Ex Parte Newman et al

Patent Trial and Appeal Board

Jun 21, 2016

12521965 (P.T.A.B. Jun. 21, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/521,965 06/02/2010
86738 7590 06/23/2016
MCCARTER & ENGLISH, LLP BOSTON
265 Franklin Street
Boston, MA 02110
FIRST NAMED INVENTOR
Walter Newman
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.
120485-00202 4431
EXAMINER
SOROUSH, LAYLA
ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
06/23/2016 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):
docket@mccarter.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte WALTER NEWMAN,
ANJALI KUMAR, and LYNNE LIBERTINE1
Appeal2014-007157
Application 12/521,965
Technology Center 1600
Before MELANIE L. McCOLLUM, JEFFREY N. FREDMAN, and
RICHARD J. SMITH, Administrative Patent Judges.
McCOLLUM, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a
treatment method. The Examiner has rejected the claims for anticipation,
obviousness, and/or obviousness-type double patenting. We have
jurisdiction under 35 U.S.C. § 6(b). We affirm.
1 Appellants identify the real party in interest as Cornerstone Therapeutics
Inc. (App. Br. 3).
Appeal2014-007157
Application 12/521,965
STATEMENT OF THE CASE
Claims 1-16, 19-22, and 39 are on appeal and are set forth in the
Claims Appendix to Appellants' Appeal Brief (App. Br. 24--27).2 Claims 1
and 3 are representative and read as follows:
1. A method of treating a condition selected from the group
consisting of asthma, rheumatoid arthritis, gout, psoriasis, allergy, rhinitis,
adult respiratory distress syndrome, chronic obstructive pulmonary disease,
acne, atopic dermatitis, conjunctivitis, ischemia/reperfusion injury,
atherosclerosis, aortic aneurysm, nasal polyposis, inflammatory bowel
disease, irritable bowel syndrome, cancer, tumor, respiratory syncytial virus,
Sjogren-Larsson syndrome, sickle cell disease, sepsis, endotoxin shock,
myocardial infarction, cystic fibrosis and stroke in a patient suffering
therefrom comprising administering to said patient a composition
comprising: i) zileuton substantially free of (S)-zileuton; and ii) a
pharmaceutically acceptable excipient, wherein said zileuton is administered
at a daily dose from about 450 milligrams to about 1200 milligrams per day.
3. The method of Claim 1, wherein said zileuton is administered at a
daily dose from about 500 milligrams to about 1000 milligrams per day.
Claims 1, 2, 4, 5, 8-11, 13, 15, 16, 19-21, and 39 stand rejected under
35 U.S.C. § 102(b) as anticipated by Gray3 (Ans. 2).
Claims 3, 6, 7, 12, and 14 stand rejected under 35 U.S.C. § 103(a) as
obvious over Gray (id. at 5).
Claim 22 stands rejected under 35 U.S.C. § 103(a) as obvious over
Gray in view of Rabe4 (id. at 6).
2 Claims 40 and 41 are also pending but have been withdrawn from
consideration (App. Br. 27).
3 Gray, WO 94/26268 Al, Nov. 24, 1994.
4 Klaus F. Rabe et al., Worldwide Severity and Control of Asthma in
Children and Adults: The Global Asthma Insights and Reality Surveys, 114
J. ALLERGY CLIN. lMMUNOL. 40-47 (2004).
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Application 12/521,965
Claims 1-16 and 19-21 stand rejected on the ground ofnonstatutory
obviousness-type double patenting as being unpatentable over claim 15 of
US Patent No. 8,003,684 B2 to Hanko (patented Aug. 23, 2011) (hereinafter
"Hanko") (id. at 7).
Claim 22 stands rejected on the ground of nonstatutory obviousness-
type double patenting as being unpatentable over claim 15 of Hanko in view
of Rabe (id. at 9).
I
The Examiner finds that Gray anticipates representative claim 1 and
renders representative claim 3 obvious (Ans. 2-5). Appellants have
discussed these rejections together (App. Br. 5-19). We are, therefore,
discussing these rejections together, although, as noted below, some of the
arguments raised by Appellants do not appear to be applicable to the
anticipation rejection.
Findings of Fact
1. Gray discloses that, "[ c ]hemically, the active compound is the
(+)isomer ofN-(1-benzo[b ]thien-2-ylethyl)-N-hydroxyurea, hereinafter
referred to as zileuton[, which] appears to have the R absolute
stereochemistry" (Gray 2: 3-7).
2. Gray also discloses that the "separation of racemic zileuton into
(+) zileuton and(-) zileuton has not been described; however, the
enantioselective synthesis of ( + )-zileuton from L-( +)-lactic acid has been
described by Hsiao and Kolasa [Tetra. Letters 33, 2629-2632 (1992)]" (id. at
3: 20-25).
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Application 12/521,965
3. In addition, Gray discloses that it "has now been discovered
that the optically pure ( +) isomer of zileuton is an effective agent for treating
asthma, ulcerative colitis, rheumatoid arthritis, psoriasis, [and] allergic
rhinitis" (id. at 6: 2-5).
4. In particular, Gray discloses "a method of treating asthma,
which comprises administering to a human in need of such therapy, an
amount of ( + )-zileuton, or a pharmaceutically acceptable salt thereof,
substantially free of its(-) stereoisomer, said amount being sufficient to
alleviate the symptoms of asthma" (id. at 6: 20-26).
5. Gray also discloses that the "term 'substantially free of its (-)
stereoisomer' as used herein means that the compositions contain at least
90% by weight of ( + )-zileuton and 10% by weight or less of(-) zileuton"
(id. at 10: 31 to 11: 1 ).
6. In addition, Gray discloses:
The magnitude of a prophylactic or therapeutic dose of
( + )-zileuton in the acute or chronic management of disease will
vary with the severity and nature of the condition to be treated
and the route of administration. The dose and perhaps the dose
frequency will also vary according to the age, body weight and
response of the individual patient. In general, the total daily dose
range for ( + )-zileuton for the conditions described herein is from
about 200 mg to about 2 gin single or divided doses. Preferably
a daily dose range should be about 400 mg to about 1600 mg in
single or divided doses, while most preferably a daily dose range
should be about 600 mg to about 1200 mg in single or divided
doses. In managing the patient, the therapy should be initiated at
a lower dose, perhaps at about 400 mg to about 600 mg, and
increased up to about 1200 mg or higher depending on the
patient's global response. It is further recommended that
children and patients over 65 years and those with impaired renal
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Application 12/521,965
or hepatic function initially receive low doses and that they be
titrated based on individual response(s) and blood level(s).
(Id. at 13: 4--26.)
7. Appellants' Specification discloses that "a tablet comprising
600 milligrams (mg) of zileuton [ racemate] (ZYFLO® and Zyflo® CR
zileuton tablets) is currently marketed for the treatment of asthma" and that
the "current recommended dosing regimen for zileuton [ racemate] is
administration four times a day for a total daily dose of 2400 mg (as well as
twice daily Zyflo® CR at 1200 mg each dose)" (Spec. 1: 22 to 2: 18).
8. A 2009 ZYFLO® Patient Information Leaflet provided by
Appellants indicates that the "recommended dosage of ZYFLO for the
symptomatic treatment of patients with asthma is one 600-mg tablet four
times a day for a total dose of 2400 mg" (App. Br. Evidence Appendix G).
Analysis
In view of the foregoing findings of fact (FF), we conclude that the
Examiner has set forth a prima facie case that representative claim 1 is
anticipated and that representative claim 3 would have been obvious. In
particular, Gray discloses "a daily dose range should be about 600 mg to
about 1200 mg" (FF 6). This range is encompassed by and, therefore,
clearly anticipates the range recited in claim 1. In addition, this range
overlaps and, therefore, provides a prima facie case that the range of claim 3
would have been obvious.
We recognize Appellants' argument that the Federal Circuit has held,
in Sanofi-Synthelabo v. Apotex, Inc., 550 F.3d 1075 (2008), that enantiomers
can be "patentable, even in view of prior knowledge of the racemate" (App.
Br. 7). However, in that case, the Federal Circuit found that the "district
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Application 12/521,965
court correctly held that neither the [applied] patent nor its Canadian
counterpart contains an anticipating disclosure of the [claimed enantiomer]."
550 F.3d at 1084. Here, we do not find Appellants' argument persuasive
that Gray does not anticipate the claimed enantiomer.
In particular, Appellants argue that "Gray et al. does not indicate
which enantiomer of zileuton would have surprising and unexpected
properties, or even ![one enantiomer of zileuton is better than the other
enantiomer" (App. Br. 8). However, Appellants have not adequately
explained why this would be necessary to a prima facie case of anticipation
or obviousness.
In addition, Appellants argue that "the disclosure of Gray et al. is not
properly enabled" (id. at 9 (emphasis omitted)). In support of this position,
Appellants cite to Impax Labs., Inc. v. Aventis Pharms. Inc., 545 F.3d 1312
(Fed. Cir. 2008), and refer to WO 94/26269 Al published November 24,
1994 (hereinafter "the '269 publication") (App. Br. 9-12), which was filed
on the same day as Gray by the same Applicant and inventor and is directed
to (-)-zileuton (the '269 publication, cover page). We are not persuaded.
"In order to anticipate a claimed invention, a prior art reference must
enable one of ordinary skill in the art to make the invention without undue
experimentation." Impax Labs., 545 F.3d at 1314. However, "a prior art
printed publication cited by an examiner is presumptively enabling barring
any showing to the contrary by a patent applicant." In re Antor Media
Corp., 689 F.3d 1282, 1288 (Fed. Cir. 2012). In the present case, we do not
find that Appellants have provided sufficient basis to conclude that Gray is
not enabled.
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Gray discloses that it "has now been discovered that the optically pure
( +) isomer of zileuton is an effective agent for treating asthma, ulcerative
colitis, rheumatoid arthritis, psoriasis, [and] allergic rhinitis" (FF 3 ). We
understand Appellants' argument that Gray does not provide data supporting
this statement. However, although "working examples are desirable in
complex technologies ... examples are not required to satisfy [the
enablement requirement]." In re Strahilevitz, 668 F.2d 1229, 1232 (CCPA
1982) (emphasis in original). In addition, we do not agree with Appellants
that the filing of the '269 publication in and of itself is sufficient to
demonstrate that undue experimentation would have been required to
practice Gray's method.
Appellants also argue that, "similar to Impax, the dosage guidelines of
Gray et al. are broad and general without sufficient direction or guidance
to prescribe the specifically claimed treatment regimen" (App. Br. 13).
However, unlike Impax, where "the dosage guidelines [were] ... not
specific to any of the hundreds of [prior art] compounds" (545 F.3d at 1315),
Gray specifically discloses amounts for ( + )-zileuton (FF 6). Appellants have
not adequately explained why it would have required undue experimentation
to practice the invention using these dosage guidelines.
In addition, Appellants argue that, "since the data are merely
speculative, Gray ... fail[ s] to provide a reasonable expectation of success
for the ordinary skilled artisan to arrive at the presently claimed invention"
(App. Br. 14). However, we conclude that Appellants have not adequately
shown that there was not a reasonable expectation for success. We note
Appellants' evidence that the "recommended dosage of ZYFLO for the
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Application 12/521,965
symptomatic treatment of patients with asthma is one 600-mg tablet four
times a day for a total dose of 2400 mg" (FF 8). However, to the extent that
this argument is even relevant to the anticipation rejection, we do not agree
that this evidence is sufficient to demonstrate that there would not have been
a reasonable expectation for success in the amounts recited in claim 1, nor
do we agree that this evidence is sufficient to demonstrate that there would
not have been a reasonable expectation for success in the amounts recited in
claim 3.
Appellants also argue that, "similar to Sanofi, it is clear that the
claimed methods exploiting the unexpected properties of zileuton
substantially free of (S)-zileuton are patentable" (App. Br. 9). In particular,
based on the data provided in their Specification, Appellants argue that
"[ n ]either Gray et al. nor the '269 publication provide any indication that
either enantiomer has superior properties to the racemic mixture and,
therefore, neither reference provides the person of ordinary skill in the art
with a reason to try the instantly claimed dosage regimen, using lower doses
of ( + )-zileuton" (id. at 15). We are not persuaded.
With regard to the anticipation rejection of claim 1, Gray teaches the
claimed lower dosages (FF 6). In addition, evidence of unexpected results is
not relevant to an anticipation rejection. In re Malagari, 499 F.2d 1297,
1302 (CCPA 1974); In re Wiggins, 488 F.2d 538, 543 (CCPA 1973).
With regard to the obviousness rejection of claim 3, Appellants have
not provided sufficient evidence indicating that the results are "unexpected
compared with the closest prior art." In re Baxter Travenol Labs., 952 F.2d
388, 392 (Fed. Cir. 1991).
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Application 12/521,965
In addition, Appellants argue that "there was a long-felt need for a
more effective dosing strategy" (App. Br. 15 (emphasis omitted)). We are
not persuaded.
"[O]bjective evidence of nonobviousness includes ... long felt but
unsolved need." In re Rouffet, 149 F.3d 1350, 1355 (Fed. Cir. 1998).
"[L]ong-felt need is analyzed as of the date of an articulated identified
problem and evidence of efforts to solve that problem." Texas Instruments,
Inc. v. Int'! Trade Comm 'n, 988 F.2d 1165, 1178 (Fed. Cir. 1993). See also
Leo Pharm. Products, Ltd. v. Rea, 726 F.3d 1346, 1359 (Fed. Cir. 2013), in
which the Federal Circuit found:
Here, the researchers were aware of the benefits of using both
vitamin D and corticosteroids in the treatment of psoriasis as
early as 1986 .... Yet, it was not until the ... patent's filing in
2000 ... that the solution to the long felt but unsolved need for a
combined treatment of vitamin D and corticosteroid was created.
In the present case, Appellants have not provided sufficient evidence that
there was a recognized need for a more effective dosing strategy or of efforts
to meet this need.
We recognize that "Gray et al. was published on November 24, 1994,
and the instant application was filed on January 4, 2008" (App. Br. 17),
more than 13 years later. In addition, the Federal Circuit has stated that the
"length of the intervening time between the publication dates of the prior art
and the claimed invention can ... qualify as an objective indicator of
nonobviousness." Leo Pharm., 726 F.3d at 1359. However, Appellants
have provided no basis for the proposition that such evidence is relevant to
an anticipation rejection. In addition, given that Appellants have not
provided evidence of a recognized need or of efforts to meet this need,
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Application 12/521,965
Appellants have not adequately shown that this time lag reflects problems in
the art.
For example, we note that Gray discloses that "the enantioselective
synthesis of ( + )-zileuton from L-( +)-lactic acid has been described" (FF 2).
However, the cost of the enantioselective synthesis of ( + )-zileuton may
outweigh the benefit of a smaller dose, particularly given that Appellants
have not pointed to evidence that this smaller dose would reduce side
effects. Cf Sanofi-Synthelabo, 550 F.3d at 1081 ("the enantiomers ... had
the rare characteristic of 'absolute stereoselectivity': the dextrorotatory
enantiomer provided all of the favorable antiplatelet activity but with no
significant neurotoxicity, while the levorotatory enantiomer produced no
antiplatelet activity but virtually all of the neurotoxicity").
With regard to the anticipation rejection of claim 39, Appellants argue
that "Gray et al. does not appreciate that ( + )-zileuton has greater potency
over the racemic mixture such that it can be used at significantly lower doses
than racemic zileuton" (App. Br. 18). However, as discussed above, Gray
discloses the doses recited in claim 39 (via its dependency from claim 1).
With regard to the anticipation rejection of claims 4, 5, and 8,
Appellants additionally argue that "there is no specific direction or guidance
in Gray et al. to prescribe the specifically claimed daily dose required by the
claims, i.e., ... from about 600 mg to about 900 mg per day (claim 4 ), about
600 mg per day (claim 5), ... or about 1200 mg per day (claim 8)" (id. at
13-14). We are not persuaded.
Gray discloses that "most preferably a daily dose range should be
about 600 mg to about 1200 mg" (FF 6). We are aware that, inAtofina v.
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Application 12/521,965
Great Lakes Chem. Corp., the Federal Circuit indicated that disclosure of a
range does not necessarily disclose any particular species within the range,
even the endpoints. 441F.3d991, 1000 (Fed. Cir. 2006) ("the disclosure of
a range of 150 to 350 °C does not constitute a specific disclosure of the
endpoints of that range, i.e., 150 °C and 350 °C" and "the disclosure of a
0.001 to 1.0 percent range is not a disclosure of the end points of that
range"). However, the Federal Circuit subsequently held that, "when the
prior art discloses a range, rather than a point, the court must evaluate
whether the patentee has established that the claimed range is critical to the
operability of the claimed invention." Ineos USA LLC v. Berry Plastics
Corp., 783 F.3d 865, 871 (Fed. Cir. 2015). Here, we conclude that
Appellants have not adequately explained why the claimed range and points
recited in claims 4, 5, and 8 are critical. Therefore, in view of recent case
law, we conclude that Appellants have not adequately explained why
claims 4, 5, and 8 are not anticipated by Gray.
With regard to the obviousness rejection of claims 6 and 7, Appellants
additionally argue that "there is no specific direction or guidance in Gray et
al. to prescribe the specifically claimed daily dose required by the claims,
i.e., ... about 900 mg per day (claim 6), [or] about 1000 mg per day
(claim 7)" (App. Br. 13-14). However, Appellants do not adequately
explain why these amounts would not have been obvious over the teachings
in Gray (FF 6).
Conclusion
The evidence supports the Examiner's finding that Gray discloses the
methods of claims 1, 4, 5, 8, and 39. We, therefore, affirm the anticipation
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rejection of these claims. Claims 2, 9-11, 13, 15, 16, and 19-21 have not
been argued separately and, therefore, fall with claim 1. 37 C.F.R.
§ 41.37(c)(l)(iv).
The evidence also supports the Examiner's conclusion that Gray
suggests the methods of claims 3, 6, and 7. We, therefore, affirm the
obviousness rejection of claims 3, 6, and 7. Claims 12 and 14 have not been
argued separately and, therefore, fall with claim 3.
II
In rejecting claim 22, which ultimately depends from claim 1, the
Examiner relies on Gray "as discussed above" (Ans. 6). However, the
Examiner finds that Gray "does not specify the condition is selected from
the group consisting of moderate persistent asthma and severe persistent
asthma" (id.).
The Examiner relies on Rabe for teaching "moderate persistent
asthma" (id.). The Examiner concludes that it would have been obvious "to
treat moderate persistent asthma ... because Gray generally teaches the
treatment of asthma" (id.).
Analysis
Appellants argue that Gray does not teach or suggest the invention for
the reasons discussed above and that Rabe does not overcome the
deficiencies of Gray (App. Br. 20-22). We are not persuaded by these
arguments for the reasons discussed above.
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Conclusion
The evidence supports the Examiner's conclusion that Gray and Rabe
suggest the method of claim 22. We, therefore, affirm the obviousness
rejection of claim 22.
III
On the ground of nonstatutory obviousness-type double patenting, the
Examiner rejects claims 1-16 and 19-21 over claim 15 of Hanko and rejects
claim 22 over claim 15 of Hanko in view of Rabe (Ans. 7 & 9). Appellants
do not traverse these rejections (App. Br. 22-23). We, therefore, summarily
affirm them.
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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