OpenCell Technologies, Inc.

Patent Trials and Appeals Board

Apr 23, 2021

2020003696 (P.T.A.B. Apr. 23, 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.
15/629,162 06/21/2017 John Mark Meacham 221501-1011 9763
24504 7590 04/23/2021
THOMAS | HORSTEMEYER, LLP
3200 WINDY HILL ROAD, SE
SUITE 1600E
ATLANTA, GA 30339
EXAMINER
BOWERS, NATHAN ANDREW
ART UNIT PAPER NUMBER
1799
NOTIFICATION DATE DELIVERY MODE
04/23/2021 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@thomashorstemeyer.com
ozzie.liggins@tkhr.com
uspatents@tkhr.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JOHN MARK MEACHAM, KIRANMAI DURVASULA,
ANDREI G. FEDOROV, FAHRETTIN LEVENT DEGERTEKIN, and
AKASH MEHTA
Appeal 2020-003696
Application 15/629,162
Technology Center 1700
Before JEFFREY B. ROBERTSON, JAMES C. HOUSEL, and
JULIA HEANEY, Administrative Patent Judges.
ROBERTSON, Administrative Patent Judge.
DECISION ON APPEAL1

1 This Decision includes citations to the following documents:
Specification filed June 21, 2017 (“Spec.”); Final Office Action mailed May
13, 2019 (“Final Act.”); Appeal Brief filed Dec. 10, 2019 (“Appeal Br.”);
Examiner’s Answer mailed February 19, 2020 (“Ans.”), and Reply Brief
filed April 15, 2020 (“Reply Br.”).
Appeal 2020-003696
Application 15/629,162

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STATEMENT OF THE CASE
Pursuant to 35 U.S.C. § 134(a), Appellant2 appeals from the
Examiner’s decision to reject claims 1 and 3–35. See Appeal Br. 12. We
have jurisdiction under 35 U.S.C. § 6(b).
We affirm, but we designate our affirmance as a new ground of
rejection.
CLAIMED SUBJECT MATTER
Appellant states the invention relates to intracellular delivery and
transfection methods and devices for treatment of biological samples with a
substance. Spec. 2. Claim 1, reproduced below, is illustrative of the
claimed subject matter (Appeal Br., Claims Appendix 2):
1. A delivery system for delivering a substance into a living cell
having a cell membrane, comprising:
a) a permeabilization system configured for permeabilization
of the cell membrane to form pores in the membrane of a cell in
suspension, wherein the permeabilization system is further
configured for permeabilization of the cell membrane using
mechanical poration, thermal poration, or a combination thereof;
and
b) an active insertion system configured to actively transport
and incorporate a substance into one or more of the cell interior,
a vesicle, a nanostructure defined by a membrane, and a
microstructure defined by a membrane.
Claims 18 and 23 also recite systems for delivering a substance into a
living cell including a permeabilization system and an active insertion
system. Appeal Br., Claims Appendix 3–4.

2 We use the term “Appellant” to refer to “applicant” as defined in 37 C.F.R.
§ 1.42. Appellant identifies the real party in interest as OpenCell
Technologies, Inc. Appeal Br. 3.
Appeal 2020-003696
Application 15/629,162

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REFERENCES
The prior art relied upon by the Examiner is:
Name Reference Date
Ackley US 6,638,482 B1 Oct. 28, 2003
Harrold US 2002/0187503 A1 Dec. 12, 2002
Sharei US 2014/0287509 A1 Sept. 25, 2014

REJECTION3
Claims 1 and 3–35 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over Sharei, Ackley and/or Harrold. Final Act. 3–6.

OPINION
Appellant presents separate arguments with respect to claims 1, 16,
17, 20, 25, and 28–35 subject to this rejection. See Appeal Br. 15–37; Reply
Br. 6–7. We select claims 1, 16, and 20 as representative for disposition of
this rejection. 37 C.F.R. § 41.37(c)(1)(iv)(2019).

Claim 1
The Examiner’s Rejection
In rejecting claim 1 as unpatentable over Sharei, Ackley and/or
Harold, the Examiner found Sharei discloses a delivery system for delivering
a substance into a living cell having a cell membrane including a
permeabilization system, which provides a mechanical shear force that
induces a tension in the cell membrane. Final Act. 3, citing Sharei, Fig. 1A,

3 The Examiner withdrew the rejection of claims 20 and 25 under 35 U.S.C.
§ 112 (pre-AIA) as being indefinite in the Answer. See Final Act. 2; Ans. 3.
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Application 15/629,162

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¶¶ 91–97. The Examiner found Sharei does not appear to teach an active
insertion system configured to actively transport a substance into the cell
interior following poration. Id. The Examiner found Ackley and Harrold
each disclose a microfluidic system for controlling the motion of
biochemical analytes in a sample volume using an electrophoretic bus
including driving electrodes or a plurality of electrodes to generate
controllable electric fields to actively transport molecules. Id. at 3–4, citing
Ackley, Fig. 3, col. 8, l. 40 – col. 12, l. 53; Harrold, Fig. 1, ¶¶ 7, 77, 91.
The Examiner determined it would have been obvious to have
modified Sharei’s system to include an electrophoretic active insertion
system to controllably transport a substance, such as a nucleic acid, into cells
following poration by the permeabilization system. Id. at 4. The Examiner
determined that in view of the disclosures of Ackley and Harrold, which
each show how dielectrophoresis transport systems are well known in the art
and effective for selectively moving molecules of interest to desired
processing locations, one of ordinary skill in the art would have recognized
the benefit of such systems ensure that nucleic acids are in communication
with porated cells to complete the transfection process. Id.

Appellant’s Arguments
Appellant argues that biological sciences are unpredictable, such that
one of ordinary skill in the art would not have a reasonable expectation of
success in combining Ackley and Harrold, which are directed to translating a
substance after cell lysis, with Sharei, which is directed to transport of
biomolecules through pores of a cell membrane of a living cell. See Appeal
Br. 16–17. In this regard, Appellant argues Sharei suggests that there may
Appeal 2020-003696
Application 15/629,162

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be complications arising from the use of electric fields on living cells, and
thus teaches away from the use of electrophoresis. Id. at 17–18, 32.
Appellant contends the Examiner’s reasoning, which equates the
translocation techniques disclosed in Ackley and Harrold with an active
insertions system, is conclusory and ignores that Ackley and Harrold do not
teach insertion through a cell membrane. See id. at 34.

Issue
Did the Examiner err in determining that it would have been obvious
to have utilized the electrophoretic systems of Ackley and/or Harrold in
combination with the permeabilization system disclosed in Sharei in order to
provide an active insertion system to aid in delivering a substance into a
living cell having a cell membrane as recited in claim 1?

Discussion
We have carefully considered the evidence of record,4 and find that
the preponderance of the evidence supports the Examiner’s position that

4 Appellant disputes the Examiner’s refusal to consider Exhibits A–E,
because such evidence was previously submitted with the Response to Final
Office Action filed August 13, 2019. See Appeal Br. 24–31; Reply Br. 3,
12–13; Advisory Action entered February 3, 2020 (Box 1b); Ans. 4. We
note that the Examiner has apparently also considered this evidence in the
Answer. Ans. 4 (referring to “affidavits” submitted with the Appeal Brief,
which we understand to be the scientific articles identified as Exhibits A–E.)
We also observe that the Advisory Action entered August 26, 2019, although
indicating the proposed amendments to the claims were not entered (Boxes
3a, 7), does not indicate that Exhibits A–E were either not entered (Box 9) or
entered (Box 11). In view of the Examiner’s statements in the Answer and
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claim 1 would have been obvious over Sharei in combination with Ackley
and/or Harrold. However, because our discussion points to different
portions of Sharei that were not discussed either by the Examiner or
Appellant, we designate our affirmance as a new ground of rejection for the
following reasons.
Sharei discloses a permeabilization system in the form of mechanical
deformation of a cell in order to deliver a payload, such as a DNA molecule,
into the cell. Sharei ¶¶ 6, 7, 91–97. In contrast to Appellant’s arguments
that Sharei teaches away from electrophoresis, Sharei discloses combination
treatments for permeabilization may also be used, where mechanical
deformation may be followed or preceded by electroporation. Id. ¶¶ 7, 229.
Most significantly, Sharei expressly discloses: “Additionally, electric
fields can be used as a driving force to deliver larger charged molecules,
such as DNA, that suffer from low diffusion rates.” Id. ¶ 235. Thus,
although Sharei discloses embodiments avoiding the use of electromagnetic
fields and electroporation (e.g., ¶ 38), Sharei discloses expressly
embodiments where electric fields may be used to deliver charged
molecules, and as such, the embodiments disclosed in Sharei including
permeabilization that does not include electroporation would not discourage
the use of electrophoresis as an insertion system in combination with
Sharei’s permeabilization techniques. The prior art must be considered as a
whole, including non-preferred embodiments disclosed therein. See Merck
& Co., Inc. v. Biocraft Laboratories, Inc., 874 F.2d 804, 807 (Fed. Cir.),

because we are entering a new ground of rejection, we have considered
Exhibits A–E.
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Application 15/629,162

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cert. denied, 493 U.S. 975 (1989) (quoting In re Lamberti, 545 F.2d 747,
750 (CCPA 1976)).
As a result, we are not persuaded by Appellant’s arguments with
respect to the unpredictability of the biological sciences or that the
disclosures of Ackley and Harrold are focused on translocation techniques.
Sharei expressly supports the Examiner’s rationale that one of ordinary skill
in the art would have applied techniques based on electrophoresis as
disclosed in Ackley and Harrold in order to ensure the delivery of larger
charged molecules such as DNA into the porated living cell. In this regard,
Sharei does not indicate any special difficulties in applying electric fields for
this purpose. Rather, the evidence supports the Examiner’s position that
applying the disclosures of Ackley and Harrold to Sharei is, as the Examiner
determined, no more than applying a known technique to a known device
ready for the improvement. Final Act. 4.
In this regard, we have considered the articles (Attachments A–E)
cited by Appellant as to the difficulty of delivering substances through cell
membranes as a response to the Examiner’s position that electrophoretic
forces will move biomolecules in the same way regardless of assay purpose
such that it should not matter whether the biomolecules are transported after
cell death or into a live cell. Appeal Br. 24–31; Reply Br. 3. However, we
are not persuaded, because, as the Examiner stated, Sharei already accounts
for the complexities associated with moving a nucleic acid or protein
through a porated cell membrane. Ans. 5.
In addition, Sharei provides evidence of the level of skill in the art and
as such, we are not persuaded by Appellant’s argument (Appeal Br. 14) that
the Examiner erred by not assessing the level of skill in the art. See Okajima
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Application 15/629,162

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v. Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001); In re GPAC Inc., 57
F.3d 1573, 1579 (Fed. Cir. 1995); In re Oelrich, 579 F.2d 86, 91 (CCPA
1978).

Claim 16
Appellant also argues that there is insufficient support for the position
that Harrold discloses a field strength that lies within 0.001 volts to 1
kilovolt per centimeter for the transporting and incorporating step that is part
of the active insertion system as recited in claim 16. Appeal Br. 19–21.
We are not persuaded by Appellant’s argument, because, as the
Examiner further explained, Harrold discloses the field strength may be
1,000 volts across a channel that is greater than 1 cm long, and discloses a
channel length of 8.5 cm, such that Harrold discloses a field strength of 118
V/cm. Ans. 10, citing Harrold ¶¶ 7, 58, 77, 91. Alternatively, the Examiner
determined that it would have been within the ability of one of ordinary skill
in the art to select a desired field when practicing electrophoresis through
routine experimentation and the claimed field strength characterizes the vast
majority of prior art electrophoresis techniques. Id. at 10–11.
Although Appellant appears to challenge the Examiner’s further
explanation that electric field strength is a result-effective variable (Reply
Br. 11), we find the Examiner’s position to be reasonably supported by the
record. See Sharei, ¶ 235 (“[s]ubsequent experiments can identify operating
parameter values (electric field strength, frequency, and operating speed)
that demonstrate an improved performance over current methods.”). As a
result, we are not persuaded the Examiner erred in rejecting claim 16.

Appeal 2020-003696
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Claim 20
Claim 20 depends from claim 19 and recites “wherein the delivery
system is self-pumping.” Appeal Br, Claims Appendix 4. Claim 19,
depends from claim 18, and recites “wherein the delivery system is
configured for continuous flow of a suspension of one or more cells or drop-
wise flow of a suspension of one or more cells.” Id.
Appellant argues the Examiner has not provided sufficient rationale to
show how Sharei discloses a “self-pumping” system. Reply Br. 7.5 We are
not persuaded by Appellant’s argument, because although Appellant
contends there is no reasoning to explain how a continuous flow or drop-
wise flow of a suspension equates to a self-pumping system (id.), Appellant
does not provide any meaningful discussion as to what constitutes a “self-
pumping” system in sufficient detail such that a difference would be readily
discernable.
The Specification only mentions “self-pumping” once in conjunction
with actuators. Spec. 13. In addition, Sharei discloses methods for driving
the cell including gravity, which is consistent with the Examiner’s
determination that Sharei’s system is capable of being used with a
continuous flow of a suspension or drop-wise flow of a suspension. Sharei
¶ 11; Final Act. 6.

5 Although Appellant makes no substantive arguments with respect to the
obviousness rejection of claim 20 in the Appeal Brief, because we are
entering a new ground of rejection, we find it prudent to address Appellant’s
arguments as presented in the Reply Brief. We do not find the Examiner’s
withdrawal of the § 112 rejections in the Answer to constitute a showing of
“good cause” as to why arguments with respect to the obviousness rejection
of claim 20 were not previously presented in the Appeal Brief. See
37 C.F.R. § 41.41(b)(2).
Appeal 2020-003696
Application 15/629,162

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DECISION SUMMARY
In summary:
Claims
Rejected
35
U.S.C.
§
Reference(s)/Basis Affirmed Reversed New
Ground
1, 3–35 103 Sharei, Ackley,
Harrold
1, 3–35 1, 3–35

TIME PERIOD FOR RESPONSE
This Decision contains a new ground of rejection pursuant to
37 C.F.R. § 41.50(b). 37 C.F.R. § 41.50(b) provides “[a] new ground of
rejection pursuant to this paragraph shall not be considered final for judicial
review.”
37 C.F.R. § 41.50(b) also provides that the Appellant, WITHIN TWO
MONTHS FROM THE DATE OF THE DECISION, must exercise one of
the following two options with respect to the new ground of rejection to
avoid termination of the appeal as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate
amendment of the claims so rejected or new Evidence relating
to the claims so rejected, or both, and have the matter
reconsidered by the examiner, in which event the proceeding
will be remanded to the examiner. . . .
(2) Request rehearing. Request that the proceeding be
reheard under § 41.52 by the Board upon the same Record. . . .

Appeal 2020-003696
Application 15/629,162

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Further guidance on responding to a new ground of rejection can be
found in the Manual of Patent Examining Procedure § 1214.01.

AFFIRMED
37 C.F.R. § 41.50(b)