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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11/10/2025 has been entered.
Response to Amendment
The Amendment filed 11/10/2025 in which no claims were amended is acknowledged. Claim 9 was previously canceled. Claims 10-14 were previously withdrawn.
Claims 1-8 are under examination on the merits.
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.
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.
Claims 1-3, 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over Hu et al. (previously cited), in view of Higgins “The use of heparin in preparing samples for blood gas analysis” published in April 2007, available online at https://acutecaretesting.org/en/articles/the-use-of-heparin-in-preparing-samples-for-blood-gas-analysis, accessed on 07/02/2026. See PTO-892: Notice of References Cited.
See claims 1-3, 6-8 as submitted on 11/10/2025.
Regarding claims 1 and 2, as previously explained, Hu et al. teaches assays for detecting, quantitating, and monitoring amounts of 5-fluorouracil (5-FU) in a sample such as in blood plasma (Abstract). Hu et al. further teaches an immunoassay reagent (Example 16, ¶ [0228]) comprising: one or more binding agent(s) or antigen(s) in a diluent containing lithium heparin (¶ [0235] "5-FU antigen in charcoal stripped lithium heparin human plasma"), wherein the lithium heparin is used in sufficient amounts to act as an anticoagulant (¶ [0263]) or in an amount sufficient to reduce non-specific binding in an assay. Hu et al. do not explicitly teach the amounts of lithium heparin in the diluent.
However, Higgins teaches the use of lithium heparin for preparing blood samples (page 1). Higgins further teaches that low concentration of heparin might not eliminate the clotting process within samples. Higgins writes “even concentrations as high as 150 IU/mL are insufficient” (page 5). It is noted that instant claims recite an optimal amount lithium heparin from about 0.25 mg/mL to about 4 mg/mL (equivalent to about 0.025% to about 0.4 %) (Specification, page 6) and 150 IU/mL of lithium heparin ≈ 150 USP/mL ≈ 1.0 mg/mL.
It would have been prima facie obvious to one of skill in the art to have combined the teachings of Hu et al. and Higgins to formulate an immunoassay reagent comprising enough lithium heparin to ensure anti-coagulation activity in an assay for Hepatitis C virus detection. Further, in view of the teachings of Hu et al. and Higgins, the amount of lithium heparin recited in instant claims is considered to be one determined by routine optimization in the absence of new or unexpected results according to one of skill in the art. See MPEP 2144.05. Optimization Within Prior Art Conditions or Through Routine Experimentation: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[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)).
One of ordinary skill in the art would have had reasonable expectation of success in formulating a diluent comprising lithium heparin in the amount range as encompassed by instant claims for the benefit of achieving anticoagulation given that the methods of preventing coagulation in a biological sample are well known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Regarding claim 3, it is noted that no amendments were introduced to claim 3 in the amendment filed on 11/10/2025. As previously explained, Hu et al. further teaches an immunoassay reagent (Example 16, ¶ [0228]) comprising: one or more binding agent(s) or antigen(s) (¶ [0235])
Regarding claims 6 and 7, it is noted that no amendments were introduced to claims 6 and 7 in the amendment filed on 11/10/2025. As previously explained, Hu et al. further teaches an immunoassay reagent further comprising horseradish peroxidase (HRP) as a conjugate reagent for detection of specific labeled molecules in an immunoassay (¶ [0118], [0169]).
Regarding claim 8, it is noted that no amendments were introduced to claim 8 in the amendment filed on 11/10/2025. As previously explained, Hu et al. further teaches an immunoassay reagent further comprising an anti-microbial agent, wherein the anti-microbial agent is ProClinTM 300 (¶ [0231]).
Accordingly, the limitations of claims 1-3, 6-8 would have been prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claims 4 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Hu et al., and Higgins as applied to claims 1-3, 6-8 above, in view of publication by D'Angelo RG, et al. (prior art of record).
See claims 4 and 5 as submitted on 11/10/2025.
Regarding claims 4 and 5, it is noted that no amendments were introduced to claims 4 and 5 in the amendment filed on 10/11/2025. As explained above, Hu et al. disclose an immunoassay reagent comprising a diluent, wherein the diluent comprises containing lithium heparin (¶ [0235] "5-FU antigen in charcoal stripped lithium heparin human plasma").
Hu et al. do not teach antigen is a Hepatitis C virus recombinant antigen selected from NS5, c22-3, c200, or a combination thereof.
However, D’Angelo et al. teach a recombinant immunoblot assays (RIBAs), which are used as follow-up tests for detecting anti-hepatitis C virus (HCV) immunoglobulins or antibodies lgGs in serum (page 14). D’Angelo et al. further teaches RIBAs for HCV include steps where synthetic and recombinant NS3, NS5, and core peptides are each impregnated onto a membrane in bands for detection of anti-HCV lgGs which become immobilized on these bands if present (page 16). D’Angelo et al. further teach the use of anticoagulants including lithium heparin in RIBAs (page 16).
It would have been prima facie obvious to one of skill in the art to have incorporated the immunoassay reagent as taught by Hu et al. and Higgins into the RIBAs taught by D’Angelo et al. for the benefit of preventing coagulation in an assay for Hepatitis C virus detection. See MPEP 2144.07. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945)
One of ordinary skill in the art would have had reasonable expectation of success in incorporating a diluent comprising lithium heparin in the RIBAs taught by D’Angelo et al. given that the methods of preventing coagulation in a biological sample used for antibody detection are well known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Accordingly, the limitations of claims 4 and 5 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 11/10/2025 have been fully considered but they are not persuasive.
Applicant contends on page 7 of the Remarks submitted on 11/10/2025:
It is clearer that Hu is not referring to any lithium heparin concentration where Hu states: "A calibrator range of 0.0-20,000 ng/mL 5-FU was used."7 This sentence provides clarity for the ambiguous language discussed above. It is evident that Hu is using 0, 50, 100, 250, 625, 2500, 10000, and 20000 ng/mL of 5-FU in this sentence. This is to prepare a 5-FU calibration curve, not a lithium heparin calibration curve. Hu is silent regarding lithium heparin concentrations.
In response:
The rejections to instant claims set forth in the present Office Action are based on a different combination of references than those from previous Office Actions. Even if the amounts taught by Hu et al. do not refer to the amount of lithium heparin, it was known in the art that higher amounts of lithium heparin are required to prevent coagulation in a biological sample. Further, the amount of lithium heparin as recited in instant claims is considered to be one determined by routine optimization in the absence of new or unexpected results according to one of skill in the art. See MPEP 2144.05. Optimization Within Prior Art Conditions or Through Routine Experimentation: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[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)).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARLENE V BUCKMASTER whose telephone number is (703)756-5371. The examiner can normally be reached M-R 8:00 AM - 5:00 PM.
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/MARLENE V BUCKMASTER/Examiner, Art Unit 1672
/NICOLE KINSEY WHITE/ Primary Examiner, Art Unit 1672
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