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 .
DETAILED ACTION
Responsive to communication entered 06/04/2025.
The Examiner charged with the present case has changed. See contact information below.
Priority
This application, Pub. No. US 2022/0221472 A1, published 07/14/2022, is a § 371 National Stage of International Patent Application No. PCT/JP2020/017595, filed 04/24/2020, Pub. No. WO 2020/218465 A1, published 10/29/2020, which claims foreign priority to JP 2019-086223, filed·04/26/2019.
Status of Claims
Claims 1-21 are currently pending. Claims 1-15 have been originally filed. Claims 1-15 have been amended and Claims 16-21 have been added, as set forth in Applicant’s Preliminary amendment filed 05/25/2022. Claims 1-21 have been subject to restriction/election requirement mailed 12/05/2024. Claim 13 has been amended, as set forth in Applicant’s Preliminary amendment filed 06/04/2025. Claims 5, 9-16 and 19-21 are withdrawn from consideration. Claims 1-4, 6-8, 17 and 18 are examined.
Election/Restriction
An inadvertent typographical error is noted in the restriction/election requirement mailed 12/05/2024. Specifically, Group I should include Claims 1-8, 16-19 and 21, but not Claims 1-8 and 16-21, because Claim 20 is drawn to the kit and, therefore, belongs
to non-elected Group II.
Applicant's election, without traverse, of Group I, Claims 1-8, 16-19 and 21, drawn to a method comprising measuring at least one marker, and, without traverse, the species:
(a1) Neutrophil-activating peptide 2 as the marker, corresponding to the peptide sequence recited in SEQ ID NO:8;
(b6) monitoring the three pathological conditions of endometriosis, which are the extent of endometrial fibrosis, the extent of endometrial adhesion, and the degree of progression of endometriosis, as the type of clinical goal;
(c) the election of a corresponding species is not applicable since species b(6) is elected;
(d2) LC-MS as the type of measuring; and
(e5) a subject at risk for having a degree of progression due to having endometriosis as the type of subject,
in the reply filed on 06/04/2025 is acknowledged.
Applicant indicated that Claims 1-8 and 16-21 are believed to read on the elected species. The Examiner respectfully disagrees with this assessment and believes that the elected species are encompassed by Claims 1-4, 6-8, 17 and 18 of the elected Group I, because Claims 5, 16 and 21 do not read on the elected species (b6), whereas Claim 19 depends on Claim 9 (withdrawn) of non-elected Group II.
Claims 5, 9-16 and 19-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention/species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on
06/04/2025.
Information Disclosure Statement
The information disclosure statements, submitted on 05/25/2022, 06/28/2023, 09/18/2023, 02/07/2024, 03/06/2024 and 11/25/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the Examiner.
On 09/04/2025, two versions of the information disclosure statement have been submitted by Applicant, one of which has been crossed-out by the Examiner as being duplicative.
The information disclosure statement, submitted on 09/04/2025, fails in part to comply with to comply with 37 CFR 1.98(a)(3):
1.98 Content of information disclosure statement.
(3)
(i) A concise explanation of the relevance, as it is presently understood by the individual designated in § 1.56(c) most knowledgeable about the content of the information, of each patent, publication, or other information listed that is not in the English language. The concise explanation may be either separate from applicant’s specification or incorporated therein.
(ii) A copy of the translation if a written English-language translation of a non-English-language document, or portion thereof, is within the possession, custody, or control of, or is readily available to any individual designated in § 1.56(c).
Emphasis added.
Accordingly, the following reference that is not in the English language is crossed-out by the Examiner:
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It has been placed in the application file, but the information referred to therein has not been considered as to the merits. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
Claim Objections
Claims 1-4, 6 and 7 are objected to because of recitations “a marker shown in Table 1A, a marker shown in Table 2A, a marker shown in Table 5A, and a marker shown in Table 6A” and “a marker shown in Table 1B, a marker shown in Table 2B, a marker shown in Table 5B, and a marker shown in Table 6B.” See MPEP § 2173.05(s) “Reference to Figures or Tables”:
“Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).”
Emphasis added.
Appropriate correction is required.
Claim Rejection - 35 USC § 112
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 112 that form the basis for the rejections under this section made in this Office action.
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
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.
Claims 1-4, 6-8, 17 and 18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1 and 8, as recited in independent Claim 1, are drawn to:
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Claims 2-4, 6 and 17, as recited in independent Claim 2, are drawn to:
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Claims 7 and 18, as recited in independent Claim 7, are drawn to:
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It is the Examiner' position that the instant specification fails to provide adequate written description and clear guidance for the method as claimed and does not reasonable convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
The Examiner' position is based on the following facts and considerations.
First, it is not clear what markers are implemented by recitation “a marker shown in Group 1A, a marker shown in Group 2A, a marker shown in Group 1B, a marker shown in Group 2B, a marker shown in Group 3A, a marker shown in Group 4A, a marker shown in Group 3B, and a marker shown in Group 4B” because the only appearance of Groups 1A through 4B is found in the original Claim 1 but not in the specification as filed.
Second, the specification broadly defined the term a “sample” as follows:
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Specification filed 06/04/2025; Emphasis added.
Third, the instant application expressly limits
the “laundry” lists of the markers set forth in Tables 1A, 2A, 5A, 6A, which abundance is higher than a predetermined value or is higher than the abundance of the same at least one marker in a sample obtained from a healthy subject, to:
the plasma concentration of the type V collagen MMP degradation product (C5M) (See Example 3); 12 proteins showed the highest value in endometriosis patients at the time of surgery and a decreased value one month after surgery, and also showed the lowest value in healthy individuals as determined by Luminex xMAP™ Technology using plasma of healthy human individuals and patients with endometriosis (See Example 4; Table 7A); and 16 proteins showed the highest value in endometriosis patients at the time of surgery and a decreased value one month after surgery, and also showed the lowest value in healthy individuals as determined by LC-MS Analysis using plasma of healthy human individuals and patients with endometriosis (Example 5; Table 8A); and
(II) the “laundry” lists of the markers set forth in Table 1B, Table 2B, Table 5B, Table 6B, which abundance is lower than a predetermined value or is lower than the abundance of the same at least one marker in a sample obtained from a healthy subject, to:
3 proteins showed the highest value in endometriosis patients at the time of surgery and a decreased value one month after surgery, and also showed the lowest value in healthy individuals as determined by Luminex xMAP™ Technology using plasma of healthy human individuals and patients with endometriosis (See Example 4; Table 7B); and 8 proteins showed the highest value in endometriosis patients at the time of surgery and a decreased value one month after surgery, and also showed the lowest value in healthy individuals as determined by LC-MS Analysis using plasma of healthy human individuals and patients with endometriosis (Example 5; Table 8B).
Therefore, the methods of Claims 1-4, 6-8, 17 and 18, which methods comprise detecting the “laundry” lists of the markers set forth in Tables 1A, 2A, 5A, 6A, 1B, 2B, 5B, and 6B in any samples from organs, tissues, cells, body fluids, or mixtures thereof contained in living bodies, do not meet the written description provision of 35 U.S.C. §112(a) or 35 U.S.C. §112 (pre-AIA ), first paragraph.
Claims 1-4, 6-8, 17 and 18 are 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 pre-AIA the applicant regards as the invention.
Regarding Claims 1, 2 and 7, it is not clear what markers are implemented by recitation “a marker shown in Group 1A, a marker shown in Group 2A, a marker shown in Group 1B, a marker shown in Group 2B, a marker shown in Group 3A, a marker shown in Group 4A, a marker shown in Group 3B, and a marker shown in Group 4B,” because the only appearance of Groups 1A through 4B is found in the original Claim 1 but not in the specification as filed.
Claim 8, Claims 3, 4, 6 and 17 and Claim 18 are rejected as being dependent upon the rejected Claims 1, 2 and 7, respectively, and fail to cure the indefiniteness of Claims 1, 2 and 7.
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 1-4, 6-8, 17 and 18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Claim interpretation: The broadest reasonable interpretation of independent Claims 1, 2 and 7 is a method of measuring the concentration of at least one marker in a sample from a subject for diagnosing endometriosis, determining whether or not a subject is affected by endometriosis, or monitoring pathological conditions of endometriosis, respectively.
Step 1: This part of the eligibility analysis evaluates whether the claim falls within any statutory category. MPEP § 2106.03. The claim recites at least one step or act, such as “measuring the abundance of at least one marker.” Thus, the claim is to a process, which is one of the statutory categories of invention (Step 1: YES).
Step 2A Prong One: This part of the eligibility analysis evaluates whether the claim recites a judicial exception. As explained in MPEP § 2106.04(II), a claim “recites” a judicial exception when the judicial exception is “set forth” or “described” in the claim. While the terms "set forth" and "described" are thus both equated with "recite", their different language is intended to indicate that there are two ways in which an exception can be recited in a claim. For instance, the claims in Diehr, 450 U.S. at 178 n. 2, 179 n.5, 191-92, 209 USPQ at 4-5 (1981), clearly stated a mathematical equation in the repetitively calculating step, and the claims in Mayo, 566 U.S. 66, 75-77, 101 USPQ2d 1961, 1967-68 (2012), clearly stated laws of nature in the wherein clause, such that the claims “set forth” an identifiable judicial exception. Alternatively, the claims in Alice Corp., 573 U.S. at 218, 110 USPQ2d at 1982, described the concept of intermediated settlement without ever explicitly using the words “intermediated” or “settlement.” Since Claims 1, 2 and 7 and Claims 3, 4, 6, 8, 17 and 18 dependent thereon describe a naturally occurring relationship between the concentration of at least one marker in a sample from a subject for diagnosing endometriosis, determining whether or not a subject is affected by endometriosis, or monitoring pathological conditions of endometriosis, respectively, the claims are considered to recite a law of nature. In addition, Claims 1-4, 6 and 7 recite the “the subject is diagnosed as having endometriosis when …,” “the subject is determined to be affected by endometriosis when …,” “determines the extent of endometrial fibrosis in the subject by (a) determining …,” “determines the extent of endometrial adhesion in the subject by (a) determining …,” “determines the degree of progression of endometriosis in a subject affected or suspected of being affected by endometriosis by (a) determining that …” or “(a) determining that the abundance of at least one marker …”, respectively, that can be practically performed in the human mind, and thus falls into the “mental process” groupings of abstract ideas.
Accordingly, Claims 1-4, 6-8, 17 and 18 recite a judicial exception (a law of nature and “mental process” grouping).
Step 2A Prong Two: This part of the eligibility analysis evaluates whether the claim as a whole integrates the recited judicial exception into a practical application of the exception. This evaluation is performed by (a) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application.
Besides the abstract idea/law of nature, Claims 1 and 2 recite the additional element of “measuring the abundance of at least one marker selected from the group consisting of …,” and Claim 7 recites “measuring the abundance of at least one marker selected from the group consisting of … in a plurality of samples collected from the subject at different points of time.”
However, steps of measuring/determining markers in a sample are insufficient to integrate the judicial exception(s) into a practical application because the purpose is merely to obtain data. This does not go beyond insignificant presolution activity, i.e., a mere data gathering step necessary to use the correlation, similar to the fact pattern in In re Grams, 888 F.2d 835 (Fed. Cir. 1989) and Ariosa Diagnostics, Inc. v. Sequenom, Inc. (Fed. Cir. 2015). Such steps that merely “add insignificant extra-solution activity to the judicial exception” are insufficient to integrate the exception into a practical application (MPEP 2106.05(g)). Data gathering steps typically constitute such insignificant extra-solution activity. See Mayo (concluding that additional element of measuring metabolites of a drug administered to a patient was extra-solution activity); OIP Techs., Inc. v. Amazon.com, Inc., 788 F.3d 1359, 1363 (Fed. Cir. 2015) (holding that mere data gathering is insufficient to confer patent eligibility). In addition, these limitations fail to meaningfully limit the claim because they require selecting at least one marker from the group consisting of a type V collagen MMP degradation product, a marker shown in Group 1A, a marker shown in Group 2A, a marker shown in Group 1B, a marker shown in Group 2B, a marker shown in Group 3A, a marker shown in Group 4A, a marker shown in Group 3B, and a marker shown in Group 4B, and do not provide any information as to how marker’s concentration is to be detected. In fact, these limitations are recited at a high level of generality, making the limitations’ inclusion in this claim at best nominal.
The further defined additional elements recited in the claims, do not represent an improvement to a technical field, as such techniques were previously known (see discussion below), and, accordingly, do not apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception.
Accordingly, these limitations do not integrate the recited judicial exception into a practical application and the claims are therefore directed to the judicial exception (Step 2A: YES).
Step 2B: This part of the eligibility analysis evaluates whether the claim as a whole amounts to significantly more than the recited exception, i.e., whether any additional element, or combination of additional elements, adds an inventive concept to the claim. See MPEP § 2106.05.
Regarding Claims 1, 2 and 7, as above, steps of measuring/determining markers in a sample are insufficient to integrate the judicial exception(s) into a practical application because the purpose is merely to obtain data. This does not go beyond insignificant presolution activity, i.e., a mere data gathering step necessary to use the correlation, similar to the fact pattern in In re Grams, 888 F.2d 835 (Fed. Cir. 1989) and Ariosa Diagnostics, Inc. v. Sequenom, Inc. (Fed. Cir. 2015). Such steps that merely “add insignificant extra-solution activity to the judicial exception” are insufficient to integrate the exception into a practical application (MPEP 2106.05(g)). Data gathering steps typically constitute such insignificant extra-solution activity. See Mayo (concluding that additional element of measuring metabolites of a drug administered to a patient was extra-solution activity); OIP Techs., Inc. v. Amazon.com, Inc., 788 F.3d 1359, 1363 (Fed. Cir. 2015) (holding that mere data gathering is insufficient to confer patent eligibility). In addition, these limitations fail to meaningfully limit the claim because they require selecting at least one marker from the group consisting of a type V collagen MMP degradation product, a marker shown in Group 1A, a marker shown in Group 2A, a marker shown in Group 1B, a marker shown in Group 2B, a marker shown in Group 3A, a marker shown in Group 4A, a marker shown in Group 3B, and a marker shown in Group 4B, and do not provide any information as to how marker’s concentration is to be detected.. In fact, these limitations are recited at a high level of generality, making the limitations’ inclusion in the claims at best nominal.
Claims 3, 4 and 6 are not eligible because, besides the abstract idea/law of nature, the claims do not recite any additional element(s).
Claims 17 and 18 are not eligible because the existence and location of at least one marker is a natural phenomenon and thus identifying their presence in blood is merely claiming the natural phenomena itself. See MPEP 2106.04(c):
“Similarly, claims to detecting naturally occurring cell-free fetal DNA (cffDNA) in maternal blood were held to be directed to the cffDNA, because the "existence and location of cffDNA is a natural phenomenon [and thus] identifying its presence was merely claiming the natural phenomena itself." Rapid Litig. Mgmt., 827 F.3d at 1048, 119 USPQ2d at 1374, (explaining the holding in Ariosa Diagnostics, Inc. v. Sequenom, 788 F.3d 1371, 115 USPQ2d 1152 (Fed. Cir. 2015)).”
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-4, 6 and 7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Küpker et al., "Paracrine changes in the peritoneal environment of women with endometriosis", Human Reproduction Update, vol. 4, no. 5, 1 September 1998 (1998-09-01), pages 719-723 (IDS submitted 09/18/2023).
Küpker et al., throughout the publication, and, for example, in Abstract, teach a method of diagnosing endometriosis, comprising measuring the abundance of at least one marker selected from the group consisting of Transforming growth factor β and ICAM-1 in a sample obtained from a subject:
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Emphasis added.
Küpker et al. further teach endometrial adhesion:
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Emphasis added.
Although Küpker et al. do not expressly teach endometrial fibrosis, one of skill in the art would have known that endometrial fibrosis is the development of scar tissue in the endometrium, often called intrauterine adhesions, is also a significant factor in all subtypes of endometriosis:
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Therefore, Küpker et al. teach all limitations of the instant Claims 1-4, 6 and 7.
Claims 1-4, 6-8, 17 and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kubatova et al., "Serum cytokine and growth factor levels in patients with endometriosis," Central Eur. J. Immunol., 2013; vol. 38, No 4, pp. 500-504 (IDS submitted 09/04/2025).
Kubatova et al., throughout the publication, and, for example, in Abstract, teach a method of diagnosing endometriosis, comprising measuring the abundance of Transforming growth factor β1 (TGF-β1) in a blood (serum) sample obtained from a subject:
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Emphasis added.
Küpker et al. further teach endometrial adhesion:
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Page 503, left column, 2nd paragraph, Emphasis added.
Although Kubatova et al. do not expressly teach endometrial fibrosis, one of skill in the art would have known that endometrial fibrosis is the development of scar tissue in the endometrium, often called intrauterine adhesions, is also a significant factor in all subtypes of endometriosis:
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Therefore, Kubatova et al. teach all limitations of the instant Claims 1-4, 6-8, 17 and 18.
With regard to the elected species (a1), no prior art teaching Neutrophil-activating peptide 2 as a marker of endometriosis was found.
With regard to the elected species (d2), the use of LC-MS for measuring biomarkers of endometriosis in blood is well known in the art, as evidence, for example by Vouk et al., US 2015/0185238 A1, published 07/02/2015 (See paragraphs [0079], [0087]).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GALINA M YAKOVLEVA whose telephone number is (571)270-3282. The examiner can normally be reached on M-F 8:30 AM-5:00 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, GREGORY S EMCH can be reached on (571)272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/GALINA M. YAKOVLEVA/Primary Examiner, Art Unit 1678