LIPIDOID NANOPARTICLES FOR THE TREATMENT OF DISEASES AND DISORDERS

DETAILED ACTION Notice of Pre-AIA or AIA Status The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Continued Examination Under 37 CFR 1.114 A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on September 8, 2026 has been entered. Summary Claims 1, 3-5, 24, 41, 98-99, 120-122, 136, 154, and 156-160 are pending in this office action. Claims 2, 6-23, 25-40, 42-97, 100-119, 123-135, 137-153, and 155 are cancelled. All pending claims are under examination in this application. Priority The current application was filed on October 26, 2023. The current application is a 371 of PCT/US2022/027256 filed on May 2, 2022, which in turn claims domestic priority to provisional patent application 63/182,245 filed on April 30, 2021. Information Disclosure Statement Receipt of the Information Disclosure Statement dated September 8, 2026 is acknowledged. A signed copy of the document is attached to this office action. Claim Objections Claims 6-23, 25-40, 42-97, and 137-153 are objected to because of the following informalities: Within the most recent claim set submitted on August 4, 2026 please amend the cancelled claims to read: Claims 6-23. (Cancelled) Claims 25-40. (Cancelled) Claims 42-97. (Cancelled) Claims 137-153. (Cancelled) Appropriate correction is required. Claim Rejections - 35 USC § 103 In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status. 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. 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 non-obviousness. 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. Claims 1, 3-5, 24, 41, 98-99, 120-122, 136, 154, and 156-160 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (Molecular Therapy: Nucleic Acids, published in March 2020) in view of Ciaramella et al. (US2020/0069794A1, published in March 2020), Nguyen et al. (PNAS, 2011), Xu et al. (WO2019/152848A1), and Zeng et al. (Advanced Materials, published in September 2020). [The Examiner is going to introduce each new reference and then combine them where appropriate to reject the instant claims.] 1. Yang et al. Yang et al. is considered the closest prior art as it teaches efficient delivery of antisense oligonucleotides using bioreducible lipid nanoparticles in vitro and in vivo (see title). In addition, Yang et al. disclose that the efficient delivery of antisense oligonucleotides (ASOs) to the targeted cells and organs remains a challenge, in particular, in vivo. Here, we investigated the ability of a library of biodegradable lipid nanoparticles (LNPs) in delivering ASO to both cultured human cells and animal models. We first identified three top-performing lipids through in vitro screening using GFP-expressing HEK293 cells. Next, we explored these three candidates for delivering ASO to target proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA in mice. We found that lipid 306-O12B-3 showed efficiency with the median effective dose (ED50) as low as 0.034 mg•kg-1, which is a notable improvement over the efficiency reported in the literature. No liver or kidney toxicity was observed with a dose up to 5 mg•kg-1 of this ASO/LNP formulation. The biodegradable LNPs are efficient and safe in the delivery of ASO and pave the way for clinical translation (see abstract). 2. Ciaramella et al. Ciaramella et al. teach respiratory virus nucleic acid vaccines (see title). Additionally, Ciaramella et al. disclose that provided herein, in some embodiments, are vaccines (and vaccination methods) that include a ribonucleic acid (RNA), polynucleotide encoding a human metapneumovims (hMPV) F protein, and a RNA polynucleotide encoding a human parainfluenza virus 3 (hPrV3) F protein (see abstract). 3. Nguyen et al. Nguyen et al. teach lipid-derived nanoparticles for immunostimulatory RNA adjuvant delivery (see title). Also, Nguyen et al. disclose that the specific activation of Toll-like receptors (TLRs) has potential utility for a variety of therapeutic indications including antiviral immunotherapy and as vaccine adjuvants. TLR7 and TLR 8 may be activated by their native ligands, single-stranded RNA, or by small molecules of the imidazoquinoline family. However, the use of TLR7/8 agonists for in vivo therapy is limited by instability, in the case of RNA, or systemic biodistribution and toxicity in the case of small molecule agonists. We hypothesized that unique lipid-like materials, termed "lipidoids," could be designed to efficiently deliver immunostimulatory RNA (isRNA) to TLR-expressing cells to drive innate and adaptive immune responses. A library of lipidoids was synthesized and screened for the ability to induce type I IFN activation in human peripheral blood mononuclear cells when combined with isRNA oligonucleotides. Effective lipidoid-isRNA nanoparticles, when tested in mice, stimulated strong IFN-a responses following subcutaneous injection, had robust antiviral activity that suppressed influenza virus replication, and enhanced antiovalbumin humoral and cell-mediated responses when used as a vaccine adjuvant. Further, we demonstrate that whereas all immunological activity was MyD88-dependent, certain materials were found to engage both TLR7-dependent and TLR7-independent activity in the mouse suggestive of cell-specific delivery. These lipidoid formulations, which are materials designed specifically for delivery of isRNA to Toll-like receptors, were superior to the commonly used N-(1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate--RNA delivery system and may provide new tools for the manipulation of TLR responses in vitro and in vivo (see abstract). 4. Xu et al. Xu et al. teach lipid-like nanocomplexes and uses thereof (see title). Furthermore, Xu et al. disclose that provided herein, are compounds of formula (I) below: (I), wherein each of the variable’s A, B, X, W, V, R1-R5, and m is defined herein. Also disclosed are pharmaceutical compositions containing a nanocomplex, wherein the nanocomplex is formed of one of the compounds, and a protein, a nucleic acid, or a small molecule; and methods of treating a medical condition with one of the pharmaceutical compositions (see abstract). PNG media_image1.png 200 400 media_image1.png Greyscale 5. Zeng et al. Zeng et al. teach leveraging mRNA sequences and nanoparticles to deliver SARS-CoV-2 antigens in vivo (see title). Also, Zeng et al. disclose that SARS-CoV-2 has become a pandemic worldwide; therefore, an effective vaccine is urgently needed. Recently, messenger RNAs (mRNAs) have emerged as a promising platform for vaccination. In this work, the untranslated regions (UTRs) of mRNAs are systematically engineered in order to enhance protein production. Through a comprehensive analysis of endogenous gene expression and de novo design of UTRs, the optimal combination of 5′ and 3′ UTR are identified and termed NASAR, which are 5- to 10-fold more efficient than the tested endogenous UTRs. More importantly, NASAR mRNAs delivered by lipid-derived TT3 nanoparticles trigger a dramatic expression of potential SARS-CoV-2 antigens. The antigen-specific antibodies induced by TT3-nanoparticles and NASAR mRNAs are over two orders of magnitude more than that induced by the FDA-approved lipid nanoparticle material MC3 in vaccinated mice. These NASAR mRNAs merit further development as alternative SARS-CoV-2 vaccines (see abstract). Combination of Yang et al., Ciaramella et al., and Nguyen et al. Regarding instant claim 1, Yang et al., Ciaramella et al., and Nguyen et al. teach a nanoparticle, comprising a plurality of lipidoids. The necessary citations of Yang et al., Ciaramella et al., and Nguyen et al. that pertain to instant claim 1 are presented in Table I. Table I Instant Claim 1 Yang et al., Ciaramella et al., and Nguyen et al. Citations A nanoparticle, comprising a plurality of lipidoids; and an RNA, Yang et al. disclose a nanoparticle (see abstract within Yang et al.) comprising lipidoids (see PTO-892 NPL W), and nucleic acids (antisense oligonucleotides; see abstract within Yang et al.). Antisense oligonucleotides (ASOs) are single-strand DNAs serving as effective drugs to reduce the messenger RNA level in cells (see page 1357, left column, introduction, within Yang et al.). Yang et al. does not disclose the use of a nucleic acid such as RNA and mRNA. However, Ciaramella et al. disclose using lipidoid nucleic acid or antigen nanoparticles which can comprise RNA or mRNA (see paragraphs [0004-0008], [0223], [0418], and Example 11 all within Ciaramella et al.). Furthermore, Nguyen et al. also is in the lipidoid nanoparticle arts (see title and abstract within Nguyen et al.). Nguyen et al. disclose the use of immunostimulatory RNA which is larger than the ASOs disclosed by Yang et al. (see PTO-892 NPL U). wherein each lipidoid has a structure represented by formula I: PNG media_image2.png 200 400 media_image2.png Greyscale I Yang et al. disclose: Construction of Lipid Library; The bioreducible lipids were synthesized by the Michael addition between the primary or secondary amines and acrylate containing a disulfide bond (see Figure 1BI within Yang et al.), according to our published procedure. Bioreducible lipids were named “R-O[x]B-n” using the following method: the amine head is indicated by a two- or three-digit serial number (R). The letter “O” indicates an acrylate linker between the amine head and hydrophobic tail. The number [x] indicates the number of carbon atoms in the hydrophobic tail of the acrylate. The “B” refers to a bioreducible lipid, i.e., containing a disulfide bond in the tail. The last number “n” indicates the total number of hydrophobic tails of the synthetic lipids and is usually either 3 or 4. For example, 306-O12B-3 indicates the lipid prepared by reacting amine 306 with acrylate O12B, resulting in a lipid with 3 tails. Figure 1BII within Yang et al. shows the chemical structure of the lipid, termed “306-O12B-3” (see pages 1358-1359 bridging, 1358 right column, 1359 left column, within Yang et al.; also see Figure 1 below) or a pharmaceutically acceptable salt thereof; each Y1, Y2, Y3, Y4, X1, X2, X3, and X4 is independently selected from the group consisting of O, S, and NR5; Ro is H or alkyl; R1, R2, R3, and R4 are each independently selected from the group consisting of alkyl, alkyloxyalkyl, alkylaminoalkyl, alkylthioalkyl, alkyldisulphidealkyl, alkylamidoalkyl, alkylesteralkyl, alkylcarbamatealkyl, alkylcarbonatealkyl, and alkylurealylalkyl; each R5 is independently selected from hydrogen, alkyl, or aralkyl; n1, n2, n3, and n4 are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10; and m1 and m2 are each independently 1, 2, 3, 4, or 5. Yang et al. disclose Figure 1: PNG media_image3.png 200 400 media_image3.png Greyscale The substituents disclosed within Yang et al. support the claim limitations to the left. For the smaller ASO, Yang et al. supports the use of three lipid tails (306-O12B-3; see page 1363, right column, paragraph 2 within Yang et al.). Additionally, Nguyen et al. disclose lipidoids as shown below: PNG media_image4.png 200 400 media_image4.png Greyscale (see Figure 2 within Nguyen et al.). Despite the “core” of the lipidoid shown in red not being identical to the “core” of instant claim 1, a skilled artisan (POSITA; person of ordinary skill in the art) would easily make substitution to generate the desired lipidoid. Moreover, Lipidoids I-4 and II-4 consistently outperformed DOTAP and ND(S)-98-1. In direct comparisons, the dialyzed formulations of second-gen­eration 100-core lipidoids I-4 and II-4 at a 15:1 UR ratio had the highest propensity for cytokine induction (see Fig. 3 within Nguyen et al.). Furthermore, T, B, and NK cells were all activated in response to both I-4 and II-4 lipidoid nanoparticles. Both I-4 and II-4 nanoparticles exhibited dose-dependent immunostimulation following s.c. administration. Thus, dialyzed lipidoid-RNA nanoparticles (LRNP) of lipidoids I-4 and II-4 at an UR ratio of 15:1 were used for all subsequent in vivo investigations (see page E798, right column, paragraph 3 within Nguyen et al.). Thus, Nguyen et al. supports the use of four lipids within their lipidoid formulation for the larger immunostimulatory RNA. It would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to modify Yang et al. with the teachings of Ciaramella et al. and Nguyen et al. For the smaller ASO, Yang et al. supports the use of three lipid tails (306-O12B-3; see page 1363, right column, paragraph 2 within Yang et al.). Alternatively, Nguyen et al. supports the use of four lipids within their lipidoid formulation for the larger immunostimulatory RNA (see page E798, right column, paragraph 3 within Nguyen et al.). The motivation to combine the three references would be to expand the set of nucleic acids from ASOs in Yang et al., to immunostimulatory RNA as disclosed in Nguyen et al., and finally to RNA and mRNA within Ciaramella et al. for lipidoid nanoparticles. The remaining instant claims are directly or indirectly taught by the combination of Yang et al., Ciaramella et al., and Nguyen et al. Regarding instant claims 3-5, 24, 41, 154, and 158, Yang et al., Ciaramella et al., and Nguyen et al. teach the necessary substituent instant claim limitations. Please see the discussion and citations within instant claim 1 (Table I). Regarding instant claim 120, Yang et al., Ciaramella et al., and Nguyen et al. teach a pharmaceutical composition comprising a nanoparticle of instant claim 1 and a pharmaceutically acceptable excipient. Ciaramella et al. disclose the use of a pharmaceutically acceptable excipient (see paragraph [0411] within Ciaramella et al.). Regarding instant claim 136, Yang et al., Ciaramella et al., and Nguyen et al. teach a method of treating or preventing a viral infection in a subject in need thereof comprising administering a therapeutically effective amount of the nanoparticle of instant claim 1 or a pharmaceutically acceptable salt thereof to the subject. Ciaramella et al. disclose the administration of a vaccine (prevention) for a viral infection or load using their lipidoid nucleic acid nanoparticle (see claims 15-16, 20-21, 55-57, and 61-62 within Ciaramella et al.). Regarding instant claims 157 and 160, Yang et al., Ciaramella et al., and Nguyen et al. teach wherein the RNA is an mRNA. Ciaramella et al. disclose using lipidoid nucleic acid or antigen nanoparticles comprising RNA or mRNA (see paragraphs [0004-0008], [0223], [0418], and Example 11 all within Ciaramella et al.). Regarding instant claims 156 and 159, Yang et al., Ciaramella et al., and Nguyen et al. teach wherein the nanoparticle further comprises: cholesterol; distearoylphosphatidylcholine (DSPC) or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE); and 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (DMG-PEG2000). Yang et al. disclose the use of cholesterol, DOPE, and DSPE-PEG2000 within their lipidoid nanoparticles (see page 1364, left column, paragraph 4 within Yang et al.). Ciaramella et al. disclose using DMG-PEG2000 (see paragraph [0515] within Ciaramella et al.) Therefore, a skilled artisan (POSITA) would be able to select the desired PEG-lipid supplied by Ciaramella et al. under routine experimental conditions and combine it with the cholesterol and DOPE supplied by Yang et al. Combination of Yang et al., Ciaramella et al., Nguyen et al., and Zeng et al. Motivation to combine: This analogous art (Zeng et al.) would allow both the teachings of Yang et al., Ciaramella et al., and Nguyen et al. to expand their nucleic acid lipid nanoparticle into the SARS-CoV-2 vaccine therapeutic area. Zeng et al. disclose the use of mRNA (see title and abstract within Zeng et al.) within lipid nanoparticles (nanoparticles trigger a dramatic expression of potential SARS-CoV-2 antigens; see abstract and page 2004452 (7 of 8), left column, 4th paragraph, both within Zeng et al.). Despite the fact that Zeng et al. does not specifically disclose lipidoids, the substitution of the lipidoids taught by Yang et al. and Ciaramella et al. for the lipids used by Zeng et al. would be an excellent alternative used for the nucleic acid mRNA (see PTO-892 NPL W). Regarding instant claim 98, Yang et al., Ciaramella et al., Nguyen et al., and Zeng et al. teach wherein the RNA is an mRNA; and when the mRNA contacts a cell, the mRNA induces synthesis of a spike protein of SARS-CoV-2. Zeng et al. disclose that therefore, five NASAR [optimal untranslated (UTR) regions] mRNAs were prepared to express the spike (S), nucleocapsid (N), membrane (M), envelope (E), and receptor-binding domain (RBD) structural proteins/fragment of SARS-CoV-2 as the vaccine candidates [see page 2004452 (5 of 8), left column, 1st paragraph within Zeng et al.]. Regarding instant claim 99, Yang et al., Ciaramella et al., Nguyen et al., and Zeng et al. teach wherein the RNA has at least 85%, 90%, 95%, or 99% sequence identity to any one of the sequences recited within SEQ ID NOs 3-49. Zeng et al. disclose microRNAs were previously considered to mainly target the 3′ UTR of mRNA for gene regulations. However, recent data showed that miRNAs also interfered with ribosomal scanning by binding to target sites within 5′ UTR. Therefore, we used the prediction tool available at miRDB to examine possible miRNA target sites within NCA-7 and NCA-8. The prediction revealed that both NCA-7 and NCA-8 contained miRNA target sites. Then, we shuffled the nucleotides of NCA-7 and NCA-8 and created NCA-7d and NCA-8d, which maintained their nucleotide composition and minimal secondary structures. Interestingly, NCA-7d showed a slightly increased expression than NCA-7, while NCA-8d was less active than NCA-8 (see Figure 3c within Zeng et al.). Based on these results, NCA-7d was selected as the lead 5′ UTR [see page 2004452 (3 of 8), 2nd paragraph within Zeng et al.]. Yang et al., Ciaramella et al., Nguyen et al., and Xu et al. Motivation to combine: This analogous art (Xu et al.) would allow both the teachings of Yang et al., Ciaramella et al., and Nguyen et al. to expand the therapeutic use of their nucleic acid lipid nanoparticle into the anti-cancer chemotherapeutic agents arena, and thus make it more commercially attractive. Xu et al. disclose the use of lipidoid (see page 8, lines 7-12 within Xu et al.) nucleic acid (see page 23, lines 3-7 within Xu et al.) nanoparticles (see page 29, lines 13-17 within Xu et al.). Regarding instant claims 121 and 122, Yang et al., Ciaramella et al., Nguyen et al., and Xu et al. teach a method of treating cancer in a subject in need thereof comprising administering a therapeutically effective amount of the nanoparticle of instant claim 1 or a pharmaceutically acceptable salt thereof to the subject. Xu et al. disclose the treatment of a variety of medical conditions (see claims 35-36 and 45-46 within Xu et al.) with the pharmaceutical composition (nanoparticle as disclosed by Xu et al.; see motivation to combine above). A small molecule, such as a chemotherapeutic agent (see claims 37-38 and 41-42 within Xu et al.), can be included within the pharmaceutical composition (nanoparticle). Analogous Art The Yang et al., Ciaramella et al., Nguyen et al., Xu et al., and Zeng et al. references are directed to the same field of endeavor as the instant claims, that is, a nanoparticle, comprising a plurality of lipidoids (of formula I); and an adjuvant, an antigen, or a nucleic acid. Obviousness It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the nucleic acid lipidoid nanoparticle disclosed by Yang et al., using the teachings of Ciaramella et al., Nguyen et al., Xu et al., and Zeng et al. to incorporate the necessary claim limitations. A skilled artisan (POSITA) would be motivated to combine the primary reference Yang et al. and the secondary references of Ciaramella et al. and Nguyen et al. due to the significant overlap of many of the instant claim 1 limitations (see Table I). The disclosures of Xu et al. and Zeng et al. would allow both the teachings of Yang et al., Ciaramella et al., and Nguyen et al. to expand the therapeutic use of their nucleic acid lipid nanoparticle into the anti-cancer chemotherapeutic agents and SARS-CoV-2 vaccine arena, and thus make it more commercially attractive. Xu et al. disclose the use of lipidoid (see page 8, lines 7-12 within Xu et al.) nucleic acid (see page 23, lines 3-7 within Xu et al.) nanoparticles (see page 29, lines 13-17 within Xu et al.). Zeng et al. disclose the use of mRNA (see title and abstract within Zeng et al.) within lipid nanoparticles (nanoparticles trigger a dramatic expression of potential SARS-CoV-2 antigens; see abstract and page 2004452 (7 of 8), left column, 4th paragraph, both within Zeng et al.). Despite the fact that Zeng et al. does not specifically disclose lipidoids, the substitution of the lipidoids taught by Yang et al., Ciaramella et al., and Nguyen et al. for the lipids used by Zeng et al. would be an excellent alternative used for the nucleic acid mRNA (see PTO-892 NPL W). Starting with Yang et al., the skilled person only had to try the necessary claim limitations disclosed by Ciaramella et al., Nguyen et al., Xu et al., and Zeng et al. The combination of Yang et al., Ciaramella et al., Nguyen et al., Xu et al., and Zeng et al. would allow one to arrive at the present application without employing inventive skill. This combination of the nucleic acid lipidoid nanoparticle taught by Yang et al. along with the use of the necessary claim limitations taught by Ciaramella et al., Nguyen et al., Xu et al., and Zeng et al. would allow a research and development scientist (POSITA) to develop the invention taught in the instant application. It would have only required routine experimentation to modify the nucleic acid lipidoid nanoparticle disclosed by Yang et al. with the use of the necessary claim limitations taught by Ciaramella et al., Nguyen et al., Xu et al., and Zeng et al. This combined modification would have led to an enhanced composition comprising lipidoid nanoparticles that would be beneficial for patients. In the context of method claims 121-122 and 136, the desired purpose defines an effect that arises from, and is implicit in the method step(s). Thus, where the purpose is limited to stating a technical effect that inevitably occurs during the performance of the claimed method step(s), and is therefore inherent in that/those step(s), that technical effect is not limiting to the subject-matter of the claim. Thus, the present method claim, defining the application/use of the composition according to the prior art and defining its purpose as "use", is anticipated by any document of the state of the art describing a method of application/use although not mentioning this specific use. Response to Arguments Applicant's arguments filed August 4, 2026 have been fully considered but they are not persuasive. The Applicant arguments and Examiner rebuttals are identical to those filed with the Advisory Action (PTOL-303) dated August 18, 2026. The Applicant is referred to those remarks. Therefore, the 35 U.S.C. 103 rejection is maintained for instant claims 1, 3-5, 24, 41, 98-99, 120-122, 136, 154, and 156-160. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN W LIPPERT III whose telephone number is (571)270-0862. The examiner can normally be reached Monday - Thursday 9:00 AM - 5:00 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, Robert A Wax can be reached on 571-272-0623. 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. /JOHN W LIPPERT III/Examiner, Art Unit 1615