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 .
This Office Action is in reply to Applicants’ correspondence of 01/06/2026.
Applicants’ 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 Applicants’ amendments. Any rejections or objections not reiterated herein have been withdrawn in light of the amendments to the claims or as discussed in this Office Action.
This Action is made FINAL.
Please Note: The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election/Restrictions
In the reply filed on 07/16/2025 Applicants elected, without traverses, the invention of Group I (claims drawn to methods).
Claim 20 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b) as set forth on page 2 of the Office Action of 09/18/2025.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) as follows:
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 application, US Provisional Application No. 62/991,477, fails 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 13 (from which claims 15-19 depend) and claim 14 recite limitations requiring administering an arylamine drug or a hydrazine drug at a dose greater than (claim 13) or less that (claim 14) the prescribed dose where SNPs are not (claim 13) or are (claim 14) detected. The prior filed provisional application does not provide any teaching or basis for a required “prescribed dose”, or the particular required different administration as recited in the claims.
As such the effective filing date of the subject matter of claims 13-19 is the filing date of the PCT application (PCT/US2021/023029) which is 03/18/2021.
New Claim Rejections - 35 USC § 112 – New Matter
Necessitated by Claim Amendments
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, 3, 10-19 and 30 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. This is a new matter rejection.
The rejection of claims for including subject matter that is not particularly supported by the disclosure of the application as originally filed is relevant to the combination of limitations in the amended claims. Amended claim requires “simultaneously detecting five unphased single nucleotide polymorphisms … by a method comprising multiplex qPCR-based amplification and multicolor melt curve analysis”. While the claim requires that the SNPs a “simultaneously detected” the detection is performed “by a method comprising multiplex qPCR-based amplification and multicolor melt curve analysis”. In this analysis it is noted that the method “comprising” MMCA nay include other non-MMCA methods in the detecting (i.e.: “comprising” in an open transitional phrase which allows for the inclusion of other non recited elements; MPEP 2111.03). The specification as filed provides a variety of different methods (e.g.: para 0087) for detecting nucleotide content at polymorphic positions including 5’ exonuclease polymerase chain reaction, DNA sequencing, restriction fragment length polymorphism, chip hybridization or single base extension assay. But the requirement that 5 SNPs are analyzed with simultaneous detection is only provided in the specification as being performed in a 5-plex multicolor melt curve analysis (e.g.: para 0178). The claims may be consonant with the teachings of the application as filed if amended to recite: simultaneously detecting the nucleotide content at each allele of five unphased single nucleotide polymorphisms (SNPs) of N-acetyltransferase-2 (NAT2) in a biological sample of the subject in a 5-plex qPCR-based amplification and multicolor melt curve analysis (MMCA).
Withdrawn Claim Objections
The objection to claim 11, as set forth on page 3 of the Office Action of 09/18/2025, is withdrawn in light of the amendments to the claims.
New Claim Objections
Necessitated by Claim Amendments
Claim 1 is objected to because of the following informalities: the abbreviations of the terms SNPs, NAT2 and MMCA, which appear in parentheses, are not required to be in side quotation marks. See for examples paragraphs 0032, 0141and 0189 of the specification as filed. Appropriate correction is required.
Withdrawn Claim Rejections - 35 USC § 112 - Indefiniteness
The rejection of claims 13-19 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as set forth on page 5 of the Office Action of 09/15/2025 is withdrawn in light of the amendments to the claims.
Claim Rejections - 35 USC § 112 – Indefiniteness
Maintained and Newly Applied as Necessitated by Claim Amendments
Claims 1, 3, 10-19 and 30 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 1, 3, 10-19 and 30 are unclear over recitation of limitations related to “detecting five unphased single nucleotide polymorphisms ("SNPs") of N-acetyltransferase-2 ("NAT2") in a biological sample of the subject”. (as recited in claim 1), and “determining whether” a SNP is present or not present (as recited in claim 7) and relevant to the limitations recited in claims 13 and 14. As used in the art, and consonant with the definition provided in the instant specification (para [0030]), a single nucleotide polymorphism (SNP) is a position of variable nucleotide content in the genomes of a population of individuals, and reference to the identification that more than one allele occupies the locus within a population. So, in the context of the claims, it is unclear what is meant by detecting SNPs in a subject (i.e.: in an individual, as recited in the claims). It is unclear what is required to be detected to determine the presence or absence of polymorphisms when considering only a sample from a subject. The claims may be made more clear in this regard if amended to recite a step related to detecting particular allele content in the sample from the subject, where the specification (as consonant with the related art) teaches that “the term "allele" refers to varying forms of the genomic DNA located at a given site. For example, "allele" refers to a genetic variant of a specific genomic location (locus)”. The indefiniteness of the claim limitation is apparent when considering the requirements of claim 1 (i.e.: a positive recitation of detecting SNPs in a sample from a subject), and then considering the requirements of claim 13 (which depends form claim 1) which requires that “a G191A NAT2 SNP, C282T NAT2 SNP, T341C NAT2 SNP, G590A NAT2 SNP and G857A NAT2 SNP are not detected”.
Response to Remarks
Applicants have traversed the rejection of claims under 35 USC 112 as unclear over recitations related to detecting SNPs in a sample from a subject. Applicants’ arguments (p.5-6 of the Remarks of 01/06/2026) have been fully considered but are not persuasive to withdraw the rejection. Applicants have argued that the claims as amended are clear because they recite that the SNPs detected are “unphased” SNPs, and that the detection in via MMCA and that NAT2 genotype and phenotype is assigned. The arguments are not persuasive. The Examiner maintains that while a biological sample form a particular subject may be analyzed to determine which alleles of a SNP are present the sample, using the terminology “detecting a SNP” in the sample makes it unclear as to what detection is required by, or encompassed by, the methods of the claims. As noted in the rejection the lack of clarity is demonstrated when considering the requirements of claim 1 (i.e.: the five SNPs are detected) and the requirements of claim 13 (i.e.: the same five SNPs are not detected). The claims may be made more clear if amended to address detecting alleles of the SNPs.
Withdrawn Claim Rejections - 35 USC § 102 and 103
The rejections of claims made under 35 USC 102 and 103, as set forth on pages 5-10 of the Office Action of 09/18/2025 are withdrawn in light of the amendments to the claims, and Applicants remarks (p.6-8 of the Remarks of 01/06/2026).
New Claim Rejections - 35 USC § 101
Necessitated by Claim Amendments
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 1, 3, 10-19 and 30 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception(s) that are abstract ideas and natural phenomena without significantly more.
The claim(s) recite(s) a step of “assigning, via implementation of a pretrained random forest algorithm, a NAT2 acetylation genotype and phenotype based on the detected unphased NAT2 SNPs”. The claims are thus directed to an abstract idea which is a mental process (see MPEP 2106.04(a)(2)III); using a pretrained algorithm is an evaluation or comparison of collected information to reach a conclusion. Additionally, the concept of a random forest algorithm, where data is processed to determine associations and relationships for a decision making algorithm, can be considered a mathematical concept where the data can be presented as values that are compared (see MPEP 2106.04(a)(2)I). It is also noted that where the judicial exception is the association between genotypes at 5 SNPs, and the NAT2 genotype/phenotype, such an association is a natural phenomenon (see MPEP 2106.04(b)I) which is the natural association of various different SNPs (e.g.: linkage disequilibrium) and the genotype:phenotype associations that are part of a biological organism. In this regard it is noted that the selection of particular SNPs for the detecting of the claims (e.g.: the limitation that “the method does not comprise detecting additional NAT2 SNPs in the biological sample” is essential a recitation of the natural phenomenon in which particular SNPs are representative of a larger genotype or particular phenotype of the NAT2 gene.
This judicial exception is not integrated into a practical application because the claims end with the assignment of a genotype and phenotype, and the assigned NAT2 acetylation genotype and phenotype is now used as part of any additional practical step. Here it is noted that while some claims include a step of administering an arylamine or hydrazine drug where particular SNPs are or are not detected, the requirements of these claims (i.e.: with regard to “detecting a SNP”) are unclear and have been addressed previously in this Office Action.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements of the claims are the data collection steps required to apply the judicial exception. In this regard it is noted that the specification of the instant application provides evidence of the routine nature of the data collection methods encompassed by the claims. Paragraph 0088 of the specification as filed teaches that the detection methods are “known in the art”. Additionally, the methods of the claims, for example as they require multicolor melt curve analysis, are considered well understood, routine and conventional when considering the prior art. For example, the prior art of Liao et al (2013) and Nicklas et al (2008) teach the detection of allele content using multiplex amplification and multicolor melt curve analysis. And while claim 30 broadly includes the detection of mycobacterium in the sample, Pai et al (2016) demonstrates that such an analysis for the detection of MTB complex organisms was routine in the art. As such the additional elements of the claims are properly considered insignificant extra-solution activity when determining if the claims are directed to significantly more than the judicial exceptions included in the claims.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 STEPHEN THOMAS KAPUSHOC whose telephone number is (571)272-3312. The examiner can normally be reached M-F, 8am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at 571-272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Stephen Kapushoc
Primary Examiner
Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683