Illumina, Inc. v. Qiagen, N.V.

207 F. Supp. 3d 1081, 2016 U.S. Dist. LEXIS 122571, 2016 WL 4719269
CourtDistrict Court, N.D. California
DecidedSeptember 9, 2016
DocketNo. C 16-02788 WHA
StatusPublished
Cited by1 cases

This text of 207 F. Supp. 3d 1081 (Illumina, Inc. v. Qiagen, N.V.) is published on Counsel Stack Legal Research, covering District Court, N.D. California primary law. Counsel Stack provides free access to over 12 million legal documents including statutes, case law, regulations, and constitutions.

Bluebook
Illumina, Inc. v. Qiagen, N.V., 207 F. Supp. 3d 1081, 2016 U.S. Dist. LEXIS 122571, 2016 WL 4719269 (N.D. Cal. 2016).

Opinion

ORDER GRANTING MOTION FOR PRELIMINARY INJUNCTION

William Alsup, United States District Judge

INTRODUCTION

In this patent infringement action involving DNA sequencing technology, the patent owner moves for a preliminary injunction. For the reasons stated below, the motion for a preliminary injunction is Granted.

STATEMENT

Plaintiff Illumina Cambridge, Inc., owns U.S. Patent No. 7,566,537, which covers “Labelled Nucleotides.” Plaintiff Illumina, Inc., is the exclusive licensee of the ’537 patent. Illumina and Illumina Cambridge (collectively, “Illumina”) sell DNA sequencing equipment that practices the ’537 patent (Van Oene Deck ¶ 6).

Defendant Qiagen N.V. and several of its subsidiaries, defendants Qiagen GmbH, Qiagen Gaithersburg, Inc., Qiagen Sciences, LLC, Qiagen Inc. (USA), Qiagen Redwood City, Inc., and Intelligent Bio-Systems, Inc. (collectively, “Qiagen”), jointly developed and announced the launch of a competing product, the GeneR-eader NGS System, with plans to begin distribution later this year. Illumina now seeks to enjoin sales of Qiagen’s GeneR-eader products.

Before discussing the details of the technology at issue herein, some background on the science of DNA is necessary.

1. DNA.

DNA, which stands for deoxyribonucleic acid, encodes the genetic material of most organisms. DNA comprises a double helix of strands of linked molecules called nucleotides. Each nucleotide contains a sugar, a phosphate, and one of four different chemical bases, adenine (“A”), cytosine (“C”), guanine (“G”), and thymine (“T”). The bases pair with each other—A with T and C with G—and the two strands of the double helix are held together by the bonds between complementary bases. In other words, each side of a DNA double helix is a perfect complement of the other. The sequence of the bases in a DNA [1084]*1084strand reflects genetic information (Metzker Decl. ¶¶ 28-31).

As stated, each nucleotide contains a sugar chemical group, which is a ring comprising five carbon atoms. By convention, the carbon atoms are numbered one prime (1’) through five prime (5’), and each such atom can be bound to another atom or chemical group, depending on the specific kind of sugar used in that nucleotide. The nucleotides in DNA use the sugar deoxyri-bose. Deoxyribose has a hydroxyl group (one hydrogen atom and one oxygen atom) at the 3’ position (known as a “3’-OH group”). Deoxyribose has only a hydrogen atom at its 2’ position. The name deoxyri-bose indicates the lack of an oxygen atom at the 2’ group as compared to ribose, a sugar used in a different kind of genetic material known as RNA, which has a hy-droxyl at the 2’ position (as well as at the 3’ position).

The phosphate group of a nucleotide is attached at the 5’ position of the sugar. As stated, the strands of DNA comprise a series of nucleotides. The nucleotides in the series are connected via bonds between the 3’-OH group of the sugar on one nucleotide and the phosphate group of the next nucleotide. This sugar-phosphate bond forms the backbone of each strand of a DNA double helix, and the pairwise bonds between the bases (A-T and C-G) form the cross-bars of the helix.

Below is an image depicting a single nucleotide featuring deoxyribose (Metzker Deck, Fig. 1):

[[Image here]]

The chemical group labeled “Base” is a G (guanine) group. The vertices of the sugar ring (labeled 1’ through 4’) and the additional point extending from the 4’ position (labeled 5’), are carbon atoms. They are not labeled with a “C” by convention. The circled 3’-OH group is, as stated, the connecting point between each nucleotide and the phosphate group of the next. It is a key aspect of the technology herein, to which this order now turns.

2. Sequencing-by-Synthesis.

Because DNA contains two perfectly complementary strands of nucleotides, the full sequence of DNA can be determined by identifying the sequence of bases in the nucleotides on one of the strands and inferring (from the A-T/C-G pairing) the sequence of the other strand. One technique, used by both Illumina and Qiagen, for identifying sequence of A, T, C, and G that make up one strand is called “sequencing by synthesis.” This process first involves unwinding the double.helix of the DNA [1085]*1085sought to be analyzed, retaining one strand as a template, and affixing that template to a surface to maintain stability throughout the sequencing process. Once the template is affixed, an enzyme proceeds along the template, adding complementary nucleotides to an adjacent “primer” strand, which is positioned to be read by the sequencing device. The enzyme proceeds stepwise until it has added a complementary nucleotide for the entire chain.

The nucleotides added in the sequencing-by-synthesis process differ from the natural nucleotides in two critical ways. First, each nucleotide is modified to include a chemical label, unique to each base (A, T, C, or G) and attached to that base, that can be detected by an external device, such as by emitting a unique fluorescent display. Second, each nucleotide is modified to include a “blocking group” or “protecting group” (the terms are used interchangeably) that prevents further nucleotides from binding with the 3’-OH group of the sugar. This forces the enzyme to pause and wait until the label for a nucleotide has been detected before adding the next nucleotide.

Once the nucleotide label has been detected, the label can be removed (to avoid interference with further detection), and, critically for our case, the protecting group can be removed in a manner that leaves the 3’-OH group of the sugar exposed, allowing another nucleotide to be added.

The ’537 patent claims a method for labeling nucleotides in this manner and specifically using an “azido group” as the protecting group. (The patent does not specifically require sequencing.) Specifically, Claim 1 of the patent, the only independent claim asserted herein, reads as follows:

A method of labeling a nucleic acid molecule, the method comprising incorporating into the nucleic acid molecule a nucleotide or nucleoside molecule, wherein the nucleotide or nucleoside molecule has a base that is linked to a detectable label via a cleavable linker and the nucleotide or nucleoside molecule has a ribose or deoxyribose sugar moiety, wherein the ribose or deoxyri-bose sugar moiety comprises a protecting group attached via the 2’ or 3’ oxygen atom, and said protecting group can be modified or removed to expose a 3’ OH group and the protecting group comprises an azido group.

An azido group is a chemical group including three nitrogen atoms (Ns), inter alia. The set of OH protecting groups comprising an azido group encompasses a broad class of more than one thousand chemical structures (Metzker Decl. ¶ 100). Claim 6 of the patent, which depends from Claim 1, is limited to a single protecting group known as azidomethyl.

The patent defines the term “nucleo-side” as follows (’537 patent, col. 4, l. 59-63):

A “nucleoside” is structurally similar to a nucleotide, but are [sic] missing the phosphate moieties. An example of a nucleoside analog would be one in which the label is linked to the base and there is no phosphate group attached to the sugar molecule.

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207 F. Supp. 3d 1081, 2016 U.S. Dist. LEXIS 122571, 2016 WL 4719269, Counsel Stack Legal Research, https://law.counselstack.com/opinion/illumina-inc-v-qiagen-nv-cand-2016.