DETAILED CORRESPONDENCE
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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 April 28, 2026 has been entered.
This action is in response to the papers filed April 28, 2026. Currently, claims 21, 23-24, 28-30, 32 are pending.
All arguments have been thoroughly reviewed but are deemed non-persuasive for the reasons which follow.
Any objections and rejections not reiterated below are hereby withdrawn.
Election/Restrictions
Applicant's election without traverse of Group II, Claims 21-25, 28-32 in the paper filed June 23, 2025 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Priority
This application claims priority to
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Drawings
The drawings are acceptable.
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 21, 23-24, 28-30, 32 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Question 1
The claimed invention is directed to a process that involves a natural principle and a judicial exception.
Question 2A Prong I
The claims are taken to be directed to an abstract idea, a law of nature and a natural phenomenon.
Claim 21 is directed to “a method of measuring an amount of converted methylation marker DNA” by treating a sample, measuring the amount of a methylation marker DNA and B3GALT6 DNA and “determining a normalized value for the amount of the methylation marker DNA using the amount of converted B3GALT6 DNA is indicative of the amount of the converted methylation marker DNA”.
Claims 21 and the claims dependent thereon are directed to a process that involves the judicial exceptions of an abstract idea (i.e. the abstract steps of determining a normalized value of methylation marker which is a mathematical calculation of a percentage and the natural correlation of indicating the amount of DNA).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Herein, claim 21 recites the patent-ineligible concept of an abstract process. Claim 21 requires determining a normalized value for the amount of the methylation marker amplicon DNA. The claims do not provide how normalization is accomplished. The specification also does not teach how normalization is accomplished. However, the art teaches normalization may be determining an amount by calculating a percentage. This is an arithmetic calculation to generate an amount of DNA which is a “mathematical calculation” and falls into the mathematical concepts grouping of abstract ideas. Thus, the determining a normalized value step constitutes an abstract process idea.
Question 2A Prong II
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception. While the claim recites obtaining a sample and treating DNA with a methylation-specific agent and measuring an amount of DNA, this is not an integration of the exception into a practical application. Instead, these elements are data gathering required to perform the method. Thus, the claim is “directed to” the exception.
Accordingly, the claims are directed to judicial exceptions.
Question 2B
The second step of Alice involves determining whether the remaining elements, either in isolation or combination with the other non patent ineligible elements, are sufficient to “’transform the nature of the claim’ into a patent eligible application” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
The claims are not sufficiently defined to provide a method which is significantly more from a statement of a natural principle for at least these reasons:
The claims do not include applying the judicial exception, or by use of, a particular machine. The claims do not tie the steps to a “particular machine" and therefore do not meet the machine or transformation test on these grounds. The use of machines generally does not impose a meaningful limit on claim scope.
The claims also do not add a specific limitation other than what is well-understood, routine and conventional in the field. The measuring of an amount of DNA methylation is mere data gathering step that amounts to extra solution activity to the judicial exception. It merely tells the users of the method to determine the biomarkers of a sample without further specification as to how the sample should be analyzed. The claim does not recite a new, innovative method for such determination. The determining step essentially tells users to determine the markers through whatever known processes they wish to use.
The step of determining the methylation was well known in the art at the time the invention was made. The prior art teaches methylation analysis using commercially available biochips and arrays that comprise the claimed genes. The steps are recited at a high level of generality. The claim merely instructs a scientist to use any methylation analysis to determine the methylation amount. The claim does not require the use of any particular non-conventional reagents. When recited at this high level of generality, there is no meaningful limitation that distinguishes this step from well understood, routine and conventional activities engaged in by scientists prior to applicant’s invention and at the time the application was filed.
Additionally, the teachings in the specification demonstrate the well understood, routine, conventional nature of additional elements because it teaches that the additional elements were well known. Specifically, the specification teaches methylation assay refers to any assay for determining methylation state of one or more CpG dinucleotide sequences. The specification then provides numerous well known methylation detection assays including MS-AP-PCR, MethyLight, HeavyMethyl, MSP and Ms-SNuPE (see page 21).
Further it is noted that the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014)
For these reasons the claims are rejected under section 101 as being directed to non-statutory subject matter.
Response to Arguments
The response traverses the rejection. The response asserts the claims are directed to characterizing non-naturally occurring products. This argument has been considered but is not convincing because the claim remains directed to abstract ideas and natural correlations. The analysis of non-naturally occurring products does not render the claims patent eligible. The analysis requires determining whether the claim recites natural correlations and abstract ideas such as mathematical calculations. The instant claims require both a correlation, namely “indicative of the normalized amount”, and a mathematical calculation, namely determining a normalized value which encompasses determination of a percentage.
The response does not consider the presence of judicial exceptions in the claims and the well understood routine nature of bisulfite treatment followed by amplification of genes. The response asserts analysis of the quantities of the molecules/for determining their relative amounts of amplicons is not a “law of nature” or “natural phenomenon”. This argument has been reviewed but is not persuasive. The rejection identifies step d as a judicial exception as it requires a comparison, a mathematical concept and a natural phenomena. The steps in addition to the judicial exception, namely step a, b, c are well understood routine and conventional.
Specifically, the response states step (d) is a quantitative relationship between measured amounts of two DNA species. This relationship is a judicial exception. The relationship is a mathematical calculation and concept. Normalized values are a comparison between two amounts to make a determination of the normalized value. The courts have found that a comparison step is an abstract idea. A comparison between a methylation marker DNA and a reference, namely B3GALT6 that is deemed an abstract idea (see MPEP 2106.04(a)(2)(III)(A); • claims to “comparing BRCA sequences and determining the existence of alterations,” where the claims cover any way of comparing BRCA sequences such that the comparison steps can practically be performed in the human mind, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 763, 113 USPQ2d 1241, 1246 (Fed. Cir. 2014)).
The response argues the claim integrates the judicial exception into a practical application. The response identifies steps a, b and c as converting DNA are an integration. This argument has been reviewed but is not persuasive. The analysis of DNA with bisulfite treatment, for example is merely data collection steps. There is no integration of the judicial exception. These steps take place prior to the judicial exception.
The response argues the claims are an improvement in technology. The newly issued 101 Examples (July 2024), Example 49, claim 1 discusses improvements. Example 49, claim 1 state there is no improvement to the functioning of a computer nor to any other technology. Furthermore, MPEP 2106.05(a)(II) provides "However, it is important to keep in mind that an improvement in the abstract idea itself (e.g. a recited fundamental economic concept) is not an improvement in technology. For example, in Trading Technologies Int’l v. IBG, 921 F.3d 1084, 1093-94, 2019 USPQ2d 138290 (Fed. Cir. 2019), the court determined that the claimed user interface simply provided a trader with more information to facilitate market trades, which improved the business process of market trading but did not improve computers or technology." Similarly, the claims may amount to an improvement to the abstract idea of determining normalized methylated DNA rather than to any technology. See MPEP 2106.05(a). Thus, there is no integration of the recited exception into a practical application.
Thus, for the reasons above and those already of record, the rejection is maintained.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 21, 23-24, 28-30, 32 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over Claims 1, 3-6 of U.S. Patent No. 12,049,671.
Although the conflicting claims are not identical, they are not patentable distinct from each other because Claims 21-25, 28-32 of the instant application is generic to all that is recited in Claims 1, 3-6 of U.S. Patent No. 12,049,671. That is, claims 1, 3-6 of U.S. Patent No. 12,049,671 falls entirely within the scope of Claim 21-25, 28-32, or in other words, Claims 21-25, 28-32 are anticipated by Claims 1, 3-6 of U.S. Patent No. 12,049,671. Here, Claims 1, 3-6 of U.S. Patent No. 12,049,671 recites
1. A method of characterizing a sample from a human subject, the method comprising assaying the sample for amounts of each of a plurality of different methylated marker DNAs and an amount of at least one control DNA, the method comprising: a) amplifying DNA from the sample with PCR amplification reagents in one or more reaction mixtures, wherein the PCR amplification reagents comprise: i) methylation marker primer pairs for amplifying target regions from two to thirteen different methylated marker DNAs selected from the group consisting of …; and ii) at least one control primer pair for amplifying a target region from at least one control DNA; and b) measuring amplified amounts of the target regions of the two to thirteen different methylated marker DNAs, and an amplified amount of the target region from the at least one control DNA, wherein the at least one control DNA comprises a region of a B3GALT6 gene.
Claim 4 of ‘671 requires treating DNA obtained with a methylation specific reagent. Claim 6 of ‘671 provides the methylation specific reagent comprises a bisulfite reagent.
The patented claims do not require calculating the amount of the DNA marker to B3GALT6, however, the claims specifically state B3GALT6 is a control DNA. At the time the invention was made, it was prima facie obvious to determine the amount of a DNA marker as a percentage of a control DNA.
With regard to Claim 24 of the instant application, the claims require B3GALT6 is a complement and has primers bind within SEQ ID NO: 2. Figure 1 of ‘671 illustrates the treated and untreated B3GALT6 sequence.
Claims 21, 23-24, 28-30, 32 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over Claims 1, 4-6 of U.S. Patent No. 11,118,228.
Although the conflicting claims are not identical, they are not patentable distinct from each other because Claims 21-25, 28-32 of the instant application is generic to all that is recited in Claims 1, 4-6 of U.S. Patent No. 11,118,228. That is, Claims 1, 4-6 of U.S. Patent No. 11,118,228 falls entirely within the scope of Claims 21-25, 28-32, or in other words, Claims 21-25, 28-32 are anticipated by Claims 1, 4-6 of U.S. Patent No. 11,118,228. Here, Claims 1, 4-6 of U.S. Patent No. 11,118,228 recites
1. A method of characterizing a sample from a human subject, the method comprising assaying the sample for amounts of a plurality of different methylated marker DNAs and amounts of at least one control DNA, the method comprising: a) combining DNA from the sample in a pre-amplification reaction mixture comprising PCR amplification reagents, wherein the PCR amplification reagents comprise: i) a plurality of methylation marker primer pairs for amplifying target regions from two to twenty-four different methylated marker DNAs selected from the group of ….and ii) a control primer pair for amplifying a target region from beta-1,3- galactosyltransferase 6 (B3GALT6) control DNA; b) exposing the pre-amplification reaction mixture to thermal cycling conditions wherein two to twenty-four different methylation marker target regions and a B3GALT6 control DNA target region are amplified to produce a pre-amplified mixture; c) partitioning the pre-amplified mixture into a plurality of assay reaction mixtures, wherein each assay reaction mixture comprises: i) additional amounts of at least one methylation marker primer pair and of the control primer pair for amplifying a target region from B3GALT6 control DNA used in step a); and ii) oligonucleotides hybridizable to the methylation marker target region(s) and B3GALT6 control DNA target region amplifiable with the primer pairs of c) i); d) measuring amounts of two to twenty-four different methylation marker target regions and the target region from B3GALT6 control DNA in the plurality of assay reaction mixtures in a process comprising exposing the plurality of assay reaction mixtures to thermal cycling conditions wherein amplification of two to twenty-four different methylated marker target regions and the B3GALT6 control DNA target region occurs; and e) calculating values for the amounts of the two to twenty-four different methylated marker target regions amplified in each of the assay reaction mixtures in step d) as a percentage of the amount of the B3GALT6 control DNA target region amplified in each of the assay reaction mixtures, wherein the calculated values indicate the amount of each of the two to twenty-four different methylated marker DNAs in the sample.
Claim 4 of ‘228 provides the sample is a blood, stool or tissue sample.
Claim 5 of ‘228 requires treating DNA obtained with a methylation specific reagent. Claim 6 of ‘228 provides the methylation specific reagent comprises a bisulfite reagent.
Response to Double Patenting Arguments
The response traverses the rejection. Applicant requests that this rejection be held in abeyance until allowable subject matter is found in the pending application. This request has been noted and is denied. See 804(I)(b)(1) and 37 C.F.R. 1.111(b), which allows that some objections may be held in abeyance but includes no provision for holding rejections in abeyance.
The response previously asserted neither ‘228 nor ‘671 qualifies as a reference patent for obviousness-type double patenting because they are later-filed than the effective filing date of the instant application. The response states that the purpose of nonstatutory double patenting doctrine is to prevent patentees from obtaining a second patent on a patentably indistinct invention to effectively extend the life of a first patent to the subject matter. This argument has been considered but is not convincing. Further, MPEP 804 makes clear that NSDP addresses two public-policy concerns: improper timewise extension and harassment by multiple parties. A double patenting rejection also serves public policy interests by preventing the possibility of multiple suits against an accused infringer by different assignees of patents claiming patentably indistinct variations of the same invention. The arguments do not address the harassment by multiple parties policy concern.
Also, in MPEP 804(II)(4), the MPEP discusses one-way test for distinctness that talks about patent term filing date of an application being before, later or the same and discusses the DP rejection should be made. Therefore, preventing patentees from obtaining a second patent on a patentably indistinct invention, i.e. extending the life of a first patent to the subject matter.
The Examiner makes no determination of expiration dates for patents as PTA, payment of issue fees etc are unknowns.
Thus, for the reasons above and those already of record, the rejection is maintained.
Conclusion
No claims allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
September 14, 2026
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