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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because of the inclusion of legal phraseology such as “comprises”. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The disclosure is objected to because of the following informalities: On page 5, lines 2-16 of the specification, there is no brief description of panel F in Figure 1.
Appropriate correction is required.
Claim Objections
Claims 5-8 are objected to because of the following informalities: In clam 5, the full meaning for the abbreviations “VASP” and “VASP-P” should be recited. In claim 6, the full meaning for the abbreviation “TF” should be recited. In claim 8, the full meaning for the abbreviations “ADP” and “PGE1” should be recited. Also, on line 2 of claim 8, the phrase “VASP phosphorylation inhibitors comprise ” should be changed to -- VASP phosphorylation inhibitor comprises—since only a singular VASP phosphorylation inhibitor is recited in claim 5. Appropriate correction is required.
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 1-4 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.
Claim 1 is indefinite since it is not clear how the determined vasodilator-stimulated phosphoprotein phosphorylation status and the platelet tissue factor expression are used to assess residual platelet thrombotic potential in the patient. The only step recited in the method is the step of determining vasodilator-stimulated phosphoprotein phosphorylation status and platelet tissue factor expression in a blood sample of the patient. No other steps are recited that indicate how these determined parameters are used to assess residual platelet thrombotic potential in the patient. It is also not clear what values of the determined parameters indicate what levels of platelet thrombotic potential in the patient. On lines 4-5 of claim 1, the phrase “determining in a patient’s blood sample of vasodilator-stimulated phosphoprotein phosphorylation” should be changed to –determining in a blood sample of the patient a vasodilator-stimulated phosphoprotein phosphorylation —so as to positively refer back to the patient recited on line 2 of claim 1.
Claim 2 is indefinite since it does not further limit claim 1 since claim 1 already recites that the method is for assessing residual thrombotic potential in a patient undergoing treatment with P2Y12 receptor inhibitors. Therefore, the recitation of claim 2 is redundant with what is already recited in claim 1.
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 1-4 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e. a law of nature, a natural phenomenon, or an abstract idea) without significantly more. The claim(s) recite(s) the natural correlation or phenomenon between a vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) status and platelet tissue factor (TF) expression in a blood sample of a patient and residual platelet thrombotic potential in the patient. This judicial exception is not integrated into a practical application because the claims do not apply or use the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment or field of use. 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 in the method concerning measurement of the VASP-P and TF in the blood sample constitute a “well understood, routine and conventional activity” under 35 USC 101
When considering the claims under the 2019 Revised Patent Subject Matter Eligibility Guidance (January 2019), it is noted that the claims meet step 1 of the guidance since the claims are directed to one of the statutory categories of invention (i.e. are directed to a process). The claims meet prong one of revised step 2A since the claims recite a natural phenomenon between a vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) status and platelet tissue factor (TF) expression in a blood sample of a patient and residual platelet thrombotic potential in the patient. The claims do not meet prong two of revised step 2A since the claims do not recite additional elements that integrate the judicial exception into a practical application. The only step recited in the method recited in claim 1 is the determination of a vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) status and platelet tissue factor (TF) expression in a blood sample of a patient undergoing treatment with a P2Y12 receptor inhibitor selected from clopidogrel, prasugrel or ticagrelor, which is a part of the natural correlation. No other steps of the method recite a practical application of the natural correlation, such as a particular treatment of the patient, implementing the judicial exception with a particular machine or manufacture that is integral to the claim, or applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception. See MPEP 2106.04(d). Claims 2 and 3 merely define the type of patient to perform the method on (i.e. a patient undergoing treatment with a P2Y12 receptor inhibitor selected from clopidogrel, prasugrel or ticagrelor). With regards to claim 4, the recitation of the type of measurement method or technique used to measure the VASP-P and TF in the method (i.e. flow cytometry) does not amount to a practical application of the judicial exception since flow cytometry is well-known and routinely used to measure these parameters in a blood sample, and therefore, only amounts to insignificant extra-solution activity to the judicial exception.
The claims also do not meet step 2B of the guidance since the additional elements of the claims concerning obtaining a blood sample from a subject and determining the VASP-P status and TF expression in the sample using flow cytometry are both well-understood, conventional and routine sample analysis steps that must be taken by those of skill in the art in order to establish the conditions under which the natural correlation exists. These additional steps are merely well understood, routine and conventional limitations that are necessary for all practical applications of the natural correlation, such that everyone practicing the natural correlation would be required to perform those steps. See the references to Brambilla et al (NPL refence no. 3 on the IDS filed on January 12, 2024 from Blood Transfusion, vol. 18, suppl 4, November 1, 2020, page S460) and Camera et al (article from Blood, volume 116, number 23, December 2, 2010, pages 5076-5077) who both teach of methods for measuring TF expression in a blood sample using flow cytometry. Also, see the reference to Aleil et al (NPL reference no. 1 on the IDS filed on January 12, 2024 from the Journal of Thrombosis and Haemostasis, vol. 3, no. 1, January 1, 2005, pages 85-92), which teaches that measuring VASP-P in a blood sample using flow cytometry and anti-VASP-P monoclonal antibodies is well understood, routine and conventional in the prior art. For this reason, the additional steps recited in the method do not recite an inventive concept that renders the claims patent eligible under step 2B of the 35 USC 101 analysis.
Inventorship
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 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.
Claim(s) 1-3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Brambilla et al (NPL refence no. 3 on the IDS filed on January 12, 2024 from Blood Transfusion, vol. 18, suppl 4, November 1, 2020, page S460).
With regards to claims 1-3, Brambilla et al teach of a method for evaluating the anti-platelet effect of the P2Y12 receptor inhibitor clopidogrel in patients treated with clopidogrel. The method comprises performing both an assay for vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) status on a blood sample obtained from a patient treated with clopidogrel, and analyzing the expression of platelet tissue factor (TF) using flow cytometry. See the abstract in Brambilla et al.
Brambilla et al fail to teach that the method can be used for assessing residual platelet thrombotic potential in the patient. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method taught by Brambilla et al to assess residual platelet thrombotic potential in the patient because Brambilla et al teach that the antiplatelet effect of clopidogrel is assessed by a VASP assay, and platelets that expose a functionally active TF on their surface serve to trigger a coagulation process that gives rise to thrombin generation. Thus, both the VASP assay and the analysis of the amount of platelet tissue factor (TF) in the method taught by Brambilla et al can determine the potential of platelets to initiate a thrombotic coagulation event.
Claim(s) 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Brambilla et al (NPL refence no. 3 on the IDS filed on January 12, 2024 from Blood Transfusion, vol. 18, suppl 4, November 1, 2020, page S460) in view of Aleil et al(NPL reference no. 1 on the IDS filed on January 12, 2024 from the Journal of Thrombosis and Haemostasis, vol. 3, no. 1, January 1, 2005, pages 85-92). For a teaching of Brambilla et al, see previous paragraphs in this Office action.
With regards to claim 4, Brambilla et al teach that the platelet tissue factor (TF) expression in the method is determined by flow cytometry, but fails to teach that the VASP-P status of the blood sample is also determined by flow cytometry.
Aleil et al teach that VASP phosphorylation in a blood sample can be measured using flow cytometry and anti-VASP-P monoclonal antibodies. See the paragraph entitled “Analysis of VASP phosphorylation by Flow Cytometry” on page 86 of Aleil et al.
Based upon the combination of Brambilla et al and Aleil et al, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use flow cytometry to measure both the platelet tissue factor expression and the VASP-P in the method taught by Brambilla et al because Brambilla et al teach that the platelet tissue factor expression in the method is determined by flow cytometry, and Aleil et al teach that it is commonly known to measure VASP phosphorylation in a blood sample using flow cytometry and anti-VASP-P monoclonal antibodies.
Claim(s) 5-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Brambilla et al (NPL refence no. 3 on the IDS filed on January 12, 2024 from Blood Transfusion, vol. 18, suppl 4, November 1, 2020, page S460) in view of the BioCytex PLT VASP/P2Y12 kit brochure and Camera et al (article from Blood, volume 116, number 23, December 2, 2010, pages 5076-5077). For a teaching of Brambilla et al, see previous paragraphs in this Office action.
With regards to claims 5-8, Brambilla et al fail to teach that the components required to measure the vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) status and the platelet tissue factor (TF) expression of the blood sample obtained from a patient treated with clopidogrel in the method are packaged into a kit.
The BioCytex PLT VASP/P2Y12 kit brochure teaches of a kit for measuring vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) status of a blood sample. The kit comprises a diluent (claim 5), a fixative (claim 5), a selective ligand for VASP-P comprising anti-VASP-P mouse monoclonal antibodies (claim 6), a VASP phosphorylation inhibitor comprising PGE1 and ADP (claim 8), and a detection system for the anti-VASP-P mouse monoclonal antibodies, wherein the detection system comprises anti-IgG-FITC mouse antibodies (claim 7). See section 3 of the BioCytex PLT VASP/P2Y12 brochure which lists the components of the kit.
Camera et al teach measuring platelet-associated TF expression in a blood sample using flow cytometry and a selective ligand for platelet TF, wherein the selective ligand comprises monoclonal antibodies against TF. See the fourth paragraph on page 5076 of Camera et al.
Based upon the combination of Brambilla et al, the BioCytex PLT VASP/P2Y12 kit brochure, and Camera et al, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to package the components necessary to measure the vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) status and the platelet tissue factor (TF) expression of the blood sample obtained from a patient in the method taught by Brambilla et al into a kit because both the BioCytex PLT VASP/P2Y12 kit brochure and Camera et al teach of the components necessary to measure both VASP-P and TF in a blood sample, and the BioCytex PLT VASP/P2Y12 kit brochure provides the motivation to package these components into a kit since doing so allows all of the components to be readily assessable in their ready-to-use format by a user for the quick and easy performance of the method.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Please make note of: Chapman-Montgomery et al (US 2010/0173339) who teach of a method for determining the appropriateness of anti-platelet therapy in a patient; Camera et al (WO 2025/215545) who teach of a method for the evaluation of residual platelet thrombotic potential in patients undergoing antiplatelet therapy with acetylsalicylic acid; Payrastre et al (WO 2010/060918) who teach of methods and kits for monitoring anti-platelet therapy; and Brambilla et al (article from Arteriosclerosis, Thrombosis and Vascular Biology, vol. 43, October 2023, pages 2042-2057) who teach of a method for assessing TF expression and VASP-P in a blood sample from a patient treated with a P2Y12 receptor inhibitor.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAUREEN M WALLENHORST whose telephone number is (571)272-1266. The examiner can normally be reached on Monday-Thursday from 6:30 AM to 4:30 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander, can be reached at telephone number 571-272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MAUREEN WALLENHORST/Primary Examiner, Art Unit 1797 August 11, 2026
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