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 .
Applicant’s response of 08/08/2026, including replacement drawings and a substitute specification, has been received and entered into the application file.
Claims 5-9 were amended in the claim set filed 08/08/2026.
Claims 1-9 are pending, of which claims 1-4 were previously withdrawn.
Accordingly, claims 5-9 are pending and under consideration.
Election/Restrictions
Applicant’s previous election without traverse of claims 5-9 (Group II) in the reply filed on 03/27/2026 is acknowledged.
Claims 1-4 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/27/2026.
Accordingly, claims 5-9 are pending and under consideration.
Status of Prior Objections/Rejections
RE: Drawings
►The drawings were previously objected to for being of insufficient quality to be clearly legible/interpretable.
The replacement drawings received 08/08/2026 have obviated most, but not all, of the prior grounds of objection. Those objections not repeated below are hereby withdrawn.
RE: Claim Objections
►Claims 5-9 were previously objected to for various informalities.
The amendments to the instant claim set received 08/08/2026 have obviated the prior grounds of objection. However, further review of the claim set has necessitated new grounds of objection, as set forth below.
RE: Claim Rejections - 35 USC § 103
►Claims 5-7 were previously rejected under 35 U.S.C. 103 as being unpatentable over Cheng et al., 2016 (hereinafter Cheng; as cited in the IDS filed 07/11/2023; of record) in view of WO 2018/232502 A1 (hereinafter Uludag) and Sang et al., 2015 (hereinafter Sang).
Applicant has traversed the rejection of record, asserting that the cited art does not teach or suggest the gene delivery agent of the amended claim set. Particularly, Applicant asserts that Cheng is directed to nanohemostats, while Uludag is drawn to covalently linked cholic acid and polyethylenimine (PEI). Applicant further asserts that the reliance on routine optimization to reach the recited range is misplaced.
Regarding Applicant’s assertion that Cheng and Uludag do not collectively disclose an effective gene delivery agent comprised of ionically bonded cholic acid and PEI, this is not found persuasive. While Cheng is drawn to nanohemostats, as set forth in the prior action, Uludag is drawn to delivery of nucleic acids using bonded cholic acid and PEI. While Uludag is drawn to covalent bonding, Cheng discloses that ionic bonding is also feasible between PEI and cholic acid. A person of ordinary skill in the art would not reasonably predict that the ionic bonding disclosed in Cheng would not also be relevant to the methods of Uludag, as both require bonded PEI and cholic acid.
Regarding Applicant’s assertion that the reliance on routine optimization is misplaced, as previously set forth, the art teaches that the repeating units corresponding to “m” and “n” in the instant claim set may be varied. Per MPEP § 2144.05(I)(A), “it is not inventive to discover the optimum or workable ranges by routine experimentation” (In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)). Given that the art explicitly teaches that the number of repeating units may be varied (as set forth in greater detail below), it is not found persuasive that the recited ranges of “m” and “n” sufficiently distinguish the instant structure from that disclosed in the prior art.
However, it is found persuasive that the cited art does not teach or suggest the gene delivery agent of the amended claim set. New grounds of rejection necessitated by amendment are set forth below.
►Claims 8-9 were previously rejected under 35 U.S.C. 103 as being unpatentable over Cheng et al., 2016 (hereinafter Cheng; as cited in the IDS filed 07/11/2023; of record) in view of WO 2018/232502 A1 (hereinafter Uludag), Wei et al., 2018 (hereinafter Wei), and Gallops et al., 2019 (hereinafter Gallops).
Applicant has traversed the rejection of record, asserting that neither Cheng nor Uludag suggests or teaches an ionically bonded, linear polyethylenimine-cholic acid gene delivery agent of the recited molecular weight for gene delivery and that these deficiencies are not cured by Wei or Gallops.
Applicant has asserted that Wei is nonanalogous art. In response, this is not found persuasive. Wei is explicitly drawn to ionic bonding of PEI. A person of ordinary skill in the art researching and developing an ionically bonded PEI-cholic acid delivery agent would certainly look to the prior art for guidance regarding ionic bonding of PEI. As Applicant has indicated, PEI is commonly covalently conjugated (as in Uludag), meaning one of ordinary skill in the art would be motivated to comb the prior art for guidance regarding ionic bonding of PEI, to which Wei is drawn.
Applicant further asserts that Gallops discloses neither cholic acid nor the preparation of a gene delivery agent. While the Examiner concurs that Gallops is not drawn to preparation of a gene delivery agent, Gallops was applied to teach the protonation range of PEI for purposes of informing a person of ordinary skill in the art about the pH range at which PEI is most likely to be able to engage in ionic bonding, the methodology of which is expounded upon in Wei. As set forth above, Cheng establishes that PEI and cholic acid may be ionically bonded, while Uludag establishes that a complex of PEI and cholic acid bonded together is an effective gene delivery agent.
Regarding Applicant’s assertion that Gallops teaches away from the near-neutral window of 6.9 to 7.1, this is not found persuasive. As is known to those of ordinary skill in the art, as pH decreases, acidity increases. As per Applicant, Gallops teaches that PEI becomes increasingly protonated as pH decreases from 7.4. The pH range of 6.9 to 7.1 may be near-neutral, but it is also more acidic (i.e. a lower pH) than the physiological pH of 7.4 disclosed in Gallops. It is thus unclear how Gallops teaches away from a decreased pH of 7.4, as Gallops teaches that protonation increases as pH decreases from 7.4, thereby motivating someone of ordinary skill in the art to experiment with routine optimization to establish the ideal pH range for ionically bonding PEI and cholic acid. Regarding the unexpected benefit disclosed by Applicant, this unexpected benefit is not in the claim language, nor is it found persuasive that reduced toxicity associated with “near neutral” pH is indeed an unexpected benefit.
However, it is found persuasive that the cited art does not teach or suggest the gene delivery agent of the amended claim set. New grounds of rejection necessitated by amendment are set forth below.
New/Maintained Grounds of Objection/Rejection
Drawings
The drawings are objected to because:
Regarding Figures 3c, 3d, 4c, 4d, 5c, 5d, 5e, 5c, 6d, 6e, 6f, 6g, 6h, and 7c all include bright field imaging, green fluorescence imaging, and merging thereof. In all of the images, while the green fluorescence imaging is clearly viewable, the bright field and merge channels are of poor quality such that they are uninterpretable. It would be remedial to increase the image quality such that they are clearly interpretable and/or to add color to aid in interpretation of the imaging. Should Applicant wish to file color drawings, a petition must be filed under 37 CFR 1.84(a)(2).
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 5 and 8 are objected to because of the following informalities:
Claims 5 and 8 recite in part “wherein, in the Chemical Formula 1, m is an integer of 2 to 930, and n is an integer of 58 to 930, and the polyethylenimine is a linear polyethylenimine having a weight-average molecular weight of 2,500 to 40,000” (bolded emphasis added). Conventionally, “and” is only used once preceding the final component of a recited list. It would be remedial to amend the instant claim language to recite in part “wherein, in the Chemical Formula 1, m is an integer of 2 to 930, n is an integer of 58 to 930, and the polyethylenimine is a linear polyethylenimine having a weight-average molecular weight of 2,500 to 40,000” (bolded emphasis added).
Independent claims 5 and 8 also recite in part “the polyethylenimine is a linear polyethylenimine having a weight-average molecular weight of 2,500 to 40,000,” which lacks appropriate units defining the molecular weight. While molecular weight is technically a unitless ratio, it is typically reported with units of atomic mass units or Daltons. For purposes of clarity and ease of interpretation, it would be remedial to amend the instant claims to recite units such as atomic mass units or Daltons.
With further regard to claim 5, the recitation of “contacting the composition with cells” does not comport with standard grammatical and/or linguistic conventions. Usually, such a phrase is written as “contacting cells with the composition.” It would be remedial to amend the instant claim language to recite a similar structure, such as “contacting a cell with the composition.”
Appropriate correction is required.
Claim Rejections - 35 USC § 103
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.
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 5-7 are rejected under 35 U.S.C. 103 as being unpatentable over Cheng et al., 2016 (hereinafter Cheng; as cited in the IDS filed 07/11/2023; of record) in view of WO 2018/232502 A1 (hereinafter Uludag; of record), Sang et al., 2015 (hereinafter Sang; of record), and Wang et al., 2019 (hereinafter Wang), as evidenced by Dube et al., 2017 (hereinafter Dube).
With regard to claim 5, which recites “a gene delivery method, comprising:
providing a composition comprising a gene delivery agent in which polyethylenimine and cholic acid are ionically bonded and which is represented by the following Chemical Formula 1 and a gene,…wherein in the Chemical Formula 1, m is an integer of 2 to 930, and n is an integer of 58 to 930, and the polyethylenimine is a linear polyethylenimine having a weight-average molecular weight of 2,500 to 40,000; and contacting the composition with cells,” as set forth in the restriction requirement dated 02/26/2026, gene delivery agents wherein polyethylenimine and cholic acid are ionically bonded are known in the art. As previously set forth, Cheng discloses nanohemostats formed by cholic-acid-mediated self-assembly of polyethylenimine (PEI), wherein said assembly process is dominated by electrostatic (i.e. ionic) interactions (abstract; page 9961, column 1, paragraph 2; page 9968, column 1, paragraph 1; Figures 1 and 2). The cholic acid structure disclosed in Figure 1B of Cheng is identical to the instantly claimed cholic acid molecule bonded to PEI. While Cheng does not disclose that the nanohemostat structures taught therein may be used as a gene (or nucleic acid) carrier, this deficiency is cured by Uludag. Uludag discloses gene delivery compositions and methods of using the same (abstract), wherein said gene delivery compositions comprise PEI and cholic acid (page 5, lines 14-17). Per Uludag, these compositions may be administered to cells in order to deliver the nucleic acid cargo carried therein (page 1, lines 4-6). Uludag further discloses that the PEI of said gene delivery compositions is of variable weight (page 5, lines 17-20), which is impacted by variable numbers of repeating PEI units/subunits (page 50, claim 5). Per Uludag, x, y, and z are repeating units, wherein “x” corresponds to the instantly claimed “m” and is disclosed to have 7 to 22 repeating units (which falls within the instantly claimed range of 2 to 930), and wherein “y” corresponds to the instantly claimed “n” and is disclosed to have 14 to 44 repeating units (which does not fall within the instantly claimed range of 58 to 930). Thus, the disclosure of Uludag establishes that it is within the realm of routine optimization/experimentation to vary the number of subunits within PEI to generate effective gene delivery compositions. Per MPEP § 2144.05(I)(A), “it is not inventive to discover the optimum or workable ranges by routine experimentation” (In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)). Therefore, based on the disclosure of Uludag and MPEP § 2144.05(I)(A) it would have been obvious to someone of ordinary skill in the art prior to the effective filing date of the instant application to vary the number of PEI subunits, as disclosed in Uludag, to optimize the gene delivery agents comprising PEI and cholic acid taught therein.
While Uludag is drawn to covalent bonding of PEI and cholic acid, Cheng discloses that ionic bonding is also possible, as supported by the teachings of Dube, which also discloses ionic bonding of PEI and cholic acid, specifically for purposes of gene delivery (abstract).
Regarding the claimed molecular weight, Wang discloses that PEI is a known cationic polymer that has been explored as a gene carrier on the basis of high charge density and proton-sponge effects (page 1, column 1, paragraph 1). Wang further discloses that PEI exhibits cytotoxicity due to its high molecular weight and excessive positive charges. While low molecular weight PEI shows reduced cytotoxicity, it also loses transfection efficiency due to inadequate DNA complexation and protection (page 1, column 2, paragraph 1). Wang further discloses that linear PEI having a molecular weight of 2.5 kDa (i.e. 2,500 Da) was modified with lithocholic acid to overcome these challenges (abstract; section 2.1).
With regard to claim 6, which recites “the method of claim 5, wherein the gene is selected from the group consisting of gDNA, cDNA, plasmid DNA, mRNA, tRNA, rRNA, antisense nucleotides, missense nucleotides, and protein-producing nucleotides,” as set forth above, Uludag discloses gene delivery compositions and methods of using the same (abstract), wherein said gene delivery compositions comprise PEI and cholic acid (page 5, lines 14-17). As set forth above, Cheng discloses that ionic bonding is also possible, as supported by the teachings of Dube, which also discloses ionic bonding of PEI and cholic acid, specifically for purposes of gene delivery (abstract). Uludag further discloses that the nucleic acid delivered by the agents taught therein may be an antisense oligonucleotide or plasmid DNA (page 7, lines 1-6), as instantly claimed.
With regard to claim 7, which recites “the method of claim 5, wherein the gene delivery agent and the gene are included in a weight ratio of 4 to 6:1,” as set forth above, Uludag discloses gene delivery compositions and methods of using the same (abstract), wherein said gene delivery compositions comprise PEI and cholic acid (page 5, lines 14-17). Uludag further discloses that it is essential to understand the cellular uptake of polyplexes to gain better insight into the overall efficacy of carriers, teaching a ratio of 12:1 of a similar gene delivery agent to assay said cellular uptake (page 32, lines 20-30). However, Uludag does not specifically teach that a weight ratio of 4 to 6:1 is the most effective ratio of gene delivery agent:gene, particularly when said gene delivery agent comprises PEI and cholic acid. This deficiency is cured by Sang, which discloses that transfection efficiency of PEI-DNA particles is directly influenced by the ratio of PEI to DNA, teaching that a ratio of 4:1 of PEI:DNA achieves optimal transfection efficiency. Furthermore, as set forth above, per MPEP § 2144.05(I)(A), “it is not inventive to discover the optimum or workable ranges by routine experimentation” (In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)). Based on the collective disclosures of Uludag and Sang, it is clearly within the realm of routine optimization via routine experimentation to vary the ratio of gene delivery agent:gene being delivered in order to optimize transfection efficiency. Therefore, it would have been obvious to someone of ordinary skill in the art prior to the effective filing date of the instant application to vary the ratio of gene delivery agent:gene being delivered, as disclosed in both Uludag and Sang, in order to optimize transfection efficiency of the agents taught therein.
Given that Cheng discloses ionically bonded PEI and cholic acid (as does Dube), that Uludag discloses that PEI and cholic acid compositions (wherein the number of subunits and ratio of PEI are optimized to facilitate the function thereof) may be used to delivery nucleic acid species such as antisense oligonucleotides or plasmid DNA, that Wang discloses that linear 2.5 kDa PEI overcomes the challenges associated with PEI cytotoxicity while maintaining its transfection efficacy, and that Sang discloses further optimization of PEI to DNA ratios for purposes of optimizing transfection efficiency thereof, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to ionically bond PEI and cholic acid (as disclosed in Cheng), wherein the subunits and ratio of PEI are optimized to facilitate the function thereof (as disclosed in Uludag and Sang) to predictably form an optimized nucleic acid delivery agent capable of delivering said nucleic acid species (i.e. antisense oligonucleotide as per Uludag) to a cell. One would have been motivated to make such a modification in order to receive the expected benefit of effectively delivering a nucleic acid species such as an antisense oligonucleotide to a cell.
Claims 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Cheng et al., 2016 (hereinafter Cheng; as cited in the IDS filed 07/11/2023; of record) in view of WO 2018/232502 A1 (hereinafter Uludag; of record), Wang et al., 2019 (hereinafter Wang), Wei et al., 2018 (hereinafter Wei; of record), and Gallops et al., 2019 (hereinafter Gallops; of record), as evidenced by Dube et al., 2017 (hereinafter Dube).
With regard to claim 8, which recites “a method of preparing a gene delivery agent, the method comprising:
dissolving polyethylenimine in an alcohol solution and adding an acid solution to carry out [the] reaction; and
mixing cholic acid with the solution and carrying out a reaction followed by sonicating to obtain the gene delivery agent in which the polyethylenimine and the cholic acid are ionically bonded and which is represented by the following Chemical Formula 1…wherein, in the Chemical Formula 1,…
m is an integer of 2 to 930, and n is an integer of 58 to 930, and the polyethylenimine is a linear polyethylenimine having a weight-average molecular weight of 2,500 to 40,000,”
as set forth above, Cheng and Uludag collectively disclose Chemical Formula 1. As set forth above, Cheng discloses nanohemostats formed by cholic-acid-mediated self-assembly of polyethylenimine (PEI), wherein said assembly process is dominated by electrostatic (i.e. ionic) interactions (abstract; page 9961, column 1, paragraph 2; page 9968, column 1, paragraph 1; Figures 1 and 2). The cholic acid structure disclosed in Figure 1B of Cheng is identical to the instantly claimed cholic acid molecule bonded to PEI. While Cheng does not disclose that the nanohemostat structures taught therein may be used as a gene (or nucleic acid) carrier, this deficiency is cured by Uludag. Uludag discloses gene delivery compositions and methods of using the same (abstract), wherein said gene delivery compositions comprise PEI and cholic acid (page 5, lines 14-17). Per Uludag, these compositions may be administered to cells in order to deliver the nucleic acid cargo carried therein (page 1, lines 4-6). Uludag further discloses that the PEI of said gene delivery compositions is of variable weight (page 5, lines 17-20), which is impacted by variable numbers of repeating PEI units/subunits (page 50, claim 5). Per Uludag, x, y, and z are repeating units, wherein “x” corresponds to the instantly claimed “m” and is disclosed to have 7 to 22 repeating units (which falls within the instantly claimed range of 2 to 930), and wherein “y” corresponds to the instantly claimed “n” and is disclosed to have 14 to 44 repeating units (which does not fall within the instantly claimed range of 58 to 930). Thus, the disclosure of Uludag establishes that it is within the realm of routine optimization/experimentation to vary the number of subunits within PEI to generate effective gene delivery compositions. Per MPEP § 2144.05(I)(A), “it is not inventive to discover the optimum or workable ranges by routine experimentation” (In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)). Therefore, based on the disclosure of Uludag and MPEP § 2144.05(I)(A) it would have been obvious to someone of ordinary skill in the art prior to the effective filing date of the instant application to vary the number of PEI subunits, as disclosed in Uludag, to optimize the gene delivery agents comprising PEI and cholic acid taught therein.
While Uludag is drawn to covalent bonding of PEI and cholic acid, Cheng discloses that ionic bonding is also possible, as supported by the teachings of Dube, which also discloses ionic bonding of PEI and cholic acid, specifically for purposes of gene delivery (abstract).
Regarding the claimed molecular weight, Wang discloses that PEI is a known cationic polymer that has been explored as a gene carrier on the basis of high charge density and proton-sponge effects (page 1, column 1, paragraph 1). Wang further discloses that PEI exhibits cytotoxicity due to its high molecular weight and excessive positive charges. While low molecular weight PEI shows reduced cytotoxicity, it also loses transfection efficiency due to inadequate DNA complexation and protection (page 1, column 2, paragraph 1). Wang further discloses that linear PEI having a molecular weight of 2.5 kDa (i.e. 2,500 Da) was modified with lithocholic acid to overcome these challenges (abstract; section 2.1).
However, the cited art does not fully disclose the instantly claimed method of preparing said gene delivery agent. This deficiency is cured by Wei.
Wei discloses ionically bonded PEI utilized to modify perovskite films (abstract). While Wei is not drawn to usage of PEI for purposes of gene delivery, Wei is drawn to ionic compounds comprising PEI, and Uludag, Wang, and Dube, disclose usage of PEI for purposes of gene delivery, as set forth above. As disclosed in the “Experimental” section of Wei, ionically bonded PEI was prepared by dissolving PEI in a solution comprising hydroiodic acid and methanol (page 653, column 2, paragraph 2), which constitute an alcohol and acid solution, as recited at (a) of instant claim 8.
Regarding the cholic acid limitations of (b) of instant claim 8, as set forth above, Cheng discloses ionically bonded PEI and a cholic acid species (abstract). As shown in Figure 1 of Cheng, these cholic acid species include cholic acid and ursodeoxycholic acid (UDCA). Per the methods of Cheng, such ionically bonded PEI and cholic acid species (i.e. cholic acid or UDCA) are produced by sonicating a solution comprising PEI to which the cholic acid species is added (page 9969, column 2, paragraph 3).
With regard to claim 9, which recites “the step (b) [of the method of claim 8] further comprises adjusting the pH of the solution comprising the polyethylenimine and cholic acid to 6.9 to 7.1,” as set forth above, Cheng, Uludag, and Wei collectively disclose each and every limitation of instant claim 8. However, these disclosures do not teach the instantly claimed pH range. This deficiency is cured by Gallops. Gallops discloses that PEI is a highly studied vector for nonviral gene delivery with a high transfection efficiency that has been linked with its pH responsiveness (abstract; graphical abstract). Gallops further discloses that a key feature underlying the mechanism of PEI-mediated gene delivery is that PEI is not fully protonated at physiological pH of ~7.4 and becomes increasingly protonated (i.e. cationic) in acidic environments, such as endosomal environments encountered by gene delivery polyplexes (page 7255, column 1, paragraph 1). As shown in the graphical abstract, as pH increases, PEI becomes more weakly charged, meaning it is less able to participate in ionic bonds as a cation. On the other hand, as pH decreases, PEI becomes more highly charged, meaning it is more able to participate in ionic bonds as a cation. As set forth above, per MPEP § 2144.05(I)(A), “it is not inventive to discover the optimum or workable ranges by routine experimentation” (In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)). Based on the disclosure of Gallops, one of ordinary skill in the art would have been motivated to optimize the pH of the reaction to generate ionically bonded PEI and cholic acid such that PEI is able to participate in ionic bonds as a cation, thereby facilitating delivery of nucleic acids, as disclosed in Uludag and Gallops. The graphical abstract of Gallops discloses that pH influences the protonation state and charge of PEI, with PEI becoming more highly charged as pH decreases from a physiological pH of ~7.4 (page 7255, column 1, paragraph 1). Given that the claimed pH range of 6.9 to 7.1 is lower (i.e. more acidic) than said physiological pH of ~7.4, one of ordinary skill in the art would reasonably predict that PEI would be more highly charged, and therefore more able to participate in ionic bonds, at a pH of 6.9 to 7.1 as depicted in the graphical abstract of Gallops.
Given that Cheng discloses ionically bonded PEI and cholic acid (said bond facilitated by sonication of a mixture thereof; as does Dube), that Uludag discloses that PEI and cholic acid compositions (wherein the number of subunits of PEI are optimized to facilitate the function thereof) may be used to delivery nucleic acid species such as antisense oligonucleotides or plasmid DNA, that Wang discloses that linear 2.5 kDa PEI overcomes the challenges associated with PEI cytotoxicity while maintaining its transfection efficacy, that Wei discloses preparation of ionically bonded PEI by dissolving PEI in a solution comprising hydroiodic acid and methanol, and that Gallops discloses that PEI becomes more highly charged as pH decreases and that PEI is not fully protonated at a physiological pH of ~7.4, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention treat linear 2.5 kDa PEI (as disclosed in Wang) with a mixture of alcohol and acid (as disclosed in Wei) followed by sonication with a mixture of PEI and cholic acid (as disclosed in Cheng) at a pH that facilitates more highly charged PEI (as disclosed in Gallops) to predictably generate an optimized ionically bonded PEI and cholic acid (as disclosed in Cheng and Dube) that is capable of delivering nucleic acids to a cell (as in Uludag, Wang, and Dube). One would have been motivated to make such a modification in order to receive the expected benefit of producing an optimized gene delivery agent capable of effectively delivering a nucleic acid species such as an antisense oligonucleotide to a cell.
Conclusion
No claims are allowed.
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 Sarah E Allen whose telephone number is (571)272-0408. The examiner can normally be reached M-F 8-5.
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879
/SARAH E ALLEN/ Examiner, Art Unit 1637
/J. E. ANGELL/ Primary Examiner, Art Unit 1637
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