Wouter Van't Hof

Patent Trials and Appeals Board

Feb 10, 2021

2020002346 (P.T.A.B. Feb. 10, 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.
12/840,420 07/21/2010 Wouter Van't Hof ATY-0005US 1111
26294 7590 02/10/2021
TAROLLI, SUNDHEIM, COVELL & TUMMINO L.L.P.
1300 EAST NINTH STREET, SUITE 1700
CLEVELAND, OH 44114
EXAMINER
PYLA, PAUL D
ART UNIT PAPER NUMBER
1653
NOTIFICATION DATE DELIVERY MODE
02/10/2021 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@tarolli.com
rkline@tarolli.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte WOUTER VAN’T HOF

Appeal 2020-002346
Application 12/840,420
Technology Center 1600
Before ERIC B. GRIMES, JOHN G. NEW, and
JAMIE T. WISZ, Administrative Patent Judges.

WISZ, Administrative Patent Judge.

DECISION ON APPEAL

Appeal 2020-002346
Application 12/840,420

2
STATEMENT OF THE CASE
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 13, 16, 18, 22–24, and 30–36. We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
CLAIMED SUBJECT MATTER
According to the instant Specification, “[t]he process of acute
inflammation is initiated by the blood vessels local to the injured tissue,
which alter to allow the exudation of plasma proteins and leukocytes into the
surrounding tissue.” Spec. ¶ 2. The Specification describes the invention as
being directed to “cell banks that can be used to provide cells for
administration to a subject, the banks comprising cells having a desired
potency with respect to downregulating expression of cellular adhesion
molecules in leukocytes and reducing leukocyte adhesion and
extravasation.” Id. at ¶ 1. Claim 13, the only independent claim, is
illustrative of the claimed subject matter and is reproduced below:
13. An in vitro method of detecting the effect of cells (I) on on
(1) leukocyte extravasation, (2) leukocyte adhesion to vascular
endothelium or to isolated endothelial cells, (3) Fut-7
expression on a leukocyte or (4) expression of CD15s on a
leukocyte, the method comprising contacting cells (I) with a
leukocyte and detecting the level of one or more of effects (1)-
(4), the cells (I) being non-embryonic, non-germ cells that
express one or more of oct4, telomerase, rex-1 and rox-1, and
can differentiate into cell types of at least two of endodermal,
ectodermal, and mesodermal germ layers.

1 We use the word “Appellant” to refer to “applicant” as defined in
37 C.F.R. § 1.42. Appellant identifies the real party in interest as ABT
Holding Company. Appeal Br. 3.
Appeal 2020-002346
Application 12/840,420

3
Appeal Br. 17 (Claims App.).
REJECTIONS
The Examiner rejected claims 13, 22–24, and 30–36 under 35 U.S.C.
§ 102(b) as being anticipated by Maziarz2 as evidenced by Korngold.3
The Examiner rejected claims 16 and 18 under 35 U.S.C. § 103(a) as
being obvious over Maziarz (as evidenced by Korngold), further in view of
Nguyen.4
ISSUES AND ANALYSIS
Rejection of claims 13, 22–24, and 30–36 under 35 U.S.C. § 102(b) as being
anticipated by Maziarz as evidenced by Korngold
The Examiner finds that Maziarz teaches “cells that are multipotent
adult progenitor cells (MAPCs), which are not embryonal stem (ES),
embryonal germ (EG) or germ cells and that they have the capacity to
differentiate into cell types of at least two of the three primitive germ layer
lineages (ectoderm, mesoderm, and endoderm), and, in many cases, into
cells of all three primitive lineages.” Final Act. 3 (citing Maziarz ¶ 40).
According to the Examiner, Maziarz teaches that the MAPCs have the
limitations recited in claim 13 as shown in the chart below:

2 Maziarz et al., US 2006/0263337 A1, published Nov. 23, 2006
(“Maziarz”).
3 Robert Korngold, et al., Role of Tumor Necrosis Factor-α in Graft-versus-
Host Disease and Graft-versus-Leukemia Responses, Biology of Blood and
Marrow Transplantation 9:292–303 (2003) (“Korngold”).
4 Xuan Duc Nguyen, et al., Flow cytometric analysis of T cell proliferation
in a mixed lymphocyte reaction with dendritic cells, Journal of
Immunological Methods, 275, 57–68 (2003) (“Nguyen”).
Appeal 2020-002346
Application 12/840,420

4

Id. 4. Overall, the Examiner finds that “Maziarz teaches the same cells
(MAPCs) that express the same markers for the same purpose as Applicant.”
Id. at 4.
With regard to the in vitro assay recited in the claims, the Examiner
finds that the assay is not defined in the claims or the Specification such that
it would provide any definitive meaning as to how the generic cell in vitro
assay that detects the claimed effects is to be interpreted. Final Act. 2–3;
Ans. 24–25. Therefore, giving the claim terms their broadest reasonable
interpretation, the Examiner finds that the method “can be any physical wet
lab assay known in the art that is able to assay any functional or physical
properties of cells related to one of the four recited properties.” Final Act 3;
Ans. 25. The Examiner further finds that the claims encompass detection
that can be a direct or an indirect effect (and are not limited to a positive,
negative, or neutral effect). Ans. 25.
The Examiner finds that Example 6 of Maziarz teaches an assay in
which ConA (a T-cell activator), responder T-cells (prepared from lymph
nodes) and MAPCs were added to microtiter plate wells (e.g., MAPCs are in
contact with lymphocytes-leukocytes). Final Act. 6 (citing Maziarz ¶¶ 405–
409). The plates were incubated for 4–5 days, pulsed with 3H-thymidine,
Appeal 2020-002346
Application 12/840,420

5
and then the cells were harvested and thymidine uptake was quantified in a
micro-plate scintillation counter (i.e., detecting an effect of the cells on
leukocytes). Id. (citing Maziarz ¶ 409). The results showed that MAPCs
inhibited proliferation of ConA-activated T-cells and the amount of
inhibition depended on the dose of MAPCs. Id. (citing Maziarz ¶ 412,
Fig. 4).
Furthermore, the Examiner finds that, in Example 7, Maziarz teaches
that the addition of increasing doses of syngeneic Lewis MAPCs and non-
matched (allogeneic) third-party Sprague-Dawley MAPCs resulted in a
significant and dose-dependent inhibition of T-cell activation, where
maximal levels of inhibition were ~80% and even at the lowest doses of
MAPCs, there was 40–50% inhibition. Id. at 7 (citing Maziarz ¶ 421).
The Examiner further finds that Korngold provides evidence that
when leukocytes are activated, they produce inflammatory cytokines, such
as TNF-α, IFN-γ, and IL-2, and these inflammatory cytokines cause
leukocyte extravasation and adhesion. Id. at 5–6 (citing Korngold 292–293).
The Examiner also finds that, “if MAPCs suppress activation of leukocytes,
the MAPCs suppress production of the inflammatory cytokines (such as
TNF-α, IFN-γ, IL-2) and therefore MAPCs suppress . . . leukocyte
extravasation or leukocyte adhesion to vascular endothelium.” Id. at 9.
The Examiner concludes:
Consequently, where Maziarz teaches an in vitro assay of
observing of the effect of MAPCs [on] leukocyte activation, that
assay is inherently a detection of the effect of MAPCs on
leukocyte extravasation or leukocyte adhesion to vascular
endothelium (MPEP § 2112 (II)).
Final Act. 9.
Appeal 2020-002346
Application 12/840,420

6
Appellant does not appear to contest that the MAPCs disclosed in
Maziarz meet the limitations of the “cells (I)” recited in the claims.
Appellant’s main argument is that “the only conclusion that can be drawn
from Maziarz is that MAPCs suppress T cell proliferation” and that “the
mechanism underlying suppression of T cell proliferation is not inherently
biologically linked” to leukocyte extravasation or adhesion “because the
factors (e.g., cytokines, signaling molecules and cellular components)
involved in T cell proliferation and leukocyte extravasation are distinct.”
Appeal Br. 11. Appellant also cites to the Declaration of Dr. Busch as
support for this argument. Id. at 12 (“[T]here is no data provided by
Maziarz that suggests identifying a factor (or factors) or a biological effect
directly related to leukocyte extravasation, adhesion to vascular endothelium
or to isolated endothelial cells, Fut-7 expression, or expression of CD15s on
a leukocyte.” Busch Decl. 3.))
Appellant asserts that Maziarz fails to teach that MAPCs inherently
affect T cell activation. Appeal Br. 13. Specifically, Appellant argues that,
in the MLR (mixed lymphocyte reaction) assay described in Maziarz,
responder T cells were stimulated with ConA and contacted with MAPCs to
assess the effect of MAPCs on the proliferation of stimulated T cells but it is
the presence of ConA in the MLR, and not the MAPCs, that affects T cell
activation because ConA is a known T cell mitogen. Id. Appellant
concludes that the Examiner incorrectly assumes that there is an inherent
association between the ability of MAPCs to suppress T cell activation and
leukocyte extravasation or adhesion because it is not the MAPCs that are
affecting T cell activation. Id.
Appeal 2020-002346
Application 12/840,420

7
With regard to the statement in Example 7 of Maziarz that MAPCs
inhibited T-cell activation, Appellant responds by contending that it is not
clear what the term “T-cell activation” means in this context at the time of
the claimed invention and, furthermore, the Declaration of Dr. Busch
indicates that the skilled artisan would have only understood from Maziarz
that MAPCs suppress T cell proliferation. Reply 2.
Appellant also asserts that Korngold does not remedy the deficiencies
of Maziarz because it does not say anything about the action of MAPCs in
inflammation. Appeal Br. 13.
We find that the Examiner has the better position. We begin with
claim interpretation because before a claim is properly interpreted, its scope
cannot be compared to the prior art. “[D]uring examination proceedings,
claims are given their broadest reasonable interpretation consistent with the
specification.” In re Hyatt, 211 F.3d 1367, 1372 (Fed. Cir. 2000). We agree
with the Examiner that, under the broadest reasonable interpretation, the
limitation of an “in vitro method of detecting the effect of cells” can be any
physical or wet lab assay known in the art that is able to assay one of the
four recited properties. We also agree that this limitation encompasses
detection that is direct or indirect and the effect can be positive, negative, or
neutral. Therefore, the assays disclosed in Maziarz, which detect the effect
of MAPCs on T-cell proliferation and/or activation, indirectly detect the
effect of MAPCs on leukocyte extravasation and adhesion as evidenced by
Korngold. See Korngold 292–293.
Appellant argues that the Declaration of Dr. Busch establishes that the
skilled artisan would have understood from Maziarz only that MAPCs
suppress T cell proliferation (Appeal Br. 12, Reply 2); however, we do not
Appeal 2020-002346
Application 12/840,420

8
find this contention to be supported by the Busch Declaration. The Busch
Declaration does not include such a broad statement nor does it specifically
address the results of Example 7 from Maziarz, which found that addition of
increasing doses of syngeneic Lewis MAPCs and non-matched (allogenic)
MAPCs “resulted in a significant and dose-dependent inhibition of T-cell
activation.” Maziarz ¶ 421 (emphasis added). As discussed in Korngold, T-
cell activation leads to a cascade of cytokines, which ultimately leads to
leukocyte extravasation and leukocyte adhesion on vascular endothelium.
Korngold 292–293.
Furthermore, we agree with the Examiner that Maziarz teaches that
MAPCs were known to have pleiotropic functions, not limited to a narrow
subset of functions. See, e.g., Maziarz ¶¶ 205–210. Therefore, by
contacting MAPCs with a leukocyte, as disclosed in Maziarz (and as
claimed), and observing the effect on activation, one is inherently detecting
in vitro the effect of the cells on, e.g., leukocyte extravasation and/or
leukocyte adhesion.
Therefore, we affirm the Examiner’s rejection of claim 13 as
anticipated by Maziarz as evidenced by Korngold. Claims 22–24 and 30–36
are not argued separately apart from the independent claim, and, therefore,
fall with claim 13. See 37 C.F.R. § 41.37(c)(1)(iv).
Rejection of claims 16 and 18 under 35 U.S.C. § 103(a) as being obvious
over Maziarz (as evidenced by Korngold), further in view of Nguyen
The Examiner’s findings with respect to Maziarz in view of Korngold
are discussed supra. With regard to claims 16 and 18, the Examiner
concedes that Maziarz (as evidenced by Korngold) does not teach that the
lymphocytes are CD34+ or CD8+ (claim 16) or CD4+ or CD8+ (claim 18),
Appeal 2020-002346
Application 12/840,420

9
but that this deficiency is cured by Nguyen. Final Act. 24–25 (citing
Nguyen, Abstract, 59). The Examiner finds that Nguyen teaches an assay in
which “CD3+/CD4+ or CD3+/CD8+ antibodies were used separately to
distinguish [T helper] cells or [cytotoxic T lymphocytes] from other cell
populations.” Id. at 25 (citing Nguyen 59). The Examiner concludes that
“[a] person of ordinary skill in the art would have been motivated to utilize a
subset of T-cells within a MLR assay . . . using the techniques in Nguyen so
that all non T-cell populations are depleted for more accurate cell
proliferation assays.” Id.
Appellant asserts that claims 16 and 18 are patentable for at least the
reasons that claim 13 is patentable over Maziarz (as evidenced by
Korngold). Appeal Br. 15.
For the reasons discussed supra with respect to Maziarz and
Korngold, we affirm the Examiner’s obviousness rejection of claims 16 and
18.
CONCLUSION
For the reasons described herein and those already of record, we
affirm the Examiner’s rejection of claims 13, 16, 18, 22–24, and 30–36.

DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
13, 22–24,
30–36
102(b) Maziarz (as
evidenced by
Korngold)
13, 22–24,
30–36

Appeal 2020-002346
Application 12/840,420

10
16, 18 103(a) Maziarz,
Korngold, Nguyen
16, 18
Overall
Outcome
13, 16, 18,
22–24, 30–
36

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