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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The IDS received on June 18, 2024 is proper and is being considered by the Examiner.
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because the clarity of the drawings is poor and the texts of the figures are illegible (see Figures 2A, 2B, 3, for example). Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
Comment regarding Claims
The Office suggest amending the claims to adopt the claim language conventional to the U.S. practice. For example, phrase, “consisting in” is suggested to replaced with the phrase, “consisting of”.
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
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 1-13 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 1 combines two transitional languages, “comprising” and “consisting of,” resulting in the claimed method being indefinite in whether the method is “closed” for inclusion of additional steps or “open” for the inclusion.
Specifically, claim 1 recites that the method is “characterized in that it [i.e., method] comprises carrying out the steps consisting in,” followed by the recited steps (a)-(c). The Office has construed this phrase to mean that the method can comprise additional elements connoted by the method “comprising the carrying out steps” for the purpose of prosecution.
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 4, 7, 9, 10, 12, and 13 are indefinite for the following reasons:
Claims 4, 7, 9, and 12 recite the word, “preferably” preceding a recited limitation;
Claim 10 recites the word, “more particularly” preceding a recited limitation; and
Claim 13 recites the word, “such as” preceding a recited limitation.
The usage of the above words render a claim indefinite because it becomes unclear whether the limitation following said words are actively required or not, as well as under what conditions the limitation are “preferred,” or “particularly” required.
Claim 6 is indefinite because the claim is missing a conjunction between steps (c) and (d). For the purpose of prosecution, the conjunction, “and” has been assumed.
Claim 10 is indefinite for the following reasons. Claim 10 depends from claim 1. Claim 1 recites that the method is for the in vitro or ex vivo evaluation of the risk of complications in a patient admitted to a healthcare facility”. Claim 10 however, recites that the biological sample is from a subject already experiencing complication, such as septic shock. Because the subject is already admitted in a healthcare facility and already has a complication to begin with it is unclear just what exactly the method is achieving by evaluating a risk of complication in the patient.
Claim 11 is indefinite for the same reason.
Claim 12 is indefinite because the claim employs a Markush group from which an element is “selected from.” The usage of a Markush is interpreted as selecting a member from a defined group (i.e., Markush group). The phrase, “preferably EBV” renders the claim indefinite because it becomes unclear whether the claim is allowing the selection of any recited members of the group, or is limited to only EBV, in which the case, the usage of Markush group itself becomes indefinite.
Claim 13 is indefinite because it is completely unclear what members are part of the Markush group. The claim recites that the biological fluid is selected from the group consisting of “blood or derivative thereof, such as plasma and/or serum, cerebrospinal fluid, and bronchoalveolar lavage”.
Claims 2-13 are also indefinite by way of their dependency on claim 1.
Claim Rejections - 35 USC § 101
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 1-13 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.
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.
Claim Rejections - 35 USC § 103
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 1, 3, 4, and 6-13 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 1, 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)
With regard to claim 3, Strassl et al. teach that values greater this threshold (3.1 x 109 copies/mL).
With regard to claims 4 and 12, the artisans also measure for the presence of at least one herpesvirus DNAemia (CMV, see “[s]creening for CMV and BK polyomavirus … by PCR from peripheral blood …”, page 1192, 2nd column).
With regard to claims 8-11, the risk is a healthcare-associated infection occurring (occurs in hospital stay after surgery).
With regard to claim 13, 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 a reference value being useful for predicting an infection post-surgery, as well as measuring the levels of TTV before the surgery and duration of recovery thereafter, the artisans do not explicitly teach that DTTV level is calculated between two timepoints, wherein the value range specified in claim 8 is used for risk assessment.
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)
While the TTV reference level determined by Strassl et al. covered periods of time during which the subject received the immunosuppressant therapy, because the reference level of TTV was nevertheless correlated with a risk of infection, in combination with the prior knowledge of TTV level being related to immunocompetence and infection, one of ordinary skill in the art would have reasonably concluded that the same reference level of TTV in a sample of a patient in a healthcare facility, would have equally provided a predictive value in assessing the patient’s risk of developing infection during healthcare stay.
As to taking the level of the TTV at time period T1 and T2 and taking the difference of the two points (i.e., DTTV), doing so would have revealed whether the level of TTV had increased or remained constant in the patient, wherein a significant increase beyond standard deviation levels (i.e., -1.25 to +1.25) would have revealed whether the level of TTV had significantly increased beyond the threshold level or remained constant, yielding no more than a predictable outcome.
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.
Claims 2 and 5 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), 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).
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
The teachings of Strassl et al. have already been discussed above.
Strassl et al. do not teach that the reference value of 10,000 copies/mL can be utilized as a threshold in determining a subject’s risk of complication.
Mallet et al. teach that 10,000 copies/mL of TTV can be used as a reference value when determining the risk of a subject’s risk of complication:
“we chose to analyze blood DNAemia of CMV, EBV … and TTV … over 1 month of follow-up …” (page 2, 2nd column)
“among TTV DNA-positive individuals, 32% had TTV viral titres >10,000 copies/ml … as compared to 10% of healthy volunteers … Patients with higher TTV viraemia were more severely unwell, with higher severity scores and increased need for supportive treatment … male sex bias has been described for TTV … and this was also observed in the current study. This bias was significantly more marked in patients with TTV titres above 10,000 copies/ml” (page 4, 2nd column)
Therefore, it would have been prima facie obvious to combine the teachings of Strassl et al. with the teachings of Mallet et al., thereby arriving at the invention as claimed as Mallet et al. taught a reference level to which TTV can be associated with a subject’s risk of developing infections in a healthcare facility, providing a reasonable expectation of success.
Therefore, the invention as claimed is deemed prima facie obvious over the cited references.
Conclusion
No claims are allowed.
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 March 9, 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)