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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on April 25th, 2022 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
The listing of references in 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, they have not been considered.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-28, in the reply filed on October 30th, 2025 is acknowledged. However, because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 29-35 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 October 30th, 2025.
Claim Summary
Claims 1-35 are pending. Claims 29-35 are withdrawn from consideration as being drawn to a non-elected invention/species. Claims 1-28 are under examination and discussed in this Office action.
Specification
The use of terms like EsophaCap and Oregon Green, which are trade names or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 7, 19 and 25 are objected to because of the following informalities:
Claim 7 is missing a parenthesis after “(b”. This should be added so it reads “(b)”. Claim 7 is also missing an “a” between “using” and “methylation” which should be inserted.
Claim 19 is missing an “a” between “using” and “methylation” which should be inserted.
Claim 25 is missing an “a” between “using” and “methylation” which should be inserted.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claim 13 is 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 13 recites the limitation “wherein an endoscopy is performed prior to the treatment of step (e)”. There is insufficient antecedent basis for this limitation in the claim. Claims 11 and 12, from which claim 13 depends, do not introduce a step (e) as the treatment step, but instead a step (d) as the treatment step. For the purpose of compact prosecution, “wherein an endoscopy is performed prior to the treatment of step (e)” will be interpreted as wherein an endoscopy is performed prior to the treatment of step (d).
Claim Rejections - 35 USC § 112(a)
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.
Scope of Enablement
Claims 1-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. The specification, while being enabling for detecting nucleic acid methylation of one or more genes comprising ABCB1, BMP3, COL23A1, FBN1, FADS1, and PRDM1 to identify a subject with esophageal adenocarcinoma (EAC), does not reasonably provide enablement for detecting nucleic acid methylation of any one or more genes to identify a subject with EAC as embraced by the claims. Furthermore, the specification, while being enabling for detecting increased methylation in a particular area of the above recited one or more genes as compared to controls identifies the subject as having EAC, does not reasonably provide enablement for generically detecting nucleic acid methylation of one or more genes to identify the subject as having EAC as embraced by the claims. Finally, the specification, while being enabling for a human subject, does not reasonably provide enablement for any subject as embraced by the claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” See MPEP § 2164. These factors include, but are not limited to: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The office has analyzed the specification in direct accordance to the factors outlines in In re Wands. MPEP 2164.04 states: “[W]hile the analysis and conclusion of a lack of enablement are based on factors discussed in MPEP 2164.01(a) and the evidence as whole, it is not necessary to discuss each factor in written enablement rejection.” These factors will be analyzed, in turn, to demonstrate that one of ordinary skill in the art would have had to perform “undue experimentation” to make and/or use the invention and therefore, applicant’s claims are not enabled.
(A) With respect to the breadth of the claims: Claim 1 as currently drafted encompasses a method for identifying a subject with EAC comprising steps of extracting genomic DNA from a sample, converting unmethylated cytosines to uracil, and generically detecting nucleic acid methylation of one or more genes in the converted DNA to identify the subject as having EAC. Claim 11 as currently drafted claims a method equivalent to claim 1, while additionally administering treatment after identifying the subject having EAC. “One or more genes” does not limit the genes in question to the 6 genes of ABCB1, BMP3, COL23A1, FBN1, FADS1, and PRDM2 as described in the specification. “Detecting nucleic acid methylation” also does not limit methylation to detecting increased methylation in a particular area of the recited genes as compared to controls as described in the specification. Finally, “a subject” and “the subject” does not limit the subject to a human subject to the analysis of human samples as described in the specification. Consequently, the breadth of the claims is expansive since they encompass any gene and any methylation level in any kind of subject. Claims 2-10 and 12-21 encompass the same breadth as claims 1 and 11 since they do not limit the genes to the 6 genes of ABCB1, BMP3, COL23A1, FBN1, FADS1, and PRDM2, detecting nucleic acid methylation to detecting increased methylation at particular places in the recited genes as compared to controls, and human subjects.
(B) The nature of the invention: The invention is in the field using gene methylation to detect and treat EAC.
(C), (D), (E) With respect to the state of the prior art, the level of one of ordinary skill and predictability of the art: Ahlquist (US20180037958A1) teaches a method for identifying a subject having esophageal adenocarcinoma (EAC) comprising the steps of: (a) extracting DNA from a sample obtained from the subject (Page 6, paragraph [0053]); (b) performing a conversion reaction on the genomic DNA in vitro to convert unmethylated cytosine (Page 6, paragraph [0053]); and (c) detecting nucleic acid methylation of one or more specific genes in the converted genomic DNA (DMR Nos. 77, 90, and 135), wherein detecting differences in nucleic acid methylation as compared to several different controls identifies the subject as having EAC (Page 6, paragraph [0053]). This art indicates that there are specific regions of specific genes with particular methylation levels associated with EAC, not any gene with any methylation at any location in those genes. Any gene with any methylation at any location in the genes would be unpredictable.
Furthermore, by the Applicant’s own specification, while the whole Cancer Genome Atlas database was screened, it only returned 1327 candidate genes that met the criteria for identifying EAC (Paragraph [0166]). There are approximately 20,000 genes in the human genome, of which only around 5% are associated with EAC based on the Applicant’s own methods (Paragraph [0166]). This indicates that there are specific genes with particular methylation levels associated with EAC, not any gene with any methylation at any location in those genes. Any gene with any methylation at any location in the genes would be unpredictable.
In addition, because the claims encompass methylation in any part of a gene, whereas the specification teaches the particular increased methylation of particular regions of ABCB1, BMP3, COL23A1, FBN1, FADS1, and PRDM2 as associated with EAC, it is relevant to point out that it is unpredictable to extrapolate the effect of methylation on even physically close CpG positions. This unpredictability is particularly relevant where the specification provides an asserted connection between gene methylation and expression (Paragraph [0096]). Costello (Graded methylation in the promoter and body of the O6-methylguanine DNA methyltransferase (MGMT) gene correlates with MGMT expression in human glioma cells, Journal of Biological Chemistry, June 1994, 269, 177228-17237) indicates the unpredictability in examining methylation status of different parts of the MGMT promoter. For example, position 13 of the 'Region II CpG sites' (Fig 5B) indicates a reverse role for methylation of the position with regard to gene expression. At position 13, there is greater unmethylation in the nonexpressing cell line, and there is less unmethylation in the high expressing cell line. This art indicates that even closely related methylation sites are not necessarily equivalently related to expression in cancer, indicating that it is unpredictable for methylation of unspecified locations within any one or more unspecified genes to all be related to one particular cancer.
Finally, Juppner (Functional properties of the PTH/PTHrP receptor, Bone, August 1995, S39-S42) teaches that despite significant structural conservation, rat, opossum, and human PTH/PTHrP receptor homologs display distinct functional characteristics (Abstract; Pages 39S-40S). This art indicates that there is known functional differences between homologs in different organisms, and therefore inter-species extrapolation would be unpredictable.
The art supports use of differences in methylation of particular locations in specific genes between test and control subjects for identifying EAC as described. However, methods comprising any one or more genes, any methylation level, and any location are highly unpredictable.
The invention is drawn to biological molecules, and is therefore in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001). The level of skill in the art is therefore deemed to be high.
(F), (G) With respect to the amount of direction and working examples provided by the applicant: The Applicant has provided both description (Paragraphs [0009], [0011], [0035], [0036], [0130], [0131], [0135], as specific examples; Figures 4 and 5) and working examples (Examples from page 43-48) directed towards using methylation levels of one or more of the 6 genes of ABCB1, BMP3, COL23A1, FBN1, FADS1, and PRDM2 to identify a subject as having EAC. The Applicant has also provided both description (Paragraphs [0009], [0063], and [0130], as specific examples; Figures 4 and 5) and working examples (Examples from page 44) directed towards detecting increased methylation as compared to controls for identifying the subject as having EAC (Paragraphs [0009], [0063], [0130], [0167], [0168], as specific examples; Figures 4 and 5). Furthermore, the Applicant has described specific regions of the claimed genes wherein increased methylation is being assessed with relation to EAC (Paragraph [0127]; Table 1, given the provided primers and probes). Finally, the Applicant’s working examples are related specifically to human subjects (Examples from page 43-48).
Overall, the Applicant’s instant disclosure provides adequate direction and working examples for detecting increased methylation in specific regions of their claimed genes in human subjects to identify the subject as having EAC. The Applicant’s instant disclosure has not provided adequate direction and working examples for using any one or more genes with any level or area of methylation to identify any organism with EAC.
(H) Undue experimentation would be required to practice the invention as claimed due to the amount of experimentation necessary because of the expansive breadth of the claims, the state of the prior art and its high predictability, and the limited amount of guidance in the form of varied working examples in the specification.
A skilled artisan recognizes that using one or more genes very broadly refers to any gene in the genome and thus applicability of the claimed method to one or more genes as embraced by the claim remains unpredictable, requiring undue experimentation. Similarly, a skilled artisan recognizes that generically detecting nucleic acid methylation very broadly refers to even a single methylation change being able to identify EAC, and thus applicability of the claimed method to generically detecting nucleic acid methylation as embraced by the claim remains unpredictable, requiring undue experimentation. For example, an artisan would need to determine methylation levels for every gene, determine genes that appear to be most relevant, and then apply those genes in a test setting to see if they can identify a subject with esophageal adenocarcinoma. Furthermore, the artisan would need to look at methylation levels down to a single methylation change in each gene in the genome to determine if they are capable of identifying a subject with esophageal adenocarcinoma, as well as determine the locations of methylation that are relevant to EAC. In addition, all of this experimentation would need to be performed in an expansive number of different organisms, with the controls to match. This reasonably represents undue experimentation.
MPEP §2164.01(a), 4th paragraph, provides that, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1157, 1562; 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (CA FC), states that, “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable,” citing Brenner v. Manson, 383 U.S. 519, 536 (1966) (stating, in the context of the utility requirement, that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion”). The Genentech decision continued, “tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Id. at p. 1005.
After applying the Wands factors and analysis to claims 1-21, in view of the applicant’s entire disclosure, and considering the In re Wright, In re Fisher and Genentech decisions discussed above, it is concluded that the practice of the full scope of the invention as claimed would not be enabled by the written disclosure. Therefore, claims 1-21 are rejected under 35 U.S.C. §112(a) for failing to disclose sufficient information to enable a person of skill in the art to practice the claimed invention to it the full scope embraced by the claims. The following is provided as a final example of the permitted scope for the claims: detecting increased nucleic acid methylation in a particular area of a gene as compared to controls of one or more genes comprising ABCB1, BMP3, COL23A1, FBN1, FADS1, and PRDM1 to identify a human subject with esophageal adenocarcinoma (EAC).
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 1-11 and 14-28 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more. While the claims are directed to processes, and therefore meet step 1 of the subject matter eligibility test (see MPEP 2106.03), the claims recite the natural correlation between gene methylation and EAC and the abstract idea of detecting nucleic acid methylation of genes. Such correlation is a natural phenomenon because it describes a consequence of natural processes in the human body (e.g. a change in gene methylation profile due to disease). Detecting nucleic acid methylation of genes is an abstract idea because it can reasonably be considered an abstract mental process, wherein the detecting nucleic acid methylation step can be performed in the human mind (e.g. seeing methylation of the genes in the acquired data and concluding the gene is methylation).
Step 2A of the subject matter eligibility test requires a two-pronged analysis. Prong One asks: does the claim recite an abstract idea, law of nature or natural phenomenon? As discussed in MPEP 2106.04(II)(A)(1), the meaning of “recites” is “set forth” or “describes”. That is, a claim recites a judicial exception when the judicial exception is “set forth” or “described” in the claim. In the instant case, the claims describe a natural phenomenon and an abstract idea: the natural correlation between gene methylation and EAC, and the mental process of detecting nucleic acid methylation.
Prong Two of the analysis under step 2A asks: does the claim recite additional elements that integrate the judicial exception into a practical application of the judicial exception? As discussed in MPEP 2106.04(II)(A)(2), “Because a judicial exception is not eligible subject matter, Bilski, 561 U.S. at 601, 95 USPQ2d at 1005-06 (quoting Chakrabarty, 447 U.S. at 309, 206 USPQ at 197 (1980)), if there are no additional claim elements besides the judicial exception, or if the additional claim elements merely recite another judicial exception, that is insufficient to integrate the judicial exception into a practical application. See, e.g., RecogniCorp, LLC v. Nintendo Co., 855 F.3d 1322, 1327, 122 USPQ2d 1377 (Fed. Cir. 2017) ("Adding one abstract idea (math) to another abstract idea (encoding and decoding) does not render the claim non-abstract"); Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016) (eligibility "cannot be furnished by the unpatentable law of nature (or natural phenomenon or abstract idea) itself."). For a claim reciting a judicial exception to be eligible, the additional elements (if any) in the claim must "transform the nature of the claim" into a patent-eligible application of the judicial exception, Alice Corp., 573 U.S. at 217, 110 USPQ2d at 1981, either at Prong Two or in Step 2B.” The considerations to be used are set forth at MPEP 2106.05(a) through (c) and (e) through (h). Turning to those sections of the MPEP:
MPEP 2106.05(a) has to do with improvements to the functioning of a computer or to any other technology or technical field. The claims at issue do not improve the functioning of a computer or other technology. While the instant claims recite steps of extracting genomic DNA from a sample; converting unmethylated cytosines to uracil; detecting methylation in one or more genes to identify EAC; the one or more genes comprising ABCB1, BMP3, COL23A1, FBN1, FADS1, and PRDM2, or at least 3 or 4 of these genes; detecting methylation with quantitative methylation specific PCR; extracting DNA and converting unmethylated cytosines using methylation on beads; a cell sample; the cell sample retrieved with a swallowable sponge device; performing endoscopy; and generically administering treatment, the claims do not improve upon techniques for sample collection, unmethylated cytosine conversion, or quantitative methylation specific PCR. The claims merely use existing methods for these steps. Note that MPEP 2106.05(a) indicates that “[u]sing well-known standard laboratory techniques to detect enzyme levels in a bodily sample” is an example that the courts have indicated may not be sufficient to show an improvement to technology.
MPEP 2106.05(b) has to do with whether the claims involve the use of a particular machine. In this case, the claims do not involve the use of a particular machine. While the instant claims recite steps of extracting genomic DNA from a sample; converting unmethylated cytosines to uracil; detecting methylation in one or more genes to identify EAC; the one or more genes comprising ABCB1, BMP3, COL23A1, FBN1, FADS1, and PRDM2, or at least 3 or 4 of these genes; detecting methylation with quantitative methylation specific PCR; extracting DNA and converting unmethylated cytosines using methylation on beads; a cell sample; the cell sample retrieved with a swallowable sponge device; performing endoscopy; and generically administering treatment, no such machines are required by the claim, and certainly no particular machines. Even if some conventional machine were recited in the claims, like a quantitative PCR machine, further considerations such as the particularity or generality of the recited machine must be taken into account, as well as whether the involvement of the machine is merely extra-solution activity. MPEP 2106.05(g) describes “extra-solution activity”, noting that “[d]etermining the level of a biomarker in blood” is an example of “mere data gathering” which the courts have found to be insignificant extra-solution activity.
MPEP 2106.05(c) has to do with whether the claims involve a particular transformation. Here, none of the limitations of the claims involve a particular transformation. For example, the extraction of genomic DNA does not transform that genomic DNA into something else. It is noted by the Examiner that deamination of cytosines to uracil could constitute a particular transformation. However, based on the art cited below, deamination of cytosine to uracil for the purpose of detecting methylation was routine and conventional in the art.
MPEP 2106.05(e) has to do with “other meaningful limitations”. The additional limitations imposed upon the natural correlation between gene methylation and EAC and the mental process of detecting nucleic acid methylation in the instant case have to do with extracting genomic DNA from a sample; converting unmethylated cytosines to uracil; detecting methylation in one or more genes to identify EAC; the one or more genes comprising ABCB1, BMP3, COL23A1, FBN1, FADS1, and PRDM2, or at least 3 or 4 of these genes; detecting methylation with quantitative methylation specific PCR; extracting DNA and converting unmethylated cytosines using methylation on beads; a cell sample; the cell sample retrieved with a swallowable sponge device; performing endoscopy; and generically administering treatment. These limitations are not considered “meaningful limitations”. MPEP 2106.05(e) states: “The phrase "meaningful limitations" has been used by the courts even before Alice and Mayo in various contexts to describe additional elements that provide an inventive concept to the claim as a whole.” In addition, as has been discussed, they represent insignificant extra-solution activity, i.e. “data gathering”.
MPEP 2106.05(f) raises the question as to whether the additional elements recited in the claim represent “mere instructions to apply an exception”. Here, the judicial exception is the natural correlation between gene methylation and EAC, and the mental process of detecting nucleic acid methylation. The additional elements recited in the claims (i.e. extracting genomic DNA from a sample; converting unmethylated cytosines to uracil; detecting methylation in one or more genes to identify EAC; the one or more genes comprising ABCB1, BMP3, COL23A1, FBN1, FADS1, and PRDM2, or at least 3 or 4 of these genes; detecting methylation with quantitative methylation specific PCR; extracting DNA and converting unmethylated cytosines using methylation on beads; a cell sample; the cell sample retrieved with a swallowable sponge device; performing endoscopy; and generically administering treatment) does amount to mere instructions to apply the exceptions, since the collection of particular biological samples, extracting genomic DNA from those samples, converting unmethylated cytosines to uracil, and detecting nucleic acid methylation serve as mere conventional steps taken for the purpose of gathering data about the methylation of the subject, which any practical use of the exceptions would require.
MPEP 2106.05(g) has to do with whether the additional elements of the claim amount to insignificant extra-solution activity. MPEP 2106.05(g) notes that “[d]etermining the level of a biomarker in blood” is an example of “mere data gathering” which the courts have found to be insignificant extra - solution activity. Likewise, MPEP 2106.05(g) notes that “[p]erforming clinical tests on individuals to obtain input for an equation” also represents insignificant extra-solution activity. This aligns closely with the instant claims, where the additional elements of the claims amount to gathering samples, extracting genomic DNA, and detecting nucleic acid methylation via deamination.
MPEP 2106.05(h) has to do with whether the additional elements amount to more than generally linking the use of a judicial exception to a particular technological environment or field of use. Here, the recitation of the invention providing compositions and methods useful for detecting and treating esophageal cancer is considered a “field of use”. However, as MPEP 2106.05(h) indications, such limiting to a particular “field of use” does not confer patentability on otherwise ineligible subject matter.
In addition, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception (as set forth in step 2B of the subject matter eligibility test; see MPEP 2106-III) because it was routine and conventional in the prior art to ascertain methylation levels as it relates to EAC or in general using the methods as claimed:
Ahlquist (US20180037958A1) teaches a method for identifying a subject having esophageal adenocarcinoma (EAC) comprising the steps of: (a) extracting DNA from a sample obtained from the subject (Page 6, paragraph [0053]); (b) performing a conversion reaction on the genomic DNA in vitro to convert unmethylated cytosine (Page 6, paragraph [0053]); and (c) detecting nucleic acid methylation of one or more genes in the converted genomic DNA, wherein detecting nucleic acid methylation identifies the subject as having EAC (Page 6, paragraph [0053]). Ahlquist further teaches using genomic DNA isolated from esophageal tissue to look at differences in methylation related to esophageal adenocarcinoma (Page 20, paragraph [0202]). Ahlquist later details that a reagent that modifies a nucleotide as a function of the methylation state of a nucleic acid molecule can be a reagent that deaminates unmethylated cytosine nucleotides (Page 12, paragraph [0106]). Ahlquist further teaches wherein the PCR-based technique is quantitative methylation specific PCR (QMSP) (Pages 6-7, paragraph [0057]). Ahlquist further teaches a number of different sample types, wherein a sample can be a cell sample (Page 14, paragraph [0133]; Page 20, paragraph [0205]; Page 21, paragraph [0213]). Ahlquist further teaches wherein the cell sample is retrieved using a swallowable sponge device (Page 7, paragraph [0058]). Ahlquist further teaches that subjects identified as having an esophageal disorder via methylation, including EAC, can be placed under regular screening, including endoscopic surveillance (Page 23, paragraph [0228]). Ahlquist further teaches on treating a patient with EAC by determining a methylation state of differentially methylated regions and administering a treatment based on these results, meaning necessarily appropriate for EAC (Page 21, paragraph [0215]).
Ahlquist II (US20190161804A1) teaches a method comprising the steps of: (a) extracting genomic DNA from a sample obtained from a subject (Page 5, paragraph [0045]; Page 6, paragraph [0052]); (b) performing a conversion reaction on the genomic DNA in vitro to convert unmethylated cytosine (Page 5, paragraph [0045]); and (c) detecting nucleic acid methylation of ABCB1, BMP3, and COL23A1 in the converted genomic DNA (Page 5, paragraph [0045]; Tables 2 and 6 for DMRs). Ahlquist II further teaches wherein the PCR-based technique is quantitative methylation specific PCR (QMSP) (Page 6, paragraph [0052]). Ahlquist II further teaches a number of different sample types, wherein a sample can be a cell sample (Pages 18-19, paragraph [0214]).
Having considered the factors discussed in MPEP 2106.05 (a)-(c) and (e)-(h), as well as the prior art of Ahlquist and Ahlquist II, it is clear that the additional elements recited in the claims, whether considered individually or as a combination, do not integrate the judicial exception into a practical application of that exception in such a way as to provide meaningful limits on the use of the judicial exception. Therefore, claims 1-11 and 14-28 are rejected here under 35 U.S.C. 101.
Claim Rejections - 35 USC § 103
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.
Claims 1, 5-6, 8-12, 17-18, and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Ahlquist (US20180037958A1).
Regarding instant claim 1, Ahlquist teaches a method for identifying a subject having esophageal adenocarcinoma (EAC) comprising the steps of: (a) extracting DNA from a sample obtained from the subject (Page 6, paragraph [0053]); (b) performing a conversion reaction on the genomic DNA in vitro to convert unmethylated cytosine (Page 6, paragraph [0053]); and (c) detecting nucleic acid methylation of one or more genes in the converted genomic DNA, wherein detecting nucleic acid methylation identifies the subject as having EAC (Page 6, paragraph [0053]).
The above referenced embodiment of Ahlquist does not specify that genomic DNA is extracted from the sample. However, later detailed embodiments specifically state using genomic DNA isolated from esophageal tissue to look at differences in methylation related to esophageal adenocarcinoma (Page 20, paragraph [0202]). Therefore, it would be obvious to use extract genomic DNA from a sample for the purposes of the earlier embodiment of Ahlquist.
The above referenced embodiment of Ahlquist also does not specify that that the conversion reaction converts unmethylated cytosine to uracil by deamination. Instead, it more generally states treating with a reagent for selective modification of unmethylated cytosines. However, Ahlquist later details that a reagent that modifies a nucleotide as a function of the methylation state of a nucleic acid molecule can be a reagent that deaminates unmethylated cytosine nucleotides (Page 12, paragraph [0106]). Therefore, it would be obvious to perform a conversion reaction with a reagent that deaminates unmethylated cytosines to uracils.
In addition, it is noted that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results (In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930); Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959)). See MPEP §2144.04 IV C. Thus, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Regarding instant claim 5, Ahlquist teaches the method of claim 1. Ahlquist further teaches wherein the detecting step (c) comprises a polymerase chain reaction (PCR)-based technique (Pages 6-7, paragraph [0057]).
Regarding instant claim 6, Ahlquist teaches the method of claim 5. Ahlquist further teaches wherein the PCR-based technique is quantitative methylation specific PCR (QMSP) (Pages 6-7, paragraph [0057]).
Regarding instant claim 8, Ahlquist teaches the method of claim 1. Ahlquist further teaches the sample is a cell sample (Page 14, paragraph [0133]; Page 20, paragraph [0205]; Page 21, paragraph [0213]).
Regarding instant claim 9, Ahlquist teaches the method of claim 8. Ahlquist further teaches wherein the cell sample is retrieved using a swallowable sponge device (Page 7, paragraph [0058]).
Regarding instant claim 10, Ahlquist teaches the method of claim 1. The embodiment referenced in claim 1 does not teach performing an endoscopy after detecting methylation to identify the subject as having EAC. However, Ahlquist later details that subjects identified as having an esophageal disorder via methylation, including EAC, can be placed under regular screening, including endoscopic surveillance (Page 23, paragraph [0228]). Therefore, it would be obvious to perform an endoscopy after identifying the subject as having EAC.
In addition, it is noted that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results (In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930); Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959)). See MPEP §2144.04 IV C. Thus, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Regarding instant claim 11, Ahlquist teaches a method for identifying a subject having EAC comprising the steps of: (a) extracting DNA from a sample obtained from the subject (Page 6, paragraph [0053]); (b) performing a conversion reaction on the genomic DNA in vitro to convert unmethylated cytosine (Page 6, paragraph [0053]); and (c) detecting nucleic acid methylation of one or more genes in the converted genomic DNA, wherein detecting nucleic acid methylation identifies the subject as having EAC (Page 6, paragraph [0053]).
The above referenced embodiment of Ahlquist does not specify that genomic DNA is extracted from the sample. However, later detailed embodiments specifically state using genomic DNA isolated from esophageal tissue to look at differences in methylation related to esophageal adenocarcinoma (Page 20, paragraph [0202]). Therefore, it would be obvious to use extract genomic DNA from a sample for the purposes of the earlier embodiment of Ahlquist.
The above referenced embodiment of Ahlquist also does not specify that that the conversion reaction converts unmethylated cytosine to uracil by deamination. Instead, it more generally states treating with a reagent for selective modification of unmethylated cytosines. However, Ahlquist later details that a reagent that modifies a nucleotide as a function of the methylation state of a nucleic acid molecule can be a reagent that deaminates unmethylated cytosine nucleotides (Page 12, paragraph [0106]). Therefore, it would be obvious to perform a conversion reaction with a reagent that deaminates unmethylated cytosines.
Finally, the above referenced embodiment of Ahlquist does not teach treating a subject having EAC by the method, and further administering to the subject one or more treatment modalities appropriate for a subject having EAC. However, a later embodiment teaches on treating a patient with EAC. This embodiment comprises determining a methylation state of differentially methylated regions and administering a treatment based on these results, meaning necessarily appropriate for EAC (Page 21, paragraph [0215]). These include performing a surgery (Page 21, paragraph [0215]). Therefore, it would be obvious to administer to the subject one or more treatment modalities appropriate for a subject having EAC.
In addition, it is noted that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results (In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930); Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959)). See MPEP §2144.04 IV C. Thus, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Regarding instant claim 12, Ahlquist teaches the method of claim 11. Ahlquist further teaches wherein the one or more treatment modalities comprises surgery (Page 21, paragraph [0215]).
Regarding instant claim 17, Ahlquist teaches the method of claim 11. Ahlquist further teaches wherein the detecting step (c) comprises a polymerase chain reaction (PCR)-based technique (Pages 6-7, paragraph [0057]).
Regarding instant claim 18, Ahlquist teaches the method of claim 17. Ahlquist further teaches wherein the PCR-based technique is quantitative methylation specific PCR (QMSP) (Pages 6-7, paragraph [0057]).
Regarding instant claim 20, Ahlquist teaches the method of claim 11. Ahlquist further teaches a number of different sample types, wherein a sample can be a cell sample (Page 14, paragraph [0133]; Page 20, paragraph [0205]; Page 21, paragraph [0213]).
Regarding instant claim 21, Ahlquist teaches the method of claim 20. Ahlquist further teaches wherein the cell sample is retrieved using a swallowable sponge device (Page 7, paragraph [0058]).
Claims 2 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Ahlquist (US20180037958A1), as applied to claims 1, 5-6, 8-12, 17-18, and 20-21 above, in view of Qin (Discovery, Validation, and Application of Novel Methylated DNA Markers for Detection of Esophageal Cancer in Plasma, Precision Medicine and Imaging, December 2019, 25, 7396-7404).
Regarding instant claim 2, Ahlquist teaches the method of claim 1.
Ahlquist does not teach wherein the one or more genes comprise BMP3.
Qin, in the same field of endeavor, teaches detecting methylation of BMP3 to identify esophageal adenocarcinoma (Table 1).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Ahlquist with BMP3 of Qin. Since Qin teaches on methylated DNA markers for detection of esophageal cancer, which is reasonably pertinent to the method of Ahlquist, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to simple substitution of one known element for another to obtain predictable results (see MPEP 2141(III)). Ahlquist already teaches on detecting methylation to identify esophageal adenocarcinoma, detecting methylation of BMP3 could simply be substituted into the method since it is capable of discriminating between healthy samples and esophageal adenocarcinoma (Qin, Table 1).
Regarding instant claim 14, Ahlquist teaches the method of claim 11.
Ahlquist does not teach wherein the one or more genes comprise BMP3.
Qin, in the same field of endeavor, teaches detecting methylation of BMP3 to identify esophageal adenocarcinoma (Table 1).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Ahlquist with BMP3 of Qin. Since Qin teaches on methylated DNA markers for detection of esophageal cancer, which is reasonably pertinent to the method of Ahlquist, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to simple substitution of one known element for another to obtain predictable results (see MPEP 2141(III)). Ahlquist already teaches on detecting methylation to identify esophageal adenocarcinoma, detecting methylation of BMP3 could simply be substituted into the method since it is capable of discriminating between healthy samples and esophageal adenocarcinoma (Qin, Table 1).
Claims 7 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Ahlquist (US20180037958A1), as applied to claims 1, 5-6, 8-12, 17-18, and 20-21 above, in view of Wang (US20110165565A1).
Regarding instant claim 7, Ahlquist teaches the method of claim 1.
Ahlquist does not teach wherein steps (a) and (b) are performed using methylation on beads technique.
Wang, in a reasonably pertinent field, teaches wherein extracting genomic DNA from a sample and performing a conversion reaction on the genomic DNA to convert unmethylated cytosine to uracil by deamination are performed using methylation on beads technique (Page 7, paragraph [0075]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Ahlquist with the methylation on beads method from Wang. Since Wang teaches on DNA extraction and conversion reaction for unmethylated cytosines, which is reasonably pertinent to Ahlquist’s method requiring DNA extraction and conversion reaction for unmethylated cytosines, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because methylation on beads provides superior yields relative to conventional methods for NA extraction and bisulfite conversion (Wang, Page 7, paragraph [0075]).
Regarding instant claim 19, Ahlquist teaches the method of claim 11.
Ahlquist does not teach wherein steps (a) and (b) are performed using methylation on beads technique.
Wang, in a reasonably pertinent field, teaches wherein extracting genomic DNA from a sample and performing a conversion reaction on the genomic DNA to convert unmethylated cytosine to uracil by deamination are performed using methylation on beads technique (Page 7, paragraph [0075]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Ahlquist with the methylation on beads method from Wang. Since Wang teaches on DNA extraction and conversion reaction for unmethylated cytosines, which is reasonably pertinent to Ahlquist’s method requiring DNA extraction and conversion reaction for unmethylated cytosines, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because methylation on beads provides superior yields relative to conventional methods for NA extraction and bisulfite conversion (Wang, Page 7, paragraph [0075]).
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Ahlquist (US20180037958A1), as applied to claims 1, 5-6, 8-12, 17-18, and 20-21, in view of Arnal (Esophageal cancer: Risk factors, screening and endoscopic treatment in Western and Eastern countries, World Journal of Gastroenterology, July 2015, 21, 7933-7943).
Regarding instant claim 13, Ahlquist teaches the method of claim 12. Ahlquist further teaches that subjects identified as having an esophageal disorder via methylation, including EAC, can be placed under regular screening, including endoscopic surveillance (Page 23, paragraph [0228]).
Ahlquist does not specifically teach wherein an endoscopy is performed prior to the treatment of step (e).
Arnal, in the same field of endeavor, teaches that treatment of esophageal adenocarcinoma can follow endoscopy screening (Figure 2).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Ahlquist with the endoscopy timing of Arnal. Since both Ahlquist and Arnal are in the same field of endeavor (e.g. esophageal adenocarcinoma), one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to combining prior art elements according to known methods to yield predictable results (see MPEP 2141(III)).
Claims 22-24 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Ahlquist (US20190161804A1), hereafter referred to as Ahlquist II for clarity.
Regarding instant claim 22, Ahlquist II teaches a method comprising the steps of: (a) extracting genomic DNA from a sample obtained from a subject (Page 5, paragraph [0045]; Page 6, paragraph [0052]); (b) performing a conversion reaction on the genomic DNA in vitro to convert unmethylated cytosine (Page 5, paragraph [0045]); and (c) detecting nucleic acid methylation of ABCB1, BMP3, and COL23A1 in the converted genomic DNA (Page 5, paragraph [0045]; Tables 2 and 6 for DMRs).
The above referenced embodiment of Ahlquist II also does not specify that that the conversion reaction converts unmethylated cytosine to uracil by deamination. Instead, it more generally states treating with a reagent for selective modification of unmethylated cytosines. However, Ahlquist II later details that a reagent that modifies a nucleotide as a function of the methylation state of a nucleic acid molecule can be a reagent that deaminates unmethylated cytosine nucleotides (Page 11, paragraph [0122]). Therefore, it would be obvious to perform a conversion reaction with a reagent that deaminates unmethylated cytosines to uracils.
Regarding instant claim 23, Ahlquist II teaches the method of claim 22. Ahlquist II further teaches wherein the detecting step (c) comprises a polymerase chain reaction (PCR)-based technique (Page 6, paragraph [0052]).
Regarding instant claim 24, Ahlquist II teaches the method of claim 23. Ahlquist II further teaches wherein the PCR-based technique is quantitative methylation specific PCR (QMSP) (Page 6, paragraph [0052]).
Regarding instant claim 26, Ahlquist II teaches the method of claim 22. Ahlquist II further teaches a number of different sample types, wherein a sample can be a cell sample (Pages 18-19, paragraph [0214]).
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Ahlquist II (US20190161804A1), as applied to claims 22-24 and 26 above, in view of Wang (US20110165565A1).
Regarding instant claim 25, Ahlquist II teaches the method of claim 22.
Ahlquist II does not teach wherein steps (a) and (b) are performed using methylation on beads technique.
Wang, in a reasonably pertinent field, teaches wherein extracting genomic DNA from a sample and performing a conversion reaction on the genomic DNA to convert unmethylation cytosine to uracil by deamination using methylation on beads technique (Page 7, paragraph [0075]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Ahlquist with the methylation on beads method from Wang. Since Wang teaches on DNA extraction and conversion reaction for unmethylated cytosines, which is reasonably pertinent to Ahlquist’s method requiring DNA extraction and conversion reaction for unmethylated cytosines, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because methylation on beads provides superior yields relative to conventional methods for NA extraction and bisulfite conversion (Wang, Page 7, paragraph [0075]).
Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over Ahlquist II (US20190161804A1), as applied to claims 22-24 and 26, in view of Ahlquist (US20180037958A1).
Regarding instant claim 27, Ahlquist II teaches the method of claim 26. Ahlquist II further teaches that a sample may include cells from the esophagus (Pages 18-19, paragraph [0214]).
Ahlquist II does not teach wherein the cell sample is retrieved using a swallowable sponge device.
Ahlquist, in a reasonably pertinent field teaches wherein a sample is retrieved from the esophagus using a swallowable sponge device (Page 7, paragraph [0058]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Ahlquist II with the swallowable sponge device of Ahlquist. Since Ahlquist teaches on retrieval of cells from the esophagus, which is reasonably pertinent to Ahlquist II’s sample types, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it was known that swallowable sponge devices are feasible, safe, and accurate for measuring biomarkers (Pages 7-8, paragraph [0066]).
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Ahlquist II (US20190161804A1), as applied to claims 22-24 and 26, in view of Ballard (WO2015157557A1).
Regarding instant claim 28, Ahlquist II teaches the method of claim 22.
Ahlquist II does not teach further comprising the step (d) of performing an endoscopy on the subject.
Ballard, in the same field of endeavor, teaches performing an endoscopy after detecting biomarkers related to pancreatic cancer (Pages 1-2, paragraph [0003]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Ahlquist II with the endoscopy of Ballard. Since both Ahlquist II and Ballard are in the same field of endeavor (e.g. pancreatic cancer), one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because endoscopic examination allows for confirmation of diagnosis with biomarkers (Ballard, Page 25, paragraph [0008]).
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of copending Application No. 18654593 in view of Ahlquist (US20180037958A1), Wang (US20110165565A1), Arnal (Esophageal cancer: Risk factors, screening and endoscopic treatment in Western and Eastern countries, World Journal of Gastroenterology, July 2015, 21, 7933-7943), Ahlquist II (US20190161804A1), and Ballard (WO2015157557A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘593 reference application and the instant application claim a method and/or system for detecting an esophageal disorder comprising using a cell sample and biochemical assay; detecting methylation at one or more genes in the sample; detecting via quantitative methylation specific PCR; detecting methylation of one or more genes comprising FBN1, ABCB1, BMP3, COL23A1, FADS1, and/or PRDM2; and collecting the sample with a non-endoscopic method of a swallowable sponge device.
The ‘593 application claims do not require the esophageal disorder to be EAC; extracting genomic DNA; performing a conversion reaction on the genomic DNA; performing the extracting and conversion with a methylation on beads technique; performing an endoscopy after identifying with methylation detection; administering treatment appropriate for EAC; and performing an endoscopy after identifying with methylation detection and before treating. However, Ahlquist and Ahlquist II, in view of the provided art in the 103 rejections above, teaches these claimed limitations as discussed in the above 103 rejections, obviating these variations to the claims of the ‘593 application.
Furthermore, with regard to a computer algorithm determining a parameter and providing an output, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use this computer method of the ‘593 application in the method of the instant application. See In re Venner, 262 F.2d 91, 120 USPQ 193 (CCPA (1958), where the court held that broadly providing an automatic or mechanical means to replace a manual activity which accomplished the same result is not sufficient to distinguish over the prior art. Any additional limitations of the claims of Application No. 18654593 are encompassed by the open claim language “comprising” found in the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allison E Schloop whose telephone number is (703)756-4597. The examiner can normally be reached Monday-Friday 8:30-5 ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at (571) 272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALLISON E SCHLOOP/Examiner, Art Unit 1683
/Robert T. Crow/Primary Examiner, Art Unit 1683