Gregory Bleck et al.

Patent Trials and Appeals Board

May 4, 2021

2019006293 (P.T.A.B. May. 4, 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.
13/419,045 03/13/2012 Gregory Thomas Bleck GALA-31720.202 6788
145292 7590 05/04/2021
Casimir Jones, S.C.
2275 Deming Way, Suite 310
Middleton, WI 53562
EXAMINER
HOLLAND, PAUL J
ART UNIT PAPER NUMBER
1656
NOTIFICATION DATE DELIVERY MODE
05/04/2021 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
docketing@casimirjones.com
pto.correspondence@casimirjones.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
________________

Ex parte GREGORY THOMAS BLECK,
IAN JOHN COLLINS, and MARK JOSEPH FREY1
________________

Appeal 2019-006293
Application 13/419,045
Technology Center 1600
________________

Before JOHN G. NEW, TAWEN CHANG, and RACHEL H. TOWNSEND,
Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1 We use the term “Appellant” to refer to the “applicant” as defined in
37 C.F.R. § 1.142. Appellant identifies Catalent Pharma Solutions, LLC as
the real party-in-interest. App. Br. 3.
Appeal 2019-006293
Application 13/419,045

2
SUMMARY
Appellant files this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Non-Final Rejection of claims 10–12 and 17–25. Specifically,
claim 10 stands rejected as unpatentable under 35 U.S.C. § 103 as being
obvious over the combination of Ruoslahti et al. (US 6,277,812 B1, August
21, 2001) (“Ruoslahti I”), Meade et al. (US 2005/0160483 A1, July 21,
2005) (“Meade”), Do et al. (WO 03/089636 A1, October 30, 2003) (“Do”),
Z. von Marschall et al., Decorin is Processed by Three Isoforms of Bone
Morphogenetic Protein-1 (BMP1), 391 BIOCHEM. AND BIOPHYS. RES.
COMMS. 1374–78 (2010) (“von Marschall”) and Bremel et al. (US 6,852,510
B2, February 8, 2005) (“Bremel”).
Claims 11, 12, 19, and 25 stand rejected as unpatentable under 35
U.S.C. § 103(a) as being obvious over Ruoslahti I, Meade, Do, von
Marschall, Bremel, and Pang (US 2003/0124152 A1, July 3, 2003) (“Pang”).
Claims 17, 18, 20, and 21 stand rejected as unpatentable under 35
U.S.C. § 103(a) as being obvious over Ruoslahti I, Meade, Pang, Do, von
Marschall, Bremel, and Ohigashi (US 2010/0145020 A1, June 10, 2010)
(“Ohigashi”).2
Claims 22–24 stand rejected as unpatentable under 35 U.S.C. § 103(a)
as being obvious over Ruoslahti I, Meade, Pang, Do, von Marschall, Bremel,

2 The Examiner also cites to Ohigashi (WO 2008/117735 A1, October 2,
2008) (in Japanese).
Appeal 2019-006293
Application 13/419,045

3
Ohigashi, and Hasslacher et al. (WO 2011/012726 A2, February 3, 2011)
(“Hasslacher”).
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

NATURE OF THE CLAIMED INVENTION
Appellant’s claimed invention is directed to improved decorin
compositions and methods of their production. Spec. Abstr.

REPRESENTATIVE CLAIM
Independent claim 10 is representative of the claims on appeal,
and recites:
10. A host cell comprising a retroviral vector comprising a
nucleic acid sequence encoding a fusion protein comprising an
alpha-lactalbumin signal sequence operably linked to a sequence
encoding a decorin core protein, wherein said fusion protein
comprises the amino acid sequence of SEQ ID NO:4, said host
cell is a Chinese Hamster Ovary (CHO) cell, and said host cell
secretes non-gagylated mature decorin core protein at a rate of
greater than 10 picograms/cell/day when cultured.

App. Br. 13.

ISSUES AND ANALYSES
We adopt the Examiner’s findings, reasoning, and conclusion that the
claims on appeal are prima facie obvious over the combined cited prior art.
We address the arguments raised by Appellant below.

Appeal 2019-006293
Application 13/419,045

4
Issue

Appellant argues that the Examiner erred because nothing in the prior
art would have led a person of ordinary skill in the art to identify Ruoslahti I
as the lead prior art or motivated such person to make the specific
modification to Ruoslahti I (viz., use of retroviral vectors and the claimed
signal sequence in the Ruoslahti I process), as concluded by the Examiner.
App. Br. 7.

Analysis
The Examiner finds that Ruoslahti I teaches a vector comprising a
nucleic acid encoding a fusion protein comprising a maltose binding protein
operably linked to a decorin core protein, in which the decorin core protein
comprises a mutation at the serine in position 4, which is changed to coding
for threonine or alanine. Non-Final Act. 4 (see Ruoslahti I col. 3, ll. 37–41).
The Examiner notes that the mutation of serine at position 4 to alanine
would cause the decorin core protein of Ruoslahti I to share 100% identity
with full-length human decorin, and 95.6% identity to the amino acid
sequence of SEQ ID NO: 4. Id. The Examiner finds that the mutation at
serine 4 to alanine would result in a non-gagylated decorin protein. Id.
(citing Ruoslahti I col. 3, ll. 10–23, col. 10, ll. 40–52; see also Non-Final
Act. App’x A, B).
The Examiner further finds that Ruoslahti I teaches that the decorin
can be rendered glycosylaminoglycan-free by, inter alia, mutation. Non-
Final Act. 4 (citing Ruoslahti I col. 7, ll. 64–67). The Examiner finds that
Ruoslahti I also teaches host cells, e.g., Chinese Hamster Ovary (“CHO”)
Appeal 2019-006293
Application 13/419,045

5
and COS-1 cells, comprising the vector. Id. at 5 (citing Ruoslahti I col. 10,
ll. 59–67, col. 11, ll. 18–20).
However, the Examiner finds that Ruoslahti I does not teach that the
vector of claim 10 is a retroviral vector encoding an alpha-lactalbumin signal
sequence operably linked to a [sequence encoding a] decorin core protein, in
which the fusion protein comprises the amino acid sequence of SEQ ID
NO:4, and in which the host cell secretes non-gagylated mature decorin
protein at a rate of greater than 10 picograms/cell/day when cultured. Non-
Final Act. 5.
The Examiner finds that Meade teaches a vector comprising a nucleic
acid including a decorin protein-coding sequence operatively linked to a
tissue specific promoter, such as an alpha-lactalbumin signal sequence,
which directs the expression of decorin and that results in the secretion of
the protein. Non-Final Act. 5 (citing Meade ¶¶ 23, 31, 128, 161–163).
The Examiner finds that Do teaches fusion proteins combining alpha-
lactalbumin with glycoproteins for transfection and recombinant expression
of the proteins in cells. Non-Final Act. 5 (citing Do Abstr., 1). The
Examiner finds that Do also teaches an alpha-lactalbumin signal peptide
sequence that is 100% identical to the alpha-lactalbumin signal sequence of
SEQ ID NO: 4. Id. (see also Non-Final Act. App’x C).
The Examiner finds that von Marschall teaches that the amino-
terminus of decorin and the propeptide begins with GPFQQ by processing of
the leader sequence and teach the leader sequence, propeptide, and mature
peptide of human decorin. Non-Final Act. 5 (citing von Marschall 1376).
Appeal 2019-006293
Application 13/419,045

6
The Examiner also points to Figure 18 of von Marschall, which is
reproduced below.

Figure 18 of von Marschall depicts the notation of the leader,
propeptide, and first several amino acids of the human
preprodecorin sequence

The Examiner finds that Bremel teaches the production of proteins in
host cells, such as CHO cells, containing multiple integrated copies of a
retroviral integrating vector useful for the production of pharmaceutical
proteins at high levels. Non-Final Act. 6. The Examiner finds that Bremel
teaches that the integrating vectors contain at least one exogenous gene
operably linked to a promoter, and that, in some embodiments, the promoter
is an alpha-lactalbumin promoter and a secretion signal that facilitate
secretion of the protein when cultured, whereby the host cells synthesize a
protein greater than about 10 picograms/cell/day of the protein of interest.
Id. (citing Bremel Abstr., col. 2, ll. 19–35, cols. 2–3, ll. 61–25, cols. 4–5, ll.
61–6).
The Examiner concludes that it would have been obvious to a person
of ordinary skill in the art to combine the teachings of Ruoslahti I, Meade,
Do, von Marschall, and Bremel to design a retroviral vector encoding a
construct having the amino acid sequence of SEQ ID NO: 4 for expression
in a CHO host cell. Non-Final Act. 6. The Examiner notes that both
Ruoslahti I and Meade teach fusion proteins of decorin having an alpha-
lactalbumin signal sequence and production in a CHO cell. Id. The
Appeal 2019-006293
Application 13/419,045

7
Examiner further notes that Do teaches alpha lactalbumin fusion to
glycoproteins aids in protein expression, and that von Marschall teaches the
leader sequence and propeptide of human decorin. Id. The Examiner
further cites Bremel as teaching that production of proteins in host cells,
such as CHO cells containing multiple integrated copies of a retroviral
integrating vector, are useful for the production of pharmaceutical proteins at
high levels of greater than about 10 pg/cell/day. Id.
The Examiner concludes that a skilled artisan would have had a
reasonable expectation of success, with a reasonable level of predictability,
and would be motivated to combine the teachings of the references. The
Examiner reasons that this is so, because a skilled artisan would understand
that (1) Meade teaches that the alpha-lactalbumin signal sequence can be
operably linked to decorin to target its expression in host cells; (2) Do
teaches alpha lactalbumin fusion to glycoproteins aids in protein expression;
(3) von Marschall teaches that the leader sequence of human decorin is
processed and cleaved off in the cell; and (4) Bremel teaches that production
of proteins in host cells, such as CHO cells, containing multiple integrated
copies of a retroviral integrating vector containing promoters such as alpha
lactalbumin are useful for the production of pharmaceutical proteins at high
levels of greater than about 10 pg/cell/day. Id. at 7. Therefore, the
Examiner concludes, the claimed invention would have been prima facie
obvious to one of ordinary skill in the art at the time of invention. Id.
Appellant argues that, as the Examiner acknowledges, Ruoslahti I
does not teach the use of retroviral vectors or the claimed signal sequence.
App. Br. 7. Appellant asserts that nothing in the prior art would have led a
person of ordinary skill in the art to identify Ruoslahti I as the lead prior art
Appeal 2019-006293
Application 13/419,045

8
or would have motivated such a person to make specific modifications to
Ruoslahti I (viz., use of retroviral vectors and the claimed signal sequence in
the Ruoslahti I process) to make the invention. Id. (citing Procter & Gamble
Co. v. Teva Pharms. USA, Inc., 566 F.3d 989 (Fed. Cir. 2009) and Daiichi
Sankyo Co., Ltd v. Matrix Labs, Ltd., 619 F.3d 1346 (Fed. Cir. 2010)).
Specifically, Appellant asserts, given the state of the art in 2010, a skilled
artisan would not have looked to Ruoslahti I, because Ruoslahti personally
stated in 2010 that the previously described methods for producing decorin
had been insufficient for producing clinically useful amounts of decorin. Id.
According to Appellant, at the time the invention was made, the art was
looking away from expression of decorin as a stand-alone protein and was
instead attempting to target decorin via a “coxsackie adenovirus receptor”
(“CAR”) protein system due to problems with decorin production. Id.
Appellant points to the Declaration of Dr. Gregory Bleck3 (the “Bleck
Declaration”) as establishing that the art at the time of invention had tried
and failed to solve the problem, notwithstanding presumed knowledge of the
references cited by the Examiner. App. Br. 7. Appellant notes that each of
the Examiner’s four rejections in the appeal before us relies at least on a
base combination of Ruoslahti I, Meade, and Bremel. Id. Appellant
contends that the evidence presented in the Bleck Declaration establishes
that Dr. Ruoslahti is a pioneer in the biology of decorin and has published
extensively upon that subject. Id. (citing Bleck Decl. ¶ 4). However, Dr.
Bleck testifies that, 20 years after the publication of Ruoslahti I, and 10
years after the publication of Meade and Bremel, Dr. Ruoslahti observed in a

3 Dr. Bleck is one of the named inventors.
Appeal 2019-006293
Application 13/419,045

9
peer-reviewed publication that decorin had not yet reached the clinic
because of difficulties in production, stating that:
Despite the positive results in animal models, decorin has not
reached the clinic. One reason is that as a protein therapeutic, it
is relatively difficult to manufacture. Enhancing the activity of
decorin is a potential solution to this problem, as it would make
it possible to achieve the same result with a lower dosage.

Id. at 7–8 (citing Bleck Decl. ¶ 4 (quoting T.A.H. Järvinen et al., Target-
Seeking Antifibrotic Compound Enhances Wound Healing and Suppresses
Scar Formation in Mice, 107(50) PNAS 21671–76 (2010) (“Järvinen”)
(internal citations omitted))).
Appellant notes that Dr. Bleck further opines that, instead of
employing CHO cells to manufacture decorin, as taught by Ruoslahti I,
transgenic animal milk, as taught by Meade, or a retroviral expression
system, as taught in Bremel, Dr. Ruoslahti used a complicated fusion with a
CAR peptide to target decorin, so that lower dosages could be employed.
App. Br. 8 (citing Bleck Decl. ¶ 6). Similarly, argues Appellant, Dr.
Ruoslahti did not use any of the many commercial expression systems
available in 2010 for the expression of decorin core protein or glycosylated
decorin. Id. Appellant asserts that, based upon the prior art as a whole, it
would have been evident to a skilled artisan in 2010 that there would not
have been a reasonable expectation of success in obtaining high-level
expression (i.e., greater than 10 picograms/cell/day) of decorin core protein
in any expression system. Appellant further asserts that there likewise
would have been no reason to expect that the retroviral expression system
recited in the claims would be better than any of the expression systems used
Appeal 2019-006293
Application 13/419,045

10
for the twenty years prior to 2010, all of which had failed to produce
sufficient amounts of decorin for clinical use. Id. (citing Bleck Decl. ¶ 7).
Appellant points to the analysis set forth in KSR Int’l Co. v. Teleflex
Inc., 550 U.S. 398 (2007), which requires identifying a starting reference
point or points “in the art, prior to the time of invention, from which a
skilled artisan might identify a problem and pursue potential solutions. App.
Br. 8 (quoting Eisai Co. Ltd v. Dr. Reddy’s Labs., Ltd., 533 F.3d 1353, 1359
(Fed. Cir. 2008)). Appellant argues that, to the contrary, the state of the art
in 2010 was such that contemporaneous methods to produce clinically
sufficient amounts of decorin were unsuccessful. Id. Appellant asserts that,
against this background, to solve the problem of decorin production, a
person of ordinary skill in the art could have tried a potentially infinite
combination of expression systems and vectors, signal sequences, host cells,
etc., in attempting to produce decorin in clinically useful amounts. Id.
Therefore, Appellant contends, the prior art provides no reason as to why a
skilled artisan would have narrowed the prior art universe to the use of the
claimed expression system for the production of decorin. Id.
The Examiner responds that one cannot show nonobviousness by
attacking references individually where the rejections are based on
combinations of references. Ans. 16 (citing, e.g., In re Keller, 642 F.2d 413,
426 (C.C.P.A. 1981)). The Examiner finds that Appellant’s arguments are
apparently based upon the premise that the claims are not obvious because
they are not anticipated, however, the Examiner notes, lack of anticipation is
not evidence of non-obviousness. Id.
The Examiner finds that Appellant’s arguments do not apply the
appropriate standard for obviousness, because obviousness does not rely
Appeal 2019-006293
Application 13/419,045

11
upon what a single researcher has done or attempted to do in expressing a
protein. Ans. 17. Rather, explains the Examiner, the standard of
obviousness relies upon whether the differences that exist between the
claims and the closest prior art would have been obvious to one of ordinary
skill in the art based on the prior art as a whole. Id. (citing KSR, 550 U.S. at
415–21).
It is the Examiner’s position that it would have been predictable for a
person of ordinary skill in the art to combine and substitute the proteins of
Bremel with the decorin proteins of Ruoslahti I, and to use retroviral vectors
for the expression of recombinant decorin, with a high level of predictability
and a reasonable expectation of success. App. Br. 17. The Examiner finds
that Bremel acknowledges that these retroviral vectors overcome the
problem of stability and the expression of recombinant proteins in
mammalian cell lines, and would increase the expression of the recombinant
proteins to high levels. Id. at 17–18. The Examiner reasons that, given that
Bremel is focused on high level expression of therapeutic proteins, and
because decorin is a therapeutic protein, one of ordinary skill in the art
would have had a reasonable expectation of success in applying the
techniques of Bremel to the decorin proteins of Ruoslahti I. Id. at 18.
The Examiner notes that Bremel acknowledges that production of
proteins in host cells, such as CHO cells, containing multiple integrated
copies of a retroviral-integrating vector with promoters such as alpha
lactalbumin, are useful for the production of pharmaceutical proteins at high
levels of greater than about 10 pg/cell/day. Ans. 18. The Examiner further
finds that Bremel also acknowledges the problem, taught by Järvinen, of
generating stable cell lines and production of high expression levels of
Appeal 2019-006293
Application 13/419,045

12
recombinant protein for therapeutic purposes. Id. (citing Bremel cols. 1–2,
ll. 46–11). The Examiner finds that Bremel remedies this perceived problem
through multiple integration of copies of a retroviral integrating vector
containing promoters such as alpha lactalbumin to produce high levels of
recombinant protein. Id.
The Examiner concludes that the preponderance of the evidence in the
prior art outweighs the opinions presented in the Bleck Declaration. Ans.
18–19. The Examiner finds that although Dr. Ruoslahti was admittedly a
pioneer in the field, he did not use any of the many commercial expression
systems available in 2010 for expression of decorin core protein or
glycosylated decorin. Id. at 19. The Examiner concludes that Dr. Bleck’s
opinion that a person of ordinary skill in the art would not have had a
reasonable expectation of success in obtaining high-level expression of
decorin core protein, amounts to an opinion unsupported by a factual basis.
Id.
We are also not persuaded by Appellant’s arguments. As an initial
matter, we disagree with the Examiner’s standard of obviousness. KSR
holds that Section 103:
[F]orbids issuance of a patent when “the differences between the
subject matter sought to be patented and the prior art are such
that the subject matter as a whole would have been obvious at
the time the invention was made to a person having ordinary skill
in the art to which said subject matter pertains.

KSR, 550 U.S. at 399.
Nevertheless, we find that Appellant does not contest the Examiner’s
findings that the cited prior art teaches or suggests all of the limitations of
the claims on appeal. Rather, Appellant contends, a person of ordinary skill
Appeal 2019-006293
Application 13/419,045

13
would have had no reason to start with the teachings of Ruoslahti I, and thus
would have had no motivation to combine the teachings of that reference
with the other references cited by the Examiner. Furthermore, Appellant
argues, given the state of the art at the time of invention, a person of
ordinary skill in the art would have had no reasonable expectation of success
in combining the references to produce the claimed composition “at a rate of
greater than 10 picograms/cell/day when cultured,” as recited in claim 10.
With respect to Appellant’s argument that a person of ordinary skill in
the art would “would certainly not have started with Ruoslahti 1” (see App.
Br. 7), we disagree. Ruoslahti I is directed to “a general method whereby
one skilled in the art can identify proteins which can bind to cell regulatory
factors or identify cell regulatory factors which bind to a certain family of
proteins.” Ruoslahti I col. 8, ll. 14–17. Specifically, Ruoslahti I teaches
that:
[T]he invention teaches the discovery that decorin and biglycan
bind TGF-ßs and MRF and that such binding can inhibit the cell
regulatory functions of TGF-ßs. Further, both decorin and
biglycan are about 80% homologous and contain a leucine-rich
repeat of about 24 amino acids in which the arrangement of the
leucine residues is conserved.

Id. at col. 8, ll. 20–27. Ruoslahti I thus teaches the importance of decorin
and provides motivation to a person of ordinary skill in the art to seek a way
to synthesize the protein in significant quantities. Furthermore, it is logical
to believe that a skilled artisan, seeking to synthesize decorin, would look
initially to the teachings of a “pioneer in the biology of decorin and [one
who] has published extensively on decorin,” as the Bleck Declaration
admits. See Standard Oil Co. v. Am. Cyanamid Co., 774 F.2d 448, 454
Appeal 2019-006293
Application 13/419,045

14
(Fed. Cir. 1985) (holding that a person of ordinary skill in the art “thinks
along the line of conventional wisdom in the art,” they are also “presumed to
be aware of all the pertinent prior art”).
In support of Appellant’s argument that a skilled artisan would have
had no reasonable expectation of success in combining the teachings of the
references, Appellant relies primarily upon the Bleck Declaration which, in
turn relies primarily upon Järvinen. Dr. Bleck acknowledges that Dr.
Ruoslahti “is a pioneer in the biology of decorin and has published
extensively on decorin.” Bleck Decl. ¶ 4. Dr. Bleck then points to Järvinen
(of which Dr. Ruoslahti is a co-author), which states that: “Despite the
positive results in animal models, decorin has not reached the clinic. One
reason is that as a protein therapeutic, it is relatively difficult to
manufacture.” Id. (quoting Järvinen 21671 (internal citations omitted)).
Appellant points out that Järvinen, which was published in 2010, describes
the state of the art considerably after the filing of Ruoslahti I, which was
filed in 1995 and Bremel, which was filed in 2001.
However, Järvinen states that, due to the relative difficulty of
manufacturing decorin as a protein therapeutic, decorin “has not reached the
clinic.” We interpret this latter phrase to mean that, as of 2010, the
difficulties of manufacturing pharmaceutical decorin prevented it from being
produced at a scale suitable for clinical trials regarding efficacy to be carried
out in humans, which involves trials in large patient groups. However, such
a scaled-up level of production, with its attendant difficulties, is not recited
by the claims on appeal, which require only that cultured host CHO cells
“secrete[ ] non-gagylated mature decorin core protein at a rate of greater
than 10 picograms/cell/day….”
Appeal 2019-006293
Application 13/419,045

15
Bremel teaches:
[T]he production of proteins in host cells, and, more particularly
to host cells containing multiple integrated copies of an
integrating vector. Suitable integrating vectors for use in the
present invention include retrovirus vectors, lentivirus vectors,
transposon vectors, and adeno-associated virus vectors.… by
using the integrating vectors at a high multiplicity of infection.
The host cells are useful for producing pharmaceutical proteins,
variants of proteins for use in screening assays, and for direct use
in high throughput screening.

Bremel Abstr. (emphasis added). Specifically, Bremel teaches:
The present invention further provides a method of producing a
protein of interest comprising: 1) providing a host cell
comprising a genome, the genome comprising at least two
integrated copies of at least one integrating vector comprising an
exogenous gene operably linked to a promotor, wherein the
exogenous gene encodes a protein of interest, and 2) culturing
the host cells under conditions such that the protein of interest is
produced. In some preferred embodiments, the integrating vector
further comprises a secretion signal sequence operably linked to
said exogenous gene. In other embodiments, the methods further
comprise step 3) isolating the protein of interest.

Id. at col. 4, ll. 25–36. Bremel also teaches that:
In some embodiments of the present invention, the promoter is
selected from the group consisting of the alpha-lactalbumin
promoter, cytomegalovirus promoter and the long terminal
repeat of Moloney murine leukemia virus. In other preferred
embodiments, the integrating vectors further comprise a
secretion signal operably linked to the exogenous gene.

Id. at cols 2–3, ll. 65–4. Finally, Bremel teaches, in its Examples, protein
yields of 22.5 pg/cell/day. See id. at Ex. 7.
We agree with the Examiner (and Appellant does not contest), that the
remaining references teach the remaining limitations of the claims. Most
Appeal 2019-006293
Application 13/419,045

16
importantly, aside from noting the lack of manufacture at clinical testing
scale in Järvinen, Appellant provides no fact-based reason why a person of
skill in the art would have arrived at the conclusion that combining the
teachings of the cited references could not reasonably be expected to work to
achieve the production of decorin from a cultured CHO cell at a rate of
greater than 10 picograms/cell/day. We accord due deference to the quoted
statement in Järvinen, but neither Järvinen nor Appellant tells us what is
meant by “relative difficulty” in manufacturing decorin, what is difficult, or
how, or if that difficulty in manufacturing decorin at the clinical-level relates
to why one of ordinary skill in the art would not have combined the
teachings of the references cited by the Examiner. Absent any such
evidence or reasoning, we do not agree with Appellant that a skilled artisan
would not have had a reasonable expectation of success.
Appellant also argues that the Examiner’s reliance upon In re Wright,
569 F.2d 1124 (C.C.P.A. 1977) is inapposite, and that Wright supports the
non-obviousness of the claims. App. Br. 9. Specifically, Appellant points to
the Examiner’s reasoning that Appellant’s “contentions that the reference
patents are old are not impressive absent a showing that the art tried and
failed to solve the same problem notwithstanding its presumed knowledge of
the references.” Id. (quoting Non-Final Act. 16 (citing Wright)).
Appellant contends that Dr. Bleck’s testimony in his Declaration
establishes that the art tried, and failed, to solve the problem of decorin
production as a stand-alone protein, notwithstanding the teachings of the
references. App. Br. 9–10. Appellant points out that each of the four
rejections relies at least on a combination of Ruoslahti I, Meade, and
Bremel. Appellant asserts that Dr. Bleck’s testimony that, despite the fact
Appeal 2019-006293
Application 13/419,045

17
that Dr. Ruoslahti is a pioneer in the biology of decorin, even years after the
publication of Ruoslahti I, Meade, and Bremel references, Järvinen teaches
that decorin had not reached the clinic because of difficulties in production.
Id. at 10.
We do not find this persuasive for the reasons we have already
explained. Appellant has not provided any evidence or argument as to why
the difficulties in producing decorin at clinical trial levels would persuade a
person of ordinary skill in the art that there could be no reasonable
expectation of success in combining the teachings of the references to obtain
cultured host CHO cells that “secrete[ ] non-gagylated mature decorin core
protein at a rate of greater than 10 picograms/cell/day….” Absent any such
evidence or argument, we do not find Appellant’s reliance upon Wright as
showing why the claims are not obvious to be persuasive.
Finally, Appellant argues that the Examiner erred by not properly
considering the evidence presented in the Bleck Declaration. App. Br. 10.
Appellant contends that Dr. Bleck’s statements are based on the statements
made by Järvinen, and further based on Dr. Bleck’s experience in the field.
Id. at 11. Appellant asserts that the Examiner has failed to consider, or
failed to give any weight, to this evidence, and the related testimony by Dr.
Bleck. Id.
We disagree. The Examiner, in a prior Final Office Action, stated
that:
In the instant case, it is the examiner’s position that the
preponderance of the evidence in the prior art [see
rejection above and preceding paragraph] outweighs the
opinions presented in the declarations that because “the pioneer
in the field. Dr. Ruoslahti, did not use any of the many
commercial expression systems available in 2010 for expression
Appeal 2019-006293
Application 13/419,045

18
of decorin core protein or glycosylated decorin, it is apparent to
a person of ordinary skill in the art that there was not a
reasonable expectation of success for high level expression of
decorin core protein”, which lacks factual evidence.

Final Act. 17 (filed December 21, 2017. It is evident from this that the
Examiner weighed the testimony of Dr. Bleck against the teachings of the
prior art and finds the latter persuasive. We have explained why we are not
persuaded by Appellant’s arguments and why we agree with the Examiner’s
findings and conclusions. We consequently affirm the Examiner’s rejections
of the claims.

CONCLUSION
The Examiner’s rejection of claims 10–12 and 17–25 under 35 U.S.C.
§ 103 is affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136.

AFFIRMED

Claim(s)
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
10 103 Ruoslahti I,
Meade, Do,
von Marschall,
Bremel
10
11, 12, 19, 25 103 Ruoslahti I,
Meade, Do,
von Marschall,
Bremel, Pang
11, 12, 19,
25

Appeal 2019-006293
Application 13/419,045

19
17, 18, 20, 21 103 Ruoslahti I,
Meade, Do,
von Marschall,
Bremel, Pang,
Ohigashi
17, 18, 20,
21

22–24 103 Ruoslahti I,
Meade, Do,
von Marschall,
Bremel, Pang,
Ohigashi,
Hasslacher
22–24
Overall
Outcome
10–12,
17–25