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 .
Response to Amendment
This action is in response to the papers filed February 3, 2026. Applicant’s remarks and amendments have been fully and carefully considered but are not found to be sufficient to put the application in condition for allowance. Any new grounds of rejection presented in this Office Action are necessitated by Applicant's amendments. Any rejections or objections not reiterated herein have been withdrawn. This action is made FINAL.
Claim 1 is currently pending and has been examined herein.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on applications filed in Japan on October 3, 2022. It is noted, however, that the foreign priority date is the effective filing date of the claimed invention if
the foreign application supports the claimed invention under 112(a), and
the applicant has perfected the right of priority by providing
a certified copy of the priority application, and
a translation of the priority application (if not in English).
In the instant case, the applicant has submitted a certified copy of the priority application but it is not in English and the examiner cannot determine if it supports the claimed invention. The effective filing date of the application is considered to be August 30, 2023 which is the actual filing date of instant application 18/458,354.
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.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Ko et al. (U.S. Patent Publication US 2019/0360021 A1, published November 28, 2019) in view of Colston et al. (U.S. Patent No 9,156,010, issued October 13, 2015) and Gene Link 2014 (PCR Additives & Enhancers, found online at https://www.genelink.com/Literature/ps/M40-3021-PCR_Additives_Ver5.2.pdf).
Ko et al. teach a method of performing a nucleic acid amplification reaction (col 6, lines 7-15), using a reaction composition including an amplification target nucleic acid (col 7, lines 33-37) and a copolymer containing constitutional units derived from 2-(meth)acryloyloxyethyl phosphorylcholine and (meth)acrylic acid (col 4, lines 32-35) at a concentration between 0.005 to 0.5 w/v% (col 5, lines 30-35).
Ko et al. do not teach the presence of water in the reaction composition.
Gene Link 2014 teaches the addition of water to ‘typical’ nucleic acid amplification reactions such as PCR (page 7, “Typical PCR Premix”).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the invention to have modified the amplification reaction of Ko et al. to include water to the PCR mix, as suggested by Gene Link. Water is a conventional component of nucleic acid amplification reactions such as PCR, and it would have been obvious to a skilled artisan to use it, for example, to prepare the buffer or sample.
The combination of Ko et al. and Gene Link do not teach any particular copy number concentration of target nucleic acid.
Colston et al. teach amplification target nucleic acids at a concentration of 10,000 copies/mL or lower (paragraphs 0148-0149, 0158).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the invention to have modified the nucleic acid amplification reaction taught by the combination of Ko et al. and Gene Link so that the concentration of target nucleic acid was lower than 10,000 copies/mL. For example, one skilled in the art would have been motivated to use 1 copy of target sequence per reaction partition at less than 1 uL total volume in order to determine absolute concentration of a sample in digital PCR applications (paragraphs 0158, 0169).
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Sakaki et al. (U.S. Patent 8,252,531 B2, issued August 28, 2012) in view of Colston et al. (U.S. Patent No 9,156,010, issued October 13, 2015) and Gene Link 2014 (PCR Additives & Enhancers, found online at https://www.genelink.com/Literature/ps/M40-3021-PCR_Additives_Ver5.2.pdf).
Sakaki et al. teach a method of performing a nucleic acid amplification reaction (col 6, lines 65-67 – col 7, lines 1-3), using a reaction composition including an amplification target nucleic acid (col 6, lines 3-5) and a copolymer containing constitutional units derived from 2-(meth)acryloyloxyethylphosphorylcholine and (meth)acrylic acid (col 4, lines 18-23 & col 4, lines 38-40) at a concentration between 0.005 to 0.5 w/v% (col 6, lines 20-25).
Sakaki et al. do not teach the presence of water in the reaction composition.
Gene Link 2014 teaches the addition of water to ‘typical’ nucleic acid amplification reactions such as PCR (page 7, “Typical PCR Premix”).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the invention to have modified the amplification reaction of Sakaki et al. to include water to the nucleic acid amplification reaction, as suggested by Gene Link. Water is a conventional component of nucleic acid amplification reactions such as PCR, and it would have been obvious to a skilled artisan to use it, for example, to prepare the buffer or sample.
The combination of Sakaki et al. and Gene Link do not teach any particular copy number concentration of target nucleic acid.
Colston et al. teach amplification target nucleic acids at a concentration of 10,000 copies/mL or lower (paragraphs 0149, 0158).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the invention to have modified the nucleic acid amplification reaction taught by the combination of Sakaki et al. and Gene Link so that the concentration of target nucleic acid was lower than 10,000 copies/mL For example, one skilled in the art would have been motivated to use 1 copy of target sequence per reaction partition at less than 1 uL total volume in order to determine absolute concentration of a sample in digital PCR applications (paragraphs 0158, 0169).
Response To Arguments
Obviousness Rejection Based on Ko et al.
In the response dated 2/03/26, the Applicants traversed the rejection under 35 U.S.C. 103 based on Ko et al. In the response, the Applicants argue that Ko et al., in view of Colston et al. and Gene Link 2014, does not disclose or suggest a reaction composition comprising one or more polymers selected from:
(A1) a polymer consisting of a constitutional unit derived from 2-(meth)acryloyloxyethylphosphorylcholine, and
(A2) a copolymer containing a constitutional unit derived from 2-(meth)acryloyloxyethylphosphorylcholine and a constitutional unit derived from (meth)acrylic acid,
Additionally, the applicants argue that Ko et al. does not disclose or suggest the unexpected benefit of improved repeatability of the nucleic acid amplification resulting from said polymer(s). The Applicants further argue that neither Ko et al, nor Ko et al. in view of Colston et al. and Gene Link 2014, disclose or reasonably suggest the required reaction composition in combination with a) a concentration of a target nucleic acid lower than 10,000 copies/mL and b) improving the repeatability of the nucleic acid amplification.
Regarding the arguments that Ko does not disclose or suggest a polymer as required by the claims, these argument have been fully considered. The Examiner agrees that Ko does not disclose (A1) “a polymer consisting of a constitutional unit derived from 2-(meth)acryloyloxyethylphosphorylcholine.” However, the argument that Ko does not disclose (A2) “a copolymer containing a constitutional unit derived from 2-(meth)acryloyloxyethylphosphorylcholine and a constitutional unit derived from (meth)acrylic acid” is not persuasive.
According to MPEP 2111 (concerning the broadest reasonable interpretation of a claim limitation), the meaning given to a claim term must be consistent with the ordinary and customary meaning of the term (unless the term has been given a special definition in the specification). In the instant case, there is no special definition given for the term “derivative of” in the specification, and the ordinary and customary meaning of the “a derivative” in chemistry is a chemical which can be synthesized from a parent compound.
The language in the instant application describing the copolymer (A2) does not require precisely methacrylic acid or acrylic acid as a monomer, but instead “a constitutional unit derived from (meth)acrylic acid.” The broadest reasonable interpretation of (A2) therefore includes alkyl methacrylate, which is an ester (or derivative) of methacrylic acid. Therefore, Ko discloses one of the instant polymers (see par. 32 of Ko et al.) as required by the instant claim, and the limitation is considered to be met.
Regarding the arguments that neither Ko, nor the combination of Ko, Colston, and GeneLink discloses that the reaction composition improves the repeatability of the nucleic acid amplification, the argument has been fully considered but is not persuasive.
According to MPEP 2145 (II): “mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention.” Although the combination of Ko and Colston does not show the unexpected result of improved repeatability, this advantage would flow naturally from the combination of Ko and Colston, the motivation for which is discussed in the nonfinal rejection. The combination would possess the property of improved repeatability in nucleic acid amplification. Furthermore, having been amended 2/03/26, the pending claim no longer recites the intended use of ‘improving repeatability of a nucleic acid amplification method.’
The Applicant argued non-obviousness due to the unexpected benefit of improving the repeatability of the nucleic acid amplification at concentrations under 10,000 copies/mL – a benefit which would not have been reasonably predicted in the absence of hindsight knowledge. This argument has been fully considered but not found persuasive.
According to MPEP 716.02(b), the burden is on the Applicant to show that unexpected results are in fact unexpected, unobvious, and of statistical and practical significance. According to MPEP 716.02(d), the objective evidence of non-obviousness must be commensurate in scope with claims. To establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960).
The specification provides evidence that addition of polymer (A1) provided enhanced amplification vs reaction compositions with no polymer at concentrations of 625 and 2,500 copies/mL of nucleic acid, but not at 25,000 copies/mL of nucleic acid (Tables 5-1, 5-2). The specification provides evidence that addition of polymer (A2) provided enhanced amplification vs reaction composition without the polymer at concentrations of 2,500 and 1,250 copies/mL of nucleic acid (Tables 9-1, 9-2).
In this case, the Applicant has not provided enough evidence to show that any unexpected results occurred over the whole range of 1 – 10,000 copies/mL. The applicant has also not given a representative number of examples where amounts greater than 10,000 copies/mL and less than 10,000 copies/mL were tested and statistically comparison was conducted to show that the results are of statistical and practical significance.
The rejection is maintained.
Obviousness Rejection Based on Sakaki et al.
In the response, the Applicants traversed the rejection under 35 U.S.C. 103 based on Sakaki et al. In the response, the Applicants argue that neither Sakaki et al, nor Sakaki et al. in view of Colston et al. and Gene Link 2014, disclose or reasonably suggest the required reaction composition in combination with a) a concentration of a target nucleic acid lower than 10,000 copies/mL and b) improving the repeatability of the nucleic acid amplification
These arguments have been fully considered but are not persuasive. As discussed for the obviousness rejection over Ko, Colston, and Gene Link above, the intended use of improved repeatability is no longer a requirement of the claim, and applicant has not provided enough evidence to show that the unexpected results are in fact unexpected as well as statistically and practically significant. Nor has the Applicant provided enough evidence to show that any unexpected results occurred over the whole claimed range.
The rejection is 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.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of Application No. 19/470,188 (copending application). Although the claims at issue are not identical, they are not patentably distinct from one another. Both sets of claims require water, amplification target nucleic acids, and one or more polymers including a copolymer containing a constitutional unit derived from 2-(meth)acryloyloxyethylphosphorylcholine and a constitutional unit derived from (meth)acrylic acid (see reference claims 2-4). Though only claims 3 and 4 of the reference application are drawn to a method of improving nucleic acid amplification, claims 1 and 2 recite polymers and compositions for use with nucleic acids. It would be obvious to modify the claims to recite usage of the polymers and/or compositions for nucleic acid amplification. The instant application’s range of 10,000 or less copies per mL for target nucleic acid can be considered anticipated by the reference application’s claim to a nucleic acid at any concentration. The instant application’s claim to a polymer with a range of concentration of 0.005 to 0.5 w/v% can be considered anticipated by the reference application’s claim to the polymer at any concentration. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of Application No. 19/470,201 (copending application), in view of Gene Link 2014. Although the claims at issue are not identical, they are not patentably distinct from one another. Both sets of claims are drawn to a polymer (see reference claim 1-3) and reaction composition (see reference claim 2) used in a method of nucleic acid amplification (see reference claim 3). Both sets of claims require amplification target nucleic acids and one or more polymers including a copolymer containing a constitutional unit derived from 2-(meth)acryloyloxyethylphosphorylcholine and a constitutional unit derived from (meth)acrylic acid (see reference claims 2 and 3). Though only claim 3 of the reference application is drawn to a method of nucleic acid amplification, claims 1 and 2 recite polymers and compositions for use with nucleic acids. It would be obvious to modify the claims to recite usage of the polymer and/or composition. Although the reference application does not explicitly require water, it would be obvious to one with ordinary skill in the art that water is present in a nucleic acid amplification reaction (see Gene Link 2014). The instant application’s range of 10,000 or less copies per mL for target nucleic acid can be considered anticipated by the reference application’s claim to nucleic acid at any concentration. The instant application’s claim to a polymer with a range of concentration of 0.005 to 0.5 w/v% can be considered anticipated by the reference patent’s claim to the polymer at any concentration. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of Application No. 19/130,695 (copending application). Although the claims at issue are not identical, they are not patentably distinct from one another. Both sets of claims require water, amplification target nucleic acids, and one or more polymers including a copolymer containing a constitutional unit derived from 2-(meth)acryloyloxyethylphosphorylcholine and a constitutional unit derived from (meth)acrylic acid (see reference claim 9). Though only claim 9 of the reference application is drawn to a method of nucleic acid amplification, claims 1-8 recite compositions for use in nucleic acid amplification. It would be obvious to modify the claims to recite usage of the compositions. The instant application’s range of 10,000 or less copies per mL for target nucleic acid can be considered anticipated by the reference application’s claim to a nucleic acid at any concentration. The instant application’s claim to a polymer with a range of concentration of 0.005 to 0.5 w/v% can be considered anticipated by the reference application’s claim to the polymer at any concentration. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of Application No. 19/470,881 (copending application). Although the claims at issue are not identical, they are not patentably distinct from one another. Both sets of claims require water, amplification target nucleic acids, and one or more polymers including a copolymer containing a constitutional unit derived from 2-(meth)acryloyloxyethylphosphorylcholine and a constitutional unit derived from (meth)acrylic acid (see reference claims 3-8). Though only claims 7 and 8 of the reference application are drawn to a method of improving nucleic acid amplification, claims 1-6 recite polymers and compositions for use in nucleic acid amplification. It would be obvious to modify the claims to recite usage of the polymers and/or compositions. The instant application’s range of 10,000 or less copies per mL for target nucleic acid can be considered anticipated by the reference application’s claim to a nucleic acid at any concentration. The instant application’s claim to a polymer with a range of concentration of 0.005 to 0.5 w/v% can be considered anticipated by the reference application’s claim to the polymer at any concentration. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response To Arguments
Rejections Based on the ‘188, ‘201, ‘695, and ‘881 Applications
In the response, the Applicants traversed the obviousness-type double patenting provisional rejections based on the ‘188, ‘201, ‘695, and ‘881 applications. In the response, the Applicants argue that MPEP 804 (I)(B)(1)(b)(i) states that: "If a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent…” The Applicants argue that since they believe the remainder of the rejections have been overcome by their response (including rejections made under 35 U.S.C. 103 and Double Patenting), the instant application is in condition for allowance save for the rejections based on the ‘188, ‘201, ‘695, and ‘881 applications. Therefore, they argue that the examiner should withdraw these provisional rejections.
This argument has been fully considered but is not persuasive. The rejections based on 35 U.S.C. 103 have been maintained. The provisional rejections based on the ‘188, ‘201, ‘695, and ‘881 applications are therefore not the only remaining rejections, and argument based on MPEP 804(I)(B)(1)(b)(i) is moot. The rejections are maintained.
Conclusion
No claims are 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 Christine M Jones whose telephone number is (571)272-2585. The examiner can normally be reached Monday - Friday, 8AM - 4PM.
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/C.M.J./ Examiner, Art Unit 1682
/AMANDA HANEY/ Primary Examiner, Art Unit 1682