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 .
Drawings
The drawings were received on 12/12/2025. These drawings are acceptable.
Claim Interpretation
Attention is directed to MPEP 904.01 [R-08.2012].
The breadth of the claims in the application should always be carefully noted; that is, the examiner should be fully aware of what the claims do not call for, as well as what they do require. During patent examination, the claims are given the broadest reasonable interpretation consistent with the specification. See In re Morris, 127 F.3d 1048, 44 USPQ2d 1023 (Fed. Cir. 1997). See MPEP § 2111 - § 2116.01 for case law pertinent to claim analysis.
It is noted with particularity that narrowing limitations found in the specification cannot be inferred in the claims where the elements not set forth in the claims are linchpin of patentability. In re Philips Industries v. State Stove & Mfg. Co, Inc., 186 USPQ 458 (CA6 1975). While the claims are to be interpreted in light of the specification, it does not follow that limitations from the specification may be read into the claims. On the contrary, claims must be interpreted as broadly as their terms reasonably allow. See Ex parte Oetiker, 23 USPQ2d 1641 (BPAI, 1992). In added support of this position, attention is directed to MPEP 2111 [R-11.2013], where, citing In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550-51 (CCPA 1969), is stated:
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.
Additionally, attention is directed to MPEP 2111.01 [R-01.2024], wherein is stated:
II. IT IS IMPROPER TO IMPORT CLAIM LIMITATIONS FROM THE SPECIFICATION
“Though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read into a claim when the claim language is broader than the embodiment.” Superguide Corp. v. DirecTV Enterprises, Inc., 358 F.3d 870, 875, 69 USPQ2d 1865, 1868 (Fed. Cir. 2004).
Attention is also directed to MPEP 2111.02 II [R-07.2022]. As stated herein:
II. PREAMBLE STATEMENTS RECITING PURPOSE OR INTENDED USE
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The claim preamble must be read in the context of the entire claim. The determination of whether preamble recitations are structural limitations or mere statements of purpose or use "can be resolved only on review of the entirety of the [record] to gain an understanding of what the inventors actually invented and intended to encompass by the claim" as drafted without importing "'extraneous' limitations from the specification." Corning Glass Works, 868 F.2d at 1257, 9 USPQ2d at 1966. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020) (The court found that the preamble in one patent’s claim is limiting but is not in a related patent); Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation")… (Emphasis added)
Attention is directed to MPEP 2111 [R-10.2019]. As stated therein:
During patent examination, the pending claims must be "given their broadest reasonable interpretation consistent with the specification." The Federal Circuit’s en banc decision in Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) expressly recognized that the USPTO employs the "broadest reasonable interpretation" standard:
The Patent and Trademark Office ("PTO") determines the scope of claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction "in light of the specification as it would be interpreted by one of ordinary skill in the art." In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364[, 70 USPQ2d 1827, 1830] (Fed. Cir. 2004). Indeed, the rules of the PTO require that application claims must "conform to the invention as set forth in the remainder of the specification and the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description." 37 CFR 1.75(d)(1). (Emphasis added).
Attention is directed to MPEP 2173.04 [R-10.2019]. As stated therein:
Breadth of a claim is not to be equated with indefiniteness. In re Miller, 441 F.2d 689, 169 USPQ 597 (CCPA 1971); In re Gardner, 427 F.2d 786, 788, 166 USPQ 138, 140 (CCPA 1970) ("Breadth is not indefiniteness."). A broad claim is not indefinite merely because it encompasses a wide scope of subject matter provided the scope is clearly defined. But a claim is indefinite when the boundaries of the protected subject matter are not clearly delineated and the scope is unclear. For example, a genus claim that covers multiple species is broad, but is not indefinite because of its breadth, which is otherwise clear. But a genus claim that could be interpreted in such a way that it is not clear which species are covered would be indefinite (e.g., because there is more than one reasonable interpretation of what species are included in the claim). (Emphasis added)
Claim Rejections - 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 (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.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Holding and Rationale
Claim(s) 22, 24, and 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gielis et al., “Plasma donor-derived cell-free DNA kinetics after kidney transplantation using a single tube multiplex PCR assay”, PLOS One, 6 December 2018 (Gielis I), in view of Gielis et al., “Transplantation Experimental”, Nephrology Dialysis Transplantation 31 (Supplement 1): i1-12, 2016 (Gielis II).
Gielis I, in the abstract, teach:
After transplantation, cell-free DNA derived from the donor organ (ddcfDNA) can be
detected in the recipient’s circulation. We aimed to quantify ddcfDNA levels in plasma of kidney transplant recipients thereby investigating the kinetics of this biomarker after transplantation and determining
Gielis I., at page 2, teach:
After transplantation, cell-free DNA derived from the donor organ (ddcfDNA) can be detected in the recipient’s circulation. Its release might be associated with cell damage in the graft thereby indicating a role of ddcfDNA as a biomarker for graft injury after transplantation[1].
Gielis I, at page 6 teach:
In this study, we aimed to investigate the ddcfDNA kinetics and establish a plasma ddcfDNA threshold value in stable kidney graft recipients. (Emphasis added)
Gielis I, at page 7 teach:
Kinetics of the ddcfDNA% in stable kidney transplant recipients
…
We calculated the threshold ddcfDNA value as the mean + 2SD—thus 0.46% + 2(0.21%)—resulting in a ddcfDNA% of 0.88%.
As evidenced above, Gielis I, teach of determining the amount of ddcfDNA (applicant’s “dd-cfDNA) in serum samples from stable patients that had received a kidney transplant. As evidenced above, the threshold for ddcfDNA was 0.88%. Given such, and recognizing that as the kidney tissue is damaged the amount of ddcfDNA would increase. Given such, the selection of .75% and 2% as the threshold value is deemed to be an obvious design choice and a matter of routine optimization.
Gielis II, right column, last paragraph, teach:
Abnormal ddcfDNA kinetics were observed in two cases of acute rejection. In
a 35-year old kidney recipient, a high plasma ddcfDNA fraction (50%) was measured
14 days after transplantation. At day 24, a biopsy demonstrated a Banff IIB rejection. In
another case, a 50-year old kidney recipient was diagnosed with a biopsy proven
borderline rejection 3 weeks after transplantation, although histological evaluation was
possibly imperfect due to biopsy specimen inadequacy. In this recipient, the plasma
ddcfDNA fraction dropped immediately after transplantation but started to increase
already from day 7 onwards, while serum creatinine was still stable.
Conclusions: The kinetics of the ddcfDNA fraction in the recipient’s plasma was
investigated using the NIOTT, a universal targeted ddcfDNA quantification approach.
Early alterations in ddcfDNA levels in recipients with acute rejection point to a
potential role for ddcfDNA as a rejection biomarker.
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With one knowing the values for ddcfDNA in patients that are stable with their kidney transplant, the selection of values that are higher and which are indicative of graft rejection would be a matter of obvious design choice. As evidenced above, the values for ddcfDNA in the first week exhibit a range of values. The selection of a range of values that reflect graft rejection is deemed to be a matter of obvious design choice.
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 22, 24, and 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gielis et al., “Plasma donor-derived cell-free DNA kinetics after kidney transplantation using a single tube multiplex PCR assay”, PLOS One, 6 December 2018 (Gielis I), in view of Gielis et al., “Transplantation Experimental”, Nephrology Dialysis Transplantation 31 (Supplement 1): i1-12, 2016 (Gielis II).
Claim(s) 26 and 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gielis et al., “Plasma donor-derived cell-free DNA kinetics after kidney transplantation using a single tube multiplex PCR assay”, PLOS One, 6 December 2018 (Gielis I), in view of Gielis et al., “Transplantation Experimental”, Nephrology Dialysis Transplantation 31 (Supplement 1): i1-12, 2016 (Gielis II) as applied to claims 22, 24, and 25 above, and further in view of US 2016/0328515 A1 (Campagne et al.).
See above for the basis of the rejection as it relates to the teachings of Gielis I and Gielis II.
Neither Gielis I nor Gielis II have been found to teach monitoring the eGFR score in patients that had received a kidney transplant.
Campagne et al., at paragraph [0228], teach
[0228] FIG. 7 presents an analysis where the Discovery and Validation cohorts (34 transplant kidney recipient-donor pairs) were combined, and the allogenomics scores were compared to the number of mismatches at the HLA-A, B and DR loci. The allogenomics mismatch score is moderately correlated with the number of mismatches at the HLA loci (FIG. 7A, R.sup.2 adj.=0.36, P<0.001). However, the number of HLA mismatches correlates poorly with an allogenomics score estimated from exome data when restricting the sites to the HLA loci (FIG. 7B, R.sup.2 adj.=0.1, P=0.03). Furthermore, the allogenomics mismatch score estimated outside of the HLA loci still significantly associates with serum creatinine levels (FIG. 7C) and eGFR (FIG. 7D).
In view of the above presentation, it would have been quite obvious to one of ordinary skill in the art to have monitored/measured the serum creatine level and the eGFR level in kidney transplant patients.
In view of the above presentation and in the absence of evidence to the contrary, claims 26 and 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gielis et al., “Plasma donor-derived cell-free DNA kinetics after kidney transplantation using a single tube multiplex PCR assay”, PLOS One, 6 December 2018 (Gielis I), in view of Gielis et al., “Transplantation Experimental”, Nephrology Dialysis Transplantation 31 (Supplement 1): i1-12, 2016 (Gielis II) as applied to claims 22, 24, and 25 above, and further in view of US 2016/0328515 A1 (Campagne et al.).
Claim(s) 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gielis et al., “Plasma donor-derived cell-free DNA kinetics after kidney transplantation using a single tube multiplex PCR assay”, PLOS One, 6 December 2018 (Gielis I), in view of Gielis et al., “Transplantation Experimental”, Nephrology Dialysis Transplantation 31 (Supplement 1): i1-i2, 2016 (Gielis II) as applied to claims 22, 24, and 25 above, and further in view of US 2012/0219596 A1 (Limbach et al.).
See above for the basis of the rejection as it relates to the teachings of Gielis I and Gielis II.
Neither Gielis I nor Gielis II have been found to teach providing medical intervention to a recipient of a transplanted kidney.
Limbach et al., at paragraph [0053], teach:
[0053] In a further aspect, the present invention relates to a use of a compound of the invention as defined above for the preparation of a medicament for the treatment and/or protection of patients having or being prone to produce a medical condition involving hypoxic, anoxis and/or inflamed mammalian tissue, preferably a tissue selected from the group consisting of heart, lung, liver, brain, gut, kidney, muscle, bone, skin and eye, preferably a medical condition selected from ischemia reperfusion injury, severe inflammatory response syndrome, sepsis, organ transplantation, organ resection, organ or implant rejection, inflammation, e.g. due to allergy or infection, e.g. asthma, psoriasis, pneumonia, etc., or related to a medical intervention, preferably surgery or catheterization. The pharmaceutical composition is for administration prior to, after or concomitantly to a medical condition. (Emphasis added)
In view of the above presentation, it would have been quite obvious to provide intervention either before or after having received an organ implant.
In view of the above showing and in the absence of convincing evidence to the contrary, claim 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gielis et al., “Plasma donor-derived cell-free DNA kinetics after kidney transplantation using a single tube multiplex PCR assay”, PLOS One, 6 December 2018 (Gielis I), in view of Gielis et al., “Transplantation Experimental”, Nephrology Dialysis Transplantation 31 (Supplement 1): i1-i2, 2016 (Gielis II) as applied to claims 22, 24, and 25 above, and further in view of US 2012/0219596 A1 (Limbach et al.).
Allowable Subject Matter
Claims 27 and 29 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Objections and/or rejections which appeared in the prior Office action and which have not been repeated hereinabove have been withdrawn.
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 Bradley L. Sisson whose telephone number is (571)272-0751. The examiner can normally be reached Monday to Thursday, from 6:30 AM to 5 PM..
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Shen can be reached at 571-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Bradley L. Sisson/Primary Examiner, Art Unit 1682
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