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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/22/2025 was filed after the mailing date of the Non-Final Office Action on 01/22/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of Claims / Response to Amendment
This office action is in response to an amendment filed on July 22, 2025.
Claims 51-70 were previously pending. Applicant amended claims 51, 53, 58 and 67-69; cancelled claims 52, 54-57, 59-66 and 70; claims 71-73 are newly added.
Claims 51, 53, 58, 67-69 and 71-73 are currently pending, with claim 67 withdrawn.
Claims 51, 53, 58, 68-69 and 71-73 are under consideration.
All of the previously presented rejections have been withdrawn as being obviated by the amendment of the claims.
Applicant' s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
This office action contains new grounds for rejection necessitated by amendment.
Election/Restrictions
Applicant's prior election without traverse of the following species in the reply filed on November 21, 2024 is acknowledged in light of the amended claims filed on July 22, 2025.
It is noted that the Applicant's recent amendment has removed a previously elected species from claim 67 and incorporated it into independent claim 51. Namely, the elected species pertains to the subject is a surgical subject, in "Species of subject/ Risk." Accordingly, claim 67 is now directed solely to non-elected species and is therefore withdrawn from consideration. See 37 CFR 1.142(b) and MPEP § 821.03.
Applicant's election without traverse of the following species in the reply filed on November 21, 2024 is acknowledged:
Species of method further comprises: C) determining a risk in the subject based on the obtained amount of total cf-DNA or based on a comparison of a threshold total cf-DNA value or other total cf-DNA value from a different point in time (claim 53);
Species of subject/ Risk: I) the subject is a surgical subject (claim 51);
Species of Assaying for cfDNA: S) Quantitative PCR.
Priority
Regarding claims 51, 53, 58, 68-69 and 71-73, the earliest priority is 12/17/2019 because the priority document (PCT/US2019/066974) filed that date is the first to disclose "a threshold of 50 ng/mL," recited in claim 51.
Claim Interpretation -- Updated
In evaluating the patentability of the claims presented in this application, claim terms have been given their broadest reasonable interpretation (BRI) consistent with the specification, as understood by one of ordinary skill in the art, as outlined in MPEP§ 2111.
For the purpose of applying prior art, claim 53 has been amended to recite "post-surgical complication," which is a term not defined in the application's disclosure.
Page 5 of the specification provides the following relevant description regarding "post-surgical complication":
" As used herein, the compositions and methods provided herein can be used to determine an amount of total cell-free DNA and a subject's risk of complications associated with, or following, a procedure (e.g., a heart surgery). Examples of complications include, but are not limited to, death, cardiac arrest, prolonged ventilation, prolonged length of stay in the hospital, infection, and requirement of mechanical circulatory support."
Therefore, under BRI and in light of the specification, the term "post-surgical complication" is interpreted as any unfavorable medical condition, event, or outcome occurring after a surgical procedure, including but not limited to those listed in the specification.
Thus, this term under BRI encompasses any condition deviating from a healthy recovery, as such deviation could be reasonably viewed as unfavorable.
For the purpose of applying prior art, regarding claim 68, it recites "amplification-based quantification assay," which is described by the application's disclosure as follows:
"In some embodiments of any one of the methods provided herein, the amplification-based quantitative assay is any quantitative assay, such as whereby nucleic acids are amplified and the amounts of the nucleic acids can be determined. Such assays include those whereby nucleic acids are amplified with the MOMA primers as described herein and quantified, or other primers. Such assays also include simple amplification and detection, hybridization techniques, separation technologies, such as electrophoresis, next generation sequencing and the like." (specification, page 11-12)
Therefore, while the disclosure refers to the amplification-based quantification assay as any quantitative assay, it also indicates that the term further encompasses broader assay types, such as hybridization and separation techniques like electrophoresis, which is typically qualitative rather than quantitative 1.
Therefore, under BRI the term "amplification-based quantification assay" is interpreted to encompass any assay.
Claim Rejections - 35 USC § 112(b) -- New Grounds
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.
Claim 71 is rejected under 35 U.S.C. 112(b), 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 71 recites:"[t]he method of claim 51, wherein the threshold total cf-DNA value is 100 ng/mL." However, this recitation is indefinite because claim 51 does not recite "a threshold total cf-DNA value," instead it recites "a threshold of 50 ng/mL." It is unclear whether claim 71 introduces a new and additional threshold or is intended to replace the threshold recited in claim 51. As the recited threshold in claim 51 represents a specific point and not a range, a threshold of 50ng/mL cannot encompass a threshold of 100ng/mL. Therefore, the scope of the claim is indefinite because the relationship between the two thresholds is unclear.
Claim Rejections - 35 USC § 112(a) -- New Grounds
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.
Claims 51, 53, 58, 68-69 and 71-73 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claims 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 51 recites a method of determining an amount of total cf-DNA in a sample from a surgical subject, comprising a step of comparing the amount of total cf-DNA to a threshold of 50 ng/mL to determine whether or not the total cf-DNA is equal to or exceeds the threshold.
However, the applicant's disclosure lacks sufficient detail to demonstrate possession of the invention, as required under 35 U.S.C. 112(a).
The claim requires applying a specific threshold of 50 ng/mL for total cf-DNA in a sample from a surgical subject. The only detailed relevant disclosure for using this specific threshold of 50 ng/mL for surgical subjects' total cf-DNA are found in a study in the specification involving pediatric patients undergoing cardiopulmonary bypass surgery (page 20-21).
The data from this study indicates that total cell-free DNA peak levels 2 less than 50 ng/ml were associated with low risk 3.
Accordingly to MPEP 2163 (written description requirement), the specification must clearly demonstrate that the inventor was in possession of the claimed invention at the time of filling.
In this instant case, claim 51 broadly recites "a surgical subject," encompassing a genus far beyond the single disclosed species of pediatric patients undergoing a specific surgical procedure. There is no support for the applicability of the 50 ng/mL threshold to subjects of different non-pediatric ages or undergoing different types of surgeries for having different medical conditions. Therefore, the specification does not reasonably convey to a skilled artisan that the inventors, at the time of filling, had possession of applying the specific threshold of 50ng/mL to any and all surgical subjects.
Furthermore, the state of the art at the time of filling indicated that cf-DNA levels vary depending on physiological/medical conditions, population differences, and quantification techniques (see Salvianti 4, page 2, para 1; Park 5, page 921, right-hand col, para 3). For example, overtrained athletes show increased amounts of circulating DNA, whereas fetal DNA can be detected during pregnancy. (see van der Vaart 6, page 19, left-hand col, para 1).
Thus, the art recognized that cf-DNA levels could not be generalized across subjects with different conditions.
Accordingly, the disclosure of a single species ꟷ pediatric patients post-cardiopulmonary bypass surgery ꟷ as relevant to the specific threshold of 50ng/mL is insufficient to support the broader claimed genus of all surgical subjects.
Therefore, the application's disclosure does not meet the written description requirement under 35 U.S.C. 112(a), for there is insufficient disclosure that convey to a person skilled in the art that the inventor was in possession of the full breadth of the claim at the time of filling.
Claims 53, 58, 68-69 and 71-73 are rejected because they depend from claim 51 and inherit the deficiencies of the base claim.
Claim Rejections - 35 USC § 101– New Grounds
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 51, 53, 58, 68-69 and 71-73 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Independent claim 51 is drawn to a method of determining an amount of total cf-DNA in a sample from a surgical subject, comprising:
(a) extracting an amount of cell-free DNA (cf-DNA) from the sample from the subject;
(b) determining an amount of total cf-DNA in the cf-DNA extracted in (a); and
(c) comparing the amount of total cf-DNA to a threshold of 50 ng/mL to determine whether or not the total cf-DNA is equal to or exceeds the threshold.
Therefore, the claims are directed to steps to determine an amount of cf-DNA from a subject, and compare the determined amount to a pre-defined threshold.
Following the analysis below the claims are not patent eligible under 35 U.S.C. 101.
Step 1 - Whether the Claim is to a Statutory Category: YES. The claims are drawn to a method, therefore to one of the of statutory categories.
Step 2A Prong 1 - Whether the Claim Recite an Abstract idea, Law of Nature, or Natural Phenomenon: Yes. The claim recites a natural phenomenon of a subject having an amount of cf-DNA. Circulating Cf-DNA are naturally occurring and can be found in subjects' blood samples (see van der Vaart et al. Circulating DNA. Its origin and fluctuation. Ann N Y Acad Sci. 2008 Aug;1137:18-26. doi: 10.1196/annals.1448.022. PMID: 18837919.).
As stated in MPEP 2106.04(b)(I), laws of nature and natural phenomena, as identified by the courts, include naturally occurring principles/relations and nature-based products that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature.
Here, the presence of an amount of cf-DNA in a subject is classified as naturally occurring principles/relations, because a certain amount of cf-DNA naturally exist in every individual, although the levels may vary. Any level of cf-DNA in a subject reflects a naturally occurring biological correlation and is thus a natural correlation. While the claim also recites "comparing the amount of total cf-DNA to a threshold of 50 ng/mL to determine whether or not the total cf-DNA is equal to or exceeds the threshold." This merely describes the natural correlation further and is therefore part of the judicial exception.
The amount of cf-DNA naturally occurring in a subject could be lower than, equal to, or exceed any set threshold as a matter of natural principle. While human action may be involved in deciding on or discovering a specific threshold, the relation itself exists in principle apart from any human action. See Mayo v Prometheus, 566 US 66 (2012).
In conclusion, the claims recite laws of nature and natural phenomena.
Step 2A Prong 2- Whether the Claim Recite Additional Elements that Integrate the Judicial Exception into a Practical Application: No. The claim does not integrate the judicial exception into a practical application.
For a claim reciting a judicial exception to be eligible, the additional elements (if any) in the claim must “transform the nature of the claim” into a patent-eligible application of the judicial exception, Alice Corp., 573 U.S. at 217, 110 USPQ2d at 1981.
Claim 51 recites steps of extracting an amount of cell-free DNA (cf-DNA) from the sample from the subject, and determining an amount of total cf-DNA in the cf-DNA extracted; however, no detailed methods or techniques are recited to carry out these steps. This merely applies the judicial exception, encompassing any conventional techniques (e.g., detecting DNA in a sample, using polymerase chain reaction to amplify and detect DNA) without any additional elements that impose a meaningful limit on the judicial exception. See MPEP §2106.04(d). The steps are recited at a high level of generality and reflect extra-solution activities for data gathering.
In addition, the comparing step is a mental process and therefore a judicial exception as an abstract idea, thus cannot form the basis for patent eligibility. RecogniCorp, LLC v. Nintendo Co., Ltd. 855 F.3d 1322 (2017) ( “Adding one abstract idea (math) to another abstract idea (encoding and decoding) does not render the claim non-abstract.”).
Step 2B - Whether a Claim Amounts to Significantly More: No.
According to MPEP§ 2106.05, The second part of the Alice/Mayo test is often referred to as a search for an inventive concept. Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 217, 110 USPQ2d 1976, 1981 (2014) (citing Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 71-72, 101 USPQ2d 1961, 1966 (2012)). An “inventive concept” is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself. Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966).
For method claims that encompass natural phenomena, the method steps are the additional features that must be new and useful. See Parker v. Flook, 437 U.S. 584, 591, 98 S.Ct. 2522, 57 L.Ed.2d 451 (1978) ("The process itself, not merely the mathematical algorithm, must be new and useful.").
In this instant case, the claims, when considered as a whole, do not recite any inventive concept with additional elements that amount to significantly more than the judicial exception. The claims recite a method for measuring cf-DNA level in a subject and comparing the measured amount to a threshold, but it fails to include any additional steps or elements that apply, rely on or use the natural principle so that the claims amount to significantly more than the natural principle itself.
The dependent claims do not recite additional elements that amount to significantly more than the judicial exception, as they represent mere general linkage of the judicial exception to the additional elements in the claims (MPEP § 2106.05(h)). For example, claim 53 further recites determining a risk based on the comparison step. This is another mental step that merely involves making an observation of the natural principle of cfDNA level in a subject, without any active step that is new and useful beyond the observation itself.
In conclusion, the claims are not patent eligible under 35 U.S.C. 101.
Claim Rejections - 35 USC § 103 – New Grounds
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 51, 53, 58, 68-69 and 71-73 are rejected under 35 U.S.C. 103 as being unpatentable over Lin (Lin et al. Increased Plasma Circulating Cell-Free DNA Could Be a Potential Marker for Oral Cancer. Int J Mol Sci. 2018 Oct 24;19(11):3303. doi: 10.3390/ijms19113303. PMID: 30352977; PMCID: PMC6274798.), as evidenced by Habibzadeh (Habibzadeh et al. On determining the most appropriate test cut-off value: the case of tests with continuous results. Biochem Med (Zagreb). 2016 Oct 15;26(3):297-307. doi: 10.11613/BM.2016.034. PMID: 27812299; PMCID: PMC5082211.).
A) Lin teaches extracting and measuring total cf-DNA levels in Oral squamous cell carcinoma (OSCC) patients undergoing tumor excision surgery, with higher plasma cfDNA levels associated with a poor prognosis of OSCC (entire document, Abstract for example).
Regarding claim 51, Lin teaches a method of determining an amount of total cf-DNA in a sample from a surgical subject (Fig 2F; page 5, para 1), the method comprising:
(a) extracting an amount of cell-free DNA (cf-DNA) from the sample from the subject (page 8-9, “cfDNA Extraction”); (b) determining an amount of total cf-DNA in the cf-DNA extracted in (a) (page 9, “Plasma DNA Quantification”); and (c) comparing the amount of total cf-DNA to a threshold to determine whether or not the total cf-DNA is equal to or exceeds the threshold (Fig. 3 C and D).
While Lin does not explicitly teach a threshold of 50ng/ml, it teaches setting cf-DNA thresholds at 20 ng/mL and 42 ng/mL, and that plasma cf-DNA concentrations above 42 ng/mL are associated with poor prognosis and higher relapse in OSCC patients. The use of different thresholds or cutoff points results in varying area under the curve (AUC) and accuracy in ROC analysis.
A person of ordinary skill in the art would have found it prima facie obvious to apply a threshold of 50 ng/mL in the method of Lin as part of routine optimization. Lin already demonstrates movement from 20 ng/mL to 42 ng/mL threshold in its teachings. A skilled artisan would have recognized that adjusting the threshold is a known approach for optimizing assay performance, and that a 50 ng/mL threshold is close to the disclosed 42 ng/mL, representing a predictable adjustment.
Habibzadeh provides additional supporting evidence in its teaching of determining cut-off points (threshold) in ROC analysis:
"In a test with continuous (or multiple) results, every possible test value can be considered a cut-off point. This cut-off value determines the test Se and Sp. However, for a given test, we cannot increase the Se and Sp concomitantly; Se will be enhanced at the expense of Sp and vice versa. Decreasing the cut-off value to increase the test Se causes the Sp to decrease. If you want to have a more specific test (by increasing the cut-off value), you will have a less sensitive test.” (page 298, left-hand col, para 1)
Thus, Habibzadeh teaches that in a test with continuous results, any value may serve as a threshold, and that increasing the threshold improves specificity. A skilled artisan would have understood that threshold selection in ROC analysis is a tunable parameter for adjusting assay sensitivity and specificity.
Accordingly, in light of the knowledge in the art as evidenced by Habibzadeh, a skilled artisan aiming to increase specificity would have found it obvious to raise the threshold or cut-off point from 42 to 50 ng/mL in view of the teachings of Lin, yielding the predictable result of improved specificity in cf-DNA-based prognostic testing for Oral squamous cell carcinoma (OSCC) patients undergone tumor excision surgery.
One having ordinary skill in the art would have had a reasonable expectation of success because performing optimization of known process parameters, such as adjusting the threshold in ROC analysis, to improve assay performance is well within the skill level of the ordinary artisan. Therefore, adjusting the threshold value to achieve optimal assay specificity would have been an obvious, routine optimization process for a skilled artisan, see MPEP 2143.
B) Regarding claim 53, Lin teaches determining a risk of a post-surgical complication in the subject based on the comparison in (c) (Fig. 3 C and D, determining risk of poor prognosis and more relapse post-surgery; page 8, para 4, lines 11-12).
Regarding claim 58, Lin teaches preparations of amplified cf-DNA (page 6, para 2, lines 2-3, polymerase chain reaction (PCR)–based techniques along with sequencing).
Regarding claim 68, Lin teaches determining cf-DNA amount using sequencing (page 6, para 2, lines 2-3, polymerase chain reaction (PCR)–based techniques along with sequencing).
Regarding claim 69, it recites:
"wherein a risk of a post-surgical complication is increased or increasing if the amount of total cf-DNA is greater than the threshold or an amount from an earlier time point; and
wherein the risk of a post-surgical complication is decreased or decreasing if the amount of total cf- DNA is less than the threshold or an amount from an earlier time point."
This limitation is obvious in view of the teachings of Lin because it does not further limit the claimed method.
Per MPEP 2111.04, a wherein clause can limit a method claim if it contributes meaning and purpose to the manipulative steps.
In claim 69, however, the wherein clauses do not integrate any additional action or decision-making process into the method, and merely presents a scenario for correlating cf-DNA values with indication for change in risk.
Therefore, this claim language is interpreted as descriptive statement without any associated active steps and do not distinguish the claim from the prior art.
Claim 71 recites "wherein the threshold total cf-DNA value is 100 ng/mL." This limitation is obvious in view of the teachings of Lin as evidenced by Habibzadeh.
As discussed above for claim 51, adjusting threshold would have been an obvious, routine optimization by a skilled artisan aiming to improve specificity in cf-DNA-based prognostic, as taught by the references.
Regarding claim 72, Lin teaches plasma sample (page 8, para 4 “plasma samples”).
Regarding claim 73, Lin teaches non-transplant surgery (page 8, para 4, line 1, surgical excision of Oral squamous cell carcinoma).
Double Patenting- Obvious Type -- New Grounds
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 51 and 68 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 10, 18 and 63 of copending Application No. 17/960,904 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the claims (filed on 01/23/2023) of the '904 application.
Instant claim 51 recites:
A method of determining an amount of total cf-DNA in a sample from a surgical subject, the method comprising:
(a) extracting an amount of cell-free DNA (cf-DNA) from the sample from the subject (‘904 Application, claim 10) ;
(b) determining an amount of total cf-DNA in the cf-DNA extracted in (a) (‘904 Application, claim 1); and
(c) comparing the amount of total cf-DNA to a threshold of 50 ng/mL to determine whether or not the total cf-DNA is equal to or exceeds the threshold (‘904 Application, claims 10 and 63).
Therefore, instant claim 51 is anticipated by claims 1, 10 and 63 of the '904 application. Instant claim 68 is anticipated by claim 18 of the '904 application, respectively.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are 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.
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/TIAN NMN YU/Examiner , Art Unit 1681 /AARON A PRIEST/Primary Examiner, Art Unit 1681
1 See Medberry et al. Overview of digital electrophoresis analysis. Curr Protoc Mol Biol. 2004 May;Chapter 10:Unit 10.5. doi: 10.1002/0471142727.mb1005s66. PMID: 18265337.
2 The term "peak level" appears synonymous with "peak amount," defined as "the highest value of serial samples." (specification, page 9, lines 21-22)
3 Risk including event of mortality, cardiac arrest (CA) or mechanical support (MS); individual critical events of mortality, cardiac arrest (CA), and mechanical support (MS); and infection, etc. See specification, page 20, lines 19-23.
4 Salvianti et al. Integrity and Quantity of Total Cell-Free DNA in the Diagnosis of Thyroid Cancer: Correlation with Cytological Classification. Int J Mol Sci. 2017 Jun 24;18(7):1350. doi: 10.3390/ijms18071350. PMID: 28672797; PMCID: PMC5535843.
5 Park et al. Quantitative analysis of cell-free DNA in the plasma of gastric cancer patients. Oncol Lett. 2012 Apr 1;3(4):921-926. doi: 10.3892/ol.2012.592. Epub 2012 Feb 3. PMID: 22741019; PMCID: PMC3362424.
6 van der Vaart et al. Circulating DNA. Its origin and fluctuation. Ann N Y Acad Sci. 2008 Aug;1137:18-26. doi: 10.1196/annals.1448.022. PMID: 18837919.