CTNF 18/294,123 CTNF 99541 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. 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. Priority The instant application is a 371 of PCT/EP2022/071786 filed on 08/03/2022 and claims domestic benefit to US provisional application no. 63/229,666 filed on 08/05/2021. Information Disclosure Statement The information disclosure statement (IDS) submitted on 01/31/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. Status of the Claims The preliminary claim amendments filed on 01/31/2024 is acknowledged. Claims 2-15 are amended. Claims 16-17 are newly added. Accordingly, claims 1-17 are pending and being examined on the merits herein. Specification 07-29 AIA The disclosure is objected to because of the following informalities: The text in the table on page 24, in the last table on page 25, in the first table on page 26, and the second table on page 28 are cut-off . Appropriate correction is required. Claim Rejections - 35 USC § 112(b) 07-30-02 AIA The following is a quotation of 35 U.S.C. 112(b): (b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. 07-34-01 Claims 1-17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 1 recites “… to a chromatographic separation on a membrane or monolith comprising anion exchange groups …”. Claim 1 is indefinite because it is not clear if the recited membrane must comprise anion exchange groups, or if the recited membrane does not require comprising anion exchange groups. Claims 2-17 depend from claim 1, but do not overcome the described indefinite issue. For purposes of examination, claim 1 is being interpreted as a membrane comprising anion exchange groups. Claims 4 and 6 recite “between 0.01% and 10% (w/v)”. Claims 4 and 6 are indefinite because it is not clear if the parenthetical (w/v) is meant to limit the recited percentage range to weight per volume percent, or if the parenthetical (w/v) is merely exemplary. For purposes of examination, the percentage range “between 0.01% and 10%” is being interpreted as between 0.01% w/v and 10% w/v. Claim 12 recites the trademark Triton X100. Claim 12 is therefore indefinite because a trademark or trade name cannot be used in the claim as a limitation to identify or describe a particular material or product. See MPEP 2173.05(u). Claims 14-15 recites “wherein the detection in c)”. There is insufficient antecedent basis for this limitation in the claim because there is no prior recitation of a step c). Claim Rejections - 35 USC § 103 07-20-aia AIA The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. 07-23-aia AIA The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. 07-21-aia AIA Claim (s) 1-17 is rejected under 35 U.S.C. 103 as being unpatentable over Ray et al. (US20050245733A1 in IDS filed 01/31/2024)in view of Hendriks et al. (US20030068810A1 in IDS filed 01/31/2024) . Ray discloses methods for the reduction of endotoxins in a plasmid preparation using a carbohydrate non-ionic detergent with silica chromatography (Abstract). Ray disclose their method comprises the following: a) preparation of a solution which comprises a medium of the nucleic acids to be purified, a binding solution and a carbohydrate non-ionic detergent; b) application of the solution from step a) to a binding matrix; c) washing of the binding matrix from step b) with one or more wash solutions, wherein the wash solutions comprise, alone or in combination, a binding solution, an alcohol solution and optionally a carbohydrate non-ionic detergent; and d) elution of the nucleic acids from the binding matrix of step c) (claim 1). Ray discloses that the biological source to be purified contains plasmid DNA (claim 2). Ray discloses the carbohydrate non-ionic detergent is an alkyl carbohydrate non-ionic detergent selected from the group consisting of alkyl thioglucosides, alkyl glucosides, alkyl thiomaltosides, alkyl maltosides and sucrose monoalkyl esters (claim 10). Ray discloses that the binding matrix is an inorganic material such as silica (claims 12 and 14) or an organic material such as cellulose, dextran, agarose, anion exchange resins, acrylic amides, polystyrene resins and copolymers (claims 15-16). Ray demonstrates their method in Example 1 (paragraphs 0106-0114). Here, cell lysate from E. coli strain HB101 harboring pBICEP-CMV-1-LacZ was prepared for silica column by first mixing in 9mL of Binding solution (5% n-octyl-β-D-thioglucopyranoside, 8M guanidine hydrochloride). Here, as evidenced by ThermoFisher, the n-octyl-β-D-thioglucopyranoside is an alkylglycoside used as a non-ionic detergent (page 1). The mixture was then loaded onto the silica column and drawn through by vacuum, in which the plasmid DNA absorbed onto the silica membrane while the endotoxins were prevented from binding to the matrix. Contaminants were further removed by the addition of 12 ml of Wash Solution 1 (100 mM Tris Acetate, 4.5 M guanidine hydrochloride, 25% Isopropanol, pH 6.9), followed by 12 ml of Wash Solution 2 (10 mM Tris-HCl, 10 mM NaCl, 80% Ethanol, pH 8.0). The plasmid DNA were then eluted by addition of 3 ml of endotoxin-free water and centrifuging. The recovered eluates were then ready for analysis and for use in downstream applications. Endotoxin levels were determined to be 24 EU/mg by using a QCL-1000 LAL kit (LAL assay) with the results shown in Table 7 (paragraph 0114). Ray further demonstrates in Example 3 (paragraphs 0117) the purification of plasmid using the method in Example 1 described above but using different types of detergents listed in Table 10 (paragraph 0117). Here, Triton X100 2.5% was used with the endotoxin levels being 4700 EU/mg as shown in Table 7, which was much higher the endotoxin levels using the n-octyl-β-D-thioglucopyranoside detergent from Example 1. Ray discloses that their results indicate that only carbohydrate non-ionic detergents provide good plasmid yields along with low endotoxin levels (paragraph 0117). Even though Ray does not exemplify the use of an anion-exchange resin, it would have been prima facie obvious before the effective filing date of the claimed invention to have selected anion exchange resin as the binding matrix in the method of Ray. One of ordinary skill in the art would have combined prior art elements according to known methods to yield predictable results and would have a reasonable expectation of success in doing so because Ray discloses that that the binding matrix in their chromatography method can be selected from a list of organic material which include cellulose, dextran, agarose, anion exchange resins, acrylic amides, polystyrene resins and copolymers. Even though Ray teaches the use of anion-exchange resin as described above, Ray does not teach a membrane form comprising anion exchange groups. Hendriks discloses a method for removing endotoxins from nucleic acids, and the endotoxins are removed by pre-incubating the nucleic acids in a salt-free detergent solution and subsequent anion exchange chromatography on a tentacle anion exchanger (Abstract). Hendriks discloses that their anion exchange chromatography consists of organic or inorganic polymeric moldings, which are taken to mean porous and non-porous polymeric materials, such as, for example, bead-shaped moldings, membranes, tubes, hollow-fiber membranes or sponges (paragraph 0029). Hendriks discloses that the functional groups on the anion exchange material are bonded to monomer units of polymer chains which are polymerized onto a base support (paragraph 0030). Hendriks disclose preferred functional groups include trimethylammoniumethyl (TMAE), diethylaminoethyl (DEAE) or dimethylaminoethyl (DMAE) (paragraph 0072). Hendriks discloses that the base support for the anion exchange can be natural polymers, such as dextran, agarose or cellulose, silica gel or synthetic polymers, such as polystyrene and methacrylate (paragraph 0034). It would have been prima facie obvious before the effective filing date of the claimed invention to have further substituted the resin material in the anion exchange resin as disclosed in the teachings of Ray described above with a membrane polymer material such as cellulose or dextran membranes as disclosed in Hendriks to arrive at the claimed invention. One of ordinary skill in the would have substituted one known element (resin material) for another (membrane polymer material) to obtain predictable results and would have a reasonable expectation of success in doing so because both Ray and Hendriks teach the same method of removing endotoxins from nucleic acids using the same steps of pre-treating with a detergent solution and performing chromatographic separation using anion exchange. Furthermore, Hendriks provides guidance that suitable forms for the anion exchange include membranes and further discloses that the base material can be polymers such as cellulose or dextran. Double Patenting 08-33 AIA The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg , 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman , 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi , 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum , 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel , 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington , 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA/25, or PTO/AIA/26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer. Claims 1-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 6,617,443 in view of Ray et al. (US20050245733A1 in IDS filed 01/31/2024) and as evidenced by ThermoFisher (n-Octyl β-D-thioglucopyranoside information from ThermoFisher website in PTO-892). US’443 recites a method for the reduction in endotoxin levels in nucleic acids originating from natural, genetic engineering or biotechnological sources, comprising the following steps: a) preparation of a medium which contains the nucleic acids to be purified; b) pre-incubation of the medium from step a) with a salt-free detergent solution; c) application of the incubation solution from step b) to anion exchanger material whose functional groups are bonded to tentacles on the surface of the support; d) washing of the anion exchanger, in which the impurities are washed out by increasing the ion strength and/or by pH changes; e) elution of the sample by a further increase in the ion strength and/or by a pH change (claim 1). US’443 recites wherein the biological source to be purified contains plasmid DNA (claim 2). US’443 recites wherein the anion exchanger is washed by a buffer that contains an organic solvent or solvent mixture up to 20% by volume, and wherein the solvent is or the solvent mixture comprises ethanol or methanol or both ethanol and methanol (claims 7-8). US’443 recites that the anion-exchanger material can be several different polymeric materials including polyamide, polyvinyl alcohol or copolymers of (meth)acrylate derivatives (claims 12-16). US’443, however, does not recite a non-ionic detergent as well as a further LAL assay detection step. The teachings of Ray are as described above. It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the method of US’443 by adding in 5% n-octyl-β-D-thioglucopyranoside into the salt-free detergent solution and further including the LAL detection step disclosed in Ray to arrive at the claimed invention. One of ordinary skill in the art would have combined known prior art elements according to known methods to yield predictable results and would have a reasonable expectation of success in doing so because both US’443 and Ray disclose the same method of reducing endotoxin in plasmid DNA using the same steps of pre-treating with a detergent solution and performing chromatographic separation using anion exchange. Claim 1-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/845,072 (‘072) in view of Ray et al. (US20050245733A1 in IDS filed 01/31/2024) and as evidenced by ThermoFisher (n-Octyl β-D-thioglucopyranoside information from ThermoFisher website in PTO-892). ‘072 recites all of the same steps and limitation as the instant method except ‘072 recites the use of a zwitterionic detergent instead of the recited nonionic detergent and also does not recite a further step of detection using LAL assay. It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the method of ‘072 by substituting the zwitterionic detergent of ‘072 with the 5% n-octyl-β-D-thioglucopyranoside as disclosed in Ray and further including the LAL detection step disclosed in Ray to arrive at the claimed invention. One of ordinary skill in the art would have substituted one known element (zwitterionic detergent) for another (5% n-octyl-β-D-thioglucopyranoside) to obtain predictable results as well as combine known prior art elements according to known methods to yield predictable results of including the LAL detection step and would have a reasonable expectation of success in doing so because both ‘072 and Ray disclose the same method of removing endotoxins from nucleic acid using the same steps of pre-treating with a detergent solution and performing chromatographic separation using anion exchange. This is a provisional nonstatutory double patenting rejection. Conclusion No claim is found allowable. Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID H CHO whose telephone number is (571)270-0691. The examiner can normally be reached M-F 8AM-5PM. 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, Scarlett Goon can be reached at 571-270-5241. 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. /D.H.C./Examiner, Art Unit 1693 /SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693 Application/Control Number: 18/294,123 Page 2 Art Unit: 1693 Application/Control Number: 18/294,123 Page 3 Art Unit: 1693 Application/Control Number: 18/294,123 Page 4 Art Unit: 1693 Application/Control Number: 18/294,123 Page 5 Art Unit: 1693 Application/Control Number: 18/294,123 Page 6 Art Unit: 1693 Application/Control Number: 18/294,123 Page 7 Art Unit: 1693 Application/Control Number: 18/294,123 Page 8 Art Unit: 1693 Application/Control Number: 18/294,123 Page 9 Art Unit: 1693 Application/Control Number: 18/294,123 Page 10 Art Unit: 1693 Application/Control Number: 18/294,123 Page 11 Art Unit: 1693 Application/Control Number: 18/294,123 Page 12 Art Unit: 1693
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