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 October 31, 2025. Currently, claims 9, 12-13, 20, 28, 30, 32, 34-36, 40, 42, 53, 65-71 are pending.
Election/Restrictions
Applicant's election without traverse of Group II and nucleic acids, Claims 9, 12, 13, 20, 28, 30, 32, 34-36, 40, 42,53 in the paper filed October 31, 2025 is acknowledged.
Applicant did not select a gene or combination of genes as required in the restriction requirement. The examiner called Applicant and Nathan Hsu elected Panel B on January 6, 2026.
The requirement is still deemed proper and is therefore made FINAL.
Priority
This application claims priority to
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Drawings
The drawings are acceptable.
Improper Markush Rejection
Claims 9, 12, 13, 20, 28, 30, 32, 34, 36, 40, 42 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 be each of the two or more biomarkers in Claim 9.
The recited alternative species in the groups 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 sequences 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 chronic lymphocytic leukemia (CLL), 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 chronic lymphocytic leukemia (CLL).
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 chronic lymphocytic leukemia (CLL).
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 9, 12, 13, 20, 28, 30, 32, 34, 36, 40, 42 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 9 is directed to “a method for characterizing a chronic lymphocytic leukemia (CLL) …to classify the CLL”.
Claim 9 is directed to a process that involves the judicial exceptions of an abstract idea (i.e. the abstract steps of “characterizing a CLL” and “using the measured levels to classify the CLL as having an expression subtype”) and a law of nature/natural phenomenon (i.e. the natural correlation between the level of elected Panel B and CLL expression subtypes).
Claims 12-13 is further directed to a classifier. A classifier is merely a mathematical calculation and may be performed mentally. The courts continue to treat analyzing information by mathematical algorithms as essentially mental processes within the abstract-idea category.
Claim 34, 36, 40, 42, 71 are directed to selecting a subject having CLL for inclusion or exclusion in a clinical trial. The mere selection of a subject provides nothing more than mentally identifying the subject for a trial.
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 9 involves the patent-ineligible concept of an abstract process. Claim 9 requires performing the step of “using the measured levels to classify the CLL as having an expression subtype”. Neither the specification nor the claims set forth a limiting definition for "classifying" and the claims do not set forth how “classifying” is accomplished. As broadly recited the classifying step may be accomplished mentally by thinking about a subject’s expression and assessing whether the subject has an expression subtype of CLL. Thus, the determining step constitutes an abstract process idea.
Claim 69 further recites a comparison between the expression level and a reference 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 levels, namely Panel B, and expression subtypes of CLL is a law of nature/natural phenomenon. The "classify" step which tells users of the process to predict subtypes of CLL in the sample, amounts to no more than an "instruction to apply the natural law". This 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 "classifying" step does not require the process user to do anything in light of the correlation. The "classifying" 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. While the claim recites obtaining a sample and measuring expression, this is not an integration of the exception into a practical application. Instead, these elements are data gathering required to perform the method. Thus, the claim is “directed to” the exception.
Claims 40, 42, 71 are directed to “the agent” however, Claim 34 does not require administering any agent to any particular patient.
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 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 expression of 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 measuring step essentially tells users to determine the expression of markers 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 and mutation and methylation 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.
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-Description
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 9, 12, 13, 20, 28, 30, 32, 34, 36, 40, 42 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Panel B comprises over 120 markers. The claims are broadly drawn to methods which comprise characterizing CLL using elected Panel B which possess the functionality of being associated with CLL subtype classifications. The specification does not teach any particular characterization using these 120 markers to classify the subtype. For example, VSIG10 is provided in Table 4, but it provides no guidance which subtype is identified if the expression is increased or decreased compared to a reference sequence. Similarly, MZB1 has not guidance how to use the expression pattern for determining subtype of CLL.
In the case of the instant claims, the functionality of identifying expression patterns diagnostic of CLL subtype is a critical feature of the claimed methods. The specification does not describe how to determine subtypes of CLL using Panel B.
The specification teaches identifying genes are over expressed in certain subtypes, but it is not clear that all of these genes are associated with subtypes of CLL. Given the guidance in the specification and what was taught in the art prior to the invention, the skilled artisan would be unable to predictably correlate expression changes in the genes in Panel B with CLL subtypes, simply based on their existence.
Thus, considering the breadth of the claimed methods, their specific required functionalities, and the teachings of the instant specification, it is the conclusion that the specification does not provide an adequate written description of the broadly claimed subject matter.
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 35-36, 40, 42, 53, 71 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.
Claims 35, 53 are indefinite as being both incomplete, by its dependence on a cancelled claim, namely Claim 1; and for lack of antecedent basis for its limitation (“a panel of Claim 1”) which is not present in cancelled base claim Amending claim 35 and 53 to refer to a claim which recites a panel of markers, or deleting the claim, would obviate the rejection.
Claim 36, 40, 42, 71, are indefinite over the recitation “the agent”. Claims 36, 40, 42, 71 depend on Claim 34 which does not provide an agent. Thus, “the agent” lacks proper antecedent basis.
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) 9, 12-13, 20, 32, 65-68, is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wu et al. (US Pub 2014/0364439, December 11, 2014).
Wu teaches markers associated with chronic lymphocytic leukemia prognosis and progression. Wu teaches analyzing gene expression using the Affymetrix U133 chip (para 262) and GENE-E for analyzing the data. The data may be accessed at NCBI website with accession number GSE37168 (para 262). Each of the genes from panel B may be found in the U133 chip data. Wu teaches classifying the data using algorithms and models including machine learning classifiers (see para 97).
With respect to Claim 65-68, Wu teaches the biological sample is whole blood or tissue biopsies (para 108).
With respect to Claims 69-70, Wu teaches the levels are compared to healthy references for normalization (para 97).
Conclusion
No claims allowable.
The art made of record and not relied upon is considered pertinent to applicant's disclosure.
Knisbacher et al. (Nature Genetics, Vol. 54, No. 11, pages 1664-1674, November 2022) is applicant’s post filing date work for classification of CLL using markers.
US2025/0255889, August 14, 2025 is directed to methods for treatment selection for CLL with common inventors with the instant application. The genes listed in dependent claims overlap with Panel B but are not identical.
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
January 23, 2026