DETAILED ACTION
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 .
Election/Restrictions
Applicant’s election without traverse of small deletion burden and brain cancer in the reply filed on 04/27/2026 is acknowledged.
While the response did not traverse the rejection, the response does address a number of small deletion, amount of small deletions and length of small deletion are encompassed by small deletion burden. However the species requirement included amount, length, or quantity of small deletions and applicant elected burden and did not elect deletion amount, length or quantity. As such the election of only small deletion burden is under examination.
Claims 11-14, 20, 30-32, 34-35 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/27/2026.
Claims 1, 4-8, 15, 17-19, 21-22, 26 is under examination. Claim 4 is under examination with regard to small deletion burden. Claim 26 is under examination with regard to brain cancer.
Specification
The amendment to the specification filed 04/27/2026 has been entered.
Improper Markush Rejection
Claim 4 is 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.
The Markush grouping of presence of the plurality of small deletions, small deletion burden, absence of the plurality of small deletions, absolute quantity of the small deletions in the plurality of small deletions, relative quantity of the small deletions in the plurality of small deletions, size of the small deletions in the plurality of small deletions, and genetic identity of one or more of the plurality of the small deletions is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
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. Markush group applies when there is an expectation from the knowledge in the art that the members of the class will behave in the same way in the context of the claimed invention. There is no evidence that claimed classes encompassing a wide range of deletions will behave in the same way in the context of the claimed invention. There is no common use that flows from the substantial structural feature, see MPEP 2117 (II) B. There is no structural feature that is common use for selecting cancer treatment. While the claim recites characteristic of plurality of small deletions, the characteristic types of the small deletion encompass a wide range of characteristics that are not structurally or functionally similar.
The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons: each member of small deletion characteristics are structurally unique relative to one another. Each of the members encompass different characteristics that results in different structures. The members encompass presence of the plurality of small deletions, small deletion burden, absence of the plurality of small deletions, absolute quantity of the small deletions in the plurality of small deletions, relative quantity of the small deletions in the plurality of small deletions, size of the small deletions in the plurality of small deletions, and genetic identity of one or more of the plurality of the small deletions. For example the presence of a deletion is structurally and functionally distinct from quantity of small deletion, size of small deletion and genetic identify of small deletion. Each of the members have different structures and functions. There is no disclosed common substantial structural feature. While the claim recites small deletion, the structural features of a deletion is inherently distinct. The claim does not recite a specific deletion among the claimed characteristics and thus the deletion itself is not structurally similar. The only structural similarity present is that all the deletions are part of nucleic acid molecules that have been deleted. Each of the deletions are located in separate regions of the genome and have its own structure. The fact that the markers comprise deleted 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 cancer treatment. Accordingly, while the different deletion characteristics are asserted to have the property of being indicative of cancer treatment, they do not share a single structural similarity. Additionally there is no expectation from the knowledge in the art that the members of the class will behave in the same way in the context of the gastric cancer, in other words there is no expectation from the art that each of the claimed mutations will be associated with predisposition to gastric cancer.
Following this analysis, the claims are rejected as containing an improper Markush grouping.
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.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 4-8, 15, 17-19, 21-22, 26 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites selecting a treatment for the subject based at least in part on the comparison of the determined characteristic of the small deletions with the control. While the claim requires selecting a treatment the claim further recites based on at least in part on the comparison of determined characteristic of the small deletion with the control, it is unclear how a person is selected for a treatment because it is unclear what the role of the comparison step is required on the selection of treatment and how this relates to the active process step of the claim, specifically sleeting a treatment. While the claim requires selecting a treatment based at least in part on the comparison, there are no recited steps that correlate specific comparison with selecting a treatment and therefore it is unclear when or how a treatment is selected and how the comparing step limit the selection of treatment. According the recitation of selecting treatment based at least in part of comparison of determined characteristic without any recitation of what part of the comparing step is required for step of selecting renders the claim indefinite. The metes and bounds of the claim are unclear and one or ordinary skill in the art would not be apprised of scope of the invention and infringing on the claimed method.
Claim 15 recites the selected treatment comprises abstaining from administering a radiotherapy to the subject. Claim 19 recites abstaining from administering a radiotherapy to the subject. Claim 21 recites the selected treatment further comprises abstention from radiotherapy and abstention from administration of a pharmaceutical agent. These recitations renders the claim indefinite. Claim 15, 19 and 21 depend from claim 1 but claim 1 does not require or recite administering a pharmaceutical agent or radiotherapy. It is unclear the scope of claim 15, 19 and 21 with regard to abstention from radiotherapy and administration of a pharmaceutical agent. Does claim 15, 19 and 21 encompass previously administering or currently administering radiotherapy or a pharmaceutical agent and when did this prior or current administration occur as claim 1 does not require administering or previously administering any therapy. The metes and bounds of the claim are unclear and one of ordinary skill in the art would not be readily apprised of the scope of the invention or infringing on the claimed method.
Claim 15 recites wherein a means for determining the small deletion burden comprising determining the at least one characteristic of the plurality of small deletions in somatic DNA in the biological sample. Claim 15 depends from claim 1 and claim 1 requires determining the at least one characteristic of the plurality of the small deletion in somatic DNA in the biological sample and it is unclear how this wherein phrase limits the determining the small deletion burden as this is encompassed by the determining step of claim 1. It is unclear if this step is requiring additional determining or a different method of determining and renders the claim indefinite. The scope of the claim is indefinite and it is unclear what is encompassed by determining the small deletion burden.
Claims 4-8, 15, 17-19, 21-22, 26 depend from claim 1 and indefinite for the reasons applied to claim 1.
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 1, 4-8, 15, 17-19, 21-22, 26 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception of abstract idea and law of nature without significantly more.
Claim 1, 15, 19 recite an abstract idea that is a mental process. Claim 1 recites selecting a cancer treatment, comparing the determined small deletion characteristic to a control of the small deletion characteristic previously determined for the subject and selecting a treatment based at least in part on the comparison of the determined characteristic of the small deletions with the controls. Claim 15 recites if the small deletion burden determined statistically significantly higher than a control small burden, the selected treatment comprises abstaining from administering a radiotherapy to the subject. Claim 19 recites the determination of a small deletion burden is statistically significantly greater than zero in the subject small. The steps of “selecting”, “comparing”, “previously determined”, “determined” and “determination” and the comparison of the deletion burden of the control to subject sample are all mental processes. Neither the specification or the claims set forth limiting definitions for selecting, comparing, previously determined, and determined. The claims do not set forth how each of the steps are accomplished and the broadest reasonable interpretation is a step that can be accomplished mentally by evaluating data and critical thinking process such that one mentally reads information in a database or report regarding small deletion characteristics then draws a mental conclusion. Such selecting, comparing, determined encompass process that may be performed mentally and this is an abstract idea.
The claims recite a law of nature/natural phenomenon. Claim 1 recites a law of nature/natural phenomenon. Claim 1 recites selecting a treatment for the subject based on the comparison of the determined characteristic of the small deletions with the control. This recited relationship is a natural phenomenon that exists apart from any human action.
This judicial exception is not integrated into a practical application because the claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application. For example, the claims do not practically apply the judicial exception by including one or more additional elements that the courts have stated integrate the exception into a practical application:
An additional element reflects an improvement in the functioning of a computer, or
improvement to other technology or technical field;
An additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
An additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
An additional element effects a transformation or reduction of a particular article to a different state or thing; and
An additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological
environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
Claim 1 recites selecting a treatment, however selecting is an mental process and the broadest reasonably interpretation of selecting encompasses mental process. Additionally the selecting a treatment is further based at least in part on the comparison of the determined characteristic of the small deletions with the control and is an additional mental process, the comparison of a characteristic with a control is a mental process.
Claim 6 recites the subject has been administer a radiotherapy before the biological sample is obtained. This step occurs before the selecting and comparison step. This step does not integrate the abstract ideas as it occurs before not after the mental processes. This step is not actively administering treatment by the recitation of “has been administered” which is administering in the past. These additional elements of has been administered do not apply the judicial exception.
Claim 15 recites if the small deletion burden determine din the subject sample is statistically significantly higher than a control small deletion, the selected treatment comprises abstaining form administering a radiotherapy and if the small deletion burden determined in the subject sample is statistically significantly lower or is equal to eh control the selected treatment comprises administering a radiotherapy to the subject. While step (b) of claim 15 does integrate the judicial exception, this step is conditional is not required. Additionally step (a) of claim 15 does not integrate the judicial exception as this step encompasses performing no treatment. The recitation of abstaining from administering a radiotherapy encompasses no treatment.
Claim 19 recites determination of a small deletion burden is greater than zero the selected treatment comprises abstaining from administering a radiotherapy to the subject. This limitation does not integration the judicial exceptions because this step encompassing performing no treatment.
As mentioned above, a claim limitation can integrate a judicial exception by applying or using the judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. When evaluating this consideration one must the following:
(i) the particularity or generality of the treatment or prophylaxis limitation;
(ii) whether the limitations have more than a nominal or insignificant relationship to the exception; and
(iii) whether the limitations are merely extra solution activity or field of use.
In addition to the judicial exceptions the claims recite type of deletion characteristic (claim 4 and 15, 17-19) type of therapy (claim 21), biological sample (claim 22) and cancer (claim 26). These additional steps/elements are not considered to integrate the judicial exception into a practical application because they merely add insignificant extra-solution activity (data gathering) to the judicial exception and further limit the judicial exception.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The claims as a whole are not considered to recite any additional steps or elements that amount to significantly more than well-understood, routine, and conventional activities in the art and do not add something significantly more so as to render the claims patent-eligible. The step of determining a plurality of small deletion in somatic DNA merely instructs a scientist to use well-established routine and conventional nucleic acid techniques to gather samples for diagnostic analysis. As address in the instant specification the step of determining a plurality of small deletions in somatic DNA is well known, routine and conventional in the art as the specification uses previously obtained data from Kucab (2019, cited on IDS) and Barthel (2019, cited on IDS) (see fig 2 and ex 1)
The step of determining a plurality of small deletions in somatic DNA constitutes a data gathering step required to apply the law of nature/natural phenomenon. It is acknowledged that the claims recite deletion burden to be determined however the claims do not require a particular, non-conventional primer or probe consisting of or comprising a specific nucleotide sequence or any other specific reagent that is used to accomplish such determining such that the claims would recite significantly more than the judicial exception. The targets to be detected are part of the judicial exception and thereby the naming of the targets does not add something “significantly more” to the recited judicial exceptions.
The additional steps and elements are recited at a high degree of generality and are all routine, well understood and conventional in the prior art. The recited steps and elements do not provide inventive concept necessary to render the claims patient eligible. There is no combination of elements 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. Many cited prior art references in this record demonstrate that these techniques were conventional at the time of the invention. The specification uses previously determined deletion burden to arrive at the selection step (See fig 2 and example 1) Thus the prior art and specification demonstrates it was routine, well-known and conventional in the art to determine deletion burden in biological samples. The dependent claims do not provide significantly more to the claims outside of the judicial exception as they encompass conventional techniques as described in the instant specification as noted above.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
Claims 1, 4-8, 15, 17-19, 21-22, 26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Barthel (2019, cited on IDS).
With regard to claim 1, 5, 26, Barthel teaches obtaining a glioma tumor sample from a subject from glioma patients and DNA sequencing of data sets (brain cancer, exome and whole genome sequencing, tissue sample) (Claim 5 and 26) (see GLASS cohort and DNA sequencing and data collection). Barthel teaches two time points for each patient was determined, initial and recurrence (see GLASS cohort) (previously determined characteristic). Barthel teaches deletions burdens between two time points in subjects (See mutational burdens and processes over time) (claim 4). Barthel teaches patients included recurrence of cancers (See DNA sequencing and data collect) (claim 8)
With regard to claim 6-7, Barthel teaches treatment of glioma by alkylating agents and induction of hypermutation after treatment which occurs in tumors with deletions (see mutational burdens and processes over time). Barthel teaches subject have been administered radiotherapy before determining deletion analysis (claim 6-7) (See fig 1a, received RT and pg. 115). Barthel teaches determining initial tumor data, recurrent tumor data, metastatic tumor sample (see GLASS identifiers) (control comprises previously determined for subject before radiotherapy was administered).
With regard to claim 15, 17-19, and 21 Barthel teaches the characteristic of small deletions includes small deletion burden (see mutational burdens). Barthel teaches selection of neoantigens based on deletion burdens (see figure 4). Barthel does not teach administering a radiotherapy to the subject (claim 15, 19, 21) and teaches selection of neoantigens in deletion greater than 1 (immunotherapy) (See figure 4).
Claims 1, 4-5, 15, 17-19, 21-22, 26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vogelstein (US 2014/0221219A1).
Vogelstein teaches obtaining a brain tissue sample or cells or nucleic acids shed from the tumor (see para 6). Vogelstein teaches monitoring status of a patient with a brain tumor for a mutation by obtaining a blood or cerebrospinal fluid from the patient to determine amount of nucleic acid with mutations and repeating the testing one or more times taken at distinct time points (claim 22 and 26). The initial time point is a control. An increase in amount of nucleic acid indicates an increase in brain tumor (compared to control, initial sample) (see para 10) (claim 15). Vogelstein teaches deletion mutations (see para 22-24) (claim 4). Vogelstein teaches exomic sequencing of mutations (see para 37) (claim 5). Vogelstein teaches stratification of patients to assign treatment regimen (selecting treatment). Vogelstein teaches stratification includes chemotherapy, radiotherapy sensitivity (See para 24) (selecting treatment). Vogelstein anticipates claim 15, 17-19, because claim 15 recites conditional limitations that only occur if the small deletion burden is determined and Vogelstein does not teach the limitation however the limitations are not required and therefore anticipates the claim.
Conclusion
No claims are allowable.
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/SARAE L BAUSCH/Primary Examiner, Art Unit 1699
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