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1 
 
 
 
 
 
Order 
of the Court of Appeal of the Unified Patent Court 
issued on 26/02/2024 
in the proceedings for provisional measures 
concerning EP 4 108 782 
 
 
HEADNOTES: 
1. Compliance with the requirements set out in R. 206.2(b) to (e) RoP concerns the merits of 
the applicaƟon for provisional measures, the examinaƟon of which is the responsibility of the 
judge and must be considered by the judge when making orders under Rules 209, 211 and 
212 RoP. 
2. The patent claim is not only the starƟng point, but the decisive basis for determining the 
protecƟve scope of a European patent under Art. 69 EPC in conjuncƟon with the Protocol on 
the InterpretaƟon of Art. 69 EPC. 
The interpretaƟon of a patent claim does not depend solely on the strict, literal meaning of 
the wording used. Rather, the descripƟon and the drawings must always be used as 
explanatory aids for the interpretaƟon of the patent claim and not only to resolve any 
ambiguiƟes in the patent claim. 
This does not mean that the patent claim merely serves as a guideline but that its subject-
mater also extends to what, aŌer examinaƟon of the descripƟon and drawings, appears to be 
the subject-mater for which the patent proprietor seeks protecƟon. 
The patent claim is to be interpreted from the point of view of a person skilled in the art. 
In applying these principles, the aim is to combine adequate protecƟon for the patent 
proprietor with suﬃcient legal certainty for third parƟes. 
These principles for the interpretaƟon of a patent claim apply equally to the assessment of 
the infringement and the validity of a European patent. 
AcƟon number: 
UPC_CoA_335/2023 
App_576355/2023

2 
 
3. A suﬃcient degree of certainty pursuant to R. 211.2 RoP, in conjuncƟon with Art. 62(4) UPCA 
(see also Art. 9(3) DirecƟve 2004/48/EC) requires that the court considers it on the balance of 
probabiliƟes at least more likely than not that the Applicant is enƟtled to iniƟate proceedings 
and that the patent is infringed. A suﬃcient degree of certainty is lacking if the court considers 
it on the balance of probabiliƟes to be more likely than not that the patent is not valid. 
The burden of presentaƟon and proof for facts allegedly establishing the enƟtlement to iniƟate 
proceedings and the infringement or imminent infringement of the patent, as well as for all 
other circumstances allegedly supporƟng the Applicant's request, lies with the Applicant, 
whereas, unless the subject-mater of the decision is the ordering of measures without hearing 
the defendant pursuant to Art. 60(5) in conjuncƟon with Art. 62(5) UPCA, the burden of 
presentaƟon and proof for facts concerning the lack of validity of the patent and other 
circumstances allegedly supporƟng the Defendant's posiƟon lies with the Defendant. 
KEYWORDS: 
Appeal, applicaƟon for provisional measures, burden of proof, claim construcƟon, examinaƟon 
of formal requirements, extent of protecƟon, infringement, invenƟve step, novelty, person 
skilled in the art, provisional injuncƟon, suﬃcient degree of certainty, summary proceedings, 
validity of patent. 
 
DEFENDANTS and APPELLANTS 
1. NanoString Technologies Inc 
530 Fairview Ave N - 98109 - Seatle (WA) - US 
2. NanoString Technologies Germany GmbH 
Birketweg 31 - 80639 - München - DE 
3. NanoString Technologies Netherlands B.V. 
Paasheuvelweg 25 - 1105BP - Amsterdam - NL 
Represented by: Oliver Jan Jüngst, Atorney at Law (Bird & Bird LLP) 
 
APPLICANTS and RESPONDENTS 
1. 10x Genomics, Inc. 
6230 Stoneridge Mall Road - 94588-3260 - Pleasanton (CA) - US 
2. President and Fellows of Harvard College 
Suite 727E, 1350 Massachusets Avenue - 02138 - Cambridge (MA) - US 
Represented by: Prof. Dr. Tilman Müller-Stoy, Atorney at Law (Bardehle Pagenberg 
PartnerschaŌ mbB)

3 
 
PATENT AT ISSUE 
EP 4108782 
 
PANEL AND DECIDING JUDGES 
First panel 
Klaus Grabinski 
President of the Court of Appeal and judge-rapporteur 
Françoise Barutel 
legally qualiﬁed judge 
Peter Blok 
legally qualiﬁed judge 
Rainer Friedrich 
 technically qualiﬁed judge 
Cornelis Schüller 
technically qualiﬁed judge 
LANGUAGE OF PROCEEDINGS 
German 
IMPUGNED ORDER 
Order (“Decision and orders”) of the Court of First Instance (Munich Local Division) of 19/09/2023 – 
UPC CFI 2/2023 
ORAL HEARING OF: 
18/12/2023

4 
 
FACTS AND REQUESTS OF THE PARTIES 
1. The Applicants and Respondents (hereinaŌer the “Applicants”) seek a cease-and-desist 
order against the Defendants and Appellants (hereinaŌer the “Defendants”) by way of 
provisional legal protecƟon for direct and indirect infringement of the European patent with 
unitary eﬀect (unitary patent) 4 108 782 (patent at issue). 
The patent at issue was ﬁled on 27 April 2022 as a divisional applicaƟon of the applicaƟon 
EP 18173059.9, which in turn had been ﬁled as a divisional applicaƟon for the applicaƟon 
EP 12860433.7 (parent applicaƟon). The parent applicaƟon was ﬁled on 21 December 2012 as 
an internaƟonal applicaƟon (PCT/US2012/071398) and led to the grant of European patent 
2 794 928 (parent patent). The patent at issue claims US priority dated 22 December 2011. The 
menƟon of grant of the patent at issue was published on 7 June 2023. 
The patent at issue relates to composiƟons and methods for analyte detecƟon. Its claim 1 
reads as follows in the language of proceedings under Art. 70(1) EPC: 
A method for detecƟng a plurality of analytes in a cell or Ɵssue sample, comprising: 
(a) mounƟng the cell or Ɵssue sample on a solid support; 
(b) contacƟng the cell or Ɵssue sample with a composiƟon comprising a plurality of 
detecƟon reagents, the plurality of detecƟon reagents comprising a plurality of 
subpopulaƟons of detecƟon reagents; 
(c) incubaƟng the cell or Ɵssue sample together with the plurality of detecƟon reagents 
for a suﬃcient amount of Ɵme to allow binding of the plurality of detecƟon reagents to 
the analytes; 
wherein each subpopulaƟon of the plurality of detecƟon reagents targets a diﬀerent 
analyte, wherein each of the plurality of detecƟon reagents comprises: a probe reagent 
targeƟng an analyte of the plurality of analytes and one or a plurality of pre-determined 
subsequences, wherein the probe reagent and the one or the plurality of pre-determined 
subsequences are conjugated together; 
(d) detecƟng in a temporally-sequenƟal manner the one or the plurality of pre-determined 
subsequences, wherein the detecƟng comprises:

5 
 
(i) hybridizing a set of decoder probes with a subsequence of the detecƟon reagents, 
wherein the set of decoder probes comprises a plurality of subpopulaƟons of decoder 
probes and wherein each subpopulaƟon of the decoder probes comprises a detectable 
label, each detectable label producing a signal signature; 
(ii) detecƟng the signal signature produced by the hybridizaƟon of the set of decoder 
probes; 
(iii) removing the signal signature; and 
(iv) repeaƟng (i) and (iii) using a diﬀerent set of decoder probes to detect other 
subsequences of the detecƟon reagents, thereby producing a temporal order of the signal 
signatures unique for each subpopulaƟon of the plurality of detecƟon reagents; and 
(e) using the temporal order of the signal signatures corresponding to the one or the 
plurality of the pre-determined subsequences of the detecƟon reagent to idenƟfy a 
subpopulaƟon of the detecƟon reagents, thereby detecƟng the plurality of analytes in the 
cell or Ɵssue sample. 
The research on which the parent applicaƟon is based was ﬁnancially supported with public 
funds from the US NaƟonal InsƟtutes of Health (NIH). The funding is based on a contract 
between the Applicant and the NIH. The contract also gives rise to obligaƟons for Applicant 2, 
the exact nature of which is disputed between the parƟes. 
Applicants 2 are registered as the proprietor of the patent at issue. According to the 
contractual agreement, they have granted Applicant 1 an exclusive licence to the German part 
of the parent patent and “any divisional patent” thereof with eﬀect from 14 February 2023, 
and an exclusive licence to all naƟonal parts of the parent patent except the German part and 
“any divisional patent” thereof with eﬀect from 30 May 2023. 
Defendant 1 is an American company. It is the parent company of a group of companies 
operaƟng under the name “NanoString”. Defendant 2 is the German sales and markeƟng 
company in this group of companies. Defendant 3 maintains the European headquarters of 
the group of companies in Amsterdam. 
Contested embodiment 1 (“CosMx SpaƟal Molecular Imager”, abbreviated as “CosMx SMI”) 
enables highly sensiƟve, subcellular imaging of a variety of RNAs or proteins directly from 
individual cells in morphologically intact Ɵssue samples. Samples, in parƟcular biological

6 
 
samples such as ﬁxed cells and Ɵssue secƟons, can be automaƟcally analysed for the presence 
of certain analytes, namely RNA and proteins. Contested embodiment 1 has been available on 
the market since December 2022. It is also used in the Defendants' so-called CX-Lab in 
Amsterdam, whereby the data obtained is analysed in the cloud, on servers that are not 
operated on the territory of the UPC ContracƟng Member States. 
Contested embodiment 2 is a detecƟon reagent that can be used only for the detecƟon of 
RNA. Contested embodiment 2 is sold in a kit as a so-called “CosMx RNA Panel” in a standard 
variant (“oﬀ-the-shelf RNA Add-On”) and according to customer speciﬁcaƟons (“Custom RNA 
Add-On Probes”). 
Contested embodiment 3 is a probe that binds as a secondary probe to the primary probe that 
has already bound to its analyte (RNA or protein); contested embodiment 3 is marketed in so-
called “CosMx RNA Imaging Trays”. These products are available for the detecƟon of 100 RNAs 
(100-plex) or 1000 RNAs (1000-plex), each for 2 or 4 slides. Contested embodiment 3 can be 
used for the detecƟon of RNA as well as for the detecƟon of proteins. 
The Defendants oﬀer the contested embodiments individually or in combinaƟon. 
The Defendant side repeatedly requested the Applicant 2 to put forward a licence oﬀer on 
reasonable terms with regard to the patent at issue. 
Defendant 1 has ﬁled an ObjecƟon against the grant of the patent at issue with the European 
Patent Oﬃce. 
On 1 June 2023, the Applicants applied to the Court of First Instance (Munich Local Division) 
for an order for a preliminary injuncƟon for direct and indirect infringement of the patent at 
issue. In addiƟon, the Applicants have requested the imposiƟon of a penalty payment in the 
event of any breach of the court orders that they have requested. 
The Applicants iniƟally chose a wording for the applicaƟon that matched claim 1 of the patent 
at issue word-for-word and referred geographically to “the parƟcipaƟng Member States”. In 
view of Defendant 1's objecƟon, the Applicants later amended their applicaƟon by naming the 
ContracƟng States of the UPC Agreement and deleƟng the words “one or” before “a plurality 
of pre-determined subsequences”.

7 
 
In response to the Court of First Instance's indicaƟon at the oral hearing that the quesƟon of 
the validity of the patent at issue was open aŌer the preliminary deliberaƟons and that the 
requests for orders in parallel proceedings concerning the parent patent had been lodged in a 
version restricƟng the patent claim of the parent patent, the Applicants added an auxiliary 
request to their main request. 
The Defendants have requested that the Applicants' main and auxiliary requests be rejected 
and, in the alternaƟve, that they be permited to conƟnue the allegedly infringing acƟvity 
against the provision of security and, in the further alternaƟve, that the granƟng of provisional 
measures be made dependent on the provision of security by the Applicants. 
2. By its Order (“Decision and Orders”) dated 19 September 2023 (hereinaŌer the “Order”), 
the Court of First Instance considered the Applicants' main request to be admissible and largely 
jusƟﬁed and essenƟally stated the following in its reasoning: 
The Munich Local Division of the Uniﬁed Patent Court had jurisdicƟon to decide on the 
ApplicaƟon for provisional measures, since the contested embodiments had also been oﬀered 
in Germany. 
The request was admissible. The Request fulﬁlled the requirements of R. 206.2(a), (c), (d) and 
(e)of the Rules of Procedure of the Uniﬁed Patent Court (RoP). In this respect, it was not a 
quesƟon of content but of form. In that respect, the submissions in the Request were 
suﬃcient. 
The Applicants were enƟtled to ﬁle an applicaƟon. Applicant 2 was the registered proprietor 
of the patent at issue and Applicant 1 was enƟtled to ﬁle an applicaƟon at least as the holder 
of a non-exclusive licence pursuant to Art. 47(3) of the Agreement on a Uniﬁed Patent Court 
(UPCA). 
According to the wording of claim 1 of the patent at issue, a part of the genomic DNA that has 
been isolated from a cell and ampliﬁed cannot be termed a cell or Ɵssue sample according to 
the claim. For a subpopulaƟon of the detecƟon reagents, it is not necessary for the probe 
reagent to be idenƟcal. The only decisive factor is that it targets the same analyte. Claim 1 
presupposes that the bond between the analyte and the detecƟon reagent, established by

8 
 
incubaƟng the cell or Ɵssue sample with the detecƟon reagents, conƟnues to exist during the 
second stage of the process. In addiƟon to steps (i) and (iii), step (ii) is also the object of the 
repeƟƟon of the steps to be carried out for the detecƟon of the subsequences in a temporally-
sequenƟal manner, since the intended use of the temporal order of the signal signatures would 
no longer be possible without repeaƟng the detecƟon of the signal signature provided for in 
step (ii). 
Against the background of this interpretaƟon, the fact that step (ii) was no longer provided for 
in the patent claim could not consƟtute an inadmissible extension of the content of the original 
applicaƟon. 
The Court of First Instance is also saƟsﬁed that the subject mater of patent claim 1 is novel. 
The object of the detecƟon in D6 (Jenny Göransson et al., A single molecule array for digital 
targeted molecular analyses, Nucleic Acids Research, 2009, Vol. 37, No. 1, e7) is not analytes 
from cell or Ɵssue samples, but so-called ampliﬁed single molecules (ASMs), which are 
obtained from “padlock or selector probes”. In addiƟon, with D6 the bond between analyte 
and reagent is broken “aŌer each imaging”. 
It was also not to be expected that the subject mater of patent claim 1 would be declared 
invalid due to a lack of invenƟve step. It was not shown what reason there was for a person 
skilled in the art to deviate from the soluƟon, described in D8 (Dzifa Y. Duose et al., Multiplexed 
and Reiterative Fluorescence Labeling via DNA Circuitry, Bioconjugate Chem. 2010, 21, 2327-
2331), for in situ analysis for cell or Ɵssue samples and instead apply a fundamentally diﬀerent 
method from a fundamentally diﬀerent context in order to be able to detect more analytes, as 
taught in D6. D6 itself does not give a person skilled in the art any reason to transfer the 
encoding and decoding method disclosed for an array of ASMs to cell or Ɵssue samples that 
have been mounted on a solid support. 
The Court of First Instance was also saƟsﬁed that a person skilled in the art would have been 
able to carry out the invenƟon and, in parƟcular, would have been able to choose an 
appropriate sequence length for the implementaƟon of the patented method. 
It was also suﬃciently certain that patent claim 1 was directly and indirectly infringed. The fact 
that the detecƟon is based on a cycle-based order of the signal signatures and thus not simply

9 
 
on a temporal order does not mean that the teaching according to the patent has not been 
realised. In addiƟon, the fact that the data is analysed with a cloud-based soluƟon outside the 
territory of the UPC Agreement does not mean that the patent at issue has not been infringed. 
The order for provisional measures was necessary. The interest of the right holder in not having 
their rights infringed outweighs the interest of the potenƟal infringer in securing now, through 
the conƟnuaƟon of the infringement, market share which it might be impossible for them to 
obtain at a later stage through a possible licence agreement. A licence claim of Defendant 2 
under US law had not been established either on a contractual or anƟtrust basis. The same 
applies with regard to a licence claim under European law in accordance with the 
“Huawei/ZTE” case law of the European Court of JusƟce. 
Considering and assessing all the circumstances of the case and weighing up all the interests 
of the parƟes, the measures requested should be ordered without the provision of security 
and a conƟnuaƟon of the infringement against the provision of security is not appropriate. 
The Court of First Instance’s Order instructed the Defendants 
to cease and desist, in the territories of the Republic of Austria, the Kingdom of Belgium, 
the Republic of Bulgaria, the Kingdom of Denmark, the Republic of Estonia, the Republic 
of Finland, the French Republic, the Federal Republic of Germany, the Italian Republic, 
the Republic of Latvia, the Republic of Lithuania, the Grand Duchy of Luxembourg, the 
Republic of Malta, the Kingdom of the Netherlands, the Portuguese Republic, the 
Republic of Slovenia and/or the Kingdom of Sweden, from 
I. 
using or oﬀering for use, in the territory of one or more of the States menƟoned 
in A: 
a method for detecƟng a plurality of analytes in a cell or Ɵssue sample comprising 
(a) 
mounƟng the cell or Ɵssue sample on a solid support; 
(b) 
contacƟng the cell or Ɵssue sample with a composiƟon comprising a plurality 
of detecƟon reagents, the plurality of detecƟon reagents comprising a 
plurality of subpopulaƟons of detecƟon reagents;

10 
 
(c) 
incubaƟng the cell or Ɵssue sample together with the plurality of detecƟon 
reagents for a suﬃcient amount of Ɵme to allow binding of the plurality of 
detecƟon reagents to the analytes; wherein 
each subpopulaƟon of the plurality of detecƟon reagents targets a diﬀerent 
analyte, wherein 
each of the plurality of detecƟon reagents comprises: a probe reagent 
targeƟng an analyte of the plurality of analytes; and 
a plurality of pre-determined subsequences, wherein the probe reagent and 
the plurality of pre-determined subsequences are conjugated together; 
(d) 
detecƟng in a temporally-sequenƟal manner the plurality of pre-determined 
subsequences, wherein the detecƟng comprises: 
(i) 
hybridizing a set of decoder probes with a subsequence of the 
detecƟon reagents, wherein the set of decoder probes comprises a 
plurality of subpopulaƟons of decoder probes and wherein each 
subpopulaƟon of the decoder probes comprises a detectable label, 
each detectable label producing a signal signature; 
(ii) 
detecƟng the signal signature produced by the hybridizaƟon of the set 
of decoder probes; 
(iii) 
removing the signal signature; and 
(iv) 
repeaƟng (i) and (iii) using a diﬀerent set of decoder probes to detect 
other subsequences of the detecƟon reagents, thereby producing a 
temporal order of the signal signatures unique for each subpopulaƟon 
of the plurality of detecƟon reagents; and 
(e) 
using the temporal order of the signal signatures corresponding to the 
plurality of the pre-determined subsequences of the detecƟon reagent to 
idenƟfy a subpopulaƟon of the detecƟon reagents, thereby detecƟng the 
plurality of analytes in the cell or Ɵssue sample, 
(direct infringement of claim 1 of EP 4 108 782)

11 
 
II. 
oﬀering and/or supplying in the territory of one of the States referred to in A. for 
use of the method in the territory of one of the States referred to in A. or in the 
territories of several of these States for use in the territory of one or more of the 
States referred to under A: 
devices suitable for carrying out a method for detecƟng a plurality of RNAs in a cell 
or Ɵssue sample comprising 
(a) 
 mounƟng the cell or Ɵssue sample on a solid support; 
(b) 
contacƟng the cell or Ɵssue sample with a composiƟon comprising a plurality 
of detecƟon reagents, the plurality of detecƟon reagents comprising a 
plurality of subpopulaƟons of detecƟon reagents; 
(c) 
incubaƟng the cell or Ɵssue sample together with the plurality of detecƟon 
reagents for a suﬃcient amount of Ɵme to allow binding of the plurality of 
detecƟon reagents to the RNAs; wherein 
each subpopulaƟon of the plurality of detecƟon reagents targets a diﬀerent 
analyte, wherein 
each of the plurality of detecƟon reagents comprises: a probe reagent 
targeƟng an RNA of the plurality of RNAs, and 
a plurality of pre-determined subsequences, wherein the probe reagent and 
the plurality of pre-determined subsequences are conjugated together; 
(d) 
detecƟng in a temporally-sequenƟal manner the plurality of pre-determined 
subsequences, wherein the detecƟng comprises: 
(i) 
hybridizing a set of decoder probes with a subsequence of the 
detecƟon reagents, wherein the set of decoder probes comprises a 
plurality of subpopulaƟons of decoder probes and wherein each 
subpopulaƟon of the decoder probes comprises a detectable label, 
each detectable label producing a signal signature; 
(ii) 
detecƟng the signal signature produced by the hybridizaƟon of the 
set of decoder probes;

12 
 
(iii) 
removing the signal signature; and 
(iv) 
repeaƟng (i) and (iii) using a diﬀerent set of decoder probes to detect 
other subsequences of the detecƟon reagents, thereby producing a 
temporal order of the signal signatures unique for each 
subpopulaƟon of the plurality of detecƟon reagents; and 
(e) 
using the temporal order of the signal signatures corresponding to the 
plurality of the pre-determined subsequences of the detecƟon reagent to 
idenƟfy a subpopulaƟon of the detecƟon reagents, thereby detecƟng the 
plurality of RNAs in the cell or Ɵssue sample, 
without 
(1) 
 staƟng explicitly, conspicuously and prominently on each oﬀer, on the ﬁrst 
page of the operaƟng instrucƟons, in the delivery documents and on the 
packaging that the devices may not be used for the detecƟon of RNA in a 
method pursuant to secƟon A.I. without the consent of Applicant 2) as 
proprietor of EP 4 108 782 and that they must not be used for the detecƟon 
of RNA without the consent of Applicant 2), 
(2) 
imposing on the purchasers a writen obligaƟon not to use the devices for 
the detecƟon of RNA without the prior consent of Applicant 2), subject to 
the imposiƟon of a reasonable contractual penalty to be paid to Applicant 
2), to be determined by Applicant 2) and, if necessary, to be reviewed by the 
competent court, for each individual breach 
(indirect infringement of claim 1 of EP 4 108 782) 
III. 
oﬀering and/or supplying in the territory of one of the States referred to in A. for 
use of the method in the territory of one of the States referred to in A. or in the 
territories of several of these States for use in the territory of one or more of the 
States referred to in A. 
detecƟon reagents suitable for carrying out a method for detecƟng a plurality of 
analytes in a cell or Ɵssue sample, comprising 
(a) 
mounƟng the cell or Ɵssue sample on a solid support;

13 
 
(b) 
contacƟng the cell or Ɵssue sample with a composiƟon comprising a plurality 
of detecƟon reagents, the plurality of detecƟon reagents comprising a 
plurality of subpopulaƟons of detecƟon reagents; 
(c) 
incubaƟng the cell or Ɵssue sample together with the plurality of detecƟon 
reagents for a suﬃcient amount of Ɵme to allow binding of the plurality of 
detecƟon reagents to the analytes; wherein 
each subpopulaƟon of the plurality of detecƟon reagents targets a diﬀerent 
analyte, wherein 
each of the plurality of detecƟon reagents comprises: a probe reagent 
targeƟng an analyte of the plurality of analytes and 
a plurality of pre-determined subsequences, wherein the probe reagent and 
the plurality of pre-determined subsequences are conjugated together; 
(d) 
detecƟng in a temporally-sequenƟal manner the plurality of pre-determined 
subsequences, wherein the detecƟng comprises: 
(i) 
hybridizing a set of decoder probes with a subsequence of the 
detecƟon reagents, wherein the set of decoder probes comprises a 
plurality of subpopulaƟons of decoder probes and wherein each 
subpopulaƟon of the decoder probes comprises a detectable label, 
each detectable label producing a signal signature; 
(ii) 
detecƟng the signal signature produced by the hybridizaƟon of the set 
of decoder probes; 
(iii) removing the signal signature; and 
(iv) repeaƟng (i) and (iii) using a diﬀerent set of decoder probes to detect 
other subsequences of the detecƟon reagents, thereby producing a 
temporal order of the signal signatures unique for each subpopulaƟon 
of the plurality of detecƟon reagents; and 
(e) 
using the temporal order of the signal signatures corresponding to the 
plurality of the pre-determined subsequences of the detecƟon reagent to

14 
 
idenƟfy a subpopulaƟon of the detecƟon reagents, thereby detecƟng the 
plurality of analytes in the cell or Ɵssue sample, 
(indirect infringement of claim 1 of EP 4 108 782) 
IV. 
oﬀering and/or supplying in the territory of one of the States referred to in A. for 
use of the method in the territory of one of the States referred to in A. or in the 
territories of several of these States for use in the territory of one or more of the 
States referred to in A. 
decoder probes suitable for carrying out a method for detecƟng a plurality of RNAs 
in a cell or Ɵssue sample, comprising 
(a) 
mounƟng the cell or Ɵssue sample on a solid support; 
(b) 
contacƟng the cell or Ɵssue sample with a composiƟon comprising a plurality 
of detecƟon reagents, the plurality of detecƟon reagents comprising a 
plurality of subpopulaƟons of detecƟon reagents; 
(c) 
incubaƟng the cell or Ɵssue sample together with the plurality of detecƟon 
reagents for a suﬃcient amount of Ɵme to allow binding of the plurality of 
detecƟon reagents to the RNAs; wherein 
each subpopulaƟon of the plurality of detecƟon reagents targets a diﬀerent 
RNA, wherein 
each of the plurality of detecƟon reagents comprises: a probe reagent 
targeƟng an RNA of the plurality of RNAs and 
a plurality of pre-determined subsequences, wherein the probe reagent and 
the plurality of pre-determined subsequences are conjugated together; 
(d) 
detecƟng in a temporally-sequenƟal manner the plurality of pre-determined 
subsequences, wherein the detecƟng comprises: 
(i) 
hybridizing a set of decoder probes with a subsequence of the 
detecƟon reagents, wherein the set of decoder probes comprises a 
plurality of subpopulaƟons of decoder probes and wherein each 
subpopulaƟon of the decoder probes comprises a detectable label, 
each detectable label producing a signal signature;

15 
 
(ii) 
detecƟng the signal signature produced by the hybridizaƟon of the 
set of decoder probes; 
(iii) 
removing the signal signature; and 
(iv) 
repeaƟng (i) and (iii) using a diﬀerent set of decoder probes to detect 
other subsequences of the detecƟon reagents, thereby producing a 
temporal order of the signal signatures unique for each 
subpopulaƟon of the plurality of detecƟon reagents; and 
(e) 
using the temporal order of the signal signatures corresponding to the 
plurality of the pre-determined subsequences of the detecƟon reagent to 
idenƟfy a subpopulaƟon of the detecƟon reagents, thereby detecƟng the 
plurality of RNAs in the cell or Ɵssue sample, 
without 
(1) 
 staƟng explicitly, conspicuously and prominently on each oﬀer, on the ﬁrst 
page of the operaƟng instrucƟons, in the delivery documents and on the 
packaging that the decoder probes may not be used for the detecƟon of RNA 
in a method pursuant to secƟon A.I. without the consent of Applicant 2) as 
proprietor of EP 4 108 782 and that they must not be used for the detecƟon 
of RNA without the consent of Applicant 2), 
(2) 
imposing on the purchasers a writen obligaƟon not to use the decoder 
probes for the detecƟon of RNA without the prior consent of Applicant 2), 
subject to the imposiƟon of a reasonable contractual penalty to be paid to 
Applicant 2), to be determined by Applicant 2) and, if necessary, to be 
reviewed by the competent court, for each individual breach 
(indirect infringement of claim 1 of EP 4 108 782). 
The Court of First Instance also ordered the respecƟve Defendants to pay to the court a 
(possibly repeated) penalty payment of up to EUR 250,000 for each individual breach of these 
orders. 
The Court of First Instance rejected the Applicants’ other requests and the Defendants’ 
requests.

16 
 
3. The Defendants have brought an appeal against the Court of First Instance’s Order and have 
substanƟated it in a separate pleading essenƟally as follows: 
The Local Division erred in law in assuming its jurisdicƟon. 
The Court of First Instance's Order was erroneous in law because the Applicants had breached 
mandatory procedural rules. 
The Court of First Instance erred in its narrow interpretaƟon of the feature of a “cell or Ɵssue 
sample” in claim 1. It was also erroneous to infer that the detecƟon reagents of a 
subpopulaƟon did not have to be idenƟcal overall, but rather that a match of the pre-
determined subsequences was suﬃcient. Furthermore, patent claim 1 does not require that 
the detecƟon reagents remain bound to the corresponding analyte throughout the enƟre 
method. 
According to the interpretaƟon, there is already no infringement by the contested method 
because several subpopulaƟons of detecƟon reagents are used to idenƟfy each analyte. 
Furthermore, contrary to the wording of patent claim 1, a detecƟon step (ii) is carried out in 
each hybridisaƟon round and the idenƟﬁcaƟon of the detecƟon reagents is carried out on a 
cycle basis instead of the mere temporal order provided for according to the claim. The data 
obtained in the laboratory at the headquarters in Amsterdam by applying the detecƟon 
method is analysed on a server outside the territory of the UPC ContracƟng States. 
The Court of First Instance erred in assuming that the patent at issue was most likely valid. Its 
subject-mater is not novel over D6. D6 discloses that genomic DNA is isolated from a blood 
sample and modiﬁed by RCA (rolling circle ampliﬁcaƟon) to yield ASMs (ampliﬁed single 
molecules). This does not cause the origin as a cell or Ɵssue sample within the meaning of 
patent claim 1 to be lost. Furthermore, claim 1 does not exclude the possibility that the signal 
signature is removed by washing aŌer each staining. How this occurs at the molecular level, 
whether only the decoder probe or both the decoder probe and the detecƟon reagent are 
removed, remains undetermined (para. 181, Statement of grounds of appeal). 
In any event, the subject-mater of claim 1 was not based on an invenƟve step. In this respect, 
D8 and D6 were suitable starƟng points. For a person skilled in the art starƟng from D6, it

17 
 
would be rouƟne to want to apply in vitro results to an in situ or in vivo context. This also 
applies to ASMs, as can also be seen from B30 (Magnus Stougaard et al., In situ detection of 
non-polyadenylated RNA molecules using Turtle Probes and target primed rolling circle PRINS, 
BMC Biotechnology 2007, 7:69, htp://www.biomedcentral.com/1472-6750/7/69). 
Contrary to the opinion of the Court of First Instance, the subject-mater of patent claim 1 goes 
beyond the content of the original applicaƟon and the invenƟon in the patent at issue is not 
disclosed so clearly and completely that a person skilled in the art could carry it out. 
On the basis of the agreement with the NIH and US anƟtrust law as well as EU compeƟƟon law 
from the point of view of abuse of a dominant market posiƟon pursuant to Art. 102 of the 
Treaty on the FuncƟoning of the European Union (TFEU), and in accordance
 with the principles 
of the Huawei case law of the Court of JusƟce of the EU, Applicant 2 has an obligaƟon to grant 
the Defendants a licence to the patent at issue. 
The Court of First Instance did not take suﬃcient account of the fact that the issuing of a 
provisional injuncƟon would cause irreparable harm to the Defendants, would be 
disproporƟonate and that the request lacked the necessary urgency. 
In the alternaƟve, the Defendants should at least be allowed to conƟnue the allegedly 
infringing acƟvity upon the provision of security and, in the further alternaƟve, the 
eﬀecƟveness of the provisional injuncƟon should be made dependent on the provision of 
appropriate security by the Applicants. 
The Defendants request that the Court 
revoke the Court of First Instance’s Order and reject the Applicants' request for the 
granƟng of provisional measures, 
in the alternaƟve, allow them (the Defendants) to conƟnue the allegedly infringing 
acƟvity against the provision of security, the amount of which is set at the discreƟon of 
the Court,

18 
 
in the further alternaƟve, make the eﬀecƟveness of the provisional measures dependent 
on the provision of security by the Applicants, the amount of which is to be determined 
by the court but should not be less than EUR 20,000,000, 
order the Applicants to bear the costs of the proceedings, 
declare the Decision (regarding the costs) immediately enforceable. 
The Applicants request that the Court 
reject the Appeal against the Order of the Court of First Instance, 
in the alternaƟve, rule in accordance with the Court of First Instance's prohibitory 
injuncƟon, with the proviso that in each case aŌer the words 
"1. 
a method for detecƟng a plurality of analytes in a cell or Ɵssue sample,” 
the words 
“used in (i) immunohistochemistry and/or ﬂuorescence in situ hybridisaƟon,” 
be inserted and 
in each case aŌer the words 
"(e) using the temporal order of the signal signatures corresponding to the plurality of 
pre-determined subsequences of the detecƟon reagent to idenƟfy a 
subpopulaƟon of the detecƟon reagents, thereby detecƟng the plurality of RNAs 
in the cell or Ɵssue sample,” 
the words

19 
 
“wherein the analytes are selected from the group consisƟng of proteins, pepƟdes 
and nucleic acids, wherein the nucleic acids are selected from the group consisƟng 
of cellular RNA, messenger RNA, microRNA, ribosomal RNA and any combinaƟons 
thereof” 
be inserted, 
order the Defendants to bear the costs of the appeal proceedings. 
The Applicants defend the Order of the Court of First Instance. 
The term cell or Ɵssue sample according to the claim is to be understood as a sample 
comprising one or more cells which may be organised in a Ɵssue, the locaƟon of the analytes 
relaƟve to each other corresponding to the naƟve locaƟon in the cell or Ɵssue. The assignment 
to a subpopulaƟon according to the claim does not depend on whether the probe reagents of 
diﬀerent detecƟon reagents are chemically idenƟcal. Patent claim 1 is to be understood as 
meaning that the detecƟon reagents bind once at their binding site and are then detected by 
repeated method steps. The detecƟon according to steps (i) to (iii) provided for in patent claim 
1 is repeated, according to (iv), unƟl a unique code has been created for each subpopulaƟon 
of the detecƟon reagents. 
Patent claim 1 is infringed by the Defendants' method. The repeƟƟon of the veriﬁcaƟon step 
(ii) and the creaƟon of a so-called cycle-based order when using the infringing subject-mater 
do not change this, nor does the fact that, according to the Defendants' contested submission, 
the data matching of the cycle-based order of the signal signatures is to take place by means 
of a cloud-based soluƟon on a server outside the territory of the UPC. 
The subject-mater of claim 1 is novel. If claim 1 is interpreted correctly, D6 discloses neither 
the detecƟon of analytes in a cell or Ɵssue sample nor that the sandwich probes remain on 
the respecƟve analyte. 
The subject-mater of claim 1 is also invenƟve. D8 does not teach the creaƟon of a temporal 
order of signal signatures for diﬀerent subpopulaƟons and their use for the detecƟon of 
diﬀerent analytes and does not suggest this to a person skilled in the art. There is no reason 
to transfer D6 to the in situ context. The same applies to B30, which was only submited with

20 
 
the Statement of grounds of appeal and which uses “turtle probes” but no “sandwich probes” 
or “selector probes” or comparable constructs. At most, B30 shows that at the priority date of 
the patent at issue, various probes and methods for the producƟon of ASMs were known, 
these being of varying suitability for use in situ. It would be obvious to a person skilled in the 
art that a probe or method that could be successfully used in vitro would not necessarily work 
in the in situ context, and also that transferability from one type of analyte to another was not 
guaranteed. 
The subject-mater of patent claim 1 was also disclosed in the original applicaƟon and the 
invenƟon could be carried out by a person skilled in the art on the basis of the informaƟon in 
the patent at issue. 
The Defendants are not enƟtled to a licence claim, either on a contractual or anƟtrust basis 
under US law or due to abuse of a dominant market posiƟon under EU law. 
The applicaƟon for provisional measures was procedurally admissible and necessary in terms 
of both Ɵming and substance. 
There are no grounds for granƟng the Defendants the power to avert the enforceability of the 
injuncƟon against the provision of security or to make the eﬀecƟveness of the provisional 
injuncƟon dependent on the provision of security by the Applicants. 
The auxiliary request is admissible. Claim 1, concreƟsed by the addiƟon of two features, is 
admissible. The methods used therein in immunohistochemistry (“IHC”) or ﬂuorescence in situ 
hybridisaƟon (“FISH”) are encompassed by claim 1, as is apparent from paragraphs 234 et seq. 
of the patent at issue. The analytes also further deﬁned in claim 1 (cellular RNA, messenger 
RNA, microRNA, ribosomal RNA) are derived from dependent claims 7 and 8. 
The Defendants request that the Applicants' applicaƟon for a provisional injuncƟon also be 
rejected in the version presented in the auxiliary request. 
 
GROUNDS FOR THE ORDER 
The Defendants' appeal against the order of the Court of First Instance (Munich Local Division) 
is admissible and well-founded.

21 
 
1. The objecƟon raised in the Appeal that the Munich Local Division of the Court of First 
Instance lacked jurisdicƟon to decide on the applicaƟon for provisional measures is not well-
founded. The Local Division aﬃrmed its jurisdicƟon because the embodiments atacked as 
infringing the patent had been oﬀered in Germany, Art. 33(1)(a), 32(1)(c), 26(1) UPCA. The 
Appeal has not shown that this assessment is incorrect. 
2. The objecƟon raised in the Appeal that the applicaƟon for provisional measures was not 
admissible due to an infringement of R. 206.2(c), (d) and (e) RoP is not upheld. 
In the case of R. 206.2 RoP concerning the applicaƟon for provisional measures, a disƟncƟon 
must be made between the provision of leter (a) and the provisions of the other leters (b) to 
(e). 
The requirements for the applicaƟon for provisional measures set out in R. 206.2(a) RoP in 
conjuncƟon with Rules 13.1(a) to (i) RoP are of a formal nature. They shall be examined by the 
Registry as soon as possible aŌer the applicaƟon has been ﬁled (R. 208.1 RoP in conjuncƟon 
with R. 16.2 RoP). If the examinaƟon reveals that the requirements have not been met, the 
Registry will give the Applicant the opportunity to correct the deﬁciencies within 14 days, in 
accordance with R. 16.3(a) RoP. If the deﬁciencies are not corrected within this period, a 
decision by default may be issued in accordance with R. 16.5 in conjuncƟon with 
R. 355.1(a) RoP. 
By contrast, the requirements set out in R. 206.2(b) to (e) RoP relate to the content of the 
applicaƟon for provisional measures. Accordingly, compliance with these requirements is not 
checked by the Registry and no Ɵme limit is set in the event of non-compliance, which can lead 
to a decision by default under R. 355.1(a) RoP. Rather, compliance with the requirements set 
out in R. 206.2(b) to (e) RoP concerns the merits of the applicaƟon for provisional measures, 
the examinaƟon of which is the responsibility of the judge and must be considered by the 
judge when making orders under Rules 209, 211 and 212 RoP. In the context of the orders to 
be made by the judge in the exercise of his discreƟon, non-compliance with the requirements 
set out in R. 206.2(b) to (e) RoP may be to the detriment of the Applicant. 
Contrary to the Defendants’ view the alleged breach of R. 206.2(c), (d) and (e) RoP does not 
render the applicaƟon inadmissible. In the present case, the Appeal has also not shown that

22 
 
the Court of First Instance - erroneously in law - did not consider the non-compliance with the 
requirements of Rules 206.2(b) to (e) RoP in its discreƟonary decision.. 
3. The concerns raised in the Appeal against the enƟtlement of Applicants 2 to ﬁle the 
applicaƟon are not jusƟﬁed. Due to their corresponding entry in the Register for Unitary Patent 
ProtecƟon, Applicants 2 are to be treated as the proprietor of the patent at issue, in 
accordance with R. 8.4 RoP. As such, they are enƟtled to apply for provisional measures in 
accordance with Art. 47(1) UPCA. 
According to the ﬁndings of the Court of First Instance, which are not contested in the Appeal, 
Applicant 1 is in any case enƟtled to ﬁle an applicaƟon as the holder of a non-exclusive licence 
granted to it by Applicants 2 under Art. 47(3) UPCA. 
4. The patent at issue relates to a method for detecƟng a plurality of analytes in a cell or Ɵssue 
sample. 
a) According to the descripƟon of the patent at issue, there is a need for mulƟplexing 
techniques in biology. Test samples are precious and researchers who want to analyse them 
do not know in advance what they have to look for or must ﬁrst obtain this informaƟon from 
individual samples. It is therefore desirable for researchers to subject each sample to a large 
set of probes (patent at issue, para. 2). 
According to the descripƟon, opƟcal readout is widely used in biology and can be very 
eﬀecƟve. However, it is typically limited to a relaƟvely small number of available ﬂuorophores 
or chromophores (patent at issue, para. 3). 
MulƟplexing in opƟcal processes can be improved by increasing the number of available 
colours. Quantum dots, mixtures of ﬂuorophores as new colours or nanostrings have been 
used for this purpose. However, there are also limitaƟons and diﬃculƟes in this respect (patent 
at issue, para. 4). 
The problem of the limited number of colours in opƟcal displays could be addressed by 
subjecƟng the same sample to repeated detecƟon using mulƟple small sets of diﬀerent 
probes. However, the order of detecƟon of diﬀerent target analytes may need to be prioriƟsed,

23 
 
because some target analytes in the sample can degrade in successive probings (patent at 
issue, para. 6). 
b) Against this background, the problem underlying the invenƟon is to develop high-
throughput opƟcal mulƟplexing methods for detecƟng target molecules in a sample (see 
patent at issue, para. 6). 
c) According to claim 1 of the patent at issue in the version of the main request (the feature 
omited compared to the granted version is crossed out in each case), this problem is to be 
solved by the following method: 
A method for detecƟng a plurality of analytes in a cell or Ɵssue sample, comprising: 
1. (a) mounƟng the cell or Ɵssue sample on a solid support; 
2. (b) contacƟng the cell or Ɵssue sample with a composiƟon comprising a plurality of 
detecƟon reagents, 
2.1. the plurality of detecƟon reagents comprising a plurality of subpopulaƟons of 
detecƟon reagents; 
3. (c) incubaƟng the cell or Ɵssue sample together with the plurality of detecƟon reagents for 
a suﬃcient amount of Ɵme to allow binding of the plurality of detecƟon reagents to the 
analytes; 
3.1. wherein each subpopulaƟon of the plurality of detecƟon reagents targets a diﬀerent 
analyte, 
3.2. wherein each of the plurality of detecƟon reagents comprises: 
3.2.1. a probe reagent targeƟng an analyte of the plurality of analytes, and 
3.2.2. one or a plurality of pre-determined subsequences, 
3.2.3. wherein the probe reagent and the one or the plurality of pre-determined 
subsequences are conjugated together; 
4. (d) detecƟng in a temporally-sequenƟal manner the one or the plurality of pre-determined 
subsequences, wherein the detecƟng comprises: 
4.1. (i) hybridising a set of decoder probes with a subsequence of the detecƟon reagents, 
4.1.1. wherein the set of decoder probes comprises a plurality of subpopulaƟons of 
decoder probes and 
4.1.2. wherein each subpopulaƟon of the decoder probes comprises a detectable 
label, 
4.1.3. each detectable label producing a signal signature;

24 
 
4.2. (ii) detecƟng the signal signature produced by hybridisaƟon of the set of decoder 
probes; 
4.3. (iii) removing the signal signature; and 
4.4. (iv) repeaƟng (i) and (iii) using a diﬀerent set of decoder probes to detect other 
subsequences of the detecƟon reagents, thereby producing a temporal order of signal 
signatures unique for each subpopulaƟon of the plurality of detecƟon reagents; and 
5. using the temporal order of the signal signatures corresponding to the one or the plurality 
of the pre-determined subsequences of the detecƟon reagent to idenƟfy a subpopulaƟon 
of the detecƟon reagents, thereby detecƟng the plurality of analytes in the cell or Ɵssue 
sample. 
d) Claim 1 of the patent at issue requires interpretaƟon with regard to some of its features. 
aa) The UPC Court of Appeal proceeds from the following principles in accordance with Art. 69 
of the ConvenƟon on the Grant of European Patents (EPC) and the Protocol on its 
InterpretaƟon. 
The patent claim is not only the starƟng point, but the decisive basis for determining the 
protecƟve scope of a European patent. 
The interpretaƟon of a patent claim does not depend solely on the strict, literal meaning of 
the wording used (see also the German and French language versions of the Protocol on 
InterpretaƟon: “aus dem genauen Wortlaut der Patentansprüche”, “sens étroit et litéral du 
texte des revendicaƟons”). Rather, the descripƟon and the drawings must always be used as 
explanatory aids for the interpretaƟon of the patent claim and not only to resolve any 
ambiguiƟes in the patent claim. 
However, this does not mean that the patent claim merely serves as a guideline and that its 
subject-mater also extends to what, aŌer examinaƟon of the descripƟon and drawings, 
appears to be the subject-mater for which the patent proprietor seeks protecƟon. 
The patent claim is to be interpreted from the point of view of a person skilled in the art. 
In applying these principles, the aim is to combine adequate protecƟon for the patent 
proprietor with suﬃcient legal certainty for third parƟes.

25 
 
These principles for the interpretaƟon of a patent claim apply equally to the assessment of the 
infringement and the validity of a European patent. This follows from the funcƟon of the 
patent claims, which under the European Patent ConvenƟon serve to deﬁne the scope of 
protecƟon of the patent under Art. 69 EPC and thus the rights of the patent proprietor in the 
designated ContracƟng States under Art. 64 EPC, taking into account the condiƟons for 
patentability under Art. 52 to 57 EPC (see EPO EBA, 11 December 1989, G 2/88, OJ 1990, 93 
para. 2.5). 
bb) The Court of First Instance's interpretaƟon that a cell or Ɵssue sample within the 
meaning of claim 1 is to be understood as a sample which is sƟll structurally recognisable as a 
cell or Ɵssue must be accepted. 
Such an understanding is supported by the wording of the claim, which disƟnguishes between 
the plurality of analytes to be detected and the cell or Ɵssue sample, so that the two cannot 
be idenƟcal. Although the analytes are indeed part of the cell or Ɵssue sample, the cell or 
Ɵssue sample must be structurally recognisable as such even beyond the analytes, which is 
expressed in the wording of the claim by the phrase “... analytes in a cell or Ɵssue sample”. 
It is consistent with the wording of the claim understood in this way that at the beginning of 
the descripƟon it is stated that the need for mulƟplexing techniques in biology is oŌen due to 
the fact that test samples are precious and researchers do not know precisely what to look for 
(patent at issue, para. 2). 
Such an interpretaƟon is not precluded by the fact that the descripƟon in paragraphs 48 and 
49 menƟons various types of sample processing, including, in addiƟon to those in which the 
cell or Ɵssue sample is preserved, such as ﬁxaƟon, permeabilisaƟon, mounƟng on a solid 
support, blocking of non-speciﬁc binding sites (patent at issue, para. 49, ﬁrst sentence), also 
those in which proteins or nucleic acids are isolated from a cell or Ɵssue sample, separated 
electrophoreƟcally on a separaƟon medium and then applied to a bloƫng membrane (patent 
at issue, para. 49, second sentence). It does not follow from the mere menƟon in the 
descripƟon that the proteins or nucleic acids are to be regarded as analytes in a cell or Ɵssue 
sample within the meaning of patent claim 1 even aŌer they have been processed as last 
menƟoned.

26 
 
The same applies to paragraphs 209 to 223 of the descripƟon, which contain, on the one hand, 
statements on analytes and target molecules and, on the other hand, statements on samples. 
Contrary to the view of the Defendants and their expert Dr Furneaux (B27, p. 3), the indicaƟon 
that a target molecule or an analyte can be a component of a whole cell, a Ɵssue or a body 
ﬂuid, a cell or Ɵssue extract, a fracƟonated lysate thereof or a substanƟally puriﬁed molecule 
(patent at issue, para. 211, second sentence), does not lead to the conclusion that fracƟonated 
lysates or a substanƟally puriﬁed molecule are also to be regarded as analytes in a cell or Ɵssue 
sample according to claim 1. 
cc) Contrary to the Court of First Instance's understanding, it cannot be inferred from patent 
claim 1 that the detecƟon reagents must remain bound to the respecƟve analytes throughout 
the enƟre detecƟon procedure according to feature group 4. 
The Court of Appeal agrees with the Court of First Instance that the detecƟon reagents must 
bind securely to the respecƟve analytes and, in order to make this possible, a suﬃcient 
incubaƟon Ɵme of the cell or Ɵssue sample together with the plurality of detecƟon reagents 
must be provided, in accordance with feature 3. Contrary to the opinion of the Court of First 
Instance, however, the need for a suﬃcient incubaƟon period does not preclude the decoder 
samples, once they have securely bound to the respecƟve analytes, from being removed again 
at a later stage, for example together with the removal of the signal signatures provided for in 
feature 4.3, and from being replaced again with the same detecƟon reagents. 
This is consistent with the wording of claim 1, which provides for a detecƟon method 
“comprising” the method steps “(c) incubaƟng” and “(d) detecƟng” but does not specify that 
the former may not be carried out mulƟple Ɵmes. 
The argument put forward by the Applicants at the oral hearing with reference to paragraph 
45 of the descripƟon of the patent at issue that repeated replacement of the detecƟon 
reagents during the performance of the detecƟon procedure is to be regarded as impracƟcable 
due to the long incubaƟon Ɵme cannot be accepted. Paragraph 45 describes a wide range of 
possible incubaƟon Ɵmes. On the one hand, incubaƟon periods of at least about 12, 24 or 48 
hours or longer are menƟoned. On the other hand, incubaƟon Ɵmes of at least about 30 
seconds, 1, 5, 10, 15 or 30 minutes and further incubaƟon Ɵmes between these extremes are

27 
 
also described. If this wide range of incubaƟon Ɵmes is considered as a whole, it was also not 
impossible for pracƟcal reasons to consider as being in accordance with the claims a method 
in which the detecƟon reagents, aŌer binding with the analytes, are removed again with the 
signal signature and replaced by the same detecƟon reagents. 
5. The objecƟon in the Appeal that, contrary to the judgement of the Court of First Instance, 
the validity of the patent at issue is not established with a suﬃcient degree of certainty for the 
injuncƟon requested to be issued is rightly raised. 
a) Since the order for provisional measures is issued by way of summary proceedings pursuant 
to R. 205 et seq. RoP, in which the opportuniƟes for the parƟes to present facts and evidence 
are limited, the Court of Appeal agrees with the Court of First Instance that the standard of 
proof must not be set too high, in parƟcular if delays associated with a reference to 
proceedings on the merits would cause irreparable harm to the proprietor of the patent as 
provided for in Art. 62(2) and (5), 60(5) UPCA (see CJEU, judgment of 28 April 2022, Phoenix 
Contact, C-44/21, EU:C:2022:309, para. 32 with reference to Art. 9(1)(a) DirecƟve 
2004/48/EC). On the other hand, it must not be set too low in order to prevent the defendant 
from being harmed by an order for a provisional measure that is revoked at a later date 
pursuant to Art. 62(5), Art. 60(8) and (9) UPCA, R. 213 RoP, Art. 62(2) UPCA, cf. also Art. 9(7) 
DirecƟve 2004/48/EC. 
R. 211.2 RoP, in conjuncƟon with Art. 62(4) UPCA (see also Art. 9(3) DirecƟve 2004/48/EC), 
provides that the court may invite the applicant for provisional measures to provide 
reasonable evidence to saƟsfy the court to a suﬃcient degree of certainty that the applicant 
is enƟtled to insƟtute proceedings under Art. 47 UPCA, that the patent is valid and that his 
right is being infringed, or that such infringement is imminent. 
Such a suﬃcient degree of certainty requires that the court considers it at least more likely 
than not that the Applicant is enƟtled to iniƟate proceedings and that the patent is infringed. 
A suﬃcient degree of certainty is lacking if the court considers it on the balance of probabiliƟes 
to be more likely than not that the patent is not valid. 
The burden of presentaƟon and proof for facts allegedly establishing the enƟtlement to iniƟate 
proceedings and the infringement or imminent infringement of the patent, as well as for all

28 
 
other circumstances allegedly supporƟng the Applicant's request, lies with the Applicant, 
whereas, unless the subject-mater of the decision is the ordering of measures without hearing 
the defendant pursuant to Art. 60(5) in conjuncƟon with Art. 62(5) UPCA, the burden of 
presentaƟon and proof for facts concerning the lack of validity of the patent and other 
circumstances allegedly supporƟng the Defendant's posiƟon lies with the Defendant. 
The aforemenƟoned allocaƟon of the burden of presentaƟon and proof in summary 
proceedings is in line with the allocaƟon of the burden of presentaƟon and proof in 
proceedings on the merits, in which facts giving rise to the enƟtlement to iniƟate proceedings 
and the infringement or imminent infringement of the patent, as well as other circumstances 
favourable to the infringement acƟon, are to be presented and proven by the rightholder 
(Art. 54, 63, 64 and 68 UPCA, R. 13.1(f) and (l)-(n) RoP), whereas the burden of presentaƟon 
and proof with regard to the facts from which the lack of validity of the patent is derived and 
other circumstances favourable to the invalidity or revocaƟon lies with the opponent (Art. 54 
and 65(1) UPCA, Rules 44(e)-(g), 25.1(b)-(d) RoP). 
b) Contrary to the opinion of the Court of First Instance, in the judgement of The Court of 
Appeal it is, on the balance of probability, more likely than not that the subject-mater of claim 
1 in the version asserted in the main request will prove to be not patentable under Art. 65(2) 
UPCA, Art. 52(1), 138(1)(a) EPC. 
aa) The Court of Appeal assumes the admissibility of the version of patent claim 1 asserted by 
the Applicants in the main request (deleƟon of the words “the one or” in features 3.2.2., 3.2.3, 
4 and 5). The Appeal did not claim that the Court of First Instance was incorrect in ﬁnding that 
the claim version of the main request was admissible. Therefore, the admissibility of the 
version of the main request does not form part of the subject-mater of the proceedings before 
the Court of Appeal (R. 222.1 RoP in conjuncƟon with R. 226(a)). 
bb) The objecƟon raised in the Appeal that the Court of First Instance incorrectly assumed that 
the subject-mater of patent claim 1 would prove to be novel over D6 is unfounded. 
(1) D6 relates to an array format with a decoding scheme for targeted digital mulƟplex 
molecular analyses. As can also be seen from Figure 3 reproduced below, D6 discloses 
mulƟplex encoding and decoding of genomic loci.

29 
 
 
 
As shown under “A”, genomic DNA circles are formed from speciﬁc genomic DNA sequences 
and selector probes (i) and the DNA circles are ampliﬁed by RCA (rolling-circle ampliﬁcaƟon) 
(ii) or otherwise enriched (iii) to generate ampliﬁed single molecules (ASMs). The ASMs are 
then immobilised and a random array is generated on a microscopy glass slide. 
As shown under “B”, the ASMs immobilised in the array are decoded by sequenƟal 
hybridisaƟon of sandwich probes, tag probes (red or blue) and a general probe aŌer they have 
been incubated for 1 hour on shake at 55°C (D6, p. 3, leŌ-hand column under “HybridisaƟon 
of ASMs”). The sandwich probes are complementary to a speciﬁc ASM and contain two

30 
 
decoding tags (tag 1 and tag 2) that hybridise with corresponding tag probes. A small 20 x 20 
pixel image secƟon shows the tagged ASMs aŌer the diﬀerent hybridisaƟon reacƟons together 
with an image showing the idenƟﬁed ASMs. The ASM arrays were decoded in four cycles of 
hybridisaƟon and dehybridisaƟon (D6, p. 4, leŌ-hand column/p.5, right-hand column). 
A decoding scheme used for mulƟplex decoding is shown under “C”, in which the names of the 
gene loci and the corresponding numbers are listed verƟcally and the markings of the two tags 
are shown horizontally. The coloured markers represent the ﬂuorescent dyes Cy3 (green), 
Texas Red (red) and Cy5 (blue) and the black marker represents no detectable signal (D6, under 
Figure 3; Abstract; p. 4, right-hand column under “MulƟplex targeted copy-number variaƟon 
analysis”). 
(2) D6 thus discloses all the features of claim 1 (see also Bundespatentgericht, Qualiﬁzierter 
Hinweis of 7 February 2023 [BP9], p. 5 et seq, regarding the parent patent) with the excepƟon 
of the feature that the method is intended to detect a plurality of analytes “in a cell or Ɵssue 
sample”, since the method described in D6 is intended to detect ASMs (ampliﬁed DNA 
molecules) and thus a plurality of analytes, but these are not present in a cell or Ɵssue sample. 
A person of average skill in the art would not consider a part of the genomic DNA that has 
been isolated from a cell and ampliﬁed to yield the ASMs to be cell or Ɵssue material within 
the meaning of the patent. Contrary to the opinion of the Defendants, it is not suﬃcient for 
the sample to have a cellular origin. As established above, only a sample which is sƟll 
structurally recognisable as a cell or Ɵssue is a cell or Ɵssue sample within the meaning of claim 
1. It is undisputed that an ASM is not recognisable as a cell or Ɵssue. 
According to D6, the ASMs are mounted on a glass slide and contacted and incubated with a 
plurality of sandwich probes in order to bind each to the other. The sandwich probes have the 
funcƟon of a plurality of detecƟon reagents or a plurality of subpopulaƟons thereof as deﬁned 
in claim 1, as they target a speciﬁc ASM on the one hand and hybridise (tag 1 and tag 2) with 
a plurality of predetermined subsequences using a set of tag probes (the decoder probes as 
deﬁned in claim 1) on the other hand. Each subpopulaƟon of tag probes comprises a 
detectable tag that produces a signal signature (one of the ﬂuorescent dyes Cy3, Texas Red or 
Cy5). The signal signatures generated by the hybridisaƟon are captured (see the 20 x 20 pixel 
image secƟons in Figure 3) and thus detected. AŌer detecƟon, signal signatures are removed

31 
 
during dehybridisaƟon, and a new hybridisaƟon cycle begins with diﬀerent sets of decoder 
probes. 
The Court of First Instance and the Applicants correctly stated that in D6 the hybridisaƟon and 
dehybridisaƟon are carried out in four cycles, with the addiƟon of new sandwich probes at 
each hybridisaƟon. However, this circumstance does not conﬂict with the disclosure of the 
teaching of claim 1 since, as explained above, it does not require the binding between the 
detecƟon reagents and the respecƟve analytes to persist throughout the enƟre duraƟon of the 
process. 
cc) Contrary to the judgement of the Court of First Instance, it is more likely than not that the 
subject-mater of claim 1 in the version of the main request will prove to be obvious. 
D6 would have been of interest to a person skilled in the art who, at the priority date of the 
patent at issue, was seeking to develop high-throughput opƟcal mulƟplexing methods for 
detecƟng target molecules in a sample, as it discloses a method for detecƟng a plurality of 
ampliﬁed single molecules (ASMs) by encoding and decoding the single molecules, wherein 
the encoding is performed via probe-mediated generaƟon of ring-shaped DNA and the 
decoding is performed by temporally sequenƟal detecƟon of the targeted ASMs (cf. D6, 
Abstract) (see also the Swedish Intellectual Property Oﬃce, PRV ConsulƟng Report of 28 June 
2023, B10, p. 5). 
This is admitedly disclosed in D6 for ASMs ordered in vitro in an array format. However, given 
the demand for mulƟplex analysis techniques, especially for test samples, at the priority date 
(see patent at issue, para. 2), there was a need to consider whether the encoding and decoding 
method disclosed in D6 could be transferred to the detecƟon of ASMs in cell or Ɵssue samples. 
An incenƟve or conﬁrmaƟon for thinking in this direcƟon also resulted from the indicaƟon in 
D6 that in the prior art rolling-circle ASMs had been used for the readout of various genotyping 
assays as well as for the detecƟon of proteins and protein complexes in situ using proximity 
ligaƟon. The fact that the "genotyping assays" were carried out in situ can be seen from 
footnote 20 of D6, which refers to Larsson et al, "In situ genotyping individual DNA molecules 
by target-primed rolling-circle ampliﬁcaƟon of Padlock probes", Nat. Methods 2004, 1, 227 ﬀ, 
which describes an in situ procedure already according to the Ɵtle. In addiƟon, D6 refers to a

32 
 
publicaƟon on the in situ observaƟon of protein complexes (Söderberg et al., Direct 
observation of individual endogenous protein complexes in situ by proximity ligation, Nat. 
Methods 2006, vol. 3 no. 12 [D19]). 
That for a person skilled in the art at the priority date of the patent at issue, aŌer successful 
applicaƟon of an in vitro mulƟplex method for the detecƟon of ASMs, the next step was to 
consider transferring the method to an in situ environment is further evidenced by B30 
(Stougaard et al., In situ detection of non-polyadenylated RNA molecules using Turtle Probes 
and target primed rolling circle PRINS, BMC Biotechnology 2007, 7:69). This publicaƟon 
describes a method for the detecƟon of non-polyadenylated RNA molecules using “a new 
probe format” (“Turtle Probes”), which was iniƟally carried out in vitro in “a controlled 
environment” (B30, p. 4, right-hand column, last para.) and, aŌer successful implementaƟon, 
was also tested in situ with posiƟve results (B
30, p. 4, leŌ-hand column, - p.5; Abstract, 
Results). 
Even if it is assumed with the Applicants that various probes and methods for the producƟon 
of ASMs were known at the Ɵme, whose suitability for in situ applicaƟon varied and that a 
person skilled in the art would not have readily concluded from the successful applicaƟon of a 
probe or method in vitro that this probe or method would also work in an in situ context, it 
should be noted that this aspect did not prevent the authors of B30 from carrying out the 
detecƟon procedure with “Turtle Probes” in situ aŌer it had ﬁrst been successfully performed 
in vitro. There are no apparent grounds why this would have been any diﬀerent based on the 
detecƟon method carried out in vitro with selector probes in D6. 
The diﬀerence cited by the Applicants in this respect, namely that according to D6 the nucleic 
acids (analytes) were subjected to restricƟon digesƟon before the selector probes were used, 
whereas this was not necessary when using the “turtle probes” according to B30, is explained 
by the fact that in B30 the detecƟon is aimed at RNA molecules, whereas the detecƟon in D6 
is aimed at genomic DNA material, which ﬁrst had to be prepared for hybridisaƟon with the 
selector probes by restricƟon digesƟon (cf. Figure 3 A and the explanaƟon under Figure 3). 
Unlike in B30, there is no reason that would have prevented a person skilled in the art from 
applying the mulƟplex method for the detecƟon of nucleic acids disclosed in vitro in D6 to an 
in situ environment with cell or Ɵssue samples.

33 
 
The Applicants' objecƟon that there was no reasonable expectaƟon of success from a technical 
point of view because they would have been confronted with problems such as “molecular 
crowding” (the diﬃculty of disƟnguishing between mulƟple analytes occurring in close 
proximity) or “autoﬂuorescence” (unpredictable interacƟons) in the cell or Ɵssue sample 
cannot be accepted either. In the opinion of the Court of Appeal, adjudicaƟng with two 
technically qualiﬁed judges, these are problems that regularly arise in connecƟon with the in 
situ detecƟon of analytes in Ɵssue or cell samples – but which a person skilled in the art would 
have been able to deal with on the basis of their experƟse at the priority date and which 
therefore would not have prevented them from carrying out tests in the aforemenƟoned sense 
due to insuﬃcient prospects of success (see also the Swedish Intellectual Property Oﬃce, PRV 
ConsulƟng Report, B10, p. 5). This assessment is supported by the fact that the patent at issue 
does not provide any informaƟon on how to deal with the aforemenƟoned problems with in 
situ detecƟon, such as when using immunohistochemistry methods or RNA ﬂuorescence in 
situ hybridisaƟon (FISH) (patent at issue, cf. para. 48 et seq, para. 212 et seq, “Sample”, para. 
224 et seq “ApplicaƟons of the detecƟon reagents”; para. 234 “Immunohistochemistry”; para. 
235 “In-situ-hybridisaƟon”, “Fluorescence in-situ hybridisaƟon”). 
Finally, the Ɵme component would not have given a person skilled in the art any grounds to 
refrain from atempƟng to transfer the method disclosed in D6 to the detecƟon of analytes in 
cell or Ɵssue samples. On the contrary, it can be assumed that a person skilled in the art would 
have been able to adjust the Ɵme duraƟon based on their experƟse, taking into account other 
factors such as the binding aﬃniƟes, the incubaƟon condiƟons and the concentraƟon of the 
selector probes, in such a way that the detecƟon reagents would bind suﬃciently ﬁrmly to the 
analytes. This assessment is conﬁrmed by the fact that even the patent at issue, which in claim 
1 provides for incubaƟon for a period of Ɵme that is suﬃcient to enable the plurality of 
detecƟon reagents to bind to the analytes, does not provide any more detailed informaƟon on 
the speciﬁc seƫng. Rather, the descripƟon in the patent at issue merely menƟons Ɵmes 
between 30 seconds and 48 hours or longer for contacƟng the samples with the detecƟon 
reagents and factors that may be relevant to the length of the contact Ɵmes, such as binding 
aﬃniƟes, concentraƟons of the probe reagents or analytes, concentraƟons of the detecƟon 
reagents and/or the incubaƟon condiƟons (patent at issue, para. 45). This suggests that the

34 
 
patent at issue also assumes that a person skilled in the art would be capable of correctly 
measuring the Ɵme component based on his or her general qualiﬁcaƟons. 
c) Since, given all the above, it is more likely than not that the patent at issue will prove to be 
invalid in proceedings on the merits due to a lack of invenƟve step, there is no suﬃcient basis 
for the issuance of a preliminary injuncƟon in accordance with the Applicants' main request. 
6. The issuance of an injuncƟon is also not jusƟﬁed on the basis of the Applicants' auxiliary 
request. 
a) In this respect, it can remain undecided whether the auxiliary request is already 
inadmissible because the Defendants had no opportunity in the proceedings before the Court 
of First Instance to review the validity of the patent at issue in the form of the auxiliary request, 
since the Applicants only lodged this request at the oral hearing aŌer the court had drawn the 
parƟes' atenƟon to the fact that in the parallel proceedings concerning the parent patent, the 
requests for injuncƟve relief had been lodged in a version that restricted the patent claim of 
the parent patent. 
b) The applicaƟon for a preliminary injuncƟon is in any case unfounded because on the 
balance of probability it is more likely than not that the patent at issue will not prove to be 
valid even in the version of the auxiliary request. 
aa) With the auxiliary request, the Applicants assert an infringement of the patent at issue 
with the following two amendments to patent claim 1 compared to the version of the main 
applicaƟon: 
- 
The method of detecƟng a variety of analytes in a cell or Ɵssue sample is used in 
immunohistochemistry and/or ﬂorescence in situ hybridisaƟon. 
- 
The analytes are selected from the group consisƟng of proteins, pepƟdes and nucleic 
acids, wherein the nucleic acids are selected from the group consisƟng of cellular RNA, 
messenger RNA, microRNA, ribosomal RNA and any combinaƟons thereof.

35 
 
bb) Immunohistochemistry is a technique which, at the priority date, would have been known 
to a person skilled in the art, and by which analytes can be visualised for microscopic 
evaluaƟon with the aid of labelled anƟbodies (cf. patent at issue, para. 234). 
Fluorescence in situ hybridisaƟon is a technique for detecƟng cellular DNA or RNA, also known 
to a person skilled in the art at the priority date, in which the probe hybridising with the target 
analyte is detected by means of a ﬂuorescent dye (see patent at issue, para. 235). 
For a person skilled in the art who, proceeding from D6, was prompted to transfer the in vitro 
mulƟplex detecƟon method disclosed therein to cell or Ɵssue samples, it was obvious to also 
use the techniques of immunohistochemistry and/or ﬂuorescence in situ hybridisaƟon known 
to him or her on the basis of his or her experƟse (see also, however, Bundespatentgericht, 
Qualiﬁzierter Hinweis of 7 February 2023 [BP9], p. 10). 
From the point of view of a person skilled in the art, in addiƟon to the DNA molecules explicitly 
menƟoned in D6, RNA molecules and proteins and pepƟdes could also be considered as 
analytes for an in situ mulƟplex detecƟon method, as well as combinaƟons thereof (see also 
D6, Abstract: “[t]he decoding strategy is generic in that the target can be any biomolecule 
which has been encoded into a DNA circle via a molecular probing reacƟon” and page 7 
“[h]owever, any biomolecule that can be represented as a DNA circle can be converted to an 
easily idenƟﬁable ASM. Padlock probes can be applied for gene-copy number analysis, as well 
as analysis of infecƟous pathogens and for mRNA expression. Also proteins or interacƟng pairs 
of proteins can be digitally monitored in this manner via the proximity ligaƟon assay.”). 
(cc) The Court of Appeal holds that the fact that the Defendants did not present their 
arguments for the lack of invenƟve step unƟl the oral hearing in the appeal proceedings did 
not violate R. 222.1 RoP in the present case. Although the Defendants focused their arguments 
regarding the auxiliary request exclusively on the admissibility of the request in the Statement 
of grounds of appeal, they expressly requested a “judicial reference” if a submission on the 
content of the request was required. In view also of the fact that this is the ﬁrst appeal case in 
which auxiliary requests and R. 222.1 RoP are being used for the decision, the court instructed 
the parƟes at the oral hearing to also comment on the validity of the auxiliary request. Since 
the argumentaƟon on the lack of invenƟveness of the auxiliary request largely matches the

36 
 
argumentaƟon on the invenƟveness of the main request, the Applicants' defence was not 
unduly disadvantaged by this. 
7. As the unsuccessful party, the Applicants are required to bear the costs of the proceedings. 
8. Since the Decision on costs has no directly enforceable character, its immediate 
enforceability cannot be ordered. The Defendants' request must be rejected in this respect.

37 
 
ORDERS 
1. On appeal by the Defendants, the orders of the Court of First Instance (Munich 
Local Division) are revoked and the Applicants' request for an injuncƟon is 
rejected. 
2. The Applicants are required to bear the costs of the proceedings. 
3. The Defendants’ request to declare order 2) immediately enforceable is 
rejected. 
4. The amount in dispute is set at EUR 7 million. 
 
 
 
 
 
Klaus Grabinski 
President of the Court of Appeal and 
judge-rapporteur 
 
 
Françoise Barutel 
legally qualified judge 
 
 
 
Peter Blok 
legally qualified judge 
 
 
 
Rainer Friedrich 
technically qualified judge 
 
 
 
Cornelis Schüler 
technically qualified judge 
 
 
 
Eurico Igreja 
Employee of the Registry

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