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 .
Claim Rejections - 35 USC § 112
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 1-3, 7, and 9-23 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Independent claims 1, 18, and 19, recites “wherein the patient is suspected of having or has stage I endometriosis according to revised Americal Society for Reproductive Medicine (rASRM) staging or stage II endometriosis according to rASRM staging”.
Some of the claims dependent on these independent claims also refer to the “revised American Society for Reproductive Medicine (rASRM) stagin or stage II endometriosis according to rASRM staging”.
It is not clear as to what comprises the “revised Americal Society for Reproductive Medicine (rASRM) staging or stage II endometriosis according to rASRM staging”.
Applicant’s specification states: “The term "rASRM stage" or "rASRM staging" refers to the revised classification system established by the American Society for Reproductive Medicine (ASRM) describing the severity of endometriosis based on the findings at surgery (laparoscopy).” This classification system appears to be incorporated into Applicant’s claim 1. However, what this revised system comprises is not clear. Moreover, a classification system can or may have been revised at different times, and it is not clear as to which revised classification system is being referred. Also, a “revised” system appears to be subject to change, which further renders the claim vague and indefinite.
The remaining claims are rejected because they depend on one of the claims above without remedying the lack of clarity.
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 1-3, 7, and 9-23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature or an abstract idea without significantly more.
Independent claim 1 recites “comparing the measuring amount or concentration to reference”.
Examiner notes that “comparing” is a mental step and thus an abstract idea, which is a judicial exception.
In other words, these limitations require a comparison between i) a measurement or observation of the individual and ii) the standard recited (the revised American Society for Reproductive Medicine (rASRM) staging or stage II endometriosis according to rASRM staging.) Such a comparison is an abstract idea. The limitations of claim 20 and its dependent claims also require an assessment “whether the patient has endometriosis or is at risk of developing endometriosis”. Such an assessment is also an abstract idea, which is a judicial exception. Examiner also notes that such an assessment is based on a correlation between a measurement or observation and the state of having stage I endometriosis. Such correlation is a natural law, which is a judicial exception.
These judicial exceptions are not integrated into a practical application because the combination of additional elements fail to integrate the judicial exception into a practical application. The data gathering step of measuring the amount or concentration of S100A12, in a sample that is blood, serum, or plasma, do not add a meaningful limitation to the method as it is an insignificant extra-solution activity.
Moreover, the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the following reasons. Regarding claim 1, there are no further limitations in addition to the data gathering step, and the judicial exception of comparing and assessing.
Regarding claims dependent on claim 1, they either recite limitations that are details of the judicial exception (such as the particular type of endometriosis), and/or they do not recite a practical application or additional limitations that are not well-known, conventional, and routine in the art. Therefore when considered separately and in combination, any additional recitations in the remaining claims do not add significantly more (also known as an “inventive concept”) to the exception.
Similarly, independent claims 2 and 3 each recite “comparing the measured amount or concentration to a reference”.
As mentioned further above, such comparing is an abstract idea, i.e., a judicial exception. Moreover, such an assessment is also an abstract idea (a judicial exception) and is also based on a correlation that is a natural law, which is also a judicial exception
These judicial exceptions are not integrated into a practical application because the combin.ation of additional elements fail to integrate the judicial exception into a practical application. The data gathering step of measuring the amount or concentration of S100A12 in blood, serum or plasma do not add a meaningful limitation to the method as it is an insignificant extra-solution activity.
Moreover, the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the following reasons. Regarding claim 1, there are no further limitations in addition to the data gathering step recited at a high level of generality, and the judicial exceptions mentioned above.
These judicial exceptions are not integrated into a practical application because the combination of additional elements fail to integrate the judicial exception into a practical application. The data gathering step of detecting the elevated amount or concentration of S100A12, and contacting the sample, that is blood, serum, or plasma, with an antibody that bind to S100A12, do not add a meaningful limitation to the method as it is an insignificant extra-solution activity.
Moreover, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. For example, the step of contacting the sample with an agent that is an antibody that binds S100A12 is well-known, conventional, and routine in the art, as exemplified by US 20120171694 (Mansfield), which discloses methods for predicting the presence of ovarian cancer (see abstract), by detecting biomarkers that includes…. EN-RAGE…….and CA-125 (see para. 0032) (Examiner notes that EN-RAGE is the same as S100A12), through performing immunoassays, such as enzyme-linked immunosorbent assays and multiplexed immunoassays (para. 0031) using antibodies as binding molecules to measure the biomarkers (para. 0034).
Similarly, independent claim 20 recites:
“comparing the measure amount or concentration to a reference”, and
“assessing whether the patient has endometriosis or is at risk of developing endometriosis”.
For the same reasons as discussed above regarding claim 1, such comparing is an abstract idea, i.e., a judicial exception. Moreover, such an assessment is also an abstract idea (a judicial exception) and is also based on a correlation that is a natural law, which is also a judicial exception (as discussed above, regarding claim 1).
These judicial exceptions are not integrated into a practical application because the combination of additional elements fail to integrate the judicial exception into a practical application. The data gathering step of measuring the amount of S100A12, and incubating the sample, that is blood, serum, or plasma, with an antibody that bind to S100A12, and quantifying the complex do not add a meaningful limitation to the method as it is an insignificant extra-solution activity.
Moreover, claim 20 does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception. For example, the step of incubating the sample with an agent that is an antibody that binds S100A12 and quantifying the complex are well-known, conventional, and routine in the art, as exemplified by US 20120171694 (Mansfield), which discloses methods for predicting the presence of ovarian cancer (see abstract), by detecting biomarkers that includes…. EN-RAGE…….and CA-125 (see para. 0032) (Examiner notes that EN-RAGE is the same as S100A12), through performing immunoassays, such as enzyme-linked immunosorbent assays and multiplexed immunoassays (para. 0031) using antibodies as binding molecules to measure the biomarkers (para. 0034).
Regarding claims dependent on claim 20, they do not recite a practical application or additional limitations that are not well-known, conventional, and routine in the art. Therefore when considered separately and in combination, any additional recitations in the remaining claims do not add significantly more (also known as an “inventive concept”) to the exception.
Examiner further notes that amendment to claim 2 has NOT overcome the rejection of claim 2 under 35 USC 101 since the drug-based therapy of endometriosis or surgical-based therapy is not required by the claim. Claim 2 merely recites “selecting the patient for drug-based therapy of endometriosis or surgical therapy of endometriosis (laparoscopy) based on the comparison”. Examiner notes that selecting a patient for a therapy is not actually providing the therapy. Examiner notes that the therapies recited in claim 2 as well as 24 appear to be sufficiently tailored to endometriosis, however, the claim does not require these therapies. Therefore the claims (including claims 2 and 24) do not recite a practical application to the judicial exception.
Similarly, regarding amended claim 3, which recites “monitoring the patient suffering from endometriosis or being treated for endometriosis based on the comparison” is not a specific or tailored practical application. For example, monitoring is not a therapy.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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.
Claims 17-23 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
The claims require an agent that binds to S100A12, wherein the agent is an antibody. The specification does not describe which amino acid residues, nucleic acid residues or other molecular components are responsible for the functions claimed. The specification fails to disclose the structures common to all members of the genus encompassed by the broad definition provided by applicant. The specification does not disclose the structure of all of the claimed variant agents and fails to disclose which regions of the agents are responsible for the functions claimed. In the absence of a known or disclosed correlation between structure and function, claims which encompass variants defined by their function are generally not considered described.
Applicant is directed to MPEP § 2163 for guidelines on compliance with the written description requirement. Here, applicant has not described a reasonable number of members of the genus of agents or antibodies that bind to S100A12, i.e. the required starting materials for the claims, but rather has presented the public with an idea of how to perform an assay that might identify some peptides that fall within the scope of the claim. Of course, depending on what agents are used in the screening assay, it may well identify none. The Court of Appeals for the Federal Circuit addressed claims of this sort in great detail in University of Rochester v. G.D. Searle and Co. (69 USPQ 2nd 1886, CAFC 2004). In Rochester, the Federal Circuit upheld the district court's ruling that patent claims which recited administration of compounds not disclosed, but rather to be identified in a screening assay, were invalid on their face.
Regarding the scope of the claims that includes antibodies that bind to S100A12, the specification does not describe the structure of the full genus of antibodies responsible for each of the functions claimed. The Federal Circuit has clarified Written Description as it applies to antibodies in the recent decision Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. 112(a) (or pre-AIA first paragraph) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called “newly characterized antigen” test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the “newly characterized antigen” test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad, 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of an antigen alone is not considered adequate written description of a claimed antibody to that antigen, even when preparation of such an antibody is routine and conventional. Id.
While generically the structure of antibodies is known, the structure of the presently recited antibodies can vary substantially within the above given claimed recitations. As noted in Amgen, knowledge that an antibody binds to a particular epitope on an antigen tells one nothing at all about the structure of the antibody, wherein “instead of analogizing the antibody-antigen relationship to a ‘key in a lock,’ it [is] more apt to analogize it to a lock and ‘a ring with a million keys on it.” (Internal citations omitted). The relevant antibody art confirms this quandary, indicating that “knowledge of an epitope or antigen used to generate a monoclonal antibody is insufficient for making the original antibody available, even if suitable in vitro test systems for screening are used.” See p. 8, lines 3-5 of WO 2009/033743 A1. Therefore, those of skill in the art would not accept that the inventor had been in possession of the full genus of antibodies presently claimed.
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Abbvie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (759 F.3d 1285 (Fed. Cir. 2014). “When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus." Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005).
Consequently, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus of binding agents (including antibodies) nor guidance as to which of the myriad of molecules encompassed by the binding agents would meet the limitations of the claims. Further, given the well-known high level of polymorphism of immunoglobulins and antibodies, the skilled artisan would not have recognized that applicant was in possession of the vast repertoire of antibodies encompassed by the claimed invention.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991), clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
The skilled artisan cannot envision the detailed chemical structure of the genus of binding agents, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of identification. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991). Therefore, the instant claims do not meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
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.
Claim(s) 1-3, 7, 9-12, and 18-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over EP 3961217 (hereinafter “Kobayashi”).
Kobayashi discloses a method of diagnosing endometriosis, comprising measuring S100-A12. See claim 1 and paras. 0001 and 0011 and 0018-0021. The marker S100A12 is found to be highest in plasma of endometriosis patients, and lowest in health individuals (para. 01116). Kobayahishi also discloses monitoring patients diagnosed with or affected by endometriosis (para. 0094).
Thus Applicant’s claims 1-3, 7, 9, 10, 11, and 18-22 is rendered obvious given these disclosures by Kobayashi.
The claims are either directed to detecting or measuring S100A12 (such as in claim 1, 18, 19, and their dependent claims) or assessing or monitoring whether the patient has endometriosis or is at risk of developing endometriosis (such as in claims 2, 3, 20, and their dependent claims) and are not tied to use of S100A12 for diagnosing endometriosis. Based on the broadest reasonable interpretation, the assessing can encompass any known means, such as rASRM staging, which is known, and the detection of S100A12 is also known, as shown by Kobayashi. Thus Applicant’s present claims are not distinct over the prior art.
Applicant recites known limitations, including detection of S100A12 (e.g., claim 1) and endometriosis according to rASRM staging, and such combinations in a claim is rendered obvious given that one skilled in the art would study the biomarker from those with endometriosis. Likewise, selecting a patient for drug-based therapy or surgical therapy of endometriosis (e.g., claim 2) and endometriosis according to rASRM staging are known in the art, and such combinations in a claim is rendered obvious given that one skilled in the art would provide therapy to those having symptoms of endometriosis.
As to claim 2, selecting a patient for drug-based therapy or surgical therapy based on the comparison would have been obvious to one skilled in the art as it would have been predictable that therapy would be desirable in the case of diagnosis of endometriosis. Kobayashi also shows that treatments are known, and that a delay in diagnosis would lead to a delay in the start of treatment of endometriosis (para. 0003).
Regarding claims 11-12, Kobayashi discloses diagnosing endometriosis, and does not exclude any particular endometriosis, and thus Kobayashi’s teaching provides a prima face case of obviousness regarding specific types of endometriosis.
As to claims 20-21, use of a second antibody that is labeled is well known in the art, and such is also disclosed by Kobayashi (see for example para. 0011).
Claim(s) 13 and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over EP 3961217 (Kobayashi) in view of Ameade et al. “Menstrual Pain Assessment: Comparing Verbal Rating Scale (VRS) with Numerical Rating Scales (NRS) as Pain Measurement Tools” Int J Womens Health Wellness 2016, 2:017, Vol. 2, Issue 1.
Kobayashi has been discussed above.
However, regarding claim 13, Kobayashi is silent as to the disclosed method further comprising an assessment of dysmenorrhea according to a VAS scale.
Regarding claim 15, Kobayashi is silent as calculating a ratio of the amount or concentration of S100A12 and dysmenorrhea.
The Kobayashi disclosure as mentioned above encompasses monitoring or diagnosing patients with endometriosis (paras. 0001 and 0011 and 0018-002 and 0094), thus rendering claim 13 obvious as it would have been obvious that such patients suspected of having endometriosis symptoms should be tested for endometriosis.
Moreover, assessment of dysmenorrhea according to a VAS scale is known in the art, as shown by Armeade, (see first page under “Introduction”) and providing such an assessment in addition to assessing whether the patient has endometriosis (as discussed regarding claim 1 above) requires ordinary skills in the art since it merely adds a second assessment that is known in the art, shown by Armeade, as may be desirable for a more comprehensive assessment of a woman’s health, and in particular reproductive health.
Claim(s) 14 and 16 and 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over EP 3961217 (Kobayashi) in view of Irungu et al. “Discovery of non-invasive biomarkers for the diagnsosis of endometriosis”, Clinical Proteomics, Vol. 16, no. 1, 6 April 2019, pages 1-16.
Kobayahsi has been discussed above regarding claim 1.
Regarding claim 14, Kobayashi is silent as to the method further comprising determining the amount of CA-125.
Regarding claims 16 and 23, Kobayashi is silent as to calculating a ratio of the amount of [S100A12] and the amount of CA-125.
Determining the amount of S100A12 is disclosed by Kobayashi as discussed above regarding claim 1.
Moreover, CA-125 is a known biomarker of endometriosis, as shown by Irungu (see “Abstract” on the first page, under the subheading “Methods”.) Determining the amount of S100A12 and the amount of CA-125 in a patient to have been obvious given that these two biomarkers are known markers of endometriosis. Thus determining the ratio of the amount of these two biomarkers appear to be prima facie obvious, as it merely provides data to the clinician or doctor as may be desirable in assessing endometriosis or comparing assessments of endometriosis of a patient compared to other patients or compared to the same patient over time, for study in general or for the medical care of the patient.
Response to Arguments
The following arguments made by Applicant have been fully considered. Some rejections are no longer held as Applicant’s amendments have overcome those rejections. However, Applicant’s amendments and arguments are not persuasive as to the remaining rejections.
With respect to the rejections under 35 USC 112 regarding “wherein the patient is suspected of having or has stage I endometriosis according to revised Amerian Society for Reproducitve Medicine (rASRM) staging or stage II endometriosis according to rASRM staging”, Applicant’s arguments are not persuasive. Applicant submits Exhibit E3 and states that the American Fertility Society, renamed the American Society for Reproducitve Medicine (ASRM) in 1995, appointed an Endometriosis Classification Subcommitte to assess formally the current revised AFS classification. The earlier iterations of the classification were published under the American Fertility Society name and are identified in Exhibit E3 as the AFS classification of 1979 and the revised AFS classification of 1985. Applicant further states that “rASRM” is not a generic reference to whichever revision is current at a given time, but rather identifies the single revised classification published under the American Society for Reproductive Medine name, that being the classification adopted in 1996 and published in Fertility and Sterility in May 1997. Applicant asserts that a person of ordinary skill in the at would understand that “rASRM staging” to refer to that one publication and to no other.
Applicant also asserts that no further revision of the rASRM classification was published between its publication in 1997 and the January 13, 202 filing date of the present application, a period of more than twenty-four years.
This is not found persuasive. The claim recites, for example, “stage I endometriosis according to revised American Society for Reproductive Medicine (rASRM) staging or stage II endometriosis according to rASRM staging”. The broadest reasonable interpretation is that it refers to the American Society for Reproductive Medicine, which in itself is vague and indefinite limitation as it relies on a limitation that is subject to change, and it also refers to a “revised” staging, which is also vague and indefinite since it refers to a revision without limiting what this revision is. While Applicant may intend to refer to a single revised classification published under the American Society for Reproductive Medine name, that being the classification adopted in 1996 and published in Fertility and Sterility in May 1997, this is not in the claim itself. In any case, even if it was in the claim, it is not clear as to what the staging encompass in order to diagnose endometriosis. The metes and bounds of Applicant’s claim cannot be ascertained, and therefore the claims are vague and indefinite.
Regarding claim 13, Applicant’s amendment and disclosures on pages 9-10 render the limitation in claim 13 clear.
Regarding the rejections under 35 USC 101, Applicant states that the Office relies on Mansfield as demonstrating contacting a sample with an antibody that binds S100A12 is well-understood, routine, and convention. The Office itself expressly stated in the Non-Final Office action dated June 18, 2025 that Mansfield does not support use of S100A12 as a biomarker for diagnosing or determining risk of developing endometriosis.
Examiner clarifies here that Mansfield is cited in this Office action to show that the assay steps [the data gathering technique] is well-known, conventional, and routine. That is, incubating a sample with a specific antibody for binding and detection is well-known, conventional, and routine, exemplified shown by Mansfield. Applicant cannot rely on a judicial exception itself to support that the claim is significantly more than the judicial exception. Detection of SA10012 in a blood sample to diagnose or determine risk of developing endometriosis is itself the judicial exception. There is no need to provide a reference to show that the judicial exception itself is significantly more than the judicial exception [that is, there is no need to provide a reference to show that detection of SA10012 in a blood sample to diagnose or determine risk of developing endometriosis is well-known, conventional, and routine, since this is the judicial exception itself, and in order to overcome the rejection under 35 USC 101, there must be limitations in the claim that is significantly more than the judicial exception, or a practical application]. There must be other limitations (beyond the judicial exception itself) that must be recited that amounts to significantly more than the judicial exception in order to overcome the present rejection under 35 USC 101.
Applicant asserts that the Office has cited no evidence that measuring S100A12 in blood, serum, or plasma of a patient having rASRM stage I or stage II endometriosis was routine or conventional in that field, and its own statements on this record indicate the contrary.
Examiner notes that measuring S100A12 is data gather and does not integrate the judicial exception into a practical application and do not add meaningful limitation to the method as it is an insignificant extra-solution activity.
Applicant further asserts that in the Final Office action dated December 2, 2025, the Office withdrew the rejections under 35 USC 103 and found that given the unpredictability in biochemistry and therefore the diagnostic art, the prior art does not teach or fairly suggest detecting S100A12 in a sample that is blood, serum or plasma. (Final Office Action, p. 16).
Examiner would like to clarify that Mansfield is no longer being relied upon for rejection under 35 USC 103. However, the rejection under discussion here is not 35 USC 103, but 35 USC 101. Mansfield is relied upon to show that Applicant’s data gathering step of measuring an analyte (as recited in claims 1, 2, 3 and their dependent claims) or measuring an analyte by contacting a sample with a binding agent and detecting binding (as recited in claims 18, 19, 20 and their dependent claims) is recited at a high level of generality such that they encompass assay techniques that are well-known, conventional, and routine in the art, as exemplified by Mansfield.
The grounds for rejection on this matter have been clarified and are reproduced below.
For example, the step of contacting the sample with an agent that is an antibody that specifically binds the analyte is well-known, conventional, and routine in the art, as exemplified by US 20120171694 (Mansfield), which discloses detecting biomarkers that includes…. EN-RAGE…….and CA-125 (see para. 0032; Examiner notes that EN-RAGE is the same as S100A12), through performing immunoassays, such as enzyme-linked immunosorbent assays and multiplexed immunoassays (para. 0031) using antibodies as binding molecules to measure the biomarkers (para. 0034). Applicant’s claims recite the assay at a high level of generality such that it encompasses well-known, routine, and conventional assays.
Applicant’s response regarding the written description rejections under 35 USC 112 is not persusasive. Applicant concludes that the specification discloses two independently sourced antibody systems that the inventors obtained and used: a commercial sandwich ELISA kit identified by manufacturer, distributor, and catalogue number CY-8058V2, employing a monoclonal capture antibody and enzyme-linked monoclonal detection antibody specific for human S100A12; and a pre-commerical sandwich eCLIA assay comprising a biotinylated and a ruthenylated monoclonal antibody specific for s100A12, run on a cabas e 801 analyzer. Both were used to generate the diagnostic performance data reported in Tables 1 and 3 through 5, across three clinical studies.
This is not found to be persuasive. As noted in the grounds for rejection, the specification does not describe the structure of the full genus of antibodies responsible for each of the functions claimed. The Federal Circuit has clarified Written Description as it applies to antibodies in the recent decision Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. 112(a) (or pre-AIA first paragraph) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called “newly characterized antigen” test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the “newly characterized antigen” test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad, 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of an antigen alone is not considered adequate written description of a claimed antibody to that antigen, even when preparation of such an antibody is routine and conventional. Id.
While generically the structure of antibodies is known, the structure of the presently recited antibodies can vary substantially within the above given claimed recitations. As noted in Amgen, knowledge that an antibody binds to a particular epitope on an antigen tells one nothing at all about the structure of the antibody, wherein “instead of analogizing the antibody-antigen relationship to a ‘key in a lock,’ it [is] more apt to analogize it to a lock and ‘a ring with a million keys on it.” (Internal citations omitted). The relevant antibody art confirms this quandary, indicating that “knowledge of an epitope or antigen used to generate a monoclonal antibody is insufficient for making the original antibody available, even if suitable in vitro test systems for screening are used.” See p. 8, lines 3-5 of WO 2009/033743 A1. Therefore, those of skill in the art would not accept that the inventor had been in possession of the full genus of antibodies presently claimed.
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Abbvie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (759 F.3d 1285 (Fed. Cir. 2014). “When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus." Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005).
Consequently, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus of binding agents (including antibodies) nor guidance as to which of the myriad of molecules encompassed by the binding agents would meet the limitations of the claims. Further, given the well-known high level of polymorphism of immunoglobulins and antibodies, the skilled artisan would not have recognized that applicant was in possession of the vast repertoire of antibodies encompassed by the claimed invention.
Regarding the rejections under 35 USC 103, Applicant asserts that the only listing of S100A12 that qualifies is entry in Table 2A, among approximately one hundred proteins. Applicant argues that Kobayashi does not indicate how S100A12 would perform as a diagnostic marker.
Examiner acknowledges Applicant’s points, but notes that nothing in Applicant’s claims requires use of S100A12 as a diagnostic marker.
Independent Claim 1 recites a “non-invasive method of determining whether a sample has an elevated amount or concentration of S100A12” (preamble), and there is no recitation of use of S100A12 as a diagnostic marker in claim 1 or any dependent claim.
Claim 2 recites a “non-invasive method of selecting a patient for drug-based therapy or surgical therapy (laparascopy) of endometriosis” (preamble), and there is no recitation of use of S100A12 as a diagnostic marker in claim 2 or any dependent claim.
Claim 3 recites a “non-invasive method of monitoring a patient suffering from endometriosis or being treated for endometriosis” (preamble), and there is no recitation of use of S100A12 as a diagnostic marker in claim 3 or any dependent claim.
Claim 18 recites a “method of detecting an amount or concentration of S100A12 in a patient” (preamble), and there is no recitation of use of S100A12 as a diagnostic marker in claim 18 or any dependent claim.
Claim 19 recites a “method for measuring the amount of S100A12 in a sample from a patient”, and there is no recitation of use of S100A12 as a diagnostic marker in claim 19 or any dependent claim.
Claim 20 recites a “non-invasive method of assessing whether a patient has endometriosis or is at risk of developing endometriosis”, and there is no recitation of use of S100A12 as a diagnostic marker in claim 19 or any dependent claim.
Examiner notes that “assessing whether the patient has endometriosis or is at risk of developing endometriosis” is not tied to use of S100A12. Based on the broadest reasonable interpretation, the assessing can encompass any known means, such as rASRM staging.
Examiner suggests that Applicant consider how Applicant’s claimed invention may be recited to be different from what is known in the prior art.
Endometriosis and its symptoms are known in the art, such as according to rASRM. Applicant recites known limitations, including detection of S100A12 (e.g., claim 1) and endometriosis according to rASRM staging, and such combinations in a claim is rendered obvious given that one skilled in the art would study the biomarker from those with endometriosis. Likewise, selecting a patient for drug-based therapy or surgical therapy of endometriosis (e.g., claim 2) and endometriosis according to rASRM staging are known in the art, and such combinations in a claim is rendered obvious given that one skilled in the art would provide therapy to those having symptoms of endometriosis.
The claims are either directed to detecting or measuring S100A12 (such as in claim 1, 18, 19, and their dependent claims) or assessing or monitoring whether the patient has endometriosis or is at risk of developing endometriosis (such as in claims 2, 3, 20, and their dependent claims) and are not tied to use of S100A12 for diagnosing endometriosis. Based on the broadest reasonable interpretation, the assessing can encompass any known means, such as rASRM staging, which is known, and the detection of S100A12 is also known, as shown by Kobayashi. Thus Applicant’s present claims are not distinct over the prior art.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/Ann Montgomery/ Primary Examiner, Art Unit 1678
