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 claims filed 3/6/2026 are under consideration.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1, 4, 6, 8, 13, 14, 15, 18, 20, 25, 28, 29, 31 and 32, in the reply filed on 3/6/2026 is acknowledged. The traversal is on the ground(s) that the pending claims are linked by the special technical feature according to PCT Rule 13.2 of the recited genomic loci listed in Table 5, which indicate the regions with hypermethylated DNA in neuroendocrine prostate cancer (NEPC) versus prostate adenocarcinoma (PRAD). The traversal is also on the grounds that UCSC Genome Browser and/or Illumina 850K EPIC methylation array do not teach, suggest, or render obvious the special technical feature. This is not found persuasive because the one or more genomic loci listed in Table 5 are known and have been studied as demonstrated by the cited references. The feature of the genomic loci of Table 5 being linked to NEPC and PRAD does not need to be appreciated by the cited references. MPEP 2112.II. See also, Beltran (Nature Medicine. 2016. 22(3):298-305 and Online Methods) as detailed in the prior art rejections below.
The requirement is still deemed proper and is therefore made FINAL.
Upon further search and consideration of the elected species of chr5:32712001- 32712300, the election of species requirement is withdrawn.
Priority
The present application is a 371 national stage entry of PCT/US22/13462 (filed 1/24/2022), which claims benefit of: US provisional application 63/288,283 (filed 12/10/2021); and US provisional application 63/141,108 (filed 1/25/2021).
Priority is recognized.
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 cited on a submitted IDS, they have not been considered.
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 1, 4, 6, 8, 13, 14, 15, 18, 20, 25, 28, 29, 31 and 32 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exceptions without significantly more.
The claims recite steps and thus are drawn to a process, one of the statutory categories.
The claim(s) recite(s):
“detecting the presence, absence, or level of altered methylation relative to a control of one or more of the genomic loci listed in Table 5 in genomic DNA (gDNA), cell free DNA (cfDNA), and/or circulating tumor DNA (ctDNA) in a sample derived from the subject” (claim 1);
“the presence of altered methylation of the one or more of the genomic loci indicates that the subject has or is at risk for developing NEPC” (claim 1);
“generating a methylation profile from the detected presence, absence, or level of methylation at the one or more genomic loci listed in Table 5” (claim 4);
“comparing the presence, absence, and/or level of methylation at the one or more of the genomic loci listed in Table 5 or the methylation profile to a control” (claim 4);
“the one or more the genomic loci have increased methylation relative to the same region in a tissue control sample or a sample derived from a subject having or at risk of developing PRAD” (claim 15);
“the one or more genomic loci have less methylation relative to the same region in a tissue control sample or a sample derived from a subject having or at risk of developing PRAD” (claim 15);
“determining a methylation score for the one or more genomic loci and/or the methylation profile” (claim 18);
“comparing the methylation score for the one or more genomic loci and/or the methylation profile to a predetermined threshold for each of the one or more genomic loci listed in Tables 1-8 or to a predetermined threshold for the methylation profile, wherein the predetermined threshold discriminates between NEPC and PRAD” (claim 18);
“comparing the methylation score to a control” (claim 20); and
“a higher methylation score compared to the control indicates that the subject has or is at risk for developing NEPC” (claim 20).
The judicial exceptions are not integrated into a practical application because the claims do not involve:
improvements to the functioning of a computer or to any other technology or technical field;
applying or using the judicial exceptions to effect a particular treatment or prophylaxis for a disease or medical condition;
applying the judicial exception with, or by use of, a particular machine; or
effecting a transformation or reduction of a particular article to a different state or thing.
The “detecting” step encompasses data gathering. MPEP 2106.05(g). The claimed limitations add insignificant extra-solution activity to the judicial exceptions. While claims 29 and 31-32 further comprises “administering…a therapeutically effective amount of an anti-cancer therapy, the step is not targeted to PRAD or NEPC as the patient is not diagnosed as having PRAD or NEPC. The therapy is a generic therapy and encompasses administering any treatment for any type of cancer. Thus, there is no nexus between the above judicial exceptions and the treating step of claims 29 and 31-32.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims encompass the use of “techniques known to the skilled artisan” as described on pages 268-269 of the specification.
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 1, 4, 6, 8, 13, 14, 15, 18, 20, 25, 28, 29, 31 and 32 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), at the time the application was filed, had possession of the claimed invention.
Regarding claim 1, the claim is intended to use methylation levels to determine whether a subject has NEPC or is at risk of developing NEPC. The methylation levels detected is based on the genomic loci listed in Table 5. The instant specification states the table lists regions with hypermethylated DNA in NEPC versus PRAD. The instant specification does not describe any of the genomic loci of Table 5 being differentially methylated in NEPC relative to any other type of sample. There is no indication that disclosed genomic loci are also differentially methylated between NEPC and, for example, normal tissue samples or in samples derived from tissue other than PRAD samples.
Methylation levels are well-accepted to vary between cell types, tissue types and disease states. Thus, the differential methylation between NEPC and PRAD described in the specification cannot be reasonably extrapolated or used as a guide to determine what other types of samples may be used to determine differential methylation. The applicant has not demonstrated possession of the full scope of claimed genus based on the disclosure of a single species based on the biology underlining the different species.
Regarding claim 1, the claim is intended to use methylation levels to determine whether a subject has NEPC or is at risk of developing NEPC based on the feature that “the presence of altered methylation of the one or more of the genomic loci indicates that the subject has or is at risk for developing NEPC”. The methylation levels detected is based on the genomic loci listed in Table 5. The instant specification states the table lists regions with hypermethylated DNA in NEPC versus PRAD with log2 fold-difference threshold >1 and FDR-adjusted p-value <0.001. There is no indication that NEPC or risk of NEPC can be determined based on hypomethylation or the absence of methylation in the genomic loci listed in Table 5. The applicant has not demonstrated possession of the full scope of claimed genus based on the disclosure of a single species based on the biology underlining the different species.
Regarding claim 4, the claim is intended to use methylation levels of the genomic loci of Table 5 to determine whether a subject has NEPC or is at risk of developing NEPC based making a comparison to a control. The instant specification states the table lists regions with hypermethylated DNA in NEPC versus PRAD with log2 fold-difference threshold >1 and FDR-adjusted p-value <0.001. The instant specification does not describe any of the genomic loci of Table 5 being differentially methylated relative to any other “control”. There is no indication that disclosed genomic loci are also differentially methylated between NEPC and, for example, normal tissue samples or in samples derived from tissue other than PRAD samples.
Methylation levels are well-accepted to vary between cell types, tissue types and disease states. Thus, the differential methylation between NEPC and PRAD described in the specification cannot be reasonably extrapolated or used as a guide to determine what other types of samples may be used to determine differential methylation. The applicant has not demonstrated possession of the full scope of claimed genus based on the disclosure of a single species based on the biology underlining the different species.
Regarding claim 13, the claim limits the genomic loci of claim 1, which are those listed in Table 5. The instant specification states the table lists regions with hypermethylated DNA in NEPC versus PRAD with log2 fold-difference threshold >1 and FDR-adjusted p-value <0.001. The instant specification does not describe any of the genomic loci of Table 5 being differentially methylated relative to any other “control sample” or a sample derived from a subject having or at risk of developing prostate adenocarcinoma. There is no indication that disclosed genomic loci are also differentially methylated between NEPC and, for example, normal tissue samples or in samples derived from tissue other than PRAD samples.
Methylation levels are well-accepted to vary between cell types, tissue types and disease states. Thus, the differential methylation between NEPC and PRAD described in the specification cannot be reasonably extrapolated or used as a guide to determine what other types of samples may be used to determine differential methylation. The applicant has not demonstrated possession of the full scope of claimed genus based on the disclosure of a single species based on the biology underlining the different species.
Regarding claim 14, the claim limits the scope of the one or more genomic loci of claim 1, which are those of Table 5. The instant specification does not identify any AUROCs of the genomic loci in Table 5. There is no guidance as to which species of the genus of Table 5 are encompassed by claim 14 and those that are not.
Regarding claim 15, the claim further limits the genomic loci of claim 1 to those that have increased methylation to any tissue control sample or to a sample derived from a subject at risk of developing PRAD. Alternatively, the genomic loci are those that have decreased methylation to any tissue control sample or to a sample derived from a subject at risk of developing PRAD. The instant specification states the table lists regions with hypermethylated DNA in NEPC versus PRAD with log2 fold-difference threshold >1 and FDR-adjusted p-value <0.001. There is no guidance as to which additional tissue control samples or a subject at risk of developing PRAD may be used to identify which species of the genus of Table 5 are encompassed by claim 15 and those that are not.
There is no guidance regarding any situations in which the genomic loci of Table 5 are identified as having decreased methylation. Table 5 identifies the genomic loci as being hypermethylated in NEPC versus PRAD.
Regarding claim 18, the claim encompasses comparing a methylation level of a genomic locus of Table 5 to a predetermined threshold for one or more loci listed in Tables 1-8. Tables 1-4 and 6-8 have less genomic loci listed than Table 5. The instant specification does not describe which of the non-overlapping genomic loci between Table 5 and those of Tables 1-4 and 6-8 can be used or compared. There is no indication, for example, that a genomic loci of chromosome 3 and listed in Table 5 may be compared to a threshold for any of the genomic loci of Table 8, which does not include any from chromosome 3 or 6.
Regarding claim 20, the claim encompasses comparing the detected methylation level to any “control sample”. The instant specification states the table lists regions with hypermethylated DNA in NEPC versus PRAD with log2 fold-difference threshold >1 and FDR-adjusted p-value <0.001. There is no indication of any additional species of “control sample” that is encompassed by the claimed genus of “control samples”. The applicant has not demonstrated possession of the full scope of claimed genus based on the disclosure of a single species based on the biology underlining the different species.
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, 4, 6, 8, 13, 14, 15, 18, 20, 25, 28, 29, 31 and 32 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.
Regarding claim 1, it is not clear how the recited preamble is intended to breathe life and meaning into the claims. The preamble of the claim recites a “method of determining if a subject has or is at risk for developing neuroendocrine prostate cancer (NEPC)”. However, the method steps in the claim only require “detecting the presence, absence, or level of altered methylation relative to a control of one or more of the genomic loci listed in Table 5 in genomic DNA (gDNA), cell free DNA (cfDNA), and/or circulating tumor DNA (ctDNA) in a sample derived from the subject”. Thus, it is unclear if applicant intends to cover any method of “detecting the presence, absence, or level of altered methylation relative to a control of one or more of the genomic loci listed in Table 5 in genomic DNA (gDNA), cell free DNA (cfDNA), and/or circulating tumor DNA (ctDNA) in a sample derived from the subject”, or if the method is intended to somehow require more to accomplish the goal as set forth in the preamble. If it is the later, then it appears that the claims are incomplete, as they fail to provide any active steps that clearly accomplish the goal of determining if a subject has or is at risk for developing NEPC as set forth by the preamble of the claim. Amending the claim to include an active process step directed towards “determining the subject has or is at risk for developing NEPC”. If applicant is to make such an amendment, it is suggested applicant also consider including an additional step that integrates an amended “determining” step into a practical application so at to avoid any issues under section 101.
Claims 4, 6, 8, 13, 14, 15, 18, 20, 25, 28, 29, 31 and 32 depend from claim 1 and are rejected for the same reason.
Regarding claims 1, 4, 6 and 18, the claims each reference a table, e.g., Table 5 or Tables 1-8, each of which sets forth a collection of genomic loci. The claims are incomplete based on the reference to incorporate the tables recited in each of the claims. Claims are to be complete in themselves, and incorporation by reference of a table is a necessity doctrine and not one of convenience. See MPEP 2173.05(s).
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.
Claim(s) 1, 4, 8, 13, 14, 15, 18, 20, 25, 29, 31 and 32 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Beltran (Nature Medicine. 2016. 22(3):298-305 and Online Methods; cited on the 8/11/2023 IDS).
Claim 1 is drawn to a “method of determining if a subject has or is at risk for developing neuroendocrine prostate cancer (NEPC)”; however, the active method steps do not explicitly require “determining” whether the subject has or is at risk for developing NEPC. MPEP 2111.02 states:
If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention's limitations, then the preamble is not considered a limitation and is of no significance to claim construction.
Accordingly, the claim language of "determining if a subject has or is at risk for developing neuroendocrine prostate cancer (NEPC)" merely sets forth the intended use or purpose of the claimed methods, but does not limit the scope of the claims. The claims are given the broadest reasonable interpretation as requiring a single step of: detecting the presence, absence, or level of altered methylation relative to a control of one or more of the genomic loci listed in Table 5 in genomic DNA (gDNA), cell free DNA (cfDNA), and/or circulating tumor DNA (ctDNA) in a sample derived from the subject that comprises a step of detecting the presence, absence, or level of altered methylation comprises determining the level of methylation of the one or more genomic loci.
Claim 1 concludes with a “wherein” clause stating “the presence of altered methylation of the one or more of the genomic loci indicates that the subject has or is at risk for developing NEPC”. The clause does not recite any active method steps or further limit any of the steps identified above as being required by the claim. MPEP 2111.04 states that such a clause "in a method claim is not given weight when it simply expresses the intended result of a process step positively recited”, which applies in this situation.
Regarding claim 1, Beltran teaches detecting altered methylation between CRPC-NE as compared to CRPC-adeno across a number of genomic loci (Figure 3). The genomic loci includes the following examples from Supplementary Table 8, which are encompassed by presently claimed Table 5:
Chr1:10695916-10696199 (encompassed by chr1:10695901-10696200);
Chr1:10691690-10695882 (encompassed by chr1:10565601-10695900);
Chr1:8937448-8937529 (encompassed by chr1:8937301-8937600);
Chr1:8936-739-8923752 (encompassed by chr1:8936701-8937000);
Chr12:114885231-114885231 (encompassed by chr12:114885001- 114885300);
Chr13:112201037-1122010347 (encompassed by chr13: 112200901-112201200);
Chr15:96877244-96877445 (encompassed by chr15: 96877201-96877500);
Chr2:11810146-11810271 (encompassed by chr2:11810101-11810400);
Chr2:11809992-11810070 (encompassed by chr2:11809801-11810100);
Chr3:10858318-10858360 (encompassed by chr3:10858201-10858500);
Chr5:175306066-175306139 (encompassed by chr5:175305901-175306200);
Chr5:175305736-175305808 (encompassed by chr5:175305601-175305900);
Chr5:141133243-141133280 (encompassed by chr5:141133201-141133500);
Chr5:79552232-79552265 (encompassed by chr5:79552201-79552500);
Chr5:79552120-79552145 (encompassed by chr5:79551901-79552200);
Chr5:25200373-25200379 (encompassed by chr5:25200301-25200600);
Chr5:7002334-7002365 (encompassed by chr5:7002301-7002600); and
Chr5:1246221-1246221 (encompassed by chr5:1246201-1246500).
Beltran teaches using enhanced reduced representation bisulfite sequencing to determine methylation levels (Online Methods, Methylation profiling and data processing).
Regarding claim 4, Beltran teaches generating a methylation profile for CRPC-NE samples and for CRPC-adeno and comparing them, which resulted in the generation of Supplementary Table 8.
Regarding claim 8, the above examples of genomic loci observed by Beltran have a length between 50 and 1000 nucleotides.
Regarding claim 13, Beltran teaches the above examples of genomic loci are differentially methylated in CRPC-NE as compared to CRPC-adeno as a “tissue control sample”.
Regarding claim 14, the claim describes a feature of the genomic loci listed in Table 5. Beltran teaches genomic loci encompassed by those of Table 5 as described above. Thus, Beltran teaches genomic loci encompassed by claim 14.
Regarding claim 15, Beltran teaches the above examples of genomic loci are hypermethylated in CRPC-NE as compared to CRPC-adeno as a “tissue control sample”.
Regarding claims 18 and 20, Beltran teaches “determining a methylation score” of hypermethylated for the above genomic loci in CRPC-NE samples as compared to CRPC-adeno samples as a “threshold”.
Regarding claim 25, Beltran teaches the sample is a CRPC-NE or CRPC-adeno tissue sample (Online Methods, Methylation profiling and data processing).
Regarding claims 29 and 32, Beltran teaches the patients were treated with abiraterone, enzalutamide, taxane or platinum (Supplementary Table 1).
Regarding claim 31, Beltran teaches most CRPC patients are ultimately resistant to AR-targeted therapies (p. 298, left column).
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.
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) 6 and 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Beltran (Nature Medicine. 2016. 22(3):298-305 and Online Methods; cited on the 8/11/2023 IDS) in view of De Carvalho (WO 2019/010564 A1).
Claims 6 and 28 are drawn to a “method of determining if a subject has or is at risk for developing neuroendocrine prostate cancer (NEPC)”; however, the active method steps do not explicitly require “determining” whether the subject has or is at risk for developing NEPC. MPEP 2111.02 states:
If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention's limitations, then the preamble is not considered a limitation and is of no significance to claim construction.
Accordingly, the claim language of "determining if a subject has or is at risk for developing neuroendocrine prostate cancer (NEPC)" merely sets forth the intended use or purpose of the claimed methods, but does not limit the scope of the claims. The claims are given the broadest reasonable interpretation as requiring a single step of: detecting the presence, absence, or level of altered methylation relative to a control of one or more of the genomic loci listed in Table 5 in genomic DNA (gDNA), cell free DNA (cfDNA), and/or circulating tumor DNA (ctDNA) in a sample derived from the subject that comprises a step of detecting the presence, absence, or level of altered methylation comprises determining the level of methylation of the one or more genomic loci.
The claims conclude with a “wherein” clause stating “the presence of altered methylation of the one or more of the genomic loci indicates that the subject has or is at risk for developing NEPC”. The clause does not recite any active method steps or further limit and of the steps identified above as being required by the claim. MPEP 2111.04 states that such a clause "in a method claim is not given weight when it simply expresses the intended result of a process step positively recited”, which applies in this situation.
Regarding claims 6 and 28, Beltran teaches detecting altered methylation between CRPC-NE as compared to CRPC-adeno across a number of genomic loci (Figure 3). The genomic loci includes the following examples from Supplementary Table 8, which are encompassed by presently claimed Table 5:
Chr1:10695916-10696199 (encompassed by chr1:10695901-10696200);
Chr1:10691690-10695882 (encompassed by chr1:10565601-10695900);
Chr1:8937448-8937529 (encompassed by chr1:8937301-8937600);
Chr1:8936-739-8923752 (encompassed by chr1:8936701-8937000);
Chr12:114885231-114885231 (encompassed by chr12:114885001- 114885300);
Chr13:112201037-1122010347 (encompassed by chr13: 112200901-112201200);
Chr15:96877244-96877445 (encompassed by chr15: 96877201-96877500);
Chr2:11810146-11810271 (encompassed by chr2:11810101-11810400);
Chr2:11809992-11810070 (encompassed by chr2:11809801-11810100);
Chr3:10858318-10858360 (encompassed by chr3:10858201-10858500);
Chr5:175306066-175306139 (encompassed by chr5:175305901-175306200);
Chr5:175305736-175305808 (encompassed by chr5:175305601-175305900);
Chr5:141133243-141133280 (encompassed by chr5:141133201-141133500);
Chr5:79552232-79552265 (encompassed by chr5:79552201-79552500);
Chr5:79552120-79552145 (encompassed by chr5:79551901-79552200);
Chr5:25200373-25200379 (encompassed by chr5:25200301-25200600);
Chr5:7002334-7002365 (encompassed by chr5:7002301-7002600); and
Chr5:1246221-1246221 (encompassed by chr5:1246201-1246500).
Beltran teaches using enhanced reduced representation bisulfite sequencing to determine methylation levels (Online Methods, Methylation profiling and data processing).
Beltran does not specifically teach an analysis with cfMeDIP-seq as encompassed by claim 6 or the use of a plasma sample and isolating cell-free DNA from the plasma sample as encompassed by claim 28.
However, De Carvalho teaches the accuracy and versatility of cfMeDIP-seq may be useful to inform therapeutic decisions in settings where resistance is correlated to epigenetic alterations, such as sensitivity to androgen receptor inhibition in prostate cancer (p. 26, line 31 to p. 27, line 1). De Carvalho further teaches that plasma was a known source of cfDNA in cancer patients (p. 5, lines 16-17; p. 6, lines 29-31; and p. 8, line 32 to p. 9, line 2).
It would have been prima facie obvious to have modified the method of Beltran by using the plasma samples and cfMeDIP-seq of De Carvalho. One would have been motivated to make the modification because plasma represents a source of genomic DNA that can be obtained in a non-invasive manner and cfMeDIP-seq is accurate and versatile as stated by De Carvalho. One would have been further motivated based on De Carvalho’s suggestion that it may be beneficial in the context of prostate cancer.
Conclusion
No claims allowed.
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH G. DAUNER/Primary Examiner, Art Unit 1682
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