DETAILED CORRESPONDENCE 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. This action is in response to the papers filed December 4, 2023 . Currently, claims 13-18 are pending. Priority This application claims priority to It is noted that a translation of the foreign document has not been received. Drawings The drawings are acceptable. 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 13-1 8 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. 35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson , 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106, part II. Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility. Question 1 The claimed invention is directed to a process that involves a natural principle and a judicial exception. Question 2 A Prong I The claims are taken to be directed to a n abstract idea, a law of nature and a natural phenomenon. Claim 13 is directed to “ a method for treating cancer” by measuring expression level of SPSB2 wherein the measured expression is higher than that of a control indicates the subject is affected by cancer and excising a cancer tissue or performing anti-cancer agent treatment to the subject . Claim 13 is directed to a process that involves the judicial exceptions of an abstract idea (i.e. the abstract idea of “indicates that the subject is affected by cancer” and “the expression level …is higher than that of a control ”) and a law of nature/natural phenomenon (i.e. the natural correlation between the expression level and cancer ). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow. Herein, claim 13 involves the patent-ineligible concept of an abstract process . Claim 13 requires performing the step of “ indicates that the subject is affected by cancer ”. Neither the specification nor the claims set forth a limiting definition for " indicates " and the claims do not set forth how “ indicates ” is accomplished. As broadly recited the indicates recitation may be accomplished mentally by thinking about a subject’s expression level and mentally determining whether the subject has cancer . Thus, the determining step constitutes an abstract process idea . Claim 13 further recites a comparison between the expression level and a normal control that is deemed an abstract idea (see MPEP 2106.04(a)(2)(III)(A); • claims to “comparing BRCA sequences and determining the existence of alterations,” where the claims cover any way of comparing BRCA sequences such that the comparison steps can practically be performed in the human mind, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 763, 113 USPQ2d 1241, 1246 (Fed. Cir. 2014) ). A correlation that preexists in the human is an unpatentable phenomenon . The association between expression level of SPSB2 and cancer is a law of nature/natural phenomenon. The indicates recitation which tells users of the pr ocess to predict cancer in the sample, amounts to no more than an "instruction to apply the natural law". This indication is no more than a mental step. Even if the step requires something more such as to verbalize the discovery of the natural law, this mere verbalization is not an application of the law of nature to a new and useful end. The indicates does not require the process user to do anything in light of the correlation. The indicates recitation fails to provide the “practical assurance” sought by the Prometheus Court that the “process is more than a drafting effort designed to monopolize the law of nature itself.” Question 2 A Prong II The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception. While the claim recites measuring expression level of SPSB2 and excising a cancer tissue or performing anti-cancer agent treatment , this is not an integration of the exception into a practical application. The measuring expression step is a data collection step. The excising a cancer tissue or performing anti-cancer agent treatment is general in nature and not particularly drawn to the judicial exception. While the claim recites excising a cancer tissue or performing anti-cancer agent treatment , this is not an integration of the exception into a practical application. The limitation does not indicate how the patient is to be treated, or what the treatment is but instead covers any possible anti-cancer agent treatment that a doctor decides to administer to the patient. The excising a cancer tissue or performing anti-cancer agent treatment limitation fails to meaningfully limit the claim because it does not require any particular application of the recited calculation, and is at best the equivalent of merely adding the words “apply it” to the judicial exception. Furthermore, it is not clear that the treatment step is required or whether the step is optional. The claim provides the treatment is performed where the subject is affected by cancer. It is not clear if this requires the treatment or only “if” the subject is affected by cancer. In the event the treatment step is conditional and not required, the claim does not require administering the treatment and as such does not provide an integration of the judicial exception. Accordingly, the claims are directed to judicial exceptions. Question 2B The second step of Alice involves determining whether the remaining elements, either in isolation or combination with the other non patent ineligible elements, are sufficient to “’transform the nature of the claim’ into a patent eligible application” Alice , 134 S. Ct. at 2355 (quoting Mayo , 132 S. Ct. at 1297). The claims are not sufficiently defined to provide a method which is significantly more from a statement of a natural principle for at least these reasons: The claims do not include applying the judicial exception, or by use of, a particular machine. The claims do not tie the steps to a “particular machine" and therefore do not meet the machine or transformation test on these grounds. The use of machines generally does not impose a meaningful limit on claim scope. The claims also do not add a specific limitation other than what is well-understood, routine and conventional in the field. The measuring expression level is mere data gathering step that amounts to extra solution activity to the judicial exception. It merely tells the users of the method to determine the biomarkers of a sample without further specification as to how the sample should be analyzed. The claim s do not recite a new, innovative method for such determination. The measuring expression level essentially tells users to determine the expression through whatever known processes they wish to use. The step of determining the expression levels was well known in the art at the time the invention was made. The prior art teaches that expression analysis using commercially available biochips and arrays that comprise the claimed genes. The steps are recited at a high level of generality. The claim merely instructs a scientist to use any expression analysis assay to determine the expression level status. The claim does not require the use of any particular non-conventional reagents. When recited at this high level of generality, there is no meaningful limitation that distinguishes this step from well understood, routine and conventional activities engaged in by scientists prior to applicant’s invention and at the time the application was filed. Additionally, the teachings in the specification demonstrate the well understood, routine, conventional nature of additional elements because it teaches that the additional elements were well known. Specifically, the specification teaches the expression level of the SPSB2 gene was examined using the Cancer Genome Atlas which is a public database (page 15, para 43). Further it is noted that the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity. Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546; Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014) For these reasons the claims are rejected under section 101 as being directed to non-statutory subject matter. Claim Rejections - 35 USC § 112-Scope of Enablement The following is a quotation of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. Claim s 13-18 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 methods of determining the expression level of SPSB2 , does not reasonably provide enablement for a method of treating any cancer by measuring an expression level of SPSB2 in any sample . 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 t he 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 and breadth of claims The claims are drawn to a method of treating any cancer by measuring an expression level of SPSB2 in any sample. The invention is in 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 unpredictability of the art and the state of the prior art The art teaches analysis of Spsb2 in heptocellular carcinoma (see Tian et al. Genes, Vol. 16, No. 346, March 17, 2025). Tian teaches differential expression analysis of SPSB2 in pan-cancer and Liver cancer. Tian illustrates not all cancers overexpress SPSB2. As seen in Figure 2A, many of the comparison were not significant. Even more, KICH, KIRC, LUSC, PCPG, PRAD showed decreased expression. Habermann et al. (US 2013/0196876, August 1, 2013) teaches analyzing SPSB2 protein by incubating a sample with antibodies with a protein encoded by SPSB2 (see para 10) and comparing the amount to a control. Habermann teaches SPSB2 is d ownregulated compared to healthy controls. Guidance in the Specification. The specification provides no evidence that the broad scope of the claims is enabled. The specification teaches SPSB2 gene is not over expressed in all cancers. The specification teaches SPSB2 was strongly expressed in pancreatic cancer and moderately expressed in hepatocellular carcinoma and ovarian cancer, but not expressed in kidney, prostate, esophageal, gastric, colon, breast or lung cancers (para 60). The specification teaches SPSB2 can not be detected in all types of samples. In particular, SPSB2 protein was not found in exosomes from serum or normal healthy patients (para 68). The specification teaches urinary tract infections also show expression of SPSB2 in patients with urinary tract infection is higher than bladder cancer patients (para 75). The guidance provided by the specification amounts to an invitation for the skilled artisan to try and follow the disclosed instructions to make and use the claimed invention. Quantity of Experimentation The quantity of experimentation in this area is extremely large since there is significant number of parameters which would have to be studied to enable the skilled artisan to practice the claimed invention as broadly as claimed. The claims are directed to a method that requires measuring an expression level of SPSB2 and detecting overexpression of SPSB2 as indicative of cancer. Neither the specification nor the art teaches that all cancers are associated with over expression of SPSB2. The specification teaches SPSB2 gene is not over expressed in all cancers. The specification teaches SPSB2 was strongly expressed in pancreatic cancer and moderately expressed in hepatocellular carcinoma and ovarian cancer, but not expressed in kidney, prostate, esophageal, gastric, colon, breast or lung cancers (para 60). Tian illustrates not all cancers overexpress SPSB2. As seen in Figure 2A, many of the comparison were not significant. Even more, KICH, KIRC, LUSC, PCPG, PRAD showed decreased expression. Therefore, it would require further unpredictable experimentation to determine which cancers overexpress SPSB2 and which cancers do not show an association or are under expressed . The art teaches pancreatic cancer is downregulated in pancreatic adenomas compared to healthy controls. This would require further unpredictable and undue experimentation to study the vast number of cancers encompassed by the claims. The claims are directed to measuring expression level of SPSB in any biological sample including exosomes extracted from urine and urine. The specification teaches SPSB2 can not be detected in all types of samples. In particular, SPSB2 protein was not found in exosomes from serum or normal healthy patients (para 68). The skilled artisan would be unable to use exosome from serum to determine whether a subject has overexpression of SPSB2. The claims are directed to using any control subject including subject that have with urinary tract infections. T he specification teaches urinary tract infections also show expression of SPSB 2 in patients with urinary tract infection is higher than bladder cancer patients (para 75). It would require further unpredictable and undue experimentation to determine how to diagnose cancer in patients with urinary tract infections using SPSB2 expression. This would require significant inventive effort, with each of the many intervening steps, upon effective reduction to practice, not providing any guarantee of success in the succeeding steps. Level of Skill in the Art The level of skill in the art is deemed to be high. Conclusion 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 a working example and the negative teachings 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. Claim Rejections - 35 USC § 112- Second Paragraph 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. Claim s 13-18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention. Claim 13 recites “where the subject is affected by cancer”. It is unclear whether the claim requires detecting a subject who is affected by cancer and cancer tissue is excised or an anti-cancer agent is administered. It is unclear whether the claim only excises a cancer tissue or performs anti-cancer agent treatment if SPSB2 over expression is detected or whether the claim requires the SPSB2 over expression was detected. The claim does not clearly set forth any active method steps other than measuring. The claim only provides wherein clauses that do not require actively detecting higher than a control level of expression. Clarification is required. Claim 18 contain s trademark/trade names to anti-cancer agents . Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe anti-cancer agents and, accordingly, the identification/description is indefinite. Claim Rejections - 35 USC § 102 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention. 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 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. Claim(s) 13, 15, 18 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Ping et al. (Carcinogenesis, Vol. 41, No. 7, pages 887-893, 2020). Ping teaches analyzing differences in gene-expression profiles in breast cancer. Ping teaches analyzing SPSB2 (see Table 2, halfway down). The claim encompasses not performing any surgery or treatment to subject who were not affected by cancer. Figure 1 illustrates normal patients were treated. These patients were not treated. With respect to Claim 15, Ping teaches using tissue samples. With respect to Claim 18, no treatment is administered. Claim(s) 13-15, 18 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Habermann et al. (US 2013/0196876, August 1, 2013). Habermann teaches analyzing SPSB2 protein by incubating a sample with antibodies with a protein encoded by SPSB2 (see para 10) and comparing the amount to a control. Habermann teaches SPSB2 is downregulated compared to healthy controls. With respect to Claim 15, Habermann teaches using blood or sera samples (para 39). With respect to Claim 18, no treatment is administered. Conclusion No claims allowable over the art. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Zeng et al. (Gastroenterology, Vol. 150, pages 1633-1645, 2016) teaches SPSB2 has a SNP that is associated with colorectal risk (see Table 1). 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