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 .
.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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 filed on July 22, 2026 has been entered.
This action is in response to the papers filed July 22, 2026. Currently, claims 13, 16, 18-20 are pending.
All arguments have been thoroughly reviewed but are deemed non-persuasive for the reasons which follow.
Any objections and rejections not reiterated below are hereby withdrawn.
The 102 rejection over Matsumoto has been withdrawn in view of the amendments to the claims to determine whether the subject has a UTI.
Priority
This application claims priority to
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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, 16, 18-20 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 2A Prong I
The claims are taken to be directed to an 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 and excising a cancer tissue or performing anti-cancer agent treatment to the subject. The claim has been further amended to include a law of nature, namely “wherein presence of both (i) and (ii) indicates the subject is affected by cancer.
Claim 13 is directed to a process that involves the judicial exceptions of an abstract idea (i.e. the abstract idea of “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 presence of UTI 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.
Claim 13 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, presence of UTI and cancer is a law of nature/natural phenomenon. The indicates recitation which tells users of the process 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 2A 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, the treatment step is optional. The claim provides the treatment is performed “only when the measured expression level is higher than a control and the subject does not have a UTI”. Since the claim is conditional and cancer tissue is only excised “in response to determining that” the measured expression level is higher and a control the claim does not require the excising or 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 claims 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.
Response to Arguments
The response traverses the rejection. The response asserts the subject matter is analogous to that claimed in Vanda Pharmaceuticals. As noted by the response, the claims of Vanda required a step of treating the patient with….a particular medication that was tailored to the patient’s genotype. Specifically, Vanda provided a much more particular and tailored treatment (see below).
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This is in stark contrast to the instant claims that measure an expression level and determine “whether” the subject has a urinary tract infection and “excise a cancer tissue from the subject or performing anti-cancer agent treatment to the subject” only in response to determining that the measured expression is higher than a control. Unlike the claims in Vanda, the instant claims are directed to excising cancer tissue or performing anti-cancer agent treatment of an unspecified therapeutic agent. This is not a step of treating the patient with a particular medication tailored to the patient’s expression level. As such, this claim is directed to the relationship and is not a practical application of the judicial exception.
The response also argues that a single claim element related to comparing is not sufficient to warrant a 101 rejection particularly when the claim includes concrete physical steps and not mere mental processes. This argument has been considered but is not convincing because the claim remains directed to a judicial exception. The rejection above carefully considers each element required for patent eligibility. The claim recites several judicial exceptions. The limitations of the claims in addition to the judicial exceptions are recited at a high level of generality and there is no meaningful limitation, such as a particular or unconventional machine or a transformation of a particular article, in this step that distinguishes it from well-understood, routine, and conventional data gathering activity engaged in by scientists prior to applicant' s invention, and at the time the application was filed, e.g., the routine and conventional techniques of detecting a protein using an antibody to that protein. Further, it is well established that the mere physical or tangible nature of additional elements such as the obtaining and detecting steps does not automatically confer eligibility on a claim directed to an abstract idea (see, e.g., Alice Corp. v. CLS Bank Int' l, 134 S.Ct. 2347, 2358-59 (2014)).
Claim 13 is further conditional and only requires existing cancer tissue “only in response to determining that the measured expression level is higher than a control and the subject does not have a UTI”. Thus, the claim does not require performing any “treatment” step if the subject has a UTI or the expression level is not higher than a control. The claim could be amended to clarify the treatment step is required. It is noted this would not overcome all aspects of the 101 rejection but would clarify the conditional nature and render the claim more concise.
13. (Currently Amended) A method for treating bladder cancer, comprising:
a) measuring an expression level of an SPSB2 protein or an SPSB2 gene in a biological sample derived from a subject;
b) determining whether the subject has a urinary tract infection (UTI);
c) determining that the subject has a measured expression level of SPSB2 protein or gene is higher than a control and the subject does not have a UTI,
d) excising a cancer tissue from the subject by surgical operation or performing anti-cancer agent treatment on the subject
wherein the biological sample is tissue or urine of the subject.
Thus for the reasons above and those already of record, the rejection is maintained.
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.
Claims 13, 16, 18-20 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 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 and breadth of claims
The claims are drawn to a method of treating bladder 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 hepatocellular 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 downregulated compared to healthy controls in pancreatic adenomas (Table 1).
Guidance in the Specification.
The specification provides no evidence that the broad scope of the claims is enabled.
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 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 measuring expression level of SPSB in any biological sample including exosomes extracted from urine and urine. The specification teaches SPSB2 cannot 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.
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.
Response to Arguments
The response traverses the rejection. The response does not particularly argue the samples may include exosomes. The specification teaches SPSB2 was not found in exosomes. It would require further unpredictable and undue experimentation to determine how to diagnose bladder cancer in patients without urinary tract infections using SPSB2 expression in samples with exosomes. 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.
Thus for the reasons above and those already of record, the rejection is maintained.
Duplicate Claim warning
Applicant is advised that should claim 16 be found allowable, claim 20 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Conclusion
No claims allowable.
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).
Ping et al. (Carcinogenesis, Vol. 41, No. 7, pages 887-893, 2020) 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng (Winston) Shen can be reached on (571) 272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
August 25, 2026
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