Ex Parte Davis

Patent Trial and Appeal Board

Jun 17, 2016

11916410 (P.T.A.B. Jun. 17, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
111916,410 05/21/2008 Pamela B. Davis
68705 7590 06/21/2016
TAROLLI, SUNDHEIM, COVELL & TUMMINO, LLP
1300 EAST NINTH STREET
SUITE 1700
CLEVELAND, OH 44114
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.
CWR-8155PCT 4824
EXAMINER
PURDY, KYLE A
ART UNIT PAPER NUMBER
1611
NOTIFICATION DATE DELIVERY MODE
06/21/2016 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):
rkline@tarolli.com
docketing@tarolli.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte PAMELA B. DA VIS
Appeal2014-004127
Application 11/916,410 1
Technology Center 1600
Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
RYAN H. FLAX, Administrative Patent Judges.
FLAX, Administrative Patent Judge.
DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134(a) involving
claims directed to treating cystic fibrosis by administering a PPARy agonist
(i.e., Pioglitazone) to airway epithelial cells to inhibit NF-KB activation
therein. Claims 1, 2, 17, and 18 are on appeal as rejected under 35 U.S.C.
§ 103(a). We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
1 The Real Party in Interest is Case Western Reserve University. App. Br. 2.
Appeal2014-004127
Application 11/916,410
STATEMENT OF THE CASE
The appealed claims can be found in the Claims Appendix of the
Appeal Brief. Claims 1 and 17 are independent claims. Claim 1 is
representative and reads as follows:
1. A method of treating a subject with a cystic fibrosis related
disorder comprising:
administering at least one PPARy agonist or a derivative thereof
to cystic fibrosis airway epithelial cells of the subject in an
amount effective to inhibit NF-KB activation in the cystic fibrosis
airway epithelial cells, the PPARy agonist or the derivative
thereof compnsmg 5-[ 4-[2-( 5-ethylpyridin-2-
yl)ethoxyl]benzyl]thiazolidine-2,4-dione (Pioglitazone) or a
derivative thereof.
App. Br. 19 (Claims Appendix).
The following rejection is on appeal:
Claims 1, 2, 17, and 18 rejected under 35 U.S.C. § 103(a) as obvious
over Freedman, 2 Cantoma, 3 and Desai. 4
FINDINGS OF FACT
FPL Freedman disclosed "CYSTIC FIBROSIS THERAPY" and
"[t]he present invention relates to the treatment of cystic fibrosis and other
diseases associated with mutations in the CFTR gene." Freedman 1 (Title,
2 International Patent Application Pub. No. WO 2004/098510 Al (published
Nov. 18, 2004) (hereinafter "Freedman").
3 U.S. Patent Application Pub. No. US 2004/0122059 Al (published June
24, 2 004) (hereinafter "Cantoma").
4 U.S. Patent Application Pub. No. US 2002/0037911 Al (published Mar.
28, 2002) (hereinafter "Desai").
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Field of the Invention). The focus of Freedman's disclosure is on treating
cystic fibrosis.
FF2. Freedman disclosed "cystic fibrosis (CF), a genetic disorder
caused by inactivating mutations in the cystic fibrosis transmembrane
conductance regulator (CFTR) gene" and "[e]xpression of the CFTR gene is
highest in cells that line the passageways of the lungs, pancreas, colon,
ileum, and genitourinary tract." Freedman 1; see also Final Action 3
(discussing Freedman).
FF3. Freedman disclosed:
[A] method for treating a disease in a human patient that has a
mutation in the CFTR gene by administering to the patient a
therapeutically effective amount of a peroxisome proliferator-
activated receptor gamma (PP ARy) inducer, a peroxisome
proliferator-activated receptor gamma (PPARy) agonist, an AP-
1 inhibitor, a ST AT inhibitor, or an NFkB inhibitor. Diseases
caused by mutations in a CFTR gene include, for example, cystic
fibrosis, pancreatitis, chronic obstructive pulmonary disease
(COPD), asthma, chronic sinusitis, pnmaP; sclerosing
cholangitis, and congenital bilateral absence of the vas deferens.
Freedman 2, 11. 12-20; see also Final Action 3 (discussing Freedman).
FF4. Freedman disclosed "[u]seful PPARy inducers and agonists ...
[include] any of the thiazolidinediones, but particularly troglitazone," and
"useful PPARy ligands include the thiazolidinediones, but particularly
rosiglitazone." Freedman 2, 1. 25 to 3, 1. 5; see also Final Action 3
(discussing Freedman).
FF5. Freedman disclosed "PPARy agonists inhibit the expression of
the pro inflammatory and insulin resistance-inducing cytokine TNF a,
increase other insulin signaling mediators, and block the NFkB
proinflammatory signaling pathway. The PPARy synthetic agonists
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Application 11/916,410
thiazolidinediones (TZDs) have been used as anti-diabetic drugs and exert
anti-inflammatory effects in the colon." Freedman 9, 11. 21-26; see also
Final Action 3 (discussing Freedman).
FF6. Freedman disclosed "[t ]he results of this experiments [sic]
described below demonstrate that PPARy mRNA expression is decreased in
those tissues specifically regulated by CFTR (colon, ileum and lung)," thus
equating PPARy expression and related disease among these tissues.
Freedman 10, 11. 3-5.
FF7. Freedman disclosed:
Lower but detectable expression levels of PPARyl have also been
reported in both mouse and human lung tissue (Lambe et al., Eur.
J. Biochem 23 9: 1-7, 1996; Zhu et al., J. Biol. Chem. 268: 26817-
26820, 1993). Expression in lung has been localized in alveolar
type-II pneumocytes whereas receptor activity has been found in
human airway epithelial cells, as well as in several human lung
epithelial cell lines.
Freedman 11, 11. 5-1 O; see also Final Action 3 (discussing Freedman).
FF8. Freedman disclosed:
PPARy activation has been shown to result in decreased
inflammation through inhibition of AP-1, ST AT and NFkB
pathways in monocytes and macrophages that results in a
modulatory effect on cytokine secretion (Jiang et al., Nature 391:
82-86, 1998; Nagy et al., Cell 93: 229-240, 1998; Ricote et al.,
Nature 391: 79-82, 1998), inhibition of IL-2 secretion from T
cells (Clark et al., J. Immunol. 164: 1364-1371, 2000), and
inhibition of NFkB activity in epithelial cells (Su et al., J. Clin.
Invest. 104: 383-389, 1999). Thus a decrease in PPAR
expression and function could explain several sequelae that are
associated with the cystic fibrosis phenotype such as an
excessive host inflammatory response, increased peripheral
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Application 11/916,410
insulin resistance, and alterations in lipid metabolism within the
peroxisomal compartment.
Freedman 11, 1. 25 to 12, 1. 6. Thus, Freedman taught that PPARy activation
inhibits NFKB pathways and activity in epithelial cells and expressly
suggested a connection between PP ARy activation, decreased inflammation,
and inhibition ofNFKB activity in colonic epithelial cells, and the cystic
fibrosis phenotype.
FF9. Freedman disclosed "any of these compounds [that bind to the
PPARy binding domain, e.g., thiazolidinediones (including rosiglitazone and
troglitazone)] can be used to treat cystic fibrosis or any other disorder caused
by a mutation in the CFTR gene." Freedman 12, 11. 14--21.
FF 10. Cantoma disclosed "treating ... asthma ... [by] administering
a therapeutically effective amount of at least one PP AR-y agonist."
Cantoma i-f 19; see also Final Action 4 (discussing Cantoma).
FFl 1. Cantoma disclosed "the PPAR-y agonist is selected from the
group consisting of a thiazolidinedione and a non-thiazolidinedione PPAR-y
agonist. In a preferred embodiment of the method, the at least one PP ARy
agonist is selected from the group consisting of Ciglitazone, Troglitazone,
Rosiglitazone, Pioglitazone, Englitazone, RXR activator LGD1069, and
prostaglandin J2." Cantoma i-f 20; see also Final Action 4 (discussing
Cantoma).
FF12. Cantoma disclosed:
Delivery of therapeutic agents to the lung by way of inhalation is
an important means of treating asthma and chronic obstructive
pulmonary disease .... The invention herein involves a method
of treatment using an aerosol formulation which comprises
(a) one or more PP ARy agonists; and (b) a suitable fluid carrier.
Cantoma i-f 77; see also Final Action 4 (discussing Cantoma).
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FF13. Desai disclosed "[s]ubstituted 5-aryl-2,4-thiazolidinediones and
oxazolidinediones are potent agonists of PP AR, and are therefore useful in
the treatment, control or prevention of diabetes, hyperglycemia,
hyperlipidemia (including hypercholesterolemia and hypertriglyceridemia),
atherosclerosis, obesity, vascular restenosis, and other PPAR a and/or y
mediated diseases, disorders and conditions." Desai (Abstract); see also
Final Action 4 (discussing Desai).
FF 14. Desai disclosed "[ e ]xamples of other active ingredients that
may be combined with a compound of Formula I, either administered
separately or in the same pharmaceutical compositions, include, but are not
limited to: ... PP ARy agonists such as the glitazones (e.g. troglitazone,
pioglitazone, englitazone, MCC-555, BRL49653 (rosiglitazone ), and the
like)." Desai i-fi-f 188-189; see also Final Action 4 (discussing Desai).
DISCUSSION
The Examiner determined that the combination of Freedman,
Cantoma, and Desai taught and suggested the subject matter of claims 1, 2,
17, and 18. More specifically, the Examiner determined that Freedman
disclosed administering a PP ARy agonist (i.e., any thiazolidinedione) to treat
cystic fibrosis (FF3-FF6, FF9), that PP ARy works therapeutically by
inhibiting NF-Kl3 activation in epithelial cells (FF5, FF8), that expression of
the gene causing cystic fibrosis is highest in cells lining the passageways of
the lungs (FF1-FF3, FF6) and PPARyl expression is detectable in human
lung epithelial cell lines (FF7), and that activating PPARy in patients
(suffering from colitis) inhibits NF-KB activity in colon epithelial cells and
has a therapeutic effect, and expressly suggested that these results related to
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cystic fibrosis phenotype (FF8). Further, the Examiner determined that,
although Freedman did not expressly disclose the thiazolidinedione
pioglitazone and administering it to airway epithelial cells, it suggested
thiazolidinediones generally and that it would have been obvious to combine
a known equivalent thiazolidinedione compound based on the disclosure
thereof from Cantoma. FF9--FF 12. Moreover, the Examiner determined
that the pioglitazone disclosed by Cantoma is a PP ARy agonist (like the
troglitazone, rosiglitazone, englitazone, MCC-55, and ciglitazone disclosed
by Freedman and Cantoma). FF9, FFl 1, FF13, FF14.
We adopt the Examiner's findings of fact, reasoning on scope and
content of the prior art, and conclusions set out in the Final Action and
Answer. We agree that the evidence of record supports that the claims
would have been obvious over the cited prior art combination and address
Appellant's arguments below.
Appellant's arguments center on the contention that the combined
references do not teach or suggest that a PPARy agonist can inhibit
activation ofNF-Kl3 in cystic fibrosis airway epithelial cells. See App. Br. 5.
Appellant contends that the prior art combination fails to disclose this and
that a skilled artisan would not have found it obvious to try because of
unpredictability and lack of reasonable expectation of success. Id.
Appellant contends that Freedman's failure to specifically identify
pioglitazone and its administration to inhibit NF-Kl3 in airway epithelial cells
is fatal to the obviousness case. But, as set forth above, Freedman teaches
and suggests that any thiazolidinedione, which would have included the
well-known pioglitazone, can be used to treat cystic fibrosis because it will
inhibit NF-KB activity. See, e.g., FF8-FF9, FFlO. Freedman identified
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successful treatment of colitis by treating epithelial cells using PP AR y
agonists to inhibit NF-KB activity and specifically suggested that the same
could be expected for cystic fibrosis phenotype. FF8. Combining the
asthma drug pioglitazone (which is from the very class identified as useful in
Freedman) in the aerosol-inhalant mode of administration to lungs (which
would supply the cystic fibrosis drug directly to a patient's airway in need of
treatment) from Cantoma would have been obvious (Freedman explicitly
links the diseases cystic fibrosis and asthma as being caused by the same
mutated gene - see FF3).
Appellant also argues that Freedman's citation to Su et al. (FF8),
which is directed to treating colitis with a PPARy agonist to block NF-kB
activity, cannot teach or suggest that the same treatment would work when
administered to cystic fibrosis airway epithelial cell. App. Br. 10. However,
Freedman explicitly makes this connection in the very same paragraph. FF8.
In fact, Freedman repeatedly equates CFTR-gene-related diseases and
associated treatments among the lungs and colon (and other tissues). FF2,
FF3, FF5, FF6, FF8.
Appellant also argues that the effects of different thiazolidinediones
on mammalian cells was unpredictable. App. Br. 13. Even if that were true,
evidence of which is essentially limited to a single sentence in Freedman
indicating diverse effects ofrosiglitazone and troglitaozone on PPARy
mRNA expression, the prior art combination identified a set of
thiazolidinediones numbering as few as six and Freedman urges that any
such compound is suitable to treat cystic fibrosis. Where there is a need or
market pressure (as there would be here), picking one of a finite number of
known solutions to a known problem is obvious. KSR Int 'l Co. v. Teleflex
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Application 11/916,410
Inc., 550 U.S. 398, 421 (2007). Here, selecting any one of the identified
drugs would have been obvious to try and the evidence of record does not
establish an unreasonable lack of predictability, in fact, it does just the
opposite. See, e.g. Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1366 (Fed.
Cir. 2007) ("[T]his is not the case where there are 'numerous parameters' to
try. Rather, the only parameter to be varied is the anion ... [the prior art]
pointed the skilled artisan to 53 anions."). Here, the prior art pointed to six
different thiazolidinediones.
While we understand Appellant has not separately argued claims 2,
17, and 18 because they have not been properly set apart as required (see 37
C.F.R. § 41.37(c)(l)(iv) (2016); see also MPEP 1205.02 (Rev. 9, Aug.
2012) (failure to separately argue constitutes waiver), we are nevertheless
not persuaded by Appellant's contentions regarding the patentability of
claims 2, 17, and 18 (App. Br. 17).
For the above reasons, we find that the evidence of record supports
the Examiner's determination that claim 1 (and claims 2, 17, and 18, which
fall with claim 1) would have been obvious over Freedman, Cantoma, and
Desai and, therefore, the respective rejection is affirmed.
SUMMARY
The rejection of claims 1, 2, 17, and 18 under 35 U.S.C. § 103(a) over
Freedman, Cantoma, and Desai is affirmed.
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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).
AFFIRMED
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