Cristianne Johanna Ferdinand. Rijcken et al.

Patent Trials and Appeals Board

Oct 9, 2019

14129529 - (D) (P.T.A.B. Oct. 9, 2019)

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.
14/129,529 02/12/2014 Cristianne Johanna Ferdinand Rijcken 31363-20168.00 4872
25225 7590 10/09/2019
MORRISON & FOERSTER LLP
12531 HIGH BLUFF DRIVE
SUITE 100
SAN DIEGO, CA 92130-2040
EXAMINER
VU, JAKE MINH
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
10/09/2019 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):
EOfficeSD@mofo.com
PatentDocket@mofo.com
pair_mofo@firsttofile.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte CRISTIANNE JOHANNA FERDINAND RIJCKEN,
MARTIN STIGTER, and
JOSEPHUS JOHANNES MARIA HOLTHUIS
____________

Appeal 2018-007684
Application 14/129,5291
Technology Center 1600
____________

Before FRANCISCO C. PRATS, TAWEN CHANG, and DAVID COTTA,
Administrative Patent Judges.

COTTA, Administrative Patent Judge.

DECISION ON APPEAL

This is an appeal under 35 U.S.C. § 134 involving claims to a method
for providing the bloodstream of a vertebrate subject with an intact
nanoparticulate control release system comprising at least one active
ingredient for systemic treatment of a disease. The Examiner rejected the
claims on appeal as obvious under 35 U.S.C. § 103(a).
We reverse.

1 We use the word “Appellant” to refer to “applicant” as defined in
37 C.F.R. § 1.42. According to Appellant, the real party in interest is Cristal
Delivery B.V. App. Br. 1.

Appeal 2018-007684
Application 14/129,529

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STATEMENT OF THE CASE
The Specification discloses that “[n]anoparticulate carriers and
controlled release systems are often administered intravenously, however it
would be desirable to have other administration routes available.” Spec. 1.
The Specification teaches that “[u]pon subcutaneous administration,
nanocarriers do not have direct access to bloodstream. They either enter
lymphatic capillaries draining the injection site or remain at the site of
injection.” Id. at 2. “For those particles remaining at the injection site,
destabilization and degradation take place with time, thereby possibly
releasing the therapeutic agents” which “may have toxic effect and may
harm the injection site, causing inflammation and discomfort to the patient.”
Id. According to the Specification, “[t]here is thus a need for [a] control
release system such as nanoparticles and micelles that may [be] administered
other than intravenously.” Id. at 3.
The Specification discloses that “the present invention is directed to
use of [a] control release system to administer an active ingredient to an
organism, wherein the administration is not intravenous.” Id. at 4. The
Specification discloses that controlled release by non-intravenous
administration is accomplished by “a control release system wherein active
ingredients such as drug molecules are first non-covalently entrapped in
polymer phases, and especially in polymer-rich phases, in an aqueous
environment, and subsequently are conjugated to a 3D-polymer network.”
Id. at 5. The Specification states that “[s]urprisingly it has been found that
[this] control release system . . . has good properties when administered in
routes other than intravenously.” Id. at 4.
Appeal 2018-007684
Application 14/129,529

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Claims 1, 10–20, 22, 23, and 27–33 are on appeal. Claim 1 is
representative and reads as follows:
1. Method to provide the bloodstream of a vertebrate
subject with an intact nanoparticulate control release system
comprising at least one active ingredient for systemic treatment
of a disease which method comprises administering the
nanoparticulate control release system via a subcutaneous or
intraperitoneal route, and
wherein the control release system is obtained by
(i) mixing active ingredient comprising a first
reactive moiety with an aqueous solution or
dispersion comprising polymer chains, said
polymer chains comprising at least one second
reactive moiety capable of reacting with said first
reactive moiety of said at least one active
ingredient, the polymer chains further being
capable of cross-linking intra- or intermolecularly;
and
(ii) subjecting this mixture to cross-linking
forming a 3D-matrix under such conditions that
simultaneously with the formation of the 3D-
matrix, said at least one active ingredient is
entrapped,
wherein the polymer chains comprise polymers of
hydrophobically modified esters of N-hydroxyalkyl-
(meth)acrylamide and N-(meth)acryloyl amino acids; and
wherein said at least one active ingredient is covalently coupled
to the 3D matrix.
App. Br. 7.

Appeal 2018-007684
Application 14/129,529

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The claims were rejected as follows:
Claims 1, 10–18, 22, 23, and 27–33 were rejected under 35 U.S.C. §
103(a) as being obvious over the combination of Rijcken 1,2 and Palliative
Care Tips.3
Claims 1, 10–20, 22, 23, and 27–33 were rejected under 35 U.S.C.
§ 103(a) as being obvious over the combination of Rijcken 1, Palliative Care
Tips, Rijcken 2,4 and Lavasanifar.5

ANALYSIS
The same issue is dispositive with respect to both rejections.
Accordingly, we address both rejections together.
Rijcken 1 discloses a method in which “active ingredients such as
drug molecules are first noncovalently entrapped in polymer phases and
especially in polymer-rich phases, in an aqueous environment, and
subsequently are conjugated to a 3D-polymer network.” Rijcken 1, 4. In
finding the pending claims obvious over the cited art, the Examiner found
that Rijcken 1 disclosed most of the elements of claim 1. The Examiner
acknowledged, however, that Rijcken 1 did not disclose “administering the

2 Rijcken et al., WO 2010/033022 A1, published Mar. 25, 2010 (“Rijcken
1”).
3 Royal Alexandria Hospital, Palliative Care Tips, Issue 14: Subcutaneous
Administration of Opioids and Anti-Emetics (May 2006) (“Palliative Care
Tips”).
4 Rijcken et al., WO 2012/039602, published Mar. 29, 2012 (“Rijcken 2”).
5 Lavasanifar et al., US Patent Publication No. 2010/0137206 A1, published
June 3, 2010 (“Lavasanifar”).
Appeal 2018-007684
Application 14/129,529

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nanoparticulate control release system via a subcutaneous or intraperitoneal
route,” as required by all of the pending claims. Final Act.6 5.
The Examiner concluded that it would have been obvious to
administer the composition disclosed in Rijcken subcutaneously because
“the prior art had routinely administered dexamethasone and chemo drugs
via subcutaneous injection.” Id. As evidence, the Examiner relies upon
Palliative Care Tips as teaching “that subcutaneous route is preferred
whenever possible, wherein dexamethasone are commonly given by the
subcutaneous route.” Id. The Examiner also asserted that subcutaneous
administration was obvious because “RIJCKEN1 teaches injecting
nanoparticles into the blood stream or direct injection into the tumor or
organ (see RIJCKEN1 at pg. 14, line 5-10), wherein skin (cutaneous) and
other tissues (subcutaneous) are considered to be an organ.” Ans. 8.
Appellant “do[es] not disagree with the assertion that the structural
features of the nanoparticulate control release system are disclosed in the
art”; Appellant argues, however, that it is “unable to discern how the
disclosure of Palliative Care Tips would lead one skilled in the art to
administer these structures subcutaneously.” Reply Br. 2.
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
“[T]he examiner bears the initial burden . . . of presenting a prima facie case
of unpatentability.” Appellant has persuaded us that the Examiner has not
carried the burden of establishing that the claimed invention would have
been obvious over the cited art.
Palliative Care Tips discloses that “60%-70% of palliative patients
will become unable to take oral medications during the course of their

6 Office Action mailed September 27, 2017 (“Final Act.”).
Appeal 2018-007684
Application 14/129,529

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illness, and will require medications through either the rectal or the
parenteral route (intravenous, subcutaneous or intramuscular).” Palliative
Care Tips, 1. It then discusses intravenous, intramuscular, and subcutaneous
administration, concluding that “the subcutaneous route is preferred
whenever possible.” Id. As Appellant points out, however, all of the drugs
listed in Palliative Care Tips are small molecule drugs. Reply Br. 2.
Accordingly, we agree with Appellant that this teaching does not provide a
reasonable expectation that subcutaneous administration would have been
successful with respect to the claimed nanoparticulate control release
system, particularly given the knowledge in the art that nanocarriers injected
subcutaneously either degrade or are taken up by the lymphatic system.
Spec. 2.
We also disagree with the Examiner that Rijcken 1 teaches
subcutaneous injection. Rijcken 1 discloses “controlled release of (drug)
molecules entrapped in the cross-linked micelles upon administration in
vivo. e.g. by oral application, injection in the blood stream, or by direct
injection in an organ or tumour.” Rijcken 1, 14. The Examiner asserts that
this disclosure teaches subcutaneous administration because “skin
(cutaneous) and other tissues (subcutaneous) are considered to be an organ.”
Ans. 8. We are not persuaded because we do not consider subcutaneous
injection to be injection into an organ. To the contrary, subcutaneous
administration requires administration under the skin. Spec. 22.
Subcutaneous administration is distinct from intradermal (administration
into the skin) and intramuscular (into a muscle) administration. Id. While
the skin and muscles are organs, we do not identify in the Specification or in
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Application 14/129,529

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the art of record sufficient support for the Examiner’s position that a
composition administered subcutaneously is injected into an organ.
Accordingly, we reverse the Examiner’s rejections of claims 1, 10–20,
22, 23, and 27–33.
SUMMARY
In summary:
Claims
Rejected
Basis Affirmed Reversed
1, 10–18, 22, 23,
and 27–33
§ 103(a), Rijcken 1,
and Palliative Care
Tips.

1, 10–18, 22,
23, and 27–33
1, 10–20, 22, 23,
and 27–33
§ 103(a), Rijcken 1,
Palliative Care Tips,
Rijcken 2, and
Lavasanifar
1, 10–20, 22,
23, and 27–33
Overall Outcome 1, 10–20, 22,
23, and 27–33

REVERSED