This document summarizes a patent for a multiplex method of determining whether a sample contains at least 100 different target sequences. It involves: (1) providing a sample with target sequences attached to a solid support; (2) contacting the targets with probes containing universal priming sites and target-specific domains to form hybridization complexes; and (3) amplifying and detecting the complexes to determine if at least 100 targets are present. The method was used in a patent infringement case where Illumina was awarded $26.7 million for Ariosa Diagnostics infringing on their patents for non-invasive prenatal testing.

1. US 7,955,794
Shu-Yi Lin

2. Scope
A multiplex method for determining whether a sample contains at least 100
different target sequences, comprising:
a) providing a sample which may contain at least 100 different single-stranded
target sequences attached to a first solid support;
b) contacting said target sequences with a probe set comprising more than
100 different single-stranded probes, wherein each of said more than 100
different probes comprises:
i) a first universal priming site, wherein each of said more than 100
different probes has identical universal priming sites, and
ii) a target specific domain, such that different double-stranded
hybridization complexes are formed, each of the different hybridization
complexes comprising one of said more than 100 different single-
stranded probes and one of the different single-stranded target
sequences from the sample;
2

3. Scope (cont.)
c) removing unhybridized probes;
d) contacting said probes of the hybridization complexes with a first enzyme
and forming different modified probes;
e) contacting said modified probes with:
i) at least a first primer that hybridizes to said universal priming site;
ii) NTPs; and
iii) an extension enzyme; wherein said different modified probes are
amplified and forming different amplicons;
f) immobilizing said different amplicons to a second solid support, and
g) detecting said different amplicons immobilized to said second solid support,
thereby determining whether the sample contains at least 100 different target
sequences.
3

4. Exemplified by Figure
4
a) providing a sample which
may contain at least 100
different single-stranded
target sequences attached
to a first solid support;

5. Exemplified by Figure (cont.)
5
b) contacting said target
sequences with a probe
set … wherein each of said …
probes comprises:
i) a first universal priming
site… and
ii) a target specific domain,
such that different double-
stranded hybridization
complexes are formed…

6. Exemplified by Figure (cont.)
6
c) removing unhybridized
probes;
d) contacting said probes of
the hybridization complexes
with a first enzyme and
forming different modified
probes;

7. Exemplified by Figure (cont.)
7
e) contacting said modified
probes with:
i) at least a first primer that
hybridizes to said universal
priming site;
ii) NTPs; and
iii) an extension enzyme;
wherein said different
modified probes are
amplified and forming
different amplicons;

8. Litigation
8
Press Release
Illumina Awarded $26.7M in Patent Suit Against Ariosa Diagnostics, Inc.
SAN DIEGO--(BUSINESS WIRE)--Jan. 26, 2018-- Illumina, Inc. (NASDAQ: ILMN)
announced today that a federal jury in San Francisco has ruled in its favor in a patent
infringement suit filed against Ariosa Diagnostics, Inc., now owned by Roche.
The jury found that both Ariosa’s previous and current version of the Harmony non-
invasive prenatal test (NIPT) infringe US Patent 8,318,430 and US Patent 7,955,794.
The jury awarded Illumina approximately $26.7 million for past damages.
The jury rejected counterclaims by Ariosa that Illumina had breached a supply
agreement between the companies by bringing the lawsuit.
The US Patent and Trademark Office previously upheld the validity of the patents
rejecting multiple challenges filed by Ariosa.
“We are pleased with the outcome reached by the jury,” said Charles Dadswell, Senior
Vice President and General Counsel for Illumina. “This verdict again validates these
patents, the hard work and ingenuity of the inventors, and their significant
contribution to the field of NIPT.”
Illumina intends to seek injunctive relief for ongoing infringement by Ariosa’s
continuing sale of its Harmony test.
source: www.illumina.com

9. Market
9
source: GRAND VIEW RESEARCH
27.8 B