Ex Parte Yin et alDownload PDFPatent Trial and Appeal BoardDec 19, 201613503494 (P.T.A.B. Dec. 19, 2016) 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. 13/503,494 05/14/2012 Kingsley Yin 125107.00020 3638 29880 7590 12/21/2016 FOX ROTHSCHILD LLP PRINCETON PIKE CORPORATE CENTER 997 LENOX DRIVE BLDG. #3 EAWRENCEVTT.TE, NJ 08648 EXAMINER CARTER, KENDRA D ART UNIT PAPER NUMBER 1627 NOTIFICATION DATE DELIVERY MODE 12/21/2016 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): ipdocket @ foxrothschild. com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte KINGSLEY YIN, ANA RODRIGUEZ, BERND W. SPUR, and JEAN WALKER Appeal 2015-005617 Application 13/503,4941 Technology Center 1600 Before and DONALD E. ADAMS, TIMOTHY G. MAJORS, DAVID COTTA, Administrative Patent Judges. COTTA, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a method for treating sepsis or septic shock. The Examiner rejected the claims on appeal as obvious under 35 U.S.C. § 103(a). We affirm. 1 According to Appellants, the real party in interest is Rowan University. App. Br. 4. Appeal 2015-005617 Application 13/503,494 STATEMENT OF THE CASE Claims 1—3 are on appeal. Claim 1 is illustrative and reads as follows 1. A method for treating sepsis or septic shock comprising administering to a subject in need thereof a single dose regimen of an effective amount of at least a 95% purified isolated Lipoxin A4 thereby treating the subject’s sepsis or septic shock, wherein the regimen is a single dose of Lipoxin A4 administered within six hours of the onset of sepsis or septic shock. The Examiner rejected claims 1—3 under 35 U.S.C. § 103(a) over the combination of Serhan ‘248,2 Ereso,3 Serhan ‘953,4 Sobrado,5 Calbiochem.6 FINDINGS OF FACT 1. Serhan‘248 discloses: It has been surprisingly discovered that lipoxins (LX’s) and aspirin-triggered lipoxins (ATLa’s) of the invention, discussed infra, can be utilized for the stimulation, release and increased secretion of bactericidal permeability increasing protein (BPI) from various tissues, i.e., mucosal cells, epithelial cells, for combating infection and/or the invasion of bacteria in a subject. 2 Serhan et al., US Patent Publication 2003/0195248 Al, published Oct. 16, 2003 (“Serhan ‘248”). 3 Ereso et al., Lipoxin A4 Attenuates Microvascular Fluid Leak During Inflammation, 156(2) J. Surg. Res. 183—188 (2009) (“Ereso”). 4 Serhan et al., US Patent No. 6,387,953 Bl, issued May 14, 2002 (“Serhan ‘953”). 5 Sobrado et al., Synthesis of Lipoxin A4 by 5-Lipoxygenase Mediates PPAR y-Dependent, Neuroprotective Effects of Rosiglitazone in Experimental Stroke, 29(12) Journal of Neuroscience, 3875-3884 (2009) (“Sobrado”). 6 Calbiochem catalog entry, Lipoxin A4, obtained March 31, 2014 (“Calbiochem”). 2 Appeal 2015-005617 Application 13/503,494 Consequently, the compounds disclosed herein are useful for the treatment and prevention of infection in a subject. Serhan ‘248 126. 2. Serhan ‘248 discloses: BPI is a potent and specific bactericidal compound. The disease targets include, for example, sepsis and infectious diseases. The present invention provide[s] a non antibiotic mechanism to fight infectious disease caused by Gram negative bacteria. Therefore, use of the therapeutic compounds of the invention to stimulate production of BPI by a subject, helps to treat, ameliorate, or prevent such disease. Id. at 128 (emphasis added); see also id. at || 11—12. 3. Serhan ‘248 discloses: A number of recent in vitro and in vivo studies have revealed that lipoxins, and specifically lipoxin A4 (LXA4), function as innate “stop signals”, serving to control local inflammatory processes. Synthetic lipoxin analogs exhibit greater potency for these actions than the native compound, due to decreased metabolism to inactive compounds. 4. Serhan ‘248 discloses: In another preferred embodiment of this invention, lipoxin analogs have the following structural formula VII: Id. at 13. o Id. at 1332. 3 Appeal 2015-005617 Application 13/503,494 5. Serhan ‘248 discloses: Lipoxins have been widely studied as anti-inflammatory agents and have been demonstrated to inhibit PMN transmigration across both endothelia and epithelia, block PMN diapedesis within the microcirculation and may initiate the resolution phase of ongoing inflammation. Noteworthy is the finding that lipoxins are potent inhibitors of bacterial-induced inflammation in the murine air pouch model. In this model, lipoxins inhibited expression of COX-2, an endotoxin-stimulated gene product. Thus, lipoxins may dampen inflammatory processes by controlling bacterial overgrowth and/or inhibit endotoxin activation via transcriptional induction ofBPI. Id. at 1696. 6. Serhan ‘248 discloses: Dosage regimens may be adjusted to provide the optimum desired response (e.g., a therapeutic or prophylactic response). For example, a single bolus may be administered, several divided doses may be administered over time or the dose may be proportionally reduced or increased as indicated by the exigencies of the therapeutic situation. It is especially advantageous to formulate parenteral compositions in dosage unit form for ease of administration and uniformity of dosage. Id. at | 650. 7. Ereso discloses: “The ability to attenuate the increase in microvascular fluid leak during inflammatory conditions identifies lipoxins as a mediator that promotes the resolution of inflammation and thereby suggests a potential pharmacologic role for LXA4 during sepsis and trauma.” Ereso 7. 4 Appeal 2015-005617 Application 13/503,494 8. Serhan ‘953 discloses: The impact of lipoxin A4 (LXA4) and aspirin-triggered lipoxins (ATL) was investigated in tumor necrosis factor (TNFa)-initiated neutrophil (PMN) responses in vitro and in vivo using metabolically stable LX analogs. At concentrations as low as 1-10 nM, the LXA4 and ATL analogs each inhibited TNFa-stimulated superoxide anion generation and IL-1P release by human PMN. Serhan ‘953 Abstract. 9. Serhan ‘953 discloses: “The cytokines TNFa and IL-ip play major roles in inflammation, septic shock and tissue injury.” Id. at col. 1,11. 25-26. 10. Buechler7 discloses: The term “early sepsis therapy regimen” refers to a set of supportive therapies designed to reduce the risk of mortality when administered within the initial 24 hours, more preferably within the initial 12 hours, and most preferably within the initial 6 hours or earlier, of assigning a diagnosis of SIRS, sepsis, severe sepsis, septic shock, or MODS to a subject. Buechler | 52. ANALYSIS 7 Buechler et al., US Patent Publication No. 2005/0148029 Al, published July 7, 2005 (“Buechler”). The Examiner cited Buechler in Final Office action in connection with the rejection of now-cancelled claim 4. Final Act. 6—7. Buechler was not cited in the Final Office action in connection with the rejection of claims 1—3. Id. at 3—6. Appellants identify Buechler as part of the rejection on appeal, see App. Br. 8, and both Appellants and the Examiner discuss Buechler in connection with this appeal. See id. at 12—13; Ans. 5. While we address Appellants arguments related to Buechler herein, we note that we do not consider Buechler necessary to our affirmance of the Examiner’s rejection of claims 1—3. 5 Appeal 2015-005617 Application 13/503,494 Appellants argue claims 1—3 as a group. We designate claim 1 as representative for claims 1—3. The Examiner found that Serhan ‘248 taught a method of increasing the release of bactericidal permeability increasing protein (BPI) in order to treat disease states like sepsis by administering a compound of the formula VII (reproduced below). Final Act. 3^4. The Examiner found that the above formula encompasses lipoxin A4. Id. at 4. The Examiner concluded, however, that Serhan ‘248 did not specifically teach administering lipoxin A4 to treat sepsis. Id. The Examiner found that Ereso taught that lipoxin A4 promoted resolution of inflammation, suggesting a potential pharmacological role during sepsis. Id. The Examiner found that Serhan‘958 taught that the cytokines TNFa and IL-ip play major roles in inflammation, septic shock and tissue injury and that lipoxin A4 inhibited TNFa and IL-ip generation and release. Id. The Examiner then concluded that the claimed method would have been obvious based on the combined teachings of Serhan ‘248, Ereso and Serhan ‘958. Final Act 5—6. Appellants argue that “Serhan et al. describes the use of millions of possible Lipoxin A4 analogs, not purified native or authentic Lipoxin A4.” App. Br. 9. Appellants thus argue that “[mjerely because the prior art has allegedly a very broad sweeping generic disclosure of all active ingredients 6 Appeal 2015-005617 Application 13/503,494 in a ‘haystack, ’ does not render each species of such active ingredients, the ‘needles,’ obvious.” Id. at 10 (citing In re Baird, 16 F.3d 380, 383 (Fed. Cir. 1994). In fact, Appellants contend, “there are no specific teachings directed to the use of 95% purified isolated native Lipoxin A4 for treatment of sepsis in any of the cited references.” Id. at 9. We are not persuaded. One cannot show nonobviousness by attacking references individually when the rejection is based on a combination of references. In re Keller, 642 F.2d 413, 425 (CCPA 1981). Here, the combination of references identified by the Examiner clearly suggests the use of lipoxin A4 to treat sepsis. Serhan ‘248 teaches that BPI is a “potent and specific bactericidal compound” with “disease targets” that include sepsis, FF2, and that lipoxins can be used to stimulate the secretion of BPI for combating infection. FF1.8 Ereso teaches that lipoxin A4 may be useful for treatment of sepsis. FF7 (“The ability to attenuate the increase in microvascular fluid leak during inflammatory conditions identifies lipoxins as a mediator that promotes the resolution of inflammation and thereby suggests a potential pharmacologic role for LXA4 [lipoxin A4] during sepsis and trauma.”). Serhan ‘953 similarly suggests that lipoxin A4 may be useful for treating sepsis by teaching that lipoxin A4 inhibits TNFa- and IL-ip, FF8, both of which are taught to play major roles in inflammation, septic shock and tissue injury. FF9. Contrary to Appellants’ argument, the Examiner’s obviousness analysis does not require looking for a needle in a haystack because Ereso and Serhan ‘953 specifically identify the needle — lipoxin A4. 8 Serhan ‘248 also teaches that lipoxins “may dampen inflammatory processes by controlling bacterial overgrowth and/or inhibit endotoxin activation via transcriptional induction of BPI.” FF5. 7 Appeal 2015-005617 Application 13/503,494 Appellants contend that Serhan ‘248 teaches away from Lipoxin A4 because “it describes Lipoxin A4 analogs to have greater activity compared to native Lipoxin A4.” App. Br. 9 (citing Serhan ‘248’s teaching that lipoxin A4 analogs “exhibit greater potency” for “control[ing] local inflammatory response” than lipoxin A4.). We disagree. As discussed above, Lipoxin A4 is taught to be useful for treating sepsis. That lipoxin analogs may have greater potency than lipoxin A4 in controlling local inflammatory response does not mean that lipoxin A4 is not useful for treating sepsis. See, In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994). Indeed, that lipoxin analogs may have greater potency than lipoxin A4 in controlling local inflammatory response does not necessarily mean that lipoxin A4 is less useful for treating sepsis than its analogs. See, App. Br. 14 (noting that “treatment of sepsis does not solely correlate with degree of inflammation”). Accordingly, Appellants have not provided persuasive evidence or argument to support a conclusion that Serhan ‘248 teaches away from the use of lipoxin A4 for treatment of sepsis. Appellants similarly contend that Buechler teaches away from the claimed invention. Appellants find a teaching away in Buechler’s statement that “a therapy regimen refers to one or more interventions made by a care giver in hopes of treating a disease or condition.” Id. at 12. Appellants argue that Buechler’s failure to express certainty — evident in the phrase “in hopes of treating” — shows the “unpredictability in the art for treating sepsis.” Id. Buechler, however, does not address treatment of sepsis with lipoxins. Moreover, any uncertainty imputed by Apppellants into Buechler’s disclosure is outweighed by the clear suggestions in the art to treat sepsis with lipoxin A4. See, FF1—FF3, FF5, and FF7—FF9. 8 Appeal 2015-005617 Application 13/503,494 Appellants argue that the Examiner improperly relied upon hindsight in finding the claimed single dose regimen obvious. App. Br. 10. We disagree. Serhan ‘248 teaches that the “selected dosage level will depend on a variety of factors,” that “a physician or veterinarian having ordinary skill in the art can readily determine and prescribe the effective amount of the pharmaceutical composition required,” and that “[djosage regimens may be adjusted to provide the optimum desired response.” Serhan ‘248 645, 646, and 650. In view of these teachings, we agree with the Examiner that it would have been obvious to optimize the dose to arrive at the claimed dose regimen. See In re Alter, 220 F.2d 454, 456 (CCPA 1955) (“[Wjhere the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.”). Appellants contend that the claimed invention is nonobvious because Examples 2 and 3 in the Specification demonstrate unexpected results. App. Br. 15. As described by Appellants, Examples 2 and 3 demonstrate that administration of lipoxin A4 as claimed “provides [a] substantial degree of improvement in life expectancy of subjects [rats] suffering from sepsis.” Id. Appellants assert that these results are unexpected because Serhan ‘248 teaches that native lipoxin A4 is “less potent than its lipoxin analogs.” Id. We disagree. The data relied upon as establishing unexpected results shows that administration of lipoxin A4 increased the survival of rats as compared to rats receiving a saline control. See, Specification || 37 and 38. Appellants compare this data to a statement in the prior art that native lipoxin A4 is less effective than its lipoxin analogs in “serving to control local inflammatory processes.” App. Br. 15;FF3. Appellants admit, however, that “treatment 9 Appeal 2015-005617 Application 13/503,494 of sepsis does not solely correlate with degree of inflammation, rather eradicating the immune offensive source.” App. Br. 14. Comparing control of local inflammation to survival rate is thus not a like-to-like comparison. Accordingly, Appellants’ comparison does not provide a basis on which to compare the effectiveness of lipoxin A4 to that of its analogs with respect to treating sepsis. In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991) (“[W]hen unexpected results are used as evidence of nonobviousness, the results must be shown to be unexpected compared with the closest prior art.”). Moreover, as discussed above, based on the teaching of the art, the person of ordinary skill would have reasonably expected lipoxin A4 to be effective in treating sepsis irrespective of its anti-inflammatory potency relative to that of its analogs. See, FF1—FF3, FF5, and FF7—FF9. Accordingly, we affirm the Examiner’s decision to reject claim 1 as obvious over the combination of Serhan ‘248, Ereso, Serhan ‘953, Sobrado, and Calbiochem. Because they were not argued separately claims 2 and 3 fall with claim 1. SUMMARY For these reasons and those set forth in the Examiner's Answer, the Examiner's final decision to reject claims 1—3 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)(1). AFFIRMED 10 Copy with citationCopy as parenthetical citation