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 .
The amended claims dated 1/21/2026 are under consideration.
The amendments and arguments presented in the papers filed 1/21/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 10/21/2025 listed below have been reconsidered as indicated.
a) The objection to the specification is withdrawn in view of the amendments to the specification.
b) The amendments to the specification addressing trade name and mark usage are acknowledged.
c) The rejections of claims 2, 3, 83-84, 86-87 and 89 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, are withdrawn in view of the amendments to the claims.
d) The rejection of claim 89 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of the amendments to the claim.
e) The rejections of claim(s) 83, 84,85, 86, 87 and 89 under 35 U.S.C. 102(a)(1) and 102(a)(2) as anticipated by Struble (US 2013/0275103 A1), are withdrawn in view of the amendments to claim 83.
f) The rejections of claim(s) 1-9, 11 and 22-24 under 35 U.S.C. 102(a)(1) and 102(a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Struble (US 2013/0275103 A1) are withdrawn in view of the amendments.
g) The rejection of claim(s) 10 under 35 U.S.C. 103 as being unpatentable over Struble (US 2013/0275103 A1) in view of Oliphant (US 2014/0242582 A1) is withdrawn in view of the amendments to the claims.
The Examiner’s responses to the Remarks regarding issues not listed above are detailed below in this Office action.
New and modified grounds of rejection necessitated by amendment are detailed below and this action is made FINAL.
The ADS dated 12/20/2022 lists the mailing address for the inventors as “Affymetric, Inc.” The filing receipt and the Oaths list “Affymetrix, Inc.”
The Remarks state that applicant has submitted a corrected ADS changing the mailing address to Affymetrix, Inc (p. 10-11). The Examiner was unable to locate a corrected ADS in the file wrapper at the time of this Office action.
Priority
The present application is a continuation of US 16/616,735 (filed 12/25/2019; issued as US 11,603,557), which is a 371 national stage entry of PCT/US2018/035686 (filed 6/1/2018), which claims benefit of US provisional applications: 62/514,629 (filed 6/2/2017); 62/514,681 (filed 6/2/2017); and 62/514,714 (filed 6/2/2017).
Information Disclosure Statement
The listing of references in the specification or the citation of references throughout the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892 or on a submitted IDS, they have not been considered.
Claim Rejections - 35 USC § 102/103
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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) 1-5, 7, 22, 24 and 139-140 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Foster (BMC Medical Genomics. 2015. 8:5; 13 pages) as evidenced by Jung (Applied Cancer Research. 2017. 37:1, 8 pages; published 1/10/2017).
Regarding claims 1, 22, 24 and 139-140, Foster teaches obtaining a “nucleic acid sample” from an “organism” by extracting DNA from 162 FFPE tissue samples from cancer patients (p. 2, Methods).
Cancer tissue samples include mixed nucleic acid populations comprising a “major subpopulation” and a “minor subpopulation”, in the form of DNA from cancer and non-cancerous cells. The DNA includes polymorphic sites having two variants or alleles.
Foster teaches genotyping the polymorphic sites by contacting the extracted DNA with MIP probes from OncoScan® (p. 3, left column) as “a pool of linear molecular inversion probes”. As demonstrated in Figures 3 and 7 of Foster, the MIPs bind DNA fragments from chromosomes 1, 5, 13, 18, 21, X and Y, as copy numbers were determined.
Foster teaches hybridizing a nucleic acid fragment derived from the nucleic acid population and containing the polymorphic site to an oligonucleotide probe on the OncoScan® assay arrays (p. 3, paragraph spanning the left and right columns).
Foster teaches detecting from the oligonucleotide assay arrays signals corresponding to an A/T variant and a signal corresponding to a G/C variant using a GeneChip® Scanner 3000 7G (p. 3, right column).
While Foster teaches using the OncoScan® assay, Foster does not detail all of the steps.
Jung demonstrates that part of the detecting of the variants includes biotinylating fragments, hybridizing the fragments to arrays and using streptavidin-Phycoerythrin for detection (Fig. 1). Jung further teaches using an anti-streptavidin biotinylated antibody to bind surface bound biotinylated nucleic acids reacted with a streptavidin-phycoerythrin conjugate (p. 4, left column).
Jung further demonstrates using 30 ng of extracted DNA (p. 2) and 335,000 probes for CNVs and allele frequencies and 541 probes for cancer somatic mutations (p. 5). This, renders obvious the ratio of claim 140, which through routine optimization would be set for efficient hybridization and target detection.
As evidenced by Jung, Foster anticipates claim 1.
Alternatively, Foster renders obvious claim 1 as Jung demonstrates that the missing details of Foster were elements of the OncoScan® assay as known in the field.
Regarding claim 2, Foster teaches determining a copy number of nucleic acid loci using the first and second signals from a major or minor subpopulation by reporting an aberrant cell fraction estimate (p. 6, TuScan Comparison). In order to determine a cell fraction, the variants detected must be different between two types of cells.
Regarding claim 3, Foster teaches determining the copy number of a chromosome containing a nucleic acid locus using a CNNLOH analysis (Fig. 5).
Regarding claims 4 and 5, Foster teaches determining the genotypes of the subpopulations using the signals (p. 3).
Regarding claim 7, Foster teaches DNA extracted from tumour-enriched regions (p. 2, Methods), which contains DNA from tumour cells and non-tumour cells.
Claim(s) 1-10, 22, 24, 139 and 140 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Togneri (European Journal of Human Genetics. 2016. 24:1167-1174) as evidenced by Jung (Applied Cancer Research. 2017. 37:1, 8 pages; published 1/10/2017).
Regarding claims 1, 8, 9, 22, 24 and 139-140, Togneri teaches obtaining a “nucleic acid sample” from an “organism” by extracting cfDNA from urine from bladder cancer patients (p. 1168, DNA extraction).
Urine from bladder cancer patients include mixed nucleic acid populations comprising a “major subpopulation” and a “minor subpopulation”, in the form of cfDNA from cancer and non-cancerous cells. The cfDNA includes polymorphic sites having two nucleotide variants or alleles.
Togneri teaches genotyping the polymorphic sites by contacting the extracted cfDNA with MIP probes from OncoScan® (p. 1168, OncoScan assay) as “a pool of linear molecular inversion probes”. As demonstrated in Figure 1 of Togneri, the MIPs bind DNA fragments from chromosomes 1, 5, 13, 18, 21, X and Y, as copy numbers were determined.
While Togneri teaches using the OncoScan® assay, Togneri does not detail all of the steps.
Jung demonstrates the OncoScan® assay involves hybridizing a nucleic acid fragment derived from the nucleic acid population and containing the polymorphic site to an oligonucleotide probe on the OncoScan® assay arrays (Fig. 1).
Jung teaches detecting from the oligonucleotide assay arrays signals corresponding to an A/T variant and a signal corresponding to a G/C variant using a GeneChip® Scanner 3000 7G (p. 3, right column).
Jung demonstrates that part of the detecting of the variants includes biotinylating fragments, hybridizing the fragments to arrays and using streptavidin-Phycoerythrin for detection (Fig. 1). Jung further teaches using an anti-streptavidin biotinylated antibody to bind surface bound biotinylated nucleic acids reacted with a streptavidin-phycoerythrin conjugate (p. 4, left column).
Jung further demonstrates using 30 ng of extracted DNA (p. 2) and 335,000 probes for CNVs and allele frequencies and 541 probes for cancer somatic mutations (p. 5). This, renders obvious the ratio of claim 140, which through routine optimization would be set for efficient hybridization and target detection.
As evidenced by Jung, Togneri anticipates claim 1.
Alternatively, Togneri renders obvious claim 1 as Jung demonstrates that the missing details of Togneri were elements of the OncoScan® assay as known in the field.
Regarding claim 2, Togneri teaches determining a copy number of nucleic acid loci using the first and second signals from a major or minor subpopulation by reporting an aberrant cell fraction estimate (p. 1168, Data analysis). In order to determine a cell fraction, the variants detected must be different between two types of cells.
Regarding claim 3, Togneri teaches determining the copy number of a chromosome containing a nucleic acid locus (Fig. 4).
Regarding claims 4 and 5, Togneri teaches determining the genotypes of the subpopulations using the signals (p. 1168, OncoScan assay).
Regarding claim 6, Togneri teaches determining relative amounts by analyzing for biallelic loss (Figure 1).
Regarding claims 7 and 10, Togneri teaches cfDNA extracted urine as noted above. Urine from patients with a bladder tumor includes major and minor subpopulations of nucleic acids derived from non-cancerous and cancerous cells.
Claim(s) 11 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Foster (BMC Medical Genomics. 2015. 8:5; 13 pages) as evidenced by Jung (Applied Cancer Research. 2017. 37:1, 8 pages; published 1/10/2017) and in view of Oliphant (WO 2016/018986 A1).
Regarding claim 11, Foster teaches obtaining a “nucleic acid sample” from an “organism” by extracting DNA from 162 FFPE tissue samples from cancer patients (p. 2, Methods).
Cancer tissue samples include mixed nucleic acid populations comprising a “major subpopulation” and a “minor subpopulation”, in the form of DNA from cancer and non-cancerous cells. The DNA includes polymorphic sites having two variants or alleles.
Foster teaches genotyping the polymorphic sites by contacting the extracted DNA with MIP probes from OncoScan® (p. 3, left column) as “a pool of linear molecular inversion probes”. As demonstrated in Figures 3 and 7 of Foster, the MIPs bind DNA fragments from chromosomes 1, 5, 13, 18, 21, X and Y, as copy numbers were determined.
Foster teaches hybridizing a nucleic acid fragment derived from the nucleic acid population and containing the polymorphic site to an oligonucleotide probe on the OncoScan® assay arrays (p. 3, paragraph spanning the left and right columns).
Foster teaches detecting from the oligonucleotide assay arrays signals corresponding to an A/T variant and a signal corresponding to a G/C variant using a GeneChip® Scanner 3000 7G (p. 3, right column).
While Foster teaches using the OncoScan® assay, Foster does not detail all of the steps.
Jung demonstrates that part of the detecting of the variants includes biotinylating fragments, hybridizing the fragments to arrays and using streptavidin-Phycoerythrin for detection (Fig. 1). Jung further teaches using an anti-streptavidin biotinylated antibody to bind surface bound biotinylated nucleic acids reacted with a streptavidin-phycoerythrin conjugate (p. 4, left column).
Jung further demonstrates using 30 ng of extracted DNA (p. 2) and 335,000 probes for CNVs and allele frequencies and 541 probes for cancer somatic mutations (p. 5). This, renders obvious the ratio of claim 140, which through routine optimization would be set for efficient hybridization and target detection.
Foster does not teach the organism is a pregnant female, with the major subpopulation being from the pregnant female's blood and the minor subpopulation is from fetal nucleic acid.
However, Oliphant teaches using nucleic acids extracted from the plasma of pregnant female blood (paras. 79, 195-196) as a non-invasive prenatal diagnosis (para. 79).
Oliphant further describes an interest in evaluating the alleles and mutations relevant to cancer (paras. 4, 5 and 141).
It would have been prima facie obvious to the ordinary artisan at the time of invention to have modified the method of Foster by using the nucleic acids extracted from the blood of pregnant females. One would be motivated to do so to detect the possibility of cancer nucleic acids presents in the blood as a non-invasive detection system and to monitor for fetal development abnormalities. The modification has a reasonable expectation of success the assays of Foster and Oliphant are substantially similar, e.g., based on probe hybridization, ligation, amplification and array hybridization.
Claim(s) 83, 84, 85, 86, 87 and 89 is/are rejected under 35 U.S.C. 103 as being unpatentable over Oliphant (WO 2016/018986 A1) and Tobe (Nucleic Acids Research. 1996. 24(19):3728-3732).
Regarding claims 83, 86 and 87, Oliphant teaches obtaining cfDNA from the plasma of pregnant females (paras. 195-196). The cfDNA includes a subpopulations of minor nucleic acids from a fetus and a major nucleic acids from the pregnant female. The nucleic acids include polymorphic sites having to possible alleles that may be genotyped.
Oliphant teaches genotyping the nucleic acids using a ligation assay (Figs. 2-13), that in some embodiments uses molecular inversion probes (para. 34).
Fragments of the ligation assay are hybridized to an oligonucleotide of an array (Figs. 2-13).
Oliphant teaches detecting two different signals for the different alleles of a polymorphic site to determine the genotype (Figs. 2-13). Detecting different signals would involve using different detection channels.
Oliphant teaches the labels are attached to the nucleic acid fragments via binding pairs (Figs. 2-13), including antibodies and their epitopes (para 72).
Oliphant does not teach the use of antibodies that bind to the first or second allelic variant.
However, Tobe demonstrates the antibodies against different antigens for the detection of alleles was known (Figure 1).
It would have been prima facie to have modified the method of Oliphant by attaching different antigens to different alleles using the approach of Tobe and to use specific antibodies labeled with the labels of Oliphant to detect the different alleles. The modification has a reasonable expectation of success because Oliphant describes using antibodies and antigens as binding pairs. One would have been modified to make such modifications based on design preferences.
Regarding claims 84, 85, Oliphant teaches determining the fetal fraction (para. 201). Oliphant teaches determining a “B-allele frequency” by determining the fetal fraction based on the ratio of maternal variants to fetal variants (para. 201).
Regarding claim 89, Oliphant teaches determining copy number based on the chromosomal ratios (para. 182-183).
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 1-11, 22-24, 83-87 and 89 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,603,557 B2 in view of Jung (Applied Cancer Research. 2017. 37:1, 8 pages; published 1/10/2017).
Although the claims at issue are not identical, they are not patentably distinct from each other because the present claims are of sufficient breadth so as to encompass the claims of the ‘557 patent. The claims differ based on the use of an antibody as an agent; however, Jung teaches this is known as described above.
Claims 1-11, 22-24, 83-87 and 89 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/078,737 (reference application) in view of Jung (Applied Cancer Research. 2017. 37:1, 8 pages; published 1/10/2017).
Although the claims at issue are not identical, they are not patentably distinct from each other because the use of the system of the ‘737 as described in the instructions assigned to the computer performs the methods of the present claims. The claims differ based on the use of an antibody as an agent; however, Jung teaches this is known as described above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-11, 22-24, 83-87 and 89 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,535,886 B2 in view of Jung (Applied Cancer Research. 2017. 37:1, 8 pages; published 1/10/2017).
Although the claims at issue are not identical, they are not patentably distinct from each other because the present claims are of sufficient breadth so as to encompass the claims of the ‘886 patent. in view of Jung (Applied Cancer Research. 2017. 37:1, 8 pages; published 1/10/2017).
Response to the Remarks regarding the double patenting rejections
The Remarks request the rejections be held in abeyance until such time that the claim are found to be otherwise allowable (p. 15).
The above rejections are new rejections as necessitated by the amendments to the claims.
Conclusion
No claims 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 JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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/JOSEPH G. DAUNER/ Primary Examiner, Art Unit 1682