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 .
Status of the Applications, Amendments and/or Claims
This action is written in response to applicant's correspondence(s) submitted on 07/18/2025. In the paper of 07/18/2025, Applicant amended claims 1, 7-9 and canceled claims 6, 12-15, 17, 19-22, 30-37 and 40-42. Claims 4, 10, 23-29 and 38-39 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention(s), there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 02/05/2025.
Accordingly, claims 1-5, 7-11, 16, 18, 23-29 and 38-39 are pending and claims 1-3, 5, 7-9, 11, 16 and 18 are still under review.
Response to Arguments
Withdrawn Rejection(s)
The rejection of claims 1-3, 5, 7-9, 11, 16 and 18 under 35 U.S.C. 103 as being unpatentable over MacDonald (WO2019/169043A, pub. September 06, 2019) in view of Lianidiou et al. (WO2024/027961A1, filed 04/07/2023) and Lun et al. (2008, P.N.A.S., 105(50), pp.19920-19925) is withdrawn in favor of the new rejection(s) presented below which address the claim limitations better.
Maintained Rejection(s)
The rejection of claims 5 and 11 under 35 U.S.C. §101 are maintained as Applicant’s arguments are not found to be persuasive.
The rejection of claims 1-3, 5, 7-9, 11, 16 and 18 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite are maintained as Applicant’s arguments are not found to be persuasive.
Argument(s)
Applicant's arguments filed 07/18/2025 have been fully considered but they are not persuasive because of the following.
To the extent that Applicants arguments rely on teachings of MacDonald (WO2019/169043A, pub. September 06, 2019), Lianidiou et al. (WO2024/027961A1, filed 04/07/2023) and Lun et al. (2008, P.N.A.S., 105(50), pp.19920-19925), the arguments are not persuasive as the rejection below no longer relies on these references.
The arguments that claims 5 and 11 are patent eligible are not found to be persuasive as the claims still rely on judicially excluded natural law and processes of analysis that are generically recited and these claims do not recite additional elements/processes that are applied after the judicial exception are realized and that allow the claims to amount to more than the judicially excluded subject matter.
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 5 and 11 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) 5 and 11 do not recite something significantly more than a judicial exception. The rationale for this determination is explained below:
According to the 2019 Revised Patent Subject Matter Eligibility Guidance, Docket No. PTO-P-2018-0053 (January 7, 2019), an initial two step analysis is required for determining statutory eligibility.
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.
Step 2
The Step 2 analysis is a two-part analysis, Step 2A and Step 2B.
Step 2A, prong 1
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 2A, prong 2
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
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.
Following the analysis below the claims are not patent eligible under 35 U.S.C. 101.
Concerning Step 1: YES. Claims 5 and 11 are directed to methods, therefore the claims are directed to a process, which is a statutory category.
Concerning Step 2A: YES. Claims 5 and 11 recite methods directed to determining a classification of a pathology for a subject by analyzing cell free nucleic acids and determining at least a specified number of bases in length between a first region of a reference sequence that binds a first probe and the second region of a reference sequence that binds a second probe within the cell free nucleic acid sample. The method comprises performing a plurality of digital reactions and determining of a parameter that corresponds to a relative amount between positive digital signals collected from only one of the first probe or the second probe; and positive digital reactions that are positive for both of the first probe and the second probe.
Claims 5 and 11 rely on a naturally-occurring correlation between pathology and spacing or the specified number of bases between the first reference sequence and the second reference sequence within a cell-free nucleic acid sample of a subject, the specified number of bases length is 5 kilobases or less; and/or is 500 bases or more.
Concerning Step 2A, prong 1, claims 5 and 11 are directed towards a judicial exception, i.e. a law of nature, as noted above. Claims 5 and 11 also recite relying on judicially excluded abstract ideas of comparing and parsing data without significantly more, as these claims recite steps of determining of a parameter that corresponds to a relative amount between positive digital signals collected from only one of the first probe or the second probe; and positive digital reactions that are positive for both of the first probe and the second probe. The determining of a parameter step fall within the grouping of abstract ideas and as it merely instructs a user to analyze spacing/specific number of bases between two target sequences within a reference sequence of cell free nucleic acids (analyze the natural law) and to draw a conclusion about pathology.
Concerning Step 2A, prong 2, for claims 5 and 11, the judicial exception(s) noted above are not integrated into a practical application.
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 amount to significantly more than the judicial exception.
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.
Claims 5 and 11 do not recite steps/elements that are construed to be a practical application that apply, rely on, or use the judicial exceptions e.g. the claims do not recite any specific diagnosis/conclusion to be inferred are the specific number of bases between two target sequence of a reference sequence of a cell-free nucleic acid sample, nor is any treatment i.e. practical application recited, once the specific number of bases are determined.
While the steps of distributing a plurality of cell-free nucleic acid molecules into a plurality of digital reactions, adding a plurality of reagents comprising a first probe and a second probe into each of the plurality of digital reactions, detecting a first signal from the first probe and a second signal from the second probe are not practical applications, they must be applied to realize the judicial exception(s).
They are also recited with a high level of generality and therefore do not add any meaningful limitation to practicing the natural law and/or abstract idea.
Concerning Step 2B, claims 5 and 11 do not recite any additional elements that ensure that the claims as a whole amount to significantly more than the judicial exception(s).
The steps of analyzing amplification data and determining that a first reaction includes a cell-free nucleic acid molecule that is at least the specified number of bases in length and that covers the first region and the second region of the nucleic acid molecule, constitute well-understood, routine, conventional activity as shown by To et al. (2020, Lancet infectious diseases, 20(5), pp.565-574: see pg 569, Fig. 2) (see Berkheimer v. HP, Inc., 881 F.3d 1360, 1368, 125 USPQ2d 1649, 1654 (Fed. Cir. 2018) (see M.P.E.P. 2106.05(d), section I, (2) for more on well-understood, routine, conventional activity).
There is no inventive concept in claims 5 and 11, and thus they are rejected as being ineligible under 35 U.S.C. 101.
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 1-3, 5, 7-9, 11, 16 and 18 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 recites the limitation “based on detecting the first signal and the second signal, determining that the first digital reaction includes a cell-free nucleic acid molecule of the plurality of the cell-free nucleic acid molecules that is at least the specified number of bases in length and that covers the first region and the second region”.
This limitation as a whole lacks clarity as it does not sufficiently establish a nexus between the first signal and second signal of the first and second probes respectively, and the number of bases detected between the first and second amplified regions of the reference sequence.
It is suggested that the limitation be further amended in a manner to make clear that the detection of both the first signal and the second signal using the first and second probes that bind to the first and second amplified regions generated respectively by the first primer set and the second primer set conclude the positive presence of both a first region and a second region that are positioned at least 5 kilobases or less apart on the reference sequence within the cell-free nucleic acid.
Claims 2-3, 5, 7-9, 11, 16 and 18 are further rejected as they depend from claim 1.
Claim 5 recites the limitation “determining a classification of a pathology for the subject using the parameter” but omits the essential active process steps to direct an ordinary skilled artisan of how to establish a pathology classification using a ratio between the positive signals from one of either the first probe or second probe from a plurality of digital reactions; and positive signals from both the first probe and second probe from the plurality of digital reactions.
Claim 8 recites the limitation, “wherein the parameter is a first parameter” which lacks clarity and clarity of scope. Claims 8 depends from claims 3 and 7 and claim 3 provides the instant first parameter as
a relative amount between a first number and a second number, wherein the first number is the “sum/total” number of digital reactions that are positive for only one of the first signal and the second signal; and the second number is the number of digital reactions that are positive for both of the first signal and the second signal.
Because of the presence of this noted limitation in claim 8, it is confusing how to determine the instant second parameter consisting the relative amount between the first number and a third number, when the parameter is a first parameter. Claim 8 is rejected because of the requirement for “the parameter” to be equivalent to the “first parameter”.
Claim 9 recites the limitation, “wherein the parameter is a first parameter. This limitation as a whole lacks clarity because of the construction around the limitation “the parameter”. It is unclear whether claim 9 requires the parameter that is a first parameter (construed as equivalent to the relative amount between the first number and the second number); or whether claim 9 intends to change the instant “the parameter” to become the relative amount between the second number and the third number.
It is not permitted that “the parameter” in claim 9 be construed as both relative amount between the first number and the second number and relative amount between the second number and the third number.
Claim Rejections - 35 USC § 102
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.
Claims 1, 3, 5, 7-9, 11, 16 and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Han et al. (August 2019, Biochimica et Biophysica Acta (BBA)-General Subjects, 1863(8), pp.1235-1242: newly cited).
Regarding claim 1, Han et al. teach a set of digital PCR assays (dPCR) for measuring DNA fragmentation from cells exhibiting induced cytotoxic response. The assays quantitatively measure the degree of cell death by quantifying targets of increasing sizes within the RNase P (RP) gene locus (see pg 1235, section of the abstract entitled “Methods and results” and pg 1238, Fig. 2A and pg 1236, right col., 2nd para of section 2.2).
Han et al. teach a hypothesis that “if template DNA is fragmented, the copy number concentration of smaller DNA targets will be higher than that of larger ones in a given sample. In contrast, if template DNA is not fragmented (i.e. high molecular weight genomic DNA), the copy number concentrations from any sample will be constant regardless of the size of amplicons, given that a comparable PCR efficiency was first verified” (pg 1236, right col., 3rd para of section 2.2).
Han et al. teach determining the “ratio between short and long target copy numbers”, which implies the degree of DNA fragmentation resulting from cell cytotoxicity, necrosis or apoptosis.
The ratio is termed “RP fragmentation index”, and is a valid indicator in the measure of the degree of cell-death (see pg 1235, section of the abstract entitled “Methods and results” and pg 1235, section of the abstract entitled “Conclusions”).
Concerning claim 1, Han et al. teach receiving a sample comprising a plurality of cell-free nucleic acid molecules (see pg 1236, all para of section 2.1 and pg 1236, left col., 2nd para: wherein Han et al discloses their method aims to analyze levels of DNA fragmentation derived from dPCR analysis using cellular untruncated genomic DNA isolated from cell pellet, and cell-free DNA from human cells SW480, SW620, THP-1 and MCF7 as templates; see also pg 1240, right col, section 4.1 and pg 1242, sections 4.2 and 4.4).
Concerning claim 1, Han et al. teach distributing cell-free nucleic acid molecules into a plurality of digital reactions (pg 1236, 3rd para of section 2.2 and pg 1241, section 4.5) and adding reagents into each of the plurality of digital reactions (see pg 1241, all para of section 4.5).
Concerning claim 1, Han et al. teach a first primer set comprising a first forward primer, a first reverse primer, and a first probe that generates a first signal associated with amplification of the first region using the first forward and reverse primers (see pg 1236, 3rd para of section 2.2 and pg 1238, Fig. 2A and pg 1241, all text of section 4.5).
Concerning claim 1, Han et al. teach a second primer set comprising a second forward primer, a second reverse primer, and a second probe that generates a second signal associated with amplification of the second region using the second forward and reverse primers (see pg 1236, 3rd para of section 2.2 and pg 1238, Fig. 2A and pg 1241, all text of section 4.5).
First primer pair and probe (amplifies and detects a 208 nt fragment consisting of nt 552-759 of GenBank AL590622.7) (see pg 1238, Fig. 2A and pg 1241, section 4.5).
Specifically, Han et al. teach a RP2 primer set (“the set comprising the instant first primer pair and first probe as follows:
see disclosure of RP2 forward primer consisting 5’-GATGGGTCTCGGTCAGGT-‘3 (for hybridizing nucleotides 552-569 of GenBank Accession No. AL590622/ chromosome 10);
see disclosure of RP2 reverse primer consisting 5’-GGCTTCTGTCACCTATCAGC-‘3 (for hybridizing nucleotides 759-740 of GenBank Accession No. AL590622/ chromosome 10);
see disclosure of RP2 probe consisting 5’- HEX-CAGAGTCTCTGGGATGTCCCT-BHQ1-‘3 (for hybridizing nucleotides 574-594 of GenBank Accession No. AL590622/ chromosome 10)).
Second primer pair and probe (amplifies and detects a 195 nt fragment consisting of nt 904-1098 of GenBank AL590622.7) (see pg 1238, Fig. 2A and pg 1241, section 4.5).
Specifically, Han et al. teach a RP1 primer set (“the set comprising the instant second primer pair and second probe as follows:
see disclosure of RP1 forward primer consisting 5’- GGGAGTGTTGGAACAATACTATCTA-‘3 (for hybridizing nucleotides 904-928 of GenBank Accession No. AL590622/ chromosome 10);
see disclosure of RP1 reverse primer consisting 5’-CCAACACTTTACAGTCTACGGAAT-‘3 (for hybridizing nucleotides 1098-1075 of GenBank Accession No. AL590622/ chromosome 10);
see disclosure of RP1 probe consisting 5’- HEX-AGAGGACATACACAGCGGAGTG-BHQ1-‘3 (for hybridizing nucleotides 953-974 of GenBank Accession No. AL590622/ chromosome 10)).
In view of the above, Han et al. teach the second forward primer (RP1 primer hybridizing nucleotides 904-928 of GenBank Accession No. AL590622/ chromosome 10) is downstream from the first reverse primer (RP2 primer hybridizing nucleotides 759-740 of GenBank Accession No. AL590622/ chromosome 10) in the reference sequence.
Han et al. teach the specified number of bases is 5 kilobases or less (The distance between amplified first region using the first primer pair and probe set and the amplified second region using the second primer pair and probe set is 146 nucleobases which is less than 5000 nucleobases).
Han et al. teach detecting the first signal from the first probe and the second signal from the second probe (pg 1238, Fig. 2A and pg 1239, Figs. 3A-3D).
Han et al. teach determining the specified number of bases in length (see pg 1239, Figs. 3A-3D and see pg 1236, right col., 3rd para of section 2.2 and pg 1238, Fig. 2A: Han et al. particularly discloses RP2 and RP1 amplicon lengths and teach that RP fragmentation index becomes higher than 1 when shorter amplicons are more abundant than longer ones).
Regarding claim 3, Han et al. teach the method further comprising:
detecting a first number of the plurality of digital reactions that are positive for only one of the first signal and the second signal (see pg 1239, Figs. 3B and 3C, positive for RP2 amplicons, positive for first signal and Figs. 3A and 3C, positive for RP1 amplicons/i.e. second signal);
detecting a second number of the plurality of digital reactions that are positive for both of the first signal and the second signal (pg 1238, Fig. 2D and pg 1239, Figs. 3C-3D); and
determining a parameter using the first number and the second number, the parameter measuring a relative amount between the first number and the second number (pg 1238, Fig. 2D and pg 1239, Fig. 3D).
Regarding claims 5 and 11, Han et al. teach determining a classification of a pathology for the subject using the parameter and determining a classification of a pathology for the subject using the first parameter and the second parameter (detecting cytotoxicity from genomic human cellular DNA, RP fragmentation index =1, no cell death, see pg 1238, Fig. 2D; and detecting cytotoxicity from cfDNA from human cell line after drug exposure: see pg 1239, Fig. 3D: cell death detected in THP-1 cells as RP fragmentation index rises above 1).
Regarding claim 7, Han et al. teach a third primer set including a third forward primer, a third reverse primer, and a third probe that generates a third signal associated with amplification of the third region using the third forward and reverse primers (see below).
Han et al. teach the third forward primer is downstream from the first reverse primer in the reference sequence.
Han et al. teach the second forward primer is downstream from the third reverse primer in the reference sequence, and
Han et al. teach detecting the first signal, the second signal, and the third signal, wherein the third signal is from the third probe.
Specifically, Han et al. teach the second primer pair and probe (amplifies and/or detects a 195 nt fragment consisting of nt 904-1098 of GenBank AL590622.7) (see pg 1238, Fig. 2A and pg 1241, section 4.5).
Specifically, Han et al. teach a RP1 primer set (“the set comprising the instant second primer pair and second probe as follows:
see disclosure of RP1 forward primer consisting 5’- GGGAGTGTTGGAACAATACTATCTA-‘3 (for hybridizing nucleotides 904-928 of GenBank Accession No. AL590622/ chromosome 10);
see disclosure of RP1 reverse primer consisting 5’-CCAACACTTTACAGTCTACGGAAT-‘3 (for hybridizing nucleotides 1098-1075 of GenBank Accession No. AL590622/ chromosome 10);
see disclosure of RP1 probe consisting 5’- HEX-AGAGGACATACACAGCGGAGTG-BHQ1-‘3 (for hybridizing nucleotides 953-974 of GenBank Accession No. AL590622/ chromosome 10)).
Han et al. teach the third primer pair and probe (which amplifies and/or detects a 119 nt fragment consisting of nt 904-1022 of GenBank AL590622.7) (see pg 1238, Fig. 2A and pg 1241, section 4.5).
Specifically, Han et al. teach a RP1 primer set (“the set comprising the instant third primer pair and third probe as follows:
see disclosure of RP1 forward primer consisting 5’- GGGAGTGTTGGAACAATACTATCTA-‘3 (for hybridizing nucleotides 904-928 of GenBank Accession No. AL590622/ chromosome 10);
see disclosure of RP1 reverse primer consisting 5’-CCAACACTTTACAGTCTACGGAAT-‘3 (for hybridizing nucleotides 1022-1005 of GenBank Accession No. AL590622/ chromosome 10);
see disclosure of RP1 probe consisting 5’- HEX-AGAGGACATACACAGCGGAGTG-BHQ1-‘3 (for hybridizing nucleotides 953-974 of GenBank Accession No. AL590622/ chromosome 10)).
The first reverse primer hybridizes at nucleotides 759-740 of GenBank Accession No. AL590622/ chromosome 10) and the third forward primer hybridizes at nucleotides 904-928 of GenBank Accession No. AL590622/ chromosome 10, therefore the third forward primer is downstream of the forward primer.
The second forward primer initially hybridizes at nucleotides 904-928 of GenBank Accession No. AL590622/ chromosome 10 while the third reverse primer initially hybridizes at nucleotides 1022-1005 of GenBank Accession No. AL590622/chromosome 10. However, as primer extension continues to generate the first amplified region, the extended forward primer hybridizes nucleotides 904-1097 of GenBank Accession No. AL590622/chromosome 10 and this extended primer comprises nucleotides 1023-1097 beyond and downstream of the nucleotides of the third reverse primer hybridizing at nucleotides 1022-1005 of GenBank Accession No. AL590622/chromosome 10.
Regarding claim 8, Han et al. teach detecting a third number of the plurality of digital reactions that are positive for the third signal and only one of the first signal and the second signal (pg 1239, Fig. 3C); and determining a second parameter using the first number and the third number, the second parameter measuring a relative amount between the first number and the third number (pg 1239, Fig. 3D).
Regarding claim 9, Han et al. teach detecting a third number of the plurality of digital reactions that are positive for the third signal and only one of the first signal and the second signal (pg 1239, Fig. 3C); and determining a second parameter using the second number and the third number, the second parameter measuring a relative amount between the second number and the third number (pg 1239, Fig. 3D).
Regarding claim 11, Han et al. teach determining a classification of a pathology for the subject using the first parameter and the second parameter (detecting cytotoxicity from genomic human cellular DNA, RP fragmentation index =1, no cell death, see pg 1238, Fig. 2D; and detecting cytotoxicity from cfDNA from human cell line after drug exposure: see pg 1239, Fig. 3D: cell death detected in THP-1 cells as RP fragmentation index rises above 1).
Regarding claim 16, Han et al. teach the first region and the second region each independently have a length that is less than 500 bp (pg 1238, Fig. 2A: nucleobase distance difference in RP1-RP2 amplified regions are as follows: 146, 192, 209, 260 and 269 nucleobases apart for RP2 (208)-RP1(70) and RP2 (162)-RP1(70) and RP2(145)-RP1(70) and RP2 (92)-RP1(70) and RP2 (85)-RP1(70) respectively).
Regarding claim 18, Han et al. teach between 100 cell-free nucleic acid molecules and 500,000 cell-free nucleic acid molecules (pg 1241, section 4.5).
Accordingly, the instant claims 1, 3, 5, 7-9, 11, 16 and 18 are anticipated by Han et al.
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.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Han et al. (August 2019, Biochimica et Biophysica Acta (BBA)-General Subjects, 1863(8), pp.1235-1242: newly cited) as applied to claim 1 above, and further in view of Lun et al. (2008, P.N.A.S., 105(50), pp.19920-19925: previously cited).
The teachings of claim 1 are applied from above.
Regarding claim 2, Han et al. do not teach number of bases between first amplified region generated by first primer set and the second amplified region generated by second primer set is at least 500 bases but less than 5000 bases.
Han et al. only teach number of bases between amplified first and second region that are 146 bases, 192 bases, 209 bases, 260 bases and 269 bases.
Lun et al. (2008) (claim 2)
Regarding claim 2, Lun et al. teach it already a matter of routine practice in the prior art to generate amplicons of different lengths which allow for maternal genotypes to be distinguishable from fetal genotypes and to analyze the amplicon length to determine a digital relative chromosome dosage (RCD) value. Lun et al. teach the RCD value implies aneuploidy (.eg trisomy 21 fetus) by detecting the presence of overrepresentation of chromosome 21 sequences in maternal plasma sample of pregnant females (pg 19920, last para of right col., and pg 19921, paragraphs 1-2 of left col.)
Lun et al. teach a scheme in Figs. 1A-1B on pg 19921, whereby differential spatial combinations of primer sets generate amplicons of different lengths which allow for maternal genotypes to be distinguishable from fetal genotypes.
It would have been prima facie obvious to an ordinary skilled artisan before the effective filing date of the invention to modify the method of Han by providing a set of primers that bind a same reference sequence and amplify a region of the reference sequence in a manner so that the number of bases separating two generated amplified regions is at least 500 bases but 5000 bases or less.
Both Han et al. and Lun et al. particularly teach primer placement schemes where different spatial combination of primers are indicated so as to allow an ordinary skilled artisan to the use of various amplicon lengths to determine a first, second or nth parameter. Accordingly, the ordinary skilled artisan would have been readily apprised that provides a first primer set to generate a first amplified fragment that is at least 500 bases upstream to that generated by a downstream second primer set hybridizing and amplifying a region of a same reference sequence, so as to enable the detection of the first amplicon independently from the second amplicon and thus, the specified length between both amplicon regions using primer sets.
In view of the combined teachings of all of the cited reference(s), the instant claim 2 is prima facie obvious.
Conclusion
No claims are currently allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLAYINKA A OYEYEMI whose telephone number is (571)270-5956. The examiner can normally be reached Monday -Thursday: 9:00 am - 5:00 pm, EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, GARY Benzion can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
OLAYINKA A. OYEYEMI
Examiner
Art Unit 1681
/OLAYINKA A OYEYEMI/Examiner, Art Unit 1681
/GARY BENZION/Supervisory Patent Examiner, Art Unit 1681
Prosecution Insights