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 .
Claim Status
Currently, claims 1, 3-4, 6, 17, 20, 22-23, 25, 31, 35-43 are pending in the instant application. Claims 2, 5, 7-16, 18-19, 21, 24, 26-30, 32-34 have been canceled and claims 36-43 have been added. This action is written in response to applicant’s correspondence submitted 12/29/2025 and 6/22/2026. All the amendments and arguments have been thoroughly reviewed but were found insufficient to place the instantly examined claims in condition for allowance. The following rejections are either newly presented, as necessitated by amendment, or are reiterated from the previous office action. Any rejections not reiterated in this action have been withdrawn as necessitated by applicant’s amendments to the claims. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. This action is FINAL.
Election/Restrictions
Applicant’s election without traverse of 5 to 80 ecDNA count and CDC6 in the reply filed on 06/22/2026 is acknowledged.
Claims 41 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/22/2026.
Withdrawn Rejections
The rejection of claim 12 under 35 USC 101 is withdrawn in view of the amendment to the claims.
The rejection of claims 1 and 9 under 35 U.S.C. 102(a)(1) as being anticipated by Mischel (US2018/0355416 A1) is withdrawn in view of the amendment to the claims.
The rejection of claims 1, 8-9, 12 under 35 U.S.C. 102(a)(1) as being anticipated by Kim (Nature Genetics 2020, vol 52, pp 891-897) is withdrawn in view of the amendment to the claims.
The rejection of claims 1, 8-9, and 12 under 35 U.S.C. 102(a)(1) as being anticipated by Nones (Nature Communication, 2014, 5:5224, p 1-9) is withdrawn in view of the amendment to the claims.
The rejection of claims 2-4, 6, 8, 12-13, 15, 17, 20-23, 25, 27, 31, 33, 35 under 35 U.S.C. 103 as being unpatentable over Mischel (US2018/0355416 A1) in view of Bandla (Annals of Surgery, 2014, vol 260, 72-80) is withdrawn in view of the amendment to the claims.
The rejection of claims 2-4, 6, 13, 15, 17, 20-23, 25, 27, 31, 33, 35 under 35 U.S.C. 103 as being unpatentable over Nones (Nature Communication, 2014, 5:5224, p 1-9) in view of Bandla (Annals of Surgery, 2014, vol 260, pp 72-80) is withdrawn in view of the amendment to the claims.
Improper Markush Rejection
Claims 1 and 20 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of CDC6, CSF3, HMGA1, RARA, THRA, CTNNB1, and TNS4 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons.
Regarding “single structural similarity”, the MPEP at 2117 IIA states that a recognized physical, chemical, or an art recognized class is a class where there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. It is specifically stated that “Thus a Markush grouping is ordinarily proper if all the members for the group belong to a recognized class (whether physical, chemical, or art recognized) and are disclosed in the specification to possess at least one property in common which is mainly responsible for their function in the claimed invention, and it is clear from their very nature or from the prior art that all members possess this property (emphasis added)”.
Therefore, in analysis of whether a claim contains an improper Markush grouping, the MPEP states: A Markush claim contains an “improper Markush grouping” if either (emphasis added): (1) the members of the Markush group do not share a ‘single structural similarity’ or (2) the members do not share a common use.”
In the instant case, the genes do not share any common structural elements that is essential to the asserted utility of being associated with Barrett’s esophagus. The different genes are from different parts of the human genome and are composed of different nucleic acids sequences encoding functionally different proteins. Additionally, the prior art does not teach, nor is it clear from their nature, that all of the functional different genes posse the property set forth in the claims.
For example with regard to claim 1:
The gene encoding CDC6 is located on chromosome 17. CDC6 is a protein coding gene and essential for the initiation of DNA replication. The protein functions as a regulator at the early steps of DNA replication.
The gene CTNNB1 is located on chromosome 3. CTNNB1 encodes beta-catenin a cytoplasmic and nuclear scaffold protein that is key effector of the canonical Wnt signaling pathway.
The gene HMGA1 is located on chromosome 6. HMGA1 encodes a chromatic-associated transcription regulator that binds AT-rich DNA and helps control gene expression.
Therefore, it is clear that when considering the different genes, even in different combinations, there does not appear to be any common structure related to the function of the genes individually, or any particular combination.
Furthermore, the recited alternative species in the groups set forth here do not share a single structural similarity, as each method relies on detection of different gene combinations. The only structural similarity present is that all the genes are made up of nucleotides. However, comprising nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising a nucleotide alone is not essential to the common activity of being correlated with Barret’s esophagus.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112-New Matter
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, 3-4, 6, 17, 20, 22-23, 25, 31, 35-40, 42-43 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. This rejection is a new matter rejection.
The amendment to claims 1 and claim 17 to recite “detecting an average extrachromosomal oncogene count of at least 5 per esophageal cell” changes the scope of the claim and raises the issue of new matter. The specification teaches determining the extrachromosomal DNA count per esophageal cell from about 1 to about 100, including at least 5 ecDNA per esophageal cells (See para 123-129). The specification does not teach oncogene count of at least 5. The specification teaches about 2 to about 32 amplified oncogene counts per esophageal cell, at least 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 and at least 10, 20,30, (See para 132-137) but the specification does not teach at an average extrachromosomal oncogene count of at least 5 per esophageal cell as recited in claim 1 and claim 17. The disclosure does not provide support for an average extrachromosomal oncogene count of at least 5 per esophageal cell and this recitation introduces new matter.
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.
Claims 1, 3-4, 6, 17, 20, 22-23, 25, 31, 35-40, 42-43 are rejected under 35 U.S.C. 103 as being unpatentable over Mischel (US2018/0355416A1) in view of Bandla (Annals of Surgery, 2014, vol 260, pp 72-80), Gotovac (Gastroenterol Hepatol 2021, 12:689-713) and Patowary (Informatics in Medicine Unlocked, 2020, 18:1-19). This is a new grounds of rejection.
Mischel teaches a method to detect and treat cancer by identification of extrachromosomal oncogenes. Mischel teaches obtaining a biological sample from a subject and detecting amplified extrachromosomal oncogene present (sese para 6). Mischel teaches at least 5 extrachromosomal DNA per tumor cell (see fig 2A, fig 20-28). Mischel teaches administering to the subject an effective amount of anti-cancer agent (see para 7). Mischel teaches the cancer includes esophageal cancer (see para 117). Mischel teaches the biological sample includes a tumor sample or a tumor fluid sample (see para 147, 151). Mischel teaches the tumor includes esophageal cancer, as such Mischel teaches obtaining a biological sample containing a plurality of esophageal cells from the subject. Mischel teaches detecting amplified extrachromosomal oncogenes (See para 152). Mischel teaches copy count of oncogene greater than 5 (see para 274). Mischel teaches a method of treating cancer by obtaining a biological sample, detecting oncogene amplification on circular extrachromosomal DNA and administering a therapeutically effective amount of an anti-cancer drug (see para 151). Mischel does not teach a subject with Barrett’s esophagus, biological sample comprising epithelium tissue, cells having metaplasia or dysplasia including columnar epithelial cells. Mischel does not teach preventative treatment of esophageal cancer. Mischel does not teach oncogene of CDC6.
Bandla teaches obtaining esophageal mucosa specimens from subject diagnosed with EAC having dysplasia and intestinal metaplasia (see specimen screening and subject cohort). Bandla teaches mucosal tissue pieces were obtained from 4 subjects that underwent esophagectomies (see pg. 73, 1st column) (administering treatment, esophagectomy) (claim 17, 35, 39, 43). Bandla teaches patients underwent upper endoscopy (see subject cohort) (preventative treatment, diagnostic test) (claim 13, 15, 31), Bandla teaches isolating DNA and performing FISH analysis. Bandla teaches isolating columnar cell metaplasia (Barrett’s esophagus) (see specimen screening) (claim 3-4 and 6, 22-23, and 25). Bandla teaches analysis of metaplasia versus EAC to determine disease progression (see pg. 78, 1st column) (claim 12).
Gotovac teaches analysis of Barrett’s esophagus progression toward EAC. Gotovac teaches a role of increased expression of CDC6 in cancer including gastrointestinal cancer (See pg. 693). Gotovac teaches increased expression of CDC6 in Barrett’s esophagus cells (see fig 5).
Patoway teaches CDC6 is one of the genes responsible for esophageal squamous cell carcinoma (see pg. 4). Patoway teaches CDC6 is upregulated in ESCC (see pg. 17). Patoway teaches
Given Mischel teaches detecting extrachromosomal DNA in esophageal carcinoma and teaches administering therapy to subjects with extrachromosomal DNA, it would have been prima facie obvious to the ordinary artisan at the time the invention was to include different types of samples from different tissues of esophagus cells, including samples from Barrett’s esophagus, epithelium samples and metaplasia for the analysis of extrachromosomal DNA as taught by Mischel. Additionally because Mischel teaches detecting extrachromosomal oncogene count of at least 5 in tumor cells, the ordinary artisan would include analysis of additional known oncogene count, including CDC6 because Gotovac and Patoway teaches oncogene, CDC6 is upregulated in esophageal carcinoma and Barrett’s esophagus. The skilled artisan would have been motivated to include analysis of different cell samples because both Mischel and Bandla teaches analysis of esophageal cells including esophageal carcinoma and the skilled artisan would have been motivated to include additional samples of esophageal cells in the method of Mischel for a more robust analysis of different cancer samples and different cell samples. The skilled artisan would have been motivated to include detecting oncogene, CDC6 because both Mischel and Bandla teaches analysis of esophageal cells including esophageal carcinoma. Mischel teaches analysis of oncogenes in tumor cells, and Gotovac and Patoway teaches increased expression of oncogene CDC6 with progression of Barrett’s esophagus to EAC to detect additional markers for EAC. The skilled artisan would have been motivated to include treatment of subjects with or at risk of developing EAC in the method of Mischel with anticancer therapy including esophagectomy because Bandla teaches endoscopy as a diagnostic test and preventative as well as teaches esophagectomy as a treatment. The skilled artisan would have a reasonable expectation of success that extrachromosomal DNA including oncogene CDC6 can be tested in additional esophageal samples including Barrett’s esophagus, epithelium samples and metaplasia for extrachromosomal DNA because Mischel teaches extrachromosomal DNA detection in EAC, Bandla teaches analysis of chromosomal DNA in Barrett’s esophagus, epithelium samples and metaplasia, Gotovac and Patoway both teach increased expression of oncogene CDC6 is associated with EAC.
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 SARAE L BAUSCH whose telephone number is (571)272-2912. The examiner can normally be reached M-F 9a-4p.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Fereydoun Sajjadi can be reached at 571-272-3311. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARAE L BAUSCH/ Primary Examiner, Art Unit 1699
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