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 .
Status of Claims
Claims 3, 6, and 9 are cancelled.
Claims 1, 2, 4, 5, 7, and 8 are pending and examined herein.
Withdrawn Rejections
The rejections of claims 1-9 on the grounds of 35 U.S.C. 102(a)(1) have been withdrawn, necessitated by amendments filed 07/16/2025.
New rejections, necessitated by amendments filed 07/16/2025, are discussed below.
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 1, 2, 4, 5, 7, and 8 are newly rejected under 35 U.S.C. 103 as being unpatentable over Kjeld, et al. (cited in IDS filed 02/14/2023) in view of Klug, et al. (cited in IDS filed 02/14/2023) and Al-Dujaili, et al. (cited in IDS filed 02/14/2023) and evidenced by Puah, et al. (“MEASUREMENT OF UNCONJUGATED TESTOSTERONE, 5α-DIHYDROTESTOSTERONE AND OESTRADIOL IN HUMAN URINE”, published 1977) and Cox, et al. (“Immunoassay Methods”, published 2012), necessitated by amendments filed 07/16/2025.
Note: in a previous office action filed 04/18/2025, the office erroneously referred to the reference of Puah as “Pua”. The reference will be correctly attributed to Puah in this office action.
Kjeld teaches a method for measuring a steroid (i.e. testosterone) in a urine sample, comprising: an acid treatment step of mixing and reacting an acid solution with a urine sample such that a normality of acid becomes between 0.6 to 4 N to obtain an acid-treated solution, wherein a reaction time in the acid treatment step is 1 to 60 minutes; a neutralization treatment step of mixing and reacting the acid-treated solution and a neutralizing solution to obtain a neutralization-treated solution; and a measurement step of mixing the neutralization-treated solution and an antibody capable of specifically binding to a steroid to measure the steroid, as in claim 1 (see, e.g., acid treatment step – p. 236, under “1. Acid hydrolysis”, para. 1, and p. 238, under “Fig. 1”; reaction time - p. 240, under “Fig. 4”, first time point; neutralization-treatment step and measurement step – p. 237, under “Radioimmunoassay of T”: “The T-assay has been described already [8]”). It is understood that 1 M sulfuric acid is equivalent to 2 N sulfuric acid, and the dilution with the urine sample would decrease the acid normality by a factor of 2. It is understood that at least the first time point of “Fig. 4” of Kjeld has the acid-treatment step between 1 to 60 minutes. The “T-assay” referenced in Kjeld was described in Kjeld’s reference [8], Puah (cited above). Puah gives evidence that the testosterone assay of Kjeld includes a neutralization-treatment step and a measurement step, as in claim 1 (see, e.g., Puah, p. 275, under “Assay procedure”, para. 1). Puah gives evidence that the working buffer of Kjeld is equivalent to a neutralization-treatment solution. The buffer of Kjeld is a neutralization-treatment solution that increases the pH because K2HPO4 is a basic substance (see, e.g., Puah, p. 273, under “Buffers”). Puah gives evidence that the measurement steps of Kjeld include specific-binding antibodies, as in claim 1 (see, e.g., Puah, p. 275, under “Assay procedure”, para. 3-4). Kjeld teaches the pH of the acid-treated solution at 37°C is 1.0 to 6.0, as in claim 2 (see, e.g., p. 240, under “Fig. 3”; and p. 239, under “3. Effects of hydrochloric acid”). Kjeld teaches wherein a normality of acid of the acid solution is 1 to 6 N, as in claim 4 (see, e.g., p. 236, under “1. Acid hydrolysis”, para. 1, and p. 239, under “Fig. 2”). Kjeld teaches the pH of the neutralization-treated solution at 25°C is 7.4, as in claim 5 (see, e.g., p. 237, under “Radioimmunoassay of T”: “The T-assay has been described already [8].”). The “T-assay” referenced in Kjeld was described in Puah (cited above), which disclosed the testosterone assay (see, e.g., Puah, p. 275, under “Assay procedure”, para. 1). Puah gives evidence that the working buffer of Kjeld is equivalent to a neutralization-treatment solution. The buffer of Kjeld is a neutralization-treatment solution that increases the pH because K2HPO4 is a basic substance, as in claim 5 (see, e.g., Puah, p. 273, under “Buffers”). It is understood that 25°C is room temperature and is assumed unless stated otherwise. Kjeld teaches wherein the pKa of the neutralizing solution at 20°C is 7.2, as in claim 7 (see, e.g., p. 237, under “Radioimmunoassay of T”: “The T-assay has been described already [8].”). The “T-assay” referenced in Kjeld was described in Puah (cited above), which gives evidence that the working buffer of Kjeld is equivalent to a neutralization-treatment solution (see, e.g., Puah, p. 273, under “Buffers”). The working buffer described has a pKa of 7.2 based on the office’s calculation using the Henderson-Hasselbalch equation. Kjeld teaches an acid solution having a normality of acid of 1 to 6 N, a neutralizing solution, and an antibody capable of specifically binding to a steroid, as in claim 8 (see, e.g., acid solution - p. 236, under “1. Acid hydrolysis”, para. 1, and p. 239, under “Fig. 2”; neutralizing solution and specifically binding antibody - p. 237, under “Radioimmunoassay of T”: “The T-assay has been described already [8].”). The “T-assay” referenced in Kjeld was described in Puah (cited above) and discloses the method of the testosterone assay (see, e.g., Puah, p. 275, under “Assay procedure”, para. 1). Puah gives evidence that the working buffer of Kjeld is equivalent to a neutralization-treatment solution. The buffer of Kjeld is a neutralization-treatment solution that increases the pH because K2HPO4 is a basic substance, as in claim 8 (see, e.g., Puah, p. 273, under “Buffers”). The measurement steps including the specific-binding antibodies are disclosed (see, e.g., Puah, p. 275, under “Assay procedure”, para. 3-4).
Kjeld fails to teach the neutralizing solution comprises a Tris buffer agent, as in claims 1 and 8. Kjeld fails to teach the steroid is aldosterone, as in claims 1 and 8.
However, in journal articles on steroid measurements, Klug and Al-Dujaili rectify these deficiencies. Klug teaches the use of a Tris buffer as a neutralizing solution after treating a urine sample with an acidic deconjugation diluent (or acid-treating solution), as in claims 1 and 8 (see, e.g., p. 250, col. 1, para. 4).
Al-Dujaili teaches measuring aldosterone with an acid treatment step and a neutralization step, as in claims 1 and 8 (see, e.g., p. 281, para. 4, under “(b) Direct assay protocol.”).
Kjeld, Al-Dujaili, and Klug teach all the components after the word “comprising”. Thus, they render obvious the kit even though they do not explicitly recite the word “kit”, as in claim 8.
Kjeld, Klug, and Al-Dujaili are analogous to the field of the claimed invention because they are all in the field of steroid measurements. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to substitute the neutralization buffer of Klug into the assay of Kjeld because they are identified as functional equivalents. Klug identifies the tris-buffer as a “neutralization buffer” after the urine sample has been added to an acidic deconjugation diluent (see, e.g., p. 250, col. 1, para. 4). Tris-buffers are more commonly used than phosphate buffers as neutralization buffers, as evidenced by Cox (see, e.g., p. 12, under “Reagents and basic concepts”). In addition, one of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the assay of Kjeld to detect aldosterone, such as taught by Al-Dujaili. An artisan would be motivated to do so because Al-Dujaili discloses an aldosterone assay with an acid-treatment step of 24 hours while the assay of Kjeld is substantially faster (see, e.g., Kjeld, p. 281, para. 4, under “(b) Direct assay protocol.”). Using the assay of Kjeld to detect aldosterone, such as taught by Al-Dujaili, would be beneficial because the aldosterone assay would be performed in less time. An artisan would have a reasonable expectation of success based on the given disclosures.
Response to Arguments
The applicant states that none of the asserted references teach the method of claim 1. The amendments filed 7/26/2025 necessitated a new rejection to claim 1 on the grounds of 35 U.S.C. 103; the new rejection is stated above.
The applicant states that it is novel and unexpected for a method measuring a steroid in urine including an acid pretreatment step with such a high normality would result in disassembly of the steroid. However, Kjeld (cited above) teaches that decreasing the pH leads to an increase in testosterone release in urine (see, e.g., p. 240, under “Fig. 3”). Therefore, the method is not novel or unexpected.
The applicant states that Kjeld and Puah do not teach the specific neutralizing solution or that the reaction time in the acid treatment step is 1 to 60 minutes. While the office agrees that the specific neutralizing solution in amended claims 1 and 8 is not taught by Kjeld and Puah, a new 35 U.S.C. 103 rejection discussed above, necessitated by amendment, provides disclosure and motivation for substituting the neutralizing solution of Kjeld and Puah with the specific neutralizing solution of claims 1 and 8. Also, as discussed above, Kjeld does teach an acid treatment step of 1 to 60 minutes (see, e.g., p. 240, under “Fig. 4”, first time point).
The applicant is correct when they state that Kjeld and Puah do not teach aldosterone. However, a new 35 U.S.C. 103 rejection discussed above, necessitated by amendment, provides disclosure and motivation for substituting the steroid Kjeld with aldosterone.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/MICHAEL CAMERON SVEIVEN/Examiner, Art Unit 1678
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 October 22, 2025
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