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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Inventorship
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 Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 7 and 13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exceptions comprising abstract ideas and a natural correlation without significantly more. The claim(s) recite(s) making mental comparisons of a prostate-specific antigen (PSA) level in serum of a subject to a first threshold value and an α1-antitrypsin (AAT) level in urine of the subject to a second threshold value, and correlating the comparisons to whether the subject has developed prostate cancer or is suspected to have developed prostate cancer. These judicial exceptions are not integrated into a practical application because the claims do not apply or use the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment or field of use (i.e. disease diagnosis). The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional step in the method of standardizing the ATT level in urine with a creatinine internal standard constitutes a “well understood, routine and conventional activity” under 35 USC 101.
When considering the claims under the 2019 Revised Patent Subject Matter Eligibility Guidance (January 2019), it is noted that the claims meet step 1 of the guidance since the claims are directed to one of the statutory categories of invention (i.e. are directed to a process). The claims meet prong one of revised step 2A since the claims recite making mental comparisons of a prostate-specific antigen (PSA) level in serum of a subject to a first threshold value and an α1-antitrypsin (AAT) level in urine of the subject to a second threshold value, which are abstract ideas, and also recite a natural phenomenon or correlation between the measured levels of PSA and AAT in the serum and urine with a presence or a suspected presence of prostate cancer in a subject. The comparisons in the claims are abstract ideas in that they can be performed in the human mind. See (MPEP 2106.04(a)(2) III) where it states “In contrast, claims do recite a mental process when they contain limitations that can practically be performed in the human mind, including for example, observations, evaluations, judgments, and opinions. Examples of claims that recite mental processes include: a claim to collecting and comparing known information (claim 1), which are steps that can be practically performed in the human mind, Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1067, 100 USPQ2d 1492, 1500 (Fed. Cir. 2011)”. Additionally, the Examiner notes that even if the claims recited performing the mental analysis steps using a computer or processor, this would also not make the claims patent eligible under 35 US C 101 since performing a mental process on a generic computer, or using a generic computer as a tool to perform a mental process or calculation represents abstract ideas when the computer is presented at a high level of generality. See MPEP 2106.04(a)(2) III and MPEP 2106.04(a)(2)(C).
The claims do not meet prong two of revised step 2A since the claims do not recite additional elements that integrate the judicial exception into a practical application, such as an improvement in the functioning of a computer or other technology, effecting a particular treatment or prophylaxis for a disease or medical condition, implementing the judicial exception with a particular machine or manufacture that is integral to the claim, effecting a transformation or reduction of a particular article to a different state or thing, or applying the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception. The steps of comparing a PSA level in serum to a first threshold value and an AAT level in urine to a second threshold value, and then determining whether a subject has or is suspected of having prostate cancer when the PSA level in serum is more than the first threshold value and the AAT level in urine is more than the second threshold value both constitute judicial exceptions themselves (i.e. abstract ideas and a natural correlation). Nothing else is done after these steps are performed in the method that constitutes a practical application of the judicial exceptions. With regards to claims 1,7 and 13, the standardization of the AAT level in urine with creatinine as an internal standard substance is not a practical application of the judicial exceptions because this step amounts to extra-solution activity that is well-known and is only nominally or tangentially related to the invention. The standardization of analyte levels measured in urine with creatinine as an internal standard is well-known in the prior art to compensate for different volumes of urine analyzed since creatinine is always present in urine at a constant concentration. With regards to claims 1, 7 and 13, the recitation of the specific first and second threshold values for PSA in serum and AAT in urine does not amount to a practical application of the judicial exceptions because comparing measured levels of analytes in a diagnostic procedure to established threshold levels is commonly performed by a doctor or medical professional in order to assess the meaning of the analyte levels and make a diagnosis. In addition, the comparison of the measured PSA and AAT levels to the first and second threshold values in the methods recited in claims 1, 7 and 13 is a part of the natural correlation itself rather than additional steps to the natural correlation which may provide a practical application of the natural correlation. Therefore, this comparison step to first and second threshold values in claims 1, 7 and 13 does not provide an improvement to a technology because according to MPEP 2106.05(a), “It is important to note, the judicial exception alone cannot provide the improvement. The improvement can be provided by one or more additional elements.”
The claims also do not meet step 2B of the guidance since the elements recited in the claims that are in addition to the mental comparison steps and the natural phenomenon of correlating the comparisons to a presence or suspected presence of prostate cancer in a subject are well-understood, routine and conventional activities rather than additional steps that provide an inventive concept to confer patent eligibility under 35 USC 101. According to MPEP 2106.05, “An inventive concept "cannot be furnished by the unpatentable law of nature (or natural phenomenon or abstract idea) itself." Genetic Techs. Ltd. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016). See also Alice Corp., 573 U.S. at 21-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 78, 101 USPQ2d at 1968 (after determining that a claim is directed to a judicial exception, "we then ask, ‘[w]hat else is there in the claims before us?") (emphasis added)); RecogniCorp, LLC v. Nintendo Co., 855 F.3d 1322, 1327, 122 USPQ2d 1377 (Fed. Cir. 2017) ("Adding one abstract idea (math) to another abstract idea (encoding and decoding) does not render the claim non-abstract"). Instead, an "inventive concept" is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself. Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966)”. The additional step of standardizing the AAT level in urine with creatinine as an internal standard substance is well-understood, routine and conventional in the prior art as a way to compensate for different volumes of urine analyzed since creatinine is always present in urine at a constant concentration. The comparisons of the PSA level in serum and the AAT level in urine to the specific threshold values recited in claims 1, 7 and 13 are part of the judicial exception comprising a natural correlation, and therefore, do not constitute additional steps that are not well-understood, routine and conventional in the prior art under step 2B of the 35 USC 101 analysis. For these reasons, the additional steps recited in the method do not recite an inventive concept that renders the claims patent eligible under step 2B of the 35 USC 101 analysis.
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.
Claim(s) 1, 7 and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al (US 2023/0393136) in view of Matsumoto et al (JP 2015169608A, submitted in the IDS filed on November 14, 2023).
With regards to claims 1, 7 and 13, Zhang et al teach of a screening and data collection method for the detection of prostate cancer in a subject by measuring one or more glycoproteins in both urine and serum samples obtained from the subject. In one embodiment, the method comprises detecting a level of alpha-1-antitrypsin (SERPINA1) in a urine sample obtained from a subject, and detecting a level of prostate-specific antigen (PSA) in as serum sample obtained from the subject. See paragraphs 0012, 0016 and 0017 in Zhang et al, especially the embodiment labeled (h) in paragraph 0017 where both urine alpha-1-antitrypsin (SERPINA1) and serum PSA are measured in the method. The measured levels of both the urine alpha-1-antitrypsin (SERPINA1) and serum PSA in the subject are then compared to control threshold values for each glycoprotein, and based upon the comparisons, the subject is identified as having prostate cancer if there is a statistically significant difference in the levels of the glycoproteins as compared to the corresponding levels in a control sample, wherein the control sample comprises measured amounts of the glycoproteins in a person who does not suffer from prostate cancer. In particular, the method determines whether each level of measured glycoprotein, including both urine alpha-1-antitrypsin (SERPINA1) and serum PSA, exceeds a threshold control level for the glycoprotein, and when the measured levels of the glycoproteins in the subject exceed the threshold control levels, the subject is determined to have prostate cancer or is suspected to have prostate cancer. See paragraphs 0012, 0016-0017, 0026, 0030, 0066, 0072, 0075-0077 and 0104 in Zhang et al.
With regards to claims 1, 7 and 13, Zhang et al fail to teach that the alpha-1-antitrypsin (SERPINA1 or AAT) level measured in urine is a level standardized with a creatinine internal standard by dividing the SERPINA1 or AAT level by a creatinine level, and also fail to teach that a first threshold value for prostate-specific antigen is in a range of equal to or more than 1 ng/mL and equal to or less than 5 ng/mL, and that a second threshold value for alpha-1-antitrypsin (SERPINA1 or AAT) in the method is in a range of equal to or more than 0.01 µg/mg to less than 2 µg/mg.
Matsumoto et al (JP 2015169608A) teach of a method for detecting whether or not a subject suffers from a cancer including prostate cancer. The method comprises quantifying an amount of alpha-1-antitrypsin (called alpha1-ATin in Matsumoto et al) in a urine sample obtained from a subject using an enzyme-linked immunosorbent assay (ELISA), and determining whether the subject suffers from a cancer such as prostate cancer or is at risk of suffering from prostate cancer when the obtained quantitative value exceeds a preliminarily set threshold value. Matsumoto et al teach that the measured value of alpha-1-antitrypsin in the urine sample of the subject is normalized with a measured amount of a creatinine internal standard in the urine sample by dividing the measured level of alpha-1-antitrypsin by the measured level of creatinine. This normalization step allows errors in the method caused by various operations for quantifying alpha-1-antitrypsin in urine to be corrected with little variation between subjects. See the abstract and pages 5-6 and 9-10 of the English-language translation of Matsumoto et al provided herein.
Based upon the combination of Zhang et al and Matsumoto et al, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to standardize or normalize the alpha-1-antitrypsin (SERPINA1 or AAT) level measured in a urine sample of a subject in the method taught by Zhang et al with a creatinine internal standard by dividing the SERPINA1 or AAT level by a creatinine level because Matsumoto et al teach that such a normalization step in a method for detecting prostate cancer in a subject based upon a measured urine alpha-1-antitrypsin level in a subject is advantageous since it allows errors in the method caused by various operations for quantifying alpha-1-antitrypsin in urine to be corrected with little variation between subjects. It also would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to establish and set a first threshold value for prostate-specific antigen in the method taught by Zhang et al to the range of equal to or more than 1 ng/mL and equal to or less than 5 ng/mL and the second threshold value for alpha-1-antitrypsin in the method taught by Zhang et al to a range of equal to or more than 0.01 µg/mg to less than 2 µg/mg because threshold levels of analytes measured in biological fluids (i.e. serum and urine) are normally arbitrarily set based upon desired levels of specificity and sensitivity in an assay, and one of ordinary skill in the art could be expected to use routine experimentation to set the first and second threshold values for prostate-specific antigen and alpha-1-antitrypsin in the method taught by Zhang et al to the range of levels recited in claims 1, 7 and 13 since these ranges would allow for both high sensitivity in combination with high specificity to provide accurate results with low false positives and/or false negatives.
Response to Arguments
Applicant's arguments filed June 15, 2026 have been fully considered but they are not persuasive.
The previous objection to the abstract made in the last Office action mailed on April 20, 2026 has been withdrawn in view of the amendments made to the abstract. The previous rejections of the claims under 35 USC 112(b) have also been withdrawn in view of the amendments made to the claims.
Applicant argues the rejection of the claims under 35 USC 101 by stating that the amendments made to the claims now fully satisfy the requirements of 35 USC 101, and that by reciting the combined specific threshold ranges of PSA and AAT in the claims, the claimed method solves a specific technological problem in conventional PSA testing (i.e. a high rate of false positives) and drastically improves specificity. This argument is not persuasive since the added physical steps of “quantitatively measuring” a prostate-specific antigen (PSA) and alpha-1-antitrypsin (AAT) levels in serum and urine from a subject are merely necessary data gathering to obtain the data used in making the natural correlation, which is the correlation between the naturally occurring PSA and AAT in serum and urine of a subject and whether the subject has developed or is suspected to have developed prostate cancer. The standardization of the AAT level in urine with creatinine as an internal standard substance added to independent claims 1, 7 and 13 is not a practical application of the judicial exceptions because this step amounts to extra-solution activity that is well-known and is only nominally or tangentially related to the invention. The standardization of analyte levels measured in urine with creatinine as an internal standard is well-known in the prior art to compensate for different volumes of urine analyzed since creatinine is always present in urine at a constant concentration. The recitation of the specific first and second threshold values for PSA in serum and AAT in urine in claims 1, 7 and 13 does not amount to a practical application of the judicial exceptions because comparing measured levels of analytes in a diagnostic procedure to established threshold levels is commonly performed by a doctor or medical professional in order to assess the meaning of the analyte levels and make a diagnosis. In addition, the comparison of the measured PSA and AAT levels to the first and second threshold values in the methods recited in claims 1, 7 and 13 is a part of the natural correlation itself rather than additional steps to the natural correlation which may provide a practical application of the natural correlation. Therefore, this comparison step to first and second threshold values in claims 1, 7 and 13 does not provide an improvement to a technology because according to MPEP 2106.05(a), “It is important to note, the judicial exception alone cannot provide the improvement. The improvement can be provided by one or more additional elements.” In addition, the specification describes the improvement to the technology of detecting or diagnosing prostate cancer in a subject as being obtained when the first threshold level for PSA in serum is 4.0 ng/mL and the second threshold value for AAT/Cre in urine is 1.3 µg/mg. See paragraph 0065 and Table 1 in the specification. The specification indicates that when the first and second thresholds are at these values, the specificity of prostate cancer detection is about 0.993 (99.3%) while maintaining the sensitivity to 1 (100%), and there were only 5 subjects who were so-called false positives. The specification also indicates that when the combined first and second threshold values for PSA and AAT are above or below these values, the combined sensitivity and specificity of the methods recited in the claims decreases with more false positive subjects being identified. However, claims 1, 7 and 13 recite a much broader range of values for the first threshold value of PSA and the second threshold value of AAT than 4.0 ng/mL for PSA and 1.3 µg/mg for AAT (i.e. the claims recite a range of equal to or more than 1 ng/mL and equal to or less than 5 ng/mL for PSA, and a range of equal to or more than 0.01 µg/mg to less than 2 µg/mg for AAT). The specification has not demonstrated that there is any improvement to the technology of prostate cancer detection over the entire broad ranges for the first and second threshold values recited in claims 1, 7 and 13, but instead only describes and demonstrates an improvement in the combined specificity and sensitivity of prostate cancer detection when the threshold value of PSA is 4.0 ng/mL and when the threshold level of AAT is 1.3 µg/mg. According to MPEP 2106.05(a), “After the examiner has consulted the specification and determined that the disclosed invention improves technology, the claim must be evaluated to ensure the claim itself reflects the disclosed improvement in technology. Intellectual Ventures I LLC v. Symantec Corp., 838 F.3d 1307, 1316, 120 USPQ2d 1353, 1359 (Fed. Cir. 2016) (patent owner argued that the claimed email filtering system improved technology by shrinking the protection gap and mooting the volume problem, but the court disagreed because the claims themselves did not have any limitations that addressed these issues). That is, the claim must include the components or steps of the invention that provide the improvement described in the specification.” In the instant case, the claims recite a broader range for the first and second threshold values than is described in the specification as providing the improvement to the technology of prostate cancer detection. Regardless, however, it is maintained that the recitation of the comparison of the measured PSA and AAT levels to the first and second threshold values in the methods recited in claims 1, 7 and 13 is a part of the natural correlation itself rather than additional steps to the natural correlation which may provide a practical application of the natural correlation. The comparison step to first and second threshold values in claims 1, 7 and 13 does not provide an improvement to a technology because according to MPEP 2106.05(a), “It is important to note, the judicial exception alone cannot provide the improvement. The improvement can be provided by one or more additional elements.”
Applicant argues the previous rejections of the claims under 35 USC 102(a)(2) as being anticipated by Zhang et al (US 2023/0393136), and under 35 USC 103 as being obvious over Zhang et al or Zhang et al in view of Matsumoto et al (JP 2015169608A, submitted in the IDS filed on November 14, 2023) by stating that the specific combination of the claimed threshold ranges for PSA and AAT yields “unexpected results” (i.e. synergistic effects) that would not have been predictable by a person of ordinary skill in the art because when the specific claimed threshold ranges of 1-5 ng/mL for PSA and 0.01-2 µg/mg for AAT are combined, the number of false positives is drastically reduced to only 5, achieving a specificity of 99.3% while maintaining 100% sensitivity, and this dramatic elimination of false positives is a synergistic effect that goes far beyond routine optimization. This argument is persuasive with regards to the specific values of 4.0 ng/mL for PSA and 1.3 µg/mg for AAT since the specification clearly describes and demonstrates that these combined threshold values for PSA and AAT result in a specificity of 99.3% while maintaining 100% sensitivity in prostate cancer detection while producing only 5 false positive subjects. See paragraph 0065 and Table 1 in the specification. However, Applicant’s argument is not persuasive with regards to the entire scope of the threshold ranges recited in the claims for PSA and AAT since the specification only states that a threshold level of 4.0 ng/mL for PSA was tested in the method (see paragraph 0065 and Tables 1 and 2 in the specification), and threshold levels less than 2 µg/mg for AAT that were tested in the method were 0.03 µg/mg, 0.2 µg/mg, 0.8 µg/mg, and 1.3 µg/mg. Additionally, the specification does not describe and demonstrate that “unexpected results” were obtained in the method for prostate cancer detection in terms of sensitivity and specificity over the entire broad ranges for the PSA and AAT threshold values presently recited in independent claims 1, 7 and 13. The specification only describes “unexpected results” in detecting or diagnosing prostate cancer in a subject as being obtained when the first threshold level for PSA in serum is 4.0 ng/mL and the second threshold value for AAT/Cre in urine is 1.3 µg/mg. The specification describes that when the combined first and second threshold values for PSA and AAT are above or below these values, the combined sensitivity and specificity of the methods recited in the claims decreases with more false positive subjects being identified. Therefore, the specification has not demonstrated that there is any “unexpected results” in prostate cancer detection over the entire broad ranges for the first and second threshold values recited in claims 1, 7 and 13, but instead only describes and demonstrates an improvement in the combined specificity and sensitivity of prostate cancer detection when the threshold value of PSA is 4.0 ng/mL and when the threshold level of AAT is 1.3 µg/mg. For this reason, Applicant’s argument with regards to the current prior art rejection of the claims under 35 USC 103 is not persuasive since it is not commensurate in scope with the amended claims as presently recited.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAUREEN M WALLENHORST whose telephone number is (571)272-1266. The examiner can normally be reached on Monday-Thursday from 6:30 AM to 4:30 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander, can be reached at telephone number 571-272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MAUREEN WALLENHORST/Primary Examiner, Art Unit 1797 July 8, 2026
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