CTFR 17/759,729 CTFR 88185 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Applicant’s reply and amendment filed 3/26/2026, are acknowledged. Claims 1, 2, 5-14, 26, 27, 40, 51 and 54-64 are pending. Claims 58-64 are new. Response to Arguments Applicant’s arguments have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. Claim Rejections - 35 USC § 112 07-30-01 AIA The following is a quotation of the first paragraph of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention. Claim 56 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Specifically, the specification fails to describe "wherein at least about 35% of the population remains viable after the electroporation." That is, at least about 35% would include 100% of the population remaining viable, which is described in the specification. Claim Rejections - 35 USC § 102 07-07-aia AIA 07-07 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – 07-08-aia AIA (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. 07-15-aia AIA Claim(s) 10, 59, 61-62 and 64 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Bulte et al. (WO2008/144028 A1) . Regarding claim 10, Bulte et al. teaches “in vivo imaging of cells using one or more imaging modalities.” Abstract. In general, the invention “provides methods of ex-vivo labeling of a cell for in vivo imaging by contacting a cell ex vivo with a labeling agent such that cell becomes labeled, thereby labeling a cell for in vivo imaging. In one embodiment, the cell is transplanted into a subject.” Page 2, lines 6-9. Further, Bulte et al. teaches that “the cell is electroporated in the presence of a labeling agent.” Page 2, lines 28-29. Also, the cell may be a stem cell or β islet cells. See page 4, lines 19 and 27. Regarding claim 59, Bulte et al. teaches a raman detectable agent. Page 6, line 5. Regarding claim 61, Bulte et al. teaches “injection into a structure, organ, or body cavity in situ.” Page 24, Regarding claim 62, Bulte et al. teaches that the term “cell” is understood to mean embryonic cells including but not limited to stem cells. See page 10, lines 22-23. Regarding claim 64, Bulte et al. teaches treating Type II diabetes. See page 24, lines 29-30 . Claim Rejections - 35 USC § 103 07-20-aia AIA The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. 07-23-aia AIA The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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. 07-20-02-aia AIA This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention. 07-21-aia AIA Claim (s) 1, 2, 5-14, 26, 27, 40, 51 and 57-62 is/are rejected under 35 U.S.C. 103 as being unpatentable over Vo-Dinh et al. (US 2016/0076086) in view of Bulte et al. (WO2008/144028 A1) . Regarding claim 10, Vo-Dinh et al. teaches “nanoprobes can be used in vivo for treatment of undesirable cells in a subject.” Abstract. To this end, Vo-Dinh et al. teaches “contacting an undesirable cell with a nanoprobe.” Para. [0150]. Vo-Dinh et al. describes a nanoprobe that reads on (i)-(iii) of claim 1: the nanoprobe comprises: at least one metal nanoparticle; an oligonucleotide attached at one end to the nanoparticle, the oligonucleotide including a stem-Land a stem-R sequence capable of hybridizing to form a hairpin structure and a placeholder binding sequence in between the stem-L and stem-R sequences; a placeholder nucleic acid complementary to the placeholder binding sequence and complementary to the target, wherein the placeholder nucleic acid is hybridized to the placeholder sequence in the absence of the target such that formation of the hairpin structure is prevented; and an optical label attached to the oligonucleotide, irradiating the sample with electromagnetic radiation from an excitation source; and detecting the electromagnetic radiation originated by the label, wherein a level of electromagnetic radiation originated by the label in the presence of the target is changed due to movement of the label into the vicinity of the nanoparticle electromagnetic enhancement upon formation of the hairpin structure. Para. [0020]. In addition to being used for treatment of undesirable cells, the nanoprobes “are useful for a wide variety of applications based on DNA/RNA/protein detection including, but not limited to: biomedical applications, point-of-care diagnostics, food safety, environmental monitoring, industrial process sensing, quality control applications, biotechnology industrial control, quality control, global health, cancer research, heart disease diagnostics, homeland defense.” Para. [0140]. Vo-Dinh et al. does not teach a stem-cell derived cell or electroporation. Bulte et al. teaches “in vivo imaging of cells using one or more imaging modalities.” Abstract. In general, the invention “provides methods of ex-vivo labeling of a cell for in vivo imaging by contacting a cell ex vivo with a labeling agent such that cell becomes labeled, thereby labeling a cell for in vivo imaging. In one embodiment, the cell is transplanted into a subject.” Page 2, lines 6-9. Further, Bulte et al. teaches that “the cell is electroporated in the presence of a labeling agent.” Page 2, lines 28-29. Also, the cell may be a stem cell or β islet cells (current claim 40). See page 4, lines 19 and 27. It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the invention in view of the combined teachings of Vo-Dinh et al. and Bulte et al. to arrive at the claimed invention. In this instance, the rational to support a conclusion that the claim would have been obvious would be applying a known technique to a known device ready for improvement to yield predictable results. Here, Bulte et al. teaches the base components of a method of in vivo imaging of cells, including stem cells-derived cells, using or more imaging modalities. Vo-Dinh et al. teaches a known technique using nanoprobes that are useful for a wide variety of applications based on DNA/RNA/protein detection. A skilled artisan would have recognized that applying the nanoprobes of Vo-Dinh et al. to the base method of Bulte et al.’s in vivo imaging of cells including stem cell-derived cells would have yielded predictable results and resulted in an improved system. Regarding claim 2, Vo-Dinh et al. teaches that the nanoprobes may be used “to detect nucleic acid biomarkers for medical applications.” Para. [0168]. Regarding claim 5, Vo-Dinh et al. illustrates an example of the invention for detecting nucleic acid targets using a target DNA. See para. [0164]. Regarding claim 6, Vo-Dinh et al. discloses the use of bioreceptors. See paras. [0026] and [0027]. Regarding claim 7, Vo-Dinh et al. discloses the use of ligands. See paras. [0028] and [0029]. Regarding claim 8, Vo-Dinh et al. teaches a Raman label at one end of a nanoprobe probe (current claims 27 and 60). See para. [0041]. Regarding claim 9, Vo-Dinh et al. teaches subcutaneous injection (current claim 61). See para. [0136]. Regarding claim 10, anticipation being the epitome of obviousness, the claim is anticipated by Bulte et al. as discussed in §102 rejection above. Regarding claims 11-14, Vo-Dinh et al. teaches the use of fiberoptics excitation and detection which can be remotely operated by an iPhone. See para. [0139]. Regarding claim 26, Vo-Dinh et al. discloses silver-coated gold nanostars (current claims 51 and 58). See para. [0149]. Regarding claims 57 and 60, Vo-Dinh et al. teaches DTDC. See para. [0151]. Regarding claim 62, Bulte et al. teaches that the term “cell” is understood to mean embryonic cells including but not limited to stem cells. See page 10, lines 22-23 . 07-22-aia AIA Claim (s) 54-56 is/are rejected under 35 U.S.C. 103 as being unpatentable over Vo-Dinh et al. (US 2016/0076086) in view of Bulte et al. (WO2008/144028 A1) as applied to claim s 1, 2, 5-14, 26, 27, 40, 51 and 57-62 above, and further in view of Zhao et al., Mol. Ther. 2006 January; 13(1):151-159 . Teachings of Vo-Dinh et al. and Bulte et al. are discussed above. Regarding claim 54, neither reference teaches “wherein the electroporation comprises a voltage of 200V-500V.” Regarding claim 55, neither reference teaches “wherein the electroporation comprises a pulse length of 0.5-10 milliseconds (ms).” Zhao et al. teaches a voltage of 300V and 10 ms. See page 2. It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to further combine Zhao et al. with Vo-Dinh et al. and Bulte et al. and arrive at the claimed invention. In this instance a skilled artisan looking to practice the suggestion of Bulte et al. would turn to Zhao et al. for more specific teaching in the transfection protocol. Regarding claim 56, wherein clauses are not considered limitations because they merely express the intended results of a process step positively recited. MPEP 2111.04 ("Claim scope is not limited by claim language that does not limit a claim to a particular structure.") . 07-22-aia AIA Claim (s) 63 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bulte et al. (WO2008/144028 A1) as applied to claim s 10, 59, 61-62 and 64 above, and further in view of Calafiore et al., Am J Stem Cells 2015;4(1):22-31 . Teachings of Bulte et al. are discussed above. Regarding claim 63, Bulte et al. does not teach “wherein the subject has Type I diabetes.” Calafiore et al. teaches stem cells for the cell and molecular therapy of type 1 diabetes. See Title. According to Calafiore et al., fully novel attempts to replace the destroyed cell mass in T1D could be . . . substitution of cells by endogenous or exogenously grafted stem cells.” It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to arrive at the claimed invention in view of Bulte et al. and Calafiore et al. combined. Here, the rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the arrive at the claimed invention. Here, Bulte et al. teaches Type 2 diabetes but not Type 1. Meanwhile, both types are taught by Calafiore et al. An ordinarily skill artisan could have combined the elements as claimed, i.e., treating Type 1 with the method of Bulte et al., and in that combination each element merely performs the same function as it does separately which would yield predictable results. Conclusion 07-40 AIA Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL . See MPEP § 706.07(a). 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 nonprovisional extension fee (37 CFR 1.17(a)) 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. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT S CABRAL whose telephone number is (571)270-3769. The examiner can normally be reached M-F 8 am - 5 pm. 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.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at 571-272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /ROBERT S CABRAL/ Primary Examiner, Art Unit 1614 Application/Control Number: 17/759,729 Page 2 Art Unit: 1614 Application/Control Number: 17/759,729 Page 3 Art Unit: 1614 Application/Control Number: 17/759,729 Page 4 Art Unit: 1614 Application/Control Number: 17/759,729 Page 5 Art Unit: 1614 Application/Control Number: 17/759,729 Page 6 Art Unit: 1614 Application/Control Number: 17/759,729 Page 7 Art Unit: 1614 Application/Control Number: 17/759,729 Page 8 Art Unit: 1614 Application/Control Number: 17/759,729 Page 9 Art Unit: 1614
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