DETAILED ACTION
The present Office Action is responsive to the Amendment received on August 11, 2026.
Preliminary Remark
Claim 2 is canceled.
Claims 14-21 are new.
Drawings
The replacement drawings received on August 11, 2026 are acceptable.
Claim Interpretation
The term, “DNAemia” recited in claim 4 is not deemed a trademark as the term is known in the art in describing the presence of DNA in the blood with reference to viral replication.
Claim Rejections - 35 USC § 112
Some of the rejections pertaining to the rejection rationale of claims 1-13 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particularly point out and distinctly claim the subject matter, made in the Office Action mailed on March 11, 2026 is withdrawn in view of the Amendment received on August 11, 2026. Rejections maintained are reproduced below.
Rejection – Maintained
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.
The below-reproduced rejection of claims 1-13 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, made in the Office Action mailed on March 11, 2026 is maintained for the reasons of record.
Applicants’ claim amendment and arguments presented in the Amendment received on August 11, 2026 have been carefully considered but they have not been found persuasive for the reasons discussed in the, “Response to Arguments” section.
The Rejection:
Claim 1 is also indefinite because the breadth covering what is considered “complications” is infinitely large. While the breadth of a claim can at times be large without being indefinite, the claimed method does not recite what a “complication” is. A complication can include anything from physical element, mental element, situational element, etc. Therefore, simply reciting that a method is for evaluation of a risk of “complications” without reciting that the complication is results in an indeterminable breadth.
Claims 2-13 are indefinite by way of their dependency on claim 1.
Response to Arguments:
Applicants contend that claims have been amended in a manner that is believed to render the rejections moot (page 10, Response).
The Office acknowledges that most of the rejections have been overcome by the Amendment. However, the rejection of claim 1 based on the rationale discussed above has not been overcome.
While claim 1 has been amended to more particularly recite the risk of complication, the claim nevertheless embraces an embodiment directed to a method for in vitro or ex vivo evaluation of the risk of complications requiring the implementation of one of more invasive medical devices, prolonging treatment in a healthcare facility which continues to embrace a infinitely large coverage. The application is directed to a limited application of the measurement of TTV for the risk assessment of a patient experiencing hospital acquired infection. Therefore, the claim is not commensurate with this limited disclosure and continues to embrace any so-called “complications” that has nothing to do with HAI, but other issues such as physical, mental, situational, etc.
The rejection is therefore, not overcome.
Rejection – New Grounds, Necessitated by Amendment
Claims 7 and 15 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 7 is indefinite for the following reasons.
Claim 7 depends from claim 1.
Claim 1 recites a step of “establishing a risk of the complications when the viral load determined for the biological sample is greater than or less than the predetermined reference value”, wherein the predetermined reference value is set at 10,000 copies/mL.
Claim 1 explicitlys require that the predetermined values of 10,000 copies/mL is the cut off value where in values above or below result in the determination.
Claim 7, however, recites that the risk of the “complications” is absent when the value of TTV (calculated by TTVT2(value) – TTVT1(value)) is + 1.25 (for example), indicating that the amount of TTV has not meaningfully increased from the time the patient was admitted to a second time point. However, these two calculations are two independent indicia.
Claim 1 requires that the determination is based on whether the amount (not the delta value) of TTV is greater than or lesser than 10,000 copies/mL, but claims 7 and 16-18, now contravenes that requirement and seek to make the determination based on the change of TTV present in the subject at two time points. For example, a patient could have a TTV value of greater than 10,000 copies/mL at T1, but the variance between its value at T2 may still be within + 1.25, at which point it becomes unclear whether the subject is at risk of complications (having greater than 10,000 copies/mL of TTV) or not at risk (having DTTV within + 1.25). therefore, this results in the confusion how the threshold value of 10,000 copies/mL and the DTTV are to be used together.
Claim 7 has not been further considered on their merits as no reasonable interpretation could be made as a result.
Claim 15 is new and is indefinite because the claim contains a grammatical error and makes no sense:
“evaluation of the risk of complications requiring the implementation or one or more invasive medical devices”
It would appear that the subject-phrase should recite the below:
“evaluation of the risk of complications requiring the implementation of one or more invasive medical devices”
Claim Rejections - 35 USC § 101
The rejection of claim 2 under 35 U.S.C. 101 because the claimed invention is non-patent eligible for the reasons discussed in the Office Action mailed on March 11, 2026 is withdrawn in view of the Amendment received on August 11, 2026, canceling the rejected claim.
The rejection of claim 7 under 35 U.S.C. 101 because the claimed invention is non-patent eligible for the reasons discussed in the Office Action mailed on March 11, 2026 is withdrawn in view of the Amendment received on August 11, 2026, because no meaningful interpretation could be made as discussed above under section 112b.
Maintained & New, Necessitated by Amendment
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.
The rejection of Claims 1, 3-6, and 8-13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to either: a) judicial exception of naturally existing phenomenon; or b) judicial exception of abstract idea (i.e., data manipulation) without significantly more. The claims recite either: a) collection of data (i.e., measurement of viral load) and their manipulation (i.e., comparison and conclusion); or natural correlation that exists between the TTV viral load and a subject’s propensity to develop complications from a healthcare facility.
In addition, claims 14-21 are rejected herein as being necessitated by Amendment (their addition). These claims are addressed in the, “Response to Arguments” section, along with the Office’s response to Applicants’ arguments presented in the Amendment received on August 11, 2026.
The Rejection:
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception based on the analysis under the current Patent Eligibility Guidelines (herein, “PEG”) as discussed below.
Step 1 Inquiry under PEG
Step 1 inquiry under Patent Eligibility Guidelines (herein, “PEG”) determines whether or not the claimed invention is drawn to one of the recognized statutory classes of invention. Claims 1-13 satisfy the present inquiry as being drawn to a method.
Step 2A Inquiry under PEG
A recently revised PEG now performs step 2A inquiry under a 2-prong analysis, and the subject claims analyzed accordingly as follows:
Prong 1:
Prong-1 inquiry under step 2A determines whether the claim(s) recites an abstract idea, a law of nature, or a natural phenomenon.
I – Data Collection/manipulation (claims 1-13):
The breadth of claim 1 embraces a method that involve steps of collecting a set of data and processing the data, which is considered a judicial exception under abstract idea.
Specifically, claim 1 recites the steps of: a) measuring a viral load of TTV; b) comparing the viral load to a reference value; and c) establishing a risk of complication from the comparison.
Because the claimed steps employ a highly general language of “measuring” a viral load which embraces, collection of data from an assay, this step can broadly be construed as data collection. Following the data collection (i.e., a numeral value), the claimed steps employ the comparison of this numerical value to a reference value, which is broadly construed as data manipulation/processing. The final step of the method results in the output made from this comparison, which is construed to be a simple output of a data based on the processing. Therefore, the claims embrace judicial exceptions based on abstract idea.
II – Naturally existing correlation (claims 1-13):
The breadth of claim 1 can alternatively be construed to require the steps of: a) actively performing a measurement of a viral load of TTV (by conventionally performed assay); b) comparing the measured amount to a reference amount; and c) establishing a risk of complication based on the comparison.
Even if one were to construe that the step of “measuring” implies an active assay, the amount of TTV that exists in a patient and the predisposition of that patient to develop complication when said TTV viral load exceed a certain value, that correlation is a naturally existing phenomenon. While Applicants may have discovered this phenomenon, this is, nevertheless, a natural correlation, which is deemed a judicial exception.
For these reasons, claims recite a judicial exception.
Prong 2:
Prong-2 inquiry under step 2A determines whether or not the claims recite additional elements that integrate the judicial exception into a practical application in a manner that imposes a meaningful limit on the judicial exception.
I – Data Collection/manipulation (claims 1-13):
Claim 1 recites an additional feature of comparing a collected data point to a pre-established value determined from a reference (i.e., predetermined reference value), and establishment of a risk complication based on that comparison.
Claims 2-5 recite additional elements in the form of the actual reference value being set at 10,000 copies/ml of TTV and determination based on the comparison to that value, as well as collecting further data point in the form of whether herpesvirus is present.
Claims 6 recite an additional element of collecting the data points at different time points and calculating a difference, with claim 7 reciting a range of values that pertain to a significant difference (i.e., DTTV).
Claims 8-12 further clarifies the source from which the data are collected.
However, none of these additional features are deemed to place a meaningful limit to the abstract idea of data collection and manipulation to derive an output because no active steps are performed to “apply” the data output in a meaningfully significant way. At the conclusion of the method that involve all of the additional features, the method suspends at a data output with no actual application of the data.
“Diehr explained that while an abstract idea, law of nature, or mathematical formula could not be patented, ‘an application of a law of nature or mathematical formula to a known structure or process may well be deserving of patent protection.’ (Bilski v. Kappos, 561 U.S. 593, 611, 95 USPQ2d 1001, 1010 (2010))
As well, combining judicial exception (i.e., data collection) with another judicial exception (i.e., data manipulation such as calculating DTTV value) does not render that combination a practical application:
Bilski, 561 U.S. at 601, 95 USPQ2d at 1005-06 (quoting Chakrabarty, 447 U.S. at 309, 206 USPQ at 197 (1980)), if there are no additional claim elements besides the judicial exception, or if the additional claim elements merely recite another judicial exception, that is insufficient to integrate the judicial exception into a practical application. See, e.g., RecogniCorp, LLC v. Nintendo Co., 855 F.3d 1322, 1327, 122 USPQ2d 1377 (Fed. Cir. 2017) (“Adding one abstract idea (math) to another abstract idea (encoding and decoding) does not render the claim non-abstract”) (see MPEP 2106.04(II))
II – Naturally existing correlation (claims 1-13):
Claim 1 recites an additional step of “measuring” by an assay and “comparing the viral load” to a pre-established reference value and establishing a risk based on the comparison.
Claims 2-5 recite additional elements in the form of the actual reference value being set at 10,000 copies/ml of TTV and determination based on the comparison to that value, as well as collecting further data point in the form of whether herpesvirus is present.
However, the reference value that can delineate between a patient’s predisposition for risk of complication is a naturally existing level and therefore is not an additional feature. Rather this is a judicial exception. As to the step of “measuring” the level of TTV load, the step of measuring is recited in a highly general way and therefore does not add a meaningful limit to observing the viral load.
This fact pattern is analogous to that which was present in Mayo (citation omitted), where the method under contention recited a mean to determining the levels of a drug metabolite using a highly general language, to which the court expressed as involving “well-understood routine and conventional activity previously engaged in the researcher in the field”.
“What else is there in the claims before us? The process that each claim recites tells doctors interested in the subject about the correlations that the researcher discovered. In doing so, it recites an ‘administering’ step, a ‘determining’ step, and a ‘wherein’ wherein step. These additional steps are not themselves natural laws but neither are they sufficient to transform the nature of the claim.”
“the ‘determining’ step tells the doctor to determine the level of the relevant metabolites in the blood, through whatever process the doctor or the laboratory wishes to use. As the patents state, methods for determining metabolite levels were well known in the art. ‘623 patent, col. 9, ll. 12-65, 2. App. 11. … Thus, this step tells doctors to engage in well understood, routine, conventional activity previously engaged in by scientists who work in the field. Purely ‘conventional or obvious’ ‘[pre]-solution activity’ is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law. Flook, 437 U.S., at 590; see also Bilski, 561 U.S., at __ (slip op., at 14) (‘[T]he prohibition against patenting abstract ideas ‘cannot be circumvented by’ … adding ‘insignificant post-solution activity’’ (quoting Diehr, supra, at 191-192)).”
Claims 6 recite an additional element of collecting the data points at different time points and calculating a difference, with claim 7 reciting a range of values that pertain to a significant difference (i.e., DTTV). However, these steps are not considered to meaningfully limit the natural correlation as taking a value prior to the admission and after admission for observance of a change in the amount of TTV load would have been a routine and conventional means in data analysis in measuring significance of the data.
Claims 8-12 further clarifies the source from which the data are collected. However, the source from which the TTV load is measured is also a naturally existing phenomenon as the value, regardless of the source would have been correlated to the patient’s predisposition to developing complications in a patient.
As explained by the Supreme Court, in order to transform a judicial exception into a patent-eligible application, the additional element or combination of elements must do ‘more than simply stat[e] the [judicial exception] while adding the words ‘apply it’”. Alice Corp. v. CLS Bank, 573 U.S. __, 134 S. Ct. 2347, 2357, 110 USPQ2d 1976, 1982-83 (2014) (quoting Mayo Collaborative Servs. V. Prometheus Labs., Inc., 566 U.S. 66, 72, 101 USPQ2d 1961, 1965). Thus, for example, claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. Alice Corp., 134 S. Ct. at 2358, 110 USPQ2d at 1983. See also 134 S. Ct. at 2389, 110 USPQ2d at 1984 (warning against a § 101 analysis that turns on “the draftsman’s art”) (MPEP 2106.05(f))
Step 2B Inquiry under PEG
Step 2B inquiry of the PEG determines whether or not additional elements are provided and whether such elements amount to significantly more than the judicial exception in the claims.
Presently, the additional elements which are provided in the claims that recite that the judicial exceptions are recited in a highly general way so as to capture means of determining and comparing that are conventionally known, routine adopted in the art of molecular diagnostics, and fail to place a significantly more to the recited judicial exception.
Therefore, the present claims lack patent eligibility.
Response to Arguments:
Applicants traverse the rejection.
Applicants state that claim 1 has been amended to recite, “a method for the in vitro or ex vivo evaluation of the risk of complications requiring the implementation of one or more invasive medical devices, prolonging treatment in a healthcare facility, or leading to the development of a secondary infection or an opportunistic infection in a patient admitted to a healthcare facility to who is not undergoing immunosuppressive treatment” which further recite the recitation of “predetermined reference value of 10 000 copies/ml”.
This amendment introduces additional limitation into the preamble of the claims and incorporates the limitation of previously rejected claim 2 into the parent claim 1.
Applicants contend that claims as amended require the application of a specific predetermined reference value which is necessarily a meaningful limit on the abstract idea of data collection and manipulation to derive an output.
This argument has been carefully considered but has not been found persuasive.
With regard to the recitation of the additional limitations placed on the preamble of the claim in the form of “risk of complications requiring the implementation of one of more invasive medical devices, prolonging treatment in a healthcare facility, or leading to the development of a secondary infection or an opportunistic infection in a patient admitted to a healthcare facility” (new limitations, underlined), the Office does not find the addition places the claims patent eligible because the limitations are an intended purpose of the claim, and the claims do not contain an active step of such interventions. As well, an alternative embodiment of the limitation embraces the inherent property (i.e., judicial exception) of the patient “developing” a secondary infection or an opportunistic infection, which places no additional active application to the claim.
Most importantly, the Office respectfully disagrees that the comparison of the collected data point of TTV value to a reference number of 10,000 copies/mL places meaningful application, when considering both judicial exception issues that are: a) data manipulation; and b) naturally existing correlation.
A – Data Collection/manipulation (claims 1, 3-6, and 8-13):
Claim 1 recites the steps of: a) measuring a viral load of TTV; b) comparing the viral load to a reference value; and c) establishing a risk of complication from the comparison.
The claimed steps employ a highly general language of “measuring” a viral load which embraces, collection of data from an assay, this step can broadly be construed as data collection. Following the data collection (i.e., a numeral value), the claimed steps employ the comparison of this numerical value to a reference value, which is broadly construed as data manipulation/processing. The final step of the method results in the output made from this comparison, which is construed to be a simple output of a data based on the processing. Therefore, the claims embrace judicial exceptions based on abstract idea.
While Applicants contend that the predetermined value of 10,000 copies/mL and a step of comparing that value to the measured value of TTV (i.e., data), such comparison only results to produce an output that indicates an observed data being greater or lesser than a reference value. At the conclusion of the method that involve all of the additional features, the method suspends at a data output with no actual application of the data.
“Diehr explained that while an abstract idea, law of nature, or mathematical formula could not be patented, ‘an application of a law of nature or mathematical formula to a known structure or process may well be deserving of patent protection.’ (Bilski v. Kappos, 561 U.S. 593, 611, 95 USPQ2d 1001, 1010 (2010))
Bilski, 561 U.S. at 601, 95 USPQ2d at 1005-06 (quoting Chakrabarty, 447 U.S. at 309, 206 USPQ at 197 (1980)), if there are no additional claim elements besides the judicial exception, or if the additional claim elements merely recite another judicial exception, that is insufficient to integrate the judicial exception into a practical application. See, e.g., RecogniCorp, LLC v. Nintendo Co., 855 F.3d 1322, 1327, 122 USPQ2d 1377 (Fed. Cir. 2017) (“Adding one abstract idea (math) to another abstract idea (encoding and decoding) does not render the claim non-abstract”) (see MPEP 2106.04(II))
Presently, the claims do not result in any meaningful application other than a conclusion that the measured TTV value from a subject is either greater or lesser than a predetermined value. While the claim recites that a “risk” is established, absent any actual meaningful step of applying the resulting output, such “establishing” is simply a word attached to the output produced from the data comparison.
Therefore, Applicants’ arguments are not found persuasive under this assessment.
II – Naturally existing correlation (claims 1, 3-6, and 8-13):
The breadth of claim 1 can alternatively be construed to require the steps of: a) actively performing a measurement of a viral load of TTV (by conventionally performed assay); b) comparing the measured amount to a reference amount; and c) establishing a risk of complication based on the comparison.
Even if one were to construe that the step of “measuring” implies an active assay, the amount of TTV that exists in a patient and the predisposition of that patient to develop complication when said TTV viral load exceed a certain value, that correlation is a naturally existing phenomenon. While Applicants may have discovered this phenomenon, this is, nevertheless, a natural correlation, which is deemed a judicial exception.
For these reasons, claims recite a judicial exception.
Claim 1 recites an additional step of “measuring” by an assay and “comparing the viral load” to a pre-established reference value and establishing a risk based on the comparison.
Claim 2-5 recite additional elements in the form of the actual reference value being set at 10,000 copies/ml of TTV and determination based on the comparison to that value, as well as collecting further data point in the form of whether herpesvirus is present.
However, the reference value that can delineate between a patient’s predisposition for risk of complication is a naturally existing level and therefore is not an additional feature. Rather this is a judicial exception. As to the step of “measuring” the level of TTV load, the step of measuring is recited in a highly general way and therefore does not add a meaningful limit to observing the viral load.
This fact pattern is analogous to that which was present in Mayo (citation omitted), where the method under contention recited a mean to determining the levels of a drug metabolite using a highly general language, to which the court expressed as involving “well-understood routine and conventional activity previously engaged in the researcher in the field”.
“What else is there in the claims before us? The process that each claim recites tells doctors interested in the subject about the correlations that the researcher discovered. In doing so, it recites an ‘administering’ step, a ‘determining’ step, and a ‘wherein’ wherein step. These additional steps are not themselves natural laws but neither are they sufficient to transform the nature of the claim.”
“the ‘determining’ step tells the doctor to determine the level of the relevant metabolites in the blood, through whatever process the doctor or the laboratory wishes to use. As the patents state, methods for determining metabolite levels were well known in the art. ‘623 patent, col. 9, ll. 12-65, 2. App. 11. … Thus, this step tells doctors to engage in well understood, routine, conventional activity previously engaged in by scientists who work in the field. Purely ‘conventional or obvious’ ‘[pre]-solution activity’ is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law. Flook, 437 U.S., at 590; see also Bilski, 561 U.S., at __ (slip op., at 14) (‘[T]he prohibition against patenting abstract ideas ‘cannot be circumvented by’ … adding ‘insignificant post-solution activity’’ (quoting Diehr, supra, at 191-192)).”
To this end, Applicants have not provided any arguments, and therefore, the rejection is maintained.
Re: New claims 14-20:
Claim 14 recites the detecting the presence of at least one herpes virus by measuring DNAemia, the sample being from a patient admitted to an healthcare unit (i.e., ER, resus departement, ICU, or high-dependency unit), and that the at least one herpes virus is EBV, or that the sample is blood derivative, plasma or serum.
Claim 15 is an independent claim that seeks to combine the limitations of claim 1 (for the measurement of at least one TTV in a biological sample of a subject) and claim 6, which measures the TTV level at two different time points.
With regard to claim 15, the claim fails the patent eligibility requirement under data manipulation.
A – Data manipulation & Mental Process (claims 15-18):
As discussed above, claim 15 is directed to the obtainment of two data points at time point T1 and T2, and calculation of their difference. As discussed above, the calculated value is associated with a “conclusion” regarding the risk, but there is no active meaningful application of this conclusion. Therefore, the claim simply amounts to the obtainment of two data points, calculation of their difference, and while a “conclusion” is reached, that conclusion is generically recited and does not amount to more than a word being attached to a data as the conclusion does not result in any actual application that is meaningful.
In addition, claim 15 also is patent ineligible based on mental processing, as the claims simply embraces a practitioner looking at two data points of TTV values, calculating their differences in their head, and simply thinking about what the difference means.
With regard to claims 16-18, the calculation of the difference is deemed manipulation of data, and because claims contain no active application of the resulting data, such steps are not deemed to meaningfully limit the abstract idea. As well, the calculation of the differences also embraces a mental process of a practitioner and therefore is not deemed patent eligible.
B – Naturally existing correlation (claims 14 and 19-20; and 15-16):
With regard to claim 14 and 19-20, the measurement of at least herpesvirus, such as EBV being present along with TTV, and the surrounding in which they are found (i.e., serum or plasma), these additional limitations further combine a naturally existing correlation. In other words, while Applicants may have discovered that a patent’s risk of complication may increase with the presence of TTV and other herpesvirus such as EBV, in plasma or serum, this discovery is nevertheless that which was naturally existing phenomenon. And as already discussed above, combination of judicial exceptions do not result patent eligibility when that combination nevertheless is a naturally existing phenomenon.
With regard to claims 15-16, the naturally existing correlation is between the increasing levels of TTV in a subject and their predisposition to acquiring HAI. And for the same reasons as discussed above, the claims do not meaningfully apply this naturally existing correlation to a patentable subject matter.
Therefore, for these reasons, the invention as claimed is not deemed patent eligible.
Claim Rejections - 35 USC § 103
The rejection of claims 1, 3, 4, and 6-13 under 35 U.S.C. 103 as being unpatentable over Strassl et al. (The Journal of Infectious Diseases, published on-line July 2018, pages 1191-1199), made in the Office Action mailed on March 11, 2026 is withdrawn in view of the Amendment received on August 11, 2026. Specifically, the limitation of claim 2 has been incorporated into claim 1, and effective filing date of the instant claim 2 has been overcome by an English translation of the foreign priority document.
The rejection of claims 2 and 5 under 35 U.S.C. 103 as being unpatentable over Strassl et al. (The Journal of Infectious Diseases, published on-line July 2018, pages 1191-1199), as applied to claims 1, 3, 4, and 6-13 above, and further in view of Mallet et al. (Frontiers in Immunology, November 2021, vol. 12, pages 1-15; IDS ref) made in the Office Action mailed on March 11, 2026 is withdrawn in view of the Amendment received on August 11, 2026.
Rejection – New Grounds, Necessitated by Amendment
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 15-18 are rejected under 35 U.S.C. 103 as being unpatentable over Strassl et al. (The Journal of Infectious Diseases, published on-line July 2018, pages 1191-1199).
With regard to claim 15, Strassl et al. teach a method comprising measuring the viral level of at last one Torque Teno Virus (TTV) in a biological sample from a patient (“TTV was quantified prospectively in the peripheral blood at the following time points: before1 transplantation and after transplantation”, page 1192, 2nd column) and teach that before the transplantation, 80% of the patients were TTV positive and before transplantation, “a median of 1.9 x104 TTV/copies/mL … was detected …” (page 1192, 1st column, 1st paragraph)
Strassl et al. teach that the level of TTV is used to predict infectious disease posttransplantation (“test the value of TTV quantification to predict infectious disease posttransplantation we included all TTV measurements taken after stabilization of TTV viremia (>day 92 posttransplantation) and analyzed the corresponding follow-up periods for the presence of infectious disease events”, page 1194, 1st column).
Strassl et al. teach that TTV levels detected before the occurrence of an infection were higher compared to levels preceding a follow-up period without infection, wherein the artisans state that TTV levels above 3.1 x 109 copies/ml corresponded to a sensitivity of 90%, specificity of 20%, negative predictive value of 92%, and positive predictive value of 17% for the prediction of an infection (page 1194, 2nd column)
The risk is a healthcare-associated infection occurring (occurs in hospital stay after surgery).
The biological sample is plasma (see “TTV DNA was extracted from 200 mL of plasma”, page 1192, 2nd column, 3rd paragraph).
While Strassl et al. explicitly teach that the level of TTV was determined before the surgery where the subject was not prior treated with immunosuppressive treatment, the artisans’ determination of reference TTV level was based on all three stages of the patient that included pre-surgical state, post-surgical state, and post discharge-state which included immunosuppressive treatment (“TTV was quantified prospectively in the peripheral blood at the following time points: before the transplantation and after transplantation once per week until discharge from the ward, on the first visit at the outpatient clinic, on month 3 after transplantation, and every 3 months thereafter”, page 1192, 2nd column). That is, the risk of complication (i.e., infection) was not assessed for a patient who is not undergoing an immunosuppressive treatment.
While Strassl et al. do teach that TTV levels detected before the occurrence of an infection were higher compared to levels preceding a follow-up period without infection, wherein the artisans state that TTV levels above 3.1 x 109 copies/ml corresponded to a sensitivity of 90%, specificity of 20%, negative predictive value of 92%, and positive predictive value of 17% for the prediction of an infection (page 1194, 2nd column), the artisans do not explicitly teach the calculation of DTTV from two different time points, or the conclusion that low variation between the two timepoints being associated with lower risk of complication.
However, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to take the teachings of Strassl et al. and conventional wisdom in the art, thereby arriving at the invention as claimed for the following reasons.
Strassl et al. teach that the levels of TTV have long been known to be associated with the immunocompetence of an individual with high levels being associated with infections:
“Peripheral blood levels of TTV might mirror the overall strength of innate and specific immunity and thus viral load is closely related to the immunocompetence of the host” (page 1191, 2st column)
“high TTV levels were found to be associated with infection after lung transplantation” (page 1191, 2nd column)
Given such correlation between the levels of TTV and immunocompetence of a host (i.e., subject), one of ordinary skill in the art would have been motivated to determine whether the level of the TTV of a subject is increasing by taking the measurement of TTV levels at time period T1 and T2, taking the difference of the two points (i.e., DTTV), wherein a significant increase at a later timepoint would have revealed the level of TTV had significantly increased, thus indicating that the subject would likely have a higher risk of a hospital acquired infection due to loss of immunocompetence, or in the alternative, TTV levels remaining substantially constant (i.e., not significantly increasing) indicative that the subject’s immune system remained competent.
In KSR, the Supreme Court particularly emphasized “the need for caution in granting a patent based on the combination of elements found in the prior art,” Id. at 415, 82 USPQ2d at 1395, and discussed circumstances in which a patent might be determined to be obvious. Importantly, the Supreme Court reaffirmed principles based on its precedent that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” Id. at 415-16, 82 USPQ2d at 1395. The Supreme Court stated that there are “[t]hree cases decided after Graham [that] illustrate this doctrine.” Id. at 416, 82 USPQ2d at 1395. (1) “In United States v. Adams, . . . [t]he Court recognized that when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result.”
Therefore, the invention as claimed is deemed prima facie obvious over the cited references.
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.
Inquiries
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Young J. Kim whose telephone number is (571) 272-0785. The Examiner can best be reached from 7:30 a.m. to 4:00 p.m (M-F). The Examiner can also be reached via e-mail to Young.Kim@uspto.gov. However, the office cannot guarantee security through the e-mail system nor should official papers be transmitted through this route.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Gary Benzion, can be reached at (571) 272-0782.
Papers related to this application may be submitted to Art Unit 1681 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 CFR 1.6(d)). NOTE: If applicant does submit a paper by FAX, the original copy should be retained by applicant or applicant’s representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED, so as to avoid the processing of duplicate papers in the Office. All official documents must be sent to the Official Tech Center Fax number: (571) 273-8300. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
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/YOUNG J KIM/Primary Examiner
Art Unit 1637 October 12, 2026
/YJK/
1 Strassl et al. is clear that the subject’s TTV levels were taken before transplantation and it is clear that the subjects received a prophylactic immunosuppressant treatment only after the transplantation: “[a]ll patients received prophylaxis with trimethoprim and sulfamethoxazole for 6 months after transplantation and valganciclovir for 3 months in cytomegalovirus (CMV) Ig-G negative recipients of a CMV IgG-positive organ … after treatment with antithymoglobulin and IgG immuoasphereis …” (page 1192)
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