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. Priority The present application claims priority to the application, 63/161 , 719 and PCT/US2022/0071137, with the effective filing dates of 16 Mar 2021 and 14 Mar 2022, respectively. Claim Status This Office Action is in response to Applicant’s Response to Restriction Requirement filed, 6 February 2026. Applicant's election with traverse of Group I and Compound 11: in the reply filed on 6 February 2026 is acknowledged. The traversal is on the ground(s) that because the claims of Group II recite methods of using the compounds of Group I, Applicant asserts their examination falls squarely within 37 CFR 1.475(b)(2). Applicant further asserts that amendment to claim 1 to include the limitation of claim 2 (R1 and R2 are independently X- Lm ) obviates the lack of special technical feature in Ho ( Int. J. Pharm. , 2018 , 543(1) , 52-59 , of record, PTO-892 filed 16 Dec 2025 ). However, this is not found persuasive, because Groups I and II are written independently from each other and thus Group II does not necessarily read on the same compounds as claimed in Group I. Group II consists of methods of inhibiting viral reverse transcriptase bioactivity or treating a viral infection in a patient, which would require a serious search burden due to different key terms from Group I, as evidenced by Yang ( J Virology , 2013 , 87(1) , 683-687). In addition, while Ho no longer teaches compounds that anticipate Formula I, wherein R1 and R2 are independently X- Lm is not a special technical feature as it does not make a contribution over the prior art in view of Zhang (U.S. Patent Publication No. 2020/0239513, published 30 Jul 2020 , see IDS 6 Feb 2026), Rautio ( Nat . Rev . Drug Discovery , 2008 , 7 , 255-270), Jung ( Molecules , 2018 , 23(731) , 1-12), and Mehellou ( J. Med. Chem. , 2018 , 61 , 2211-2226) as evidenced by Organic Portal 1 (“Esterifications,” Organic Portal , 2026 , < https://www.organic-chemistry.org/synthesis/C1O/esters/esterifications.shtm >, accessed 20 Mar 2026) and Organic Portal 2 (“P-O Bond Formation,” Organic Portal , 2026 , < https://www.organic-chemistry.org/synthesis/P1O/index.shtm >, accessed 20 Mar 2026). Zhang teaches prodrugs of entecavir for treating hepatitis B virus (HBV; abstract). Zhang specifically teaches substitution at R1 and R2 as compounds: and (pages 5 and 6). Further, Zhang teaches modifications to entecavir are to develop a prodrug that will be released slowly, sustainably, and steady in order to achieve a long-acting effect (abstract). Additionally, Zhang teaches that 130 million people in China are infected with chronic HBV ([0004]). Zhang fails to teach a di-substituted benzyl ester prodrug for slow release in the GI tract. Rautio teaches ester prodrugs and derivatives thereof (carbamates and carbonates; page 256, column 2, paragraph 2). Rautio further teaches that esters are the most common prodrugs used to enhance lipophilicity and thus passive membrane permeability (page 256, column 2, paragraph 3). Rautio teaches that carboxyl and phosphate esters are both straightforward to synthesize (page 256, column 2, paragraph 2; page 258, column 1, paragraph 1; page 258, column 2, paragraph 1) as evidenced by Organic Portal 1 and Organic Portal 2 (Organic Portal 1: Box 6; Organic Portal 2: Box 9). Rautio specifically teaches di-substituted ester prodrugs: dipivefrin and bambuterol (Table 5, page 263; Table 6, page 264). Rautio further teaches that the di-substituted ester prodrug, dipivefrin, penetrates the human cornea 17-times more rapidly than the parent drug (adrenaline) due to its lipophilicity (page 265, column 1, paragraph 4). Additionally, Rautio teaches a di-substituted prodrug ester derivative (a carbamate) with sustained drug action due to protection of the hydroxyls to avoid first-pass intestinal and hepatic metabolism (page 267, column 1, paragraph 2). Rautio then teaches that because of the prolonged action, the prodrug is administered once-daily as opposed to the parent drug, which is administered three times a day (page 267, column 1, paragraph 2). Jung teaches mono-substituted prodrugs of entecavir (abstract). Jung teaches that entecavir possesses low permeability in the GI tract (abstract). Jung further teaches that there is a negative food effect in entecavir oral therapy on intestinal absorption, that the patient experiences a decrease in the extent of drug absorption (18-20%), and that alternative entecavir dosage forms are needed to minimize negative food effects on intestinal absorption (page 1, paragraph 2; page 2, paragraph 1). Mehellou teaches benzyl ester ligands on phosphate prodrugs for HIV (abstract; Table 1, stages 5-6, page 2213). Mehellou further teaches that benzyl esters are used as masks in prodrugs for targeting HIV in similar scaffolds and that those prodrugs are now in clinical trials (Figure 10, page 2218). Mehellou specifically teaches the compound, , with benzyl ester ligand on a carbon backbone (Figure 10, page 2218). It would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention to select the naphthyl entecavir derivative of Zhang and substitute it with the phenyl of the benzyl ester ligand of Mehellou in a di-substituted fashion as taught by Rautio to increase lipophilicity and cell permeability as taught by Rautio and Jung to arrive at instant claim 1 (Compound 11). One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because: Zhang teaches prodrugs of entecavir for treating hepatitis B virus (HBV); Zhang specifically teaches substitution at R1 and R2 (pages 5 and 6); Zhang teaches substituting R2 as the naphthyl ester: (page 5); Zhang teaches that modifications to entecavir are to develop a prodrug that will be released slowly, sustainably, and steadily in order to achieve a long-acting effect (abstract); Zhang teaches that 130 million people in China are infected with chronic HBV ([0004]); Zhang teaches that about 500,000 people die from hepatopathy every year, leading to a large economic impact ([0004]); Zhang teaches that HBV is a chronic disease, which requires long-lasting medicine to control the virus level in the body ([0005]); Zhang teaches there is no long-acting preparation of entecavir ([0005]); Zhang suggests that R1 and R2 can both be an ester ([0009]-[0013]); Rautio teaches ester prodrugs and derivatives thereof (carbamates and carbonates); Rautio teaches that esters are the most common prodrugs used to enhance lipophilicity and thus passive membrane permeability; Rautio teaches that carboxyl and phosphate esters are both straightforward to synthesize as evidenced by Organic Portal 1 and Organic Portal 2 . Rautio teaches di-substituted ester prodrugs: dipivefrin and bambuterol and that the di-substituted ester prodrug, dipivefrin, penetrates the human cornea 17-times more rapidly than the parent drug (adrenaline) due to its lipophilicity; Rautio teaches a di-substituted prodrug ester derivative (bambuterol, a carbamate) with sustained drug action due to protection of the hydroxyls to avoid first-pass intestinal and hepatic metabolism; Rautio teaches that because of the prolonged action, the prodrug is administered once-daily as opposed to the parent drug, which is administered three times a day; Jung teaches mono-substituted prodrugs of entecavir, which possesses low permeability in the GI tract; Jung teaches that there is a negative food effect in entecavir oral therapy on intestinal absorption, that the patient experiences a decrease in the extent of drug absorption (18-20%), and that alternative entecavir dosage forms are needed to minimize negative food effects on intestinal absorption; Mehellou teaches benzyl ester ligands on phosphate prodrugs for HIV and hepatitis B virus (page 2211, column 1, paragraph 1); Mehellou teaches that nucleoside drugs often demonstrate poor oral bioavailability due to low intestinal permeability (page 2211, column 2, paragraph 1); Mehellou teaches that benzyl esters are more slowly hydrolyzed than naphthyl counterparts (page 2217, column 1, paragraph 2); Mehellou teaches that benzyl esters were are used as masks in prodrugs for targeting HIV in similar scaffolds and that those prodrugs are now in clinical trials; and Mehellou teaches the compounds, and , with benzyl and naphthyl ester ligand, which are now in clinical trials. Mehellou teaches that benzyl esters were are used as masks in prodrugs for targeting HIV in similar scaffolds and that those prodrugs are now in clinical trials; and Mehellou teaches the compound, , with benzyl ester ligand on a carbon backbone, which is now in clinical trials. Thus, an artisan having ordinary skill in the art would have been motivated to make such a selection to predictably arrive at a compound of Formula (I). Thus, an artisan having ordinary skill in the art would have been motivated to make such a selection to predictably arrive at a di-substituted prodrug of entecavir . As such, in view of the above teachings, is not a special technical feature. Thus, the requirement is still deemed proper and is therefore made FINAL. Claims 26 and 28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group (Group II: claims 26 and 28), there being no allowable generic or linking claim. Claims 7-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Claims 7-8 specify a crystal of the formula: , which does not read on the elected species. Claims 9-10 specify a crystal of the formula: , which does not read on the species. Information Disclosure Statement The Information Disclosure Statements filed 6 February 2026 and 18 Mar 2026 and the references cited therein have been considered, unless indicated otherwise. The references, wherein no copy with an English abstract or translation thereof was provided in that particular IDS submission, are lined through. These references are the following: Japanese Publication (Japanese Pharmacopoeia, 16 th edition, 2011, 2070, 64-68). 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 nonobviousness. 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. 1. Claim (s) 1, 3-4, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (U.S. Patent Publication No. 2020/0239513, published 30 Jul 2020 , see IDS 6 Feb 2026) in view of Rautio ( Nat Rev Drug Discovery , 2008 , 7 , 255-270) , Jung ( Molecules , 2018 , 23(731) , 1-12) , and Mehellou ( J. Med. Chem. , 2018 , 61 , 2211-2226) as evidenced by Organic Portal 1 (“Esterifications,” Organic Portal , 2026 , < https://www.organic-chemistry.org/synthesis/C1O/esters/esterifications.shtm >, accessed 20 Mar 2026) and Organic Portal 2 (“P-O Bond Formation,” Organic Portal , 2026 , < https://www.organic-chemistry.org/synthesis/P1O/index.shtm >, accessed 20 Mar 2026). Zhang teaches prodrugs of entecavir for treating hepatitis B virus (HBV; abstract). Zhang specifically teaches substitution at R1 and R2 as compounds: and (pages 5 and 6). Further, Zhang teaches modifications to entecavir are to develop a prodrug that will be released slowly, sustainably, and steady in order to achieve a long-acting effect (abstract) . Additionally, Zhang teaches that 130 million people in China are infected with chronic HBV ([0004]). Regarding claim 1, Zhang fails to teach a di-substituted benzyl ester prodrug for slow release in the GI tract . Rautio teaches ester prodrugs and derivatives thereof (page 256, column 2, paragraph 2). Rautio further teaches that esters are the most common prodrugs used to enhance lipophilicity and thus passive membrane permeability (page 256, column 2, paragraph 3). Rautio teaches that carboxyl and phosphate esters are both straightforward to synthesize (page 256, column 2, paragraph 2; page 258, column 1, paragraph 1; page 258, column 2, paragraph 1) as evidenced by Organic Portal 1 and Organic Portal 2 (Organic Portal 1: Box 6; Organic Portal 2: Box 9). Rautio specifically teaches di-substituted ester prodrugs: dipivefrin and bambuterol (Table 5, page 263; Table 6, page 264). Rautio further teaches that the di-substituted ester prodrug, dipivefrin, penetrates the human cornea 17-times more rapidly than the parent drug (adrenaline) due to its lipophilicity (page 265, column 1, paragraph 4). Additionally, Rautio teaches a di-substituted prodrug ester derivative (a carbamate) with sustained drug action due to protection of the hydroxyls to avoid first-pass intestinal and hepatic metabolism (page 267, column 1, paragraph 2). Rautio then teaches that because of the prolonged action, the prodrug is administered once-daily as opposed to the parent drug, which is administered three times a day (page 267, column 1, paragraph 2). Jung teaches mono-substituted prodrugs of entecavir (abstract). Jung teaches that entecavir possesses low permeability in the GI tract (abstract). Jung further teaches that there is a negative food effect in entecavir oral therapy on intestinal absorption, that the patient experiences a decrease in the extent of drug absorption (18-20%), and that alternative entecavir dosage forms are needed to minimize negative food effects on intestinal absorption (page 1, paragraph 2; page 2, paragraph 1). Mehellou teaches benzyl ester ligands on phosphate prodrugs for HIV (abstract; Table 1, stages 5-6, page 2213). Mehellou further teaches that benzyl esters were are used as masks in prodrugs for targeting HIV in similar scaffolds and that those prodrugs are now in clinical trials (Figure 10, page 2218). Mehellou specifically teaches the compound s , and , with benzyl and naphthyl ester ligand (Figure 10, page 2218). It would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention to select the naphthyl entecavir derivative of Zhang and substitute it with the phenyl of the benzyl ester ligand of Mehellou in a di-substituted fashion as taught by Rautio to increase lipophilicity and cell permeability as taught by Rautio and Jung to arrive at instant claim 1 (Compound 11). One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because: -Zhang teaches prodrugs of entecavir for treating hepatitis B virus (HBV) , - Zhang specifically teaches substitution at R1 and R2 (pages 5 and 6), -Zhang teaches substituting R2 as the naphthyl ester: (page 5), - Zhang teaches that modifications to entecavir are to develop a prodrug that will be released slowly, sustainably, and stead ily in order to achieve a long-acting effect (abstract ), -Zhang teaches that 130 million people in China are infected with chronic HBV ([0004]), -Zhang teaches that about 500,000 people die from hepatopathy every year, leading to a large economic impact ([0004]), -Zhang teaches that HBV is a chronic disease, which requires long-lasting medicine to control the virus level in the body ([0005]) , -Zhang teaches there is no long-acting preparation of entecavir ([0005]) , -Zhang suggests that R1 and R2 can both be an ester ([0009]-[0013]), - Rautio teaches ester prodrugs and derivatives thereof, -Rautio teaches that esters are the most common prodrugs used to enhance lipophilicity and thus passive membrane permeability, - Rautio teaches that carboxyl and phosphate esters are both straightforward to synthesize as evidenced by Organic Portal 1 and Organic Portal 2, -Rautio teaches di-substituted ester prodrugs: dipivefrin and bambuterol and that the di-substituted ester prodrug, dipivefrin, penetrates the human cornea 17-times more rapidly than the parent drug (adrenaline) due to its lipophilicity, -Rautio teaches a di-substituted prodrug ester derivative ( bambuterol, a carbamate) with sustained drug action due to protection of the hydroxyls to avoid first-pass intestinal and hepatic metabolism, -Rautio teaches that because of the prolonged action, the prodrug is administered once-daily as opposed to the parent drug, which is administered three times a day, -Jung teaches mono-substituted prodrugs of entecavir, which possesses low permeability in the GI tract, -Jung teaches that there is a negative food effect in entecavir oral therapy on intestinal absorption, that the patient experiences a decrease in the extent of drug absorption (18-20%), and that alternative entecavir dosage forms are needed to minimize negative food effects on intestinal absorption, -Mehellou teaches benzyl ester ligands on phosphate prodrugs for HIV and hepatitis B virus (page 2211, column 1, paragraph 1) , -Mehellou teaches that nucleoside drugs often demonstrate poor oral bioavailability due to low intestinal permeability (page 2211, column 2, paragraph 1), -Mehellou teaches that benzyl esters are more slowly hydrolyzed than naphthyl counterparts (page 2217, column 1, paragraph 2), -Mehellou teaches that benzyl esters were are used as masks in prodrugs for targeting HIV in similar scaffolds and that those prodrugs are now in clinical trials, and -Mehellou teaches the compounds, and , with benzyl and naphthyl ester ligand , which are now in clinical trials. Thus, an artisan having ordinary skill in the art would have been motivated to make such a selection to predictably arrive at Compound 11: . Regarding claim 3, Zhang teaches a compound where X- Lm is -C(=O)L (pages 5 and 6), and Rautio teaches di-substituted ester prodrugs (Table 5, page 263; Table 6, page 264). Additionally, Mehellou teaches the compound containing a benzyl ester ligand: (Figure 10, page 2218). Accordingly, the combination of Zhang, Rautio, and Mehellou teaches a compound wherein R1 and R2 are X- Lm , which is -C(=O)L. Regarding claim 4, Zhang teaches the compound: (page 5), and Rautio teaches di-substituted ester prodrugs used to enhance lipophilicity and thus passive membrane permeability (Table 5, page 263; Table 6, page 264). Jung teaches that mono-substituted prodrugs of entecavir suffer from low permeability in the GI tract (abstract). Additionally, Mehellou teaches the compound containing a benzyl ester ligand: , which is not hydrolyzed as quickly as naphthyl and thus would be a sustained release (Figure 10, page 2218; page 2217, column 1, paragraph 2). Accordingly, a person of skill in the art would make the d-substituted benzyl ester prodrug of entecavir to enhance lipophilicity and cell permeability and ultimately create a slow-release, sustained entecavir prodrug. Thus, the combination of Zhang, Rautio, Jung, and Mehellou teaches Compound 11: . Additionally, regarding claim 4, for purposes of compact prosecution, the following compounds are taught or suggested by the combination of Zhang, Rautio, Jung, and Mehellou: Compounds 1-7, 11-15, 20-26, 29-33, and 36-38. Regarding claim 11, Zhang teaches a pharmaceutical composition ([0054]). 2. Claim (s) 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (U.S. Patent Publication No. 2020/0239513, published 30 Jul 2020 , see IDS 6 Feb 2026), Rautio ( Nat Rev Drug Discovery , 2008 , 7 , 255-270), Jung ( Molecules , 2018 , 23(731) , 1-12), and Mehellou ( J. Med. Chem. , 2018 , 61 , 2211-2226) as evidenced by Organic Portal 1 (“Esterifications,” Organic Portal , 2026 , < https://www.organic- chemistry.org/synthesis/C1O/esters/esterifications.shtm >, accessed 20 Mar 2026) and Organic Portal 2 (“P-O Bond Formation,” Organic Portal , 2026 , < https://www.organic-chemistry.org/synthesis/P1O/index.shtm >, accessed 20 Mar 2026) as applied to claims 1, 3-4, and 11 above, and further in view of Morissette ( Adv. Drug Delivery Rev. , 2004 , 56 , 275-300). Zhang (U.S. Patent Publication No. 2020/0239513, published 30 Jul 2020 , see IDS 6 Feb 2026), Rautio ( Nat Rev Drug Discovery , 2008 , 7 , 255-270), Jung ( Molecules , 2018 , 23(731) , 1-12), and Mehellou ( J. Med. Chem. , 2018 , 61 , 2211-2226) as evidenced by Organic Portal 1 (“Esterifications,” Organic Portal , 2026 , < https://www.organic-chemistry.org/synthesis/C1O/esters/esterifications.shtm >, accessed 20 Mar 2026) and Organic Portal 2 (“P-O Bond Formation,” Organic Portal , 2026 , < https://www.organic-chemistry.org/synthesis/P1O/index.shtm >, accessed 20 Mar 2026) are applied as discussed in the 35 U.S.C. 103 rejection above. Regarding claim 5, while the combination of Zhang , Rautio, Jung, and Mehellou t eaches prodrugs of entecavir (Compound 11), they differ from that of the instantly claimed invention in that they do not explicitly teach a polymorph having XRPD comprising the following peak: 9.00, 17.28, 21.72, and 23.80 °2θ ± 0.20 °2θ. It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to exemplify the compound of Zhang , Rautio, Jung, and Mehellou with the polymorphs of Morissette to arrive at the instantly claimed invention. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because Morissette teaches a high throughput method of generating polymorphs (crystals) of active pharmaceutical ingredients (abstract). Morissette teaches that multiple forms of active pharmaceutical ingredients exist and that each form displays unique physiochemical properties that can profoundly influence the bioavailability, manufacturability purification, stability, and other performance characteristics of the drug (page 276, column 1, paragraph 1). Morissette further teaches that most active pharmaceutical ingredients are purified and isolated by crystallization from an appropriate solvent during the final step in the synthetic process and that a large number of factors can influence crystal nucleation and growth during this process, including composition of the crystallization medium and process(es) used to generate supersaturation and promote crystallization ( page 276, column 2, paragraph 2). Morissette then specifies that high throughput crystallization systems have been developed to more rapidly and comprehensively explore the multiparameter space that contributes to solid form diversity (page 278, column 2, paragraph 2). Morissette further teaches the generation of polymorphs of acetaminophen using a 96-well plate system (e.g. Form III of acetaminophen), while previously, the crystal structure of Form III of acetaminophen was proposed 20 years after it was observed in 1982 by thermal microscopy (page 288, column 1, paragraph 2; page 289, column 1, paragraph 3). Further, Morissette teaches utilizing high throughput crystallization experiments to generate polymorphs of MK-996: over 1500 discrete recrystallization trials from a set of 21 solvents or solvent mixtures yielded 186 solids, which were harvested over a period of 7 days, and produced at least 18 distinct forms (page 289, column 2, paragraph 3; page 290, column 1, paragraph 1). Additionally, Morissette teaches that pharmaceutical companies currently use high throughput screening of polymorphs to save time and reduce costs (page 288, column 1, paragraph 1). Thus, Morissette teaches that high throughput screening produces many polymorphs in a short period of time. Accordingly , Morissette teaches a polymorph having XRPD comprising the following peak: 9.00, 17.28, 21.72, and 23.80 °2θ ± 0.20 °2θ. Thus, one of ordinary skill in the art would have substituted one known element for another, and the results would be predictable. Regarding claim 6, Morissette teaches that high throughput screening produces many polymorphs in a short period of time (page 289, column 2, paragraph 3; page 290, column 1, paragraph 1). Thus, one of ordinary skill in the art would use the high throughput screening technology as described by Morissette to access a polymorph wherein the diffractogram comprises the following peaks: 11.74, 19.48, 25.00, and 27.16 °2θ ± 0.20 °2θ. 3 . Claim (s) 12 is rejected under 35 U.S.C. 103 as being unpatentable over Zhang (U.S. Patent Publication No. 2020/0239513, published 30 Jul 2020 , see IDS 6 Feb 2026), Rautio ( Nat Rev Drug Discovery , 2008 , 7 , 255-270), Jung ( Molecules , 2018 , 23(731) , 1-12), and Mehellou ( J. Med. Chem. , 2018 , 61 , 2211-2226) as evidenced by Organic Portal 1 (“Esterifications,” Organic Portal , 2026 , < https://www.organic-chemistry.org/synthesis/C1O/esters/esterifications.shtm >, accessed 20 Mar 2026) and Organic Portal 2 (“P-O Bond Formation,” Organic Portal , 2026 , < https://www.organic-chemistry.org/synthesis/P1O/index.shtm >, accessed 20 Mar 2026) as applied to claims 1, 3-4, and 11 above, and further in view of Ahmed (WO2017/119936, published 13 July 2017 ). Zhang (U.S. Patent Publication No. 2020/0239513, published 30 Jul 2020 , see IDS 6 Feb 2026), Rautio ( Nat Rev Drug Discovery , 2008 , 7 , 255-270), Jung ( Molecules , 2018 , 23(731) , 1-12), and Mehellou ( J. Med. Chem. , 2018 , 61 , 2211-2226) as evidenced by Organic Portal 1 (“Esterifications,” Organic Portal , 2026 , < https://www.organic-chemistry.org/synthesis/C1O/esters/esterifications.shtm >, accessed 20 Mar 2026) and Organic Portal 2 (“P-O Bond Formation,” Organic Portal , 2026 , < https://www.organic-chemistry.org/synthesis/P1O/index.shtm >, accessed 20 Mar 2026) are applied as discussed in the 35 U.S.C. 103 rejection above. Regarding claim 12, while the combination of Zhang , Rautio, Jung, and Mehellou teach es prodrugs of entecavir (Compound 11) and compositions thereof, they differ from that of the instantly claimed invention in that they do not explicitly teach a pharmaceutical composition of Compound 11 wherein the pharmaceutically acceptable carrier comprises sesame oil or castor oil. It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to exemplify the composition of Zhang , Rautio, Jung, and Mehellou with the compositions of Ahmed to arrive at the instantly claimed invention. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because Ahmed teaches extended-release formulations of antiviral drugs, specifically entecavir (abstract; [0015] ; [0085] ). Ahmed specifically teaches formulations containing a hydrophobic lipid, such as castor oil or sesame oil ([0094]). Further, Ahmed teaches that some active pharmaceutical ingredients are poorly water soluble and require to be injected as a non-aqueous formulation ([001]; [008]). Additionally, Ahmed teaches that long-acting formulations improve the bioavailability of active pharmaceutical ingredients after intramuscular or subcutaneous administration as compared to oral routes ([006]) . Further, Ahmed specifies that injectable formulations would provide therapeutic plasma concentration levels with a dose that can be administered intramuscularly or subcutaneously once every week, month, or every three months , with the possibility of the total injected dose being lower than the daily dose required over the same time period, which reduces toxicity and improves patient compliance ([006]). Thus, Ahmed teaches a composition of entecavir with a hydrophobic lipid, such as castor oil or sesame oil. Thus, one of ordinary skill in the art would have substituted one known element for another, and the results would be predictable. 4. Claim (s) 13 is rejected under 35 U.S.C. 103 as being unpatentable over Zhang (U.S. Patent Publication No. 2020/0239513, published 30 Jul 2020 , see IDS 6 Feb 2026), Rautio ( Nat Rev Drug Discovery , 2008 , 7 , 255-270), Jung ( Molecules , 2018 , 23(731) , 1-12), and Mehellou ( J. Med. Chem. , 2018 , 61 , 2211-2226) as evidenced by Organic Portal 1 (“Esterifications,” Organic Portal , 2026 , < https://www.organic-chemistry.org/synthesis/C1O/esters/esterifications.shtm >, accessed 20 Mar 2026) and Organic Portal 2 (“P-O Bond Formation,” Organic Portal , 2026 , < https://www.organic- chemistry.org/synthesis/P1O/index.shtm >, accessed 20 Mar 2026) as applied to claims 1, 3-4, and 11 above, and further in view of Patel ( Int. J. Mol. Sci. , 2020 , 21(8224) , 1-21) as evidenced by Wikipedia 1 (“Carboxymethyl cellulose,” Wikipedia , < en.wikipedia.org/wiki/ Carboxymethyl_cellulose >, 2026 , accessed 11 Mar 2026) , Wikipedia 2 (“Hypromellose,” Wikipedia , 2026 < en.wikipedia.org/wiki/Hypromellose >, accessed 11 Mar 2026), and Wikipedia 3 (“Hydroxypropyl cellulose,” Wikipedia , 2026 , < en.wikipedia.org/wiki/ Hydroxypropyl_cellulose >, accessed 11 Mar 2026). Zhang (U.S. Patent Publication No. 2020/0239513, published 30 Jul 2020 , see IDS 6 Feb 2026), Rautio ( Nat Rev Drug Discovery , 2008 , 7 , 255-270), Jung ( Molecules , 2018 , 23(731) , 1-12), and Mehellou ( J. Med. Chem. , 2018 , 61 , 2211-2226) as evidenced by Organic Portal 1 (“Esterifications,” Organic Portal , 2026 , < https://www.organic-chemistry.org/synthesis/C1O/esters/esterifications.shtm >, accessed 20 Mar 2026) and Organic Portal 2 (“P-O Bond Formation,” Organic Portal , 2026 , < https://www.organic-chemistry.org/synthesis/P1O/index.shtm >, accessed 20 Mar 2026) are applied as discussed in the 35 U.S.C. 103 rejection above. Regarding claim 13, while the combination of Zhang , Rautio, Jung, and Mehellou teach es prodrugs of entecavir (Compound 11) and compositions thereof, they differ from that of the instantly claimed invention in that they do not explicitly teach a formulation of Compound 11 , wherein the compound is suspended in an aqueous solution comprising a water-soluble cellulose-based polymer and a non-ionic surfactant. It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to exemplify the composition of Zhang , Rautio, Jung, and Mehellou with the formulations of Patel to arrive at the instantly claimed invention. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because Patel teaches formulations and that the pharmacokinetics (absorption, distribution, metabolism, and elimination) of active pharmaceutical ingredients are possibly altered because of their transport and metabolism modulation from incorporated excipients (abstract). Patel specifically teaches semi-synthetic cellulose derivatives, such as sodium carboxymethyl cellulose hydroxypropyl methylcellulose, and hydroxypropyl cellulose (Table 3 , page 9; page 9, paragraph 3) , which are water soluble as evidenced by Wikipedia 1, 2, and 3 (Wikipedia 1: page 1, paragraph 1; Wikipedia 2: page 1, paragraph 1; Wikipedia 3: page 1, paragraph 3). Patel additionally specifies non-ionic surfactants (Table 2, pages 7-8). Additionally, Patel teaches that most popular route for drug delivery is oral administration because of pain avoidance, ease of ingestion, patient compliance and versatility of drug candidates and that poor bioavailability of oral formulation is a limiting factor that can alter efficacy and therapeutic effect (page 1, paragraph 1). Further, Patel teaches that addition of commonly-used pharmaceutical excipients can be a potential solution to these problems (page 4, paragraph 4). Patel specifies that pharmaceutical excipients are ingredients other than the active pharmaceutical ingredient (API) present in a finished pharmaceutical drug formulation and that excipients are frequently used as lubricants, diluent, binders, flavorings, coating and coloring agents for the formulation (page 4, paragraph 4). Patel further teaches that addition of pharmaceutical excipients in drug formulations have gained attention which can alter the pharmacokinetics of drugs, resulting in improved bioavailability (page 4, paragraph 5). Patel teaches a review of the current literature and evaluates the effect of different pharmaceutical excipients on metabolic enzymes (page 4, paragraph 5). Thus, Patel teaches a formulation of Compound 11, wherein the compound is suspended in an aqueous solution, comprising a water-soluble cellulose-based polymer and a non-ionic surfactant. Thus, one of ordinary skill in the art would have substituted one known element for another, and the results would be predictable. Conclusion No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT Madeline M Dekarske whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-1789 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Monday - Thursday 10am - 4pm . 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. 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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. /MADELINE M. DEKARSKE/ Examiner, Art Unit 1622 /JAMES H ALSTRUM-ACEVEDO/ Supervisory Patent Examiner, Art Unit 1622