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 .
This action is in response to papers filed 9/02/2025.
Applicant’s election without traverse of the species of the combination of the cancers: sarcoma, myeloid neoplasm, prostate cancer, breast cancer, uterine cancer, ovarian cancer, bladder and urothelial cancer, cervical cancer, liver and bile duct cancer, and pancreas and gallbladder cancer in the reply filed on 12/06/2024 is acknowledged.
Claims 64,66,76-77,80,99,100,103,107-109,114,144,152,206,209,216-217,221,241,248. 264-265 are pending. Claim 77 is withdrawn a being drawn to a nonelected species.
The reply asserts that claim 77 should be rejoined as “c” includes the elected combination. However, it is noted that this is a specific combination and it is different from the entire combination required by “c”. These are considered two distinct combinations as each specifically encompasses a different group of cancers. It is noted that Claim 77 will be rejoined once the species elected is in condition for allowance.
Claims 1-63,65,67-75,78-79,81-98,101-102,104-106,110-113,115-143,145-151,153-205,207-208,210-215,218-220,222-240,242-247,249-263 have been cancelled.
The following rejections for 64,66,76,80,99,100,103,107-109,114,144,152,206,209,216-217,221,241,248. 264-265 are maintained necessitated by amendment. Response to arguments follows
This action is FINAL.
Withdrawn Rejections
The Obviousness double patenting rejection is withdrawn based upon amendments to the claims.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 64,66,76,80,99,100,103,107-109,114,144,152,206,209,216-217,221,241,248. 264-265 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s),
Claims 64,66,76,80,99,100,103,107-109,114,144,152, 264-265 are drawn to a method of detecting cells of a cancer type in a subject comprising capturing cfDNA with a plurality of different bait oligonucleotides wherein in each bait oligonucleotide is at least 45 nucleotides in length, collectively hybridize to at least 1000 target genomic regions that are differentially methylated in at least one cancer type relative to a different cancer type or noncancer and for at least 80% of all possible parrs of cancer types selected from a set comprising at least 10 cancer types at least one target genomic region is differentially methylated between the pair of cancer types, and capturing. The claims further requires sequencing the captured cfDNA, detecting cells of the cancer type with a trained classifier wherein the trained classifier detects a number of sequencing reads above a threshold as hypermethylated or hypomethylated. The likelihood of false positive determination of cancer is less than 1% and the likelihood of accurate assignment of a cancer type is at least 75%.
Claims 206,209,216-217,221241,248 are drawn a method of detecting cells of a cancer type comprising processing cfDNA with a deaminating agent, enriching the cfDNA wherein the enriching comprising contacting with different bait oligonucleotides, each bait oligonucleotides at least 45 nucleotides and the plurality of different bait oligonucleotides hybridize to at least 1000 targets genomic regions from SEQ ID No.s 1-452706, sequencing detecting sequencing reads from the cells of the cancer type.
The claims therefore are drawn to detecting cells of a cancer type based upon methylation of at least 1000 target genomic regions that are differentially methylated in at least one cancer type relative to a different cancer type or relative to noncancer. The specification has not provided guidance for the breadth of 200 target genomic regions. The specification in the tables provide some examples of target genomic regions but the claims are not limited to these regions. Rather, the specification has not provided critical guidance to determine which target genomic regions comprise for at least 80% of all possible pairs of cancer types ones that are differentially methylated. Therefore the skilled artisan would not know from genomic regions which ones could be selected to detect cells of a cancer type without the critical guidance as to know which ones are differentially methylation in at least one cancer type.
The claims are further limited to at least 1000 target genomic regions of any one of the combination of at least 1000 target genomic regions of SEQ ID No. 1-452706. The table includes 452706 sequence Id numbers. The specification has not provided which ones are hypermethylated or hypomethylated in any of the cell types. Table 3 appears to describe specific sequence ID numbers that are associated with methylation of particular cancer types, however, these are not the same seq id numbers in the lists. As such the specification has not described which of the genomic regions would functionality provide cell types based upon any methylation differences in at least one of the regions.
Further the trainer sets are limited to “at least 10 cancer types”, however, the selection of these types have not been described by the specification. The specification has not described how the selection will affect the functionality of determining cancer type. Each of these collections would provide different data and the specification has not provided how to determine any cancer type based upon these different combinations of cancer types for the trainer.
Accordingly, the specification has not provided the critical elements needed in the structure to predictive functionally. Therefore the specification lacks written description of any subject representative of the broadly claimed genus.
In analysis of the claims for compliance with the written description requirement of 35 U.S.C. 112, first paragraph, the written description guidelines note regarding genus/species situations that “Satisfactory disclosure of a ``representative number'' depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the species disclosed.” (See: 'Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001.)
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following.
The reply asserts that the claims have been modified to includes at least 1000 target genomic regions and “selected as a marker included in a trained classifier as being differentially methylated” and that the sequencing regards “of the at least 1000 target genomic regions…” (p 13). The reply assert s that there that target genetic regions are selected for particular characteristics by pairwise analysis of different types of cancers and training a classifier (p. 14). The reply asserts that the application illustrates the processes using particular data as examples but any marker could be used that have these characteristics (p. 14).
These arguments have been reviewed but have not been found persuasive.
The instant specification describes how to identify differentially methylated regions using analyses and to train a classifier. This was done using available sequences in the specification. Within these datasets, genomic regions were identified as being useful or differentially methylated between cancers and non-cancer. There is no indication that additional genomic regions exist in these databases that are differentially methylated nor is there an indication on how to determinate additional genomic regions that are not recited in the specification. Thus, applicant has not demonstrated how to use any additional genomic regions for classification. Thus, while additional genomic regions may be considered, there is no indication how one is to utilize a genomic region, did not identify as being differentially methylated, and did not identify which would accurately detect.
Furthermore, even for the genomic regions There is no evidence that target genomic regions identified in bladder cancer may be used to identify useful target genomic regions in the context of brain cancer or skin cancer. The ordinary artisan is not able to reasonably envisage the full scope of the genus encompassed by the claim. The instant specification is an invitation for one to experiment and identify any and all useful target genomic regions.
The reply asserts that the application provides examples (p. 14 -15) and lists of targets to distinguish at least 20 cancer types (p. 15). The reply asserts that the skilled artisan is taught how to select “at least 1000 target genomic regions” to distinguish “at least 10 cancer types” (p. 15). The examples in the specificaoin provides specific examples of target regions and detection of particular cancer types. However, knowing these sequences does not provide the skilled artisan to select the target genomic regions to distinguish cancer types.
These arguments have been reviewed but have not been found persuasive.
The specification provides a specific correlation of target regions to cancer types using a classifier designed to detect those cancers. The specification therefore identifies a limited number of species, but does not adequately describe all the other species within the genus of target genomic regions. The steps of the claims assert that the target genomic regions are selected as a marker included in a trained classifier as being differentially methylated in reference subjects with a cancer selected form a set of at least 10 cancer types. As such to determine the target genomic region one must first determine if the marker can be selected based upon methylation patterns to a particular cancer selected from a set of at least 10 cancer types. There is no indication in the specification which target regions can be encompassed by these conditions.
The reply asserts that different SEQ ID numbers can be assigned to the same sequence (p. 16).
These arguments have been reviewed but have not been found persuasive.
The issue is not that different SEQ ID Numbers are assigned to the same sequence but the methylation of each of these regions. The claims are further limited to at least 1000 target genomic regions of any one of the combination of at least 1000 target genomic regions of SEQ ID No. 1-452706. The table includes 452706 sequence Id numbers. The specification has not provided which ones are hypermethylated or hypomethylated in any of the cell types. Table 3 appears to describe specific sequence ID numbers that are associated with methylation of particular cancer types, however, these are not the same seq id numbers in the lists. As such the SEQ ID Numbers claimed are not those claimed in table 3. Accordingly, the person of skill in the art based upon the description in the specification would not be able to readily ascertain the methylation of the target regions claimed and detection of cancer.
The reply asserts that that the selection of cancer types have been described (p. 17). The reply states that example 3 provides target regions for distinguishing 25 cancer types and example 5 illustrated the use of different sets of target genomic regions in detecting cancer for each of several different cancer types (p. 17).
These arguments have been reviewed but have not been found persuasive.
The specification provides a listing a target regions that have particular methylation patterns that are associated with particular cancers. The specification has not provided guidance to ascertain any other genetic target regions that (1) are methylated (2) associated with detection of a particular cancer from a group of hundreds of different cancers. Furthermore these target regions may overlap in some cancers, but the artisan would not be able to ascertain which regions are associated based upon the description in the specification.
The reply asserts that there is no reason to suspect that applying the same method to a different training set of cancer samples or types of cancers would fail to identify target genomic regions (p. 17-18).
These arguments have been reviewed but have not been found persuasive.
In particular different sets of cancer samples or types of cancers would have different associations with methylation of different genes. In particular a training set of a bladder cancer would not provide guidance for breast cancer detection. There is no indication of whether a particular genomic region is to be hypermethylated, hypomethylated or have a particular methylation pattern to be used in the identification of a cancer. The classifier functions by comparing known sequencing data regarding methylation to sequencing data obtained from a cfDNA sample. However, there is no indication of what information is required by the classifier in order to be used and rely on a particular target genomic region.
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 66, 80 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 66 and 80 are indefinite over the “likelihood of accurately detecting” or “likelihood of detecting” the claims are unclear as the false positive and accurate assignment would require further steps than are in the claims. In particular the last active step is detecting the cells of the cancer type with a trained classifier. In particular these likelihoods would require a further statistical step more than merely detection or require a further step of clinical testing the results of step c of claim 64. Therefore the metes and bounds are unclear.
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following. It is noted that some aspects of the 35 USC 112b have been overcome, and as such only the pending rejection will be responded to with respect to the arguments. The reply asserts that the instant application provides guidance of how to determine accuracy of assignment/detection without having to perform additional clinical testing such as by splitting data for already obtained reference samples (example 5) (p. 19). The reply asserts that further the claims are amended to specific that “the at least 1000 target genomic regions are selected such that” the likelihoods are achieved (p. 19). These arguments have been reviewed but have not been found persuasive. The claims are drawn to having a “likelihood of accurately detecting”, however, the claims only require the positive active steps of Claim 64. The reply asserts that one would not have to perform additional clinical testing as claim cold be performed by, for example, splitting data. The claims do not require any such analysis. Furthermore, the claims do not encompass any step that provides how one knowns that the “at least 1000 target genomic regions are selected” that the likelihoods are achieved. The reply appears to be suggesting that one could use the method steps in the specification, however, example 5 details the classification using specific sequences and using ROC curve analysis (p. 94-95), neither which is required by the claims. .Furthermore, it appears that the accuracy is based upon the use of particular sequences, cancer types and analysis (p. 96-98), however, the claims are drawn to any “at least 1000 target genes”. The claims are not limited to particular target genomic regions, but rather appear to be limited the ones that “are selected such that the likelihood of accurately detecting” which appears to indicate that the user must have some prior knowledge for the selection of the target genes.
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 64,66,76,80,99,100,103,107-109,114,144 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exceptions without significantly more. The claim(s) recite(s) both a law of nature and an abstract idea. The claim(s) do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The rational for this finding is explained below:
The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., No. 10-1150 (March 20, 2012).
The unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, No. 08-964, 2010 WL 2555192 (June 28, 2010) and in Alice Corp. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014).
The following three inquiries are used to determine whether a claim is drawn to patent-eligible subject matter:
Step 1. Is the claim to a process, machine, manufacture, or composition of matter? Yes- the claims are clearly directed to a process.
Step 2A. Is the claim directed to a law of nature, a natural phenomenon, or an abstract idea (judicially recognized exceptions)? Yes- The claims are directed to a natural phenomenon/law of nature and abstract ideas.
The natural phenomenon/law of nature is the correlation between the recited the trained classifier of DNA sequences and likelihood of a presence or absence of cancer. These correlations are naturally occurring and exist apart from any human action. The claims further recite abstract ideas. The step of the applying a trained classifier. These steps broadly encompass a general computer and mental activity comparison of any number of sequences and trained classifier.
Mental activities, data analysis, and mathematical analysis are all considered to be abstract ideas.
Step 2B. Does the claim recite additional elements that amount to significantly more than the judicial exception? No-there are no elements or combination of elements in the claim that are sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception:
In the instant case it is noted that all of the method steps recited are considered to be judicial exceptions themselves (see discussion above). Applicants cannot rely on a judicial exception to show that the claims as a whole amount to significantly more than a judicial exception.
The present claims do not require performing any steps that are not routine and conventional. For example, the claims do not require using a novel reagent to measure the loci. See Ariosa Diagnostics, Inc. v. Sequenom, Inc., F. Supp. 2d, 2013 WL 5863022, at *10 (N.D. Cal. Oct. 30, 2013) noting that "had the inventors of the [patent-in-suit] created an innovative method of performing DNA detection while searching for paternally inherited cffDNA, such as a new method of amplification or fractionation, those claims would be patentable.”
The art teaches methods of generating sequencing data, sequences from nucleic acid molecules, and using methylation differences are well known in the art. Mazloom et al. (US Patent Application 2018/0032671 Feb 1, 2018). teaches a method of capturing DNA molecules with bait oligonucleotides and sequencing (para 124 and 136-139). Mazloom et al. teaches applying a trained classifier (para 194). Mazloom et al. teaches the bait can hybridize to methylated target genomic regions of size of 10Kb, 100 KB, 500KB, 1000KB, 5000 Kb or 10000kb in length wherein the fragments include sets of 100 sampled regions (para 54 and 349).
The claims are drawn to limiting the statistical method used, limit the cancer types, however, these types are naturally occurring populations using routine statistical methods .
For these reasons the claims are rejected under section 101 as being directed to non-statutory subject matter.
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following.
The reply asserts that there is a transformative improvement over the technical field of cancer detection as target genomic regions is an improvement over whole genome bisulfite sequencing (p. 22).
These arguments have been reviewed but have not been found persuasive.
The arguments have been fully considered but are not persuasive. A transformation of an article is not a stand-alone test for eligibility (MPEP 2106.05(c)). The isolation of cfDNA having particular sequences from those that don’t does not confer a different function or use on the cfDNA sample. The nucleic acids isolated are not transformed in a manner that they would have a different function or use. The reply has not presented an improvement based upon the claims, but rather, the claims merely provide data that was within the samples themselves prior to analysis.
The reply asserts that the step of applying a trained classifier is not an abstract idea because it requires a comparison of sequencing reads for the 1000 target genomic regions that are identified as hyper methylation or hypomethylated to a threshold of at least 10 cancers, and it would not be practical as it would take years or lifetimes (p. 23). The reply points to the memorandum issued on 8/4/2025 pointing to page 2 that “the mental process grouping is not without limits…”… and “claim limitations that encompass AI in a way that cannot be practically performed in the human mind do not fall within this grouping” (p. 23).
These arguments have been reviewed but have not been found persuasive.
The 000argument appears to be suggesting that the steps are not able to be performed by the mind because its is a 1000 target genomic regions. However, the claims as pending merely takes a 1000 target genomic regions (that in of themselves can be 45 mer in length) determines differentially methylated in at least 10 cancer types (which can be a print out). The claims then further takes this database (classifier) and compares any number of sequencing reads for the 1000 target genomic regions to a threshold. This can be performed by a human mind with pencil and paper.
With regard to the memorandum and rather a mental process with AI can be performed by the human mind is irrelevant to the pending claims as the pending claims do not recite any AI step. Rather the claims are drawn to a training classifier but does not provide any training algorithm or particular method steps for the training other than comparisons and determining if the target regions are differentially methylated.
The reply asserts that there is no finding that the combination is routine or conventional and has only been provided with teaching in US20180032671) (p. 12).
These arguetmsn have been reviewed but have not been found persuasive.
The reply asserts that the claims are not routine and conventional because only one teaching is provided. However methods of generating sequencing data, sequences from nucleic acid molecules, and using methylation differences are well known in the art. In particular the steps of capturing a bait, sequencing, training and detection are performed in the specification using well known assays and commercially available sequencing equipment (see pages 36-39, 42, 75-76).
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(s) 64,66,76,80,99,100,103,114,144 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mazloom et al. (US Patent Application 2018/0032671 Feb 1, 2018 pervious cited ) in view of Zhang et al. (US Patent Application Publication 2018/0341745 November 29, 2018).
With regard to claim 64, Mazloom et al. teaches detection of different types of cancer compared to healthy individuals (para 374-376). Mazloom et al. teaches a method of capturing DNA molecules with bait oligonucleotides and sequencing (para 124 and 136-139). Mazloom et al. teaches applying a trained classifiers (para 194). Mazloom et al. teaches the bait can hybridize to methylated target genomic regions of size of 10Kb, 100 KB, 500KB, 1000KB, 5000 Kb or 10000kb in length wherein the fragments include sets of 100 or more sampled regions (para 54 and 349). Therefore Mazloom et al. teaches measuring multiple regions of methylated target genomic regions as training vectors, however, Mazloom et al. does not specifically teach that a selection of sequencing reads are selected based upon a first trainer set and then comparison of the sequence reads to a second trainer set that provides likelihood of false positive determination and likelihood of accurate assignment.
It would be prima facie obvious for the classification to be as accurate as possible in order to keep the false positives low and classification accurate. As Mazloom et al. teaches methods of assigning type it would be obvious that these assignments that positively determined type are accurate and not a false positive as Mazloom et al. confirmed the correct assignment of type.
With regard to claim 66 and 80, Mazloom et al. teaches a method wherein he cancers include colorectal, breast and ovarian (para 4 and 100). Mazloom teaches that the sensitivity and specificity should be greater than 94, 95, 96, 97,98 or 99% (para 300).
With regard to claim 76, Mazloom et al. teaches used cfDNA (para 224). Mazloom et al. teaches DNA molecules are converted for methylation analysis with enzymatic conversion reactions (para 116).
With regard to claim 99, Mazloom et al. teaches the bait can hybridize to methylated target genomic regions of size of 10Kb, 100 KB, 500KB, 1000KB, 5000 Kb or 10000kb in length wherein the fragments include sets of 100 or more sampled regions (para 54 and 349). As such includes 0.2 MB regions.
With regard to claim 100, Mazloom et al. teaches generating test sample sequence reads sets and applying to a model of those with cancer including at least one of the cancer types and non-cancer subjects to design training sets (para 32-36).
With regard to claims 103, Mazloom teaches that the converted DNA can be from more than 100 subjects as compared to healthy subjects (no cancer) (para 191).
With regard to claim 114, Mazloom teaches a method further comprising anticancer therapy (para 306).
With regard to claim 64, Although Mazloom et al teaches using training classifiers, Mazloom et al. does not teach using these training classifiers to determine and capture the set of bait nucleic acids and then sequence this set and compare to a second set of classifiers. Zhang et al. teaches selection of profiles based upon multiple training sets (para 233-239). Zhang et al. teaches with regard to training to measure plurality of CpGs sites and determine hypo or hyper methylation fragments (para 25-35) and as such suggests the training sets that comprise CpG methylation profiles that can generate a cancer correlation. As such Zhang et al. suggests that particular profiles are selected based upon the comparison to a training set, and that further these sets can be used to compare to determine cancer status.
Therefore it would be prima facie obvious to one of ordinary skill at the time of the effective filing date to modify the method of Mazloom et al. to use at least a first and second classifier as taught by Zhang et al. to screen for methylation biomarkers associated with cancer. The ordinary artisan would be motivated as this comparison to trainings sets allows for cross validation of biomarker panels (Zhang et al para 232).
With regard to Claim 144, Zhang et al. teaches to determination methylation that CpG probes are used (para 84).
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following. The reply asserts that the combination of art does not teach bait oligonucleotides that hybridize to a set of at least 1000 target genomic regions (p. 25). The reply asserts that Mazloom and Zhang do not teaches “at least 1000 target genomic regions are selected such that for at least 80% of all possible pairs of cancer types selected from the set of at least….” (p. 25).
The reply asserts that Mazloom does not identify any methylation markers for detection of any cancer (p. 25-26). The reply asserts that the reference combines different disclosers and that paragraph 54 teaches that the regions are randomly sampled, and that methylation is part of a laundry lists of features (p. 26). The reply asserts that Zhang does not identify any target genomic regions with a plurality of CpG sites but rather biomarkers with individual CpG sites (p. 26).
These arguments have been reviewed but have not been found fully persuasive.
Mazloom et al. teaches a method of capturing DNA molecules with bait oligonucleotides and sequencing (para 124 and 136-139). Mazloom et al. teaches applying a trained classifiers (para 194). Mazloom et al. teaches the bait can hybridize to methylated target genomic regions of size of 10Kb, 100 KB, 500KB, 1000KB, 5000 Kb or 10000kb in length wherein the fragments include sets of 100 or more sampled regions (para 54 and 349). As such Mazloom suggest the “at least 1000 target genomic regions”. The reply asserts that the reference comprise different disclosers within Mazloom and the Mazloom is based upon randomly sampled regions. It is noted that the rejection is not under anticipatory analysis but rather obviousness. The reply has not provided any particular step that Mazloom et al does not teach or suggest, but rather asserts that the steps are at differently places in the reference. With regard to paragraph 54, the randomly sampled regions is one embodiment, however, the target regions are not restricted to randomly sampling. Mazloom et al. teaches that once the regions are generated that the sequence reads can be quantified for particular phenotypes (para 55). Furthermore the instant claims are not limited to target regions that aren’t randomly sampled and then screed for methylation differences. The reply asserts that methylation is based upon a laundry list, however, as suggested by Mazloom methylation is one feature that target regions can be selected for. The reply asserts that Zhang only analyses one CpG per biomarker, however, as provided in paragraphs 6, 71mutliple CgG sites can be determined. Paragraph 227 states “each probe correlated to a CpG site”, however, this does not limit the target region to one CpG sites but rather limits probes which are not used in the combination set forth above.
Conclusion
No claims are 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 KATHERINE D SALMON whose telephone number is (571)272-3316. The examiner can normally be reached 9-530.
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/KATHERINE D SALMON/Primary Examiner, Art Unit 1682