DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s election of Group I in the reply filed on August 22, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-5, 10, 13, 17, 20, 22, 26, 28-31, 35, 39, 43-46, 51, 85 are currently pending.
Claims 17, 20, 22, 26, 28-31, 35, 39, 43-46, and 51 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on August 22, 2025.
Applicants are reminded that the current status of all of the claims in the application, including any previously canceled or withdrawn claims, must be given. It is noted that claims 17, 20, 22, 26, 28-31, 35, 39, 43-46, and 51 have the wrong status identifier. Correction is required.
Claim Rejections - 35 USC § 101
3. 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 1-5, 10, 13, and 85 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more. The claims recite a judicial exception that is not integrated into a practical application. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The claim analysis is set forth below.
Step 1: The claims are directed to the statutory category of a process.
Step 2A, prong one: Evaluate Whether the Claim Recites a Judicial Exception
The instant claims recite abstract ideas.
The claims recite a step of “determining” an amount of DS cf-DNA in a sample from a subject (clm 1). The claims do not clearly require performing any wet laboratory steps to make the determination. The “determining” step broadly encompasses a mental processes. For example, one may “determine” the amount of DS-cfDNA in a sample by reading a laboratory report.
The claims recite a step of “reporting and/or recording” the amount of DS cf-DNA (clm 1). The “reporting” broadly encompasses a mental process. For example one could “report” the amount of DS-cfDNA by verbally telling someone the amount.
The claims recite a step of “comparing” the amount of DS cf-DNA to a threshold or a prior DS cf-DNA value (clms 2, 4). The broadest reasonable interpretation of the “comparing” step is that it may be accomplished by a mental processes. For example, one may “compare” the amount of DS-cfDNA and threshold/prior value by looking at both side by side in a laboratory report.
The claims recite a step of “assigning” a cellular rejection grade based on the amount of DS cf-DNA (clms 3, 5). The broadest reasonable interpretation of the “assigning” step is that it may be accomplished by a mental processes. For example, one may “assign” the cellular grade by thinking about the amount of DS cf-DNA.
The claims recite a step of “obtaining” an amount of donor specific cell free DNA in a sample from a subject (clm 4). The claims do not clearly require performing any wet laboratory steps to obtain the amount. The “obtaining” step broadly encompasses a mental processes. For example, one may “obtain” the amount of DS-cfDNA in a sample by reading a laboratory report.
The claims recite a step of “determining” a treatment or monitoring regime for the subject based on the determined amount of DS cf-DNA (clm 4). The “determining” step broadly encompasses a mental processes. For example, one may “determine” the treatment or monitoring regime for a subject by thinking about the amount of DS cf-DNA.
The claims recite a step of “selecting or suggesting” a treatment for the subject (clm 85). The broadest reasonable interpretation of the “selecting or suggesting” step is that it may be accomplished by a mental processes. For example, one may “select” a treatment by thinking about the amount of DS cf-DNA. Further suggesting can be done verbally.
The instant claims recite a law of nature.
The claims recite a correlation between the amount of DS cfDNA and cellular rejection grade (clms 3, 5, 13). This type of correlation is a consequence of natural processes, similar to the naturally occurring correlation found to be a law of nature by the Supreme Court in Mayo.
Step 2A, prong two: Evaluate Whether the Judicial Exception Is Integrated Into a Practical Application
The claims do NOT recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s). For example, the claims do not practically apply the judicial exception by including one or more additional elements that the courts have stated integrate the exception into a practical application:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
An additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
An additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
An additional element effects a transformation or reduction of a particular article to a different state or thing; and
An additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological
environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
In addition to the judicial exceptions claim 1 recites (in the alternative) a step “recording” the amount of DS cf-DNA. Merely presenting the results of a process otherwise unpatentable under section 101 is, however, insufficient to establish eligibility under the statute. See FairWarning IP, LLC v. Iatric Sys., Inc., (Fed. Cir. Oct. 11, 2016) (claim unpatentable despite recitation of the step: "providing notification if [an] event has occurred").
The courts have affirmed that merely collecting data, extracting information from the data and/or storing data are not patent-eligible (see, For example, Content Extraction and Transmission LLC v. Wells Fargo Bank., N.A. 776 F.3d 1343, 112 USPQ2d 1354 (Fed. Cir. 2014) and Electric Power Group LLC v Alstom S.A. CAFC 2015-1778).
In addition to the judicial exceptions claim 85 recites a step of “treating” the subject. It is noted that a claim limitation can integrate a judicial exception by applying or using the judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. However the treatment or prophylaxis limitation must be “particular”, i.e., specifically identified so that it does not encompass all applications of the judicial exceptions. Here the administration step is not particular, and is instead merely instructions to “apply” the exception in a generic way. Thus, the administration step does not integrate the judicial exceptions into a practical application.
Step 2B: Evaluate Whether the Claim Provides an Inventive Concept
In addition to the judicial exceptions claim 1 recites (in the alternative) a step “recording” the amount of DS cf-DNA. Merely presenting the results of a process otherwise unpatentable under section 101 is, however, insufficient to establish eligibility under the statute. See FairWarning IP, LLC v. Iatric Sys., Inc., (Fed. Cir. Oct. 11, 2016) (claim unpatentable despite recitation of the step: "providing notification if [an] event has occurred").
The courts have affirmed that merely collecting data, extracting information from the data and/or storing data are not patent-eligible (see, For example, Content Extraction and Transmission LLC v. Wells Fargo Bank., N.A. 776 F.3d 1343, 112 USPQ2d 1354 (Fed. Cir. 2014) and Electric Power Group LLC v Alstom S.A. CAFC 2015-1778). Further reporting and/or recording the amount of DS cf-DNA does NOT amount to significantly more because it is recited at a high level of generality and it appends well understood, routine, and conventional activities previously known in the art to the judicial exceptions.
Further it is noted that the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015);
Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017);
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014)
For the reasons set forth above the claims are not directed to patent eligible subject matter.
Claim Rejections - 35 USC § 112
4. 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 1-5, 10, 13, and 85 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.
Claims 1-5, 10, 13, and 85 are rejected over the recitation of the phrase “a cellular rejection grade, such as of CR1, CR2 or lower, CR1 or greater, or CR2 or greater” in claims 1 and 4. The phrase "such as" renders the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 13 recites a method wherein
(a) a cellular rejection grade of CR0 is assigned to the subject if the amount DS cf-DNA is less than 0.14, 0.15 or 0.2;
(b) a cellular rejection grade of CR1 is assigned to the subject if the amount of DS cf-DNA is greater than 0.14, 0.15 or 0.2 or between 0.14 and 0.8, 0.15 and 0.8 or 0.2 and 0.8;
(c) a cellular rejection grade of CR2 or greater is assigned to the subject if the amount of DS cf-DNA is 0.8 or greater.
The claim is problematic because the skilled artisan would not be able to determine the cellular rejection grade based on these recitations. For example if a subject had 0.19 DS cf-DNA it’s unclear if they would be considered CR0 since 0.19 is less than 0.2 OR if they would be considered CR1 since 0.19 is between 0.14 and 0.8. Further if a subject had 0.9 DS cf-DNA it’s unclear if they would be considered CR1 since 0.9 is greater than 0.2 or if they would be CR2 since 0.9 is greater than 0.8. One of skill in the art would not be able to determine the metes and bounds of the claimed subject matter so as to avoid infringement.
Claim Rejections - 35 USC § 102
5. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-5, 10, 13, and 85 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by De Vlaminck (Science Translational Medicine June 18, 2014 Vol 6 Issue 241 pages 1-8).
Regarding Claim 1 De Vlaminck presents the results of a prospective cohort study (65 patients, 565 samples) that tested the utility of cell-free donor-derived DNA (cfdDNA) in measuring acute rejection after heart transplantation. Circulating cell-free DNA was purified from plasma and sequenced (mean depth, 1.2 giga–base pairs) to quantify the fraction of cfdDNA. Through a comparison with endomyocardial biopsy results, De Vlaminck demonstrates that cfdDNA enables diagnosis of acute rejection after heart transplantation, with an area under the receiver operating characteristic curve of 0.83 and sensitivity and specificity that are comparable to the intrinsic performance of the biopsy itself. Figures 4 shows the time-dependence of cfdDNA fraction in the absence of rejection (a), and three examples of acute rejection (b-d).
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In the first case (Fig. 4B), an elevated donor fraction was recorded at month 15 (cfdDNA = 5.75%), coinciding with a biopsy-defined 3R/3B acute rejection episode. In a second case (Fig. 4C), the donor-derived DNA fraction was quantified as >10%, coinciding with a 3R/3B rejection event (month 9). This patient required repeat heart transplantation after month 10 owing to development of severe cardiac allograft vasculopathy. After the second transplant, the donor-derived DNA signal returned to a low level. In a final example (Fig. 4D), elevated donor DNA fractions were observed in a patient with consecutive episodes of ACR (month 4, 2R/3A; month 12, 3R/3B; donor fractions, 2.0 and 9.0%, respectively) and AMR (month 4; donor fraction, 4.9%). This example illustrates the application of this technique for detection of both ACR and AMR events (page 2, col 2 to page 3 col 1). Thus De Vlaminck teaches a method of assessing a sample from a transplant subject comprising determining an amount of donor-specific cell-free DNA (DS cf-DNA) in a sample from the subject, and reporting and/or recording the amount of DS cf-DNA (the graphs). The subjects of De Vlaminck are being interpreted as subjects suspected of having or at risk of having cellular rejection since all transplant subjects are at risk and should be monitored after receiving a transplant.
Regarding Claim 2 De Vlaminck teaches comparing the amount of DS cf-DNA to at least one prior DS cf-DNA value since in Figures 4 the amounts were compared over a 15 month period.
Regarding Claims 3 and 5 De Vlaminck teaches that they analyzed the performance of the GTD approach for acute rejection diagnosis through a direct comparison with endomyocardial biopsy data. De Vlaminck teaches that the cfdDNA levels were significantly higher for heart transplant recipients during acute rejection and correlated with the severity of the rejection episode as determined by biopsy (comparing biopsy grades 0 and 1R/1A and biopsy grades 0 and ≥2R/3A or AMR). A receiver operating characteristic (ROC) analysis of the performance of cfdDNA as a marker of ACR (≥2R/3A or AMR) yielded an area under the curve (AUC) of 0.83 (sensitivity = 0.58 and specificity = 0.93 at a cfdDNA threshold level of 0.25%) (page 3 col 2 and Fig 5a and 5b).
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Thus De Vlaminck teaches assigning a cellular rejection grade for the subject based on the determined amount of DS cf-DNA compared to the threshold DS cf-DNA value since De Vlaminck teaches that a DS cf-DNA greater than 0.25 is a marker of ACR (≥2R/3A or AMR).
Regarding Claim 4 De Vlaminck presents the results of a prospective cohort study (65 patients, 565 samples) that tested the utility of cell-free donor-derived DNA (cfdDNA) in measuring acute rejection after heart transplantation. Circulating cell-free DNA was purified from plasma and sequenced (mean depth, 1.2 giga–base pairs) to quantify the fraction of cfdDNA. Through a comparison with endomyocardial biopsy results, DE Vlaminck demonstrates that cfdDNA enables diagnosis of acute rejection after heart transplantation, with an area under the receiver operating characteristic curve of 0.83 and sensitivity and specificity that are comparable to the intrinsic performance of the biopsy itself. Figures 4 shows the time-dependence of cfdDNA fraction in the absence of rejection (a), and three examples of acute rejection (b-d).
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In the first case (Fig. 4B), an elevated donor fraction was recorded at month 15 (cfdDNA = 5.75%), coinciding with a biopsy-defined 3R/3B acute rejection episode. In a second case (Fig. 4C), the donor-derived DNA fraction was quantified as >10%, coinciding with a 3R/3B rejection event (month 9). This patient required repeat heart transplantation after month 10 owing to development of severe cardiac allograft vasculopathy. After the second transplant, the donor-derived DNA signal returned to a low level. In a final example (Fig. 4D), elevated donor DNA fractions were observed in a patient with consecutive episodes of ACR (month 4, 2R/3A; month 12, 3R/3B; donor fractions, 2.0 and 9.0%, respectively) and AMR (month 4; donor fraction, 4.9%). This example illustrates the application of this technique for detection of both ACR and AMR events (page 2, col 2 to page 3 col 1). De Vlaminck teaches that the GTD assay allows for improved modulation and tracking efficacy of anti-rejection therapies. De Vlaminck teaches that the GTD assay allows for early diagnosis of acute rejection and therefore presents an opportunity for early diagnosis and treatment (page 6 col 1-2). Thus De Vlaminck teaches a method of assessing a transplant subject comprising obtaining an amount of donor-specific cell-free DNA (DS cf-DNA) in a sample from the subject, comparing the amount of DS cf-DNA to prior DS cf-DNA amounts; and then determining a treatment or monitoring regimen for the subject based on the determined amount of DS cf-DNA compared to the prior DS cf-DNA amount. The subjects of De Vlaminck are being interpreted as subjects suspected of having or at risk of having cellular rejection since all transplant subjects are at risk and should be monitored after receiving a transplant.
Regarding Claim 10 De Vlaminck teaches that they analyzed the performance of the GTD approach for acute rejection diagnosis through a direct comparison with endomyocardial biopsy data. De Vlaminck teaches that the cfdDNA levels were significantly higher for heart transplant recipients during acute rejection and correlated with the severity of the rejection episode as determined by biopsy (comparing biopsy grades 0 and 1R/1A and biopsy grades 0 and ≥2R/3A or AMR). A receiver operating characteristic (ROC) analysis of the performance of cfdDNA as a marker of ACR (≥2R/3A or AMR) yielded an area under the curve (AUC) of 0.83 (sensitivity = 0.58 and specificity = 0.93 at a cfdDNA threshold level of 0.25%) (page 3 col 2 and Fig 5a and 5b).
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Thus De Vlaminck teaches that DS cf-DNA values can be compared to a threshold value that is 0.2.
Claim 13 recites “wherein” a cellular rejection grade of CR0 is assigned to the subject if the amount DS cf- DNA is less than 0.14, 0.15 or 0.2;(b) a cellular rejection grade of CR1 is assigned to the subject if the amount of DS cf- DNA is greater than 0.14, 0.15 or 0.2 or between 0.14 and 0.8, 0.15 and 0.8 or 0.2 and 0.8; or(c) a cellular rejection grade of CR2 or greater is assigned to the subject if the amount of DS cf-DNA is 0.8 or greater. Applicants are reminded that claim scope is not limited by claim language (such as wherein clauses) that suggests or makes optional but does not require steps to be performed. In the instant case there is no active process step of assigning a cellular rejection grade.
Regarding Claim 85 De Vlaminck teaches that that elevations of cfdDNA can occur before the development of rejection on endomyocardial biopsy, and may therefore present an opportunity for early diagnosis and treatment (page 6, col 2). Thus De Vlaminck teaches a method comprising treating the subject.
Double Patenting
7. 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
8a. Claims 1-2, 4, 10, 13, and 85 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6, 9, 12, 16, 18-19, 21-31, 37-38, 40, 43-44, 46, and 51 of US Application 18/015,834. Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding Claim 1 both sets of claims are drawn to a method of assessing a sample from a transplant subject (clm 1 of the copending application). Both sets of claims require determining an amount of donor-specific cell-free DNA (DS cf-DNA) in a sample from a subject (see clm 1 of the copending claims). Both sets of claims require reporting and/or recording the amount of DS cf-DNA (see clm 31 of the copending application). Regarding Claim 2 both sets of claims further comprise comparing the amount of DS cf-DNA to a threshold DS cf-DNA value (see clm 1 of the copending application). Regarding Claim 4 both sets of claims are drawn to a method of assessing a sample from a transplant subject (clm 1 of the copending application). Both sets of claims require obtaining an amount of donor-specific cell-free DNA (DS cf-DNA) in a sample from a subject (see clm 1 of the copending claims). Both sets of claims require comparing the amount of DS cf-DNA to a threshold DS cf-DNA value (see clm 1 of the copending application). Both sets of claims require determining a treatment or monitoring regimen for the subject based on the determined amount of DS cf-DNA compared to the threshold DS cf-DNA value and/or at least one prior DS cf-DNA amount (see clm 4 of the copending application). Regarding Claim 10 both sets of claims state that the threshold value is 0.2 (see clm 1 of the copending application. Regarding Claim 13, as discussed in the 103 rejection claim scope is not limited by claim language (such as wherein clauses) that suggests or makes optional but does not require steps to be performed. In the instant case there is no active process step of assigning a cellular rejection grade. Regarding Claim 85 both sets of claims require
selecting or suggesting a treatment for the subject or treating the subject (see clms 4, 16, 18 of the copending claims).
8b. Claim 3 and 5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6, 9, 12, 16, 18-19, 21-31, 37-38, 40, 43-44, 46, and 51 of US Application 18/015,834 in view of De Vlaminck (Science Translational Medicine June 18, 2014 Vol 6 Issue 241 pages 1-8).
The claims of the copending application are discussed above. The instant claims are different from the copending application because they further comprise assigning a cellular rejection grade for the subject, or as being at increased risk, based on the determined amount of DS cf-DNA compared to the threshold DS cf-DNA value and/or at least one prior DS cf-DNA amount. However as discussed above in the 103 rejections the prior art of De Vlaminck teaches this. Accordingly, it would have been obvious to have modified the method of the copending claims by assigning a cellular rejection grade based on the amount of DS cf-DNA for the benefit of being able to determine the best treatment for the subject.
9. Claims 1-5, 10, 13, and 85 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 50, 57, 60, 66, 70, 74, 78, 89 of US Application 16/623,719 in view of De Vlaminck (Science Translational Medicine June 18, 2014 Vol 6 Issue 241 pages 1-8). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding Claim 1 both sets of claims are drawn to a method of assessing a sample from a transplant subject (clm 1 of the copending application). Both sets of claims require determining an amount of donor-specific cell-free DNA (DS cf-DNA) in a sample from a subject (see clm 1 of the copending claims). Regarding Claim 2 both sets of claims further comprise comparing the amount of DS cf-DNA to a threshold DS cf-DNA value (see clm 2 of the copending application). Regarding Claims 3 and 5 both sets of claims require assigning a cellular rejection grade for the subject based on the amount of DS cfDNA (see clm 1 of the copending application). Regarding Claim 4 both sets of claims are drawn to a method of assessing a sample from a transplant subject (clm 1 of the copending application). Both sets of claims require obtaining an amount of donor-specific cell-free DNA (DS cf-DNA) in a sample from a subject (see clm 1 of the copending claims). Both sets of claims require comparing the amount of DS cf-DNA to a threshold DS cf-DNA value (see clm 2 of the copending application). Both sets of claims require determining a treatment or monitoring regimen for the subject based on the determined amount of DS cf-DNA compared to the threshold DS cf-DNA value and/or at least one prior DS cf-DNA amount (see clm 4 of the copending application). Regarding Claim 10 both sets of claims state that the threshold value is 0.2 (see clm 1 of the copending application. Regarding Claim 13 both sets of claims state that a cellular rejection grade of CR0 is assigned to the subject if the amount DS cf- DNA is less than 0.14, 0.15 or 0.2;(b) a cellular rejection grade of CR1 is assigned to the subject if the amount of DS cf- DNA is greater than 0.14, 0.15 or 0.2 or between 0.14 and 0.8, 0.15 and 0.8 or 0.2 and 0.8;or(c) a cellular rejection grade of CR2 or greater is assigned to the subject if the amount of DS cf-DNA is 0.8 or greater (see clm 1 of the copending application). Regarding Claim 85 both sets of claims require selecting or suggesting a treatment for the subject or treating the subject (see clms 4, 74, 78 the copending claims).
The instant claims are different from the copending claims because they recite reporting and/or recording the amount of DS cf-DNA. However as discussed above in the 103 rejections the prior art of De Vlaminck teaches this. Accordingly, it would have been obvious to have modified the method of the copending claims by recording the level of DS cf-DNA in a chart for the benefit of being able to compare measurements over time more easily.
10. Claims 1-5, 10, 13, and 85 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 12, 14, 48, 82, 104118, 134, 158 of US Application 16/666,210 in view of De Vlaminck (Science Translational Medicine June 18, 2014 Vol 6 Issue 241 pages 1-8). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding Claim 1 both sets of claims are drawn to a method of assessing a sample from a transplant subject (clm 1 of the copending application). Both sets of claims require determining an amount of donor-specific cell-free DNA (DS cf-DNA) in a sample from a subject (see clm 1 of the copending claims). Regarding Claim 2 both sets of claims further comprise comparing the amount of DS cf-DNA to a threshold DS cf-DNA value (see clm 158 of the copending application). Regarding Claim 4 both sets of claims are drawn to a method of assessing a sample from a transplant subject (clm 1 of the copending application). Both sets of claims require obtaining an amount of donor-specific cell-free DNA (DS cf-DNA) in a sample from a subject (see clm 1 of the copending claims). Both sets of claims require comparing the amount of DS cf-DNA to a threshold DS cf-DNA value (see clm 158 of the copending application). Both sets of claims require determining a treatment or monitoring regimen for the subject based on the determined amount of DS cf-DNA compared to the threshold DS cf-DNA value and/or at least one prior DS cf-DNA amount (see clm 1 of the copending application). Regarding Claim 13, as discussed in the 103 rejection claim scope is not limited by claim language (such as wherein clauses) that suggests or makes optional but does not require steps to be performed. Regarding Claim 85 both sets of claims require
selecting or suggesting a treatment for the subject or treating the subject (see clm 1 of the copending claims).
The instant claims are different from the copending claims because they require reporting and/or recording the amount of DS cf-DNA (clm 1). The instant claims are different from the copending claims because they require assigning a cellular rejection grade for the subject, or as being at increased risk, based on the determined amount of DS cf-DNA compared to the threshold DS cf-DNA value and/or at least one prior DS cf-DNA amount (clms 3 and 5). The instant claims are different from the copending claims because they state that the threshold value is 0.2 (clm 10). However as discussed above in the 103 rejections the prior art of De Vlaminck teaches this. Accordingly, it would have been obvious to have modified the method of the copending claims by recording the level of DS cf-DNA in a chart for the benefit of being able to compare measurements over time more easily. Additionally it would have been obvious to have modified the method of the copending claims by assigning a cellular rejection grade based on the amount of DS cf-DNA for the benefit of being able to determine the best treatment for the subject.
11. Claims 1-5, 10, 13, and 85 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14, 48, 82, 104, 118, 158 of US Application 16/504,469 in view of De Vlaminck (Science Translational Medicine June 18, 2014 Vol 6 Issue 241 pages 1-8). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding Claim 1 both sets of claims are drawn to a method of assessing a sample from a transplant subject (clms 1, 2 of the copending application). Both sets of claims require determining an amount of donor-specific cell-free DNA (DS cf-DNA) in a sample from a subject (see clm 1 of the copending claims). Regarding Claim 2 both sets of claims further comprise comparing the amount of DS cf-DNA to a threshold DS cf-DNA value (see clm 158 of the copending application). Regarding Claim 4 both sets of claims are drawn to a method of assessing a sample from a transplant subject (clm 1, 2 of the copending application). Both sets of claims require obtaining an amount of donor-specific cell-free DNA (DS cf-DNA) in a sample from a subject (see clm 1 of the copending claims). Both sets of claims require comparing the amount of DS cf-DNA to a threshold DS cf-DNA value (see clm 158 of the copending application). Both sets of claims require determining a treatment or monitoring regimen for the subject based on the determined amount of DS cf-DNA compared to the threshold DS cf-DNA value and/or at least one prior DS cf-DNA amount (see clm 1 of the copending application). Regarding Claim 13, as discussed in the 103 rejection claim scope is not limited by claim language (such as wherein clauses) that suggests or makes optional but does not require steps to be performed. Regarding Claim 85 both sets of claims require
selecting or suggesting a treatment for the subject or treating the subject (see clm 1 of the copending claims).
The instant claims are different from the copending claims because they require reporting and/or recording the amount of DS cf-DNA (clm 1). The instant claims are different from the copending claims because they require assigning a cellular rejection grade for the subject, or as being at increased risk, based on the determined amount of DS cf-DNA compared to the threshold DS cf-DNA value and/or at least one prior DS cf-DNA amount (clms 3 and 5). The instant claims are different from the copending claims because they state that the threshold value is 0.2 (clm 10). However as discussed above in the 103 rejections the prior art of De Vlaminck teaches this. Accordingly, it would have been obvious to have modified the method of the copending claims by recording the level of DS cf-DNA in a chart for the benefit of being able to compare measurements over time more easily. Additionally it would have been obvious to have modified the method of the copending claims by assigning a cellular rejection grade based on the amount of DS cf-DNA for the benefit of being able to determine the best treatment for the subject.
12. Claims 1-5, 10, 13, and 85 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of US Patent 10,385,396 in view of De Vlaminck (Science Translational Medicine June 18, 2014 Vol 6 Issue 241 pages 1-8). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding Claim 1 both sets of claims are drawn to a method of assessing a sample from a transplant subject (clms 1 of Patent). Both sets of claims require determining an amount of donor-specific cell-free DNA (DS cf-DNA) in a sample from a subject (see clm 1 of the Patent). Regarding Claim 2 both sets of claims further comprise comparing the amount of DS cf-DNA to a threshold DS cf-DNA value (see clm 1 of the Patent). Regarding Claim 4 both sets of claims are drawn to a method of assessing a sample from a transplant subject (clm 1 of the Patent). Both sets of claims require obtaining an amount of donor-specific cell-free DNA (DS cf-DNA) in a sample from a subject (see clm 1 of the Patent). Both sets of claims require comparing the amount of DS cf-DNA to a threshold DS cf-DNA value (see clm 1 of the Patent). Both sets of claims require determining a treatment or monitoring regimen for the subject based on the determined amount of DS cf-DNA compared to the threshold DS cf-DNA value and/or at least one prior DS cf-DNA amount (see clm 1 of the Patent). Regarding Claim 13, as discussed in the 103 rejection claim scope is not limited by claim language (such as wherein clauses) that suggests or makes optional but does not require steps to be performed. Regarding Claim 85 both sets of claims require selecting or suggesting a treatment for the subject or treating the subject (see clm 1 of the Patent).
The instant claims are different from the copending claims because they require reporting and/or recording the amount of DS cf-DNA (clm 1). The instant claims are different from the copending claims because they require assigning a cellular rejection grade for the subject, or as being at increased risk, based on the determined amount of DS cf-DNA compared to the threshold DS cf-DNA value and/or at least one prior DS cf-DNA amount (clms 3 and 5). The instant claims are different from the copending claims because they state that the threshold value is 0.2 (clm 10). However as discussed above in the 103 rejections the prior art of De Vlaminck teaches this. Accordingly, it would have been obvious to have modified the method of the copending claims by recording the level of DS cf-DNA in a chart for the benefit of being able to compare measurements over time more easily. Additionally it would have been obvious to have modified the method of the copending claims by assigning a cellular rejection grade based on the amount of DS cf-DNA for the benefit of being able to determine the best treatment for the subject.
13a. Claims 1, 2, 4, 13, and 85 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 5-9, 13, 17-26, 29 of US Application 17/493,293. Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding Claim 1 both sets of claims are drawn to a method of assessing a sample from a transplant subject (clm 1 of the copending application). Both sets of claims require determining an amount of donor-specific cell-free DNA (DS cf-DNA) in a sample from a subject (see clm 1 of the copending claims). Both sets of claims require reporting and/or recording the amount of DS cf-DNA (see clm 1 of the copending application). Regarding Claim 2 both sets of claims further comprise comparing the amount of DS cf-DNA to a threshold DS cf-DNA value (see clm 5 of the copending application). Regarding Claim 4 both sets of claims are drawn to a method of assessing a sample from a transplant subject (clm 1 of the copending application). Both sets of claims require obtaining an amount of donor-specific cell-free DNA (DS cf-DNA) in a sample from a subject (see clm 1 of the copending claims). Both sets of claims require comparing the amount of DS cf-DNA to a threshold DS cf-DNA value (see clm 5 of the copending application). Both sets of claims require determining a treatment or monitoring regimen for the subject based on the determined amount of DS cf-DNA compared to the threshold DS cf-DNA value and/or at least one prior DS cf-DNA amount (see clm 7 of the copending application). Regarding Claim 13, as discussed in the 103 rejection claim scope is not limited by claim language (such as wherein clauses) that suggests or makes optional but does not require steps to be performed. Regarding Claim 85 both sets of claims require
selecting or suggesting a treatment for the subject or treating the subject (see clm 7 of the copending claims).
13b. Claims 3, 5, and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 5-9, 13, 17-26, 29 of US Application 17/493,293 in view of De Vlaminck (Science Translational Medicine June 18, 2014 Vol 6 Issue 241 pages 1-8). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are different from the copending claims because they require assigning a cellular rejection grade for the subject, or as being at increased risk, based on the determined amount of DS cf-DNA compared to the threshold DS cf-DNA value and/or at least one prior DS cf-DNA amount (clms 3 and 5). The instant claims are different from the copending claims because they state that the threshold value is 0.2 (clm 10). However as discussed above in the 103 rejections the prior art of De Vlaminck teaches this. Accordingly, it would have been obvious to have modified the method of the copending claims by assigning a cellular rejection grade based on the amount of DS cf-DNA for the benefit of being able to determine the best treatment for the subject.
14. Claims 1-5, 10, 13, and 85 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of US Patent 10,472,680 in view of De Vlaminck (Science Translational Medicine June 18, 2014 Vol 6 Issue 241 pages 1-8). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding Claim 1 both sets of claims are drawn to a method of assessing a sample from a transplant subject (clms 1 of Patent). Both sets of claims require determining an amount of donor-specific cell-free DNA (DS cf-DNA) in a sample from a subject (see clm 1 of the Patent). Regarding Claim 2 both sets of claims further comprise comparing the amount of DS cf-DNA to a threshold DS cf-DNA value (see clm 1 of the Patent). Regarding Claim 4 both sets of claims are drawn to a method of assessing a sample from a transplant subject (clm 1 of the Patent). Both sets of claims require obtaining an amount of donor-specific cell-free DNA (DS cf-DNA) in a sample from a subject (see clm 1 of the Patent). Both sets of claims require comparing the amount of DS cf-DNA to a threshold DS cf-DNA value (see clm 1 of the Patent). Both sets of claims require determining a treatment or monitoring regimen for the subject based on the determined amount of DS cf-DNA compared to the threshold DS cf-DNA value and/or at least one prior DS cf-DNA amount (see clm 1 of the Patent). Regarding Claim 13, as discussed in the 103 rejection claim scope is not limited by claim language (such as wherein clauses) that suggests or makes optional but does not require steps to be performed. Regarding Claim 85 both sets of claims require selecting or suggesting a treatment for the subject or treating the subject (see clm 1 of the Patent).
The instant claims are different from the copending claims because they require reporting and/or recording the amount of DS cf-DNA (clm 1). The instant claims are different from the copending claims because they require assigning a cellular rejection grade for the subject, or as being at increased risk, based on the determined amount of DS cf-DNA compared to the threshold DS cf-DNA value and/or at least one prior DS cf-DNA amount (clms 3 and 5). The instant claims are different from the copending claims because they state that the threshold value is 0.2 (clm 10). However as discussed above in the 103 rejections the prior art of De Vlaminck teaches this. Accordingly, it would have been obvious to have modified the method of the copending claims by recording the level of DS cf-DNA in a chart for the benefit of being able to compare measurements over time more easily. Additionally it would have been obvious to have modified the method of the copending claims by assigning a cellular rejection grade based on the amount of DS cf-DNA for the benefit of being able to determine the best treatment for the subject.
15. Claims 1-5, 10, 13, and 85 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-5, 9, 13, 15, 37, 41, 43-44 of US Application 16/623,725 in view of De Vlaminck (Science Translational Medicine June 18, 2014 Vol 6 Issue 241 pages 1-8). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding Claim 1 both sets of claims are drawn to a method of assessing a sample from a transplant subject (clm 13 of the copending application). Both sets of claims require determining an amount of donor-specific cell-free DNA (DS cf-DNA) in a sample from a subject (see clm 13 of the copending claims). Regarding Claim 4 both sets of claims are drawn to a method of assessing a sample from a transplant subject (clm 13 of the copending application). Both sets of claims require obtaining an amount of donor-specific cell-free DNA (DS cf-DNA) in a sample from a subject (see clm 13 of the copending claims). Both sets of claims require determining a treatment or monitoring regimen for the subject based on the determined amount of DS cf-DNA compared to the threshold DS cf-DNA value and/or at least one prior DS cf-DNA amount (see clm 15of the copending application). Regarding Claim 13, as discussed in the 103 rejection claim scope is not limited by claim language (such as wherein clauses) that suggests or makes optional but does not require steps to be performed. Regarding Claim 85 both sets of claims require selecting or suggesting a treatment for the subject or treating the subject (see clm 41 of the copending claims).
The instant claims are different from the copending claims because they require reporting and/or recording the amount of DS cf-DNA (clm 1). The instant claims are different from the copending claims because they require comparing the amount of DS cf-DNA to a threshold DS cf-DNA value (clms 2 and 5). The instant claims are different from the copending claims because they require assigning a cellular rejection grade for the subject, or as being at increased risk, based on the determined amount of DS cf-DNA compared to the threshold DS cf-DNA value and/or at least one prior DS cf-DNA amount (clms 3 and 5). The instant claims are different from the copending claims because they state that the threshold value is 0.2 (clm 10). However as discussed above in the 103 rejections the prior art of De Vlaminck teaches this. Accordingly, it would have been obvious to have modified the method of the copending claims by recording the level of DS cf-DNA in a chart for the benefit of being able to compare measurements over time more easily. Additionally it would have been obvious to have modified the method of the copending claims by assigning a cellular rejection grade based on the amount of DS cf-DNA for the benefit of being able to determine the best treatment for the subject.
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/AMANDA HANEY/Primary Examiner, Art Unit 1682