DETAILED ACTION
Notice of 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 .
Election/Restrictions
Restriction to one of the following inventions is required under 35 U.S.C. 121:
I. Claims 1-29, 31-34, 40-42, 45 and 112, drawn to 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; polynucleotides encoding, vectors and host cells comprising the same and methods of producing an engineered host cell comprising the same, classified in C12N 9/12.
II. Claims 46, 49, 53-58, 60-61, 64 and 66-67, 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; and wherein said 3′O-kinase comprises 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 (claim 64), classified in C12P 19/38.
The inventions are independent or distinct, each from the other because:
Inventions I and II are related as product and process of use. The inventions can be shown to be distinct if either or both of the following can be shown: (1) the process for using the product as claimed can be practiced with another materially different product or (2) the product as claimed can be used in a materially different process of using that product. See MPEP § 806.05(h). In the instant case the products as claimed can be used in materially difference processes such as enzyme substrate binding assays, or structure determination methods such as electron microscopy or NMR.
Restriction for examination purposes as indicated is proper because all the inventions listed in this action are independent or distinct for the reasons given above and there would be a serious search and/or examination burden if restriction were not required because one or more of the following reasons apply:
the inventions have acquired a separate status in the art in view of their different classification;
the inventions have acquired a separate status in the art due to their recognized divergent subject matter;
the inventions require a different field of search (for example, searching different classes/subclasses or electronic resources, or employing different search queries);
the prior art applicable to one invention would not likely be applicable to another invention;
the inventions are likely to raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112(a)..
Applicant is advised that the reply to this requirement to be complete must include (i) an election of an invention to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected invention.
The election of an invention may be made with or without traverse. To reserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the restriction requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Election of Species
This application contains claims directed to the following patentably distinct species an engineered 3’O-kinase having at least 85% sequence identity selected from SEQ ID NOs: 10, 142, 372, 450, 496, 1042, 1180, 1412, 1464, 1800 and 2078. The species are independent or distinct because each comprises a unique structure. In addition, these species are not obvious variants of each other based on the current record.
Applicant is required under 35 U.S.C. 121 to elect a single disclosed species, or a single grouping of patentably indistinct species, for prosecution on the merits to which the claims shall be restricted if no generic claim is finally held to be allowable. Currently, claims 46, 49, 53-58, 60-61 and 66-67 are generic.
There is a serious search and/or examination burden for the patentably distinct species as set forth above because at least the following reason(s) apply: each comprises a unique structure and requires a separate search.
Applicant is advised that the reply to this requirement to be complete must include (i) an election of a species to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected species or grouping of patentably indistinct species, including any claims subsequently added. An argument that a claim is allowable or that all claims are generic is considered nonresponsive unless accompanied by an election.
The election may be made with or without traverse. To preserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the election of species requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable on the elected species or grouping of patentably indistinct species.
Should applicant traverse on the ground that the species, or groupings of patentably indistinct species from which election is required, are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing them to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the species unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other species.
Upon the allowance of a generic claim, applicant will be entitled to consideration of claims to additional species which depend from or otherwise require all the limitations of an allowable generic claim as provided by 37 CFR 1.141.
Inventorship
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Rejoinder
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Oral Election
During a telephone conversation with attorney Adam Whiting on 06 April 2026 a provisional election was made to prosecute the invention of Group II, claims 46, 49, 53-58, 60-61, 64 and 66-67; and the species SEQ ID NO: 2078. Affirmation of this election must be made by applicant in replying to this Office action. Claims 1-29, 31-34, 40-42, 45 and 112 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Status of Application
Claims 1-29, 31-34, 40-42, 45-46, 49, 53-58, 60-61, 64, 66-67 and 112 are pending; Claims 46, 49, 53-58, 60-61, 64 and 66-67 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Thus, claims 46, 49, 53-58, 60-61, 64 and 66-67 are subject to examination on the merits.
Priority
The instant application claims benefit of US Provisional application 63/387,908 filed 16 December 2022 and is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 11 December 2024 (x2) have been considered by the examiner. See initialed and signed PTO/SB/08’s.
Claim Rejections - 35 USC § 112(b)
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 57 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 57 recites the limitation "the substrate NTP" in reference to the methods steps of claims 55 and 46. There is insufficient antecedent basis for this limitation in the claim because “substrate NTP” is not utilized in the claims from which it depends.
It is suggested this can be remedied by amendment of claim 46 to recite “substrate NTP” in part (ii) of the claim.
Claims 66-67 are 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.
Claims 66-67 are deemed indefinite because they recite increases/decreases of various activities of the engineered 3’O-kinase as compared to any wild-type 3’O-kinase. However, there are numerous wild-type 3’O-kinases known in the art, each which may have different activities. Thus, it is unclear exactly which wild-type enzymes need to be compared to ascertain any kind of difference making the metes and bounds of the claim unclear.
To overcome this rejection it is suggested to recite the increase/decrease of activity is compared to the relative reference sequence not having any modifications.
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.
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).
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 U.S. Patent No. 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. Dependnet 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 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).
Conclusion
No claim is allowed.
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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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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/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656 07 April 2026
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