DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 17 November 2025 has been entered.
Claims 1, 11, 22, 23 have been amended. Claims 27 and 28 are newly added. Claims 12 and 25 have been cancelled. Claims 1, 3, 4, 7-11, 14-16, 19-24, and 26-28 are currently pending and under examination.
This application is a Divisional Application of U.S. Application No. 15/491152, filed April 19, 2017, now U.S. Patent No. 10,935,560, which claims benefit of priority to U.S. Provisional Application No. 62/327028, filed April 25, 2016.
Withdrawal of Rejections:
The rejection of claims 1, 3, 4, 7-12, 14-16, and 19-21 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, is withdrawn.
New/Modified Rejections:
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.
Claim 27 is 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 27 recites in relevant part “wherein the coagulation inhibitor comprises” (emphasis added). This limitation is indefinite, because independent claim 1, from which this claim depends, requires at least two inhibitors. As such, it is unclear which coagulation inhibitor is being referred to here.
Claim Rejections - 35 USC § 103
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.
Claims 22-24, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Greenfield et al. (IDS; US 7,932,021; Published 2011), as evidenced by Okuda et al. (US 2004/0197837; Published 2004 – Previously Presented).
With regard to claims 22-24, Greenfield et al. teach a kit for detecting lupus anticoagulant in a sample (Abs). The kit including a phospholipid-dependent clotting reagent comprising a first concentration of phospholipid; coagulation inhibitors (anticoagulants) including argatroban and hirudin, which together with the first phospholipid-dependent clotting reagent, are necessarily capable of causing a first part of the sample that is coagulation-inhibited to clot in a first clotting time; a second phospholipid-dependent clotting reagent comprising a higher concentration of phospholipid (Abs.; Col. 4, Line 60 to Col. 5, Line 59; Col. 6, Line 9-23; Col. 12, Line 10-20; Col. 16, line 60-62), which is necessarily capable of causing a second part of the sample that is coagulation-inhibited to clot in a second clotting time.
Greenfield et al. further teach that the first and/or second phospholipid-dependent clotting reagent comprises APTT and dRVVT (Col. 4, Line 4-25). A known technique for judging whether a blood sample is lupus anticoagulant positive or not, is done by using an APTT reagent, which is a combination of two kinds of reagents having different concentrations of phospholipid from each other, and by calculating Rosner Index or Lupus Ratio (LR) based on the coagulation times respectively obtained with use of the two kinds of reagents (see Okuda et al.). Thus, the kit of Greenfield, which includes APTT, would be usable to determine a ratio.
Greenfield et al. render obvious the kit as claimed, including the components as claimed. As the components in the kit cannot be separated from their properties, the kit of Greenfield is necessarily capable of detecting lupus anticoagulant in a sample that is coagulation-inhibited. Further, as argatroban and hirudin are expressly claimed coagulation inhibitors (see claim 22), argatroban and hirudin as taught by Greenfield et al. are necessarily a coagulation inhibitor for causing a first part of the sample that is coagulation-inhibited to clot in a first clotting time. Likewise, as APTT and dRVVT are expressly claimed as a first and/or second phospholipid-dependent clotting reagent (see claims 23, 24), APTT and dRVVT as taught by Greenfield et al. are necessarily a second phospholipid-dependent clotting reagent for causing a second part of the sample that is coagulation-inhibited to clot in a second clotting time.
With regard to claim 26, Greenfield et al. teach that the first phospholipid has about a 50 µg/ml (0.05 g/l) phospholipid concentration, which is encompassed within about 0.002 to about 0.2 g/l; and the second phospholipid has at least about a 1 mg/ml (1 g/l) phospholipid concentration, which is encompassed within about 0.2 to about 5.0 g/l (Col. 16, Line 60-62).
Claims 1, 3, 4, 8-11, 14-16, 20, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Greenfield et al. (IDS; US 7,932,021; Published 2011), in view of Zhang et al. (A Simplified Algorithm for the Laboratory Detection of Lupus Anticoagulants, Coagulation and Transfusion Medicine, American Society for Clinical Pathology, Vol. 124, (2005), pp. 894-901 – Previously Presented), as evidenced by George King Bio-Medical Inc. (Pooled Normal Plasma, Product No. 0010-1, Accessed 1/3/2025, Available online at: kingbiomed.com/product/pooled-normal-plasma/ - Previously Presented), and as evidenced by Okuda et al. (US 2004/0197837; Published 2004 – Previously Presented).
With regard to claims 1, 3, 4, and 16, Greenfield et al. teach a kit for detecting lupus anticoagulant in a sample (Abs). The kit including a phospholipid-dependent clotting reagent comprising a first concentration of phospholipid; coagulation inhibitors (anticoagulants), which together with the first phospholipid-dependent clotting reagent, are necessarily capable of causing the sample to clot in a first clotting time; a second phospholipid-dependent clotting reagent comprising a higher concentration of phospholipid (Abs.; Col. 4, Line 60 to Col. 5, Line 59; Col. 6, Line 9-23; Col. 12, Line 14-20; Col. 16, line 60-62), which is necessarily capable of causing the sample to clot in a second clotting time; and pooled plasma derived from control subjects (Col. 4, Line 20; Col. 11, Line 50-61).
Greenfield teaches that “anticoagulants” (plural), including argatroban and hirudin, are useful in the taught methods and kits (Col. 12, Line 10-18). As such, it would have been obvious to one of ordinary skill in the art to include more than one anticoagulant in the kit, including argatroban and hirudin, which is at least a combination of at least two different coagulation inhibitors, to provide multiple options for the end user to utilize as appropriate for the subject the kit is being used for.
Greenfield et al. further teach that the first and/or second phospholipid-dependent clotting reagent comprises APTT and dRVVT (Col. 4, Line 4-25). A known technique for judging whether a blood sample is lupus anticoagulant positive or not, is done by using an APTT reagent, which is a combination of two kinds of reagents having different concentrations of phospholipid from each other, and by calculating Rosner Index or Lupus Ratio (LR) based on the coagulation times respectively obtained with use of the two kinds of reagents (see Okuda et al.). Thus, the kit of Greenfield, which includes APTT, would be usable to determine a ratio.
As argatroban and hirudin are expressly claimed coagulation inhibitors (see claim 1), argatroban and hirudin as taught by Greenfield et al. are necessarily a coagulation inhibitor for causing a first part of the sample that is coagulation-inhibited to clot in a first clotting time. Likewise, as APTT and dRVVT are expressly claimed as a first and/or second phospholipid-dependent clotting reagent (see claims 3, 4), APTT and dRVVT as taught by Greenfield et al. are necessarily a second phospholipid-dependent clotting reagent for causing a second part of the sample that is coagulation-inhibited to clot in a second clotting time.
Greenfield et al. do not specifically teach that the normal pooled plasma is platelet poor plasma present in sufficient quantity to dilute the sample plasma by a ratio of 1:1, 1:2, 1:3, or 1:4.
Zhang et al. teach that testing for lupus anticoagulants utilizes APTT and dRVVT reagents, and includes the need to mix normal pooled plasma in a 1:1 ratio with the test plasma (Fig. 1; p. 896, Left Col., Interpretation, para. 1), wherein the normal pooled plasma utilized (George King Normal Poled Plasma, catalog No. 0010-1) is platelet poor plasma (see George King Bio-Medical Inc., p. 2, Product Information: Normal Factor Activity).
It would have been obvious to one of ordinary skill in the art to combine the teachings of Greenfield et al. and Zhang et al., because both teach testing for lupus anticoagulants, including utilizing APTT and dRVVT reagents, where normal pooled plasma is utilized for testing. Normal pooled plasma being platelet poor, and being present in sufficient quantity to be mixed in a 1:1 ratio with a test sample plasma, is known in the art as taught by Zhang et al. The normal pooled plasma of Greenfield et al. being platelet-poor plasma as taught by Zhang et al. amounts to the simple substitution of one known type of normal pooled plasma used in lupus anticoagulant testing for another, and would have been expected to predictably and successfully provide normal pooled plasma usable in the kit of Greenfield et al. for lupus anticoagulant testing. Additionally, one would have been motivated to provide the normal platelet-poor pooled plasma in sufficient quantity for use in testing for lupus anticoagulants utilizing APTT and dRVVT reagents in the kit of Greenfield et al. As Zhang et al. teach that a 1:1 ratio of normal platelet-poor pooled plasma to the test sample is a sufficient amount of normal platelet-poor pooled plasma, it would have been obvious to one of ordinary skill in the art to likewise provide an amount of normal platelet-poor pooled plasma sufficient to provide a 1:1 ratio of normal platelet-poor pooled plasma to the test sample in the kit of Greenfield et al.
It is noted that the claims as currently presented are directed to a kit for detecting lupus anticoagulant in a sample, and not to a method of detecting lupus anticoagulant, such as by determining differences in first and second clotting times to provide a ratio. As such, to meet the limitations of the claims, the components of the kit must be present or obviously present. The intended use of those components does not change the components of the kit structurally or functionally.
Taken together, Greenfield et al. and Zhang et al. render obvious the kit as claimed, including the components as claimed. As the components in the kit cannot be separated from their properties, the kit of Greenfield and Zhang et al. is necessarily capable of detecting lupus anticoagulant in a sample that is coagulation-inhibited, including a first and second part of the samples being coagulation-inhibited.
With regard to claims 8-10, 14, and 15, Greenfield et al. teach that with regard to packaging of the kit, the components can all be mixed together in any combination in one or more containers (Col. 15, Line 42-44), which encompasses packaging the first phospholipid-dependent clotting reagent, the portion of, or at least one of, the coagulation inhibitors, the second phospholipid-dependent clotting reagent, and the platelet-poor plasma, in the same container.
With regard to claims 11, 20, and 21, Greenfield et al. teach that the second phospholipid has at least about a 1 mg/ml (1 g/l) phospholipid concentration, which is encompassed within about 0.2 to about 5.0 g/l, 0.5 g/l to 3 g/l, or 1.0 g/l to 2.0 g/l; and the first phospholipid has about a 50 µg/ml (0.05 g/l) phospholipid concentration, which is encompassed within about 0.002 to about 0.2, 0.002 g/l to 0.15 g/l, 0.01 to 0.1 g/l, or 0.04 g/l to 0.08 g/l (Col. 16, Line 60-62).
Claims 1, 4, 7, 16, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Greenfield et al., in view of Zhang et al., as evidenced by Okuda et al. and George King Bio-Medical Inc., as applied to claims 1, 4, and 16 above, and further in view of Mani et al. (IDS; Ex vivo effects of low-dose rivaroxaban on specific coagulation assays and coagulation factor activities in patients under real life conditions, Thrombosis and Haemostasis, Vol. 109, No. 1 (2012), pp. 127-136).
The teachings of Greenfield et al. and Zhang et al. as applied to claims 1, 4, and 16 have been set forth above.
With regard to claims 7 and 19, Greenfield et al. further teach that it is desirable to control for the effect of coagulation inhibitors, including the thrombin inhibitors argatroban and hirudin, which interfere with results of lupus anticoagulant testing (Col. 12, Line 4-20). Greenfield et al. and Zhang et al. do not specifically teach that the coagulation inhibitors tested include factor Xa inhibitors including rivaroxaban, apixaban, edoxaban, betrixaban, antistasin, TAP, and combinations thereof.
Mani et al. teach a method and components for detecting lupus anticoagulants associated with antiphospholipid syndrome in a patient, where the aim of the study is to determine the effects of rivaroxaban on screening assays (Abs.; p. 131, Left Col., Lupus anticoagulants).
It would have been obvious to one of ordinary skill in the art to combine the teachings of Greenfield et al. and Zhang et al. with Mani et al., because all teach components and a method for detecting lupus anticoagulants associated with antiphospholipid syndrome in a patient. The assessment of coagulation inhibitors, including the factor Xa inhibitor rivaroxaban, to determine the effect on screening assays, is known in the art as taught by Mani et al. The inclusion of an additional coagulation inhibitor, including rivaroxaban, would be expected to predictably improve the kit of Greenfield et al. and Zhang et al., by allowing for testing of a broader range of coagulation inhibitors, thus rendering the kit more efficient and cost effective.
Claims 22 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Greenfield et al., as evidenced by Okuda et al., as applied to claim 22 above, and further in view of Filip et al. (US 2011/0065807; Published 2011).
The teachings of Greenfield et al. as applied 22 have been set forth above.
With regard to claim 28, while Greenfield et al. teach anticoagulants including argatroban and hirudin (Col. 12, line 14-18), it is not specifically taught that the anticoagulants include PPACK and/or I-2581.
Filip et al. teach that anticoagulants include direct thrombin inhibitors including hirudin, agatroban, and PPACK (Para. 198, line 18-20).
It would have been obvious to one of ordinary skill in the art to combine the teachings of Greenfield et al. and Filip et al., because both teach anticoagulants, including argatroban and hirudin. It is known in the art as taught by Filip et al. that direct thrombin inhibitor anticoagulants include hirudin, agatroban, and PPACK. The substitution of PPACK for either hirudin or agatroban amounts to the simple substitution of one known direct thrombin inhibitor anticoagulant for another, and would have been expected to predictably and successfully provide a direct thrombin inhibitor anticoagulant in the method of Greenfield et al.
Claims 1 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Greenfield et al., in view of Zhang et al., as evidenced by Okuda et al. and George King Bio-Medical Inc., as applied to claim 1 above, and further in view of Filip et al. (US 2011/0065807; Published 2011).
The teachings of Greenfield et al. and Zhang et al. as applied 1 have been set forth above.
With regard to claim 27, while Greenfield et al. teach anticoagulants including argatroban and hirudin (Col. 12, line 14-18), it is not specifically taught that the anticoagulants include PPACK and/or I-2581.
Filip et al. teach that anticoagulants include direct thrombin inhibitors including hirudin, agatroban, and PPACK (Para. 198, line 18-20).
It would have been obvious to one of ordinary skill in the art to combine the teachings of Greenfield et al. and Zhang et al. with Filip et al., because Greenfield et al. and Filip et al. teach anticoagulants, including argatroban and hirudin. It is known in the art as taught by Filip et al. that direct thrombin inhibitor anticoagulants include hirudin, agatroban, and PPACK. The substitution of PPACK for either hirudin or agatroban amounts to the simple substitution of one known direct thrombin inhibitor anticoagulant for another, and would have been expected to predictably and successfully provide a direct thrombin inhibitor anticoagulant in the method of Greenfield et al. and Zhang et al.
Response to Arguments
Applicant urges that Greenfield does not teach that the kit is for use with a sample that is coagulation-inhibited; or coagulation inhibitors, the first phospholipid-dependent clotting reagent and the coagulation inhibitors for causing a first part of the sample that is coagulation-inhibited to clot in a first clotting time. Additionally, Greenfield teaches that its plasma sample is anticoagulated before the method of detecting is performed, while the coagulation inhibitors in the kit as claimed are applied to a sample that is already coagulation-inhibited to clot in a first clotting time.
Applicant’s arguments have been fully considered, but have not been found persuasive.
With regard to Applicant’s arguments, it is noted that the current claims are directed to a kit, and not to a method of using the kit. "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present (see MPEP 2112.01).
Here, as argatroban and hirudin are expressly claimed coagulation inhibitors (see claim 1, 22), argatroban and hirudin as taught by Greenfield et al. are necessarily a coagulation inhibitor for causing a first part of the sample that is coagulation-inhibited to clot in a first clotting time. Likewise, as APTT and dRVVT are expressly claimed as a first and/or second phospholipid-dependent clotting reagent (see claims 3, 4, 23, 24), APTT and dRVVT as taught by Greenfield et al. are necessarily a second phospholipid-dependent clotting reagent for causing a second part of the sample that is coagulation-inhibited to clot in a second clotting time.
As such, the argatroban, hirudin, APTT, and/or dRVVT in the kit of Greenfield are necessarily usable in a method for detecting lupus anticoagulant in a sample that is coagulation-inhibited.
Conclusion
No claims are allowable.
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/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653
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