Ex Parte Kharlampieva et al

Patent Trials and Appeals Board

May 31, 2019

14126943 - (D) (P.T.A.B. May. 31, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/126,943 12/17/2013
24504 7590 06/04/2019
THOMAS I HORSTEMEYER, LLP
3200 WINDY HILL ROAD, SE
SUITE 1600E
ATLANTA, GA 30339
FIRST NAMED INVENTOR
Eugenia P. Kharlampieva
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.
222104-1230 5163
EXAMINER
FAN,LYNNY
ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
06/04/2019 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):
uspatents@tkhr.com
ozzie. liggins@tkhr.com
docketing@thomashorstemeyer.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte EUGENIA P. KHARLAMPIEVA,
VERONIKA KOZLOVSKA YA, ANTHONY J. THOOMPSON,
and W ANXING CUI
Appeal2018-006535
Application 14/126,943
Technology Center 1600
Before DEMETRA J. MILLS, CHRISTOPHER PAULRAJ, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
MILLS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134. The Examiner has rejected
the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b ).
We REVERSE and enter a new ground of rejection.
NATURE OF THE INVENTION
The present disclosure provides multifunctional cytoprotective
materials applied to coat living cells or aggregates of cells such as, but
not limited to, pancreatic islets. The coating utilizes hydrogen-bonded
interactions of a natural polyphenol (tannic acid) with poly(N-
vinylpyrrolidone) deposited on the cell aggregate surface via non-ionic
layer-by-layer assembly. The coating is conformal over the surface of
such as mammalian islets. The coated islets maintain their viability and
cell functionality for at least 96 hours in vitro. The coating demon-
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Application 14/126,943
strates imnmnomodulatory cytoprotective properties suppressing
proinflammatory cytokine synthesis in stimulated bone marrow-derived
macrophages and diabetogenic B DC-2.5 T cells.
Spec. 6-7. In particular, pancreatic "[i]slet encapsulation can provide a
means of culturing and delivering islets for transplantation purposes (Beck et
al., (2007) Tissue Eng. 13: 589-599). This technique allows for creation of a
semi-permeable environment around a group of islets to provide an immune-
protection and to allow mass and oxygen transfer." Spec. 2.
STATEMENT OF CASE
The following claim is representative.
1. A biocompatible coating disposed on a cell or
aggregate of cells, the coating comprising a first polymer layer
attached to the membrane or membranes of a cell or aggregate
of cells by hydrogen-bonding and encapsulating said cell or cell
aggregate, wherein said first polymer layer comprises poly(N-
vinylpyrrolidone) (PVPON), wherein said PVPON has a
molecular weight of about 1,300,000 daltons, and a second
polymer layer disposed on the first polymer layer and attached
thereto by hydrogen-bonding, wherein the second polymer
layer is a polyphenolic tannin layer, and wherein the cell, or
aggregate of cells, is isolated from an animal or human tissue or
is a cultured cell or an aggregate of cultured cells.
Cited References
Sukhishvili US 2005/0163714 Al July 28, 2005
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Application 14/126,943
Veronika Kozlovskaya et al., RESPONSIVE MICROCAPSULE
REACTORS BASED ON HYDROGEN-BONDED TANNIC ACID LAYER-
BY-LAYERASSEMBLIES, 6 Soft Matter 3596-3608 (2010). 1
Seda Kizilel et al., ENCAPSULATION OF p ANCREATIC ISLETS
WITHIN NANO-THIN FUNCTIONAL POLYETHYLENE GLYCOL
COATINGS FOR ENHANCED INSULIN SECRETION, 16 Tissue
Engineering: Part A 7, 2217-2228 (2010).
Devesh Kothwala et al., PACLITAXEL DRUG DELIVERY FROM
CARDIOVASCULAR STENT, 19 Trends Biomater. Artif. Organs 2,
88-92 (2006).
John C. Stendahl et al., EXTRACELLULAR MATRIX IN
PANCREATIC ISLETS: RELEVANCE TO SCAFFOLD DESIGN AND
TRANSPLANTATION, 18 Cell Transplant. 1, 1-12 (2009).
Lien Lybaert et al., BIO-HYBRID TUMOR CELL-
TEMPLATED CAPSULES: A GENERIC FORMULATION
STRAGEGY FOR TUMOR ASSOCIATED ANTIGENS IN
VIEW OF IMMUNE THERAPY, Ad. Funct. Mater, 24, 7139-
7150 (2014).
Grounds of Rejection
Claims 1-3, 6-9, 12-15, and 192 are rejected under pre-AIA 35
U.S.C. §103(a) as being unpatentable over Sukhishvili, Kozlovskaya in view
of Kizilel and Kothwala, as evidenced by Stendahl. Final Act. 3.
We summarily reverse this rejection and enter a new ground of
rejection under 35 U.S.C. §103(a).
1 Although Kozlovskaya is a named inventor in the present application,
Appellants do not dispute that this reference qualifies as prior art under pre-
AIA 35 U.S.C. § 102(b).
2 Claims 7 and 19 were cancelled by Appellants in an Amendment filed June
7, 2017. The Examiner's Advisory Action dated June 22, 201 7 indicated
that the Amendment filed June 7, 201 7 "will be entered." Therefore, claims
1-3, 6, 8-9, and 12-15 are pending on appeal.
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New Ground of Rejection
Claims 1-3, 6, 8-9, and 12-15 are rejected under pre-AIA 35 U.S.C.
§103(a) as being unpatentable over Kozlovskaya in view ofKizilel.
FINDINGS OF FACT
The following facts are highlighted.
1. Kozlovskaya teaches a capsule comprising PVPON/T A
(poly-N-vinylpyrrolidone 1300000/tannic acid) LbL (layer-
by-layer) multilayers, wherein the second polymer layer (the
outermost polymer layer) is a polyphenolic tannin layer (p.
3599, p.3601 col right-para 3, p. 3606 col left-para 3).
Alexa Fluor 488 dye (detectable moiety) is added to the
capsule ( at least one polymer layer further comprises a
functional moiety attached thereto) (p.3607 col left-para
2).
2. Kozlovskaya states that
Interest to [sic] tannic acid (TA) as a molecule with the
ability to multiple hydrogen bonding due to the presence of
numerous terminal hydroxyl groups has been spiked
relatively recently due to its high biological activity
including antioxidant, antimicrobial, anticarcinogenic,
antimutagenic and antibacterial properties. The
anticarcinogenic and antimutagenic potentials of
polyphenols are related to their antioxidative property in
protecting cellular components from oxidative damage. It is
due to unique functional structure of tannic acid, which
possesses maximum number of hydroxyl groups compared
to other derivatives of tannins, the antioxidant properties of
TA are revealed. As reported, polyphenols possess high
ability to reduce free-radicals and inhibit radical-induced
oxidation of adjacent molecules.
P. 3597, col 1.
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3. Kozlovskaya teaches a biocompatible coating where
multiple layers are formed on various cores through a
stepwise template adsorption of proper species-biological
molecules, polymers, organic polymers, and nanoparticles.
P.3596,col. 1.
4. The Kozlovskaya encapsulation technology for therapeutic
delivery uses hydrogen-bonded Layer-by-layer (LbL)
techniques. P. 3596, col 2. Figure 2 of Kozlovskaya
discloses 3 LbL layer capsules (PEI/PVPON/TA). P. 3598,
col. 2.
5. Kozlovskaya discloses that, "the permeability of the LbL
containers can be controlled by changing pH providing an
opportunity for loading and release of a functional cargo
under mild conditions." Abstract. Kozlovskaya further
discloses that the magnitude of negative charges associated
with increasing pH is lower when PVPON with higher
molecular weight was used for the capsule shell fabrication.
P. 3602.
6. Kozlovskaya discloses that charge screening differences are
"probably reflective of better negative charge screening by
longer PVPON chains and consistent with the thicker
TA/PVPON-1300 [3] shells with the same number of
deposited layers (Table 1)." Id. PVPON/TA capsules
showed no capsule dissolution, and no distinctive change in
capsule diameter. P. 3601, col. 2.
7. Kozlovskaya tested various capsule compositions under
"biologically relevant conditions." P. 3600, col. 2. PVPON
has been investigated as a potential pH-stable material for
sustain release formulations. P. 3597.
3 PVPON 1300000 Da.
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8. Kozlovskaya discloses that
The observed high capability of T A/PVPON films to
withstand an internal ionization within the multilayer can be
explained by the ability of TA to form intra-molecular
hydrogen bonds. Such stabilizing effect can be enhanced
with the increase of a number of participating phenolic units.
P.3603,col. 1.
9. Kozlovskaya discloses that, "Hydrogen-bonded (TA/non-
ionic polymer) coatings can be fanned either through
deposition on PEI-treated silica particles (IA) starting from
TA or through direct deposition of the ( nonionic
polymer/TA) multilayer starting from a neutral polymer. P.
3598, Fig. 2 description.
10. Kozlovskaya concludes that
These properties of the reported shells can find a potential
use for the fabrication of responsive ultra thin yet robust
microcapsules for biochemical sensing and detection as well
as laser- or chemically-induced cargo release for
biotechnology applications.
P.3606,col. 1.
11. Kizilel teaches encapsulation of pancreatic islets for
transplantation of islets, within a multilayered LbL film for
enhanced insulin secretion (Title), wherein mouse pancreatic
islets are isolated from a pancreatic tissue (p. 2219 col left-
para 4), cultured (p. 2219 col right-para 2), coated via
layer-by-layer assembly technique. The capsules and are
capable of secreting more insulin (produce a molecule
modulating the physiology of an animal) (Abstract).
12. Kizilel suggests that, blood-mediated inflammatory
reactions are likely cause of both the loss of transplanted
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islet tissue and the intraportal thrombosis associated with
clinical islet transplantation. P. 2218, col. 1.
13. Kizilel suggests that LbL coatings of islet cells provides potential
for immunoisolation of pancreatic transplant cells. Abstract.
PRINCIPLES OF LAW
"The combination of familiar elements according to known
methods is likely to be obvious when it does no more than yield
predictable results." KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,416
(2007).
New Ground - Obviousness Rejection
Claims 1-3, 6, 8-9, and 12-15 are rejected under pre-AIA 35
U.S.C. § 103(a) as being unpatentable over Kozlovskaya in view of
Kizilel.
Independent claim 1 recites a biocompatible coating disposed
on a layer of isolated or cultured cell( s ), wherein the coating is
comprised of a first polymer layer of PVPON with a molecular weight
of 1,300,000 daltons attached to the cell membrane(s) by hydrogen
bonding, and a second polymer layer of polyphenolic tannin attached
to the first polymer layer also by hydrogen bonding. Kozlovskaya
teaches a biocompatible coating where multiple layers are formed on
various cores through a stepwise template adsorption of proper
species-biological molecules, polymers, organic polymers, and
nanoparticles. P. 3596, col. 1.
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Kozlovskaya discloses that, "the permeability of the LbL
containers can be controlled by changing pH providing an opportunity
for loading and release of a functional cargo under mild conditions."
Abstract. Kozlovskaya further discloses that the magnitude of
negative charges associated with increasing pH is lower when
PVPON with a higher molecular weight was used for the capsule shell
fabrication. P. 3602. In particular, Kozlovskaya teaches that charge
screening differences are "probably reflective of better negative
charge screening by longer PVPON chains and consistent with the
thicker TA/PVPON-1300 [4] shells with the same number of
deposited layers (Table 1 )." Id. Kozlovskaya tested various capsule
compositions under "biologically relevant conditions." P. 3600, col. 2.
PVPON/T A capsules showed no capsule dissolution, and no
distinctive change in capsule diameter. P. 3601, col. 2. PVPON has
been investigated as a potential pH-stable material for sustain release
formulations. P. 3597. Kozlovskaya discloses that
The observed high capability of T A/PVPON films to withstand
an internal ionization within the multilayer can be explained by
the ability of TA to form intra-molecular hydrogen bonds. Such
stabilizing effect can be enhanced with the increase of a number
of participating phenolic units.
P. 3603, col. 1. Kozlavskaya concludes that
These properties of the reported shells can find a potential use
for the fabrication of responsive ultra thin yet robust
microcapsules for biochemical sensing and detection as well as
4 PVPON 1300000 Da.
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laser- or chemically-induced cargo release for biotechnology
applications.
P. 3606, col. 1. Kozlovskaya discloses that, "Hydrogen-bonded
(TA/non-ionic polymer) coatings can be formed either through
deposition on PEI-treated silica particles (IA) starting from TA or
through direct deposition of the (nonionic polymer/TA) multilayer
starting from a neutral polymer." FF 9. While Kozlovskaya teaches
the encapsulation technology can be used with biological materials
and organic polymers, Kozlovskaya does not specifically disclose that
the encapsulation technology can be used with cells or cell aggregates.
Kizilel discloses that it was well known in the art at the time of the
invention to encapsulate pancreatic islet cells using LbL technology
(for example with a polyethylene glycol polymer) for pancreatic islet
cell transplantation. P. 2217-2218. Kizilel discloses that those of skill
in the art look for islet cell transplant structures which are stable under
physiological conditions. P. 2221, col. 1.
It would have been prima facie obvious to one of ordinary skill in the
art at the time of the invention to substitute the LbL PVPON/T A 1300
capsule technology of Kozlovskaya for the LbL encapsulation technology of
Kizilel for pancreatic islet cell transplantation, because the encapsulation
technology of Kozlovskaya exhibits greater stability under physiologic pH
conditions and Kizilel indicates that stability under physiologic conditions is
a desired property of capsules for delivery of islet cells for transplantation.
It would have been further obvious to substitute the LbL technology of
Kozlovskaya for that of Kizilel for the benefits associated with the use of
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tannic acid for its high biological activity including antioxidant,
antimicrobial, anticarcinogenic, antimutagenic and antibacterial properties,
which would have been understood by those of ordinary skill in the art to be
particularly desirable when cells are being used. Kizilel suggests that LbL
coatings of islet cells provides potential for immunoisolation of pancreatic
transplant cells. Abstract. Therefore, one of ordinary skill in the art would
have looked to stable, biocompatible, LbL coating/encapsulation
technologies, such as that of Kozlovskaya, to provide improved
immunoisolation to pancreatic cell transplants.
With respect to claims 2-3, Kozlovskaya discloses multilayer
capsules as required. P. 3597, col. 2. The term "multiple" means "consisting
of, or including more than one,"5 which encompasses as many as 3 or more
coating/capsule layers. The Kozlovskaya coating/encapsulation technology
for therapeutic delivery uses hydrogen-bonded Layer-by-layer (LbL)
techniques. P. 3596, col 2. In addition, Figure 2 of Kozlovskaya discloses 3
LbL layer capsules (PEI/PVPON/TA). P. 3598, col. 2. With respect to
claims 6, 8, 9, and 12-15, Kozlovskaya discloses functional moieties on the
capsules, such as fluorescent probe. P. 3603, col. 1. We, therefore,
determine that these dependent claims are also obvious in view of the
foregoing cited prior art teachings and rationale.
DISCUSSION
We enter a new ground of rejection in the application, but for the sake
of compact prosecution, we entertain Appellants' pending arguments of
record that address the Kozlovskaya and Kizilel references.
5 https://www.merriam-webster.com/dictionary/multiple
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Appellants contend that the
Examiner failed ... to address that the capsules taught by
Kozlovskaya were formed layer-by-layer on silicon cores that
are subsequently removed under acid (pH 2) conditions. The
acid treatment results in hollow capsules that are not shown
capable of receiving cells or aggregates of cell (pancreatic
islets).
Appellants assert that the addition of the tannic acid layer
as taught by Kozlovskaya was conducted at a pH of either 5.0 or
2.0 (see Kozlovskaya at page 3606, second col. last paragraph),
[ which are] values that one of skill in the art would readily
recognize is far below a physiological pH and will, therefore,
have likely detrimental consequences for the viability or
physiology of the cell or cell aggregate being coated. Therefore,
it cannot be construed that there is a reasonable expectation of
success contrary to the assertion of the Office Action. In short,
one skilled in the art would not use the teachings of
Kozlovskaya and apply them to the other cited references, alone
or in combination, to arrive at the coated functioning pancreatic
cells as argued by Examiner.
App. Br. 8.
Appellants further contend that
Kozlovskaya does not mention biocompatibility and its
teachings are contrary to the alleged reliance on Kozlovskaya to
demonstrate that tannic acid-based multilayer assemblies are
used as biocompatible coatings. Rather, as stated by the Non-
Final Office Action, tannic acid ( a polyphenol) has a high
biological activity that includes antioxidant, antimicrobial,
anticarcinogenic, antimutagenic and antibacterial properties,
none of which should be construed as related to, or indicating,
biocompatibility. Accordingly, Appellants maintain that the use
of tannic acid in the constructs of the present application that
are used for the maintenance of living cells is not suggested or
taught by Kozlovskaya.
App. Br. 8.
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Appellants rely on the Declaration under 35 U.S.C. § 1.132 of
Eugenia Kharlampieva Ph.D (hereinafter, Declaration), as evidence that the
state of knowledge at the time of the invention was that tannic acid is
cytotoxic, and that tannic acid would have been expected to leach from a
PVPON LbL. App. Br. 8. Dr. Kharlampieva states that only the
compositions of the present application incorporating poly-N-
vinylpyrrolidone with a molecular weight of about 1,300,000 allow tannic
acid to be incorporated into the LbL without adverse effects on the
encapsulated cells. Id.
We are not persuaded by Appellants' arguments. Kozlovskaya
expressly discloses that "tannic acid exhibits antioxidative property that
protects cellular components from oxidative damage (p.3597 col left-para
4)." Thus, we find one of ordinary skill in the art would have understood
that the coating/capsules of Kozlovskaya would be beneficial in the cellular
environment to prevent oxidative damage to cells. In addition, Kozlovskaya
does teach PVPON-1300 (MW= 1300000 Da)/tannic acid multilayer
assemblies (Table 1 ), the same structure that is claimed. FF 1. Because the
compositions of Kozlovskaya incorporating PVPON with a molecular
weight of about 1,300,000 allows tannic acid to be incorporated into the LbL
without adverse effects on the encapsulated cells, we find that the PVPON-
1300 (MW= 1300000 Da)/tannic acid multilayer assemblies of Kozlovskaya
are necessarily biocompatible.
The Declaration does not fully address the teachings of Kozlovskaya
with respect to microcapsule therapeutic delivery of biological molecules
and the biocompatibility of the microcapsules. P. 3596. The
coating/capsules of Kozlovskaya are essentially the same as those claimed,
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and therefore, would inherently possess the same chemical characteristics
and biocompatibility properties. "From the standpoint of patent law, a
compound and all of its properties are inseparable; they are one and the same
thing." In re Papesch, 315 F.2d 381, 391 (CCPA 1963).
Where ... the claimed and prior art products are identical or
substantially identical, or are produced by identical or substantially
identical processes, the PTO can require an applicant to prove that the
prior art products do not necessarily or inherently possess the
characteristics of his claimed product .... Whether the rejection is
based on "inherency" under 35 U.S.C. § 102, on "prima facie
obviousness" under 35 U.S.C. § 103, jointly or alternatively, the
burden of proof is the same, and its fairness is evidenced by the PTO' s
inability to manufacture products or to obtain and compare prior art
products.
In re Best, 562 F.2d 1252, 1255 (CCPA 1977) (emphasis added.) Appellants
have not shown that the prior art capsules of Kozlovskaya do not necessarily
or inherently possess the biocompatibility characteristics of the claimed
coating/ capsules.
Appellants argue that Kozlovskaya does not mention biocompatibility
of the capsules and its teachings are contrary to the alleged reliance on
Kozlovskaya to demonstrate that tannic acid-based multilayer assemblies are
used as biocompatible coatings. App. Br. 8. We are not persuaded.
Kozlovskaya discloses that microcapsules generally, including TA/PVPON-
1300 microcapsules disclosed therein, 6 "[c]an find a potential use for the
fabrication of responsive ultra thin yet robust microcapsules for biochemical
sensing and detection as well as laser- or chemically-induced cargo release
6 Tannie acid polyvinyl pyrrolidone capsule, molecular weight 1,300,000.
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for biotechnology applications." P. 3606, col. 1. The Kozlovskaya capsules
are made from functional polymers expressly identified as "biocompatible"
and capable of "protecting cellular components from oxidative damage." P.
3597, col. 1. Kozlovskaya further teaches that it was well known in the art
that layer-by-layer assembly of micro- and nano shells have been used with
cores of biological molecules. P. 3596, col. 1. Thus, Kozlovskaya suggests
that its microcapsules are appropriate for use with biological molecules.
Nor do we find that the Declaration provides a showing of unexpected
results for the T A/PVPON 1300000 microcapsules with islet pancreatic
cells, in view of the particular disclosures of Kozlovskaya. Kozlovskaya
teaches that, "it is evident that the magnitude of such increase [in negative
charges] is lower when PVPON with higher molecular weight was used for
the capsule shell fabrication." P. 3602 and Fig. 10. Thus, Kozlovskaya
would have suggested that one of ordinary skill in the art should use higher
molecular weight PVPON, such as 1300000 PVPON, which has favorable
pH stability.
Appellants' Declaration, Exhibit N (Lybaert), also supports a prima
facie case of obviousness. Lybaert discloses that
These data point out the superior performance of TA and PVP,
compared to polyelectrolytes to encapsulate cells in a polymeric
multilayer coating while maintaining membrane integrity as much as
possible and affecting cell viability as little as possible.
P. 7142, col. 2. Lybaert did teach a dramatic reduction in cell viability when
only two bilayers were used. Pl. 7143-7144. However, Lybaert also teaches
greater cell viability when the layered capsule begins with a PVP layer vs. a
TA layer, and when multiple layers are used. P. 7144, col. 1; p. 7146, col. 1.
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Appellants assert that Kizlel merely teaches only the placing of a
coating on cells. App. Br. 9.
Kizlel teaches a coating formed by the covalent attachment of
biotin-PEG-NHS monomers to -NH2 groups on the surfaces of
the cells (Kizlel at Fig. 1 ). Streptavidin then binds to the biotin
followed by biotin-PEG-GLPl monomers binding to the
streptavidin.
Accordingly, the interaction between the first layer (as
defined by Kizlel) and the cells is by covalent bonding of
monomers and is markedly different from the hydrogen
bonding of PVPON polymers as taught and claimed in the
present application.
App. Br. 9, without emphasis.
Kizlel is relied upon to demonstrate that an isolated pancreatic islet
dissected from a pancreas can be encapsulated in a polymer, such as
polyethylene glycol LbL, to enhance insulin secretion. Kizilel is not relied
on for the teaching of a hydrogen bonded LbL capsule, but instead for its
teaching that LbL capsule technology generally is appropriate for use in
delivery of pancreatic islet cells for transplantation and cargo release for
biotechnology applications. We find nothing in Kizilel to suggest that only
polymers that form covalent bonds with cells are appropriate for LbL
capsule technology used in biotechnology applications. As discussed above,
Kozlovskaya teaches a hydrogen bonded LbL encapsulation technology for
biomaterials. Furthermore, Kizlel teaches that there is a need to develop
islet encapsulation strategies to minimize transplant volume and
immunoisolate transplant cells (Abstract). Thus, one of ordinary skill in the
art would have looked to other biocompatible encapsulation polymers
known in the art, such as those of Kozlovskaya, with an expectation of
success because these polymer encapsulation systems are indicated to be
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appropriate for biological materials, including cells, and are stable in the
physiological environment.
Appellants argue that the capsules taught by Kozlovskaya were
formed layer-by-layer on silicon cores that are subsequently removed under
acid (pH 2) conditions. The acid treatment results in hollow capsules that
are not shown capable of receiving cells or aggregates of cell (pancreatic
islets).
We are not persuaded that the particular methodology described in the
experimental section of Kozlovskaya forecloses obviousness. According to
the experimental procedures of Kozlovskaya, the capsules were formed over
silica cores, which were later removed at low pH, 2. P. 3606, col. 1. The
capsules were then loaded with gold after exposure to borate buffers to
activate the tannic acid, and centrifugation. P. 3606, cols. 1 and 2. Thus, the
acid treatment would have occurred before the capsules are loaded with their
cargo, e.g. cells. Furthermore, Kozlovskaya generally teaches a
biocompatible coating where multiple layers are formed on various cores
through a stepwise template adsorption of proper species-biological
molecules, polymers, organic polymers, and nanoparticles. P. 3596, col. 1.
Thus, we find Kozlovskaya teaches biocompatible encapsulation technology
that can be used to coat cells in the same manner as Kizilel' s disclosure of
pancreatic islet cell transplant coatings.
CONCLUSION OF LAW
The Examiner's obviousness rejection is reversed. However, a new
ground of rejection of claims 1-3, 6, 8-9, and 12-15 is entered into the
application.
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TIME PERIOD FOR RESPONSE
This decision contains a new ground of rejection pursuant to 37
C.F.R. § 4I.50(b). 37 C.F.R. § 4I.50(b) provides that "[a] new ground of
rejection ... shall not be considered final for judicial review."
37 C.F.R. § 4I.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
exammer ....
(2) Request rehearing. Request that the proceeding be reheard under
§ 41.52 by the Board upon the same record ....
REVERSED AND NEW GROUND UNDER 37 C.F.R. § 4I.50(b)
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