DETAILED ACTION
Status of Application
The amendments and response filed 14 July 2026 are acknowledged and have been considered in their entireties. Claims 1-29, 31-34, 40-42, 45 cancelled. Thus, claims 46, 49, 53-58, 60-61, 64 and 66-67 are pending and subject to examination on the merits. SEQ ID NO: 2078 remains the elected species.
Withdrawal of Previous Rejections
The rejection of claim 57 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as lacking antecedent basis in the claim for "the substrate NTP" is withdrawn in view of the amendments to claim 46 to incorporate "substrate NTP".
The rejection of claims 66-67 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in view of the amendments to claims 66 and 67 which compare the engineered 3’O-kinase to the reference sequence.
Maintained Rejections
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 46, 49, 53-58, 60-61 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a natural phenomenon) without additional elements that integrate the judicial exception into a practical application. An analysis with respect to the claims as a whole reveals that they do not include additional elements that integrate the judicial exception into a practical application. See MPEP 2106.
Analysis of subject-matter eligibility under 35 U.S.C. § 101 requires consideration of the following steps:
Step (1) whether the claim is directed to one of the four categories recited in §101 (process, machine, manufacture or composition of matter);
Step (Revised 2A - Prong 1) do the claims recite an abstract idea (mathematical concepts, mental processes or method of organizing human activity), law of nature or natural phenomenon;
Step (Revised 2A - Prong 2) do the claims recite additional elements that integrate the judicial exception into a practical application; and
Step (2B) whether the claim as a whole recites something that amounts to significantly more than the judicial exception. (See 2019 Revised Patent Subject Matter Eligibility Guidance (2019 PEG)).
Step 1: Yes; the claims are directed to process/method.
Step 2A – Prong 1: Yes, the claims recite a natural phenomenon, namely, a naturally occurring process.
Step 2A – Prong 2: No, the claims do not recite any additional elements that integrate the judicial exception into a practical application because the claims are merely drawn to what already exists in nature. For example, Brunngraber et al. (PNAS, 1970, cited herein) teach of a naturally occurring nucleoside phosphotransferase from E. coli which is described as a low-energy nucleotide phosphotransferase, wherein said enzyme transfers organically bound ester phosphate to the 3' or 2' hydroxyl of a nucleoside 5'-phosphate or a nucleoside 5'-triphosphate, thus producing an NQP with a 3’-phosphate (See p. 107, 1st paragraph; p. 111, last paragraph and table 4). Thus, this method occurs naturally in systems such as E. coli wherein it is further well established said organisms comprise NTP’s which are involved in phosphate recycling systems to regenerate said NTP’s which involve kinases and pyruvate oxidase enzymes (See Satishchandran et al., Biochemistry, 1992 – cited on IDS 12/11/2024). There is nothing in the claims which differentiates this naturally method from that which already exists. Thus, there is ultimately nothing in the claims which integrates the judicial exception into a practical application. Even for the claims which recite that the protein is produced in a host cell (claims 26-29), there is nothing in the claims or specification which distinguishes that found in nature from that produced in a host cell.
Step 2B: As noted in answering that of 2A – Prong 2 above, there is nothing in the claims which amounts to significantly more in terms of structure and/or function and the claims read on naturally occurring enzymes. Thus, the claims are drawn to a judicial exception, namely, a naturally occurring product.
Applicant’s Arguments and Examiner’s Rebuttal:
Applicant’s traverse the rejection and state because they have amended claim 46 to recite that the 3’O-kinase is an engineered 3’O-kinase that this means the claims no longer read on a naturally occurring method (See Remarks, p. 5).
The Examiner has considered this argument but does not find it convincing. This is because it is first noted, Applicant’s definition for “engineered” in the specification at paragraph [0038] is as follows (PG-Pub paragraph numbering):
[0038] As used herein, “recombinant,” “engineered,” and “non-naturally occurring” when used with reference to a cell, nucleic acid, or polypeptide, refer to a material, or a material corresponding to the natural or native form of the material, that has been modified in a manner that would not otherwise exist in nature. In some embodiments, the cell, nucleic acid or polypeptide is identical a naturally occurring cell, nucleic acid or polypeptide, but is produced or derived from synthetic materials and/or by manipulation using recombinant techniques. Non-limiting examples include, among others, recombinant cells expressing genes that are not found within the native (non-recombinant) form of the cell or express native genes that are otherwise expressed at a different level.
Thus, this merely means that the process by which the material is produced may be different, however, the product which is produced is identical. Thus, it would be materially impossible to tell an “engineered” 3’O-kinase from the naturally occurring counterpart. And impossible to discern the natural process using a naturally occurring 3’O-kinase from the same process using identical enzymes which happen to be produced differently. The courts have established that when interpreting product by process limitations nested within method claims, the exact same analysis/construction of the product by process limitation is required just as if the product by process limitation was in a product claim. See BIOGEN MA INC., v. EMD SERONO, INC., PFIZER INC., No. 19-1133 (Fed. Cir. 2020).
As such, it is interpreted that the claims still read on a judicial exception which is a naturally occurring process.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 46, 49 and 55 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Brunngraber et al. (PNAS, 1970 – cited herein).
Brunngraber et al. teach:
Regarding claims 46 and 49, a nucleoside phosphotransferases from E. coli which is described as a low-energy nucleotide phosphotransferase, wherein said enzyme transfers organically bound ester phosphate to the 3' or 2' hydroxyl of a nucleoside 5'-phosphate or even a nucleoside 5'-triphosphate, thus producing an NQP with a 3’-phosphate (See p. 107, 1st paragraph; p. 111, last paragraph and table 4).
As defined in the instant specification (paragraph 0104 of PG-Pub), “As used herein, the term 3′O-kinase refers to any of these enzymes and any enzyme capable of phosphorylation of the 3′ position of a natural or modified NTP, NDP, NMP, nucleoside, or nucleoside analog.”. Thus, the enzyme of Brunngraber et al. is a 3’O-kinase.
Regarding claim 55, said method utilizes phosphate donors, namely, p-nitrophenylphosphate (See p. 109, last paragraph to p. 110; and p. 111, last paragraph and table 4).
Claim(s) 46 and 55-57 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Oki et al. (Biochim. et Biophys. Acta, 1975 – cited herein).
Oki et al. teach:
Regarding claim 46, a method of making a nucleoside-5’ tri-phosphates which further have 3’-diphsophates, thus generating pppApp or pppGpp or pppIpp by utilizing a pyrophosphotransferase from Streptomyces morookaensis (See Abstract and Enzyme Assay Procedures A and B, pp. 263-264). While it is noted two phosphates are added at the 3’ position, given the claim is open and comprising this is permissible.
Regarding claim 55, a phosphate donor was utilized in the method (See p. 269, last paragraph and Table IV).
Regarding claim 56 and 57, the same NTP could be used as a donor and as a substrate (See Tables IV-VI).
Applicant’s Arguments and Examiner’s Rebuttal:
Applicant’s traverse the rejections of claim(s) 46, 49 and 55 being anticipated by Brunngraber et al. (PNAS, 1970) and claims 46 and 55-57 as being anticipated by Oki et al. (Biochim. et Biophys Acta, 1975) and state because they have amended claim 46 to recite that the 3’O-kinase is an engineered 3’O-kinase that means the claims are not anticipated by either reference since they both teach utilizing naturally occurring enzymes (See Remarks, pp. 5-6).
The Examiner has considered this argument but does not find it convincing. This is because it is first noted, Applicant’s definition for “engineered” in the specification at paragraph [0038] is as follows (PG-Pub paragraph numbering):
[0038] As used herein, “recombinant,” “engineered,” and “non-naturally occurring” when used with reference to a cell, nucleic acid, or polypeptide, refer to a material, or a material corresponding to the natural or native form of the material, that has been modified in a manner that would not otherwise exist in nature. In some embodiments, the cell, nucleic acid or polypeptide is identical [sic] a naturally occurring cell, nucleic acid or polypeptide, but is produced or derived from synthetic materials and/or by manipulation using recombinant techniques. Non-limiting examples include, among others, recombinant cells expressing genes that are not found within the native (non-recombinant) form of the cell or express native genes that are otherwise expressed at a different level.
Thus, this merely means that the process by which the material/enzyme is produced may be different, however, the product/enzyme which is produced is identical. Thus, it would be materially impossible to tell an “engineered” 3’O-kinase from the naturally occurring counterpart which are utilized in the methods of both Brunngraber et al. and Oki et al. The courts have established that when interpreting product by process limitations nested within method claims, the exact same analysis/construction of the product by process limitation is required just as if the product by process limitation was in a product claim. See BIOGEN MA INC., v. EMD SERONO, INC., PFIZER INC., No. 19-1133 (Fed. Cir. 2020).
As such, merely amending the claims to recite “recombinant” or “engineered” is not seen as imparting anything different to enzymes or the claims. Thus, the rejections are maintained.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 46, 49, 53-58, 60-61, 64 and 66-67 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-46 and 87-95 of co-pending application 18486140. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘140 application anticipate the instant claims.
The instant claims in their broadest are drawn to a method of producing an NTP with a phosphate group at the 3′ position of the sugar (NQP), the method comprising (i) providing a 3′O-kinase enzyme, and (ii) contacting the 3′O-kinase enzyme with an NTP under suitable reaction conditions, such that an NQP is produced. Dependent claim 64 recites wherein the 3′O-kinase enzyme is an engineered 3′O-kinase comprising a polypeptide sequence having at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more sequence identity to a reference sequence selected from SEQ ID NO: 10, 142, 372, 450, 496, 1042, 1180, 1412 1464, 1800, and 2078, or a functional fragment thereof, and one or more amino acid residue differences relative to the reference sequence; wherein SEQ ID NO: 2078 is the elected species. Dependent claims 58 recite the method further comprises a phosphate recycling system, and that the phosphate recycling system comprises a phosphate donor and a kinase, wherein the kinase comprises acetate kinase or polyphosphate kinase/transferase; and a pyruvate oxidase enzyme (claims 58, 60-61).
The claims to the ‘140 application in their broadest are drawn to A method of producing a nucleotide triphosphate with a phosphate group at the 3′ position of the sugar (NQP), the method comprising at least:
contacting a nucleoside diphosphate (NDP) with a nucleoside diphosphate kinase, a 3′-O-kinase, and a phosphate donor under reaction conditions such that a NTP with a phosphate group on the 3′ position of the sugar moiety (NQP) is produced (Claim 1); and A method of producing a NTP with a phosphate group at the 3′ position of the sugar (NQP), the method comprising contacting a nucleoside with a nucleoside kinase, a nucleoside monophosphate kinase, nucleoside diphosphate kinase, and a 3′-O-kinase in presence of a phosphate donor under reaction conditions such that a product NTP with a phosphate group at the 3′ position of the sugar (NQP) is produced (Claim 30). Dependent claim 87 recite the method further comprises an NTP regenerating system which comprise creatine kinase, pyruvate kinase, polyphosphate kinase, and/or R-acetate-kinase; and also, further comprising a pyruvate oxidase (claim 94).
As such, the claims of the ‘140 application, while incorporating additional enzymes to the method, nonetheless still anticipate the instant claims because additional steps and enzymes are permissible in the instant claimed methods as they are open and comprising.
It is noted, the elected species SEQ ID NO: 2078 has 100% sequence identity to SEQ ID NO: 5082 of co-pending application 18486140 – See Supplemental Content, 20260406_154243_us-18-485-925-2078.rapbm, Result #1; wherein SEQ ID NO: 5082 is one of the 3’O-kinase utilized in the methods of making NQP from NTP (See claim dependent 46).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s Response and Examiner’s Rebuttal:
Applicant’s acknowledge the rejection and state that because the rejection is provisional, that it be held in abeyance or withdrawn until the claims of the ‘140 application has issued.
This request is acknowledged. The rejection is maintained for reasons of record.
Conclusion
No claim is allowed.
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 SUZANNE M NOAKES whose telephone number is (571)272-2924. The examiner can normally be reached M-F (7-4).
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/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656 11 September 2026
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