DETAILED ACTION
Notice of Pre-AIA or AIA Status
The inventor or joint inventor should note that the instant invention, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-20 are pending in the instant invention. According to the Amendments to the Claims, filed October 14, 2025, claims 1-20 were presented for prosecution on the merits.
Status of Priority
This invention is a Continuation (CON) of International Application No. PCT/US2021/028416, filed April 21, 2021, which claims priority under 35 U.S.C. § 119(e) to US Provisional Application Nos.: a) 63/015,331, filed April 24, 2020; and b) 63/014,561, filed April 23, 2020.
Restrictions / Election of Species
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The inventor’s or joint inventor’s provisional election of the following, without traverse, in the reply filed on October 14, 2025, is acknowledged: a) Group II - claims 1-16; and b) substituted purine of Formula II - undisclosed, shown to the right below, and hereafter referred to as isopropyl ((S)-(((2R,3R,4R,5R)-5-(2-amino-6-(methylamino)-9H-purin-9-yl)-3-(((benzyloxy)carbonyl)oxy)-4-fluoro-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)-L-alaninate, where R1 = -C(O)OCH2Ph. Claims 1, 2 and 7-14 read on the elected species. Affirmation of this election must be made by the inventor or joint inventor in replying to this Office action.
Similarly, the inventor or joint inventor should further note that the requirement is still deemed proper and is therefore made FINAL.
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Likewise, the inventor or joint inventor should further note that the elected species, shown to the right, was found to be free of the prior art. Thus, the examiner has expanded the forthcoming prosecution to include all claims relevant to the genus of Group II, for a first Office action and prosecution on the merits.
Moreover, the inventor or joint inventor should further note that claims 17-20 were withdrawn from further consideration, pursuant to 37 CFR 1.142(b), as being drawn to a nonelected or cancelled invention, there being no allowable generic or linking claim.
Thus, a first Office action and prosecution on the merits of claims 1-16 is contained within.
Specification Objection - Disclosure
The inventor or joint inventor is advised to format the specification according to 37 CFR 1.77(c). Revisions should particularly address bold-type, underline, and/or upper case formatting. Appropriate correction may be required.
Claim Objections
Claim 1 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
A process for preparing a compound of Formula II:
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Formula II
wherein:
R1 is benzyl carbonyl (Cbz), an alkyl benzyl carbonyl, an alkyl p-methoxybenzyl carbonyl, an alkyl o-nitrobenzyl carbonyl, an alkyl p-nitrobenzyl carbonyl, an alkyl p-nitrophenyl carbonyl, tert-butyl carbonyl (Boc), a substituted benzyl ether, 4-bromobenzoate, 1,3-benzodithiolan-2-yl ether, p-methoxybenzyloxymethyl ether (MPBM), o-nitrobenzyloxymethyl ether (NBOM), p-nitrobenzyloxymethyl ether, tert-butoxymethyl ether, 2,2,2- trichloroethoxymethyl ether, 1-methoxycyclohexyl ether, 1,4-dioxan-2-yl ether, a substituted phenyl ether, 2-picolyl ether, 4-picolyl ether, tetrahydrofuranyl ether, tetrahydropyranyl ether, 3-bromotetrahydropyranyl ether, tetrahydrothiofuranyl ether, tetrahydrothiopyranyl ether, p-chlorophenoxyacetate ester, p-phenylbenzoate ester, or 3-phenylpropionate ester, wherein the substituted benzyl ether or substituted phenyl ether is substituted with one or more substituents independently selected from the group consisting of F, Cl, Br, haloalkyl, N3, NO2, OH, and O(alkyl);
wherein the process comprises the following step:
contacting a compound of Formula I:
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Formula I
wherein:
R1 is benzyl carbonyl (Cbz), an alkyl benzyl carbonyl, an alkyl p-methoxybenzyl carbonyl, an alkyl o-nitrobenzyl carbonyl, an alkyl p-nitrobenzyl carbonyl, an alkyl p-nitrophenyl carbonyl, tert-butyl carbonyl (Boc), a substituted benzyl ether, 4-bromobenzoate, 1,3-benzodithiolan-2-yl ether, p-methoxybenzyloxymethyl ether (MPBM), o-nitrobenzyloxymethyl ether (NBOM), p-nitrobenzyloxymethyl ether, tert-butoxymethyl ether, 2,2,2- trichloroethoxymethyl ether, 1-methoxycyclohexyl ether, 1,4-dioxan-2-yl ether, a substituted phenyl ether, 2-picolyl ether, 4-picolyl ether, tetrahydrofuranyl ether, tetrahydropyranyl ether, 3-bromotetrahydropyranyl ether, tetrahydrothiofuranyl ether, tetrahydrothiopyranyl ether, p-chlorophenoxyacetate ester, p-phenylbenzoate ester, or 3-phenylpropionate ester, wherein the substituted benzyl ether or substituted phenyl ether is substituted with one or more substituents independently selected from the group consisting of F, Cl, Br, haloalkyl, N3, NO2, OH, and O(alkyl);
with a stereoselective compound of the following formula:
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,
in the presence of (a) an organolithium reagent or organomagnesium reagent and (b) lithium chloride, to afford the compound of Formula II above.
Appropriate correction is required. See MPEP § 2173.02.
Claim 2 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The process of claim 1, wherein R1 is benzyl carbonyl (Cbz), tert-butyl carbonyl (Boc), a substituted benzyl ether, p-methoxybenzyloxymethyl ether (MPBM), tetrahydropyranyl ether, or tetrahydrothiopyranyl ether, wherein the substituted benzyl ether is substituted with one or more substituents independently selected from the group consisting of F, Cl, Br, haloalkyl, N3, NO2, OH, and O(alkyl).
Appropriate correction is required. See MPEP § 2173.02.
Claim 3 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The process of claim 1, wherein R1 is a substituted benzyl ether, wherein the substituted benzyl ether is substituted with one or more substituents independently selected from the group consisting of F, Cl, Br, haloalkyl, N3, NO2, OH, and O(alkyl).
Appropriate correction is required. See MPEP § 2173.02.
Claim 4 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b) and/or 35 U.S.C. § 112(d), the existing recitation should be replaced with the following recitation:
The process of claim 1, wherein R1 is a substituted benzyl ether selected from the group consisting of 2-hydroxybenzyl ether, p-methoxybenzyl ether, 2,4-dimethoxybenzyl ether, and 3,4-dimethoxybenzyl ether.
Appropriate correction is required. See MPEP § 2173.02.
Claim 5 is objected to because of the following informalities: for brevity, clarity and precision, the existing recitation should be replaced with the following recitation:
The process of claim 1, wherein R1 is 4-bromobenzoate, p-methoxybenzyloxymethyl ether (MPBM), o-nitrobenzyloxymethyl ether (NBOM), p-nitrobenzyloxymethyl ether, or tert-butoxymethyl ether.
Appropriate correction is required. See MPEP § 2173.02.
Claim 6 is objected to because of the following informalities: for brevity, clarity and precision, the existing recitation should be replaced with the following recitation:
The process of claim 1, wherein R1 is 2,2,2- trichloroethoxymethyl ether, 1-methoxycyclohexyl ether, 1,4-dioxan-2-yl ether, tetrahydropyranyl ether, 3-bromotetrahydropyranyl ether, or tetrahydrothiopyranyl ether.
Appropriate correction is required. See MPEP § 2173.02.
Claim 7 is objected to because of the following informalities: for brevity, clarity and precision, the existing recitation should be replaced with the following recitation:
The process of claim 1, wherein R1 is benzyl carbonyl (Cbz) or tert-butyl carbonyl (Boc).
Appropriate correction is required. See MPEP § 2173.02.
Claim 8 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The process of claim 1, wherein the process comprises contacting a compound of Formula I with a stereoselective compound in the presence of an organomagnesium reagent.
Appropriate correction is required. See MPEP § 2173.02.
Claim 9 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The process of claim 8, wherein the organomagnesium reagent is isopropyl magnesium chloride (iPrMgCl).
Appropriate correction is required. See MPEP § 2173.02.
Claim 10 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The process of claim 1, wherein the process comprises contacting a compound of Formula I with a stereoselective compound in the presence of an organolithium reagent.
Appropriate correction is required. See MPEP § 2173.02.
Claim 11 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The process of claim 10, wherein the organolithium reagent is tert-butyl lithium.
Appropriate correction is required. See MPEP § 2173.02.
Claim 12 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b), the existing recitation should be replaced with the following recitation:
The process of claim 1, wherein the ratio of Sp:Rp diastereomers in the compound of Formula II is greater than 70:30.
Appropriate correction is required. See MPEP § 2173.02.
Claim 13 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b), the existing recitation should be replaced with the following recitation:
The process of claim 1, wherein the ratio of Sp:Rp diastereomers in the compound of Formula II is greater than 80:20.
Appropriate correction is required. See MPEP § 2173.02.
Claim 14 is objected to because of the following informalities: for clarity, precision and to avoid issues under 35 U.S.C. § 112(b), the existing recitation should be replaced with the following recitation:
The process of claim 1, wherein the ratio of Sp:Rp diastereomers in the compound of Formula II is greater than 60:40.
Appropriate correction is required. See MPEP § 2173.02.
Claim 15 is objected to because of the following informalities: for brevity, clarity, precision and to avoid issues under 35 U.S.C. § 112(b), 35 U.S.C. § 112(d) and/or non-compliance with the Requirement for Restriction/Election of Species, mailed on May 15, 2025, the existing recitation should be replaced with the following recitation:
The process of claim 1, wherein the process further comprises purifying the compound of Formula II to afford a diastereomerically pure Sp-purine phosphoramidate nucleotide of Formula II havmg a diastereomeric purity of greater than 90%.
Appropriate correction is required. See MPEP § 2173.02.
Claim 16 is objected to because of the following informalities: for clarity and precision, the existing recitation should be replaced with the following recitation:
The process of claim 15, wherein the purification technique is selected from the group consisting of column chromatography, selective crystallization, and trituration.
Appropriate correction is required. See MPEP § 2173.02.
Claim Rejections - 35 U.S.C. § 112(b)
The following is a quotation of the second paragraph of 35 U.S.C. § 112:
(b) CONCLUSION. The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or joint inventor regards as the invention.
Claim 12 is rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that the term, about, is a relative term which renders the claim indefinite. The term, about, is not defined by the claim, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. The specification fails to adequately define the term, about. Similarly, the meaning of a term cannot depend on the unrestrained, subjective opinion of the inventor or joint inventor practicing the invention. Moreover, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the process for preparing a substituted purine of the Formula II has been rendered indefinite by the use of the term, about. {See Ortho-McNeil Pharm., Inc. v. Caraco Pharm. Labs., Ltd., 476 F.3d 1321, 1326, 81 USPQ2d 1427, 1432 (Fed. Cir.2007); W. L. Gore & Associates, Inc. v. Garlock, Inc., 721 F.2d 1540, 220 USPQ 303 (Fed. Cir. 1983); Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991); and MPEP § 2173.05(b)}.
The examiner suggests amending the claim, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Claim 13 is rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that the term, about, is a relative term which renders the claim indefinite. The term, about, is not defined by the claim, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. The specification fails to adequately define the term, about. Similarly, the meaning of a term cannot depend on the unrestrained, subjective opinion of the inventor or joint inventor practicing the invention. Moreover, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the process for preparing a substituted purine of the Formula II has been rendered indefinite by the use of the term, about. {See Ortho-McNeil Pharm., Inc. v. Caraco Pharm. Labs., Ltd., 476 F.3d 1321, 1326, 81 USPQ2d 1427, 1432 (Fed. Cir.2007); W. L. Gore & Associates, Inc. v. Garlock, Inc., 721 F.2d 1540, 220 USPQ 303 (Fed. Cir. 1983); Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991); and MPEP § 2173.05(b)}.
The examiner suggests amending the claim, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Claim 14 is rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that the term, about, is a relative term which renders the claim indefinite. The term, about, is not defined by the claim, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. The specification fails to adequately define the term, about. Similarly, the meaning of a term cannot depend on the unrestrained, subjective opinion of the inventor or joint inventor practicing the invention. Moreover, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the process for preparing a substituted purine of the Formula II has been rendered indefinite by the use of the term, about. {See Ortho-McNeil Pharm., Inc. v. Caraco Pharm. Labs., Ltd., 476 F.3d 1321, 1326, 81 USPQ2d 1427, 1432 (Fed. Cir.2007); W. L. Gore & Associates, Inc. v. Garlock, Inc., 721 F.2d 1540, 220 USPQ 303 (Fed. Cir. 1983); Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991); and MPEP § 2173.05(b)}.
The examiner suggests amending the claim, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Claim 15 is rejected under 35 U.S.C. § 112(b) as being indefinite for failing to set forth the subject matter which the inventor or joint inventor regards as the invention.
The inventor or joint inventor should note that the term, about, is a relative term which renders the claim indefinite. The term, about, is not defined by the claim, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. The specification fails to adequately define the term, about. Similarly, the meaning of a term cannot depend on the unrestrained, subjective opinion of the inventor or joint inventor practicing the invention. Moreover, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments. Consequently, the process for preparing a substituted purine of the Formula II has been rendered indefinite by the use of the term, about. {See Ortho-McNeil Pharm., Inc. v. Caraco Pharm. Labs., Ltd., 476 F.3d 1321, 1326, 81 USPQ2d 1427, 1432 (Fed. Cir.2007); W. L. Gore & Associates, Inc. v. Garlock, Inc., 721 F.2d 1540, 220 USPQ 303 (Fed. Cir. 1983); Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991); and MPEP § 2173.05(b)}.
The examiner suggests amending the claim, particularly as stated in the section above entitled Claim Objections, to overcome this rejection.
Claim Rejections - 35 U.S.C. § 112(d)
The following is a quotation of the fourth paragraph of 35 U.S.C. § 112:
(d) REFERENCE IN DEPENDENT FORMS. Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 15 and 16 are rejected under 35 U.S.C. § 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
The inventor or joint inventor should note that claim 15 is rejected under 35 U.S.C. § 112(d) because the recitation of an additional process performed on a compound produced by a process from which the claim depends, must result in a patentably distinct procedural step in the recited process, in order to be further limiting. In the instant dependent claim, the process for preparing a substituted purine of the Formula II, as recited in claim 1, further comprises the step of deprotecting the diastereomerically pure Sp-purine phosphoramidate nucleotide of Formula II to afford Compound 1. Consequently, since the additional process performed on the diastereomerically pure Sp-purine phosphoramidate nucleotide of Formula II produced by the process for preparing a substituted purine of the Formula II, as recited in claim 1, whereby the process for preparing a substituted purine of the Formula II further comprises the step of deprotecting the diastereomerically pure Sp-purine phosphoramidate nucleotide of Formula II to afford Compound 1, (1) fails to result in a further patentably distinct procedural step in the process for preparing a substituted purine of the Formula II, as recited in claim 1, and/or (2) fails to include all the limitations of the process for preparing a substituted purine of the Formula II, as recited in claim 1, it is not given patentable weight and thus, renders the instant dependent claim, and any additional dependent claims therefrom, improperly dependent under 35 U.S.C. § 112(d). {See MPEP § 2111.02; and 37 CFR 1.75(c)}.
Similarly, the inventor or joint inventor should further note that the U.S. Court of Appeals for the Federal Circuit indicated that although the requirements of 35 U.S.C. § 112(d) are related to matters of form, non-compliance with 35 U.S.C. § 112(d) renders the claim unpatentable just as non-compliance with other subsections of 35 U.S.C. § 112 would. {See Pfizer, Inc. v. Ranbaxy Labs., Ltd., 457 F.3d 1284, 1291-92 (Fed. Cir. 2006)}.
Moreover, the inventor or joint inventor should further note that if a dependent claim does not comply with the requirements of 35 U.S.C. § 112(d) the dependent claim should be rejected under 35 U.S.C. § 112(d) as unpatentable rather than objecting to the claim. {See also MPEP § 608.01(n), Section III, Infringement Test for dependent claims}.
The examiner suggests the inventor or joint inventor (1) cancel the dependent claims, (2) amend the dependent claims to place the dependent claims in proper dependent form, particularly as stated in the section above entitled Claim Objections, (3) rewrite the dependent claims in independent form, or (4) present a sufficient showing that the dependent claims comply with the statutory requirements, to overcome this rejection.
Allowable Subject Matter
No claims are allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DOUGLAS M. WILLIS, whose telephone number is 571-270-5757. The examiner may normally be reached on Monday thru Thursday from 8:00-6:00 EST. The examiner is also available on alternate Fridays.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Mr. Jeffrey Murray, may be reached on 571-272-9023. The fax phone number for the organization where this invention or proceeding is assigned is 571-273-8300.
Information regarding the status of an invention may be obtained from Patent Center. For more information about Patent Center, see https://www.uspto.gov/patents/apply/patent-center. Should you have questions on access to Patent Center, contact the Patent Electronic Business Center (PEBC) at 866-217-9197 (toll-free) or ebc@uspto.gov.
/DOUGLAS M WILLIS/
Primary Examiner, Art Unit 1624