Ex Parte Wang et al

Patent Trial and Appeal Board

Apr 20, 2017

13320585 (P.T.A.B. Apr. 20, 2017)

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.
13/320,585 12/01/2011 Dongan Wang 055514/412509 9090
826 7590
ALSTON & BIRD LLP
BANK OF AMERICA PLAZA
101 SOUTH TRYON STREET, SUITE 4000
CHARLOTTE, NC 28280-4000
EXAMINER
MARTIN, PAUL C
ART UNIT PAPER NUMBER
1653
NOTIFICATION DATE DELIVERY MODE
04/24/2017 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):
u sptomail @ alston .com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte DONGAN WANG, KAI SU,
YIHONG GONG, and TING TING LAU
Appeal 2016-002682
Application 13/320,585
Technology Center 1600
Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
TIMOTHY G. MAJORS, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to
compositions. The Examiner rejected the claims as obvious. We have
jurisdiction under 35 U.S.C. § 6(b). We affirm.
Statement of the Case
Background
“Tissue engineering techniques generally require the use of a
temporary scaffold as a three-dimensional template for initial cell attachment
and subsequent tissue formation. The ability of the scaffold to be
metabolised by the body allows it to be gradually replaced by new cells to
1 Appellants identify the Real Party in Interest as Nanyang Technological
University (see App. Br. 2).
Appeal 2016-002682
Application 13/320,585
form functional tissue” (Spec. ^ 3). “The invention is based on the finding
that cavities can be formed in a hydrogel matrix using degradable and
surface cross-linked particles that degrade at a faster rate compared to the
hydrogel matrix at a given condition” (Spec. ^ 46).
The Claims
Claims 1-6 and 8-26 are on appeal. Claim 1 is representative and
reads as follows (underlining omitted):
1. A composition comprising one or more species of living
cells, and a mixture of at least one degradable hydrogel and at
least one kind of degradable and surface cross-linked particle,
wherein the at least one kind of degradable and surface cross-
linked particle comprises a material which degrades faster than
the at least one degradable hydrogel at a given condition,
wherein the at least one kind of degradable and surface cross-
linked particle has a surface comprising additional reactive
groups to bind the one or more species of living cells to its
surface such that it forms a degradable particle comprising a
living cell, and wherein one or more degradable particle
comprising a living cell are comprised in the at least one
degradable hydrogel, and wherein the at least one degradable
hydrogel of the mixture is formable to a hydrogel matrix
comprising cavities formable by the faster degrading surface
cross-linked particle.
2
Appeal 2016-002682
Application 13/320,585
The issues
The Examiner rejected claims 1-6 and 8-26 under 35 U.S.C. § 103(a)
as obvious over Tan,2 Risbud,3 Reginato,4 and Cosmobio5 (Final Act. 3-7).
The Examiner finds Tan teaches “PLGA/gelatin-RGDS microspheres
are potentially applicable as cell carriers, which may be further piled into a
3-D scaffold” (Ans. 4). The Examiner finds Risbud teaches “natural
polymeric gels such as hyaluronic acid, collagen, alginate and chitosan have
been used successfully for immobilization and maintain the differentiated
phenotype of chondrocytes’ '’ (Ans. 5). The Examiner finds Risbud teaches
“fiber scaffolds or other porous structures are used to achieve initial
biomechanical stability suitable synthetic biodegradable poly(a-
hydroxyesters) such as polylactic acid, polyglycolic acid and copolymer
PLGA” (id.).
The Examiner finds it inherent that “PLGA/gelatin microspheres
would degrade faster than the degradable hydrogel at a given condition, as
this appears to be a characteristic of the PLGA/microspheres” (Ans. 6).
2 Tan et al., RGD Modified PLGA/Gelatin Microspheres as Microcarriers
for Chondrocyte Delivery, 9 IB J. Biomed. Mater. Res. Part B: Appl.
Biomater. 228-238 (2009) (“Tan”).
3 Risbud et al., Tissue engineering: advances in in vitro cartilage
generation, 20 TRENDS in Biotechnology 351-356 (2002) (“Risbud”).
4 Reginato et al., Formation Of Nodular Structures Resembling Mature
Articular Cartilage In Long-Term Primary Cultures Of Human Fetal
Epiphyseal Chondrocytes On A Hydrogel Substrate, 37 Arthritis &
Rheumatism 13381349 (1994) (“Reginato”).
5 Cosmobio, http://www.cosmobio.co.jp/export_ e/products/detail/
alginate.asp?entry_id= 12589 (Accessed Sept. 12, 2014).
3
Appeal 2016-002682
Application 13/320,585
The Examiner finds the combination of Tan and Risbud obvious
because “a combined composition of degradable PLGA/gelatin microspheres
and degradable hydrogel would have the characteristics of sufficient
exchange of nutrients and wastes as well as a tissue engineering platform
suitable for the transplantation of cells characterized by 3-D immobilization
and maintaining the differentiated phenotype of chondrocytes’ ’’ {id.).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that claim 1 is obvious over Tan,
Risbud, and Reginato?
Findings of Fact
1. Tan teaches “PLGA/gelation microspheres were fabricated . . .
ED AC was used to covalently immobilize RGDS peptides onto the
PLGA/gelatin microspheres” (Tan 229, col. 2).
2. Tan teaches “after PBS ... or DMEM . . . incubation, many
micron pores emerged on the PLGA/gelatin . . . and PLGA/gelatin-RGDS
. . . microspheres” (Tan 233, col. 2).
3. Tan teaches “to detect the chondrocyte viability as a function of
culture time . . . The viability on the control PLGA, PLGA/gelatin, and
PLGA/gelatin-RGDS microspheres increased 2, 2.3, and 2.4 times compared
to 1 day after the cells were cultured for 7 day[s]” (Tan 234, col. 2).
4. Tan teaches “[cjompared to that of the control PLGA
microspheres, a significantly higher optical density (p < 0.05) which is
proportional to cell viability, was recorded on the PLGA/gelatin and
PLGA/gelatin-RGDS microspheres after the cells were cultured for 3
day[s]” (Tan 234, col. 2).
4
Appeal 2016-002682
Application 13/320,585
5. Tan teaches “the PLGA/gelatin-RGDS microspheres are
potentially applicable as cell carriers, which may be further piled into a
three-dimensional scaffold for in vivo chondrogenesis” (Tan 237, col. 1).
6. Risbud teaches:
Specially designed biomaterial scaffolds are one of the key
components in tissue engineering. Research is focused on
developing bioresorbable scaffolds that exhibit optimal physical
properties coupled with excellent biocompatibility. Scaffolds
act as shape and guidance templates for in vitro and in vivo
tissue development. For cartilage and bone tissues, a suitable
scaffold provides initial mechanical stability and supports even
cell distribution. Natural polymeric gels, such as hyaluronic
acid, collagen, alginate and chitosan, have been used
successfully. These scaffolds permit 3D immobilization of
cells and maintain the differentiated phenotype of chondrocytes.
(Risbud 352, col. 2; citations omitted).
7. Figure 3 of Risbud is reproduced below:
Polymer fiber Embedding medium
\ i'e.g. hydrogel)
Chondrocyte or MSC
TRENDS te SkijgShnoiQgy
“Fig. 3. Schematic drawing showing the strategy of developing tissue
engineered cartilage constructs using fibres and embedding substances.
5
Appeal 2016-002682
Application 13/320,585
Embedding substances offer 3D immobilization and uniform distribution of
cells in the fibre mesh” (Risbud 353, col. 2).
8. Risbud teaches “solid bio-resorbable fibre scaffolds or other
porous structures are used to achieve initial biomechanical stability.
Synthetic biodegradable poly(a-hydroxy esters) such as polylactic acid
(PLLA), polyglycolic acid (PGA) and copolymer PLGA have been used
extensively in this context” (Risbud 352, col. 2 to 353, col. 1).
9. Risbud teaches: “Injectable in situ crosslinkable polymeric
preparations that entrap cells have been designed and techniques that
combine the advantages of both porous fibre structures and gels are being
explored as suitable alternatives to either gels or fibre scaffolds” (Risbud
353, col. 1).
10. Reginato teaches chondrocytes “were cultured for up to 180
days on plastic dishes previously coated with the hydrogel, poly-(2-
hydroxyethyl methacrylate)” (Reginato 1338, 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.”
KSRInt’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
Analysis
We adopt the Examiner’s findings regarding the scope and content of
the prior art (Final Act. 3-7; FF 1-10) and agree that the claimed
6
Appeal 2016-002682
Application 13/320,585
composition would have been obvious over the teachings of Tan, Risbud,
and Reginato.6 We address Appellants’ arguments below.
Appellants contend: “In the context of Tan, where the PLGA/gelatin-
RGDS microspheres are consistently referred to as being capable of forming
scaffolds, it can be seen that the microspheres and the cells are the
components that are envisaged for forming a three-dimensional scaffold on
their own with no other components” (App. Br. 5).
We do not find this argument persuasive. “Non-obviousness cannot
be established by attacking references individually where the rejection is
based upon the teachings of a combination of references.” In re Merck &
Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). A reference “must be read, not
in isolation, but for what it fairly teaches in combination with the prior art as
a whole.” Id.
Here, Risbud teaches an engineered tissue composed of living
chondrocyte cells, a degradable hydrogel, and a degradable polymer (FF 7).
Risbud teaches the hydrogel may be composed of alginate and chitosan (FF
6; cf. Spec. 14:28) and the degradable polymer may be composed of PLGA
(FF 8).
While Risbud does not teach the PLGA polymer is in particle form or
comprises a binding reactive group, Tan teaches PLGA microspheres with
the binding reactive group of RGDS peptides (FF 1). Tan teaches the PLGA
microspheres are degradable (FF 2) and increase cell viability (FF 3—4). Tan
6 We need not rely upon CosmoBio for any limitation of claim 1. The Board
may rely on fewer than all of the references relied on by the Examiner in an
obviousness rationale without designating it as a new ground of rejection. In
re Bush, 296 F.2d 491, 496 (CCPA 1961).
7
Appeal 2016-002682
Application 13/320,585
further teaches “the PLGA/gelatin-RGDS microspheres are potentially
applicable as cell carriers, which may be further piled into a three-
dimensional scaffold for in vivo chondrogenesis” (FF 5).
We therefore agree with the Examiner’s obviousness position that the
ordinary artisan, interested in forming engineered tissue composed of cells,
hydrogel, and polymer cell carriers such as PLGA as disclosed by Risbud,
would have utilized Tan’s PLGA/gelatin-RGDS microspheres as cell
carriers for improved cell viability (FF 4) in the hydrogel matrix of Risbud
(FF 7) (see Ans. 5).
Appellants contend “Tan clearly distinguishes porous or hydrogel
scaffolds from microspheres and provides that porous scaffolds produce less
cell proliferation than cells cultured on microspheres” (App. Br. 6).
Appellants contend:
In view of these teachings of Tan against the use of porous or
hydrogel scaffolds in conjunction with the teachings of Tan
regarding forming 3D scaffolds from microspheres, one of
ordinary skill in the art would not find it obvious to use a
hydrogel formable to a hydrogel matrix comprising cavities
formable by the faster degrading surface cross-linked particle.
{id.).
We find the teaching away arguments unpersuasive. A teaching away
requires a reference to actually criticize, discredit, or otherwise discourage
the claimed solution. See In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004)
(“The prior art’s mere disclosure of more than one alternative does not
constitute a teaching away from any of these alternatives because such
disclosure does not criticize, discredit, or otherwise discourage the solution
claimed”).
8
Appeal 2016-002682
Application 13/320,585
Here, Tan recites microspheres and porous hydrogel scaffolds as
alternatives, where “cell culture on the microspheres may produce a larger
number of cells” (Tan 228, col. 2). However, Tan never specifically teaches
that hydrogel scaffolds are undesirable or will not work, only that
microspheres are a desirable approach (FF 5). Disclosed examples and
preferred embodiments do not constitute a teaching away from a broader
disclosure or non-preferred embodiments. In re Susi, 440 F.2d 442, 446 n.3
(CCPA 1971).
Appellants contend “in the unlikely event the microspheres of Tan
were combined with the hydrogel matrices of Risbud, this combination fails
to establish the subject matter of the present claims. The combination would
only result in the microspheres being grown on the surface of one of the
preformed hydrogel matrices and not in the preformed hydrogel matrices”
(App. Br. 8).
We do not find this argument persuasive because Risbud clearly
demonstrates embedding the polymers, such as PLGA, within the three
dimensional hydrogel medium (FF 7). Indeed, Risbud suggests such a
combination, teaching “polymeric preparations that entrap cells have been
designed and techniques that combine the advantages of both porous fibre
structures and gels are being explored as suitable alternatives to either gels
or fibre scaffolds” (FF 8). The ordinary artisan would find it obvious that
the microspheres would therefore be “in” the hydrogel, as required by claim
1 {see FF 7).
Appellant contends “the contemplated modification would still fail to
render obvious the recited composition where at least one degradable
9
Appeal 2016-002682
Application 13/320,585
hydrogel of the mixture is formable to a hydrogel matrix comprising cavities
formable by the faster degrading surface cross-linked particle” (App. Br. 9).
We find this argument unpersuasive because the engineered tissue
rendered obvious by Risbud and Tan, comprising chondrocytes growing
PLGA-gelatin RGDS microspheres embedded in a hydrogel matrix (FF 1-
8), would inherently result in degradation of the PLGA microspheres to form
pores as shown by Tan (FF 2). We therefore agree with the Examiner that
“as the composition of the combined prior art comprises the same
components as claimed, it is inherent in the prior art that the composition
would comprise a hydrogel matrix comprising cavities formable by the
faster degrading surface cross-linked particle” (Ans. 10).
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that claim
1 is obvious over Tan, Risbud, and Reginato.
SUMMARY
In summary, we affirm the rejection of claim 1 under 35 U.S.C.
§ 103(a) as obvious over Tan, Risbud, and Reginato. Claims 2-6 and 8-26
fall with claim 1.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
AFFIRMED
10