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 .
Election/Restrictions
Applicant’s election of the invention of Group I (claims directed to methods of detecting cancer specific mutations), and the particular cancer that is gastric cancer, and the particular gene that is TP53 (it is noted that the election recites and election of “TP5”, which is interpreted to mean TP53) in the reply filed on 09/10/2025 is acknowledged. 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)).
In light of the Examiner’s search and consideration of the elected invention, the species election requirement as it was applied between gastric cancer and colorectal cancer is withdrawn.
Claims 10 and 11 (directed to non elected cancer species), and claims 15, 20, 27 and 28 (directed to non elected methods) are withdrawn from further consideration pursuant to 37 CFR 1.142(b), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/10/2025.
Claim Rejections - 35 USC § 112 - Indefiniteness
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, 3-9, 13-14 and 31-33 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.
Claims 1, 3-9, 13-14 and 31-33 are unclear over the recitation of different tumor types in the preamble of the claim, in “detecting gastric, colorectal, lung and/or esophageal tumor specific mutations in a subject’s circulating tumor DNA”, as recited in claim 1, in combination with the final clause of the claim which specifies “thereby, identifying gastric tumor specific mutations”. The discordance between the breadth in the preamble and the specific requirements of the “identifying” makes the requirements of the claim unclear.
Claim 9 is unclear over recitation of the limitation “the tumor specific mutations are indicative of colorectal cancer”, because such a requires association is not consonant with the requirement of claim 1, form which claim 9 depends, that “gastric tumor specific mutations” are identified. It is unclear how a mutation specific for gastric cancer (as recited in claim 1) can also be specific for a different type of cancer that is colorectal cancer.
Claim Rejections - 35 USC § 112 – Failure to Limit
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 7 and 8 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
The rejected claims recite limitations directed to the identified mutations being “indicative of cancer” (claim 7) or “indicative of gastric cancer” (claim 8). But claim 1, from which the rejected claims each depend, require “identifying gastric tumor specific mutations”, which thus already requires mutations indicative of cancer, and gastric cancer in particular.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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, 3-9, 13-14 and 31-33 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas (e.g.: mental processes) and a natural phenomenon without significantly more.
The claim(s) recite(s) methods of detecting, and include, for example “identifying sequence variations …compared to a reference”, “comparing .the sequence variations”, and “identifying gastric tumor specific mutations” as recited in claim 1. The claims are thus directed to the collection and comparing of information, which is and abstract idea that is a mental process (e.g.: MPEP 2106.04(a)(2)(III)(A)), the observation and evaluation of information to reach a judgment or conclusion. Where the evaluation of data to reach a conclusion includes deducing an association between variants and cancer (see also for examples claims 7-9) the asserted correlation between the presence of a variant and the presence of a pathological phenotype is accepted part of how a biological organism functions (i.e.: a genotpye:phenotype relationship), and as such this element of the claim is a natural phenomenon (e.g.: MPEP 2106.04(b)(I)).
The judicial exceptions of the claims are not integrated into a practical application because there are no practical steps related to the identification of mutations. There are no additional steps of the claims that are directed to applying or using the judicial exception(s) noted above (e.g.: MPEP 2106.04(d)(I)). The claims end with the identifying step as recited in claims 1, which is itself a judicial exception as detailed above. Here it is noted that while claims 32 and 33 recite a step of performing surgery or administering a chemotherapeutic agent, these broadly presented treatments are not set forth as being directed to any particular pathology (i.e.: any surgery or any chemotherapeutic agent) that is relevant to the detected mutations (MPEP 2106.04(d)(2)).
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims only broadly recite steps of detection of preparing sequencing libraries. However, such steps were well understood, routine and convention in the prior art (e.g.: MPEP 2106.05(d)). For example see pages 8 and 21 of the instant specification, as well as Rothwell et al (2016) and Xia et al (2016) which each teach that generating sequencing libraries from cell-free DNA and cellular DNA from whole cells in a blood sample was well established in the prior art.
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.
Claim(s) 1, 3, 4, 5, 6, 7, 8, 9, 13, 14, 31, 32, and 33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Xia et al (2017; as cited on the IDS of 05/25/2022) in view of Liu et al (2016).
Xia et al teaches the detection of background somatic mutations in white blood cells (WBC) and the use of such mutations in filtering mutations detected in cell-free DNA from subjects with cancer to identify mutations in cell-free DNA that are of tumor-derived origin. Relevant to the limitations of the claims, Xia et al teaches generating sequence libraries and identification of sequence variations in cfDNA from plasma (e.g.: p.5- Blood plasma isolation) (relevant to claim 3) and cellular DNA from white blood cells obtained from whole blood (relevant to claim 4) as compared to a reference genomic sequence (e.g.: p.6 - Extraction of cfDNA; Multiplex PCR and sequencing library construction; Data filtering and analysis). The reference further teaches the comparison of detected mutants in the cfDNA and the cellular DNA from colon cancer subjects (relevant to claims 9) (e.g.: p.6 - Mutant allele frequency in cfDNA and WBCs in the population and in individuals; p.2 -Validating the detecting sensitivity using the standard reference and tumor samples; Table S2 – “… and all the three samples were filtered by using the white blood cells as the background” (relevant to claims 5 and 6)) to remove background somatic mutations that do not originate from the tumor (relevant to claim 7).
Relevant to claims 13, 14 and 31, as consonant with the election, Xia et al teaches cfDNA mutations that are not in the WBC samples from the subject which are in the TP53 gene locus (e.g.: see Table S2 and the mutations in chromosome 17 in positions between chr17:7,661,779-7,687,546). Additionally, Xia et al notes that mutations in TP53 mutations are frequent in solid organ tumours (e.g.: p. 5).
Xia et al does not teach identifying mutations in cell-free DNA, which are not in white blood cell DNA, that are indicative of gastric cancer in particular (as recited in claim 1 and in claim 8). Xia et al does not teach performing surgery on a subject with gastric tumor specific mutations (relevant to claims 32 and 33).
However, the detection of gastric cancer related mutations in tumor-derived cell-free DNA, and the treatment of gastric cancer with surgery, were each known in the prior art and are taught by Liu et al.
Liu et al teaches that a high frequency of gene mutations contained in circulating cell-free DNAs (cfDNAs) provides evidence to assess the tumor occurrence and progression, and that mutations in genes such TP53 occur with high frequency in human cancers (e.g.: p.2- Circulating DNAs with gene mutations). Additionally relevant to the rejected claims, Liu et al teaches the surgical resection is a typical treatment for gastric cancer (e.g.: p.1 – left col).
It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to have performed the analysis of mutations found cfDNA and WBC cellular DNA, as taught by Xia et al, using a sample from a subject with gastric cancer to detect gastric tumor related mutations in cell free DNA, as taught by Liu et al. The use of cfDNA and WBC cellular sample from a gastric patient as taught by Liu et al, in the methods of analysis of Xia et al, would be the simple substitution of one known sample for another with predictable results. The skilled artisan would have a reasonable expectation of success based on the expressed teachings of Liu et al that cfDNA from subjects with gastric tumors contains tumor-derived DNA harboring mutations. It would have further been obvious to treat a subject with gastric cancer, as taught by Liu et al, that is analyzed by the methods of Xia et al, with surgery, based on the expressed teachings of Liu et al that surgical resection is a typical treatment for gastric cancer. The skilled artisan would thus recognize that applying such a treatment may help to alleviate the pathological effects of a tumor that is within the subject.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHEN THOMAS KAPUSHOC whose telephone number is (571)272-3312. The examiner can normally be reached M-F, 8am-5pm.
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Stephen Kapushoc
Primary Examiner
Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683