CTNF 18/564,987 CTNF 97545 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. DETAILED ACTION Acknowledgement is hereby made of receipt and entry of the communication filed on July 08, 2024. Claims 1-32 are pending and are currently examined. Claim Rejections - 35 USC § 112 07-30-02 AIA The following is a quotation of 35 U.S.C. 112(b): (b) CONCLUSION. —The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. 07-34-01 Claims 1-21 and 23-32 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. These claims recite a phrase “a substituted N-(3-((2-((3-(aminomethyl) phenyl) amino)-5-methylpyrimidin-4-yl) amino propyl) acetamide analogue”, where the terms “substituted” and “analogue” in the phrase render the claims indefinite. It is unclear how many substitutions can be made to still be considered an analogue as claimed. In addition, claim 21 provides a substituted analogue with a formula, however. It also recites that “substituted forms of any of the foregoing”. This phrase renders the claim indefinite. It is not clear what exact a formula claimed in the instant claim 21. Claims 5 and 7-15 recite the term “about” that renders the claims indefinite. It is not clear what the boundary of “about” is. For example, it is not clear what is the exact percentage ranges for the claimed transduced cells or what is “about” boundaries of the MOI ranges. Accordingly, one of ordinary skill in the art will not know the metes and bounds of the claims. Claim Rejections - 35 USC § 112 (Scope of Enablement) 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. Claims 1-28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while being enabling to use LV encoding HER2-CAR.CD3~.2A. iMC to transduce NK cells by adding the Inhibitors BX795, MRT67307, and Amlexanox, does not reasonably provide enablement for a method for transducing cells comprising contacting any cells with any compositions such as any viral particles and any TBK1/IKK£ inhibitor with any substituted N-(3-((2-((3-(aminomethyl) phenyl) amino)-5-methylpyrimidin-4-yl) amino propyl) acetamide analogue. The base claim 1 is directed to a method for transducing cells comprising contacting cells with a transduction composition and a TBK1/IKK£ inhibitor; and wherein the TBK1/IKK£ inhibitor comprises a substituted N-(3-((2-((3-(aminomethyl) phenyl) amino)-5-methylpyrimidin-4-yl) amino propyl) acetamide analogue. Here the claim is directed to generic cells that used for transduction, a generic transduction composition and a generic substituted N-(3-((2-((3-(aminomethyl) phenyl) amino)-5-methylpyrimidin-4-yl) amino propyl) acetamide analogue. The instant specification discloses a method and compositions for transduction of NK cells (See title and summary), and states that the invention, in one aspect, relates to methods and compounds useful for generation of genetically modified NK cells using VSV-G LVs. In various aspects, the disclosed methods comprise inhibition of the IKK-related protein kinases, TBK1/IKK£, which are signaling molecules of the endosomal TLR4 pathway, which is activated by VSV-G. The disclosed methods enable the reliable transduction of NK cells by VSV-G L Vs (See Title; [0006]). In the instant examples, the specification discloses a transducing cell method on a specific lentiviral vector construction (see [0191]), on how to modify the NK cell (See [0192]- [0193]) and discloses the specific inhibitors they used (See [0193]) for the transduction. However, the specification does not provide evidence to support a method for transducing any cells using any compositions and any substituted N-(3-((2-((3-(aminomethyl) phenyl) amino)-5-methylpyrimidin-4-yl) amino) propyl) acetamide analogue, thus it does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wriqht, 999 F.2d 1557, 1561 (Fed. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated: The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).1 The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:1) the nature of the invention, 2) the state of the prior art, 3) the breadth of the claims, 4) the amount of guidance in the specification, 5) the presence or absence of working examples, 6) the relative skill of those in the art, 7) the predictability or unpredictability of the art, and 8) and the quantity of experimentation necessary. Id. While it is not essential that every factor be examined in detail, those factors deemed most relevant should be considered. M.P.E.P. §2164.03 [R-2] states: [I]n applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soil, 97 F.2d 623,624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833,839, 166 USPQ 18, 24 (CCPA 1970). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488,496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993). Therefore, the specification does not provide sufficient guidance to allow one skilled in the art to practice the claimed invention on the full scope with a reasonable expectation of success and without undue experimentation. In the absence of such guidance and evidence of working examples, the specification fails to provide an enabling disclosure commensurate in scope with the claims. 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. 07-21-aia AIA Claim s 1-27 and 29-32 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (J Transl Med. 2020 Sep 23;18(1):363, submitted in IDS filed on 11/28/2023, hereinafter “Li”) as evidenced by InvivoGen (https://www.invivogen.com/sites/default/files/products/files/bx795_tds.pdf) in view of Deretic et al. (US11878018 B1, patented on Jan. 23, 2024, filed on Dec. 19, 2019) as evidenced by Sigma (https://www.sigmaaldrich.com/US/en/product/mm/506306?utm_source=bing&utm_medium=cpc&utm_campaign=all+product_dsa_NA_%28bing+ebizpfs%29&utm_id=420627782&utm_content=1170981841679455&msclkid=98bf0d30bdce1886201164f35ff0222f&utm_term=%2Fproduct%2F) and Ogawa et al. (WO2021141020A1, published on July 15, 2021, priority date is Jan. 06, 2020) The base claim 1 is directed to a method for transducing cells comprising: contacting cells with a transduction composition and a TBK1/IKK£ inhibitor; and wherein the TBK1/IKK£ inhibitor comprises a substituted N-(3-((2-((3-(aminomethyl) phenyl) amino)-5-methylpyrimidin-4-yl) amino propyl) acetamide analogue; thereby transducing the cells. Li teacehs a method to improve lentiviral transduction efficiency and discloses that BX795, a pharmacological inhibitor of the TBK1/IKKɛ complex, is effective, and might be a safe approach to promote RB-340-1F lentiviral transduction of human primary T cells, where RB-340-1 is a new CAR T cell that combines two strategies in one product through a CRISPR interference (CRISPRi) circuit. Because multiple regulatory components are included in the circuit, RB-340-1 production needs delivery of two lentiviral vectors into human primary T cells, both containing long DNA sequences. (See Abstract). Accordingly, Li teaches a cell transduction comprising a composition comprising lentiviral vector and an TBK1/IKKɛ inhibitor, where the lentiviral vector also teaches claims 2-3 as well. Although Li does not explicitly point out the substituted N-(3-((2-((3-(aminomethyl) phenyl) amino)-5-methylpyrimidin-4-yl) amino propyl) acetamide analogue, The BX795 inhibitor can be a substituted analogue of the claimed chemical formula as evidenced by InvivoGen. InvivoGen teaches that BX795 is a potent inhibitor of the IkB kinases TANK-binding kinase 1 (TBK1) and IkappaB kinase-epsilon (IKKε) (See page 1, left column). The chemical properties disclosed by InvivoGen can be a substituted analogue of the required TBK1/IKK£ inhibitor (See page 1 and below ). PNG media_image1.png 230 388 media_image1.png Greyscale Nevertheless , several other studies and invention also teach the claimed substituted N-(3-((2-((3-(aminomethyl) phenyl) amino)-5-methylpyrimidin-4-yl) amino) propyl) acetamide analogue as follows: Deretic teaches a method of therapeutically treating cancer in a patient in need, the method comprising administering to said patient an effective amount of a TBK-1 inhibitor and an inhibitor of Syntaxin 17 phosphorylation to said patient, wherein said TBK-1 inhibitor is BX795, MRT67307, Bl-B206, Dl-Dl00, Fl-F-160, amlexanox or a mixture thereof and said inhibitor of Syntaxin 17 phosphorylation is Tyrphostin AG1478 and/or Tyrphostin AG1024 (See column 59, lines 1-9), where the MRT67307 can be an substituted N-(3-((2-((3-(aminomethyl) phenyl) amino)-5-methylpyrimidin-4-yl) amino) propyl) acetamide analogue as claimed. This can be evidenced by Sigma. Sigma teaches that MRT67307 is a IKKε/TBK1 Inhibitor II, N-(3-(5-Cyclopropyl-2-(3-(morpholinomethyl) phenylamino) pyrimidin-4-ylamino) propyl) cyclobutanecarboxamide (See page 1) and the GAS number 1190378-57-4 and having a structure below . PNG media_image2.png 618 819 media_image2.png Greyscale Ogawa teaches a method comprising treating cells with at least two TBK1 / IKKe inhibitors, BX795 and / or MRT67307 (See Claims, page 1), where the MRT-67307 is N- [3-[[5-cyclopropyl-2- [[3- (4-morpholinylmethyl) phenyl]amino] -4-pyrimidi-nyl] amino] propyl]-cyclobutanecarboxamide, CAS 1190378- 57-4 (See page 3, paragraph 1). Based on the chemical structure described above, Ogawa also teaches the substituted N-(3-((2-((3-(aminomethyl) phenyl) amino)-5-methylpyrimidin-4-yl) amino) propyl) acetamide analogue. Ogawa fruther teaches that an agent for improving the efficiency of nucleic acid introduction into cells comprises Amlexanox and is used in combination with BX795 and / or MRT67307 (See page 2). It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to introduce the TBK1/IKKɛ inhibitor of Deretic and Ogawa, MRT67307, into Li’s study to arrive at an invention as claimed. One of skill in the art would have been motivated to do based on the benefit to use the BX795 and MRT67307 as described above. There would be a reasonable expectation of success to develop such a method for transducing cells as claimed. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention. Regarding claims 4-5, they require a transgene with specific range of base pairs. Li teaches that a transgene expression was assessed by flow cytometry on day 6 (See Fig. 2 and below ) (teach claim 4 ). The first lentiviral vector taught by Li has a GFP insertion gene (See page 4, Fig. 1 and below ), where it is a common knowledge in the art that the sequence size of GFP about 730 base pair (teach claim 5 ). PNG media_image3.png 452 745 media_image3.png Greyscale PNG media_image4.png 648 758 media_image4.png Greyscale Regarding claims 6, Li teaches the VSV-G pseudotyped LV particle by stating “Low-density lipoprotein- receptor (LDLR), the major entry port of VSV-G pseudo-typed lentiviral vectors in human cells” (See bridging pages 4-5; Fig. 1, page 4 and above ). Regarding claims 7-11, they require a specific percentage for the transduced cells. Li teaches that with BX795 treatment, LdCK-GFP transduction rate was increased to 24.0%–31.2%, CAR-TEV-mCherry was increased to 28.9%–43.7% (See page 5, right column, paragraph 2). Li discloses that lentiviral transduction of human primary T cells with BX795 treatment is viral dose dependent and Fig. 6 teacehs that when BX795 was incorporated, MSLN CAR-TEV transduction rate increased significantly and showed a viral dose dependent pattern (See page 9, Fig. 6 and below ). Although they are not identical to the claimed numbers, Li teaches the percentage ranges of the transduced cells as claimed in claims 7-11 at about 10% to about 100% ( claim 7 ), about 30% to about 100% ( claim 8 ), about 30% ( claim 9 ), about 40% ( claim 10 ), about 50% ( claim 11 ). PNG media_image5.png 549 735 media_image5.png Greyscale Regarding claims 12-15, they require a specific MOI at about 1 to about 100 ( claim 12 ), about 1 to about 10 ( claim 13 ), about 2 to about 7 ( claim 14 ) and about 1 to about 5 ( claim 15 ). Li teacehs to assess the relationship between virus dose and infection efficiency when BX795 is used, lentiviral vectors were added to human primary T cells with different MOIs. In an experiment, the first virus LdCK MOI is fixed at 10, only the second virus CAR-TEV is tested with different MOIs. For RB-340-1F, they tested CAR-TEV MOI 5, 10, and 20, combined with BX795 treatment and the data is shown at Fig. 6 (See page 8, right column, paragraph 2; Fig. 6, page 9 and above ) that shows the tested MOI is from 1.25 to 80, which teaches the ranges of MOI as claimed. Regarding claims 16-17, they require that the transduction composition is a ribonucleoprotein (RNP) complex ( claim 16 ) and RNP is a CRISPR ribonucleoprotein (RNP) complex ( claim 17 ), respectively. Although Li does not explicitly point the term CRISPR ribonucleoprotein (RNP) complex, it teaches that RB-340-1 is a new CAR T cell that combines two strategies in one product through a CRISPR interference (CRISPRi) circuit (See Abstract) and the CRISPRi is a non-editing gene expression regulation strategy based on the nuclease de-activated CRISPR associated (dCas9) protein. Coupling of dCas9 to a transcriptional repressor domain could silence expression of multiple endogenous genes. RB-340-1 is engineered to express an anti-HER2 CAR single chain variable fragment (scFv) (4D5 clone) [16], with CD28 and CD3ζ co-stimulatory domains linked to a tobacco etch virus (TEV) protease and a PD-1 promoter region targeting short guide RNA (PD1sg). The other complex of RB-340-1 includes linker for activation of T cells (LAT) complexed to dCas9-Kruppel-associated box (Krab) via a TEV-cleavable linker (See page 2, left column, paragraph 2). Here these descriptions indicate a CRISPR ribonucleoprotein (RNP) complex including dCAS9 and the short guide RNA. Regarding claims 18 and 19, they require that the transduction composition is a protein ( claim 18 ) and the protein can be an antibody ( claim 19 ). Li teaches that CAR-TEV encodes an anti-HER2 (4D5) CAR single chain variable fragment (scFv), with CD28 and CD3ζ co-stimulatory domains linked to a tobacco etch virus (TEV) protease and a short guide RNA (PD1sg) targeting the transcription start site (TSS) of the PD-1 gene (See page 4, left column; Fig. 1a above ), where scFv is a protein and antibody. Regarding claim 20, it requires that the transduction composition is selected from a plasmid, DNA fragment, oligonucleotide, RNA, and combinations. Li teaches that 70%–80% confluent 293T cells were transfected with 108 μl TransIT-LT1 (Mirus) mixed with 32 μg lentiviral vector plasmid, 16 μg psPAX2, and 8 μg pMD2.G packaging plasmid (See page 2, right column, paragraph 3), which teacehs a plasmid. Regarding claims 21-22, they require a substituted N-(3-((2-((3-(aminomethyl) phenyl) amino)-5-methylpyrimidin-4-yl) amino) propyl) acetamide analogue with a specific formula as claimed. Based on the description above, Li teaches a IKKε/TBK1 inhibitor, BOX795. Both Deretic and Ogawa teach the MRT67307 being one of the inhibitors of IKKε/TBK1 and the structure of MRT67307 teaches claims 21-22. PNG media_image6.png 204 800 media_image6.png Greyscale Regarding claims 23-24, Li describes that the lentiviral delivery of combinatorial CAR/CRISPRi circuit into human primary T cells is enhanced by TBK1/IKKɛ complex inhibitor BX795. The mothed taught by Li including incorporating BX795 treatment into the human primary T cell transduction procedure including using BX795, Lentiviral transduction, T cell engineering, CAR-T and CRISPRi (See Abstract). Accordingly, Li’s teaching does not indicate that the method utilizes a toll-like receptor inhibitor and a cationic additive. Thus, Li teaches claims 23-24. Regarding claims 25-27, they require the cell are NK cells ( claim 25 ), innate cells ( claim 26 ) and γδ T cells (claim 27 ). Li teaches BX795 is a pharmacological inhibitor of the TBK1/IKKɛ complex, which has been reported to augment lentiviral transduction of human NK cells and some cell lines, but it has not been tested with human primary T cells. The purpose of this study was to test if BX795 treatment promotes large payload RB-340-1 lentiviral transduction of human primary T cells (See Abstract), where it is a common knowledge in the art that the NK cell is an innate cell (teacehs claims 25-26 ) and human primary T cells contain γδ T cells (teaches claim 27 ). Based on the teaching, although Li does not explicitly point out using the NK cells and γδ T cells to perform the transduction, it would have been obvious for one of ordinary skill in the art at the time the invention to be motivated to apply the method to the NK cells, innate cells or γδ T cells through routine experimentation optimization, in order to examine the efficacy of the method toward various types of cells, and the result would be predictable based on the method taught by Li. Regarding claims 29-32, they claim a kit comprising a TBK1/IKK£ inhibitor; and instructions for transducing NK cells ( claim 29 ), lentiviral vector ( claim 30 ), NK cells ( claim 31 ) and the instructions ( claim 32 ), where the TBK1/IKK£ inhibitor comprises a substituted N-(3-((2-((3-(aminomethyl) phenyl) amino)-5-methylpyrimidin-4-yl) amino) propyl) acetamide analogue. Based on the description above, Li teaches NK cells and lentiviral vector, and Deretic and Ogawa teacehs the substituted N-(3-((2-((3-(aminomethyl) phenyl) amino)-5-methylpyrimidin-4-yl) amino) propyl) acetamide analogue, MRT67307. Li teacehs an method where they construct a set of RB-340-1 constructs containing fluorescent labels named RB-340-1F, and they incorporated BX795 treatment into the human primary T cell transduction procedure that was optimized for RB-340-1F and then tested BX795 with T cells collected from multiple donors, and detected the effect of BX795 on T cell transduction, phenotype, cell growth and cell function (See Abstract). Li also teacehs that a study in human natural killer (NK) cells found that BX795 boosted on average 3.8-fold the efficiency of lentiviral genetic modification (See page 2, right column, paragraph 1), which is obvious can provide motivation to one of ordinary skill in the art at the time the invention to be motivated to apply the method to the NK cells to test the use of TBK1/IKK£ inhibitor to enhance lentiviral transduction efficiency, and the result would be predictable based on the method taught by Li, Deretic and Ogawa. Although Li does not specifically point out a term “kit”, however, the concept of packaging components into a kit is well known and routine in the art. For example, Li, Deretic and Ogawa discloses a detailed protocol for how to grow cells and construct the lentiviral vector, how to isolate the human primary T cell and how to use the TBK1/IKK£ inhibitors. It would have been obvious to one of ordinary skill in the art at the time the invention was made to package components into a kit. One would be motivated to do this for commercial exploitation of the invention by providing convenience for the end user. Thus, the claimed invention is obvious over Li’s research. Also, according to MPEP § 2112.01(III), “Where the only difference between a prior art product and a claimed product is printed matter that is not functionally related to the product, the content of the printed matter will not distinguish the claimed product from the prior art. In re Ngai, ** > 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004) < (Claim at issue was a kit requiring instructions and a buffer agent. The Federal Circuit held that the claim was anticipated by a prior art reference that taught a kit that included instructions and a buffer agent, even though the content of the instructions differed.). See also In re Gulack, 703 F.2d 1381, 1385-86, 217 USPQ 401, 404 (Fed. Cir. 1983)( "Where the printed matter is not functionally related to the substrate, the printed matter will not distinguish the invention from the prior art in terms of patentability….[T]he critical question is whether there exists any new and unobvious functional relationship between the printed matter and the substrate." ).” 07-22-aia AIA Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Li et al. as evidenced by InvivoGen, and in view of Deretic et al. as evidenced by Sigma, and Ogawa et al . as applied to claim s 1-27 and 29-32 above and further in view of Grund et al. (J Immunol Methods. 2005 Jan;296(1-2):31-6) . Claim 28 requires the transducing comprises electroporation. Based on the description above, Li teaches a method for transducing cells, however, it is silent on the electroporation. Grund teaches a cost efficient and effective gene transfer into the human natural killer cell line, NK92, and discloses that using a combination of electroporation and a defined buffer, they were able to obtain an electroporation efficiency of 40% in NK92 cell (See abstract). Grund teaches electroporation method and buffer use common electroporation equipment and reagents and therefore can be easily adapted by most labs, and they used this method, co-electroporation of YFP and dominant negative constructs, and cell sorting of YFP expressing cells to achieve the highest possible electroporation efficiencies (See page 35, left column). It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to introduce the electroporation into the teachings of Li, Deretic and Ogawa to arrive at an invention as claimed. One of skill in the art would have been motivated to do so because the electroporation provides a cost efficient and effective gene transfer method for NK cells. There would be a reasonable expectation of success to develop such a method for transducing cells as claimed. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUIXUE WANG whose telephone number is (571)272-7960. The examiner can normally be reached Monday-Friday 8:00 am to 4:30 pm, EST. 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, Thomas J. Visone can be reached on (571) 270-0684. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /RUIXUE WANG/ Examiner, Art Unit 1672 Application/Control Number: 18/564,987 Page 2 Art Unit: 1672 Application/Control Number: 18/564,987 Page 3 Art Unit: 1672 Application/Control Number: 18/564,987 Page 4 Art Unit: 1672 Application/Control Number: 18/564,987 Page 5 Art Unit: 1672 Application/Control Number: 18/564,987 Page 6 Art Unit: 1672 Application/Control Number: 18/564,987 Page 7 Art Unit: 1672 Application/Control Number: 18/564,987 Page 8 Art Unit: 1672 Application/Control Number: 18/564,987 Page 9 Art Unit: 1672 Application/Control Number: 18/564,987 Page 10 Art Unit: 1672 Application/Control Number: 18/564,987 Page 11 Art Unit: 1672 Application/Control Number: 18/564,987 Page 12 Art Unit: 1672 Application/Control Number: 18/564,987 Page 13 Art Unit: 1672 Application/Control Number: 18/564,987 Page 14 Art Unit: 1672 Application/Control Number: 18/564,987 Page 15 Art Unit: 1672 Application/Control Number: 18/564,987 Page 16 Art Unit: 1672