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 .
Response to Amendment
Claims 2 has been amended and claims 21-22 are newly added as requested in the amendment filed on 4 June 2026. Following the amendment, claims 1-22 are pending in the instant application.
Claims 5-13 and 16-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim.
Claims 2-3, 14-15, are 20-22 examined upon their merits.
Withdrawn Rejection:
As currently amended, the rejection of Claims 2-3, 14-15, are 20 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn. The current claims clarify the specific quantity/concentration/proportion of biomarker(s) within the claimed method that indicates disease, and defines the standard values that the measured amounts are compared to.
Claim Rejections - 35 USC § 101 (Maintained)
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.
As amended, Claims 2-3, 14-15, are 20-22 stand as rejected under 35 U.S.C. 101 because the claimed invention is directed to judicially excepted subject matter without significantly more, for reasons of record in the previous action as applied to Claims 2-3, 14-15, are 20.
In Remarks filed 4 June 2026, Applicant traverses this rejection on the grounds that the rejection should be moot by virtue of the policy changes adopted by the USPTO and asserted changed that occurred in the PTAB considerations of Section 101 (Remarks pgs. 7-8). Applicant asserts the “invention as currently claimed relates to diagnosing and preventing and/or treating inflammatory disease associated with inflammation-related platelet activation and reflects a practical application of any alleged abstract ideas. As a result, the combination of these elements shows that the present claims are not mere abstract ideas that can be practiced by ‘mental steps.’ Applicant goes on to state: “Further, the ‘conditional treatment’ argument of the Examiner in the Official Action is not applicable, and instead, Applicant's method as presently claimed does effect treatment when the condition is met [emphasis added], and contrary to the Examiner's position is clearly a rational, medically-grounded treatment algorithm.” Further stating: The amendments, elements b) and c) are now directed to detailed technical features which clearly are not simple abstract mental concepts. Further, with regard to element d) of Claim 2, this element allows the skilled artisan to identify an appropriate antiplatelet therapy. Lastly, Applicant argues the present claims are not directed to individual biomarkers in isolation, instead they are directed to a method wherein a specific combination of seven biomarkers is used.
These arguments have been considered in full but are not persuasive to overcome the rejection for the following reasons. First, the policy changes provide three, new Eligible Subject Matter Examples 47-49 which pertain to AI-driven improvements of methods that recite Abstract Idea Mathematical Concepts and Mental Processes but which present steps in which the exception is integrated into a practical application because they specifically recite improvements to functioning of a computer or other technology and/or a particular treatment for disease. Applicant is encouraged to read the specific examples. The current claims are not drawn to AI-enhanced diagnostic methodologies and therefore the policy changes are not applicable to the instant claims.
The claims still recite a judicial exception natural correlation/phenomenon/law of nature whereby inflammation-related platelet activation is correlated to elevated levels of three of the biomarkers selected from AKT, PKC, CD62P, CD63, RANTES, TSLP and CD40 ligand in a biological sample comprising platelets. As amended, the claims recite new Mathematical Concepts –
“wherein the standard control value is selected from the group consisting of a mean, a maximum threshold value, and a minimum threshold value of the quantity; wherein concentration or proportion of a corresponding biomarker as measured in samples taken from a reference population; wherein the minimum threshold value and the maximum threshold value are respective lower and higher endpoints of a reference interval including 95% of the values obtained in the reference population, and wherein the standard control value is qualified as: i) not activated (NA) standard control value when the reference population consists of healthy individuals, or ii) activated (A) standard control value when the reference population consists of individuals with inflammation-related platelet activation; c) deducing from the above if the that said individual has inflammation-related platelet activation when the quantity, concentration and/or the proportion of at least three of said biomarkers is: i) greater than a corresponding non-activated (NA) standard control value, and/or ii) greater than or equal to a corresponding activated (A) standard control value.”
These mathematical concepts: minimum and maximum threshold values corresponding to lower and higher endpoints, respectively, of a reference interval including 95% of the values obtained; and, deducing that the individual has inflammation-related platelet activation when the quantity, concentration and/or the proportion of at least three of said biomarkers is either greater than a corresponding non-activated (NA) standard control value, and/or greater than or equal to a corresponding activated (A) standard control value, do not constitute an improvement to functioning of a computer or other technology. Rather, determining the lower and higher endpoints and determining that the quantity, concentration and/or the proportion of at least three of said biomarkers is either greater than a reference value are all mental processes that can be performed in the mind of a practitioner.
While Applicant asserts that the claim fulfills the requirement under MPEP 2106.04(d)(2) that states, “the claim limitation in question must affirmatively recite an action that effects a particular treatment or prophylaxis for a disease or medical condition”, the treatment clause is still conditional on the quantity, concentration and/or the proportion of at least three biomarkers being greater than either the NA or A reference values. Thus, there is still a conditional clause within the method, and if the quantity, concentration and/or the proportion of at least three of said biomarkers is not greater then no treatment is affected. The broadest reasonable interpretation (BRI) of the claim is still only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met. Thus, the BRI is measuring the quantity, concentration and/or the proportion of the biomarkers AKT, PKC, CD62P, CD63, RANTES, TSLP and CD40 ligand in a biological sample comprising platelets of said individual and comparing the results obtained with a corresponding standard control value. Thus, the treatment does not necessarily and affirmatively recite an action that effects a particular treatment. Further, even when the conditions are met and the individual has an inflammation-related platelet activation, the treatment step is not particular to the condition. It does not integrate the judicial exception into a particular antiplatelet therapy. Rather, the treatment amounts to appending known antiplatelet therapies to patients having inflammation-related platelet activation, and this amounts to the words “apply it” appended to a particular field of technology. Thus, contrary to Applicant’s arguments element d) of Claim 2, does not allow the skilled artisan to identify an appropriate antiplatelet therapy but rather apply generic and known antiplatelet therapies.
Contrary to Applicant’s assertion that the method uses a specific combination of seven biomarkers, the claims require measuring the quantity, concentration and/or the proportion of the biomarkers AKT, PKC, CD62P, CD63, RANTES, TSLP and CD40 ligand in a biological sample comprising platelets of said individual, but only require the quantity, concentration and/or the proportion of at least three of said biomarkers is greater than the NA and/or A standard control value.
The Examiner has provided evidence that many of the claimed biomarkers were known to be associated with platelet inflammation before the effective filing date of the application. Oyarzun et al. (2020) teach increased P-selectin and CD40L, which is equivalent to CD40 ligand of the claims and P-selectin is also known as CD62P of the instant claims. Oyarzun et al. further teach CD63 and the chemokine RANTES is also elevated in platelets (Abstract and Figure 1). The following prior art teaches AKT, PKC, P-Selectin (a.k.a. CD62P of the claim), and CD63 are all involved in the signaling cascades that give rise to platelet activation and aggregation (See Figure 3 of Nurden and Nurden, 2011). Therefore, the steps/elements recited in addition to the judicial exception (obtaining a obtaining a sample comprising platelets and measuring the quantity, concentration and/or the proportion of the biomarkers AKT, PKC, CD62P, CD63, RANTES, TSLP and CD40 ligand in the biological sample comprising platelets) were all well-understood, routine, conventional activities in the field of lung injury prior to filing the application at hand.
Newly added Claims 21 and 22 recite “wherein said corresponding non-activated (NA) standard control value is the maximum threshold value” and “wherein said corresponding activated (A) standard control value is the minimum threshold value,” respectively. These limitations do not add additional steps/elements that either integrate the judicial exceptions into a practical application or amount to significantly more than what was known in the art before the effective filing date of the application.
For all of these reasons, Claims 2-3, 14-15, are 20-22 are directed to the judicial exception without significantly more and the rejection is maintained.
Claim Rejections - 35 USC § 103 (Maintained)
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claims 2-3, 14-15, are 20-22 stand as being rejected under 35 U.S.C. 103 as being unpatentable over Oyarzun et al., April 2020, in view of Nurden et al, 2011; Dong et al., 2015; and Lindemann et al., 2007.
It should be noted that the instant claims are still contingent claims. Thus, for purposes of applying prior art, the claims will be interpreted according to the BRI, which is requiring step (a) and comparing to a standard derived from healthy controls.
Applicant traverses the rejection based upon Oyarzun et al., 2020, in view of Nurden and Nurden, 2011; Dong et al., 2015; and Lindemann et al., 2007 on the grounds that (pg. 10 of Remarks) the Oyarzun art compares samples to patients with essential thrombocythemia rather than from healthy subjects.
This is not persuasive because the Methods of Oyarzun et al. state: “Twenty healthy individuals were studied as controls and, in all cases, a control was studied simultaneously with each patient” (pg. 3, paragraph titled “Patients”). The authors conclude that these are all important biomarkers promoting platelet-leukocyte and platelet-endothelial interaction (see paragraph bridging pages 5-6) and secretion of inflammatory mediators, as depicted in Figure 5.
Applicant further argues Oyarzun fails to teach the combination of biomarkers AKT, PKC, CD62P, CD63, RANTES, TSLP and CD40L that allows one to determine the presence of inflammation-related platelet activation with very high precision (87.6%).
This is not persuasive. The claims recite inflammation-related platelet activation is identified “when the quantity, concentration and/or the proportion of at least three of said biomarkers is: i) greater than a corresponding non-activated (NA) standard control value, and/or ii) greater than or equal to a corresponding activated (A) standard control value. Thus, while Applicant asserts that the method requires the combination of all seven, the determination, as claimed, is only made from any three of those seven.
While Oyarzun teaches four of the biomarkers listed, it does not disclose AKT, PKC and TSLP, however, the Nurden and Nurden, and Dong et al. prior art references remedy these deficiencies. The Nurden and Nurden prior art is relied upon for teaching AKT is an important intracellular biomarker in platelet activation (Fig. 3) as is PKC (pg.82, second full paragraph and Fig. 3). The Dong et al. prior art teaches, “The inflammatory cytokine TSLP triggered platelet activation and thrombus formation via TSLP-dependent PI3K/Akt signaling” (Abstract).
MPEP 2144.06 states that it is obvious to combine elements, each of which is taught by the prior art to be useful for the same purpose. No specific teaching or suggestion is needed for combination – the idea of combining them flows logically from their having been individually taught in the prior art as useful for the same purpose. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Such is the case for the claimed biomarkers. While no single reference teaches all seven, the separate references disclose the seven biomarkers each as being indicators of platelet activation. Therefore, it is obvious to combine these biomarkers since the idea of combining them flows logically from their having been individually taught in the prior art as useful for identifying platelet activation.
Regarding the newly added limitations of Claim 2: “wherein the standard control value is selected from the group consisting of a mean, a maximum threshold value, and a minimum threshold value of the quantity”; and “wherein the minimum threshold value and the maximum threshold value are respective lower and higher endpoints of a reference interval including 95% of the values obtained in the reference population”; and, regarding the limitations of newly added Claims 21 and 22, which recite “wherein said corresponding non-activated (NA) standard control value is the maximum threshold value” and “wherein said corresponding activated (A) standard control value is the minimum threshold value”, respectively. As stated in the rejection under 35 U.S.C. 101, these limitations are mathematical concepts which fall under an enumerated Abstract Idea Grouping. Therefore, these limitations are directed to patent ineligible subject matter, and therefore, cannot be the limitations that distinguish the invention over the methods disclosed in the prior art.
Regarding Claim 20, the Lindemann et al. prior art teaches activated platelets secrete CD40 L and RANTES and that these biomarkers are tools “of the platelet in acting as an inflammatory cell” (pg. 203, second to last paragraph). The prior art reference further teaches, “RANTES-induced monocyte adherence is mediated by P-selectin” (a.k.a. CD62P of the claims) and “Elevated serum levels of CD40 ligand (CD40 L) indicate an acute risk for a coronary event. The release of platelet derived CD40 L induces inflammatory responses in the endothelium. Platelets store and release high amounts of CD40 L within seconds after activation in vitro” (pg. 206 first two paragraphs). Therefore, the Lindemann prior art teaches at least three of the claimed biomarkers as playing a specific role in the instantly-elected species of atherosclerosis.
The Examiner maintains that the prior art references collectively demonstrate that there are a finite number of biomarkers involved in inflammation-related platelet signaling. Given the guidance in each of the prior art references, a person having ordinary skill would have been able to combine the teachings to predictably measure the quantity, concentration and/or proportion of all seven biomarkers AKT, PKC, CD62P, CD63, RANTES, TSLP and CD40 ligand in a biological samples comprising platelets.
Therefore, the invention of Claims 2-3, 14-15 and 20-22 is obvious in view of the prior art references, and the claims are rejected under 35 U.S.C. 103.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STACEY NEE MACFARLANE whose telephone number is (571)270-3057. The examiner can normally be reached M-F 7:30-5 (EST) & Sat. A.M..
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/STACEY N MACFARLANE/ Examiner, Art Unit 1675
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