DCT
1:18-cv-00021
bioMerieux SA v. Hologic Inc
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: bioMérieux, S.A. (France); bioMérieux, Inc. (Missouri)
- Defendant: Hologic, Inc. (Delaware); Grifols, S.A. (Spain); Grifols Diagnostic Solutions Inc. (Delaware)
- Plaintiff’s Counsel: Smith, Anderson, Blount, Dorsett, Mitchell & Jernigan, L.L.P.
- Case Identification: 1:17-cv-00102, M.D.N.C., 02/03/2017
- Venue Allegations: Plaintiff alleges venue is proper in the Middle District of North Carolina because Defendants offer for sale and sell the accused products to hospitals, blood banks, and other medical facilities within the district, placing the products into the stream of commerce with the knowledge they will be sold there.
- Core Dispute: Plaintiff alleges that Defendant’s HIV-1 diagnostic test kits infringe patents related to specific oligonucleotide primer sequences used for the nucleic acid amplification and detection of diverse HIV-1 subtypes.
- Technical Context: The technology involves nucleic acid amplification tests designed for early and broad-spectrum detection of the Human Immunodeficiency Virus Type 1 (HIV-1), a capability critical for clinical diagnosis and ensuring the safety of the global blood supply.
- Key Procedural History: The complaint alleges that Defendant Hologic had pre-suit knowledge of the asserted patents through its efforts to revoke foreign counterparts of these patents at the European Patent Office. This allegation forms a key basis for the claim of willful infringement.
Case Timeline
| Date | Event |
|---|---|
| 1997-08-08 | Earliest Priority Date for '352 and '262 Patents |
| 2014-04-15 | U.S. Patent No. 8,697,352 Issues |
| 2015-07-07 | U.S. Patent No. 9,074,262 Issues |
| 2016-12-01 | Hologic announces sale of its interest in blood screening business to Grifols (approx. date) |
| 2017-01-31 | Hologic closes sale of its interest in blood screening business |
| 2017-02-03 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,697,352 - "Nucleic Acid Sequences that Can Be Used as Primers and Probes in the Amplification and Detection of All Subtypes of HIV-1," issued April 15, 2014.
The Invention Explained
- Problem Addressed: The patent describes the challenge posed by the high genetic variability of the HIV-1 virus, which exists in numerous subtypes (e.g., A-H, Group O) ('352 Patent, col. 2:5-15). Existing nucleic acid amplification tests, often designed for the dominant "subtype B" found in Europe and the U.S., could fail to detect other subtypes, leading to false negatives that posed a significant public health risk to both individual patients and the safety of the blood supply ('352 Patent, col. 2:41-54).
- The Patented Solution: The invention identifies specific oligonucleotide sequences located in the Long Terminal Repeat (LTR) region of the HIV-1 genome, a region described as being relatively conserved across different viral strains ('352 Patent, col. 4:21-25). By using primers and probes derived from these specific sequences, the patented technology claims to enable the sensitive and reliable amplification and detection of "all presently known subtypes of HIV-1," thereby creating a more universal diagnostic tool ('352 Patent, Abstract).
- Technical Importance: The development of primers capable of detecting a broad range of viral variants was a critical step in improving the reliability of HIV screening, particularly as global travel increased the geographic spread of diverse subtypes ('352 Patent, col. 2:48-54).
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶49).
- The essential elements of claim 1 are:
- A pair of oligonucleotide primers for amplifying a target sequence within the LTR region of the HIV-1 genome.
- A first primer that "consists essentially of" a first oligonucleotide, is 15-26 nucleotides long, comprises at least 15 sequential nucleotides of the sequence "G GGC GCC ACT GCT AGA GA" (SEQ ID NO:1), and is operably linked to a T3, T7, or SP6 promoter.
- A second primer that "consists essentially of" a second oligonucleotide, is 10-26 nucleotides long, and comprises at least 10 sequential nucleotides of the sequence "CTC AAT AAA GCT TGC CTT GA" (SEQ ID NO:5).
- The complaint reserves the right to assert other claims (Compl. ¶40).
U.S. Patent No. 9,074,262 - "Nucleic Acid Sequences that Can Be Used as Primers and Probes in the Amplification and Detection of All Subtypes of HIV-1," issued July 7, 2015.
The Invention Explained
- Problem Addressed: As a divisional of the application that led to the '352 patent, the '262 patent addresses the same technical problem: the failure of existing diagnostic tests to reliably detect the wide variety of HIV-1 subtypes due to the virus's genetic heterogeneity ('262 Patent, col. 2:5-15, 2:35-44).
- The Patented Solution: The '262 patent claims a method for amplifying HIV-1 nucleic acid, rather than the primer pair itself. The claimed method involves contacting a sample with and performing nucleic acid amplification using the same specific primer sequences derived from the LTR region as described in the '352 patent, thereby enabling detection of a broad range of HIV-1 variants ('262 Patent, Abstract; col. 18:50-col. 19:11).
- Technical Importance: This patent protects the specific application and use of the novel primer sequences in a diagnostic method, complementing the composition claims of the '352 patent ('262 Patent, col. 2:35-44).
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶60).
- The essential elements of claim 1 are:
- A method for amplifying HIV-1 nucleic acid in a sample comprising:
- (a) contacting the sample with a pair of oligonucleotide primers that bind to sites within the LTR region of the HIV-1 genome.
- (b) performing nucleic acid amplification.
- The first primer "consists essentially of" an oligonucleotide that is 15-26 nucleotides long, comprises at least 15 sequential nucleotides of "G GGC GCC ACT GCT AGA GA" (SEQ ID NO:1), and is operably linked to a promoter.
- The second primer "consists essentially of" an oligonucleotide that is 10-26 nucleotides long and comprises at least 10 sequential nucleotides of "CTC AAT AAA GCT TGC CTT GA" (SEQ ID NO:5).
- The complaint reserves the right to assert other claims (Compl. ¶40).
III. The Accused Instrumentality
Product Identification
The complaint identifies two groups of products, collectively the "Accused Tests" (Compl. ¶¶35-36):
- Procleix Tests: Including the Procleix HIV-1/HCV Assay, Procleix Ultrio Assay, and Procleix Ultrio Plus Assay.
- Aptima Tests: Including the Aptima HIV-1 RNA Qualitative Assay and Aptima HIV-1 Quant DX Assay.
Functionality and Market Context
The Accused Tests are in vitro diagnostic kits used to amplify and detect HIV-1 nucleic acid in biological samples (Compl. ¶38). The complaint alleges that the Procleix Ultrio Assay, for example, utilizes a "Transcription-Mediated Amplification" method to amplify regions of HIV-1 RNA (Compl. ¶60). These tests are marketed and sold to institutions such as hospitals and blood banks for screening purposes (Compl. ¶10). The complaint alleges Hologic manufactures all the Accused Tests, selling some to Grifols for distribution and marketing its own Aptima line independently (Compl. ¶¶35-36).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
’352 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pair of oligonucleotide primers for the amplification of a target sequence between two primer binding sites located within the LTR region of the HIV-1 genome, said pair consisting of a first primer and a second primer | The Accused Products allegedly utilize a primer pair for HIV-1 amplification. | ¶49 | col. 17:30-34 |
| wherein said first primer consists essentially of a first oligonucleotide...being 15-26 nucleotides in length and comprising at least 15 sequential nucleotides of the nucleotide sequence of: G GGC GCC ACT GCT AGA GA | The Accused Products are alleged to use a first primer that contains this specific nucleotide sequence. | ¶49 | col. 17:35-43 |
| said first oligonucleotide being operably linked to a T3, T7, or SP6 promoter | The first oligonucleotide in the Accused Products is allegedly operably linked to a promoter. | ¶49 | col. 17:44-45 |
| wherein said second primer consists essentially of...a second oligonucleotide...being 10-26 nucleotides in length and comprising at least 10 sequential nucleotides of the nucleotide sequence of: CTC AAT AAA GCT TGC CTT GA | The Accused Products are alleged to use a second primer that contains this specific nucleotide sequence. | ¶49 | col. 17:46-56 |
’262 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for amplifying HIV-1 nucleic acid in a sample, comprising: a) contacting the sample with a pair of oligonucleotide primers that bind to a first primer binding site and a second primer binding site located within the LTR region of the HIV-1 genome | The instructions and promotional materials for the Accused Tests are alleged to direct users to perform a method that involves contacting a sample with primers. | ¶60 | col. 18:50-55 |
| and b) performing a nucleic acid amplification under conditions wherein said oligonucleotide primers bind only to said first and second primer binding sites, thereby amplifying HIV-1 nucleic acid in the sample | The Accused Tests are alleged to perform nucleic acid amplification, specifically citing "Transcription-Mediated Amplification" for the Procleix Ultrio Assay. | ¶60 | col. 18:56-60 |
| wherein said first primer consists essentially of a first oligonucleotide...comprising at least 15 sequential nucleotides of the nucleotide sequence of: G GGC GCC ACT GCT AGA GA...said first oligonucleotide being operably linked to a promoter | The method induced by Defendants allegedly involves using a first primer with the claimed nucleotide sequence linked to a promoter. | ¶60 | col. 18:61-col. 19:3 |
| and wherein said second primer consists essentially of a second oligonucleotide...comprising at least 10 sequential nucleotides of the nucleotide sequence of: CTC AAT AAA GCT TGC CTT GA | The method induced by Defendants allegedly involves using a second primer with the claimed nucleotide sequence. | ¶60 | col. 19:4-11 |
Identified Points of Contention
- Technical Question: The complaint alleges that the Accused Tests use primers with specific sequences, but it does not present direct evidence (e.g., from reverse engineering or sequencing) of the accused primers' structures. A central factual question for the court will be what evidence proves the primers in the Accused Tests meet the specific sequence and length limitations of the claims.
- Scope Question: The use of "consists essentially of" raises the question of whether the accused primers contain any additional components, such as modified nucleotides or different flanking sequences, and if so, whether those components materially alter the "basic and novel properties" of the claimed primers—namely, their ability to amplify a broad range of HIV-1 subtypes.
V. Key Claim Terms for Construction
- The Term: "consists essentially of"
- Context and Importance: This transitional phrase, present in both asserted independent claims, is more limiting than "comprising" but less limiting than "consisting of." Its construction will be critical to the infringement analysis. The dispute may center on whether any unrecited elements in the accused primers (e.g., additional nucleotides, chemical modifications) materially affect the primers' "basic and novel properties." Practitioners may focus on this term because the outcome could determine whether minor structural differences in the accused primers are sufficient to avoid infringement.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent specification suggests some flexibility, stating that oligonucleotides "may contain minor deletions, additions and/or substitutions of nucleic acid bases, to the extent that such alterations do not negatively affect the yield or product obtained to a significant degree" ('352 Patent, col. 6:9-13). This language may support an interpretation where the "basic and novel property" is simply the ability to amplify the target LTR region across diverse subtypes, allowing for some structural deviation.
- Evidence for a Narrower Interpretation: The patent repeatedly emphasizes the specific, disclosed sequences as the solution to the prior art's failures ('352 Patent, col. 4:21-36). A defendant could argue that the "basic and novel properties" are not just broad amplification, but also include specific performance characteristics (e.g., sensitivity, reaction kinetics, specificity) detailed in the patent's examples, and that any modifications in their primers materially alter these properties.
VI. Other Allegations
- Indirect Infringement: The complaint alleges inducement of infringement, asserting that Defendants' promotional materials, product labeling, and instructions actively encourage and direct customers to use the Accused Tests in a manner that performs the steps of the claimed method ('262 Patent) (Compl. ¶¶58, 60). It also alleges contributory infringement, stating that the Accused Tests are a material part of the invention, are not staple articles of commerce, and have no substantial non-infringing uses ('352 Patent, ¶52; '262 Patent, ¶59).
- Willful Infringement: Willfulness is alleged based on Defendants' purported pre-suit knowledge of the Asserted Patents. The complaint specifically alleges this knowledge stems from Hologic’s "efforts over the last several years to revoke foreign counterparts of these patents that issued from the European Patent Office" and from knowledge gained via bioMérieux’s own publications (Compl. ¶¶43, 45).
VII. Analyst’s Conclusion: Key Questions for the Case
- A primary issue will be an evidentiary one: what direct evidence, such as chemical analysis or sequencing data, will be presented to prove that the oligonucleotide primers within the defendants' commercial "Procleix" and "Aptima" test kits are structurally identical to or "consist essentially of" the specific nucleotide sequences claimed in the '352 and '262 patents?
- The case will also turn on the construction of the transitional phrase "consists essentially of." A key question for the court will be to define the "basic and novel properties" of the claimed primer pair. Is that property simply the ability to amplify the LTR region of diverse HIV-1 subtypes, or does it also encompass more specific performance metrics that could be materially altered by any modifications present in the accused products?
- A third core issue relates to willfulness: did Hologic's alleged attempts to invalidate European counterparts of the patents-in-suit provide the requisite knowledge and intent to support a finding of willful infringement in the U.S., potentially leading to enhanced damages?