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 .
Status of Claims
Applicant’s amendments to the claims, filed 18 September 2025, have been entered. Applicant’s remarks filed 18 September 2025 are acknowledged.
Claim 1 is in status “Currently amended.” Claims 3 – 10 are in status “Original” or “Previously presented.” Claims 2 and 11 – 12 are cancelled.
Response to Arguments
Applicant’s arguments, see Remarks page 8, filed 18 September 2025, with respect to the objections to the claims have been fully considered and are persuasive in light of the amendments. The objections to the claims have been withdrawn.
Applicant's arguments, see Remarks page 9, filed 18 September 2025, with respect to the rejection of the claims under 35 U.S.C. 101 have been fully considered but they are not persuasive. The examiner appreciates the applicant’s amendments and their strategy to align the claimed method with decision of Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals, 887 F.3d 1117 (Fed. Cir. 2018). Ultimately, however, the applicant’s amended claims do not recite the method of treatment with sufficient specificity to amount to “effect[ing] a particular treatment or prophylaxis for a disease or medical condition” per MPEP 2106.04(d)(2).
Applicant’s arguments center on Step 2A Prong Two of the Alice/Mayo test; the examiner’s response will likewise focus on eligibility under this prong. As outlined in the non-final office action filed 18 April 2025, the judicial exceptions recited in independent claim 1 are “calculating a change,” “calculating an indicator,” “setting a numerical threshold score,” and “comparing the total numerical score,” which are used in the newly-amended limitation of “determining the organ for transplantation as being transplantable.” Please see page five for a more detailed analysis of Step 1 and Step 2A Prong One.
Step 2A Prong Two asks, “Does the claim recite additional elements that integrate the judicial exception into a particular practical application?” As the “calculating,” “setting,” and “comparing” exceptions are integrated into the “determining” limitation, it is the “determining” limitation which must be further integrated into a particular practical application. This is in line with the claims addressed in the USPTO Memorandum dated June 7, 2018, entitled “Recent Subject Matter Eligibility Decision: Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals” (henceforth the Memorandum; a copy of this document has been provided with this office action).
The Memorandum identifies a representative claim which includes “…determining whether the patient is a CYP2D6 poor metabolizer…” and is analogous to the “determining” step of the instant application. To quote the Memorandum;
“The primary steps include "determining" with a genotyping assay, and then "administering" a certain quantity of drug based on that determination, in order to "treat a particular disease."
In the case of the Memorandum claim, the determining is performed with a specific assay, which yields a yes/no response. The yes/no response leads directly to the administration of a named medication at a specified dosage, for a positively identified medical condition. It’s these additional details which allow the “natural relationships” to be applied by the claims, rather than merely directed towards. As the Memorandum summarizes;
“Method of treatment claims (which apply natural relationships as opposed to being "directed to" them) were identified by the Supreme Court as not being implicated by its decisions in Mayo and Myriad because they "confine their reach to particular applications." […] The Mayo claims were not "method of treatment" claims that practically apply a natural relationship.”
The instant application lacks this specificity. It cannot be said to “practically apply a natural relationship”, nor does it “confine its reach to particular applications.” The instant claim recites “measuring contents of marker substances—” what marker substances? Oxygenation? Inflammatory markers? Viral load? Are the tissue samples taken from analogous parts of the organ? Other than the implication that the marker substance can have different concentrations, the claims are not limited. In light of the amendments, the claim does positively identify a treatment (transplanting an organ). However, this treatment is not particular (what organ?) nor is it directed to a positively identified condition. The lack of a named disease or medical condition is of particular concern when evaluating the judicial exception; it is difficult to argue that a limitation is applying a treatment when no condition requiring the treatment is invoked.
Lastly, the step of “transplanting the organ […] based on the result of the determination” is claimed broadly enough that it fails to fully integrate the determination (Based how?). The exemplary claim in the Memorandum includes specific “if/then” language, rather than the broad “based on…” language, which amounts to an instruction to apply the judicial exception.
MPEP 2106.04(d)(2)(a) recites the following, “The treatment or prophylaxis limitation must be “particular,” i.e., specifically identified so that it does not encompass all applications of the judicial exception(s).” As currently amended, the instant claims encompass all applications of the judicial exception of determining transplantability by comparing biomarkers at two points in time. As such, the rejection of the claims under 35 U.S.C. 101 is maintained.
Applicant’s arguments, see Remarks page 12, filed 18 September 2025, with respect to the rejection of independent claim 1 under 35 U.S.C. 102 have been fully considered and are persuasive in light of the amendments. Therefore, the rejection has been withdrawn. However, upon further consideration, a new grounds of rejection is made under 35 U.S.C. 103 in view of Kravitz et al.
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.
Claim 1 is rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. Claim 1 is directed to the mental processes grouping of abstract ideas. Claim 1 recites a series of steps and is therefore a process.
The limitations of “calculating a change,” “calculating an indicator,” “setting a numerical threshold score,” “expressing the tendency,” “comparing the total numerical score,” and “determining when the tendency of change in the content in the organ […] agrees” in lines 22-23 are processes that, under their broadest reasonable interpretation, cover performance of the limitation in the mind. Calculating, setting, expressing, comparing, and determining appear to be some sort of correlation or math. Nothing in the claim elements precludes these steps from practically being performed in the mind.
“Calculating” in the context of this claim encompasses an individual reviewing the raw data and mentally adding or subtracting to arrive at the change value, or applying a mental algorithm to arrive at an indicator. “Setting a numerical threshold” in the context of this claim is a mathematical process, and encompasses an individual performing a mental act of value setting. “Expressing” in the context of this claim is a mathematical process, and encompasses an individual performing a mental act of value setting. “Comparing” in the context of this claim encompasses an individual visually reviewing the data and assessing whether a number is larger or smaller than the target value. “Determining” in this context encompasses an individual visually reviewing the data and assessing whether a number is larger or smaller than the target value.
Accordingly, the claim recites abstract ideas.
This judicial exception is not integrated into a practical application. The abstract ideas of “calculating,” “setting,” and “expressing” are only integrated into the abstract ideas of “comparing” and “determining.” After the “comparing” and “determining” are completed, the claim recites the limitation of “transplanting the organ for transplantation to a recipient based on the result of determination.” This limitation amounts to instructions to “merely apply” the determining step—please see MPEP 2106.05(f). The limitation of “transplanting the organ…” cannot be considered a case of “Particular Treatment and Prophylaxis” as outlined in MPEP 2106.04(d)(2), as the treatment is not specifically identified as related to a particular condition and does not integrate the “determination” into the treatment. This is akin to the limitation of “administering a suitable medication to a patient” as discussed in MPEP 2106.04(d)(2)(a).
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception. The additional elements of “measuring contents”, and “expressing the contents” are data-gathering steps used in the final abstract idea step of “determining.” Data gathering is considered insignificant extra-solution activity and is not a particular practical application; please see MPEP 2106.05(g). The additional elements included in this claim are well-understood, routine, and conventional in the art of organ transplantation; please see the prior art rejection of record.
Accordingly, the claim is directed to the mental processes grouping of abstract ideas, the abstract ideas have not been integrated into a particular practical application, and the claim does not recite additional elements which are significantly more than the abstract idea. Therefore, the claim is ineligible.
Claim 3 is rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. Claim 3 is directed to the mental processes grouping of abstract ideas, reciting “calculating,” “setting,” “expressing,” “comparing,” and “determining” as outlined in claim 1. Claim 3 further defines the measuring steps introduced in claim 1. This additional limitation amounts to data-gathering, which is insignificant extra-solution activity and is not a particular practical application. Measurement using mass spectrometry is well-understood, routine, and conventional in the art, and the limitation is not sufficient to amount to significantly more than the judicial exception; please see the prior art rejection of claim 3.
Accordingly, the claim is directed to the mental processes grouping of abstract ideas, the abstract ideas have not been integrated into a particular practical application, and the claim does not recite additional elements which are significantly more than the abstract idea. Therefore, the claim is ineligible.
Claim 4 is rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. Claim 4 is directed to the mental processes grouping of abstract ideas, reciting “calculating,” “setting,” “expressing,” “comparing,” and “determining” as outlined in claim 1. Claim 4 further defines how the calculation is performed. Further defining the calculation does not integrate the abstract ideas into a practical application, or recite elements that are more than the abstract idea.
Accordingly, the claim is directed to the mental processes grouping of abstract ideas, the abstract ideas have not been integrated into a particular practical application, and the claim does not recite additional elements which are significantly more than the abstract idea. Therefore, the claim is ineligible.
Claim 5 is rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. Claim 5 is directed to the mental processes grouping of abstract ideas, reciting “calculating,” “setting,” “expressing,” “comparing,” and “determining” as outlined in claim 1. Claim 5 further defines the organ being evaluated and the biomarkers being measured. These limitations only address the data-gathering steps of claim 1, and so amount to insignificant extra solution activities and not a particular practical application. Claim 5 does not recite elements that are more than the abstract idea, and the new claim elements introduced are well-understood, routine, and conventional in the art; please see the prior art rejection of claim 5.
Accordingly, the claim is directed to the mental processes grouping of abstract ideas, the abstract ideas have not been integrated into a particular practical application, and the claim does not recite additional elements which are significantly more than the abstract idea. Therefore, the claim is ineligible.
Claim 6 is rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. Claim 6 is directed to the mental processes grouping of abstract ideas, reciting “calculating,” “setting,” “expressing,” “comparing,” and “determining” as outlined in claim 1. Claim 6 additionally recites “determining whether the function […] is normal…” in line 14 which is a processes that, under its broadest reasonable interpretation, covers performance of the limitation in the mind. Determining appears to be some sort of correlation or math. Nothing in the claim elements precludes this step from practically being performed in the mind. “Determining” in this context encompasses an individual visually reviewing the data and assessing whether a number is larger or smaller than the target value.
Accordingly, claim 6 recites abstract ideas.
This judicial exception is not integrated into a particular practical application. After the determining, is completed, no action is taken. The additional elements recited in the clam of “taking a […] tissue sample” and “measuring a content” amount to data-gathering later used in the determining. Data gathering is considered insignificant extra-solution activity and is not a particular practical application; please see MPEP 2106.05(g). The additional elements included in this claim are well-understood, routine, and conventional in the art of organ transplantation; please see the prior art rejection of claim 6.
Accordingly, the claim is directed to the mental processes grouping of abstract ideas, the abstract ideas have not been integrated into a particular practical application, and the claim does not recite additional elements which are significantly more than the abstract idea. Therefore, the claim is ineligible.
Claim 7 is rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. Claim 7 is directed to the mental processes grouping of abstract ideas, reciting “calculating,” “setting,” “expressing,” “comparing,” and “determining” as outlined in claim 1. Claim 7 additionally recites “determining whether the function […] is normal…” in line 10 which is a processes that, under its broadest reasonable interpretation, covers performance of the limitation in the mind. Determining appears to be some sort of correlation or math. Nothing in the claim elements precludes this step from practically being performed in the mind. “Determining” in this context encompasses an individual visually reviewing the data and assessing whether a number is larger or smaller than the target value.
Accordingly, claim 7 recites abstract ideas.
This judicial exception is not integrated into a particular practical application. After the determining, is completed, no action is taken. The additional elements recited in the clam of “taking a […] tissue sample” and “measuring a content” amount to data-gathering later used in the determining. Data gathering is considered insignificant extra-solution activity and is not a particular practical application; please see MPEP 2106.05(g). The additional elements included in this claim are well-understood, routine, and conventional in the art of organ transplantation; please see the 103 rejection of claim 7.
Accordingly, the claim is directed to the mental processes grouping of abstract ideas, the abstract ideas have not been integrated into a particular practical application, and the claim does not recite additional elements which are significantly more than the abstract idea. Therefore, the claim is ineligible.
Claim 8 is rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. Claim 8 is directed to the mental processes grouping of abstract ideas, reciting “calculating,” “setting,” “expressing,” “comparing,” and “determining” as outlined in claim 1. Claim 8 additionally recites “determining whether the function […] is normal…” in line 10 which is a processes that, under its broadest reasonable interpretation, covers performance of the limitation in the mind. Determining appears to be some sort of correlation or math. Nothing in the claim elements precludes this step from practically being performed in the mind. “Determining” in this context encompasses an individual visually reviewing the data and assessing whether a number is larger or smaller than the target value.
Accordingly, claim 8 recites abstract ideas.
This judicial exception is not integrated into a particular practical application. After the determining, is completed, no action is taken. The additional elements recited in the clam of “taking a […] tissue sample” and “measuring a content” amount to data-gathering later used in the determining. Data gathering is considered insignificant extra-solution activity and is not a particular practical application; please see MPEP 2106.05(g). The additional elements included in this claim are well-understood, routine, and conventional in the art of organ transplantation; please see the prior art rejection of claim 8.
Accordingly, the claim is directed to the mental processes grouping of abstract ideas, the abstract ideas have not been integrated into a particular practical application, and the claim does not recite additional elements which are significantly more than the abstract idea. Therefore, the claim is ineligible.
Claim 9 is rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. Claim 9 is directed to the mental processes grouping of abstract ideas, reciting “calculating,” “setting,” “expressing,” “comparing,” and “determining” as outlined in claim 1 and “determining” as outlined in claim 6. Claim 9 further defines the organ being evaluated and the biomarkers being measured. These limitations only address the data-gathering steps of claims 1 and 6 and amount to insignificant extra solution activities and are not a particular practical application. Claim 9 does not recite elements that are more than the abstract idea, and the new claim elements introduced are well-understood, routine, and conventional in the art; please see the prior art rejection of claim 9.
Accordingly, the claim is directed to the mental processes grouping of abstract ideas, the abstract ideas have not been integrated into a particular practical application, and the claim does not recite additional elements which are significantly more than the abstract idea. Therefore, the claim is ineligible.
Claim 10 is rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. Claim 10 is directed to the mental processes grouping of abstract ideas, reciting “calculating,” “setting,” “expressing,” “comparing,” and “determining” as outlined in claim 1 and “determining” as outlined in claim 8. Claim 10 further defines the organ being evaluated and the biomarkers being measured. These limitations only address the data-gathering steps of claims 1 and 8, and so amount to insignificant extra solution activities and not a particular practical application. Claim 10 does not recite elements that are more than the abstract idea, and the new claim elements introduced are well-understood, routine, and conventional in the art; please see the prior art rejection of claim 10.
Accordingly, the claim is directed to the mental processes grouping of abstract ideas, the abstract ideas have not been integrated into a particular practical application, and the claim does not recite additional elements which are significantly more than the abstract idea. Therefore, the claim is ineligible.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1, 4, and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Kravitz et al (US 20120315618 A1, cited on the IDS filed 08/09/2023).
With regards to claim 1, Kravitz et al teaches the following;
The claimed “a method of evaluating a function of an organ for transplantation harvested from a living body” has been read on the taught (Abstract, "Methods for ex vivo perfusion of organs (and/or tissues) with a perfusate […] while monitoring, sustaining and/or restoring the viability of the organ…");
The claimed “measuring contents of marker substances in a first tissue sample that is taken from the organ for transplantation at first timing in a reperfusion of the organ for transplantation” and “measuring contents of the marker substances in a second tissue sample that is taken from the organ for transplantation at second timing after the first timing in the reperfusion” have been read on the taught ([0022], "The methods of the present disclosure improve upon known methodology for assessment of the viability of machine perfused organs by monitoring the organ […] for specific biomarkers. In embodiments, the assessment occurs, for example, at various ex vivo predetermined pump time intervals (such as continuous or every 5, 10, 15 or 30 minutes, hourly and/or daily)."; [0278], "The methods of the present disclosure utilize perfusion, diagnostic, and/or transporter apparatus that have the ability to detect and monitor one or more biomarkers…"; Detecting and monitoring one or more biomarkers at specific pump time intervals reads on measuring the contents of the marker substances in the first and the second tissue samples);
The claimed “calculating a change including an increase or a decrease in content at the second timing as compared with the first timing for each of the marker substances” has been read on the taught ([0278], "In embodiments, monitoring one or more biomarkers provides data that may be compared with information compiled in a database regarding the same or different biomarkers, such that the optimum cellular chemistry of an organ to be transplanted may be manipulated and adjusted (in real time) in response any respective biomarker measurement that is outside of a predetermined range. The monitoring of one or more predetermined biomarkers and their quantitative and/or qualitative relationships…"; Monitoring a biomarker and comparing it with information complied in a database, and monitoring the biomarkers and their quantitative relationship reads on calculating a change in content at the second timing as compared with the first timing. Please see [0034] which further defines what is meant by monitoring, including calculating a change in content.);
The claimed “calculating an indicator relating to evaluation of the function of the organ for transplantation using the calculated change in content and data representing change over time in contents of the marker substances in accordance with a perfusion” has been read on the taught ();
The claimed “wherein calculating change includes calculating a tendency of change in the content” has been read on the taught ([0032], “…a viability index of the organ may be monitored, for example, automatically, by monitoring one or more "biomarkers"… "monitoring one or more biomarkers" may include, for example, monitoring the stability of a component, such as a hormone and/or other chemicals or there levels (concentrations)… monitoring the stability of a component, such as a small molecule, large molecule and/or biological substance that is introduced into the donor organ or otherwise exists in the organ; monitoring the metabolism of the organ and/or stability of the metabolism rate."; [0034], "…. calculating a ratio between the measured values for one or more biomarkers..."; The viability index reads on an indicator. Monitoring for biomarker stability and calculating a biomarker ratio reads on calculating a tendency of change.);
The claimed wherein “calculating an indicator includes expressing the tendency of change in the content for each marker substance measured as a numerical score” has been read on the taught ([0271], “In embodiments, an organ viability index may be provided, which takes into account one or more of the various monitored biomarkers identified above… The organ viability index may compile the monitored parameters and biomarkers into a diagnostic summary, which to be used for making organ therapy decisions and deciding whether to transplant the organ.”; The viability index which compiles parameters into a diagnostic summary reads on expressing the tendency of change in the content for each marker substance as a numerical score. [0320] teaches that semi-quantitative numerical scores are known in the art of diagnostic summaries, “…the relative degree of apoptosis and pathologic changes determined using a semi-quantitative 4+ scale.”);
The claimed “comparing the total numerical score with the threshold score and determining the organ for transplantation as being transplantable…” has been read on the taught ([0271], “In embodiments, an organ viability index may be provided, which takes into account one or more of the various monitored biomarkers identified above… The organ viability index may compile the monitored parameters and biomarkers into a diagnostic summary, which to be used for making organ therapy decisions and deciding whether to transplant the organ.”; Claim 17, “The method of claim 16, further comprising: making organ therapy decisions based on the first organ viability index.”; Deciding whether to transplant the organ and making organ therapy decisions based on the organ viability index reads on determining when the tendency of change in the content in the organ agrees […] so as to be transplantable.);
The claimed “transplanting the organ for transplantation to a recipient based on the result of determination” has been read on the taught ([0279], “An organ or tissue sample may be removed from a first body, modified, treated and/or analyzed outside the first body and either returned to the first body or transplanted to a second body.”).
The claimed wherein “expressing the tendency as the numerical score includes setting a score at time when the tendency of change in the content in the organ for transplantation agrees with the tendency of change in the content in an organ having normal function to be larger than a score at time when the tendency of change in the content in the organ for transplantation does not agree with the tendency of change in the content in the organ having normal function” has been read on the taught ([0032], “…a viability index of the organ may be monitored, for example, automatically, by monitoring one or more "biomarkers" […] In embodiments, "monitoring one or more biomarkers" may include, […] monitoring the metabolism of the organ and/or stability of the metabolism rate; monitoring the oxygen consumption rate and/or stability of the oxygen consumption rate; monitoring the glucose concentration and/or stability of the glucose concentration…”; A viability index reads on the numerical score. Monitoring the oxygen consumption rate and/or stability of the oxygen consumption rate reads on setting the score based on the tendency of change in the content in the organ for transplantation. [0024] teaches that the viability of an organ, based on normal organ function, can be pinned to the viability index, as read on, “For example, a method of the present disclosure using predominately hypothermic temperatures may be employed for an organ or tissue that has been evaluated and exceeds a predetermined threshold viability index… Alternatively, a method for a particular organ may be selected that first employs mid-normothermic to normothermic temperatures to improve the viability of the organ and/or tissue until an organ and/or tissue meeting a predetermined threshold viability index is obtained…”).
Kravitz et al does not explicitly disclose “determining the organ for transplantation as being transplantable when the total numerical score is larger than the numerical threshold score, and determining the organ for transplantation as not being transplantable when the total score is equal to or smaller than the numerical score.” However, no unexpected results are disclosed in the instant application’s specification regarding the assignment of “high score” to transplantable and “low score” to non-transplantable. Given Kravitz’s teaching of numerical scales (see [0320]) as well as comparative ratios (see [0034]), the designation of a “transplantable” high score as above a threshold and a “non-transplantable” low score as below a threshold would have been obvious to one of ordinary skill in the art.
With regards to claim 4, the method of claim 1 is obvious over Kravitz et al.
Kravitz et al additionally teaches;
The claimed wherein “the calculating change further includes making a determination of the increase in the content when a rate of change in the content at the second timing as compared with the content at the first timing is higher than a first threshold value larger than one, and making a determination of the decrease in the content when the rate of change is lower than a second threshold value smaller than one” has been read on the taught ([0024], “For example, a method of the present disclosure using predominately hypothermic temperatures may be employed for an organ or tissue that has been evaluated and exceeds a predetermined threshold viability index… Alternatively, a method for a particular organ may be selected that first employs mid-normothermic to normothermic temperatures to improve the viability of the organ and/or tissue until an organ and/or tissue meeting a predetermined threshold viability index is obtained…”; [0032], “…a viability index of the organ may be monitored, for example, automatically, by monitoring one or more "biomarkers"… "monitoring one or more biomarkers" may include, for example, monitoring the stability of a component, such as a hormone and/or other chemicals or there levels (concentrations)… monitoring the stability of a component, such as a small molecule, large molecule and/or biological substance that is introduced into the donor organ or otherwise exists in the organ; monitoring the metabolism of the organ and/or stability of the metabolism rate."; [0034], "…. calculating a ratio between the measured values for one or more biomarkers..."; Evaluating an organ that exceeds a threshold value reads on making a determination when the rate of change is higher than a threshold value. Monitoring/improving the viability of an organ until it meets a threshold value reads on making a determination when the rate of change is lower than a threshold value. As the viability index monitors stability and ratios (which read on the rate of change), it is well-understood in the art that the rate of change indicating a decrease in concentration is less than one, and that the rate of change indicating an increase in concentration is greater than one. Accordingly, a threshold value larger than one or smaller than one is supported by Kravitz et al’s teaching of a method that monitors rates of change (as indicated by stability of rates and calculated ratios).
With regard to claim 5, the method of claim 1 is obvious over Kravitz et al.
Kravitz et al additionally teaches;
The claimed “wherein the organ for transplantation is liver” has been read on the taught ([0045], "The methods of the present disclosure may also include steps for monitoring the predetermined biomarkers for liver function…");
The claimed “the marker substances include at least two of sedoheptulose 7-phosphate, adenosine triphosphate, glucose-6-phosphate, succinyl coenzyme A (CoA), dimethylglycine, choline, 2- aminobutyric acid, uric acid, pyruvic acid, and inosine” has been read on the taught (Table 3 teaches exemplary additives for use with tissue samples, including adenosine triphosphate. [0028] teaches monitoring the levels of these potential additives for later restoration/preservation procedures, "In embodiments, the information in the data record may be used to select one or more biomarkers and if applicable, determine optimum concentration ranges for the one or more biomarkers. Then, once the donor organ is acquired and the predetermined biomarkers of the organ are assessed, the most effective restoration and preservation procedures for the donor organ may be determined…"; [0332], "The assays […] will include […] glucose, […] and uric acid…").
Claims 3 and 6-10 are rejected under 35 U.S.C. 103 as being unpatentable over Kravitz et al (US 20120315618 A1, cited on the IDS filed 08/09/2023) in view of Hu et al (20090155826 A1).
With regards to claim 3, the method of claim 1 is obvious over Kravitz et al.
However, Kravitz et al fails to teach wherein each of the measuring contents of the marker substances in the first tissue sample and the measuring contents of the marker substances in the second tissue sample includes measuring contents of the marker substances by mass spectrometry.
In the analogous art of measuring biomarkers to assess organ function, Hu et al teaches;
The claimed “wherein measuring the contents of the marker substances in the first and the second tissue samples includes measuring contents of the marker substances by mass spectrometry” has been read on the taught ([0105], “Any suitable method may be used to analyze the biological sample in order to determine the level(s) of the one or more biomarkers in the sample. Suitable methods include […] mass spectrometry (e.g., MS, MS-MS)…”).
MPEP 2143(I)(A) states “combining known methods to yield predictable results” supports a prima facie case of obviousness. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Kravitz in view of Hu to use the well-known method of biomarker measurement using MS to achieve the well-known and expected results of determining the concentration of biomarkers in the sample (Hu et al, [0152], “Analytical techniques such as GC-MS (gas chromatography-mass spectrometry) and LC-MS (liquid chromatography-mass spectrometry) were used to analyze the metabolites. Multiple aliquots were simultaneously, and in parallel, analyzed…”).
With regards to claim 6, the method of claim 1 is obvious over Kravitz et al.
Kravitz et al additionally teaches;
The claimed “wherein after harvesting from a donor, the organ for transplantation is cold-preserved until the reperfusion” has been read on the taught ([0030], "In embodiments, normothermic treatment to restore an organ's viability may be employed, optionally after an organ has been subjected to hypothermic temperatures, statically and/or under perfusion."; Subjecting an organ to hypothermic temperatures reads on cold preservation.);
The claimed “taking a third tissue sample from the organ for transplantation at third timing before start of cold preservation” has been read on the taught ([0030], "In other words, the treatment can be applied to organs prior to cold storage and/or transport.");
The claimed “taking a fourth tissue sample from the organ for transplantation at fourth timing after end of the cold preservation and before start of the reperfusion” has been read on the taught ([0278], "The monitoring of one or more predetermined biomarkers and their quantitative and/or qualitative relationships may alert the those transporting and/or preserving the donor organ that a specific perfusate may be necessary to repair the organ and restore the organs viability before irreversible damage occurs, such as cell death, ischemic damage to the organ and/or reperfusion injury."; monitoring a biomarker to prevent reperfusion injury reads on taking a tissue sample before the start of the reperfusion.);
The claimed “measuring a content of a first marker substance of the third tissue sample; measuring a content of the first marker substance of the fourth tissue sample” has been read on the taught ([0022], "The methods of the present disclosure improve upon known methodology for assessment of the viability of machine perfused organs by monitoring the organ […] for specific biomarkers. In embodiments, the assessment occurs, for example, at various ex vivo predetermined pump time intervals (such as continuous or every 5, 10, 15 or 30 minutes, hourly and/or daily)."; [0278], "The methods of the present disclosure utilize perfusion, diagnostic, and/or transporter apparatus that have the ability to detect and monitor one or more biomarkers…"; Detecting and monitoring one or more biomarkers at specific pump time intervals reads on measuring the contents of the marker substances of the third and the fourth tissue samples);
The claimed “determining whether the function of the organ for transplantation is normal based on the contents of the first marker substance at the third timing and the fourth timing” has been read on the taught ([0045], "The methods of the present disclosure may also include steps for monitoring the predetermined biomarkers for liver function and may use information from the data in order to make organ therapy decisions…"; Claim 17, “The method of claim 16, further comprising: making organ therapy decisions based on the first organ viability index.”; Claim 18, “The method of claim 17, further comprising: comparing the first organ viability index with a second organ viability index.”; Making organ therapy decisions based on a first viability index, comparing that with a second viability index, and monitoring the predetermined biomarkers for liver function read on determining whether the function of the organ is normal based on the contents of the first marker substance at the third and fourth timing.).
However, Kravitz et al fails to teach wherein the content of a first marker substance is measured by mass spectrometry.
In the analogous art of biomarkers for organ function, Hu et al teaches;
“Measuring the content of a marker in multiple specimens by mass spectrometry” has been read on the taught ([0105], “Any suitable method may be used to analyze the biological sample in order to determine the level(s) of the one or more biomarkers in the sample. Suitable methods include […] mass spectrometry (e.g., MS, MS-MS)…”; [0152], “Multiple aliquots were simultaneously, and in parallel, analyzed…”).
MPEP 2143(I)(A) states “combining known methods to yield predictable results” supports a prima facie case of obviousness. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Kravitz in view of Hu to use the well-known method of biomarker measurement using MS to achieve the well-known and expected results of determining the concentration of biomarkers in the sample (Hu et al, [0152], “Analytical techniques such as GC-MS (gas chromatography-mass spectrometry) and LC-MS (liquid chromatography-mass spectrometry) were used to analyze the metabolites. Multiple aliquots were simultaneously, and in parallel, analyzed…”).
With regards to claim 7, the method of claim 1 is obvious Kravitz et al.
Kravitz et al additionally teaches;
The claimed wherein “after harvesting from a donor, the organ for transplantation is cold-preserved until the reperfusion” has been read on the taught ([0030], "In embodiments, normothermic treatment to restore an organ's viability may be employed, optionally after an organ has been subjected to hypothermic temperatures, statically and/or under perfusion."; Subjecting an organ to hypothermic temperatures reads on cold preservation.), and the method further comprises:
The claimed “taking a fourth tissue sample from the organ for transplantation at fourth timing after end of the cold preservation and before start of the reperfusion” has been read on the taught ([0278], "The monitoring of one or more predetermined biomarkers and their quantitative and/or qualitative relationships may alert the those transporting and/or preserving the donor organ that a specific perfusate may be necessary to repair the organ and restore the organs viability before irreversible damage occurs, such as cell death, ischemic damage to the organ and/or reperfusion injury."; monitoring a biomarker to prevent reperfusion injury reads on taking a tissue sample before the start of the reperfusion.);
The claimed “measuring a content of the first marker substance of the fourth tissue sample” has been read on the taught ([0022], "The methods of the present disclosure improve upon known methodology for assessment of the viability of machine perfused organs by monitoring the organ […] for specific biomarkers. In embodiments, the assessment occurs, for example, at various ex vivo predetermined pump time intervals (such as continuous or every 5, 10, 15 or 30 minutes, hourly and/or daily)."; [0278], "The methods of the present disclosure utilize perfusion, diagnostic, and/or transporter apparatus that have the ability to detect and monitor one or more biomarkers…"; Detecting and monitoring one or more biomarkers at specific pump time intervals reads on measuring the contents of the marker substances of the fourth tissue samples);
The claimed “determining whether the function of the organ for transplantation is normal based on the contents of the first marker substance at the fourth timing” has been read on the taught ([0045], "The methods of the present disclosure may also include steps for monitoring the predetermined biomarkers for liver function and may use information from the data in order to make organ therapy decisions…"; Claim 17, “The method of claim 16, further comprising: making organ therapy decisions based on the first organ viability index.”; Making organ therapy decisions based on a first viability index and monitoring the predetermined biomarkers for liver function read on determining whether the function of the organ is normal based on the contents of the first marker substance at the fourth timing.).
However, Kravitz et al fails to teach wherein the content of a first marker substance is measured by mass spectrometry.
In the analogous art of biomarkers for organ function, Hu et al teaches;
The claimed “measuring the content of a marker by mass spectrometry” has been read on the taught ([0105], “Any suitable method may be used to analyze the biological sample in order to determine the level(s) of the one or more biomarkers in the sample. Suitable methods include […] mass spectrometry (e.g., MS, MS-MS)…”).
MPEP 2143(I)(A) states “combining known methods to yield predictable results” supports a prima facie case of obviousness. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Kravitz in view of Hu to use the well-known method of biomarker measurement using MS to achieve the well-known and expected results of determining the concentration of biomarkers in the sample (Hu et al, [0152], “Analytical techniques such as GC-MS (gas chromatography-mass spectrometry) and LC-MS (liquid chromatography-mass spectrometry) were used to analyze the metabolites. Multiple aliquots were simultaneously, and in parallel, analyzed…”).
With regards to claim 8, the method of claim 1 is obvious over Kravitz et al.
Kravitz et al additionally teaches;
The claimed wherein “after harvesting from a donor, the organ for transplantation is cold-preserved until the reperfusion” has been read on the taught ([0030], "In embodiments, normothermic treatment to restore an organ's viability may be employed, optionally after an organ has been subjected to hypothermic temperatures, statically and/or under perfusion."; Subjecting an organ to hypothermic temperatures reads on cold preservation.);
The claimed “taking a third tissue sample from the organ for transplantation at third timing before start of cold preservation” has been read on the taught ([0030], "In other words, the treatment can be applied to organs prior to cold storage and/or transport.");
The claimed “measuring a content of a first marker substance of the third tissue sample” has been read on the taught ([0022], "The methods of the present disclosure improve upon known methodology for assessment of the viability of machine perfused organs by monitoring the organ […] for specific biomarkers. In embodiments, the assessment occurs, for example, at various ex vivo predetermined pump time intervals (such as continuous or every 5, 10, 15 or 30 minutes, hourly and/or daily)."; [0278], "The methods of the present disclosure utilize perfusion, diagnostic, and/or transporter apparatus that have the ability to detect and monitor one or more biomarkers…"; Detecting and monitoring one or more biomarkers at specific pump time intervals reads on measuring the contents of the marker substances of the third tissue sample);
The claimed “determining whether the function of the organ for transplantation is normal based on the contents of the first marker substance at the third timing and the fourth timing” has been read on the taught ([0045], "The methods of the present disclosure may also include steps for monitoring the predetermined biomarkers for liver function and may use information from the data in order to make organ therapy decisions…"; Claim 17, “The method of claim 16, further comprising: making organ therapy decisions based on the first organ viability index.”; Making organ therapy decisions based on a first viability index and monitoring the predetermined biomarkers for liver function read on determining whether the function of the organ is normal based on the contents of the first marker substance at the third timing.).
However, Kravitz et al fails to teach wherein the content of a first marker substance is measured by mass spectrometry.
In the analogous art of biomarkers for organ function, Hu et al teaches;
The claimed “measuring the content of a marker by mass spectrometry” has been read on the taught ([0105], “Any suitable method may be used to analyze the biological sample in order to determine the level(s) of the one or more biomarkers in the sample. Suitable methods include […] mass spectrometry (e.g., MS, MS-MS)…”).
MPEP 2143(I)(A) states “combining known methods to yield predictable results” supports a prima facie case of obviousness. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Kravitz in view of Hu to use the well-known method of biomarker measurement using MS to achieve the well-known and expected results of determining the concentration of biomarkers in the sample (Hu et al, [0152], “Analytical techniques such as GC-MS (gas chromatography-mass spectrometry) and LC-MS (liquid chromatography-mass spectrometry) were used to analyze the metabolites. Multiple aliquots were simultaneously, and in parallel, analyzed…”).
With regards to claim 9, the method of claim 6 is obvious over Kravitz et al in view of Hu et al.
Kravitz et al additionally teaches;
The claimed “wherein the organ for transplantation is liver” has been read on the taught ([0045], "The methods of the present disclosure may also include steps for monitoring the predetermined biomarkers for liver function…").
Kravitz et al does not explicitly disclose wherein the first marker substance is uridine. However, Hu et al additionally teaches;
The claimed wherein “the first marker substance is uridine” has been read on the taught (Table 22, page 59 lists uridine at the bottom row of the table).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of evaluating an organ for transplantation as taught by Kravitz et al with the measurement of uridine as a biomarker, as taught by Hu et al, in order to determine if the organ came from a patient with dilated cardiomyopathy or a healthy subject ([0207], “As listed below in [Table 22], biomarkers were discovered that were differentially present between […] plasma samples […] collected from dilated cardiomyopathy subjects and healthy subjects.”).
With regards to claim 10, the method of claim 8 is obvious over Kravitz et al in view of Hu et al.
Kravitz et al additionally teaches;
The claimed wherein “the organ for transplantation is liver” has been read on the taught ([0045], "The methods of the present disclosure may also include steps for monitoring the predetermined biomarkers for liver function…").
Kravitz et al does not explicitly disclose wherein the first marker substance is uridine and the second marker substance is adenylosuccinic acid. However, Hu et al additionally teaches;
The claimed wherein “the first marker substance is uridine” has been read on the taught (Table 22, page 59 lists uridine at the bottom row of the table.);
The claimed wherein “the second marker substance is adenylosuccinic acid” has been read on the taught (Table 21, page 56 lists adenylosuccinic acid in row 5 of the table.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of evaluating an organ for transplantation as taught by Kravitz et al with the measurement of uridine and adenylosuccinic acid as a biomarker, as taught by Hu et al, in order to determine if the organ came from a patient with dilated cardiomyopathy or a healthy subject ([0207], “As listed below in Tables 21 and 22, biomarkers were discovered that were differentially present between cardiac tissue and plasma samples, respectively, collected from dilated cardiomyopathy subjects and healthy subjects.”).
Conclusion
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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/ALISON CLAIRE GERHARD/ Examiner, Art Unit 1797 /LYLE ALEXANDER/ Supervisory Patent Examiner, Art Unit 1797
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