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 September 16, 2025. Currently, claims 11, 13-20, 22-26 are pending. Claims 17-20, 22-26 have been withdrawn as drawn to non-elected subject matter.
It is noted that the amended Claims filed March 30, 2022 state Claims 1-11 are cancelled and then start numbering with Claim 11. In view of the original claims, this appears to be a typo such that Claims 1-10 were cancelled. Clarification is required.
Election/Restrictions
Applicant's election without traverse of GALC (galactosylceramidase) in the paper filed September 16, 2025 is acknowledged. Claims 17-20, 22-26 are withdrawn as directed to non-elected subject matter.
The requirement is still deemed proper and is therefore made FINAL.
Priority
This application is a 371 of PCT/KR2020/010014, filed July 29, 2020 and claims priority to two Korean documents dated July 29, 2019 and July 29, 2020.
It is noted that a translation of the foreign documents have not been received.
Drawings
The drawings are acceptable.
Improper Markush Rejection
Claims 11, 13-15 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
A Markush claim contains an “improper Markush grouping” if:
(1) the species of the Markush group do not share a “single structural similarity,” or (2) the species do not share a common use. Members of a Markush group share a “single structural similarity” when they belong to the same recognized physical or chemical class or to the same art-recognized class. Members of a Markush group share a common use when they are disclosed in the specification or known in the art to be functionally equivalent. See MPEP § 2117.
Here each species is considered to each of the genes listed in Claim 11.
The recited alternative species in the group set forth here do not share a single structural similarity, as each different gene that could be detected is itself located in a separate region of the genome and has its own structure. The genes recited in the instant claims, do not share a single structural similarity since each consists of a different nucleotide sequence with different expression patterns. The only structural similarity present is that all detected positions are part of nucleic acid molecules. The fact that the markers comprise nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising a nucleotide alone is not essential to the common activity of being correlated with colorectal cancer. Accordingly, while the different markers are asserted to have the property of being expressed in colorectal cancer, they do not share a single structural similarity.
MPEP 2117 (II)(A) provides the following guidance as to what constitutes a physical, chemical, or art recognized class:
A recognized physical class, a recognized chemical class, or an art-recognized class is a class wherein “there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved”
The recited genes do not belong to a recognized chemical class because there is no expectation from the knowledge in the art that the genes will behave in the same manner and can be substituted for one another with the same intended result achieved. In other words, there is no expectation from the knowledge in the art that each of the recited genes would function in the same way in the claimed method; it is only in the context of this specification that it was disclosed that all members of this group may behave in the same way in the context of the claimed invention. Further there is no evidence of record to establish that it is clear from their very nature that each of the recited genes possess the common property of being associated with pancreatic cancer.
MPEP 2117 (II) further states the following:
Where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the compounds do not appear to be members of a recognized physical or chemical class or members of an art-recognized class, the members are considered to share a "single structural similarity" and common use when the alternatively usable compounds share a substantial structural feature that is essential to a common use. Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
The recited alternative species do not share a substantial common structure just because they all have a sugar phosphate backbone. The sugar phosphate backbone of a nucleic acid chain is not considered to be a substantial common structural feature to the group of genes being claimed because it is shared by ALL nucleic acids. Further, the fact that the genes all have a sugar phosphate backbone does not support a conclusion that they have a common single structural similarity because the structure of comprising a sugar phosphate backbone alone is not essential to the asserted common use of being associated with pancreatic cancer.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Following this analysis, the claims are rejected as containing an improper Markush grouping.
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 11, 13-16 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 11 is directed to “a method for diagnosing a risk of pancreatic cancer” by detecting mutation or functional decrease elected GALC and determining that there is a higher risk of pancreas cancer when the mutation or functional decrease of GACL is detected than when neither mutation decrease nor functional decrease is detected.
Claim 11 is directed to a process that involves the judicial exceptions of an abstract idea (i.e. the abstract steps of “diagnosing risk of pancreatic cancer”, “detecting mutation or functional decrease of GALC” and “determining a higher risk”) and a law of nature/natural phenomenon (i.e. the natural correlation between the mutation or functional decrease of GALC and pancreatic 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 11 involves the patent-ineligible concept of an abstract process. Claim 11 requires performing the step of “diagnosing risk of pancreatic cancer”, “detecting mutation or functional decrease of GALC” and “determining a higher risk”. Neither the specification nor the claims set forth a limiting definition for "detecting” or “determining" and the claims do not set forth how “detecting” or “determining” is accomplished. As broadly recited the detecting and determining step may be accomplished mentally by thinking about a subject’s data. Thus, the determining step constitutes an abstract process idea.
Claims 11 and 16 further recites a comparison of determining that there is a “higher risk” when the mutation or functional decrease of the GALC gene is detected than when neither mutation decrease nor functional decrease is detected 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 mutation or functional decrease of GALC and pancreatic cancer is a law of nature/natural phenomenon. The "determining" step which tells users of the process to predict pancreatic cancer in the sample, amounts to no more than an "instruction to apply the natural law". This assessing step 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 "determining" step does not require the process user to do anything in light of the correlation. The "determining " step 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.
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 detecting mutation or functional decrease or a gene 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 does not recite a new, innovative method for such determination. The determining step essentially tells users to determine the markers through whatever known processes they wish to use.
The step of detecting mutations and functional decrease in a gene was well known in the art at the time the invention was made. The steps are recited at a high level of generality. The claim merely instructs a scientist to use any mutation analysis to determine the functional and mutation 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.
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.
Claims 11, 13-16 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 detecting mutations in GALC, does not reasonably provide enablement for diagnosing risk of pancreatic cancer by detection mutation decrease or functional decrease of GALC. 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 for diagnosing a risk of pancreatic cancer by detecting mutation decrease or functional decrease in GALC and determining there is a higher risk of the pancreatic cancer when the mutation decrease or functional decreased is detected than when neither mutation decrease nor functional decrease is present.
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 mutations in the GALC gene are very heterogeneous (Xu et al. J. Human Genet. Vol. 51, pages 548-554, 2006). Xu teaches more than 60 GALC mutations, all with molecule heterogeneity have been reported worldwide (page 548, col. 1). Xu teaches different mutations have different concordance with diseases. Xu teaches for the Krabbe disease, there does not appear to be a correlation between residual enzyme activity and clinical severity (page 554, col. 1). Expression experiments did not reveal better residual activity in late-onset patients. Further, substrate specificity for several mutations led to loss of enzymatic activity for galctocerebroside as its natural substrate, nearly normal activity for psychosine, its second substrate was preserved. Measurement of enzyme activity with one substrate does not necessarily lead to identification of an essential defect. Xu further provides that compound alleles are required for reduced enzymatic activity (page 554, col. 1). Thus, it is unpredictable which activities are altered and associated with disease phenotypes.
Koh et al. (J. of Translational Medicine, Vol. 21, pages 1-17, 2023) (applicant’s own work) provides the mechanisms underlying lysosomal dysfunction in PDAC carcinogenesis should be further studied as increased proliferation of pancreatic cells and not complete carcinogenesis, after GALC knockdown was observed.
Guidance in the Specification.
The specification provides no evidence that the pancreatic cancer risk can be diagnosed with detecting mutation decrease or functional decrease of GALC. The specification teaches the risk of pancreatic cancer is about 5 times higher when there is mutation in the GALC gene as compared to a normal group with no mutation (page 5, lines 10-12). This is not mutation decrease compared to normal. This is increased mutation compared to normal.
The claims are directed to functional decrease. The specification does not provide how functional decrease is measured or calculated. There is no guidance what function is decreased or how the function is determined and/or measured.
The specification illustrates GALC expression level but it is not clear that decrease in expression is indicative of pancreatic cancer in the absence of PPV carrier organoids. The specification does not provide the expression level of normal controls and make a comparison of GALC expression in pancreatic cancer.
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 skilled artisan would be required to perform further unpredictable and undue experimentation to determine which mutations are associated with pancreatic cancer. The specification and the art provide a large number of mutations in the GALC gene, but fail to provide any guidance which mutations or which combinations of mutations are associated with pancreatic cancer and/or functional decrease.
With respect to functional decrease, the art teaches GALC has many functions. It is unclear which function is decreased. It is unclear whether gene expression is decreased, the break down of galactolipids is decreased, myelin maintenance is decreased, psychosine break down is decreased or lysosome function is decreased (functions of GALC enzyme).
Also, the art teaches that different mutations lead to loss of enzymatic activity for some substrates of the enzyme but not all substrates (see Xu). Thus, it is unpredictable and would require undue experimentation to determine how to measure and determine functional decrease that is diagnostic of pancreatic cancer. 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.
Claims 11, 13-16 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.
The term “higher” in claim 11 is a relative term which renders the claim indefinite. The term “higher risk of the pancreatic cancer” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. A subject may have higher than zero risk but still not be high enough risk to be diagnostic of pancreatic cancer. It is unclear how much higher the risk for cancer is.
It is unclear how there is a higher risk of pancreatic cancer when the mutation decrease is detected than when mutation decrease is detected. The specification illustrates that the higher the number of mutations the risk of pancreatic cancer is greater. Therefore, determining the presence of mutation decrease is a showing of less mutations than when there is no mutational decrease. Thus, it is unclear how the claims make a diagnosis based on mutational decrease.
Claim 11 is also directed to functional decrease of elected GALC. It is unclear which function is decreased. It is unclear whether expression is decreased, the break down of galactolipids is decreased, myelin maintenance is decreased, psychosine break down is decreased or lysosome function is decreased (functions of GALC enzyme).
Claims 13 and 14 lack proper antecedent basis. Claim 11 does not provide a subject. Claims 13 and 14 recite “the subject’. The subject lacks proper antecedent basis. Clarification is required which subject is being referred to.
Conclusion
No claims allowable.
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.
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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
November 12, 2025