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 .
Detailed Action
Pursuant to a preliminary amendment filed on October 7, 2025, claims 1 – 11, and 13 - 21 are currently pending in the instant application. Claims 1, 11, and 15 are independent claims, and claim 12 was previously canceled.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on December 30, 2024 have been considered. Initialed copies of the IDSs accompany this Office Action
Priority
The present application filed November 27, 2024, is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US2023/024307, filed June 2, 2023, which claims the benefit of Provisional Application 63/348,102, filed June 2, 2022.
Therefore, the earliest priority date is June 2, 2022.
Claim objection
Claims 1, 4, 5, 8, 11, 13, 15, 18, and 19 are objected to because of the following informalities: abbreviations such as “cfDNA”, “PCR”, and “BES-HMP”, should be spelled out at the first encounter in the claims. Appropriate correction is required.
Claim Rejection - 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 6, 7, and 9 and 20 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 6 is indefinite for the recitation of “an infusion port connected to the perfusate pump” in line 2. It is unclear what is an infusion port, and what is being infused into the perfusate. Further, “infusion port” has not been defined in the as-Filed Specification, and an infusion port is not included in Fig. 5. Thus, the metes and bounds of the claim cannot be determined.
Claim 7 is indefinite for the recitation of “sample collection port connected to the perfusate pump” in line 2. It is unclear which sample is being collected in this port. Further, “sample collection port” has not been defined in the as-Filed Specification, and an infusion port is not included in Fig. 5. Thus, the metes and bounds of the claim cannot be dermined.
Claim 9 is indefinite for the recitation of “the pressure controller maintains a pressure of 30 to 100 mmHg20” in lines 1 – 2. It is unclear what the “20” superscript is referring to. Thus, the metes and bounds of the claim cannot be determined.
Claim 20 is indefinite for the recitation of “the predetermine threshold level is about 2.0 to 3.0 ng/ml in the perfusate” in line 2. It is unclear what the metes and bounds of “about 2.0 to 3.0 ng/mL” are, and thus, the threshold level cannot be determined.
Claim Rejection - 35 USC § 103
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 1 – 11, and 13 – 21 are rejected under 35 U.S.C. 103 as being unpatentable over Bhattacharjee et al. (Bhattacharjee RN. Et al. Subnormothermic Oxygenated Perfusion Optimally Preserves Donor Kidneys Ex Vivo. Kidney Int Rep. 2019 May 22;4(9):1323-1333.), and further in view of Mitchell et al. (hereinafter referred to as “Mitchell”) (US 20210269879 A1, published September 2, 2021). (Please note: These references are listed in the IDS filed December 30, 2024).
Regarding claim 1 and 11, Bhattacharjee teaches an innovative renal pump circuit that can perfuse blood (Abstract). Bhattacharjee teaches that porcine kidneys were retrieved, flushed and subjected to static cold storage, and then cannulated for pulsatile oxygenated perfusion with blood: PlasmaLyte (Abstract). Bhattacharjee teaches the RM3 pump for blood perfusion, storage, and reperfusion in the same circuit, as shown below (Figure 1).
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Bhattacharjee teaches an organ chamber for receiving organ and perfusate, a perfusate pump, a pressure controller, an oxygenator, and a temperature regulator, as shown in Fig. 1 (referring to instant claim 1, and a hypothermic perfusion machine, claim 11). Bhattacharjee teaches that total RNA was extracted from 40 mg of thoroughly ho mogenized fresh kidney tissues in lysis solution, and then subjected to real time PCR (pg. 1325, right column, second paragraph).
Bhattacharjee does not explicitly teach a cfDNA detector connected to a perfuate pump (instant claim 1, in part, and claim 15, in part), the device with which cfDNA is quantified, that the cfDNA levls increased at least 1% relative to a control (claim 15, in part), the cfDNA detector quantifies the cfDNA by digital PCR (claim 4 and 18), the system comprises a filter to filter the perfusate before circulating through the cfDNA detector (claim 5), and that the perfusate comprises UW solution (claims 8 and 19).
Mitchell teaches a method comprising obtaining an amount of total cell free DNA and/or graft-specific cfDNA released from a potential graft (e.g., ex vivo), e.g., prior to contacting of the potential graft with blood cells of a potential recipient, and/or subsequent to contacting of the potential graft or cells thereof with blood cells from a potential recipient (Abstract). Mitchell teaches the method for obtaining an amount of total cell-free nucleic acids (such as DNA) can be done with real-time PCR (Paragraph [0017]) (interpreted as qPCR, instants claim 4, 13, and18). Mitchell teaches that this method is used in assessing the amount(s) to determine the suitability of the potential graft for transplantation or implantation (Abstract). Mitchell teaches that the organ can be contained in a perfusion system (Paragraph [0052]).
Regarding claim 5 and 14, Mitchell teaches that the plasma, which contains cf-DNA, is separated from cells present in the blood (e.g., by centrifugation or filtering), and then the cf-DNA can then be extracted using any method (Paragraph [0084]).
Regarding claim 8, Mitchell teaches that the graft storage media is the UW solution (Paragraph [0054]).
Regarding claim 15, Mitchell teaches that the concentrations of cf-DNA observed in perfusate samples are notably elevated compared to, for instance, normal circulating cf-DNA levels historically observed in plasma from normal human subjects and most patients with heart transplant rejection (Paragraph [0107]).
Regarding claim 20, Mitchell teaches a 2.69 ng/ml as the threshold (Paragraph [0055]).
Regarding claim 21, Mitchell teaches a clinician may assess the suitability of a graft for transplantation or implantation or the need to monitor the graft over time or treatment or some other remedial action (Paragraph [0067] (interpreted as implanting the organ into a patient if organ is determined to not have poor pre-transplant organ function).
Therefore, in view of the benefits of determining the suitability of the potential graft for transplantation or implantation as taught by Mitchell, it would have been prima facia obvious to modify the RM3 pump used for the blood perfusion, storage, and reperfusion of kidneys, as taught by Bhattacharjee, by adding a filter and digital PCR to determine the amount of cfDNA in the sample, as taught by Mitchell, with a reasonable expectation of success in determining the suitability of the potential graft for transplantation. It would have been prima facia obvious to combine the cited sources because Bhatacharjee teaches RM3 pump used for the blood perfusion, isolating RNA from the kidney, and subjecting RNA to real-time PCR, and Mitchell teaches filtering the sample to obtain the cell-free DNA using real-time PCR, and that the organ can be contained in a perfusion system.
Regarding claims 2, 3, 16, and 17, the combined teachings of Bhattacharjee and Mitchell render obvious the teachings of claims 1 and 15. Moreover, Bhattacharjee teaches preserving the allograft in clinical kidney preservation (pg. 1323, left column, first paragraph).
Regarding claims 6 and 7, the combined teachings of Bhattacharjee and Mitchell render obvious the teachings of claim 1. Moreover, Bhattacharjee teaches that the hypothermic machine perfusion is used to deliver oxygenated blood or perfusate at different temperatures, pressures, and degrees of oxygenation (pg. 1324, left column, fourth paragraph) Bhattacharjee teaches an organ chamber for receiving organ and perfusate, a perfusate pump, a pressure controller, an oxygenator, and a temperature regulator, as shown in Fig. 1 (the perfusate pump is interpreted as comprising an infusion pump and a sample collection port).
Regarding claim 9, the combined teachings of Bhattacharjee and Mitchell render obvious the teachings of claim 1. Moreover, Bhattacharjee teaches that a mean pressure of 70 mm Hg was maintained during RM3 pump (pg. 1324, right column, second paragraph).
Regarding claim 10, the combined teachings of Bhattacharjee and Mitchell render obvious the teachings of claim 1. Moreover, Bhattacharjee does not explicitly teach that the temperature regulator maintains a temperature of 0 – 12 C. However, Bhattacharjee teaches that RM3 renal preservation pump was modified for whole blood perfusion and reperfusion in the same unit under different temperature settings (Figure 1), such that one of ordinary skill in the can maintain the pump at the desired temperature.
Conclusion
Claims 1 – 11, and 13 – 21 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VYOMA SHUBHAM TIWARI whose telephone number is (571)272-2954. The examiner can normally be reached M-F 8:30 - 5:30 EST.
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/VYOMA SHUBHAM TIWARI/Examiner, Art Unit 1634
/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634
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