 and 63 P.S. §271.2)

The laws prohibit individuals from holding themselves out as genetic counselors unless they are licensed. There are a few notable exemptions to this licensure mandate. One exemption permits individuals licensed to practice medicine (though not licensed as genetic counselors) to provide services that constitute genetic counseling so long as two requirements are met: (1) they are acting within the scope of their licenses and training when they provide those services, and (2) they do not hold themselves out as genetic counselors.  Another exemption permits students to perform genetic counseling, so long as (1) the students are enrolled in a genetic counseling education program that is accredited by either the ABGC (i.e. the American Board of Genetic Counseling) or ABMG (i.e. the American Board of Medical Genetics), (2) the counseling is an “integral part of the student’s course of study,” and (3) the counseling “is performed under the direct supervision of a genetic counselor, licensed physician, certified registered nurse practitioner with a specialty or subspecialty in genetics or clinical nurse specialist with a specialty or subspecialty in genetics.” (63 P.S. §422.13.4(d) and §271.10.3(d))

The laws also stipulate what is required for licensure as a genetic counselor (63 P.S. §422.13.4(e) and §271.10.3(e)): the individual must (1) be at least 21 years of age, (2) be “of good moral character,” (3) have a master’s or doctoral degree in human genetics or genetic counseling from an ABGC- or ABMG-accredited program or otherwise meet the ABGC or ABMG certification requirements, (4) pass the certification exam by the ABGC or ABMG, and (5) complete the application and pay the appropriate fees.

There is a transition phase of three years that permits noncertified individuals to become licensed.

While initial licenses appear to have no continuing education requirements for the initial two years, license renewal will require no less than 30 hours of continuing education within the two years immediately preceding the renewal. (63 P.S. §422.13.4(j) and §271.10.3(j)).

Additionally, genetic counselors are required by these laws to carry professional liability insurance coverage (i.e. malpractice insurance) in the minimum amount of $1,000,000 per occurrence or claims made. (63 P.S. §422.13.4(k) and §271.10.3(k)).

Expanding or Limiting a GC’s Duties?  A provision worth noting for ELSI scholars (particularly those contemplating duties to report, ongoing duties to patients) may be 63 P.S. §422.13.4 (c)(2) and §271.10.3(c)(2)). These sections state:

“When in the course of providing genetic counseling services to a client, if a genetic counselor finds any indication of a disease or condition that requires diagnosis and treatment outside the scope of practice defined in this section, the genetic counselor shall refer the client to a licensed physician or appropriate health care practitioner.”

While it remains to be seen how this provision will be enforced, as written the statute seems to impose a number of duties on genetic counselors. Notice the language is not restricted to “patients” but, rather, imposes a duty to “clients.” It is possible that this word choice was simply in recognition of the fact that those individuals seeking genetic counseling services may not be symptomatic or otherwise fitting of the term “patients.” However, this word choice potentially conveys a much broader class of statutorily protected individuals and will likely permit a fair degree of play if legal disputes ever arise (e.g. who exactly is the client – the individuals tested, the individuals in the room during the counseling, the individual’s family members (all? only first-degree relatives? only first degree genetic relatives?), the person paying for the counseling, etc – and to whom did the genetic counselor owe duties of care).

The provisions’ introductory clause may limit these duties if the clause is interpreted as imposing a temporal restriction to the time of the counseling session (as opposed to ongoing duties if, for example, variants of unknown significance become better understood subsequently) or as suggesting a narrow definition of “client” that would release the genetic counselor from any duties to family members and extended relatives who are outside the clinic’s office door.

The provisions of Pennsylvania’s GC licensing law are scheduled to take effect 60 days after the law was signed, which would be on or about February 20, 2012.

Jennifer K. Wagner, J.D., Ph.D., is a solo-practicing attorney in State College, PA, a research associate at the University of Pennsylvania’s Center for the Integration of Genetic Healthcare Technology

Last month, the Pennsylvania General Assembly voted in favor of a bill that would expand the Commonwealth’s criminal database. PA Senate Bill 775 authorizes law enforcement to begin DNA fingerprinting of individuals upon arrest or charge for certain specified crimes (as opposed to only upon conviction) and authorizes familial searching of the state’s forensic database. After third consideration, the amended version of PA Senate Bill 775 passed by a vote of 42-6. The bill has been referred to the judiciary.

The bill had been introduced in March of 2011 by Pennsylvania Senate Majority Leader Dominic Pileggio, who was later joined by a dozen colleagues (including nine Republican and three Democratic sponsors). It immediately garnered the attention of genetics law scholars, including Penn State Dickinson’s School of Law Professor David Kaye, who submitted a thorough statement (pdf) for the Pennsylvania General Assembly’s consideration.

The bill as passed is significantly different from the original bill in at least one respect. The original version of the bill had a narrow, onerous expungement process. That process required an individual to petition the government to have its DNA sample and profile expunged. This process would have put a considerable burden on arrestees whose DNA sample and corresponding DNA profile had been collected at booking. As originally drafted, expungement could only be granted if the individual established by clear and convincing evidence (a relatively high burden of proof) that (1) the charges were dismissed or never filed, (2) there had been an acquittal of the charges, or (3) inclusion was by mistake.

The amended version (pdf) has made the expungement process automatic in some circumstances, mandating that the individual’s DNA sample, record, and profile be expunged if the:

• conviction has ultimately been reversed and the case dismissed;
• charge leading to the individual’s inclusion in the database has been dismissed with prejudice;
• individual has been acquitted of the charge that led to inclusion in the database;
• individual was never charged for the crime that led to the individual’s inclusion in the database;
• prosecutors have decided not to prosecute the individual for the crime that led to the individual’s inclusion in the database;
• charges were not filed within the statute of limitations; or
• individual has been issued an unconditional pardon for the crime that led to inclusion in the database.

It is notable that PA Senate Bill 775 does not limit familial searching to partial CODIS matches but also explicitly authorizes mitochondrial DNA analysis, Y-chromosome analysis, and “[a]ny other suitable method designed to determine that a crime scene DNA profile originated from a close relative of an individual in the State DNA Data Base.”

Ultimately, PA Senate Bill 775’s authorization of familial searching would distance the Commonwealth from its southern neighbor, as familial searching is prohibited in Maryland. Familial searching, discussed on several occasions here at the Genomics Law Report, is permitted in only a few states (including California, Colorado, Texas, and Virginia). A recently published policy report provides valuable background information for those seeking further information on the topic.

The Plaintiffs’ Petition. Two things are interesting about the plaintiffs’ petition from a procedural standpoint. First, the ACLU lawyers requested rehearing by the three-judge panel that decided the case earlier this summer, not en banc rehearing by all members of the court. (But a majority of the judges of the full court could still decide to rehear the case en banc; they could do so if they found that the case “involves a question of exceptional importance.”) Second, the plaintiffs have asked for rehearing on only two of the issues they lost: that isolated genes are proper subject matter for product patents, and that only one of the named plaintiffs—Dr. Harry Ostrer, formerly of NYU—has standing to bring the case. The plaintiffs did not challenge that portion of the panel’s decision that upheld—unanimously—Myriad’s patents on a method of screening potential cancer therapeutics.

On the product patent issue, the plaintiffs contend that the panel failed to give proper consideration to “whether the DNA fragments claimed in these patents are products of nature.” In support of this conclusion, they argue two points: First, they emphasize that the 2-1 majority’s focus on the chemical structure of isolated genes was misplaced, because the patent claims at issue talk about function. While isolated DNA might be literally different from naturally occurring DNA at a structural level, they argue, it is functionally identical, and thus properly characterized as products of nature. Their second point is that “DNA fragments identical to those claimed in the patents appear in the body.” Specifically, “nature breaks the covalent bonds that hold together the full chromosome” during meiotic recombination, cell replication, and double-stand breakage. Hence, Judge Lourie’s reliance on “cleavage” to distinguish isolated DNA fragments from products of nature was misplaced.

Standing and Myriad’s Petition. With respect to standing, the plaintiffs argue that at least two other named plaintiffs—the American College of Medical Genetics, of which Dr. Ostrer is a member, and Yale geneticist Ellen Matloff—are engaged in ongoing controversies with Myriad and thus have standing.

Adding these plaintiffs could prove critical, since the sole argument raised in Myriad’s petition is that Dr. Ostrer does not have standing. The original Federal Circuit opinion found that he had standing because of a controversy related to his work at NYU. As we reported, however, at the time that opinion was issued Ostrer was in the process of moving to Albert Einstein College of Medicine. Myriad now points out that the move is complete and argues, that since Ostrer’s controversy with Myriad was based entirely on his employment at NYU, the controversy is now moot. Since the standing requirement is ongoing, if the court agreed that Ostrer no longer had standing, and if it refused to find that the ACMG or Matloff or any other plaintiff had standing, then it would have to dismiss the case. (By the way, Myriad is trying to have it both ways: it asks the court to dismiss the case for lack of standing but not to withdraw its previous opinion as legal precedent.)

Tactically, the plaintiff’s petition is a little hard to understand. It makes sense to ask the court to revisit the product and method patents decisions—especially the product issue, since it was 2-1, with a strong dissent—but why not ask the whole Federal Circuit, instead of just the original panel? Perhaps their decision was to target Judge Moore, who agreed that isolated DNA is patentable, but took 31 additional pages to say why. The thinking may be that, since she didn’t sign on to Judge Lourie’s reasoning, she can be persuaded to change her mind entirely. It was also essential to raise the standing issue, since Ostrer, on whom the whole case currently depends, may be on thin ice. But again, why not raise this issue for the whole Federal Circuit?

Myriad’s approach makes more obvious sense. Having won most of the contested issues, why not stick with the original panel? Also, Myriad’s lawyers probably concluded that the substantive issue they lost—the patentability of a method of analyzing and comparing normal and mutant DNA sequences—was unwinnable. The standing issue was a closer call. If the panel rehears the case, Dr. Oster’s case might well be found to be moot. But Myriad would then risk having the generally favorable opinion withdrawn and the case simply dismissed. Why do anything to jeopardize what was, for the most part, a win?

What’s the next step? The Federal Circuit will rule, presumably fairly quickly, on the petitions for rehearing, and could also decide on its own to take the case en banc. “Cert” petitions seeking Supreme Court review would follow either a denial of rehearing or the Federal Circuit’s decision following rehearing.

The legal and ethical uncertainty surrounding surreptitious genetic testing—which can be broadly defined as any genetic test performed without the knowledge and/or consent of the individual tested—first piqued the public′s interest shortly after the 2008 election thanks to an editorial by Bob Green and George Annas in The New England Journal of Medicine. Green and Annas worried that “persons or groups opposing a candidate [and] hoping to harm his or her chances for election” would obtain and release genetic information without consent, a form of “genetic McCarthyism.” This would not be very difficult, the authors concluded, since “sufficient DNA for amplification and analysis can be obtained from loose hairs, coffee cups, discarded utensils, or even a handshake.”

Nearly three years later, surreptitious genetic testing is back in the news thanks in large part to an in-depth article by Eriq Gardner in the current issue of the ABA Journal. Gardner′s piece examines the practice of surreptitious genetic testing, provides a compelling anecdote from a confessed “DNA thief” and highlights many of the privacy concerns associated with the practice.

The confusing legal landscape of surreptitious genetic testing was covered in detail by the Genomics Law Report late last year, and again early this year following the introduction of legislative proposals in Massachusetts, Vermont and California, each of which would have enhanced individuals′ rights in their DNA samples and data. But Gardner′s piece has drawn new attention to the topic from several law and privacy publications, including The Wall Street Journal′s Law Blog, and also prompted a regular Genomics Law Report reader to dig up another piece of proposed state legislation, this time from Texas.

Texas to Tackle Surreptitious Genetic Testing? The Texas legislation (HB 2110), which was introduced and referred to committee in March, is short and to the point. It would revise the state′s property code to include the following key provision:

Sec. 3.002. PROPERTY RIGHT ESTABLISHED.  (a) Subject to Subsection (b), an individual has an exclusive property right in a DNA sample provided by the individual. A person may not, without the informed, written consent of the individual or the individual′s legal guardian or authorized representative:

(1) collect a DNA sample from an individual;

(2) perform a genetic test on an individual’s DNA sample; or

(3) retain an individual′s DNA sample.

The proposed legislation includes expected carve-outs for genetic testing performed in emergency medical, forensic or other similar settings, as well as civil and criminal penalties for statutory violations. Unlike legislation introduced earlier this year in other states, particularly in Massachusetts and Vermont, the Texas legislation is carefully limited in its scope. Absent from HB 2110 are declarations about the “fair market value” of a genome (MA), attempts to expand the legislation′s focus to encompass tangentially related topics such as medical records and gene patents (VT) or efforts to plug acknowledged gaps in the protections provided by the Genetic Information Nondiscrimination Act (MA, VT and CA).

Also noteworthy is HB 2110′s clear statement that the “informed, written consent of the individual or the individual′s legal guardian or authorized representative” is all that is needed to remove a genetic test from the realm of criminal conduct. This is a welcome departure from far more complicated provisions pertaining to DNA sample ownership and control contained in the MA and VT legislative proposals, which have cast doubt on the implications of those pieces of legislation, should they pass, for genomic research conducted in those states. The language in HB 2110 should reassure researchers in Texas and elsewhere that the state does not intend to interfere with ongoing or future genomic research projects (which are already premised on securing the informed, written consent of participants).

A Lesson From Texas. The Texas legislative proposal is largely a positive one, thanks primarily to its simplicity and clarity. In fact, HB 2110 bears a close resemblance to Alaska′s current genetic privacy statute (§§ 18.13.011 et seq.), which is one of the toughest and clearest genetic privacy laws in the nation. Unlike HB 2110, however, Alaska′s statute contains (1) an additional prohibition on the disclosure of results from a genetic test, (2) additional carve-outs from the prohibition on genetic testing, including for paternity testing (one of the most common instances of surreptitious testing) and (3) far more aggressive civil penalties (more than $100,000 if the violation occurred in a for-profit setting).

Differences aside, HB 2110 would make it crystal clear that surreptitious genetic testing is a crime under Texas law, and it would do so without raising concerns about the legislation′s unintended effects on genomic research or the use of genetic information in healthcare, as is the case with the Massachusetts and Vermont proposals. In addition to its clarity and simplicity, HB 2110 is also timely. As we wrote late last year:

Each year, the availability of low-cost, high-quality genetic information expands. Along with a wide array of legitimate and beneficial uses, the growing accessibility of this genetic information brings with it an increasing number of opportunities to employ and to abuse surreptitious genetic testing. As we continue to push forward into the era of personal genomics, the time has come to seriously discuss a comprehensive legal framework for surreptitious genetic testing.

As the swarm of presidential hopefuls, media and political partisans gather in Iowa this weekend, HB 2110 should serve as yet another reminder that there is no comprehensive federal legal framework for addressing surreptitious genetic testing (as for Iowa, at least as of 2008, it too lacked a law clearly banning such testing). This is a fact that the various presidential candidates (including Texans Ron Paul and Rick Perry) would do well to keep in mind as they head off down a campaign trail which will see them traverse the country to shake hands with thousands of strangers, leaving untold used coffee cups and uneaten pizza crusts in their wake, each one a target ripe for surreptitious genetic testing.

For the most part, the Federal Circuit’s 2-1 decision returned the law to the state it was in before District Judge Sweet’s opinion turned things upside-down last March.  Although full of interesting rhetoric, the court’s three lengthy opinions (a total of 105 pages) are less remarkable for what they decide than for what they invite higher authorities—the Supreme Court and the Congress—to decide down the road.

First, the scorecard.  The court’s judgment—that is, the holding, or outcome—was joined by Judges Lourie and Moore.  A third member of the panel, Judge Bryson, dissented in part, meaning that he joined only a portion of the judgment (more on that below) and disagreed with another part.

The majority held as follows:

1. On the threshold procedural question of standing, the district court’s ruling was affirmed, with one plaintiff (Dr. Harry Ostrer) having sufficient standing to challenge Myriad’s patent claims.
2. Isolated genes, cDNAs and partial isolated gene sequences are patentable subject matter under § 101 of the Patent Act.  Consequently, the district court’s judgment invalidating all of Myriad’s product claims to BRCA genes and fragments was reversed in its entirety.
3. Myriad’s claims to methods of screening potential cancer therapeutics by analyzing growth rates of cells with altered BRCA genes in the presence or absence of the treatments were also held to be directed to patentable subject matter, so the district court’s judgment of invalidity was reversed here as well.
4. Myriad’s claims to methods of analyzing BRCA gene sequences and comparing those with cancer-predisposing mutations to normal or wild-type gene sequences were held not to be directed to patentable subject matter.  The district court’s decision was thus affirmed with respect to these claims.

Counting up the votes. Judge Lourie wrote the so-called “opinion of the court” that announces the judgment and gives the rationale.  Judge Moore wrote a concurring opinion, meaning that she joined all aspects of the judgment.  She also agreed with Judge Lourie’s reasoning with respect to the method claims and the patentability of isolated cDNA sequences.  However, she had a slightly different reason for upholding the patentability of DNA sequences, and decided to explain her thinking at some length (31 pages!).  Finally, Judge Bryson joined in the judgment with respect to the method claims and the patentability of longer sequences of cDNA.  However, he voted against the patentability of all isolated DNA sequences as well as very short cDNA sequences, and would thus have affirmed the district court on that specific point.  His somewhat more succinct opinion (19 pages) explains his thinking.  Since he was in the minority on this point, his opinion does not have the force of law.

So, for those keeping score at home, here is how the judges came down on each issue:

1. Standing: 3-0, since one plaintiff has standing to challenge Myriad’s patents, the case can proceed.
2. cDNA: 3-0, cDNA is patentable (although for smaller cDNA molecules, the vote was 2-1, with Bryson dissenting).
3. Method claims: 3-0, with therapeutic screening claims upheld and comparing or analyzing claims invalidated.
4. Isolated DNA: 2-1, isolated DNA is patentable.

The majority’s rationale. With the bookkeeping out of the way, let’s take a look at how the judges reasoned their way through Myriad.

The plaintiffs’ standing.  After opening with a genetics tutorial, the Lourie opinion addressed the very technical but nonetheless critical issue of standing.  As we discussed after the Myriad oral argument, standing is a constitutional question, and it boils down to whether the plaintiffs have a sufficiently direct and immediate interest in the outcome to be proper parties to file the case.  Had the court found no plaintiffs to satisfy the threshold standing requirement, it would have dismissed the case without ever reaching the patent issues.  The court found that there was standing, but it was very close.

Only one plaintiff—Dr. Harry Ostrer of (for the moment; more on that below) NYU Langone Medical Center—was held to have standing.  That was because he alleged that Myriad forced him to stop offering BRCA clinical testing more than ten years ago by threatening infringement litigation, and that he remained ready, willing, and able to resume testing if the patents were held invalid.  One plaintiff with standing was enough for the court to proceed to the merits.

It should be noted, however, that last Wednesday, just before the Federal Circuit released its opinion, counsel for Myriad submitted a letter to the court (pdf) alleging that Dr. Ostrer’s impending move from NYU to Albert Einstein College of Medicine deprives Dr. Ostrer, and thus the Myriad plaintiffs, of standing.  While the Federal Circuit apparently did not see enough in Myriad’s last-minute letter to alter its standing analysis, the letter points out, correctly, that the standing requirement is an ongoing one which must continue to be met at all points during the appellate process.  As Myriad heads through subsequent appeals (discussed below), the issue of the plaintiffs’ standing to maintain their challenge will continue to loom in the background.

Turning to the product claims (the so-called “gene patents”), Judge Lourie reviewed more than 100 years of cases dealing with all kinds of substances with natural precursors or analogs.  He identified—correctly, in our view—the two key authorities as the Supreme Court’s opinions in Chakrabarty (holding genetically engineered bacteria to be patentable subject matter) and Funk Brothers (holding unpatentable an inoculum that combined bacterial species not known to co-exist in nature).  He concluded that the test was whether the claimed substances were “markedly different—have a distinctive chemical identity and nature”—from the naturally-occurring version.

The patentability of DNA.  cDNA sequences presented the easiest question for the court.  Even Judge Bryson agreed that cDNA is generally patentable, since it is a human-made molecule and the body does not naturally contain DNA in exactly this form (with introns spliced out).  However, as discussed below, Judge Bryson would have ruled differently with respect to particularly short sequences (as few as 15 base pairs) of cDNA.

When it came to the product claims, the real controversy concerned isolated genes and sequences in DNA form.  The district court had focused on the similarity in function and information content between natural and isolated genes, downplaying the chemical and structural differences that patent lawyers and the USPTO had always relied on.  As Judge Sweet wrote last year (pdf):

DNA represents the physical embodiment of biological information, distinct in its essential characteristics from any other chemical found in nature. It is concluded that DNA’s existence in an ‘isolated’ form alters neither this fundamental quality as it exists in the body nor the information it encodes.

Sixteen months later, Judge Lourie came down on the other side, focusing on the “cleaving” of isolated DNA out of its chromosomal environment as conclusive evidence of its fundamentally different nature.  (Curiously, he claimed that “cleaving” DNA from its chemical environment is fundamentally different from “isolating” a substance from an impure environment, which has sometimes been held insufficient to support patentability.)

The arguments about whether isolated DNA is sufficiently distinct from its natural counterpart are well-known, and neither side has an absolutely compelling case.  It seems to come down to an economic value judgment, and the Lourie and Moore opinions both reflect this reality.  Both majority judges put great emphasis on the dangers of upsetting thirty years (and 2,654 isolated DNA patents, by Judge Lourie’s count) of what Judge Moore called “settled expectations and extensive property rights.”  Both counseled deference to Congress, while Judge Lourie was “particularly wary” about a lower court expanding on an exception to patentability (the product of nature doctrine) that comes out of Supreme Court case law, not the Patent Act itself.

The method claims.  The judgments from the court on both categories of method claims were unanimous, as noted above.  Recall from our previous articles that the state of the law (such as it is) on methods generally is reflected in the Supreme Court’s confused and confusing 2010 decision in Bilski v. Kappos.  That case focuses on whether a method patent claims abstract processes (unpatentable) or specific applications (patentable), and expresses particular concern about method patents that preempt all uses of an abstract process.  In addition, Bilski held that the Federal Circuit’s machine-or-transformation (MoT) test could not be used exclusively, but could be an “important clue” to patentability.

In Bilski, the Supreme Court declined to provide any guidance for the proper application of the MoT test in a biotechnology context.  However, earlier this summer the Supreme Court agreed to review the Federal Circuit’s decision in Prometheus v. Mayo, which has twice upheld the patentability of a method of administering a drug, determining the level of the drug in a patient’s bloodstream, and then adjusting the dosage accordingly to maximize therapeutic efficacy.

Myriad’s analysis and comparison claims failed the test completely, earning a solid “F” from the Federal Circuit.  Judge Lourie wrote that such claims lack any “necessarily transformative step” and, in the end, “recite nothing more than the abstract mental steps necessary to compare two different nucleotide sequences.”

Myriad’s claim on a method of screening potential cancer therapeutics, on the other hand, was “not so manifestly abstract as to claim only a scientific principle.”  It also passed the still-breathing MoT test, since it involves the “transformative” steps of growing host cells in the presence or absence of a cancer therapeutic and then determining and comparing their growth rates.”  This was viewed as fundamentally different from simply comparing two DNA sequences.

Returning to the unpatentable claims to the analysis and comparison of DNA sequences, it is striking how much Judge Lourie emphasized the semantics of patent claim-drafting.  With Prometheus undoubtedly on their minds, Myriad’s lawyers had argued that this method actually did involve transformation.  They pointed out, for example, that here, just as in Prometheus, there was a “determining” step—in this case, of “the sequence of BRCA genes by, e.g., isolating the genes from a blood sample and sequencing them.”  Judge Lourie noted, though, that this step, while described elsewhere in the patent, was not part of the claims, by which patentable subject matter must be exclusively judged.  In Prometheus, by contrast, the determining step was in the claims.

It is hard to read this as anything but an invitation to patent lawyers to bring methods as abstract as Myriad’s within the ambit of patentable subject matter simply by putting more (perfunctory?) technical detail in the claims themselves.  As we have written previously, if clever draftsmanship is all that is ultimately required to satisfy the MoT test in many instance, the courts will have created “a potentially enormous opening through which to push all manner of personalized medicine patents replete with diagnostic, measurement, correlation and other interpretive or mental steps.”

The isolated DNA dissent. Judge Bryson argued in the same terms as the majority about the isolated DNA clams, and then reached the opposite conclusion.  Taking on Judge Lourie’s cleaving argument, he wrote that “there is no magic to a chemical bond that requires us to recognize a new product when a chemical bond is altered or broken.”  Agreeing with the district court about the paramount importance of the information content of genes, he concluded that “what is claimed in the BRCA genes is the genetic coding material, and that material is the same, structurally and functionally, in both the native gene and the isolated form of the gene.”

Perhaps more significantly, Judge Bryson also reached the opposite conclusion with respect to the economic implications of invalidating Myriad’s patents.  The—to him—“breathtakingly broad” claims to cDNA and DNA sequences as short as 15 nucleotides led Judge Bryson to look beyond the possibility of overturning biotechnology’s “settled expectations” and to the future effect of “a thicket of patents.”  This patent thicket, at least to Judge Bryson, presents “a significant obstacle to the next generation of innovation in genetic medicine—multiplex tests and whole-genome sequencing.”  He made a further point that we can confirm on the basis of our own experience: that “the costs involved in determining the scope of all those patents [in the thicket] could be prohibitive.”

Judge Bryson also departed from his colleagues in declining to give any deference to the USPTO’s 30-year practice of allowing isolated gene patents, on the grounds that it had never done any serious analysis of the subject matter issue.  Judge Bryson’s argument was buttressed by the Department of Justice’s amicus brief last fall, which advocated a dramatic departure from the PTO’s prior gene patent practice, as well as by a citation to an article by one of us (John) detailing the PTO’s limited review of these issues.

What happens next in Myriad? Since both Myriad and the plaintiffs both won and lost, both parties are eligible to seek further review, and both probably will.  One possibility is to ask the Federal Circuit for en banc review by all of its active judges (currently ten) sitting together.  This is relatively rarely granted, but more often in the Federal Circuit than in other federal courts of appeals because of its judges’ penchant for split decisions and major disagreements about fundamental doctrine.  So it is a real possibility.

After review en banc, or sooner if that appeal is not granted, both parties could petition for certiorari (cert), or further review, by the Supreme Court.  The Court grants cert in fewer than 100 cases in most years, denying the vast majority of cert petitions.  However, the Court has taken more patent cases in recent years, and this is an important one, with obvious economic and scientific implications, so it is a promising candidate.

But—remember that the Court already has Prometheus on its docket, which could settle the methods questions present in Myriad.  Among the possibilities here (yes, that was a reference to Monty Python’s Spanish Inquisition skit) are: (1) the Court takes the whole Myriad case; (2) it takes only the product claims issues, assuming that the method issues will be settled—at least for future cases—by Prometheus; (3) it takes Myriad and consolidates it wholly or in part with Prometheus, which would likely delay both cases until the 2012 term; or (4) it denies cert in Myriad and lets the Federal Circuit’s ruling stand as is.  All we can know for sure is that Myriad, still, likely has quite a ways to go before a final resolution.

What does the Myriad decision mean for the real world? First and foremost, this opinion restores—at least for the time being—the gene product patent world to the state it was in before the district court’s bolt out of the blue last spring.  So one reaction is, move along, people, nothing to see here.  But we emphasize at least for the time being.

As we said, this case has miles to go before it sleeps.  And it was a 2-1 decision, so the anti-gene patent position is neither crazy nor hopeless.  Judge Lourie ended up making a very debatable call (on how different isolated genes are from their natural counterparts) on which reasonable minds can differ.  Judge Moore was sufficiently dissatisfied with Judge Lourie’s reasoning that she took 31 pages to explain her own, ultimately (in our view) adding very little.

So there remains a high probability that there will be more said about the patentability of (in particular) isolated DNA sequences, probably by the courts (either the Federal Circuit en banc) or the Supreme Court, and possibly by Congress (if they ever manage to fix their debt ceiling distractions).

That said, how much difference will the final product patent decision in this case really make?  Myriad’s own product patents will begin to expire in 2014.  By the time Myriad wends its way through all available appeals, the biotechnology industry and clinical geneticists may have, collectively, innovated their way around the patents held by companies like Myriad.

Recall Judge Bryson’s fears about the impact on whole-gene sequencing.  Are those fears justified?  Judge Lourie repeatedly stressed cleaving the claimed isolated gene out of its natural environment.  Whatever you think of that argument in the context of the isolation of single genes, do present and forthcoming whole-genome sequencing technologies require the same cleavage?  In other words, do/will those technologies infringe patents on isolated DNA sequences using the analysis presented in Myriad?  That question has yet to be fully and formally asked, and will almost assuredly not be addressed by the Myriad litigation.  Which means that, whatever the outcome in this case, patent litigators with Ph.D.s in genetics should remain gainfully employed for the foreseeable future.

We should also look beyond the threshold question of patentability under Section 101.  As we have written previously, the real action on gene product patents is occurring under other sections of the Patent Act that deal with novelty, non-obviousness, and the written description requirement.  These sections’ requirements have been repeatedly tightened, with an overall effect of “nibbling around the edges” of gene patents, as we have put it.  The Myriad court’s reference to all of these sections—none of which is in play here—underscores the point that passing the subject matter test barely gets you out of the batter’s box, let alone to first base.

We have also written (e.g., here) that the disposition of method claims, in Myriad but also in Prometheus and other cases, will ultimately prove more important to the personalized medicine industry.  This case—unanimously—invalidates some of the broadest diagnostic method claims.  But even that rejection comes across as relatively toothless, given that Judge Lourie offered a roadmap for the alert patent lawyer to reword such claims so that they might survive.  That’s good news for those who might profit from broad method claims, cause for concern for those who might be inhibited by them, and a clear reminder that plenty more work (and, likely, litigation) is yet to come.

Ultimately, as Myriad pushes into its third year, our advice remains the same as before: keep watching—not just Myriad, but Prometheus as well, which is running slightly ahead on a parallel track—and know that, while the debt ceiling may yet cave in around us, whether the pigs will ultimately rule the gene patent sky remains to be seen.

Patent Reform Legislation Passes House. Several months after the U.S. Senate passed patent reform legislation that would make sweeping changes to America’ patent system, including a switch from a first-to-invent to a first-to-file system for awarding patents, the U.S. House of Representatives finally followed suit yesterday, passing a similar piece of legislation by a vote of 304-117. The version passed by the House, while similar to that passed by the Senate, contained a number of last-minute amendments (pdf).

One change of particular relevance to the personalized medicine community was the removal of a proposed safe harbor for second opinion genetic diagnostic testing, which was replaced by a requirement that the U.S. Patent and Trademark Office (USPTO) investigate the relationship between genetic diagnostic tests, gene patents and exclusive licenses. The USPTO would be given nine months to complete its investigation and to return to Congress recommendations for ensuring the availability of second opinion genetic diagnostic testing. (The USPTO study on genetic diagnostic testing was not included in the bill passed by the Senate in March.)

With both the House and the Senate having now passed patent reform legislation, the next step appears to be a House-Senate conference to resolve inconsistent provisions in the two bills, although according to The Hill it is unclear how soon such a conference will take place.

UK Government Pulls Plug on Human Provenance Project. Nearly two years after the Human Provenance Project was first unveiled (to substantial scientific criticism), the government agency responsible for the project, the UK Border Agency, has finally pulled the plug. The project would have used DNA and isotope analysis of tissues from asylum seekers in an attempt to evaluate their nationality and render immigration decisions. After a wave of criticism following the program′s announcement, and after spending more than $300,000 on screening, the UK Border Agency has scrapped the program in its entirety.

As we wrote back in 2009, the poorly conceived project threatened to disrupt what has been—in both the UK and in the United States—a slow and delicate process to craft legislation, regulation and policies that promote genomic science and the use of personalized genomic data while addressing concerns over the potential misuse of those data. As we wrote then, “with so much genomic science and policy yet to be written, even minor developments produce outsized effects, which makes the potential consequences of the Border Agency’s project so worrisome.”

Thankfully, the UK Border Agency quickly paused the project following initial concerns and, nearly two years later, it appears that no lasting damage has been done. Still, the Human Provenance Project should serve as a reminder to governments worldwide of the need to carefully and publicly vet state-directed personal genomics programs prior to their implementation.

Roundup of tweets from the intersection of genomics, personalized medicine and the law:

• Combined w/ this week’s GenomeQuest announcement (http://bit.ly/kCp0j2) & it’s clear clinical, commercial WGS is here. Now.
• Omicia releases genome annotation software (incl. for clinical/commercial applications) http://bit.ly/l1XpJ6 HT @neandrothal @EricTopol
• FDA report on challenge of monitoring imported food, drugs (http://1.usa.gov/mmWpgd) hints at > difficulty monitoring info-based Dx/devices.
• Study: FDA device clearance times rose 37% since 2006: http://bit.ly/jRxrrV Other news: FDA device studies criticized: http://bit.ly/jGVBH0
• FDA accused of focusing too much on safety (http://bo.st/mCCad9) & of doing too little: http://bit.ly/il4maZ Damned if you do…
• Finally responding to this @genomesunzipped thread. Agree w/ @dkgppc re: need for more data: http://bit.ly/mERhg8 Any ideas how to collect?
• The beat(down) goes on: FDA accused of being a “wet blanket” & “crushing innovation” by MA senator: http://bo.st/kTWrmk
• GLR Post: Prometheus Returns to the Supreme Court, Medical Method Patent Speculation Intensifies: http://bit.ly/kqnDWP
• MT @danielg280: Doing a Webinar 6/21 on legal issues re healthcare & social media w/ @healthblawg http://bit.ly/l2SFvY
• High-level explanation from @wilbanks why for patents, unlike copyrights, transparency is priority #1: http://bit.ly/mRqJAv
• Great idea. MT @RyanMFierce: NC wants to help cash-strapped biotechs w/ $100M in loans http://bit.ly/mau3Gj cc @GlenCaplan
• Still, for efforts like the Human Provenance Project, it can be difficult to unring the bell: http://bit.ly/kRciNK
• $300K too late, but right decision. RT @NatureNews: UK immigration cancels DNA screening programme http://goo.gl/fb/YwQ49
• “The 3 letter word for-the gene FOR something-is the most dangerous word in genetics.” http://bbc.in/mKTY1P HT @eurogene
• MT @matthewherper @ivanoransky @charlesornstein: Despite FDA Criticism, Cancer Drugs Reach Pts Sooner In US Than Europe http://bit.ly/msJTuL
• RT @SampleGW: New Consortium Aims to Streamline Accreditation, Proficiency Testing: http://bit.ly/lBJBLD
• Let’s just hope we do better than MSWord. RT @FierceHealth: Patient rights, safety at heart of #EHR track changes debate http://htl.li/5jkIR
• RT @SampleGW: Medicare to Cover Pathwork Diagnostics’ Tissue of Origin IVD Nationwide: http://bit.ly/kIIOmW
• Well said, @23andMe: “research is a two-way process, where participants are valued as partners in sci. discovery.” http://bit.ly/lgWLrW
• GLR Post: Update: Proposed Second Opinion Safe Harbor for Genetic Diagnostic Testing Withdrawn: http://bit.ly/kOX7qx
• ACLU-led coalition opposes proposed safe harbor for 2nd opinion Dx testing, citing “unintended harms”: http://bit.ly/lJKrqL
• Not only co. to shift focus, at least for moment. MT @RyanMFierce 95% of @Knome revenue from R&D, 5% from customers. http://bit.ly/lFwPow
• House debate on patent reform bill delayed until (at least) next week: http://bit.ly/jtbjY1
• RT @dgmacarthur: New community forum for @CompleteGenomic users: http://bit.ly/kHoys3 Just signed up – interested to see how active it gets.
• GLR Post: DTC Genetic Testing and the FDA: is there an end in sight to the regulatory uncertainty? http://bit.ly/koxrjn
• GLR Post: House Introduces Patent Reform Proposal to Permit 2nd Opinions in Genetic Diagnostic Testing http://bit.ly/j5DeWl
• AdvaMed’s “competitiveness policy” urges creation of “office of medical innovation policy” w/in White House: http://bit.ly/iqXXv9 Good idea.
• “Med-tech CEOs storm Capitol Hill”: http://bit.ly/iBBJNz by @MassDevice Seem unlikely to hear Shuren’s plea for mercy
• Meanwhile, @dgmacarthur @lukejostins & I wonder when DTC regulatory uncertainty might end: http://bit.ly/lxLKda
• CDRH Director Shuren says criticism is affecting hiring, slowing agency: http://bit.ly/maZddr HT @dgmacarthur
• Ion Torrent ($LIFE) expects 400bp reads by year end, $1K genome beginning of ’13: http://bit.ly/kf3tVZ @InSequence
• Update on Noblegen’s “optipore” sequencing tech; targeting clinical seq tests, ’14 debut: http://bit.ly/m55KhH @InSequence
• RT @BVBigelow: BioNanomatrix Moves HQ and nano-scale molecular analysis tech to San Diego’s diagnostics cluster. http://bit.ly/iA2JHx
• RT @RyanMFierce: Broad Institute’s planned expansion roughly the size of two Wal-Mart stores. Wow. http://bit.ly/lCBlsf by @BBJNewsroom
• RT @DailyNewsGW: NIH Awards $200M for New CTSA Sites: http://bit.ly/lO3pdA
• Twin’s rare disease diagnosed, cured. Another “win” for whole-genome seq: http://bit.ly/kuxupr by @Erika_Check HT @drgitlin
• RT @PGxReporter: MDx/PGx Highlights from ASCO 2011: http://bit.ly/mJSwL1
• GLR Post: House Introduces Patent Reform Proposal to Permit 2nd Opinions in Genetic Diagnostic Testing http://bit.ly/j5DeWl
• RT @JohnCFierce: Cancer collaborations are all the rage – but you already knew that. http://bloom.bg/jyuqHA by @robertlangreth
• The “strangest biotech of all” ($UTHR) by @matthewherper, incl a look at its comic book annual report (really): http://onforb.es/lNfZ9w
• RT @dgmacarthur: MT @westr Illumina launching 5M-variant whole-genome genotyping array – the Omni5 – focus on rare variants: bit.ly/ilnaL2
• RT @ldtimmerman: Getting ready for debate on open source bio w/ @sagebio founder Stephen Friend, MIT’s Phil Sharp http://bit.ly/jshQ77
• +1. RT @neandrothal: Chrome extension soon? MT @dgmacarthur: update to handy @SNPTips FireFox plugin for @23andMe data: http://bit.ly/iCDxuP
• The perfect Father’s Day gift? It’s probably not a paternity test: http://bit.ly/iG1QJ9 by @SampleGW
• Here’s more from @23andMe on the breakdown of their database: http://bit.ly/lfldx2 Note that not entire 100K have opted in for research.
• DTC company @23andMe continues to reposition itself, emphasizing reasearch database (now 100K): http://bit.ly/mNnJPF
• Following @phylogenomics for tweets from #synbio5, including current coverage of @geochurch’s talk.
• RT @dgmacarthur: Serious congrats to @markgfh, who won both the European Best Cancer Reporter award & Royal Statistical Society prize today!
• Beginning w/ improved understanding of heterogeneity. RT @FierceBiotech @MaverickNY: changing cancer research paradigm. http://bit.ly/mtJc4y
• RT @JohnCFierce: My take on E&Y’s annual biotech report: It’s tough out there, says Giovannetti http://bit.ly/mm2pN3
• MT @Knome: Today we announce the launch of kGAP 2.0, the 2nd ver. of our #genome interpretation engine http://ow.ly/5hfR7
• RT @genomesunzipped: New Interpretome website provides many handy tools for analysing your @23andMe data: http://bit.ly/lHd2Yw
• RT @LifeSciVC: Welcome my Atlas partner @JFFormela to the Twittersphere. He will undoubtedly have blazing content & sharp wit to add
• RT @westr: 23andMe’s customer breakdown by ethnicity, via @CeCeLMoore http://tinyurl.com/3h5zcv8
• RT @GenCounsNews: Update on advanced degree task force for genetic counselors, including a webinar later this summer http://bit.ly/ilBTHD
• & SEC. Still, can be done. RT @elainewestwick: suspect IP/secrecy concerns a challenge re: Twitter/biotech http://bit.ly/kTWx63 @ldtimmerman
• Brief recap from last week’s MDMA meeting, including familiar FDA criticism from Senator Hatch: http://bit.ly/jwEzdv by @FierceMedDev
• Commons Principles from @Sagebio posted: http://bit.ly/jHEAp2 Ambitious, essential & endorsement-worthy. Add your voice.
• Congrats to @KeonaHealth, Sarda Tech (my dad’s new venture) & others on NC IDEA innovation grants: http://bit.ly/mKsgJd
• Exciting news. RT @neandrothal @NextBio: blog is back w/ a screenshot of upcoming new public site! http://wp.me/pmGXL-e6
• DTC genetic testing company @Lumigenix: “our response to a recent letter from the FDA”: http://bit.ly/lzfL6o
• “I joined GenomeQuest b/c they offer technology to make whole genome dx avail. to patients today-not 10 yrs from now.” http://bit.ly/jR2gVx
• Why Twitter matters for biotech, by @ldtimmerman: http://bit.ly/kTWx63 No surprise, lawyers even slower to adopt Twitter.
• Post by @eurogene on breast feeding, IQ, genetic testing & DTC: http://bit.ly/lGjrDp Comments from @23andMe or @ExistenceG?
• $0.02 from @matthewherper on @patientslikeme tool to match patients to trials using Clinicaltrials.gov: http://onforb.es/m3VmVw
• RT @dgmacarthur: Congrats to @genomesunzipped colleague Don Conrad on his new Nat Genet paper on human mutation rates: http://bit.ly/mhyXgu
• RT @drjonboyg: Raised in this wk’s In Our Time: was germ theory or cracking genetic code biggest leap in human health? http://bit.ly/mkY7p8
• Will need more than 31 senators. RT @NatureNews: NIH finds a few new friends in budget chill http://goo.gl/fb/mfM8O
• RT @westr: “Consumer Genetics Conference Wrap-up – Most Interesting Moments?: http://bit.ly/m5BStq #CGC2011″ -via @wimufi
• MT @mary_carmichael: @dgmacarthur Screenshots don’t do it justice. Key is in use: easy to navigate, cross-ref diff types of content.
• Privacy vs. efficacy driving debate over opt-in or opt-out approach to state EHR systems: http://bit.ly/fD5mF8
• GLR Post: News Roundup: Perception Gaps and Progress in Personalized Medicine: http://bit.ly/kWv9nn
• Company for Shuren? “Health Canada upbraided for inspections of medical devices.” http://bit.ly/l4Kw9e
• RT @BiotechPatent: FDA takes ‘first step’ toward greater regulatory certainty around nanotechnology http://1.usa.gov/jipVTX
• Drugmakers’ Commitment to Personalized Rx Growing Despite Barriers, PhRMA CEO Says: http://bit.ly/jBcQ73 by @PGxReporter
• RT @dgmacarthur: Screenshots of the $ILMN iPad personal genome browser (HT @BioITEditor): http://bit.ly/k06xA9 Surprisingly amateurish.
• RT @genome_gov: Cool 7/18 meeting: Using crowdsourcing for scientific innovation @ NIH’s Natcher auditorium (also webcast) http://qoo.ly/4z7
• FDA ruling on $OREX’s Contravene obesity drug risks driving scarce R&D resources from important field, says @LifeSciVC: http://bit.ly/la5nsi
• RT @cwhogg: Wireless dominates patents for heart, glucose monitors http://tinyurl.com/3ur7jmz
• RT @scotthensley: Curious to see how it’ll work. RT @phrma: Forthcoming @US_FDA Facebook page that will answer ppl’s questions about drugs
• #ASCO11 wrap-up from @ldtimmerman for those (read: all of us) who had difficulty following all of the news: http://bit.ly/kDFaA2

Editor’s Note: This was first published at Genomes Unzipped and was co-authored by Daniel MacArthur and Luke Jostins. Genomes Unzipped received 12 free kits from Lumigenix for review purposes, and Dan Vorhaus has provided legal advice to the company. Genomes Unzipped plans to release a full review of the Lumigenix service in early July.

Last month three direct-to-consumer (DTC) genetic testing companies opened their mailboxes to find a slightly ominous but entirely expected letter from the FDA. The three recipients (Lumigenix, American International Biotechnology Services and Precision Quality DNA) received substantively equivalent letters, with the FDA warning each company that its genetic testing service “appears to meet the definition of a device as that term is defined in section 201(h) of the Federal Food Drug and Cosmetic Act,” and that the agency would like to meet with company representatives “to discuss whether the service [they] are promoting requires review by FDA and what information [they] would need to submit in order for [their] product to be legally marketed.”

Translated from bureaucratese, that means that the FDA views these services as ones that may need to be formally reviewed by the agency and either approved or cleared before they can be legally sold. The FDA letter asks each company to describe its service and to explain either (1) why it does not require FDA approval or (2) how the company plans to pursue such approval.

This is a strategy that the FDA has pursued with a growing cadre of DTC service providers. These letters (currently 23 and counting¹) represent the only public and company-specific actions the agency has taken to date with respect to DTC genetic testing. While many DTC letter recipients are engaged in dialogue with the FDA, those conversations have occurred beyond the public’s view. Until now.

Ending the regulation guessing game? For more than a year, the FDA has dealt with DTC genetic testing providers by mailing (and publishing) an initial letter followed by the initiation of a private dialogue and a company-specific regulatory determination. The agency has yet to publish, or even to propose, anything resembling industry-wide regulatory guidance for current or prospective personal genomics companies.

For their part, personal genomics companies have been reluctant to publicly disclose the nature of their conversations with the FDA. Recently, however, a new approach appears to be emerging, at least on the company side.

Last month, a recent DTC letter recipient (Precision Quality DNA) published a strongly worded response to the FDA on its website. Another letter recipient, Lumigenix, soon followed suit, launching a new corporate blog with the publication of its own more measured response to the agency. Each company undoubtedly has its own reasons for bucking the prevailing trend and choosing to take its conversation with the FDA into the public square. There should be little doubt, however, that the FDA’s current company-by-company approach to personal genomics regulation, which has left the industry with a considerable measure of uncertainty, was a major contributing factor in each decision. As Dan and his colleague Allain Andry noted last summer, the effects of that regulatory uncertainty can be substantial.

They include:

• Reduced access to capital. Genetic testing companies may find that investors are more cautious about making new and add-on investments.
• Fewer new products. Companies may delay plans to introduce new products both because of lack of funds and concern about the regulatory response to innovative products or business models.
• Fewer entrants. Numerous investors, and companies in related industries, have been preparing to enter into the genetic testing field. Many of those plans may be put on hold.
• Litigation risks. The well-publicized GAO report and Congressional hearings, which highlighted apparent operational deficiencies of some DTC companies, could lead to tort (e.g., negligence, emotional distress, malpractice), securities or other lawsuits from plaintiffs’ lawyers and litigious customers. Although the GAO report and Congressional investigation focused on DTC genetic tests, the broad and negative public attention focused on genetic testing could spur similar litigation against more traditional genetic testing developers and providers.
• Reduced access to technology. Companies dependent on third-party providers for some portion of their own test or business might find their options limited if regulatory uncertainty or changes discourage such collaborations.
• Encouraging overseas development. Increased regulation – or even the possibility of increased regulation – may encourage companies and investors to focus on developing new products and businesses overseas in advance of, or instead of in, the United States, with potentially detrimental consequences for patients and consumers in this country.

Current and prospective DTC genetic testing providers alike are no doubt burdened by some or all of these challenges. Lumigenix, in particular, appears hopeful that a more public DTC discussion might help to lessen the effects of regulatory uncertainty, noting at several points in its response to the FDA the company’s desire to work with the agency to develop “a clear and reasonable system of oversight for the emerging field of personal genomics.”

The challenge of “clinical” DTC claims. Perhaps the greatest area of current DTC regulatory uncertainty concerns the ability of companies to provide interpretations of personal genomic data with potential clinical or medical significance. The FDA has consistently maintained that its regulatory interest lies first and foremost with clinical genetic tests, with a test’s intended use determining whether it qualifies as clinical.

The FDA’s emphasis on clinical genetic testing has presented personal genomics companies with a dilemma: offer medically relevant personal genomic results in response to consumer demand and thereby risk stricter scrutiny from regulators, or attempt to cater to regulators (but risk losing customers) by removing or deemphasizing results that could be construed as clinical.

Personal genomics companies have deployed a variety of solutions in response to this dilemma. 23andMe, for instance, has simply braved regulatory ire by continuing to offer tests for the BRCA breast cancer risk variants, pharmacogenomic response and other serious disease mutations. Pathway Genomics responded to its own FDA letter by promptly eliminating the ability of consumers to purchase its product without physician involvement. Carrier testing company Counsyl avoided a letter entirely by dropping DTC marketing as soon as the FDA began to make serious regulatory overtures.

Lumigenix, for its part, has thus far taken an intermediate approach, steering clear of reporting on variants with unambiguous clinical relevance while maintaining DTC access to its service. In its response to the FDA, Lumigenix emphasizes that the company “strongly believes that individuals should have the right to access their own genetic information,” but explains that Lumigenix has opted to exclude certain information from its current service to avoid any clinical confusion:

In order to ensure there is no doubt about the educational purpose of our service, Lumigenix’s current service intentionally excludes certain categories of genetic tests. For that reason, Lumigenix’s does not currently include in its customers’ genomic reports results from genotype data known to be associated with or to indicate:

• carrier status for a recessive disease (e.g., Cystic Fibrosis or Tay-Sachs disease);
• pharmacogenomic status related to an individual’s likely response to certain medications (e.g., Warfarin or Clopidogrel); or
• a serious or untreatable illnesses with a large genetic component (e.g., breast cancer, Huntington’s disease or Alzheimer’s disease).

We understand that some individuals desire such results for their informational value. But we also acknowledge that the risks associated with personal genomics, including the risk that an individual will make an important medical or other decision without first consulting a healthcare professional, are not equal across all categories of genetic tests.

For that reason, Lumigenix has decided to focus its current service on providing personalized genetic information pertaining to genetic ancestry, non-medical traits and conditions, and certain relatively common medical- or health-related conditions that tend to be influenced by many genes and include a substantial environmental component.

It’s worth noting that Lumigenix is still early in its conversation with the FDA and has not yet had the same length of time to respond (e.g., in the form of modifications to its service or business model) as earlier DTC letter recipients, including 23andMe and Pathway Genomics. Lumigenix’s response does, however, hint that changes may be in store: the company applies the adjective “current” in describing its service eight separate times in its response to the FDA.

The range of approaches taken by personal genomics companies on this issue alone reflects a much broader uncertainty about the industry’s regulatory future in the hands of the FDA. The agency’s reluctance to publicly pursue a comprehensive personal genomics regulatory framework is understandable, particularly in light of the rapid pace of scientific and technological innovation and the paucity of data about DTC genetic tests and their affect on consumer behavior. Still, for so long as the FDA continues with its current private, company-by-company regulatory approach, personal genomics innovation and investment are likely to remain hampered by uncertainty.

A glimpse into the regulatory future. Interestingly, despite Lumigenix’s focus on non-medical data as part of the formal interpretations it provides to its customers, the raw data generated by the company’s genome-wide test contains plenty of medically relevant genetic variants. For example, there are at least 196 sites on the chip that match the position and sequence of known Mendelian disease mutations, including 12 in the BRCA1/2 genes and 6 in the cystic fibrosis gene CFTR². Lumigenix simply does not report on or interpret these variants, although customers can choose to explore those variants on their own, including through the use of free software such as SNPedia’s Promethease.

This approach to medically relevant personal genomic data, at first blush needlessly confusing and inefficient, is unsurprising in light of the FDA’s insistence that their regulatory target is not genomic data but the claims – particularly clinical or medical claims – made on the basis of those data. Last August, for example, reporter Mary Carmichael and Dr. Elizabeth Mansfield, Director of Personalized Medicine for the Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD), had the following exchange:

[MC]: I want to move on to whether the issue with direct-to-consumer is actually providing data to people, or is it the interpretation algorithms these companies are using? So, would a company need to be approved just to provide a raw SNP list to people?
EM: They would if they made medical claims about that data. If they don’t make any medical claims about that data, then they’re free to provide information as far as we’re concerned.

Over the past year, nothing has happened that would suggest that the FDA has revised its policy on this point. This bodes well for both DTC companies and their customers because, barring a striking reversal by the FDA, high-quality personal genomic data appears likely to remain readily available, including via direct-to-consumer channels. Whatever else the FDA may have in store for the personal genomics industry, the availability of raw genomic data should enable DTC companies to remain on the market in some form.

Still, the increasing availability of raw personal genomic data will itself soon pose a challenge for the FDA. Already widely accessible and inexpensive, personal genomic data will soon transition from SNP chips to whole-genome sequences. As data proliferates alongside increasingly numerous and sophisticated publicly available software tools (like Promethease, SNPTips and Interpretome, the topic of a recent post) used to mine those data, the FDA will find that focusing on all-inclusive providers of DTC personal genomics services is insufficient. As the separation of testing (genomic data generation) from interpretation (genomic data analysis) accelerates, the FDA will be faced with a growing array of personal genomics service providers, many of whom are likely to provide software-only tools and will see no pressing need to operate from within the United States (and within easy reach of the FDA).

How the agency responds to the inevitable expansion and diversification of the personal genomics industry – e.g., with an expanded letter-writing campaign or a concerted effort to develop flexible and forward-looking industry guidance – remains to be seen.

_____________________________________________

1. The count: Pathway Genomics (May 2010); 23andMe, Navigenics, Knome, deCODE Genetics, Illumina (June 2010); Graceful Earth, SeqWright DNA Technology Services, Interleukin Genetics, DNATraits, CyGene Direct, Consumer Genetics, Matrix Genomics, The Genetic Testing Laboratories, Sequenom, EnteroLab Reference Laboratory, BioMarker Pharmaceuticals, DNA Dimensions, HealthCheckUSA, easy DNA (July 2010); Lumigenix, Precision Quality DNA, American International Biotechnology Services (May 2011).

2. Analysis by DM: I looked at the overlap between the SNPs included in my raw data from Lumigenix (available for download here) and the disease mutations in the full version of the Human Gene Mutation Database (available only via an academic collaboration or a license fee, unfortunately). I counted positions where both the position and both alleles matched. Note that this approach won’t detect disease-causing insertions and deletions, only SNPs.

Following its passage in the Senate, the legislation promptly stalled in the House of Representatives and, several months and numerous committee hearings later, that is where it remains. Fierce lobbying and political maneuvering have thrown multiple key provisions of the reform legislation into doubt. Leading areas of debate include the constitutionality of a proposed change from a “first-to-invent” to a “first-to-file” patent system and a provision that would allow the patent office to retain user fees to fund its own operations.

While it remains unclear whether patent reform will actually occur, the latest round of legislative wrangling has introduced one proposal of particular interest to Genomics Law Report readers. Among 86 pages of proposed amendments (pdf) to H.R.1249 (the House version of the patent reform legislation) offered earlier this week is a provision that, if adopted, would provide an infringement safe harbor for second opinion genetic diagnostic testing.

Permitting Second Opinions in Certain Genetic Diagnostic Testing. Introduced as part of the Manager’s Amendment (pdf) submitted by Representative Lamar Smith (R-TX), the proposal is conceptually simple. It would create a new Section 287(d) under the Patent Act to establish a safe harbor for second opinion genetic diagnostic testing providers, much like the safe harbor that already exists at Section 287(c) for medical practitioners’ performance of medical activities.

Under certain conditions (more on those below),  performing a genetic test “solely for the purpose of providing the individual with an independent confirmation of results” previously obtained from a patented diagnostic test would not subject the second opinion test provider to infringement liability under the Patent Act. The safe harbor provision would not actually define second opinion testing as non-infringing behavior—the act of performing the second opinion test could still constitute infringement under Section 271 of the Patent Act—but it would eliminate the normal infringement remedies (Sections 281, 283, 284 and 285) from the patent owner’s arsenal.

The actual legislative proposal, of course, is slightly more complex. Here is the full text:

Sec. 27. PERMITTING SECOND OPINIONS IN CERTAIN GENETIC DIAGNOSTIC TESTING

(a) IN GENERAL. – Section 287 of title 35, United States Code, is amended by adding at the end the following:

(d)(1) With respect to a genetic diagnostic test provider’s performance of, or offering to perform, a confirming genetic diagnostic test activity that constitutes infringement of a patent under section 271(a) or (b) of this title, the provisions of section 281, 283, 284 and 285 of this title shall not apply against the genetic diagnostic test provider with respect to such confirming genetic diagnostic test activity.

(2) For the purposes of this subsection:

(A) The term “confirming genetic diagnostic test activity” –

(i) means the performance of a patented genetic diagnostic test, by a genetic diagnostic test provider, on an individual solely for the purpose of providing the individual with an independent confirmation of results obtained from another test provider’s prior performance of the test on the individual, where such prior test was performed by, or under license from, the owner of the patent that is infringed by the acts specified in paragraph (1), and where independent confirmation of the prior test is not available from another test provider under a license from the patent owner; but

(ii) does not include –

(I) the performance of a patented genetic diagnostic test on an individual for the purpose of monitoring or reconfirming the individual’s medical or genetic status over time, for therapeutic treatment selection or determining responsiveness to treatment, and for other purposes that require repeated genetic diagnostic testing of the individual;

(II) the use of a patented machine or article of manufacture in violation of such patent;

(III) the use of a patented composition of matter that is commercially available to the genetic diagnostic test provider; and

(IV) the practice of a patented process other than the process of testing claimed in the patent owner’s patent referred to in paragraph (I).

(B) The term “genetic diagnostic test provider” means any person or entity that performs a confirming genetic diagnostic test activity, and includes a clinical laboratory or other health care entity at which, on behalf of which, or in association with which the confirming genetic diagnostic test activity is conducted, such as a nursing home, hospital, university, medical school, health maintenance organization, group medical practice, or medical clinic.

(C) The term “patented genetic diagnostic test” means a patented diagnostic method that is specific to the detection of a mutation or a pattern of mutations of one or more particular genes in an individual, as well as the use of a patented composition of matter, or the practice of a patented use of a composition of matter, where such composition of matter is specific to and necessary for the practice of the diagnostic method and is not commercially available to the genetic diagnostic test provider. When performed in the course of a confirming genetic diagnostic test activity, such term is not limited to the particular embodiments of the patented diagnostic method or composition of matter that were practiced by or under the authority of the patent owner in providing the prior genetic diagnostic test.

(D) The term “independent confirmation” is not limited to the replication of the results of a prior genetic diagnostic test, and includes providing the individual with information that is not otherwise available from the provider of such prior test and that affirms, clarifies, disproves, corroborates, or otherwise aids the individual in interpreting the results of such prior test, including in instance where such results were inconclusive.

(3) The infringer shall have the burden of establishing the limitation on remedies under paragraph (1), including the production of contemporaneous documentary evidence proving, or tending to prove, that the diagnostic test activity meets the definition of a confirming diagnostic test activity under paragraph (2)(A) at the time the confirming diagnostic test activity was performed.

(b) EFFECTIVE DATE. – The amendment made by subsection (a) shall take effect on the date of the enactment of this Act and shall apply to confirming diagnostic test activity performed on or after such date.

A Safe Harbor’s Uncertain Waters. A close examination of the text reveals that, however simple its intent, if passed as drafted the second opinion safe harbor would leave genetic testing developers and providers, patent holders and courts with considerable uncertainty about the safe harbor’s appropriate interpretation and application.

Perhaps the easiest way to identify many of the unclear and (likely) controversial provisions of the second opinion safe harbor provision is to read the amendment proposed by Rep. Smith side-by-side with the amendment-to-the-amendment (pdf) proposed by Representative Debbie Wasserman Schultz (D-FL) who, as Patent Docs notes, first offered the second opinion safe harbor amendment on the House floor in April.

An examination of the first three amendments suggested by Rep. Wasserman Schultz reveals the high degree of uncertainty and controversy embedded in the current second opinion safe harbor proposal:

WS Amendment #1. As proposed by Rep. Smith, Section 287(d)(2)(A)(i) limits a “confirming genetic diagnostic test activity” subject to the safe harbor protections to those situations where independent confirmation is “not available from another test provider under a license from the patent owner.” That would seem to close the safe harbor except when there was, in fact, only a single licensed provider of a particular test (as is currently the case with Myriad Genetics and its diagnostic test for mutations in the BRCA1 and BRCA2 genes). The safe harbor would appear to be inapplicable in any scenario in which there were two providers.

It is unclear, however, whether this would be the case even if both “test providers” offered the exact same test using the exact same laboratory procedures (would that even be a truly confirmatory test?) or if the multiple test providers were controlled by a common entity. Also uncertain is when a test would be considered “available” for purposes of the safe harbor provision. Would the requirement of availability require that the test be “affordable and readily accessible to the patient” or simply “available in some form, to some patients at some price”?

Rep. Wasserman Schultz addresses these concerns in her own amendment by simply striking the requirement that the test be unavailable except from the sole test provider, which would appear to broaden the provision to apply even in situations where the patents were licensed on a non-exclusive basis to multiple genetic testing providers.

WS Amendment #2. Rep. Smith’s version of the safe harbor provision would also not apply where a genetic diagnostic test was used for “therapeutic treatment selection” (Section 287(d)(2)(A)(ii)(I)). While that term is not defined, it could be interpreted broadly to exclude from the second opinion safe harbor any genetic diagnostic test the results of which could cause a new or modified clinical course of care.

Such a reading would dramatically limit the scope and relevance of the safe harbor, since most patients, providers and payers are likely to pursue a second opinion only in those situations where a different test result would alter the course of the patient’s care.

In her own amendments, Rep. Wasserman Schultz’s proposal simply strikes the “therapeutic treatment selection” limitation.

WS Amendment #3. In addition to the “therapeutic treatment selection” exception to the safe harbor, Section 287(d)(2)(A)(ii)(I) would also exclude genetic tests “for the purpose of monitoring or reconfirming the individual’s medical status over time” or for any other purpose that required “repeated genetic diagnostic testing.” The presumed intent is to avoid depriving the rights-holder (the patent owner or its licensee) from serving as the first option for any re-testing conducted later in time.

Rep. Wasserman Schultz’s proposal retains this language, but provides an exception-to-the-exception that would permit an infringing genetic diagnostic test to take advantage of the safe harbor, even for repeated diagnostic testing, if the test “utilizes different technologies or has performance characteristics that are sufficiently different from the patented tests that the results can provide information not provided by the patented test.”

The goal would appear to be the encouragement of second opinion testing using non-identical genetic tests (“different technologies or…performance characteristics”), although it is unclear whether this would operate in conjunction with Rep. Wasserman Schultz’s first amendment to prevent the developer of a separate and patented diagnostic test from enforcing its rights when its test was performed following any previous diagnostic test covering the same condition.

All told, Rep. Wasserman Schultz offers ten amendments to the language proposed by Rep. Smith, including this “Rule of Construction”:

The amendment made by subsection (a) [the second opinion safe harbor amendment] shall not be construed to reflect any expression by the Congress with respect to the patentability of genetic material or genetic diagnostic testing.

Will Congress Intervene in the Gene Patent Controversy? It remains highly uncertain whether Congress will manage to pass any patent reform legislation during its current session. Furthermore, should patent reform become a reality, there is no guarantee that the second opinion exemption will be retained. The safe harbor for genetic diagnostic testing was not included in the version of the legislation the Senate passed in March and, even if the House manages to include the provision in its version of the legislation, it could easily be removed during the reconciliation process.

Finally, even if Congress is ultimately able to reach an agreement, the questions about how to interpret and apply a second opinion safe harbor are unlikely to end there. They would almost certainly carry over from Congress to the courts if and when companies and individuals begin seeking shelter in the new safe harbor, should it ever materialize.

Despite these several barriers to the adoption of a second opinion safe harbor for genetic diagnostic testing, the possibility that change could come to the personalized medicine patent landscape should not be entirely ignored.

It is no coincidence that the safe harbor proposal comes just one year after the now-defunct Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS) published its controversial report on Gene Patents and Licensing Practices and Their Impact on Patient Access to Genetic Tests (pdf). In that report, SACGHS found that “when there is a patent-enforcing sole provider [of a genetic test], patients cannot obtain independent second-opinion testing” and, as a result, recommended several statutory changes, including “the creation of an exemption from liability for infringement of patent claims on genes for anyone making, using, ordering, offering for sale, or selling a test developed under the patent for patient-care purposes.”

And Rep. Wasserman Schultz’s “Rule of Construction” notwithstanding, the safe harbor proposal must also be viewed as a direct Congressional reply to the ongoing and widely publicized Myriad gene patent litigation. The Myriad litigation was initiated more than two years ago by a diverse group of plaintiffs, including several women seeking genetic testing for mutations linked to breast and ovarian cancer. The plaintiffs’ complaint (pdf) included the allegation that Myriad Genetics’ patents and licensing practices operated to prevent women from “obtaining information about their health risks from anyone other than” Myriad, including denying women access to second opinion testing. As the Myriad litigation enters its third year, some members of Congress are undoubtedly feeling pressure to address the effects of gene patents in the practice and development of personalized medicine using more expeditious means.

[Update, 6/16: The American Civil Liberties Union (ACLU), the group largely responsible for coordinating the Myriad litigation, is leading a group of organizations in opposition to the proposed amendment (pdf). The ACLU-led coalition argues that the proposed second opinion safe harbor “would fail to block all patent holder objections to [second opinion] testing, fails to address the many other limitations on scientific research arising out of the issuance of [gene patents], and risks allowing gene patent holders to argue that Congress implicitly endorses the validity of such patents.” The group urges Congress to reject the amendment to avoid creating “unintended harms to patients, medical professionals and genetic researchers.” According to the ACLU’s letter, the American Medical Association has also written separately to Congress to oppose the amendment. The swift response from organizations like the ACLU, the AMA and others suggests that the second opinion safe harbor may be closer to becoming a reality than was previously suspected.]

Although the second opinion safe harbor proposal seems unlikely to pass at this time, at least in its current form, Whether the safe harbor proposal passes or not, it should serve as a stark reminder that even as patent attorneys and biotechnology companies anxiously await the Federal Circuit’s ruling in Myriad—which could come any day now and significantly alter the personalized medicine patent landscape—Congress will continue to loom in the background, with the ability at any moment to completely rewrite the rules of the game.

Personalized Medicine’s Perception Gaps. A new report released this week by the biopharmaceuticals company Quintiles (pdf) examines the perspectives of four key stakeholder groups – biopharma executives (n=200), managed care executives (n=153), physicians (n=503) and patients (n=1,000) – across a wide range of personalized medicine issues.

The report contains a number of interesting statistical nuggets about how these groups perceive their strengths, weaknesses and future role in the advancement of personalized medicine. These include the following:

• Only 44% of biopharmaceutical executives believe that their organization provides “readily available” outcomes data to demonstrate the value of medications;
• Healthcare professionals generally agree (65%) that patients who seek out information on their own achieve better health outcomes, but more than a third (36%) believe that patients are more frequently misinformed than they were five years ago;
• Fewer than half (44%) of doctors surveyed are optimistic that the quality of healthcare will be significantly improved over the coming decade; and
• At least a third of payers (33%) and biopharma execs (38%) believe that personalized medicine will have a negative effect on job and healthcare discrimination (this despite the passage of 2008 legislation (GINA) designed to prevent discrimination on the basis of genetic information in both cases).

Perhaps the most surprising finding of all is that patients appear to be largely unfamiliar with the entire concept of personalized medicine. Only 24% of patients surveyed had previously even heard of “personalized medicine,” indicating that healthcare companies and providers alike have considerable work remaining in order to bring personalized medicine into the mainstream.

The report concludes that there is “considerable misalignment among healthcare stakeholders on various aspects of the healthcare universe.” According to the report, physicians are frustrated by payers, payers are frustrated by a complex and ill-suited regulatory regime, biopharma executives are torn between maximizing health outcomes and maximizing value to shareholders and patients are “viewed by all groups as not doing enough to improve their own healthcare.”

Clinical Trial Innovations. One major barrier to the development of increasingly personalized therapies is clinical trial recruitment. The more personalized the therapeutic or diagnostic tool in development, the more difficult it is to locate patients who satisfy the trial’s enrollment criteria.

Enter PatientsLikeMe, the patient-driven health platform, which this week announced a new feature to help match patients with clinical trials more effectively. PatientsLikeMe’s new tool will query a government database of ongoing clinical trials (ClinicalTrials.gov) and “automatically match up members of the website with every clinical trial they may be eligible for based on their conditions and location.”

Also this week, pharmaceutical giant Pfizer announced a new form of “virtual” clinical trial which, according to NatureNews, will lower barriers to clinical trial enrollment by allowing “participants to receive medication, video-conference with clinicians, and report symptoms in the comfort of their own home.”

The announcements from Pfizer and PatientsLikeMe are just the latest in a serious of innovations seeking to leverage digital and social media tools to encourage more widespread and efficient personalized medicine research.

Personalized Medicine and Cancer. Despite the many challenges it faces – from scientific complexity to regulatory, reimbursement and intellectual property regimes ill-equipped to accommodate innovation – the present and future of personalized medicine was on display this past week as thousands gathered in Chicago for the annual American Society of Clinical Oncology (ASCO) meeting (see previous news).

To help us keep up with the latest developments in oncology, Luke Timmerman of Xconomy offered a detailed wrap-up of the major developments announced at ASCO by U.S. companies. In addition, at the Consumer Genetics Conference in Boston this past week, Illumina CEO Jay Flatley announced cuts in the company’s pricing for individual whole-genome sequencing, including an attractive $10,000 price point for tumor-normal pair sequencing of cancer patients. Finally, Matthew Herper of Forbes elegantly recapped outgoing ASCO president George Sledge’s big-picture perspective on “cancer’s new era of promise and chaos.”

Whatever the challenges, it remains clear that opportunities abound for personalized medicine companies and investors. A new survey from PwC’s Health Research Institute found that consumers are willing to spend approximately $13.6 billion per year of their own money on healthcare services. It found further that more than three-quarters (76%) of the Fortune 50 is comprised of either healthcare companies or companies with a health division.

Roundup of tweets from the intersection of genomics, personalized medicine and the law:

• Troubling: 1/3 of managed care execs think personalized medicine will have negative effect on job/healthcare discrimination #quintiles
• Sad that more than 56% of MDs think that quality of healthcare will improve over next decade #quintiles
• MDs agree (65%) that patients who seek out information achieve better health outcomes, but 36% worry about patient misinformation #quintiles
• Also, managed care execs appear to have a dramatically inflated view of the value they add in educating/understanding patients #quintiles
• Note that only 44% of biopharma execs say outcomes data readily available to support value of new medications #quintiles cc @wilbanks
• Quintiles healthcare report is goldmine of data on MD, pharma, managed care & patient views http://bit.ly/jBNzx5 HT @cwhogg
• 76% of Fortune 50 companies are in healthcare or have a health division: http://bit.ly/iZaw6x HT @FierceHealth
• Re: last tweet, HIPAA as a floor, & not preemptive, will make compliance/sharing more difficult cc @wilbanks @danielg280
• Michigan court rules state law trumps HIPAA data disclosure/privacy provisions: http://bit.ly/jmeCkE
• The @Forbes NGS piece is garbage, but @matthewherper’s piece on genomic medicine & cancer remains a #mustread: http://onforb.es/iuOHrX
• Glad to see it. Hopefully would-be investors read to bottom. RT @matthewherper: I added my thoughts on the post. We agree (not surprising.)
• Health app accelerator @Rock_Health funds 11 startups, including @genomera: http://bit.ly/jWoJcI HT @InVivoBlogEllen
• Includes this gem: “[NGS] will also open door to creating superhumans w/ unusual intelligence or physical skills.” Really? @matthewherper?
• Unimpressed by @Forbes NGS article which amounts to advert for two cos ($ILMN, $LIFE) in which author holds shares: http://onforb.es/mr2jpx
• HHS releases add’l details on NIH reorg needed to produce NCATS, incl. proposed budget of $722M: http://bit.ly/makQKQ
• More clinical trial innovation: $PFE’s online-only trial aims to lower participation barriers: http://bit.ly/kX5P7B HT @bmahersciwriter
• Cont. innovation from @patientslikeme, using ClinicalTrials.gov to improve patient recruitment: http://bit.ly/joJuiP by @RyanMFierce
• My #sonyc slides from last night are online: http://bit.ly/ldIXMO Did my best to cover personal genomics in 5 slides.
• MT @LouWoodley: If you missed last night’s #sonyc on Science+Law it is now online: http://bit.ly/l4QCsO HT @science3point0
• RT @BiotechPatent: SCOTUS affirms clear & convincing standard for invalidity defense in #patent challenge http://tinyurl.com/44ga9b8
• Belated update re: House hearing on FDA med device approvals, feat. testy exchange with Shuren: http://bit.ly/m6TrhL HT @dgmacarthur
• Prev article on AUS nobel / genome publication mistakenly implies US law (GINA) prohibits life insurers from using genetic info. It doesn’t.
• RT @dgmacarthur: Awesome – Australian Nobel Laureate announces plan to publish his complete genome on the internet: http://bit.ly/j8yJyi
• Agenda here: http://bit.ly/jRmhfd Anybody live-tweeting? RT @FierceMedDev: Hatch, Hamburg, Shuren speaking at MDMA.
• Interesting. 63% (n=2137) said “yes” to FMR1. RT @PHGFoundation: Should babies be screened for untreatable disorders? http://bit.ly/k50xx8
• RT @DailyNewsGW: Roche, Merck Partner on Cancer Therapy Diagnostics: http://bit.ly/kRaB7o
• Genetic privacy may be doomed, as @razibkhan argues (http://bit.ly/jKKUY0). Question is, will that matter and, if so, what are our options?
• “Suggests online collection of self-reported data in recontactable cohort may be viable method for broad & deep phenotyping in large pop’n”
• MT @mary_carmichael: Just read @23andMe GWAS replications paper-in-progress. Neat stuff there. Congrats, @nkeriks! http://bit.ly/m0YJwb
• RT @dgmacarthur: Post on the wondrous Cambridge BioResource by @elainewestwick: http://bit.ly/ljKGjp (I’m in there too!)
• Wonderful time at #sonyc event on science & law w/ @SLSingh et al. Thx to @LouWoodley @JeanneGarb @j_timmer & rest of @S_O_NYC for invite.
• Although, to be fair, $10K for tumor/normal pair does represent a more significant price drop for $ILMN. #cgc2011
• Wonder how much extra $ILMN capacity is due to emergence of $GNOM, which is targeting $4K by 2nd half of ’11: http://bit.ly/iNrqo3 #cgc2011
• The fact that the WGS floor only dropped $2K (non-clinical drop is $10K) may be better indicator of ILMN capacity #cgc2011
• Here’s today’s $ILMN presser on WGS pricing: http://bit.ly/l9IPmB Compare to last June: http://bit.ly/j8KLeu #cgc2011
• Wish I could be at (or at least following along) #cgc2011. Follow @wimufi @davidpendletonk @RDGene & others for live tweets
• Ready for the $1K genome? 3 great posts @genomesunzipped: http://bit.ly/l7kQYEhttp://bit.ly/iqnH6vhttp://bit.ly/jfYNj1
• Pfizer ($PFE) investing $100m in Boston research collab; another attempt to bridge “valley of death”: http://bo.st/iFUcip by @Globecarolynyj
• Done panicking cell phone users, WHO shifts focus to genomic “grand challenges” for developing world: http://bit.ly/mfucTd
• Another NGS play: “sequencing by expansion” RT @DailyNewsGW: Stratos Genomics Raises $2.1M: http://bit.ly/jCzLXX
• Looking forward to participating in tonight’s #sonyc panel on Science & the Law w/ @SLSingh et al. http://bit.ly/koLQ6c
• Sen. Sanders introduces legislation (again) to reward new drugs with cash prizes, not patents: http://bit.ly/lcgm5S
• Updating the DTC Debate: Trial by PR, More FDA Letters, the Problem of Pleiotropy & New RUO Guidance http://bit.ly/jXJzHh
• RT @EdwardWinstead: RT @matthewherper: Cancer’s new era of promise and chaos. #ASCO11 #genomics http://onforb.es/jNZVtr
• Chicago for #ASCO11 to discuss current state of DTC genetic testing. For those not here, an update: http://bit.ly/jXJzHh
• RT @Sagebio: disclose full results and data to address epidemic of false claims; J. Ioannidis in SciAm http://bit.ly/jsaxDZ
• Rescheduled House committee hearing on FDA/medical devices to be held tomorrow: http://bit.ly/iDRdzz
• Follow @DNAlawyer for #UVAGEL tweets http://bit.ly/jcnHFv Muin Khoury arguing “no sci foundation” for personal genomics, incl. PGx?
• RT @dgmacarthur: More press-release scare-mongering about personal genomics – my response: http://bit.ly/j0VWxf
• NYU opening Center for Genomics and Systems Biology tomorrow: http://bit.ly/jnYIbB HT @DailyNewsGW cc @S_O_NYC
• Looks like a great program. RT @DNAlawyer: UVA GEL symposium is tomorrow and Thursday. I’ll be there. http://bit.ly/jcnHFv
• Interesting GINA proposed as a model. Focus on use makes sense; outright ban doesn’t. Health & genetic data must be used, just used properly
• NYT examines health data privacy, re-identification & control. http://nyti.ms/jlgEeu HT @FierceHealth
• MT @mary_carmichael: Study: “strong link b/w happiness & 5-HTT:” http://bit.ly/mHXjP3 More news, green jelly beans cause acne: xkcd.com/882/
• ESHG annual conf starts today, incl. plenty of anti-DTC genetic testing sentiment: http://bit.ly/iZ7fnd HT @shwu
• FDA mtg to nominally focus on analytical validity for NGS. But that’s only one part of broader debate re: FDA & next gen of clinical tools.
• More FDA: on 6/23, FDA holding public meeting on use of NGS platforms in clinical setting: http://1.usa.gov/liUKNg
• Summary of April’s FDA strategic priorities plan by@GENbio: http://bit.ly/iRhcZa Very high level, funding a challenge.
• amednews on the coming regulation of FDA medical apps: http://bit.ly/lshHTQ HT @GeneSherpas cc @mobilehealth
• Asked as an aside: how would FDA regulate Dr. Watson? (Not as far off as it appears. WGS Dx software coming soon, poses similar challenge.)
• For more on Dr. Watson, highly recommend this Feb piece from @PGxReporter: http://bit.ly/iF3VNC Major need: better data collection, sharing
• IBM’s Watson now “as good as smartest second year med student”; widespread use still 8-10 yrs out http://onforb.es/llIAO2
• 1st issue (& t-shirts) already out. RT @wilbanks: Citizen Science Quarterly, a CC licensed journal. via @doctorow http://bit.ly/lLGYjw
• British Columbia court rules against anonymous sperm & egg donation. Will rest of Canada follow suit? Will US be next? http://bit.ly/jTJADw
• Here’s the link to the survey on “the informational aspects of genetic tests” (takes ~5 min): http://bit.ly/kZjjdD
• Genetics of CF severity, a survey of DTC customers and the value of a genetic diagnosis from @genomesunzipped: http://bit.ly/mTYMQi
• Telomeres predicting lifespan? Blackburn: “that’s just silly, isn’t it?” Interview w/ @NatureNews on future of field: http://bit.ly/kEmbwp
• Update on Patent Reform Act progress in Congress from @GENbio: http://bit.ly/jZHH0l
• Poor job by NYT failing to link DNA fish fraud story to earlier teen citizen scientists http://nyti.ms/jh49yA @matthewherper @leonidkruglyak
• RT @DailyNewsGW: $MYGN Teams with Topin to Market OnDose to Oncologists: http://bit.ly/merPqJ
• $GNOM continues to raise more $, talk expansion: http://bit.ly/mwUb06
• Facebook & pharma seeking to sort out social medial policy: http://bit.ly/lek4cG
• RT @wilbanks: Bob Cook-Deegan, a living legend in the gene wars, talks about gene patents. Read. http://bit.ly/lT2n3O
• And on a Friday to boot. RT @Duncande: With my full genome sequenced (by PGP at Harvard & $GNOM), I’ve been designated “PGP 13″ – lucky 13!
• Good question MT @blaine_5: DTC ELSI issue: why aren’t bone marrow donors informed of risk of genomic analysis by bone marrow recipients?
• Authors: “to delay policy-making decisions until all poss qs answered wrt DTC unrealistic given state of field.” I agree. HT @eurogene
• Good NEJM back-&-forth re: Bloss, @EricTopol, et al.’s Feb article on effect of DTC genetic testing: http://bit.ly/lhhqbj
• Genetic Technologies Sues 10 Firms for Infringement on a Method to Determine Haplotype: http://bit.ly/imgHmE HT @blaine_5
• Inspection, Compliance Data Disclosure to Be Widened by U.S. FDA: http://bloom.bg/mJEyCi
• Survey: 2/3 of small med device & Dx firms prefer EU in seeking 1st regulatory approval. Shuren: “we’re on it”: http://bit.ly/kIjqkD
• RT @PGxReporter: In latest PGx pact w/ Population Genetics, Quintiles aims to save Pharma money & time http://bit.ly/lFbogm
• RT @PHGFoundation: Retention of cleared suspects’ DNA by police ruled unlawful http://bit.ly/lRfyIN
• +1 RT @genetics_blog: neat RT @moorejh: Topic map of all grants awarded by the #NIH in 2010 http://is.gd/IfzuzG
• Good, but won’t WGS soon obviate need for mult tests? RT @westr @DivaBiotech: New Genetic Testing Tech for IVF Embryos http://bit.ly/iHNBPc
• Nuffield launches public consultation on ethical/social issues arising from emerging biotechnologies: http://bit.ly/lf07df
• RT @rzeiger: Interesting Google job to run internal health + wellness programs. Ping me if u want to learn more http://goo.gl/ULPvF
• RT @girlscientist @ClinSeqNews: HudsonAlpha Researchers to Sequence Immune Repertoires of 10K Indiv. for 100 Diseases http://bit.ly/kQmHH3
• From Toll House cookies to gastrointestinal diagnostics. RT @DailyNewsGW: Nestle Health Science Buying Prometheus Labs: http://bit.ly/kp1IkI
• RT @InSequence: Life Tech, Gen-Probe to Collaborate on FDA Clearance for Dx Assays on CE Sequencer: http://bit.ly/jH9YiK
• The license out as the biotech end game? MT @ldtimmerman: How to make $ in biotech beyond IPO, M&A http://bit.ly/kczVun
• A new model for @23andMe? @ldtimmerman reports it is rebranding itself as “a research company”? http://bit.ly/k8ImME
• RT @matthewherper: Biopharm execs: We want to focus on the future, but investors won’t let us. http://ow.ly/51GRS
• The challenge of therapeutic success. Or “Innovations of today increase cost of innovations tomorrow”: http://bit.ly/ltLLoj HT @MishaAngrist
• GLR Post: Patent Update: Looking Beyond Section 101 & Continued Murkiness of Method Patents: http://bit.ly/ii5arT
• Precision Quality DNA (recent FDA letter: http://1.usa.gov/mgciWO) has strong feelings re: DTC reg: http://fda.pqdna.com
• Looking forward to some great brainstorming at “The Future of Pathology in Personalized Medicine”: http://bit.ly/ll5LqQ
• Great @DanielSolove column: “Why Privacy Matters Even if You Have ‘Nothing to Hide’”: http://bit.ly/lXG6O7 HT @MishaAngrist
• “The Privacy Challenge in Online Prize Contests” in NYT http://nyti.ms/kFVVgt w/ a HT to @23andMe’s consent form.
• What does the future hold for biotech & VCs? Interesting Q&A in Nature’s bioentrepreneur: http://bit.ly/ki35i3
• First VT, now CA. RT @FierceHealth: Another state considers single-payer #health system http://bit.ly/lTvRec
• RT @FierceBiotech @ScottKirsner: VCs on boards of directors: 1 not enough but > 2 is dangerous. Like martinis. -Bob Higgins @HighlandCapital
• Good. incls dedicated investment to improving reimbursement. RT @DailyNewsGW: UK Groups Investing in Pers Med Projects: http://bit.ly/lbORVW
• +1 RT @matthewherper: Should we just let athletes use performance-enhancers? Why we’re dopes about doping: http://ow.ly/4Zqc9
• Yes, re: NIH budget cuts RT @drjonboyg: the @Battelle & UMR reports show how short sighted that is given huge economic impact of NIH funding
• Collins comments on BGI at end of article also interesting. Maybe NIH funding bump if China viewed as more of a threat?
• Looming NIH budget cuts “sobering”; may drive grant success rate to “lowest in history”: http://bit.ly/jt14vo
• RT @WSJHealthBlog: The CDC’s zombie apocalypse juggernaut: next up, a video contest…..http://on.wsj.com/kShypJ cc @kashhill
• My anecdotal data similarly bleak. RT @DNAlawyer: Anecdotal data: only 2 of my undergrad students @ Duke heard of GINA before I covered it.
• Two comments: 1) pre-06/07 DTC surveys tough to compare to post-07 DTC surveys (diff products). 2) wish some actual data on GINA awareness.
• Oregon has collected data on state-led pop’n surveys of genetic testing use/awareness: http://1.usa.gov/mTMmRj HT @ewencallaway
• RT @dgmacarthur: Joe Pickrell’s discusses potential artefacts in the Science RNA-editing paper at @genomesunzipped: http://bit.ly/jUVz6t
• Note $MYGN’s planned EU expansion to begin in Germany. New Gene/Myriad headed for conflict? Prev GLR: http://bit.ly/fylYeL
• NewGene’s NGS-Based BRCA1 & BRCA2 test coming to France, Germany http://bit.ly/lXZmxk HT @MattMealiffeMD @BRCAscoop
• Missed ind. research results (IRR) & incidental findings (IF) conf (http://bit.ly/epMlQm)? Great live tweets by @genome_gov et al. #ifirr
• RT @bigs: keep liking NIH’s Kathy Hudson more & more. ‘what we want is for every (person) to be a (research participant) as well’ #IRBreform
• RT @Erika_Check: Pickrell will be posting more on possible artifacts in DNA/RNA mismatch study tomorrow @GenomesUnzipped.
• RT @Erika_Check: DNA/RNA mismatch story getting more interesting. Joe Pickrell: “many of the results reported are potentially artifactual”
• Surprised? RT @GENbio: Pres bioethics panels sometimes choose topics driven by political pressure than scientific need http://bit.ly/iIYhdN
• NIDS Eyes Next-Gen Sequencing Needs: http://bit.ly/mRQohw
• Looking forward to @crossborderbio ongoing series on “Valuation and Other Biotech Mysteries”: http://bit.ly/j8Sb5R
• RT @matthewherper: @BiotechPatent This Forbes writer thinks the idea that medical prices are closely connected to dev costs is wrong.
• Forbes columnist takes aim at impending medical device tax: http://onforb.es/jJdYIb HT @BiotechPatent
• Stem Cells: The growing pains of pluripotency: http://bit.ly/m077oj Excellent, comprehensive piece by @Erika_Check
• RT @LifeSciVC: Good to see positive trend. RT @nvca: Venture Capital Performance Continues to Improve http://bit.ly/klA8fi cc @JCainHart
• Intrigued by @HelicosUnveiled (http://bit.ly/iqLNz5) which appears to be unsanctioned PR for Helicos. Other exs of this?
• RT @EdwardWinstead: Timely… Eric Lander at NIH 5/20 11:30 a.m.: From the ‘Genetic Code’ to the ‘Genetic Code’ webcast
• Enough frustration to actually produce change? RT @NatureNews: US panel calls for reform in human subject protection http://goo.gl/fb/kS28S
• RT @MattMealiffeMD: RT @adamfeuerstein: The thing you will mostly notice about #ASCO11 abstracts is that there isn’t a ton of new data.
• RT @genome_gov: Joseph Thankuria – Informed Consent, Biobanking, and Data distribution in the Personal Genome Project #ifirr
• I look fwd to “intense criticism” forecast by @dgmacarthur. MT @Erika_Check: DNA/RNA mismatches challenge central dogma http://bit.ly/ijeWvd
• A personal genomics challenge from @blaine_5 to @genomesunzipped readers (& the rest of you as well): http://bit.ly/jUeXqB
• Telome Health suggesting monthly telomere checkups? http://bit.ly/ldvZpD (see sidebar) Great business model if you can sell it.
• Yes. Life, disability & long-term not covered by GINA (state rules vary) RT @drjonboyg: @genomicslawyer except for long term life insurance!
• Also, I don’t understand the confusion/concern about telomere testing (DTC or otherwise) & discrimination. Clearly covered by GINA.
• On DTC telomeres, #1 I would not be surprised to see another round of “come meet with us” letters from the FDA.
• While the Post tackles DTC athletics, the NYT is featuring an even newer DTC fad: telomere testing: http://nyti.ms/kKtk77
• Canada pursuing its own version of GINA (genetic nondiscrimination legislation): http://bit.ly/iA8bjC HT @mikesgene
• Medco Drug Trend Report predicts cancer drug spending could rise up to 15%/year through 2013: http://bit.ly/ioLIPn
• RT @MichelleNMeyer: @drjonboyg & @genome_gov live tweeting conf on return indiv research results (IRRs) & incidental findings (IFs) #ifirr
• HT to CDC for realizing that best way to teach emergency preparedness is via zombie apocalypse: http://on.wsj.com/kkAD0W
• Rob Stein tackles DTC genetic testing for child athletes in today’s Post: http://wapo.st/lsrkpH AIBS just received FDA ltr
• PGP-1K continues progress. MT @Duncande: It’s official, my complete genome has been sequenced! Thx to PGP (@PGorg) & $GNOM
• Chinese biotechs wrestle with transparency, cultural hurdles (NBT): http://bit.ly/jw3zcU (And you think it’s tough here)
• Interesting post on @23andMe, data sharing and “the altruism instinct”: http://bit.ly/jHfkG1
• More med companies adopting social media (& policies), but 52% say lack of FDA guidance impeding uptake: http://bit.ly/jC1tE0
• RT @MishaAngrist: ENCODE gets ENGORGED http://bit.ly/kvs7S7
• 1K genomes project update from @InSequence: http://bit.ly/lesrH3 WGS & exomes for 1K ppl, another 1K+ on the way
• Genomic Health repaid $800K in royalties due to Incyte’s failure to maintain IP: http://bit.ly/j3H1PN Lesson: pay the PTO on time
• U of Washington, Pharmigene resolve IP dispute around warfarin dosing, agree to license: http://bit.ly/joZucZ
• RT @ldtimmerman: Hood: I despair whether in US we can sequence enough ppl, families. China will. IRBs too much of an obstacle here isb2011p4
• RT @ldtimmerman: Schadt talked all about PacBio machine, not Mt. Sinai, or Sage, to this high-science audience #isb2011p4
• Good overview in NBT of NGS providers & why they are eying clinical seq as their next market opp: http://bit.ly/lYUGRS
• RT @PGxReporter: Medco to Evaluate Clinical Utility of AssureRx’s PGx Test in Guiding Psychiatric Treatment: http://bit.ly/lWZWvL
• RT @dgmacarthur: How a @23andMe test profoundly changed a woman’s life in two very different ways: http://bit.ly/jbO7Yq
• #ASCO11 abstracts come out today. @brianreid has a modest proposal to ‘socialize’ the process for 4,000+ abstracts: http://bit.ly/lZMCzy
• Upcoming debate b/w Phil Sharp & Stephen Friend (moderated by @ldtimmerman) on pro/con of open source biology: http://bit.ly/jshQ77
• European Society of Cardiology says Europe needs a “single, coordinated” system for regulating medical devices: http://bit.ly/iCelNF
• Some candid advice from @LifeSciVC on how to pitch a biotech startup to VCs: http://onforb.es/jwO8LP
• Genetics as Culture in a Consumerist Age: http://bit.ly/kPvgiX Submit a poster/presentation & come join me in Innsbruck.
• Some good talks over the weekend at #ISB2011P4, tweeting supplied by @ldtimmerman, @finchtalk, etc.
• RT @MishaAngrist: Does Pac-Bio have a PR problem? http://bit.ly/jUAFar $PACB
• Here’s @ldtimmerman detailed take to the Schadt/$PACB/Mt. Sinai move: http://bit.ly/k2xjI8 Good to see more genomics $/talent coming to NYC
• AMP position statement recommends against using brand names in companion Dx labeling: http://bit.ly/mjbpPi by @SampleGW
• RT @Sagebio: “a brilliant rebel in the field of genomics” A. Pollack on Eric Schadt move to Mnt Sinai http://nyti.ms/lIwJ7S
• RT @RyanMFierce: More buyouts to come? RT @FierceBiotech: PerkinElmer acquires Labtronics, buyouts pile up. http://bit.ly/l5owst
• Short @techreview piece on another nanopore-based seq play, Noblegen: http://bit.ly/kqAs25 Gaudy goal: 30 genomes, 15 min
• Lumigenix FDA/DTC letter (http://1.usa.gov/jxBtS6) far more conciliatory in tone than similar letters last summer (http://bit.ly/aGpLU0)
• Australian DTC company @Lumigenix receives FDA inquiry letter: http://1.usa.gov/jxBtS6
• Health Insurers Making Record Profits as Many Postpone Care: http://nyti.ms/k1jwBs via @twilli2861
• Summary of Battelle report on economic impact from Human Genome Project from @drjonboyg / @genome_gov: http://1.usa.gov/itBVMr
• RT @JohnCFierce: In-depth article from Forbes on the development of India’s biotech hubs. http://onforb.es/iesQxC
• Verghese op-ed (http://nyti.ms/mD8twZ) led to post on ‘iPatient’ (http://bit.ly/lqqR5M). Lots of work to do redefining what “patient” means.
• Hah RT @bmahersciwriter: I’m so tempted to buy plush microbes from the CSHL gift shop. Wife: What did you bring me? Me: Chlamydia. bg2011
• Detailed summary of FutureMed Day 1 from @Medgadget http://bit.ly/kq1XIc HT @daniel_kraft & congrats to @tgoetz on his new company, 1+1 Labs
• RT @matthewherper: Beating Moore’s Law Since January 2008! My post on bg2011 http://ow.ly/4U4u8
• In context, this is incredible. MT @lukejostins: GM on 1000 Genomes Project. Now have 1094 whole-genome, 977 exomes, 1542 2.5M chips BG2011
• MT @dgmacarthur: GM: Feb 2000, 98% of SNPs in sequenced individual were novel. Now # is down to ~1%. bg2011 (Gabor Marth on 1K Genomes proj)
• 41yo woman w/ BRCA mutation & recent history of Breast Cancer (NEJM): http://bit.ly/isJG0O Interesting patient perspective on testing, risks
• How to calculate your own Alzheimer’s risk, based on genetic and environmental data http://bit.ly/jZ5Dlh @genomesunzipped by @lukejostins
• RT @dgmacarthur: Key message from the meeting so far: we are assigning function to non-coding variation at an astonishing rate. bg2011
• Great idea. See @matthewherper’s latest for related. RT @bigs: Teller proposes ‘sequencing the human lifestyle’ in add. to genome #futuremed
• RT @matthewherper: What should we sequence after the genome? Mark Changizi has an interesting answer: http://onforb.es/iqmBu6
• Also includes working catalog of other public genomic data RT @razibkhan: Ashkenazi 23andMe v3 genotype for the taking: http://bit.ly/iCiKPE
• RT @genome_gov: Watch NHGRI’s Advisory Council meeting May 16, 8:30 a.m. Webcast: http://bit.ly/jsFeIA. Agenda: http://1.usa.gov/mvmMTs.
• GLR Post: New Diagnostic Guidelines & DTC Testing for Alzheimer’s Disease: http://bit.ly/mHDi6Y
• SAS forming “think tank” to look at how healthcare & life sciences cos use its analytics software: http://bit.ly/ldjJeW via @RyanMFierce
• Latest on Fabrazyme dispute: patients allege Genzyme diverting ltd drug supply to European patients: http://bit.ly/kMs3nG
• Good q. Payors have leverage, GH knows it. RT @MattMealiffeMD: can you be both payors “agent” & “neutral arbiter”? http://bit.ly/jpt0KB
• CardioDx closes out Series E to the tune of $60M, will focus on expanding reimbursement coverage: http://bit.ly/k2uvyp
• Generation Health program tackles two key challenges: lack of transparency (runs in both directions) & lack of data. Here’s hoping it works.
• Generation Health launches ambitious pilot program to bridge the gap b/w Dx providers & payors: http://bit.ly/jpt0KB
• MT @dgmacarthur: analyses of early @iontorrent data by @pathogenomenick (http://bit.ly/miHnoj) & Keith Robison (http://bit.ly/jYemtG)
• Interesting @NatureNews piece on Anil Potti & how scientists view & manage their online reputations: http://bit.ly/iHFAx8
• $GNOM update: a backlog of genomes (>2k) & plans for aggressive pricing, new machines & ~1K genomes/month by year end: http://bit.ly/mCeeJC
• RT @PGxReporter: Continuing Push to Diversify Offerings, Myriad Licenses Chronix’s Early Cancer Detection Technology: http://bit.ly/ijzK1t
• Is public’s (not scientists’) reluctance to question Bin Laden DNA ID evid. of genetic exceptionalism? http://bit.ly/jCG7me by @Erika_Check
• VA db a great potential resource. Too bad it’s relatively closed & researcher-only (i.e., no EHR linking or participant data return)
• Veterans Affairs to create genomic research database with 1M vets: http://bit.ly/m6zWSg via @PGxReporter
• RT @MishaAngrist: Of 113 med devices recalled from 05-09, 80 (71%) fast-tracked by FDA: http://bit.ly/jLNN2s (via journalistsresource.org)
• $800B or not, Jim Evans says expectations for personalized genomic info remain too high: http://bit.ly/e0eBdA HT @MishaAngrist
• RT @bmahersciwriter: Great piece dissecting the logic of an $800bn return on investment for the human genome http://bit.ly/jW0pAO
• $LIFE-funded study: $800bn = economic impact of human genome project http://on.wsj.com/lnmQkL Report http://bit.ly/mAXixa
• CDER chief Woodcock says FDA expects to issue biosimilar guidance this year: http://reut.rs/j5nlCi
• RT @lukejostins: A conversation with @elainewestwick about sharing data, newborn screening and carrying cystic fibrosis http://bit.ly/mQjdBa
• Settlement in MA wrongful birth case: http://bit.ly/jZSXBt For past GLR coverage: http://bit.ly/9u060V
• RT @InSequence: Granting PacBio’s Reexamination Request, USPTO Invalidates All Four Helicos Patents: http://bit.ly/mT4fZF
• Study on how info affects DTC genetic testing decision: http://bit.ly/ki7QqR Anybody read/have the underlying study?
• RT @dgmacarthur: Have a burning question to ask genome visionary George Church (@geochurch)? Ask away: http://bit.ly/kHX0bF (via @ianholmes)
• PerkinElmer acquires Geospiza (@finchtalk), beefing up software for DNA analysis http://bit.ly/jGYiiM by @ldtimmerman
• Recent case further evid Fed Cir may leave 101 open, tighten other patentability criteria. See: http://bit.ly/gba0FI
• Fed Cir recently invalidated pair of DNA diagnostic patents: http://bit.ly/l411JS Will try to get analysis on GLR nxt wk
• The latest PGM vs. MiSeq ad from @iontorrent is out: http://youtu.be/gStCvyGpnRU Prev discussion here: http://bit.ly/fTkxlD
• Second rd of #FDADTC comments now appearing on regulations.gov (search FDA-20111-N-0066). Expect more in coming days.
• ZyGem, Lockheed developing portable forensic DNA platform: http://bit.ly/kha4Nj Goal: ID next Bin Laden in field in < 1 hr.
• GLR Post: News Roundup: Biotech Funding & LDT Regulation: http://bit.ly/jYTzWz
• This piece on Sulston, the human genome project & the Wellcome Trust by @markgfh is simply fantastic: http://bit.ly/miiX4X
• RT @dgmacarthur: .@nilshomer has joined the genome sharing gang – his @23andMe data are publicly available under CC0: http://bit.ly/lfLM22
• GLR Post: The Next Social Media Revolution Will Occur In…Personalized Medicine? http://bit.ly/lMimh7
• BRACAnalysis drives $MYGN revenues higher; company expects Euro launch in ’12: http://bit.ly/jyQ5Yj
• Supreme Court Case on Script Data Sale Presents ‘Gray Area’ for PBM Personalized Rx Efforts: http://bit.ly/lygTKo
• FTC continues fight against pay-for-delay drug deals, chairman calls them “outrageous”: http://bloom.bg/msSVrG
• RT @crossborderbio: Based on survey of clinical research site pros RT @JohnCFierce: top 10 CROs in CenterWatch survey: http://bit.ly/moqDGu

This will, I believe, mark direct-to-consumer (DTC) genetic testing’s formal debut at ASCO. It should also serve as another reminder that, despite its relatively small numbers (both in terms of dollars and customers), DTC genetic testing continues to exert an outsized influence when it comes to conversations about the future of genomic medicine. This is particularly true when the discussion turns to appropriate policy and regulatory oversight.

In advance of ASCO, here are several items of interest from the past few weeks in DTC genetic testing.

“Trial by Press Release.” That’s exactly what Daniel MacArthur of Genetic Future termed this week’s press release from the European Society of Human Genetics (ESHG) highlighting two presentations on DTC genetic testing at the recent ESHG annual meeting.

The studies themselves have yet to be published, but preliminary findings were meant to provide new evidence that (a) the risk prediction models employed by personal genomics companies are neither perfect nor consistent and (b) clinical geneticists are skeptical of the value of DTC genetic tests.

Neither finding is surprising, although, as MacArthur points out, the first study – from Rachel Kalf of Erasmus University – will need to be published in full before its claims, including the claim that one DTC company (deCODEme) utilizes fundamentally flawed risk prediction models, can be fully vetted.

The desire to encourage greater transparency and consistency among the risk prediction models employed by DTC genetic testing companies has been expressed numerous times in the past (higher-profile examples include current NIH Director Francis Collins, genomic pioneer Craig Venter and colleagues and last summer’s GAO report) and repeatedly embraced by DTC companies themselves (see, e.g., here and here).

When it comes to debating the future of the DTC genetic testing industry there are plenty of areas of legitimate disagreement. For example, should different types of DTC tests (e.g., carrier screening vs. pharmacogenomic testing vs. genetic ancestry testing) which make different types of claims be regulated differently? And how, if at all, should the concept of utility, whether clinical or personal, be incorporated into a genetic test evaluation?

But the need to improve transparency and consistency in DTC risk prediction models already appears to be shared nearly universally among DTC stakeholders.

The second study included in the ESHG release, conducted by Heidi Howard of the University of Leuven, Belgium, includes the finding that 63% of a “representative sample of clinical geneticists” from across Europe “wanted to proscribe whole genome scans carried out by DTC companies.”

That statistic has bounced around the internet echo chamber the past few days, but, again, is it offering us anything we did not already know (or at least strongly suspect)? As MacArthur points out, asking the current cohort of genetic testing gatekeepers how they feel about being sidestepped by genetic testing companies seeking to engage directly with individuals feels slightly rhetorical:

While it is important that personal genomics companies consult with medical professionals in devising their risk prediction algorithms and interfaces, regulation of genetic testing should not be based on the views of the traditional gatekeepers of genetic information.

As both MacArthur and Razib Khan of Gene Expression note, the appropriate question to ask is not whether clinicians believe genetic tests are harmful in the hands of consumers, but whether genetic tests are actually harmful in the hands of consumers.

Thankfully, a growing list of researchers is asking that very question, including Bloss et al. (see also a recent back-and-forth in the NEJM), Kauffman et al. and the recently launched Impact of Personal Genomic Services (IPeG) study (some details here), about which my co-presenter Stacy Gray will be providing more details during today’s panel.

As the Food and Drug Administration (FDA) and others continue to wrestle with the difficult job of shaping DTC regulatory policy, the data generated by these and other studies will be critical in ensuring that any policy which eventually emerges responds to the demonstrated challenges of DTC genetic testing, and not merely to hypothesized harms.

The FDA Sends Three More DTC Letters. Speaking of the FDA, nearly a year to the day after it sent its first letter of concern to a DTC genetic testing company (Pathway Genomics), the agency sent out its latest batch of DTC letters. The recipients this time: Lumigenix, American International Biotechnology Services and Precision Quality DNA.

Much has transpired since that first FDA letter – including many more DTC letters, a Congressional hearing last summer and a closely watched advisory panel meeting earlier this spring – but for now, at least in public, the FDA is continuing to employ the same case-by-case approach to DTC genetic testing oversight it has utilized from the outset.

Not everyone is happy with the FDA’s current approach. One of the most recent companies to receive a letter, Precision Quality DNA, has devoted a section of its company website to the FDA’s handling of DTC regulation, and has published its strongly worded reply to the agency’s most recent letter.

While it would be inaccurate to characterize Precision Quality DNA’s response as representative of the views held throughout the DTC industry, several of the points the company raises – including the need for greater transparency surrounding the FDA’s review and oversight of DTC genetic testing products – seem likely to resonate with other companies, whether they are currently in dialogue with the FDA or anxiously awaiting their own letter from the agency. (A good bet for a future FDA letter: companies offering direct-to-consumer telomere measurement tests, several of which drew criticism in recent weeks for over-inflating the ability of telomere length to predict individual longevity.)

The Latest in DTC Offerings. American International Biotechnology Services (AIBioTech), another company to receive a recent DTC letter from the FDA, found itself under the FDA’s microscope thanks to its Sports X Factor Genetic Athletic Assessment Test. The test purports to “reveal a person’s genetic athletic performance indicators as well as the potential for several risk factors,” including the risk of “negative results after an injury to an individual, such as a concussion,” or the possibility of an “undiagnosed heart condition.”

AIBioTech is not the first company to attempt to combine genetic testing and athletics – we dissected offerings from Athleticode and Atlas Sports Genetics back in 2009 – but the company’s test has received additional scrutiny due to its inclusion of markers for the apolipoprotein E (APOE) gene. The APOE gene, which comes in at least three different versions or alleles (ε2, ε3 and ε4), has been shown to affect an individual’s risk of coronary heart disease, as well as for developing late-onset Alzheimer’s disease.

Providing APOE results directly to consumers raises a host of delicate ethical and legal issues, as we discussed last month when DTC veteran 23andMe unveiled APOE reporting as part of its standard service. AIBioTech has drawn criticism for largely ignoring these issues in offering its athletics-focused test. (This in addition to criticism of the scientific validity of the claims offered up by AIBioTech and other athletic genetic testing companies.)

The inclusion of APOE in the AIBioTech test also highlights one of the frequently discussed challenges of trying to regulate any genetic test – whether DTC or otherwise – on the basis of its claims or intended use. As the proliferation of genomic data continues and our collective genomic understanding grows, the number of genetic markers which exert influence upon multiple traits of varying significance is likely to rise.

APOE’s implication in both heart disease and Alzheimer’s is a classic illustration of the phenomenon of pleiotropy – the ability of a single gene to influence multiple phenotypic traits – although it is hardly the only pleiotropic gene (genes responsible for sickle-cell disease, PKU and albinism, among others, also exert pleiotropic effects). As additional pleiotropic biomarkers are identified, the notion that genetic tests should be evaluated based on their intended use is likely to come under increasing pressure. How, for instance, will regulators address a genetic ancestry test when one or more of the biomarkers employed by the test could be used to predict an individual’s genetic risk for a serious disease? While this dilemma is not a conceptually new one, as the regulatory framework for genetic testing evolves, the nonlinearity of gene-trait relationships seems likely to pose a significant challenge for regulators, clinicians and companies who would prefer the ability to provide precisely targeted genetic test results to individuals.

Regardless, the issue seems likely to be mooted in large part at the point in the not-too-distant future where individuals have routine and early access to complete whole-genome sequences. Then the issue will no longer be whether or how to provide data with the potential to help predict multiple phenotypic effects, but how to exert any control whatsoever on the interpretative tools available (including, perhaps, IBM’s Dr. Watson, which is now reportedly “as good as the smartest second year med student”) to individuals who have access to complete and portable personal genomic data.

Are You Ready for RUO? Finally, one very recent development of potential significance to the DTC industry is the applicability of the just-released FDA draft guidance for research-use-only (RUO) and investigational-use-only (IUO) in vitro diagnostic products.

Published earlier this week, the RUO/IUO guidance clarifies the rules for marketing and commercializing diagnostic products under the widely used RUO and IUO exemptions, which allow device manufacturers to avoid submitting their products under the FDA’s rigorous medical device approval pathway. (For more see this article in Pharmacogenomics Reporter.)

The draft guidance, which is open for public comment for the next 90 days, is a significant event for manufacturers of laboratory developed tests (LDTs), many of which are thought to incorporate RUO/IUO components despite being offered for clinical or diagnostic purposes. Expect LDT manufacturers and industry groups, such as the Association of Molecular Pathology and American Clinical Laboratory Association, to have plenty to say on the RUO/IUO draft guidance before the comment period expires at the end of the summer.

Less clear is what impact the RUO/IUO guidance might have on the DTC industry. As with LDTs, it is not known exactly how many DTC genetic test providers utilize RUO/IUO components in their products. However, the pairing of an RUO or IUO device with a DTC product certainly occurs. For instance, 23andMe utilizes the Illumina OmniExpress Plus in its popular DTC service. The OmniExpress is part of a family of popular DNA microarray products offered by Illumina and labeled for research use only (pdf).

This exact issue appeared last summer when the FDA included Illumina in its first batch of DTC letters following the Pathway/Walgreens dust-up. From our coverage last June:

Of all the companies receiving letters, Illumina is the only one not to offer at least one product directly to consumers (the company does offer a commercial whole-genome sequencing service, although that product requires the participation of a healthcare professional). Illumina’s letter notes that the company has “received FDA clearance or approval for several of its devices,” but not for the HumanHap550 array. “Yet Illumina is knowingly providing the HumanHap550 array to 23andMe and deCODE Genetics for clinical diagnostic use without FDA clearance or approval” despite its being labeled “For Research Use Only.” As Gutierrez notes, “…Illumina has to follow the law, and they are aware that the chips are not being used for research only.”

Although the specific product has changed over the past year, the fundamental issue has not. The new RUO/IUO guidance, if approved in its current form, places a heavier burden on providers of RUO/IUO devices to “not sell such products to laboratories they know use the product for clinical diagnostic use.”

Which brings us back to one of the fundamental tensions concerning DTC genetic testing services: whether such services are intended, at least in the eyes of the FDA, for clinical diagnostic use. While the FDA and DTC genetic testing companies may not agree on the reasonably intended uses of these services, the FDA’s draft RUO/IUO guidance threatens to insert another key player – platform technology providers, like Illumina – squarely into the middle of the DTC debate.

If the FDA continues to maintain that the genetic testing services offered by 23andMe, Lumigenix and other DTC providers are intended for use in clinical and/or diagnostic testing, the Illuminas of the world will find themselves with a difficult choice to make. They will likely be forced to (a) defy the FDA’s RUO/IUO guidance, (b) stop selling their RUO/IUO devices to DTC companies or (c) attempt to shepherd their RUO/IUO devices through the FDA’s resource-intensive medical device approval process.

Or as the FDA puts it:

FDA is aware that laboratories sometimes use IVD products labeled RUO in clinical diagnosis and that many manufacturers, importers, and distributors of IVD products labeled RUO are also aware of such use. Manufacturers who label their IVD products: “For Research Use Only. Not for use in diagnostic procedures,” should not sell such products to laboratories that they know use the product for clinical diagnostic use. If a manufacturer learns that a laboratory to which it sells its RUO-labeled IVD product is using it in clinical diagnosis, it should halt such sales or comply with FDA requirements for IVD products, including premarket review requirements, if applicable.

If it were only DTC companies utilizing RUO/IUO devices, manufacturers like Illumina might simply stop selling those devices in light of the small (current) size of the DTC industry. But because those same devices also appear to be used by a number of LDT manufacturers, who represent a much larger market, there is a strong possibility that RUO/IUO device suppliers like Illumina will seek to obtain FDA approval for those devices, hopefully while working with the FDA to keep those devices on the market in the interim to avoid interruptions to patient care (or, in the case of their DTC customers, consumer product supply).

Regardless, the next few months will bear close watching to see whether the FDA’s attempt to more strictly enforce RUO/IUO labeling results in any significant shift in the relationships between DTC genetic testing companies and their technology suppliers.

What’s Next for DTC? Remember that it was roughly this time last year when Pathway Genomics’ failed partnership with Walgreens kicked off a busy summer of DTC (and related) activities at the FDA and on Capitol Hill. Up until this week, Washington had been relatively quiet since the end of last summer, at least in public. While the RUO/IUO situation bears watching, there are some who expect this summer to bring further fireworks on a par with last year.

While several important initiatives continue to loom as possibilities – including the FDA’s long-anticipated LDT guidance and new diagnostic-focused legislation from Congress – with 2011 nearly halfway gone I continue to think that the prospects for industry-wide regulation of DTC genetic testing in 2011 remain dim.