Ex Parte Zakrzewski

Patent Trials and Appeals Board

Apr 11, 2019

14477034 - (D) (P.T.A.B. Apr. 11, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/477,034 09/04/2014
113568 7590 04/15/2019
Perkins Coie LLP - Amarin Corporation PLC
1201 Third Avenue
Suite 4900
Seattle, WA 98101
FIRST NAMED INVENTOR
Joseph S. Zakrzewski
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
88896-8063.USOl 8748
EXAMINER
GEMBEH, SHIRLEY V
ART UNIT PAPER NUMBER
1615
NOTIFICATION DATE DELIVERY MODE
04/15/2019 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):
patentprocurement@perkinscoie.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JOSEPHS. ZAKRZEWSKI 1
Appeal2018-003236
Application 14/477,034
Technology Center 1600
Before DONALD E. ADAMS, JOHN G. NEW, and DAVID COTTA,
Administrative Patent Judges.
NEW, Administrative Patent Judge.
DECISION ON APPEAL
1 Appellant identifies Amarin Pharmaceuticals Ireland Limited as the real
party-in-interest. App. Br. 1.
Appeal2018-003236
Application 14/477,034
SUMMARY
Appellant files this appeal under 35 U.S.C. § I34(a) from the
Examiner's Final Rejection of claims 1-20. Specifically, claims 1-5, 9-12,
and 19 stand rejected as unpatentable under 35 U.S.C. § I03(a) as being
obvious over the combination of E. Higashihara et al., Effects of
Eicosapentaenoic Acid on Biochemical Failure after Radical Prostatectomy
for Prostate Cancer, 24 IN VIVO 561---66 (2010) ("Higashihara"), Fortin (US
2010/0160261 Al, June 24, 2010) ("Fortin"), Breivik et al. (US
2011/0130458 Al, June 2, 2011) ("Breivik"), M. Peet et al., Dose-Ranging
Study of the Effects of Ethyl-Eicosapentaenoate in Patients With Ongoing
Depression Despite Apparently Adequate Treatment With Standard Drugs,
59(10) ARCH. GEN. PSYCHIATRY 913-19 (2002) ("Peet"), and Horrobin (US
6,479,544 Bl, November 12, 2002) ("Horrobin").
Claims 1, 6-8, and 13-20 stand rejected as unpatentable under 35
U.S.C. § I03(a) as being obvious over the combination of Higashihara,
Fortin, Breivik, Peet, Horrobin, E. Opalinska et al., Increasing Level of
Prostate-Specific Antigen and Prostate Cancer Risk Factors among 193
Men Examined in Screening Procedure (Abstract), 58(2) ANN. UNIV. CURIE
SKLODOWSKA MED. 57---63 (2003) ("Opalinska"), and D.J. Gallagher et al.,
Germline BRCA Mutations Denote a Clinicopathologic Subset of Prostate
Cancer, 16(7) CLIN. CANCER RES. 2115-121 (2010) ("Gallagher").
We have jurisdiction under 35 U.S.C. § 6(b ).
We AFFIRM.
2
Appeal2018-003236
Application 14/477,034
NATURE OF THE CLAIMED INVENTION
Appellant's invention is directed to methods of treating and/or
preventing prostate cancer, comprising administering to a subject in need
thereof a pharmaceutical composition comprising eicosapentaenoic acid or a
derivative thereof. Abstract.
REPRESENTATIVE CLAIM
Claim 1 is representative of the claims on appeal and recites:
1. A method of treating prostate cancer in a subject, the
method comprising administering to the subject about 4 g of
ethyl eicosapentaenoate per day.
App. Br. 26.
ISSUES AND ANALYSES
We adopt the Examiner's findings, reasoning, and conclusion that the
claims are prima facie obvious over the combined cited prior art. We
address the arguments raised by Appellant below.
A. Claims 1-5, 9-12, and 19
Issue 1
Appellant argues that the Examiner has failed to establish a prima
facie case of obviousness at least because the scope and content of the prior
art have not been properly discerned, actual differences between the claims
and the prior art are not identified, and the requirements set forth in MPEP §
2143(I)(G) have not been articulated. App. Br. 11-12.
3
Appeal2018-003236
Application 14/477,034
Analysis
The Examiner finds that Higashihara teaches treating prostate cancer
with eicosapentaenoic acid. Final Act. 4 (citing Higashihara 562).
However, the Examiner finds, that Higashihara does not teach that the
composition dosage comprises about 4 g of eicosapentanoate per day, but
rather teaches administering 2.4 g/day. Id. ( citing Higashihara Abstr.).
The Examiner finds that Fortin teaches that polyunsaturated fatty acid
monoglycerides are useful as cancer treating agents, and that one such
polyunsaturated monoglyceride is ethyl eicosapentaenoate, which can also
be used in combination with other anticancer agents. Final Act. 4 ( citing
Abstr., ,r,r 97, 26).
The Examiner finds that Breivik teaches treating various diseases such
as coronary heart disease by administering a composition comprising high
concentrations of omega-3 fatty acids from krill (Breivik ,r 44), in which the
omega-3 fatty acid comprises at least 75 weight% of eicosapentaenoic acid
("EPA") and/or docosahexaenoic acid ("DHA") or, more preferably, 80
weight% EPA and DHA (Breivik ,r 52) and about 90% by weight of all fatty
acids. Final Act. 5---6 (citing Breivik ,r,r 36, 44, 52). The Examiner finds
Breivik additionally teaches compositions comprising both EPA and DHA.
Id. at 6 (citing Breivik ,r 53).
The Examiner finds that Peet teaches dose-ranging effects of ethyl-
eicosapentanoate in which 1 to 4 g/day of ethyl-eicosapentanoate is
administered in the treatment of depression and cardiovascular-related
disease. Final Act. 6 ( citing Peet 17). The Examiner finds that Horrobin
teaches using pharmaceutical formulations containing EPA, or a derivative
of EPA, and arachidonic acid ("AA") for the treatment of, inter alia, prostate
4
Appeal2018-003236
Application 14/477,034
cancer in which the dosage amount is 4.0 g per day. Id. ( citing Horrobin col.
3, 11. 1-25, col. 4, 11. 8-13; see also col. 2, 11. 16-20).
The Examiner concludes that a person of ordinary skill in the art
would have been motivated to treat prostate cancer with EPA, as taught by
Higashihara, and to incorporate into these teachings the method of treating
prostate cancer taught by Fortin, Peet, and Horrobin. Final Act. 6. The
Examiner further concludes that person of skill in the art would have had a
reasonable expectation of success in combining the references, because the
dosage ranges of the compositions taught by Breivik, Peet, and Horrobin
overlap the claimed dosage of 4 g/day of ethyl-eicosapentanoate in the
treatment of prostate cancer. Id.
Appellant argues that the Examiner finds that Higashihara: "teaches ...
treating prostate cancer with eicosapentaenoic acid (i.e. and [sic] ethyl ester
... a.k.a. Epadel)." App. Br. 12 (quoting Final Act. 4). Appellant contends
that the Examiner mischaracterizes the teachings of Higashihara, asserting
that Higashihara teaches administering Epadel to patients having prostate
cancer, but also makes clear that the Epadel treatment had no significant
effect on the outcomes of the treated prostate cancer patients compared to
the control group. Id. (citing Higashihara 562, 563, Table II). Therefore,
Appellant argues, Higashihara does not teach: "treating prostate cancer in a
subject, the method comprising administering to the subject a
pharmaceutical composition comprising about 4g of E-EP A per day," as
recited by claim 1. Id. at 12-13.
With respect to Fortin, Appellant disputes the Examiner's finding that
paragraphs [0097]-[0098] of Fortin teach eicosapentaenoic acid and that
neither of the compounds depicted in paragraph [0097] depict ethyl-
5
Appeal2018-003236
Application 14/477,034
eicosapentaenoic acid. App. Br. 12-13. The formulae of paragraph [0097]
are reproduced below.
~)
r,
/,c=-... ......... "', ... -··············,, .. -··""··············-,~--·/··············-< ... ,,.:,·/-... ... ~
\
\-:::.::.::.::.:;.:;. .• ,. ..... , .......... ......_....,,.:::.::.::.::.::.::. ....... /' ............ ,......_:::.::.::.::.::.::.:..-·.,,.,.,, ............... _ ....
" ,:;··
//···············'·'-....._ ... .-=-.. .... ~,.r·' ·············· .............. /.----4!~·-,: 1·_,,,·, ........
. \
~ ................ -, ... -.:::::::::::::...-""/ ............ ....._ ............................... ...._..._~,
Appellant asserts that the upper depicted compound is ethyl
docosapentaenoate (C22:5 n-3) (Compound 2), and the lower structure on
the bottom is ethyl docosahexaenoate (C22:6 n-3) (Compound 7). Id. at 13.
Appellant contends that E-EP A, in contrast, has a 20-carbon backbone
( excluding the ethyl radical covalently bound to the ester), whereas the
structures of paragraph [0097] each have a 22-carbon backbone. Id.
Appellant asserts that E-EPA and the depicted compounds of Fortin
also differ in the intermediate structural regions, particularly in the location
and number of the double bonds, and not in just pendant substitutions. App.
Br. 13. Appellant compares the structures of Fortin's Compound 2 and
Compound 7 with E-EPA (Fortin's Compound 8), as depicted below:
(- ~..-= ............... ~~_....n,....._./
'=~-~- ')
These differences are significant, Appellant argues, because the
carbon-carbon double bonds in Fortin's Compounds 2 and 7 and in E-EPA
represent important locations for biological processes, including chemical
transformations and site-specific interactions with other biomolecules. Id.
Furthermore, Appellant points out, the repetitive groups in E-EP A and
Compounds 2 and 7 are located in the intermediate regions of the molecules
6
Appeal2018-003236
Application 14/477,034
and not at the N-tenninal pendant groups, and are thus distinguishable from
homologs at issue in In re Wilder, 563 F.2d 457 (C.C.P.A. 1977). Id.
Therefore, Appellant argues, E-EPA and Compounds 2 and 7 are not
homologs. Id. at 14--15. Appellant asserts that a person of ordinary skill in
the art would have recognized that, although Compounds 2 and 7 share
general similarities with E-EPA, the differences in chain length, number of
carbon-carbon double bonds, and positions of carbon-carbon double bonds
relative to the ester functional group are key technical differences that would
result in significant differences in biological activity observed among
different fatty acids. Id.
Appellant argues further that Fortin' s only mention of E-EP A is in its
presence as just one of many components of a fatty acid ethyl ester mixture.
App. Br. 15. Appellant asserts that Fortin does not teach the use of the
mixture of fatty acid ethy 1 esters (including E-EP A) to treat any disease or
disorder. Id.
With respect to Horrobin, Appellant acknowledges that the reference
teaches a combination of EPA and arachidonic acid ("AA") or, in some
embodiments, gamma-linolenic acid ("GLA") or dihomogamma-linolenic
acid ("DGLA"). App. Br. 20 ( citing Horrobin col. 1, 11. 19-20, col. 2, 11. 20-
21 ). Appellant notes that Horrobin teaches that its compositions may
include EPA and arachidonic acid in a ratio "preferably between 1: 1 and
20:1." Id. (citing Horrobin col. 2, 11. 21-22). However, Appellant asserts
that Horrobin teaches EPA in combination with arachidonic acid, but not as
EPA alone. Id. Therefore, Appellant contends, the Examiner failed to find
to teaching or suggestion of Horrobin portion disclosing administering to the
subject about 4g ofE-EPA per day. Id.
7
Appeal2018-003236
Application 14/477,034
Appellant argues further that, although Horrobin teaches
administering its compositions to treat a wide range of diseases and
disorders, Horrobin does not teach or suggest the benefit of using the
claimed composition in treating prostate cancer over other listed diseases or
disorders. App. Br. 20.
We do not find Appellant's arguments persuasive. As an initial
matter, we remind Appellant that: "[O]ne cannot show non-obviousness by
attacking references individually where ... the rejections are based on
combinations of references." In re Keller, 642 F.2d 413, 426 (C.C.P.A.
1981 ). Rather, the test for obviousness is what the combined teachings of
the references would have suggested to those of ordinary skill in the art. Id.
at 425.
Higashihara teaches the use of E-EPA (Epadel-S) administered at a
daily dose of 2.4 g to post-radical prostatectomy patients, commencing 30
days post-surgery. Higashihara Abstr., 562. Higashihara summarizes the
prior art as teaching: "EPA and DHA [ docosahexaenoic acid] are promising
dietary agents to reduce PSA [prostate-specific antigen] recurrence after
radical prostatectomy in patients with PC [prostate cancer]." Id. at 562.
Although Higashihara teaches that: "The PSA [prostate-specific antigen]
recurrence rates during a mean follow-up of 53.8 months were not different
between the two groups [i.e., treatment and control] (p=0.16)," Higashihara
also teaches that: "A longer and/or larger intervention or docosahexaenoic
acid supplementation might be necessary to identify significant preventive
effects of mega-3 polyunsaturated fatty acids on PSA recurrence." Id. at
Abstr. ( emphasis added). Higashihara thus directly suggests that a dosage
higher than 2.4 g/day could be effective.
8
Appeal2018-003236
Application 14/477,034
Fortin is cited by the Examiner as teaching, generally, that
polyunsaturated fatty acid monoglycerides are useful as cancer treating
agents, and that one such polyunsaturated monoglyceride is E-EPA, which
can also be used in combination with other anticancer agents. See Final Act.
4 (citing Fortin, Abstr., ,r,r 97, 26). Specifically, Fortin teaches that it was
known in the prior art that:
A diet containing LA (n-6 PUP A[2J) stimulated the growth and
metastasis of human breast cancer cells transplanted into athymic
nude mice, whereas EPA or DHA exerted suppressive effects
compared with palmitic acid (PA). Thus, in agreement with the
epidemiological observations, LA (n-6 PUPA) accelerates,
whereas EPA and DHA (n-3 PUP A) suppress mammary cancer
compared with PA diet in experimental systems (Rose D P, and
al., JNCI 87, 1995) (Senzaki H, and al., Anticancer Res 18,
1998).
Fortin ,r 6.
Horrobin is directed to: "Eicosapentaenoic acid or any appropriate
derivative (EPA) ... in combination with arachidonic acid (AA) or an AA
precursor, selected from DGLA and GLA, to give a pharmaceutical
formulation." Horrobin Abstr. Specifically, Horrobin teaches:
The present invention provides pharmaceutical formulations
containing eicosapentaenoic acid or any appropriate derivative
(hereinafter collectively referred to as EPA) and arachidonic acid
(AA), as set out in the claims attached. The EPA is preferably
provided in a dose of between 100 mg and 10,000 mg/day. The
formulation may be a single preparation comprising 100-10,000
mg EPA. An alternative upper limit is 5,000 mg EPA. Preferably,
the formulations of the invention comprise 1--4 g EPA and O .1-
2 Polyunsaturated fatty acid.
9
Appeal2018-003236
Application 14/477,034
2.0 g arachidonic acid (AA). Still preferred amounts are 1.5-3 g
EPA and 0.2-1 g AA.
Horrobin col. 2, 11. 16-29. Horrobin further teaches that: "The EPA is
preferably composed of a triglyceride or ethyl ester which is 50% pure or
purer, more preferably more than 90% pure." Id. at 11. 55-57. Horrobin also
teaches that: "The formulations of the present invention may be used for the
treatment of a wide range of diseases and disorders including: ... disease of
the male or female reproductive organs such as the breast or the prostate
gland." Id. at col. 3, 11. 1-22.
Appellant contends that the teachings of Horrobin are inapposite
because Horrobin teaches administration of EPA in combination with AA,
and not by itself. However, Appellant's independent claim 1 recites: "A
method of treating prostate cancer in a subject, the method comprising
administering to the subject about 4 g of ethyl eicosapentaenoate per day."
Use of the transition "comprising" in the language of a claim creates a
presumption that the claim does not exclude additional, unrecited elements.
See Crystal Semiconductor Corp. v. Tri Tech Microelectronics Int 'l, Inc., 246
F.3d 1336, 1348 (Fed. Cir. 2001). Consequently, the scope of claim 1 does
not exclude the co-administration of AA with E-EP A, as expressly taught by
Horrobin.
Consequently, we are not persuaded by Appellant's argument that the
Examiner failed to accurately ascertain the differences between the claimed
invention and the applied references. On the contrary, we agree with the
Examiner that the combined cited prior art teaches or suggests the
limitations of claim 1.
10
Appeal2018-003236
Application 14/477,034
Issue 2
Appellant argues that the Examiner erred because a person of ordinary
skill in the art, understanding the teachings of the cited prior art, would have
had no motivation to combine the references, and no reasonable expectation
of success in so doing. App. Br. 20.
Analysis
Appellant repeats the argument, presented supra, that Higashihara
teaches that administering 2.4g of Epadel per day to patients who had
already undergone radical prostatectomy and had plasma PSA levels of 0.2
ng/mL or less 3 months after surgery had no significant effects compared to
control. App. Br. 21 (citing Higashihara Abstr., 562, 563).
Appellant also argues that the Examiner acknowledges that Fortin
does not disclose administering E-EPA, in any amount, to a subject, or using
E-EPA to treat any type of cancer. Id. Appellant then points to M. Y. Wei et
al., Effects of Eicosapentaenoic Acid Versus Docosahexaenoic Acid on
Serum Lipids: A Systematic Review and Meta-Analysis, 13 CURR.
ATHEROSCLER. REP. 474--83 (2011) ("Wei"). App. Br. 22. According to
Appellant, both Wei and Higashihara teach that DP A ethyl ester or DHA
ethyl ester (i.e., Fortin's Compounds 2 and 7, respectfully) and are not
relevant to the claims on appeal, because Higashihara expressly teaches that
DHA ethyl ester likely has different biological activity in prostate cancer
patients than the inactivity observed for EPA ethyl ester. Id. ( citing
Higashihara 564).
Appellant next argues that Breivik is relied upon by the Examiner as
teaching: "treating various diseases such as coronary heart disease ... " but
11
Appeal2018-003236
Application 14/477,034
does not teach treating prostate cancer with E-EPA. App. Br. 22. Appellant
also argues that Peet traches that E-EP A acts as an antidepressive agent in
patients. Id. (citing Peet Abstr.). Appellant also contends that, because Peet
teaches administering a dose of 1 g/day ofE-EPA. Id. (citing Peet 915-16).
Therefore, argues Appellant, a person of ordinary skill in the art,
understanding the combined teachings of Higashihara, Horrobin, Breivik,
Peet, and Fortin would not expect to be successful in treating prostate cancer
using 4g of E-EP A, because none of the applied references either alone or in
combination suggest or teach administration of 4g E-EPA in the treatment of
prostate cancer, as recited in claim 1.
We do not agree, for the reasons we have set forth supra. Although
Higashihara does not report effective results following daily post-radical
prostatectomy administration of 2.4g of E-EP A, Higashihara expressly
encourages the administration of higher dosages. See Higashihara Abstr.
Fortin is cited generally for the purpose of establishing that the prior art
recognized that polyunsaturated fatty acids, such as E-EPA, may be effective
in the treatment of prostate cancer. Furthermore, Horrobin (which Appellant
does not discuss in this section) teaches administration of E-EP A in the
dosage recited in the claims for the treatment of, inter alia, prostate cancer.
See Horrobin col. 2, 11. 16-29, 55-57, col. 3, 11. 1-22. As we have also
explained, the fact that Horrobin also teaches co-administration of AA does
not place the teachings of Horrobin beyond the scope of the claims on
appeal.
We agree with the Examiner that a person of ordinary skill in the art
would be motivated to combine the teachings of the cited prior art to
increase the dosage taught by Higashihara to the range taught by Horrobin,
12
Appeal2018-003236
Application 14/477,034
and as generally suggested by Fortin, and that the skilled artisan would have,
based upon the combined teachings of the references, a reasonable
expectation of success. See In re Langi, 759 F.2d 887, 897 (Fed. Cir. 1985)
("Only a reasonable expectation of success, not absolute predictability, is
necessary for a conclusion of obviousness").
We consequently affirm the Examiner's rejection of independent
claim 1. Furthermore, Appellant relies upon the same arguments with
respect to the Examiner's rejection of dependent claims 2-5, 9-12, and 19.
App. Br. 23. For the reasons we have explained supra, we similarly affirm
the rejection of those claims.
B. Claims 1, 6-8, and 13-20
Appellant argues that the teachings of Opalinska and Gallagher
Fail to cure the alleged deficiencies of Higashihara, Fortin, Breivik,
Horrobin, and Peet. App. Br. 24--25.
We have explained in Section A of this Decision why we do not find
Appellant's arguments with respect to the combined cited prior art
persuasive. We incorporate those arguments herein, and we affirm the
Examiner's rejection of the claims.
13
Appeal2018-003236
Application 14/477,034
DECISION
The Examiner's rejection of claims 1-20 under 35 U.S.C. § 103(a) is
affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l )(iv).
AFFIRMED
14