Ex Parte Bombardelli et alDownload PDFPatent Trial and Appeal BoardDec 29, 201612856786 (P.T.A.B. Dec. 29, 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. 12/856,786 08/16/2010 Ezio Bombardelli 7914-119-999 2831 20583 7590 12/29/2016 Jones Day 250 Vesey Street New York, NY 10281-1047 EXAMINER JIANG, SHAOJIA A ART UNIT PAPER NUMBER 1673 MAIL DATE DELIVERY MODE 12/29/2016 PAPER 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. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte EZIO BOMBARDELLI and PAOLO MORAZZONI1 __________ Appeal 2014-007226 Application 12/856,786 Technology Center 1600 __________ Before JEFFREY N. FREDMAN, TIMOTHY G. MAJORS, and KRISTI L. R. SAWERT, 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 treating mucositis, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm-in-part. STATEMENT OF THE CASE According to the Specification, “[o]ne of the side effects of radiotherapy, and above all chemotherapy, is mucositis, which normally affects the gastroenteric tract, especially the mouth, esophagus, stomach, 1 Appellants identify the Real Party in Interest as Indena S.p.A. (App. Br. 2.) Appeal 2014-007226 Application 12/856,786 2 [etc.].” (Spec. ¶ 4.) Appellants’ inventions “are methods of treating or preventing mucositis in a patient . . . comprising administering to the patient a therapeutically effective amount of at least one of an anthocyanoside, a proanthocyanidin, or an extract, such as a plant extract, comprising at least one of an anthocyanoside or a proanthocyanidin.” (Id. at ¶ 7.) Claims 98–146 are on appeal. Claim 98 is illustrative: 98. A method for the treatment of mucositis in a patient comprising administering to the patient a therapeutically effective composition for the treatment of mucositis, wherein the composition comprises: (1) one or more extracts of Vaccinium myrtillus, Vitis vinifera or combinations thereof; (2) one or more extracts of Macleaya cordata, Sanguinaria canadensis, Macleaya microcarpa or combinations thereof; and (3) one or more extracts of Echinacea angustifolia, Zanthoxylum bungeanum or combinations thereof, wherein the mucositis occurs in connection with the administration of chemotherapy and/or radiotherapy to the patient. (App. Br. 25 (Claims App’x).) The claims stand rejected as follows: I. Claims 98–108, 110–124, 126–141, and 143–146 as obvious under 35 U.S.C. § 103(a) over Bombardelli PCT,2 as evidenced 2 Bombardelli et al., WO 2006/063716 A1, published June 22, 2006 (“Bombardelli PCT”). The Examiner uses Bombardelli PCT as the English- language equivalent of IT publication MI20042414 (A1). (Ans. 3.) Appeal 2014-007226 Application 12/856,786 3 by Bombardelli ’3653 and Gabetta,4 in view of Rubenstein5 and Rosenbloom6 (“Rejection I”). II. Claims 109, 125, and 142 as obvious under 35 U.S.C. § 103(a) over Bombardelli PCT, as evidenced by Bombardelli ’365 and Gabetta, in view of Rubenstein, Rosenbloom, and Goodman & Gilman’s7 (“Rejection II”). REJECTION I Issue Has the Examiner established by a preponderance of the evidence that claims 98–108, 110–124, 126–141, and 143–146 would have been obvious over Bombardelli PCT, Bombardelli ’365, Gabetta, Rubenstein, and Rosenbloom? Findings of Fact FF 1. The Examiner’s findings of fact and statement of Rejection I may be found at pages 2–9 of the Examiner’s Answer. Except as discussed below, we adopt those findings and provide the following for emphasis. FF 2. Bombardelli PCT teaches “novel compositions containing anthocyanosides and/or procyanidins in combination with bactericidal 3 Bombardelli et al., 5,665,365, issued Sept. 9, 1997. 4 Gabetta et al., 5,200,186, issued Apr. 6, 1993. 5 Rubenstein et al., Clinical Practice Guidelines for the Prevention and Treatment of Cancer Therapy–Induced Oral and Gastrointestinal Mucositis, 100:9 CANCER 2026–2046 (Supplement May 1, 2004). 6 Rosenbloom, WO 03/013428 A2, published Feb. 20, 2003 7 GOODMAN & GILMAN’S THE PHARMACOLOGICAL BASIS OF THERAPEUTICS 5–8 (Joel G. Hardman, Ph.D. et al. eds., 10th ed. 2001). Appeal 2014-007226 Application 12/856,786 4 isoquinolone alkaloids and optionally with a lipophilic extract of Zanthoxylum bungeanum and/or Echinacea angustifolia.” (Bombardelli PCT 1.) Bombardelli PCT further teaches “[a]nthocyanosides preferably derive from extracts of Vaccinium myrtillus . . . [,] known to have marked, particularly topical, anti-inflammatory activity . . . [and] bacteriostatic action which prevents bacterial and fungal adhesion, for example at the dental, paradental and mucous membrane levels.” (Id. at 2:4–11.) FF 3. Bombardelli PCT teaches isoquinolone alkaloids include “extracts of Sanguinaria canadensis, Macleaya cordata or Macleaya microcarpa . . . [, which] have broad-spectrum antimicrobial activity.” (Id. at 2:18–22.) Bombardelli PCT teaches “extracts containing these alkaloids have shown strong anti-inflammatory topical activity.” (Id. at 2:25–26.) FF 4. Bombardelli PCT teaches “lipophilic extracts of Zanthoxylum bungeanum and/or Echinacea angustifolia . . . have useful analgesic topical activity through inhibition of nervous conduction.” (Id. at 2:28–3:3.) FF 5. Bombardelli PCT teaches “[t]hroat redness and inflammation with formation of plaques are a frequent aspect of common influenza, cold and other cold diseases.” (Id. at 1.) Bombardelli PCT teaches compositions of the invention are capable of preventing the formation of purulent plaques infected with various saprophytes of the oral cavity, thus avoiding the use of antibiotics, while reducing the progress of the infection. In particular, the compositions of the invention proved to exert synergistic effect mainly on the duration of the condition. Furthermore, the compositions of the invention are capable of exerting favourable actions, cleaning the oral cavity and removing dental plaque. Appeal 2014-007226 Application 12/856,786 5 (Id. at 3:11–18.) Bombardelli PCT further teaches “[t]hese compositions are used in both prophylactic and curative treatments, as well as for the hygiene of the oral cavity.” (Id. at 3:24–25.) FF 6. Rubenstein teaches “[o]ral and gastrointestinal (GI) mucositis can affect up to 100% of patients undergoing high-dose chemotherapy . . . [and] 80% of patients with malignancies of the head and neck receiving radiotherapy.” (Rubenstein 2026.) Rubenstein teaches [m]ucosal injury is the collective consequence of a number of concurrent and sequential biologic processes. After radiotherapy or chemotherapy, oral mucositis is heralded by an initiation phase that is characterized by injury to tissues of the submucosa. . . . The initial injury precipitates connective tissue deterioration and the rapid up-regulation of a second set of genes that results in direct and indirect signaling and early apoptosis of clonogenic stem cells in the basal epithelium. The proinflammatory cytokines . . . are likely to be among the signaling molecules . . . [that] amplify the up-regulation of transcription factors . . . leading to production of additional proinflammatory cytokines, tissue injury, and apoptosis. Epithelial apoptosis and necrosis . . . result in an ulcerative phase . . . [that] is exacerbated by local bacterial colonization, which results in a barrage of cell wall products penetrating into the submucosa and amplifying damaging mechanisms. (Id. at 2030.) FF 7. Rubenstein also teaches it is important to recognize that although there is not sufficient scientific evidence to provide a guideline for basic oral care, its importance in maintaining mucosal health, integrity, and function generally is accepted. . . . The purpose of basic oral care is to reduce the impact of the oral microbial flora, reduce cancer- related symptoms of pain and bleeding, and prevent soft-tissue infections that may have systemic sequelae. In addition, Appeal 2014-007226 Application 12/856,786 6 maintenance of good oral hygiene will reduce the risk of dental complications, including caries and gingivitis. For these reasons, basic oral care is an important component of care of the patient with cancer. (Id. at 2031.) FF 8. Rubenstein teaches “[i]mproved oral status (i.e., reduced mucositis or increased oral comfort) was reported in three randomized clinical studies,[] and only one[] study reported no change in mucositis at the conclusion of the study. . . . [T]he collective results suggest that using a systematic [oral-care] protocol improves patient outcomes.” (Id. at 2032.) Rubenstein further describes “[t]hree quasiexperimental, nonrandomized studies of oral care protocols [that] also support their use in reducing the incidence or severity of mucositis.” (Id. at 2032.) For example, in one study “pediatric patients with leukemia who followed a daily preventative protocol (plaque removal, chlorhexidine rinse, iodopovidone, and nystatin) experienced a significant decrease in moderate mucositis and candidiasis and had improved oral hygiene.” (Id.) FF 9. Rubenstein discloses that, based on other studies where institutions were surveyed about oral care, the studies “revealed widely disparate practices and little agreement on standardized approaches to oral care.” (Id.) Principles of Law “[T]he Board need only establish motivation to combine by a preponderance of the evidence to make its prima facie case.” In re Kahn, 441 F. 3d 977, 989 (Fed. Cir. 2006). Nevertheless, “[f]acts established by Appeal 2014-007226 Application 12/856,786 7 rebuttal evidence must be evaluated along with the facts on which the earlier conclusion was reached, not against the conclusion itself. Though the tribunal must begin anew, a final finding of obviousness may of course be reached, but such finding will rest upon evaluation of all facts in evidence, uninfluenced by any earlier conclusion reached . . . upon a different record.” In re Rinehart, 531 F.2d 1048, 1052 (CCPA 1976). Analysis Appellants argue the patentability of the claims subject to Rejection I as a group. We select claim 98 as representative. We nevertheless address independent claim 119, and its dependent claims, separately below. Claim 98 The Examiner finds that Bombardelli PCT teaches a composition with the three ingredients recited in Appellants’ claim 98. (Ans. 3.) According to the Examiner, Bombardelli PCT teaches administering the composition “for the prevention and treatment of bacterial infections of the oral cavity and for the hygiene of the oral cavity” and that it “is useful for the treatment of throat redness and inflammation with formation of plaques.” (Ans. 3.) The Examiner finds that Bombardelli PCT “do[es] not expressly teach that the composition is useful in a method for the treatment of mucositis which occurs in connection with the administration of chemotherapy and/or radiotherapy.” (Id. at 5.) The Examiner thus turns to Rubenstein. The Examiner finds that Rubenstein relates to “clinical practice guidelines for the treatment of cancer therapy” and describes mucositis occurring in connection with chemotherapy and radiotherapy. (Id. at 5–6.) According to the Examiner, although Rubenstein notes “there is not Appeal 2014-007226 Application 12/856,786 8 sufficient scientific evidence to provide a guideline for basic oral care, [Rubenstein teaches] its importance in maintaining mucosal health, integrity, and function is generally accepted.” (Id. at 6.) More specifically, the Examiner finds Rubenstein teaches “[t]he purpose of basic oral care is to reduce the impact of the oral microbial flora, reduce cancer therapy-related symptoms of pain and bleeding, and prevent soft tissue infections . . . [and that] maintenance of good oral hygiene will reduce the risk of dental complications, including caries and gingivitis.” (Id.) The Examiner further finds that Rubenstein describes studies showing improved oral status (e.g., decreased mucositis) in patients undergoing cancer treatment when oral-care protocols were implemented. (Id.) The Examiner finds the skilled artisan would have combined the teachings of Bombardelli PCT “with the teachings of Rubenstein [], regarding the importance of basic oral care and hygiene in maintaining mucosal health, integrity, and function.” (Id.) The Examiner reasons [s]ince Bombardelli [PCT] teach[es] that the disclosed composition is useful for cleaning the oral cavity and removing dental plaque, and for maintaining good hygiene of the oral cavity, and Rubenstein [] teach[es] that an oral care protocol is important in managing mucositis, one of ordinary skill in the art would have been motivated to combine the teachings . . . in order to receive the expected benefit, as suggested by Rubenstein [], that the use of an oral care protocol would aid in maintaining mucosal health, integrity, and function in cancer patients, thereby reducing the impact of the oral microbial flora and reducing cancer therapy-related symptoms. (Id. at 7–8.) The Examiner thus concludes claim 98 would have been obvious. (Id. at 9; see also id. at 22.) Appeal 2014-007226 Application 12/856,786 9 We agree with the Examiner’s findings with respect to Bombardelli PCT and Rubenstein, as well as the Examiner’s reasoning and conclusion that claim 98 would have been obvious. We address below Appellants’ arguments. Appellants and the Examiner dispute whether Bombardelli PCT teaches or suggests a method of treating mucositis, and whether the throat redness and inflammation of Bombardelli PCT is a type of mucositis. (App. Br. 7–10; Reply Br. 2–5; Ans. 13.) Yet these are not the decisive questions because Appellants’ claims do not merely recite treatment of “mucositis.” The more significant question is whether Bombardelli PCT discloses use of its composition to treat the mucositis of claim 98. It does not. (FF 2–5.) Claim 98 recites that “the mucositis occurs in connection with the administration of chemotherapy and/or radiotherapy to the patient.” In other words, and even assuming “mucositis” alone is a broader condition with varied causes as the Examiner found, Appellants’ method addresses treatment of a more severe form of mucositis caused by chemotherapy or radiotherapy. (See Spec. ¶¶ 3–6.) But the absence of an express teaching in Bombardelli PCT of treatment of mucositis that occurs in connection with chemotherapy or radiotherapy is not fatal to the Examiner’s prima facie case. That is because the Examiner relies on Rubenstein as teaching treatment of mucositis that arises in patients receiving chemotherapy, for example. (FF 6–9.) Appellants, in arguing that Bombardelli PCT does not teach mucositis, “let alone mucositis in connection with the administration of chemotherapy and radiotherapy” thus do not persuasively address the rejection as framed, based Appeal 2014-007226 Application 12/856,786 10 on the combination of references. 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 argue “Rubenstein fails to disclose or suggest a method of treating mucositis by administering the compositions recited in the pending claims.” (App. Br. 11.) This argument — attacking Rubenstein individually — also fails. The Examiner relies on Bombardelli PCT as teaching the composition recited in claim 98, and the compositions’ use for reducing mucosal inflammation, removing purulent plaques, and improving hygiene of the oral cavity. (Ans. 3–5 and 8–9; FF 3–5.) Appellants argue that because “the oral care protocols for addressing mucositis [described in Rubenstein] do not involve or focus on the administration of any specific active agent,” the skilled person would not use the composition disclosed in Bombardelli PCT in an oral care protocol. (App. Br. 12.) Moreover, according to Appellants, “Rubenstein teaches away from using antimicrobial agents, which are used for treating infections, for treating mucositis.” (Id. at 13–14.) These arguments are unpersuasive. Rubenstein was assessing development of “clinical practice guidelines” (i.e., standardized protocols) for prevention and treatment of cancer-therapy induced mucositis. (Rubenstein 2026.) And, it was in this context that Rubenstein found the data inconclusive and thus specific guidelines involving certain specific active agents could not be provided. (Ans. 18; FF 9; Rubenstein 2032 (“The current review did not evaluate specific agents or approaches used in Appeal 2014-007226 Application 12/856,786 11 protocols, and insufficient evidence prevents the recommendation of one protocol over any other.”).) Rubenstein nevertheless teaches that “basic oral care, its importance in maintaining mucosal health, integrity, and function generally is accepted . . . [and] is an important component of care of the patient with cancer.” (FF 7.) Rubenstein also describes several studies where oral care protocols — involving administration of various agents, including antimicrobials — did show beneficial reduction in mucositis among cancer patients. (FF 8.) Even considered with Barasch,8 we are not persuaded that Rubenstein teaches away from the Examiner’s combination. Rubenstein recognizes that “some of these agents [e.g., mucosal surface protectants, anti-inflammatory agents, and antimicrobial agents] are potentially attractive, because they are associated with rationales for targeting specific pathways known to be involved in the etiology of mucositis; however, the evidence in support of these agents’ efficacy is not rigorous enough for the creation of a prescriptive guideline.” (Rubenstein 2039.) The absence of evidence necessary to meet Rubenstein’s (or Barasch’s) threshold for recommending specific active agents as part of prescriptive guidelines does not rise to the level of a teaching away — especially because Rubenstein elsewhere discusses the attractiveness and benefits of active agents and oral-care protocols for reducing mucositis in patients undergoing cancer therapy. (FF 6–8; Ans. 18–19.) We thus agree with the Examiner that the skilled artisan 8 Barasch et al., Antimicrobials, mucosal coating agents, anesthetics, analgesics, and nutritional supplements for alimentary tract mucositis, 14 SUPPORT CARE CANCER 528–532 (2006). Appeal 2014-007226 Application 12/856,786 12 would have predictably, and with a reasonable expectation of success, administered the composition of Bombardelli PCT to the patient with cancer-therapy induced mucositis as part of an oral-care protocol, and for the composition’s anti-inflammatory, antimicrobial, and other beneficial properties. (FF 3–5; Ans. 7–9 and 22.) Appellants argue Rosenbloom does not remedy the Examiner’s erroneous combination of Bombardelli PCT and Rubenstein. We are unpersuaded because the combination of Bombardelli PCT and Rubenstein is not erroneous for the reasons discussed above. We do, however, agree with Appellants that the skilled artisan would not ascertain from Rosenbloom that delphinidin is effective in treating mucositis as suggested by the Examiner.9 (Ans. 7.) As Appellants point out, Rosenbloom discloses treatment of a common cold, congestion, mucositis, or a host of other conditions with a composition that combines ingredients from turmeric, horseradish, and ginger (and delphinidin is listed among over 100 extracts of ginger). (App. Br. 16–17.) The Examiner has not provided sufficient evidence or reasoning to show that the skilled person would understand Rosenbloom as teaching extracts of ginger alone, much less the anthocyanin delphinidin, would be expected to treat mucositis. We are unpersuaded the Examiner based the rejection on improper hindsight as Appellants contend. (App. Br. 18.) The preponderance of the evidence — particularly the teachings of Bombardelli PCT and Rubenstein — supports the Examiner’s proposed combination of the art. (FF 2–8.) 9 See generally, In re Bush, 296 F.2d 491, 496 (CCPA 1961) (the Board may rely on less than all of the references relied upon by Examiner). Appeal 2014-007226 Application 12/856,786 13 Bombardelli PCT teaches the ingredients in its composition have anti- inflammatory, antimicrobial, and analgesic properties, and that the composition, among other things, reduces oral inflammation and improves oral hygiene. (FF 2–5.) Rubenstein teaches mucositis arising from cancer- therapy is characterized by inflammation, pain, and potential infection due to tissue ulceration. (FF 6–8.) Rubenstein further teaches observance of oral- care protocols is generally accepted and has provided benefits to patients with cancer-therapy induced mucositis. (FF 7–8.) These teachings lead directly and predictably to the Examiner’s combination and “do[] not include knowledge gleaned only from [Appellants’] disclosure.” In re McLaughlin, 443 F.2d 1392, 1395 (CCPA 1971). Unexpected Results Finally, Appellants argue unexpected results, as provided in declaration evidence,10 show that the claims are nonobvious. (App. Br. 19– 24; Reply Br. 12–13.) More specifically, Appellants argue that administering a composition with the three ingredients recited in the claims provides unexpected and synergistic reduction in cancer-therapy induced mucositis. (Id. at 20–22.) Appellants’ evidence describes a study of 28 patients having mucositis caused by chemotherapy or radiotherapy. (Bombardelli Decl. ¶¶ 7–9.) These patients were administered one of four compositions (A–D) containing certain extracts encompassed by Appellants’ claims. (Id.) The Bombardelli Declaration shows that “Composition A,” which included 10 Declaration of Ezio Bombardelli dated February 6, 2013 (“Bombardelli Decl.”). Appeal 2014-007226 Application 12/856,786 14 extracts of Vaccinium myrtillus, Macleaya cordata, and Echinacea angustifolia, provided an 88.72% reduction in mucositis severity and a 97.41% reduction in lesion intensity following seven days of administration. (Id. at ¶¶ 10–11.) Comparatively, “Composition B” (containing only the extract of Vaccinium myrtillus) provided respective reductions of 23.12% and 36.21%. (Id.) Compositions including extracts of Macleaya cordata or Echinacea angustifolia alone “did not exhibit any activity in reducing the severity of mucositis” and so treatment with those compositions was discontinued after three days. (Id. at ¶¶ 9–11.) We evaluate the Examiner’s case for obviousness against Appellants’ evidence of secondary considerations. In re Rinehart, 531 F.2d at 1052. With respect to claim 98, however, we are unpersuaded that Appellants’ evidence shows the claim is nonobvious. Claim 98 is not limited to administration of a composition with the three extracts found in Composition A of Appellants’ study. (Final Act. 23–24.) It is broader and, in fact, encompasses administration of a composition with none of the extracts tested. In re Lindner, 457 F.2d 506, 508 (CCPA 1972) (“It is well established that the objective evidence of nonobviousness must be commensurate in scope with the claims.”). Appellants have not provided persuasive evidence that the alleged unexpected results apply to administering compositions with different ingredients than those tested, such as encompassed in independent claims 98 and 130. Appellants contend “Dr. Bombardelli does not limit [the] statement regarding unexpected results to only three-component compositions having a certain amount of ingredients.” (App. Br. 23.) Appeal 2014-007226 Application 12/856,786 15 Neither does Appellants’ evidence show — through actual testing or persuasive scientific reasoning — what happens or would be expected when compositions with other ingredients falling within the scope of Appellants’ claims are administered to treat cancer-therapy induced mucositis. Indeed, during the hearing on appeal, Appellants’ counsel was unable to cite to further persuasive evidence on this topic and acknowledged that testing of other compositions encompassed by claim 98 had not been done. (See Dec. 8, 2016 Hr’g Tr. 5:5–8:14.) For these reasons we conclude that Appellants’ evidence does not demonstrate that claim 98 is nonobvious. Claim 119 We reach a different conclusion on claim 119, which recites treating cancer-therapy induced mucositis with a composition having the same ingredients found in Composition A of Appellants’ testing evidence. (App. Br. 26–27 (Claims App’x).) The testing shows that administration of Composition A including Vaccinium myrtillus, Macleaya cordata, and Echinacea angustifolia provided a greater than 3x reduction in mucositis severity and a greater than 2x reduction in the intensity of lesion symptoms compared to administration of a composition having Vaccinium myrtillus alone. (Bombardelli Decl. ¶¶ 10–11.) Compositions including the other ingredients alone showed no apparent effect. (Id.) On the present record, we are persuaded that administration of claim 119’s composition provided an unexpected synergistic effect sufficient to overcome the Examiner’s prima facie case. Appeal 2014-007226 Application 12/856,786 16 The Examiner is correct to point out that evidence of unexpected results must ordinarily show that the results are unexpected compared to the closest prior art. (Ans. 25.) In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991). But the closest prior art here (Bombardelli PCT) does not disclose treatment of mucositis induced by cancer therapy, and none of Bombardelli PCT’s examples include the combination of ingredients recited in claim 119. (Bombardelli PCT 4–6.) Further, Bombardelli PCT requires two ingredients; other ingredients are optional. (FF 2.) While possible to find a disclosure of each ingredient of claim 119 within Bombardelli PCT, based on the facts presented here, we are not persuaded that Appellants should have to construct a hypothetical composition from the prior art and, in effect, test the composition of claim 119 against itself. For these reasons, we reverse the Examiner’s rejection of claim 119. Conclusion of Law We conclude the Examiner established by a preponderance of the evidence that claim 98 would have been obvious over Bombardelli PCT, Bombardelli ’365, Gabetta, Rubenstein, and Rosenbloom. Claims 99–108, 110–118, 130–141, and 143–146 have not been argued separately and so fall with claim 98. 37 C.F.R. § 41.37(c)(1)(iv). Because the preponderance of the evidence does not support the Examiner’s rejection of claim 119, we reverse the rejection of claim 119 and dependent claims 120–124 and 126–129. Appeal 2014-007226 Application 12/856,786 17 REJECTION II Issue Has the Examiner established by a preponderance of the evidence that claims 109, 125, and 142 would have been obvious over Bombardelli PCT, Bombardelli ’365, Gabetta, Rubenstein, Rosenbloom, and Goodman & Gilman’s? Findings of Fact FF 10. The Examiner’s findings and statement of Rejection II may be found at pages 2–9 of the Examiner’s Answer. Except as otherwise noted, we adopt those findings and provide the following for emphasis. FF 11. Bombardelli PCT teaches “[t]he pharmaceutical compositions will preferably be formulated as tablets for the slow dissolution in the oral cavity or as chewable forms, particularly gums, which provide slow release of the active principles.” (Bombardelli PCT 3.) FF 12. Goodman & Gilman’s disclose “[d]rugs are applied to the mucous membranes of the conjunctiva, nasopharynx, oropharynx, vagina, colon, [etc.] . . . primarily for their local effects. . . . Absorption through mucous membranes occurs readily.” (Goodman & Gilman’s 8.) Analysis Claims 109, 125, and 142 relate to “topical administration” of the compositions according to the methods of 98, 119, and 130 respectively. The Examiner relies on the findings concerning Bombardelli PCT and Rubenstein as discussed above, and further finds that “Goodman & Gilman’s teaches that drugs are commonly administered parenterally or orally . . . Appeal 2014-007226 Application 12/856,786 18 [and] can be administered topically to the mucous membranes.” (Ans. 10.) According to the Examiner, “[d]rugs are applied to the mucous membrane for their local effects where absorption occurs readily” as discussed in Goodman & Gilman’s. (Id.) The Examiner concludes that, because Bombardelli PCT teaches administration of its composition for treatment of the oral cavity, “one of ordinary skill in the art would have been motivated to apply the composition topically . . . to achieve local effect where absorption through mucous membranes occur readily.” (Id. at 11.) Appellants reprise their arguments concerning Rejection I. (App. Br. 18–19.) Those arguments are unpersuasive for the reasons discussed above. Bombardelli PCT teaches treatment of the oral cavity, and describes formulations for dissolution in the oral cavity, such as chewable gums, which is reasonably understood as “topically” administering the medicaments. (FF 11.) Goodman & Gilman’s teaches that topical administration is common for local effect. (FF 12.) We are persuaded that it would have been obvious to administer the composition of Bombardelli PCT topically to patients with cancer-therapy induced mucositis. Conclusion of Law We conclude that the Examiner established by a preponderance of the evidence that claims 109 and 142 would have been obvious over Bombardelli PCT, Bombardelli ’365, Gabetta, Rubenstein, Rosenbloom, and Goodman & Gilman’s. We reverse the rejection, however, as to claim 125 for the reasons provided concerning claim 119 and Rejection I. Appeal 2014-007226 Application 12/856,786 19 SUMMARY We affirm the rejection of claims 98–108, 110–118, 130–141, and 143–146 under 35 U.S.C. § 103(a) over Bombardelli PCT, Bombardelli ’365, Gabetta, Rubenstein, and Rosenbloom. We reverse the rejection, however, as to claims 119–124 and 126–129. We affirm the rejection of claims 109 and 142 over Bombardelli PCT, Bombardelli ’365, Gabetta, Rubenstein, Rosenbloom, and Goodman & Gilman. We reverse the rejection as to claim 125. 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-IN-PART Copy with citationCopy as parenthetical citation