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 .
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 1-14, 16,18-19, and 21-27 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea and a judicial exception without significantly more.
The claim(s) recite(s) “determining the proliferative capacity,” “comparing the TTV load measured in a) with a reference TTV load,” “comparing the proliferative capacity of the T-cells measured in a) with a reference proliferative capacity of the T cells,” “determining a change in activity of the T cells,” “comparing the TTV viral loads,” “determining the change in the patient’s T cells activity,” “determining susceptibility to microbial infections,” and “determining susceptibility to graft-versus-host disease” which are all steps that can be practiced in the mind and are mental process judicial exceptions. Furthermore, the claims set forth the relationship between torque teno virus load in a biological sample and the proliferated capacity of the cells in a subject, as well as the relationship between proliferation capacity and risk for microbial infection and graft-versus-host disease which are a naturally occurring relationships and are law of nature judicial exceptions.
This judicial exception is not integrated into a practical application because the claims do not recite or use the judicial exceptions in any way.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the step in addition to the judicial exception (i.e. “measuring a Torque Teno Virus” load from a biological sample) is recited at an extremely high level of generality and employs techniques which were well established at the time of filing such as amplification, sequencing or hybridization. See specification p. 16 which teaches that commercial diagnostic kit was available for measuring TTV load by amplification, and paragraph 59-65 which list many techniques that were well known and readily available for a person skilled in the art (see especially paragraph 59).
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-7 and 9, is/are rejected under 35 U.S.C. 103 as being unpatentable over Focosi et al., Maggi F et al. (Transplantation 2008; 85: 1867), and Brenchley et al. (Blood, 1 April 2003, Volume 101, Number 7).
Focosi et al. teach that TTV viremia increased parallel to the increase of circulating CD8+CD57+ lymphocytes, which are known to be an indirect marker of functional immune deficiency. The kinetics of TTV viremia correlated with both the absolute number and the percentage of CD8+57+ T lymphocytes (Figures 1C, 2, and 3).
Fosoci et al. teach obtaining peripheral blood samples from HSCT patients on days at multiple time points before and post-HSCT (see 3.1). Torque teno virus (TTV) in plasma was quantified using a real-time PCR assay (see 3.2).
Fosoci et al. suggest that monitoring TTV plasma levels over time may help predict the likelihood of infectious complications and the duration of antimicrobial prophylaxis (section 5).
Thus, with regard to step (a) of claim 1 and 9 the reference teaches determining a TTV viral load from a biological sample taken from the patient at a first time point and,
Additionally with regard to claims with regard to step (b) of claims 9, at a second time point later than the first time point in step (a). See Table 1 and figure 1.
The reference teaches comparing the TTV viral loads measured in (a) and (b), and determining a change in the patient’s TTV load. See Table 1 and Figure 1, for example.
Regarding claim 2, the TTV load was measured by amplification (see 3.2).
Regarding claim 3, the biological sample was plasma (see 3.2).
Regarding claim 4, reference values for TTV relative to CD8+57+cells are given in Figures 3A and B. Reference values include values for the proliferative capacity (i.e. the level of CD8+57+ cells) of immunosuppressed individuals. The reference also teaches comparing the value of individuals at different time points, see Table 1. Furthermore, the reference teaches that for an individual, once the basal peaks is known, it becomes possible to extrapolate the time to when TVV levels will return to basal value (Section 5; Figure 4).
Regarding claims 5, 6, the subjects have received HSCT. See throughout.
Regarding claim 7, the patients received myeloablative or attenuated conditioning (melphalan and granulocyte colony stimulating factor or BEAM polychemotherapy and G-CSF). See 3.1.
Similarly, Maggi et al. teach that TTV load and percent CD8+57+ cells correlated over time, providing a demonstration of a temporal correlation between the size of a TTV chronic viremia and circulating CD8+57+ lymphocytes. The reference suggests that TTV viremia might be exploited to obtain a functional assessment of the immune status in HSCT recipients.
Fosoci and Maggi do not teach determining the proliferative potential of t-cells in the sample based on the TTV load, as required by claims 1, 8, 10, and 12.
Brenchley et al. teach that expression of CD57 in CD8-Tcells defines replicative senescence. That is, as CD57 expression goes up, the proliferation potential of the cells goes down (p. 2711, title, abstract, 2nd column).
Thus, it would have been prima facie obvious to have modified the methods taught by Fosoci and Maggi so as to have predicted that as the TTV load increases, the proliferative potential of T-cells cells decreases, since there is an increase of CD8+57+ cells and expression of CD57 defines inability of the cells to proliferate. Therefore, it follows that as the percentage of CD8+57+ T cells in a T cell population increases, the proliferation potential of the T-cell population decreases.
With regard to claims that set forth particular references to use for determining the proliferation potential, Fosoci teaches reference values for TTV relative to CD8+57+cells in Figures 3A and B. Reference values include values for the proliferative capacity (i.e. the level of CD8+57+ cells) of immunosuppressed individuals. The reference also teaches comparing the value of individuals at different time points, see Table 1. Furthermore, the reference teaches that for an individual, once the basal peaks is known, it becomes possible to extrapolate the time to when TVV levels will return to basal value (Section 5; Figure 4). It would have been well within the ordinary skill to have optimized the assay for predicting proliferation potential by selecting appropriate relevant reference values from the different options provided in the prior art.
Claim(s) 1-14, 16, 18-19, and 21-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Foscoci, Maggi, and Brenchley as applied to claims 1-7, 9, above, and further in view of Pradier et al.
The teachings of Foscoci, Maggi, and Brenchley are given previously in this Office action and are fully incorporated here. These do not teach a method wherein the patient has had an allogenic hematopoietic stem cell transplantation. The references also do not teach determining the susceptibility to microbial infections or graft versus host disease.
Pradier teaches obtaining peripheral blood samples from hematopoietic stem cell transplantation (HSCT) patients on days 0, 50, 100, 150, 200, 300, 400, and 547 and 2 to 9 years post-HSCT (p. 2, Col. 1). Torque teno virus (TTV) in plasma was quantified using a real-time PCR assay (p. 3, Col. 1). The reference teaches that in these patients TTV titers peaked at 100 days post-transplant and that higher titers after 100 days were associated with worse overall survival and higher risk of GVHD and infections (viral infections (see abstract and p. 8).
It would have been prima facie obvious to have modified the method taught by Foscoci, Maggi and Brenchley so as to have also applied it to patients who had allo-HSCT. One would have been motivated to do so in order to provide an additional tool for predicting outcome to allo-HSCT and guiding treatments. One would have been motivated to use proliferative capacity of T-cells, a measure of functional immunity, to predict microbial infections and GVHD in order to provide an additional tool for guiding doctors as to when to apply appropriate treatments or preventatives.
Response to Remarks
Applicant states that “determining (or measuring) a proliferative capacity of T cells cannot be performed in the mind and this is required by all the independent claims.” However, this step is a data analysis step, the claims do not recite “measuring” proliferative capacity. The recite “measuring” TTV load, and then “in view” of the load determining proliferative capacity. The “determining” is a step of reviewing the data obtained in step “a” and drawing a conclusion as to proliferative capacity. This is a mental process, and there is no argument or evidence given as to why it cannot be accomplished in the mind.
Applicant argues that one must measure the TTV load from a biological sample which cannot be performed in the mind. This is agreed; this step is treated in the claims as a step in addition to the judicial exceptions. It is a data gathering step, recited at a high level of generality. Applicant argues the claims should be considered as a whole, and they were.
Applicant argues that claim 1 integrates the relationship between TTV load and proliferative capacity since it is directed toa method of determining proliferative capacity. However, this is not an application of the judicial exception since it is a judicial exception itself.
Applicant argues that claims 8 and 9 integrate the judicial exception into a practical application of monitoring, however, there is no step that applies or uses the final judicial exceptions of “comparing” or “determining a change” in the claims.
Applicant argues that claim 10 integrates the relationship into a practical application of determining susceptibility to microbial infections in a “specific subject”, and claim 12 into a practical application of determining susceptibility to GvHD. There is no step that applies or uses the final judicial exceptions of “comparing” or “determining a change” in the claims. The claims end with judicial exceptions and do not integrate them in any way, such as by treatment or prophylaxis.
The rejection is updated to address amended and newly added claims and maintained.
The 102 rejection is withdrawn in view of amendments to the claims.
The rejection in view of Mouton is overcome by the filing of the translation of the foreign priority document.
Regarding the remaining 103, applicant argues that the findings of Brenchley are specific to HIV or CMV for certain tests and there is no mention of generalizing these findings to other types of patients/subjects. Applicant further argues that Lee et al. teaches that the phenotypic abnormalities of HIV-associated CD8+ T cells appear to be distinct form those associated with CMV infection or again, particularly with regard to CD57 expression, and that this calls into question the finding81474 s reported by Brenchley. However, Brenchley teaches that expression of CD57 is thought to result in the inability of CD8+T cells to proliferate in the introduction of the reference, and cites references to support this position. Lee also teaches that CD57 is a marker of poor proliferative capacity on page 1, col 2. Therefore, this argument is not persuasive. The rejection is maintained.
Claims 23-27 are free of the prior art. The prior art does not teach predicting the proliferative capacity of CD4+ T cells based on TTV levels.
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.
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Juliet Switzer
Primary Examiner
Art Unit 1682
/JULIET C SWITZER/ Primary Examiner, Art Unit 1682
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