DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This application is the national phase of PCT/US2021/059510, filed 16 November 2021, claiming priority to provisional application 63/114,023, filed 16 November 2020. As the claimed invention (which recites, e.g., methods comprising detecting expression levels of biomarkers CD63, AR, HIF-1alpha, and p21 and/or CD63, AR, PI3, and p21) was not disclosed in the noted provisional application, the effective priority date for purposes of comparing the claimed invention to the prior art is 16 November 2021. The International Search Report and Written Opinion issued in the PCT application have been received and reviewed.
This action is responsive to the Response to Restriction Requirement and Election of Species, including Claim Amendments, filed 23 June 2026. Claims 88, 90-91, and 94-95 have been amended, claims 96-107 have been canceled, and claims 108-131 have been added. The current status of the claims is provided below under “Election/Restrictions”.
Election/Restrictions
Applicant’s election without traverse of Group I (identified by Applicant as now corresponding to claims 88-93 and 114-131) in the reply filed on 23 June 2026 is acknowledged.
Claims 94-95 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 23 June 2026.
Applicant's election with traverse of the species of a post-translational modification for (a)(ii) and a signal transduction inhibitor for (a)(iii) in the reply filed on 23 June 2026 is also acknowledged. It is noted that Applicant has not specifically identified claims readable on each elected species (but has rather specified claims 88-93 and 114-131 as corresponding to elected Group I); therefore, those claims readable on the elected species are identified below (and see also the Interview Summary mailed 23 April 2026, as aspects of the response to the Restriction/Election were discussed 21 April 2026). Regarding the requirement of (a)(i) to elect a biomarker or combination, Applicant has (rather than specifying an elected species) amended the claims to recite a more limited number of more specific biomarker combinations, with the combinations of elected independent claim 88 forming a subcombination with respect to the combinations set forth in independent (non-elected) claim 108 (from which claims 109-113 depend) as well as dependent claim 114 (from which claims 115-125 depend). As the prior art applies against the biomarker groups of independent claim 88, search and examination has not been extended to combinations including those groups (which were identified in the Election/Restriction as separate species; see also the Interview Summary mailed 23 April 2026). It is noted that rejoinder may apply should the claims as directed to the elected species later be allowed (as discussed in the original Election/Restriction).
With regard to the species election of (a)(ii), the traversal is on the ground(s) that “the recited modifications” share technical features of common structures, detection principles, and utility, are members of a “recognized genus”, and would require overlapping search/examination. This is not found persuasive for the following reasons. First, while it is noted that search burden is not a factor considered in a 371 application, the different types of modification specified in the amended and new dependent claims 126-131) would in fact require different types of searches; further, the claims relate to structurally different types of modifications that would be expected to require different reagents and procedures to achieve detection of the particular recited “modifications”. It is noted that post-translational modifications may reasonably be considered a genus embrace the alternatives of claim 127, and thus this group of modifications has been considered. However, the other alternatives – chemical modification, truncations, mutations, promoter binding – are not members of a recognized genus, and do not meet the criteria of PCT Rule 13.2 for being considered “of a similar nature”, as set forth in the Requirement mailed 28 October 2025 (and Applicant has provided no evidence of this, or evidence in support of the assertions regarding common “detection principles” for these disparate types of modifications, etc.). Accordingly these arguments are not persuasive.
With regard to the species election of (a)(iii), while the requirement was traversed, the claims presently corresponding to the invention under consideration do not include any claims directed to this species (as the biomarker combination of claim 114 is not under consideration herein, and the recited species of molecular targeting agents are referenced in claims 115-125). In the interest of compact prosecution, it is noted that the traversal is on the grounds that the different recited molecular targeting agents (MTAs) are linked by a common method of identification, ability to modulate a common pathway, use for the same therapeutic purpose, require overlapping searches, and are “obvious variations within a single genus”. These arguments are non-persuasive because the alternatives do not meet the requirements of PCT Rule 13.2 as discussed in paragraph 7 of the Requirement mailed 28 October 2025, particularly due to the lack of any required common structure and failure to belong to a recognized class of chemical compounds. Applicant has not provided any evidence (or persuasive arguments) that the alternative species meet the criteria of PCT Rule 13.2 for being considered “of a similar nature”, and therefore these arguments are non-persuasive.
The requirement is still deemed proper and is therefore made FINAL.
Claims 108-125 and 128-131 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement of species (a)(ii) and (a)(iii) of Group I in the reply filed on 23 June 2026.
The current status of the claims is: claims 88-93 and 126-127 are under consideration as directed to the elected species (with claims 91 and 126-127 corresponding to the elected species of (a)(ii)), while claims 94-95, 108-125, and 128-131 are withdrawn.
Specification
The disclosure is objected to because of the following informalities: the Description of Figure 6 does not describe/reference both Figure 6A and Figure 6B (see MPEP 608.01(f)).
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)/second paragraph and Claim Interpretation
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 88-93 and 126-127 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.
Claims 88-93 and 126-127 are indefinite over the recitation in independent claim 88 of the language “method for use in guiding radiation therapy (RT) (1) pre-treatment (2) during/post-treatment, and (3) to monitor the potential for relapse after RT treatment completion, long-term management RT strategy, in classifying a prostate cancer patient in an individualized manner, by classifying a biological sample of said patient before commencing RT treatment, pre-treatment classifying as an assignment RT strategy, and after commencing RT treatment, during/post-treatment classifying as an adaptive RT strategy, as a (i) strong responder (SR), (ii) responder (R), (iii) weak responder (WR) or (iv) non-responder (NR) to radiation treatment”, because it is unclear what requirements are imparted on the claimed methods by this language. First, the claim refers to “guiding radiation therapy (RT) (1) pre-treatment (2) during/post-treatment and (3) to monitor the potential for relapse after RT treatment, long-term management RT strategy in classifying” a patient, which is confusing in that: a) items (1) and (2) may be interpreted as either multiple required alternatives (given the use of two different numbers) or as a single item (i.e., alternatives of which only one is required, given the lack of standard punctuation such as a comma between alternatives; and b) regarding “(3) to monitor the potential for relapse after RT treatment completion, long-term management RT strategy”, it is not clear how the claim is further limited by the language “long-term management RT strategy”. While the above noted language appears to relate to the intended use of the recited method, it also suggests that the claim may require either two or three active steps, which steps may potentially relate to different objectives; thus, clarification of this language is required to ensure that the boundaries of what is being claimed are clear. Second, the language “by classifying a biological sample of said patient before commencing RT treatment, pre-treatment classifying as an assignment RT strategy, and after commencing RT treatment, during/post-treatment classifying as an adaptive RT strategy, as a (i) strong responder (SR), (ii) responder (R), (iii) weak responder (WR) or (iv) non-responder (NR) to radiation treatment”, is confusing because it is not clear whether the language “pre-treatment classifying as an assignment RT strategy” and “during/post-treatment classifying as an adaptive strategy” is simply further descriptive of the “before commencing RT treatment” and “after commencing RT treatment”, respectively, or whether further actions/steps are required (and if so, what those are). (It is also noted that the term “strong” and “weak” are relative terms that are indefinite for the reasons indicated below.). In view of the indefiniteness of this claim language, the recitation in the claim of “by classifying…before commencing RT treatment….and after commencing RT treatment”, and the reference in the body of the claim to only two steps of “detecting expression levels” (at (1a) and (2a), the claims have been interpreted as referring to physical testing of a sample prior to RT treatment and/or at some point after commencing RT treatment (which potentially includes either during or following completion of treatment); however, see also the indefiniteness rejection below regarding “the biological sample” and lack of clear antecedent basis in claim 88 when referencing these activities.
Claims 88-93 and 126-127 are also indefinite over the recitation in claim 88 to a single common “biological sample” that is employed in both of the above noted steps. More particularly, the claim initially refers to “a biological sample of said patient” (with the term patient referencing the previously recited “prostate cancer patient), then subsequently states at (1a) “detecting expression levels of biomarkers…in the biological sample”, and again at (2a) “detecting expression levels of biomarkers…in the biological sample” (which constitutes a reference to the same previously recited biological sample, as opposed to, e.g., a sample subsequently obtained during or after treatment, etc.). This reference to the same sample at what appears to have been intended to a subsequent time point is confusing, and it is unclear whether the claims are intended to relate to further analysis of a common sample, or whether a different sample was intended (but simply not referenced accurately/correctly). Further clarification is therefore needed.
Regarding claims 88-93 and 126-127, claim 88 recites limitations “said (1) pre-treatment classifying”, “said (2) during/post-treatment classifying”, and “said (3) monitoring potentially of relapse…” There is insufficient antecedent basis for these limitations in the claim, because claim 88 previously recites multiple activities that could potentially (but which do not necessarily) correspond to these recited steps. In particularly, it is noted that the numbers (1), (2), and (3) appear in lines 1-2 of the claim, but the claim subsequently recites further activities of “classifying” that also appear to potentially correspond to these referenced actions/steps. Thus, further clarification is needed to ensure that the nature of what the claim actually requires (as well as what activities are optional) is required.
Regarding claims 88-93 and 126-127, the terms “strong”, “weak”, “high”, “medium”, “low”, “high/medium”, and “low/medium” in independent claim 88 (which appear throughout claim 88, including as noted above, as well as in (1c), (2c), and (3b)) are relative terms that render the claim indefinite. These terms are 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. It is noted that the terms “positive” and “negative” value (as recited in (1b), (2b), and (3a)) are clear as used in the claim, however, neither the claim language nor the specification make clear how such “positive”/”negative” values relate to the further classifications of “high”, “medium”, “low”, ‘strong”, “weak”, etc., as used in the claim.
Regarding claims 88-93 and 126-127, claim 88 at (2b) and at (3a) recites “assigning a….value using a…algorithm based on the relative change or change in expression(s) of the biomarkers listed….”, but does not specify with regard to what this change is relative, such that it is unclear what is required. While the claim at (1b) specifies how relative change is ascertained in that instance, no such guidance is provided at (2b) or at (3a) (each of which could potentially involve the same type of “relative change” referred to in (1b), or some type of change between samples at different time points that are not clearly referenced in the claim, etc.). Accordingly, further clarification is required.
Regarding claims 88-93 and 126-127, claim 88 in the activity specified in the body of the claim as “said (3)” includes the parenthetic material “(long term management RT strategy)”. This language renders the claim indefinite because it is unclear whether the parenthetic material is part of the claim/required, an optional element, etc. Further clarification is therefore needed.
Regarding claim 89, it is noted that the claim recites “the biological sample” (the use of which term is indefinite as it is presently used in claim 88). To the extent that claim 88 may require only a single sample, the reference to “the biological sample” is clear; however, to the extent that claim 88 may require multiple different biological samples, further clarification is needed as to what is being further limited by claim 89 (i.e., does this further requirement apply to one of multiple samples, all samples, etc.). (It is noted that this rejection is made in the interest of compact prosecution, as amendment of claim 88 may result in that claim reciting multiple biological samples.).
Claim 90 is indefinite over the recitation of the limitation ‘the expression level of the biomarkers is measured” because claim 88 refers to multiple activities involving “detecting expression levels” of biomarkers, and thus it is not clear which of these is being referenced in claim 90.
Claims 91, 126, and 127 are indefinite over the recitation in claim 91 of the limitation “the biomarker expression being detected comprises a modified form of the biomarker molecule, wherein the modified form alters a detectable state of the biomarker”. First, similar to the issue noted above regarding claim 90, there are multiple activities in claim 88 involving detecting expression levels, which activities each involve detection of multiple different biomarkers. Thus, clarification is needed with regard to what element of claim 88 is being further limited by claim 91. Second, as the claims do not recite any requirement for detection of a “state” of a biomarker, it is unclear how the recitation “the modified form alters a detectable state” further limits what is being claimed. Claim 88 simply recites “detecting expression levels” of biomarkers (encompassing, e.g., detecting mRNA levels or protein levels); thus, if further actions are required by claim 91 that pertain to further analysis of “state” or “form”, etc., clarification is needed (to ensure that the boundaries of the claims are clear).
Claim 92 is indefinite over the recitation of the limitation “the biomarker expression being detected is the localization of the biomarker molecule…”. As was noted above regarding other claims, there are multiple activities in claim 88 involving detecting expression levels, which activities each involve detection of multiple different biomarkers. Thus, clarification is needed with regard to what element of claim 88 is being further limited by claim 92.
Claim 92 is also indefinite over the recitation of the limitation “localization of the biomarker molecule including cellular localization or extracellular localization, wherein…and cytosolic localization”. The claim recites various alternatives using “and” and “or” in such a way that it is not clear whether the claim requires a single alternative or groups of alternatives, as well as what in fact must actually be detected to meet the requirements of the claim (i.e., are these examples of possible “included” options, or is there some type of further action or outcome actually required to meet the claim?). For example, it is not clear whether the language “compartmentalized localization comprises Golgi, ….and cytosolic localization” is referencing an entire group of items that are required of an alternative of “compartmentalized localization”, or whether these are alternative preferred embodiments, or whether “cytosolic localization” is a separate embodiment, etc. The claim should be amended such that it is clear how it relates to claim 88, and what further limitations are required/sufficient to satisfy the requirements of the claim.
Claim 93 is indefinite over the recitation of the limitation “wherein the RRI is determined” because it is unclear which of the many “RRIs” recited in claim 88 is being referenced. Clarification is therefore needed regarding what elements of claim 88 are further limited.
Regarding claims 126-127, claim 126 recites the limitation “the modification”. While claim 91 (from which claim 126 depends) recites “a modified form” of a biomolecule, this terminology as used in claim 91 is unclear (as discussed above), and as there is no reference to any particular “modification” in claim 91, such that clear antecedent basis is lacking, and it is not clear how claims 126-127 further limit claim 91.
Claim Rejections - 35 USC § 103
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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 88-93 and 126-127 are rejected under 35 U.S.C. 103 as being unpatentable over Spetzler et al (US 2014/0148350 A1 [29 May 2014]; cited in IDS) in view of Berlin et al Int. J. Radiation Oncol. Biol. Phys. 103(1):84-91 [2019] cited herein).
It is noted that the claims are indefinite for the reasons given above, and that the claims have been interpreted as requiring either one or two active steps of “detecting expression levels” in a biological sample of/from a prostate cancer patient (see (1a) and (2a) of claim 88, noting that the claim language at present specifies the use of the same “biological sample” in both steps, and does not make clear whether one or both of these activities are in fact required). Claim 88 recites testing of the biological sample “pre-treatment” and/or “during/post-treatment”, such that the claims encompass performing the ”detecting” at one or both of these times; furthermore, to the extent that the claims require the “detecting” of (1a), that detecting is followed by an “assigning” of an index value using an algorithm “based on” relative changes calculated via normalizing to a reference gene and comparing normalized expression to a reference “baseline”; thus, at least the activities of claim 88 at (1) require normalization of expression levels.
Spetzler et al teach analysis of “circulating biomarkers from a bodily fluid” (including nucleic acids, proteins, and/or vesicles) for applications including cancer diagnosis, staging, and determination of treatment efficacy (see entire reference, particularly the Abstract). Spetzler et al disclose the use of CD63 as a marker that facilitates identification, capture, and characterization of circulating vesicles in prostate cancer (see, e.g., Figures 68, 70, 73, 88, 90, 99 and the descriptions thereof; see also, e.g., paragraphs 17-23, noting the recitation of CD63 and the teaching that it may be combined with additional markers selected from Table 12 [which as noted below, includes the biomarkers AR, HIF1A, and p21], and the disclosure of the embodiment of prostate cancer at paragraph 24 [second to last line] and throughout the document [include Examples, Figures, etc.]). Spetzler et al also teach the use of CD63 and “Trappin-2 Elafin” (i.e., PI3, the 5th marker set forth in instant independent claim 88) in capturing/characterizing/detecting such circulating vesicles (see, e.g., paragraphs 250, 253-254, 414, 858, 1186, as well as the disclosure of probes for detection of “prostate specific vesicles” including these markers [paragraphs 1219-1220]).
Spetzler et al further teach that their methods comprise analysis of vesicles from a subject (including a cancer patient) with regard to various phenotypes, including (most relevant to the instant claims) therapy responder/non-responder status (see, e.g., paragraphs 163-166, and see Table 1 at page 16 regarding the disclosure of vesicle analysis in prostate cancer). With regard to markers that may form biosignatures of therapy response, Spetzler et al disclose groups of markers including AR, HIF1A, and p21 (see paragraphs 1059-1060 and 1171, and Table 12). It is also noted that Spetzler et al disclose radiation treatment as among the types of cancer treatments embraced by their teachings (see, e.g., paragraphs 394), with radiation treatment of prostate cancer – for purposes including “probability of being cured” with radiation/“prognostic classification” being specifically disclosed (see paragraph 969; see also Table 9). Spetzler et al also disclose assessing effectiveness of treatment, including with regard to “complete response”, ‘partial response”, “stable disease”, “progressive disease”, etc., using their biomarker profiling techniques (see, e.g., paragraph 1041), disclose generation of index values, including an index of values “for therapeutic efficiencies” (paragraph 321), and disclose that various types of algorithms may be applied to such analysis and classification, allowing a subject to be “determined to be responsive or non-responsive” to a treatment (see, e.g., paragraph 1042; see also the recitation of classifier algorithms in paragraph 1060). Regarding active steps of “detecting expression levels” and the assignment of values requiring calculations of relative changes (as set forth in claim 88 at (1b)), Spetzler et al teach and exemplify collection and purification of vesicles (see, e.g., Examples 3, 7, and 8), and disclose embodiments of their methods in which expression is profiled via well-known techniques such as by using microarray technology in which thousands of transcripts are measured relative to controls/references, including via comparisons to a reference baseline (see, e.g., paragraphs 869-888, as well as paragraphs 1227-1242). It is also noted that Spetzler et al teach “housekeeping” markers as a preferred type of reference (see, e.g., paragraph 317).
Spetzler et al do not explicitly teach measuring together the expression levels of all of their markers disclosed as being useful in prostate cancer and prostate cancer therapy response characterization, and do not explicitly teach normalizing that data as recited in claim 88 when measuring expression together of a group of such prostate-cancer/prostate-cancer therapy response related biomarkers. However, Berlin et al describe use of a genomic classifier in guiding radiation therapy of prostate cancer patients, and report that this approach, as compared to the use of traditional National Comprehensive Cancer Network (NCCN) criteria), was found to be superior (see entire reference, particularly the Abstract; page 85, right column [first full paragraph]; page 87, right column [first full paragraph]). Berlin et al state that recently “a novel clinicogenomic model was proposed stressing the necessity of incorporating molecular biomarkers (GC) into clinical indices” (page 88, left column). Berlin et al also note that that patient samples should be evaluating prior to treatment “to inform treatment recommendations a priori” (page 89, left column). Berlin et al exemplify the simultaneous measurement of expression levels of a group of biomarkers via microarray analysis (one of the embodiments taught by Spetzler et al), and disclose normalization of expression prior to calculations of a genomic classifier (GC) score, and classification of patients into categories using a previously established cut-point (page 86, both columns).
In view of the teachings of Spetzler et al and Berlin et al, it would have been prima facie obvious to one of ordinary skill in the art prior to Applicant’s effective filing date so as to have detected in samples from a prostate cancer subject expression of all five of the biomarkers set forth in claim 88 (at (1a) and (2a)) prior to and/or following and/or during radiation treatment of the subject, and to have normalized expression relative to a reference/housekeeping gene, compared normalized expression to a baseline, and thereby calculated a type of index value to be used in classifying a patient regarding radiation response (and thereby to have performed a method meeting the requirements of the claims, particularly given the lack of clarity of many aspects of the claims). Spetzler et al disclose the relevance of all 5 of the recited biomarkers to evaluation of prostate cancer and prostate cancer therapy response (with radiation being a disclosed embodiment), providing motivation to perform testing with regard to all of these markers. Both Spetzler et al and Berlin et al provide guidance with regard to expression data analysis, with Berlin et al particularly providing detailed guidance regarding normalization, calculation of scores/indices, and comparisons to achieve classification in the context of radiation therapy response (and with Spetzler et al also providing general guidance on these techniques, such that an ordinary artisan would have had a reasonable expectation of success in performing what is required by the claims). Further, given that the only wet/active method step clearly required by the present claim language is a single step of detecting expression levels of biomarkers, the teachings of Spetzler et al and Berlin et al are sufficient to suggest what is claimed (and it is also noted that several activities of the claims are instructional in nature – e.g., “assigning” an index, “classifying” a patient – with such language constituting non-functional descriptive material that need not be given patentable weight when comparing the claimed invention to the prior art (see MPEP 2111.05). Additionally, Berlin et al’s teaching of the benefits of genomic classifiers as compared to traditional indices would have provided to an ordinary artisan additional motivation to test and develop such classifiers, particularly given markers already disclosed as being relevant to prostate cancer/prostate cancer therapy response (as Spetzler et al teaches with regard to the markers of the claims). With further regard to the preamble recitation of a method “for use in” guiding therapy, etc., the methods suggested by Spetzler et al in view of Berlin et al (as discussed above) achieve such a use. Similarly, regarding the limitation “wherein the classification provides guidance…”, the methods suggested by Spetzler et al in view of Berlin et al result in the provision of guidance (and it is noted that this claim language does not set forth any further concrete limitations on what is claimed, but rather states what is accomplished by performing “classification”).
Regarding dependent claim 89, Spetzler et al clearly teach the isolation and analysis of vesicles. Regarding dependent claim 90, both Spetzler et al and Berlin et al teach nucleic acid analysis meeting the requirements of the claim. Regarding claim 91, Spetzler et al and Berlin et al teach and suggest, e.g., isolation of RNA and hybridization thereof to an array to allow for its detection, which is a type of “modified form” that “alters a detectable state” of the molecule. Regarding claim 92, one of the embodiments recited in the claim is “exosomal”, and the vesicles of Spetzler et al disclose that their teachings of vesicles comprise exosomes (see, e.g., paragraph 190), such that Spetzler et al disclose a type of biomarker expression encompassed by the claim. Regarding claim 93, reciting determining of an index “by implementing a system comprising electronic hardware and software that comprises algorithms, and a user interface” (which encompasses use of standard, generic computer equipment). It is clear from the disclosure of Berlin et al at, e.g., page 86, that such a system is employed in calculating indices and classifiers (note, e.g., the use of “the single channel array normalization algorithm”, a “locked random forest model”, a “survival C-index” estimated from combined models, etc.), and Spetzler et al teach a computer system for use in their methods (see paragraphs 1243-1245, Fig 65 and the description thereof, as well as the disclosure of the use of commercial software in data display [paragraph 877], and the storage of expression profiles on a computer readable medium [paragraph 1226]); thus, Spetzler et al and Berlin et al clearly suggest the use of such systems in their methods.
With further regard to claims 126-127, Spetzler et al further teach that their methods may comprise analysis of biomarkers with regard to a variety of features, including post-translational modifications such as glycosylation, phosphorylation, ubiquitination, and amidation (see, e.g, paragraphs 317 and 382). Thus, inclusion of these features in analysis of biomarkers and in a sample “biosignature” is also prima facie obvious over the teachings of Spetzler et al and Berlin et al, because it is taught by Spetzler et al as another “useful component” of a biosignature (see again paragraph 382).
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 88-93 and 126-127 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Independent claim 88 (from which claims 89-93 and 126-127 depend) is drawn to a method “for use in guiding” prostate cancer therapy that recites “classifying” a sample or samples by detecting biomarker expression levels, “assigning” an index value using an algorithm that in some cases requires calculations (see (1b)), with different values recited as “indicating” features of a tumor, which information is employed “classifying a patient” in multiple different ways. Such “assigning” and “classifying” are activities that may be performed entirely in the human mind are mental processes, and calculations are mathematical concepts; thus, claim 88 recites multiple abstract ideas (see MPEP 2106.04(a)). This judicial exception is not integrated into a practical application because the only active step/steps of the claims are “detecting expression levels of biomarkers” in a sample or samples (the claims are indefinite as discussed above); this data gathering does not add a meaningful limitation to the method as it constitutes insignificant extra-solution activity. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the broadly recited activity of “detecting expression levels”, encompassing any manner of achieving such “detecting” in any type of biological sample from a patient, corresponds to types of laboratory techniques/activities that the courts have recognized as well-understood, routine, and conventional activity in the life science arts when claimed a generic manner (as they are in the instant claims); see MPEP 2106.05(d)(II). Further, while it is noted that the claims recite particular biomarkers, altered expression of such markers is a natural phenomenon/law of nature, not something more than a JE. An inventive concept cannot be furnished by a judicial exception (i.e., a law of nature/natural phenomenon/abstract idea) itself (see MPEP 2106.05(I)). With further regard to dependent claim 89, the claim recites a variety of well-known sample types that may be employed the broadly recited “detecting” of the claims, rather than any type of application of a JE, or something “significantly more” than a JE. Regarding claim 90, this claim again recites broad categories of potential target molecules about which data is to be gathered; nothing amounting to an application, or something “significantly more” than a JE, is added. Regarding claim 91 and its dependent claims 126-127, claim 91 is indefinite, but appears to recite a more particular type of naturally occurring target molecule. Again, this relates to what is being detected (data gathering), and there are no further actions required by the claim language that might amount to something “significantly more” than a JE. To the extent that the claims may require detection of features such as those set forth in claims 126-127, identification/characterization of post-translational modifications of markers encompassed by the claims (see (1a) and (2a) of claim 88), including with regard to phosphorylation, ubiquitination, etc., was well-known as of Applicant’s effective filing date, such that this type of further activity does not add anything “significantly more”; see, e.g., Gioeli et al (Molecular and Cellular Endocrinology 352:70-78 [2012]; cited herein) regarding the androgen receptor, and see also the teachings of Berlin et al regarding post-translational modifications of their disclosed biomarkers (cited and discussed above). Claim 92, which is also indefinite, again appears to relate to a type of data being gathered, and as activities to detect locations of nucleic acids and proteins within cells/samples were well-known before the effective filing date of the claimed invention, nothing “significantly more” is added. Claim 93 recites determining an index ‘by implementing a system” comprising generic computer components/features. Such “determining” relates to data gathering (rather than any kind of application of a JE), and this amounts to nothing more than an instruction to apply an abstract idea using a generic computer, which does not render an abstract idea patent eligible (see, e.g., MPEP 2106.05(f). Further, “electronic hardware and software that comprises algorithms, and a user interface”, were clearly well-understood, routine, and conventional as of Applicant’s effective filing date, such that nothing more than a JE is added.
Accordingly, none of claims 88-93 and 126-127 is directed to patent eligible subject matter.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Zhao et al (Lancet Oncol 17:1612-1620 [2016]; cited herein) teach a 24-gene predictor of response to postoperative radiotherapy in prostate cancer (see entire reference).
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/DIANA B JOHANNSEN/Primary Examiner, Art Unit 1682
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