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
Claims 7, 9-10, 12-13, 15, 17-19, 31 are pending. Claims 1-6, 8, 11, 14, 16, 20 are canceled and claims 15 and 25-31 withdrawn. Claims 7, 9-10, 12-13, 17-19, 21-24 and 26-27 are pending with respect to liver and pancreatic cancer, as digestive system tumors were previously elected. Claim 22 and 24 are under examination with respect to primers SEQ ID NO 9 and 10. Claim 23 and 26 is under examination with respect to 5-methylation. Claims 26 and 27 were erroneously indicated on the PTO326 dated 09/25/2025 as being withdrawn however as indicated in the office action mailed 09/25/2025 these claims were not withdrawn but under examination and previously rejected. This action is written in response to applicant' s correspondence submitted 1/26/2026. 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 Any rejections not reiterated in this action have been withdrawn as necessitated by applicant' s amendments to the claims.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.
Withdrawn Rejections
The objection to claim 1 is withdrawn in view of the amendment to the claims.
The objection to claim 19 is withdrawn in view of the amendment to the claims.
The rejection of claims 7-10, 12-13, 16-24, 26, and 27 under 35 USC 112(b) is withdrawn in view of the amendment to the claims.
The rejection of claims 7-10, 12-13, 16-21, 23, 26, and 27 under 35 U.S.C. 102(a)(1) as being anticipated by Toung (US20170175205 A1) is withdrawn in view of the amendment to the claims.
New Grounds of Rejection Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 10, 12-13, 17 and 19 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 10 recites the broad recitation the full length or fragment of the polynucleotide, and the claim also recites polynucleotide consists of residues 281-309 or 282-308 of SEQ ID NO 1 which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Because the claim requires the full length of the polynucleotide but then requires a fragment that consists of only residues 281-309 or 282-309 of SEQ ID NO 1 (which is a polynucleotide) it is unclear what is required for the claims. Additionally claim 10 is unclear because it is unclear what is encompassed by the method of preparing a pan-cancer detection agent because the claim requires providing a polynucleotide and designing a detection agent but the detection agent is for detecting a target sequence which is the full length or fragment of the polynucleotide. It is unclear if said polynucleotide consists of residues 281-309 or 282-308 of SEQ ID NO 1 limits the polynucleotide that is provided or the designing of the detection agent. Further there is no nexus between preparing a pan-cancer detection agent the process steps recited. The claim only requires providing a polynucleotide and designing a detection marker, there is no active steps of preparing a pan-cancer detection agent and it is unclear how providing a polynucleotide results in preparing a pan-cancer detection agent as providing a polynucleotide does not necessarily result in a pan-cancer detection agent.
Claims 12 recites “the gene sequences comprises gene panels or gene groups” however neither claim 12 or claim 10 requires a gene panel or a gene group. Claim 12 depends from claim 10 which requires a fragment of only 26-28 nucleotides as claim 10 recites polynucleotide that consists of residues 281-309 and 282-308 of SEQ ID NO 1, which does not constitute a gene, much less a gene panel or gene group. It is unclear what is required for the detection agent when the agent detects a gene sequence that comprises a gene panel or group of genes. It is unclear how the gene sequence comprises a gene panel or group of genes when the gene sequence is only 26-28 nucleotides in length and provides no gene panel or group of genes but merely a fragment of a sequence.
Claim 17 recites the limitation "the combined gene group of partial or all of the methylation sites" in 7 line of the claim. There is insufficient antecedent basis for this limitation in the claim. Claim 17 depends from claim 7. Claim 7 requires a polynucleotide that consists of residues 281-309 or 282-308 of SEQ ID NO1. Claim 7 does not require a gene group or a combined gene group. It is unclear what the combined gene group encompasses is the combined gene group SEQ ID NO 1 and additional gene groups or is the group limited to methylation sites of 281-309 and 282-308 of SEQ ID NO 1? There are no recitations of any genes or combined gene groups recited in claim 7. Claim 7 limits the polynucleotide to 26-28 nucleotides in length and it is unclear how detection of this region encompasses a combined gene group.
Claim 19 recites said tumor detection agent or kit specifically detects the polynucleotide or a gene panel or gene group containing the polynucleotide. This recitation renders the claim indefinite. It is unclear what is required for the detection agent or kit. Claim 19 depends from claim 7 and claim 7 requires that the polynucleotide is only 26 or 28 nucleotides in length. It is unclear what is required for the tumor detection agent or kit encompassed by claim 19 because claim 7 limits the detection agent to only 26 or 28 nucleotides in length. It is unclear if claim 19 requires that it is part of a larger sequence or gene, even though the claim requires only the recited residues of SEQ I DNO 1 or if tumor detection agent further comprises additional genes or gene panels, however the claims do not recite or require additional genes only that the agent comprises a gene panel or gene group containing the polynucleotide. As such it is unclear what the limitations of the detection agent or kit, the metes and bounds of the claim are unclear and one of ordinary skill in the art would not be reasonably apprised of the scope of the claim.
Claim Rejections - 35 USC § 112 4th paragraph
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.
Claim 17 and 19 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.
Claim 17 and claim 19 depend from claim 7. Claim 7 limits the polynucleotide to consist of residues 281-309 or 282-308 of SEQ ID NO 1 and therefore excludes any additional sequence. Claim 17 requires a combined gene panel group and claim 19 requires a gene panel or gene group containing the polynucleotide, however claim 7 limits the polynucleotide to only a small fragment. Claim 17 and claim 19 do not further limit the polynucleotide and but broaden the scope of the polynucleotide as both claims require the polynucleotide to be part of a gene panel or gene group. 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.
Response to Arguments
The response traverses the rejection on page 10 of the remarks mailed 01/26/2026. The response asserts the claims have been amended to recite a gene panel or gene group in claim 19. This response has been reviewed but not found persuasive. While claim 19 no longer recites back to a limitation in the previous claim, claim 19 renders the claim vague and indefinite because it is unclear the polynucleotide recited in claim 1 is a gene panel or gene group. Claim 19 does not require nor recite further comprising additional genes, gene groups, etc. but requires the detection reagent to be a gene panel or gene group but claim 1 requires the polynucleotide to only consist of a small region without additional sequence. It is unclear how the tumor detection agent or kit specifically detecting the polynucleotide or a gene panel or a gene group containing the polynucleotide when claim 7 does not require any additional genes and limits the polynucleotide to only a 26 or 28 nucleotide region of SEQ ID NO 1 without additional sequence. For these reasons the rejection is maintained.
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 10, 12-13 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.
The amendment to claim 10 to recite “pan-cancer detection agent” changes the scope of the claims and is not supported in the disclosure and raises the issue of new matter. The specification provides no indication of a pan-cancer detection agent. The specification teaches a designing a tumor detection agent but does not disclose a pan-cancer detection agent. The specification teaches a universal DNA methylation tumor marker, STAMP (specific tumor aligned methylation of pan-cancer) (see pg. 6) but does not teach a pan-cancer detection agent. While STAMP is a universal DNA methylation tumor marker, as asserted by the specification this does not provide support or teach a pan-cancer detection agent or method of preparing a pan-cancer detection agent, this only provides support for a universal DNA methylation tumor marker and not pan-cancer detection agent. The disclosure only has support for preparing a tumor detection agent but not a pan-cancer detection agent.
Maintained Rejections
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 7, 9-10, 12-13, 17-19, 21, 23 and 26-27 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more. The claims recite a law of nature and an abstract idea including mental processes. This judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. This rejection was previously presented and has been rewritten to address amendment to the claims.
The following inquiries are used to determine whether a claim is drawn to patent-eligible subject matter.
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? Yes, all of the claims are directed to a process.
Step 2A. Is the claim directed to a law of nature, a natural phenomenon or an abstract idea (judicially recognized exception) and does the claim recite additional elements that integrate the judicial exception into a practical application?
Yes, the claims are directed to law of nature/natural phenomenon. Claim 7 recites a method of detecting one or more tumors by detecting modification of CpG sites. The recited relationship is a natural phenomenon that exists apart from any human action. This type of correlation is a consequence of natural processes.
The claims also recite the judicial exception of an abstract idea and particularly mental processes. Claim 7 recites the abstract idea of a mental process. Claim 7 recites the step of “detecting” one or more tumors in a subject. Claim 10 recites “designing” a pan-cancer detection agent for specifically detecting a target sequence. Claim 18 recites “analyzing” the modification. The broadest reasonable interpretation of the detecting, identifying, designing, and analyzing steps are a step that can be accomplished mentally by evaluating data and critical thinking process wherein one mentally reads information in a database or report regarding methylation levels then draws a mental conclusion. Designing can be accomplish mentally by evaluating data and critical thinking process to design an oligonucleotide. Such detecting, analyzing, designing and identifying thereby encompasses process that may be performed mentally and this is an abstract idea.
Having determined that the claims recite a judicial exception, it is then determined whether the claims recite additional elements that integrate the judicial exception into a practical application.
The claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s). For example, the claims do not practically apply the judicial exception by including one or more additional elements that the courts have stated integrate the exception into a practical application:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
An additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
An additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
An additional element effects a transformation or reduction of a particular article to a different state or thing; and
An additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological
environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
In addition to the judicial exceptions the claims recite the type of tumor, type of sample (claim 9), type of detection agent (claim 12-13, 18, 21, 23).. These additional steps/elements are not considered to integrate the judicial exception into a practical application because they merely add insignificant extra-solution activity (data gathering) to the judicial exception.
Step 2B - Does the claim recite additional elements that amount to significantly more than the judicial exception? No.
Herein the claims as a whole are not considered to recite any additional steps or elements that amount to significantly more than well-understood, routine, and conventional activities in the art and do not add something “significantly more” so as to render the claims patent-eligible. The step of specific tumor sample, tumor type, detection agent, and assay merely instructs a scientist to use well established, routine and conventional nucleic acid techniques to gather samples for diagnostic analysis. As address in the instant specification methods of methylation analysis are well-known in the art (See pg. 8 and 9).
The step of detecting methylation in a tumor sample constitutes a data gathering step required to apply the law of nature/natural phenomenon. It is acknowledged that the claims name a particular fragment of SEQ ID NO 1, to determine a CpG methylation modification however the claims do not require a particular, non-conventional primer or probe consisting of or comprising a specific nucleotide sequence or any other specific reagent that is used to accomplish such determining such that the claims would recite significantly more than the judicial exception. It is noted that claims that require the primer pair of SEQ ID NO 9 and 10 are patent eligible and not rejected. The targets to be detected are part of the judicial exception and thereby the naming of the targets does not add something “significantly more” to the recited judicial exceptions.
The additional steps and elements are recited at a high degree of generality and are all routine, well understood and conventional in the prior art. The recited steps and elements do not provide inventive concept necessary to render the claims patient eligible. There is no combination of elements in this step that distinguishes it from well-understood, routine and conventional data gathering activity engaged in by scientists prior to applicant’s invention and at the time the application was filed. Many cited prior art references in this record demonstrate that these techniques were conventional at the time of the invention. The prior art demonstrates that CpG sites and fragments of SEQ ID NO 1 encompass CpG probes and locations on the Illumina Human Methylation 450k array. Toung (US20170175205 A1) teaches methylation and methylation detection at positions cg26248878 and cg18240143 both of which comprise Ch14:60951976-60952946 which is a sequence of SEQ ID NO 1. Thus the prior art and specification demonstrates it was routine, well-known and conventional in the art to determine methylation of SEQ ID NO 1 in biological samples. The dependent claims do not provide significantly more to the claims outside of the judicial exception as they encompass conventional techniques as described in the instant specification as noted above.
Response to Arguments
The response traverses the rejection on pages 11-13 of the remarks mailed 01/26/2026. The response asserts that claim 7 include a step of treating DNA extracted from one or more samples comprising tumor cells with a reagent that modified DNA in a methylation specific manner and thereby adding significantly more than the judicial exception. The response further asserts that the claim as amended detects a wide variety of tumors detected by the method based on methylation patterns of specific polynucleotides. This response has been thoroughly reviewed but not found persuasive. As addressed in the rejection above, treating DNA extracted from a sample comprising a tumor cell with a reagent to modify DNA in a methylation specific manner was well known, routine, and conventional in the art and is not significantly more than the judicial exception. This step does not integrate the judicial exception as the steps are data gather steps that do not apply or integrate the judicial exception in any way. The steps in addition to the judicial exception are data gathering steps recited at a high level of generality employing techniques that were well-established, routine and convention at the time of the invention. Here the claims include extracting DNA from a sample, modifying DNA in a methylation specific manner and detecting methylation. Prior to the invention, Toung teaches isolating DNA from a sample, bisulfite treating DNA and detecting methylation using bisulfite sequencing libraries (see para 161-163). Additionally detecting a wide variety of tumors based on methylation pattern of specific polynucleotides is a judicial exception, the methylation pattern is a result of the presence of the tumor and as such cannot be relied upon to integrate a judicial expectation as it encompasses a natural correlation which is a judicial exception.
The response addresses claim 10 on page 12-13 of the remarks as asserts that rejection of claim 10 is based solely on the word “designing” and without the context of the remainder of the claim or specification. The response asserts that claim 10 is directed to method of preparing a pan-cancer detection agent based on a specific target sequence consisting of residues 281-309 and 282-308 of SEQ ID NO 1. The response asserts that the pan-cancer utility is a technical improvement over the general methods available in the art and takes the claimed invention beyond mere mental process and points to para 17-18 and asserts that claim 10 is directed to patent eligible subject matter. This response has been thoroughly reviewed but not found persuasive. The process steps of claim 10 encompass providing a polynucleotide and designing a detection agent for specifically detecting a target sequence which is the full length or fragment of the polynucleotide, wherein said polynucleotide consists of residues 281-309 or 282-308 of SEQ ID NO 1. Claim 10 does not integrate the step of designing a detection agent, the claim merely requires providing a polynucleotide and designing a detection agent which is for detecting a target sequence, the claim does not require any other limitations. The claim does not require preparing or making a detection agent, there are no method steps directed to making a detection agent. The step of designing does not require preparing or making, the step of designing broadly encompasses a mental step. The response points to para 17-18 of pgpub of the instant application, however para 17 and 18 of US20220275452 A1 only address the use of a polynucleotide and the tumors of the preferred embodiment. This does not define “designing” and none of the steps recited in claim 10 limit designing to using, making or preparing a detection agent. The claim only requires providing a polynucleotide and designing a tumor agent. Additionally limitations of the specification cannot be read into the claims as such the claims have been given their broadest reasonable interpretation to encompass a mental step of creating or planning that is a problem solving activity that can be performed solely in the mind. The claim does not require producing a detection agent only designing. There are no additional steps that integrate the design of a detection agent into a practical application. As such the rejection is maintained for these reasons and reasons of record.
Conclusion
Claims 22 and 24 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
As addressed previously and restated above, the claims requiring specific primers, SEQ ID NO 9 and SEQ ID NO 10 are patent eligible as the specific primer sequence was not routine, well-known or conventional in the art. If claim 7 was amended to require the use of SEQ ID NO 9 and SEQ ID NO 10 to amplifying the claimed polynucleotide region this would be free of the prior art and patent eligible.
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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/SARAE L BAUSCH/ Primary Examiner, Art Unit 1699
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