Manuel Marquez et al.

Patent Trials and Appeals Board

Oct 1, 2021

2020000779 (P.T.A.B. Oct. 1, 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.
15/606,042 05/26/2017 Manuel Marquez marquez042 7732
24221 7590 10/01/2021
LOUIS VENTRE, JR
2483 OAKTON HILLS DRIVE
OAKTON, VA 22124-1530
EXAMINER
WILSON, MICHAEL C
ART UNIT PAPER NUMBER
1632
NOTIFICATION DATE DELIVERY MODE
10/01/2021 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):
lventre@lventre.com
ventre.louis@verizon.net
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MANUEL MARQUEZ and SAMANTHA M. MARQUEZ
Appeal 2020-000779
Application 15/606,042
Technology Center 1600
Before JEFFREY N. FREDMAN, TAWEN CHANG, and RYAN H. FLAX,
Administrative Patent Judges.
CHANG, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 1–10. We have jurisdiction under
35 U.S.C. § 6(b).
We AFFIRM.

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 the named
inventors, Manuel Marquez and Samantha Marquez. Appeal Br. 3.
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STATEMENT OF THE CASE
According to the Specification, the invention relates to “a method of
making an artificial gland of micro-scale with a cellular membrane and
bioreactor reservoir, wherein the artificial gland is useful for biological
tissue and organ repair and replacement and stem cell engineering and
biotechnology applications.” Spec. ¶ 2.
CLAIMED SUBJECT MATTER
The claims are directed to a method of making a micro-capsule by
taxis. Claim 1 is illustrative:
1. A method of making a micro-capsule by taxis, the micro-
capsule comprising a continuous membrane of living cells, the
continuous membrane defining an enclosed volume, the
enclosed volume comprising a reservoir serving as a bioreactor,
the method comprising the steps of:
producing a monodisperse multiple emulsion, the
monodisperse multiple emulsion comprising:
a first fluid serving as a host environment, the first fluid
being water plus any additive compatible with the
living cells;
a second fluid confined within the host environment, the
second fluid being immiscible in the first fluid;
a third fluid within the second fluid, the third fluid being
immiscible in the second fluid such that there is an
interface between the second fluid and the third fluid,
the third fluid comprising a plurality of living cells
dispersed therein, said living cells capable of metabolic
activity; and,
an agent capable of affecting the metabolic activity of the
living cells, the agent present within the second fluid at a
higher concentration than in the third fluid;
waiting until the living cells migrate to the interface between
the second fluid and the third fluid to form the
continuous membrane around the third fluid; and,
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removing the first fluid and the second fluid from the
monodisperse multiple emulsion to produce the micro-
capsule.
Appeal Br. 169–170 (Claims App.).

REJECTION(S)
A. Claims 1–10 are rejected under 35 U.S.C. § 112 (pre-AIA), first
paragraph, as failing to comply with the enablement requirement.
Ans. 3.
B. Claims 1–10 are rejected under 35 U.S.C. § 112 (pre-AIA), first
paragraph, as failing to comply with the written description
requirement. Ans. 39.
C. Claims 1–10 are rejected under 35 U.S.C. § 112 (pre-AIA), second
paragraph, as being indefinite for failing to particularly point out and
distinctly claim the subject matter which the applicant regards as the
invention. Ans. 48.

OPINION
A. Lack of enablement (claim 1–10)
1. Issue
The Examiner finds that the Specification does not enable the claimed
invention on six grounds. Specifically, the Examiner finds that the
Specification does not enable
A) using the method to make microcapsules capable of use in
vivo, B) using the method to make microcapsules for 3D tissue
culture, C) the combination of liquids, cells and agents required
to perform the method such that microcapsules with a
continuous membrane of living cells around a 3rd fluid that is
bioreactor are obtained, D) for using any agent in the methods
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claimed, E) obtaining any multiple emulsion other than a
double emulsion, and F) how to perform the final step of
separating other than pouring the multiple emulsion on glass.
Ans. 51.
Appellant contends that “[t]he claims do not contain anything not
explained in the description, or that is not well known in the prior art for the
field.” Appeal Br. ¶ 59.
Appellant does not separately argue the claims. We therefore focus
our analysis on claim 1 as representative. The issue with respect to this
rejection is whether a preponderance of the evidence of record supports the
Examiner’s conclusion that the Specification does not enable the full scope
of the invention of claim 1.
2. Analysis
To satisfy the enablement requirement, “an applicant must describe
the manner of making and using the invention ‘in such full, clear, concise,
and exact terms as to enable any person skilled in the art . . . to make and use
the same,’” without undue experimentation. Rasmusson v. SmithKline
Beecham Corp., 413 F.3d 1318, 1323 (Fed. Cir. 2005). Moreover, “the
scope of the claims must bear a reasonable correlation to the scope of
enablement provided by the specification to persons of ordinary skill in the
art.” In re Fisher, 427 F.2d 833, 839 (CCPA 1970). Finally, to determine
whether the disclosure would require undue experimentation, we consider
the following factors:
(1) the quantity of experimentation necessary, (2) the amount of
direction or guidance presented, (3) the presence or absence of
working examples, (4) the nature of the invention, (5) the state
of the prior art, (6) the relative skill of those in the art, (7) the
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predictability or unpredictability of the art, and (8) the breadth
of the claims.
In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988).
Applying these standards of law to the instant case, we agree with the
Examiner that the Specification does not enable the full scope of claim 1, at
least because it does not enable a skilled artisan to practice the claimed
method of making a micro-capsule by taxis using the full scope of the fluids,
living cells, and “agent[s] capable of affecting the metabolic activity of the
living cells” (i.e., rejection grounds C & D) encompassed by the claim.

Claim Breadth
As set forth above, claim 1 is directed to “[a] method of making a
micro-capsule by taxis,” comprising a step of producing a monodisperse
multiple emulsion comprising a first fluid, a second fluid, and a third fluid.
Appeal Br. 169 (Claims App.). Claim 1 requires the second and third fluids
to comprise, respectively, “an agent capable of affecting the metabolic
activity of the living cells . . . at a higher concentration than in the third
fluid” and “a plurality of living cells,” such that “the living cells migrate to
the interface between the second fluid and the third fluid to form [a]
continuous membrane around the third fluid.” Id. at 169–170.
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To facilitate our analysis, Figure 1 from the Specification is
reproduced below:

Spec. Fig. 1. Figure 1 “illustrates a first preferred embodiment of the
method of the invention.” Id. ¶ 23.
Figure 1 depicts a monodisperse multiple emulsion (110) that includes
a first fluid (115), which serves as a host environment, a second fluid (120)
immiscible in the first fluid, a third fluid (125) immiscible in the second
fluid, and an interface (130) between the second fluid (120) and the third
fluid (125).2 Spec. ¶ 23. The Specification states that Figure 1 depicts
the third fluid (125) comprising a plurality of living cells
(135) dispersed therein, said living cells (135) capable of
metabolic activity; and, an agent (140) (figuratively
represented by the wide shaded arrows in FIG.[]1)
capable of affecting the metabolic activity of the living
cells, the agent present within the second fluid (120) at a
higher concentration than in the third fluid (125). The

2 The Specification states that, for Figure 1, the emulsion is a water/oil/water
emulsion. Spec. ¶ 14.
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arrow (150) indicates the direction of movement of the
living cells (135) by taxis.
Id. As further described in the Specification, Figure 1 also depicts
a step of waiting until the living cells (135) migrate to the
interface (130) between the second fluid (120) and the
third fluid (125) to form the continuous membrane (145)
(represented by the living cells (135) approximately
between the dashed circles in the sectional view of
FIG.[]1) around the third fluid (125).
Id. ¶ 24.
We find claim 1 to be extremely broad. Although the first fluid is
limited to “water plus any additive compatible with the living cells,” the
second and third fluids encompass any liquid or gas immiscible in,
respectively, the first and second fluid. Appeal Br. 169; Spec. ¶ 70 (stating
that the term “fluid” for purposes of the invention “may include a gas or a
liquid”); see also ’158 application3 ¶ 48 (stating that “[t]he contents of the
bio-reactor preferably include a substance comprising a fluid in the form of a
gas, liquid, gel, or a combination of these”); Appeal Br. ¶ 70 (asserting that
the second fluid encompasses, e.g., corn syrup and honey), ¶ 72 (asserting
that the second liquid may be a gas), ¶¶ 76–77 (stating that fluids include
liquids, gases, free flowing solid particles, viscoelastic fluids, and the like)
(quoting Link4 ¶ 77); ¶¶ 406–414 (reiterating that a fluid may be a gas).
Claim 1 similarly encompasses using a broad range of cells and
biological units to make the micro-capsule recited in the claim — i.e., living

3 US Application 12/726,158, filed March 17, 2010. The instant application
is a continuation-in-part of the ’158 application and incorporates it by
reference. Spec. ¶ 1.
4 Link et al., US 2006/0163385 A1, published July 27, 2006.
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cells capable of metabolic activity. See, e.g., Spec. ¶ 3 (stating that “[t]he
term ‘living cells’ is intended to broadly encompass biological units and
cells as defined [in] the parent application,” including e.g., fungi, algae,
fibroblasts, yeast, and bacteria); ’158 application ¶ 55 (reciting list of over
eighty example cell types), ¶ 58 (describing biological units as including
“fungi, algae, spores, pollen, yeast, bacteria, and viruses”); Appeal Br. ¶ 96
(asserting that “living cells” also encompasses “cells in stasis”).
Finally, claim 1 encompasses the use of a broad range of agents —
i.e., any agent “capable of affecting the metabolic activity of the living
cells.” The Specification notes, for example, that agents “capable of
affecting the metabolic activity of the living cells” encompass oxygen and
carbon dioxide, as well as “nitrogen oxide; sugar; phosphates, nitrates,
sulphates, and potassium salts; cyclic adenosine monophosphate (cAMP);
inositon phospholipid (mPIP3); actin; histamine; serotonin (5HT); [platelet]
acting factors (PAF); arachidonic acid metabolites; diacykglyseril (IP3);
leukotine B4; lipoxins; prostaglandins; cytotaxin; f-met-leu-phe tripeptide;
cytokines; kinins, cytotaxins; anaphylatoxin peptide (C5a); aspartic acid
(ASP); serine (SER); and, chemo-attractants.” Spec. ¶ 34.
Appellant does not appear to dispute that the claims are broad, arguing
only that the breadth of the claim is “not unusual for a breakthrough
invention long sought in the field.” Appeal Br. ¶ 253.
Nascent technology, however, must be enabled with a “specific
and useful teaching.” The law requires an enabling disclosure
for nascent technology because a person of ordinary skill in the
art has little or no knowledge independent from the patentee’s
[or applicant’s] instruction. Thus, the public’s end of the
bargain struck by the patent system is a full enabling disclosure
of the claimed technology.
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Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254 (Fed. Cir. 2004)
(citations omitted). The breadth of the claim favors a finding that it lacks
enablement because it is more likely that undue experimentation would be
needed to practice the full scope of the claimed invention.

Nature of the Invention / Prior Art / Predictability
The invention relates to creation of structures comprising living cells.
Prior art references cited by the Examiner and Appellant demonstrate that
the field of biomaterials is highly complex and unpredictable, and that the
creation of structures using live cells was not routine at the time of
invention. “In cases involving unpredictable factors, such as most chemical
reactions and physiological activity, the scope of enablement obviously
varies inversely with the degree of unpredictability of the factors involved.”
In re Fisher, 427 F.2d 833, 839 (CCPA 1970).
For example, Gupta,5 published in 2008 and disclosing a method of
co-assembling live cells and microparticles into membranes using
electrically controlled chips, teaches that “the precise and controllable
fabrication of biomaterials from live cells still remains one of the most
promising, yet largely unrealized applications of colloidal assembly.” Gupta
726, left column (emphasis added). Gupta explains that one of the problems
in assembling cells into freely suspended and oriented structures, such as
chains or membranes, is that “live cells collected and arranged on their own

5 Shalini Gupta et al., On-chip Electric Field Driven Assembly of
Biocomposites from Live Cells and Functionalized Particles, 4 SOFT
MATTER 726 (2008).
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typically do not possess the mechanical cohesiveness required to form
materials and device components.” Id.
Similarly, Kress,6 cited by the Examiner, suggests that predicting the
movement of cells based on chemotaxis is not straightforward. For instance,
Kress teaches that, although “mathematical models of eukaryotic chemotaxis
have matured and incorporated various biochemical reaction-diffusion
schemes,” “[d]ifferent models describe qualitatively different modes of
gradient sensing and show qualitatively different spatial and temporal
dynamics.” Kress 905, left column. Kress teaches that to test predictions
from competing models in experiments or to investigate chemotaxis requires
“control over chemical microenvironments of cells.” Id. at Abstr. Kress
further teaches that prokaryotes and eukaryotes have different mechanisms
of chemotaxis. Id. at 905, left column (endnote omitted).
Finally, Gundabala7 teaches that cell viability is a factor that should
be considered when working with cell assemblies. Gundabala Abstract
(suggesting “surface encapsulation technique can potentially overcome cell
viability issues usually associated with bulk cell encapsulation techniques”).

6 Holger Kress et al., Cell Stimulation With Optically Manipulated
Microsources, 6 NATURE METHODS 905 (2009).
7 V R Gundabala et al., Celloidosomes via Glass-Based Microfluidics, 46 J.
PHYSICS D: APPLIED PHYSICS 114006 (2013). We note that Gundabala is
published in 2013, which is after the priority date of April 2, 2009 claimed
by Appellant in the Appeal Brief. Appeal Br. ¶ 127. Assuming for
argument’s sake that the priority date is in fact April 2009, Gundabala
nevertheless shows that maintaining cell viability when working with live
cells remained a significant issue several years after Appellant’s claimed
priority date, which provides evidence of the state of the art at the time of
the invention.
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Appellant cites various prior art articles to show that individual
portions of claim 1 (e.g., monodisperse multiple emulsions and use of living
cells in biocompatible fluids in, e.g., microfluidics) are known in the art.
See, e.g., Appeal Br. ¶¶ 182–184, 245 (citing Kenis8 and Link as disclosing
streams of fluids within microchannels and creating micro-capsules at the
interface of two fluid flows using a microchannel); id. ¶ 179 (citing Link for
showing “biocompatible fluids”); id. ¶¶ 185, 189, 191–194, 202–205, 263–
264, & 347–363 (citing the alleged working examples in the ’158
application,9 together with Link, Subramaniam,10 Zhao,11 Shah,12 and
references cited in Chang,13 for use of cells in micro-fluidic devices and
chemical reactions occurring at the interface of the fluids; cell deposition on
surfaces; and encapsulation of cells).
Appellant contends the above prior art teachings incorporated by
reference into the present application “reduce uncertainty to a minimum.”
Appeal Br. ¶ 195.14 Appellant contends that “because of the use of a known

8 Paul J. A. Kenis et al., Microfabrication Inside Capillaries Using
Multiphase Laminar Flow Patterning, 285 SCIENCE 83 (1999).
9 As discussed below, the figures in the ’158 application are not in fact
working examples of the claimed invention.
10 Anand Bala Subramanian et al., Controlled Assembly of Jammed
Colloidal Shells on Fluid Droplets, 4 NATURE MATERIALS 553 (2005).
11 L.B. Zhao et al., Generation of Janus Alginate Hydrogel Particles with
Magnetic Anisotropy for Cell Encapsulation, 9 LAP CHIP 2981 (2009).
12 Rhutesh K. Shah et al., Designer Emulsions Using Microfluids, 11
MATERIALS TODAY 19 (2008).
13 Ya-Wen Chang et al., Uniform Yeast Cell Assembly via Microfluidics, 6
BIOMICROFLUICS 024118 (2012).
14 Appellant cites to paragraph 5 of the Specification as showing that the
references discussed were incorporated by reference. However, paragraph 5
only incorporates by reference Liang-Yin Chu et al., Controllable
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micro-fluidic technology and known biotechnology of cellular compatible
fluids, similarly applied to the steps of the present invention using well
established practices, it would be evident that any person of skill in the art of
micro-fluidics and biotechnology would readily understand and be able to
use the disclosed method.” Id. ¶ 190.
We are not persuaded. The rejection is based on the failure to enable
the full scope of the method of “making a micro-capsule by taxis” (rather
than microfluidics or other techniques), through the use of differential
concentration in fluids of “an agent capable of affecting the metabolic
activity of the living cells” and the “living cells migrat[ing] to the interface
between [two fluids] to form [a] continuous membrane.” None of the
references cited by Appellant provides any guidance as to what combination
of second and third fluids, type of living cells, and type of agent capable of
affecting metabolic activity would result in successfully practicing the
method of making a micro-capsule by taxis as claimed.15 Indeed, prior art
references such as Gupta suggests that applying potentially related
technology, such as colloidal assembly, to the fabrication of biomaterials

Monodisperse Multiple Emulsions, 46 ANGEWANDTE CHEMIE INT’L EDITION
8970 (2007). We thus address Appellant’s arguments here as they relate to
the state of the art. To the extent these references have been incorporated by
reference into the present application, our analysis does not change.
15 Chang is cited by Appellant as teaching an example of micro-capsules
called yeastosomes. See Appeal Br. ¶ 160. It is not clear that even this
reference, which is published after the priority date Appellant claims,
provides a successful example of making a micro-capsule through the
claimed method (i.e., via taxis and differential concentration of an agent
capable of affecting metabolic activity), relying instead on electrostatic
attractions between a template and cells via surface charging. Chang Abstr.
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from live cells, such as proposed by the claim, remained unpredictable and
non-routine at the time of the invention.
Accordingly, we find that the factors regarding the nature of the
invention, the state of the art, and the predictability or unpredictability of the
art also favor a finding that the claims are not enabled because it is likely
that undue experimentation would be needed to practice the full scope of the
claimed invention.

Direction or Guidance Presented / Working Examples
The Specification does not provide any working examples of the
claimed method.
Appellant contends that Example 1 of the Specification, and Figures 7
and 8 of the ’158 application, are working examples. Appeal Br. ¶¶ 166–
172, 207–214, 262. However, as noted in our prior decision in Appeal No.
2015-005900, Example 1 is described in the present tense, except for the
statement that “[e]xamples of bacteria actually used are pseudomonas
aeruginosa, b. subtilis and p. aeruginos.” Spec. ¶ 29 (emphasis added).
Neither has Appellant provided any evidence, rather than attorney argument,
that the work in Example 1 was actually performed. Johnston v. IVAC
Corp., 885 F.2d 1574, 1581 (Fed. Cir. 1989) (“Attorneys’ argument is no
substitute for evidence.”).16
Likewise, Figures 7 and 8 of the ’158 application are not working
examples of the claimed invention, because, contrary to Appellant’s

16 We note that, even if Example 1 were a working example, it would not
enable the full scope of the invention of claim 1, given the breadth of the
claim discussed above and the consideration of the other Wands factors.
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contention, they do not disclose a method of “creation via taxis of a cellular
membrane surrounding a core.” Appeal Br. ¶ 166. Instead, both Figures 7
and 8 of the ’158 application describe a method of making an artificial gland
wherein cell migration occurs through controlled gelation, ’158 application
¶¶ 64, 69, 77–79, 86. Micrograph 76 of Figure 7 also shows “an artificial
gland having a cellular membrane [of red blood cells (761)] that coats a
volvox algae colony (762) within the reservoir,” wherein the artificial gland
appears to be formed by collision of the cells and volvox algae in a
microchannel rather than taxis. ’158 application ¶¶ 142, 146.
The Specification also includes minimal guidance directed to the
combination of second fluid, third fluid, living cells, and agents capable of
affecting their metabolic activity that, when used in the claimed method,
would result in the claimed steps of “the living cell migrating to the interface
between the second fluid and the third fluid to form the continuous
membrane around the third fluid” and the production of the micro-capsule.
For example, the Specification provides only bacteria/oxygen and
algae/carbon dioxide, in emulsions comprising water and oil, as example
combinations of cells, “agents capable of affecting . . . metabolic activity,”
and fluids that may be used in the claimed methods.
Appellant contends that the Specification “explicitly spells out a list of
typical agents capable of affecting the metabolic activity of the living cells”
and “makes clear that it is not any specific combination or protocol that is
important, only that there be differential concentration of the agent in the
different fluids within the monodisperse multiple emulsion.” Appeal Br.
¶¶ 149–150; see also id. ¶¶ 226–284. Appellant also cites to paragraph 5 of
the Specification, which incorporates the Chu paper by reference,
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contending that Chu “describ[es] protocols for forming a monodisperse
multiple emulsion [using capillary microfluidics], eliminating all undue
experimentation.” Id. ¶¶ 157, 159, 177–178, 196–197. Appellant contends
that “[t]he protocols involving specific quantities of agents are disclosed in
Example 1 . . . and Example 2.” Id. ¶¶ 155, 159.
We are not persuaded. As discussed above, the rejection is based on
lack of enablement over the full scope of the claimed method, because a
skilled artisan is not able to determine, without undue experimentation, what
combinations of second fluid, third fluid, type of living cell, and agent
capable of affecting metabolic activity, will allow the artisan to successfully
make a micro-capsule having the claimed characteristics (i.e., comprising a
continuous membrane of living cells defining an enclosed volume
comprising a reservoir serving as a bioreactor) using the claimed steps (i.e.,
via taxis, cell migration, and differential concentration of the agent in the
second and third fluid). Appellant has not cited persuasive evidence,
whether in the Specification or the prior art, that all combination of any
immiscible fluids with any living cell and any agent capable of affecting
metabolic activity will allow a skilled artisan to successfully practice the
claimed method, so long as the agent is in a higher concentration in the
second fluid as compared to the third fluid. Thus, merely listing all possible
fluids, cell types, and agents capable of affecting metabolic activity that may
be used in the claimed method, without any guidance as to which of them
may be successfully used together, does not enable the claim.
Neither are we persuaded by Appellant’s citation to paragraph 5 of the
Specification or Examples 1 and 2. While Chu teaches methods of creating
multiple emulsions, it provides no guidance regarding creation of a
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continuous membrane through taxis. Likewise, even if Examples 1 and 2
were working examples, they would at most enable a small subset of all
possible combinations of second and third fluids, living cells, and agents
capable of affecting metabolic activity that are encompassed within claim 1.
Accordingly, the factors regarding the amount of direction or
guidance presented and the presence of absence of working examples also
favor a finding that the claims are not enabled because undue
experimentation would be needed to practice the full scope of the claimed
invention.

Relative Skill of Those in the Art
Appellant suggests that the relevant field of art is micro-fluidics and
biotechnology, Appeal Br. ¶ 190, but neither the Examiner nor Appellant
identified the level of skill in the art. However, prior art cited by the
Examiner and Appellant, which are generally authored by research scientists
working in the fields of biotechnology and engineering in academic
institutions, demonstrates a high level of skill in the relevant art. This factor
favors a finding that the claims are enabled because it suggests that undue
experimentation would not be necessary to practice the claimed invention.

Quantity of Experimentation Necessary
Given the lack of guidance in the Specification and the
unpredictability of biological processes, we find that enabling the full scope
of claim 1 would likely involve a significant amount of unpredictable
experimentation. Experimentation may be required to, for example,
determine the appropriate third fluid for use in the multiple emulsion that
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would allow the living cells to maintain capability for metabolic activity and
to migrate; the appropriate combination of cell type, second and third fluids,
and agent that would allow the cells in the third fluid to migrate to the
interface between the fluids and form a continuous membrane around the
third fluid, taking into consideration different agents that may affect
different cell types, the ability of a chosen agent to affect the cells through
the second and third fluids via, e.g., diffusion; and how to maintain the
continuous membrane after the first and second fluids are removed from the
monodisperse multiple emulsion. Experimentation for combinations of cell
type and fluids would require the skilled artisan to vary virtually every
parameter and try each of numerous possible choices until one possibly
arrived at a single successful result, and Appellant provides no evidence that
the Specification or prior art give either an indication of which parameters
are critical or direction as to which of many possible choices is likely to be
successful. Therefore, this factor also favors a finding that undue
experimentation would be needed to practice the full scope of the claimed
invention.
Appellant contends that “[t]he full scope of the claims involves a
method of making a micro-capsule.” Appeal Br. ¶ 254. Appellant suggests
that little experimentation is needed to practice the invention because the
claimed method of making a micro-capsule “[u]ses known technology
(micro-fluidics)”; “[u]ses known components”; “[u]ses known fluids that
include a broad spectrum known and regularly used in the art” and providing
working examples; “[u]ses unique steps, which are variation of steps
regularly implemented in the prior art to produce colloidosomes.” Appeal
Br. ¶¶ 254–261 (citing Link and Chu for microfluidics and monodisperse
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multiple emulsions and Dinsmore17 for colloidsomes); see also id. ¶ 243
(contending that the claimed method “uses known micro-fluidic technology
and a variation of known fluid flow steps to create the micro-capsule” and,
thus, “very little additional instruction” is needed to enable a skilled artisan
to “employ the claimed method to create the micro-capsules”).
We are not persuaded for reasons similar to those already discussed.
The claim is not simply to a method of making a micro-capsule, or making a
micro-capsule using micro-fluidics. Instead, it requires making a micro-
capsule having particular characteristics (i.e., a continuous membrane of
living cells defining an enclosed volume comprising a reservoir serving as a
bioreactor) using a particular set of steps (i.e., by taxis, through cell
migration and differential concentration, in the fluids of the emulsion, of an
agent capable of affecting metabolic activity) where the claim encompasses
a wide range of cell types (i.e., any that are living and capable of metabolic
activity), agents capable of affecting metabolic activity, and emulsion fluids.
Furthermore, as illustrated by Gupta and other prior art, adapting a known
technique to create biomaterials from live cells is not a trivial matter. See,
e.g., Gupta 726, left column (explaining that “the precise and controllable
fabrication of biomaterials from live cells still remains one of the most
promising, yet largely unrealized applications of colloidal assembly”)
(emphasis added).
With respect to the issue of how to maintain the continuous membrane
after the first and second fluids are removed from the monodisperse multiple

17 A.D. Dinsmore et al., Colloidosomes: Selectively Permeable Capsules
Composed of Colloidal Particles, 298 SCIENCE 1006 (2002).
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emulsion, Appellant contends that “[s]ignificant prior art in this field of in
vitro testing using micro-capsules deals with ‘cell to cell’ contact during in
vitro testing. Appeal Br. ¶ 314 (citing Gartner18 and Appeal Br. ¶¶ 219–230,
which in turn cites to Napolitano,19 Gartner, Lee,20 and Moon21). As
discussed above, we base our affirmance on the lack of enablement of the
full scope of the invention with respect to the second and third fluids, cells,
and agents capable of affecting metabolic activity that are encompassed by
the claimed method. Nevertheless, we note that Gartner, cited by Appellant,
teaches that
[r]econstituting functional cell–cell contacts ex vivo and in 3
dimensions remains an important challenge in tissue
engineering, whether for the purpose of building materials for
in vivo tissue repair or for constructing realistic in vitro tissue
models. Although considerable progress has been made toward
defining the interactions between cells and their surrounding
matrix, the ability to control interconnectivity among cells in 3
dimensions has been elusive.
Gartner 4606 (emphasis added, endnote omitted). Neither has Appellant
provided any persuasive argument or evidence why adapting the methods
described in Gartner (“functionaliz[ing] cells with short oligonucleotides to
impart specific adhesive properties”) and other references to the claimed

18 Zev J. Gartner et al., Programmed Assembly of 3-Dimensional
Microtissues With Defined Cellular Connectivity, 106 Proc. Nat’l Acad. Sci.
4606 (2009).
19 Anthony P. Napolitano et al., Scaffold-Free Three-Dimensional Cell
Culture Utilizing Micromolded Nonadhesive Hydrogels, 43 BIO TECHNIQUES
494 (2007).
20 Won Gu Lee et al., A Hollow Sphere Soft Lithography Approach for Long-
Term Hanging Drop Methods, 15 TISSUE ENGINEERING 249 (2009).
21 SangJun Moon et al., Layer by Layer Three-Dimensional Tissue Epitaxy
by Cell-Laden Hydrogel Droplets, 16 TISSUE ENGINEERING PART C (2009).
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method of making micro-capsules would not require a significant quantity of
(likely unpredictable) experimentation, particularly given the large number
of cell types encompassed by the claims.
Finally, Appellant contends that
[t]he choices available to a person of skill in the art amount to
selecting which cells are desired in the shell of the micro-
capsule, and which agent stimulates cell motion, i.e. causes
taxis, to select (among numerous known agents discussed at
paragraph [0034] [of] the description). There is little
uncertainty involved in the patentable method once a person
decides on what cells are needed and which agent to pick.
Appeal Br. ¶ 181; see also id. ¶ 155 (arguing that “[a]ny combination of
reagents and protocols may be used as long as there is a differential
concentration among the fluid emulsions” and that “[t]here is little
uncertainty or experimentation involved in making these choices to
implement the steps”).
We are not persuaded for the reasons already discussed above. In
particular, Appellant has provided no persuasive teaching, either expressed
in the Specification or the prior art, suggesting that all combinations of any
immiscible fluids with any living cell and any agent capable of affecting
metabolic activity (as claimed) will allow a skilled artisan to successfully
practice the claimed method, so long as the agent is in a higher concentration
in the second fluid as compared to the third fluid.
In short, all of the Wands factors, except for the relative level of skill
in the art, support a finding that the claims are not enabled because undue
experimentation would be needed to practice the full scope of the invention.
The high level of skill in the art, however, is not sufficient to counterbalance
the extreme breadth of the claim, the state of the relevant art, which is highly
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unpredictable, and the lack of guidance in the Specification resulting in the
need for significant quantity of experimentation to practice the full scope of
the invention. Accordingly, we affirm the Examiner’s rejection of claim 1
as lacking enablement.22 Claims 2–10 are not separately argued and fall
with claim 1. See In re Kaslow, 707 F.2d 1366, 1376 (Fed. Cir. 1983).
B. Inadequate Written Description (claims 1–10)
1. Issue
The Examiner finds that “[t]he claim(s) contains subject matter which
was not described in the specification in such a way as to reasonably convey
to one skilled in the relevant art that . . . the inventor(s), at the time the
application was filed, had possession of the claimed invention.” Ans. 39. In
particular, the Examiner finds that the Specification does not adequately
describe (A) the first, second, and third fluids in the monodisperse multiple
emulsion used in the claimed method (Ans. 41–43); (B) “an agent capable of
affecting the metabolic activity of the living cells . . . present within the
second fluid at a higher concentration than in the third fluid” in the claimed
method (Ans. 43–46); (C) multiple emulsions (Ans. 46); and (D) the step of
“removing the first fluid and second fluid from the monodisperse multiple
emulsion to produce the microcapsule” (Ans. 47).

22 Because we affirm the Examiner’s enablement rejection on the ground
that the Specification does not enable the full scope of the claimed method
with respect to the fluids, living cells, and “agent[s] capable of affecting the
metabolic activity of living cells” (i.e., rejection grounds C & D)
encompassed by the claim, we do not address the other bases for the
Examiner’s enablement rejection (i.e., rejection grounds A, B, E, & F) and
Appellant’s arguments thereto.
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22
Appellant contends that “[t]he specification fully teaches the invention
in a manner that . . . reasonably convey to the artisan that the inventor had
possession at the time of filing for patent protection of the claimed subject
matter.” Appeal Br. ¶ 432.
Appellant does not separately argue the claims. We therefore focus
our analysis on claim 1 as representative. The issue with respect to this
rejection is whether a preponderance of evidence of record supports the
Examiner’s finding that the Specification fails to provide written descriptive
support for the invention of claim 1.
2. Analysis
“[T]he test for sufficiency [of the written description] 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.” Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351
(Fed. Cir. 2010) (en banc).
Relevant to the instant application, our reviewing court has explained
that a “sufficient description of a genus . . . requires the disclosure of either a
representative number of species falling within the scope of the genus or
structural features common to the members of the genus so that one of skill
in the art can ‘visualize or recognize’ the members of the genus.” Ariad,
598 F.3d at 1350. “[A]n adequate written description requires a precise
definition, such as by structure, formula, chemical name, physical properties,
or other properties, of species falling within the genus sufficient to
distinguish the genus from other materials.” Id. Although “functional claim
language can meet the written description requirement when the art has
established a correlation between structure and function,” “merely drawing a
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fence around the outer limits of a purported genus is not an adequate
substitute for describing a variety of materials constituting the genus and
showing that one has invented a genus and not just a species.” Id. This
standard applies to method as well as product claims. See University of
Rochester v. G.D. Searle & Co., 358 F.3d 916, 926 (Fed. Cir. 2004).
We find that the Specification fails to provide written descriptive
support commensurate with the scope of Appellant’s claimed invention. In
particular, claim 1 encompasses the genus of all combinations of second
fluid, third fluid, living cells, and agents capable of affecting the metabolic
activity of the living cells that will allow “living cells [to] migrate to the
interface between the second and third fluid to form [a] continuous
membrane around the third fluid.” However, as discussed above, the
Specification has not provided a representative number of combinations that
fall within the scope of this genus, providing only bacteria/oxygen and
algae/carbon dioxide, in emulsions comprising water and oil, as example
combinations of cells, “agents capable of affecting . . . metabolic activity,”
and fluids that may be used in the claimed methods. Neither has the
Appellant identified “structural features common to the members of the
genus so that one of skill in the art can ‘visualize or recognize’ the members
of the genus.” As the Examiner explained,
claiming . . . making any [micro-capsule by taxis] without
defining the specific combination of reagents for making the
[micro-capsule] comprising any prokaryotic or eukaryotic cell
as encompassed by the independent claims is not in compliance
with the description requirement. Rather, it is an attempt to
preempt the future before it has arrived.
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Final Act. 52.23
Appellant first reiterates its contentions with respect to the enablement
rejection. We are not persuaded for the reasons already discussed. We note,
furthermore, that enablement and written description are separate
requirements, and that a claim that is enabled may nevertheless not have
been described. See Ariad, 598 F.3d at 1345 (recognizing separate
requirements and noting that “a description that merely renders the invention
obvious does not satisfy the [written description] requirement”).
Appellant contends that a skilled artisan “can clearly see that [the]
inventor possessed” the invention with respect to monodisperse multiple
emulsion, the use of immiscible fluids, an interface between two fluids, the
use of living cells in fluids, and agents that affect cellular metabolic activity.
Appeal Br. ¶¶ 434–441. Appellant contends that a skilled artisan “can
clearly see that inventor possessed the means for enabling cell migration, as
required in the claims,” because cell migration is “an established
phenomen[on] in the prior art work on colloidosomes, which are colloidal
micro-capsules that essentially encapsulate living cells via cell migration to
the interface of fluid flows in a micro-fluidic device.” Appeal Br. ¶¶ 455–
456 (citing Appeal Br. ¶¶ 110, 173–175).
Appellant contends that “a skilled artisan can clearly see that inventor
possessed the practice of removing the micro-capsule from the emulsion,”
because “[a]ny person of skill in the art would comprehend the many

23 The Examiner uses the term “artificial micro-gland” in the Final Action.
However, the claim has been amended to recite “micro-capsule.” The
principle recited by the Examiner remains the same, however.
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protocols for removing micro-capsules from a solution.” Appeal Br.
¶¶ 457–461 (citing Spec. ¶ 31 and Bocanegra24).
Appellant contends that “Applicant’s invention is a method of making
a micro-capsule,” that all of the claims steps including the making of a
monodisperse multiple emulsion is fully explained, and that “[t]here is no
claim to any biological property other than the micro-capsule having a
membrane of living cells enclosing a core reservoir” and “no claim to a
‘specific combination’ of reagents, since only a single agent may be used
and these are fully explained.” Appeal Br. ¶¶ 467–470.
We are not persuaded for the reasons similar to those already
discussed. Even if the inventor has possession of individual pieces of the
invention (e.g., generic description of living cell types, identities of agents
that may affect metabolic activity, and fluids that may be used in a
monodisperse multiple emulsion), the invention is not directed to these
pieces individually, or even to a method limited to such specific pieces, but
is directed to a method of making a micro-capsule having the claimed
biological properties using the claimed steps that broadly cover using any
living cells and any second and third fluids of certain immiscibilities, for
example. In light of the unpredictability of biomaterials engineering using
living cells, discussed above, we find that disclosures of disparate pieces of
the invention, without a description of how such pieces are combined in the
claimed method, essentially provides “only a research plan, leaving it to
others to explore unknown contours of the claimed genus” of combinations

24 Rodrigo Bocanegra et al., Monodisperse Structured Multi-Vesicle
Microencapsulation Using Flow-Focusing and Controlled Disturbance,
22 J. Microencapsulation 745 (2005).
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of second and third fluids, living cells, and agents capable of affecting
metabolic activity useful in the claimed method of making micro-capsule by
taxis. See, e.g., Capon v. Eshhar, 418 F.3d 1349, 1359 (Fed. Cir. 2005)
(explaining that “what is needed to support generic claims to biological
subject matter” depends on, e.g., “the existing knowledge in the particular
field, the extent and content of the prior art, the maturity of the science or
technology, the predictability of the aspect at issue, and other considerations
appropriate to the subject matter”); Abbvie Deutschland GmbH & Co., KG v.
Janssen Biotech, Inc., 759 F.3d 1285, 1300 (Fed. Cir. 2014) (explaining that
a Specification fails to comply with the written description requirement
when providing “only a research plan, leaving it to others to explore the
unknown contours of the claimed genus”).
Accordingly, we affirm the Examiner’s rejection of claim 1 as lacking
in written description. Claims 2–10, which are not separately argued, fall
with claim 1.25

25 In the Appeal Brief Appellant contends that the “examiner often repeats
the same reasoning to support different alleged legal infirmities involving
indefiniteness, written description and enablement” and that “using the same
reasoning for ‘separate and distinct’ legal requirements is improper and is
itself reversible error.” Appeal Br. ¶¶ 2–3. We agree that indefiniteness,
written description, and enablement are distinct. See, e.g., Ariad, 598 F.3d
at 1344 (holding that written description is a requirement separate from the
enablement requirement). Nevertheless, we do not agree that the fact written
description and enablement are separate requirements preclude the Examiner
from using the same or similar sets of facts to support both rejections.
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C. Indefiniteness (claims 1–10)
1. Issue
The Examiner concludes that the claims are indefinite because
[i]t is unclear whether the structure set forth in the preamble
must occur in the final product because the method steps in the
body of the claim do not appear to result in the product of the
preamble. The scope of the product in the preamble is not the
same as the scope of the product made by the method steps . . . .
Accordingly, those of skill would not be able to determine if
they were infringing on the claim.
Ans. 55–56. The Examiner asserts, for example, that “it is unclear whether
the 3rd fluid [in the body of the claim] is the ‘enclosed volume’ [recited in
the preamble that comprises] a ‘bioreactor.’” Id. at 48–49. Similarly, the
Examiner asserts that “[i]t is unclear if the ‘microcapsule’ in the last lines of
the independent claims must contain the cells, whether they must be in a
continuous layer (as in the preamble) or whether it encompasses a product
made up of only the 3rd fluid.” Id. at 49.
2. Analysis
“A claim is indefinite if, when read in light of the specification, it
does not reasonably apprise those skilled in the art of the scope of the
invention.” SmithKline Beecham Corp. v. Apotex Corp., 403 F.3d 1331,
1352 (Fed. Cir. 2005) (citation omitted).
We conclude the Examiner has not established a prima facie case that
the claims are indefinite. As an initial matter, under well-established
principles of claim construction, the preamble is limiting if it “recites
limitations of the claim, or . . . is ‘necessary to give life, meaning, and
vitality’ to the claim.” Pitney Bowes Inc. v. Hewlett Packard Co., 182 F.3d
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1298, 1305 (Fed. Cir. 1999). Thus, it is not necessary that the entirety of the
invention be set forth in the body of the claim.
In this case, the preamble of claim 1 recites “[a] method of making a
micro-capsule by taxis, the micro-capsule comprising a continuous
membrane of living cells, the continuous membrane defining an enclosed
volume, the enclosed volume comprising a reservoir serving as a
bioreactor.” Appeal Br. 169 (Claims App.) (emphasis added). The body of
the claim recites, among others, the steps of (1) “producing a monodisperse
multiple emulsion” comprising a first, second, and third fluid, with the third
fluid “comprising a plurality of living cells dispersed therein”; (2) “waiting
until the living cells migrate to the interface between the second fluid and
the third fluid to form the continuous membrane around the third fluid”; and
(3) “removing the first fluid and the second fluid from the monodisperse
multiple emulsion to produce the micro-capsule.” Id. at 169–170 (Claims
App.) (emphasis added).
The micro-capsule in the final step of the claim body refers back to
the micro-capsule in the preamble; thus, the micro-capsule resulting from the
final step must have the structure recited for the micro-capsule in the
preamble, i.e., comprising a continuous membrane of living cells, the
continuous membrane defining an enclosed volume, the enclosed volume
comprising a reservoir serving as a bioreactor. It does not encompass a
product made up of only the 3rd fluid without the continuous membrane of
living cells, as the Examiner appears to suggest.
Similarly, we do not find the issue of whether the third fluid in the
body of the claim is the enclosed volume recited in the preamble, and vice
versa, to render the claims indefinite.
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In particular, when read in light of the Specification, it appears clear
that the enclosed volume recited in the preamble can be the third fluid, if the
third fluid is defined by the continuous membrane of living cells. The
Specification, for example, describes the third fluid in several instances as
the “reservoir [i.e., part of the “enclosed volume”] of the artificial micro-
gland.” See, e.g., Spec. ¶¶ 30, 32, 38, 39. However, because limitations are
not to be imported from the Specification into the claims, and because the
claimed method uses the open transitional phrase “comprising,” which
permits inclusion of additional steps not specifically recited in the claim, it
also appears that the enclosed volume need not be the third fluid, so long as
the enclosed volume is defined by the continuous membrane of living cells
and “compris[e] a reservoir serving as a bioreactor.” In any event, we need
not definitively decide these issues, other than to note that the Examiner has
not persuasively shown that a skilled artisan would not be able to determine
whether the third fluid in the body of the claim is the enclosed volume
recited in the preamble, and vice versa, by applying the ordinary rules of
claim construction.
Finally, to the extent the Examiner’s concern is that the disclosure
does not allow a skilled artisan to arrive at the micro-capsule recited in the
preamble of claim 1, or that the disclosure does not reasonably convey to
skilled artisans that the inventors were in possession of such a micro-
capsule, the appropriate rejection is lack of enablement and written
description, respectively, rather than indefiniteness.
For the reasons stated above, we affirm the Examiner’s rejections of
claims 1–10 as lacking enablement and adequate written description, but
reverse the rejection of claims 1–10 as indefinite.
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CONCLUSION
In summary:
Claim(s)
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1–10 112 Enablement 1–10
1–10 112 Written Description 1–10
1–10 112 Indefiniteness 1–10
Overall
Outcome
1–10

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