Ex Parte Du et al

Patent Trial and Appeal Board

Mar 31, 2017

13133894 (P.T.A.B. Mar. 31, 2017)

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.
13/133,894 06/09/2011 Guanhua Du 2434.006US1 6360
21186 7590 04/04/2017
SCHWEGMAN LUNDBERG & WOESSNER, P.A.
P.O. BOX 2938
MINNEAPOLIS, MN 55402
EXAMINER
SOROUSH, LAYLA
ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
04/04/2017 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
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte GUANHUA DU, JINXU WANG, SONG WU, YING SHI,
MEI GAO, YINGUI LI, YAN QI, DONGMIN SHEN, HONGMEI
GUANG, HAILI LIU, RUI LIU, and XIAOLONG FENG1
Appeal 2016-005393
Application 13/133,894
Technology Center 1600
Before DEMETRA J. MILLS, ERIC B. GRIMES,
and TIMOTHY G. MAJORS, Administrative Patent Judges.
MAJORS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to methods
for treatment of a stroke, which have been rejected as obvious and
provisionally rejected for 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 CSPC Zhongqi
Pharmaceutical Technology (Shijiazhuang) Co. Ltd. (App. Br. 2.)
Appeal 2016-005393
Application 13/133,894
STATEMENT OF THE CASE
Appellants’ “invention relates to the use of pinocembrin racemate in
preparing a medicament for treatment and prophylaxis of stroke.” (Spec.
I-)2
Claims 7, 9, and 13—16 are on appeal. Claim 7 is illustrative:
7. A method for treatment of a stroke caused by
hypertension, comprising administering a racemate of
pinocembrin, a racemate of pinocembrin salt, or a racemate of
pinocembrin hydrate in a concentration effective to reduce nerve
damage and inflammation.
(App. Br. 11 (Claims App’x).)
The claims stand rejected as follows:
I. Claims 7, 9, 13, 15, and 16 under 35 U.S.C. § 103(a) over Gao3
and Fu4 (“Rejection I”).
II. Claims 7, 9, 13, 15, and 16 under 35 U.S.C. § 103(a) over Lu5
and Fu (“Rejection II”).
2 Specification or “Spec.” refers the English translation of
PCT/CN2009/075456 that is of record.
3 Gao et al., Acute neurovascular unit protective action of pinocembrin
against permanent cerebral ischemia in rats, 10:6 J. of Asian Natural
Products Research 551-58 (2008).
4 Fu et al., US 2009/0232782 Al, published Sept. 17, 2009.
5 Lu, et al., CN 101307044 (A) (English translation of Abstract only).
Applicant indicated the publication date of Lu as Nov. 19, 2008. (See
Information Disclosure Statement dated July 20, 2013).
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III. Claim 14 under 35 U.S.C. § 103(a) over Gao, Fu, Chunhua,6
and Markonius7 (“Rejection III”).
IV. Claim 14 under 35 U.S.C. § 103(a) over Lu, Fu, Chunhua, and
Markonius (“Rejection IV”).
V. Claims 7 and 9 provisionally for obviousness-type double
patenting over claims 1—9 of US Application No. 13/128,896
(“the ’896 Application”)8 (“Rejection V”).
VI. Claims 7, 9, 13, 15, and 16 provisionally for obviousness-type
double patenting over US Application No. 13/128,602 (“the
’602 Application”) (“Rejection VI”).
REJECTION I
Issue
The Examiner finds that Gao teaches administration of a racemate of
pinocembrin to protect against cerebral ischemia and to treat ischemic
stroke. (Ans. 4, 12.) The Examiner finds that Gao does not teach treatment
of stroke caused by hypertension in a concentration effective to reduce nerve
damage and inflammation. {Id. at 4.) Nevertheless, according to the
Examiner, “the prior art’s teaching of pinocembrin useful in treating a stroke
will render obvious pinocembrin treating a stroke caused by hypertension.”
(Id. at 12—13; see also id. 4—5.) In support, the Examiner cites Fu as
teaching that hypertension is a risk factor for stroke and that stroke causes
6 Chunhua et al., CN 1879656 B, issued Apr. 21, 2010 (translation of
record).
7 Markonius, US 5,591,771, issued Jan. 7, 1997.
8 The’896 Application issued on March 19, 2013 (as US 8,399,511).
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nerve damage and inflammation. (Id. at 4—5, 13.) The Examiner also notes
that Fu teaches treatment of ischemic and hemorrhagic stroke with the same
method. (Id. at 4.) Accordingly, the Examiner concludes, it would have
been obvious to the skilled person to treat stroke caused by hypertension
with pinocembrin in a concentration effective to reduce nerve damage and
inflammation with the composition of Gao. (Id. at 4—5.)
Appellants admit “Gao discloses a use of rac-pinocembrin for treating
ischemic stroke,” but argue Fu does not teach “a method for treating any
kind of stroke” — much less treating stroke caused by hypertension. (App.
Br. 5.) According to Appellants, “Fu discloses a method of treating
ischemic brain injury” but ‘Tilschemic brain injury is not a stroke.” (Id. at
6.) Appellants contend “Fu is totally unconcerned with stroke or any other
specific condition that causes ischemic brain injury.” (Id. at 7.) Thus,
Appellants argue, “Gao in combination with Fu does not teach or suggest the
claimed method for treating stroke caused by hypertension, i.e., hemorrhagic
stroke, with pinocembrin, its salt, or its hydrate.” (Id.)
The issue is whether the Examiner established by a preponderance of
the evidence that claims 1,9, 12, 13, 15, and 16 would have been obvious
over Gao and Fu.
Findings of Fact (FF)
FF 1. The Examiner’s findings of fact and statement of the rejection
of claims 1,9, 13, 15, and 16 as obvious over Gao and Fu is provided at
pages 10—12 of the Final Rejection dated March 31, 2015 and at pages 3—5
of the Examiner’s Answer. (See also Final Act. 3—5 and Ans. 12—14
(Examiner’s Response to Argument).)
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FF 2. Gao teaches “strategies for comprehensive stroke treatment are
now focusing on treating the complete neurovascular unit that consists of the
blood brain barrier (BBB). . . and the brain tissue (neurons, glia, their
processes, and the extracellular or interstitial space).” (Gao 551
(Introduction).) Gao further teaches “[disruption of the BBB plays an
important role in the pathogenesis of many acute neuronal damages ... In
particular, cerebral ischemia elicits biphasic elevations in the BBB
permeability.” {Id.) According to Gao, “increase in the BBB permeability is
correlated with reversible and irreversible damage to the neurovascular unit,
and may subsequently result in brain edema, inflammation, and, further,
hemorrhagic transformation after stroke.” (Id.)
FF 3. Gao teaches “[a]cute vascular and neuroprotective effects of
pinocembrin (1) were evaluated in a rat model of focal cerebral ischemia.”
(Id. at Abstract.) Gao teaches the racemic form of pinocembrin [compound
(1)] was used in its study and administered at concentrations of 3, 10, and 30
mg/kg. (Id. at 556 (left col., second full paragraph and Section 3.1).)
FF 4. Gao teaches administering compound 1 “reduced the cerebral
infarct volumes ...[,] reduced brain swelling and improved behavioral
deficits significantly.” (Id. at Abstract.) Gao also teaches:
The findings of [the] present paper are the first to show that
treatment with [compound] 1 (3, 10, and 30 mg/kg) at the acute
phase improved rCBF [regional cortical blood perfusion] and
reduced the postischemic damage to the neurovascular unit
following permanent focal cerebral ischemia in rats.
Additionally, treatment with 1 at the early phase after ischemic
stroke is effective in preserving anatomical, biochemical, and
functional integrity of the BBB permeability.
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(Id. at 554 (right col., first full paragraph).)
FF 5. Fu teaches a method for treating or preventing ischemic brain
injury or neurological damage due to ischemia in a subject by transplanting
stem cells to the area of brain injury. (Fu Abstract.)
FF 6. Fu teaches
[t]he term “stroke” as used herein refers to a sudden loss of
function caused by an abnormality in the blood supply to the
brain. Ischemia (diminished or stopped blood flow) and
infarction (cell damage and death within the zone of ischemia)
are the pathologic processes in stroke that lead to neurologic
deficits. Risk factors for stroke include advanced age,
hypertension (high blood pressure), previous stroke or transient
ischemic attack (TIA), diabetes, high cholesterol .... Blood
pressure is the most important modifiable risk factor of stroke.
(Id. at 122.) Fu teaches “[sjtrokes can be classified into two major
categories: ischemic and hemorrhagic.” (Id. at 123.)
FF 7. Fu teaches treatment of “ischemic brain injury [] caused by
ischemic stroke, hemorrhage stroke, or a head trauma.” (Id. at 127; see also
id. at claim 4.) Fu teaches ischemic brain injury “refers to an absolute or
relative shortage of blood supply to the brain, with resultant damage or
dysfunction of cerebral tissue, especially central nerve cells.” (Id. at 121.)
Fu further teaches the cortex in stroke rats was examined and “analysis of
infarcted brain volume demonstrated that the damaged cortex was inflamed
and edemic.” (Id. at | 56.)
Analysis
Appellants argue the patentability of claims 7, 9, 13, 15, and 16 as a
group. We select claim 7 as representative. 37 C.F.R. § 41.37(c)(l)(iv).
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We begin with claim construction. Claim 7 recites, inter alia, a
“method for treatment of a stroke caused by hypertension.” (App. Br. 11
(emphasis added).) The word “hemorrhagic” appears nowhere in the claim.
Appellants’ brief states “stroke caused by hypertension, i.e.,
hemorrhagic stroke” (App. Br. 7) and thus Appellants seem to construe
“stroke caused by hypertension” as limited to hemorrhagic stroke. We
disagree that such a construction is the broadest reasonable interpretation of
the claim. Turning to the Specification, we find no disclosure or special
definition for “stroke caused by hypertension” that would suggest the phrase
means hemorrhagic stroke alone.9 Indeed, Appellants’ disclosure suggests a
broader meaning. To the extent the word “hypertensive” is mentioned at all,
the Specification describes testing pinocembrin on “spontaneously
hypertensive rats of stroke prone (SHRSP).” (Spec. 8.) The Specification
discloses that 24 of these rats died during the testing and “it was found that 4
of them died of hemorrhagic stroke and the other 20 rats died of ischemic
stroke.” (Id. at 11.) From this, we do not agree that “stroke caused by
hypertension” excludes ischemic stroke.
The cited prior art also suggests that stroke caused by hypertension is
not limited to hemorrhagic stroke. Fu teaches that hypertension is a risk
factor — indeed “the most modifiable risk factor” — of stroke generally.
(FF 6.) Asa key risk factor, hypertension is reasonably interpreted as a
contributing cause of stroke (including ischemic stroke) as with several other
risk factors noted in Fu, such as advanced age and high cholesterol. (Id.)
9 The phrase “stroke caused by hypertension” and word “hypertension”
appear to be absent from Appellants’ Specification as filed.
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Accordingly, we conclude that “stroke caused by hypertension”
encompasses ischemic or hemorrhagic stroke in which hypertension is a
contributing cause of the stroke.
With this construction in mind, we agree with the Examiner that claim
7 would have been obvious. Gao teaches administration of racemic
pinocembrin for the treatment of ischemic stroke. (FF 2—4.)10 Gao teaches
administration of this compound reduced the infarct, reduced swelling and
damage to the neurovascular unit, and reduced disruption of the blood brain
barrier. (FF 4.) Fu teaches that hypertension is a risk factor for ischemic
stroke, that stroke results in ischemic brain injury, and that sequelae of
stroke include damage to nerve cells and inflammation. (FF 6—7.) Based on
the combined teachings of Gao and Fu, it would have been obvious to the
skilled artisan to treat ischemic stroke, including ischemic stroke where
hypertension is a contributing factor or cause. The skilled person would
have had a reasonable expectation of success that administering the
compound of Gao would reduce damage to the neurovascular unit and blood
brain barrier, and therein reduce inflammation and damage to nerve cells as
evidenced by the prior art’s combined teachings. (FF 2-4, 6—7.)
Appellants’ argument that Fu does not teach treating any kind of
stroke and that Fu is unconcerned with stroke is unpersuasive. (App. Br. 5—
7; Reply Br. 3—4.) Contrary to Appellants’ contentions, Fu teaches treating
or preventing ischemic brain injury resulting from ischemic or hemorrhagic
10 The concentrations administered in Gao (3, 10, 30 mg/kg) overlap
partially with the concentrations disclosed by Appellants (1,3, 10 mg/kg).
('Compare FF 3—4 with Spec. 8.)
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stroke. (FF 6—7.) Treating the symptoms or sequelae (e.g., ischemic brain
injury) of a condition (e.g., stroke) is a treatment of the condition itself. And
Gao teaches treatment of ischemic stroke — and the reduction of ischemic
injury caused by stroke — by administering racemic pinocembrin (FF 2-4).
In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986) (“Non­
obviousness cannot be established by attacking references individually
where the rejection is based upon the teachings of a combination of
references.”).
Appellants’ argument that the combination of Gao and Fu does not
teach treatment of stroke caused by hypertension is also unpersuasive. (App.
Br. 4—7; Reply Br. 2—3.) Hypertension is a key risk factor, and thus a
contributing cause, for stroke generally as suggested by Fu. The skilled
artisan would have been motivated to treat ischemic stroke with racemic
pinocembrin as taught in Gao, including in those instances where
hypertension is one of the contributing causes of the stroke. The claims do
not require that hypertension be the sole cause, and the claims are not
limited to hemorrhagic stroke as already discussed.
Appellants contend Gao relates to stroke caused by a specific
pathology where the stroke is induced by middle cerebral artery occlusion
(MCAO), and that “[sjtroke induced by MCAO differs fundamentally from
stroke caused by hypertension.” (Reply Br. 2.) In support, Appellants assert
that stroke caused by hypertension and MCAO-induced stroke: (i) are
different types of stroke (severe versus relatively not severe); (ii) occur at
different sites (small vessels versus major artery); and (iii) exhibit different
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potential pathological characteristics (e.g., atherosclerosis in small vessels
versus acute attack unrelated to changes in vessels). {Id. at 2—3.)
We remain unpersuaded. First, Appellants provide no persuasive
evidentiary support — from the Specification or otherwise — for their
contentions concerning a distinction between stroke induced by MCAO and
stroke caused by hypertension. See In re Pearson, 494 F.2d 1399, 1405
(CCPA 1974) (“Attorney’s argument in a brief cannot take the place of
evidence.”). Second, Appellants could have and should have raised these
contentions in their opening brief, rather than waiting for the reply, so the
contentions are untimely. 37 C.F.R. § 41.41(b)(1) & (2). Third, inasmuch
as Appellants appear to rely on the unreasonably narrow interpretation of
“stroke caused by hypertension” in drawing this distinction, we reiterate that
the claims are not limited to hemorrhagic stroke. Hypertension may be a
contributing factor behind ischemic stroke as well.
Conclusion of Law
We conclude that the Examiner established by a preponderance of the
evidence that claim 7 would have been obvious over Gao and Fu.
Claims 9, 13, 15, and 16 have not been argued separately and
therefore fall with claim 7. 37 C.F.R. § 41.37(c)(l)(iv).
REJECTION II
The Examiner rejected claims 7, 9, 13, 15, and 16 as obvious over Lu
and Fu. (Ans. 6.) Lu is a translated abstract from a Chinese patent
application. (Lu Abstract.) Lu does not specifically mention stroke and
without a more complete translation so that Lu’s teachings can be considered
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in context, we are unpersuaded that the Examiner established a prima facie
case of obviousness.
REJECTIONS III-IV
The Examiner made two separate rejections of dependent claim 14.
First, the Examiner concludes claim 14 would have been obvious over Gao,
Fu, Chunhua, and Markonius. (Ans. 7—9.) Second, the Examiner concludes
claim 14 would have been obvious over Lu, Fu, Chunhua, and Markonius.
(Id. at 8—9.)
Appellants argue only that the secondary references (Chunhua and
Markonius) fail to make up for the deficiencies of the respective
combinations of Gao and Fu, or Lu and Fu. (App. Br. 8—9.)
Having found no deficiencies with respect to the combination of Gao
and Fu, we adopt the Examiner’s findings of fact, reasoning, and conclusion
of obviousness with respect to claim 14 over the combination of Gao, Fu,
Chunhua, and Markonius. Because the Examiner did not establish a prima
facie case that claim 7 (from which claim 14 depends) would have been
obvious over Lu and Fu, we reverse the Examiner’s rejection of claim 14
over Lu, Fu, Chunhua, and Markonius.
REJECTIONS V-VI
The Examiner provisionally rejected claims 7 and 9 for obviousness-
type double patenting over the ’896 Application. (Ans. 11.) Appellants
contend this rejection applies only to claim 12 and is moot because claim 12
is canceled. (Reply Br. 5.) We agree the rejection is moot as to claim 12,
but the Examiner maintained the rejection of claims 7 and 9. (Ans. 11.)
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Appellants identify no withdrawal of the rejection as to claims 7 and 9 in the
record.11 We thus affirm the rejection as to claims 7 and 9.
The Examiner provisionally rejected claims 1,9, 13, 15, and 16 for
obviousness-type double patenting over the ’602 Application. (Ans. 11—12.)
The rejection is affirmed as to claims 1,9, 13, 15, and 16. Appellants’
statement in a footnote that “the Examiner has offered no comment” on the
rejection (App. Br. 5, n. 11) and Appellants’ request to hold the rejection in
abeyance (Reply Br. 5) fails to provide persuasive argument on the merits.
SUMMARY
We affirm the rejection of claims 1,9, 13, 15, and 16 as obvious over
Gao and Fu. We also affirm the rejection of claim 14 as obvious over Gao,
Fu, Chunhua, and Markonius.
We reverse the rejection of claims 7, 9, 13, 15, and 16 as obvious over
Lu and Fu. We also reverse the rejection of claim 14 as obvious over Fu,
Fu, Chunhua, and Markonius.
We affirm the provisional obviousness-type double patenting rejection
of claims 7 and 9 over the ’896 Application.
We affirm the provisional obviousness-type double patenting rejection
of claims 7, 9, 13, 15, and 16 over the ’602 Application.
11 Appellants contend the Examiner clarified that the rejection applied only
to claim 12 during a telephonic interview and Appellants cite their own
Remarks filed July 9, 2015. (Reply Br. 5, n. 17.) However, in the Answer
the Examiner applied the rejection to claims 7, 9, and 12. (Ans. 11.)
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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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