DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. 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
2. Applicant’s election without traverse of Group II in the reply filed on 02 June 2026 is acknowledged.
Claim Status
3. Claims 1-6, 8-10, 12, 14-18, 20, 22 and 24-26 are pending.
Claims 1-6, 8-10, 12, 13, 18 and 26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 14-17, 20, 22, 24 and 25 read on the elected invention and have been examined herein.
Claim Objections
4. Claims 14-17, 20, 22, 24 and 25 are objected to because of the following informalities:
A. Claims 14-17, 20, 22, 24 and 25 are objected to because an “and” should be inserted prior to “an amplification primer” so that the claim is “close-ended.” That is, claim 14 should recite “…the primer group comprising the following primers: an identification primer…; and an amplification primer…”.
B. Claim 24 recites “HiFI-KAPA polymerase” whereas it appears the claim should recite “KAPA HiFi DNA polymerase.” See attached product sheet from Roche (“KAPA HiFi plus dNTPs”, available via URL: <rochesequencingstore.com/catalog/kapa-hifi-plus-dntps/>, printed 08 July 2026, 1 page) which states “KAPA HiFi DNA Polymerase is an innovative single-enzyme system designed with enhanced affinity for DNA, yielding superior performance in PCR.”
Appropriate correction is required.
Claim Rejections - 35 USC § 101
5. 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 14-17, 20, 22, 24 and 25 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of a natural phenomenon / naturally occurring product without significantly more. The judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Applicant’s attention is directed to MPEP 2106 “Patent Subject Matter Eligibility” and particularly 2106.04(b)II and 2106.04(c) “Examples of Products Lacking Markedly Different Characteristics.”
Regarding Step 1 of the analysis, the claims are directed to the statutory category of a product.
Regarding Step 2A, prong one, the claims recite the judicial exception of a natural phenomenon – i.e., a naturally occurring product.
Pursuant to the Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics, Inc. (June 2013), a naturally-occurring nucleic acid or fragment thereof, whether isolated or not, is not patent-eligible subject matter. Specifically, the Supreme Court held that “a naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated.”
In the present situation, the claims recite an identification primer and an amplification primer. The identification primer comprises contiguous nucleotides complementary to a target sequence and a nucleotide complementary to a mutated nucleotide or a non-mutated nucleotide. The amplification amplifies an amplification product synthesized by the identification primer - i.e., a sequence that is the complement of the target nucleic acid. As broadly recited, the primers comprise naturally occurring segments of a genome. The naturally occurring DNA segments do not have markedly different characteristics from their naturally occurring counterparts because the DNA segments convey the same genetic information.
Regarding the recitation of primers, Applicant’s attention is further directed to MPEP 2106.04(c)IIC which states:
“In Ambry Genetics, the court identified claimed DNA fragments known as "primers" as products of nature, because they lacked markedly different characteristics. University of Utah Research Foundation v. Ambry Genetics Corp., 774 F.3d 755, 113 USPQ2d 1241 (Fed. Cir. 2014). The claimed primers were single-stranded pieces of DNA, each of which corresponded to a naturally occurring double-stranded DNA sequence in or near the BRCA genes. The patentee argued that these primers had markedly different structural characteristics from the natural DNA, because the primers were synthetically created and because "single-stranded DNA cannot be found in the human body". The court disagreed, concluding that the primers’ structural characteristics were not markedly different than the corresponding strands of DNA in nature, because the primers and their counterparts had the same genetic structure and nucleotide sequence.”
In response to the patentee’s position that the primers “have a fundamentally different function than when they are part of the DNA strand,” the Court rejected this position on the basis that the natural DNA performed a similar function to bind to complementary nucleotide sequences – i.e., “just as in nature, primers utilize the innate ability of DNA to bind to itself.” Thereby, the Court held that the primers did not have a different structure as compared to their full length naturally occurring nucleic acid counterparts and were therefore patent ineligible.
Additionally, regarding claim 25 of a reagent for detecting an amplification product, as broadly recited such product may be a probe. Probes complementary to naturally occurring nucleic acids are also naturally occurring products that do not have any markedly different structural properties as compared to their naturally occurring counterparts.
Regarding the recitation of a kit (claims 20, 24 and 25) and a device (claim 22) comprising the primers, MPEP 2106.04(c)IA states “Where the claim is to a nature-based product in combination with non-nature based elements (e.g., a claim to "a yogurt starter kit comprising Lactobacillus in a container with instructions for culturing Lactobacillus with milk to produce yogurt"), the markedly different characteristics analysis should be applied only to the nature-based product limitation.”
In particular, regarding claim 24, while the recited DNA polymerases are not naturally occurring, their presence in a kit with the primers does not markedly change the properties of the primers over their naturally occurring counterparts since the primers and DNA polymerases may exist in separate compartments or tubes and need not interact with one another.
Thereby, herein the markedly different characteristics analysis is applied to the nature-based product limitations.
Regarding Step 2A, prong two, having determined that the claims recite a judicial exception, it is then determined whether the claims recite additional elements that integrate the judicial exception into a practical application.
Herein, the claims do not recite additional elements that integrate the recited judicial exceptions into a practical application of the exception(s).
Regarding Step 2B, the next question is whether the remaining elements – i.e., the non-patent-ineligible elements - either in isolation or combination, amount to significantly more than the judicial exception.
Regarding the claimed kits, the packaging of the natural products in a kit does not change their characteristics. The products may exist separately from one another and need not interact with one another in a manner which would change their characteristics from their natural counterparts.
Similarly, regarding claim 22, the recitation of a device comprising the primers does not change the characteristics of the primers so as to materially distinguish the primers per se over their naturally occurring counterparts.
Regarding claim 24, while the recited DNA polymerases are not naturally occurring, the inclusion of these DNA polymerases in a kit was well-known, routine and conventional in the prior art. For example, Zheng et al (CN101565759A; English translation included, 31 pages total) teaches kits comprising primers and hot start Taq DNA polymerase (see English translation of the abstract). Chen et al (CN 104120180 A, English translation included, 17 pages total) also teaches kits comprising primers and hot start Taq DNA polymerase (see English translation of the abstract). Similarly, Carter et al (Chapter 2. PCR Methodology in M. Schuller et al. (eds.), PCR for Clinical Microbiology, 2010, p. 11-47) teaches PCR reaction mixtures comprising hot-start Taq DNA polymerase (section 2.2.3 “PCR Amplification and Product Detection” at p. 20). Thus, the presence of these DNA polymerases in the claimed kits does not add something significantly more to the recited judicial exception.
For the reasons set forth above, the claims are not considered to recite something significantly different than a judicial exception and thereby are not directed to patent eligible subject matter.
Claim Rejections - 35 USC § 112(b) - Indefiniteness
6. 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 14-17, 20, 22, 24 and 25 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.
A. Claims 14-17, 20, 22, 24 and 25 are indefinite and confusing. The claims require “an identification primer, which is composed of, from the 5' end to the 3' end, (a) a nucleotide sequence which complements a segment of continuous nucleotides in a nucleic acid sequence to be detected, wherein the 5' end of the continuous nucleotides starts at a first nucleotide downstream of an expected mutation site; and (b) a nucleotide which complements a non-mutated nucleotide or an expected mutated nucleotide at an expected single-base mutation site of a nucleic acid sequence to be detected.” First, the language “the 5’ end of the continuous nucleotides” lacks proper antecedent basis since the claim previously only refers to a 5’ end of the identification primer. While it appears that this language is intended to refer the continuous nucleotides of the nucleic acid sequence to be detected, the language is confusing since it defines the identification primer from its 5’ to 3’ end in terms of the nucleic acid sequence to be detected in terms of its 5’ end. The language “3’ end” is also vague because it is not clear as to whether this means any nucleotide from the middles to the 3’ terminal nucleotide or if this is intended to be limited to the 3’ terminal nucleotide. In the former instance, the “3’ end” would thereby allow for additional nucleotides 3’ of the nucleotide that is the complement of the potentially mutated nucleotide. However, this does not appear to be consistent with the description of the identification primer in Figure 1 or with the majority of the teachings in the specification or the exemplified primers in the specification. For example, para [0025] of the specification states:
“The “identification primer” is a short-chain primer (compared with the length of a conventional PCR primer), which can realize SNP recognition only by the base at the 3′ end, thus avoiding the introduction of a second artificial mismatched base, and ensuring the specificity of the method.”
The claims are also indefinite over the language of “composed of” because, in the context of the claim, it is not clear as to whether “composed of” is intended to be limited to “consisting of” or encompasses “comprising.” If “composed of” is intended to mean “comprising,” then the claims encompass identification primers in which any number of nucleotides (or e.g., in claim 15, up to 13 or 14 nucleotides) are present 3’ of the nucleotide complementary to the potentially mutated or non-mutated site in the nucleic acid sequence to be detected. Accordingly, the metes and bounds of the claimed subject matter is not clear.
This rejection may be obviated by amendment of claim 14 to recite “…an identification primer which consists of, from the 5’ end to the 3’ end, (a) a nucleotide sequence complementary to a segment of contiguous nucleotides in a nucleic acid sequence to be detected; and (b) a 3’ terminal nucleotide that is the complement of a non-mutated nucleotide or an expected mutated nucleotide at an expected single-base mutation in the nucleic acid sequence to be detected….”.
B. Claim 24 is indefinite over the recitation of “the DNA polymerase” because this phrase lacks proper antecedent basis since the claim does not previously refer to a DNA polymerase.
Double Patenting
7. 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 14-17, 20, 22, 24 and 25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 11 and 15-20 of copending Application No. 18/293,339 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the present claims and the claims of ‘339 are both inclusive of a primer group for detecting a single-base mutation in a nucleic acid sequence, the primer group (i.e., a “set of primers” in ‘339) comprising: an identification primer (an “identifying primer” in ‘339), which is composed of, from the 5' end to the 3' end, (a) a nucleotide sequence which complements a segment of continuous nucleotides in a nucleic acid sequence to be detected, wherein the 5' end of the continuous nucleotides starts at a first nucleotide downstream of an expected mutation site; and (b) a nucleotide which complements a non-mutated nucleotide or an expected mutated nucleotide at an expected single-base mutation site of a nucleic acid sequence to be detected; and an amplification primer capable of amplifying an amplification product obtained by amplifying the nucleic acid sequence to be detected using the identification primer, wherein the identification primer is 1 to 19 nucleotides less than the amplification primer (see claim 5 of ‘339 which recites “he identifying primer are in total 1 to 19 nucleotides shorter than the amplification primer in length”).
In the claims of ‘339, the identifying primer includes additional 5’ nucleotides or elements - i.e., a nucleotide sequence that can specifically bind to a detection tool; b) a spacer arm molecule. However, the present claims recite that the identifying primer is composed of the listed components. Absent a limiting definition in the specification or claims for “composed of”, this language is considered to encompass “comprising” and thereby additional nucleotides and other components may be included in the identifying primer. Further, while the claims of ‘339 do not recite that the identification / identifying primer includes “(b) a nucleotide which complements a non-mutated nucleotide or an expected mutated nucleotide at an expected single-base mutation site of a nucleic acid sequence to be detected,” the claims of ‘339 require that the identification / identifying primer has at its 3’ end any one of A, T, C or G. This 3’ end nucleotide would include a nucleotide that is the complement of the mutated or non-mutated nucleotide since the claims of ‘339 are drawn to a primer set for detecting a single base mutation and recite the same limitation as in the present claims regarding the identification / identifying primer that “the 5' end of the contiguous nucleotides starts from the first nucleotide downstream of a mutation detection site.”
Regarding present claims 15-17, claim 6 of ‘339 recites that the dentification / identifying primer is 11 to 16 nucleotides in length, which includes the 12 to 15 nucleotides, and claim 7 of ‘339 recites that the amplification primer is 15 to 30 nucleotides in length, which includes 15 to 25 or 15-20 nucleotides in length.
Regarding present claims 20 and 24-25, claims 15 and 16 of ‘339 recite kits comprising the group of primers / primer set.
Further, regarding present claim 24, claim 16 of ‘339 recites that the kit also comprises a high fidelity DNA polymerase. As shown in claim 11 of ‘339 a high fidelity DNA polymerase includes a Hot-Start Taq polymerase, TaqNova Stoffel DNA polymerase, HiFi-KAPA polymerase, and Hemo KlenTaq polymerase.
Regarding present claim 25, the claims of ‘339 do not recite that the kits further comprise a reagent for detecting an amplification product. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the kits claimed in ‘339 so as to have included a reagent for detecting an amplification product since the kits of ‘339 are for “detecting a single base mutation in a nucleic acid sequence” and to detect the single base mutation would necessarily require detecting the amplification product formed using the identification / identify primer and amplification primer.
Regarding present claim 22, the kits comprising the group of primers / primer set of claims 15 and 16 of ‘339 are considered to be a detection device comprising the primer group / primer set. Note that neither the specification nor claim 22 recite any limitations regarding the device which would distinguish the claimed device comprising the group of primers over a kit comprising the group of primers /set of primers.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 102
8. 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.
Claim(s) 14-17, 20, 22, and 25 is/are rejected under 35 U.S.C. 102(a)(1)as being anticipated by Xu et al (CN107841548A; English translation included, 46 pages total).
Xu (e.g., p. 40 of printout) teaches a set of primers for detecting a mutation in the MTHFR gene, wherein the set of primers includes a forward primer having a C nucleotide at the mutated position in the MTHFR gene (i.e., an “identifying primer”) and a reverse primer (i.e., an amplifying primer):
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The forward primer of Xu includes a 5’ nucleotide sequence that is complementary to the target nucleic acid and a 3’ terminal nucleotide that is the complement of an expected mutation site (or a wildtype site). The “+” in the forward primer indicates that the 3’ terminal nucleotide of the primer is modified with a LNA (see p. 40 of printout). The reverse primer consists of a nucleotide sequence complementary to a second strand of the target nucleic acid (MTHRF gene) and is capable of amplifying the nucleic acid sequence amplified by the forward (identification) primer.
As shown above, the forward (identification) primer is 15 nucleotides in length and the reverse (amplifying) primer is 20 nucleotides in length. Thereby, this set of primers of Xu meets the limitations of present claims 14-17.
Regarding claims 20 and 25, Xu teaches packaging the above primers in a kit (e.g., claims 5 and 16 of ‘339 recite kits comprising the group of primers / primer set (e.g., claims 1 and 5).
Further, regarding claim 25, Xu teaches that the kit includes SYBR fluorescent dye (p. 38 of the printed document; i.e., “The PCR reaction kit can also comprise a PCR reaction mixture SYBR Master Mix, wherein the SYBR Master Mix comprises a PCR reaction buffer solution Tris-HCl, dNTP, SYBR fluorescent dye, taq DNA polymerase”). SYBR is considered to be a reagent for detecting an amplification product since it binds to the newly synthesized / amplified dsDNA.
Regarding claim 22, the kits comprising the set of primers of Xu is considered to be a detection device comprising the set of primers (primer group). Note that neither the specification nor claim 22 recite any limitations regarding the device which would distinguish the claimed device comprising the primers over a kit comprising the group of primers /set of primers.
Claim Rejections - 35 USC § 103
9. 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al (CN107841548A; English translation included, 46 pages total) in view of Carter et al (Chapter 2. PCR Methodology in M. Schuller et al. (eds.), PCR for Clinical Microbiology, 2010, p. 11-47).
The teachings of Xu et al are presented above.
As discussed above, Xu et al teaches a kit comprising a set of primers, which primers meet the limitations of the claims of an identification primer and an amplifying primer. Xu (e.g., claims 1 and 5) teaches PCR kits comprising the set of primers and further comprising a Taq DNA polymerase - i.e., “The PCR reaction kit can also comprise a PCR reaction mixture SYBR Master Mix, wherein the SYBR Master Mix comprises a PCR reaction buffer solution Tris-HCl, dNTP, SYBR fluorescent dye, taq DNA polymerase” (p. 38 of the printed document).
Xu does not teach that the Taq DNA polymerase is a Hot-start Taq DNA polymerase.
Carter teaches methods of performing PCR using hot-start Taq DNA polymerase (section 2.2.3 “PCR Amplification and Product Detection” at p. 20). Therein it is stated:““Hot-start” PCR was developed to improve PCR amplification and specificity
by reducing non-specific amplification during PCR set-up. The Hot-start Taq DNA
polymerase enzyme is inactive at ambient temperature, preventing the extension of
non-specifically annealed primers or the formation of primer dimer. The functional
activity of the enzyme is restored during incubation at 95◦C for 5–10 min.”
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the kits of Xu so as to have included the particular Taq DNA polymerase of Hot-start DNA polymerase. One would have been motivated to have done so in view of the benefits set forth by Carter et al that Hot-start Taq DNA polymerase improves the specificity of PCR amplification assays and prevents the formation of primer-dimers.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CARLA J MYERS whose telephone number is (571)272-0747. The examiner can normally be reached M-Th 6:30-5:00 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached on 571-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CARLA J MYERS/Primary Examiner, Art Unit 1682
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