DCT
1:18-cv-01436
Quest Diagnostics Investments LLC v. Laboratory Corp Of America Holdings
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Quest Diagnostics Investments LLC (Delaware)
- Defendant: Laboratory Corporation of America Holdings, Esoterix, Inc., and Endocrine Sciences, Inc. (Delaware)
- Plaintiff’s Counsel: Morris James LLP
- Case Identification: 1:18-cv-01436, D. Del., 09/17/2018
- Venue Allegations: Venue is based on Defendants’ incorporation in Delaware, which establishes residency for purposes of patent venue.
- Core Dispute: Plaintiff alleges that Defendant’s clinical diagnostic tests for testosterone and various vitamin D metabolites infringe four patents related to methods of analyte detection using mass spectrometry.
- Technical Context: The technology at issue involves the use of liquid chromatography and tandem mass spectrometry (LC/MS-MS) for the sensitive and specific quantification of hormones and metabolites in human biological samples, a foundational technique in modern clinical diagnostics.
- Key Procedural History: The complaint alleges that Plaintiff engaged in pre-suit communications with Defendant regarding the methodologies of the Accused Vitamin D Tests, including an in-person meeting where claims of the ’427 and ’868 patents were raised. The complaint also alleges Defendant had actual notice of the ’862, ’427, and ’867 patents as of June 15, 2017. These allegations form part of the basis for the claims of willful infringement.
Case Timeline
| Date | Event |
|---|---|
| 2003-09-08 | U.S. Patent 8,409,862 Priority Date |
| 2005-04-06 | U.S. Patent 8,101,427 Priority Date |
| 2005-04-06 | U.S. Patent 7,972,867 Priority Date |
| 2007-11-28 | U.S. Patent 7,972,868 Priority Date |
| 2011-07-05 | U.S. Patent 7,972,867 Issued |
| 2011-07-05 | U.S. Patent 7,972,868 Issued |
| 2012-01-24 | U.S. Patent 8,101,427 Issued |
| 2013-04-02 | U.S. Patent 8,409,862 Issued |
| 2017-06-15 | Alleged Actual Notice Date for ’862, ’427, and ’867 Patents |
| 2018-09-17 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
No probative visual evidence provided in complaint.
U.S. Patent No. 8,409,862 - "Determination of Testosterone by Mass Spectrometry," issued April 2, 2013
The Invention Explained
- Problem Addressed: The patent addresses the need for a sensitive and efficient method to measure testosterone, particularly the very low levels typically present in human females, which can be diagnostically significant (’862 Patent, col. 1:49-50; Compl. ¶12).
- The Patented Solution: The invention provides a method using mass spectrometry that involves first purifying testosterone from a female human sample (e.g., via chromatography) and then ionizing the purified, non-derivatized testosterone for detection (’862 Patent, col. 2:8-12, col. 3:7-15). This process is described as a "high-throughput assay system" with "enhanced specificity" that is more efficient than earlier assays, making it suitable for large clinical laboratories (’862 Patent, col. 5:50-62).
- Technical Importance: The method’s claimed high-throughput capability and enhanced specificity offered an improved tool for large-scale clinical diagnostics, especially for patient populations with low testosterone levels (Compl. ¶14).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶49).
- Claim 1 requires a method for determining testosterone in a sample from a female human, comprising the steps of:
- (a) purifying testosterone from the sample, which includes extracting it;
- (b) ionizing the purified testosterone to produce detectable ions;
- (c) detecting the amount of the testosterone ion(s) with a mass spectrometer;
- wherein the testosterone is not derivatized prior to mass spectrometry; and
- wherein the method can detect testosterone at concentrations below 10 ng/dL.
- The complaint’s phrasing suggests a reservation of the right to assert other claims (Compl. ¶49).
U.S. Patent No. 8,101,427 - "Methods for Detecting Vitamin D Metabolites by Mass Spectrometry," issued January 24, 2012
The Invention Explained
- Problem Addressed: The patent’s background section explains that while measuring vitamin D metabolites is clinically important for diagnosing calcium metabolism disorders, prior immunologically-based assays could not distinguish between different forms like vitamin D2 and vitamin D3, limiting their diagnostic precision (’427 Patent, col. 1:53-2:21).
- The Patented Solution: The invention uses tandem mass spectrometry to specifically quantify vitamin D metabolites by first generating a "protonated and dehydrated precursor ion" of the target metabolite, fragmenting this specific precursor ion, and then detecting the resulting fragment ions (’427 Patent, col. 2:58-65; Compl. ¶19). This approach avoids the chemical derivatization step that some prior art mass spectrometry methods required (’427 Patent, col. 2:38-42).
- Technical Importance: This method enables the specific and simultaneous measurement of multiple vitamin D metabolites in a single assay, offering a more precise diagnostic tool than earlier immunoassays that could not resolve different forms of the vitamin (’427 Patent, col. 3:19-25).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶56).
- Claim 1 requires a method for determining the amount of a vitamin D metabolite in a sample by tandem mass spectrometry, comprising the steps of:
- (a) generating a protonated and dehydrated precursor ion of the vitamin D metabolite;
- (b) generating one or more fragment ions from that precursor ion; and
- (c) detecting the amount of ions from step (a) and/or (b) and relating it to the amount of the metabolite in the sample.
- The complaint reserves the right to assert other claims (Compl. ¶56).
U.S. Patent No. 7,972,867 - "Methods for Detecting Vitamin D Metabolites by Mass Spectrometry," issued July 5, 2011
- Technology Synopsis: This patent discloses methods for determining the amount of a vitamin D metabolite in a sample using tandem mass spectrometry (Compl. ¶21). The asserted claim is specifically directed to a method for detecting 25-hydroxyvitamin D2 by generating a "protonated and dehydrated precursor ion" of that metabolite with a mass-to-charge (m/z) ratio of 395.30 ± 0.5, fragmenting this precursor ion, and detecting the resulting ions (Compl. ¶23).
- Asserted Claims: At least independent claim 21 (Compl. ¶68).
- Accused Features: The Accused Vitamin D Tests are alleged to infringe by using tandem mass spectrometry to measure 25-hydroxyvitamin D2, which allegedly involves generating and fragmenting a precursor ion with the specific m/z ratio recited in the claim (Compl. ¶¶69, 71).
U.S. Patent No. 7,972,868 - "Methods for Detecting Dihydroxyvitamin D Metabolites by Mass Spectrometry," issued July 5, 2011
- Technology Synopsis: The patent relates to methods for determining the amount of dihydroxyvitamin D metabolites (such as 1α,25-dihydroxyvitamin D2) in a human biological sample via tandem mass spectrometry (Compl. ¶25, ¶27). The asserted claims cover two distinct approaches: one that uses atmospheric pressure chemical ionization (APCI) on a non-derivatized metabolite (claim 1), and another that first derivatizes the metabolite with a specific chemical agent (4'-carboxyphenyl-TAD) before mass spectrometry analysis (claim 9) (Compl. ¶27-28).
- Asserted Claims: At least independent claims 1 and/or 9 (Compl. ¶81).
- Accused Features: Certain of the Accused Vitamin D Tests (specifically Esoterix Test 500342) are alleged to infringe by using tandem mass spectrometry to measure dihydroxyvitamin D metabolites, allegedly employing methods that meet the limitations of either the non-derivatized or derivatized claimed processes (Compl. ¶¶82-84).
III. The Accused Instrumentality
Product Identification
The accused instrumentalities are two categories of clinical diagnostic services offered by Defendants:
- The "Accused Testosterone Tests": A collection of five specified test services (e.g., LabCorp Test No. 070001) that measure testosterone levels (Compl. ¶29).
- The "Accused Vitamin D Tests": A collection of five specified test services (e.g., LabCorp Test No. 504115) that measure various vitamin D metabolites (Compl. ¶40).
Functionality and Market Context
- The complaint alleges that both categories of tests are performed using "Liquid chromatography/tandem mass spectrometry (LC/MS-MS)" on human serum samples (Compl. ¶30, ¶41).
- The Accused Testosterone Tests are marketed as providing the "sensitivity and specificity required for the assessment of the low testosterone levels found in women, children, and hypogonadal males" and are alleged to be capable of reporting results below 10 ng/dL (Compl. ¶30).
- The Accused Vitamin D Tests are alleged to measure various metabolites, including 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, and dihydroxyvitamin D metabolites, using methods that include purification steps such as liquid chromatography (Compl. ¶41, ¶46, ¶57, ¶69, ¶82).
IV. Analysis of Infringement Allegations
U.S. Patent 8,409,862 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| (a) purifying testosterone from a sample from a female human, wherein said purifying comprises extracting testosterone from said sample | The Accused Testosterone Tests include purifying testosterone from the sample using extraction techniques such as liquid chromatography, liquid-liquid extraction, or solid phase extraction. | ¶35 | col. 3:7-15 |
| (b) ionizing said purified testosterone to produce one or more testosterone ions detectable by a mass spectrometer | The Accused Testosterone Tests include a step of ionizing the purified testosterone to create detectable ions. | ¶36 | col. 2:8-12 |
| (c) detecting the amount of one or more of the testosterone ion(s) by a mass spectrometer, wherein the amount...is related to the amount of testosterone in the sample | The Accused Testosterone Tests use tandem mass spectrometry to detect the amount of testosterone ions, which is related to the amount of testosterone in the original sample. | ¶37 | col. 2:13-16 |
| wherein said testosterone is not derivatized prior to mass spectrometry | The complaint alleges on information and belief that the Accused Testosterone Tests use testosterone that is not chemically derivatized before mass spectrometry. | ¶38 | col. 2:8-12 |
| wherein the method is capable of detecting testosterone at concentrations of less than 10 ng/dL in the sample | The Accused Testosterone Tests are alleged to be capable of this detection level, as evidenced by their own published reference ranges for female populations, which include values below 10 ng/dL. | ¶39 | col. 5:50-51 |
- Identified Points of Contention:
- Scope Questions: The definition of "purifying" may be a point of contention. The question may arise whether the standard sample preparation and extraction techniques allegedly used by Defendant meet the scope of "purifying" as understood in the context of the patent, which describes an innovative method "superior to the methods described in the prior art" (Compl. ¶12).
- Technical Questions: A key factual question for the court will be whether the Accused Testosterone Tests in fact use non-derivatized testosterone, as required by the claim. The complaint makes this allegation "on information and belief," suggesting it may be a central point of evidentiary dispute (Compl. ¶38).
U.S. Patent 8,101,427 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| (a) generating a protonated and dehydrated precursor ion of said vitamin D metabolite | The complaint alleges on information and belief that as part of the Accused Vitamin D Tests, Defendants generate a protonated and dehydrated precursor ion of the vitamin D metabolite being measured. | ¶58 | col. 2:63-65 |
| (b) generating one or more fragment ions of said precursor ion | On information and belief, the Accused Vitamin D Tests are alleged to generate fragment ions from the precursor ion, for example by inducing collisions. | ¶59 | col. 3:5-9 |
| (c) detecting the amount of one or more of said ions generated in step (a) or (b) or both and relating the detected ions to the amount of said vitamin D metabolite in said sample | On information and belief, Defendants are alleged to detect the precursor and/or fragment ions and relate their amount to the quantity of the vitamin D metabolite in the original sample. | ¶60, ¶61 | col. 3:10-12 |
- Identified Points of Contention:
- Technical Questions: The complaint explicitly states that Plaintiff is "unaware of any publicly-available information describing certain aspects of LabCorp's Accused Vitamin D Tests, such as the specific details of LabCorp's mass spectrometry analysis" (Compl. ¶46). Therefore, a primary technical question will be what evidence discovery yields regarding the precise nature of the precursor ions generated in the accused methods. The case may turn on whether these ions are in fact "protonated and dehydrated," as specifically required by the claim, or a different ionic species.
V. Key Claim Terms for Construction
The Term: "purifying" (from ’862 Patent, claim 1)
- Context and Importance: This term appears in the first step of the claimed method. Its construction will be critical to determining whether standard laboratory sample preparation techniques, such as the alleged use of liquid chromatography or solid phase extraction, fall within the scope of the claim.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: Claim 1 provides its own definition: "wherein said purifying comprises extracting testosterone from said sample" (’862 Patent, claim 1). This language may support an argument that any method of extraction constitutes "purifying."
- Evidence for a Narrower Interpretation: The specification describes the invention as providing "enhanced specificity" and being "superior to the methods described in the prior art" (Compl. ¶12; ’862 Patent, col. 5:50-62). This context could support an argument that "purifying" implies more than routine sample cleanup and requires a step that achieves a specific level of purity necessary for the claimed low-level detection.
The Term: "a protonated and dehydrated precursor ion" (from ’427 Patent, claim 1)
- Context and Importance: This term defines the specific chemical species that is generated and fragmented in the claimed tandem mass spectrometry method. Infringement of the ’427 patent hinges on whether the accused tests generate this exact type of ion. Practitioners may focus on this term because the complaint acknowledges a lack of detailed information about the accused process, making the nature of the generated ions a central unknown (Compl. ¶46).
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification does not provide a special definition beyond the plain chemical meaning of the words. This may suggest that any process resulting in an ion that is both protonated and has lost a water molecule would suffice.
- Evidence for a Narrower Interpretation: The patent consistently and specifically recites this "protonated and dehydrated" ion in the Summary of the Invention and the claims, distinguishing it from merely ionized molecules (’427 Patent, Abstract; col. 2:63-65). This repeated emphasis may support a narrow construction that requires the specific formation of this dual-state ion as a distinct step.
VI. Other Allegations
- Willful Infringement: The complaint alleges willful infringement for all four patents-in-suit. The allegations are based on a combination of constructive notice from the patents' issue dates and alleged actual notice. For the ’862, ’427, and ’867 patents, actual notice is alleged as of June 15, 2017 (Compl. ¶50, ¶62, ¶75). For the ’427 and ’868 patents, the basis for willfulness is further supported by allegations of pre-suit meetings where Plaintiff specifically raised claims of those patents with Defendant (Compl. ¶47). The complaint also asserts that Defendant's own involvement in seeking patent protection in the same technical field supports its knowledge of Plaintiff's patents (Compl. ¶51, ¶63, ¶76, ¶89).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central evidentiary issue for the Vitamin D patents (’427, ’867, ’868) will be one of process confirmation: does the accused testing methodology, once revealed in discovery, actually generate the specific "protonated and dehydrated precursor ion" required by the claims? The complaint's infringement theory rests on "information and belief," making the precise technical details of the accused process the dispositive factual question.
- For the testosterone patent (’862), a core issue will be one of definitional scope: can the term "purifying," which the claim states "comprises extracting," be construed to cover the standard liquid chromatography and sample preparation techniques allegedly used by Defendant, or does the patent’s context require a more specific purification step designed to achieve the claimed sensitivity?
- A key factual question for the ’862 patent will be proof of a negative limitation: what evidence demonstrates that the accused tests are performed on testosterone that is "not derivatized" prior to mass spectrometry, as alleged in the complaint and required by the claim?