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 .
Response to Amendment
The amendment filed 07/01/2026 is acknowledged. Regarding the Office action mailed 04/01/2026:
The objection to the specification for failure to comply with 37 CFR 1.831(c) is withdrawn in view of the substitute specification.
The objection to claim 1 is moot in view of the amendment.
The provisional double patenting rejection over co-pending application 18/580,445 is withdrawn in view of the terminal disclaimer.
The rejections under 35 USC 112(b) are withdrawn in view of the amendments to the claims.
The rejection under 35 USC 101 is withdrawn in view of the amendment to claim 1.
New grounds of rejection are set forth below as necessitated by the amendment.
Claim Objections
Claim 1 is objected to because of the following informalities: in line 5, “second esophageal biomarker” should read “second esophageal cancer biomarker”. As all other claims depend from claim 1, they are objected to for the same reason. Appropriate correction is required.
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 4, 6, 18, 116, 117 and 118 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 requires that the “first esophageal cancer biomarker” is “on the surface of the EVs”.
However, claim 4, which depends from claim 1, allows for the biomarker to be RNA, which would not be found “on the surface of the EVs”. Therefore, claim 4 encompasses alternatives that are not compatible with the requirements of claim 1.
Likewise, claim 6 recites alternatives where the first biomarker is an intravesicular biomarker or intravesicular RNA biomarker, neither of which is compatible with the requirements of claim 1.
Likewise, claim 116 permits the first biomarker to be RNA, which is not compatible with claim 1. Claim 18 depends from claim 116 and is rejected for the same reason.
Claim 117 requires the first biomarker to be selected from a list of “intravesicular biomarkers” and is therefore incompatible with claim 1.
Claim 118 requires the first biomarker to be an RNA transcript, which again, would not be found on the surface of an EV. In addition, among the recited list, are markers that, even in protein/polypeptide form, are indicated elsewhere in the disclosure as being intravesicular, and therefore not on the surface of the EVs. For example, ACP5 (the third marker in the list) is an intravesicular marker according to claim 117. Therefore, claim 118 is not compatible with the requirements of claim 1, and even if the claim were amended to recite polypeptide or protein, rather than RNA, would still contain members which are intravesicular markers and not markers “on the surface of the EVs” as required by claim 1.
Claim 17 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 17 recites the limitation "the detecting step" in line 3. There is insufficient antecedent basis for this limitation in the claim.
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 4, 6, 17, 18, 116 and 118 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.
Claim 1 requires that a first oligonucleotide comprised by a capture agent directed to an EV surface biomarker is ligated to a second oligonucleotide comprised by a probe that binds to a second biomarker. In the case of claims 4, 6, 17, 18, 116 and 118, an RNA biomarker is recited. There is no support in the disclosure as-filed where an oligonucleotide of a probe targeting an RNA biomarker is ligated to the oligonucleotide of the capture agent targeting an EV surface marker.
Indeed, the specification states (paragraph [38]): “…in some embodiments where a target biomarker is or comprises a surface biomarker and/or an intravesicular marker, such a target biomarker may be detected involving a proximity ligation assay…”. On the other hand, the specification states (paragraph [39]): “…where a target biomarker is or comprises an intravesicular RNA (e.g., but not limited to mRNA and noncoding RNA such as, e.g., orphan noncoding RNA, long noncoding RNA, piwi-interacting RNA, microRNA, circular RNA, etc.) marker, such a target biomarker may be detected involving a nucleic acid detection assay. In some embodiments, an exemplary nucleic acid detection assay may be or comprise reverse-transcription PCR…”.
Wherever the specification discusses detection by ligation, as recited in claim 1, it refers to surface biomarkers or intravesicular biomarkers but not RNA biomarkers. For example, at paragraph [114]: “In some embodiments, "detecting" may include determining, measuring, assessing, or quantifying a form of measurement indicative of an entity of interest (e.g., a ligated template indicative of a surface biomarker and/or an intravesicular biomarker, or a PCR amplification product indicative of an intravesicular mRNA).” At paragraph [217]: “Exemplary protein-based methods of detecting one or more provided markers include, but are not limited to, proximity ligation assay…”.
Applicant may overcome this rejection by pointing to clear disclosure in the application as-filed where an RNA biomarker is detected by using a probe targeting said RNA, wherein said probe is coupled to an oligonucleotide, which oligonucleotide is ligated to another oligonucleotide coupled to a capture agent or probe targeting another biomarker.
Conclusion
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 SAMUEL C WOOLWINE whose telephone number is (571)272-1144. The examiner can normally be reached 9am-5:30pm.
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/SAMUEL C WOOLWINE/Primary Examiner, Art Unit 1681
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