DETAILED ACTION
Applicant’s response, filed Sep 29 2025, has been fully considered. Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 .
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 Status
Claims 23-46 are pending.
Claims 1-22 are canceled.
Claims 23-25, 27, and 35 are objected to.
Claims 23-46 are rejected.
Priority
This application is a CON of 15/493,722, filed Apr 21 2017 (now USP 11,107,217), which claims priority to PRO 62/325,764, filed Apr 21 2016, and PRO 62/484,034, filed Apr 11 2017.
Accordingly, each of claims 1-25 are afforded the effective filing date of Apr 21 2016.
Specification
The amendments to the specification submitted Sep 29 2025 are accepted and the outstanding objections from the previous Office Action are withdrawn.
Claim Objections
The outstanding objections to the claims are withdrawn in view of the amendments submitted herein.
The claims are objected to because of the following informalities. Unless otherwise noted, the instant objection is newly stated and is necessitated by claim amendment.
The “and” at the end of the 1st limitation of claim 23 should be removed.
In claim 23, the recitation of “EGFR” on the sixth line should be amended to recite “epidermal growth factor receptor (EGFR)” because it is the first recitation of this abbreviation in the claim.
In claim 23, line 7, there should be an “a” inserted in front of “separate”. Claim 24 is similarly objected to.
In claim 23, last limitation, “when differing levels of neovascularization is” and “when similar levels of neovascularization is” should both be amended to recite “are” instead of “is”. Claims 24-25 are similarly objected to.
Claim 23, second to last line, should be amended to recite “EGFR-positive mutation status” to maintain consistent claim language. Claims 24-25 and 35 are similarly objected to.
In claim 24, line 2, there is a line between “EGFR” and “)” that should be removed. The objection is newly stated based upon further consideration of the claim.
In claim 24, line 8, “analyzing” should be amended to recite “analyze”.
Claim 25 recites multiple limitations which include a plurality of steps, such as: “performing” on line 3 of (a); and “assigning” on line 6 of (a). As set forth in 37 CFR 1.75, where a claim sets forth a plurality of steps, each step of the claim should be separated by a line indentation (see MPEP 608.01(i)).
In claim 25, line 9, “with” should be amended to recite “within”.
Claim 27 recites “a region of tissue adjacent an enhancing part of a tumor”, which should be amended to recite “… adjacent to an…” or similar.
Claim Rejections- 35 USC § 112
The outstanding rejections to the claims are withdrawn in view of the amendments submitted herein.
35 USC § 112(b)
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 26, 36, and 38 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention. The instant rejection is newly stated and is necessitated by claim amendment.
Claims 26 and 36 recite “wherein the mutation is selected from EGFR variant III (vIII), a EGFR variant at position A289, a point mutation at EGFR G598V, and/or a point mutation of EGFR variant position R108, with reference to the residue numbering of SEQ ID NO:1”. It is unclear whether the wherein clause is intended to require selecting the mutation within the metes and bounds of the claimed invention, or if it is only further limiting the type of EGFR mutation that may occur in the patient such that selecting the mutation is not required within the metes and bounds of the invention. As set forth in MPEP 2111.04.I, “wherein” clauses raise the question as to the limiting effect of the language in a claim. As the claims do not recite an active selecting of the mutation, the metes and bounds of the claims are unclear. For compact examination, it is assumed that the selecting is not required to be performed and that the claim merely intends to limit the types of mutations that can contribute to EGFR-positive mutation status. The rejection may be overcome by clarifying whether a mutation is required to be or if the listed mutations are merely exemplary of the types which contribute to EGFR-positive mutation status. It is noted that even if the claims were to require “selecting” one of the types of specific mutations, it would not be clear what that action would require within the metes and bounds of the independent claims.
Claim 38 recites “wherein, during said performing operation, imaging data of at least separate first and second regions of interest (ROIs) within the in vivo peritumoral edematous tissue are analyzed and compared to determine the level of spatial heterogeneity or similarity therebetween”. However, Claim 23, from which claim 38 depends, already recites a separate “analyzing” step of “the MRI data corresponding to the separate first and second ROIs to determine a level of spatial heterogeneity or similarity therebetween”. It is therefore not clear if claim 38 intends to further limit the performing operation such that a prior analyzing and comparing step is required in addition to the analyzing step already recited in claim 23, or if claim 38 fails to further limit claim 23 because it intends to recite the same step as is already recited therein. For compact examination, any art reading on comparing ROIs will be considered relevant. The rejection may be overcome by clarifying the scope of the claim.
35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 35 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 35 recites “wherein, during said assigning operation, EGFR - negative mutation status is assigned when differing levels of neovascularization is determined to exist between said first and second ROIs and EGFR -positive status is assigned when similar levels of neovascularization is determined to exist in said first and second ROIs”. However, claim 24, from which claim 35 depends, already recites “wherein EGFR -negative mutation status is assigned when differing levels of neovascularization is determined to exist between said first and second ROIs and EGFR - positive status is assigned when similar levels of neovascularization is determined to exist in said first and second ROIs”.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 101
The outstanding rejection from the previous Office Action for claim 25 is withdrawn in view of the amendments submitted herein. Specifically, claim 25 recites “(a) non-invasively detecting EGFR variant III positive mutation status within peritumoral edematous tissue of the patient” and “(b) treating the EGFR positive patient with a EGFR-targeting therapy”. The treatment step provides a particular treatment which integrates the recited judicial exceptions into a practical application at Step 2A, Prong 2 (see MPEP 2106.04(d)(2)).
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 23-24 and 26-45 are rejected under 35 U.S.C. 101 because the claimed invention is directed to one or more judicial exceptions without significantly more. Any newly recited portions are necessitated by claim amendment.
MPEP 2106 organizes judicial exception analysis into Steps 1, 2A (Prongs One and Two) and 2B as follows below. MPEP 2106 and the following USPTO website provide further explanation and case law citations: uspto.gov/patent/laws-and-regulations/examination-policy/examination-guidance-and-training-materials.
Framework with which to Evaluate Subject Matter Eligibility:
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter;
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e. a law of nature, a natural phenomenon, or an abstract idea;
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application (Prong Two); and
Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept.
Framework Analysis as Pertains to the Instant Claims:
Step 1
With respect to Step 1: yes, the claims are directed to methods, a non-transitory computer-readable storage medium, and a system, i.e., a process, machine, or manufacture within the above 101 categories [Step 1: YES; See MPEP § 2106.03].
Step 2A, Prong One
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. The MPEP at 2106.04(a)(2) further explains that abstract ideas are defined as:
mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations);
certain methods of organizing human activity (fundamental economic practices or principles, managing personal behavior or relationships or interactions between people); and/or
mental processes (procedures for observing, evaluating, analyzing/ judging and organizing information).
The claims also recite a law of nature or a natural phenomenon. The MPEP at 2106.04(b) further explains that laws of nature and natural phenomena include naturally occurring principles/relations and nature-based products that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature.
With respect to the instant claims, under the Step 2A, Prong One evaluation, the claims are found to recite abstract ideas that fall into the grouping of mental processes (in particular procedures for observing, analyzing and organizing information) and mathematical concepts (in particular mathematical relationships and formulas) as well as a law of nature or a natural phenomenon are as follows:
Independent claims 23-24: performing quantitative pattern analysis of magnetic resonance imaging (MRI) data corresponding to MRI of peritumoral edematous tissue of a patient suspected of having a neoplasm associated with an EGFR mutation to determine a level of spatial heterogeneity or similarity within the peritumoral edematous tissue comprising identifying separate, non- overlapping first region of interest (ROI) and a second ROI within the peritumoral edematous tissue;
analyzing the MRI data corresponding to the separate first and second ROIs to determine a level of spatial heterogeneity or similarity therebetween; and
assigning EGFR mutation status as one of negative or positive based on the level of spatial heterogeneity or similarity determined during said analyzing step, wherein EGFR - negative mutation status is assigned when differing levels of neovascularization is determined to exist between said first and second ROIs and EGFR -positive status is assigned when similar levels of neovascularization is determined to exist in said first and second ROIs.
Dependent claims 26-27, 29, 31-40, and 42-44 recite further steps that limit the judicial exceptions in independent claims 1 and 12 and, as such, also are directed to those abstract ideas. For example, claims 26 and 36 further limit the EGFR mutation; claims 27 and 39 further limit the location of the ROIs; claims 31-32, 40, and 42 and further limit the performing step to including applying the multi-variance statistical procedure of principal component analysis; claims 29 and 37 further limits the performing step to determining perfusion temporal dynamics between said first and second ROIs is determined via a time-series of MRI data; claims 33-34 and 43-44 further limit the performing step to including measuring separability between the ROIs using a Bhattacharyya coefficient analysis; claim 35 repeats the conditions of claim 24 for assigning EGFR negative or positive mutation status; and claim 38 further limits performing the quantitative pattern analysis step of claim 23.
The abstract ideas recited in the claims are evaluated under the Broadest Reasonable Interpretation (BRI) and determined to each cover performance either in the mind and/or by mathematical operation because the method only requires a user to manually determine EGFR mutation status based on MRI data. Without further detail as to the methodology involved in “identifying” ROIs, “performing quantitative pattern analysis” or “analyzing” the ROIs, and “assigning” mutation status, under the BRI, one may simply, for example, receive data by hand and use pen and paper to identify regions adjacent to and further away from the tumor, determine the level of heterogeneity or similarity between the regions, and, based on that heterogeneity or similarity, assign EGFR mutation status. Some of these steps and those recited in the dependent claims, such as using a multi-variance statistical approach such as principal component analysis to perform the quantitative pattern analysis or analyzing step, require mathematical techniques as the only supported embodiments, as is disclosed in the specification as published at: [0037; 0065; 0080; 0112].
The claims also recite a natural relationship between the spatial heterogeneity or similarity between regions of peritumoral edematous tissue and the mutation status of EGFR. Therefore, the claims recite a law of nature or a natural phenomenon (see MPEP 2106.04(b)).
Therefore, claims 23-24 and those claims dependent therefrom recite an abstract idea and a law of nature/natural phenomenon [Step 2A, Prong 1: YES; See MPEP § 2106.04].
Step 2A, Prong Two
Because the claims do recite judicial exceptions, direction under Step 2A, Prong Two, provides that the claims must be examined further to determine whether they integrate the judicial exceptions into a practical application (MPEP 2106.04(d)). A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception. This is performed by analyzing the additional elements of the claim to determine if the judicial exceptions are integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exceptions, the claim is said to fail to integrate the judicial exceptions into a practical application (MPEP 2106.04(d).III).
Additional elements, Step 2A, Prong Two
With respect to the instant recitations, the claims recite the following additional elements:
Claims 28, 30, 41, and 45 further limit the type of MRI data being analyzed in claims 23-24.
The claims also include non-abstract computing elements. For example, independent claim 23 includes a non-transitory computer-readable storage medium comprising stored instructions which, when executed by one or more computer processors, cause the one or more computer processors to perform a method; independent claim 24 includes a system comprising at least one processor configured to perform a method.
Considerations under Step 2A, Prong Two
With respect to Step 2A, Prong Two, the additional elements of the claims do not integrate the judicial exceptions into a practical application for the following reasons. Those steps directed to data gathering, such as “acquiring” MRI data, perform functions of collecting the data needed to carry out the judicial exceptions. Further claims which limit the type of MRI data being analyzed, as recited in claims 28, 30, 41, and 45, do not affect the performance of the judicial exception and also serve a data gathering function. Data gathering and outputting do not impose any meaningful limitation on the judicial exceptions, or on how the judicial exceptions are performed. Data gathering and outputting steps are not sufficient to integrate judicial exceptions into a practical application (MPEP 2106.05(g)).
Further steps directed to additional non-abstract computing elements do not describe any specific computational steps by which the “computer parts” perform or carry out the judicial exceptions, nor do they provide any details of how specific structures of the computer, such as the computer-readable recording media, are used to implement these functions. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions. Hence, these are mere instructions to apply the judicial exceptions using a computer, and therefore the claim does not integrate that judicial exceptions into a practical application. The courts have weighed in and consistently maintained that when, for example, a memory, display, processor, machine, etc.… are recited so generically (i.e., no details are provided) that they represent no more than mere instructions to apply the judicial exception on a computer, and these limitations may be viewed as nothing more than generally linking the use of the judicial exception to the technological environment of a computer (MPEP 2106.05(f)).
The specification as published discloses that the calculated index contributes to precision medicine in order to provide an improvement at [0080], but does not provide a clear explanation for how the additional elements provide these improvements. Therefore, the additional elements do not clearly improve the functioning of a computer, or comprise an improvement to any other technical field. Further, the additional elements do not clearly affect a particular treatment; they do not clearly require or set forth a particular machine; they do not clearly effect a transformation of matter; nor do they clearly provide a nonconventional or unconventional step (MPEP2106.04(d)).
Thus, none of the claims recite additional elements which would integrate a judicial exception into a practical application, and the claims are directed to one or more judicial exceptions [Step 2A, Prong 2: NO; See MPEP § 2106.04(d)].
Step 2B (MPEP 2106.05.A i-vi)
According to analysis so far, the additional elements described above do not provide significantly more than the judicial exception. A determination of whether additional elements provide significantly more also rests on whether the additional elements or a combination of elements represents other than what is well-understood, routine, and conventional. Conventionality is a question of fact and may be evidenced as: a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to the instant claims, the prior art review to Lemee et al. (Neuro-Oncology, 2015, 17(10):1322-1332; cited on the Oct 26 2021 IDS) discloses that acquiring MRI data consisting of DCE, T1, T2, and T2-FLAIR data, is a data gathering element that is routine, well-understood and conventional in the art. Said portions of the prior art are, for example, (p. 1322, col. 2, par. 2; p. 1326, col. 1, par. 1; Table 1). As such, the claims simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception (MPEP2106.05(d)). The data gathering steps as recited in the instant claims constitute a general link to a technological environment which is insufficient to constitute an inventive concept which would render the claims significantly more than the judicial exception (MPEP2106.05(g)&(h)).
With respect to claims 23-24 and those claims dependent therefrom, the computer-related elements or the general purpose computer do not rise to the level of significantly more than the judicial exception. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions. Hence, these are mere instructions to apply the judicial exceptions using a computer, which the courts have found to not provide significantly more when recited in a claim with a judicial exception (Alice Corp., 573 U.S. at 225-26, 110 USPQ2d at 1984; see MPEP 2106.05(A)). The specification as published also notes that computer processors and systems, as example, are commercially available or widely used at [0038-0039; 0090]. The additional elements are set forth at such a high level of generality that they can be met by a general purpose computer. Therefore, the computer components constitute no more than a general link to a technological environment, which is insufficient to constitute an inventive concept that would render the claims significantly more than the judicial exceptions (see MPEP 2106.05(b)I-III).
Taken alone, the additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception itself [Step 2B: NO; See MPEP § 2106.05].
Therefore, instant claims 23-24 and 26-45 are not drawn to eligible subject matter as they are directed to one or more judicial exceptions without significantly more. For additional guidance, applicant is directed generally to the MPEP § 2106.
Response to Applicant Arguments
At p. 13, par. 1, Applicant submits that claims 23-25 are patent eligible because the medium and system have been configured to perform a series of operations.
It is respectfully submitted that this is not persuasive for claims 23-24. The courts do not distinguish between mental processes that are performed entirely in the human mind and mental processes that require a human to use a physical aid (e.g., pen and paper or a slide rule) to perform the claim limitation (See MPEP 2104(a)(2), III: e.g., Benson, 409 U.S. at 67, 65, 175 USPQ at 674-75, 674 (noting that the claimed "conversion of [binary-coded decimal] numerals to pure binary numerals can be done mentally," i.e., "as a person would do it by head and hand."); Synopsys, Inc. v. Mentor Graphics Corp., 839 F.3d 1138, 1139, 120 USPQ2d 1473, 1474 (Fed. Cir. 2016) (holding that claims to a mental process of "translating a functional description of a logic circuit into a hardware component description of the logic circuit" are directed to an abstract idea, because the claims "read on an individual performing the claimed steps mentally or with pencil and paper")). Nor do the courts distinguish between claims that recite mental processes performed by humans and claims that recite mental processes performed on a computer. As the Federal Circuit has explained, "[c]ourts have examined claims that required the use of a computer and still found that the underlying, patent-ineligible invention could be performed via pen and paper or in a person’s mind." Versata Dev. Group v. SAP Am., Inc., 793 F.3d 1306, 1335, 115 USPQ2d 1681, 1702 (Fed. Cir. 2015). See also Intellectual Ventures I LLC v. Symantec Corp., 838 F.3d 1307, 1318, 120 USPQ2d 1353, 1360 (Fed. Cir. 2016) (‘‘[W]ith the exception of generic computer-implemented steps, there is nothing in the claims themselves that foreclose them from being performed by a human, mentally or with pen and paper.’’); Mortgage Grader, Inc. v. First Choice Loan Servs. Inc., 811 F.3d 1314, 1324, 117 USPQ2d 1693, 1699 (Fed. Cir. 2016) (holding that computer-implemented method for "anonymous loan shopping" was an abstract idea because it could be "performed by humans without a computer").
If a claim recites a limitation that can practically be performed in the human mind, with or without the use of a physical aid such as pen and paper, the limitation falls within the mental processes grouping, and the claim recites an abstract idea. See, e.g., Benson, 409 U.S. at 67, 65, 175 USPQ at 674-75, 674 (noting that the claimed "conversion of [binary-coded decimal] numerals to pure binary numerals can be done mentally," i.e., "as a person would do it by head and hand."); Synopsys, 839 F.3d at 1139, 120 USPQ2d at 1474 (holding that claims to the mental process of "translating a functional description of a logic circuit into a hardware component description of the logic circuit" are directed to an abstract idea, because the claims "read on an individual performing the claimed steps mentally or with pencil and paper"). That the claims require the execution of the method steps on a computer processor does not change the mental nature of the limitations, but merely recites the application of a computer to carry out the judicial exception on a large number of sequences.
At p. 13, par. 2, Applicant submits that the claims as a whole provides significantly more than any judicial exceptions and are patent eligible.
It is respectfully submitted that this is not persuasive. MPEP 2106.05(d) sets forth that, at Step 2B, it is the additional elements which are examined to determine whether they are well-understood, routine, conventional activities previously known to the industry. The analysis at Step 2A, Prong 2, considers the claims as a whole, i.e., the additional elements in combination with the judicial exceptions (see MPEP 2106.05(a)), although the integration or improvement provided in the claim must flow from the additional elements and not the judicial exceptions to be considered persuasive. However, Step 2B requires examining only the additional elements, either alone or in combination with one another, for conventionality. An “inventive concept” is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself (Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966)). As set forth in the above rejection, the additional elements of the claims, either separately or together, do not provide significantly more. It is further noted that Applicant has not provided any reasoning for why the additional elements are considered to provide significantly more or a description of which additional elements in the claim provide such a feature. Therefore, there is a lack of factual support in Applicant's arguments because the arguments are not evidentiary.
Claim Rejections - 35 USC § 102
The outstanding rejections from the previous Office Action are withdrawn in view of the amendments submitted herein. As set forth by Applicant at p. 13, par. 4, independent claims 23-25 have been amended to include limitations from claims which were not rejected by the primary references in the previous Office Action.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
1A. Claims 23-45 are rejected under 35 U.S.C. 103 as being unpatentable over Bakas et al. (Neuro-Oncology, Nov 2015, 17; previously cited) in view of Hu et al. (US 2017/0103525; previously cited). The instant rejection is newly stated and is necessitated by claim amendment.
Bakas teaches: Glioblastoma (GBM) is the most common and aggressive adult brain tumor, with 14 months average survival. Epidermal growth factor receptor variant III (EGFRvIII) mutation is an important factor in driving tumor progression and defining prognosis in GBM patients, hence evidence of its presence can affect treatment decisions. The aim of this study is to identify quantitative imaging signatures of EGFRvIII. We used preoperative multi-parametric (T1-Gad, T2-FLAIR, Dynamic-Susceptibility-Contrast) magnetic resonance imaging data from a retrospective cohort of 64 patients (42 EGFRvIII-negative) with de novo GBM. We hypothesized that EGFRvIII-positive tumors, the more aggressive subtype, have a uniformly dense distribution of tumor cells throughout the peritumoral edematous region, as opposed to EGFRvIII-negative tumors, where tumor cell burden decreases farther from the tumor. To assess this peritumoral heterogeneity, we defined one region of interest (ROI) adjacent to the tumor and another at the farthest from the tumor but still within the edematous tissue. Perfusion temporal dynamics of each ROI were summarized via principal component analysis. The Bhattacharyya coefficient was used as a measure of separability (range [0,1]) between the dynamics of the two ROIs, for each patient. Values close to 0 indicate similar perfusion dynamics between the ROIs, which is consistent with uniformly and aggressively infiltrating tumors. Conversely, values close to 1 indicate substantial difference between the two ROIs, which would be consistent with less infiltrative tumors. The distributions of these separability measurements between EGFRvIII-negative and EGFRvIII-positive patients were very highly separable, with median values of 0.48 (Interquartile range: 0.251-0.647) and 0.209 (Interquartile range: 0.064-0.309), respectively. A two-tailed paired t-test confirmed the statistical significance of the results (p-value = 0.00007). These results suggest that discrimination of the EGFRvIII mutation status, which is critical for personalized treatment decisions and response evaluation, can be achieved based solely on assessing the peritumoral heterogeneity on in vivo imaging data.
Bakas is therefore considered to teach claims 23-45 except for assigning EGFR mutation status based on differing or similar levels of neovascularization.
However, the prior art to Hu discloses a system and method for characterizing tissues of a subject using multi-parametric magnetic resonance (MR) imaging (abstract). Hu teaches that EGFR amplification showed highly significant correlations with LBP texture on rCBV maps as well as three separate features on T2W imaging: two texture-based features (on DOST and GLCM) and standard deviation (SD) of raw T2W signal [0120]. Hu teaches that rCBV texture captures the contributions and signal patterns of the individual voxels within that ROI, giving insight to microvascular distribution and heterogeneity, and that that texture of rCBV correlates with EGFR status [0126]. Hu teaches the link between EGFR and T2W signal patterns of tumoral/vasogenic edema has been suggested previously [0126]. Therefore, it is considered that the method of Hu fairly teaches assigning EGFR status based on differences in neovascularization as instantly claimed.
Regarding claims 23-45 in view of the rejection over Bakas, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Bakas and Hu because each disclose methods for determining spatial heterogeneity around glioblastomas based on EGFR status. The motivation would been to examine vascularization, as taught by Hu [0126].
1B. Claim 46 is rejected under 35 U.S.C. 103 as being unpatentable over Bakas in view of Hu, as applied to claim 25 above, and in further view of Johnson et al. (Science Translational Medicine, 20157(275), pp.275ra22-275ra22, p. 1-14; newly cited). The instant rejection is newly stated and is necessitated by claim amendment.
Regarding claim 46, Bakas in view of Hu teaches claim 25. Claim 46 further adds that the EGFR-targeting therapy is a chimeric antibody receptor (CAR) T-cell therapy comprising an anti-EGFR targeted component.
The prior art to Johnson discloses the development and characterization of anti-EGFR variant III chimeric antigen receptor T cells for glioblastoma (title; abstract; entire document is relevant).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Bakas in view of Hu and Johnson because each reference discloses methods for examining EGFR mutations. As anti-EGFR variant III chimeric antigen receptor T cells for glioblastoma are a known EGFR-targeting therapy, as taught by Johnson, it would have been obvious to use such a therapy to treat an EGFR positive patient with such a therapy.
2A. Claims 23-24, 27-33, 35, 37-43, and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Hu et al. (US 2017/0103525; previously cited) in view of Akbari et al. (Radiology, 2014, 273(2):502-510; cited on the Oct 26 2021 IDS). The instant rejection is newly stated and is necessitated by claim amendment.
The prior art to Hu discloses a system and method for characterizing tissues of a subject using multi-parametric magnetic resonance (MR) imaging (abstract). Hu teaches the instant features as follows.
Claim 23 discloses a non-transitory computer-readable storage medium comprising stored instructions which, when executed by one or more computer processors, cause the one or more computer processors to perform operations of the method. Claim 24 discloses a system for in vivo detection of epidermal growth factor receptor (EGFR) mutation status within peritumoral edematous tissue of a patient suspected of having a neoplasm associated with an EGFR mutation, comprising: at least one processor configured to perform steps of the method.
Hu teaches a computer-implemented method, a computer-readable medium, and a processor programmed for characterizing tissues of a subject using multi-parametric imaging [0009; 0011; 0043].
The steps of claims 23-24 comprise:
performing quantitative pattern analysis of magnetic resonance imaging (MRI) data corresponding to MRI of peritumoral edematous tissue of a patient suspected of having a neoplasm associated with an EGFR mutation to determine a level of spatial heterogeneity or similarity within the peritumoral edematous tissue comprising identifying separate, non- overlapping first region of interest (ROI) and a second ROI within the peritumoral edematous tissue;
Hu teaches selecting at least one region of interest (ROI) in the MR images acquired from a subject, performing a texture analysis on corresponding ROIs, and applying a classification scheme (abstract; [0009-0012; 0029-0040]). Hu teaches that texture features used in texture analysis generally capture different aspects of the spatial distribution of intensities to provide a quantitative indication of image texture (i.e., performing quantitative pattern analysis to determine a level of spatial heterogeneity or similarity) [0036]. Hu teaches examining images taken from the surrounding non-enhancing parenchyma, or Brain Around Tumor (BAT) which is indistinguishable from non-tumor vasogenic edema, in patients with Glioblastoma [0005; 0031; 0054]. Hu is therefore considered to fairly teach examining in vivo peritumoral edematous tissue as instantly claimed.
Hu does not teach separate, non-overlapping first and second ROI’s.
analyzing the MRI data corresponding to the separate first and second ROIs to determine a level of spatial heterogeneity or similarity therebetween; and
Hu does not teach this limitation.
assigning EGFR mutation status as one of negative or positive based on the level of spatial heterogeneity or similarity determined during said analyzing step, wherein EGFR - negative mutation status is assigned when differing levels of neovascularization is determined to exist between said first and second ROIs and EGFR -positive status is assigned when similar levels of neovascularization is determined to exist in said first and second ROIs.
Hu teaches applying a classification scheme to generate a report which indicate regions or locations of high and/or low tumor content, or with specific genetic profiles (i.e., assigning mutation status) [0040]. Hu teaches that in imaging-genetic correlative studies of MR images, EGFR amplification (i.e., EGFR mutation status) showed highly significant correlations with LBP texture on rCBV maps and T2W imaging from the MR images of BAT tissue and edema (Tables 5-6; [0120]). Hu teaches that EGFR amplification showed highly significant correlations with LBP texture on rCBV maps as well as three separate features on T2W imaging: two texture-based features (on DOST and GLCM) and standard deviation (SD) of raw T2W signal [0120]. Hu teaches that rCBV texture captures the contributions and signal patterns of the individual voxels within that ROI, giving insight to microvascular distribution and heterogeneity, and that that texture of rCBV correlates with EGFR status [0126]. Hu teaches the link between EGFR and T2W signal patterns of tumoral/vasogenic edema has been suggested previously [0126]. Therefore, it is considered that the method of Hu fairly teaches assigning EGFR status based on differences in neovascularization as instantly claimed.
Hu does not teach separate, non-overlapping first and second ROI’s.
However, the prior art to Akbari discloses an analysis of dynamic susceptibility contrast material–enhanced magnetic resonance (MR) images to uncover unique tissue characteristics in patients with glioblastoma (abstract). Akbari teaches obtaining dynamic susceptibility contrast-enhanced MR imaging data and creating a map of heterogeneity within the peritumoral region to determine a heterogeneity score (abstract; p. 504, col. 1, p.ar 2 through p. 506, col. 2, par. 2; entire document is relevant). Akbari teaches defining several regions of interest, including two near-far ROIs within the edema and/or peritumoral region (p. 504, col. 3, par. 1). Akbari teaches training a model using the near-far ROIs to generate heterogeneity scores (i.e., determine a level of spatial heterogeneity or similarity between separate first and second ROIs) (p. 505, col. 3, par. 2 through p. 506, col. 2, par. 2).
Regarding claims 23-24, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Hu and Akbari because both references disclose methods for analyzing spatial heterogeneity in peritumoral samples of glioblastomas. The motivation to compare the near and far ROIs as taught by Akbari using the method of Hu would have been to examine levels of infiltration of the tumor, as taught by Akbari (p. 504, col. 3, par. 1).
Regarding claims 27 and 39, Hu in view of Akbari teaches claims 23-24 as described above. Claims 27 and 39 add that said first ROI within the in vivo peritumoral edematous tissue corresponds to a region of tissue adjacent an enhancing part of a tumor, and wherein said second ROI corresponds to a separate region of tissue within the in vivo peritumoral edematous tissue located at a location spaced farthest from the enhancing part of the tumor along a periphery of the in vivo peritumoral edematous tissue.
Hu does not teach this limitation.
However, Akbari teaches determining two ROIs within the edema and/or peritumoral region, one immediately adjacent to the enhancing tumor (near) and the other at the distal edema boundary (far) (. 504, col. 2, par. 1).
Regarding claims 28 and 45, Hu in view of Akbari teaches claims 23-24 as described above. Claims 28 and 45 add that the MRI data is selected from the group consisting of dynamic susceptibility contrast material-enhanced magnetic resonance imaging (DSC-MRI) data, dynamic contrast enhanced (DCE) MRI perfusion image data, T1-weighted (pre- and post-contrast) data, T2-weighted (pre- and post-contrast) data, and T2-weighted fluid-attenuated inversion recovery (T2-FLAIR) data.
Hu teaches that the set of multi-parametric MR images may include T1-Weighted (“T1W”) images, T2-Weighted (“T2W”) images, diffusion tensor images (“DTI”), perfusion MR images, dynamic susceptibility-weighted contrast-enhanced (“DSC”) perfusion MR images, and other image types [0032]. Hu also teaches T2W/FLAIR MR images [0087].
Regarding claim 29, Hu in view of Akbari teaches claim 24 as described above. The method of claim 29 adds that during said analyzing step, heterogeneity or similarity of perfusion temporal dynamics between said first and second ROIs is determined via a time-series of MRI data.
Hu teaches that the MR images can include a perfusion image (claim 2; [0032; 0044; 0056] and using those images for analysis [0073; 0109], but does not teach determining perfusion temporal dynamics as instantly claimed.
However, the prior art to Akbari discloses an analysis of dynamic susceptibility contrast material–enhanced magnetic resonance (MR) images to uncover unique tissue characteristics in patients with glioblastoma (abstract). Akbari teaches determining temporal dynamics of blood perfusion from MR imaging (p. 504, col. 2, par. 2 through p. 505, col. 3, par. 1).
Regarding claims 31-32, 40, and 42, Hu in view of Akbari teaches claims 23-24 as described above. Claims 31 and 40 add that said performing step includes applying a multi-variance statistical procedure to the MRI data to determine perfusion temporal dynamics of the first and second ROIs. Claims 32 and 42 add that said multi-variance statistical procedure is Principal Component Analysis (PCA).
Hu teaches using a Principal Component Analysis to reduce the features generated using the texture algorithm [0037; 0047; 0065-0066].
Regarding claim 30 and 41, Hu in view of Akbari teaches claims 23-24 and 40 as described above. Claims 30 and 41 further add that the MRI data is dynamic susceptibility contrast material-enhanced magnetic resonance imaging (DSC- MRI).
Hu teaches that the MR images may be dynamic susceptibility-weighted contrast-enhanced (“DSC”) perfusion MR images [0032; 0044; 0058; 0109].
Regarding claims 33 and 43, Hu in view of Akbari teaches claims 23-24 and 40 as described above. Claims 33 and 43 further add that said analyzing operation includes measuring separability between the perfusion temporal dynamics determined for the first and second ROIs, and wherein said assigning operation includes an assignment of EGFR-positive mutation status when the separability is low and indicates that the perfusion temporal dynamics between the first and second ROIs are similar and an assignment of EGFR- negative mutation status when the separability is high and indicates that perfusion temporal dynamics between the first and second ROIs are heterogeneous.
Hu teaches that EGFR amplification showed highly significant correlations with LBP texture on rCBV maps as well as three separate features on T2W imaging: two texture-based features (on DOST and GLCM) and standard deviation (SD) of raw T2W signal [0120]. Hu teaches that rCBV texture captures the contributions and signal patterns of the individual voxels within that ROI, giving insight to microvascular distribution and heterogeneity, and that that texture of rCBV correlates with EGFR status [0126], which is interpreted to mean that high texture in rCBV indicates EGFR-positive status as instantly claimed.
As claim 35 does not further limit claim 24 as described above in the 35 USC 112(d) rejection, and as Hu in view of Akbari teaches claim 24, it is considered that Hu in view of Akbari also teaches claim 35.
Regarding claim 37, Hu in view of Akbari teaches claim 23 as described above. The method of claim 37 adds that during said performing step, spatial heterogeneity or similarity of perfusion temporal dynamics is determined within the in vivo peritumoral edematous tissue.
Hu teaches that the MR images can include a perfusion image (claim 2; [0032; 0044; 0056] and using those images for analysis [0073; 0109], but does not teach determining perfusion temporal dynamics as instantly claimed.
However, the prior art to Akbari discloses an analysis of dynamic susceptibility contrast material–enhanced magnetic resonance (MR) images to uncover unique tissue characteristics in patients with glioblastoma (abstract). Akbari teaches determining temporal dynamics of blood perfusion from MR imaging (p. 504, col. 2, par. 2 through p. 505, col. 3, par. 1).
Regarding claim 38, Hu in view of Akbari teaches claim 23 as described above. The method of claim 38 adds that during said performing operation, imaging data of at least separate first and second regions of interest (ROIs) within the in vivo peritumoral edematous tissue are analyzed and compared to determine the level of spatial heterogeneity or similarity therebetween, which Akbari is considered to teach as described above (p. 504, col. 3, par. 1) (p. 505, col. 3, par. 2 through p. 506, col. 2, par. 2).
2B. Claims 26 and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Hu in view of Akbari, as applied to claims 26 and 36 above, and in further view of Lemee et al. (Neuro-Oncology, 2015, 17(10):1322-1332; cited on the Oct 26 2021 IDS). The instant rejection is newly stated and is necessitated by claim amendment.
Regarding claims 26 and 36, Hu in view of Akbari teaches claims 23-24 as described above. Claims 26 and 36 further add that the mutation is selected from EGFR variant III (vIII), a point mutation at EGFR A289V, a point mutation at EGFR variant G598, and/or a point mutation at EGFR variant R108, with reference to the residue numbering of SEQ ID NO:1.
Hu teaches detecting EGFR amplification [0120], but does not teach the mutation is selected from the recited variants.
However, the prior art to Lemee discloses that intratumoral heterogeneity in the peritumoral brain zone around glioblastomas is an important region for prognosis (abstract). Lemee teaches that glioblastomas that had infiltrated the peritumoral brain zone had amplification of EGFR (p. 1324, col. 2, par. 2). Lemee teaches that EGFR variant III (EGFRvIII) is a target for glioblastoma therapy (p. 1326, col. 1, par. 1).
Regarding claims 26 and 36, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Hu and Lemee because both references disclose methods analyzing glioblastomas. The motivation to examine EGFRvIII and to treat it with a targeted therapy would have to examine common types of EGFR mutations and treat glioblastomas with promising new therapies, as taught by Lemee (p. 1326, col. 1, par. 1).
2C. Claims 34 and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Hu in view of Akbari, as applied to claims 23-24, 33, 40, and 43 above, and in further view of Sumana et al. (IJESR, 2013, 4(1):1350-1354; previously cited). The instant rejection is newly stated and is necessitated by claim amendment.
Regarding claims 34 and 44, Hu in view of Akbari teaches claims 23-24, 33, 40, and 43 as described above. Claims 34 and 44 further adds that separability is measured via Bhattacharyya coefficient analysis.
Hu does not teach this limitation.
However, the prior art to Sumana discloses a new region merging based interactive image segmentation method (abstract) which employs the well-known goodness-of-fit statistical metric Bhattacharyya coefficient to define a similarity measure between two regions (p. 1351, par. 4).
Regarding claims 34 and 44, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Hu in view of Akbari with Sumana because each reference discloses methods for analyzing MRI data. The motivation to use the Bhattacharyya coefficient as taught by Sumana would have been to use a well-known metric define a similarity measure between two regions, as taught by Sumana (p. 1351, par. 4).
2D. Claims 25 and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Hu et al. (US 2017/0103525; previously cited) in view of Akbari et al. (Radiology, 2014, 273(2):502-510; cited on the Oct 26 2021 IDS) and Johnson et al. (Science Translational Medicine, 20157(275), pp.275ra22-275ra22, p. 1-14; newly cited). The instant rejection is newly stated and is necessitated by claim amendment.
Claim 25 discloses a method for targeted treatment of a patient having a neoplasm associated with an epidermal growth factor receptor (EGFR) mutation, the method comprising:
(a) non-invasively detecting EGFR variant III positive mutation status within peritumoral edematous tissue of a the patient using a computer-implemented method comprising executing on a processor: performing quantitative pattern analysis of magnetic resonance imaging (MRI) data corresponding to MRI of an in vivo peritumoral edematous tissue to determine a level of spatial heterogeneity or similarity with the in vivo peritumoral edematous tissue; assigning EGFR variant III mutation status as one of negative or positive based on the level of spatial heterogeneity or similarity determined during said performing step, wherein EGFR -negative mutation status is assigned when differing levels of neovascularization is determined to exist between a first region of interest (ROI) and a second ROI, and EGFR -positive status is assigned when similar levels of neovascularization is determined to exist in said first and second ROIs; and
(b) treating the EGFR positive patient with a EGFR-targeting therapy.
Hu teaches selecting at least one region of interest (ROI) in the MR images acquired from a subject, performing a texture analysis on corresponding ROIs, and applying a classification scheme (abstract; [0009-0012; 0029-0040]). Hu teaches that texture features used in texture analysis generally capture different aspects of the spatial distribution of intensities to provide a quantitative indication of image texture (i.e., performing quantitative pattern analysis to determine a level of spatial heterogeneity or similarity) [0036]. Hu teaches examining images taken from the surrounding non-enhancing parenchyma, or Brain Around Tumor (BAT) which is indistinguishable from non-tumor vasogenic edema, in patients with Glioblastoma [0005; 0031; 0054]. Hu is therefore considered to fairly teach examining in vivo peritumoral edematous tissue as instantly claimed. Hu teaches that EGFR amplification showed highly significant correlations with LBP texture on rCBV maps as well as three separate features on T2W imaging: two texture-based features (on DOST and GLCM) and standard deviation (SD) of raw T2W signal [0120]. Hu teaches that rCBV texture captures the contributions and signal patterns of the individual voxels within that ROI, giving insight to microvascular distribution and heterogeneity, and that that texture of rCBV correlates with EGFR status [0126]. Hu teaches the link between EGFR and T2W signal patterns of tumoral/vasogenic edema has been suggested previously [0126]. Therefore, it is considered that the method of Hu fairly teaches assigning EGFR status based on differences in neovascularization as instantly claimed.
Hu does not specifically teach detecting EGFR variant III positive mutation status. Hu teaches targeted therapies for different genes [0099], but not for EGFR.
However, the prior art to Johnson discloses the development and characterization of anti-EGFR variant III chimeric antigen receptor T cells for glioblastoma (title; abstract; entire document is relevant).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Hu and Johnson because both references disclose methods concerning EGFR mutation status. The instant specification as published discloses that EGFR version III causes constitutive signaling in the absence of ligand binding [0006], which would have a similar effect to EGFR amplification as taught by Hu. As the claims do not recite features for determining the molecular sequence of the EGFR gene in the patient, and rely merely on the changes caused by the mutation on features visible in MRI data, it is considered that different mutations which similarly affect EGFR function would result in similar features. Therefore, one of ordinary skill in the art would expect to detect EGFR positive mutation status, including either EGFR amplification or EGFR version III and such a substitution is no more than the simple substitution of one known element for another.
Hu does not teach separate, non-overlapping first and second ROI’s.
However, the prior art to Akbari discloses an analysis of dynamic susceptibility contrast material–enhanced magnetic resonance (MR) images to uncover unique tissue characteristics in patients with glioblastoma (abstract). Akbari teaches obtaining dynamic susceptibility contrast-enhanced MR imaging data and creating a map of heterogeneity within the peritumoral region to determine a heterogeneity score (abstract; p. 504, col. 1, p.ar 2 through p. 506, col. 2, par. 2; entire document is relevant). Akbari teaches defining several regions of interest, including two near-far ROIs within the edema and/or peritumoral region (p. 504, col. 3, par. 1). Akbari teaches training a model using the near-far ROIs to generate heterogeneity scores (i.e., determine a level of spatial heterogeneity or similarity between separate first and second ROIs) (p. 505, col. 3, par. 2 through p. 506, col. 2, par. 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Hu in view of Johnson and Akbari because both references disclose methods for analyzing spatial heterogeneity in peritumoral samples of glioblastomas. The motivation to compare the near and far ROIs as taught by Akbari using the method of Hu would have been to examine levels of infiltration of the tumor, as taught by Akbari (p. 504, col. 3, par. 1).
Claim 46 further adds that the EGFR-targeting therapy is a chimeric antibody receptor (CAR) T-cell therapy comprising an anti-EGFR targeted component.
The prior art to Johnson discloses the development and characterization of anti-EGFR variant III chimeric antigen receptor T cells for glioblastoma (title; abstract; entire document is relevant).
Response to Applicant Arguments
At p. 13-14, Applicant submits that the prior art rejections should be withdrawn for the following reasons. First, Bakas does not teach or suggest the means for determining EGFR mutation status recited in the claims. Second, Applicant summarizes what Hu does and does not teach. Third, Applicant submits that Akbari does not specifically identify EGFR mutations, and that there is no suggestion to use the method of Akbari and Hu together to assign EGFR mutation status.
It is respectfully submitted that this is not persuasive. Regarding Bakas, Applicant has not explained which means recited in the claims that they do not think Bakas teaches. As described in the above rejection, Bakas is considered to teach most of the features. Therefore, Applicant’s remarks lack factual evidence and are not evidentiary. Regarding Hu, it is agreed that Hu does not teach the features outlined by Applicant. Regarding the suggestion to combine Hu and Akbari, it is noted that as Hu teaches effects in MRI data from EGFR mutation status on the tissue in the brain around the glioblastoma tumor [0086-0127], one of ordinary skill in the art would have been motivated to use the method of Akbari to examine changes caused by EGFR mutation near and further away from the tumor.
Statutory Double Patenting
The outstanding rejections from the previous Office Action are withdrawn in view of the amendments and arguments on p. 14-15 submitted herein.
Non-Statutory Double Patenting
The terminal disclaimer filed on Sep 29 2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent No. 11,107,217 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANNA NICOLE SCHULTZHAUS whose telephone number is (571)272-0812. The examiner can normally be reached on Monday - Friday 8-4.
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, Olivia Wise can be reached on (571)272-2249. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see https://ppair-my.uspto.gov/pair/PrivatePair. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/J.N.S./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685