Enzo Life Scis., Inc. v. Roche Molecular Sys., Inc.

• Decision Date: 20 June 2019
• Docket Number: 2017-2498, 2017-2499, 2017-2545, 2017-2546
• Citation: 928 F.3d 1340
• Parties: ENZO LIFE SCIENCES, INC., Plaintiff-Appellant v. ROCHE MOLECULAR SYSTEMS, INC., Roche Diagnostics Corporation, Roche Diagnostics Operations, Inc., Roche Nimblegen, Inc., Becton, Dickinson and Company, aka Becton Dickson and Company, Becton Dickinson Diagnostics Inc., aka Becton Dickson Diagnostics, GeneOhm Sciences Inc., Abbott Laboratories, Abbott Molecular, Inc., Defendants-appellees
• Court: U.S. Court of Appeals — Federal Circuit

928 F.3d 1340

ENZO LIFE SCIENCES, INC., Plaintiff-Appellant

v.ROCHE MOLECULAR SYSTEMS, INC., Roche Diagnostics Corporation, Roche Diagnostics Operations, Inc., Roche Nimblegen, Inc., Becton, Dickinson and Company, aka Becton Dickson and Company, Becton Dickinson Diagnostics Inc., aka Becton Dickson Diagnostics, GeneOhm Sciences Inc., Abbott Laboratories, Abbott Molecular, Inc., Defendants-appellees

2017-2498, 2017-2499, 2017-2545, 2017-2546

United States Court of Appeals, Federal Circuit.

Sealed Opinion Issued: June 20, 2019

Public Opinion Issued: July 5, 2019^*

Justin P.D. Wilcox, Desmarais LLP, New York, NY, argued for plaintiff-appellant. Also represented by John M. Desmarais ; Peter Curtis Magic, San Francisco, CA.

Matthew Wolf, Arnold & Porter Kaye Scholer LLP, Washington, DC, argued for defendants-appellees Roche Molecular Systems, Inc., Roche Diagnostics Corporation, Roche Diagnostics Operations, Inc., Roche NimbleGen, Inc., Becton, Dickinson and Company, Becton Dickinson Diagnostics Inc., GeneOhm Sciences Inc.

John C. O'Quinn, Kirkland & Ellis LLP, Washington, DC, argued for defendants-appellees Abbott Laboratories, Abbott Molecular, Inc. Also represented by Michael Pearson, Jason M. Wilcox ; James F. Hurst, Amanda J. Hollis, Chicago, IL; Benjamin Adam Lasky, New York, NY.

Omar Khan, Wilmer Cutler Pickering Hale and Dorr LLP, New York, NY, for defendants-appellees Roche Molecular Systems, Inc., Roche Diagnostics Corporation, Roche Diagnostics Operations, Inc., Roche NimbleGen, Inc., Becton Dickinson and Company, Becton Dickinson Diagnostics Inc., GeneOhm Sciences Inc. Also represented by Robert J. Gunther, Jr., Christopher R. Noyes ; William G. McElwain, Thomas Saunders, Washington, DC.

Before Prost, Chief Judge, Reyna and Wallach, Circuit Judges.

Prost, Chief Judge.

Enzo Life Sciences, Inc. ("Enzo") appeals the decision of the U.S. District Court for the District of Delaware granting summary judgment against Enzo and holding that the asserted claims are invalid for lack of enablement. We affirm as to non-enablement and do not reach the other issues presented on appeal.

I

Deoxyribonucleic acid ("DNA") and ribonucleic acid ("RNA") are nucleic acids. They are made of a series of building blocks, called nucleotides, linked together in a chain. A single nucleotide is made up of a sugar, a phosphate, and a nitrogenous base. DNA nucleotides have one of four nitrogenous bases: adenine (A); guanine (G); cytosine (C); and thymine (T). RNA has the same bases, except it uses uracil (U) instead of thymine (T).

A polynucleotide refers to multiple nucleotides linked together in a chain.¹ The nucleotides located at each end of a polynucleotide chain are referred to as terminal nucleotides. All other nucleotides in a polynucleotide chain are referred to as internal nucleotides.

Two strands of polynucleotides can pair with each other, i.e., hybridize, through hydrogen bonding between the bases on each polynucleotide strand. The bases T and U pair with A, while G pairs with C. This is referred to as complementary base pairing or "Watson-Crick base pairing," and this pairing is how the now-familiar double helix shape is formed. Two polynucleotide strands will hybridize if the arrangement of nucleotides in each strand is such that enough bases can pair with each other. For example, whether two strands will hybridize depends in part on the number of complementary base pairs that exist between the two polynucleotides.

Hybridization techniques are used to detect the presence of certain nucleic acid sequences of interest, i.e., target sequences, such as genetic alterations. In such procedures, scientists use a hybridization "probe"—i.e., a labeled polynucleotide that is hybridizable and remains detectable after hybridization occurs—that is sufficiently complementary to the target sequence. The probe will hybridize with the target sequence if the target sequence is present, and the label on the probe then allows scientists to detect the hybridized probe.

Nucleic acid hybridization was well understood by June 1982, which is the claimed priority date of the patents at issue in this appeal. The prevailing method of labeling probes at that time was via radioactive labeling. Radioactive labeling generally involved replacing certain atoms in the nucleotide sequence with corresponding radioactive isotopes.

Non-radioactive labeling was just developing at the time of the claimed inventions. In 1981, Dr. David Ward and others at Yale University successfully developed a nonradioactive probe by attaching a label to a polynucleotide via a chemical linker at a base position of a nucleotide. See J.A. 4129–33 (publication by Dr. Ward and others titled "Enzymatic synthesis of biotin-labeled polynucleotides: Novel nucleic acid affinity probes"). Dr. Ward demonstrated that attaching labels at certain positions of the nucleotide ("the Ward positions") would not disrupt the polynucleotide’s ability to hybridize and be detected upon hybridization.

In December 1981, Enzo licensed the exclusive rights to the patent portfolio covering Dr. Ward’s discovery. See J.A. 4258–75. Shortly thereafter, in June 1982, Enzo filed a patent application covering non-radioactive labeling at additional positions on a nucleotide. The two patents in this appeal issued from applications filed in 1995 that claim priority from this 1982 application.

Both patents in this appeal generally relate to the use of non-radioactively labeled polynucleotides in nucleic acid hybridization and detection applications. The patents share the same specification in relevant part. See J.A. 90 n.6.

A

U.S. Patent No. 6,992,180 ("the ’180 patent") relates to non-radioactive labeling of polynucleotides where the label is attached at the phosphate position of a nucleotide. The claims are not directed to any specific polynucleotide, nor do they focus on the chemistry or linker used to attach a label, the number of labels to attach to a polynucleotide, or where within the polynucleotide to attach those labels. Instead, the claims encompass all polynucleotides with labels attached to a phosphate, as long as the polynucleotide remains hybridizable and detectable upon hybridization. Claim 1 of the ’180 patent is representative:

1. An oligo- or polynucleotide which is complementary to a nucleic acid of interest or a portion thereof, said oligo- or polynucleotide comprising at least one modified nucleotide or modified nucleotide analog having the formula

Sig-PM-SM-BASE

wherein PM is a phosphate moiety, SM is a furanosyl moiety and BASE is a base moiety comprising a pyrimidine, a pyrimidine analog, a purine, a purine analog, a deazapurine or a deazapurine analog wherein said analog can be attached to or coupled to or incorporated into DNA or RNA wherein said analog does not substantially interfere with double helix formation or nucleic acid hybridization , said PM being attached to SM, said BASE being attached to SM, and said Sig being covalently attached to PM directly or through a non-nucleotidyl chemical linkage, and wherein said Sig comprises a non-polypeptide, non-nucleotidyl, non-radioactive label moiety which can be directly or indirectly detected when attached to PM or when said modified nucleotide is incorporated into said oligo- or polynucleotide or when said oligo- or polynucleotide is hybridized to said complementary nucleic acid of interest or a portion thereof , and wherein Sig comprises biotin, imino-biotin, an electron dense component, a magnetic component, a metal-containing component, a fluorescent component, a chemiluminescent component, a chromogenic component, a hapten or a combination of any of the foregoing.

’180 patent claim 1 (emphases added).

"Sig" represents a signaling moiety (i.e., a label); PM represents a phosphate moiety; SM represents a sugar moiety; and BASE represents a base moiety.

B

The asserted claims of U.S. Patent No. 8,097,405 ("the ’405 patent") fall into two categories: (1) in situ hybridization claims; and (2) liquid phase hybridization claims.

The in situ hybridization claims (claims 63, 64, 65, 95, 103, 128, and 144) describe a process that uses a probe non-radioactively labeled at any non-Ward position to identify chromosomes. In situ hybridization is where probes are hybridized to a target that is fixed, usually on a glass slide. Claim 64 is exemplary.

The liquid phase hybridization claims (claims 196 and 198) describe a process that uses a non-radioactively labeled probe to hybridize and detect a target sequence in a liquid medium, rather than on a glass slide. These claims cover using probes labeled non-radioactively at any position on the nucleotide, including the three Ward positions. The asserted liquid phase hybridization claims depend from claim 189.

C

This consolidated appeal involves four district court cases.² The ’180 patent is at issue in all four cases, while the ’405 patent is at issue only in the cases against Abbott.

In January 2012, Enzo filed suit against Roche Molecular Systems, Inc., Roche Diagnostics Corp., Roche Diagnostics Operations, Inc., and Roche Nimblegen, Inc. (collectively, "Roche") alleging infringement of the ’180 patent. J.A. 1212–16 (Compl.) (Case No. 1:12-cv-106). In March 2012, Enzo filed separate suits against Becton, Dickinson and Co., Becton Dickinson Diagnostics Inc., and GeneOhm Sciences, Inc. (collectively, "BD"); and Abbott Laboratories and Abbott Molecular, Inc. (collectively, "Abbott") alleging infringement of the ’180 patent. J.A. 2833–36 (Compl.) (Case No. 1:12-cv-275 against BD); J.A. 1964–67 (Compl.) (Case No. 1:12-cv-274 against Abbott). In February 2013, Enzo filed a second suit against Abbott alleging infringement of the ’405 patent. J.A. 3973–77 (Compl.) (Case No. 1:13-cv-225).

In June 2017, in the cases against Roche and BD, the district court denied summary judgment with respect to written description, but granted summary judgment in favor of the defendants, holding that all asserted claims of the ’180 patent were invalid as...