DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . The amendment filed on 10/13/2025 has been entered. Claims 5-7, 11, 15-20, and 24-67 are cancelled. Claims 1-4, 8-10, 12-14, and 21-23 are pending in this application, and are currently under examination.
Priority
This application is a 371 of PCT/US2021/043769 filed on 07/29/2021 and claims benefit of US PRO 63/058,179 filed on 07/29/2020.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/058,179, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Claims 1-4, 8-10, 12-14, and 21-23 recite “the pH of the acidic binding solution is between 2.0 and 4”, “a particle”, “a fiber”, “a magnetic particle”, “a magnetic fiber”, “partially-sulfonated DNA or fully sulfonated DNA”, “glycine, malate, formate”, “guanidine isothiocyanate”, “single-stranded non-sulfonated DNA or partially-sulfonated DNA”, “sodium bisulfite”, “separating sulfonated DNA bound to the silica support from the acidic binding solution to produce separated sulfonated DNA”, and/or “a portion (or all) of the sulfonation reaction solution is removed”, “size exclusion filtration”, which are not disclosed or supported by the prior-filed Application No. 63/058,179. Thus, the priority date of claims 1-4, 8-10, 12-14, and 21-23 is 07/29/2021.
Election/Restrictions
Applicant's election without traverse of Group I invention (claims 1-4, 8-14, and 21-23) and species (in claim 10 step i), separating sulfonated DNA bound to the silica support from the acidic binding solution to produce separated sulfonated DNA), in the reply filed on 10/13/2025 is acknowledged. Claim 11 is cancelled. Preliminary search found art that teaches other steps of claim 10. Thus, claims 1-4, 8-10, 12-14, and 21-23 are currently under examination.
Information Disclosure Statement
Three information disclosure statement (IDS) filed on 03/31/2023, 11/26/2024, and 11/18/2025 with appropriate assertion under 37 CFR 1.98 have been considered.
Claim Objections
Claims 1, 4, 10, 12-14, 21, and 22 are objected to because of the following informalities: In claim 1, change the incorrect recitation “combining sulfonated DNA and a silica” (line 1) to “a process for binding sulfonated DNA to a silica” to be consistent with intended purpose or result. In claim 4, insert the missing phrase “the group consisting of” immediately after the recitation “selected from” (line 5) to comply with Markush group format ending with conjunction “and” before the last species “citrate buffer”. In claim 10, insert the phrase “steps in sequence” immediately after the recitation “at least one of” (line 1) because, for example, the “treating separated sulfonated DNA” cannot be performed without the preceding “separating sulfonated DNA…to produce separated sulfonated DNA”; and change the incorrect recitation “conditions wherein the separated” (line 5) to “conditions in which the separated” to define the “conditions”. In claim 12, change the incorrect recitation “claim 10, wherein” (line 1) to “claim 8, wherein” because claim 10 is further step after binding of the sulfonated DNA, not the claimed “prior to”; replace the incorrect recitation “sulfonation reaction solution is removed” (line 2) with “sulfonation reagent is removed” because the reaction solution contains sulfonated DNA according to claim 8; and change the incorrect recitation “combining the sulfonated DNA and the silica” (lines 2 to 3) to “binding of the sulfonated DNA to the silica” to be consistent with intended purpose or result. In claim 13, change the incorrect recitation “claim 12, wherein” (line 1) to “claim 8, wherein” because claim 12 is further step, not the claimed “prior to”; replace the incorrect recitation “sulfonation reaction solution is removed” (lines 1 to 2) with “sulfonation reagent is removed” because the reaction solution contains sulfonated DNA; and change the incorrect recitation “combining the sulfonated DNA and the silica” (lines 2 to 3) to “binding of the sulfonated DNA to the silica” to be consistent with intended purpose or result. In claim 14, change the incorrect recitation “sulfonation reaction solution is removed” (lines 1 to 2) to “sulfonation reagent is removed” because the reaction solution contains sulfonated DNA. In claim 21, delete excessive recitation “incubated with the sulfonation reagent” (line 2) because the recitation “comprises one or more unmethylated” (line 3) refers directed to the preceding “DNA”, not “reagent”. In claim 22, change the incorrect recitation “conditions wherein the separated” (line 3) to “conditions in which the separated” to define the “conditions”; and replace the grammatically incorrect recitation “desulfonated comprises combining” (lines 2 to 3) with “desulfonated by combining”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 2, 4, and 12-14 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claims 2 and 4 recite the broad recitation “at least one of a particle… a fiber” (line 2 of claim 2), or “more of… acid binding buffer comprises… acetate… comprises a chaotropic salt” (lines 2 and 5-7 of claim 4), and the claim also recites “a magnetic particle… a magnetic fiber” (lines 2 to 3 of claim 2), or “a chaotropic salt comprising at least one of guanidine hydrochloride (GuHCl) and guanidine isothiocyanate… acid binding buffer comprises… acetate… a chaotropic salt; and a chaotropic salt solution” (lines 8-14 of claim 4), which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 12 and 14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The omitted structural cooperative relationships are: Claims 12 and 14, recite “at least a portion”, in which the “a” means any and encompasses entire portion. The “at least” entre portion would be confusing.
The term “essentially all” in claim 13 is a relative term which renders the claim indefinite. The term “essentially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Taken together, Applicant is advised to delete the recitation “at least” (line 2 of claim 2); to delete the recitation “or more” (line 2 of claim 4); to delete the recitation “a chaotropic salt;” (2nd line from the end of claim 4); delete the recitation “at least” (line 1 of claims 12 and 14); and delete the recitation “essentially” (line 1 of claim 13).
Claim Rejections - 35 USC § 102/103
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
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.
(I) Claims 1-4, 8-10, and 21-23 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Markert-Hahn et al. (US 9,394,332, Jul. 19, 2016, hereinafter referred to as Markert ‘332) incorporated by Michelsen et al. (WO 99/40098, January 22, 1999, also listed in IDS filed on 11/26/2024, English cited from US 6,355,792, Mar. 12, 2002, hereinafter referred to as Michelsen ‘792).
With regard to structural limitations “a method comprising a process for binding sulfonated DNA (or partially- or fully sulfonated DNA) to a silica support (or a bead or particle; or a magnetic bead or particle) in an acidic binding solution having pH between 2.0 and 4 (or comprising an acetate, formate, or citrate buffer solution; or comprising a chaotropic salt)” (claims 1-4 and 21), “further comprising incubating single-stranded non-sulfonated DNA or partially-sulfonated DNA (or comprising one or more unmethylated cytosine nucleotides) with a sulfonation reagent (or sodium bisulfite) to produce the sulfonated DNA (or claim 8, further separating sulfonated DNA bound to the silica support from the acidic binding solution to produce separated sulfonated DNA; washing a silica support bound to sulfonated DNA; treating separated sulfonated DNA under conditions in which the separated sulfonated DNA is desulfonated (or by combining with a desulfonation solution; or while bound to the silica support) to produce desulfonated DNA; and eluting the-desulfonated DNA from the silica support)” (claims 8-10, 22, and 23):
Markert ‘332 disclosed a method for the conversion of cytosine bases in a nucleic acid to uracil bases whereby 5-methyl-cytosine bases are not significantly converted ("bisulfite reaction"), comprising the steps of: a) incubating the nucleic acid in the presence of sulfite ions whereby the nucleic acid is deaminated, b) binding the deaminated nucleic acid to a solid phase, c) optionally washing the deaminated solid phase bound nucleic acid, d) incubating the deaminated solid phase bound nucleic acid under alkaline conditions whereby the deaminated nucleic acid is desulfonated, e) optionally washing the deaminated and desulfonated solid phase bound nucleic acid, and f) optionally eluting the deaminated and desulfonated nucleic acid from the solid phase. In an embodiment, the nucleic acid is desoxyribonucleic acid (DNA). In a particularly preferred embodiment, the solid phase is a material comprising glass or silica, preferably with an unmodified (glass or silica) surface, e.g. glass fibers or, diatomaceous earth, glass beads or particles. In a very preferred embodiment, the solid phase is a magnetic glass particle. Preferably, binding of the nucleic acid to the magnetic glass particles is preferably performed in the presence of chaotropic salts. Chaotropic salts can be sodium iodide, sodium perchlorate, guanidinium thiocyanate, guanidinium isothiocyanate or guanidinium hydrochloride. The material with the bound nucleic acid may then be washed at least once, preferably in an acidic wash solution as described in WO 99/40098. A wash solution is used that does not cause the nucleic acids and the target nucleic acid to be released from the material surface but that washes away the undesired contaminants as thoroughly as possible. This wash step preferably takes place by incubating the glass or silica with the bound nucleic acid (page 5/17, col. 3, lines 62-67; col. 4, lines 1-10, 35, and 36; page 6/17, col. 5, lines 15-19 and 53-55; page 7/17, col. 8, lines 28-35 and 64-67; page 8/17, col. 9, lines 1-6). Bisulfite reaction: (i) Denaturation of DNA: 100 μl of methylated DNA dilution and 12 μl 2 M NaOH are mixed and incubated for 15 min at 37° C; (ii) Deamination of DNA: 112 μI of the denatured DNA are mixed with 200 μI bisulfite reagent (2.5M sodium disulfite, 125 mM hydroquinone, pH 5.0) and incubated for 16 h at 50° C (page 11/17, col. 16, lines 40-51). Michelsen ‘792 (incorporated here as cited by Markert ‘332 above) disclosed that binding of nucleic acids to inorganic oxide carrier materials is possible even without addition of chaotropic substances if the pH is lowered to 1 to 6 by the binding buffer. Preferred carrier materials are silica gel and hydroxyapatite. The binding of the nucleic acids from the sample is carried out by means of simple lowering of the pH to below pH 6. For this, a binding buffer can maintain a pH range from 1 to 6, preferably from 3 to 5. Suitable buffers are, for example, formate, acetate, citrate buffers. Preferably, a binding buffer of concentration of 50 mM is used which has a pH of about 4.5, e.g. a buffer consisting of acetic acid which has been adjusted to a pH of between 4 and 5 (page 2/6, col. 2, lines 5-9, 35, and 36; page 4/6, col. 3, lines 11-24).
Thus, these teachings of Markert ‘332 incorporated by Michelsen ‘792 anticipate Applicant’s claims 1-4, 8-10, and 21-23 because (a) the sulfite-cytosine when incubating DNA with bisulfite compound or deaminated DNA is sulfonated DNA, either partially or fully sulfonated depending on the degree of sulfonation, and (b) the acid wash buffer and acid binding buffer are exchangeable because they maintain the binding of DNA onto the silica material, and the preferable pH 3 to 5, pH between 4 and 5, and pH about 4.5 provide specifically an alternative pH range of 3 to 4. Or, in an alternative, one of skilled artisan would follow the teachings of Markert ‘332 incorporated by Michelsen ‘792 to obtain acid pH of 2 to 4 or 3 to 4 because several alternative pH ranges were taught by Michelsen ‘792 as acid wash/binding buffer to retain DNA binding to the silica material.
(II) Claims 1-4, 8-10, 12-14, and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Markert-Hahn et al. (US 9,394,332, Jul. 19, 2016, hereinafter referred to as Markert ‘332) incorporated by Michelsen et al. (WO 99/40098, January 22, 1999, also listed in IDS filed on 11/26/2024, English cited from US 6,355,792, Mar. 12, 2002, hereinafter referred to as Michelsen ‘792), in view of Domanico et al. (US 10,144,953, Dec. 4, 2018, hereinafter referred to as Domanico ‘953, also listed in IDS filed on 03/31/2023). Claims 1-4, 8-10, and 21-23 are rejected here because they have been rejected by the primary reference under 102 above, and thus the above disclosure by Markert ‘332 incorporated by Michelsen ‘792 is incorporated entirely here. Michelsen ‘792 also disclosed that High molecular weight, genomic DNA of eukaryotic cells can likewise be captured and purified by simple lysis of the cells by means of detergence and physical interaction of the long DNA threads with microparticles or large-pore filters (page 3/6, col. 1, lines 19-23).
Markert ‘332 incorporated by Michelsen ‘792 did not explicitly disclose the limitations “a portion (or all) of the sulfonation reagent is removed (or by size exclusion filtration) from the sulfonated DNA prior to the binding of the sulfonated DNA to the silica support”, required by claims 12-14.
Domanico ‘953 disclosed that, in some embodiments, aspects of the technology relating to the bisulfate reaction are combined with other suitable methods of DNA isolation (e.g., precipitation, column chromatography (e.g., a spin column) (page 18/26, col. 9, lines 53-57).
Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to combine the bisulfite treatment method of Markert ‘332 incorporated by Michelsen ‘792 with a further step of using a spin column to retain DNA according to pore size of filter or spin column in view of Michelsen ‘792 and Domanico ‘953 to remove bisulfite reagent prior binding to the silica particle or bead, because filter or spin column retains or purifies DNA according to the size or molecular weight of the DNA. Thus, one of skill in the art would have a reasonable expectation that by combining the bisulfite treatment method of Markert ‘332 incorporated by Michelsen ‘792 with a further step of using a spin column to retain DNA according to pore size of filter or spin column in view of Michelsen ‘792 and Domanico ‘953 to remove bisulfite reagent prior binding to the silica particle or bead, one would achieve Applicant’s claims 1-4, 8-10, 12-14, and 21-23. “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” Id. at ___, 82 USPQ2d at 1395. See MPEP § 2141 [R-01.2024].
Conclusion
No claims are allowed.
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/YIH-HORNG SHIAO/Primary Examiner, Art Unit 1691