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 .
Election/Restrictions
Claims 1-22 are pending.
Applicant’s election without traverse of the following species DNA nucleic acid substrate, DNA synthesized nucleic acid, and Y family DNA pol. in the reply filed on 08/03/2026 is acknowledged.
Claims 2, 4, 5, 7-8, 10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/03/2026.
Claims 1, 3, 6, 9, 11-22 are examined here.
Priority
The benefit of claims to application 63/210,429, filed on 06/14/2021, via its 371 of PCT/US2022/033312, filed on 06/13/2022, is recognized.
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, Application No. 63/210,429 and PCT.US2022/033312, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Claim 1 recites “without any changes to or in the reaction triggering or inducing changes in the activity of the template-independent nucleic acid polymerase.” The language of this limitation does not appear to be noted in the ‘429 nor the ‘312. Thus, benefit of ‘429 filing is denied.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/13/2023, 08/05/2024, and 08/03/2026 were filed before the mailing date of this Office Action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Cite #21 of 08/05/2024 is listed in IDS of 12/13/2023 and is crossed out.
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: Claim 1 recites “without any changes to or in the reaction triggering or inducing changes in the activity of the template-independent nucleic acid polymerase”. The specification does not provide antecedent basis for this language.
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 and its dependent claims (3, 6, 9, 11-22) 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.
Claim 1 recites the limitation of “without any changes to or in the reaction triggering or inducing changes in the activity of the template-independent nucleic acid polymerase.” This language is not properly described in the international application. Although the plain meaning of the language is interpreted as no material changes can be made to the reaction or not manipulating the reaction condition, the specification fails to provide what changes or inducement that is considered triggering or that changes activity the TINAP.
Dependent claims 3, 6, 9, 11-22 are also rejected for containing the new subject matter.
Claims 1, 3, 6, 9, 11-22 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.
Claim 1 recites in limitation 1(b) a requirement of “adds only a single nucleotide to the nucleic acid substrate molecule present in the reaction to form a new nucleic acid molecule without any changes to or in the reaction triggering or inducing changes in the activity of the template-independent nucleic acid polymerase.”
When claim 1 is analyzed in light of the specification, instant invention encompasses that 1) only 1 nucleotide, which would be any nucleotide, is added to 2) any nucleic acid (NA) substrate, which would be by any oligonucleotide substrate of any length (can be 1 to 100,000 or longer, see par. 88) and 3) by any template independent nucleic acid polymerase (TINAP) with an excess of free unblocked nucleoside triphosphate. Under BRI, TINAP can be any DNA or RNA polymerase (par. 68). Under BRI, the NA substrate can be RNA or DNA (par. 68).
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. In the instant case, it should be made clear that the specification does not disclose any species of TINAP that adds only one of any nucleotide to any oligonucleotide 100% of the time (see Fig. 2, 3, Table 2). However, the specification does describe TINAP species of EDS053 and EDS054 when adding a dGTP to SEQ ID NO: 45 template (a 20-nt. ssDNA sequence ending in thymidine) whose complete structure is disclosed, thus adding only a single dGTP to the nucleic acid substrate molecule 100% of the time (Table 2, RXN# 30 for EDS053 and RXN# 31 for EDSO54, see excerpt below of Table 2). The genus of template-independent nucleic acid polymerase (TINAP) encompasses a large number of variants and molecules that have a different structure. The specification does not describe the complete structure of a representative number of species of the large genus of TINAP or functional equivalents thereof that are capable of adding only any single nucleotide to any nucleic acid substrate molecule.
Jensen’s (2021, Biochemistry, 57, 1821-1832, in IDS) review article of template-independent enzymatic oligonucleotide synthesis (TiEOS) focusing on studies of terminal deoxynucleotidyl transferase (TdT), a X-family DNA polymerase, indicates that one drawback of TdT is that it adds more than one nucleotide (i.e. > n+1) (abstract). Other polymerases have similar issue (see Pomerantz et al., US20210171920, for a family A DNA polymerase, Fig. 2A-B).
Similarly, reviewing instant specification, Fig. 2 legend on pg. 6-7, and reviewing starting length and the final length, most species of enzymes added more than 1 nt. (ES029 added 2, EDS048 and ESD015 added more than 40, EDS017 added 25, etc. . . ). The species of EDS053 and 054 looked promising, since their final length was 1 more than the starting length (pg. 7). However, when reviewing results provided in Table 2, only when EDS053 and EDS054 use a nucleic substrate of SEQ ID NO: 45 (a single stranded DNA substrate) with dGTP is there addition of only 1 nt. 100% of the time (see RXN# 30, 31 from excerpt of Table 2 provided below; results of just polymerases EDS053/EDS054 are noted). While for some reactions, polymerases EDS053 and EDS054 do not add a nucleotide to the substrate in certain percent of product analysis (see, e.g., rxn# 18, 199; i.e. no “new nucleic acid molecule” as required of cl. 1).
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Although the specification indicates that ribonucleotide triphosphates (rNTPs) can be added to single stranded DNA substrate by DNA polymerases, with EDS029 adding only a single rNTP for synthesis of a chimeric nucleic acid product (Fig. 5A/5B, par. 25; Table 3, par. 153), the specification does not disclose any polymerase adding nucleotides to a RNA substrate. Nor does the specification disclose RNA polymerase adding only a single nucleotide to a nucleic acid substrate.
Similarly, Pomerantz discloses that a family A polymerase (pol theta) adds numerous rNTPs to a ssDNA molecule more effectively than TdT (Fig. 28B, par. 246). Pomerantz also discloses pol theta’s ability to add rNTP to RNA substrate (Fig. 28E). However, pol theta adds more than one nt.
There is also some confusion regarding the results. E.g., Table 2 lists polymerase EDS030 when mixed with NA substrate SEQ ID NO: 45 and dGTP resulting in 100% addition of one nucleotide (“%N+1” column). But Legend of Fig. 2 indicates that EDS030 adds 3 nt. when the reaction mixture contains all dNTPs, thus suggesting that it has a preference to add more than one specific dNTP (pg. 7).
Regardless, not any template independent nucleic acid polymerase meets the claimed limitation of adding only any single nucleotide to any nucleic acid substrate.
Next, then, it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics (i.e. other than structural requirements), specific features and functional attributes that would distinguish different members of the claimed genus. No specific features and functional attributes of the TINAP are provided that would distinguish different members of the claimed genus of TINAP with the ability to add just one nt.
Regarding instant cl. 10, the specification fails to designate which of the enzyme(s) of Table 1 is a Y family polymerase (or for that matter X family polymerase). Based on homology analysis, it appears EDS053 and EDS054 are Y family polymerases.
The inventions of dependent claims 3, 6, 9, 11-22 require the use of the inventions of Claim 1 and therefore are likewise rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement.
Further, regarding instant cl. 13-17, the “efficiency” varies based on multiple factors, including template type, the 3’-end of the template, the NTP in the mixture, the polymerase, thus it is difficult to point to the structure that results in a particular “efficiency.” Thus, the subject matter of cl. 13-17 is 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.
Applicant’s attention is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112(a) or Pre-AIA 35 U.S.C. 112, first paragraph, "Written Description" Requirement (MPEP2163).
In conclusion, Applicant’s disclosure of only the species of EDS053 and EDS054 when adding a dGTP to SEQ ID NO: 45 template (a 20-nt. sequence ending in thymidine) is not deemed sufficient to reasonably convey to one skilled in the art that Applicant was in possession of the claimed broad genus TINAP that adds only a single nucleotide to the nucleic acid substrate molecule with free unblocked nucleoside triphosphate at the time the application was filed. Thus, it is concluded that the written description requirement is not satisfied for the claimed genus.
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.
Claims 13-17 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.
There is confusion regarding the term “efficient.” The claim appears to conflate the concept of probability with efficiency based on data of Table 2. Efficiency for an enzyme is its reaction rate, measured in various manner, one is Michaelis-Menten kinetic parameters, i.e. Kcat/Km (see Boule et al., 2001, JBC, 276, 31388-31393; see pg. 31388 for TdT enzymatic assays and determination of Kinetic parameters and Kcat/Km data in Table I). Conflating efficiency with probability confuses the speed of a reaction with how likely it is to happen. Kinetics provides the rate of the reaction, while probability suggests favorability of a reaction. Due to the possibility of a reaction not occurring, it’s not clear what is causing the reaction to occur or not occur in a particular mixture.
The specification does not describe TINAP by its reaction rate. The specification describes the data of Table 2 for “efficiency” purposes: “the table clearly shows a yield of the desired N+1 extension product in each example, with single nucleotide addition efficiencies ranging from 36% to 100%” (pg. 37).
E.g. for reaction # 199, of the 100% of the products analyzed of the mixture of EDS054 enzyme, dATP, and NA substrate SEQ ID NO: 43, 60% of the products did not have dATP added to NA substrate, while for 40% there was a single dATP added. The result indicates that out of approximately 3 products analyzed, the probability is that one would have a single nucleotide added. In this reaction, the issue is that EDS054 enzyme when both substrates are present (nucleic acid substrate and nucleoside triphosphate) does not result in the desired N+1 product at 60% of the time. Due to the possibility of a reaction not occurring, it’s not clear what is causing the reaction to occur or not occur in a particular mixture. Does it require more time, change in temperature, or some other favorable condition for reaction to begin?
Thus, cl. 13-17 are rejected for indefiniteness.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 3, 6, 9 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Magyar et al. (US Pub. US20200263152, pub. 8/20/2020, “Magyar”).
Regarding cl. 1 and 9, Magyar discloses terminal deoxynucleotidyl transferase (TdT), a DNA polymerase capable of catalyzing random addition of nucleotides in a template-independent manner to a DNA strand in vitro but has a drawback of adding more than one nucleotide (par. 5, relevant to instant cl. 9). Magyar demonstrates that modifying the position 403 of TdT from K (Lys) to R (Arg) results in the enzyme adding one nucleotide to a seed oligonucleotide in a reaction with a duration of 30 sec. (par. 58, see K403R lane of Fig. 24 below). The reaction mixture includes excess 125 uM dNTP mix, an oligo seed strand, and incubated at 37oC for desired amount of time (30s to 1 hr.) (par. 265)
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Further, Magyar discloses conducting a reaction in a reaction chamber with a TdT enzyme and excess nucleotides are flushed, and repeating the procedure by adding a new nucleotide and steps are repeated until the desired sequence has been synthesized (par. 131-138, 263).
Thus, the repeating of cycles by separating nucleic acid molecule from free nt. and repeating the steps to synthesize the desired NA sequence is disclosed by Magyar. Thus, it would be obvious for a skilled artisan with expectation of reasonable success to synthesize a desired nucleic acid by mixing a modified TdT enzyme variant K403R (a template independent nucleic acid polymerase that is active) to add a single nucleotide with dNTPs (unblocked nucleoside triphosphate) on a seed strand in a repeating step process (relevant to instant cl. 1).
Regarding instant cl. 3, Magyar discloses oligo DNA seed strand (par. 132).
Regarding instant cl. 6, Magyar discloses synthesized nucleic acid is DNA, since a dNTP is added to the 3’ end of a seed oligo strand (par. 33).
Regarding instant cl. 12, Magyar in claim 28 discloses a method of template-independent polynucleotide synthesis comprising the steps of contacting a nucleotide on a solid support with the genetically engineered TdT, wherein the TdT is capable of attaching a mononucleotide to the 3’ end of a single-stranded polynucleotide.
Claims 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Magyar et al. (US Pub. US20200263152, pub. 8/20/2020, “Magyar”) as applied to claims 1, 3, 6, 9, and 12 above, and in view of Boule et al. (2001, JBC, 276, 31388-31393, “Boule”).
Regarding instant cl. 18-20, the disclosure of Magyar regarding cl. 1, 3, 6, 9, 12 is disclosed above.
Here, nucleic acid substrate ends is interpreted as nucleic acid substrates, since DNA polymerase TdT adds to the 3’ hydroxyl end of a single stranded substrate and there is only one 3’ hydroxyl end on a substrate.
Magyar does not disclose various concentration of nucleic acid substrates and polymerases.
MPEP 2144.05(II)(A) discloses that differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical.
Here, both molar excess of enzyme relative to NA substrate ends and NA substrate ends to enzyme is recited in cl. 18, 19 and cl. 20 recites that there are equimolar amounts.
Boule discloses characterizing TdT enzyme in its ability to incorporate ribonucleotides and deoxyribonucleotides (title) and tests only a polyA DNA strand ((dA)10 aka “initiator”) of 5 uM, TdT of 250 nM (see legend of Fig. 3), thus there is excess of NA substrate ends relative to polymerase; a skilled artisan recognizes that to characterize the enzyme it would be obvious to vary the concentration of enzymes and substrates, including excess of enzyme relative to substrate(s) or vice versa. Thus, cl. 18-20 would be prima facie obvious as noted in obvious.
Claims 11, 22 are rejected under 35 U.S.C. 103 as being unpatentable over Magyar et al. (US Pub. US20200263152, pub. 8/20/2020, “Magyar”) as applied to claims 1, 2, 6, 9, and 12 above, and further in view of Pomerantz et al. (US Pub. US20210171920, pub. 06/10/2021, “Pomerantz”).
Magyar’s disclosure pertaining to claims 1, 3, 6, 9, and 12 are noted above.
Magyar does not disclose a template independent nucleic acid polymerase is immobilized on a solid support (cl. 22) nor a Y-polymerase (cl. 11).
Pomerantz discloses that DNA polymerase theta (pol Θ) is a capable of replicating past lesions, i.e. a double-strand break, and the polymerase can replicate across a DNA synapse stabilized by a minimal amount of sequence homology (par. 3). Pomerantz discloses a method of de novo synthesis using pol Θ’s transferase activity by mixing pol Θ, a representative of DNA polymerase A family, substrate, at least one nucleobase and a reaction solution further comprising a divalent cation and then isolating the nucleic acid (par. 17, 172). Pomerantz discloses that pol Θ comprises a template independent transferase activity, i.e. ability to add dNTPs to a single-stranded DNA substrate (Fig. 1A-E, par. 22; uses poly-dC single-stranded DNA of 29 nt., dTTP to test various conditions; with MES/TRIS buffer at pH 7, the results indicate a single dTTP added; however, for all other conditions, it adds multiple dTTPs). In a series of experiments to characterize pol Θ’s terminal transferase activity, it was immobilized to magnetic streptavidin beads and then mixed with single-stranded DNA for binding activity, and excess unbound pol Θ was washed away (par. 211, relevant to instant cl. 22).
Further Pomerantz discloses that error-prone polymerases due to their open active sites which enable them to tolerate particular DNA lesions are referred to as translesion polymerases and are mostly among the Y-family polymerase and adds that pol Θ of polymerase A family is also a similar enzyme in its ability to tolerate bulky lesions and is capable of replicating past the most lethal lesion, a double-strand break (DSB) (par. 3, relevant to instant cl. 11).
One of the KSR rationale that may be used to support a conclusion of obviousness is that there is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the TdT variant of Magyar in view of Pomerantz and arrive at the claimed invention with a reasonable expectation of success. Thus, to examine the terminal transferase activity of TdT variant, a skilled artisan would reasonably expect success by binding the TdT variant of Magyar to a magnetic streptavidin beads of Pomerantz to test transferase activity of TdT. Thus, cl. 22 would be prima facie obvious.
One of the KSR’s rationale for supporting conclusion of obviousness is “obvious to try,” requiring the following three findings: (1) a finding that at the relevant time, there had been a recognized problem or need in the art, which may include a design need or market pressure to solve a problem; (2) a finding that there had been a finite number of identified, predictable potential solutions to the recognized need or problem; (3) a finding that one of ordinary skill in the art could have pursued the known potential solutions with a reasonable expectation of success.
Here, Pomerantz discloses a need for composition and methods providing an effective template-independent transfer of canonical and modified deoxyribonucleotides to DNA (par. 6) and discloses that pol Θ and DNA polymerase of Y-family have similar translesion activity. Thus, it would be obvious for a skilled artisan to pursue a known potential solution of substituting DNA polymerase Y for the TdT variant of Magyar to identify an effective template-independent transfer activity to add canonical deoxyribonucleotides to a DNA. Thus, cl. 11 would be prima facie obvious.
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 1, 3, 6, 9, 11, 13-17, 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 14 of copending Application No. 18/569,883 (‘883), as evidenced by Vaisman et al. (2005, EMBO J., 24, 2957-2967, “Vaisman”) and GenBank Acc# WP_124690524.1 (www.ncbi.nlm.nih.gov/protein/WP_124690524; accessed 09/15/2026) for cl. 11. Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 14 of ‘883 teaches the following:
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Table 1 of ‘883 defines the SEQ ID NOs of cl. 14 of ‘883.
Table 1s of ‘883 and of instant application are the same.
Thus, the cl. 14 of ‘883 teaches SEQ ID NOs, which are species of instant template independent nucleic acid polymerase, thus corresponding to instant cl. 1.
Par. 127 of ‘883 indicates that “Genes encoding the DNA polymerases listed in Table 1,” i.e. defining the polymerases of Table 1, which correspond to instant cl. 9.
Regarding instant cl. 3 and 6, since the polymerases are DNA polymerases, it would be inherent that they utilize dNTPs to synthesize DNA strand.
Regarding instant cl. 11, Table 1 of ‘883 defines EDS054 represented by NCBI Ref. # WP_124690524.1 (pg. 30), and as evidenced by NCBI site of WP_124690524.1 discloses a publication by Vaisman et al., which indicates that translesion DNA polymerase, Dpo4, as a member of a Y-family polymerase (pg. 2957-2958).
Regarding instant cl. 13-17, the “efficiency” is the inherent function of the enzymes represented by the SEQ ID NOs taught by ‘883.
Regarding instant cl. 21, since the claim of 14 of ‘883 teaches species of Markush claim, one polymerase can be replaced with the other equivalent functioning polymerase for the same result.
Claims 18-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 14 of copending Application No. 18/569,883 (‘883) in view of Boule et al. (2001, JBC, 276, 31388-31393, “Boule”).
Regarding instant cl. 18-20, the disclosure of ‘883 regarding cl. X is disclosed above.
Here, nucleic acid substrate ends is interpreted as nucleic acid substrates, since DNA polymerase TdT adds to the 3’ hydroxyl end of a single stranded substrate and there is only one 3’ hydroxyl end on a substrate.
‘833 does not disclose various concentration of nucleic acid substrates and polymerases.
MPEP 2144.05(II)(A) discloses that differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical.
Here, both molar excess of enzyme relative to NA substrate ends and NA substrate ends to enzyme is recited in cl. 18, 19 and cl. 20 recites that there are equimolar amounts.
Boule discloses characterizing TdT enzyme in its ability to incorporate ribonucleotides and deoxyribonucleotides (title) and tests only a polyA DNA strand ((dA)10 aka “initiator”) of 5 uM, TdT of 250 nM (see legend of Fig. 3), thus there is excess of NA substrate ends relative to polymerase; a skilled artisan recognizes that to characterize the enzyme it would be obvious to vary the concentration of enzymes and substrates, including excess of enzyme relative to substrate(s) or vice versa. Thus, cl. 18-20 would be prima facie obvious as noted in obvious.
This is a provisional nonstatutory double patenting rejection.
Claims 12 and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 14 of copending Application No. 18/569,883 (‘883) in view of Pomerantz et al. (US Pub. US20210171920, pub. 06/10/2021, “Pomerantz”)
Disclosure of cl. 14 of ‘883 is noted above.
Claims of ‘883 do not disclose nucleic acid substrate (cl. 12) nor TINAP (cl. 22) is immobilized on a solid support.
Pomerantz discloses immobilization of either oligonucleotide substrate or DNA polymerase A, specifically pol theta, immobilized on streptavidin bead for the characterization of the enzyme’s activity (par. 79, 145, Fig. 18A).
Thus, immobilizing enzymes of ‘883 to characterize their activity would be prima facie obvious.
This is a provisional nonstatutory double patenting rejection.
Allowable Subject Matter
No claim allowed.
Conclusion
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Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at 571-272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KEYUR A VYAS/Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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