PLEDPHARMA AB

Patent Trials and Appeals Board

Feb 12, 2020

14439471 - (D) (P.T.A.B. Feb. 12, 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.
14/439,471 04/29/2015 Jan Olof Karlsson 4011216-191613 8149
23570 7590 02/12/2020
PORTER WRIGHT MORRIS & ARTHUR, LLP
INTELLECTUAL PROPERTY GROUP
41 SOUTH HIGH STREET
29TH FLOOR
COLUMBUS, OH 43215
EXAMINER
DRAPER, LESLIE A ROYDS
ART UNIT PAPER NUMBER
1629
NOTIFICATION DATE DELIVERY MODE
02/12/2020 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):
ipdocket@porterwright.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte JAN OLOF KARLSSON, TINO KURZ, and
ROLF ANDERSSON
____________

Appeal 2019-001366
Application 14/439,471
Technology Center 1600
____________

Before ERIC B. GRIMES, DEBORAH KATZ, and
MICHAEL A. VALEK, Administrative Patent Judges.

VALEK, Administrative Patent Judge.

DECISION ON APPEAL
Appellant1 submits this appeal under 35 U.S.C. § 134(a) involving
claims to methods for the treatment of selected cancers by administration of
a compound of recited Formula I. 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 PledPharma AB as the real party in
interest.
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STATEMENT OF THE CASE
According to the Specification, “[t]he invention . . . comprises a
method employing a compound of Formula I, and in a specific embodiment,
the compound DPDP [i.e., N,N’-bis-(pyridoxal-5-phosphate)-
ethylenediamine-N,N’-diacetic acid] . . . for treating various cancer diseases,
alone or in combination with a cyto-protective compound and/or other
cytostatic drugs and/or radiotherapy.” Spec. ¶ 33.
Claims 1–3, 5, 8, 20, 21, and 25 are on appeal and can be found in the
Claims Appendix of the Appeal Brief. Claim 1 is illustrative and reads as
follows:
1. A method for treatment of cancer selected from lung cancer,
lung cancer metastasis, ovarian cancer, ovarian cancer
metastasis, squamous cell carcinoma, squamous cell carcinoma
metastasis, pancreas exocrine cancer, pancreas exocrine cancer
metastasis, malignant melanoma, malignant melanoma
metastasis, gastric cancer, gastric cancer metastasis, esophageal
cancer, esophageal cancer metastasis, and leukemia, in a human
or non-human patient in need of treatment of said cancer, said
method comprising administering to said patient a cancer-
inhibiting amount of a first compound of Formula I:
(I)

or a physiologically acceptable salt thereof, wherein
X is CH or N,
each R1 independently is hydrogen or -CH2COR5;
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R5 is hydroxy, ethylene glycol, optionally hydroxylated alkoxy,
amino or alkylamido;
each R2 independently is a group ZYR6;
Z is a bond, CO, or a C1-3 alkylene or oxoalkylene group,
wherein said alkylene or oxoalkylene group is optionally
substituted by a group R7;
Y is a bond, an oxygen atom or a group NR6;
R6 is a hydrogen atom, COOR8, an alkyl, alkenyl, cycloalkyl,
aryl or aralkyl group, any of which is optionally substituted by
one or more groups selected from COOR8, CONR82, NR82,
OR8, =NR8, =O, OP(O)(OR8)R7 and OSO3M;
R7 is hydroxy, an alkyl group, or an aminoalkyl group, wherein
said alkyl group or aminoalkyl group is optionally hydroxylated
and/or optionally alkoxylated;
R8 is a hydrogen atom or an optionally hydroxylated, optionally
alkoxylated alkyl group;
M is a hydrogen atom;
R3 is a C1-8 alkylene group, a 1,2-cycloalkylene group, or a 1,2-
arylene group, any of which is optionally substituted with R7;
and
each R4 independently is hydrogen or C1-3 alkyl.
Appeal Br. 40–41. Claim 5 depends from claim 1 and further recites
“wherein the first compound” of Formula I is DPDP. Id. at 42. Claims 8
and 25 depend from claims 1 and 5 respectively and further recite “wherein
the cancer is ovarian cancer and/or metastases thereof.” Id.
Appellant seeks review of the following rejections:
I. Claims 1–3, 5, 8, 20, 21, and 25 U.S.C. § 103 as unpatentable over
Armstrong2 in view of Towart3 and Karlsson.4

2 Deborah K. Armstrong et al., Intraperitoneal Cisplatin and Paclitaxel in
Ovarian Cancer, 354 N. Eng. J. Med., 34–43 (2006) (“Armstrong”).
3 US 6,147,094, issued Nov. 14, 2000 (“Towart”).
4 US 2010/0298271 A1, published Nov. 25, 2010 (“Karlsson”).
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II. Claims 1–3, 5, 8, 20, 21, and 25 for obviousness-type double
patenting (“ODP”) over claims 1–8 of Towart in view of Armstrong
and Karlsson.
III. Claims 1–3, 5, 8, 20, 21, and 25 for ODP over claims 1–17 of Towart
’8285 in view of Towart, Armstrong, and Karlsson.
IV. Claims 1–3, 5, 8, 20, 21, and 25 for ODP over claims 1–15 of
Karlsson ’0516 in view of Towart, Armstrong, and Karlsson.
V. Claims 1–3, 5, 8, 20, 21, and 25 for ODP over claims 1–7, 14, 15,
20–22, and 27–35 of Towart ’8957 in view of Towart, Armstrong,
and Karlsson.
Findings of Fact
FF1. Armstrong teaches that “[i]n the United States, the standard
chemotherapy for the initial treatment of ovarian cancer is a combination of a
platinum analogue with paclitaxel.” Armstrong 35, left col.
FF2. Towart teaches that paclitaxel is an anti-tumor agent, “which has
shown anti-neoplastic action against a variety of malignant tissues, including
those of the breast, colon, lung and ovary as well as in malignant melanoma,”
but has “a number of adverse side-effects which can include cardiovascular
irregularities.” Towart 1:19–27.
FF3. Towart teaches the “use of a compound of formula I . . . or a metal
chelate or salt thereof in the manufacture of a therapeutic agent for use in
reducing the cardiotoxicity of an anti-tumor agent, e.g.[,] an anthracycline

5 US 6,258,828 B1, issued July 10, 2001 (“Towart ’828”).
6 US 6,310,051 B1, issued Oct. 30, 2001 (“Karlsson ’051”).
7 US 6,391,895 B1, issued May 21, 2002 (“Towart ’895”).

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and/or paclitaxel.” Towart 2:42–58. Towart describes DPDP as a
“particularly preferred” compound of Formula I for use in this invention. Id.
at 4:31–36.
FF4. Towart discloses data showing that both DPDP, and the manganese
complex of DPDP (MnDPDP), provide a protective effect “against
Doxorubicin-induced Cardiotoxicity.” See Towart 9:40–62 (Table 2 showing
that DPDP provides a 6%, 15%, and 10% protective effect at doses of 1, 10,
and 30 μmole/kg respectively). According to Towart, “[e]quimolar doses of
either manganese (as the chloride) or DPDP alone, although less effective
[than MnDPDP] still provide a degree of protection of the atrial muscle.” Id.
at 9:14–18.
FF5. Karlsson teaches a “[c]ompound of Formula I or a salt thereof for
treating cancer.” Karlsson, Abstr. According to Karlsson, “[w]hen the
present inventors compared MnDPDP and DPDP they surprisingly found that
DPDP was more efficacious than MnDPDP in its ability to kill cancer cells
and they concluded that the previously described cancer cell killing ability of
MnDPDP is an inherent property of DPDP.” Id. ¶¶ 54, 73, 77.
Analysis
I. 103 Rejection: Armstrong, Towart, and Karlsson
The issue for this rejection is: Does the preponderance of evidence of
record support Examiner’s conclusion that the method in claims 1–3, 5, 8,
20, 21, and 25 is obvious over the cited references?
Claim 1
Examiner determines that
[a] person of ordinary skill in the art at the time of the
invention would have had a reasonable expectation of success
in administering [DPDP] to a human ovarian cancer patient
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receiving intraperitoneal paclitaxel and cisplatin chemotherapy
for ovarian cancer to prevent or treat the well-known
cardiotoxic effects of paclitaxel therapy. The skilled artisan
would have been motivated to do so in view of the fact that (i)
Armstrong et al. clearly teaches the efficacy of paclitaxel and
cisplatin therapy for ovarian cancer, with associated grade 3 and
4 cardiovascular toxicity; (ii) Towart et al. clearly teaches the
cardiotoxic effects of paclitaxel administration; and (iii) Towart
et al. teaches the dipyridoxal agent [DPDP] as a known
cardioprotective agent effective to treat or minimize
cardiotoxicity associated with paclitaxel administration. It
would, therefore, have been prima facie obvious to one of
ordinary skill in the art at the time of the invention to
administer [DPDP] to a human ovarian cancer patient receiving
intraperitoneal cisplatin and paclitaxel chemotherapy to
minimize paclitaxel cardiotoxicity.
Ans. 5. Examiner concludes that administering DPDP at the doses taught in
Towart would inherently provide “a cancer-inhibiting amount,” as recited in
claim 1, because Karlsson teaches “that cancer cell-killing properties of
DPDP are inherent to the compound.” Id.
Appellant argues that Towart “does not provide any teaching of a
compound of Formula I having cancer inhibiting activity, and . . . does not
provide any teaching of administering a compound of Formula I to a patient
in need of treatment of a cancer selected from the group recited in claim 1 in
a cancer-inhibiting amount.” Appeal Br. 9. According to Appellant, those
skilled in the art as of the priority date of the present application “recognized
that the cardioprotective uses of the compounds disclosed in Towart ‘094 are
derived from their superoxide dismutase (SOD) mimetic activity, which is
attributable to the metal component of the metal chelates, specifically
manganese.” Id. Thus, urges Appellant, one skilled in the art, following
“the then-accepted wisdom, would have used a manganese chelate
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compound,” such as MnDPDP, not a “non-manganese compound[] of
Formula I,” like DPDP, to provide a cardioprotective effect. Id. at 10. In
addition, Appellant contends that because Karlsson was rejected as “not
enabling under 35 U.S.C. 112, first paragraph, for treating every known
cancer” during prosecution, it “cannot be relied [on] in a rejection under 35
U.S.C. 103 as teaching . . . that a compound of Formula I is inherently
effective for treating every known cancer or, specifically, treating the
cancers recited in claim 1.” Id. at 11.
Based on the record before us, we determine that the preponderance of
the evidence supports Examiner’s rejection of claim 1 over the cited
references. We agree with, and adopt, Examiner’s findings (see FF1–FF5)
and reasoning in support of that rejection. We are not persuaded by
Appellant’s arguments, which we address below.
Appellant’s argument that a skilled artisan would not have considered
administration of DPDP to provide a cardioprotective effect for an ovarian
cancer patient being treated with paclitaxel is not persuasive. Towart
specifically teaches that DPDP provides a protective effect against
cardiotoxic side effects of such drugs. FF4. Accordingly, Towart supports
Examiner’s finding that a skilled artisan would be motivated to administer
DPDP with paclitaxel to treat ovarian cancer and would have a reasonable
expectation the DPDP would provide a protective effect against cardiotoxic
side effects. Ans. 5. The evidence Appellant cites in the Appeal Brief
attributes the protective effect provided by “MnDPDP and its
dephosphorylated counterpart MnPLED” to their “superoxide dismutase
(SOD) mimetic activity.” See Appeal Br. 9–10 (quoting US 8,377,969 B2,
1:44–61). But that evidence says nothing about the protective effect that
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Towart teaches the use of DPDP “alone” provides, nor does it address the
data in Towart demonstrating that administration of DPDP, in fact, provides
such an effect. FF4. Moreover, contrary to Appellant’s assertion (see
Appeal Br. 11–12), the evidence it cites concerning SOD mimetic activity
does not teach away from the use of DPDP to provide a cardioprotective
effect because it does not “criticize, discredit, or otherwise discourage
investigation into” the use of DPDP for that purpose. See Galderma Labs.,
L.P. v. Tolmar, Inc., 737 F.3d 731, 738 (Fed. Cir. 2013) (quoting DePuy
Spine, Inc. v. Medtronic Sofamor Danek, Inc., 567 F.3d 1314, 1327 (Fed.
Cir. 2009)).
We are also unpersuaded by Appellant’s argument that the teachings
in Karlsson cannot be considered because that reference does not enable
treatment of “every known cancer.” See Appeal Br. 11. It is well-settled
that “a non-enabling reference may qualify as prior art for the purpose of
determining obviousness under § 103.” Symbol Techs., Inc. v. Opticon, Inc.,
935 F.2d 1569, 1578 (Fed. Cir. 1991); see also Beckman Instruments, Inc. v.
LKB Produkter AB, 892 F.2d 1547, 1551 (Fed. Cir. 1989) (“[e]ven if a
reference discloses an inoperative device, it is prior art for all that it
teaches”). Here, Karlsson teaches that the “cancer cell killing ability of
MnDPDP is an inherent property of DPDP.” FF5. Thus, Karlsson supports
Examiner’s determination that the administration of DPDP, in the amounts
taught in Towart,8 would inherently be cancer-inhibiting and, therefore, that

8 Towart teaches that DPDP exhibited a protective effect at 1, 10, and 30
μmole/kg. FF4. These amounts overlap with the dosage range described in
Appellant’s Specification. Spec. ¶ 47; see also In re Peterson, 315 F.3d
1325, 1329 (Fed. Cir. 2003) (“In cases involving overlapping ranges, we and
our predecessor court have consistently held that even a slight overlap in
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claim 1 would have been obvious over the cited combination of references.
For these reasons, we affirm the rejection.
Claims 2, 3, and 5
Claims 2, 3, and 5 further “define the compound of Formula I”
administered according to claim 1. See Appeal Br. 12–13. But the
compound DPDP remains within the scope of each of these claims. See
Appeal Br. 12–13. Thus, claims 2, 3, and 5 read upon the combination of
Armstrong, Towart, and Karlsson, as articulated by Examiner for claim 1.
Appellant does not present any additional reason why Examiner’s rejection
should be reversed for these claims. Accordingly, we determine the
preponderance of the evidence supports the rejection of claims 2, 3, and 5
for the same reasons articulated above.
Claims 8 and 25
Claims 8 and 25 additionally “recite that the cancer is ovarian cancer
and/or metastases thereof.” See Appeal Br. 13–14. Thus, each of these
claims reads upon the combination of Armstrong, Towart, and Karlsson, as
articulated by Examiner for claim 1. Appellant does not present any
additional reason why Examiner’s rejection should be reversed for these
claims. Accordingly, we determine the preponderance of the evidence
supports the rejection of claims 8 and 25 for the same reasons articulated
above.
Claims 20 and 21
Claims 20 and 21 additionally “recite that the first compound, i.e., the
compound of Formula I, is administered together with one or more other

range establishes a prima facie case of obviousness.”).
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anti-cancer drugs selected from” a group that includes paclitaxel. See
Appeal Br. 14–15. Thus, each of these claims reads upon the combination
of Armstrong, Towart, and Karlsson, as articulated by Examiner for claim 1.
Appellant argues claims 20 and 21 are further patentable over that
combination because Armstrong does not teach paclitaxel in combination
with a compound of Formula I and Towart does not teach a compound of
Formula I in combination with paclitaxel in a cancer-inhibiting amount. See
Appeal Br. 15. That argument is unpersuasive for several reasons. First, as
our reviewing Court has explained, “non-obviousness cannot be established
by attacking references individually where the rejection is based on the
teachings of a combination of references.” Soft Gel Techs., Inc. v. Jarrow
Formulas, Inc., 864 F.3d 1334, 1341 (Fed. Cir. 2017) (quoting In re Merck
& Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986)). Second, Towart does, in fact,
teach the administration of a compound of Formula I, e.g., DPDP, in
combination with paclitaxel to provide a protective effect against cardiotoxic
side effects. FF2, FF3. And, as explained above in our analysis of claim 1,
the record supports that the amounts of DPDP taught to have a protective
effect in Towart (see FF4) are inherently cancer-inhibiting. For these
reasons, Examiner’s obviousness rejection of claims 20 and 21 is supported
by the preponderance of the evidence.
II. ODP Rejection: Towart Claims 1–8, Armstrong, and Karlsson
The issue for this rejection is: Does the preponderance of evidence of
record support Examiner’s conclusion that the method in claims 1–3, 5, 8,
20, 21, and 25 is obvious over claims 1–8 of Towart in view of Armstrong
and Karlsson?
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Since it involves the same references as the obviousness rejection,
Examiner premises this ODP rejection on findings similar to those described
above. See Ans. 7–9. Appellant contends that the present claims are
patentably distinct from claims 1–8 of Towart because “[a] method for
treating a cancer selected from the group recited in claim 1 is not an obvious
variation of a method of reducing the cardiotoxicity of an anti-tumor agent.”
Appeal Br. 16.
We are not persuaded by Appellant’s argument. In particular, claim 4
of Towart recites the simultaneous administration of a compound of Formula
I, such as DPDP, and paclitaxel. Towart 12:19–20. While the claims of
Towart do not recite that DPDP has cancer-inhibiting activity, the record
supports that such activity is in inherent property of DPDP. FF5. Thus, the
administration of DPDP as claimed in Towart would inherently provide the
cancer-inhibiting activity recited in Appellant’s claims. That Towart’s
claims recite that the administration of Formula I for a different, albeit
related, purpose, i.e., to provide a protective effect against cardiotoxic side
effects of a chemotherapeutic agent like paclitaxel as opposed to acting as a
chemotherapeutic agent itself, does not distinguish Appellant’s claims. The
record supports that paclitaxel was a known drug for treating ovarian cancer.
FF1, FF2. Thus, it would have been obvious to use the method of Towart
claim 4 to treat a patient with ovarian cancer as recited in Appellant’s
claims.
In addition to the argument above, Appellant repeats the same
arguments it presented for the obviousness rejection of claim 1 and for its
groupings of claims 2, 3, and 5; claims 8 and 25; and claims 20 and 21. See
Appeal Br. at 17–21. We are not persuaded by those arguments for the same
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reasons articulated above. Accordingly, we determine that Examiner’s
rejection of claims 1–3, 5, 8, 20, 21, and 25 for ODP over claims 1–8 of
Towart in view of Armstrong and Karlsson is supported by the
preponderance of the evidence.
III. Examiner’s Other ODP Rejections
Examiner groups the other three ODP rejections together, basing them
on a common finding that the specified claims of Towart ’828, Karlsson
’051, and Towart ’895 “provide[] for a product of [DPDP] and/or methods
of administering [DPDP] to a subject for therapeutic purposes.” Ans. 10.
Thus, according to Examiner, these claims are directed to obvious variations
of the methods recited in Appellant’s claims. Id. at 10–11. We determine
these rejections are not supported by the preponderance of the evidence.
The claims of these references are not directed to treating cancer, nor
has Examiner shown that they are directed to related treatments such as
reducing side effects associated with cancer therapy. Unlike the claims of
Towart, the claims of these references do not recite the co-administration of
a compound of Formula I with paclitaxel or another drug known for treating
the types of cancer recited in Appellant’s claims. Indeed, the claims these
ODP rejections are based upon appear to be drawn to wholly unrelated
indications. See, e.g., Karlsson ’051 claim 1 (reciting a “method of
treatment . . . to combat or prevent atherosclerosis”). Examiner has not
sufficiently articulated why one of ordinary skill in the art would consider
such claims to be obvious variations of the methods in claims 1–3, 5, 8, 20,
21, and 25 of Appellant’s present application. Accordingly, we reverse
Examiner’s other ODP rejections.
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CONCLUSION
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1–3, 5, 8,
20, 21, 25
103 Armstrong, Towart,
Karlsson
1–3, 5, 8,
20, 21, 25

1–3, 5, 8,
20, 21, 25
Nonstatutory
Double Patenting:
Towart
1–3, 5, 8,
20, 21, 25

1–3, 5, 8,
20, 21, 25
Nonstatutory
Double Patenting:
Towart ’828
1–3, 5, 8,
20, 21, 25
1–3, 5, 8,
20, 21, 25
Nonstatutory
Double Patenting:
Karlsson ’051
1–3, 5, 8,
20, 21, 25
1–3, 5, 8,
20, 21, 25
Nonstatutory
Double Patenting:
Towart ’895
1–3, 5, 8,
20, 21, 25
Overall
Outcome
1–3, 5, 8,
20, 21, 25

No time period for taking any subsequent action in connection with this
appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv).

AFFIRMED