Beverly A. Rzigalinski et al.Download PDFPatent Trials and Appeals BoardMay 19, 202012252905 - (D) (P.T.A.B. May. 19, 2020) 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. 12/252,905 10/16/2008 Beverly A. Rzigalinski VCOM-021299 US CIP 8293 26294 7590 05/19/2020 TAROLLI, SUNDHEIM, COVELL & TUMMINO L.L.P. 1300 EAST NINTH STREET, SUITE 1700 CLEVELAND, OH 44114 EXAMINER LIU, SUE XU ART UNIT PAPER NUMBER 1616 NOTIFICATION DATE DELIVERY MODE 05/19/2020 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): docketing@tarolli.com rkline@tarolli.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte BEVERLY A. RZIGALINSKI, NEERAJ SINGH, and COURTNEY A. COHEN1 Appeal 2019-001476 Application 12/252,905 Technology Center 1600 Before DONALD E. ADAMS, ERIC B. GRIMES, and RICHARD M. LEBOVITZ, Administrative Patent Judges. GRIMES, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a) involving claims to a method of treatment, which have been rejected as obvious and lacking adequate written description. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM the rejection for lack of adequate written description. STATEMENT OF THE CASE The Specification states that “Alzheimer’s and Parkinson’s diseases, neuromuscular disorders, and mitochondrial diseases are associated with increased oxidative stress, production of free radicals, and/or destruction of 1 Appellant identifies the real parties in interest as “the inventors Beverly A. Rzigalinski, Neeraj Singh, and Courtney A. Cohen.” Appeal Br. 3. We use the word Appellant to refer to “applicant” as defined in 37 C.F.R. § 1.42(a). Appeal 2019-001476 Application 12/252,905 2 mitochondria.” Spec. ¶ 4. The Specification also states that “[i]t has previously been shown that cerium oxide nanoparticles (CeONP) decrease oxidative stress, reduce free radical production, and extend cell and organism longevity.” Id. The Specification discloses that “cerium oxide nanoparticles (CeONP) can be used to treat or prevent neurodegenerative diseases, including for example Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease, AIDS-related dementia, ALS, . . . , as well as mitochondrial diseases.” Id. ¶ 15. Claims 1, 8, 9, 11, and 15–17 are on appeal. Claims 1 and 8, reproduced below, are the independent claims: 1. A method of treating a subject for Alzheimer’s Disease, Huntington’s Disease, Parkinson’s Disease, or amyotrophic lateral sclerosis (ALS), said method comprising: administering a non-agglomerating composition comprising cerium oxide nanoparticles having an average particle diameter size of about 10 nm to about 20 nm in an amount sufficient to provide a therapeutically effective dose of about 10 ng, 50 ng, 100 ng, 500 ng, 1 μg, 5 μg, 10 μg, or 50 μg per kg body mass to a subject having Alzheimer’s Disease, Huntington’s Disease, Parkinson’s Disease, or amyotrophic lateral sclerosis (ALS). 8. A method of treating a subject for a mitochondrial disease or the suffering from the effects of a mitochondrial toxin, comprising: administering a non-agglomerating composition comprising cerium oxide nanoparticles having an average particle diameter size of about 10 nm to about 20 nm in an amount sufficient to provide a therapeutically effective dose of about 10 ng, 50 ng, 100 ng, 500 ng, 1 μg, 5 μg, 10 μg, or 50 μg per kg body mass to a subject having mitochondrial disease or suffering from the effects of a mitochondrial toxin. Appeal 2019-001476 Application 12/252,905 3 The claims stand rejected as follows: Claims 1, 8, 9, 11, and 15–17 under 35 U.S.C. § 112, first paragraph, for lack of adequate written description (Final Action2 5) and Claims 1, 8, 9, 11, and 15–17 under 35 U.S.C. § 103(a) as obvious based on McGinnis,3 Chinopoulos,4 and Wang5 (Final Action 11). OPINION Written Description Claims 1, 8, 9, 11, and 15–17 stand rejected for “failing to comply with the written description requirement,” because [t]he claims have been amended to claim doses of 10 ng, 50 ng, 100 ng, 500 ng, 1 mg, 5 mg, 10 mg, or 50 mg per kg body mass. The Applicant cites to paragraph 0055 of the 11/993,260 application (which entire disclosure is incorporated by reference by the present Specification (see paragraph 0001 of the Specification) as support for the claimed dosage range but . . . the incorporation by reference is not proper as the US Patent Application Publication must be cited. As such, the dosage range lacks written description support. Final Action 5. Appellant argues that “37 CFR l.57(d) . . . corresponds to the situation in the present case, where incorporation by reference was present in 2 Final Office Action mailed February 23, 2018. 3 McGinnis et al. (US 7,347,987 B2; iss. Mar. 25, 2008). 4 Christos Chinopoulos & Vera Adam-Vizi, Mitochondria Deficient in Complex I Activity are Depolarized by Hydrogen Peroxide in Nerve Terminals: Relevance to Parkinson’s Disease, J. Neurochem. 76:302–306 (2001). 5 Jinsheng Wang et al., Protective Effect of Cerium on Mitochondria Wheat Under Salinity Stress, Zhongguo Xitu Xuebao 17:187–190 (abstract only) (1999). Appeal 2019-001476 Application 12/252,905 4 paragraph [0001] of the application.” Appeal Br. 8. Appellant argues that “the application satisfies the requirements of 37 CFR l.57(d).” Id. As the Examiner has pointed out, however, “37 CFR 1.57 (d) clearly requires reference to a US Patent or US Patent Application Publication.” Ans. 4. Currently, and in relevant part, the instant Specification states that “this application is a continuation-in-part application of U.S. Patent Application No. 11/993,260, filed December 20, 2007 . . . , the disclosure[] of which [is] incorporated herein by reference.” Spec. ¶ 2. There is no dispute that the incorporation by reference of the ’260 application is required to provide support for the dosages recited in the claims. Thus, Appellant seeks to incorporate by reference essential material from the ’260 application, and 37 C.F.R. § 1.57(d) applies. See Appeal Br. 8 (“37 CFR l.57(d) . . . corresponds to the situation in the present case.”) That rule states that “‘[e]ssential material’ may be incorporated by reference, but only by way of an incorporation by reference to a U.S. patent or U.S. patent application publication.” 37 C.F.R. § 1.57(d) (emphasis added). The instant Specification does not refer to the U.S. patent application publication number, but only to the application serial number, and therefore does not comply with 37 C.F.R. § 1.57(d). As the Examiner has pointed out, the ’260 application “was published on July 1, 2010 as US Patent Application Publication US 2010/0166821 A1. As such, the Appellants need only amend the Specification to also cite said US Patent Application Publication in order to comply with 37 CFR 1.57 (d).” Ans. 4 (emphasis added). Appeal 2019-001476 Application 12/252,905 5 At present, however, the incorporation by reference of the ’260 application is improper and the dosages recited in the claims lack adequate written support in the instant Specification. We therefore affirm the rejection of claims 1, 8, 9, 11, and 15–17 under 35 U.S.C. § 112, first paragraph, for lack of adequate written description. Obviousness Claims 1, 8, 9, 11, and 15–17 stand rejected as obvious based on McGinnis, Chinopoulos, and Wang. The Examiner finds that McGinnis “disclose[s] a method of promoting the longevity of retinal neuron[s] by administering cerium oxide particles having a diameter range between about 1 nanometer and about 10 nm to the eye . . . at a dosage of about 3 nanomolar to about 50 nanomolar.” Final Action 11. The Examiner finds that McGinnis discloses “that the cerium oxide particles can be used to inhibit neurodegeneration, e.g. Alzheimer’s, Parkinson’s, dementia and amyotrophic lateral sclerosis, by destroying toxic product of metabolism known as reactive oxygen species.” Id. The Examiner also finds that McGinnis describes an experiment “in which 2 microliters of cerium oxide nanoparticles at a concentration of 0.1 to 1.0 micromolar is injected into rats which protected retinal cells from damage due to reactive oxygen species.” Id. The Examiner finds that Chinopoulos “disclose[s] that deficiency of mitochondrial complex I activity is believed to be a critical factor in the development of Parkinson’s disease” and that “mitochondria have increased vulnerability to hydrogen peroxide induced oxidative stress when the activity of complex I is reduced to a similar extent as found in Parkinson’s Appeal 2019-001476 Application 12/252,905 6 disease by rotenone.” Id. at 12. The Examiner finds that Wang “disclose[s] that that cerium reduced levels of O2 [O2] and OH thereby normalizing lipid hydroperoxide and fluidity of the mitochondria membrane . . . such that the function of mitrochondria [sic] is on relatively normal levels.” Id. The Examiner concludes that “nanoceria[6] within the claimed size range and dosages have been used in the treatment of retinal neuron degeneration due to reactive oxygen species. As the nanoceria have shown to be effective as an antioxidant, one of ordinary skill in the art would expect that they can be used as an antioxidant in patients.” Id. at 13. The Examiner also concludes that “one of ordinary skill in the art would have expected that nanoparticles of cerium oxide can be administered to subjects having Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis and mitochondrial disease . . . where the mitochondrial dysfunction is due to inhibition of mitochondrial complex I.” Id. Appellant argues that the claims have been amended “to recite providing a ‘therapeutically effective’ dose. Because the claims recite use of an effective dosage, . . . Applicants respectfully request that the rejection of claims 1, 8, 9, 11, 15, 16, and 17 for obviousness be reversed.” Appeal Br. 19. More specifically, Appellant argues that McGinnis “describe[s] administering a concentration of cerium oxide nanoparticles in a range between 3 nanomolar and 50 nanomolar.” Reply Br. 7. Appellant argues that such concentration values do not provide therapeutically useful dosage information, since the amount administered can vary widely from the concentration used for administration, and it is 6 Cerium oxide nanoparticles are also referred to as nanoceria. See, e.g., McGinnis 1:13–17, 2:42–45. Appeal 2019-001476 Application 12/252,905 7 the amount administered compared to the size of the subject that is important. The claimed dosage amounts, on the other hand, are provided in nanograms or micrograms per kilogram of body mass. Id. Appellant argues that “the claimed dosages are non-obvious in view of the cited prior art.” Id. We agree with Appellant that the Examiner has not adequately shown that the dosages recited in the claims would have been obvious based on the cited references. Both claim 1 and claim 8 recite administering specific dosages of “10 ng, 50 ng, 100 ng, 500 ng, 1 μg, 5 μg, 10 μg, or 50 μg per kg body mass to a subject.” The Examiner cites McGinnis as disclosing “a dosage of about 3 nanomolar to about 50 nanomolar.” Final Action 11. However, as Appellant has pointed out, “nanomolar” is a unit of concentration; specifically, nanomoles per liter—not a dosage of nanograms per kilogram of body mass. A composition having a particular concentration of an active agent does not teach or suggest any specific dosage of that agent, because any desired dosage can be administered by varying the volume of the composition that is administered. With regard to Appellant’s argument that the claims require a “therapeutically effective dose,” the Examiner reasons that “the claims do not define the therapeutic effect. As such, the claims do not require that doses be effective to treat Alzheimer’s Disease, [etc.,] . . . only that the subject treated with the cerium oxide nanoparticles have said diseases and/or conditions.” Ans. 4. We do not agree with the Examiner’s reasoning. First, the claims recite a method of “treating” specific conditions by administering a Appeal 2019-001476 Application 12/252,905 8 “therapeutically effective dose” of cerium oxide nanoparticles. A dose of a drug is not “therapeutically effective” unless it is effective to treat the condition being treated. The claims therefore do require that the dosage of cerium oxide nanoparticles is effective to treat the specified disease or disorder. In addition, the claims go on to define what a “therapeutically effective dose” is: “10 ng, 50 ng, 100 ng, 500 ng, 1 μg, 5 μg, 10 μg, or 50 μg per kg body mass to a subject.” Claims 1, 8. In order to support a prima facie case of obviousness, therefore, the cited references must teach or suggest one of the specific dosages recited in the claims. The Examiner has not shown that they do so, and because this burden was not met, we reverse the rejection of claims 1, 8, 9, 11, and 15–17 under 35 U.S.C. § 103(a). DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1, 8, 9, 11, 15–17 112, first paragraph Written Description 1, 8, 9, 11, 15–17 1, 8, 9, 11, 15–17 103(a) McGinnis, Chinopoulos, Wang 1, 8, 9, 11, 15–17 Overall Outcome 1, 8, 9, 11, 15–17 Appeal 2019-001476 Application 12/252,905 9 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). See 37 C.F.R. § 1.136(a)(1)(iv) (2017). AFFIRMED Copy with citationCopy as parenthetical citation