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
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on April 14, 2026 has been entered. Claims 1-4, 10-15, 17-19, 21-22, and 24-28 are pending.
The following is a new rejection.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-4, 10-15, 17-19, 21-22, and 24-28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claims 1 and 27-28 were amended to recite a flow rate of at least 5 column volumes per min. Claim 4 was amended to recite a flow rate of at least 10 column volumes per minute. The amendments introduce new matter because the flow rate is recited with no upper limit. The specification provides support for a flow rate up to 1,000 CV/minute but not “at least” a flow rate with no upper limit. See MPEP 2163. A claim limitation “at least 35%” did not meet the description requirement because “at least” had no upper limit and caused the claim to read literally on embodiments outside of the disclosed range.
The following is a modified rejection.
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) 1-4, 11, 14, 19, 22, and 24-28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhou (US 20200188859A1, June 18, 2020, cited on IDS) in view of Boschetti (FR2981651A1, 2013, machine translation and original document)
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. Zhou exemplifies a macroporous support comprising a regenerated cellulose membrane with a specific surface area of 0.1-20 m2/mL (claim 2) which is derivatized with a Protein A ligand and is used for purifying a protein [0011]. The dynamic binding capacity is 20-90 mg/ml membrane [0011]. The process of purification includes load, rinse, elution, and regeneration steps [0059]. Zhou also teaches that a membrane can be prepared to purify messenger RNA [0007]. An oligonucleotide solution is used to target plasmid DNA or messenger RNA [0076]. The ligand can be oligo-deoxythymidine [0061]. The pore size is 0.2, .45 or 1 µm [0065].
Zhou does not teach a spacer linking the affinity ligand and the membrane, is silent about the flow rate, and the dynamic binding capacity taught by Zhou is higher than the claimed dynamic binding capacity (at least 20 versus the claimed maximum 15).
Like Zhou, 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.
It would have been obvious to one of ordinary skill in the art at the time the application was filed to prepare Zhou’s membrane comprising an oligo-deoxythmidine ligand for purifying RNA or DNA because Zhou suggests it. It would have been further obvious to include a spacer for the reasons taught by Boschetti, such as to increase reactivity and decrease steric hindrance. The skilled artisan would have optimized the dynamic binding capacity using routine experimentation to achieve the most efficient separation. See MPEP 2144. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.”
The skilled artisan would have optimized the flow rate using routine experimentation, and the claimed ranges are 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 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhou in view of Boschetti and Goss (Journal of Chromatography, 588 (1991) 157-164, previously cited by the examiner).
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 Zhou’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 Zhou in view of Boschetti 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 Zhou’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 Zhou in view of Boschetti and Jacobsen (Nucleic Acids Research 2004, Vol. 32, No. 7 e64, previously cited by the examiner).
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 Zhou’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 moot because the modified rejection does not rely on the inherency of dynamic binding capacity.
Conclusion
No claims are allowed.
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/LAYLA D BERRY/ Primary Examiner, Art Unit 1693
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