Olink Bioscience AB

Patent Trials and Appeals Board

Nov 17, 2021

2021001167 (P.T.A.B. Nov. 17, 2021)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
15/500,418 01/30/2017 Ulf LANDEGREN 3995937-208997 7763
23570 7590 11/17/2021
PORTER WRIGHT MORRIS & ARTHUR, LLP
INTELLECTUAL PROPERTY GROUP
41 SOUTH HIGH STREET
29TH FLOOR
COLUMBUS, OH 43215
EXAMINER
SISSON, BRADLEY L
ART UNIT PAPER NUMBER
1634
NOTIFICATION DATE DELIVERY MODE
11/17/2021 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
ipdocket@porterwright.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ULF LANDEGREN and RACHEL YUAN NONG1
Appeal 2021-001167
Application 15/500,418
Technology Center 1600
Before DONALD E. ADAMS, ERIC B. GRIMES, and
ULRIKE W. JENKS, Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of selecting a region of interest in a nucleic acid, which have been
rejected as lacking adequate written description. We have jurisdiction under
35 U.S.C. § 6(b).
We REVERSE.

1 Appellant identifies the real party in interest as Olink Bioscience AB,
although Appellant states that “Olink Bioscience AB is now, by change of
name, Navinci Diagnostics AB.” Appeal Br. 1. “Appellant” refers to
“applicant” as defined in 37 C.F.R. § 1.42.
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Application 15/500,418

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STATEMENT OF THE CASE
The “invention relates to a method of selecting a target region of
interest (ROI) in a target nucleic acid molecule using a particular nucleic
acid probe comprising a 3' sequence capable of hybridising to a target
nucleic acid molecule and acting as a primer.” Spec. 1:4–7. The method
results in a circularized molecule containing the reverse complement of the
ROI that can be further analyzed or amplified. Id. at 1:10–11.
Claims 1–3, 5, 7, 9, 10, 12, 13, 15–42, 44–55, and 60–62 are on
appeal. Claim 1, the only independent claim, is illustrative and is reproduced
below:
1. A method of selecting a target region of interest (ROI)
in a target nucleic acid molecule, said ROI being flanked by a 3'
flanking sequence and a 5' flanking sequence in the target
molecule, said method comprising:
(a) providing a probe comprising
(i) a first target-binding site at a 3' end region of
said probe, which target-binding site is capable of
hybridising to a complementary binding site in the target
molecule, said complementary binding site being the 3'
flanking sequence flanking the 3' end of the ROI, and is
capable of being extended to generate a complement of
the target molecule in a target-templated extension
reaction, said target complement comprising the
complement of said 3' flanking sequence and at least of
the ROI and the 5' flanking sequence; and
(ii) a second binding site which is homologous to
the 5' flanking sequence flanking the 5' end of the ROI
and is capable of hybridising to a complement of said 5'
flanking sequence in said target complement;
wherein said probe is provided as an oligonucleotide
comprising a stem-loop structure which comprises the second
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binding site in the loop of the structure and further comprises a
cleavage site 3' of the second binding site which is cleavable to
open the loop, and a single-stranded region at the 3' end
comprising the first target-binding site; or
wherein said probe is provided as a partially double-
stranded construct comprising a first strand comprising a
single-stranded 3' end region comprising the first target-binding
site at the 3' end of the first strand, and a second strand
hybridised at the 5' end of said first strand and comprising a
single-stranded 3' end region comprising the second binding
site;
(b) contacting the probe with the target molecule and
allowing the first target-binding site to hybridise to its
complementary binding site in the target molecule, wherein the
target molecule is at least partially single stranded including in
the region comprising the complementary binding site, and
optionally the ROI and the 5' flanking sequence;
(c) extending the hybridised 3' end of the probe using the
target molecule as an extension template to generate a
complement of the target molecule;
(d) removing the target molecule, leaving an extended
probe comprising 3' to 5' in the extended region complements
of the 5' flanking sequence, the ROI and the 3' flanking
sequence of the target molecule, wherein the second binding
site remains in the probe;
(e) allowing the extended probe to undergo an
intramolecular rearrangement such that the second binding site
hybridises to its complementary binding site in the target
complement, being the complement of the 5' flanking sequence
of the target molecule,
wherein if said probe comprises a stem-loop structure,
the rearrangement comprises cleavage of the extended probe at
the cleavage site in the stem-loop structure of the probe to
release a 3' end of the probe comprising the second binding site
thereby generating a partially double-stranded construct
comprising a first extended strand comprising the target
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complement and a second strand hybridised to the first strand in
the stem and comprising the released 3' end which is then able
to hybridise to its complementary binding site in the first strand,
and
wherein if said 5' flanking sequence is internal to the 5'
end of the target molecule and the target complement in the first
extended strand contains an additional sequence 3' of the
complement of the 5' flanking sequence, the rearrangement
comprises a cleavage in or of the additional sequence to release
the 3' end of the first strand comprising the complementary
binding site for the second binding site,
such that the, optionally released, 5' end of the first,
extended, strand and the, optionally released, 3' end of the first,
extended, strand are brought into juxtaposition for ligation
directly or indirectly to each other, using the second binding
site as ligation template;
(f) ligating the ends of the extended strand of the probe
directly or indirectly to one another to circularise the extended
strand of the probe;
(g) amplifying or separating the circularised extended
strand, thereby to select the ROI.
OPINION
Claims 1–3, 5, 7, 9, 10, 12, 13, 15–42, 44–55, and 60–62 stand
rejected under 35 U.S.C. § 112(a) on the basis that they lack adequate
written description in the Specification. Final Action2 19. The Examiner
finds that the claimed “method requires use of a new type of probes that
hybridize to the target.” Id. at 21.
The Examiner finds that “the claimed method requires the use of a
single-stranded probe whose sequence of nucleotides is highly complex,

2 Office Action mailed Nov. 8, 2019.
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with multiple regions within this single molecule being required to perform
separate functions.” Id. at 22. That is, “the probe can comprise multiple
sequences that will bind to different target sequences, . . . as well as being
able to serve as priming sequences and the end result being capable of being
ligated.” Id. at 24. The Examiner finds that “[t]he aspect of having to
perform such a combination of steps, . . . further compounds the complexity
issue of the admittedly ‘new kind of probe’.” Id. at 25.
The Examiner also finds that “the ROI can range from 10 nucleotides
to 100,000 nucleotides in length.” Id. at 26–27. The Examiner finds that the
Specification describes only three human target sequences, and
[w]hile the disclosure clearly teaches that the size of the target
can be up to 100,000 nucleotides in length, applicant has not
disclosed the first target sequence that is even 200 nucleotides
in length, much less 1,000, and lesser still 100,000 nucleotides
in length. Such limited disclosure has not been found to
constitute the requisite “representative number of species
falling within the scope of the genus or structural features
common to the members of the genus.”
Id. at 29, quoting Amgen, Inc. v. Sanofi, 872 F.3d 1367, 1373 (Fed. Cir.
2017). The Examiner concludes that “the disclosure has not been found to
satisfy the requirements as set forth in the en banc decision in Ariad
[Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010)], nor
provide the ‘representative number of species falling within the scope of the
genus’ as reiterated in Sanofi.” Id. at 30.
Appellant argues that “the probes employed in the claimed methods[]
comprise defined binding sites and cleavage sites which are in defined
locations of the probe, with the binding sites recited as capable of
hybridising with sequences in defined locations in a target nucleic acid
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molecule.” Appeal Br. 36. Appellant argues that “the evidence of record . . .
show[s] that nucleotide sequencing and hybridisation are routine techniques
in the art and probe functional components are conventional materials in the
art,” and thus the claims are sufficiently described to those of skill in the art.
Id. at 37. Appellant notes that the claims are not directed to “methods
employing probes defined by a sequence per se, or for selecting a ROI of a
nucleic acid molecule of a specific sequence. Rather, the probes are defined
by their functional components and the location of those functional
components in the probe.” Id. at 38.
Finally, Appellant argues that
the determination of what is needed to support generic claims to
biological subject matter depends on, inter alia, the existing
knowledge in the particular field, the extent and content of the
prior art, the maturity of the science or technology, and the
predictability of the aspect at issue . . . , all of which evidence
that the description of the claimed methods and probes in the
present specification sufficiently describes the invention to one
of ordinary skill in the art.
Id. at 40.
We agree with Appellant that the Examiner has not shown that a
skilled artisan would not recognize an adequate written description of the
claimed method in Appellant’s Specification. “[T]he examiner bears the
initial burden, on review of the prior art or on any other ground, of
presenting a prima facie case of unpatentability.” In re Oetiker, 977 F.2d
1443, 1445 (Fed. Cir. 1992). “Insofar as the written description requirement
is concerned, that burden is discharged by ‘presenting evidence or reasons
why persons skilled in the art would not recognize in the disclosure a
description of the invention defined by the claims.’” In re Alton, 76 F.3d
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1168, 1175 (Fed. Cir. 1996) (citation omitted). See also Ariad, 598 F.3d at
1351 (“[T]he test for sufficiency is whether the disclosure of the application
relied upon reasonably conveys to those skilled in the art that the inventor
had possession of the claimed subject matter as of the filing date.”).
“The ‘written description’ requirement must be applied in the context
of the particular invention and the state of the knowledge.” Capon v. Eshhar,
418 F.3d 1349, 1358 (Fed. Cir. 2005). “[W]hat is needed to support generic
claims to biological subject matter depends on a variety of factors, such as
the existing knowledge in the particular field, the extent and content of the
prior art, the maturity of the science or technology, [and] the predictability
of the aspect at issue,” among others. Id. at 1359.
In this case, Examiner does not clearly explain the basis of the
rejection. The Examiner notes certain features of the claimed method (Final
Action 21) and functional and structural features of the probe used in the
claimed method (id. at 22–23, 24–25). The Examiner does not, however,
explain why these features of the claims require the Specification to provide
more written descriptive support than it already does.
The Examiner also notes that the Specification discloses embodiments
“where ‘a plurality of probes’ are used” (id. at 26), and notes that the
Specification states that “the ROI can range from 10 nucleotides to 100,000
nucleotides in length” (id. at 27). The Examiner concludes that,
[w]hile the disclosure clearly teaches that the method is to be
applied to the simultaneous detection of 10,000 targets, only 3
human sequences have been identified. While the disclosure
clearly teaches that the size of the target can be up to 100,000
nucleotides in length, applicant has not disclosed the first target
sequence that is even 200 nucleotides in length, much less
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1,000, and lesser still 100,000 nucleotides in length. Such
limited disclosure has not been found to constitute the requisite
“representative number of species falling within the scope of
the genus or structural features common to the members of the
genus.” Sanofi.
Id. at 29.
We disagree with the Examiner’s reasoning and conclusion. First, to
provide an adequate written description, an applicant must “convey with
reasonable clarity to those skilled in the art that, as of the filing date sought,
he or she was in possession of the invention. The invention is, for purposes
of the ‘written description’ inquiry, whatever is now claimed.” Vas-Cath Inc.
v. Mahurkar, 935 F.2d 1555, 1563 (Fed. Cir. 1991).
Here, regardless of the possible embodiments that are disclosed in
Appellant’s Specification, claim 1 only requires a single probe capable of
binding to sequences flanking a single target region of interest (ROI). Claim
1 also does not require the target ROI to be any particular length. Thus, the
Specification need not provide a detailed description of embodiments
involving multiplexing or targets of a specific length in order to show
possession of the claimed method to those skilled in the art.
In addition, the Specification describes the probe used in the claimed
method as being designed, based on the specific target ROI, to have parts of
each strand that hybridize to sequences flanking the target ROI and parts that
hybridize to the other strand of the probe, to form either a stem-and-loop
structure or a partially double-stranded structure with single-stranded
portions extending from it. Spec. 2:27–29, 2:35 to 3:4, 8:22–31.
The Examiner has not shown that those skilled in the art would not
have recognized the Specification’s description as showing possession of a
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probe that hybridizes to complementary sequences flanking a specific target,
and that hybridize to itself in such a way that it forms a stem and loop, or a
partially double-stranded region with single-stranded regions extending from
it. See Capon v. Eshhar, 418 F.3d 1359 (What is required for adequate
written description “depends on a variety of factors, such as the existing
knowledge in the particular field, the extent and content of the prior art, the
maturity of the science or technology, [and] the predictability of the aspect at
issue.”).
In view of the state of the art and the knowledge of those working in
the areas such as nucleic acid hybridization, ligation, and amplification, the
Examiner has not shown that the description provided by the Specification
of the claimed method, and of the probes used in it, would fail to show
possession to those of ordinary skill in the art. We therefore reverse the
rejection of the claims for lack of adequate written description.
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference/Basis Affirmed Reversed
1–3, 5, 7, 9,
10, 12, 13,
15–42, 44–
55, 60–62
112(a) Written Description 1–3, 5, 7,
9, 10, 12,
13, 15–42,
44–55, 60–
62

REVERSED