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 .
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.
Claim 13 is 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.
Claim 13 is vague and indefinite because it is unclear what are the metes and bounds for the terms “short-chain”, “long-chain”, “amino-short-chain”, “amino-long-chain”, “diacyl short-chain”, “diacyl long-chain” in the phrase “wherein the linker is short-chain alkylene, long-chain alkylene, amino-short-chain alkylene, amino-long-chain alkylene, diacyl short-chain alkylene, diacyl long-chain alkylene, or dialkylene sulfonyl”.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1 and 5 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Torii et al. EP3015467.
With regards to claim 1, Torii et al. discloses a method of preparation of a morpholino nucleic acid oligomer (similar to compound of formula (II’) comprising a step of treating a compound DPM-suc-mo(Tr)cbz (similar to the compound of formula (II)), wherein L is an acyl group, R1 is trityl with a solution containing and acid (trifluoroacetic acid) and scavenger (ethanol and 2,2,2-trifluoroethanol) to obtain a compound DPM-suc-mocbz similar to compound of formula (III) (page 54).
With regards to claim 5, Torii et al. discloses the method further comprises a step of reacting the compound DPM-suc-mocbz similar to compound of formula (III) in a presence of N,N-diisopropylethylamine (an organic amine) with CIPONMe-mo(Tr)Cbz (similar to compound of formula (VIII) to obtain DPM-suc-PMO[Cbz Cbz] -Tr (similar to compound of formula (II’) (page 54).
Claim(s) 1-8, 11-13 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ueda US 20130197220.
With regards to claim 1, Ueda discloses a method of preparation of a morpholino nucleic acid oligomer comprising a step of treating a compound compound of formula (II), wherein R1 is trityl with a solution containing an acid and scavenger (ethanol and 2,2,2-trifluoroethanol [0057]) to obtain a compound of formula (III) (step A, Page 5).
With regards to claims 2-3, Ueda discloses “Also after completion of this process, a base may be added if necessary to neutralize the acid remaining in the system. The "base" is not limited particularly and can include for example, diisopropylamine. The base may be used as being diluted with a suitable solvent to a concentration within the range from 0.1% (v/v) to 30% (v/v)” [0060].
With regards to claim 4, Ueda discloses the morpholino monomer compound can include a compound represented by the following formula (VIII). [0076]; and can be diluted with suitable solvents to concentrations within the range from 0.1% (v/v) to 30% (v/v). The solvent is not limited particularly as long as it is inert to the reaction, and can include N,N-dimethylimidazolidone, N-methylpiperidone, DMF, dichloromethane, acetonitrile, tetrahydrofuran or a mixture thereof [0078].
With regards to claim 5, Ueda discloses the method further comprises a step of reacting the compound of formula (III), in the presence of a base [0074] and [0077], with compound of formula (VIII) to obtain a compound VII (similar to compound of formula (II’) (step B, Page 5).
With regards to claim 6, Ueda discloses after completion of Step B, an acylating agent may be added if necessary. The acylating agent may be diluted with a suitable solvent to a concentration within the range from 0.1% (v/v) to 30% (v/v). The solvent to be used in this step is not limited particularly as long as it is inert to the reaction and can include dichloromethane (halogen solvent) and alcohols [0081].
With regards to claims 7-8, Ueda discloses a method of preparation of a morpholino nucleic acid oligomer comprising a step of treating a compound compound of formula (II), wherein R1 is trityl with a solution containing an acid and scavenger (ethanol and 2,2,2-trifluoroethanol [0057]) to obtain a compound of formula (III) (step A, Page 5). “Also after completion of this process, a base may be added if necessary to neutralize the acid remaining in the system. The "base" is not limited particularly and can include for example, diisopropylamine. The base may be used as being diluted with a suitable solvent to a concentration within the range from 0.1% (v/v) to 30% (v/v)” [0060]. The morpholino monomer compound can include a compound represented by the following formula (VIII). [0076]; and can be diluted with suitable solvents to concentrations within the range from 0.1% (v/v) to 30% (v/v). The solvent is not limited particularly as long as it is inert to the reaction, and can include N,N-dimethylimidazolidone, N-methylpiperidone, DMF, dichloromethane, acetonitrile, tetrahydrofuran or a mixture thereof [0078]. The method further comprises a step of reacting the compound of formula (III), in a presence of a base [0074] and [0077], with compound of formula (VIII) to obtain a compound VII (similar to compound of formula (II’) (step B, Page 5). Ueda discloses after completion of Step B, an acylating agent may be added if necessary. The acylating agent may be diluted with a suitable solvent to a concentration within the range from 0.1% (v/v) to 30% (v/v). The solvent to be used in this step is not limited particularly as long as it is inert to the reaction and can include dichloromethane (halogen solvent) and alcohols [0081].
With regards to claim 11, Ueda discloses the uses of a solution comprising an organic amine and N-ethylmorpholine and dimethyl-2-imidazolidinone [0032]-[0036] [0077], [0082]
With regards to claims 12-13, Ueda discloses L can be a solid-phase support-Linker (see page 5) and that “the "solid support" is not limited particularly as long as it can be used in a solid phase reaction of a nucleic acid, and is desirably one which (i) is sparingly soluble in a reagent which can be used in the synthesis of morpholino nucleic acid derivatives (for example, dichloromethane, acetonitrile, tetrazole, N-methylimidamole, pyridine, acetic anhydride, lutidine, trifluoroacetic acid), (ii) is stable chemically to a reagent which can be used in the synthesis of morpholino nucleic acid derivatives, (iii) can be modified chemically, (iv) enables a desired loading of a morpholino nucleic acid derivative, (v) has a strength sufficient to tolerate a high pressure exerted during treatment, (vi) has a constant particle size range and distribution. Those exemplified typically can include swellable polystyrene …non-swellable polystyrene … PEG-chain binding type polystyrene… controlled pore glass… oxalylated controlled … TentaGel support-aminopolyethylene glycol derivatized support …and Poros-polystyrene/divinylbenzene copolymer” (see page 5, [0051]). Ueda discloses wherein the Linker can include 3-aminopropyl, succinyl, 2,2-diethanolsulfonyl and a long chain alkylamino.
Claim Rejections - 35 USC § 103
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) 1-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ueda US 20130197220 in view of Kotobuki US 2021/0261596 A1 and Kotobuki EP 4059943 A1, .
With regards to claim 1, Ueda discloses a method of preparation of a morpholino nucleic acid oligomer comprising a step of treating a compound compound of formula (II), wherein R1 is trityl with a solution containing an acid and scavenger (ethanol and 2,2,2-trifluoroethanol [0057]) to obtain a compound of formula (III) (step A, Page 5).
With regards to claims 2-3, Ueda discloses “Also after completion of this process, a base may be added if necessary to neutralize the acid remaining in the system. The "base" is not limited particularly and can include for example, diisopropylamine. The base may be used as being diluted with a suitable solvent to a concentration within the range from 0.1% (v/v) to 30% (v/v)” [0060].
With regards to claim 4, Ueda discloses the morpholino monomer compound can include a compound represented by the following formula (VIII). [0076]; and can be diluted with suitable solvents to concentrations within the range from 0.1% (v/v) to 30% (v/v). The solvent is not limited particularly as long as it is inert to the reaction, and can include N,N-dimethylimidazolidone, N-methylpiperidone, DMF, dichloromethane, acetonitrile, tetrahydrofuran or a mixture thereof [0078].
With regards to claim 5, Ueda discloses the method further comprises a step of reacting the compound of formula (III), in the presence of a base [0074] and [0077], with compound of formula (VIII) to obtain a compound VII (similar to compound of formula (II’) (step B, Page 5).
With regards to claim 6, Ueda discloses after completion of Step B, an acylating agent may be added if necessary. The acylating agent may be diluted with a suitable solvent to a concentration within the range from 0.1% (v/v) to 30% (v/v). The solvent to be used in this step is not limited particularly as long as it is inert to the reaction and can include dichloromethane (halogen solvent) and alcohols [0081].
With regards to claims 7-8, Ueda discloses a method of preparation of a morpholino nucleic acid oligomer comprising a step of treating a compound compound of formula (II), wherein R1 is trityl with a solution containing an acid and scavenger (ethanol and 2,2,2-trifluoroethanol [0057]) to obtain a compound of formula (III) (step A, Page 5). “Also after completion of this process, a base may be added if necessary to neutralize the acid remaining in the system. The "base" is not limited particularly and can include for example, diisopropylamine. The base may be used as being diluted with a suitable solvent to a concentration within the range from 0.1% (v/v) to 30% (v/v)” [0060]. The morpholino monomer compound can include a compound represented by the following formula (VIII). [0076]; and can be diluted with suitable solvents to concentrations within the range from 0.1% (v/v) to 30% (v/v). The solvent is not limited particularly as long as it is inert to the reaction, and can include N,N-dimethylimidazolidone, N-methylpiperidone, DMF, dichloromethane, acetonitrile, tetrahydrofuran or a mixture thereof [0078]. The method further comprises a step of reacting the compound of formula (III), in a presence of a base [0074] and [0077], with compound of formula (VIII) to obtain a compound VII (similar to compound of formula (II’) (step B, Page 5). Ueda discloses after completion of Step B, an acylating agent may be added if necessary. The acylating agent may be diluted with a suitable solvent to a concentration within the range from 0.1% (v/v) to 30% (v/v). The solvent to be used in this step is not limited particularly as long as it is inert to the reaction and can include dichloromethane (halogen solvent) and alcohols [0081].
With regards to claim 11, Ueda discloses the uses of a solution comprising an organic amine and N-ethylmorpholine and dimethyl-2-imidazolidinone [0032]-[0036] [0077], [0082]
With regards to claims 12-13, Ueda discloses L can be a solid-phase support-Linker (see page 5) and that “the "solid support" is not limited particularly as long as it can be used in a solid phase reaction of a nucleic acid, and is desirably one which (i) is sparingly soluble in a reagent which can be used in the synthesis of morpholino nucleic acid derivatives (for example, dichloromethane, acetonitrile, tetrazole, N-methylimidamole, pyridine, acetic anhydride, lutidine, trifluoroacetic acid), (ii) is stable chemically to a reagent which can be used in the synthesis of morpholino nucleic acid derivatives, (iii) can be modified chemically, (iv) enables a desired loading of a morpholino nucleic acid derivative, (v) has a strength sufficient to tolerate a high pressure exerted during treatment, (vi) has a constant particle size range and distribution. Those exemplified typically can include swellable polystyrene …non-swellable polystyrene … PEG-chain binding type polystyrene… controlled pore glass… oxalylated controlled … TentaGel support-aminopolyethylene glycol derivatized support …and Poros-polystyrene/divinylbenzene copolymer” (see page 5, [0051]). Ueda discloses wherein the Linker can include 3-aminopropyl, succinyl, 2,2-diethanolsulfonyl and a long chain alkylamino.
Ueda does not disclose triisopropylsilane as a scavenger.
However, the extension reaction of a morpholinonucleic acid oligomer which includes the step for treatment with a solution containing both an acid and a scavenger; or a solution comprising a base, an alcohol, and a halogenated solvent, or a solution comprising an organic amine and an aprotic polar solvent made of trifluoroacetic acid, triethylamine, 2,2,2-trifluoroethanol, dichloromethane, N-ethylmorpholine, and 1,3-dimcthyl-2-imidazolidinone, or a solution comprising triisopropylsilane as a scavenger are well known in art. (see US 2021/0261596 A1, page 20, [0296], Table 4, claim 12; EP 4059943 A1, particularly paragraphs [0115]-[0165], [0191]). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use triisopropylsilane as the scavenger for the method of Ueda without exercising inventive skill, to achieve the expected benefits, optimizations and/or expanded applications as this is well known practice in the art.
MPEP states wherein the “[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.” In re Alter, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Routine optimization is not considered inventive and no evidence has been presented that the selection of a specific scavenger was other than routine, that the products resulting from the optimization have any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEZIA RILEY whose telephone number is (571)272-0786. The examiner can normally be reached 7:30-6:00pm.
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/JEZIA RILEY/ Primary Examiner, Art Unit 1681 15 September 2026
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