Microsoft Technology Licensing, LLC

Patent Trials and Appeals Board

Jul 26, 2021

2020005457 (P.T.A.B. Jul. 26, 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.
15/626,021 06/16/2017 Kris K. Ganjam MS2-0133US 7725
142810 7590 07/26/2021
Newport IP, LLC
1400 112th Ave SE
Suite 100
Bellevue, WA 98004
EXAMINER
LEITH, NANCY J
ART UNIT PAPER NUMBER
1636
NOTIFICATION DATE DELIVERY MODE
07/26/2021 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):
docketing@newportip.com
eofficeaction@appcoll.com
scott@newportip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte KRIS K. GANJAM
Appeal 2020-005457
Application 15/626,021
Technology Center 1600
Before ERIC B. GRIMES, JEFFREY N. FREDMAN, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject as obvious claims to a homology directed
repair system that adds a barcode that uniquely identifies a gene. We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM-IN-PART.

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42(a). Appellant identifies the real party in interest as Microsoft
Technology Licensing, LLC. (Appeal Br. 3.)
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Application 15/626,021

2
STATEMENT OF THE CASE
Homologous directed repair (HDR) is a mechanism that cells use to
repair double stranded breaks (DSB) in a strand of deoxyribonucleic acid
(DNA). (Spec. ¶ 29.) Appellant’s claim is directed to a system for use in
HDR.
Claims 9–20 are before us on appeal. Claim 16, reproduced below, is
illustrative of the claimed subject matter:
16. A system comprising:
a gene, that when expressed, produces a homology direct
repair (HDR) template;
a double stranded polynucleotide including a target site,
wherein the target site is not in the gene;
the HDR template including a first sequence
complementary to a first subsequence of the target site, a
second sequence complementary to a second subsequence of
the target site, and a barcode region having a sequence of
nucleotides that uniquely identifies the gene; and
an enzyme configured to create a double strand break in
the double stranded polynucleotide at the target site;
wherein the HDR template is configured to add the
barcode region into the double stranded polynucleotide by HDR
to produce a modified double stranded polynucleotide.
(Appeal Br. 27.)

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The prior art relied upon by the Examiner is:
Name Reference Date
Gill et al. US 2017/0369870 A1 Dec. 28, 2017
Holmes et al. US 9,957,526 B2 May 1, 2018
Dominik Paquet et al. Efficient introduction
of specific homozygous
and heterozygous
mutations using
CRISPR/Cas9, 533
Nature, 125–129
2016

The following grounds of rejection by the Examiner are before us on
review:
Claims 9–11 and 14–20 under 35 U.S.C. § 103 as unpatentable over
Paquet and Gill.2
Claims 12 and 13 under 35 U.S.C. § 103 as unpatentable over Paquet,
Gill, and Holmes.
DISCUSSION
Claim 16: Obviousness over Paquet and Gill
Appellant focuses its arguments with respect to this rejection on claim
16. (See Appeal Br. 12, 16–17; Reply Br. 5, 7, 9–11.) We, thus, focus on
the rejection as it relates to claim 16.
The Examiner found that Paquet discloses a homology directed repair
system that includes (1) a double stranded polynucleotide gene that has a
target site, (2) “an enzyme (CRISPR/Cas9) that will create a double stranded

2 The Examiner relies on the priority claim to US Provisional Application
62/354,516, filed June 24, 2016 (Gill ’516). (Ans. 4.) The Examiner states
that “the ’516 provisional application does provide full support for the
disclosure of the ’870 application, as applied in the rejections.” (Id. at 8.)
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break in the target site,” and (3) an HDR template that has a barcode
sequence, where the HDR template could be either single stranded or double
stranded. (Ans. 4 (citing Paquet, Abstr., and Figs. 1 and 3); Id. at 9.) The
Examiner found that Paquet does not disclose that the target sequence is not
located in the gene, as required by claim 16. (Id. at 4.)
The Examiner found that Gill also discloses HDR systems using a
CRISPR enzyme system. (Id. (citing Gill ¶¶ 55–93; Gill ’516 ¶¶ 80–91).)
The Examiner further found that Gill teaches “the target can be a genomic
locus, a genomic sequence or an extrachromosomal locus.” (Id. (citing Gill
¶ 162; Gill ’516 ¶¶ 47, 113).) The Examiner also found that Gill teaches that
the target sequence can be any nucleic acid including a gene, as well as a
non-coding nucleic acid sequence. (Id. at 4–5 (citing Gill ¶¶ 118, 169; Gill
’516 ¶¶ 112–113).) Additionally, the Examiner found that Gill discloses that
the “editing cassette . . . can introduce mutations into a target sequence,
which can be assayed for by measuring gene activity.” (Id. at 5 (citing Gill
¶¶ 206, 217).) The Examiner indicates that “Gill provides for identification
of genes and multiplex identification of genes via a barcode, which may be
outside of a target site” and that “the system can also provide for
measurement and detection of gene expression and/or alteration of gene
expression activity.” (Id. at 9.)
The Examiner determined that it would have been obvious “that the
system disclosed and suggested by Paquet and Gill can be used to target any
specific desired nucleic acid sequence, including a non-coding, non-gene
sequence because the guide sequences can be created to target any desired
sequence, whether within or not in a gene.” (Id. at 5.) The Examiner further
determined that “[o]ne of ordinary skill in the art would have a predictable
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and reasonable expectation of success in designing the system to target any
sequence in any genome or cell.” (Id.) The Examiner noted that “Gill is
deemed to provide motivation to combine the references” and that “[o]ne of
ordinary skill in the art, desiring to track edits and repair of genetic material
would turn to both Paquet and Gill.” (Id. at 9.)
We agree with the Examiner’s conclusion of obviousness of claim 16.

A. Application of Gill as prior art
Appellant does not dispute that Gill ’516 has a filing date that
precedes the filing date of Appellant’s application. (See Appeal Br. 10.)
However, Appellant argues with respect to Gill that the provisional filing
and the utility filing “are clearly different” and “[t]he burden is on the Office
to support rejections” but “[t]he Office has not shown that all of the passages
of the Gill ’870 application relied upon to support the grounds of rejection
are entitled to a priority date earlier than Appellant’s claim.” (Reply Br. 5–
6.) Appellant notes that there may be support, or not but “[t]here is nothing
in the record to support a determination either way” and that “any grounds of
rejection which rely on citations to the Gill ‘870 application fail to establish
a prima facie case of obviousness.” (Id. at 6.) Appellant argues that the
rejection does in fact rely on “some features” of Gill for which there are no
citations to any corresponding portion of Gill ’516. (Id.) Appellant asserts
that “such features are not shown in the record to have a priority date prior to
that of Appellant’s claims” and that “the Board should base its analysis of
the sufficiency of the ground of rejection only on citations to the Gill ‘516
provisional.” (Id.)
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We find that the Examiner’s rejection does cite to one feature of Gill
without pointing out where in Gill ’516 there is support; namely, that the
target sequence that was edited by the editing cassette “can be assayed for by
measuring gene activity.” (Ans. 5 (citing Gill ¶¶ 206, 217).) However, we
conclude that this feature is not relevant to any of the system claims on
appeal as it represents an intended use recitation that can be satisfied by
finding no gene activity or some gene activity. A “mere statement of a new
use for an otherwise old or obvious [product] cannot render a claim to the
[product] patentable.” In re Zierden, 411 F.2d 1325, 1328 (CCPA 1969).
And, in any event, we note that Gill ’516 paragraph 144 has a similar
disclosure to Gill paragraph 217 stating that “[i]n addition or as an
alternative to activity screens, more general properties . . . can be efficiently
tested using methods . . . disclosed herein.” And Gill ’516, like Gill, further
explains that “barcoding technology” can be used to map residue changes.
(Gill ’516 ¶¶ 145–146; see also Gill ¶¶ 218–219.) Consequently, we
conclude that the Examiner’s reliance on Gill as prior art is supported. In
any event, we base our analysis of the Examiner’s rejection with respect to
Gill on the disclosure provided in Gill ’516.
B. The claimed barcode requirement
Appellant, although conceding that the term barcode is used
throughout Gill ’516, argues that the Examiner does not cite to any passages
of Gill ’516 concerning barcodes and thus, “the record does not show how
the Office is interpreting the ‘barcode’ of Gill or which specific aspects of
the barcode allegedly teach or suggest features of Appellant’s claims.”
(Reply Br. 7.) We do not find this argument persuasive of non-obviousness.
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Appellant’s independent claim 16 requires a gene encoding a first
HDR template where the template includes a barcode sequence that uniquely
identifies the gene. Appellant’s Specification does not define the term
barcode. It simply indicates that the barcode sequence “can include any
number of nucleotides that allow for identification of the gene.” (See Spec.
¶ 139.) The Examiner cites to paragraphs 80–91 of Gill ’516, which teach
that CRISPR Enabled Trackable genome Engineering (CREATE) methods
employ a CREATE recorder system that includes a trackable sequence (Gill
’516 ¶ 81), such as a barcoding sequence that can be a unique DNA
sequence (Gill ’516 ¶ 87; see also id. ¶ 183). We conclude that such
disclosure sufficiently establishes that the barcode of Gill ’516 is one that
uniquely identifies a gene encoding the HDR template, and thus meets the
requirement of “barcode” recited by claim 16.
C. A gene that when expressed produces an HDR template that
includes the barcode
Appellant argues that the Examiner’s rejection is in error because,
although the references show some of the tools used in the claimed system,
the references do not teach or suggest, alone or in combination, a system that
includes a gene that when expressed produces the HDR template that
includes a barcode region and wherein the HDR template is configured to
add the barcode region into the double stranded polynucleotide by HDR.
(Appeal Br. 16–17.) We do not agree with Appellant’s assessment.
We find Gill ’516 teaches or suggests the foregoing. As discussed
above, the Examiner pointed to Gill ’516 paragraphs that teach a barcode as
claimed. Gill ’516, in paragraphs cited by the Examiner, also teaches that
the system includes a cassette that couples two elements, guide nucleic acids
(a gRNA encoding gene) designed for targeting a user specific site in the
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genome as well as a homology arm that includes a trackable sequence
“designed to undergo homologous recombination with the chromosome at
the site of nucleic acid-guided nuclease-mediated double strand break,” i.e.,
“the recording sequence is incorporated by homologous recombination or
homology-driven repair systems.” (Gill ’516 ¶¶ 81, 85, 87, 88, 90.) In
short, we conclude that the Examiner has provided sufficient evidence that
Gill ’516 discloses or at least suggests that the unique DNA tracking
sequence of the HDR template will be added into the double stranded
polynucleotide by HDR.
D. Reason to Combine
Appellant also argues that the Examiner’s rejection is in error because
the asserted reason to combine Paquet and Gill is merely a conclusory
statement with no supporting underlying rationale. (Appeal Br. 20–21; see
also Reply Br. 5 (“Because the language of the [new grounds of] rejection
[in the Answer] is essential identically [sic], Appellant reiterates all previous
arguments made in the Appeal Brief without repeating those arguments
here.”).) Appellant contends that “[t]he ability of one to freely select targets
for HDR directed insertion is not unique to any of the three references” but
simply a “characteristic of this well-established molecular biology tool” and
as such is not a “rationale for combining the references.” (Id.) Appellant
indicates that the Examiner does not “provide[] a clear articulation of why a
person having ordinary skill in the art would be motivated to combine the
cited references.” (Reply Br. 10.) We do not find the foregoing argument
persuasive of error.
First, for the reasons discussed above, we conclude that Gill ’516
suggests the claimed invention. In affirming a multiple reference rejection
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under 35 U.S.C. § 103, the Board may rely on fewer than all of the
references relied on by the Examiner in an obviousness rationale without
designating it as a new ground of rejection. In re Bush, 296 F.2d 491, 496
(CCPA 1961).
Second, even considering Paquet with Gill, we note “[t]he
combination of familiar elements according to known methods is likely to be
obvious when it does no more than yield predictable results.” KSR Int’l Co.
v. Teleflex Inc., 550 U.S. 398, 416 (2007). As Appellant recognizes, both
Paquet and Gill describe HDR, which is a “well-established molecular
biology tool” that is “flexible and versatile.” (Appeal Br. 20–21.) Gill ’516
teaches, as the Examiner found, that the target site to which HDR can be
directed can be in a gene or not in the gene (Gill ’516 ¶¶ 47, 113) and that
the editing cassette can introduce DNA changes into that target site which
cassette includes a barcode to track the edit, see citations to Gill ’516 supra.
We conclude that the cited prior art supports a conclusion that the claimed
invention is merely the combination of known elements yielding a
predictable result, i.e., a system with the claimed components in which the
gene would be capable of being expressed to produce the HDR template, as
evidenced by Paquet, and where the HDR template taught by Gill ’516
would reasonably be predicted to add the barcode into a double stranded
polynucleotide by HDR.
For the foregoing reasons, we affirm the Examiner’s rejection of
claim 16 as being obvious from the teachings of Paquet and Gill as
supported by Gill’s priority application Gill ’516.
Claims 9–11, 14, 15, and 17–20 have not been argued separately and
therefore fall with claim 16. 37 C.F.R. § 41.37(c)(1)(iv).
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Claim 13: Obviousness over Paquet, Gill, and Holmes
Claim 13 depends from claim 9, an independent claim with very
similar claim elements to claim 16.3 Claim 13, however, requires the gene
to include certain additional specific regions. Appellant argues that the
Examiner’s rejection of claim 13 is in error because the rejection (1) “does
not provide any evidence” that “a first splicing region” is “taught or
suggested by the prior art,” (2) “does not identify any teaching or suggestion
of ‘a 3’ untranslated region (UTR) and a 5’ UTR’ in a prior art reference,”
and (3) “does not identify any teaching or suggestion of a ‘coding region that
includes an intron and an exon’ in a prior art reference.” (Appeal Br. 18.) In
addition, Appellant argues that the rejection also “does not identify these
features in combination as an RNA precursor encoded by a gene.” (Id.)
We agree with Appellant that the Examiner has failed to establish a
prima facie case that claim 13 is obvious from the teachings of Paquet, Gill,
and Holmes. Gill ’516 describes the CRISPR system as including a gene
sequence that is expressed as a guideRNA that targets particular sites
because it is complementary to a region of the target site. (See, e.g., Gill
’516 ¶ 47, 64; see also Paquet, Fig. 1.) Such guideRNA is known to be
expressed from a sequence homologous to the target gene sequence in a
CRISPR system as precursor RNA which is further processed to result in the
guideRNA. Thus, Gill ’516 teaches or suggests the HDR template includes

3 Appellant does not separately argue the rejection of claim 12. “When the
appellant fails to contest a ground of rejection to the Board, . . . the Board
may treat any argument with respect to that ground of rejection as waived.”
Hyatt v. Dudas, 551 F.3d 1307, 1314 (Fed. Cir. 2008).
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a sequence that when expressed encodes an RNA precursor homologous to
the target gene that includes a single stranded polynucleotide.
Additionally, as the Examiner’s rejection states, Gill teaches the target
for cassette sequences that are trackable can be inserted in an untranslated
region or a gene and that the cassettes can target multiple sequences. (See
Gill ’516 ¶¶ 84, 87, 112–113; see also Ans. 4–5.) Moreover, Gill ’516
explains that the barcode can be located “outside of the open reading frame
of the gene.” (Gill ’516 ¶ 136; see also Gill ¶ 118.) Given the foregoing
teachings, we understand Gill ’516 to teach or suggest that the gene
encoding the HDR template would include a sequence that corresponds to
the barcode sequence and sequences to direct the inclusion of the barcode to
a region outside of an open reading frame such as into untranslated regions.
Holmes further supports the obviousness of including sequences in HDR
templates that are for non-coding regions. (See, e.g., Holmes 4:38–40.)
The Examiner relied on Holmes for teaching the inclusion of splice
acceptor sequences in the HDR template for targeted insertion. (Ans. 6
(citing Holmes 28:8–19).) We conclude that in light of the specific
teachings of Holmes, including specific splice acceptor sequences that may
be used, one of ordinary skill in the art would have found it obvious to
include such a sequence in the HDR templates of Gill and Paquet for its
known advantages.
On the other hand, the Examiner has not identified where the cited
prior art teaches or suggests inclusion in the sequence of the gene encoding a
first HDR template “a 3’ untranslated region (UTR) and a 5’ UTR,” and a
“coding region that includes an intron and an exon” as recited in claim 13.
Instead, the Examiner simply asserts that “one of ordinary skill in the art
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would have understood that expression of a gene would inherently progress
from an RNA precursor to an expressed protein, and that the recited
components are present in the constructs disclosed and suggested by Paquet,
Gill, and Holmes.” (Ans. 10.) The Examiner, however, does not establish
that fact and does not indicate that the recited 3’ and 5’ UTR regions, and
that an intron as well as an exon coding region are required and thus
necessarily present in an HDR template gene construct. Thus, we reverse the
Examiner’s rejection of claim 13 as being obvious from the teachings of
Paquet, Gill, and Holmes.

DECISION SUMMARY
In summary:
Claim(s)
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
9–11, 14–20 103 Paquet, Gill 9–11, 14–20
12, 13 103 Paquet, Gill,
Holmes
12 13
Overall
Outcome
9–12, 14–20 13

TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R.
§ 1.136(a)(1)(iv).
AFFIRMED-IN-PART