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 .
Applicant’s amendment filed on January 14, 2026 is acknowledged and has been entered. Claim 1 and 14 have been amended. Claims 1-16 are pending.
Claims 1-16 are discussed in this Office action.
All of the amendments and arguments have been thoroughly reviewed and considered but are not found persuasive for the reasons discussed below. Any rejection not reiterated in this action has been withdrawn as being obviated by the amendment of the claims. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is made NON-FINAL as necessitated by New Grounds of Rejection.
Previous Grounds of Rejection
Priority
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, Application No. 62147377, 61516996, 61395850, 8825412, 61994791, 61987407, 13780022, 13683604 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. While each of these priority documents include support for multiplex amplification and sequencing, none of these priority documents include sufficient (or any) support for the inclusion of transplant or transplantation patients. Therefore, as the priority documents of US Patent 10655180, 62148173, 62146188, 61982245
for example, provide support, the claims are afforded an earliest priority of April 21, 2014.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of copending Application No. 18751153 (reference application, ‘153 application herein). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the instant application are focused on analysis of 100 genomic loci while the claims of the ‘153 application are focused on analysis of 100 SNP loci. The dependent claims are nearly identical, as well. Compare claims 4-6 of the instant claims and claims of the ‘153 application, where the length of the amplicon are described. Compare claims 7-10 of the instant claims and claims of the ‘153 application, where these claims specify how many loci are amplified together. Compare claims 11-13 of the instant claims and claims of the ‘153 application, where the specific chromosomes 1, 2 and 3 are analyzed. For at least these reasons, the claims of the instant application are not patentable in view of the claims of the '153 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11, 15-17 and 19-22 of copending Application No. 16817117 (reference application, ‘117 application herein). Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed method of the instant claims and the method of the ‘117 application share many of the same steps, including extraction of cell free nucleic acids from a first and second individual, targeted PCR amplification of 100 or more target loci and analysis of the amount of one or more alleles through high throughput sequencing. The dependent claims cover similar subject matter, as well. Compare, for instance claim 1 and 14 of the instant claims to claims 3 and 22 of the ‘117 application, where each claim includes cell free DNA from a transplant. Further, compare claim 2 and 16 of the instant claims to claims 2 and 22 of the ‘117 application where the sample source includes blood, serum, plasma or urine. Also, compare claims 4-6 of the instant claims and of the ‘117 application, where the length of the amplicon are described. Compare claims 7-10 of the instant claims and claims 8-11 of the ‘117 application, where these claims specify how many loci are amplified together. Compare instant claims 14-15 to claim 21 of the ‘117 application where bias of PCR amplification is determined. For at least these reasons, the claims of the instant application are not patentable in view of the claims of the '117 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
New Grounds of Rejection
Information Disclosure Statement
The information disclosure statement (IDS) submitted on January 16, 2026 and March 5, 2026 was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 103
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) 1-9 and 11-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Quake et al. (US Patent 8,703,652; April 2014) in view of May et al. (US PGPub 20140227691; August 2014) and Fredriksson et al. (Leukemia et al. (2004, vol. 18:255-266).
With regard to claim 1, Quake teaches a method for amplifying and sequencing DNA, comprising:
(a) extracting cell-free DNA of mixed origin from a biological sample of a subject, wherein the cell-free DNA comprises DNA from the subject and DNA from a genetically distinct individual, wherein neither the subject nor the genetically distinct individual is a fetus, and wherein the DNA of mixed origin comprises DNA from a transplant (Abstract, Figure 3 and Figure 4, where donor DNA is detected in transplantation patient samples; also Figure 5, where the method of monitoring transplant patients is described; see also Examples 1 and 2, especially Example 2 where transplant donor and recipient were analyzed and genotyped using sequencing techniques, cell-free DNA and plasma);
(b) performing targeted PCR amplification of the cell-free DNA at genomic loci in a single reaction volume using PCR primer pairs (col. 14, lines 14-67, where PCR amplification is described; PCR is also used within Example 1);
(c) performing high-throughput sequencing of the amplified genomic loci (col. 15, line 1 to col. 16, line 12, where high throughput sequencing is described); and
(d) receiving an output resulting from an amount of the DNA from the genetically distinct individual present in the biological sample that has been determined using the amount of one or more alleles at the genomic loci in sequence reads produced by the high-throughput sequencing, (Abstract, Figure 3 and Figure 4, where donor DNA is detected in transplantation patient samples; also Figure 5, where the method of monitoring transplant patients is described; see also Examples 1 and 2, especially Example 2 where transplant donor and recipient were analyzed and genotyped using sequencing techniques, cell-free DNA and plasma).
With regard to claim 2, Quake teaches a method of claim 1, wherein the biological sample is a blood, serum, plasma, or urine sample (col. 6, line 56 to col. 8, line 44, where circulating nucleic acids obtained from blood or plasma; see also Figure 5; see also col. 20, line 64 to col. 21, line 4 and Example 1-2, where plasma is analyzed).
With regard to claim 3, Quake teaches a method of claim 1, wherein the extracting step comprises size selection to enrich for shorter cell-free DNA (col. 10, where blood samples can be enriched and processed).
With regard to claim 4, Quake teaches a method of claim 1, wherein the primer pairs are each designed to amplify less than about 100 bp of DNA (paragraph 76, where amplicon lengths are between 200 and 30 nucleotides in length).
With regard to claim 5, Quake teaches a method of claim 1, wherein the primer pairs are each designed to amplify less than about 80 bp of DNA (paragraph 76, where amplicon lengths are between 200 and 30 nucleotides in length).
With regard to claim 6, Quake teaches a method of claim 1, wherein the primer pairs are each designed to amplify about 65-80 bp of DNA (paragraph 76, where amplicon lengths are between 200 and 30 nucleotides in length).
With regard to claim 14, Quake teaches a method for amplifying and sequencing DNA, the method comprising:
(a) performing a targeted PCR amplification for more genomic loci on one or more chromosomes expected to be disomic in a single reaction mixture using more PCR primer pairs (col. 14, lines 14-67, where PCR amplification is described; PCR is also used within Example 1),
wherein the reaction mixture comprises cell-free DNA extracted from a biological sample of a subject comprising DNA of mixed origin, wherein the DNA of mixed origin comprises DNA from the subject and DNA from a genetically distinct individual, wherein neither the subject nor the genetically distinct individual is a fetus, wherein the DNA of mixed origin comprises DNA from a transplant, and wherein one or more of the amplified genomic loci each comprises an allele present in the genetically distinct individual but not the subject (Abstract, Figure 3 and Figure 4, where donor DNA is detected in transplantation patient samples; also Figure 5, where the method of monitoring transplant patients is described; see also Examples 1 and 2, especially Example 2 where transplant donor and recipient were analyzed and genotyped using sequencing techniques, cell-free DNA and plasma);
(b) performing high-throughput sequencing of the amplified genomic loci (col. 15, line 1 to col. 16, line 12, where high throughput sequencing is described);
(c) receiving an output resulting from an amount of the DNA from the genetically distinct individual in the biological sample that has been determined using the quantity of each allele at the genomic loci in sequence reads produced by the high-throughput sequencing and an expected quantity of each allele at the genomic loci for different DNA fractions, wherein the method is performed without prior knowledge of genotypes of the genetically distinct individual (Abstract, Figure 3 and Figure 4, where donor DNA is detected in transplantation patient samples; also Figure 5, where the method of monitoring transplant patients is described; see also Examples 1 and 2, especially Example 2 where transplant donor and recipient were analyzed and genotyped using sequencing techniques, cell-free DNA and plasma).
With regard to claim 16, Quake teaches a method of claim 14, wherein the biological sample is a blood, serum, plasma, or urine sample, wherein more than 500 genomic loci are amplified in a single reaction volume (col. 6, line 56 to col. 8, line 44, where circulating nucleic acids obtained from blood or plasma; see also Figure 5; see also col. 20, line 64 to col. 21, line 4 and Example 1-2, where plasma is analyzed).
Regarding claims 1, 7-10 and 14, while Quake teaches cell free based analysis, Quake does not teach multiplex amplification of cell-free DNA.
With regard to claim 1, May teaches (b) performing targeted PCR amplification of the cell-free DNA at more than 100 genomic loci in a single reaction volume using more than 100 PCR primer pairs (paragraph 199 where up to 1000 loci are amplified via multiplex; paragraph 71, 198, 110 where the method of amplification includes pre-amplification steps before multiplex amplification; see paragraph 76, where cell free nucleic acid is amplified using steps of pre-amplification and multiplex amplification).
With regard to claim 7, May teaches a method of claim 1, wherein more than 200 genomic loci are amplified in a single reaction volume (paragraph 199 where up to 1000 loci are amplified via multiplex; paragraph 71, 198, 110 where the method of amplification includes pre-amplification steps before multiplex amplification; see paragraph 76, where cell free nucleic acid is amplified using steps of pre-amplification and multiplex amplification).
With regard to claim 8, May teaches a method of claim 1, wherein more than 500 genomic loci are amplified in a single reaction volume (paragraph 199 where up to 1000 loci are amplified via multiplex; paragraph 71, 198, 110 where the method of amplification includes pre-amplification steps before multiplex amplification; see paragraph 76, where cell free nucleic acid is amplified using steps of pre-amplification and multiplex amplification).
With regard to claim 9, May teaches a method of claim 1, wherein more than 1000 genomic loci are amplified in a single reaction volume (paragraph 199 where up to 1000 loci are amplified via multiplex; paragraph 71, 198, 110 where the method of amplification includes pre-amplification steps before multiplex amplification; see paragraph 76, where cell free nucleic acid is amplified using steps of pre-amplification and multiplex amplification).
With regard to claim 11, May teaches a method of claim 1, wherein the amplified genomic loci comprise genomic loci on chromosome 1 (paragraph 78, 98, 109 where multiple chromosomes are analyzed; including mention of tagging each chromosome).
With regard to claim 12, May teaches a method of claim 1, wherein the amplified genomic loci comprise genomic loci on chromosome 2 (paragraph 78, 98, 109 where multiple chromosomes are analyzed; including mention of tagging each chromosome).
With regard to claim 13, May teaches a method of claim 1, wherein the amplified genomic loci comprise genomic loci on chromosome 3 (paragraph 78, 98, 109 where multiple chromosomes are analyzed; including mention of tagging each chromosome).
With regard to claim 14, May teaches (a) performing a targeted PCR amplification for more than 100 genomic loci on one or more chromosomes expected to be disomic in a single reaction mixture using more than 100 PCR primer pairs (paragraph 199 where up to 1000 loci are amplified via multiplex; paragraph 71, 198, 110 where the method of amplification includes pre-amplification steps before multiplex amplification; see paragraph 76, where cell free nucleic acid is amplified using steps of pre-amplification and multiplex amplification).
With regard to claim 15, May teaches a method of claim 14, further comprising determining a bias of the PCR amplification, and using the bias to statistically correct the determined quantity of each allele at the plurality of genomic loci on the one or more chromosomes expected to be disomic before the quantity of each allele is used to determine the amount of the DNA from the genetically distinct individual (paragraph 123 and 125, where amplicons are corrected or subject to bias in amplification).
Regarding claims 1 and 14, while Quake teaches the method of isolation and preparation as claimed, Quake does not teach the method is performed without prior knowledge or previously known genotypes.
With regard to claim 1 and 14, Fredricksson teaches wherein the method is performed without prior knowledge of genotypes of the genetically distinct individual (Abstract, Fig 4, p 264, “Determination of SNP allele fractions and proportion of donor cells” heading).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have adjusted the teachings of Quake to include the methods of multiplex amplification as described by May to arrive at the claimed invention with a reasonable expectation for success. Quake teaches “The development of markers for early, non-invasive, safe, and cost-effective detection of acute rejection and CAV, and their rapid translation to a practical and reliable test that can be used in the clinic represents a major unmet medical need for the nearly 22,000 living heart transplant recipients in the United States, and a similar number worldwide” (col. 6, lines 23-29). Quake also teaches “As mention above, monitoring transplant patients for transplant status or outcome is difficult and expensive, often requiring non-sensitive and invasive procedures. For instance, in heart transplant patients acute rejection Surveillance requires serial endomyocardial biopsies that are routinely performed at weekly and monthly intervals during the initial year after transplant, with a total of 6-8 biopsies in most patients. Advances in immunosuppression, rejection Surveillance, and early recognition and treatment of life-threatening infections have led to continuous improvements in early outcomes after cardiac transplantation” and Quake notes “…there has not been a similar improvement in late mortality, which is largely attributable to cardiac allograft vasculopathy (CAV)” (col. 5, lines 54-67). May teaches methods that include multiplex amplification and May teaches “It is known that mutations in the k-ras gene trigger the apoptosis pathway. Moreover, mutated k-ras DNA in serum is fragmented to nucleosome-length DNA. Evidence has accumulated that PCR-based mutation detection of k-ras DNA is highly dependent of the isolation method used, i.e., small DNA enrichment markedly improved mutation detection.” (paragraph 216). May also teaches “Nucleic acids of interest can be isolated using methods well known in the art, with the choice of a specific method depending on the source, the nature of nucleic acid, and similar factors. The sample nucleic acids need not be in pure form, but are typically sufficiently pure to allow the amplification steps of the methods of the invention to be performed.” (paragraph 138). May also notes “It will be recognized that, in certain embodiments, a large number of different target sequences (e.g., 2 or more, 3 or more, 5 or more, 10 or more, 15 or more, 20 or more, 50 or more, 100 or more per chromosome or other template(s)), can be tagged. Moreover using various tagging strategies, different amplification produces are readily discriminated thereby permitting the methods to be highly multiplexed” (paragraph 109). Therefore, one of ordinary skill in the art at the time the invention was made would have adjusted the teachings of Quake to include the methods of multiplex amplification as described by May to arrive at the claimed invention with a reasonable expectation for success.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have adjusted the teachings of Quake and May to include samples where the genotype of the donor are not previously known to arrive at the claimed invention with a reasonable expectation for success. Both Quake and Fredericksson are focused on samples that include analysis of transplantation patients. Fredricksson teaches “Single-nucleotide polymorphisms (SNPs) have the potential to be particularly useful as markers for monitoring of chimerism after stem cell transplantation (SCT) because they can be analyzed by accurate and robust methods” (abstract). Fredricksson also teaches “informative SNPs with alleles differing between donor and recipient were identified using a multiplex microarray-based minisequencing system screening 51 SNPs to ensure that multiple informative SNPs were detected in each
donor–recipient pair.” Next, Fredricksson teaches “Using this panel of SNPs, we identified multiple informative SNPs in nine unrelated and in 16 related donor–recipient pairs. Samples from nine of the donor–recipient pairs taken at time points ranging from 1 month to 8 years after transplantation were available for analysis. In these samples, we monitored the allelic ratios of two or three informative SNPs in individual minisequencing reactions. The results agreed well with the data obtained by microsatellite analysis” (abstract). Finally, Fredricksson teaches “Our microarray-based genotyping system based on 51 SNPs is thus superior for identifying ‘diagnostic’ SNP markers for the follow-up of SCT to the previously described panel of 14 SNPs analyzed by the pyrosequencing assay23 or a recently described set of seven SNPs analyzed by real-time PCR, which was informative only in 67% of sibling pairs.36,37 (p. 261). Therefore, one of ordinary skill in the art at the time the invention was made would have adjusted the teachings of Quake and May to include samples where the genotype of the donor are not previously known to arrive at the claimed invention with a reasonable expectation for success.
Claim(s) 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Quake et al. (US Patent 8,703,652; April 2014) in view of May et al. (US PGPub 20140227691; August 2014) and Fredriksson et al. (Leukemia et al. (2004, vol. 18:255-266) as applied over claims 1-9 and 11-16 above.
With regard to claim 10, May teaches a method of claim 1, wherein more than 2000 genomic loci are amplified in a single reaction volume (paragraph 199 where up to 1000 loci are amplified via multiplex; paragraph 71, 198, 110 where the method of amplification includes pre-amplification steps before multiplex amplification; see paragraph 76, where cell free nucleic acid is amplified using steps of pre-amplification and multiplex amplification).
May does not specifically teach amplification of 2000 primers together. However, an ordinary practitioner would have recognized that the results optimizable variables of time, product amount and level of multiplex could be adjusted to maximize the desired results. As noted in In re Aller, 105 USPQ 233 at 235,
More particularly, where the general conditions
of a claim are disclosed in the prior art, it is
not inventive to discover the optimum or workable
ranges by routine experimentation.
Routine optimization is not considered inventive and no evidence has been presented that the level of multiplex or selection of primer sets was other than routine, that the products resulting from the optimization have any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art.
Response to Arguments
Applicant’s arguments with respect to claim(s) 1-16 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
However, insofar as rejections are maintained regarding obviousness type double patenting and the priority guidance has not been changed, Applicant’s remarks will be briefly addressed. Further, in an attempt at compact prosecution, the reasoning behind maintaining the rejection over May is also addressed.
First, the request to hold the obviousness-type double patenting rejections in abeyance is denied. These are not the only outstanding issues in the case and they will be maintained until a terminal disclaimer is filed to obviate the rejections or the claims are amended sufficiently to render the claims patentably distinct.
Next, while Applicant draws attention to two priority documents 13780022 and 13300235 for teaching transplantation and arguing the documents provide support for transplantation, these arguments (see pages 5-6 of remarks) are not persuasive. The comparison of a mixed samples as required within the claimed method as including transplantation necessarily includes a mixture of donor and recipient samples. The mixture of these donor and recipient samples are the central feature of the method, as claimed, and both of the priority documents argued by Applicant only make very general mention of transplantation as a concept with no guidance or detail specific to transplantation or samples related to transplantation. As the guidance regarding priority states, “none of these priority documents include sufficient (or any) support for the inclusion of transplant or transplantation patients”. Applicant’s arguments do not change that position and the priority guidance will me maintained as previously provided.
Finally, regarding the arguments over May will be briefly addressed and the rejection over May is maintained. Applicant argues the methods of May are carried out in microfluidic devices and effectively argues the use of multiplex within May refers to simultaneous side by side amplification in separate chambers “because each amplification reaction is performed in a different chamber” (p 9 of remarks). This argument is wholly unpersuasive and this aspect of the rejection is maintained.
The argument by Applicant that May effectively teaches away from simultaneous amplification and only teaches single amplification in plural individual receptacles ignores the overall sum of the teachings of May. While May does teach a microfluidic device, that array-based device is described as useful for pairwise combinations of samples, the device can also be used for digital array amplification (paragraph 193), a method which isolates particular targets or primers, by design. However, May also teaches multiplex amplification in multiple places throughout the disclosure. For example, at paragraph 109, May teaches the tagging of “a large number of different sequences” including “2 or more, 3 or more, 5 or more, 10 or more, 15 or more, 20 or more, 50 or more, 100 or more per chromosome or other template(s)), can be tagged. Moreover using various tagging strategies, different amplification produces are readily discriminated thereby permitting the methods to be highly multiplexed”. It is also noted, while the citation in paragraph 199, as cited in the rejection mentions both multiplex detection and individual reaction chambers, the passage states “In various embodiments, up to 2, 3, 4, 5, 6, 7, 8, 9, 10, 50, 100, 500, 1000, 5000, 10000 or more amplification reactions are carried out in each individual reaction chamber”. Finally, it is noted that their method of multiplex detection “facilitates multiplex detection wherein two or more different amplification products can be detected in a given amplification mixture or aliquot thereof”. These teachings taken together implies these reactions are carried out together in the chambers, as described.
Therefore, while Applicant’s arguments are noted, they are not persuasive because May teaches and suggests high level multiplex amplification, as claimed.
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Kwok et al. (Clin Transplant 2010, 24:E178-E181).
Conclusion
No claims are allowed. All claims stand rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHANIE KANE MUMMERT whose telephone number is (571)272-8503. The examiner can normally be reached M-F 9:00-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached on 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/STEPHANIE K MUMMERT/Primary Examiner, Art Unit 1681
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