DETAILED ACTION
Notice of New examiner
The examiner reviewing your application at the PTO has changed. To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to examiner Steven Pohnert .
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 .
Claim Status and Formal Matters
This action is in response to papers filed 2/27/2026.
Claims 1, 11-12, 16, 31 have been amended.
Claims 58 and 59 have been added by amendment.
Claims 1, 11-12, 16-17, 31, 54-59 are being examined.
Priority
The instant application was filed 08/17/2022 and is a continuation of 15570130 , filed 10/27/2017 and is a National Stage entry of PCT/EP2016/059651 International filing date: 04/29/2016 and claims foreign priority to PCT/EP2015/059559, filed 04/30/2015
Specification
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required:
Claims 1 and 31 have been amended to recite, “recombinant orthodox type II restriction enzyme.” Review and searching did not reveal antecedent basis for this limitation.
Claim 58 has been amended to recite, “wherein the linker comprises one or more additional cysteine residues.” Review and searching did not reveal antecedent basis for this limitation.
Response to Arguments
This is a new objection necessitated by amendment.
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, 11-12, 16-17, 31, 54-59 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.
MPEP 2163 IB New or amended claims section II
With respect to newly added or amended claims, applicant should show support in the original disclosure for the new or amended claims. See, e.g., Hyatt v. Dudas, 492 F.3d 1365, 1370, n.4 (Fed. Cir. 2007) (citing MPEP § 2163.04 which provides that a "simple statement such as ‘applicant has not pointed out where the new (or amended) claim is supported, nor does there appear to be a written description of the claim limitation ‘___’ in the application as filed’ may be sufficient where the claim is a new or amended claim, the support for the limitation is not apparent, and applicant has not pointed out where the limitation is supported."); see also MPEP §§ 714.02 and 2163.06 ("Applicant should ... specifically point out the support for any amendments made to the disclosure."); and MPEP § 2163.04
Claims 1 and 31 have been amended to recite, “recombinant orthodox type II restriction enzyme.” The response does not specifically identify where support for the amendment can be found. Review and searching did not reveal antecedent basis for this limitation. Thus the amendment appears to limit the claims to a species not specifically envisioned by the specification.
Claim 58 has been amended to recite, “wherein the linker comprises one or more additional cysteine residues.” The response does not specifically identify where support for the amendment can be found. Review and searching did not reveal antecedent basis for this limitation. While the specification suggest mutating one or more naturally occurring wildtype cysteines, it does not appear to support linker comprises one or more additional cysteine residues. Thus the amendment appears to introduce new matter.
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.
Claim(s) 1-3, 9-11, 17-19 and 56-59 is/are rejected under 35 U.S.C. 103 as being unpatentable over .McKenna et al. [Nature Protocols 2(12) : 1270-1277 (2007) – hereinafter “McKenna”] in view of Bircakova et al. [J. of Molecular Recognition 9:683-690(1996) – hereinafter “Bircakova”] and Iwakura et al. [J. Biochemistry 114:339-343 (1993) – hereinafter “Iwakura-93’].
Claim 1 has been amended to recite, “recombinant orthodox type II restriction enzyme.” The specification does not specifically define this. However reading of the specification suggests HindIII and ECORI are orthodox type II restriction enzymes.
McKenna teach a method for the in vitro transcription/synthesis (hereinafter IVT) of RNA molecule(s), see the entire document, which method comprises most of the limitation recited by Claim 1 including a step comprising the linearization a plasmid DNA template molecule using a restriction enzyme/endonuclease. Mckenna teaches HindIII and EcoRI were appropriate restriction enzymes to cleave the vector (page 3210, 2nd column, template plasmid design).
In addition it is noted that Moderna i.e. Chen et al. [US 10,465,190(2019) – hereinafter “Moderna”] teach a method of in vitro transcription which increases the transcription efficiency and reduces the amount of abortamers produced.
While McKenna teaches restriction and IVT, these inventors do not teach the use of a restriction enzyme(s) immobilized to a solid thiol-activated support wherein said enzyme(s) is bound via a thiol group of at least one cysteine residue that has been introduced by adding the at least one cysteine residue to the C terminus of the restriction enzyme.
However, it was known to immobilize restriction enzymes to thiol-activated solid supports via a Cysteine residue as evidenced by at least Bircakova. That said, Bircakova does not expressly teach that said enzyme(s) is bound to said thiol-activated support via a thiol group of at least one cysteine residue that has been introduced by adding the at least one cysteine residue to the C terminus of the restriction enzyme. However, it was known to engineer enzymes to comprises residue(s) (e.g. a short amino acid chain spacer) at the C terminus thereof in order to facilitate the immobilization of engineered protein via its C terminus to a solid support via a Cysteine residue /linker, see Iwakura-93’.
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims modify the method of McKenna wherein the HINDIII and EcoRI utilized is one or more that has been immobilized to a solid thiol-activated support wherein said enzyme is bound via a thiol group of at least one or more cysteine residue added recombinantly introduced into the C terminus of the restriction enzyme as suggested by Iwakura -93’ rather than the restriction endonuclease as suggested by Iwakura-93’ rather than via the restriction enzyme of McKenna in view of Bircakova The substitution of one known second method/reagent with known properties for a first known method/reagent with known properties would have been prima facie obvious to the ordinary artisan at the time of the invention in the absence of an unexpected result. As regards the motivation to make the substitution recited above, the motivation to combine arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making this obviousness rejection comes from the M.P.E.P. at 2144.07 and 2144.09, as well as, the SCOTUS decision in KSR International. Co. v. Teleflex, Inc., et al., 550 U.S.398 (2007).
As regards Claim 11, see at least the abstract in Iwakura -93’.
As regards Claim 17 note that McKenna teach using “Oak Ridge tubes” a type of microfuge tube routinely used in molecular biology labs, see step 6.| on pg. 3272.
As to Claims 18-19, McKenna expressly purification of the IVT product by gel filtration see at least steps 8| - 24| on pgs.3273-3274
As to Claim 56, McKenna teach gel filtration purification of the IVT RNA product, see the entire document.
As to Claim 57 McKenna teach purification of their IVT product in a aqueous system, precipitation of said RNA and resuspension of retained RNA pellet in water (i.e. a pharmaceutically acceptable carrier). In support of this position, consider Michot et al. [US 2010/0233704 – hereinafter “Michot”] at para 258 where these inventors teach pharmaceutically acceptable carrier at least one of which comprises water.
As to claim 59, Mckenna teaches HindIII and EcoRI were appropriate restriction enzymes to cleave the vector (page 3210, 2nd column, template plasmid design).
Response to Arguments
The response traverses the rejection in view of the amendment. This argument is not persuasive in view of the teachings of the prior art as detailed in the modified rejection.
Claim(s) 11 and 54-55is/are rejected under 35 U.S.C. 103 as being unpatentable over McKenna,Bircakova and Iwakura-93’ as applied to claim 1 above, and further in view of Van Cott.
As to Claim(s) 3, 11 and 54-55. .McKenna in view of Bircakova and Iwakura-93’ do not teach the use of XbaI rather these reference(s) reasonably suggest the use of EcoRI. However, XbaI restriction enzyme was well known as evidenced by Van Cott, see at least abstract.
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to substitute XbaI for EcoRI. The artisan would be motivated to substitute one recombinant orthodox type restriction enzyme with multiple cysteines in the linker for orthodox type restriction enzyme with multiple cysteines in the linker to cut at a different site in the plasmid. The artisan would have a reasonable expectation of success as the artisan is merely substituting one known restriction enzyme for another.
Response to Arguments
The response provides no specific arguments to the instant rejection. Thus the rejection is maintained.
Claim(s) 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over McKenna, Bircakova and Iwakura-93’ as applied to claim 1 above, and further in view of Iwakura et al. [J. of Biochemistry 117:480-488 (1995) – hereinafter “Iwakura- 95’”].
As to Claim(s) 12, McKenna in view of Bircakova and Iwakura-93’ reasonably suggest a method of in vitro transcription comprising most of the limitations of Claim 12 for the reason(s) outlined above except these references fail to teach replacing one or more cysteine residues in a wild-type restriction enzyme with another amino acid.
However, it was known as evidenced by at least Iwakura-95’ to replace by protein engineering one or more cysteine residues in enzyme(s) in order to improve the thermal stability thereof, see at least for example, Iwakura- 95’.
Accordingly, absent an unexpected result it would have been prima facie obvious to one3 of skill in the art prior to the effective filing date of the claims to modify the method of McKenna, Bircakova, and Iwakura-93’ wherein the restriction enzyme utilized is one that comprises one or more cysteine replacement residue(s) as suggested by Iwakura– 953’ rather than via the wild-type restriction enzyme of McKenna in view of Bircakova and Iwakura-93’ . The substitution of one known second method/reagent with known properties for a first known method/reagent with known properties would have been prima facie obvious to the ordinary artisan at the time of the invention in the absence of an unexpected result. As regards the motivation to make the substitution recited above, the motivation to combine arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making this obviousness rejection comes from the M.P.E.P. at 2144.07 and 2144.09, as well as, the SCOTUS decision in KSR International. Co. v. Teleflex, Inc., et al., 550 U.S.398 (2007).
Response to Arguments
The response provides no specific arguments to the instant rejection. Thus the rejection is maintained.
Claim(s) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over McKenna, Bircakova ,Iwakura-93’ and Iwakura -95’ as applied to claim 1 above, and further in view of Schmitt
As regards Claims 16 it was well known to attach purification/ affinity tags (e.g. histidine tags (comprising 6 histidine residues) to proteins in order to facilitate the removal/ selection of said affinity-labeled protein(s) from biological samples, see Schmidt. Schmidt teach in part using histidine tags in order to recover protein(s) from biological samples.
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to modify the method of McKenna, Bircakova, Iwakura-93’ and Iwakura -95’ wherein the restriction enzyme use to linearize the plasmid template comprises a histidine purification tag as encompassed by claim 15 and as taught by Schmitt. The one of ordinary skill in the art would have been motivated to include a histidine purification tag on the restriction enzyme of McKenna in order to facilitate the removal of the tagged restriction enzyme from the plasmid template in order to prevent said enzyme from interfering with downstream manipulation(s) of said template (e.g. IVT).
Response to Arguments
The response provides no specific arguments to the instant rejection. Thus the rejection is maintained.
Claim(s) 31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bircakova in view of Iwakura-93’.
Claim 31 has been amended to recite, “recombinant orthodox type II restriction enzyme.” The specification does not specifically define this. However reading of the specification suggests ECORI are orthodox type II restriction enzymes.
As to Claim 31, Bircakova teach an enzyme reactor comprising a restriction enzyme (Eco RI) immobilized to a thiol- activated support via one or more thiol groups of said enzyme, see the entire document.
While Bircakova teach immobilizing their restriction enzyme(s) (hereinafter RE) to a thiol activated solid support via at least one cysteine residue of said RE these authors fail to teach immobilization via at least one cysteine residue that has be introduced to the N or C terminus of the restriction enzyme.
However, it was known to engineer enzymes to comprises residue(s) (e.g. a short amino acid chain spacer) at the C terminus thereof in order to facilitate the immobilization of engineered protein via its C terminus to a solid support, see Iwakura-93’. .
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to recombinantly modify the EcoRI of Bircakova, orthodox type II restriction enzyme, to contain a cysteine I at the N or C terminus to allow for immobilization to a solid thiol-activated support via a thiol group as suggested by Iwakura -93’ rather than via the internal Cysteine of the EcoRI of Bircakova, orthodox type II restriction enzyme. The substitution of one known second method/reagent with known properties for a first known method/reagent with known properties would have been prima facie obvious to the ordinary artisan at the time of the invention in the absence of an unexpected result. As regards the motivation to make the substitution recited above, the motivation to combine arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making this obviousness rejection comes from the M.P.E.P. at 2144.07 and 2144.09, as well as, the SCOTUS decision in KSR International. Co. v. Teleflex, Inc., et al., 550 U.S.398 (2007).
Summary
No claims are allowed.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEVEN C POHNERT PhD whose telephone number is (571)272-3803. The examiner can normally be reached Monday- Friday about 6:00 AM-5:00 PM, every second Friday off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at (571)272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Steven Pohnert/ Primary Examiner, Art Unit 1683
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