Jiang Liu et al.

Patent Trials and Appeals Board

Sep 29, 2020

12063614 - (D) (P.T.A.B. Sep. 29, 2020)

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.
12/063,614 07/19/2010 Jiang Liu 291309.00002 9374
27419 7590 09/29/2020
FASKEN MARTINEAU DUMOULIN LLP
333 Bay Street, Suite 2400
Bay Adelalde Centre, Box 20
TORONTO, ONTARIO M5H 2T6
CANADA
EXAMINER
WESTERBERG, NISSA M
ART UNIT PAPER NUMBER
1618
MAIL DATE DELIVERY MODE
09/29/2020 PAPER
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.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JIANG LIU,
MICHAEL RICHARD JOHNSTON, and XIAO YU WU
Appeal 2019-005662
Application 12/063,614
Technology Center 1600
Before FRANCISCO C. PRATS, TAWEN CHANG, and
RACHEL H. TOWNSEND, 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, 7–23, 25–33, 35, 43, 84–89, and 93.
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM IN PART.

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant did not identify the real party in interest in the
Appeal Brief.
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STATEMENT OF THE CASE
The Specification states that the lymphatic system is “an anatomical
location which is frequently affected by cancer and other diseases.” Spec.
1:5–6. The Specification further states that
[c]ontrol of lymphatic metastasis improves the outcome of
many cancers. Presently, local-regional therapies, such as
surgery and radiation, are the most effective means of treating
regional lymphatics, but often do not completely eradicate all
lymphatic metastatic disease. Systemic chemotherapy is limited
by systemic side effects and often cannot effectively penetrate
the lymphatic system, presumably because of a ‘blood-lymph
barrier’. Lymphatic drug delivery becomes even more
compromised after extensive cancer surgery due to the
disruption of blood and lymphatic vessels. Currently, there is a
lack of effective treatment options for specifically targeting
lymphatic metastasis. Therefore, effective therapeutic
modalities based on a better understanding of the
pathophysiology of lymphatic system are clearly needed to
improve the treatment of tumor within the lymphatic system.
Id. at 3:8–20.
According to the Specification, “[t]he distinct physiological function
of the lymphatic system in the clearance of foreign particulate matters has
generated interest in the use of microparticulate systems for the targeting of
therapeutic agents to regional lymph nodes.” Spec. 3:21–24. Further
according to the Specification, “th[e] invention relates to the targeted
delivery of therapeutic agents formulated in conjunction with micro- and/or
nanoparticulate carriers to the lymphatics and lymph nodes and implantable
devices containing the particulate carriers.” Id. at 1:7–10.
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CLAIMED SUBJECT MATTER
The claims are directed to an implantable biocompatible and
biodegradable matrix. Claim 1 is illustrative:
1. An implantable biocompatible and biodegradable matrix
comprising a plurality of bioactive complexes disposed
throughout the matrix, the matrix selected to release the
bioactive complexes over a predetermined first time interval
when the matrix degrades,
each bioactive complex having a range of sizes sufficient
to selectively target and enter the lymphatic system upon
release from the matrix, the bioactive complex comprising at
least one particle forming material and at least one bioactive
agent disposed throughout the particle forming material,
the bioactive complex adapted to release an effective
amount of the at least one bioactive agent within the lymphatic
system over a second time interval.
Appeal Br. 12 (Claims App.).
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REJECTION(S)
A. Claims 1, 7–14, 18–23, 25–33, 35, 43, 84–89, and 932 are rejected
under 35 U.S.C. § 112(b) or 35 U.S.C. § 112 (pre-AIA), second
paragraph, as being indefinite. Ans. 3.
B. Claims 1, 7, 8, 14, 18–22, 25–31,3 35, 43, 84–89, and 934 are rejected
under pre-AIA 35 U.S.C. § 103(a) as being unpatentable over
Haynes,5 Kennedy,6 and optionally Illum.7 Ans. 4.
C. Claims 9–14, 23, and 32 are rejected under pre-AIA 35 U.S.C.
§ 103(a) as being unpatentable over Haynes, Kennedy, Illum, and
Guire.8 Ans. 10.
D. Claim 33 is rejected under pre-AIA 35 U.S.C. § 103(a) as being
unpatentable over Haynes, Kennedy, Illum, and Hennink.9 Ans. 11.
E. Claims 84, 85, and 87–89 are rejected under pre-AIA 35 U.S.C.
§ 103(a) as being unpatentable over Haynes, Kennedy, Lee,10
Berkland,11 and optionally Illum. Ans. 12.

2 The Examiner states in the Answer that claims 1, 7–14, 18–23, 25–33, 35,
43, and 84–93 are rejected as indefinite. However, claims 90–92 have been
cancelled. Appeal Br. 19 (Claims App.).
3 The Examiner did not include claim 31, which depends from claim 1 and
additionally recites that “the bioactive complex and/or matrix contain
additives,” in the list of the claims rejected as obvious over Haynes,
Kennedy, and optionally Illum. Appeal Br. 16 (Claims App.); Final Act. 5;
Ans. 4. However, in the body of the rejection the Examiner discusses the
prior art as teaching that additives can be added. Ans. 5, 7. Accordingly, we
understand that the obviousness rejection over Haynes, Kennedy, and
optionally Illum also applies to claim 31.
4 The Examiner states in the Answer that claims 1, 7, 8, 14, 18–22, 25–31,
35, 43, and 84–93 are rejected as obvious over Haynes, Kennedy, and
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OPINION
A. Indefiniteness rejection (claims 1, 7–14, 18–23, 25–33, 35, 43, 84–
89, and 93)
1. Issue
The Examiner concludes that the claims are indefinite because “the
functional limitations in [the] claim[s] are not clearly linked to the
structure(s) that provide that function.” Ans. 3. In particular, the Examiner
finds that the Specification provides only “a single exemplary formulation
with a ‘gelatin sponge’ and microparticles comprised of the drug paclitaxel
with PLGA,” and “it is not clear if this construct releases an ‘effective’
amount of paclitaxel within the lymphatic system.” Id. at 4.
Appellant contends that “the exemplary formulation must release an
effective dose as the results of intraoperative implantation of gelatin sponges

optionally Illum. However, claims 90–92 have been cancelled. Appeal Br.
19 (Claims App.).
5 Haynes et al., US 5,972,366, issued Oct. 26, 1999.
6 Kennedy et al., US 6,488,952 B1, issued Dec. 3, 2002.
7 L. Illum et al., Development of Systems for Targeting the Regional Lymph
Nodes for Diagnostic Imaging: In Vivo Behaviour of Colloidal PEG-Coated
Magnetite Nanospheres in the Rat Following Interstitial Administration, 18
PHARMACEUTICAL RES. 640 (2001).
8 Guire et al., WO 03/030879 A1, published Apr. 17, 2003.
9 Hennink et al., US 2002/0131952 A1, published Sept. 19, 2002.
10 Woo-kyoung Lee et al., Investigation of the Factors Influencing the
Release Rates of Cyclosporin A-loaded Micro- and Nanoparticles Prepared
by High-Pressure Homogenizer, 84 J. CONTROLLED RELEASE 115 (2002).
11 Cory Berkland et al., PLG Microsphere Size Controls Drug Release Rate
through Several Competing Factors, 20 PHARMACEUTICAL RES. 1055
(2003).
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containing PLGA-PTX and PLM-Dox significantly reduced lymphatic
tumor metastases in experimental animal tumor models.” Appeal Br. 4.
In response, the Examiner asserts that the rejection is not one of lack
of written description; rather, the claims are indefinite because “[it] is not
clear if the cited structure possesses the required function and one of
ordinary skill in the art cannot [determine] the metes and bounds of the
claims.” Ans. 15.
The issue with respect to this rejection is whether a preponderance of
the evidence of record supports the Examiner’s conclusion that claims 1, 7–
14, 18–23, 25–33, 35, 43, 84–89, and 93 are indefinite.
2. Analysis
On the record before us, we find Appellant to have the better position.
The claims recite functional limitations, namely that “[the] bioactive
complex[es] ha[ve] a range of sizes sufficient to selectively target and enter
the lymphatic system upon release from the matrix” and are “adapted to
release an effective amount of the at least one bioactive agent within the
lymphatic system over a second time interval.”
Functional language in a claim does not, in and of itself, render a
claim indefinite. See, e.g., In re Swinehart, 439 F.2d 210, 213 (CCPA
1971). Nevertheless, the Examiner appears to argue that, in order to be
definite, the claim must recite the structures necessary to achieve the
functional limitation. See, e.g., Final Act. 4 (stating that “[t]he amendments
to claim 1 have not added sufficient structure to indicate how the claim[s]
are adapted to provide the claimed function”).
We are not persuaded. “[A]n inventor need not explain every detail
because a patent is read by those of skill in the art.” BASF Corp. v. Johnson
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Matthey Inc., 875 F.3d 1360, 1366 (Fed. Cir. 2017) (explaining that “[t]he
mere observation of information not ‘recited’ [in the claims] does not answer
the question whether a person of ordinary skill in the art would need to be
given the . . . information to understand . . . whether a composition is
‘effective to catalyze’ the . . . reactions”). Neither is it the function of the
claims to specifically exclude possible inoperative embodiments. In re
Dinh-Nguyen, 492 F.2d 856, 858–59 (CCPA 1974). Finally, although
functional language may render the scope of the claim broad, “breadth is not
to be equated with indefiniteness.” In re Miller, 441 F.2d 689, 693 (CCPA
1971).
To the extent the Examiner’s rejection is based on the finding that the
disclosure in the Specification does not support and/or enable the skilled
artisan to practice the full scope of the claims without undue
experimentation, the appropriate rejections are lack of written description
and/or enablement.
Accordingly, we reverse the Examiner’s rejection of claims 1, 7–14,
18–23, 25–33, 35, 43, 84–89, and 93 as indefinite.
B. Obviousness rejection over Haynes, Kennedy, and optionally Illum
(claims 1, 7, 8, 14, 18–22, 25–31, 35, 43, 84–89, and 93)
1. Issue
The Examiner finds that Haynes discloses a majority of the limitations
in claim 1, except it does not explicitly teach that a “bioactive complex
comprising at least one particle forming material and at least one bioactive
agent disposed throughout the particle forming material.” Ans. 6. However,
the Examiner finds that Kennedy discloses this limitation because it teaches
“a semisolid delivery system . . . comprised of a hydrogel . . . with a
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multiparticulate therapeutic delivery system,” including a preferred
embodiment wherein the multiparticulate component is comprised of the
biodegradable copolymer poly(lactic-co-glycolide) (PLGA)12 and the
therapeutic agent is dispersed in the particles. Id.
The Examiner concludes that it would have been obvious to a skilled
person to incorporate Kennedy’s therapeutic particles into a matrix taught by
Haynes, because Kennedy teaches that “porous matrixes can contain
particulates of therapeutic agent dispersed in a particle forming material
such as PLGA.” Ans. 7. The Examiner notes that the prior art teaches that
“[a] wide variety of drugs such as antibiotics or anti-inflammatories can be
delivered” and further notes that the prior art particle size of 20 nm–30 µm
overlap with, and thus renders prima facie obvious, the size ranges claimed
and described in the Specification as selectively targeting and entering the
lymphatic system. Id.
The Examiner finds that Haynes also does not discuss “particles
entering the lymphatic system.” Ans. 8. The Examiner finds, however, that
Illum discloses that “interstitially administered colloids with a size less than
100 nm will drain through the interstitium to initial lymphatic vessels and
should drain effectively from the site of injection th[r]ough the lymphatic
vessels to lymph nodes,” that “[t]he lymph nodes can be the site of spread of
metastatic disease and are a pathway for growth of malignancies,” that
“[u]ptake of administered colloids into the lymph system has been

12 The Specification states that “[s]uitable embodiments of the invention
include particles made from degradable polymers such as polylactides
(PLA), polyglycolides (PGA)[,] and their copolymers (PLGA).” Spec.
14:11–13.
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demonstrated for biodegradable nanospheres of PLGA surface modified
with poloxamine block co-polymers and copolymers of poly(lactide)-PEG,”
that uptake was also being demonstrated for “PEG coated magnetite
particles for use in imaging lymph nodes,” and that “[b]oth the size (<100
nm) and surface properties are necessary for satisfactory uptake in regional
lymph nodes.” Id.
The Examiner concludes that it would have been obvious to a skilled
artisan to combine Illum with the drug-containing matrix suggested by
Haynes in view of Kennedy to arrive at the claimed invention, because
Haynes teaches a general system of controlled release of drug particles from
a matrix and Illum teaches both that “metastasis can occur through the
lymph system” and that “particles can be targeted for uptake of the lymph
system by their size and surface characteristics to provide controlled release
of drug targeted to the lymphatic system.” Ans. 9.
Appellant contends that the Examiner’s suggested combination of
Haynes, Kennedy, and Illum would render Haynes unsatisfactory for its
intended purpose and/or change its principle of operation. Appeal Br. 5–6.
Appellant contends that the cited prior art does not suggest the limitation of
“the matrix selected to release the bioactive complexes over a predetermined
first time interval when the matrix degrades.” Id. at 6. Appellant contends
that the particle size to be used for the claimed invention would not have
been obvious to a skilled artisan. Id. at 7–8. Finally, Appellant contends
that secondary considerations of non-obviousness, specifically praise by
others, supports the non-obviousness of the claims. Id. at 9.
Appellant does not separately argue the claims. We therefore focus
our analysis on claim 1 as representative. The issue with respect to this
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rejection is (1) whether a preponderance of evidence supports the
Examiner’s conclusion that the combination of Haynes, Kennedy, and
optionally Illum renders claim 1 obvious, and, if so, (2) whether Appellant
has provided evidence of secondary considerations of non-obviousness that,
when considered together with the evidence of obviousness, shows claim 1
to be nonobvious.
2. Analysis
We agree with the Examiner that the combination of Haynes,
Kennedy, and Illum renders claim 1 obvious. We address Appellant’s
arguments below. Only those arguments timely made by Appellant in the
briefs have been considered; arguments not so presented are waived. See 37
C.F.R. § 41.37(c)(1)(iv) (2015); see also Ex parte Borden, 93 USPQ2d
1473, 1474 (BPAI 2010) (informative) (“Any bases for asserting error,
whether factual or legal, that are not raised in the principal brief are
waived.”).
Appellant contends that a skilled artisan would not have had reason to
combine Haynes with Kennedy and Illum to arrive at the claimed invention,
because the combination “would render the implantable absorbable sponges
in Haynes unsatisfactory for their intended purpose of providing local
therapeutic benefits.” Appeal Br. 5.
We are not persuaded. As the Examiner points out, Haynes’ invention
is not limited to providing local therapeutic benefits. Haynes states, for
example, that
[f]urther aspects of our invention include the ability to
control the rate and mode of release of the drug by choice of
concentration and type of adjuvant used, as well as the ability to
incorporate the drug at high payload (up to 4 gm Drug/gm
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Carrier Material). Thus, drugs can be delivered at high
concentrations to the adjoining tissue for long durations to
prevent the growth of bacteria, to facilitate wound healing and
to even give systemic drug delivery, when needed.
Haynes 21:51–58 (emphasis added).
Appellant next contends the prior art does not suggest the claim
limitation of “the matrix selected to release the bioactive complexes over a
predetermined first time interval when the matrix degrades.” Appeal Br. 6.
In particular, Appellant contends that, “even if the particles described in
Haynes dissociate from the matrix, such dissociation is not the result of the
degradation of the matrix nor is the matrix in Haynes selected to degrade
over a predetermined time interval as recited in Claim 1.” Id. Appellant
contends that “the mere fact that a matrix biodegrades and that particles may
be released therefrom does not suggest that the two are causally linked.” Id.
We are not persuaded. The Specification states:
[T]wo different types of biodegradation may generally be
identified. . . . [O]ne type of biodegradation may involve
cleavage of bonds (whether covalent or otherwise) in the
polymer backbone. . . . In contrast, another type of
biodegradation may involve cleavage of a bond (whether
covalent or otherwise) internal to a side chain or that connects a
side chain to the polymer backbone. For example, an
antineoplastic taxane or other chemical moiety attached as a
side chain to the polymer backbone may be released by
biodegradation. . . . As used herein, the term “biodegradation”
encompasses both general types of biodegradation.
Spec. 25:8–21. Thus, under the broadest reasonable interpretation in light of
the Specification, “matrix selected to release the bioactive complexes over a
predetermined first time interval when the matrix degrades,” as recited in
claim 1, encompasses the release of bioactive complexes resulting from
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cleavage of a bond, including a non-covalent bond, between the matrix and
the bioactive complex.
Haynes teaches that its drug microparticles may be bound to the
carrier matrix by “naturally occurring chemical affinity . . . between the . . .
microparticles and . . . the carrier,” including “hydrophobic interaction,
hydrogen bonding and ionic interactions,” as well as via “binding . . . to the
carrier . . . by means of [an] adjuvant which has chemical affinity for both.”
Haynes 7:19–37. Haynes teaches that drugs can be released from the carrier
via diffusion or flow of either the drug monomers or the drug microparticles
from the carrier matrix. Id. at 9:12–15. Haynes further teaches that the rate
of release of the drug monomers and microparticles may be adjusted by
various mechanisms including, e.g., selection of adjuvant materials. Id. at
9:11–10:15. Thus, Haynes teaches “matrix selected to release the bioactive
complexes over a predetermined first time interval when the matrix
degrades” under the broadest reasonable interpretation of that phrase,
because it suggests release of either drug monomers or microparticles
through cleavage of the bonds between the drug monomer/microparticle and
the carrier matrix.
Appellant contends that “the dual purpose in Haynes of the delivery of
. . . pharmaceuticals (or drugs) to targeted tissue at a controlled rate, while
maintaining its hemostatic function . . . requires independent degradation
and delivery mechanisms.” Appeal Br. 6. Appellant contends that “a
degradation based delivery mechanism as described in . . . instant claim 1
would change [Haynes’] principle of operation” because “Haynes
contemplates the release of drug microparticles being dependent upon the
firmness of attachment to (or entrapment within) the carrier material, which
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can be controlled by selection of primary adjuvant materials” and is
“dependent on the amount of tidal flow resulting from squeezing and
releasing of the preparation in the medium in which it is placed.” Id. Thus,
Appellant contends that “a degradation based delivery mechanism . . . would
change [Haynes’] principle of operation. Id.
As an initial matter, and as discussed above, the broadest reasonable
interpretation of the phrase “the matrix selected to release the bioactive
complexes over a predetermined first time interval when the matrix
degrades” encompasses the release of bioactive complexes bound to the
matrix through the cleavage of the bonds between drug particles or adjuvant
and the matrix, which is disclosed in Haynes. Thus, we are not persuaded
that Haynes’s dual purpose of maintaining hemostasis and delivery of drugs
“requires independent degradation and delivery mechanisms” or that the
claimed “degradation based delivery mechanism” would change Haynes’
principle of operation. As for Appellant’s argument that Haynes teaches that
the rate of release of drug particles may be “dependent on the amount of
tidal flow resulting from squeezing and releasing of the preparation in the
medium in which it is placed,” we note that, as the Examiner points out,
claim 1 does not preclude factors other than matrix degradation from
affecting release rate. Ans. 18.
Appellant also contends that a skilled artisan would not have had a
reasonable expectation of success in administering Illum’s particles
subcutaneously, because Illum teaches that “both the size (i.e., less than 100
nm) and surface properties of the particles are necessary for satisfactory
uptake in the regional lymph nodes for subcutaneously administered
nanoparticles” and, thus, a skilled artisan “would not be able to distinguish
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the qualities that would make a particle suitable for lymphatic uptake.”
Appeal Br. 7.
We are not persuaded. The relevant question for obviousness is
whether a skilled artisan would have had a reasonable expectation of success
in making or carrying out the claimed composition or process. See, e.g.,
PAR Pharm., Inc. v. TWI Pharm., Inc., 773 F.3d 1186, 1196 (Fed. Cir.
2014). Claim 1 is a composition claim and does not require subcutaneous
administration. Thus, an obviousness finding does not require a showing
that a skilled artisan would have reasonably expected to successfully
administer Illum’s particles subcutaneously.
Appellant contends that Illum teaches away from the claimed
invention because a skilled artisan in view of Illum “would not use particles
larger than 100 nm to achieve particle uptake in the regional lymph nodes
and as such Illum discourages the solution claimed.” Appeal Br. 8.
We are not persuaded. “[A] reference will teach away when it
suggests that the developments flowing from its disclosures are unlikely to
produce the objective of the applicant’s invention.” Syntex (U.S.A.) LLC v.
Apotex, Inc., 407 F.3d 1371, 1380 (Fed. Cir. 2005). In this case, claim 1
does not recite specific particle size ranges or require uptake in the regional
lymph node. Thus, Illum does not teach away from the claimed invention.
Indeed, claim 1 clearly contemplates use of particles that are 100 nm or
smaller. For example, claim 87, which depends from claim 1, recites
bioactive complex size “from about 10 nm to about 100 nm.” Appeal Br. 19
(Claims App.).
Appellant contends that Haynes’ disclosure of an overlapping range of
particle size would not render the claimed bioactive complex obvious
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because the claimed particles are “selected for a wholly different purpose
(e.g., anticancer treatment using cytotoxic agents) and are of a wholly
different structure (with particle forming material).” Appeal Br. 8.
We are not persuaded. As an initial matter, and as discussed above,
claim 1 does not recite specific ranges as to the size of the bioactive
complex. To the extent Appellant’s argument is that the limitation
“bioactive complex having a range of sizes sufficient to selectively target
and enter the lymphatic system upon release from the matrix” imposes
specific restrictions on the size of the bioactive complex, we remain
unpersuaded. Claim 84 depends from claim 1 and recites bioactive complex
“from about 10 nm to about 11.2 µm.” Appeal Br. 19 (Claims App.).
Haynes teaches that the dimension of its drug microparticle is most
preferably between 2 µm and 100 nm, which is encompassed by the range
recited in claim 84. Haynes 6:51–55. Thus, absent persuasive evidence to
the contrary, which Appellant has not provided, Haynes teaches particles
having “a range of sizes sufficient to selectively target and enter the
lymphatic system upon release from the matrix.” In re Best, 562 F.2d 1252,
1255 (CCPA 1977) (“Where . . . the claimed and prior art products are
identical or substantially identical . . . 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.”).13

13 We note in addition that Illum teaches particle size of less than 100 nm,
which also overlaps the particle size range disclosed in the Specification and
recited in claim 84, and further teaches that particle size is a result-effective
variable for targeting the lymphatic system. Illum 640 (stating that
“[i]nterstitially administered colloids with a size less than 100 nm, will drain
through the interstitium to the initial lymphatic vessels” until they are
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As to Appellant’s argument that the claimed particles are “selected for
a wholly different purpose (e.g., anticancer treatment using cytotoxic
agents)” than those disclosed in Haynes, we note that “[i]n determining
whether the subject matter of a patent claim is obvious, neither the particular
motivation nor the avowed purpose of the patentee controls,” so long as
there is a reason to combine the prior art elements in the claimed manner.
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 419–20 (2007). Thus, the fact
that the claimed particles are “selected for a wholly different purpose” does
not render the claims non-obvious.
Similarly, with respect to Appellant’s argument that Haynes’
disclosures of particle size do not render the claimed particle size obvious
because the claimed bioactive complex are “of a wholly different structure
(with particle forming material),” we note that Appellant has not disputed
that Kennedy discloses bioactive complexes comprising particle forming
materials. “Non-obviousness cannot be established by attacking references
individually where the rejection is based upon the teachings of a
combination of references. . . . [The reference] must be read, not in
isolation, but for what it fairly teaches in combination with the prior art as a
whole.” In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986).
Appellant has provided no persuasive argument why a skilled artisan would
not consider the particle size range disclosed by Haynes, which Haynes

captured within the lymph nodes); Spec. 12:3–19 (describing embodiments
where in particles range in size from 50 nm to 11.2 µm); Appeal Br. 19
(Claims App.) (claim 84 reciting bioactive complex “from about 10 nm to
about 11.2 µm).
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teaches as pertinent to the rates of release (Haynes 6:55–56), to be similarly
relevant to the particles disclosed in Kennedy.
Finally, Appellant cites to the Wu Declaration14 to argue that
secondary considerations of non-obviousness, specifically praise by others,
supports the non-obviousness of the claims. Appeal Br. 9.
We are not persuaded. The Wu Declaration states that “[t]he
invention has been praised as an important and innovative step by numerous
independent members of the scientific community.” Wu Decl. ¶ 7. While
we agree that industry praise is evidence of secondary considerations of non-
obviousness, “to be accorded substantial weight . . . the evidence of
secondary considerations must have a ‘nexus’ to the claims, i.e., there must
be ‘a legally and factually sufficient connection’ between the evidence and
the patented invention.” Henny Penny Corp. v. Frymaster LLC, 938 F.3d
1324, 1323 (Fed. Cir. 2019). In particular, “[t]he evidence presented to
rebut a prima facie case of obviousness must be commensurate in scope with
the claims to which it pertains.” In re Dill, 604 F.2d 1356, 1361 (CCPA
1979).
In this case, Appellant presents documents to show that “[a] new
drug-delivery system” developed by Dr. Jiang Liu, an inventor of the patent
application at issue, won the second-place prize in the 2008 Innovation
Challenge Award sponsored by the Natural Sciences and Engineering
Research Council of Canada (NSERC). Wu Decl., Ex. B. 1, 2, 4.15 The

14 Declaration of Xiao Yu Wu, Ph.D. (May 9, 2013). Dr. Wu is an inventor
of the patent application at issue.
15 Exhibit B to the Wu Declaration is not paginated. Thus, all references to
page numbers in Exhibit B of the Wu Declaration refer to page numbers as if
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documents describe the Microparticulate Lymphatic Targeting System
(MLTS) that won the award as “a system that successfully targets lymph
nodes in delivering chemotherapy drugs” by embedding “bioabsorbable
particles that contain anti-cancer drugs” in “a special gelfoam that is meant
to be implanted near lymph nodes.” Id. at 1. The documents note that, “[i]n
laboratory tests, [Dr. Liu] has been able to increase the drug exposure in the
desired areas to 400 times what can be achieved by regular injections, with
fewer side effects.” Id.
As an initial matter, Appellant has not provided persuasive evidence
that the bioabsorbable particles of MLTS comprises “at least one particle
forming material and at least one bioactive agent disposed throughout the
particle forming material,” as recited in claim 1. Moreover, claim 1 is
significantly broader than the system described above, and Appellant has not
persuasively argued that there is a reasonable basis for concluding the
untested embodiments encompassed by claim 1 would behave in the same
manner as MLTS. Cf. In re Lindner, 457 F.2d 506, 508 (CCPA 1972)
(finding evidence of alleged unexpected results to be insufficient to
overcome prima facie case of obviousness where claims are much broader in
scope than the tested composition and there is “no ‘adequate basis for
reasonably concluding that . . . compositions included by the claims would
behave in the same manner as the [single] tested composition’”).
Appellant also presents documents to show that Dr. Liu’s “Trans-
lymphatic Chemotherapy Technology” was the first place winner of the Ever

Exhibit B was numbered consecutively beginning with the first page after
the cover page.
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Green World Chinese Venture Creation Competition and that the American
Association for Cancer Research presented the AACR-Aflac Award to Dr.
Liu for developing “a [n]ovel [a]nti-cancer [t]echnology.” Wu Decl., Ex. B
3, 5. These documents, however, do not describe the technology being
praised and thus do not provide evidence of the nexus to the claims that is
necessary for secondary considerations to be accorded substantial weight.
Finally, Appellant presents a summary of the committee discussion of
a grant application by Dr. Wu entitled “[b]iodegradable nanoparticles for
targeted drug delivery to lymphatic metastatic cancer cells.” Wu Decl., Ex.
B. 6–7. While the summary states that “[t]he proposed research addresses
an important clinical problem with immediate relevance to the field,” that
“[t]he proposal was well-written with a good rationale and clearly-defined
hypotheses,” and that “[t]he approach is novel and is supported by the
accompanying preliminary data,” the summary does not describe the
proposed research in any detail or provide evidence of its success. Id. at 6.
Thus, we accord the summary little weight for purposes of our obviousness
analysis.
Accordingly, for the reasons discussed above, we affirm the
Examiner’s rejection of claim 1 as obvious over Haynes, Kennedy, and
Illum. Claims 7, 8, 14, 18–22, 25–31, 35, 43, 84–89, and 93, which are not
separately argued, fall with claim 1.
C. Obviousness rejection over Haynes, Kennedy, Illum, and Guire
(claims 9–14, 23, and 32)
With respect to the obviousness rejection over Haynes, Kennedy,
Illum, and Guire, Appellant contends that the combination “would result in
the bioactive complexes, as presently claimed, and the bioactive agents (e.g.,
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paclitaxel) contained therein being released locally and/or in view of Illum
not targeted for lymphatic delivery in the event the bioactive complexes are
released.” Appeal Br. 10.
Appellant does not separately argue the claims, we therefore focus our
analysis on claim 9 as representative. We are not persuaded for the same
reasons discussed above with respect to claim 1. The Examiner has
established a prima facie case that the combination of Haynes, Kennedy,
Illum, and Guire would result in a matrix comprising bioactive complexes
having structures that are “identical or substantially identical” to the matrix
and bioactive complexes recited in claim 9. Thus, the burden is shifted to
Appellant to show that the matrix and bioactive complexes suggested by the
prior art “do not necessarily or inherently possess the characteristics of [the]
claimed product,” i.e., bioactive complex that “selectively target and enter
the lymphatic system upon release from the matrix” or “release an effective
amount of the at least one bioactive agent within the lymphatic system.” In
re Best, 562 F.2d at 1255. Appellant’s conclusory attorney arguments do not
meet this burden. Accordingly, we affirm the Examiner’s rejection of claim
9 as obvious over Haynes, Kennedy, Illum, and Guire. Claims 10–14, 23,
and 32, which are not separately argued, fall with claim 9.
D. Obviousness rejection over Haynes, Kennedy, Illum, and Hennink
(claim 33)
With respect to the obviousness rejection over Haynes, Kennedy,
Illum, and Hennink, Appellant contends that
Applicants have previously noted in remarks dated April 4,
2018 that the encapsulation of free drug disclosed in Hennick
[sic], in association with the particles and matrix taught by
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Kennedy, Haynes and Illum, will result only in additional local
delivery of free (or non-encapsulated) drug.
Appeal Br. 10.16 Appellant thus appears to rely only on the same arguments
as those made with respect to the rejection of claim 1 over Haynes,
Kennedy, and optionally Illum. We are not persuaded for the reasons
already discussed above with respect to the rejection of claim 1.
E. Obviousness rejection over Haynes, Kennedy, Lee, Berkland, and
optionally Illum (claims 84, 85, and 87–89)
Appellant does not separately argue the claims. We therefore focus
our analysis on claim 84, which depends from claim 1 and further recites
that “bioactive complex is from about 10 nm to about 11.2 µm.” Appeal Br.
19 (Claims App.).
The Examiner cites Lee and Berkland as disclosing particle sizes
“above 100 nm such as a couple hundred nanometers or in the micron
range.” Ans. 12. The Examiner concludes that it would have been obvious
to a skilled artisan “to use drug containing particles as in Kennedy with
varying sizes in the hundreds of nanometers or micron size range to provide
the desired drug release,” because Lee and Berkland teach that “particle size
influences the release rate of the drug and[,] by varying particle size,
delivery rates such as zero order or pulsatile can be achieved.” Id. at 14.
The Examiner further finds that the limitations relating to the size of the
bioactive complex are obvious because such size is “clearly a result effective

16 We are unable to locate in the record Appellant’s remarks dated April 4,
2018. We assume that Appellant is referring instead to the April 30, 2018
Response to Office Action.
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parameter that a person of ordinary skill in the art would routinely
optimize.” Id.
Appellant contends that “the larger particles disclosed in Lee (Table
1) and Berkland could not have reasonably been expected to reach the
lymphatic system considering the size limitations taught for lymphatic
delivery in Illum which specifically teaches away from the invention.”
Appeal Br. 10. Appellant further argues that Berkland on its own or in view
of Illum “teaches away from the invention,” because “Berkland teaches
particles which provide localized drug delivery and high local drug
concentrations.” Id.
We are not persuaded for the reasons similar to those discussed above.
As to Appellant’s argument that a skilled artisan would not have reasonably
expected the larger particles disclosed in Lee and Berkland to reach the
lymphatic system, we note that claim 84 is a composition claim and thus
does not require its bioactive complexes to reach the lymphatic system,
merely that they have a size such that they would selectively target and enter
the lymphatic system if administered. Claim 84 recites a size range that will
achieve such a result. The obviousness issue with respect to the composition
only requires a skilled artisan to have reason to, and reasonable expectation
of success in, making bioactive complexes having the recited size, not the
knowledge that in making bioactive complexes of that size that they will
reach the lymphatic system when administered.
Furthermore, claim 84 is not limited to bioactive complex having a
“larger” particle size. Instead, claim 84 recites “bioactive complex . . . from
about 10 nm to about 11.2 µm.” Appeal Br. 19 (Claims App.) Thus, even if
obviousness requires a reasonable expectation that the prior art particle will
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be taken up by the lymphatic system, the particle size limitation in claim 84
is obvious because Illum teaches that interstitially administered colloids with
a size less than 100 nm, which overlaps the range recited by the claim, will
drain through the interstitium to the initial lymphatic vessel. Illum 640, left
column.
As for Appellant’s arguments regarding teaching away, we have
already discussed why Illum does not teach away from the claimed
invention. Berkland teaches that “biodegradable polymer microspheres that
can deliver a therapeutic at a constant rate over a prolonged time following a
single administration can . . . provide localized drug delivery and high local
drug concentrations.” Berkland 1055, left column. This, however, does not
suggest that such microspheres may not also be used to selectively target and
enter the lymphatic system. Thus, Berkland does not teach away from the
invention, either on its own or in view of Illum. See, e.g., Baxter Int’l, Inc.
v. McGaw, Inc., 149 F.3d 1321, 1328 (Fed. Cir. 1998) (explaining that
“reference will teach away if it suggests that the line of development flowing
from the reference’s disclosure is unlikely to be productive of the result
sought by the applicant”).
Accordingly, we affirm the Examiner’s rejection of claim 84 as
obvious over Haynes, Kennedy, Lee, Berkland, and Illum. Claims 85 and
87–89, which are not separately argued, fall with claim 84.
F. Claims 15–17
The Examiner states in the Final Action that all pending claims are
rejected. Final Act. 1. As Appellant points out, however, the Examiner did
not provide a specific basis of rejection for pending claims 15–17. Appeal
Br. 4. Accordingly, the Examiner has not established a prima facie case of
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invalidity as to claims 15–17, and we reverse the Examiner’s rejection of
these claims.

CONCLUSION
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/
Basis 
Affirmed Reversed
1, 7–14, 18–23,
25–33, 35, 43,
84–89, 93
112(b) or 112
(pre-AIA),
second
paragraph
Indefiniteness  1, 7–14,
18–23, 25–
33, 35, 43,
84–89, 93
1, 7, 8, 14, 18–
22, 25–31, 35,
43, 84–89, 93
103(a) Haynes,
Kennedy,
Illum
1, 7, 8, 14,
18–22,
25–31, 35,
43, 84–89,
93

9–14, 23, 32 103(a) Haynes,
Kennedy,
Illum, Guire
9–14, 23,
32

33 103(a) Haynes,
Kennedy,
Illum,
Hennink
33
84, 85, 87–89 103(a) Haynes,
Kennedy,
Lee,
Berkland,
Illum
84, 85,
87–89

15–17 15–17
Overall
Outcome
1, 7–14,
18–23,
25–33, 35,
43, 84–
89, 93
15–17
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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 IN PART