DETAILED CORRESPONDENCE
Application Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s amendment to the claims filed on 05/26/2026 in response to the Non-Final Rejection mailed on 02/26/2026 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
3. Claims 1-2, 26-30, 32-34, and 36-44 are pending.
4. Claims 1-2, 34, and 36-44 stand withdrawn pursuant to 37 CFR 1.142(b).
5. Applicant’s remarks filed on 05/26/2026 in response to the Non-Final Rejection mailed on 02/26/2026 have been fully considered and are deemed persuasive to overcome at least one of the rejections and/or objections as previously applied.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Action.
Specification/Drawings
6. The objection to the specification and drawings under 37 CFR 1.821 is withdrawn in view of applicants’ filing of a sequence listing, CRF, replacement drawings and specification on 05/26/2026 to insert appropriate sequence identifiers.
Claim Rejections - 35 USC § 112(b)
7. The rejection of claims 29-30 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for indefiniteness is withdrawn in view of applicants’ amendment to the claims to remove the term “about”.
Claim Rejections - 35 USC § 103
8. The rejection of claims 26-29 and 33 under 35 U.S.C. 103 as being unpatentable over Bosnes et al. (Invitrogen, 2017; cited on IDS filed on 01/12/2024) is maintained for the reasons of record and the reasons set forth below. The rejection has been modified in order to address applicants’ amendment to the claims.
9. As amended, claims 26-29 and 33 are drawn to a method for producing a purified ribonucleic acid (RNA) molecule, the method comprising: a) fixing a first magnetic bead in place by a magnetic field, wherein an in vitro transcription (IVT) template is linked to the first magnetic bead; b) contacting the first magnetic bead of step a) with a reagent mixture suitable for IVT of the template under condition in which IVT occurs, thereby producing an RNA molecule; c) separating the RNA molecule from the first magnetic bead, thereby producing the RNA molecule; d) contacting the purified RNA molecule of step c) with a second magnetic bead under conditions that allows for the purified RNA molecule to remain associated with the second magnetic bead during washing; e) washing of the second magnetic bead while the second magnet bead is fixed in place by a magnetic field; f) releasing the purified RNA molecule from association with the second magnetic bead, thereby producing a highly purified RNA molecule; and g) repeating steps a) to f) at least once, wherein the second magnetic bead of step f) of the (or each) immediately previous cycle is reused as the second magnetic bead in step d) of the following cycle, and optionally wherein the first magnetic bead of step c) of the (or each) immediately previous cycle is reused as the first magnetic bead in step a) of the following cycle, and wherein step g) comprises repeating steps a) to f) at least 3 times.
10. With respect to claim 26, Bosnes et al. each a method for producing a purified ribonucleic acid (RNA) molecule, the method comprising: a) fixing a streptavidin functionalized Dynabead in place by a magnetic field, wherein an in vitro transcription (IVT) template is linked to the first magnetic bead; b) contacting the first magnetic bead of step a) with a reagent mixture suitable for IVT of the template under condition in which IVT occurs, thereby producing an RNA molecule; c) separating the RNA molecule from the first magnetic bead, thereby producing the RNA molecule; d) contacting the purified RNA molecule of step c) with a second magnetic bead under conditions that allows for the purified RNA molecule to remain associated with the second magnetic bead during washing; e) washing of the second magnetic bead while the second magnet bead is fixed in place by a magnetic field; f) releasing the purified RNA molecule from association with the second magnetic bead, thereby producing a highly purified RNA molecule [see Column 1; Figures 1-4].
With respect to claim 28, Bosnes et al. teach the method wherein the first magnetic bead is a streptavidin coated magnetic bead and the second bead is a carboxylic acid coated bead [see column 1 under Materials and Figures 1 and 5].
With respect to claim 29, Bosnes et al. teach the method wherein the magnetic beads are Dynabeads. Although Bosnes et al. does not explicitly teach wherein the beads comprise a saturation mass magnetization of about 30 emu/g to about 90 emu/g, given that Dynabeads are identical to the magnetic beads used in the present disclosure, it is the examiner’s position that absent evidence otherwise, this feature is inherent to the Dynabeads taught by Bosnes et al. Since the Office does not have the facilities for examining and comparing applicants’ beads with the beads of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the Dynabeads of the prior art does not possess the same material structural and functional characteristics of the claimed magnetic beads). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
With respect to claim 33, Bosnes et al. teach the method wherein the IVT template is a DNA produced by PCR using a biotinylated forward primer [see Figure 1].
Although Bosnes et al. does not explicitly teach the method of claim 26, g) repeating steps a) to f) at least three times, wherein the second magnetic bead of step f) of the (or each) immediately previous cycle is reused as the second magnetic bead in step d) of the following cycle, and optionally wherein the first magnetic bead of step c) of the (or each) immediately previous cycle is reused as the first magnetic bead in step a) of the following cycle and 27 wherein step g) comprises repeating steps a) to f) at least 4, 5, or 6 times, Bosnes et al. does teach that IVT can be efficiently performed from a biotinylated template immobilized on Dynabeads Streptavidin beads and immobilized templates can be re-used in sequential reactions, and higher concentrations of mRNA can be obtained by including concentration steps using different beads for generic binding and elution [see column 1]. As such, before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to optimize the method conditions for repeating steps and one of ordinary skill in the art would desire to do so in order to maximize mRNA production and purification for downstream therapeutic applications as taught by Bosnes et al.
11. The rejection of claims 30 and 32 under 35 U.S.C. 103 as being unpatentable over Bosnes et al. (Invitrogen, 2017; cited on IDS filed on 01/12/2024) as applied to claims 26-29 and 33 above, and further in view of Finne et al. (WO 2006/085104 A1; cited on IDS filed on 01/12/2024) and Bosch (WO 2015/188994 A1; cited on IDS filed on 01/12/2024 with machine translation attached) is maintained for the reasons of record and the reasons set forth below. The rejection has been modified in order to address applicants’ amendment to the claims.
12. The relevant teachings of Bosnes et al. as applied to claims 26-29 and 33 are set forth above.
However, Bosnes et al. does not teach the method of claim 30, wherein the conditions of contacting the purified RNA in the presence of a binding solution comprising an oligoethylene glycol and salt, the oligoethylene glycol comprising from 2 to 70 ethylene glycol units in linear arrangement, wherein during the contacting the oligoethylene glycol is present at a concentration of at least 35% v/v and the salt is present at a concentration of between 1 M and 2 M and the method of claim 32, wherein step e) washing comprises use of a wash buffer comprising an aqueous C1-C6 alcohol and/or an aqueous C2-C10 polyol.
Finne et al. teach similar methods of purifying nucleic acids such as DNA and RNA using a magnetic bead solid support in the presence of a oligoethylene glycol comprising from about 2 to about 70 ethylene glycol units in linear arrangement at 10-90% and a salt [see Abstract; p. 6-7] in order to obtain high quality and pure nucleic acid preparations [see p. 1].
Bosch also teach similar methods for the enrichment and purification of nucleic acids bound to a solid phase wherein the concentration of the salt depends on the salt used and teach ranges of salts of 1-3M, and teach wash buffers comprising alcohol such as ethanol or isopropanol [see paragraphs 0003; 0014; 0038-0039].
Before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to combine the teachings of Bosnes et al., Finne et al. and Bosch according to the teachings of Finne et al. and Bosch to include oligoethylene glycol, salts and alcohol in the buffers and wash buffers in the nucleic acid purification methods of Bosnes et al. because Finne et al. teach that oligoethylene glycol in combination with magnetic beads is an effective method to obtain high quality and pure nucleic acid preparations. Bosch teach that high salts and alcohols are commonly used in the purification of nucleic acids. One of ordinary skill in the art would have had a reasonable expectation of success and reasonable level of predictability to combine the teachings of Bosnes et al., Finne et al. and Bosch because Finne et al. acknowledges that oligoethylene glycol in combination with magnetic beads is an effective method to obtain high quality and pure nucleic acid preparations and Bosch teach that high salts and alcohols are commonly used in the purification of nucleic acids. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Response to Remarks Regarding Prior Art Rejections
13. Beginning on p. 9 of applicants’ remarks, applicants in summary contend that Bosnes does not disclose or suggest that the purification bead, particularly a carboxylic-acid coated magnetic bead that can be reused across cycles of RNA purification. Applicants further contend that Bosnes teaches purification of polyadenylated mRNA transcripts using oligo(dT)-based hybridization, whereas the presently claimed method employs carboxylic acid-coated magnetic bead under binding conditions that enable generic capture of RNA independent of sequence-specific hybridization such as poly(A)-tail capture. Applicants contend that the rejection improperly uses impermissible hindsight reasoning to arrive at the claimed invention.
These arguments are found to be not persuasive because it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). As stated in the rejection above, Bosnes et al. acknowledged that the immobilized template (supermagnetic beads Strepavidin and oligodT) could be stored for repeated reactions. Furthermore, it is noted that the features upon which applicant relies (i.e., generic capture of RNA independent of sequence-specific hybridization such as poly(A)-tail capture) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Nevertheless, Bosnes teach that higher concentration of mRNA can be obtained using different types of Dynabeads for genetic binding and elution [see column 1].
Conclusion
14. Status of the claims:
Claims 1-2, 26-30, 32-34, and 36-44 are pending.
Claims 1-2, 34, and 36-44 stand withdrawn pursuant to 37 CFR 1.142(b).
Claims 26-30 and 32-33 are rejected.
No claims are in condition for an allowance.
THIS ACTION IS MADE FINAL. 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 PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 5PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL J HOLLAND/Primary Examiner, Art Unit 1656
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