ARAGON PHARMACEUTICALS, INC.

Patent Trials and Appeals Board

Oct 2, 2020

2020000990 (P.T.A.B. Oct. 2, 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.
15/094,113 04/08/2016 ISAN CHEN 103693.001116/
API5006USCO
9128
45511 7590 10/02/2020
BakerHostetler
Cira Centre, 12th Floor
2929 Arch Street
Philadelphia, PA 19104-2891
EXAMINER
JONES, DAMERON LEVEST
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
10/02/2020 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):
eofficemonitor@bakerlaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte ISAN CHEN,
JEFFREY H. HAGER, EDNA CHOW MANEVAL,
MARK R. HERBERT, and NICHOLAS D. SMITH
__________

Appeal 2020-000990
Application 15/094,113
Technology Center 1600
__________

Before FRANCISCO C. PRATS, JOHN G. NEW, and DAVID COTTA,
Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL

Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to finally reject claims 1, 2, 5, 6, 19–21, and 28–36.
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 Aragon Pharmaceuticals, Inc., a wholly-
owned subsidiary of Johnson & Johnson, as the real party in interest.
Appeal Br. 1.
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STATEMENT OF THE CASE
The sole rejection before us for review is the Examiner’s rejection of
claims 1, 2, 5, 6, 19–21, and 28–36 under 35 U.S.C. § 103(a) as being
unpatentable over Szmulewitz2 (Final Act. 4–6;3 Ans. 4–7)4.
Claim 1 is representative and reads as follows:
1. A method of treating metastatic castration-resistant
prostate cancer, non-metastatic castration-resistant prostate
cancer, metastatic castration-sensitive prostate cancer, non-
metastatic castration-sensitive prostate cancer or high-risk
localized prostate cancer in a male human patient comprising
orally administering the compound of Formula (I), or a
pharmaceutically acceptable salt thereof,

,

to a human male patient in need of such treatment at a dose of
about 30 mg per day to about 480 mg per day, in combination
with:
(a) abiraterone acetate; and
(b) a corticosteroid.

Appeal Br. 12.

2 US 9,289,436 B2 (issued Mar. 22, 2016).
3 Final Action entered October 5, 2018.
4 Examiner’s Answer entered September 17, 2019.
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DISCUSSION
The Examiner’s Prima Facie Case
The Examiner cited various teachings in Szmulewitz as suggesting
treatment of prostate cancer with all of the therapeutic agents recited in
Appellant’s claim 1, including the compound of Appellant’s Formula (I)
(also known as ARN-509 (see Spec. ¶ 61)), abiraterone acetate, and a
corticosteroid. Ans. 4–6. The Examiner also noted Szmulewitz’s teaching
that leuprolide and goserelin were useful for treating prostate cancer. Id. 4.
Based on the identified teachings, the Examiner concluded that
Szmulewitz “renders obvious a composition comprising . . . ARN-509[] in
combination with abiraterone acetate (tradename Zytiga) and a
corticosteroid (e.g., prednisone) wherein the dosage of composition
components may vary and the composition is used for treating various
prostate cancer conditions.” Ans. 7.
Analysis
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. . . .
After evidence or argument is submitted by the applicant in
response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
In the present case, having carefully considered all of the evidence
and arguments presented by Appellant and the Examiner, Appellant does not
persuade us that the Examiner’s conclusion of obviousness as to Appellant’s
claim 1 is not supported by a preponderance of the evidence.
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Szmulewitz describes “a method of treating castration-resistant
prostate cancer in a subject comprising administering to said subject a
glucocorticoid receptor (GR) antagonist.” Szmulewitz 3:30–33.
Szmulewitz thus describes treating a patient encompassed by Appellant’s
claim 1. See Appeal Br. 12 (claim 1 reciting “[a] method of treating
metastatic castration-resistant prostate cancer” as well as “non-metastatic
castration-resistant prostate cancer”).
As required by Appellant’s claim 1, Szmulewitz’s GR antagonist may
be a corticosteroid. See Szmulewitz 3:42–44 (“The GR antagonist may be
beclometasone, betamethasone, budesonide, ciclesonide, flunisolide,
fluticasone, GSK650394, mifepristone, mometasone, or triamcinoclone.”).5
Szmulewitz also discloses that the corticosteroid prednisone was known to
be useful for treating prostate cancer in combination with abiraterone
acetate, one of the therapeutic agents recited in Appellant’s claim 1. See id.
14:7–11 (“On Apr. 28, 2011, the U.S. Food and Drug Administration
approved abiraterone acetate in combination with prednisone to treat patients
with late-stage (metastatic) castration-resistant prostate cancer patients who
have received prior docetaxel (chemotherapy).”).
As required by Appellant’s claim 1, the subject receiving
Szmulewitz’s GR antagonist may also “currently be[]treated with an
androgen receptor (AR) antagonist, such as . . . ARN-509.” Szmulewitz

5 At the time of Appellant’s earliest priority date beclometasone,
betamethasone, budesonide, flunisolide, fluticasone, and triamcinoclone
were well known corticosteroids. See US 6,241,969 B1 (issued June 5,
2001) at 6:8–30 (listing beclometasone, betamethasone, budesonide,
flunisolide, fluticasone, and triamcinoclone as exemplary corticosteroids
useful in in corticosteroid formulations).
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3:38–39. As noted above ARN-509 is the compound of Appellant’s
Formula (I) recited in Appellant’s claim 1. See Spec. ¶ 61.
Although Szmulewitz does not expressly describe administering
ARN-509 at the dose of about 30 mg per day to about 480 mg per day
recited in Appellant’s claim 1, Szmulewitz discloses that it was known in the
art to optimize the dosage of medicaments used to treat prostate cancer. See
Szmulewitz 23:21–24 (“Some variation in dosage will necessarily occur
depending on the condition of the subject being treated. The person
responsible for administration will, in any event, determine the appropriate
dose for the individual subject.”). Szmulewitz, moreover, suggests that any
of the therapeutic agents described in its disclosure may be administered at
wide dosage ranges. See id. 21:45–58 (“A patient may be administered a
single GR antagonist or a combination of compounds described herein in an
amount that is, is at least, or is at most 0.1 . . ., 500 mg/kg/day (or any range
derivable therein).” (emphasis added)).
We therefore agree with the Examiner that, given the absence of
evidence of unexpected results, the ARN-509 dosage recited in claim 1
would have been obvious to a skilled artisan. See Iron Grip Barbell Co. v.
USA Sports, Inc., 392 F.3d 1317, 1322 (Fed. Cir. 2004) (“Where ‘the
difference between the claimed invention and the prior art is some range or
other variable within the claims . . ., the [applicant] must show that the
particular range is critical, generally by showing that the claimed range
achieves unexpected results.’”) (quoting In re Woodruff, 919 F.2d 1575,
1578 (Fed. Cir. 1990)).
As required by Appellant’s claim 1, the subject receiving
Szmulewitz’s GR antagonist “may be treated with a second prostate cancer
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therapy . . . [which] may be an androgen synthesis inhibitor, such as . . .
abiraterone.” Szmulewitz 3:46–51.
Thus, given the teachings in Szmulewitz that ARN-509, abiraterone
acetate, and a corticosteroid, would be useful in combination for treating
castration-resistant prostate cancer, we agree with the Examiner that a
skilled artisan had a good reason for, and a reasonable expectation of success
in, administering all of those agents to treat either metastatic or non-
metastatic castration-resistant prostate cancer, as recited in Appellant’s claim
1. We therefore also agree with the Examiner that the process of
Appellant’s claim 1 would have been obvious in view of Szmulewitz.
Appellant’s arguments do not persuade us to the contrary.
In particular, given Szmulewitz’s express disclosure that its GR
antagonist can be administered to a patient that is treated with an AR
antagonist, such as ARN-509, as well as an androgen synthesis inhibitor,
such as abiraterone (see Szmulewitz 3:37–51), Appellant does not persuade
us that the Examiner failed to identify a reason for combining ARN-509 and
abiraterone when treating prostate cancer, or that the Examiner’s reasoning
was based on improper hindsight. See Appeal Br. 5–7; Reply Br. 7–8. The
fact that Szmulewitz lists ARN-509 and abiraterone among other therapies
does not negate that fact that Szmulewitz expressly describes ARN-509 and
abiraterone as being useful in combination with other agents when treating
prostate cancer. See Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807
(Fed. Cir. 1989) (species claim held obvious where it recited one of 1200
possible combinations of embodiments disclosed by reference and where
reference suggested no preference for claimed embodiment); see also id.
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808 (That a reference “discloses a multitude of effective combinations does
not render any particular formulation less obvious.”).
Appellant, moreover, fails to identify any persuasive evidence of
record supporting its assertion that a skilled artisan would have viewed
ARN-509 and abiraterone as being potentially incompatible (see Appeal Br.
6), despite Szmulewitz’s express suggestion that combining an AR
antagonist such as ARN-509 and an androgen synthesis inhibitor such as
abiraterone would be useful for treating prostate cancer (see Szmulewitz
3:37–51). Appellant’s assertion as to the potential for increased side effects
when combining ARN-509 and abiraterone is therefore unsupported attorney
argument entitled to little, if any, probative weight. See Johnston v. IVAC
Corp., 885 F.2d 1574, 1581 (Fed. Cir. 1989) (“Attorneys’ argument is no
substitute for evidence.”).
Appellant also does not persuade us that Szmulewitz teaches away
from using a corticosteroid in its methods. See Appeal Br. 7–9; Reply Br. 3–
5. We acknowledge, as Appellant contends, that administration of GR
antagonists is central to Szmulewitz’s prostate cancer treatments. See
Szmulewitz, abstract (“Methods are directed to the treatment of subjects
with prostate cancer, in particular those with castration resistant prostate
cancer, with glucocorticoid receptor antagonists.”); see also id. 3:30–33 (“In
one aspect of the invention, there is provided a method of treating castration-
resistant prostate cancer in a subject comprising administering to said
subject a glucocorticoid receptor (GR) antagonist.”).
As noted above, however, Szmulewitz expressly discloses that its GR
antagonist can be any of a number of known corticosteroids, including for
example beclometasone, betamethasone, budesonide, flunisolide,
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fluticasone, and triamcinoclone. See Szmulewitz 3:42–44. Appellant does
not persuade us, therefore, that Szmulewitz teaches away from using
corticosteroids in its methods, or that Szmulewitz teaches away from treating
prostate cancer with a corticosteroid in combination with ARN-509 and
abiraterone, as recited in Appellant’s claim 1.
We acknowledge, as Appellant contends (see Appeal Br. 8–9; Reply
Br. 3–5), that Szmulewitz distinguishes between a standard treatment of
prostate cancer using a GR agonist such as prednisone (a corticosteroid), and
the use of GR antagonists for treating prostate cancer, which Szmulewitz
describes as its invention. Compare Szmulewitz 2:17–29 (questioning the
efficacy of prednisone, “a GR agonist,” in treating prostate cancer) with id.
28:18–21 (Szmulewitz noting that its experimental data in cancer cell lines
“suggest that increased GR expression and activity antagonizes AR
inhibition and sustains tumor cell survival”) and id. 28:50–54 (“[T]he
inventors believe that a GR inhibitor will synergize with second generation
AR-inhibitors, such as MDV3100, and delay the onset of CRPC [(castrate
resistant prostate cancer)] progression in patients treated with the
combination compared to patients treated with MDV3100 alone.”).
However, the fact that the inventors in Szmulewitz describe GR
antagonists as their preferred alternative to a more conventional GR agonist
treatment does not negate the fact that Szmulewitz discloses the combination
of a corticosteroid (prednisone) and abiraterone acetate, two of the three
ingredients recited in Appellant’s claim 1, as an FDA-approved prostate
cancer treatment. See Szmulewitz 14:7–11. And, as noted above,
Szmulewitz further discloses that ARN-509 was a known AR antagonist
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useful for treating prostate cancer in combination with other agents. See id.
3:37–39.
Given these teachings, Appellant does not persuade us that the
Examiner erred in determining that a skilled artisan, even advised of
Szmulewitz’s preference for GR antagonists, had motivation for combining
ARN-509 with the FDA-approved abiraterone/prednisone treatment known
in the art. See In re Fulton, 391 F.3d 1195, 1200 (Fed. Cir. 2004) (“[O]ur
case law does not require that a particular combination must be the
preferred, or the most desirable, combination described in the prior art in
order to provide motivation for the current invention.”). Indeed, given
Szmulewitz’s express teaching that its GR antagonist can be any of a
number of known corticosteroids, including for example beclometasone,
betamethasone, budesonide, flunisolide, fluticasone, and triamcinoclone (see
Szmulewitz 3:42–44), Appellant does not persuade us that Szmulewitz
teaches away from using corticosteroids in its methods, or that Szmulewitz
teaches away from treating prostate cancer with a corticosteroid in
combination with ARN-509 and abiraterone, as recited in Appellant’s claim
1.
Appellant also does not persuade us that the Examiner’s
characterization in the Final Action of ARN-509 as a GR antagonist
undermines the Examiner’s conclusion that the ARN-509 dosage of about 30
mg per day to about 480 mg per day recited in Appellant’s claim 1 would
have been obvious to a skilled artisan. See Appeal Br. 9–10. In response to
this argument the Examiner contends that that “initial reference to ARN-509
as the glucocortico[i]d receptor (GR) . . . was an obvious typographical error
as indicated by the referenced portion of Szmulewitz et al which specifically
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state[s] that ARN-509 is an androgen receptor (AR) substance (column 3,
lines 38-39).” Ans. 16. Appellant does not reply to the Examiner’s
contention directly. See Reply Br. generally.
In any event, as noted above, Szmulewitz discloses that it was known
in the art to optimize the dosage of medicaments used to treat prostate
cancer. See Szmulewitz 23:21–24 (“Some variation in dosage will
necessarily occur depending on the condition of the subject being treated.
The person responsible for administration will, in any event, determine the
appropriate dose for the individual subject.”). Szmulewitz, moreover,
suggests that any of the therapeutic agents described in its disclosure may be
administered at wide dosage ranges. See id. 21:45–58 (“A patient may be
administered a single GR antagonist or a combination of compounds
described herein in an amount that is, is at least, or is at most 0.1 . . ., 500
mg/kg/day (or any range derivable therein).” (emphasis added)). Appellant
does not persuade us, therefore, that the Examiner erred in determining that
the ARN-509 dosage recited in Appellant’s claim 1 would have been
obvious to a skilled artisan. See Iron Grip Barbell v. USA Sports, 392 F.3d
at 1322 (“Where the difference between the claimed invention and the prior
art is some range or other variable within the claims . . ., the [applicant] must
show that the particular range is critical, generally by showing that the
claimed range achieves unexpected results.”) (internal quotations omitted)).
Appellant also does not persuade that the Examiner reversibly erred in
characterizing Appellant’s claim 1 as reciting a “composition” rather than a
process (Reply Br. 2), or in characterizing Szmulewitz’s primary therapeutic
agent as a GR “substance” rather than a GR antagonist (see id. 3; see also
Ans. 4–6). To the contrary, for the reasons discussed above, we agree with
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the Examiner that the teachings of Szmulewitz would have provided a
skilled artisan with a good reason for, and a reasonable expectation of
success in, treating either metastatic or non-metastatic castration-resistant
prostate cancer, as recited in Appellant’s claim 1, using the combination of
agents recited in the claim, at the claimed dosages. We therefore affirm the
Examiner’s rejection of claim 1 for obviousness over Szmulewitz. Because
they were not argued separately, claims 2, 19, 20, and 32–36 fall with claim
1. See 37 C.F.R. § 41.37(c)(1)(iv) (2018).
Appellant argues claims 5, 6, and 21 as a separate claim grouping.
Appeal Br. 10. We select claim 21 as representative of this group of claims.
See 37 C.F.R. § 41.37(c)(1)(iv).
Claim 21 recites “[t]he method of claim 1, further comprising
administering a therapeutically effective amount of a gonadotropin-releasing
hormone [GnRH] agonist or antagonist to the male human patient.” Appeal
Br. 17. Appellant’s Specification explains that, “[i]n some embodiments,
the GnRH agonist or antagonist is leuprolide . . . .” Spec. 28
Appellant contends that the Examiner “failed to identify any
disclosure in Szmulewitz that teaches or suggests further combination with a
GnRH agonist or antagonist (claim 21) such as leuprolide (claim 5) or
goserelin acetate (claim 6).” Appeal Br. 10. Instead, Appellant contends,
“the Examiner appears to rely on a disclosure of leuprolide and goserelin as
potential combination agents with a GR antagonist at col. 3, lines 47-49.”
Id. (citing Final Act. 4).
We are not persuaded. As noted above, Szmulewitz’s GR antagonist
may be any one of a number of known corticosteroids, including for
example beclometasone, betamethasone, budesonide, flunisolide,
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fluticasone, and triamcinoclone. See Szmulewitz 3:42–44. And, in addition
to ARN-509 and abiraterone, Szmulewitz describes administering its GR
antagonist prostate cancer treatment to a subject “currently being treated
with androgen deprivation therapy, such as with leuprolide goserelin.”
Szmulewitz 3:35–36. Appellant does not persuade us, therefore, that the
Examiner erred in finding that Szmulewitz would have suggested including
a GnRH agonist or antagonist such as leuprolide in a
corticosteroid/ARN-509/abiraterone combination therapy for treating
prostate cancer. Accordingly, we also affirm the Examiner’s rejection of
claim 21 over Szmulewitz. Because they were argued in the same claim
grouping, claims 5 and 6 fall with claim 21. See 37 C.F.R. § 41.37(c)(1)(iv).
Appellant argues claims 28–31 as a separate claim grouping. Appeal
Br. 10. We select claim 29 as representative of this group of claims. See 37
C.F.R. § 41.37(c)(1)(iv).
Claim 29 recites “[t]he method according to claim 1, wherein the
[ARN-509], or a pharmaceutically acceptable salt thereof and abiraterone
acetate and the corticosteroid are administered at the same time.” Appeal
Br. 18. As to claim 29, Appellant argues that the Examiner “references the
disclosure in Szmulewitz relating to routes of administration and frequency
of administration of a GR antagonist.” Appeal Br. 10 (citing Final Act. 4–
5). We are not persuaded.
As noted above, Szmulewitz teaches that its GR antagonists, which
may be corticosteroids, may be administered to a patient that “is currently
being treated” with an AR antagonist such as ARN-509. Szmulewitz 3:38.
Szmulewitz also discloses combining its GR antagonists “with a second
prostate cancer therapy [which] . . . may be abiraterone . . . .” Id. 3:47–51.
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Szmulewitz explains further that “[t]he second prostate cancer therapy may
be given prior to said GR antagonist, after said GR antagonist, or at the same
time as said GR antagonist.” Id. at 3:54–56.
Given Szmulewitz’s disclosure that its GR antagonist, which may be a
corticosteroid, and its second prostate cancer therapy, which may
abiraterone, can be administered at the same time, we are not persuaded that
the Examiner erred in finding that Szmulewitz would have suggested
administering those agents at the same time, as recited in Appellant’s claim
29. Moreover, given Szmulewitz’s disclosure that its GR antagonist can be
administered to a patient receiving ARN-509, we discern no error in the
Examiner’s determination that it also would have been obvious to administer
ARN-509 at the same time as the other agents. We therefore affirm the
Examiner’s rejection of claim 29 over Szmulewitz. Because they were
argued in the same claim grouping, claims 28, 30, and 31 fall with claim 29.
See 37 C.F.R. § 41.37(c)(1)(iv).

DECISION SUMMARY
In summary:
Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 2, 5, 6, 19–21,
28–36
103(a) Szmulewitz 1, 2, 5, 6,
19–21,
28–36

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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