DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The claims filed 12/18/2025 are under consideration.
The amendments and arguments presented in the papers filed 12/18/2025 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 8/19/2025 listed below have been reconsidered as indicated.
a) The objection to the specification is withdrawn in view of the amendments to the specification.
b) The rejections of claims 7-9, 16-23 and 26-27 under 35 U.S.C. 101 are withdrawn in view of the amendments to claim 7.
c) The rejections of claim(s) 7-9, 16-21, 23, 26 and 27 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Dahl (WO 2017/072292 A1) are withdrawn in view of the amendments to claims 7 and 16 requiring the detection of the elected species of positions 204-223 of SEQ ID NO: 1.
d) The rejections of: claim(s) 7-9, 16-21, 23 and 26-27 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Wielscher (US 2017/0283887 A1); and claim(s) 22 under 35 U.S.C. 103 as being unpatentable over Wielscher (US 2017/0283887 A1) in view of Dahl (WO 2017/072292 A1), are withdrawn in view of the amendments to claim 7 and 16, requiring the detection of a polynucleotide or fragment consisting of positions 204-223 of SEQ ID NO: 1.
The Examiner’s responses to the Remarks regarding issues not listed above are detailed below in this Office action.
New and modified grounds of rejection necessitated by amendment are detailed below and this action is made FINAL.
Election/Restrictions
Applicant elected without traverse Group I, claims 7-9, 16-23 and 26-27, in the reply filed on 6/30/2025.
Applicant elected without traverse the species that is positions 204-223 of SEQ ID NO: 1 or 2 in the reply filed on 6/30/205. The election of positions 204-223 corresponds to methylation sites 021 to 024 of SEQ ID NO: 1, which are amplified by the primer pair having the full-length sequences of SEQ ID NOs: 15 and 16. Claim 22 is included with the election of one of the particular positions set forth in claim 20.
Claims 10, 12-13, 15, 24, 25 and 28-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 6/30/2025.
Information Disclosure Statement
The listing of references in the specification or the citation of references throughout the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892 or cited on a submitted IDS, they have not been considered.
Drawings
High resolution copies of the drawings may be accessed via PAIR/Patent Center Retrieval using the Supplemental Content tab.
Claim Interpretation
Amended claim 7 is being interpreted as follows. The claim states “detecting a 5-methylation modification on a CpG site of a polynucleotide using a tumor detection agent or kit, wherein the polynucleotide consists of positions 204-223 of SEQ IDNO: 1”. The step is limited to “detecting a 5-methylation modification on a CpG site of a polynucleotide consisting of positions 204-223 of SEQ IDNO: 1 using a tumor detection agent or kit”.
The structure of the “detection agent” or an element of a “kit” used in not defined and is not limited to primers that amplify a polynucleotide consisting of positions 204-223 of SEQ IDNO: 1 or a probe that hybridizes a polynucleotide consisting of positions 204-223 of SEQ IDNO: 1.
It is noted the treated DNA of the first recited step is not required to be used in the “detecting” step.
Amended claim 16 is interpreted as follows. The claim states “detecting a modification on CpG site(s) of a target sequence in the nucleic acid of (i), wherein the target sequence is a polynucleotide which is a fragment consisting of positions 204-223 of SEQ ID NO: 1”. The step is limited to detecting a modification on CpG site(s) of a fragment consisting of positions 204-223 of SEQ ID NO: 1 in the nucleic acid of (i).
It is noted as stated in the claim the treated extracted nucleic of step (ii) is not required for use in step (iii) as it is the nucleic acid of step (i) that is specifically referenced.
Claim 22 states primers of the tumor detection agent or kit are at least one of the recited primer pairs consisting of the specified SEQ ID NOs. It is noted the claim does not require the use of any of the primers in the “detecting” step of claims 7 or 21. It is further noted that the claim does not require the primers as part of the tumor detection agent or kit as it only limits the primer option of claim 21 and does not exclude the probes of claim 21. Claim 22 broadly encompasses:
said tumor detection agent or kit comprises:
primers,
wherein said primers are:
SEQ ID NO: 15 and 16;
SEQ ID NO: 5 and 6;
SEQ ID NO: 7 and 8;
SEQ ID NO: 9 and 10;
SEQ ID NO: 11 and 12; or
SEQ ID NO: 13 and 14,
or 2) probes.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 7, 9, 16, 17, 18, 21, 22, 23, 26 and 27 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 claims have been amended to specify “the polynucleotide consists of positions 204-223 of SEQ IDNO: 1” (claim 7) and “the target sequence is a polynucleotide which is comprises a fragment consisting of positions 204-223 of SEQ ID NO: 1” (claim 16). The polynucleotide to be detected using the detection reagent or kit consists of the following 20-nucleotides: cggagccgaa gtgatcgccg.
The instant specification does not use the word “consists” or “consisting”. The instant specification does not disclose a 20-nucleotide sequence as part of the Sequence Listing.
The specification does not provide support for or demonstrate possession of a nucleic acid, polynucleotide or fragment that “consists” of positions 204-223 of SEQ ID NO: 1. While this region is flagged in Example 1 (p. 10) of the specification, the region is only identified within the context of the entirety of SEQ ID NO: 1. Furthermore, no primers or probes that amplify or that are specific for, respectively, a nucleic acid “consisting of positions 204-223 of SEQ ID NO: 1” are disclosed. Alternatively, the specification does teach primers that amplify fragments that comprise positions 204-223 of SEQ ID NO: 1, namely primer pairs comprising the sequences of: SEQ ID NOs: 5 and 6; and SEQ ID NOs: 15 and 16.
There is no evidence that the nucleic acids from a sample include a nucleic acid “consisting of positions 204-223 of SEQ ID NO: 1”.
The instant specification does not describe any detection reagent or kit that specifically detects a polynucleotide consisting of the sequence: cggagccgaa gtgatcgccg
Detecting 5-methylation modification using a detection reagent or kit specific for a 20-nucleotide polynucleotide with the sequence cggagccgaa gtgatcgccg is new matter.
Regarding claim 18, the amended claim depends from claim 16, which was amended to require a step of “treating extracted nucleic acid from (i) with a reagent that modifies DNA in a methylation- specific manner”.
The instant specification does not support a method in which extracted a nucleic acid is treated twice. The first treatment is part of claim 16, “treating extracted nucleic acid from (i) with a reagent that modifies DNA in a methylation- specific manner” and the second treatment is part of claim 18, “treating extracted nucleic acid from (i) to convert unmodified cytosine into uracil”. The scope of claim 18 encompasses new matter.
Regarding claim 19, the claim recites “said tumor detection agent or kit specifically detects the polynucleotide”, which in claim 7 is specified as “consisting of positions 204-223 of SEQ ID NO: 1”. The instant specification discloses no such reagent. At best, the instant specification demonstrates tumor detection agents that amplify a polynucleotide comprising positions 204-223 of SEQ ID NO: 1.
Regarding claims 17 and 23, the instant specification demonstrates detecting methylation, i.e., 5-methylcytosine, of a sequence comprising positions 204-223 of SEQ ID NO: 1. The instant specification does not demonstrate detecting or the possession of a polynucleotide or fragment consisting of positions 204-223 of SEQ ID NO: 1, where the CpG site have 5-hydroxymethylation, 5-formylcytosine or 5-carboxylcytosine modifications.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 7, 9, 16, 17, 18, 21, 22, 23, 26 and 27 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:
An in vitro method of detecting a risk of a leukemia, breast cancer, colorectal cancer, esophageal cancer, liver cancer, lung cancer and pancreatic cancer, comprising:
(i) providing a sample from a subject;
(ii) extracting nucleic acid from the sample;
(iii) detecting modification on CpG site(s) of a target sequence in the extracted nucleic acid of (ii) using primer pairs comprising: SEQ ID NOs: 5 and 6; OR SEQ ID NOs: 15 and 16,
(iv) identifying the subject as having a high-risk of leukemia, breast cancer, colorectal cancer, esophageal cancer, liver cancer, lung cancer and pancreatic cancer based on hypermethylation detected in (iii) relative to methylation of the target sequence in non-cancer samples,
does not reasonably provide enablement for embodiments in which a nucleic acid consisting of positions 204-223 of SEQ ID NO: 1 is analyzed for all 5-methylation modifications of a CpG using primers that are SEQ ID NO: 15 and 16; 5 and 6; 7 and 8; 9 and 10; 11 and 12; or 13 and 14.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The claims encompass embodiments in which primers of claim 22 are not only part of the detection reagent or a part of the kit, but that are specifically used in the method of claim 7 for carrying out the “detecting” step. The instant specification demonstrates that none of the primers of claim 22 amplify or produce a polynucleotide that consists of positions 204-223 of SEQ ID NO: 1. In fact, the primers of SEQ ID NO: 15 and 16 and SEQ ID NOs: 5 and 6 only produce a polynucleotide comprising a sequence consisting of positions 204-223 of SEQ ID NO: 1.
Thus, methods in which those particular primers are used for the amplification and analysis of a polynucleotide consisting of positions 204-223 of SEQ ID NO: 1 are not enabled.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 7, 9, 19, 21, 22 and 23 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 7, the claim states “the tumor detection agent or kit comprises”, and then lists a series of methodologies as opposed to any particular product, composition or structure that is part of the detection agent or kit. It is unclear what is required by a tumor detection or kit that comprises a methodology.
Conclusion
No claims allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH G. DAUNER/Primary Examiner, Art Unit 1682