DETAILED ACTION
CONTINUED EXAMINATION UNDER 37 CFR 1.114 AFTER FINAL REJECTION
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission of RCE and the amendment filed on June 12, 2025 have been entered. The claims pending in this application are claims 16, 18-21, 23, 25-28, 30, 31, 33, 34, 37, 39, and 41-44 wherein claims 20 and 27 have been withdrawn due to the restriction requirement mailed on April 29, 2022. The rejections not reiterated from the previous office action are hereby withdrawn in view of applicant’s amendment filed on June 12, 2025. Claims 16, 18, 19, 21, 23, 25, 26, 28, 30, 31, 33, 34, 37, 39, and 41-44 will be examined.
Claim Objections
Claim 16 or 43 is objected to because of the following informalities: (1) “wherein each of said detecting molecules is used for determining the expression level of said one of said biomarker proteins” in (b) should be “wherein each of said detecting molecules is used for determining the expression level of said one of said biomarker proteins in a biological sample”; and (2) “wherein each of said additional detecting molecules is used for determining the expression level of said one of said additional biomarker proteins and/or control reference proteins in a biological sample” in (b) should be “wherein each of said additional detecting molecules is used for determining the expression level of said one of said additional biomarker proteins and/or control reference proteins in the biological sample”.
Claim 23 or 44 is objected to because of the following informality: “wherein each of said detecting molecules is used for determining the expression level of said one of said biomarker proteins in a biological sample” in b) should be “wherein each of said detecting molecules is used for determining the expression level of said one of said biomarker proteins in the biological sample”.
Claim 30 is objected to because of the following informality: “(i) comprising” in b) should be “(i)”.
Claim 33 is objected to because of the following informality: “obtaining uterine lavage fluid (UtLF) sample or a plasma sample” should be “obtaining said uterine lavage fluid (UtLF) sample or plasma sample”.
Appropriate correction is required.
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.
Scope of Enablement
This rejection is modified from the rejection under 35 U.S.C. 112(a) mailed on January 13, 2025.
Claims 16, 18, 19, 21, 23, 25, 26, 28, 30, 31, 33, 34, 37, 39, and 41-44 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for specifically determining the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins in a uterine lavage fluid (UtLF) sample using a diagnostic composition recited in claims 16, 18, 19, 41, and 43 and a kit recited in claims 21, 23, 25, 26, 28, 30, 31, 33, 34, 37, 39, 42, and 44 when at least six detecting molecules are at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins, does not reasonably provide enablement for specifically determining the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins in a plasma sample or specifically determining the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins and additional 20-30 any kind of biomarker proteins in a uterine lavage fluid (UtLF) sample or a plasma sample using a diagnostic composition recited in claims 16, 18, 19, 41, and 43 and a kit recited in claims 21, 23, 25, 26, 28, 30, 31, 33, 34, 37, 39, 42, and 44 when at least six detecting molecules are at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
The Nature of The Invention
The claims are drawn to a diagnostic composition and a kit. The invention is a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The Breadth of The Claims
Claims 16, 18, 19, 21, and 41 encompass a diagnostic composition consisting of: (a) at least six detecting molecules for specifically determining the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins, wherein each of said detecting molecules is specific for one of said biomarker proteins, and wherein each of said detecting molecules is used for determining the expression level of said one of said biomarker proteins in a biological sample or (b) at least six detecting molecules for specifically determining the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins, wherein each of said detecting molecules is specific for one of said biomarker proteins, and wherein each of said detecting molecules is used for determining the expression level of said one of said biomarker proteins in a biological sample; and at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 additional detecting molecule or molecules for specifically determining the expression level or levels of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 additional biomarker proteins and/or control reference proteins, wherein each of said additional detecting molecules is specific for one of said additional biomarker proteins and/or control reference proteins, and wherein each of said additional detecting molecules is used for determining the expression level of said one of said additional biomarker proteins and/or control reference proteins in the biological sample; wherein said biological sample is a uterine lavage fluid (UtLF) sample or a plasma sample. Claims 23, 25, 26, 28, 30, 31, 33, 34, 37, 39, and 42 encompass a kit comprising: at least six detecting molecules for specifically determining the level of expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins in a biological sample, wherein each of said detecting molecules is specific for one of said biomarker proteins, and wherein each of said detecting molecules is used for determining the expression level of said one of said biomarker proteins; or b) at least six detecting molecules for specifically determining the level of expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins in a biological sample, wherein each of said detecting molecules is specific for one of said biomarker proteins, and wherein each of said detecting molecules is used for determining the expression level of said one of said biomarker proteins in the biological sample and at least 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 detecting molecules for specifically determining the expression level/levels of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 additional biomarker proteins and/or control reference proteins in a biological sample, wherein each of said additional detecting molecules is specific for one of said biomarker proteins and/or control reference proteins, and wherein each of said additional detecting molecules is used for determining the expression level of said one of said additional biomarker proteins and/or control reference proteins; wherein said biological sample is a uterine lavage fluid (UtLF) sample or a plasma sample; the kit further comprising at least one of c) pre-determined calibration curves or predetermined standards for providing standard expression values of said biomarker proteins; and d) at least one control sample. Claim 43 encompasses a diagnostic composition consisting of: (a) at least six detecting molecules for specifically determining the expression levels of six, seven, eight or nine of: CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINBS, CLUAP1, CEACAMS5 and ENPP3 biomarker proteins, wherein each of said detecting molecules is specific for one of said biomarker proteins, and wherein each of said detecting molecules is used for determining the expression level of said one of said biomarker proteins in a biological sample; or (b) at least six detecting molecules for specifically determining the expression levels of six, seven, eight or nine of: CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINBS5, CLUAP1, CEACAMS and ENPP3 biomarker proteins, wherein each of said detecting molecules is specific for one of said biomarker proteins, and wherein each of said detecting molecules is used for determining the expression level of said one of said biomarker proteins; and at least 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 additional detecting molecule or molecules for specifically determining the expression level or levels of 1, 2, 3,4, 5,6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30, additional biomarker proteins and/or control reference proteins, wherein each of said additional detecting molecules is specific for one of said additional biomarker proteins and/or control reference proteins, and wherein each of said additional detecting molecules is used for determining the expression level of said one of said additional biomarker proteins and/or control reference proteins in a biological sample; wherein said biological sample is a uterine lavage fluid (UtLF) sample or a plasma sample. Claim 44 encompasses a kit comprising: (I) detecting molecules consisting of the composition of claim 43: a) at least six detecting molecules for specifically determining the expression levels of six, seven, eight or nine of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINBS, CLUAP1, CEACAMS and ENPP3 biomarker proteins, in a biological sample, wherein each of said detecting molecules is specific for one of said biomarker proteins, and wherein each of said detecting molecules is used for determining the expression level of said one of said biomarker proteins; or b) at least six detecting molecules for specifically determining the expression levels of six, seven, eight or nine of: CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINBS, CLUAP1, CEACAMS and ENPP3 biomarker proteins, in a biological sample, wherein each of said detecting molecules is specific for one of said biomarker proteins, and wherein each of said detecting molecules is used for determining the expression level of said one of said biomarker proteins in a biological sample; and at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 detecting molecule or molecules for specifically determining the expression level/levels of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 additional biomarker proteins and/or control reference proteins in a biological sample, wherein each of said additional detecting molecules is specific for one of said biomarker proteins and/or control reference proteins, and wherein each of said additional detecting molecules is used for determining the expression level of said one of said additional biomarker proteins and/or control reference proteins; wherein said biological sample is a uterine lavage fluid (UtLF) sample or a plasma sample; the kit further comprising at least one of: (II) pre-determined calibration curves or predetermined standards for providing standard expression values of said biomarker proteins; and (III) at least one control sample.
Working Examples
The specification provides 16 examples (see pages 38-40 of US 2020/0033351 A1, which is US publication of this instant case). However, the specification provides no working example for specifically determining the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins in a plasma sample or specifically determining the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins and additional 20-30 any kind of biomarker proteins in a uterine lavage fluid (UtLF) sample or a plasma sample using a diagnostic composition recited in claims 16, 18, 19, 41. and 43 and a kit recited in claims 21, 23, 25, 26, 28, 30, 31, 33, 34, 37, 39, 42, and 44 when at least six detecting molecules are at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins.
The Amount of Direction or Guidance Provided and The State of The Prior Art
Although the specification provides 16 examples (see pages 38-40 of US 2020/0033351 A1, which is US publication of this instant case), the specification provides no working example for specifically determining the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins in a plasma sample or specifically determining the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins and additional 20-30 any kind of biomarker proteins in a uterine lavage fluid (UtLF) sample or a plasma sample using a diagnostic composition recited in claims 16, 18, 19, 41, and 43 and a kit recited in claims 21, 23, 25, 26, 28, 30, 31, 33, 34, 37, 39, 42, and 44 when at least six detecting molecules are at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins. Furthermore, there is no experimental condition and/or experimental data in the specification to support the claimed invention. There is no prior art related to specifically determine the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins in a plasma sample or specifically determine the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins and additional 20-30 any kind of biomarker proteins in a uterine lavage fluid (UtLF) sample or a plasma sample using a diagnostic composition recited in claims 16, 18, 19, 41, and 43 and a kit recited in claims 21, 23, 25, 26, 28, 30, 31, 33, 34, 37, 39, 42, and 44 when at least six detecting molecules are at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins.
Level of Skill in The Art, The Unpredictability of The Art, and The Quantity of Experimentation Necessary
While the relative skill in the art is very high (the Ph.D. degree with laboratory experience), there is no predictability whether the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins can be specifically determined in a plasma sample or the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins and additional 20-30 any kind of biomarker proteins can be specifically determined in a uterine lavage fluid (UtLF) sample or a plasma sample using a diagnostic composition recited in claims 16, 18, 19, 41, and 43 and a kit recited in claims 21, 23, 25, 26, 28, 30, 31, 33, 34, 37, 39, 42, and 44 when at least six detecting molecules are at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins.
First, although the specification shows that the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins can be specifically determined in a uterine lavage fluid (UtLF) sample (see Figures 2, 5, and 13, Example 3 and Tables 4 and 5 in pages 39 and 40 of US 2020/0033351 A1, which is US publication of this instant case), since the claims do not require that 1-30 additional biomarker proteins are proteins in a uterine lavage fluid (UtLF) sample, and the specification and available arts do not show that a plasma sample contains at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins or a uterine lavage fluid (UtLF) sample or a plasma sample contains at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins and additional 20-30 any kind of biomarker proteins, it is unpredictable how the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins can be specifically determined in a plasma sample or the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins and additional 20-30 any kind of biomarker protein can be specifically determined in a uterine lavage fluid (UtLF) sample or a plasma sample using a diagnostic composition recited in claims 16, 18, 19, 41, and 43 and a kit recited in claims 21, 23, 25, 26, 28, 30, 31, 33, 34, 37, 39, 42, and 44 when at least six detecting molecules are at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins.
Second, since at least six detection molecules in (a) or (b) of claim 43 or 44 can be read as six detection molecules, if the at least six detection molecules in (a) or (b) of claim 43 or 44 is only six detection molecules, it is unpredictable how the six detecting molecules can specifically determine the expression levels of seven, eight or nine of: CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINBS, CLUAP1, CEACAMS5 and ENPP3 biomarker proteins wherein each of said detecting molecules is specific for one of said biomarker proteins.
Case law has established that “(t)o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’.” In re Wright 990 F.2d 1557, 1561. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) it was determined that “[T]he scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification to persons of ordinary skill in the art”. The amount of guidance needed to enable the invention is related to the amount of knowledge in the art as well as the predictability in the art. Furthermore, the Court in Genentech Inc. v Novo Nordisk 42 USPQ2d 1001 held that “[I]t is the specification, not the knowledge of one skilled in the art that must supply the novel aspects of the invention in order to constitute adequate enablement”.
In view of above discussions, the skilled artisan will have no way to predict the experimental results. Accordingly, it is concluded that undue experimentation is required to make the invention as it is claimed. These undue experimentation at least includes to test whether the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins can be specifically determined in a plasma sample or the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins and additional 20-30 any kind of biomarker protein can be specifically determined in a uterine lavage fluid (UtLF) sample or a plasma sample using a diagnostic composition recited in claims 16, 18, 19, 41, and 43 and a kit recited in claims 21, 23, 25, 26, 28, 30, 31, 33, 34, 37, 39, 42, and 44 when at least six detecting molecules are at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins.
Conclusion
In the instant case, as discussed above, the level of unpredictability in the art is high, the specification provides one with no guidance that leads one to claimed methods. One of skill in the art cannot readily anticipate the effect of a change within the subject matter to which the claimed invention pertains. Thus given the broad claims in an art whose nature is identified as unpredictable, the unpredictability of that art, the large quantity of research required to define these unpredictable variables, the lack of guidance provided in the specification, the absence of any working example related to claimed invention and the no teaching in the prior art balanced only against the high skill level in the art, it is the position of the examiner that it would require undue experimentation for one of skill in the art to perform the method of the claim as broadly written.
Response to Arguments
In page 13, last paragraph bridging to page 16, second paragraph of applicant’s remarks, applicant argues that “[F]irst, as argued previously, the specification in paragraphs [0374] to [0391], clearly teaches in detail the sample collection [0374]-[0376], the sample preparation [0377]-[0380], Microvesicle proteomics and Computational analysis of the data [0381]-[0385], the RNA Extraction and qRT-PCR [0386]-[0387], as well as immunohistochemistry [0388 ]-[0389]. Moreover, as detailed by Example 2 [0394]-[0395], and Example 3 [0396]-[0401], proteomic profiling identified a total of 8760 proteins, and an average of 3200 per sample, from which the signatory proteins were identified. Still further, detection methods and detecting molecules are extensively disclosed and described by the present disclosure, see for examples from [0206]-[0233] for protein-based detecting molecules and the corresponding methods, paragraphs [0234]-[0253] that describe nucleic acid-based detecting molecules and the corresponding methods, and paragraphs [0254]-[0266], that describe various MS methods for detecting and determining the levels of biomarker molecules. Importantly, the present disclosure provides detailed description of various biological samples applicable for the claimed compositions and kits as detailed through paragraphs [0269] to [0272], as well as in paragraphs [0276] to [0282] US 2020/0033351 A1. The present disclosure therefore provides clear guidance to detect and determine the expression levels of at least six of the signatory proteins, and in some embodiments, of additional 1- 30 biomarker proteins or reference proteins as required by the claims, in any biological sample, specifically, any of the samples disclosed by the present specification. Nevertheless, solely to advance prosecution, the claims were amended by limiting the biological sample to uterine lavage fluid (UtLF) sample or plasma sample, as supported by paragraphs [083], [085], [0346], and specifically in paragraphs [0276], [0281] and Example 2, paragraphs [0394]-[0395] of US 2020/0033351 A1. As clearly pointed in Example 2, specifically in paragraph [0395], "the previously developed method for microparticle isolation from plasma was examined for the application to UtL samples", additionally, paragraphs [0374] to [0378] describe collection and preparation of UtL samples, and paragraphs [0379] and [0380], describe collection and preparation of tumor samples. The present disclosure therefore clearly provides not only written description, but working examples for any biological sample, and in particular for uterine lavage fluid (UtLF) and plasma samples”.
These arguments have been fully considered but they are not persuasive toward the withdrawal of the rejection.
First, the rejection is a scope of enablement rejection and is not a written description rejection as argued by applicant.
Second, although the specification shows that the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins can be specifically determined in a uterine lavage fluid (UtLF) sample (see Figures 2, 5, and 13, Example 3 and Tables 4 and 5 in pages 39 and 40 of US 2020/0033351 A1, which is US publication of this instant case), since the claims do not require that 1-30 additional biomarker proteins are proteins in a uterine lavage fluid (UtLF) sample, and the specification and available arts do not show that a plasma sample contains at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins or a uterine lavage fluid (UtLF) sample or a plasma sample contains at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins and additional 20-30 any kind of biomarker proteins, it is unpredictable how the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins can be specifically determined in a plasma sample or the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins and additional 20-30 any kind of biomarker protein can be specifically determined in a uterine lavage fluid (UtLF) sample or a plasma sample using a diagnostic composition recited in claims 16, 18, 19, 41, and 43 and a kit recited in claims 21, 23, 25, 26, 28, 30, 31, 33, 34, 37, 39, 42, and 44 when at least six detecting molecules are at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINB5, CLUAP1, CEACAMS and ENPP3 biomarker proteins.
Third, since at least six detection molecules in (a) or (b) of claim 43 or 44 can be read as six detection molecules, if the at least six detection molecules in (a) or (b) of claim 43 or 44 is six detection molecules, it is unpredictable how six detecting molecules can specifically determine the expression levels of seven, eight or nine of: CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINBS, CLUAP1, CEACAMS5 and ENPP3 biomarker proteins wherein each of said detecting molecules is specific for one of said biomarker proteins.
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 16, 18, 21, 23, 25, 28, 30, 31, 33, 34, 37, and 41-44 are rejected under 35 U.S.C. 101 because the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Claims 16, 18, 21, and 43 is directed to a diagnostic composition consisting of at least six detecting molecules for specifically determining the expression levels of at least six of CLCA4, OVGP1, S100A14, SPRR3, RNASE3, SERPINBS, CLUAP1, CEACAMS and ENPP3 biomarker proteins, wherein each of said detecting molecules is specific for one of said biomarker proteins, and wherein each of said detecting molecules is used for determining the expression level of said one of said biomarker proteins in a biological sample, or/and at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 additional detecting molecule or molecules for specifically determining the expression level or levels of 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 additional biomarker proteins and/or control reference proteins, wherein each of said additional detecting molecules is specific for one of said additional biomarker proteins and/or control reference proteins, and wherein each of said additional detecting molecules is used for determining the expression level of said one of said additional biomarker proteins and/or control reference proteins in a biological sample, wherein said biological sample is a uterine lavage fluid (UtLF) sample or a plasma sample while claims 23, 25, 28, 30, 31, 33, 34, 37 and 42 or 44 are directed to a kit comprising the diagnostic composition recited in claim 16 or 43 and at least one of pre-determined calibration curves or predetermined standards for providing standard expression values of said biomarker proteins and at least one control sample. However, the detection molecules in claims 16, 18, 21, 23, 25, 28, 30, 31, 33, 34, 37, and 41-44, as written, do not sufficiently distinguish over proteins which exist naturally because the claims do not particularly point out any non-naturally occurring difference between the claimed detection molecules and the naturally occurring protein. Furthermore, pre-determined calibration curves in claims 23, 25, 28, 30, 31, 33, 34, 37 and 42 or 44 is a mental process which a human can finish with a physical aid such as pen and paper or slide rule or calculator, predetermined standards for providing standard expression values of said biomarker proteins in claims 23, 25, 28, 30, 31, 33, 34, 37 and 42 or 44 is a set of human-defined rules, at least one control sample in claims 23, 25, 28, 30, 31, 33, 34, 37 and 42 or 44 can be a uterine lavage fluid (UtLF) sample or a plasma sample from a normal subject, and the instruction in claim 30 can be written by a human based on a mental process. Therefore, the detection molecules in claims 16, 18, 21, 23, 25, 28, 30, 31, 33, 34, 37, and 41-44 and the at least one control sample in claims 23, 25, 28, 30, 31, 33, 34, 37, 42, and 44 are not eligible because they are not different enough from what exist in nature and are “product of nature” exception while the pre-determined calibration curves or predetermined standards for providing standard expression values of said biomarker proteins in claims 23, 25, 28, 30, 31, 33, 34, 37, 42, and 44 and the instruction in claim 30 fall into the “mental process” groups of abstract ideas. Because claims 16, 18, 21, 23, 25, 28, 30, 31, 33, 34, 37, and 41-44 do not include any additional features that could add significantly more to the exception, these claims do not qualify as eligible subject matter, and should be rejected under 35 U.S.C. § 101.
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.
No claim is allowed.
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/FRANK W LU/
Primary Examiner, Art Unit 1683
September 26, 2025