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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-13) and the species of claims 3, 7 and 9 in the reply filed on 5/15/2026 is acknowledged.
Specification
The use of trademarks has been noted in this application. A trademark should be capitalized wherever it appears and be accompanied by the generic terminology.
Although the use of trademarks is permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner, which might adversely affect their validity as trademarks.
Claim Objections
Claim 1 is objected to because of the following informalities: Claim 1 should recite “and” after step (v).. Appropriate correction is required.
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.
Claim(s) 1, 9, 12 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Vitale et al. (Cytometry (Communications in Clinical Cytometry), 2001, 46:290–295; cited by applicant), and further in view of Mordakhanova et al. (Int. J. Mol. Sci., 2020, 21:2556) and Maličev (Transfusion Medicine Reviews, 2020, 34:34–41; cited by applicant).
The instant claims are directed to a method of detecting a change in the percentage of thrombocytes expressing both P-selectin and phosphatidylserine on their surfaces in blood serum of a subject living being, comprising the following steps:
(i) providing the blood serum of the subject living being;
(ii) providing thrombocytes of a healthy reference living being;
(iii) determining the percentage of thrombocytes of step (ii) expressing both of P-selectin and phosphatidylserine on their surfaces to obtain a value Mpre;
(iv) incubating an aliquot of said blood serum of step (i) with an aliquot of said thrombocytes of step (ii);
(v) determining the percentage of thrombocytes after said incubation in step (iv) expressing both of P-selectin and phosphatidylserine on their surfaces to obtain a value Mpost;
(vi) identifying a difference between Mpost and Mpre.
Vitale et al. teaches a method for detecting heparin-induced thrombocytopenia (HIT). The method involves obtaining serum samples from 13 patients with HIT and 10 normal subjects [claim 1, part (i)] (see page 291). Vitale et al. also obtained platelet-rich plasma (PRP) from normal donors [claim 1, part (ii)] (see page 291). Flow cytometry was used to measure CD62p expression (P-selectin) or Annexin V (phosphatidylserine) on various samples [claim 12]. The flow cytometry assay included negative controls consisting of the PRP + normal plasma + heparin or PRP + plasma in the absence of heparin [claim 1, part (iii)] (see page 293, right column). For Annexin V and CD62p staining of the samples, platelets from normal donors were incubated with heparin (1 U/ml) and the serum from the patients. To identify activated platelets, each sample was divided into two aliquots. The first aliquot was incubated with fluorescein isothiocyanate conjugate (FITC) Annexin V, and the second aliquot was incubated with an FITC-CD62P mAb. All samples were analyzed by flow cytometry [claim 1, part (iv)] (see page 291, right column and page 293, right column). Plasma samples were positive when the percentage of Annexin V or CD62p-positive cells exceeded the mean of negative controls + 2 SD [claim 1, parts (v) and (vi)].
While Vitale et al. teaches measuring Annexin V and CD62p separately, Vitale et al. does not measuring Annexin V and CD62p at the same time. Mordakhanova et al. teaches that HIT-like pathogenic immune complexes initially caused pronounced activation of platelets detected by an increased expression of phosphatidylserine and P-selectin (see the abstract), and Maličev teaches that the most common platelet activation markers are Annexin V and CD62p (see page 37, right column).
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 methods taught by Vitale et al. and measure both Annexin V and CD62p expression on the platelets. One would have been motivated to do so and there would have been a reasonable expectation of success given the teachings of Mordakhanova et al. and Maličev that both Annexin V and CD62p are markers for activated platelets and given the fact that Vitale et al. was able to measure each marker individually.
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
For claim 9, Vitale et al. and Mordakhanova et al. teach that HIT is caused by antibodies that recognize complexes of platelet factor 4 and heparin (Mordakhanova et al.) and that platelet activation appears to be linked with the production of antibodies specific for heparin:platelet factor-4 (PF-4) complexes (Vitale et al.).
Thus, during the incubation stage of the method of Vitale et al. where platelets from normal donors were incubated with heparin (1 U/ml) and the serum from the patients, it would be obvious for one of ordinary skill in the art to also include PF4 so that any antibodies present in the patient’s serum would recognize and bind to any heparin:PF-4 complexes and activate the donor platelets. One would have been motivated to do so and there would have been a reasonable expectation of success given the teachings of Vitale et al. and Mordakhanova et al. regarding the presence and role of PF4 in platelet activation.
For claim 13, the flow cytometry assay of Vitale et al. was sufficient to determine if plasma samples were positive when the percentage of Annexin V or CD62p-positive cells exceeded the mean of negative controls + 2 SD. Thus, determining other expressions of positive samples (e.g., ≥10% of cells express both markers) is routine experimentation. Further, applicant has not demonstrated unexpected results for the claimed expression level.
Furthermore, according to section 2144.05 of the MPEP, “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”)
Claim(s) 3-6 are rejected under 35 U.S.C. 103 as being unpatentable over Vitale et al. (Cytometry (Communications in Clinical Cytometry), 2001, 46:290–295; cited by applicant), Mordakhanova et al. (Int. J. Mol. Sci., 2020, 21:2556) and Maličev (Transfusion Medicine Reviews, 2020, 34:34–41; cited by applicant) as applied to claims 1, 9, 12 and 13 above, and further in view of Greinacher et al. (New England Journal of Medicine, April 9, 2021, 384:2092-2101; cited by applicant).
The instant claims are directed to the method of claim 1, wherein the subject has been administered a vaccine, wherein said Mpost is greater than Mpre and wherein the difference is elicited by the vaccine.
The teachings of Vitale et al., Mordakhanova et al. and Maličev are outline above and incorporated herein. Vitale et al., Mordakhanova et al. and Maličev do not teach that a vaccine is administered and that Mpost is greater than Mpre due to the vaccine.
Greinacher et al. teaches that several cases of unusual thrombotic events and thrombocytopenia developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19).
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 Vitale et al. to determine the presence of activated platelets in patients who had been administered a SARS-CoV-2 vaccine (e.g., ChAdOx1 nCov-19). One would have been motivated to do so given the teachings of Greinacher et al. [several cases of unusual thrombotic events and thrombocytopenia developed after vaccination with ChAdOx1 nCov-19]. There would have been a reasonable expectation of success in performing the test given the teachings and findings of Vitale et al. regarding platelet activation and thrombocytopenia.
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Vitale et al. (Cytometry (Communications in Clinical Cytometry), 2001, 46:290–295; cited by applicant), Mordakhanova et al. (Int. J. Mol. Sci., 2020, 21:2556) and Maličev (Transfusion Medicine Reviews, 2020, 34:34–41; cited by applicant) as applied to claims 1, 9, 12 and 13 above, and further in view of Minet et al. (Molecules, 2017, 22: 617).
The instant claims are directed to the method of claim 1, wherein said thrombocytes of step (ii) are provided as washed thrombocytes.
The teachings of Vitale et al., Mordakhanova et al. and Maličev are outline above and incorporated herein. Vitale et al., Mordakhanova et al. and Maličev do not teach that the thrombocytes of step (ii) are provided as washed thrombocytes.
Minet et al. teaches that washed platelet-based assays are considered more sensitive and possibly more specific than PRP or whole blood-based assay tests for the following reasons: (i) the wash step eliminates possible interfering substances potentially causing heparin independent aggregation such as IgG or acute-phase proteins (e.g., fibrinogen); (ii) the high centrifugation during washing may induce platelet granule release of PF4 with greater formation of PF4/heparin antigen complexes; (iii) the use of apyrase prevents platelets from becoming refractory to subsequent ADP-mediated potentiation of HIT-antibody-induced activation; and (iv) the physiological calcium concentrations induce optimal IgG-mediated platelet activation (see page 6).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use washed platelets in the method taught by Vitale et al. One would have been motivated to do so and there would have been a reasonable expectation of success given the teachings of Minet et al. outlined above.
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nicole Kinsey White whose telephone number is (571)272-9943. The examiner can normally be reached M to Th 6:30 am to 6:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas Visone can be reached at 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NICOLE KINSEY WHITE/Primary Examiner, Art Unit 1672
Prosecution Insights