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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 09/29/2025 has been entered.
Status of the Applications and/or Amendments
This action is written in response to applicant's correspondence submitted 06/30/2025, 07/25/2025 and 09/29/2025 after the mailing of the Final Rejection paper of 03/28/2025. In the paper of 06/30/2025, Applicant amends claims 1 and 13 but the after-Final amendments were not entered.
Claims 1-2, 4-5, 13-14 and 16-19 remain under review while claims 3, 6-12 and 15 are canceled.
Response to Arguments
Withdrawn Objection(s) and Withdrawn Rejection(s)
The objection to claim 1 since claim 1 relies on an incorporation by reference and recites limitation where the subject that are not disclosed in the specification is withdrawn based on the amendment to the specification made on 06/20/2025.
Maintained Rejection(s)
The rejection of claims 1-2, 4-5, 13-14 and 16-19 under 35 U.S.C. §101 is maintained despite the presence of new limitations “wherein an acquisition parameter is set as 550 in said MALDI-TOF MS” in claim 1 and “and subjecting said report to the sample identification in clinical toxicology and workforce drug testing” in claims 1 and 13.
The rejection of claims 1-2, 4-5, 13-14 and 16-19 under 35 U.S.C. 103 as being unpatentable over McCarty (US2018/0328912, pub Nov. 15, 2018: previously cited) in view of Daly et al. (March 27, 2020, JOJ Urology and Nephrology, 7(2), 555707, pp. 0026-0032) as evidenced by MagMAX™ DNA Multi-Sample Ultra 2.0 Kit User Guide, Applied Biosystems, Cat No. A36570, Pub. No. MAN0017325 Rev. D.0 April 15, 2021 and further in view of Applied Biosystems (Oct 2015, Manual MAN0014348 Rev. A.0) and Applied Biosystems MagMAX™-96 DNA Multi-Sample Kit Guide with Catalog No.4413022 (2009) and Johansen et al. (2013, Forensic Science International: Genetics, 7(5), pp.482-487) and Agena Bioscience iPLEX Sample ID variant brochure, pp. 1-2, listing SNPS useful for the authentication of human genomic DNA samples (2019), and/or Agena Bioscience Sample integrity brochure, pp. 1-8 (2018-2024) and/or Agena Bioscience iPLEx Pro Sample ID brochure, pp. 1-4 (2021) is maintained.
Arguments
Applicant's arguments filed 06/20/2025 have been fully considered but they are not persuasive as follows.
Claims 1 and 13 newly recite the limitations “an acquisition parameter is set as 550 in said MALDI-TOF MS” and “subjecting said report to the sample identification in clinical toxicology and workforce drug testing”. For the rejection under 35 U.S.C 101, these limitations are not additional elements that allow these claims to be significantly more than judicial exceptions. Claims 1 and 13 are directed to analysis of matches/mismatches of SNPs, gender markers, copy number controls between a test sample of a subject and reference sample and relies on the presence and absence of the naturally occurring SNPs, gender markers among the two samples. The new limitations “acquisition parameter” and “clinical toxicology and workforce drug testing” are not defined or even explained. The Office is unable to realize any significant structural difference resulting from these limitations relative to methods that omit these limitations beyond routine optimization or an applied use that can be appreciated. It is unknown what these limitations are referring to and whether or not they achieve a superior unexpected performance or give any unexpected contribution over the prior art.
For the rejection(s) under 35 U.S.C 103, concerning the new limitation “an acquisition parameter is set as 550 in said MALDI-TOF MS”, of claims 1 and 13, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980).
Applicant has not disclosed that the specific limitations 0f “550” recited in instant claims 1 and 13 are for any particular purpose or solve any stated problem and it is reasonably apprised by the ordinary skilled artisan that optimizing one or more operational parameters of a device could enhance the device to work as equally as well as the prior art, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges for the MALDI-TOF MS device disclosed by the prior art by normal optimization procedures known in the prior art.
Further concerning the limitation of “subjecting said report to the sample identification in clinical toxicology and workforce drug testing” newly recited by claims 1 and 13, this limitation lacks clarity and clarity of scope and it is not known whether or not creates any structures differences over the prior or even the previously claimed methods that omit it.
Claim Rejections - 35 USC § 112
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 1-2, 4-5, 13-14 and 16-19 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.
Claim 1 and 13 each recite the limitation “an acquisition parameter is set as 550 in said MALDI-TOF MS” and the limitation “subjecting said report to the sample identification in clinical toxicology and workforce drug testing”. These limitations are found as lacking in clarity and clarity of scope since it is not known what parameters of MALDI-TOF MS constitute an acquisition parameter and what is intended by “in clinical toxicology and workforce drug testing”.
Neither the specification nor the claims provide a limiting definition for acquisition parameter or for what constitute clinical toxicology and workforce drug testing.
Claims 2, 4-5, 14 and 16-19 are also rejected as they depend from either claim 1 or claim 13.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-2, 4-5, 13-14 and 16-19 are rejected under 35 U.S.C. §101 because these claims are not directed to patent eligible subject matter.
Based upon an analysis with respect to the claims as a whole, claim(s) 1-2, 4-5, 13-14 and 16-19 do not recite something significantly more than a judicial exception. The rationale for this determination is explained below:
According to the Manual of Patent Examination Procedure (MPEP) sections 2103 through 2106.07(c), which now incorporates the 2019 Revised Patent Subject Matter Eligibility Guidance (2019 PEG), October 2019 Patent Eligibility Guidance Update (October 2019 Update), and the Berkheimer Memo, an initial two step analysis is required for determining statutory eligibility.
Step 1
Step 1 requires a determination of whether the claims are directed to a process, machine, manufacture, or a composition of matter. In the instant case, the Step 1 requirement is satisfied as the claims are directed towards a process.
Claims 1 and 13 recite method(s) and are therefore each directed to a process.
Step 2
The Step 2 analysis is a two-part analysis, Step 2A and Step 2B.
Step 2A, prong 1 requires a determination of whether the claims are directed towards a judicial exception, i.e. a law of nature, natural phenomenon, or an abstract idea, while
step 2A, prong 2 requires an analysis of whether the judicial exception integrated into a practical application if the claim recites a judicial exception under Prong 1.
Step 2B of the two step analysis is drawn to determining whether any element or combination of elements, in the instant claims is/are sufficient to ensure that the claims as a whole amounts to significantly more than the judicial exception.
Step 2A, prong 1
With regard to step 2A, prong 1, the claims are directed to a judicial exception because the claims rely on both natural law and an abstract idea/mental processes/use of mathematical algorithms.
Specifically, claims 1 and 13 prepares urine and reference samples and extracts DNA from the samples using a proteinase K mix on the samples placed on a 96 deep well plate, and performing a simultaneous lysis of the samples using a one-step lysis procedure performed at room temperature using the same lysis buffer. Claims 1 and 13 further provides a simultaneous multiplex polymerase chain reaction (PCR) to amplify and analyze 44 single nucleotide polymorphisms (SNPs), 3 gender markers, and 5 copy number controls on the DNA of the urine and reference samples, and provides a MALDI-TOF analysis to detect the 44 single nucleotide polymorphisms (SNPs), 3 gender markers, and 5 copy number controls in the urine sample and the reference sample(s). Claims 1 and 13 provides comparing and verifying of a match or a mismatch between the MALDI-TOF results from urine sample and the reference sample(s), where a match and mismatch verifies donor identity or a lack of donor identity respectively.
As presently claimed, neither the claims, nor the specification identify that any one or more of the markers in the set consisting of the 44 single nucleotide polymorphisms (SNPs), 3 gender markers, and 5 copy number controls as a non-naturally occurring marker(s) of a human donor.
The 44 single nucleotide polymorphisms (SNPs), 3 gender markers etc. appear to resemble naturally occurring markers of urine and other human/donor reference samples, and are predictive e.g. of the origin from a same human individual/donor, or from different human individual(s)/donor.
The claims are still found to rely solely on the presence of these generic markers (i.e. members of judicially excluded subject matter belonging to natural law) to conclude donor identity/ donor-non-identity, without a practical application.
Applicant has not invented these markers that are to be identified as being present in the urine and reference samples but instead, Applicant use conventional, well known methods to determine that they are present in these samples.
Further, claims 1 and 13 recite judicially excluded abstract idea belonging to mathematical algorithms since both claims 1 and 13 provide a step of comparing/analyzing and/or matching MALDI-TOF results of 44 single nucleotide polymorphisms (SNPs), 3 gender markers, and 5 copy number control markers of urine and reference samples with a computer to conclude a donor identity match or a donor identity mismatch.
Step 2A, prong 2
None of claims 1-2, 4-5, 13-14 and 16-19 recite any additional elements or step to apply or to integrate the judicially excluded natural law(s) and abstract idea(s) that are indicated above into a practical application.
A claim that integrates a judicial exception into a practical application will apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such that the claim is more than a drafting effort designed to monopolize the judicial exception. When the exception is so integrated, then the claim is not directed to a judicial exception.
The step of performing a simultaneous extracting and releasing of DNA of all sample (performed with reagents of the MagMAX™ DNA Multi-Sample Ultra 2.0 kit), and the step(s) of simultaneous amplifying of DNA of urine and reference samples are NOT practical applications, but instead are steps that must be performed so as to arrive at, or realize the judicial exception (i.e. judicial exception being the presence of one or more distinguishable DNA markers between a urine sample and reference samples that allow verification that both samples originated from a same donor or characterization that both samples do not originate from a same donor).
Further, the step(s) of simultaneous amplifying of 44 SNPs, 3 gender markers, and 5 copy number controls are recited at such a high level of generality that they add nothing significantly more to the claims.
Accordingly, claims 1-2, 4-5, 13-14 and 16-19 do not recite additional elements or steps beyond identifying/detecting the noted judicial exception and also do not recite additional elements/steps that serves to integrate the judicial exception into a practical application nor are they limitations that are sufficient to ensure that the claims as a whole amount to significantly more than the judicial exception.
The judicial exception/abstract idea as presently claimed, is not integrated into a practical application because does not provide any additional meaningful limitation on the claim or on practicing the abstract idea other than merely instructing the user to observe/analyze detected signals so as to draw a conclusion.
Step 2B
The second part, Step 2B of the two-step analysis is drawn to determining whether any element or combination of elements, in the instant claims is/are sufficient to ensure that the claims as a whole amounts to significantly more than the judicial exception.
None of claims 1-2, 4-5, 13-14 and 16-19 recite any additional elements that are sufficient to amount to significantly more than the judicial exception.
The final steps of claims 1, 13 and 19 are directed to step(s) of analyzing and matching DNA MALDI-TOF marker results so as to verify the match or mismatch of the results from urine and reference sample(s) as same or different, where a same result verifies/confirms a same donor and different result(s) verifies/confirms different donors.
However, these step(s) of comparing, analyzing or matching DNA MALDI-TOF markers between two or more sample(s) are judicially excluded matter and are NOT practical applications of judicially excluded subject matter (wherein a practical application may be e.g. further drug testing the urine sample that is from a verified donor), and furthermore, are NOT steps that amount to significantly more than the judicial exception.
The abstract idea (“comparing and analyzing”) is not integrated or applied into additional steps so that the claims amount to a practical application that is significantly more than a generic instruction to a user to apply judicial exception.
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.
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.
Claims 1-2, 4-5, 13-14 and 16-19 are rejected under 35 U.S.C. 103 as being unpatentable over McCarty (US2018/0328912, pub Nov. 15, 2018: previously cited) in view of Daly et al. (March 27, 2020, JOJ Urology and Nephrology, 7(2), 555707, pp. 0026-0032: previously cited) as evidenced by MagMAX™ DNA Multi-Sample Ultra 2.0 Kit User Guide (previously cited), Applied Biosystems, Cat No. A36570, Pub. No. MAN0017325 Rev. D.0 April 15, 2021 (previously cited) and further in view of Applied Biosystems (Oct 2015, Manual MAN0014348 Rev. A.0: previously cited) and Applied Biosystems MagMAX™-96 DNA Multi-Sample Kit Guide with Catalog No.4413022 (2009: previously cited) and Johansen et al. (2013, Forensic Science International: Genetics, 7(5), pp.482-487: newly cited) and Agena Bioscience iPLEX Sample ID variant brochure, pp. 1-2, listing SNPS useful for the authentication of human genomic DNA samples (2019: newly cited), and/or Agena Bioscience Sample integrity brochure, pp. 1-8 (2018-2024: newly cited) and/or Agena Bioscience iPLEx Pro Sample ID brochure, pp. 1-4 (2021: newly cited).
McCarthy (US2018/0328912) (claim 1)
Regarding claim 1, McCarty teach an authentication or matching method (for verifying donor identity or the person providing a urine sample as the same or as different from donor identity of a reference sample).
McCarty teach their genetic authentication is performed by matching the genotype of multiple Single Nucleotide Polymorphism (SNP) markers between DNA samples collected from a urine sample and from a buccal (reference) cell sample of its claimed donor (see para [0165]).
Accordingly, for claim 1, McCarty teach:
preparing a urine sample and a reference sample that is a buccal cell sample, a urine sample, a whole blood tissue sample, a saliva sample and/or an oral rinse sample from the person (para [0054]-[0055], para [0025] and para [0050]: wherein McCarty teach methods of enriching/sedimenting (epithelial) cells of a urine or reference sample);
extracting or releasing DNA from the urine sample and the reference sample, wherein the DNA from a urine sample is gDNA from epithelial cells excreted into the urine, or from white blood cells in the urine (para [0054]-[0057], [0120]);
amplifying the DNA from both samples simultaneously, wherein the amplification is performed by polymerase chain reaction (PCR) (para [0058], para [0010], para [0095], [0099]; see also abstract, para [0005], para [0042], [0087], [0115]-[0116], [0122]: wherein elongation of two or more probes to form SNP amplification products are disclosed: McCarty teach/suggests amplification methods that involve simultaneously amplification: para [0133]-[0134] e.g. iPLEX);
McCarty discloses one embodiment of SNP genotyping via an iPLEX assay and/or by MALDI-TOF mass spectrometry assay, wherein the assay(s) include(s) analysis of the masses or mass distribution of the SNP amplification products/elongated allele specific probes obtained by amplifying a sequence of extracted DNA originating from the original urine sample and obtained by amplifying a sequence of extracted DNA from control reference sample (para [0007], [0026], [0103]-[0107], [0123]).
McCarty teach wherein the donor identity of the reference sample is confirmed through polymerase chain reaction (PCR) and mass spectrometry (MS) (para [0116]-[0118], [0123], [0126]-[0128]).
Claim 1 of McCarty (US2018/0328912) recite method of matching a urine sample to a subject comprising:
(a) providing a urine sample from a subject;
(b) enriching the urine sample for mammalian cells, if present;
(c) isolating any genomic DNA from the enriched sample of step (b) to form an isolated genomic DNA test sample;
(d) contacting a set of two or more oligonucleotide primers to the genomic DNA in the isolated genomic DNA test sample, wherein each of the two or more oligonucleotide primers hybridizes to a sequence of genomic DNA that is one nucleotide upstream of a different target single nucleotide polymorphism (SNP);
(e) elongating the two or more oligonucleotide primers hybridized to the genomic DNA by one nucleotide using chain-terminating nucleotide(s) to generate a set of two or more SNP products;
(f) determining the mass distribution of the set of SNP products, wherein the mass distribution of the set of SNP products is determined using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) analysis;
(g) comparing the determined mass distribution of the set of SNP products to a control mass distribution obtained from the subject; and
(h) identifying a urine sample having a mass distribution that is the same as the control mass distribution as originating from the subject; or
identifying a urine sample having a mass distribution that is not the same as the control mass distribution as not originating from the subject.
McCarthy (US2018/0328912) (claims 2, 4-5)
Regarding claim 2, McCarty teach wherein the reference sample is a buccal cell swab (para [0165]).
Regarding claim 4, McCarty teach wherein DNA extraction from the urine sample and the reference sample is performed by commercially available DNA extraction kits, with or without automated DNA extraction instruments (para [0056]-[0057]: wherein McCarty teach various commercial kits to extract genomic DNA from sample(s) and method(s) for gDNA extraction).
Regarding claim 5, McCarty teach wherein the extracting the DNA from the urine sample and the reference sample is performed by commercially available DNA extraction kits intended for buccal cell DNA extraction with automated DNA extraction instruments. (see para [0056]-[0057]: wherein McCarty teach use of Qiagen’s Gentra Puregene Buccal cell kit or Life Technologies ChargeSwitchTM gDNA Normalized Buccal Cell Kits among many other DNA extraction buccal kits).
Claims 13-14 and 16-18
Regarding claim 13, McCarty teach an authentication or matching method (for verifying donor identity of a person providing a urine sample as the same or as different from donor identity of a reference sample).
McCarty teach their genetic authentication is performed by matching the genotype of multiple Single Nucleotide Polymorphism (SNP) markers between DNA samples collected from a urine sample and from a buccal (reference) cell sample of its claimed donor (see para [0165]).
Accordingly, for claim 13, McCarty teach:
preparing a urine sample and a reference sample that is a buccal cell sample, a urine sample, a whole blood tissue sample, a saliva sample and/or an oral rinse sample from the person (para [0054]-[0055], para [0025] and para [0050]: wherein McCarty teach methods of enriching/sedimenting cells of a urine or reference sample);
extracting or releasing DNA from the urine sample and the reference sample, wherein the DNA from a urine sample is gDNA from epithelial cells excreted into the urine or from white blood cells in the urine (para [0054]-[0057]);
amplifying the DNA from both samples simultaneously e.g. iPLEX, wherein the amplification is performed by polymerase chain reaction (PCR) (para [0058], para [0010], para [0095], [0099]; see also abstract, para [0005], para [0042], [0087], [0115]-[0116], [0122]: wherein elongation of two or more probes to form SNP amplification products are disclosed);
genotyping the DNA from both samples (para [0042], para [0101]-[0106] and [0115], [0117], [0123]-[0124], [0134]: wherein McCarty discloses one embodiment of SNP genotyping via an iPLEX assay and/or by MALDI-TOF mass spectrometry assay, wherein the assay(s) include(s) analysis of the masses or mass distribution of the SNP amplification products/elongated allele specific probes obtained by amplifying a sequence of extracted DNA originating from the original urine sample and obtained by amplifying a sequence of extracted DNA from control reference sample);
after the genotyping, analyzing and comparing the DNA from the urine sample to the DNA from the reference sample, wherein the analysis and comparison is performed through one or more methods of analyzing single nucleotide polymorphisms (SNPs) (para [0118], [0125], [0133]);
determining, and reporting a match or mismatch between a donor identity of the urine sample and the donor identity of the reference sample (para [0118], [0126]-[0128]).
Regarding claim 14, McCarty teach wherein the reference sample is buccal cell swabs (para [0165]).
Regarding claim 16, McCarty teach wherein the DNA from the urine sample is DNA from epithelial cells excreted into the urine, or DNA from white blood cells in urine (para [0165]).
Regarding claims 17-18, McCarty teach/suggest DNA extractions from samples are performed with or without automation (see para [0056]-[0057], [0115]-[0116]).
Omitted from McCarthy (US2018/0328912) (claims 1, 13, 19)
Regarding claim 1, McCarty do NOT teach extracting or releasing gDNA from urine sample and a reference sample simultaneously but notes in para [0120] that extraction methods known in the art are suitable for isolating DNA.
Regarding claim 1, McCarty do NOT teach amplification is performed by multiplex polymerase chain reaction (PCR) with reagents to multiplex amplify and analyze 44 single nucleotide polymorphisms (SNPs), 3 gender markers, and 5 copy number controls.
Regarding claims 1 and 13 and 19, McCarty do NOT teach a matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis with a computer on the 44 SNPs, 3 gender markers, and 5 copy number controls and comparing of the 44 SNPs, 3 gender markers, and 5 copy number controls of the two samples, with the computer to verify donor identity by detecting a match between the results of the samples.
McCarty did NOT teach generating a report of the determination.
Regarding claims 1 and 13, McCarty do NOT teach an acquisition parameter is set as 550 in said MALDI-TOF MS” and “subjecting said report to the sample identification in clinical toxicology and workforce drug testing”.
Regarding claim 13, McCarty do NOT teach performing a one-step lysis procedure at room temperature using a lysis buffer at room temperature.
Regarding claim 13, McCarty do NOT teach:
wherein the extracting of DNA from the urine sample and the reference sample simultaneously is performed with the same kit on the same plate at the same time, and the extracting comprises:
digesting cells from the urine sample and the reference sample with Proteinase K mix,
wherein the plate is a 96 deep-well plate; and the
releasing comprises:
performing a one-step lysis procedure using a lysis buffer formed of enzymes and detergents to free cellular contents simultaneously in both of the urine and reference samples at room temperature as well as nuclei in each cell types, thereby releasing DNA for amplification and subsequent analysis and comparison.
Daly et al. (2020) as evidenced by Applied Biosystems MagMAX™ DNA Multi-Sample Ultra 2.0 Kit; and Applied Biosystems (2015, Manual Pub. No. MAN0014348 on the best practices for collection of buccal swabs for genotyping experiments) (claims 1, 13)
Regarding claims 1 and 13, Daly et al. teach that it was already a matter of routine to provide the King Fisher/MagMAX™ Automated DNA Extraction instrument and the MagMAX™ DNA Multi-Sample Ultra Kit (Thermo Fisher, Carlsbad, CA) for extracting DNA from a plurality of urine sample(s) from two cohorts formed from 66,383 patient urine samples (see pg 0027, right col., 1st para of section entitled “DNA extraction and analysis”, pg 0026, section of the abstract entitled “Methods”).
Daly et al. teach the urine samples are transferred to 96-well deep-well plates, sealed, and centrifuged to concentrate the samples (see pg 0027, right col., 1st para of section entitled “DNA extraction and analysis”).
Daly et al. teach that “Enzyme Lysis Mix (220 μL/well) was added to the samples, which were then incubated for 20 min at 65º C. Proteinase K Mix (PK Mix) was added (50 μL/well) and
incubated for 30 min at 65º C. Lysis buffer (125 μL/well) and DNA Binding Bead Mix (40μL/well) were added, and the samples were vortexed for a minimum of 5 min. Each 96-well plate was loaded into the KingFisher/MagMAX Automated DNA Extraction instrument, which was operated in accordance with standard operating procedures” (see pg 0027, right col., 1st para of section entitled “DNA extraction and analysis”).
The component volumes taught and used by Daly et al. which are indicated above, are in compliance with the component volumes disclosed by user guideline in Applied Biosystems for the MagMAX™ DNA Multi-Sample Ultra 2.0 kit manual as indicated in Table 1 on pg 1 (Table 1 of the Manual cat no. A36570, MAN0017325 is reproduced below).
Table 1: pg 1, cat no. A36570, MagMAXTM DNA Multi-Sample Ultra 2.0 kit
PNG
media_image1.png
476
406
media_image1.png
Greyscale
PNG
media_image2.png
712
764
media_image2.png
Greyscale
Daly et al. teach an extraction procedure and a proves for releasing DNA from a urine sample using a lysis buffer. The practice of the extraction and lysis processes on the 96 well plate, Kingfisher/ MagMAX™ DNA Multi-Sample Ultra 2.0 system (i.e. where samples are processed on the same plate, same kit, at the same time, the processing being automated) afforded Daly et al. the ability to isolate DNA for a downstream DNA analysis for the presence of plurality of pathogens causative of urinary tract infections (UTIs) in the same experiment (abstract and see pg 0027, right col., 2nd para of section entitled “DNA extraction and analysis”).
Applied Biosystems MagMAX™-96 DNA Multi-Sample Kit Guide with Catalog No.4413022 (2009)
Regarding claims 1 and 13, the Applied Biosystems MagMAX™-96 DNA Multi-Sample Kit Guide with Catalog No.4413022 (2009) teach are that the multi-sample kits are designed for rapid purification of high-quality genomic DNA from a variety of sample types including blood and blood cards, tissue, mouse tails, buccal swabs, buffy coats, and cultured cells. These purification kits use MagMAX™ magnetic bead-based nucleic acid isolation technology to produce high yields of purified DNA, free from inhibitors that may affect downstream reactions such as genotyping assays, CE and next-generation sequencing, and high resolution melting analysis. The 96-prep and 5x 96-prep kits are designed for higher throughput and automated format processing (see pg 8, para entitled Product Information).
Lysis is performed at room temperature according to this guide (see pg 28, a portion of which is reproduced below: pg 28 indicates the Multi sample DNA lysis buffer is stored at room temperature; 400 ul of this buffer is added to a buccal cell swab sample).
Although Daly et al. and the Applied Biosystems MagMAX™ DNA Multi-Sample Ultra 2.0 system user guide do NOT teach a method where Kingfisher/ MagMAX™ DNA Multi-Sample Ultra 2.0 system extracts DNA from a buccal swab system additionally to urine samples, the Applied Biosystems Manual Pub. No. MAN0014348 on the best practices for collection of buccal swabs for genotyping experiments, teach/suggest that it was already a routine matter of practice to isolate DNA of buccal swabs for genotyping experiments using the MagMAX™ DNA Multi-Sample Ultra Kit as the manual is focused on best practices for this aim. Lysis is performed at room temperature according to the user guide at pg 2, last para of the left col. (see section of the left col that is entitled “General guidelines”).
Johansen et al., 2013 (claims 1, 13 and 19)
Regarding claims 1, 13 and 19, Johansen et al. teach a method of performing a multiplex PCR by simultaneously amplifying at least 44 single nucleotide polymorphisms (SNPs), 3 gender markers, and 5 copy number controls by single base extension (SBE) on DNA extracted from blood sample and conducting a SNP typing analysis using Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS)/ MASSArray (entire document).
Regarding claims 1, 13 and 19, Johansen et al. teach Sequenom launched the first commercial SNP typing kit for human identification, named the iPLEX® Sample ID Plus Panel. The kit amplifies 47 of the 52 SNPs in the SNPforID panel, amelogenin and two Y-chromosome SNPs in one multiplex PCR. The SNPs were analyzed by single base extension (SBE) and Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS)/ MASSArray (abstract and entire document, particularly pg 483, sections 2.2 - 2.3 and pg 483, right col., section 3 and pg 484, all text).
Johansen et al. teach DNA extraction and multiplex amplification of iPLEX markers from a blood sample and performing MASSArray SNP typing of the instant 44 single nucleotide polymorphisms (SNPs), 3 gender markers, and 5 copy number controls from DNA extracted from a blood sample (pg 483, sections 2.1 and 2.2 and section 3 and pg 484, all text).
The Agena/Sequenom iPLEX protocol encompasses a multiplex PCR, a multiplex single base extension (SBE) reaction and the detection of the SBE products by Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS). All the experimental reactions (PCR, Shrimp Alkaline Phosphatase (SAP) treatment, SBE and ion-exchange) are performed in the same plate until the samples are transferred to the SpectroCHIP for MALDI-TOF MS detection. Mass spectra are eventually analyzed and the SNPs called by the TYPER software on the MassARRAY analyzer system. Internal controls are also included for quality assurance in the PCR, SAP and SBE mixes (pg 483, sections 2.1 and 2.2).
Omitted from Johansen et al., 2013 (claims 1, 13)
Johansen et al. do not teach extraction of DNA and amplification of DNA of urine sample(s) and do not teach MASSArray SNP typing on DNA extracted from a urine sample.
Agena Bioscience iPLEX pro panel brochures are attached including the Sample ID variant list brochure, Sample integrity brochure and iPLEX Pro Sample ID panel brochure (2018-2021)
Agena Bioscience iPLEX Pro sample ID panel brochure teach SNP typing from DNA isolated from suitable samples including urine (see iPLEX pro sample ID panel brochure, pg 2, section entitled “Toxicology challenges”) and oral swab (pg 3, “How It works” and pg 4, Specifications).
Agena Bioscience iPLEX Pro sample ID panel brochure on page 4 teach the following SNPS as shown in Table below are analyzed.
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Agena/Sequenom iPLEX Pro sample ID. The Agena iPLEX Pro sample ID panel comprises 44 SNPs with high minor allele frequency across major HapMap populations, 3 gender markers and 5 control markers for DNA quality. The 44 SNPs and the 3 gender markers are used to generate the sample’s unique genetic fingerprint. Samples were genotyped using the iPLEX Pro sample ID panel and analysed using the MassARRAY system (Agena Bioscience, San Diego, USA).
None of the cited references teach the limitations of claim 1 and 13, i.e. “wherein an acquisition parameter is set as 550 in said MALDI-TOF MS” and “subjecting said report to the sample identification in clinical toxicology and workforce drug testing”.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the donor identity matching method(s) of McCarty that verifies a same donor for a urine sample and a reference sample, by providing the DNA isolation system/kit taught by Daly et al. which was already routinely used for simultaneous DNA extractions of a plurality of samples together at a same time on platforms of 96 well plates, said system being identified as the Kingfisher/MagMAX™ DNA Multi-Sample Ultra 2.0 kit system and being amenable to automation as disclosed by the User guide manual for MagMAX™ DNA Multi-Sample Ultra 2.0 kit.
The ordinary skilled artisan would have been apprised to select the system of Daly et al. as noted because of its amenability to automation since automating multi sample DNA extractions at the same time would readily streamline the method of McCarty into a more efficient cost-effective method that minimizes sample loss because of reduced sample handling.
It would have been obvious to provide sample(s) such as urine, buccal cells, blood, etc. on the same Kingfisher/MagMAX™ DNA Multi-Sample Ultra 2.0 kit platform for a streamlined DNA extraction since the Applied Biosystems user guide manuals for MagMAX™ DNA Multi-Sample Ultra 2.0 kit and MagMAX™-96 DNA Multi-Sample Kit, Catalog number: 4413022 discloses that these types of samples as being suitable for use with the MagMAX TM DNA Multi-Sample kit.
The ordinary skilled artisan would also have been reasonably apprised to provide a single-step direct lysis buffer for cell lysis and DNA release (i.e. the Multi-sample lysis buffer disclosed in MagMAX™-96 DNA Multi-Sample Kit, Catalog number: 4413022), with a reasonable expectation of success as one-step lysis buffer characteristically promote a streamlined and rapid and predictable assay yielding high quality DNA suitable for use in a subsequent process or downstream assay(s).
There would have been a reasonable expectation of success for an ordinary skilled artisan to provide the urine sample and a reference sample of McCarty to use with the system and/or kit(s) or lysis buffer(s) of Daly et al. so as to recover high quality DNA for downstream amplification and genotyping assay amenable to enabling the DNA analysis and verification process taught by McCarty.
It would also have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to further modify the methods of McCarty and Daly et al. according to the teachings of Johansen et al. and Agena Bioscience Sample ID manual(s) by additionally providing the kit reagents taught by Johansen et al. and Agena Bioscience as suitable to use to identify donor identity across a reference and test/clinical sample, and as taught by Johansen et al. and Agena Bioscience perform the simultaneous amplification and MALDI-TOF SNP typing of the specific SNP markers using the well known Sequenom/Agena iPLEX Pro kit reagents for a reference sample and other test/clinical sample(s) to establish a match for shared donor/donor identity, or a mismatch or lack of donor identity across the reference sample and other test/clinical sample(s).
Concerning the new limitation “an acquisition parameter is set as 550 in said MALDI-TOF MS”, of claims 1 and 13, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980).
Applicant has not disclosed that the specific limitations 0f “550” recited in instant claims 1 and 13 are for any particular purpose or solve any stated problem and it is reasonably apprised by the ordinary skilled artisan that optimizing one or more operational parameters of a device could enhance the device to work as equally as well as the prior art, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges for the MALDI-TOF MS device disclosed by the prior art by normal optimization procedures known in the prior art.
Further concerning the limitation of “subjecting said report to the sample identification in clinical toxicology and workforce drug testing” newly recited by claims 1 and 13, this limitation lacks clarity and clarity of scope and it is not known whether or not creates any structures differences over the prior or even the previously claimed methods that omit it.
In view of the combined teachings and suggestions of all of the cited prior art references, the instant claims 1-2, 4-5, 13-14 and 16-19 are prima facie obvious.
Conclusion
No claims are currently allowed
Correspondence
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OLAYINKA A. OYEYEMI
Examiner
Art Unit 1681
/OLAYINKA A OYEYEMI/Examiner, Art Unit 1681
/GARY BENZION/Supervisory Patent Examiner, Art Unit 1681