PerkinElmer Inc. v. Intema Ltd. (Fed. Cir. 2012)

By Kevin E. Noonan --

The Federal Circuit made its first attempt to implement the Supreme Court's nearly opaque jurisprudence on the scope of patent eligibility for diagnostic method claims (as set forth in Mayo v. Prometheus) in PerkinElmer, Inc. v. Intema Ltd., decided today.  (The Court's AMP v. Myriad case doesn't really count, as the diagnostic method claims in Myriad had already been held patent-ineligible under the "machine-or-transformation" test set forth in In re Bilski, and the Supreme Court's Mayo decision certainly didn't expand the scope of patent eligibility.)

The case involved claims from U.S. Patent No. 6,573,103 for prenatal diagnostic testing for Down's syndrome, intended to avoid the need for invasive testing like chorionic villus sampling that incurs the risk of miscarriage.  Claims 1 and 20 were set forth by the Federal Circuit panel as being representative:

Claim 1.  A method of determining whether a pregnant woman is at an increased risk of having a fetus with Down's syndrome, the method comprising the steps of:
    measuring the level of at least one screening marker from a first trimester of pregnancy by:
        (i) assaying a sample . . . ; and/or
        (ii) measuring at least one first ultrasound screening marker from an ultrasound scan . . . ;
    measuring the level of at least one second screening marker from a second trimester of pregnancy, the at least one second screening marker from the second trimester of pregnancy being different from the at least one first screening marker from the first trimester of pregnancy, by:
        (i) assaying a sample . . . ; and/or
        (ii) measuring at least one second ultrasound screening marker from an ultrasound scan . . . ;
    and determining the risk of Down's syndrome by comparing the measured levels of both the at least one first screening marker from the first trimester of pregnancy and the at least one second screening marker from the second trimester of pregnancy with observed relative frequency distributions of marker levels in Down's syndrome pregnancies and in unaffected pregnancies.

Claim 20.  A method of determining whether a pregnant woman is at an increased risk of having a fetus with Down's syndrome, the method comprising the steps of:
    measuring the level of at least one first screening marker from a first trimester of pregnancy by:
        (i) assaying a sample . . . ; and/or
        (ii) measuring at least one first ultrasound screening marker from an ultrasound scan . . . ;
    determining a first risk estimate of Down's syndrome by comparing the measured level of the at least one first screening marker level from the first trimester of pregnancy with observed relative frequency distributions of marker levels in Down's syndrome pregnancies and in unaffected pregnancies;
    comparing the first risk estimate with a predetermined cut-off level to initially classify the pregnant woman as screen- positive or screen-negative based on the comparison;
    and if the pregnant woman is initially classified as screen-negative; measuring the level of at least one second screening marker from a second trimester of pregnancy, the at least one second screening marker from the second trimester of pregnancy being different from the at least one
first screening marker from the first trimester of pregnancy, by:
        (i) assaying a sample . . . ; and/or
        (ii) measuring at least one second ultrasound screening marker from an ultrasound scan . . .
    and determining the risk of Down's syndrome by comparing the measured level of both the at least one first screening marker from the first trimester of pregnancy and the at least one second screening marker from second trimester of pregnancy with observed relative frequency distributions of marker levels in Down's syndrome pregnancies and in unaffected pregnancies.

The panel opinion apprehends that the "key difference" between these claims was the segregation of patients into positive or negative groups, wherein only the positive groups are screened in the second trimester, embodied in the "determining step" as the "key limitation."  The District Court had construed this "key limitation" as determining a risk of Down's syndrome by comparing distributions of certain markers in Down's syndrome pregnancies and "unaffected" pregnancies, and then combining the screened markers into a single risk calculation based on the results from the first and second trimester screenings.  The District Court rejected PerkinElmer's summary judgment motion of patent ineligibility under § 101 (and granted Intema's summary judgment motion on patent eligibility) on the grounds that the claims are directed at a data-gathering method comprising measuring steps that satisfied the machine-or-transformation test (assaying a blood sample was transformative in the District Court's view).

The panel opinion written by Judge O'Malley and joined by Judges Bryson and Wallach, reversed the District Court's finding of patent-eligible subject matter (and affirmed summary judgment against Intema on anticipation and obviousness grounds), based on the Supreme Court's Mayo decision and the Federal Circuit's Myriad decision.  "The key distinction," according to the Court, "which bears on our decision today[] is between claims that recite ineligible subject matter, and no more, and claims to specific inventive applications of that subject matter."  The opinion goes on to say that the basis for making this distinction is that claims to specific applications of "patent-ineligible subject matter" (i.e., "laws of nature, natural phenomenon or abstract ideas") "do not risk the broad preemption of 'the basic tools of scientific and technological work,'" citing Benson v. Gottschalk, 409 U.S. 63, 67 (1972).  In the panel's view, the claimed methods do not contain an "inventive concept" (defined as in Mayo as "other elements or a combination of elements [] sufficient to ensure that the patent in practice amounts to significantly more than a patent upon the natural law itself" and because these claims "contain[] nothing more than 'well-understood, routine, conventional activity previously engaged in by researchers in the field.'"

The opinion then sets forth how it arrived at this conclusion, which in a nutshell was that the panel did not see any distinction between these claims and the Mayo or Myriad claims.  While relying on extensive language from the Court's Mayo decision, the analysis focuses much more closely on the similarities between the claims at bar and the Myriad claims (calling them "indistinguishable" from the claims in Myriad).  The similarities reside completely in the fact that the Intema claims and the Myriad claims involve comparing measured biological information (between wildtype and mutant BRCA genes in Myriad and between Down's pregnancies and unaffected pregnancies here), which the panel characterizes as being merely mental activity regarding a naturally occurring relationship).  These two characteristics of the claims -- that they recite "mental steps" and "natural laws" -- are sufficient to render them patent-ineligible unless, according to the opinion, they also contain that ineffable "something more" required by the Supreme Court's Mayo opinion.  Surveying the claims, the opinion states that the "measuring" steps are insufficient, because (as in Mayo) the method steps encompass any and all methods for measuring the markers.  Here, the patentee's attempts to provide broad support for the invention was held against them, wherein the specification was cited for reciting that "'[t]he individual measurements are obtained through known methods. . . .  Any markers which are effective at each particular stage may be selected.'"  As a result, the panel was able to characterize the measuring steps as encompassing "well-understood, routine, conventional activity previously engaged in by scientists who work in the field."

Similarly, the "determining" step (characterized by the District Court as a "key" limitation) was thought by the panel to comprise merely the "mental step" of comparing marker levels in Down's and unaffected pregnancies, and that the "comparing" methods comprise statistical analysis was not enough:  these are also "well-understood" and "conventional" (although the opinion does not establish that it was conventional to apply Gaussian statistics for such comparisons, the patentee's further recitations in the specification that "Any of the known statistical techniques may be used.  Preferably the multivariate Gaussian model is used, which is appropriate where the observed distributions are reasonably Gaussian. Such multivariate Gaussian analysis is in itself known . . . ." clearly suffices to support the panel's conclusion that the statistical handling of the data was routine and conventional).  Also in this regard the panel recognizes that, as in Myriad, there is no requirement that an actual assay (BRCA gene sequencing in Myriad, taking an ultrasound here) must actually be performed; the claims are satisfied by making the comparison itself (between two printouts of gene sequences in Myriad, or between two ultrasound images here), making it a simple matter to construe the claims as encompassing the merely mental step of "comparing."

The panel gets to the heart of the matter by reaching the preemption issue, wherein "anyone who wants to use this mental step or natural law must follow the claimed process" and the root of the problem, that "there is no requirement that a doctor act on the calculated risk," both because the claims do not recite a treatment step and because the claims purportedly impact the activities of medical doctors treating patients (albeit through the intermediary of a commercial (or at least for-profit) testing laboratory (and the panel goes on to support this conclusion with reference to the different patent-eligibility fates of the claims in Classen v. Biogen Idec, where the presence of an immunization step distinguished patent-eligible from patent-ineligible subject matter).

The Court asserts the most troubling basis for its decision by comparing the claims here with Claim 20 in Myriad's U.S. Patent No. 5,747,282.  The patent-eligible distinction, according to this panel, is that in Claim 20 the cell that was used to compare growth rates in the presence or absence of a test compound was non-naturally occurring (and constituted patent-eligible subject matter, and thus "their inclusion in the process made the claims patent-eligible despite the reference to an otherwise ineligible mental step."

The panel enters into Supreme Court-sanctioned flights of fancy in finding that the claims also fail the machine-or-transformation test, on the grounds that "measuring" marker levels is not transformative because "it could be performed 'without transforming the [sample], should science develop a totally different system for [assaying for a biochemical screening marker] that did not involve such a transformation,'" citing Mayo.

While it is apparent that the point is that the claims are overbroad in this respect, it should not be too much to ask that courts base their opinions (with regard to conventionality) on the conditions and limitations existing in the reality we happen to inhabit at the time they render a decision, not some hypothetical Never-Never Land of their own imagination.

This case stands as the most recent cautionary tale of how diagnostic methods claims must be crafted -- narrow, specific, encompassing particular assaying and detection steps, and encompassing some (any) patentable feature other than the naturally occurring correlation between a marker and disease.  It may be hoped that claims drawn to a novel marker, or to the new appreciation that a known marker was diagnostically relevant to a particular disease, contained in claim language reciting sufficient specificity to recited methods, will be enough to pass muster.  After all, Intema's claims (and the claims of most existing diagnostic method patents granted prior to the Mayo decision) were drafted without foreknowledge of the Supreme Court's return to the Benson/Flook era in Mayo, and its targeting of any claim that may impact medical treatment.  Of course, the lesson from Mayo, and this case, is that such inventions should not be patented, but rather kept in a tight black box where patient data is gathered (including for security some unnecessary data) and a clinically established correlation produced.  This is, of course, the antithesis of a patent regime intended to "Promote the Progress . . . of the Useful Arts" but in a capitalist society, diagnostic assays cannot reasonably be expected to be developed, or distributed, free of charge.  Perhaps the courts, and the medical community, will come to face this reality before it is too late.

PerkinElmer, Inc. v. Intema Ltd. (Fed. Cir. 2012)
Panel: Circuit Judges Bryson, O'Malley, and Wallach
Opinion by Circuit Judge O'Malley

Comments

[Keep It Real]

Kevin, you still seem to be working very hard to not understand Prometheus v. Mayo.

"These two characteristics of the claims -- that they recite "mental steps" and "natural laws" -- are sufficient to render them patent-ineligible unless, according to the opinion, [the claims] also contain that ineffable "something more" required by the Supreme Court's Mayo opinion. "

It's very clear what constitutes "something more", Kevin: a novel transformative step, a novel machine, or a novel composition of matter. If you lack any of these things, the claim is effectively a claim to the mental step (e.g., the step thinking about a phenomenon, correlation, "law of nature", or anthing else).

This was explained to you before Prometheus. I'm explaining it to you again. All 9 judges on the Supreme Court understand and it appears that the Federal Circuit gets it as well. There may be claims on the margin (there always will be) but there is nothing very difficult to comprehend about the Prometheus decision. It was the right decision. And it was the expected decision, unless you expected the Supreme Court to open up the floodgates to the effective patenting of information itself.

"This is, of course, the antithesis of a patent regime intended to "Promote the Progress . . . of the Useful Arts" "

The patent system was not designed to protect information, Kevin. Correlations are information. If you allow people to patent methods of thinking about the results of old blood tests, you are not promoting progress in blood tests. You are merely allowing patents to protect information itself.

If you believe that people should be entitled to monopolies on publically disclosed new facts, then perhaps you should lobby Congress to create a new form of intellectual property.

[Kevin E. Noonan]

That was fast, Keep. But I don't need to ask Congress; I have the solution:

Of course, the lesson from Mayo, and this case, is that such inventions should not be patented, but rather kept in a tight black box where patient data is gathered (including for security some unnecessary data) and a clinically established correlation produced. This is, of course, the antithesis of a patent regime intended to "Promote the Progress . . . of the Useful Arts" but in a capitalist society, diagnostic assays cannot reasonably be expected to be developed, or distributed, free of charge.

I do think that there are claims, arguably these, that should fall outside the scope of patent eligibility because they are over broad. Myriad's claims, for example, could be infringed as you posit, merely by thinking. No worries, right result.

But making the equation that every claim that recites 1) assaying a biological sample for [something]; 2) comparing what you assay with the "normal" value"; and 3) making a diagnosis is per se ineligible is not the answer. It IS if 1) what you assay for is known AND 2) the relationship between what was detected and what is diagnosed is known AND 3) HOW the assay is performed is routine and conventional.

But the opinion doesn't (to me) cabin the grounds for finding patent-ineligibility (although here the statements in the spec almost amounted to detecting any marker that can be correlated with a disease using any detection method, with no indication that what is detected is novel).

Thanks for the comment.

[Gary Johnston]

Keep, I have repeatedly mentioned to Dr. Noonan the possibility of a regulatory marketing exclusivity scheme for new diagnostics (a la NCEs or orphans) and/or a new type of patent which I call a "diagnostic patent." It could work. At least it would placate the whiners who think that "life-saving" tests won't be developed in view of Prometheus v. Mayo (I always chuckle when I hear someone tell me that a test will save my life). Seems to me the biggest problem would be figuring out the appropriate requirements for granting the marketing exclusivity or the patent rights. That's actually not an easy thing to do when it comes to diagnostic correlations.

[Kevin E. Noonan]

Dear Gary:

I have no issues with the regulatory approach - indeed, I think the 12 year market exclusivity in the biosimilars law may prove much more valuable than patent protection. My argument is that shifting the incentives as Mayo does has consequences, such as encouraging less patenting and more trade secret protection. Whether you think the patentee deserves the protection or not, one thing that is certain is that patenting promotes disclosure and thus improvements - even in Mayo, one of the infringer's arguments was that they had developed a better" test, which I suspect would have been much more difficult to do if they didn't have the Prometheus test available in the first place.

Whether patentable or not, I am also concerned that the Intema test had real world benefits - avoiding invasive tests that had a finite risk of miscarriage. If such tests are not developed due to the economics of developing the tests (of which I have no specific knowledge), I don't think this is a good outcome. For me, doctrinal purity isn't as important as these benefits of diagnostic methods.

Thanks for the comment.

[Keep It Real]

"If such tests are not developed due to the economics of developing the tests (of which I have no specific knowledge),

Again, there was no "test" developed here. Someone discovered a useful fact. That' all. Are you saying that without patents people will stop discovering useful facts?

The patents we want are not to the useful facts but to the patentable methods and compositions of matter which enable those facts to be discovered more quickly and cheaply. Allowing people to monopolize the facts does not promote "progress" in anything except the "progress" of patent law into areas where it was never intended to be operating.

[EG]

"Again, there was no 'test' developed here."

Not true, Keep. What Intema's claimed method essentially does is compare the measured levels of a first ultrasound screening marker from the first trimester with the measured levels of a second ultrasound screening marker from the second trimester to determine the risk of Down's syndrome; that's a "test" if there ever was one, not simply discovering "useful facts" as you assert.

Moreover, Indema not's claiming essentially a "law of nature" either. Nature" does not and cannot "measure" those levels, nor does "nature" compare those levels to determine the Down's syndrome risk. As ruled by district court, Intema's claimed method may be anticipated/obvious, but it is patent-eligible in my opinion under 35 USC 101.

That you (or this Federal Circuit panel) believes otherwise isn't persuasive to me at all. And please no "9-0" incantation as that is also unpersuasive to me.

[Keep It Real]

EG: "What Intema's claimed method essentially does is compare the measured levels of a first ultrasound screening marker from the first trimester with the measured levels of a second ultrasound screening marker from the second trimester ...; that's a "test" if there ever was one"

No doubt. But as claimed, it's an old test, just like the test for measuring metabolite levels in Prometheus was old.

What's new is only how to interpret the results of those old tests, "to determine the risk of Down's syndrome," as you say. And that's why the patent (if it were found to be eligible) would effectively be a patent to the new way of thinking about the result (undeniably true with respect to those practicing the prior art).

"Nature" does not and cannot "measure" those levels, nor does "nature" compare those levels to determine the Down's syndrome risk."

You clearly have no idea what Prometheus was about. The logic of the Prometheus opinion is not grounded in the TYPE of information that is threatened with removal from the public domain if claims such as these are granted (removed, at least, from the perspective of those who are practicing the prior art). The logic covers ALL information -- correct information, incorrect information, facts, non-facts, laws of nature, non-laws of nature, abstract thoughts and concrete thoughts. None of this subject matter can be protected merely by appending some prior old method of procuring a result prior to a mental step of determining the relevance of that result (i.e., by considering the "new" fact, non-fact, law of nature, non-law of nature, novel abstraction, or whatever that is dedicated to the public in the patent specification).

Maybe you should go back and read the oral arguments in Prometheus and consider Justice Breyer's hypothetical about a "life-saving" discovery related to an observation of the length of one's fingernail. This all goes right back to LabCorp. It's pretty simple stuff.

"please no "9-0" incantation as that is also unpersuasive to me"

It's not supposed to persuade you. It's supposed to help you understand that Prometheus is never, ever going to be reversed. It's an important case and the only reason it wasn't decided earlier is because applicants weren't so aggressively and transparently trying to methods of thinking about results of old methods.

[EG]

"You clearly have no idea what Prometheus was about."

Just because I don't accept the nonsensical reasoning in Mayo doesn't mean I don't understand it. Do have to deal with Mayo from a practical standpoint? Yes. Do I have to agree with it/accept it? No. BTW, you might consider what was said in footnote 2 of PerkinElmer regarding Classen.

"Maybe you should go back and read the oral arguments in Prometheus and consider Justice Breyer's hypothetical."

No need to. That Breyer believes his disingenuous reasoning is consistent with Diehr tells me he was looking for the desired result only, not a principled decision. If you believe otherwise, then explain (not just tell me) how the reasoning of Mayo can be squared with Diehr.

"It's supposed to help you understand that Prometheus is never, ever going to be reversed."

Don't be so sure. Times, courts and justices do change. Most may have thought that Gottschalk v. Benson and Parker v. Flook did in patenting of computer technology. But guess what? Along came Diamond v. Diehr. Something for you to ponder in the wee hours . .

[David Koepsell]

Or maybe the lesson of Mayo is that patents ought only to issue for things that were created rather than natural correlations that are discovered. I have no doubt science will continue to find and publish its findings of natural laws, products, and such, (your fears of black boxes notwithstanding) since the motivations of scientists are different than those of businessmen, and their sources of funding also differ. Now its up to entrepreneurs to focus on creating (as I have mentioned, this involves both intention and design, not mere discovery) and not rely so much on creative claim drafting by IP attorneys.

[EG]

"Now its up to entrepreneurs to focus on creating (as I have mentioned, this involves both intention and design, not mere discovery) and not rely so much on creative claim drafting by IP attorneys."

Dream on David, dream on. Entrepreneurs do focus on "creating." But if you make it difficult for them to compete with the Goliaths of industry by narrowing the scope of that which is patent-eligible (as this case does), they must either rely upon trade secrets or give up the ghost. Innovation, like money, doesn't grow on trees. If you don't nuture it, it will die.

And science (which certainly has it's place in the innovation scheme) alone won't get you developed products and processes for making them; as even academics understand, businesses have the expertise to do that. You're also dreaming to think all scientists aren't motivated similarly to business people; many in academic world are becoming entrepreneurs because they see the potential reward.

Without vibrant entrepreneurship, you will have no job growth; ask Hank Nothhaft, a recognized entrepreneur, why the US is having such difficulty increasing job growth. As Hank will tell you, government and especially its crushing tax burden on small business is why small business is struggling in the U.S. And he'll also tell that without viable patent protection, small entrepreneurs normally won't make it trying to compete with the Goliaths.

[Keeping it Real]

"Entrepreneurs do focus on "creating." But if you make it difficult for them to compete with the Goliaths of industry "

Entrepeneurs like ... Prometheus?

LOL.

[David Koepsell]

Hi EG! I'm in favor of reducing governmental interference in markets, more so than you, I think. The "Goliaths of Industry" are such mostly due to government largess, typically through govt-sponsored monopolies (can you say "intellectual property"?). I favor eliminating those, and allowing free market competition to reign. Basic research will always go forward because of academic interests in academic careers, science itself, and the demands of publishing, even though some scientists surely have dollar signs in their eyes. The discovery of the Higgs Boson, for instance, involved thousands of scientists motivated by more than dreams of patent royalties. Finally, your diatribe is utterly besides the point, completely orthogonal to what the Supreme Court must decide regarding the patent-eligibility of what I and others claim are natural products, artificially created. Should be interesting to see what happens if they decide to take it up. I'm hopeful.

[EG]

Dear David,

Thanks for the reply. So we do have common ground on the problems with the "Goliaths of Industry." Large corporations unfortunately share many "bureaucratic" problems as do government; having worked for a larger corporation for over 19 years I understand the "beast" all too well.

My alleged "diatribe" is not beside the point on the patent-eligibity issue. If you unduly narrow the scope of what might be patent-eligible under 35 USC 101, businesses will respond by either keeping what they develop as trade secrets or else not developing it at all. The Gottchalk v. Benson and Parker v. Flook decisions by the Supreme Court in early to mid 70's (coupled with two very negative Supreme Court decisions on patentability under 35 USC 103) presented a very bleak picture for protecting innovations at the cutting edge and outside the conventional technology norm. Fortunately, Diamond v. Chakrabarty and Diamond v. Diehr came along to open up to the scope of patent-eligibility under 35 USC 101 to what it should have been. The problem with the Supreme Court in the patent law arena is that they make patent law "policy" without ever considering the economic downsides that could occur because the Supreme Court is "patent hostile" in the extreme, and strictly driven almost exclusively by an antitrust philosophy. (One of the reasons the Federal Circuit was created in 1982 to handle all patent appeals was concerns that the Supreme Court, as well as other appellate courts, had gone "overboard" with their patent "hostility.")

Your comment that the "Supreme Court must decide regarding the patent-eligibility of what I and others claim are natural products, artificially created" is interesting. In my lexicon "artificially created" does not equate to "natural product." Also, what Indema did in its claimed method goes beyond what "nature" can do. As I've noted above, "nature" cannot "measure" the levels of the markers, or make the comparison of those levels to standards to diagnose Down's Syndrome risk. As I've also said I'm fine with Indema's claimed method going down as lacking novelty/being obvious under 35 USC 102/103; that's how to separate out meritorious innovations from those that are truly "meritless." But when you restrict the scope of what technology is patent-eligibile using the reasoning and subjective standards that Breyer did in Mayo, you now have the courts making "policy" and thus invading Congress' constitutionally mandated domain. (I'm especially annoyed that the Supreme Court is making this "policy" based on "pseudoscience" and deliberate misrepresentation of proper patent claim terminology.)

You are correct that it will be "interesting to see what happens." Fortunately, I'm at a stage in my career (now over 35 years) where if the decisions in patent law (and the AIA) gets nonsenscial enough, I can simply "hang up" my IP spikes and do something else. Peace, do have a nice weekend.

[David Koepsell]

Thanks, EG. This is why I think philosophers are necessary, to clarify the ontology. The exceptions carved by the Supreme Court regarding natural laws, products of nature, and abstract ideas are, I think, founded upon sound principles. Namely, none of these is a product of man's design or intention. The rationale behind not granting patents on these things is not necessarily utilitarian. I think it would be downright unjust to grant a monopoly privilege to someone for something which he or she did not intentionally design, and which nature did, economic consequences notwithstanding.

Peace to you too. Be well, and see you here in the New Year.
D

[Keeping it Real]

"Breyer believes his disingenuous reasoning"

There is nothing "disengenuous" about the argument that when you append a step of thinking a "new thought" about a "law of nature" (or any other new thought) to an old non-mental step, that you are effectively claiming the new thought itself.

And it's not just Breyer's reasoning you are attacking. It's all 9 of the Supreme Court Justices, the Mayo Clinic, and a great many patent prosecutors in the field (myself included) who understand and fully support the reasoning. I'd love to know why you think my reasoning is "disengenuous", EG. (For the record, the government also did not believe claims such as Prometheus' claims should be patentable, but they wanted to find the claims unpatentable under 102 by ignoring the novel mental step -- same exact result, however).

"he was looking for the desired result only, not a principled decision."

No. The principle is straightforward and easy to apply. The principle is that you can't discover a new "phenomenon" (or idea or whatever) and obtain a patent that effectively prevents practitioners of the prior art (i.e., practitioners of the "old, conventional steps" referred to in the decision) from thinking about the new "phenomenon".

"explain ... how the reasoning of Mayo can be squared with Diehr"

Let me know what you think the holding of Diehr is. Obviously, if you believe that Diehr stands for the proposition that "everything except purely mental thoughts is per se eligible for patenting" is eligible for patenting, then the two cases can't be "squared". At least not in your (closed, reality-denying) mind.

[Keeping it Real]

EG: "What Intema's claimed method essentially does is compare the measured levels of a first ultrasound screening marker from the first trimester with the measured levels of a second ultrasound screening marker from the second trimester to determine the risk of Down's syndrome"

LOL. Is that all? Here's my invention: I claim a method of comparing the measured levels of a first screening method from the first trimester with the measured levels of a second screening marker from the second trimester AND a third screening marker from a month selected from months 1-6! And as many other markers as you want. And doing so multiple times, if you like. And using it to determine the relative risk of Downs syndrome and any other condition or feature of interest known to be correlated with any of the markers. And oh, what the heck, let's toss in a limitation about applying it to mothers with blonde hair and brown eyes just in case there is some allegedly anticipating art out there.

So there I just donated some "technology" in the same "class" as that claimed by Intema. Of course, without a patent, nobody will ever develop this "technology" and as a result we're all going to die.