Ex Parte Hu et al

Patent Trial and Appeal Board

Sep 11, 2018

13889015 (P.T.A.B. Sep. 11, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
13/889,015 05/07/2013 Wei-Shou Hu
26294 7590 09/13/2018
TAROLLI, SUNDHEIM, COVELL & TUMMINO L.L.P.
1300EASTNINTH STREET, SUITE 1700
CLEVELAND, OH 44114
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
ATY-OOOlUS-CON 2815
EXAMINER
NGUYEN, QUANG
ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
09/13/2018 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):
rkline@tarolli.com
docketing@tarolli.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte WEI-SHOU HU, KARTIK SUBRAMANIAN,
and CATHERINE M. VERFAILLIE
Appeal2017-009588 1
Application 13/889,015
Technology Center 1600
Before DEMETRA J. MILLS, FRANCISCO C. PRATS, and
MICHAEL J. FITZPATRICK, Administrative Patent Judges.
PRATS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134(a) involves claims to a method of
disaggregating cell aggregates composed of non-embryonic cells capable of
differentiation, and administering cells resulting from the disaggregating
step to a subject. The Examiner rejected the claims for obviousness.
We have jurisdiction under 35 U.S.C. § 6(b)(l).
We REVERSE.
1 Appellants identify the Regents of the University of Minnesota and
Katholieke Universiteit Leuven as the real parties in interest. Appeal Br. 3.
Appeal2017-009588
Application 13/889,015
STATEMENT OF THE CASE
The sole rejection before us for review is the Examiner's rejection of
claims 120-131 under 35 U.S.C. § I03(a) for obviousness over Mays2 and
Khurgel. 3 Final Act. 3-9.
Claim 120, the only independent claim on appeal, reads as follows
(indentation and paragraph separation added):
120. A method comprising
(1) disaggregating cells in an aggregate, the
aggregate having been formed by exposing cells that are
not embryonic stem cells, embryonic germ cells, or germ
cells and can differentiate into cell types of at least two of
the endodermal, ectodermal, mesodermal embryonic
lineages, to conditions under which the cells aggregate,
wherein the conditions comprise an oxygen concentration
of about 1-10%, wherein the aggregate from which the
disaggregated cells are derived does not originate from
two-dimensional culture and
(2) administering to a subject, in an amount and for
a time sufficient to achieve a desired effect in the subject,
the cells derived from disaggregating the aggregate of
cells.
Appeal Br. 29 (indentation and paragraph separation added).
DISCUSSION
The Examiner's Prima Facie Case
The Examiner cited Mays as disclosing a method in which cells
encompassed by claim 120, human MAPCs (multipotent adult progenitor
cells), were cultured and maintained either in suspension or attached to a
2 Mays, US 2008/0194024 Al (published Aug. 14, 2008).
3 Khurgel et al., US 2009/0304643 Al (published Dec. 10, 2009, hereinafter
"Khurgel").
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solid support in the presence of reduced oxygen concentrations encompassed
by claim 120. Final Act. 3--4.
As to claim 120's step of administering cells to a subject, the
Examiner cited Mays as disclosing that its cultured cells could be used "to
treat essentially any injury or disease" by transplantation into the subject.
Id. at 5 (citing Mays ,r 138) (emphasis omitted).
The Examiner found that Mays differs from Appellants' claim 120 in
that "Mays does not teach specifically a method comprising the step of
disaggregating cells in an aggregate, and administering the resulting cells to
a subject in an amount or for a time sufficient to achieve a desired effect and
wherein the aggregate does not originate from two-dimensional culture." Id.
at 6 ( emphasis omitted).
The Examiner cited Khurgel as evidence that an ordinary artisan
would have considered Appellants' claimed process obvious, despite the
differences between Mays' s process and the claimed process. Id. at 6-9.
Specifically, the Examiner cited Khurgel as disclosing a process in
which adipose-derived stem cells (AS Cs) were cultured in a manner that
produced three dimensional cell aggregates, also termed "Self-Organizing
Mesenchymal Blastemas or SOM-Bs." Id. at 6 ( emphasis omitted). The
Examiner also cited Khurgel as disclosing that its stem cell aggregates could
be administered in combination with cells dissociated from the aggregates,
and that enzymes such as collagenase and trypsin could be used to dissociate
cellular components of the aggregates. Id.
The Examiner further noted Khurgel' s disclosure that its stem cell
aggregates possessed a number of advantageous properties, including a
reduced tendency toward cell death ( anoikis ), capacity to withstand
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conditions lethal to cells in monolayer culture, capacity to survive as a three-
dimensional culture upon transplantation, and potential capacity for dynamic
interaction with an injured tissue milieu. Id. at 7 ( citing Khurgel ,r,r 174--
178).
Based on the references' combined teachings, the Examiner
concluded that an ordinary artisan would have considered it obvious
to modify the teachings of Mays by also preparing
non-embryonic cells that can form cell types of two or more
embryonic lineages such as human MAPCs in a suspension
culture to generate 3-dimensional cell aggregates and using
the aggregates of various sizes and/or dissociated cells
derived from the aggregates for transplantation in a subject
to treat diseases amendable to cell therapy in light of the
teachings of Khurgel[.]
Id. at 7-8.
The Examiner reasoned:
Id. at 8.
An ordinary skilled artisan would have been motivated
to carry out the above modifications because Khurgel et al
already taught successfully a preparation of 3-dimensional,
multipotent mesenchymal stem cell ( e.g., Adipose derived
stromal cells) aggregates ( or Self-Organizing Mesenchymal
Blastemas or SOM-Bs) in suspension culture and
administration/use of combinations of SOM-Bs with
dissociated cell suspensions of other cell types including
dissociated cells derived from SOM-Bs in suspension to
treat a subject in need thereof.
As additional motivation for modifying Mays' s process to use
Khurgel' s culturing methods, the Examiner cited Khurgel' s disclosure
regarding the advantages of stem cell aggregates, noted above. Id.
As to motivation, the Examiner additionally cited Mays's disclosure
that human MAPCs could be maintained in a suspension culture, as well as
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Mays's examples showing MAPCs being maintained at high density, with
some cultures being induced to contain large dense MAPC clusters under
certain circumstances. Id. at 8-9.
Analysis
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he [E]xaminer bears the initial burden ... of
presenting a prim a facie case of unpatentability.
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of
the record, by a preponderance of evidence with due
consideration to persuasiveness of argument.
In KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), although the
Supreme Court emphasized "an expansive and flexible approach" when
analyzing the issue of obviousness, the Court also reaffirmed the importance
of determining "whether there was an apparent reason to combine the known
elements in the fashion claimed by the patent at issue." KSR, 550 U.S. at
415, 418.
Thus, even post-KSR, "[ o ]bviousness requires more than a mere
showing that the prior art includes separate references covering each
separate limitation in a claim under examination." Unigene Laboratories,
Inc. v. Apotex, Inc., 655 F.3d 1352, 1360 (Fed. Cir. 2011).
Instead, "[i]n determining whether obviousness is established by
combining the teachings of the prior art, the test is what the combined
teachings of the references would have suggested to those of ordinary skill
in the art." In re GPAC Inc., 57 F.3d 1573, 1581 (Fed. Cir. 1995)
( quotations omitted).
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In the present appeal, having carefully considered all of the arguments
and evidence advanced by Appellants and the Examiner, Appellants
persuade us that the preponderance of the evidence does not support the
Examiner's conclusion of obviousness as to claim 120. In particular,
Appellants persuade us that the Examiner has not shown, by a
preponderance of the evidence, that the cited combination of references
would have suggested disaggregating a three-dimensional aggregate culture
of Mays' s cells prepared by the culturing techniques taught in Khurgel.
We acknowledge, as the Examiner found, and Appellants do not
dispute, that Mays describes culturing cells encompassed by Appellants'
claim 120. See, e.g., Mays ,r 3 (describing "the culture of non-embryonic
cells that can differentiate into more than one embryonic lineage, at high
density in the presence of at least one GSK3 inhibitor, such as 6-
bromoindirubin-3 '-oxime (also known as BIO)").
As the Examiner found, Mays discloses that its cells can form high
density clusters under certain culture conditions. Id. ,r 152 ("Surprisingly,
when MAPCs were maintained at high density (ESC densities), MAPCs
treated with 1 or 2 microM BIO contained large dense MAPC clusters that
expressed very high levels of Oct-4, B-catenin and E-cadherin protein.").
As to the requirement in Appellants' claim 120 of preparing an
aggregate of cells, Khurgel discloses, as the Examiner found, "multiple ways
to culture human adipose-derived stem/stromal cells (ASCs) in suspension
culture such that they ... form and organize into 3-dimensional multicellular
aggregates ( which can also be described as spheres, clusters, blastemas,
networks, etc.)." Khurgel ,r 15.
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As Appellants contend, however (see Appeal Br. 19-23), rather than
suggesting that its cell aggregates should be disaggregated before being
administered to a subject as recited in Appellants' claim 120, Khurgel
teaches that its cell aggregates should be administered in aggregated form.
See Khurgel ,r 173 ("The data described herein suggests that ASC blastemas
... may better modulate tissue repair than single cell suspensions. Several
real or potential advantages may be offered by administering ASCs
prefabricated as 3-D niches (blastemas) as compared to more traditional
single cell suspensions.").
One advantage listed by Khurgel to explain why its cell aggregates
should be administered to a subject in an aggregated form, rather than
disaggregated cell suspensions, includes the fact that the aggregated cells are
less prone to programmed cell death ("anoikis"), which "may play a critical
role in the low delivery and engraftment efficiency associated with various
methods of cell delivery." Id. ,r 174. Additional advantages to
administering the cultured cells in aggregated form included the aggregated
cells' capacity to survive as a three-dimensional culture upon
transplantation, and potential capacity for dynamic interaction with an
injured tissue milieu. Id. ,r,r 177-178.
Thus, the precise teachings relied upon by the Examiner as suggesting
the preparation of Mays' s cells in the form of an aggregate as taught by
Khurgel (see Final Act. 7-8; Ans. 6-7) suggest that the cell aggregate should
not be disaggregated, because disaggregation would eliminate the
advantages of using the aggregated form as a therapeutic agent. The
Examiner does not persuade us, therefore, that Khurgel, even when
combined with Mays' s teaching that its cells form high density clusters in
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culture, would have suggested the disaggregation step recited in Appellants'
claim 12 0.
We acknowledge, as the Examiner contends (see Ans. 5-6), that
Khurgel also discloses "cell based therapeutics and regenerative strategies
for damaged, injured, destroyed or aging tissues/organs" that involve
"administration/use of combinations of SOM-Bs [ cell aggregates] with ...
dissociated cells derived from adherent cells and/or derived from SOM-Bs in
suspension." Khurgel ,r 169.
It is well settled, however, that when evaluating claims for
obviousness, "the prior art as a whole must be considered. The teachings are
to be viewed as they would have been viewed by one of ordinary skill." In
re Hedges, 783 F.2d 1038, 1041 (Fed. Cir. 1986). Accordingly,
[i]t is impermissible within the framework of section 103
to pick and choose from any one reference only so much
of it as will support a given position, to the exclusion of
other parts necessary to the full appreciation of what such
reference fairly suggests to one of ordinary skill in the art.
Id. (citing In re Wesslau, 353 F.2d 238, 241 (CCPA 1965)).
Here, the Examiner does not identify, nor do we discern, any teaching
in Khurgel, or for that matter in Mays, specifically suggesting a process in
which aggregates are prepared and then disaggregated, as required by
Appellants' claim 120. To the contrary, given Khurgel's teachings
discussed above as to the advantages of administering the cells in aggregated
form, we are not persuaded that a skilled artisan would have been motivated
to disaggregate the aggregated culture after having prepared it, even given
Khurgel' s disclosure that dissociated cells may be present in the aggregated
cell preparation. See Khurgel ,r 169.
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SUMMARY
In sum, for the reasons discussed, Appellants persuade us that the
Examiner has not shown by a preponderance of the evidence that the process
recited in Appellants' claim 120 would have been obvious to an ordinary
artisan in view of Mays and Khurgel. We, therefore, reverse the Examiner's
rejection of claim 120, and its dependent claims, over Mays and Khurgel.
DECISION
For the reasons discussed, we reverse the Examiner's rejection of
claims 120-131 under 35 U.S.C. § 103(a) for obviousness over Mays and
Khurgel.
REVERSED
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