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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/9/2025 has been entered.
Applicant’s arguments and amendments have been thoroughly reviewed and considered. Claims 39 and 46 have been canceled. Claims 1, 25-26, and 44 are pending and are examined on the merits herein.
Response to Applicant’s Amendments
Claim Objections
Claims 1, 25-26, 39, 44, and 46 were objected to for various informalities. The objections for claims 25-26 and 44 were not fully addressed, and so these objections have been maintained-in-part. The objection for claim 1 has been withdrawn.
Applicant states in their Remarks that they have canceled claim 44 as it was a substantial duplicate of claim 26 (Remarks, page 9). However, claim 44 is still currently pending, and so this objection is maintained.
Claims 39 and 46 have been canceled, and so these rejections have been rendered moot. See also new grounds of objection below. It is noted that Applicant has not provided any arguments against these objections in their Remarks.
35 USC 112(a) Rejections
Claims 1, 25-26, 39, 44, and 46 were rejected under 35 USC 112(a) as failing to comply with the enablement requirement. Applicant’s arguments and amendments have been thoroughly reviewed and considered. These rejections have been withdrawn for all currently pending claims. Claims 39 and 46 have been canceled, so these rejections have been rendered moot. See also “Response to Applicant’s Arguments” below.
35 USC 112(b) Rejections
Claims 1, 25-26, 39, 44, and 46 were rejected for various indefinite issues. Applicant’s arguments and amendments have been thoroughly reviewed and considered. These rejections have been maintained-in-part for all currently pending claims. See also “Response to Applicant’s Arguments” and new grounds of rejection below. Claims 39 and 46 have been canceled, and so these rejections have been rendered moot.
Response to Applicant’s Arguments
Regarding the 35 USC 112(a) Rejections, Applicant’s arguments and amendments were persuasive to withdraw the rejections. In particular, it is noted that in para. 93 of the instant specification, it is stated that only the portion of the sample to be tested for gene methylation was heavy salt transformed, while the gene point mutation detection portion of the sample is not heavy salt transformed. Paras. 9 and 15 also provide support for the detection of SEQ ID NOs: 1-3 with the claimed primers and probes without altering said sequences. However, see the new grounds of rejection in the 35 USC 112(b) section below concerning the newly added limitation to claim 1.
Regarding the 35 USC 112(b) Rejections, Applicant provided arguments for the use of the phrases “driver genes,” “point mutation positive quality control,” “methylation positive quality control,” and “negative control,” in the instant claims.
Regarding “driver genes,” Applicant states that the instant specification describes said genes as those that harbor mutations that promote tumorigenesis and cancer progression (Remarks, page 11). In the “Background Art” section of the instant specification, no specific definition of driver genes is provided, though this phrase is used to describe genes that can be used for cancer diagnosis (para. 6). By Applicant’s own admission, the instant specification later refers to the claimed point mutation genes as “target genes.”
The rationale for the rejection of “driver genes” as indefinite in claims 25-26 and 44 as maintained below is that this term is not used to describe the target genes for detection in claim 1, but is then used in the dependent claims, and it is unclear if this later introduction of the term imparts any particular structure. As there is no specific definition for the term “driver genes,” in the specification, it is improper to impart limitations into the claims solely based on the teachings or examples of the specification if these limitations are not inherent or explicitly claimed. If Applicant would like to use the phrase “driver genes” within the claim set, it is recommended to incorporate this phrase into instant claim 1.
Regarding “point mutation positive quality control,” “methylation positive quality control,” and “negative control,” in the instant specification, paras. 101 and 106 state these components were used in Examples 2 and 3, but do not state the specific structure of these components. Para. 112 states the use of a point mutation positive plasmid, a methylation positive plasmid, and a negative plasmid, though it is noted that this terminology is not identical to the claimed terms. Thus, no specific definitions for these terms appear in the instant specification. Applicant states the intended meanings of these terms in their Remarks (page 12), but it does not appear that these meanings are actually incorporated into the instant specification. Thus, similar to the rejection of “driver genes” described above, it is unclear what structural components are required for the creation and use of these controls, and it is improper to impart limitations into the claims solely based on the teachings or examples of the specification if these limitations are not inherent or explicitly claimed.
Thus, Applicant’s arguments regarding the 35 USC 112(b) Rejections are not persuasive, and those terms/aspects of the claims which were deemed indefinite in the Final Rejection mailed 5/15/2025 and which were not amended in the instant claims remain indefinite.
Claim Objections
Claim 1 is objected to because of the following informalities: a phrase similar to “wherein the gene point mutation comprises a FGFR3 point mutation, a TERT point mutation, and a PLEKHS1 point mutation” should be included for the methylation genes before the disclosure of the specific sequences associated with them – for example, including “wherein the gene methylation comprises OTX1 methylation, NID2 methylation, and NRNI methylation” between paras. 3 and 4 of the claim. Finally, in the description of the primers and probes used for each gene, the phrase “the forward primers and reverse primer and probe for…” should simply read “the forward primer, reverse primer, and probe for...” Appropriate correction is required.
Claim 25 is objected to because of the following informalities: in lines 1-2, “wherein primers and probes for point mutations and methylation levels” should read “wherein the specific primers and probes for detecting the gene point mutation and/or gene methylation”. Additionally, line 4 states “wherein the reaction tube A is used to detect point mutations” but should read “wherein the reaction tube A is used to detect the gene point mutation.” Similarly, line 3 under the first table states “wherein the reaction tube B is used to detect methylation” but should read “wherein the reaction tube B is used to detect the gene methylation.” In the first wherein clause under the first table, “a mixture composed of the primer pairs and probes for point mutation of three driver genes FGFR3\TERT\PLEKHS1” should read “a mixture composed of the primer pairs and probes for detection of the point mutations in FGFR3/TERT/PLEKHS1.” Similarly, under the first wherein clause under the second table, “a mixture composed of the primer pairs and probes for methylation of three driver genes OTX1\NRN1\NID2 and internal reference gene” should read “a mixture composed of the primer pairs and probes for detection of methylation in OTX1/NRN1/NID2 and the internal reference gene.” These suggestions simplify the claim language, limit the repetition of limitations already described in claim 1, and better match the language used in claim 1. Appropriate correction is required.
Claims 26 and 44 are objected to because of the following identical informalities: the effective components description for Primer&Probe A and Primer&Probe B should read “a mixture of primer pairs and probes for detection of the point mutations in FGFR3, TERT, and PLEKHS1 and the internal reference gene” and “a mixture of primer pairs and probes for detection of methylation in OTX1, NRN1, and NID2 and the internal reference gene” respectively. Finally, the sequences for each primer pair and probe do not need to be reiterated, as these are already stated in claim 1. Appropriate correction is required.
Claim 44 is also objected to under 37 CFR 1.75 as being a substantial duplicate of claim 26. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
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.
Claims 1, 25-26, and 44 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.
Claim 1 is rejected due to the newly added limitation, “without requiring transformation or sequence alteration prior to detection.” This statement comes after the recitation of SEQ ID NO: 3, and so it is unclear if it is referring to only SEQ ID NO: 3 or all of the point mutation detection sequences. The latter will be interpreted to be Applicant’s intention. It is recommended to amend this phrase to read “wherein no transformation or sequence alteration of the gene point mutation sequences is required.”
Claim 1 is also indefinite because in lines 2-4 it states, “comprising specific primers and probes designed for a template of a region to be detected, wherein the region to be detected comprises at least one of a gene point mutation or a gene methylation,” (emphasis added). The subsequent body of the claim then recites six separate gene sequence regions for point mutations or methylations. It is unclear if these six sequences are intended to form the single “region” described by lines 2-4, or if these sequences are intended to be six separate regions. These would be two contradictory limitations, and so the scope of the claim is indefinite. Further, it is unknown if these six genes are within close proximity to one other so as to be considered a single region. This is made more unclear later in the claim, as the different sequences to be detected for each gene are referred to as “regions”. It is recommended to amend the first paragraph of the claim to read “comprising specific primers and probes designed for detection of regions in a template, wherein the regions to be detected comprise at least one of a gene point mutation or a gene methylation,” or similar phrasing. It is noted that such a change would then require a similar amendment to para. 5 of the claim.
Claims 25-26 and 44 are rejected due to their dependence on rejected claim 1
Claims 25-26 and 44 are also rejected due to the use of the phrase “driver genes.” This phrase does not appear in claim 1, from which these claims all directly depend, and so it is not clear if the use of this term in combination with the target genes first described in claim 1 indicates any additional structural or functional limitations for the target genes in these dependent claims.
Claims 26 and 44 are also rejected because the “point mutation positive quality control,” “methylation positive quality control,” and “negative control” components are unclear. These components are not detailed in the specification, and so it is unclear what structural components are required for the creation and use of these controls. Thus, the claims are indefinite.
Conclusion
No claims are currently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRANCESCA F GIAMMONA whose telephone number is (571)270-0595. The examiner can normally be reached M-Th, 7-5pm.
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/F.F.G./Examiner, Art Unit 1681
/ANGELA M. BERTAGNA/Primary Examiner, Art Unit 1681