DETAILED ACTION
Claims 1-2, 4-8, 14, 17-23, 25-26, and 30-31 are pending.
Status of Claims
Claims 1-2, 4-8, 14, 17-23, 25-26, and 30-31 are pending. Claims 1, 17, and 26 have been amended. Claims 30-31 have been withdrawn. Claims 1-2, 4-8, 14, 17-23, and 25-26 are under examination.
Withdrawn Claim Objections and/or Rejections
The objection of claims 1, 4-7, 17, and 20-21 for minor informalities as set forth on p. 2 of the previous office action (mailed on 09/10/2025) has been withdrawn in view of the amendments (filed on 12/10/2025).
The rejection of claim 26 under 35 USC 112(b) as being indefinite as set forth on pp. 2-3 of the previous office action (mailed on 09/10/2025) has been withdrawn in view of the amendments (filed on 12/10/2025).
The rejection of claims 1-4, 8, 14, 17-23, and 25-16 under 35 USC 103 as being unpatentable over Keshavjee, Lang, Gur, and Zhou et al., as set forth on pp. 10-22 of the previous office action (mailed on 09/10/2025) has been withdrawn in view of the arguments and amendments filed on 12/10/2025).
The rejection of claim 5 under 35 USC 103 as being unpatentable over Keshavjee, Lang, Gur, Zhou, and Chavez et al., as set forth on pp. 23-27 of the previous office action (mailed on 09/10/2025) has been withdrawn in view of the arguments and amendments filed on 12/10/2025).
The rejections of claims 6-7 under 35 USC 103 as being unpatentable over Keshavjee, Lang, Gur, Zhou, and Fisman et al., as set forth on pp. 27-32 of the previous office action (mailed on 09/10/2025) has been withdrawn in view of the arguments and amendments filed on 12/10/2025).
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 1-2, 4-8, 14, 17-23, and 25-26 are rejected under 35 U.S.C. 101 because the claimed method is directed towards a judicial of an abstract idea and laws of nature/natural phenomena without significantly more.
Step 1
Claims 1-2, 4-8, 14, 17-23, and 25-26 are to a statutory category of a method of
detecting or determining levels of expression for biomarkers IL-5, IL-12, IL-15, IL-16, C-
reactive protein (CRP), and VEGF.
Step 2A prong 1: does the claim recite a judicial exception?
The claim recites methods for observing the law of nature of naturally occurring
expression levels or expression of a biomarker (IL-5, IL-12, IL-15, IL-16, C-reactive
protein (CRP), and VEGF), and correlating them with suitability of an explant organ for
transplantation. Further, the claim recites “determining” which may be categorized as an
abstract idea, namely a mental process/concept performed in the human mind. The
claims, under their broadest reasonable interpretation, cover performance of identifying
a risk solely within the human mind, or by a human using pen and paper. Comparing
information regarding the sample to a control (in this case, correlating the level of a
biomarker compared to a predetermined level) represents abstract ideas.
Similar concepts involving comparing information regarding a sample or test
subject to a control or target data have been held to be an "abstract mental process", as
in University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 113
USPQ2d 1241 (Fed. Cir. 2014) which involved "comparing BRCA sequences and
determining the existence of alterations", the collecting and comparing of known
information in Classen, the comparing information regarding a sample or test subject to
a control or target data in Ambry and Myriad CAFC, as well as Mayo (which also
involved specific numerical cutoff levels).
Step 2A prong 2: Does the claim recite additional elements that integrate the exception into a practical application?
Regarding the method of using the judicial exception, the data gathering steps do
not add a meaningful limitation to the methods as they are insignificant extra-solution or
mere data gathering steps.
Step 2B:
The claim does not include additional elements that are sufficient to amount to
significantly more than the judicial exception because the claimed elements when
considered separately and in combination, do not add significantly more to the
exceptions. The natural law/phenomenon is analogous to the correlation of biomarkers
found ineligible by the courts, for example, in Mayo Collaborative Servs. v. Prometheus
Labs., Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012), Cleveland Clinic
Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081,
1088 (Fed. Cir. 2017) (Using well -known standard laboratory techniques to detect
enzyme levels in a bodily sample such as blood or plasma), and Ariosa Diagnostics, Inc.
v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015)
(ineligible claims were directed to a method of detecting paternally inherited cell
free fetal DNA, which is naturally occurring in maternal blood).
Regarding claim 1, the method of using the judicial exception, the extra solution
activity of determining the levels of i) IL-5; ii) IL-12; iii) IL-15; iv) IL-16; v) C-reactive protein
(CRP); and vi) VEGF in a sample of perfusate fluid and determining the explant
organ is suitable for transplantation based on whether a respective amount of each
protein in the sample is greater or less than a respective predetermined value; wherein the predetermined value(s) are selected from one or more of the group consisting of: a) between about 0.62 pg/ml to about 0.63 pg/ml of IL-5;b) between about 14.4 pg/ml to about 14.5 pg/ml of IL-12;c) between about 2.19 pg/ml to about 2.2 pg/ml of IL-15;d) between about 1235 pg/ml to about1250 pg/ml of IL-16;e) between about 6.28 pg/ml to about 6.29 pg/ml of VEGF; ande) between about 2.39 pg/ml to about 2.4 pg/ml CRP is directed towards judicial exceptions (i.e., law of nature, a natural phenomenon, and/or an abstract idea) without significantly more.
Regarding claim 2, determining that the explant organ is suitable for transplantation if the respective amount of each of the at least three proteins is less than the respective predetermined value is directed towards judicial exceptions (i.e., law of nature, a natural phenomenon, and/or an abstract idea) without significantly more.
Regarding claim 4, wherein step (b) of determining an amount in the sample comprises quantifying the amount present in the sample of at least three proteins selected from: i) IL-5; ii) IL-12; iii) IL-15; iv) IL-16; v) CRP; and vi) VEGF; and wherein the step of determining whether the explant organ is suitable for transplantation comprises; a) for each protein, determining whether the amount of the protein is greater or less than a predetermined value; b) assigning a score of 1 to the protein if the amount is greater than the predetermined value; and c) adding together the score of each protein; wherein the explant organ is determined as suitable for transplantation if the additive score of the proteins is less than 3 is directed towards judicial exceptions (i.e., law of nature, a natural phenomenon, and/or an abstract idea) without significantly more.
Regarding claim 5, wherein step (b) of determining an amount in the sample
comprises quantifying the amount present in the sample of at least four proteins selected
from: i) IL-5;ii) IL-12;iii) IL-15;iv) IL-16;v) CRP; and vi) VEGF, and wherein the step of
determining whether the explant organ is suitable for transplantation comprises; a) for
each protein, determining whether the amount of the protein is greater or less than a
predetermined value; b) assigning a score of 1 to the protein if the amount is greater
than the predetermined value; and c) adding together the score of each protein; wherein
the explant organ is determined as suitable for transplantation if the additive score of the
proteins is less than 3 is directed towards judicial exceptions (i.e., law of nature, a natural phenomenon, and/or an abstract idea) without significantly more.
Regarding claim 6, wherein step (b) of determining an amount in the sample comprises quantifying the amount present in the sample of at least five proteins selected from: i) IL-5; ii) IL-12; iii) IL-15; iv) IL-16; v) CRP; and vi) VEGF, and wherein the step of determining whether the explant organ is suitable for transplantation comprises; a) for each protein, determining whether the amount of the protein is greater or less than a predetermined value; b) assigning a score of 1 to the protein if the amount is greater than the predetermined value; and c) adding together the score of each protein; wherein the explant organ is determined as suitable for transplantation if the additive score of the proteins is less than 3 is directed towards judicial exceptions (i.e., law of nature, a natural phenomenon, and/or an abstract idea) without significantly more.
Regarding claim 7, quantifying the amount present in the sample of IL-5, IL-12,
IL-15; IL-16; CRP; and VEGF; assigning a score of 1 to the protein if the amount is greater than the predetermined value; and adding together the score of each protein; wherein the explant organ is determined as suitable for transplantation if the additive score of the proteins is less than 3 is directed towards judicial exceptions (i.e., law of nature, a natural phenomenon, and/or an abstract idea) without significantly more.
Regarding claim 8, wherein:(i) the explant organ is undergoing hypothermic
perfusion;(ii) the method further comprises, prior to step (a), locating the explant organ in the perfusate fluid;(iii) the method further comprises inserting an organ into a perfusion machine comprising the perfusate fluid;(iv) the perfusate fluid has a temperature of approximately 5 -10 (v) the explant organ is undergoing hypothermic perfusion; and/or (vi) the sample is obtained approximately 15-30 minutes subsequent to the initiation of the perfusion is an insignificant extra solution activity that does not add a meaningful limitation. See Keshavjee et al., (WO 2014/127462 A1) (IDS filed on 03/30/2022) teaching that (vi) the sample being obtained approximated 15-30 minutes subsequent to the initial perfusion (see [0012] and claim 20) is routine and conventional.
Regarding claim 14, wherein:(a) the perfusate fluid comprises one or more of the
following components: i) pentafraction; ii) lactobionic acid; iii) potassium phosphate monobasic; iv) magnesium sulfate heptahydrate; v) raffinose pentahydrate; vi) adenosine; vii) allopurinol; viii) glutathione; ix) potassium hydroxide; and x) sodium hydroxide:(b) the perfusate fluid further comprises N-acetylcysteine, dexamethasone and benzylpenicillin; and/or (c) the organ is a liver is an insignificant extra solution activity that does not add a meaningful limitation. See Gur, Ali et al. “Prognostic Value of Procalcitonin, CRP, Serum Amyloid A, Lactate and IL-6 Markers in Liver Transplant Patients Admitted to ED with Suspected Infection.” In vivo (Athens, Greece) vol. 31,6 (2017): 1179-1185. doi:10.21873/invivo.11187. Gur teaches the organ being a liver (see abstract) is routine and conventional.
Regarding claim 17, determining the amount in the sample of at least one protein
selected from: a) IL-7; b) IL-17a; c) IL-16; and d) CRP, wherein the sample is obtained between about 80 minutes and 150 minutes after the initiation of perfusion and further wherein the method comprises; i) determining whether the amount of the at least one protein is greater or less than a predetermined value; ii) assigning a score of 1 to the protein if the amount is greater than the predetermined value; and ii) adding together the score of each protein; wherein the explant organ is determined as suitable for transplantation if the additive score of the proteins is less than 3 is directed towards judicial exceptions (i.e., law of nature, a natural phenomenon, and/or an abstract idea) without significantly more.
Regarding claim 18, which comprises, if the amount of more than one protein is
determined, determining the amounts of proteins simultaneously is an insignificant extra
solution activity that does not add a meaningful limitation. Keshavjee teaches the proteins being determined simultaneously (see [0039]) is routine and conventional.
Regarding claim 19, wherein the step of detecting the amount of the at least one
protein comprises performing an immunoassay, wherein optionally the immunoassay is
selected from an ELISA, a radioimmunoassay, automated immunoassay, cytometric
based assay and immunoprecipitation assay is an insignificant extra solution activity that
does not add a meaningful limitation. Keshavjee teaches wherein the step of detecting the amount of the at least one protein comprises performing an immunoassay, wherein optionally the immunoassay is selected from an ELISA, a radioimmunoassay, automated immunoassay, cytometric based assay and immunoprecipitation assay (see [00132], see [00191]) is routine and conventional.
Regarding claim 20, contacting the sample with at least one detection molecule,
wherein the detection molecule is specific to a protein selected from: i) IL-5; ii) IL-12; iii)
IL-15; iv) IL-16; v) C-reactive protein (CRP); and vi) VEGF is an insignificant extra solution
activity that does not add a meaningful limitation. See Lang, T et al. “Elevated biliary interleukin 5 as an indicator of liver allograft rejection.” Transplant immunology vol. 3,4 (1995): 291-8. doi:10.1016/0966-3274(95)80014-x. Lang teaches contacting the sample with a plurality of detection molecules and the detection molecule being specific to i) IL-5 (see page 292) is routine and conventional.
Regarding claim 21, contacting the sample with a plurality of detection
molecules, the plurality of detection molecules comprising a detection molecule specific to a protein selected from: i) IL-5; ii) IL-12; iii) IL-15; iv) IL-16; v) C-reactive protein (CRP); and vi) VEGF is an insignificant extra solution activity that does not add a meaningful limitation. See Lang teaching contacting the sample with a plurality of detection molecules and the detection molecule being specific to i) IL-5 (see page 292) is routine and conventional.
Regarding claim 22, the detection molecule comprises an antibody or fragment thereof is an insignificant extra solution activity that does not add a meaningful limitation. See Keshavjee teaching the detection molecule comprising an antibody (see [00132]).
Regarding claim 23, wherein:(i) the method is an ex vivo method; and/or (ii) the organ is obtained from a donor after death is an insignificant extra solution activity that does not add a meaningful limitation. See Keshavjee teaching wherein:(i) the method is an ex vivo method death (see abstract).
Regarding claim 25, A method of transplanting an organ into a subject recipient comprising: a) performing the method of claim 1; and b) transplanting the organ into the subject recipient if the organ is assigned a score of 3 or less; or discarding the organ if the organ is assigned a score of 4 or greater is directed towards judicial exceptions (i.e., law of nature, a natural phenomenon, and/or an abstract idea) without significantly more.
Regarding claim 26, wherein:(i) the organ is a liver, e.g. a human liver;(ii) the method further comprises obtaining the organ from a donor who has undergone circulatory death prior to donation;(iii) the method further comprises placing the organ in a hypothermic perfusion system; and/or (iv) the subject is a human is an insignificant extra solution activity that does not add a meaningful limitation. See Gur teaching the organ being a liver (see abstract) is routine and conventional.
Thus, claims 1-2, 4-8, 14, 17-23, and 25-26 are rejected under 35 USC 101.
Claim Rejections - 35 USC § 101-Response to Arguments
The arguments filed on 12/10/2025 have been considered by the examiner.
On pp. 10-11 applicant argues that the claims recite the additional elements that integrate the exception into a practical application. One of the practical applications being an objective test for organ transplant viability.
However, the instant claims do not recite additional elements that integrate the exception into practical application. Regarding independent claim 1, the claim recites a) obtaining a sample of perfusate fluid in which an explant organ is located; b) determining the amount in the sample of at least three proteins selected from a group. Steps A and B are merely data gathering steps that do not integrate into a practical application.
Claim 1 further recites c) determining that the explant organ is suitable for transplantation based on whether a respective amount of protein in the sample is greater or less than a respective predetermined value; wherein the predetermined value(s) are selected from one or more from a group. Step C is an observation and/or evaluation based on the obtained information from the data gathering steps. Further, comparing the respective amount of protein in a sample to a predetermined value can be performed in the human mind. Such mental observations or evaluations fall within the “mental processing” grouping of abstract ideas. Comparing information regarding the sample to a control (in this case, correlating the level of a
biomarker compared to a predetermined level) represents abstract ideas. Thus, step C recites concepts that fall into the “mental process” grouping of abstract ideas and do not integrate into a practical application.
Further, claim 1 step C recites measuring naturally occurring biomarkers and correlating the value of those naturally occurring biomarkers to the explant organ’s suitability for transplantation. Step C recites observing the law of nature of naturally occurring biomarkers. Step C is directed to a natural law/phenomenon. Thus, step C recites the judicial exception of the law of nature and a natural phenomenon and does not integrate into a practical application.
Conclusion
No claim is allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Mota et al., “Cytokines signatures in short and long-term stable renal transplanted patients.” Cytokine vol. 62,2 (2013): 302-9. doi:10.1016/j.cyto.2013.03.001 (2013).
Mota teaches quantifying IL-5 and IL-12 together (see page 303 under section 2.4). Mota teaches that Il-5 is a good biomarker associated with short-term stable renal function and IL-12 is a relevant inflammatory element in long-term renal transplanted patients (see abstract). Mota teaches that IL-15 mediates the rejection process (see page 305).
However, Mota does not teach assessing suitability of an explant organ for transplantation. Mota teaches measuring the various biomarkers after the transplantation has already occurred (see figure 1). Mota does not teach the sample being perfusate fluid, measuring at least three proteins selected from IL-5, IL-12, IL-15, IL-16, CRP, and VEGF. Mota does not teach determining that the explant organ is suitable for transplantation based on the respective amount of each protein in the sample.
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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/MCKENZIE A DUNN/ Examiner, Art Unit 1678
/GREGORY S EMCH/ Supervisory Patent Examiner, Art Unit 1678