10X Genomics, Inc. v. Parse Biosciences, Inc.

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10X GENOMICS, INC. and THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY, Plaintiffs, v. PARSE BIOSCIENCES, INC., Defendant.

Civil Action No. 22-1117

United States District Court, D. Delaware

May 3, 2024

OPINION

Slomsky, J.

TABLE OF CONTENTS

I. INTRODUCTION 1

II. FACTUAL BACKGROUND 1

A. Scientific Background 3

i. The Brenner Patents 4

ii. The Giresi Patents ............................................................................................................ 5

III. STANDARD OF REVIEW................................................................................................... 6

IV. ANALYSIS ............................................................................................................................. 9

A. “combinational tagging” ................................................................................................ 10

B. “wherein at least 90 percent of said plurality of sample polynucleotides is associated with a unique second tag sequence” ............................................................ 17

C. “random sequences” ....................................................................................................... 23

D. “digital count” ................................................................................................................. 27

E. “adapter sequence” ......................................................................................................... 30

V. CONCLUSION ................................................................................................................... 34

I. INTRODUCTION

On August 24, 2022, Plaintiff 10x Genomics, Inc. (“Plaintiff” or “10x”) along with the Board of Trustees of the Leland Stanford Junior University (“Stanford University”) as a nominal defendant^[1]filed a Complaint alleging patent infringement by Defendant Parse Biosciences, Inc. (“Defendant” or “Parse”). (Doc. No. 1.) Six patents covering genomic technologies are alleged to have been infringed: 1) United States Patent No. 10,150,995 (“the ‘995 patent”); 2) United States Patent No. 10,619,207 (“the '207 patent”); 3) United States Patent No. 10,738,357 (“the '357 patent”); 4) United States Patent No. 10,155,981 (“the ‘981 patent”); 5) United States Patent No. 10,697,013 (“the '013 patent”); and 6) United States Patent No. 10,240,197 (“the '197 patent”) (collectively, “the Asserted Patents”).

Here, the parties seek construction of several terms of the patents-in-suit pursuant to Markman v. Westview Instruments, Inc., 52 F.3d 967, 976 (Fed. Cir. 1995), aff'd, 517 U.S. 370 (1996). On December 7, 2023, the parties filed a Joint Claim Construction brief that outlined the disputed claim terms and the parties' proposed constructions. (Doc. Nos. 104, 105.) On March 1, 2024, the Court held a Markman hearing on the disputed terms. The five (5) disputed terms are now ripe for construction.

II. FACTUAL BACKGROUND

In the Complaint, Plaintiffs allege that Defendant infringed the six (6) Asserted Patents, which can be grouped into two families. (Doc. No. 12 at 1.) Each group contains three (3) patents.

(Id.) The first one includes three patents identified as the “Giresi” patents.^[2]The Giresi patents include: 1) United States Patent No. 10,150,995 (“the '995 patent”); 2) United States Patent No. 10,619,207 (“the '207 patent”); and 3) United States Patent No. 10,738,357 (“the '357 patent”). (Id.) The second group includes three patents identified as the “Brenner” patents.^[3]The Brenner patents include: 1) United States Patent No. 10,155,981 (“the '981 patent”); 2) United States Patent No. 10,697,013 (“the '013 patent”); and 3) United States Patent No. 10,240,197 (“the '197 patent”). (Id.)

Generally, the Asserted Patents are directed to compositions and laboratory methods used to uncover genetic information that can then be used to better understand the genetic underpinnings of human life and disease. See '981 Patent, Claim 1 (“A method of analyzing nucleic acids from a plurality of single cells . . .”); '013 Patent, Claim 1 (“A method for multiplexed analysis of nucleic acids from single cells . . .”); '197 Patent, Claim 1 (“A method of counting nucleic acids in a sample . . .”); '995 Patent, Claim 1 (“A method for analyzing a biologic sample . . .”); '207 Patent, Claim 1 (“A method for generating a sequencing library from a plurality of cells . . .”); '357 Patent, Claim 1 (“A composition comprising: a permeabilized cell nucleus^[4] comprising . . . an insertional enzyme complex . . .”). The science relevant to each group of patents will be discussed below.

A. Scientific Background

A basic overview of the relevant scientific principles is necessary to understand the patent terms at issue in this case. To begin, every cell in the human body contains chromosomes that encode genetic information. The genetic information encoded in chromosomes is comprised of deoxyribonucleic acids, or “DNA.” (See '995 Patent at 8:63-9:14, 13:29-35.) DNA is a type of molecule known as a “nucleic acid” that can store genetic information. See Defs. Slide 10. Nucleic acids such as DNA are made up of chains of smaller building blocks called nucleotides. https://www.genome.gov/about-genomics/fact-sheets/Deoxyribonucleic-Acid-Fact-Sheet. A chain of nucleic acid also is referred to as a polynucleotide.^[5]Each nucleotide in a polynucleotide contains one of four nitrogen bases (also known as nucleobases): 1) adenine (A); 2) thymine (T); 3) guanine (G); and 4) cytosine (C).^[6](See Defs. Slide 10.) Another type of polynucleotides is oligonucleotides, which, put simply, are small polynucleotides.^[7]Stedman's Medical Dictionary 980 (24th ed. 1982).

In this case, the Asserted Patents are focused on compositions and methods to differentiate between polynucleotides (such as DNA) within a large population of cells (the Brenner patents) (see Doc. No. 33 at 17; see e.g., '981 Patent at 6:33-7:22, 15:36-50) and to determine epigenetic^[8]features in cells (the Giresi patents), (see Doc. No. 33 at 17; see, e.g., '995 Patent at 21:16-40).

i. The Brenner Patents

The Brenner patents refer to a group of three patents that Plaintiffs assert were infringed by Defendant: 1) the '981 patent; 2) the '013 patent; and 3) the '197 patent. The Brenner patents cover “methods for analyzing nucleic acids from single cells” through “tagging.” (See ‘981 patent, ‘013 patent, ‘197 patent.) “Tags,” which are also referred to as “molecular tags,” also would have a sequence of nucleobases. Tags can then be used to identify a polynucleotide.^[9]The method in the Brenner patents allows scientists to apply two “tags” to one polynucleotide.^[10]One tag would indicate the “source”^[11]or, for example, the specific cell the polynucleotide is from, and the other tag would identify the polynucleotide itself. (Pl. Slide 7.) The inventors refer to both a single tag and a combination of tags attached to a polynucleotide as a “MID.”^[12](See Doc. No. 104 at 16.)

Using such methods, it is possible to differentiate between vast numbers of otherwise indistinguishable polynucleotides in a sample in order to analyze it and to count the number of different polynucleotides in each cell. (Id.)

ii. The Giresi Patents

As noted above, the Giresi patents refer to three of the Asserted Patents that Plaintiffs allege were infringed by Defendant. This group of patents includes: 1) the '995 patent; 2) the '207 patent; and 3) the '357 patent. The Giresi patents largely improve on conventional methods used to analyze open chromatin regions of DNA. (See, e.g., Doc. No. 1 ¶¶ 17, 40.) Open chromatin contains regions of nucleosomes that allow access to DNA. By contrast, closed chromatin contains regions of nucleosomes where the DNA is wrapped tightly around histones^[13]and is not accessible for analysis using a MID. (‘995 patent at 1:26-31, 12:54-60, 17:15-17.) Thus, scientists are interested in methods to identify and use open chromatin, rather than closed chromatin.

The Giresi patents seek to “solve[] problems associated with determining what areas of the genome are available for transcription and translation into proteins-namely regions of open chromatin.” (Doc. No. 33 at 18; Tr. at 104:14-105:6.) Prior methods of analyzing areas of open chromatin required a 44-step process that few people could reproduce, a large sample size and extensive time to complete. (Doc. No. 33 at 18; Tr. at 103:12-104:13.) The inventors of the Giresi patents determined that an engineered insertional enzyme, known as a “transposase,” could be introduced into a cell nucleus and used to tagment^[14](i.e., cleaved and tagged in the same reaction) only the areas of open chromatin. (See Doc. No. 33 at 18; Tr. at 107:11-108:1; Tr. at 103:12104:13.) This had never been done before and reduced the 44-step process to a two-step process. (Id.)

In the Giresi patents, the inventors introduced an engineered enzyme referred to as “Tn5 transposase” that can be inserted into cell nuclei to perform tagmentation inside the cell nucleus, that is, to tag a polynucleotide. Tr. at 106:25-107:3; 106:8-107:20. Previously, tagmentation could only be performed on DNA that had already been removed from the nucleus and stripped from its chromatin complex. Tr. at 76:5-20 & Parse Slide 53. The claims in two of the Giresi patents, the '995...