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Supreme Court to Review Validity of “Test-Plus-Correlate” Claims: LabCorp v. Metabolite

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Medical research often results in discoveries correlating physiological phenomena with a disease or condition. [1] Such correlations may lead to new pharmaceuticals and disease testing methods. Because these discoveries have great commercial potential, inventors, and the institutions for which they work, are motivated to seek early and broad patent protection. This has caused inventors to claim a two-step method: (1) test for the physiological phenomena; and (2) correlate that test with the disease. In Laboratory Corp. of America v. Metabolite Laboratories (“LabCorp”), t he U.S. Supreme Court will determine the validity of such “test-plus-correlate” claims . [2]

In LabCorp, the inventors of U.S. Patent No. 4,940,658 (“‘658 Patent”) discovered a correlation between homocysteine and a vitamin deficiency. To protect this discovery, the inventors employed a test-plus-correlate claim:

13. A method for detecting a deficiency of cobalamin or folate
in warm-blooded animals comprising the steps of:
assaying a body fluid for an elevated level of total homocysteine;
and correlating an elevated level of total homocysteine in said
body fluid with a deficiency of cobalamin or folate. [3]

This claim’s two steps are: (1) testing for elevated homocysteine levels and (2) correlating the elevated homocysteine levels with a deficiency in the vitamins cobalamin or folate. In short, the inventors claim to have discovered the relationship in humans between an elevated level of total homocysteine and two particular vitamin deficiencies. [4]

Initially, the controversy began as an infringement dispute between Laboratory Corporation of America (“LabCorp”) and Metabolite Laboratories (“Metabolite”). Metabolite won at trial, and the United States Court of Appeals for the Federal Circuit (“Federal Circuit”) affirmed. On November 2, 2005, the Supreme Court granted LabCorp’s request for a writ of certiorari to review the Federal Circuit’s decision, framing the issue as whether claim 13 Metabolite’s patent improperly claims “laws of nature, natural phenomena, and abstract ideas” under 35 U.S.C. § 101. Specifically, the Court will address:

Whether a method patent setting forth an indefinite, undescribed,
and non-enabling step directing a party simply to “correlat[e]”
test results can validly claim a monopoly over a basic scientific
relationship used in medical treatment such that any doctor
necessarily infringes the patent merely by thinking about the
relationship after looking at a test result. [5]

Notably, the Supreme Court granted review against the Solicitor General’s advice. The Court had asked the Solicitor General to provide the U.S. Government’s views about a question not directly raised by the petitioner or addressed by the Federal Circuit:

Respondent’s patent claims a method for detecting a form of
vitamin B deficiency, which focuses upon a correlation in the
human body between elevated levels of certain amino acids
and deficient levels of vitamin B. The method consists of the
following: First, measure the level of the relevant amino acids
using any device, whether the device is, or is not, patented;
second, notice whether the amino acid level is elevated and,
if so, conclude that a vitamin B deficiency exists. Is the patent
invalid because one cannot patent “laws of nature, natural
phenomena, and abstract ideas“?
Diamond v. Diehr , 450 U.S. 175, 185 (1981). [6]

The Solicitor General noted that the Federal Circuit had not considered the natural phenomena question and maintained that the trial record was insufficient for considering whether claim 13 met the subject matter requirements of 35 U.S.C. § 101. [7] Nevertheless, the Court granted certiorari.

Claim 13’s Prosecution History

Interestingly, as originally filed, claim 13 failed to recite the “correlating” step. [8] During examination, the claim was rejected under 35 U.S.C. § 102 on the ground that a published paper from 1985 disclosed “assaying” for total homocysteine. [9] The examiner explained, “[t]he claim lacks a positive limitation for correlating to a particular condition and has only one method step recited.” [10] The “correlating” step was added to overcome the prior art reference.

Claim 13 in the Courts

At trial, the United States District Court for the District of Colorado construed “correlating” to mean “to establish a mutual or reciprocal relationship between.” [11] Based on this construction, the jury found LabCorp indirectly infringed claim 13 and that claim 13 was not invalid. The court assessed damages against LabCorp for indirect infringement, which were then doubled on grounds of willfulness.

On appeal, LabCorp argued the district court’s construction of “correlating” was incorrect, and that LabCorp did not infringe the claims of the ‘658 Patent, correctly construed. However, the Federal Circuit instead expanded the district court’s construction of “correlating.” The court held that correlating “includes both a mutual relationship between the presence of an elevated level of homocysteine and a vitamin deficiency and a reciprocal relationship between the absence of an elevated level of homocysteine and no vitamin deficiency.” [12] Claim 13 therefore “provides that if the assay discloses ‘an elevated level of total homocysteine,’ the physician determines whether there is a cobalamin or folate deficiency by ‘correlating,’ i.e., comparing the elevated level with the normal homocysteine level.” [13] Thus, the direct infringers are physicians performing the correlating step—they “order assays and correlate the results of those assays, thereby directly infringing.” [14] The Federal Circuit also disagreed with LabCorp’s challenges of claim 13’s validity on several grounds, [15] but failed to consider whether claim 13 validly claimed patentable subject matter under 35 U.S.C. § 101.

LabCorp’s Petition for Supreme Court Review

In its petition for certiorari, LabCorp continued to argue claim 13’s invalidity. According to LabCorp, claim 13 merely “test[s] for fact A and correlate[s] with fact B.” [16] Consequently, “thousands of doctors are daily infringing the patent by ‘correlating’ test results in their head.” [17] “Such a vague claim cannot be valid; for if it could be, parties could claim patent monopolies over basic scientific facts rather than any novel inventions.” [18] Metabolite responded that claim 13 “cannot be infringed by a physician’s mere thought processes, because the patent requires a further distinct and physical step: the step of assaying for total homocysteine.” [19]

While the Solicitor General noted that claim 13 treads close to Diehr ’s prohibition against patenting “natural phenomena,” [20] in recommending against review, he cautioned that “a decision overturning the PTO’s approach could call into question a substantial number of patent claims and undermine the settled expectations of numerous participants in technology-based industries.” [21] LabCorp responded that claim 13’s relationship between homocysteine and vitamin deficiencies is akin to Einstein’s theory of relativity, E=mc 2 . [22] Converting E=mc 2 into a test-plus-correlate claim results in the claim “test for E and correlate with mc 2 .” With this claim, “Einstein could have prevented any physicist from thinking about his famous equation.” [23] LabCorp also noted the claim’s “testing” step could not render the claim patentable, explaining that “[o]ne cannot patent an unpatentable principle merely by grafting onto it a non-inventive use.” [24]

LabCorp’s potential impact

By taking on LabCorp, a question of subject matter patentability, the Court may be responding to recent struggles in the PTO, Board of Patent Appeals and Interferences (“BPAI”), and Federal Circuit. Significantly, the Federal Circuit recently decided that expressed sequence tags (“ESTs”) are not patentable under 35 U.S.C. § 101, basing its decision on the Supreme Court’s directive in Brenner v. Mason , which requires that inventions have a substantial and specific utility under § 101. [25] The BPAI has since held “there is currently no judicially recognized separate ‘technological arts’ test to determine patent eligible subject matter under § 101.” [26] The BPAI also looked to the Supreme Court, noting the Court’s failure to adopt the so-called technological arts test. [27] Most recently, the PTO has provided examiners with new guidelines about patentable subject matter. [28] By granting review, the Court may clarify the debate over the scope of patentable subject matter, an issue not examined since Diamond v. Diehr . [29]

LabCorp’s ultimate impact may be far-reaching. Test-plus-correlate claims are a common strategy for broadly protecting early discoveries. A cursory search of published patents and patent applications on the PTO’s website reveals several such claims:

•  The correlation between abnormal skin growth (skin cancer) and a growth factor receptor:

A method of diagnosis for the detection of abnormalities in mammalian cell growth comprising obtaining a test sample from a human and assaying the sample of a truncated epidermal growth factor receptor having at least a portion of its mature amino terminus deleted, and correlating detection of said truncated growth factor receptor with abnormal growth control in mammalian cells. [30]

•  The correlation between pancreatic cancer and a biomarker:

A method of qualifying pancreatic cancer status in a subject comprising: (a) measuring at least one biomarker in a sample from the subject, wherein the biomarker is selected from the group consisting of . . . and (b) correlating the measurement with pancreatic cancer status. [31]

•  The correlation between systemic inflammatory response syndrome and biomarkers:

A method for differentiating causes of SIRS in a subject, comprising: performing an assay method on a sample obtained from said subject, wherein said assay method provides a plurality of detectable signals related to the presence or amount of a plurality of subject-derived markers independently selected from the group consisting of markers related to blood pressure regulation, markers related to inflammation, and markers related to coagulation and hemostasis; and correlating the signals obtained from said assay method to the presence or absence of infection in said subject, wherein the presence of infection identifies said subject as suffering from sepsis, severe sepsis, or septic shock. [32]

•  The correlation between breast cancer and biomarkers:

A method of qualifying breast cancer in a subject comprising: (a) measuring at least one biomarker in a sample from a subject, and (b) correlating the measurement with breast cancer status, wherein the biomarker is selected from the group consisting of: . . . . [33]

•  The correlation between Alzheimer’s disease and biomarkers:

A method for qualifying Alzheimer’s disease status in a subject comprising: a. measuring at least one biomarker in a biological sample from the subject, wherein the at least one biomarker is selected from the group consisting of . . . and b. correlating the measurement with Alzheimer’s disease status. [34]

These examples highlight the Solicitor General’s warning that the Supreme Court’s review of LabCorp may call into question all “patents on medical diagnostic methods ... [or] computer related processes,” [35] as well as LabCorp’s caution against claims seeking to monopolize mental processes. [36] If such correlations are found to be unpatentable subject matter, there may be a decrease in funding for this type of basic research, as it would be much harder to provide investors a return on their investment. However, it may also increase research into alternative testing methods and treatments, as pharmaceutical companies and others could apply such research without obtaining potentially expensive patent licenses.

 

[1] For example, the correlation between high cholesterol and heart disease.

[2] Laboratory Corp. of Am. v. Metabolite Labs. , 126 S.Ct. 601 (2005), (No. 04-607), 2005 WL 2864545.

[3] ‘658 Patent col. 41, ll. 58-65 (emphasis added).

[4] Homocysteine is a sulfur-containing amino acid that is a by-product of protein digestion. Normally, homocysteine is removed by physiological processes that require folic acid (folate), vitamin B 12 (cobalamin), and vitamin B 6 (pyridoxine). Without folate and cobalamin, homocysteine levels can build up in the blood stream. Folate and cobalamin deficiencies are a risk factor for heart attack and stroke and are linked to osteoporosis, depression, Alzheimer’s, and to fetal development and pregnancy complications. If detected early enough, however, the deficiencies may be readily treated with vitamin supplements.

[5] LabCorp , 126 S.Ct. 601 (2005), (No. 04-607), 2005 WL 2864545.

[6] Brief for the U.S. as Amicus Curiae at *1, LabCorp , No. 04-607, 2005 WL 2072283.

[7] Id. at 10, 12.

[8] LabCorp , 370 F.3d 1354, 1362 (Fed. Cir. 2004).

[9] Id. at 1367; ‘658 Patent.

[10] Id. at 1362 (quoting the prosecution history).

[11] Id. at 1361.

[12] Id. at 1364.

[13] Id. at 1363.

[14] Id. at 1364.

[15] LabCorp argued that claim 13 was indefinite, not adequately described, not enabled, anticipated, and obvious.

[16] Petition for a Writ of Certiorari at *20, LabCorp , No. 04-607, 2004 WL 2505526.

[17] Id. at *21.

[18] Id. at *19.

[19] Brief for Res. in Opposition at *7, LabCorp , No. 04-607, 2005 WL 2803464.

[20] Brief for the U.S. as Amicus Curiae at *7, LabCorp , No. 04-607, 2005 WL 2072283. Under Diehr , “[o]nly ‘when a claim containing a [law of nature] implements or applies that [law] in a structure or process which, when considered as a whole, is performing a function which the patent laws were designed to protect,’ does ‘the claim satisf[y] the requirements of § 101.’” Id. at *9 (quoting Diehr , 450 U.S. at 192).

[21] Id. at *10.

[22] Supplemental Br. for Pet. at *3, LabCorp , No. 40-607, 2005 WL 2148315.

[23] Id.

[24] Id. at *4 (citing Parker v. Flook , 437 U.S. 584, 591 (1978); Funk Bros. Seed Co. v. Kalo Inoculant Co. , 333 U.S. 127, 130 (1948)).

[25] In re Fisher , 421 F.3d 1365, 1371, 1374 (Fed. Cir. 2005) (citing Brenner v. Mason, 383 U.S. 519, 534-35 (1966)). Interestingly, the court in Fisher noted that a patent application for an invention that lacks the requisite utility under 35 U.S.C. § 101 also fails, as matter of law, to meet the enablement requirement of § 112. Id. at 1378.

[26] Ex parte Lundgren , Appeal No. 2003-2088 at 7 (BPAI April 20, 2004).

[27] Id. at 7 (citing Gottschalk v. Benson , 409 U.S. 63 (1972); Diamond v. Diehr , 450 U.S. 175, 201 (1981) (Stevens, J., dissenting)).

[28] See “Interim Guidelines for Examination of Patent Applications for Patent Subject Matter Eligibility” http://www.uspto.gov/web/offices/pac/dapp/opla/preognotice/guidelines101_20051026.pdf.

[29] 450 U.S. 175 (1981).

[30] U.S. Patent No. 4,933,294 (filed June 12, 1990) (emphasis added).

[31] U.S. Patent App. Publication No. 2005/0095611 (filed May 5, 2005) (emphasis added) .

[32] U.S. Patent App. Publication No. 2005/0164238 (filed July 28, 2005) (emphasis added) .

[33] U.S. Patent App. Publication No. 2005/0170352 (filed August 4, 2005) (emphasis added) .

[34] U.S. Patent App. Publication No. 2005/0244890 (filed November 3, 2005) (emphasis added) .

[35] Brief for the U.S. as Amicus Curiae at *14, LabCorp, No. 04-607, 2005 WL 2072283.

[36] Supplemental Br. for Pet. at *4, LabCorp , No. 40-607, 2005 WL 2148315.