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 .
CONTINUING DATA
This application is a 371 of PCT/US2021/059363 11/15/2021
PCT/US2021/059363 has PRO 63/113,594 11/13/2020
This office action is in response to Applicant’s amendment submitted December 10, 2025. Claims 1-6 and 10-23 are pending.
The rejection of claim 12 under 35 U.S.C. 112(b) is withdrawn in view of Applicant’s amendment to remove the narrow range.
The rejection of claims 1-6, 8-9, 14, 16, and 19 under 35 U.S.C. 103 as being unpatentable over Zhou is withdrawn because Zhou does not teach a spacer comprising a carbon-based monomer.
The following new rejections were necessitated by Applicant’s amendment.
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.
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.
Claim(s) 1-6, 11, 14, 16, 19, and 22-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Boschetti (FR2981651A1, 2013, machine translation and original document) in view of Zhou (US 20200188859A1, June 18, 2020, cited on IDS).
Boschetti teaches affinity supports. Nucleic acids are immobilized on a solid support such as a membrane via a spacer chain. Page 12. The spacer chain physically distances the polynucleotide from the surface of the solid support, which increases the relative mobility of the nucleotide part of the ligand and reduces steric hindrance. The spacer string is a C3, C6, or C12 carbon chain. Page 13. The spacer prevents interfering with the binding events between the nucleic acid and the target ligand. Page 18, end. The target molecules to be purified include RNA and DNA molecules. Page 7, end. The affinity support is illustrated on page 30.
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Table 4 describes Oligo 4 wherein 3’dT is the nucleic acid and is linked via a C12 spacer.
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In one example, human factor VII is retained on the affinity support and released during the elution step. Page 30.
The nucleic acid can be 5 to 120 nucleotides in length, and the nucleotide can be modified on the sugar part or the nitrogenous base. Page 6. Preferably, the nucleic acid comprises 20 to 60 nucleotides. Page 18.
In Example 1, the solid support was NHS Activated Sepharose 4 fast flow (GE), which is a macroporous beaded agarose. Page 21, top.
Boschetti is silent about the specific surface area of the support and does not exemplify purification of RNA or DNA using Oligo 4.
Zhou teaches an adsorptive media for binding biologic molecules comprising a macroporous support functionalized with nucleotides having an affinity to a biologic target molecule. See abstract. The membrane is a regenerated cellulose membrane with a specific surface area of 0.1-20 m2/mL (claim 2). The ligand can be oligo-deoxythymidine [0061]. The membrane is used to purify messenger RNA [0007]. Oligonucleotide solution is used to target plasmid DNA or messenger RNA [0076]. The process of purification includes load, rinse, elution, and regeneration steps [0059].
Zhou and Boschetti are silent about the dynamic binding capacity for polynucleotide, but the current specification illustrates that oligo-dT affinity membranes have a DBC of about 4 to about 11 (Figure 3), so the DBC is inherent. The basis in fact and/or technical reasoning for concluding that the claimed dynamic binding capacity is inherent in the prior art oligo-dT based affinity membranes is that dynamic binding capacity depends strongly on the affinity ligand used, and other oligo-dT based affinity membranes have a dynamic binding capacity well within the claimed range.
It would have been obvious to one of ordinary skill in the art at the time the application was filed to prepare Boschetti’s composition using Zhou’s solid support, and to use the composition for purifying RNA or DNA. The skilled artisan would have utilized Zhou’s solid support because Boschetti teaches that any common support can be used (page 12, top), and Zhou’s support can be attached to oligo-deoxythymidine and used for purifying RNA and DNA, like Boschetti’s support. The skilled artisan would have optimized the flow rate using routine experimentation, and the range recited in claim 4 is very broad. The skilled artisan would have optimized the volume using routine experimentation, and the range recited in claim 11 is very broad. The skilled artisan would have repeated the process in order to achieve the largest amount of pure product, and the limitations of claim 14 are inherent in Zhou’s or Boschetti’s products because the prior art products have the same ligand as was used in the current specification. It would have been obvious to employ the support wherein the oligo-deoxythymidine sequence comprises 20 to 25 bases because Boschetti teaches that the nucleic acid preferably is 20 to 60 bases in length. The claimed range lies inside the prior art range. The claimed range 5 to 100 lies inside the prior art range 5-120. MPEP 2144.05 stats that in the case where claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists.
Claim(s) 12-13, 15, 18, and 20-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Boschetti in view of Zhou and Goss (Journal of Chromatography, 588 (1991) 157-164).
Boschetti and Zhou teach as set forth above, but do not teach that the feed solution has a conductivity.
Goss teaches that mRNA is purified using a 50-mer of thymidylic acid coupled to silica inside prepacked columns using N-hydroxysuccinimide chemistry. See abstract. The separation is carried out at pH 7.5 and 1M NaCl (a conductive washing fluid) is added prior to injection (page 159, Chromatography). The length of mRNA is greater than one kilobase (page 159, Results). The flow rate was 1 ml/min and there was a salt gradient from 0% B to 100% B. Figure 2.
It would have been obvious to one of ordinary skill in the art at the time the application was filed to carry out Boschetti’s method as described above, using a conductive feed solution because Goss teaches that a salt gradient is used to elute mRNA.
Claim(s) 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Boschetti in view of Zhou (US 20200188859A1, June 18, 2020) and Utermohlen (US 5,595,879, 1997, cited on IDS).
Boschetti and Zhou teach as set forth above, but do not teach that the ligand comprises one or more base substitutions.
Utermohlen teaches purification of mRNA using an affinity ligand such as oligo-d(T). See abstract. The oligo-d(T) ligand is one example, but ligands having guanosine residues or derivatized bases may be used (column 8, first paragraph).
It would have been obvious to one of ordinary skill in the art at the time the application was filed to carry out Boschetti’s method of purifying nucleotides as discussed above, and further wherein the ligand comprises one or more base substitutions. Boschetti teaches that the ligand may be a nucleotide which can be modified at the nitrogenous base, and Utermohlen teaches that ligands used for the same purpose may comprise base substitutions, so the skilled artisan would have employed a ligand having base substitutions.
Claim(s) 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Boschetti in view of Zhou (US 20200188859A1, June 18, 2020) and Jacobsen (Nucleic Acids Research 2004, Vol. 32, No. 7 e64).
Boschetti and Zhou teach as set forth above, but do not teach that the affinity ligand comprises one or more locked nucleic acid bases.
Jacobsen teaches that LNA oligonucleotides have an exceptionally high affinity for their complementary DNA and RNA target molecules, and Jacobsen used an LNA-substituted oligo(dT) ligand. See abstract.
It would have been obvious to one of ordinary skill in the art at the time the application was filed to carry out Boschetti’s method of purifying nucleotides as discussed above, and further wherein the ligand comprises one or more locked nucleic acid bases because LNA nucleotides have an exceptionally high affinity for their complementary DNA and RNA target molecules.
Response to Arguments
Applicant argues that it is improper for the examiner to rely on Applicant’s own experimental data to support disclosure of a claim feature. This argument is not persuasive because the examiner is not using Applicant’s data for a judgment on obviousness, but as evidence supporting the inherency of the dynamic binding capacity of an affinity support having oligo-dT as the affinity ligand. It would have been obvious to the skilled artisan to utilize oligo-dT as the affinity ligand for purifying polynucleotides because the prior art suggests it, and the resulting dynamic binding capacity is inherent in the use of the oligo-dT ligand because a chemical composition and its properties are inseparable. The conclusion of obviousness does not include knowledge gleaned only from applicant’s disclosure.
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.
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/LAYLA D BERRY/ Primary Examiner, Art Unit 1693