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Patent Trials and Appeals Board

Nov 20, 2019

14404657 - (D) (P.T.A.B. Nov. 20, 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.
14/404,657 12/01/2014 Tilman Lappchen 2012P00374WOUS 3574
24737 7590 11/20/2019
PHILIPS INTELLECTUAL PROPERTY & STANDARDS
465 Columbus Avenue
Suite 340
Valhalla, NY 10595
EXAMINER
SAMALA, JAGADISHWAR RAO
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
11/20/2019 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):
katelyn.mulroy@philips.com
marianne.fox@philips.com
patti.demichele@Philips.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte TILMAN LAPPCHEN, HOLGER GRUELL,
MARC STEFAN ROBILLARD, and JOHAN LUB
____________

Appeal 2019-004876
Application 14/404,657
Technology Center 1600
____________

Before DONALD E. ADAMS, FRANCISCO C. PRATS, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s
decision to reject claims 1–10. We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the real party in interest as “Koninklijke
Philips N.V.” (Appellant’s March 8, 2019 Appeal Brief (Appeal Br.) 2).
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STATEMENT OF THE CASE
Appellant’s disclosure “relates to radiotracers and is described in
connection with Positron Emission Tomography (PET) and/or Single Photon
Emission Computed Tomography (SPECT) imaging” (Spec.2 1: 1–3).
Claims 1, 4, and 5 are representative and reproduced below:
1. A method for determining whether compound 0118 is
a candidate treatment for a patient, comprising:
processing, via a processor, image data of tissue of
interest of the patient administered a radiolabeled analog of
compound 0118 and including a cancer to determine whether
the radiolabeled analog of compound 0118 is present in the
tissue of interest represented in the image data, wherein the
radiolabeled analog of compound 0118 includes a radioactive
isotope of one of the halogens F, Cl, Br, I, or At; and
generating a signal indicating that compound 0118 is a
candidate treatment for the patient in response to the
determining that the radiolabeled analog of compound 0118 is
present in a predetermined amount in the tissue of interest
represented in the image data,
wherein the presence of the radiolabeled analog of
compound 0118 in the tissue of interest indicates presence of a
sub-type of cancer having a galectin-1 molecular target, which
is a sub-type treatable by compound 0118.
(Appeal Br. 6.)
4. The method of claim 1, further comprising:
determining the patient has cancer based on image data
from an initial scan of the patient which was performed prior to
all of the acts of claim 1.
(Id.)
5. The method of claim 4, wherein the initial scan includes one
or more of a [18F]Fluorodeoxyglucose, [18F]fluoride, [18F]

2 Appellant’s December 1, 2014 Specification.
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deoxyfluorothymidine, [18F]fluoromisonidazole, [11C]choline,
or [11C]methionine based PET scan.
(Id. at 7 (alteration original).)

Grounds of rejection before this Panel for review:
Claims 1–10 stand rejected under 35 U.S.C. § 103(a) as unpatentable
over the combination of Hsieh,3 Dings,4 and Kobus.5
Claim 5 stands rejected under 35 U.S.C. § 103(a) as unpatentable over
the combination of Hsieh, Dings, Kobus, and Weber.6

ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?

FACTUAL FINDINGS (FF)
We adopt Examiner’s findings concerning the scope and content of
the prior art (see Ans.7 4–6 and 9) and provide the following findings for
emphasis.

3 Hsieh et al., US 2009/0123381 A1, published May 14, 2009.
4 Ruud P.M. Dings et al., Antitumor Agent Calixarene 0118 Targets Human
Galectin-1 as an Allosteric Inhibitor of Carbohydrate Binding, 55 J. Med.
Chem. 5121–29 (2012).
5 D. Kobus et al., A fully automated two-step synthesis of an 18F-labelled
tyrosine kinase inhibitor for EGFR kinase activity imaging in tumors, 67
Applied Radiation and Isotopes 1977–84 (2009).
6 Wolfgang A. Weber, Technology Insight: novel imaging of molecular
targets is an emerging area crucial to the development of targeted drugs, 5
Nature 44–54 (2008).
7 Examiner’s April 12, 2019 Answer.
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FF 1. Compound 0118 (i.e., Calixarene 0118 or Calix[4]arene compound
0118) is an antitumor peptide that targets human galectin-1 (see generally
Dings Title and Abstract; Spec. 3:27 – 4:4).
FF 2. Examiner finds that the combination of Hsieh and Dings discloses
each element of Appellant’s claimed method except a “radiolabel[ed]
compound 0118” (see Ans. 4–5).
FF 3. Examiner finds that Kobus discloses a method of radiolabeling
peptides and that Kobus’ methodology can be applied to Dings’ compound
0118 peptide because “[t]he peptides are labeled on their terminus
employing well known chemistry and thus the labeling of the peptides would
be highly predictable given this is a standard method of labeling peptides to
render them radioactive” (Ans. 8; see also id. at 6).
FF 4. Examiner finds:
Weber discloses that FDG-PET has been used to assess
the glycolytic response of tumors to chemotherapy in patients
with a wide variety of malignancies. Although the FDG-PET
methodology and criteria for tumor responses varied in different
studies, changes in FDG uptake by tumors after the first
chemotherapy cycle correlate significantly with patient survival
in these various studies.
(Ans. 9 (citing Weber 51).)
FF 5. Appellant discloses:
Although anginex and other anti-angiogenic peptides
have shown promising anti-tumor effects in vivo, non-peptidic
compounds are often superior drugs, mainly because they allow
oral administration, generally lack an immune response, and
display a better pharmacokinetic profile. Using the 3-
dimensional molecular structure of anginex as a template,
Dings, et al. “Design of nonpeptidic topomimetics of
antiangiogenic proteins with antitumor activities,” J Natl
Cancer Inst 98(13): 932-936, 2006, designed a small library of
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nonpeptidic, calix[4]arene based surface topomimetics,
mimicking the spatial dimensions and the amphipathic nature of
key amino acid side chains in anginex. One of these
compounds, termed compound 0118, proved equipotent or even
more potent than anginex both in in vitro assays of endothelial
cell proliferation, endothelial cell migration, and angiogenesis,
and in tumor growth models in vivo. In the meantime,
compound 0118 has proven safe in toxicological studies and
has already entered clinical studies.
Apart from the promising (pre)-clinical results obtained
so far and the high expectations regarding development of
compound 0118 into a pharmaceutical for antiangiogenic
cancer therapy, radio labelled derivatives of compound 0118
may prove highly valuable PET- and/or SPECT-imaging tracers
for tumor diagnosis and/or for selection of patients amenable to
treatment with compound 0118. However, such radiolabeled
analogues of this compound are unknown. Unfortunately,
design of radio labelled analogues of compound 0118 is an
intrinsically difficult task given the hitherto known structure
activity relationship (SAR) of a range of similar compounds,
indicating that only minor modifications are tolerated without a
significant loss of anti-angiogenic activity. Moreover, the high
molecular weight of this drug molecule compared to other small
molecule drugs imposes additional constraints on the design of
a related radiotracer, as it is necessary to separate and remove
unreacted precursor after radiolabeling in order to obtain a final
radiotracer solution of high purity and high specific activity.
(Spec. 3:27 – 4:17.)

ANALYSIS
The rejection over the combination of Hsieh, Dings, and Kobus:
Based on the combination of Hsieh, Dings, and Kobus, Examiner
concludes that, at the time Appellant’s invention was made, it would have
been prima facie obvious to, inter alia, label compound 0118 using Kobus’
peptide labeling methodology to produce a radiolabeled analog of compound
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0118 for use in a method for determining whether compound 0118 is a
candidate treatment for a patient (see Ans. 6–7; see also FF 1–3).
Appellant contends that “there is no reasonable expectation of success
that the combination of Ding and Kobus would result in a radiolabeled
analog of compound 0118” because “[w]hen combining prior art references,
there must be a reasonable expectation of success and . . . at least some
degree of predictability is needed to arrive at a reasonable expectation of
success,” “[t]he field of chemistry is recognized as a highly unpredictable
field,” and “[t]he high degree of unpredictability and difficulty pertaining to
radiolabeling analogs of compound 0118 is” disclosed in Appellant’s
Specification (Appeal Br. 3; see FF 5; see also Reply Br.8 2). Thus,
Appellant contends
that due to the high unpredictability in the field of chemistry
and the difficulty in creating a radiolabeled analog of
compound 0118 one having ordinary skill in the art at the time
of the invention would not have had a reasonable expectation of
successfully arriving at a radiolabeled analog of compound
0118 by combining Ding and Kobus.
(Appeal Br. 4; see also Reply Br. 3.) We are not persuaded.
Initially, we note that “[o]bviousness does not require absolute
predictability of success . . . all that is required is a reasonable expectation of
success.” In re O’Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988); see also Ans.
7 (Examiner makes clear that obviousness requires only a reasonable
expectation of success). In this regard, Examiner finds that, notwithstanding
Appellant’s contention to the contrary, the chemistry required to radiolabel
the terminus of a peptide, such as Ding’s compound 0118, was well known

8 Appellant’s June 5, 2019 Reply Brief.
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in this art at the time of Appellant’s claimed invention (see Ans. 8 (citing
Kobus); see also FF 3). As Examiner explains, the evidence on this record
establishes that “peptides are labeled on their terminus employing well
known chemistry and thus the labeling of [Ding’s compound 0118] peptides
would be highly predictable given this is a standard method of labeling
peptides to render them radioactive” (Ans. 8; see generally id. at 8–9). We
find no error in Examiner’s rationale.
Although, Appellant’s Specification discloses that “promising (pre)-
clinical results [were] obtained so far” and there were “high expectations
regarding development of compound 0118 into a pharmaceutical for anti-
angiogenic cancer therapy,” we do not find, and Appellant has not identified,
a disclosure in Appellant’s Specification that supports Appellant’s
contention that “the specification directly states that the fact that analogs of
compound 0118 are anti-angiogenic, as well as other factors, make it
difficult to radiolabel as other anti-angiogenic compounds tolerate only
minor modifications before losing their anti-angiogenic properties” (Reply
Br. 2 (citing Spec. 3:27 – 4:4) (emphasis added); cf. FF 5 (reproducing the
disclosure of Appellant’s Spec. at 3:27 – 4:17).
In addition, we find no argument in Appellant’s Appeal Brief related
to whether a method of radiolabeling a peptide is dependent upon the
activity of the peptide, e.g. whether the peptide is a tyrosine kinase inhibitor
or not (see Reply Br. 2–3). Therefore, this argument is belated and will not
be addressed on the merits. See Ex parte Borden, 93 USPQ2d 1473, 1474
(BPAI 2010) (informative) (Appellant fails to “explain what ‘good cause’
there might be to consider the new argument. On this record, Appellant’s
new argument is belated.”).
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Furthermore, Appellant’s claimed invention does not require
compound 0118 to have anti-angiogenic activity and Appellant has not
explained why the molecular target (i.e. tyrosine kinase or gla-1) of the
peptide would affect its ability to be labeled.

The rejection over the combination of Hsieh, Dings, Kobus, and Weber:
Based on the combination of Hsieh, Dings, Kobus, and Weber,
Examiner concludes that, at the time Appellant’s invention was made, it
would have been prima facie obvious to include Weber’s FDG-PET method
in a method for determining whether compound 0118 is a candidate
treatment for a patient as suggested by the combination of Hsieh, Dings, and
Kobus (see Ans. 9; see also FF 1–4).
Having found no error in Examiner’s conclusion of obviousness based
on the combination of Hsieh, Dings, and Kobus, we are not persuaded by
Appellant’s contention that “Weber does not make up for the above noted
deficiencies of Hsieh, Ding and Kobus” (Appeal Br. 5).

CONCLUSION
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness.
The rejection of claim 1 under 35 U.S.C. § 103(a) as unpatentable
over the combination of Hsieh, Dings, and Kobus is affirmed. Claims 2–10
are not separately argued and fall with claim 1.
The rejection of claim 5 under 35 U.S.C. § 103(a) as unpatentable
over the combination of Hsieh, Dings, Kobus, and Weber is affirmed.

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DECISION SUMMARY
In summary:
Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1–10 103 Hsieh, Dings,
Kobus
1–10
5 103 Hsieh, Dings,
Kobus, and Weber
5
Overall Outcome 1–10

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).

AFFIRMED