Ex Parte Chung et alDownload PDFPatent Trials and Appeals BoardMay 20, 201911499936 - (D) (P.T.A.B. May. 20, 2019) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 11/499,936 08/07/2006 24267 7590 05/22/2019 CESARI AND MCKENNA, LLP ONE LIBERTY SQUARE SUITE 310 BOSTON, MA 02109 FIRST NAMED INVENTOR Yih-Lin Chung 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. 2180 l 9-0005P3 3312 EXAMINER FINN, MEGHAN R ART UNIT PAPER NUMBER 1629 NOTIFICATION DATE DELIVERY MODE 05/22/2019 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@c-m.com USPTOMail@c-m.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte YIH-LIN CHUNG and NAM-MEW PUI 1 Appeal2018-003599 Application 11/499,936 Technology Center 1600 Before ERIC B. GRIMES, ULRIKE W. JENKS, and RYAN H. FLAX, Administrative Patent Judges. FLAX, Administrative Patent Judge. DECISION ON APPEAL This is a decision on appeal under 35 U.S.C. § 134(a) involving claims to a method for treating epithelial lining tissue damage from mucositis induced by radiation exposure and/or chemotherapy. The Examiner's rejection of claims 1-3, 6-9, 12-14, 17-19, and 22 under 35 U.S.C. § 103(a) is appealed. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. 1 The Real Party in Interest is identified as "Sunny Pharmatech, Inc." Appeal Br. 3. Herein, we refer to the Specification of Aug. 7, 2006 ("Spec."); Final Office Action of Oct. 22, 2014 ("Final Action"); Appeal Brief of July 22, 2015) ("Appeal Br."); Examiner's Answer of Dec. 20, 2017 ("Answer"); and Reply Brief of Feb. 20, 2018 ("Reply Br."). Appeal2018-003599 Application 11/499,936 STATEMENT OF THE CASE The Specification states: The present invention relates to methods and compositions for treating or preventing epithelial lining tissue damage from dermatitis or mucositis induced by radiation exposure and/ or chemotherapy. More particularly, the present invention relates to a therapeutic composition comprising a histone deacetylase [HDAC] inhibitor formulated with a biocompatible polymer that is useful for treating or preventing dermatitis and mucositis in cancer therapy. Spec. ,r 2. The Specification further explains: One complication of radiation therapy and chemotherapy is the damage that occurs in the epithelial lining tissues including skin and mucosa. This kind of damage to skin and mucosa is called dermatitis and mucositis, respectively. Severe oral mucositis is especially common among patients who receive aggressive myeloablative chemotherapy for haematopoietic stem-cell transplant, and patients with head and neck cancers receiving radiotherapy and chemotherapy. Id. ,r 4. The Specification describes five phases of epithelial damage caused by radiation and/ or chemotherapy relating to mucositis, which are (I) initiation phase; (II) damage message generation phase; (III) damage signal and amplification phase; (IV) ulceration and infection phase; and (V) healing phase. Id. ,r,r 5-10. The Specification states that phases II and III are the best targets, but also that "each of the five phases previously described offers potential targets for the prevention, amelioration, and/or acceleration of healing of epithelial damage induced by chemotherapy and/or radiation." Id. ,r,r 11, 12. 2 Appeal2018-003599 Application 11/499,936 Independent claim 1, reproduced below, is representative: 1. A method for treating epithelial lining tissue damage from mucositis induced by radiation exposure and/or chemotherapy, said method comprising administering topically to a mucositis site in a human or animal subject in need thereof a therapeutic composition which comprises at least one histone deacetylase (HDAC) inhibitor formulated with an amount of a pharmaceutically acceptable biocompatible polymer sufficient to prolong retention of the HDAC inhibitor in the mucosa or other tissues of the body, wherein the pharmaceutically acceptable biocompatible polymer is a reverse-thermal gelation polymer. Appeal Br. 8 (Claims Appendix). Independent claim 7 is similar, but has a different preamble directed to treating other conditions associated with mucositis. Independent claims 13 and 18 are like claims 1 and 7, but include limitations directed to identifying ( diagnosing) the patient to be treated. In response to an election of species requirement, Appellants selected phenylbutyrate ( claim 3) as the HDAC inhibitor claimed; we limit our analysis to the elected species. Answer 4; see Ex parte Ohsaka, 2 USPQ2d 1460, 1461 (BPAI 1987) (appropriate to limit discussion on ex parte appeal to elected species; if reversing, taking no position on broader generic claims, and, if affirming, all claims including the species are unpatentable for same reasoning as for elected species). The following rejection is on appeal: Claims 1-3, 6-9, 12-14, 17-19, and 22 stand rejected under 35 U.S.C. § I03(a) over Rosenthal2 and Chung. 3 Answer 4. 2 US 2002/0119104 Al (published Aug. 29, 2002) ("Rosenthal"). 3 US 2002/0055542 Al (published May 9, 2002) ("Chung"). 3 Appeal2018-003599 Application 11/499,936 FINDINGS OF FACT Unless otherwise indicated herein, we adopt the Examiner's findings of fact and rationale on obviousness as set forth in the Final Action and Answer. Final Action 3-13; Answer 4--22. The following findings of fact highlight certain evidence: FF 1. Rosenthal discloses: This present invention provides a therapeutic composition for use in the treatment of mucositis and a method for using such a therapeutic composition. The therapeutic composition includes a pharmaceutical substance effective for treating mucositis formulated with a biocompatible polymer, such as a biocompatible reverse-thermal gelation polymer. Rosenthal Abstract. FF2. Rosenthal further discloses: Mucositis is a serious and often very painful disorder involving inflammation of the mucous membrane, with the inflammation often accompanied by infection and/or ulceration. Mucositis can occur at any of the different mucosal sites in the body. A nonlimiting list of examples of locations where mucositis can occur include mucosal sites in the oral cavity, esophagus, gastrointestinal tract, bladder, vagina, rectum, lung, nasal cavity, ear and orbita. Mucositis often develops as a side effect of cancer therapy, and especially as a side effect of chemotherapy and radiation therapy for the treatment of cancer. ... Exposure to radiation and/or chemotherapeutics often results in significant disruption of cellular integrity in mucosal epithelium, leading to inflammation, infection and/or ulceration at mucosal sites. Rosenthal ,r 3. FF3. Rosenthal discloses: Oral mucositis appears to be a four-phase process: the primary phase is inflammatory /vascular in nature resulting in a 4 Appeal2018-003599 Application 11/499,936 cytokine release from the epithelium brought on by damage caused by radiation and/or chemotherapy. The second phase, referred to as the epithelial phase, is signaled by atrophy and ulceration of the mucosal epithelium. The third phase is defined as the ulcerative/bacterial phase represented by ulcerative lesions that are prone to bacterial infection further compromising the patients' immune system. These painful lesions often limit a patient's ability to eat and drink and in some cases require hospitalization. The presence of these lesions can also interrupt scheduled chemotherapy and/or radiation treatments. The last phase, the healing phase, is characterized by a proliferation and differentiation of epithelium as well as bacterial control. Rosenthal ,r 5. FF4. Rosenthal discloses that treating mucositis includes treating "oral mucositis, esophagitis, cystitis, sinusitis, asthma, colitis, GERD, proctitis, stomatitis, celiac disease, inflammatory bowel disease, and Crohn' s disease" and "inflammation, infection and ulceration." Rosenthal claims 3, 14. FF5. Rosenthal discloses: the present invention provides a therapeutic composition for the treatment of mucositis. By treatment of mucositis, it is meant that the therapeutic composition is effective to prevent or reduce the incidence, severity and/or duration of the disease .... One preferred embodiment of the therapeutic composition includes N-acetylcysteine as the pharmaceutical substance and a polyoxyalkylene block copolymer as the biocompatible polymer. Rosenthal ,r 11. FF6. Rosenthal discloses: For many applications, reverse-thermal viscosity behavior is beneficial to permit administration in a lower viscosity fluid form that tends to convert to a higher viscosity form following administration as the temperature of the therapeutic composition increases in the body. This also facilitates administration at a 5 Appeal2018-003599 Application 11/499,936 refrigerated temperature, which is soothing and refreshing to the host in a number of situations, such as for the treatment of mucosal surfaces in the oral cavity or esophagus. Rosenthal ,r 12. FF7. Rosenthal discloses treating mucositis with the aforementioned composition with administration thereof to the oral cavity, to the esophagus, to the stomach, to the nasal mucosal surfaces, to the ocular mucosal surfaces, to the rectal or vaginal mucosal surfaces, and to pulmonary mucosal surfaces. Rosenthal ,r,r 13-19. FF8. Rosenthal teaches that N-acetylcysteine (NAC), the preferred active component of its compositions, is an antioxidant. Rosenthal ,r 22. FF9. Rosenthal discloses "[o]ptionally, the composition can also comprise a permeability enhancer and/or an active agent in addition to the oral mucositis agent(s)," i.e., in addition to N- acetylcysteine. Rosenthal ,r 35. FFlO. Chung discloses "[a] method for treating a subject having an ulcer or radiation fibrosis" by topically administering a pharmaceutical formulation with one of "2-phenylbutyrate, 3- phenylbutyrate, and 4-phenylbutyrate." Chung Abstract, ,r 4. FFl 1. Chung discloses: Radiation fibrosis, a local defect, is a frequent sequela of therapeutic or accidental radiation overexposure of normal tissues. It results from a complex tissue repair response whose predominant characteristics are massive deposition of extracellular matrix and excessive fibroblast proliferation. An 6 Appeal2018-003599 Application 11/499,936 ulcer is also a local defect, i.e., excavation of the surface of an organ or tissue. Chung ,r 2. FF12. Chung discloses "'treatment' refers to administration of a topical composition to a subject with the purpose to cure, heal, alleviate, relieve, remedy, ameliorate, improve or prevent an ulcer or radiation fibrosis, its symptoms or the predisposition toward it." Chung ,r 7. FF13. Chung discloses, regarding the effective amount of, e.g., phenylbutyrate, for treatment of radiation-induced fibrosis or ulcers, "the effective doses vary depending on route of administration, excipient usage, and the possibility of co-usage with other therapeutic treatments such as the use of other anti-ulcer or a[n]ti-radiation fibrosis agents." Chung ,r 11. FF14. Chung discloses that its topical composition can be an "oral gel, which can be particularly used in the oral mucosa. The oral gel can include a viscose-enhancing agent ( such as sodium polyacrylate) and an aromatic fatty acid." Chung ,r 14. FF15. Chung discloses administering its treatment "orally, parenterally, sublingually, rectally, enterally, or by pulmonary absorption" to "treat[] an ulcer or radiation fibrosis." Chung ,r 15. FF16. Chung discloses that topical compositions including commercially available phenylbutyrate were effective in reducing swelling associated with ulcers, reducing radiation-induced fibrosis, and slowing the development of ulcers. Chung ,r,r 17-71 (Examples 1-6). 7 Appeal2018-003599 Application 11/499,936 DISCUSSION "[T]he examiner bears the initial burden, on review of the prior art or on any other ground, of presenting aprimafacie case ofunpatentability. [Once] that burden is met, the burden of coming forward with evidence or argument shifts to the applicant." In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). "Patents [ and publications] are part of the literature of the art and are relevant for all they contain." In re Young, 927 F.2d 588, 591 (Fed. Cir. 1991 ). "[A] reference is not limited to the disclosure of specific working examples." In re Mills, 470 F.2d 649, 651 (CCPA 1972)). "The combination of familiar elements [ or steps] according to known methods is likely to be obvious when it does no more than yield predictable results." KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,416 (2007). The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem; it is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by Applicant. See, e.g., In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006). The Examiner determined the claims would have been obvious over the combination of Rosenthal and Chung. Final Action 3-13; Answer 4--22. Specifically, the Examiner determined that Rosenthal taught all claim elements except for including phenylbutyrate (the elected HDAC inhibitor) in the composition topically administered to a mucositis site. See, e.g., Answer 3, 5-8; see also FF1-FF9. The Examiner cited Chung as teaching that phenylbutyrate is effective at treating radiation-induced fibrosis and ulcers. Answer 4; see also FF10-FF16. The Examiner determined that it 8 Appeal2018-003599 Application 11/499,936 would have been obvious to combine Rosenthal's method and composition for treating mucositis with Chung's phenylbutyrate because each reference teaches methods for treating radiation-induced injury to the oral mucosa using such materials and methods. Answer 8-11; see also FF2, FF4, FF7, FF9, FF 10, FF 11, FF 13-FF 16. The Examiner further determined that the skilled artisan would have had a reasonable expectation of successfully making this combination because the two references teach similar formulations and applications thereof to a patient's physiology. Answer 11, 22; see also FF2, FF7, FF14, FF15. We discern no error in the Examiner's determinations. Appellants argue that the claims would not have been obvious over Rosenthal and Chung because radiation-induced tissue injury can be differentiated physiologically from other types of tissue injury. See Appeal Br. 4. Appellants also argue that evidence shows that radiation-induced tissue injury typically does not respond to treatments developed for other types of tissue injury. Id. ( citing Chung Declaration). 4 With the Chung Declaration, Appellants submit evidence that radiation-induced tissue injury is different than other types of tissue injury and show some specific compositions that were ineffective in treating radiation-induced mucositis. See Chung Declaration, Exhibits A-J. Appellants reiterate these arguments in their Reply Brief and also point out an error in the Examiner's Answer. See, e.g., Reply Br. 4 (the Examiner erroneously identified fibrinosis as fibrosis). 4 Declaration by Dr. Yin-Lin Chung under 37 C.F.R. § 1.132 dated Jan. 24, 2014 ("Chung Declaration"). 9 Appeal2018-003599 Application 11/499,936 We are not persuaded by Appellants' arguments or evidence. Even accepting Appellants' contentions regarding the differences between radiation-induced injury and other types of tissue injury and that the former do not respond to treatments developed for the latter as correct, the claims would have been obvious over Rosenthal and Chung and the skilled artisan would have been motivated to make the combination of art, for the reasons articulated by the Examiner. As determined by the Examiner, Rosenthal is directed to treating mucositis, of the mouth, caused by cancer therapies such as chemotherapy or radiation therapy. FF2. Rosenthal lacks a disclosure of including phenylbutyrate in its topical formulation for such treatments; however, Rosenthal expressly invites the skilled artisan to include an additional active agent in its formulation with N-acetylcysteine. FF9; see also Novo Nordisk A/S v. Caraco Pharmaceutical Laboratories, Ltd., 719 F.3d 1346, 1355 (Fed. Cir. 2013) (It is obvious to combine known compounds, for their known properties, if they would complement one another.) Here, Rosenthal's formulation and Chung's phenylbutyrate would complement one another-i.e., two radiation-induced injury treatments together. Chung discloses using phenylbutyrate in a topical composition, also applied to the mouth, for treating fibrosis caused by overexposure to therapeutic radiation, e.g., radiation cancer therapy. FFlO, FFl 1. Thus, it would have been obvious, as determined by the Examiner, to add Chung's phenylbutyrate as the additional active agent suggested by Rosenthal. See In re Kerkhoven, 626 F .2d 846, 850 (CCP A 1980) ("It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the 10 Appeal2018-003599 Application 11/499,936 same purpose, in order to form a third composition which is to be used for the very same purpose. . . . [T]he idea of combining them flows logically from their having been individually taught in the prior art."). Here, Rosenthal's and Chung's active components both treat radiation-induced injury. Once so added, all claim limitations would be met by the mucositis- treating formulation. Whether or not Chung's phenylbutyrate is added to Rosenthal's formulation for the express purpose of treating ulcers is not determinative. See In re Kahn, 441 F.3d at 988. The overall composition would have treated mucositis caused by radiation and/ or chemotherapy and would have included phenylbutyrate and a reverse-thermal gelation polymer, as required by the claims. Appellants' arguments and evidence do not persuade us that this combination of Rosenthal's and Chung's compositions and methods of treatment would not have been obvious. We conclude, in agreement with the Examiner, that for the reasons discussed above the combination of Rosenthal and Chung would have rendered the claimed subject matter obvious. SUMMARY The obviousness rejection of claims 1-3, 6-9, 12-14, 17-19, and 22 under 35 U.S.C. § 103(a) is affirmed. AFFIRMED 11 Copy with citationCopy as parenthetical citation