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 2-9 and 12-19 have been amended, and Claim 20 has been newly added as requested in the amendment filed on 29 December 2025. Following the amendment, claims 1-20 are pending in the instant application.
Election/Restrictions
Applicant's election with traverse of Group II and the species of atherosclerosis in the reply filed on is acknowledged. The traversal is on the ground(s) that the examiner did not break Unity of Invention a posteriori (after applying art) and that this is required under PCT Rule 13.1. This is not found persuasive because PCT Rule 13.1 sets forth that any set of invention groups that does not meet one of the combinations of categories set forth in bullets (1) through (5) of the Requirement breaks Unity of Invention a priori, before the application of art. This is the case of the Groups presented as Groups I through V because they are directed to 5 materially different methods and a kit, which is not one of the five categories of invention that support Unity of Invention.
The requirement is still deemed proper and is therefore made FINAL.
Claims 5-13 and 16-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim.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 examined upon their merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is the national stage entry of PCT/EP2021/061691 filed on 4 May 2021.
This application claims the benefit of French Republic Application FR20 04447 filed on 5 May 2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claims 2-3, 14-15, are 20 have an effective US filing date of 5 May 2020.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2-3, 14-15, are 20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The method of independent Claim 2 recites 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 and deducing from that data if the individual has inflammation-related platelet activation. There is no specific quantity/concentration/proportion of biomarker(s) within the claimed method that indicates disease. Further, there a directionality (i.e. increased or decreased relative to standard control) within the claimed method that indicates disease, although Figures 1 through 8 indicate specific directionalities for each of the biomarkers. Therefore, the method of the invention appears to be missing essential elements relating the quantity/concentration/proportion of biomarker(s) to the indication of disease. Absent these elements, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention and this affects the scope of all depending claims.
Claim 2 is further indefinite wherein it recites comparing with “a corresponding standard control value”. The term “corresponding standard” is a relative term which renders the claim indefinite. The term “standard” is neither defined by the claim itself, nor does the specification provide a definition as to what is the corresponding standard would be. Thus, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention and whether or not direct infringement of the invention has occurred.
Claim 20 further limits the disease to the instantly-elected atherosclerosis, but, again, it is unclear how a person of ordinary skill in the art would know when the quantity/concentration/proportion of biomarker(s) indicates this specific disease, therefore what methods would directly infringe the invention are unclear.
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 2-3, 14-15, are 20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to without significantly more. The claim(s) recite(s) comparing results and deducing from those results. This judicial exception is not integrated into a practical application because MPEP 2106.05(a-c), (e) and (h). The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional steps/elements were well-understood, routine and conventional activities at the time of filing.
The claims are directed to a method for preventing and/or treating inflammatory disease associated with inflammation-related platelet activation comprising measuring the quantity, concentration and/or the proportion of the biomarkers listed in a biological sample comprising platelets; comparing the results with a standard control value; deducing from the above if the individual has inflammation-related platelet activation; and if the individual has inflammation-related platelet activation, administering antiplatelet therapy. Methods are one of the statutory categories of invention (STEP 1:YES)
This claim recites comparing and deducing, which are abstract mental concepts that belong to enumerated group (c) of the Abstract Idea Groupings described in MPEP § 2106.04(a)(2): Mental processes — concepts performed in the human mind (including an observation, evaluation, judgment, opinion). But more importantly, the claims recite a natural correlation/phenomenon/law of nature whereby inflammation-related platelet activation is correlated with the comparison in the level of the biomarkers AKT, PKC, CD62P, CD63, RANTES, TSLP and CD40 ligand in a biological sample comprising platelets. Therefore the claims recite at least one judicial exception (STEP 2A, Prong One: YES).
According to Step 2A, Prong Two, set forth in MPEP 2106.04 II A (2), the claims are next evaluated with respect to whether the judicial exception is integrated into a practical application. These considerations are discussed in MPEP 2106.05 (a) through (c), (e), and (h). This analysis turns to the additional steps/elements recited within the claim(s). In independent claim 2 the steps/elements recited in addition to the judicially excepted subject matter are: (a) 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, which is recited at with such a high level of generality that it encompasses any means known in the art (see MPEP 2106.05(e)). Claim 2 further recites the additional step of treatment: d) if the individual has an inflammation-related platelet activation, administering antiplatelet therapy to said individual. However, MPEP 2106.04(d)(2) states: “Examiners should keep in mind that in order to qualify as a ‘treatment’ or ‘prophylaxis’ limitation for purposes of this consideration, the claim limitation in question must affirmatively recite an action that effects a particular treatment or prophylaxis for a disease or medical condition.” The instant claims only conditionally apply treatment if the comparing and deducing steps indicate inflammation-related platelet activation. Since it does not affirmatively result in active treatment, then the treating step does not integrate the judicial exception into a practical application.
There are no additional elements that reflect an improvement within the technical field; there are no additional elements that apply the natural correlation/phenomena judicial exception to a particular treatment or which utilize a particular machine; there are no additional elements that effect a transformation; and, there are no additional elements that apply the judicial exception in some other meaningful way beyond generally linking it to a field, namely, lung injury. The additional step of “treating”, this is recited with such a high level of generality that it encompasses any antiplatelet means known in the art (see MPEP 2106.05(e)).
Applicant admits in the specification that, “The platelet-rich plasma sample can be obtained by any suitable method well known to a person skilled in the art” (pg. 5) and “The measurement of the quantity, concentration and/or the proportion of the … biomarkers can be performed by any method well known to a person skilled in the art, for measuring the quantity, concentration and/or the proportion of a membrane protein.” (pgs. 9-10). Therefore, these additional steps, by Applicant’s admission, were known in the art prior to filing. Therefore, in in accordance with MPEP 2106.07(a)(III)(A), the examiner has cited express statements in the specification indicating that the additional elements were sufficiently well-known that the specification does not need to describe the particulars thereof. In other words, the disclosure describes no new technology, but merely refers to techniques and elements that were known in the art at the time of filing. (STEP 2A, Prong Two: NO).
Lastly, in accordance with MPEP 2106.07(a)(III)(C), the examiner cites publications within the field of technical expertise, that demonstrate the well-understood, routine, conventional nature of the additional element(s). The following prior art teach each of the biomarkers were known to be associated with platelet inflammation. Oyarzun et al. (Frontiers in Immunology, Vol. 11, Article 705, published 30 April 2020) teach, “increased surface translocation of α-granule-derived P-selectin and CD40L, which mediate platelet interaction with leukocytes and endothelial cells”, CD40L 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 higher levels of dense granule-derived CD63 in patients with thrombocytopenia and the chemokine RANTES is also secreted by activated 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, Journal of Thrombosis and Haemostasis, 9 (Suppl. 1): 76–91, 2011). Lastly, the following prior art teaches TSLP, of the instant claims, was well-known as an inflammatory cytokine that stimulates platelet secretion and potentiates platelet aggregation via the AKT signaling pathway (Dong et al., Cell Physiol Biochem, 35: 160-174, 2015). 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 (STEP 2B: NO). The claimed steps/elements recited in addition to the judicial exception(s), alone or in combination, do not make an inventive contribution over the methods that were known in the art prior to filing, and they amount to mere observation of the natural phenomenon itself, by any means known, with the words “apply it” in order to append it to the field of inflammation-related platelet activation.
For all of these reasons, Claims 2-3, 14-15, are 20 are directed to the judicial exception without significantly more and are rejected.
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.
Claims 2-3, 14-15, are 20 are rejected under 35 U.S.C. 103 as being unpatentable over Oyarzun et al., Frontiers in Immunology, Vol. 11, Article 705, published 30 April 2020, in view of Nurden and Nurden, Journal of Thrombosis and Haemostasis, 9 (Suppl. 1): 76–91, 2011; Dong et al., Cell Physiol Biochem, 35: 160-174, 2015; and Lindemann et al., Journal of Thrombosis and Haemostasis, 5 (Suppl. 1): 203–211, 2007.
It should be noted that the instant claims are contingent claims. Regarding such claims MPEP2111.04(II) states: “The broadest reasonable interpretation [BRI] of a method (or process) claim having contingent limitations requires 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. For example, assume a method claim requires step A if a first condition happens and step B if a second condition happens. If the claimed invention may be practiced without either the first or second condition happening, then neither step A or B is required by the broadest reasonable interpretation of the claim. If the claimed invention requires the first condition to occur, then the broadest reasonable interpretation of the claim requires step A. If the claimed invention requires both the first and second conditions to occur, then the broadest reasonable interpretation of the claim requires both steps A and B.” Since the final step of treating is contingent only upon “deducing from the [measuring the quantity, concentration and/or the proportion of the biomarkers] if the individual has inflammation-related platelet activation”, then the BRI of the method requires only steps (a) measuring and, since the scope of “a corresponding standard control” is indefinite, step (b) will be interpreted as comparing to any control. As stated above, there is not even any definitive directionality of the quantity, concentration and/or proportion that indicates disease and the subsequent treatment. Thus, for purposes of applying prior art, the claims will be interpreted as requiring step (a) and comparing to any control.
Regarding claim 2, the Oyarzun et al. prior art references teach 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 with a corresponding standard control value. Specifically, Table 2 of Oyarzun et al. teaches measuring and comparing of induced levels of P-selectin (equivalent to CD62P of the instant claims), CD40 ligand (see also Figure 1B), CD63, and RANTES (see pg. 7, second column). 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.
Regarding claim 3, Figure 5 of the Oyarzun et al. reference (reproduced below) demonstrates “a specific intra-platelet signaling pathway is activated.”
Regarding claims 14 and 15, Oyarzun et al. teach “Platelet-rich-plasma (PRP) was obtained”, thus teaching the specific sample of the claims.
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While the prior art references do not teach step(c) of the instant claims comprising “deducing” from the measurement if the individual has inflammation-related platelet activation, this is a mental process that is a judicially-created exception to patent eligible subject matter. The deducing step, therefore, cannot be what distinguishes the invention over the methods disclosed in the prior art.
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 signaling cascade in platelet activation (Fig. 3) and decreased platelet levels of PKC were linked to aggregation and secretion defects in patients with defective response to thrombin (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).
Regarding Claim 20, the Lindemann et al. prior art is relied upon as teaching platelets and inflammation were known to play a specific role in atherosclerosis before the effective filing date of the application. Lindemann and colleagues teach “Both activated platelets and endothelial
cells actively secrete … CD40 L. The release of RANTES … is platelet specific …[and] one tool 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 play a specific role in atherosclerosis.
It would have been obvious to a person having ordinary skill in the art, before the effective filing date of the application, to assess each of the claimed biomarkers - AKT, PKC, CD62P, CD63, RANTES, TSLP and CD40 ligand – taught by the individual references, in the context of atherosclerosis, as taught by Lindemann. Motivation to do so is explicit because each of the references teach these biomarkers as promoting platelet-leukocyte interaction, platelet-endothelial interaction, and/or inflammation-related platelet pathways. In KSR International Co. v. Teleflex, Inc., the Supreme Court has stated that where there is a “pressure to solve a problem and a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense” (KSR International Co. v. Teleflex, Inc. 127 S. Ct. 1727, 82 USPQ2d 1385, Supreme Court, April 30, 2007). In the instant case, the problem to be solved is measuring the quantity, concentration and/or the proportion of biomarkers associated with inflammation-related platelet activation, and specifically atherosclerosis. 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 biomarkers AKT, PKC, CD62P, CD63, RANTES, TSLP and CD40 ligand in a biological samples comprising platelets.
Therefore, the method of the invention is obvious in view of the combined teachings in the art before the effective filing date of the application. Claims 2-3, 14-15 and 20 are rejected under 35 U.S.C. 103.
Conclusion
No claim is allowed.
Correspondence
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