Ex Parte Du et alDownload PDFPatent Trial and Appeal BoardMar 31, 201713133894 (P.T.A.B. Mar. 31, 2017) Copy Citation 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 following e-mail address(es): uspto@slwip.com SLW @blackhillsip.com 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). 2 Appeal 2016-005393 Application 13/133,894 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). 3 Appeal 2016-005393 Application 13/133,894 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).) 4 Appeal 2016-005393 Application 13/133,894 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. 5 Appeal 2016-005393 Application 13/133,894 (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). 6 Appeal 2016-005393 Application 13/133,894 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. 7 Appeal 2016-005393 Application 13/133,894 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.) 8 Appeal 2016-005393 Application 13/133,894 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 9 Appeal 2016-005393 Application 13/133,894 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 10 Appeal 2016-005393 Application 13/133,894 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.) 11 Appeal 2016-005393 Application 13/133,894 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.) 12 Appeal 2016-005393 Application 13/133,894 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 13 Copy with citationCopy as parenthetical citation