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 .
The Response of 4 Feb. 2026 has been entered.
Claims 1-16, 18-21 and 26-30 are currently pending.
Election/Restrictions
Applicant’s election without traverse of Group II, claims 8-11 and 26-29, and the species of: iron as the metal, raising tau constant as the parameter, and liquefied and capacitated sperm in the reply filed on 4 Feb. 2026 is acknowledged.
Claims 1-7, 12-16, 18-21, 25 and 30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 4 Feb. 2026.
No prior art was found with respect to the elected species of raising tau constant as the parameter, and thus the search has been extended to the additional species of peak area.
Claims 8-11 and 26-29 are considered here with respect to the species of iron, peak area and liquefied and capacitated sperm.
Claim Objections
Claim 27 is objected to because of the following informalities:
Claim 27 should be amended as follows: "… the spermatozoa is diluted .
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 8-11 and 26-29 are rejected under 35 U.S.C. 112(b) 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 8 and dependent claims recite the term "dynamic or kinetic parameter of a signal spike". The specification does not expressly define the term and a search of the prior art does not evidence common usage of the term in the ICP-MS-related art. As such, it is unclear what aspects of an ICP-MS signal (other than those set forth in claim 10) would fall under the scope of the claims.
Claims 10 and 11 recite specific parameters. The meanings of dwell time, peak time and area before/after the peak can be derived from Fig. 5 of the specification. However, the meaning of "tau constant" is not provided in the specification and a search of the relevant art does not evidence usage of the term in relation to the analysis of ICP-MS results. Rather, Craig et al., Journal of Analytical Atomic Spectrometry 35.5 (2020): 1011-1021, describes a "tau constant" as an inherent property of the faraday cup collector used in ICP-MS (p. 3, under Determination of tau constant for 1013 Ω amplifiers). Thus, the scope of the claims relating to measuring of a "tau constant" is unclear.
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 8, 9 and 26-29 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Aguiar et al., Journal of the Brazilian Chemical Society 23 (2012): 573-580 in view of each of Ammar et al., Environmental science and pollution research 26.14 (2019): 14097-14105 and US20170338092 to Stephan et al. (cited in IDS of 22 May 2025).
Regarding claims 8 and 29, Aguiar teaches a method of measuring the levels of metals including iron in semen using inductively coupled plasma mass spectrometry (ICP-MS) (p. 577, last ¶ to p. 579, last full ¶). Aguiar teaches that analysis of metals in semen is critical in the investigation of disorders that are related to the animal or male reproductive system, and that measuring metals in the reproductive cells and seminal fluid can determine semen quality and fertility success (p. 574, 1st full ¶). Aguiar further teaches that ICP-MS offers several advantages, including simultaneous multielement measurement capability coupled with very low limits of detection and a wider linear dynamic range (p. 574, 2nd full ¶).
Claims 8, 9 and 26-29 differ from Aguiar in that: the method is for detecting infertile sperm by detecting a dynamic or kinetic parameter of a signal spike that falls outside a predetermined range using single cell ICP-MS (sc-ICP-MS) (claim 8); the predetermined range is from a population of fertile subjects (claim 9); the spermatozoa is diluted to a concentration of 3x106 spermatozoa/ml or less prior to the detecting step (claim 26); the spermatozoa is diluted to 10 times or more prior to the detecting step (claim 27); and the spermatozoa is centrifuged to remove the seminal plasma prior to the dilution (claim 28).
Ammar teaches that excessive levels of iron in semen can produce reactive oxygen species (ROS) and oxidative stress that negatively affect sperm quality (i.e. fertility) (p. 4097-4098, under Introduction; p. 14100, under Results; p. 14102, 2nd and 3rd full ¶s). Ammar further teaches that subjects having impaired fertility had significantly higher levels of iron and ROS/lipid peroxidation (indicators of oxidative stress) than normal subjects (p. 14100, under Results; p. 14102, 2nd and 3rd full ¶s).
Stephan teaches methods for measuring metal levels in single cells, including sperm, using sc-ICP-MS ([0019]-[0021]; [0087]-[0089]; Examples 6-8). Stephan teaches that standard ICP-MS methods determine metal levels in a population of cells as a whole whereas individual cells can accumulate metals at varying rates, and sc-ICP-MS has the advantage of allowing for a determination of analyte levels in individual cells and the variance between cells (Example 7).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to use ICP-MS to measure levels of metals including iron in sperm to assess sperm quality as taught by Aguiar wherein the method detects infertile sperm by measuring iron levels outside of a range of normal subjects as taught by Ammar and the ICP-MS detection is sc-ICP-MS as taught by Stephan because it would have been obvious to combine prior art elements according to known methods to yield predictable results. One of ordinary skill would have been motivated to use the method of Aguiar to detect infertile sperm by measuring iron levels outside of a normal range because Aguiar teaches that measuring metals in reproductive cells can determine semen quality and fertility, and Ammar teaches that iron can produce ROS and oxidative stress that negatively affects sperm fertility. One of ordinary skill would have been further motivated to use sc-ICP-MS because individual cells can uptake metals at varying levels and sc-ICP-MS has the advantage of allowing for a determination of analyte levels in individual cells. Using the method of Aguiar to detect infertile sperm by measuring iron levels outside of a normal range would have led to predictable results with a reasonable expectation of success because Ammar teaches that high iron levels are associated with sperm infertility, and Aguiar teaches use of ICP-MS to measure iron in semen samples. Using sc-ICP-MS to measure iron levels in sperm would have led to predictable results with a reasonable expectation of success because Stephan teaches that sc-ICP-MS can be used to measure metals in any type of mammalian cells including sperm cells.
Regarding the recitation in claim 8 of "detecting a dynamic or kinetic parameter of a signal spike", the term "dynamic or kinetic parameter" is not expressly defined in the specification but it is described as including an area under the curve/spike (see Spec., Fig. 5; claim 10). Stephan teaches that metal amounts (mass) can be measured by detecting/calculating the area under the spike (Stephan, Example 8 and Fig. 30), and it would have been obvious to use such analysis in the method of the cited combination.
Regarding claims 26-28, Stephan teaches preparing cells for sc-ICP-MS analysis by centrifuging to pellet the cells and resuspending the cells in a desired buffer (i.e. washing) followed by dilution to 1 x 106 cells/ml ([0114]), and it would have been obvious to use the same methodology in the method of the cited combination (which would remove seminal plasma). Regarding claim 27, one of ordinary skill would have recognized that the cells could be diluted to any extent necessary to reach a desired concentration. One would have had a reasonable expectation of success because Stephan teaches a final concentration (1 x 106 cells/ml) within the same range set forth in the instant specification (e.g., US20240230630, [0163]).
Regarding claim 29, Aguiar and Ammar teach use of semen samples and it would have been obvious to obtain sperm for sc-ICP-MS from such a semen sample. The various preparations of the sample (fixed, capacitated, cryopreserved, etc.) recited in claim 29 are optional.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT J YAMASAKI whose telephone number is (571)270-5467. The examiner can normally be reached M-F 930-6 PST.
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/ROBERT J YAMASAKI/Primary Examiner, Art Unit 1657