Unrren States PATENT AND TRADEMARK OFFICE. ae SMSO ea Tso Tomar Si "ose TORTS 7 WOLI GREENFIELD & SACKS, PC Dan 600 ATLANTICAVENUE Ta RTS BOSTON, MA 02210.2206 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 s ronically on above-indicated "Notification Date" to the following e-mail address(es): Patents_eOfficeAction® WolfGreentield.com WGS_cOificeAction@WolfGreentfield.com PIOL-90A (Rev, 08107)‘Application Wo. ‘Applicants) 14/232,250, CHANG ET AL Office Action Summary Examiner eC Unit | ARTO LIANKO GARYU 1676 cmon = The MAILING DATE of this communication appears on the cover sheet with the correspondence address = Period for Reply A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE g MONTHS FROM THE MAILING DATE OF ‘THIS COMMUNICATION. xcncions of ine maybe avalable under he prvlons ct 37 OFA 1.136(3). In poet, however, may ply be nly has Falwetorapy wan he to een pros tty m2 se eae te ayscionwtacome ABANDONED (SUSE g1S8) Aelia Ss rar hr onan an cones hs aya Status 1}B2|_Responsive to communication(s) filed on 30 March 2017. CIA ceclaration(s)/atidavit's) under 37 CFR 1.130(b) wasiwere fled on 2a){R) This action is FINAL. 26/01 This action is non-final 3)0 An election was made by the applicant in response to a restriction requirement set forth during the interview on ; the restriction requirement and election have been incorporated into this action. 4)C Since this application is in condition for allowance except for formal matters, prosecution as to the merits is closed in accordance with the practice under Ex parte Quayle, 1985 C.D. 11, 453 0.G. 213 Disposition of Claims* 5)) Claim(s) 14,19 and 21-24 is/are pending in the application. 5a) Of the above claim(s) is/are withdrawn from consideration. 610 Claims) is/are allowed 7)R Claim(s) 14,19 and 21-24isiare rejected. 810] Claims) is/are objected to. 9) Claim(s) are subject to restriction andior election requirement * if any claims have been determined allowable, you may be eligible to benef from the Patent Prosecution Highway program at a Participating intellectual property office forthe corresponding application, For more information, please see hitos/wwn uspte govipatentsfinit eventsigphvindex ise or send an inquly to PPHeadsack@uspto, Application Papers 10)L] The specification is objected to by the Examiner. 11) The drawing(s) filed on is/are: a)D) accepted or b)L] objected to by the Examiner. ‘Applicant may not request that any objection to the drawing(s) be held in abeyance. See 37 GFR 1.85(a) Replacement drawing sheet{s) including the correction is raquted if the crawing(s) is objected to, See 37 GFR, 1.121(d) Priority under 35 U.S.C. § 119 12)L] Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f. Certified copies: a)QAN 6)L] Some" c)L] None of the: 1.00 Certified copies of the priority documents have been received, 2.01 Certified copies of the priority documents have been received in Application No. 3.01 Copies of the certified copies of the priority documents have been received in this National Stage application from the International Bureau (PCT Rule 17.2(a)). “ S00 the attached detailed Office action fr a list ofthe catified copies nat recelved. Aaehment(s) 1D) notice of Retecences ited (PTO-892) 3) D inervow Summary (P7O-413) Paper No(s}Mal Date, 2) D1 intrmaton Disclosure Statements) (PTOIS8O8a andor PTOXSEIO8) Paper No(s}Mail Date 9) Dother: (otc Action SummaryApplication/Control Number: 14/232,350 Page 2 Art Unit: 1676 DETAILED ACTION Notice of Pre-AIA or AIA Status The present application is being examined under the pre-AIA first to invent, provisions. Status of Claims Claims 14, 19 and 21-24 are pending and under examination Claim Rejections - 35 USC § 112 Response to Arguments The rejection of claims 14 and 19-24 as not reasonably providing enablement for inhibiting cancer cell growth and metastasis under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph has been withdrawn as necessitated by the amendments filed March 30, 2017. Claim Rejections - 35 USC § 102 Response to Arguments The rejection of claims 14, 19 and 24 as being anticipated by Chang under pre- AIA 35 U.S.C. 102(b) has been withdrawn as necessitated by the amendments filed March 30, 2017. Claim Rejections - 35 USC § 103 The following is a quotation of pre-AlA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action: (a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skil in the art to which said subjectApplication/Control Number: 14/232,350 Page 3 Art Unit: 1676 ‘matter pertains. Patentability shall not be nagatived by the manner in which the invention was made, The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3, Resolving the level of ordinary skill in the pertinent art 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a). The claim rejections below are maintained. Claims 14, 19 and 21-24 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Chang (“Abstract 4621: Zfra regulates protein degradation and provides strong prevention against skin cancer’, Cancer Research, April 15, 2011, page 1; of record) in view of Hong et al. ("Zfra affects TNF-mediated cell death by interactingApplication/Control Number: 14/232,350 Page 4 Art Unit: 1676 with death domain protein TRADD and negatively regulates the activation of NF-kB, JNKI, p53 and WOXI during stress response", BMC Molecular Biology, 2007, pages 1- 17; of record). Chang teaches the zine finger-like protein for regulating apoptosis (Zfra) as a 31 amino acid proteins that affects the functions of tumor suppressors and participates in the mitochondrial pathway (see abstract, lines 1-3). Chang teaches the synthetic full- length Zfra1-31 (a zinc-finger like peptide comprising the amino acid sequence of SEQ ID NO: 1; the sequence of the zine finger-like peptide is SEQ ID NO: 2) and truncated Zirad-10 protein (a zinc finger-like peptide amino acid sequence of SEQ ID NO: 1; the sequence of the zinc finger-like peptide is SEQ ID NO: 1) (see the abstract, lines 3-4) Chang teaches transiently overexpressed Zfra, that is the process of expressing recombinant Zira protein in cell lines, induces apoptosis of many types of cancer cell (see the abstract, lines 7-8). Chang teaches pre-injection of Zfra1-31 and Zfrad-10 via tails veins (intravenous injection) protect mice from growing cancer xenografts (administering an effective amount of a zinc finger-liker peptide to a subject in need thereof inhibiting cancer cell growth or metastasis via intravenous injection; see the abstract, lines 8-11). Although Chang teaches that the injection of Zira1-31 and Zfrad-10 intravenously protects against the growth of cancer xenografts and transiently overexpressed Zfra induces apoptosis of many types of cancer cell, Chang does not explicitly teach the cancer is breast cancer, prostate cancer or brain cancer.Application/Control Number: 14/232,350 Page 5 Art Unit: 1676 Hong et al. teach the zine finger-like peptide, Zfra, wherein the Zira peptide is a 31 amino acid zinc finger-like protein (a zinc-finger like peptide comprising the amino acid sequence of SEQ ID NO: 1; the sequence of the zinc finger-like peptide is SEQ ID NO: 2) (see the abstract). Hong et al. teach that the Zira peptide induces cell death in prostate cancer cells (DU145 cells), in breast cancer cells (mda-mb-231 and mef7 cells), in leukemia cells (Molt4 T lymphocytes), and in neuroblastoma cancer cells (SK- N-SH; brain cancer cells) (see Figures 1 and 3 with captions). Hong et al. show that transiently overexpressed Zira induces approximately 10% cell death in DU145 cells, (prostate cancer cells), approximately 40% cell death in SK-N-SH cells (brain cancer cells) and from 30-50% cell death in mda-mb-231 and mcf7 cells (breast cancer cells) (see Figure 1A). Hong et al. show that Zfra enhances cell death by ectopic TRADD, FAADD and RIP by 100-150% in prostate cancer cells (see Figure 3 and caption) Hong et al. teach that shortening and/or modification of the naturally occurring Zfra may be of therapeutic value in controlling cancer cell growth and death (see page 13, left col.-continuing paragraph and right col.-continuing paragraph). At the time invention was made, it would have been obvious to one ordinary skill in the art to administer an effective dose of the Zfra1-31 or truncated Zfra4-10 peptide to a subject in need of treating breast, prostate or brain cancer by intravenous injection to arrive at the presently claimed invention because Zfra causes growth suppression and apoptotic cell death in many different types of cancer cells including brain cancer cells, breast cancer cells and prostate cancer cells. The teachings of Chang and Hong et al. would have lead the artisan of ordinary skill in the art to be motivated to utilize Zfrat-31Application/Control Number: 14/232,350 Page 6 Art Unit: 1676 or truncated Zfra4-10 in the treatment of subjects in need of treating breast, prostate and brain cancer because the Zfra peptide induces apoptosis, both indirectly and directly, in cancer cells as shown by both Chang and Hong et al. (see Chang, the Abstract; see e.g., Hong et al., Figures 1 and 3). There would be a reasonable expectation of success given that Zfra1-31 and truncated Zfra4-10 induce apoptosis in vivo via intravenous injection in subjects with melanoma and skin basal cell carcinoma cells and as well as induce apoptosis in vitro when transiently overexpressed in many different cells including ovarian cells, embryonic kidney cells, neuroblastoma cells, breast cancer cells and prostate cancer cells as exemplified and taught by both Chang and Hong et al. (@.g., transiently overexpressed Zira induces approximately 10% cell death in DU145 cells (prostate cancer cells), approximately 40% cell death in SK-N-SH cells (brain cancer cells) and from 30-50% cell death in mda-mb-231 and mef7 cells (breast cancer cells) as taught by Hong et al.; see Figure 1A); thus, supporting the in vivo use of intravenously administering said Zira in the treatment of other types of cancer such as breast, prostate and brain cancers, which are not skin cancer, that undergo cell death via the transient overexpression Zira . Regarding present claim 19, Zira1-31 comprises the amino acid sequence of SEQ ID NO: 2 as evidenced by Chang’ " Chang, "Naturally occurring peptide Zira inactivates tumor suppressors by covalent binding: An act of zfraction", NCKU 2008.9-2009.8; ‘p 4-21; approved for public release September 2008 cited in the IDS filed 8/27.2014; see page 13.Application/Control Number: 14/232,350 Page 7 Art Unit: 1676 Regarding present claim 24, Zirad-10 is the amino acid sequence RRSSSCK (present SEQ ID NO: 1) and Zfra1-31" is the amino acid sequence MSSRRSSSCKYCEQDFRAHTQKNAATPFLAN (present SEQ ID NO: 2) Therefore, at the time the invention was made the presently claimed invention was clearly prima facie obvious to the artisan of ordinary skill Response to Arguments In the remarks filed March 30, 2017, Applicants assert that the presently claimed invention is patentable over the teachings of Chang in view of Hong et al. Applicants assert that Chang does not teach treatment of specific types of cancer and the teachings of Hong et al. are contradictory because Hong et al. teach the Zira peptide either enhances or blocks cell death. Applicants further contend that Zfra unexpectedly showed much higher effects in reducing the growth of breast cancer cells, prostate cancer cells and brain cancer cells relative to other types of cancer cells. Applicants’ arguments have been fully considered but are not found persuasive. Hong et al. teach that Zfra may be of therapeutic value in controlling cancer cell growth and death (see page 13 of 17). Itis acknowledged that Hong et al. teach in the abstract that the Zfra peptide either enhances or blocks cell death caused by TRADD, FADD, or receptor-interacting protein in a dose-related manner; however, Hong et al. teach that Zira induces cells death in breast cancer cells and brain cancer cells. Hong et al. expressly states that “Zfra induced death of human cell lines including ovarian ME180, embryonic kidney HEK- 293, neuroblastoma SK-N-SH, Molt4 T lymphocytes, and breast MCF7 and MDA-MB-231 cells, and murine L929 fibroblasts (Figure 1A).”Application/Control Number: 14/232,350 Page 8 Art Unit: 1676 Emphasis added. Hong et al. also show in Figure 1A (reproduced below) that in addition to inducing cell death in breast and brain cancer cells, that Zfra causes cell death in prostate cancer cells (DU145) and Zira enhances cell death by ectopic TRADD, FADD and RIP (see Figure 3 and the caption). A. Ba 2 Therefore, in response to Applicants’ argument that the effects of Zfra exhibited in treating breast, prostate and brain cancer are unexpected is not found persuasive because in view of the teachings of Hong et al., the skilled artisan would reasonably conclude with a reasonable expectation of success that the administration of Zfra can be utilized in a method of treating breast, prostate and brain cancer to induce cell death of breast, prostate and brain cancer cells and thereby reduce breast, prostate and brain cancer cell growth and metastasis as claimed Conclu: No claim is allowed.Application/Control Number: 14/232,350 Page 9 Art Unit: 1676 THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a), A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action. Correspondence Any inquiry concerning this communication or earlier communications from the examiner should be directed to LANKO GARYU whose telephone number is (571)270- 7367. The examiner can normally be reached on Monday through Thursday 8:30 a.m. to 5:30 p.m. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http/www.uspto.goviinterviewpractice: If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Karlheinz R. Skowronek can be reached on (571) 272-9047. The fax phoneApplication/Control Number: 14/232,350 Page 10 Art Unit: 1676 number for the organization where this application or proceeding is assigned is 571- 273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. ILIANKO GARYU/ Lianko G. Garyu, Ph.D. Primary Examiner, Art Unit 1676 Primary Examiner Art Unit 1676: NO521.70023US00 (PATENT) IN THE UNITED STATES PATENT AND TRADEMARK OFFICE First Named Inventor: Nan-Shan Chang Application No, 1 0 Confirmation No.: 7846 Filed: October 14, 2014 For: NOVEL ZINC FINGER-LIKE PEPTIDE COMPOSITIONS AS POTENT AGENTS IN CANCER PREVENTION AND TREATMENT. Examiner: L.G. Garyu Ant Unit 1676 ‘Certificate of letronie Fling under 37 CFR §1.8 jared oa bang atach o ncosed = boing vanemtted via tho Orfcos lation fing Uno cet that bis paper (along wt any a symtem n aceocdarca win’? GPR 8 Sta). Sanat: Kent A Davi (Jenner A Davis) AMENDMENT IN RESPONSE TO NON-FINAL OFFICE ACTION UNDER 37. CER. § 1.111 Mail Stop Amendment Commissioner for Patents P.O. Box 1450 Alexandria, VA 22313-1450 Dear Sir INTRODUCTORY COMMENTS In response to the Office Action dated September 30, 2016, please amend the above- as follows: identified U.S. patent applic: Amendments to the Claims are reflected in the listing of claims which begins on page 2 of this paper. Remarks/Arguments begin on page 4 of this paperApplication No.: 14/232,350 Amendment dated March 30, 2017 Reply to Office Action of September 30, 2016 Docket No.: NOS21,70023US00 AM! DME 'S TO THE CLAIMS The following listing of claims replaces all prior versions and listings of claims in the application: 1-13. (Cancelled). 14, (Currently amended) A method for i#ibitag reducing cancer cell growth or metastasis, the method comprising: administering an effective amount of a zinc finger-like peptide to a subject in-need-thereet having a cancer via intravenous injection, wherein: the zinc finger-like peptide comprises the amino acid sequence of SEQ ID NO: 1, and cancer, 15-18. (Cancelled), 19. (Previous Presented) The method of claim 14, wherein the zine finger-like peptide comprises the amino acid sequence of SEQ ID NO: 2. 20. (Cancelled), 21. (Currently amended) The method of claim [[20]] 14, wherein the cancer is breast 22. (Currently amended) The method of claim [[20]] 14, wherein the cancer is prostate cancer. 23. (Currently amended) The method of claim {[20]] 14, wherein the cancer is brain cancer.Application No.: 14/232,350 3) Docket No.: NOS21,70023US00 Amendment dated March 30, 2017 Reply to Office Action of September 30, 2016 24, (Previously Presented) The method of claim 14, wherein the zinc finger-like peptide is set forth as SEQ ID NO:1 or SEQ ID NO:2.