DETAILED ACTION
Note: the current examiner is different from the examiner of the Non-Final Office Action (1/27/2026).
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 .
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.
Withdrawn Objections/Rejections
The objection to the claims is withdrawn in response to the amendments.
The 112a and 112b rejections are withdrawn in response to the amendments.
The 102 rejections are withdrawn in response to the amendments. However, new grounds of rejection are set forth below under 103.
Priority
The present application was filed as a proper National Stage (371) entry of PCT Application No. PCT/JP2020/017595, filed 04/24/2020. Acknowledgment is also made of applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d) to Application No. JP2019-086223, filed on 04/26/2019 in Japan.
Information Disclosure Statement
The information disclosure statement filed 5/22/2026 is being considered by the examiner.
Maintained Rejections
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 and 17-18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to at least one judicial exception without significantly more.
The U.S. Patent and Trademark Office recently revised the MPEP with regard to § 101 (see the MPEP at 2106). Regarding the MPEP at 2106, in determining what concept the claim is “directed to,” we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a fundamental economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical application (see MPEP § 2106.05(a)-(c), (e)-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim contains an “‘inventive concept’ sufficient to ‘transform’” the claimed judicial exception into a patent-eligible application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not “well-understood, routine, conventional” in the field (see MPEP § 2106.05(d)); or
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception.
See MPEP 2106.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A JUDICIAL EXCEPTION
Step 2A, Prong 1
The claims recite “ A method of diagnosing and treating endometriosis” (claim 1), “A method of determining whether or not a subject is affected by endometriosis” (claim 2) and “A method of monitoring pathological conditions of endometriosis in a subject affected or suspected of being affected by endometriosis” (claim 7), “comprising measuring the abundance of Neutrophil-activating peptide 2 (NAP2)” (claim 1) “comprising measuring the abundance of NAP2” (claims 2 and 7), “in plasma obtained from a subject” (claims 1-2), “in a plurality of plasma samples collected from the subject at different points of time” (claim 7).
The natural relationship to which the claims are directed (i.e., the relation between NAP2 levels and endometriosis) is a law of nature. Similar concepts have been held by the courts to constitute law of nature/natural phenomena, as in the identification of a correlation between the presence of myeloperoxidase in a bodily sample (such as blood or plasma) and cardiovascular disease risk in Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017). In Mayo, the Supreme Court found that a claim was directed to a natural law, where the claim required administering a drug and determining the levels of a metabolite following administration, where the level of metabolite was indicative of a need to increase or decrease the dosage of the drug. See Mayo Collaborative Services v. Prometheus Labs., Inc., 566 U.S. 66, 74 (2012).
The instant claims are similar to those in Mayo as they involve a "relation itself [which] exists in principle apart from any human action" (id. at 77), namely the relationship between the naturally occurring levels of NAP-2 in plasma and the presence of endometriosis.
The correlation between NAP-2 levels and disease is a judicial exception as it exists in principle apart from any human action; the correlation itself therefore cannot form the basis for eligibility. Similarly, it is a naturally occurring phenomenon that NAP-2 levels are elevated to different extents in endometriosis vs. in other disorders.
Additionally, the claims recite “wherein the subject is determined to be affected by endometriosis when the abundance of NAP2 is higher than a predetermined value or is higher than the abundance of the same marker in plasma obtained from a healthy subject” (claim 2), “wherein the subject is determined to have a condition of endometriosis worsening or potentially worsening when the abundance of NAP2 is higher than the abundance of the same marker in plasma collected from the subject at an earlier point in time” (claim 7).
The steps of determining endometriosis/worsening of endometriosis by comparing NAP2 levels to a predetermined value may also be categorized as abstract ideas, namely mental processes/concepts performed in the human mind (such as a doctor simply thinking about the measured level of NAP2 in relation to a cutoff value and making an evaluation, judgment, or opinion). The claims, under their broadest reasonable interpretation, cover performance of determining endometriosis/worsening of endometriosis solely within the human mind, or by a human using pen and paper. Comparing information regarding a sample to a control or target data represents abstract ideas.
Similar concepts involving comparing information regarding a sample or test subject to a control or target data have been held to be an "abstract mental process", as in University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 113 USPQ2d 1241 (Fed. Cir. 2014) which involved "comparing BRCA sequences and determining the existence of alterations", the collecting and comparing of known information in Classen, the comparing information regarding a sample or test subject to a control or target data in Ambry and Myriad CAFC, as well as Mayo.
Dependent claims 3 recites “wherein the method determines the extent of endometrial fibrosis in the subject”. This limitation is directed to the natural correlation between NAP2 and the extent of endometrial fibrosis.
Dependent claim 3 further recites “by determining that the abundance of NAP2 is higher than a predetermined value or is higher than the abundance of the same marker in plasma obtained from a healthy subject”. This limitation is directed to the mental step of comparing numerical values, i.e. an abstract idea.
Dependent claim 4 recites “wherein the method determines the extent of endometrial adhesion in the subject”. This limitation is directed to the natural correlation between NAP2 and the extent of endometrial adhesion.
Dependent claim 4 further recites “by determining that the abundance of NAP2 is higher than a predetermined value or is higher than the abundance of the same marker in plasma obtained from a healthy subject”. This limitation is directed to the mental step of comparing NAP2 levels, i.e. an abstract idea.
Dependent claim 6 recites “wherein the method determines the degree of progression of endometriosis in a subject affected or suspected of being affected by endometriosis”. This limitation is directed to the natural correlation between NAP2 and the degree of progression of endometriosis.
Dependent claim 6 further recites “by determining that the abundance of NAP2 is higher than a predetermined value or is higher than the abundance of the same marker in plasma obtained from a healthy subject”. This limitation is directed to the mental step of comparing numerical values, i.e. an abstract idea.
Dependent claims 8 and 17-18 further recites “wherein the abundance of NAP2 is the concentration of NAP2 polypeptide in plasma”. This limitation merely narrows the natural correlation to being of NAP2 polypeptide concentration in plasma. Therefore, these claims are also directed to at least one judicial exception.
Step 2A, Prong 2
Claim 1 further recites “administering a therapeutic agent for endometriosis to a subject that has been diagnosed as having endometriosis”.
Claim 2 further recites “and treating a subject that has been determined to be affected by endometriosis…administering a therapeutic agent for endometriosis to a subject that has been determined to be affected by endometriosis”.
Claim 7 further recites “and treating a subject that has been determined to have a condition of endometriosis worsening or potentially worsening…administering a therapeutic agent for endometriosis to the subject that has been determined to have a condition of endometriosis worsening or potentially worsening”
These “treating” steps are insufficient to integrate the judicial exception as they are not limited to a particular treatment.
The recited steps of “administering a therapeutic agent” are recited at a high level of generality and are not limited to a particular therapeutic. Such highly generalized treatment limitations – which do not require any specific treatment for endometriosis – do not amount to sufficient practical application to provide patentability. Although a claim limitation can integrate a judicial exception by applying or using the judicial exception(s) to effect a particular treatment or prophylaxis for a disease or medical condition, in this case no specific or particular treatment is set forth.
The level of generality in the instant claims stands in contrast to the treatment claims found patent-eligible in Vanda Pharm. Inc. v. West-Ward Pharm. Int’l Ltd., 887 F.3d 1117 (Fed. Cir. 2018) and Natural Alternatives Int’l v. Creative Compounds LLC, 2017 WL 1216226 (Fed. Cir. Mar. 15, 2019). The claims at issue in Vanda recited administering a specific drug (iloperidone) at specific dosage ranges based on a patient’s genotype. Vanda, 887 F.3d at 1135. Accordingly, the court found that although the inventors recognized the relationships between iloperidone, a patient’s genotype, and QTc prolongation, what they claimed is “an application of that relationship,” i.e., “‘a new way of using an existing drug’ that is safer for patients because it reduces the risk of QTc prolongation.” Id. (quoting Mayo, 566 U.S. at 87). The Federal Circuit characterized the Vanda claims as being directed to “a specific method of treatment for specific patients using a specific compound at specific doses to achieve a specific outcome.” Id. at 1136. Similarly, the Federal Circuit found that the claims in Natural Alternatives “contain specific elements that clearly establish they are doing more than simply reciting a natural law,” such as specifying a patient population, particular results to be obtained, specific compounds to be administered to achieve the claimed results, and dosages via an “effective” limitation. Natural Alternatives, 4-5.
In contrast to the claims in Vanda and Natural Alternatives, the present claims do not specify a particular result to be obtained, a compound to be administered to achieve a claimed result, or any specific dosage of a specific compound.
Rather, the therapeutic agent would be directed to any and all treatments. The recited treating steps do not limit the claims to a particular application; instead, the effect of the treatment limitations “is simply to tell doctors to apply the law somehow when treating their patients.” Mayo, 566 U.S. at 81-82.
Here, the claimed treatment step is instead merely an instruction to “apply” the exception in a generic way. Thus, the treatment step does not integrate the natural correlations and abstract idea(s) into a practical application.
ELIGIBILITY STEP 2B: WHETHER THE ADDITIONAL ELEMENTS CONTRIBUTE AN "INVENTIVE CONCEPT"
In this case, it was well-understood, routine and conventional to administer a therapeutic agent to a subject that has been diagnosed with endometriosis.
See for example the specification discloses in paragraph 42 that “[t]he above respective methods may also comprise administering a known therapeutic agent for endometriosis to a subject that has been shown to be affected or potentially affected by endometriosis…Various therapeutic agents for endometriosis are known to those skilled in the art, and examples thereof include, but are not limited to, estrogen/progesterone mixtures, progesterone preparations, GnRH agonists, GnRH antagonists, and danazol”.
There is also evidence that administering a therapeutic agent to a subject with elevated levels of NAP2, such as in endometriosis, is well-known in the art.
See for example Clegg et al. (WO 2011100271 A2)-Cite No. FP2 of IDS 2/7/2024 (“Clegg”).
Clegg teaches “methods of treating diseases or disorders characterised by elevated or unbalanced level of human …NAP2……particularly…endometriosis” (page 85 lines 25-27 and 32). Clegg further teaches “Pharmaceutical compositions of the invention may be lyophilized (freeze dried) for reconstitution prior to administration according to methods well known or apparent to those skilled in the art” (page 85 lines 4-6).
See also Busch-Petersen et al. (WO 2007150015 A2) (“Petersen”).
Petersen teaches “the use of sulfonamide substituted diphenyl urea compounds to treat IL-8, GROa, GROβ, GROγ, NAP-2, and ENA-78 mediated diseases, particularly endometriosis” (page 1 lines 4-5).
The record further indicates that the additional elements, alone or in combination, do not go beyond well-understood, routine and conventional activity in that others had previously measured the concentration of NAP-2 in plasma samples and administered a therapeutic agent to the subject with endometriosis.
See for example Pages et al. (WO 2014184384 Al) (“Pages”).
Pages teaches “prevention and treatment of diseases related to the chemokines CXCLI, CXCL7 and CXCL8, particularly of pathological angiogenesis diseases” (page 1 lines 3-5). Pages further teaches that the “pathological angiogenesis diseases…are selected from the group consisting of:…endometriosis” (page 30 lines 23-24 and page 31 line 2). Pages further teaches “detecting in a sample at least one chemokine selected from the group consisting of CXCL1, CXCL7 and CXCL8… said sample is a biological sample. The term "biological sample" encompasses…plasma” (page 33 lines 4-5, 7-8 and 14). Note that CXCL7 is NAP2. Pages further teaches that “[t]he therapeutic method according to the invention can further comprise the step of administering to a patient in need thereof of a therapeutically or prophylactic amount of at least another compound of interest ( e.g. an anti-tumor agent, an anti-angiogenic compound, an anti-inflammatory compound)” (page 31 lines 23-26).
In summary, while the claims further recite treating endometriosis, there is nothing of record to suggest that the claims involve novel treatment steps. Treating is recited at a high level of generality.
Appending a generic, routine, and obvious post-solution treatment step does not provide a sufficient inventive concept to satisfy § 101. As was the case in Mayo and Ariosa, the method claims at issue here amount to "nothing significantly more than an instruction to doctors to apply the applicable laws when treating their patients" using "conventional steps, specified at a high level of generality." Mayo, 132 S. Ct. at 1298, 1300; Ariosa, 788 F.3d at 1377-78.
For all of these reasons, the claims fail to include additional elements that are sufficient to amount to significantly more than the judicial exception(s).
New Rejections
In further consideration of Applicant’s amendments, remarks and the prior art, a new issue of obviousness is raised.
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 1-4, 6, 8 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Pages et al. (WO 2014184384 Al) (“Pages”) in view of Busch-Petersen et al. (WO 2007150015 A2) (“Petersen”) as evidenced by Vigano et al. Human Reproduction, Vol.33, No.3 pp. 347–352, 2018 doi:10.1093/humrep/dex354 (“Vigano”).
Regarding claims 1-2, Pages suggests a method of diagnosing and treating endometriosis, a method of determining whether or not a subject is affected by endometriosis and treating a subject that has been determined to be affected by endometriosis (“prevention and treatment of diseases related to the chemokines CXCLI, CXCL7 and CXCL8, particularly of pathological angiogenesis diseases” page 1 lines 3-5, “pathological angiogenesis diseases…are selected from the group consisting of:…endometriosis” page 30 lines 23-24 and page 31 line 2, “The invention also relates to in vitro or ex vitro diagnostic and/or prognostic method, and particularly to an in vitro diagnostic and/or prognostic method of a disease related to the chemokines CXCLI, CXCL7 and CXCL8, particularly of a pathological angiogenesis disease” page 35 lines 5-8), comprising measuring the abundance of Neutrophil-activating peptide 2 (NAP2) in plasma obtained from a subject (“determining the expression and/or the level of expression of at least one human chemokine chosen in the group consisting of CXCLI, CXCL7 and CXCL8 in a biological sample of said subject” page 35 lines 9-11, “The term "biological sample" encompasses…plasma” page 33 lines 7-8 and 14). Note that CXCL7 is the same as NAP2 (“NAP2 (CXCL7)” page 2 lines 13-14). Pages further teaches administering a therapeutic agent for endometriosis to a subject that has been diagnosed as having endometriosis or be determined to be affected by endometriosis (“The invention also relates to a method of treatment and/or prophylaxis of diseases related to the chemokines CXCLI, CXCL7 and CXCL8, particularly of pathological angiogenesis diseases , or diseases characterized by undesirable excessive neovascularization, said method comprises the step of administering to a patient in need thereof a therapeutically or prophylactic amount of at least one compound selected from the group consisting of: - an antibody and a fragment thereof according to the invention” page 31 lines 14-19). Note that although Pages fails to use the language “administering a therapeutic agent for endometriosis to a subject that has been diagnosed as having endometriosis” or “be determined to be affected by endometriosis” the teaching of administering a therapeutic antibody for treating a pathological angiogenic disease “to a patient in need thereof” together with the teaching that the pathological angiogenic disease may be endometriosis (page 31 line 2) inherently provides the administering a therapeutic agent for endometriosis to a subject that has been diagnosed as having endometriosis” or “be determined to be affected by endometriosis”. Pages further teaches wherein the subject is determined to be affected by endometriosis when the abundance of NAP2 is higher than a predetermined value or is higher than the abundance of the same marker in plasma obtained from a healthy subject (“the method of the invention comprises the step ii) of comparing said level of expression determined at step i) to a control level and determining if said level of expression determined at step i) is significantly higher than said control level; said significantly higher level of expression indicates that the subject is affected with a disease related to the chemokines CXCLI, CXCL7 and CXCL8, particularly with a pathological angiogenesis disease…wherein said control level is the expression level of said at least one chemokine determined in at least a biological sample from an healthy subject, or from a subject who is not affected with a disease related to the chemokines CXCLI, CXCL7 and CXCL8, particularly with a pathological angiogenesis disease” page 35 lines 31-32 and page 36 lines 1-8).
Pages fails to teach the methods of claims 1-2 in a manner consistent with anticipation, i.e. there is some picking and choosing involved in order to arrive at the claimed methods. Pages teaches the claimed methods but directed to a list of 15 pathological angiogenesis diseases, “endometriosis” being one of the 15 diseases listed (see page 30 lines 23-33 and page 31 lines 1-3).
Petersen teaches a “method of treatment” (Title). Petersen further teaches “the use of sulfonamide substituted diphenyl urea compounds to treat IL-8, GROa, GROβ, GROγ, NAP-2, and ENA-78 mediated diseases, particularly endometriosis” (page 1 lines 4-5, emphasis added). Petersen further teaches that “[t]he prevalence of the disease [endometriosis] is about 7-10% of women of reproductive years, with a familial association risk increase of tenfold. Definitive diagnosis is only reached by laparoscopy, but typically there is about a ten year delay from disease onset to conclusive diagnosis” (page 1 lines 11-14).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have applied the methods of diagnosing and treating taught by Pages to the disease of endometriosis taught by Pages from a list of other 14 diseases, that is to have picked endometriosis from the finite list of diseases, because Petersen teaches that there is a need for better diagnostic methods of endometriosis given that there is a ten year delay from disease onset to conclusive diagnosis. One would have been motivated to have tried picking endometriosis in order to help the 7-10% of women of reproductive years who are suffering from endometriosis. A person having ordinary skill in the art would have had a reasonable expectation of success because Petersen teaches that endometriosis is a NAP2-mediated disease. Furthermore, Pages and Petersen are interested in methods of treating endometriosis.
Regarding claims 3-4, Pages in view of Petersen teach the method of claim 2 as discussed above.
Pages in view of Petersen further suggest wherein the method determines the extent of endometrial fibrosis and adhesion in the subject by determining that the abundance of NAP2 higher than a predetermined value or is higher than the abundance of the same marker in plasma obtained from a healthy subject (page 30 lines 23-24 and page 31 line 2, page 33 lines 7-8 and 14, “diagnostic and/or prognostic method” page 35 lines 5-8 and 31-32 and page 36 lines 1-8 of Pages, emphasis added). Note that although Pages in view of Petersen fail to use the language “the method determines the extent of endometrial fibrosis and adhesion” the teaching of diagnosing/prognosing endometriosis inherently provides the determination of the extent of endometrial fibrosis and adhesion because adhesion and fibrosis are characteristics of endometriosis as evidenced by Vigano. Vigano teaches that “fibrosis appears as the phenomenon underpinning endometriosis-associated morbidity and some manifestations of the disease (i.e. adhesions)” page 349 col. 2 para. 3). Therefore, the method of diagnosing and/or prognosing endometriosis inherently provides the determination of endometrial fibrosis and adhesion, i.e. the extent of endometriosis progression.
Regarding claim 6, Pages in view of Petersen teach the method of claim 2 as discussed above.
Pages in view of Petersen further suggest wherein the method determines the degree of progression of endometriosis in a subject affected or suspected of being affected by endometriosis by determining that the abundance of NAP2 higher than a predetermined value or is higher than the abundance of the same marker in plasma obtained from a healthy subject (page 30 lines 23-24 and page 31 line 2, page 33 lines 7-8 and 14, “diagnostic and/or prognostic method” page 35 lines 5-8 and 31-32 and page 36 lines 1-8 of Pages, emphasis added). Note that although Pages in view of Petersen fail to use the language “the method determines the degree of progression of endometriosis in a subject affected or suspected of being affected by endometriosis” the teaching of diagnostic and/or prognostic methods for endometriosis inherently provides the determining the degree of progression of endometriosis in a subject affected or suspected of being affected by endometriosis because a diagnostic and/or prognostic method for endometriosis is applied to subjects who are affected or suspected of being affected by the disease.
Regarding claims 8 and 17, Pages in view of Petersen teach the method of claims 1-2 as discussed above.
Pages in view of Petersen further suggest wherein the abundance of NAP2 is the concentration of NAP2 polypeptide in plasma (page 33 lines 7-8 and 14, “The term "expression" generally refers to the process by which a polynucleotide sequence undergoes successful transcription and translation such that detectable levels of the amino acid sequence or protein are expressed” page 39 lines 18-20 of Pages).
Claims 7 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Pages et al. (WO 2014184384 Al) (“Pages”) in view of Busch-Petersen et al. (WO 2007150015 A2) (“Petersen”) and Guidowani (JP 2018520353 A).
Regarding claim 7, Pages suggests a method of monitoring pathological conditions of endometriosis in a subject affected or suspected of being affected by endometriosis and treating a subject that has been determined to have a condition of endometriosis worsening or potentially worsening (“prevention and treatment of diseases related to the chemokines CXCLI, CXCL7 and CXCL8, particularly of pathological angiogenesis diseases” page 1 lines 3-5, “pathological angiogenesis diseases…are selected from the group consisting of:…endometriosis” page 30 lines 23-24 and page 31 line 2, “The term "biological sample" encompasses a variety of sample types obtained from an organism that may be used in a diagnostic or monitoring assay” page 33 lines 8-9 (emphasis added), “The invention also relates to in vitro or ex vitro diagnostic and/or prognostic method, and particularly to an in vitro diagnostic and/or prognostic method of a disease related to the chemokines CXCLI, CXCL7 and CXCL8, particularly of a pathological angiogenesis disease” page 35 lines 5-8), comprising measuring the abundance of Neutrophil-activating peptide 2 (NAP2) in a plasma sample collected from the subject (“determining the expression and/or the level of expression of at least one human chemokine chosen in the group consisting of CXCLI, CXCL7 and CXCL8 in a biological sample of said subject” page 35 lines 9-11, “The term "biological sample" encompasses…plasma” page 33 lines 7-8 and 14). Note that CXCL7 is the same as NAP2 (“NAP2 (CXCL7)” page 2 lines 13-14). Pages further teaches administering a therapeutic agent for endometriosis to the subject that has been determined to have a condition of endometriosis worsening or potentially worsening (“The invention also relates to a method of treatment and/or prophylaxis of diseases related to the chemokines CXCLI, CXCL7 and CXCL8, particularly of pathological angiogenesis diseases , or diseases characterized by undesirable excessive neovascularization, said method comprises the step of administering to a patient in need thereof a therapeutically or prophylactic amount of at least one compound selected from the group consisting of: - an antibody and a fragment thereof according to the invention” page 31 lines 14-19). Note that although Pages fails to use the language “administering a therapeutic agent for endometriosis to the subject that has been determined to have a condition of endometriosis worsening or potentially worsening” the teaching of administering a therapeutic antibody for treating a pathological angiogenic disease “to a patient in need thereof” together with the teaching that the pathological angiogenic disease may be endometriosis (page 31 line 2) inherently provides the administering a therapeutic agent for endometriosis to the subject that has been determined to have a condition of endometriosis worsening or potentially worsening. Pages further teaches wherein the subject is determined to have a condition of endometriosis worsening or potentially worsening when the abundance of NAP2 is higher than a predetermined value or is higher than the abundance of the same marker in plasma obtained from a healthy subject (“the method of the invention comprises the step ii) of comparing said level of expression determined at step i) to a control level and determining if said level of expression determined at step i) is significantly higher than said control level; said significantly higher level of expression indicates that the subject is affected with a disease related to the chemokines CXCLI, CXCL7 and CXCL8, particularly with a pathological angiogenesis disease…wherein said control level is the expression level of said at least one chemokine determined in at least a biological sample from an healthy subject, or from a subject who is not affected with a disease related to the chemokines CXCLI, CXCL7 and CXCL8, particularly with a pathological angiogenesis disease” page 35 lines 31-32 and page 36 lines 1-8).
Pages teaches the claimed method but directed to a list of 15 pathological angiogenesis diseases, “endometriosis” being one of the 15 diseases listed (see page 30 lines 23-33 and page 31 lines 1-3). Pages fails to teach a plurality of plasma samples collected from the subject at different points of time, wherein the subject is determined to have a condition of endometriosis worsening or potentially worsening when the abundance of NAP2 is higher than the abundance of the same marker in plasma collected from the subject at an earlier point in time.
Petersen teaches a “method of treatment” (Title). Petersen further teaches “the use of sulfonamide substituted diphenyl urea compounds to treat IL-8, GROa, GROβ, GROγ, NAP-2, and ENA-78 mediated diseases, particularly endometriosis” (page 1 lines 4-5, emphasis added). Petersen further teaches that “[t]he prevalence of the disease [endometriosis] is about 7-10% of women of reproductive years, with a familial association risk increase of tenfold. Definitive diagnosis is only reached by laparoscopy, but typically there is about a ten year delay from disease onset to conclusive diagnosis” (page 1 lines 11-14).
Guidowani teaches “methods and kits for diagnosing, predicting and / or monitoring gynecological diseases…based on changes in the glycosylation pattern of CA125” (Abstract). Guidowani further suggests a method of monitoring endometriosis in a subject affected or suspected of being affected by endometriosis (“particularly gynecological disease selected from the group consisting of EOC, endometriosis and endometrial cancer. Provided are means and methods for determining a gynecological disease state in a subject suspected of having or at risk of suffering from” bridge paragraph pages 1-2 and page 2 para. 2 emphasis added). Guidowani further suggests the method comprising measuring the abundance of a biomarker in a plurality of plasma samples, wherein the subject is determined to have a condition of endometriosis worsening or potentially worsening when the abundance of the biomarker is higher than the abundance of the same marker in plasma collected from the subject at an earlier point in time (“a blood sample, serum sample or plasma sample is the most preferred sample type used in the present method and all embodiments thereof… different samples taken from the subject whose gynecological disease status is to be determined can be used for each assessment” page 3 paras. 4-5, “monitoring endometriosis…[t]he method may comprise the steps of assaying a sample for CA125 .sup.MGL and assaying the same or different sample taken from the subject for CA125 protein concentration. In such methods, a non-increased CA125 .sup.MGL level combined with an increased CA125 protein concentration indicates that the subject is suffering from endometriosis or is at risk of suffering from endometriosis” page 10 para. 4, the term “level” is interchangeable with the terms “amount” and “concentration” unless otherwise indicated. To determine whether the detection level of a biomarker is indicative of the presence or risk of a disease associated with the biomarker, that level in the relevant control must be determined” page 3 paras. 6-7, “the term `` control sample '' is a sample taken from the same subject from which a gynecological disease state is to be determined, but a sample taken at a time different from the time of disease state determination. Point to. Non-limiting examples of such different include one or more before diagnosis of the disease” page 4 para. 3). Note that although Guidowani fails to use the language “wherein the subject is determined to have a condition of endometriosis worsening or potentially worsening when the abundance of the biomarker is higher than the abundance of the same marker in plasma collected from the subject at an earlier point in time” the teaching of an increase in plasma biomarker concentration being indicative of endometriosis together with the teaching that the control sample may be a sample taken from the same subject from a time before diagnosis, inherently provides “wherein the subject is determined to have a condition of endometriosis worsening or potentially worsening when the abundance of the biomarker is higher than the abundance of the same marker in plasma collected from the subject at an earlier point in time”. Guidowani further teaches that measuring the abundance of a biomarker in a plurality of plasma samples, wherein the subject is determined to have a condition of endometriosis worsening or potentially worsening when the abundance of the biomarker is higher than the abundance of the same marker in plasma collected from the subject at an earlier point in time enables “a population screening protocol…This allows not only early diagnosis of EOC, endometriosis or endometrial cancer, but also effective monitoring for the development of EOC, endometriosis or endometrial cancer in the subject. And an increased risk of developing EOC, endometriosis or endometrial cancer in later life is identified. Furthermore, early detection of EOC, endometriosis or endometrial cancer allows the disease to be treated at an early stage when the chance of healing is greatest” (page 13 para. 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have applied the method of monitoring and treating pathological conditions taught by Pages to the disease of endometriosis taught by Pages from a list of other 14 diseases, that is to have picked endometriosis from the finite list of diseases, because Petersen teaches that there is a need for methods of monitoring endometriosis given that there is a ten year delay from disease onset to conclusive diagnosis. One would have been motivated to have tried picking endometriosis in order to help the 7-10% of women of reproductive years who are suffering from endometriosis. A person having ordinary skill in the art would have had a reasonable expectation of success because Petersen teaches that endometriosis is a NAP2-mediated disease. Furthermore, Pages and Petersen are interested in methods of treating endometriosis.
It would have been further prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Pages in view of Petersen to include a plurality of plasma samples collected from the subject at different points of time, wherein the subject is determined to have a condition of endometriosis worsening or potentially worsening when the abundance of NAP2 is higher than the abundance of the same marker in plasma collected from the subject at an earlier point in time suggested by Guidowani because Guidowani teaches that this enables the screening and early stage treatment of endometriosis, which is when the chance of healing is greatest. One would have been motivated to make such a modification in order to help the 7-10% of women of reproductive years who are suffering from endometriosis. A person having ordinary skill in the art would have had a reasonable expectation of success because Pages in view of Petersen and Guidowani are interested in monitoring endometriosis.
Regarding claim 18, Pages in view of Petersen and Guidowani teach the method of claim 7 as discussed above.
Pages in view of Petersen and Guidowani further suggest wherein the abundance of NAP2 is the concentration of NAP2 polypeptide in plasma (page 33 lines 7-8 and 14, “The term "expression" generally refers to the process by which a polynucleotide sequence undergoes successful transcription and translation such that detectable levels of the amino acid sequence or protein are expressed” page 39 lines 18-20 of Pages).
Response to Arguments
Applicant's arguments filed 5/22/2026 have been fully considered but they are not persuasive.
Regarding the 101 rejections,
Applicant argues that “Applicants have herein amended the claims to recite "A method of diagnosing and treating endometriosis ... and administering a therapeutic agent for endometriosis to a subject that has been diagnosed as having endometriosis ... "…Applicants submit that the claims as amended are believed to accommodate, remedy and/or render moot the rejection under 35 USC § 101” (page 11 para. 6 and page 12 para. 1).
However, the claim amendments fail to integrate the judicial exceptions into a practical application given that the treatment step is not a particular treatment, i.e. the treatment reads on mere instructions to “apply” the exception in a generic way. Furthermore, the treatment steps are well-understood, routine and conventional, and fail to add significantly more than the judicial exception. See the rejection above for the complete analysis.
Regarding the prior art rejections,
Applicant argues that “the claims as amended accommodate, remedy and/or render moot the rejection under 35 U.S.C. 102…Applicants welcome the Examiner's acknowledgement that "no prior art teaching Neutrophil-activating peptide 2 as a marker of endometriosis was found." See, OA, p. 20” (page 12 paras. 4-5).
However, in further consideration of the amendments, remarks and the prior art, a new issue of obviousness is raised (see 103 rejection above). In this case, the current examiner’s search uncovered references that render obvious the claimed methods. Thus, new grounds of rejection are set forth under 103, necessitated by the amendments.
Applicant further “Request for Rejoinder of Claim 16” (page 12 para. 6).
However, no claim is allowed.
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 FERNANDO IVICH whose telephone number is (703)756-5386. The examiner can normally be reached M-F 9:30-6:00 (E.T.).
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 at (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 published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Fernando Ivich/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
Prosecution Insights