DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Arguments
Applicants' arguments, filed December 9, 2025, have been fully considered but they are not deemed to be fully persuasive. The following rejections and/or objections constitute the complete set presently being applied to the instant application.
Drawings
In view of the granted petition to accept color drawings mailed January 21, 2026, the drawings received on December 9, 2025 are acceptable.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Such limitations appear once in step (a)(i), twice in step (a)(ii) and once in step (c). Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
Claim Rejections - 35 USC § 112 – New Matter
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 2 and 12 were rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This new matter rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed June 9, 2025 and those set forth herein.
The amendments to the claims have not fully resolved the new matter issues that were identified in the Office Action and have introduced additional new matter as discussed below.
For part (a) of the claimed method, ¶¶ [0015] and [0020] describing Fig 1 and 5 seem to be the closest possible support. But the methods in the paragraphs are narrow with an unknown number of gradient echoes for Figure 1 and it appears 4 data points only for Figure 5 with the instant claims are silent as to the number of images obtained. Specific formulas are used in the processing of the images (Equations 1 – 4 and the modifications discussed in ¶ [0020] to equation 4 when 4D rapid T1-w acquisition was used rather than the gradient echo images of Figure 1.
Step (a)(i) was rejected as containing new matter and still contains new matter. The recitation “means to fit the estimation of the longitudinal relaxation (T1) at every voxel” is not disclosed in the specification as originally filed and the disclosure relating to such data processing does not clearly link or associate the disclosed acts to the claimed function as required when means plus function language is invoked (see MPEP 2181(II)(C)) by the phrase “means to fit the estimation of the longitudinal relaxation (T1) at every voxel”.
In amended step (a)(ii), “permeability score of the contrast agent” is not used in the disclosure as filed. The disclosure is limited to the first pass to arterial measurements when discussing the first pass (e.g., ¶¶ [0015] and [0020]) but the claims encompass the first pass of the entirety of the vascular system. Various permeabilities are discussed in the disclosure as originally filed and in the claims with PermMEAN representing the sum of the permeability scores of all tumor voxels divided by the number of all tumor voxels (¶ [0027] of the PGPub of the instant application) which might align with the language of amended step (a)(ii). As above, the disclosure does not clearly link or associate the disclosed acts to the claimed function as required when means plus function language is invoked (see MPEP 2181(II)(C)) by the phrases “means to estimate the concentration of the contrast agent over time at every voxel in the series of MRI images” and “means for deconvolving tissue leakage of contrast agent into the patient’s tissue”.
In step (iii), there is no support for the claimed range of threshold values used in determining the Uth score. Figure 2D is stated to have a threshold value of 0.8E-03 (0.8 x 10-3) but this is set forth as an exact value for the particular experiment shown in Figure 2D and not a range of values as recited in amended step (iii) with the Examiner unable to locate any disclosure of the lower end point or points in between.
As for step (b), ¶ [0065] seems to provide the closest support as determination of the TMEM site count by a simultaneous measure of MenaINV expression from the cells obtained from a fine needle aspirate is disclosed, but there is no indication of assessment using “relative MenaINV expression in tumor cells” as this paragraph just states “measure of MenaINV expression in tumor cells”. This biopsy sample collection is also required to occur “at about the same time” as step (a) and there is no disclosure of such a time frame in the disclosure as originally filed. ¶ [0065] states that the “simultaneous measure of MenaINV expression … in the same patient receiving the TMEM-MRI”, but “simultaneous” means occurring at the same time or exactly coincident (definition 1 from definition of simultaneous from merriam-webster.com, accessed February 10, 2026 that accompanies this action). “[A]bout the same time” as claimed does not have the same scope as “simultaneous” and therefore the relative timing of steps (a) and (b) is not supported by the disclosure as originally filed.
As for step (c), the use of the Uth score and the MenaINV score to express TMEM activity is disclosed (e.g., ¶¶ [0027]) alone or relative to a TMEM score obtained by immunohistochemistry, a MenaINV score or a MenaCalc score (¶ [0030]) but the Examiner was unable to locate support for the ratio of Uth score to the MenaINV score, not a TMEM score obtained by such a measurement. The disclosure does not clearly link or associate the disclosed acts to the claimed function as required when means plus function language is invoked (see MPEP 2181(II)(C)). The determined activity score is a “means for (i) predicting metastatic risk associated with the tumor or for (ii) assessing effectiveness of a treatment for the tumor”, ¶ [0051] indicates that “a high TMEM activity score indicates that the subject is at increased risk of hematogenous metastasis and should be treated for a metastatic tumor”. ¶ [0043] discusses part (ii) of this phrase but requires obtaining two TMEM activity scores, either before and after treatment of at the first and second stage of treatment, that are then compared to evaluate the treatment. Step (c) of claim 1 does not require the generation of two scores at such times points to determine the effectiveness of a treatment.
The dependent claims fall therewith.
Applicants traverse by various citations from the specification inserted verbatim into the remarks and statements that the material in these sections has been incorporated into the claims as currently amended.
These arguments and citations are insufficient to establish that the claims as currently presented are fully supported by the disclosure as originally filed. The amended claims are not supported verbatim by the disclosure as originally filed including in the numerous sections cited in the response. When the overall claimed subject matter is evaluated, the full scope of the claims is not supported explicitly. There is no explanation as to how implicit and/or inherent support for the claim limitations arises from the claimed sections or elsewhere in the specification as filed. Therefore the claims are still rejected as containing new matter as discussed above.
Claim Rejections - 35 USC § 112 – Written Description
Claims 1, 2 and 12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
As part of the quid pro quo for the convenience of employing 35 USC 112(f), a particular structure must be clearly linked with the claimed function in order to qualify as required corresponding structure disclosed in the written description of the specification as an indefinite, unbounded functional limitation would cover all ways of performing a function and the disclosure as originally filed does not provide sufficient disclosure to show possession of the full scope of the claimed method (see MPEP 2163.03(VI)). Here the disclosure as originally filed does not clearly link the means plus function language of the four means plus function limitations in claim 1 (steps (a)(i), (a)(ii) and (c)) with the particular acts encompassed by this language to demonstrate the necessary possession of the claimed subject matter.
Claim Rejections - 35 USC § 112 – Indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 2 and 12 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.
These claims were previously rejected as indefinite and extensive amendments were made to the claims. As discussed below, the metes and bounds of the claims as currently amended still cannot be determined and therefore remain rejected as indefinite for the reasons set forth below.
As discussed above, steps (a)(i), (a)(ii) and (c) all contain means plus function language. As such, the disclosure must disclose the corresponding acts for each means plus limitation found in claim 1 and those corresponding acts must be clearly linked or associated with the disclosed acts. Here the disclosure fails to specifically disclose any such means explicitly linked to each of the means plus function limitations recited in claim 1 and does not clearly link the act(s) encompassed by each of these limitations.
In step (a)(iii), it is ambiguous to what “permeability scores” refers. Does this refer to the permeability score of the contrast agent during its first pass through the tumor which is done for every voxel so there are many such scores? Or does “permeability scores” in this step not preceded by “an” or “the” refer to a different score that was not previously recited?
Step (b) requires a score that is “assessed by relative MenaINV expression in tumor cells from the tumor” but relative expression levels require a basis for comparison which is not specified in the claims. Is the relative assessment the same as the normalization of Mena expression discussed in ¶ [0041] of the PGPub of the instant application? It would also appear that some addition undisclosed data manipulation might be required given that the step begins with “measuring TMEM count in the tumor” (emphasis added) and which is not the same as protein expression levels and would seem to require extrapolation from the cells in the sample to that of the tumor in its entirely. If such a step is actually required, that may not be supported by the disclosure as originally filed.
The steps recited in claim 1 result in a number that is reflective of TMEM activity, but step (c) requires that the activity score, which might be referring to the “the activity of the TMEM” or potentially some other activity score, then be used to predict metastatic risk or treatment effectiveness. It is not clear how a single time point can be used to determine treatment effectiveness. The disclosure as filed calculates two TMEM activity scores before and after treatment (¶ [0043] of the PGPub of the instant application) and the comparison provides such information about treatment effectiveness. But there is no discussion of a single TMEM activity measurement having the means to provide such information so the scope of the claimed method is unclear.
The dependent claims fall therewith.
Please clarify.
Claim 2 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 2 references “wherein permeability is increased” and it is not clear if this is a new permeability term not previously presented in the claims or if this in fact refers to one of more of the longitudinal relaxation (T1) permeability map, the permeability score of the contrast agent during its first pass through the tumor and/or the permeability scores in step (a)(iii). Please clarify.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 2, and 12 were rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas without significantly more. This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed June 9, 2025 and those set forth herein.
The claims now recite a method of measuring activity of a particular type of site, a tumor micro-environment for metastasis (TMEM), in which a well-known contrast agent is administered to a patient, MRI images are collected and data manipulation carrier out to generate information as to leakage of the intravascularly administered contrast agent from the vascular system; cells are collected via biopsy and MenaINV expression levels determined; and then further data analysis is carried out to generate a score that provides a means for predicting metastatic risk or to assess treatment effectiveness from the determined TMEM activity. This judicial exception is not integrated into a practical application because the physical steps that are carried out are required to generate the information used in the abstract idea to generate an activity score and further information about metastatic risk or treatment effectiveness and the abstract ideas do not result in sufficient integration of the judicial exception to render the claimed subject matter patent eligible. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because all of the physical steps are required to generate the activity score claimed and once that determination is made as to metastasis risk or treatment effectiveness, no further action is taken. All uses of the judicial exception require the data collected in the physical steps that are carried out. Vascular permeability measurements using Gd-DTPA in conjunction with MRI and menaINV expression determination in cell such as those collected during a biopsy are known in the art (for example, the references cited in the obviousness rejection below), amounting to insignificant extrasolution activity to the judicial exception. A determination of the activity as now recited in the preamble of the claim as defined in the body of the claim is therefore not drawn to eligible subject matter given the steps and determinations required of the claims as currently amended.
Applicants traverse this rejection on the grounds that the features of claim 1 are not well-understood, routine or conventional in the field and the office action acknowledges that the type and information in step (a) as to TMEM activity are not routine parameters. The claimed combination of steps provides a non-obvious advantage of being able to measure TMEM activity in a minimally invasive method in contrast to the more invasive methods that are known in the art. Features that are not well-understood, routine or conventional may constitute significantly more than a judicial exception and as such, the claims are not directed merely to a law of nature or abstract idea but recites an inventive concept sufficient to confer eligibility under § 101.
These arguments are unpersuasive. The claim as a whole must be analyzed and the measurement of vascular permeability using a contrast agent such as Gd-DTPA is well known in the art and analysis of cells from biopsies to determination expression levels of proteins such as MenaINV known to be present at TMEM sites, a known marker for metastatic risk, is known in the art. The claimed processing of information obtained from these two different experiments to determine the activity of the TMEM is not anticipated by the prior art, but all steps are necessary to carry out the judicial exception as without the information from such steps, the TMEM activity cannot be determined. There is also no action taken with the information obtained from the judicial exception. Therefore, even as amended, the instant claims as a whole do not amount to significantly more than the judicial exception.
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.
Claim(s) 1, 2 and 12 were rejected under 35 U.S.C. 103 as being unpatentable over Harney et al. (Cancer Discov, 2015) in view of Bhujwalla et al. (Neoplasia, 2001), Radjenovic et al. (Br J Radiology, 2008), Li et al. (Br J Radiol, 2003) and Roussos et al. (Clin Exp Metastasis, 2011). This rejection is MAINTAINED for the reasons of record set forth in the Office action mailed June 9, 2025 and those set forth herein.
As to the amended claims, Li et al. discloses T1 weighted 3D images that are acquired at different times at varying flip angles and the sequences with the highest flip angle was repeated (¶ bridging cols 1 and 2 on p 40), with time being the 4th dimension in the claimed method step so such data acquisition reads on the 4D rapid T1-w acquisition of the amended claims. Rapid intravenous injection of Gd-DTPA was immediately followed by another dynamic data acquisition with a temporal resolution of 5.1 sec with data from the first minute of acquisition being used for analysis based the first pass pharmacokinetic model (¶ bridging cols 1 and 2 on p 40). The approach taken uses decomposition tissue residue functions measured during the first passage of CA (contrast agent) bolus on T1W images intro intravascular and extravascular components (p 40, col 1, ¶ 2) so the data analysis will result in score as required by amended step (a)(ii) is rendered obvious as intravascular and extravascular components determines leakage from the vascular system into extravascular tissue. Data collected in close temporal proximity can provide improved information about vascular leakage as once leaked from the vascular system, the Gd-DTPA has less time to diffuse in the extravascular space, potentially leading to a lower MRI signal. Roussos et al. discloses the positive correlation between TMEM sites and metastasis and the measurement of MenaINV expression in fine needle aspirate biopsy samples. While this reference does not disclose vascular permeability measurements using MRI and Gd-DTPA in conjunction with such sample collection and therefore cannot disclose the relative timing of the two steps, given the potential for a tumor to change over time, one of ordinary skill in the art would be motivated to carry out these two tests in as close temporal proximity as practical. This could permit the patient to have both tests done on the same date and overall location such as a hospital to minimize burdens on the patient while also maximizing the overlap of the information provided by each test result. As discussed by Harney et al., transient vascular permeability is part of TMEM sites that are known in the art to be associated with tumor cell intravasation and information about not only the number of sites but that are also exhibiting vascular permeability, reflected in the results from the MRI measurements with Gd-DTPA so an indication of the activity levels of such sites would be reasonably be expected by one of ordinary skill in the art to provide information as to at least the metastatic risk of the tumor being investigated.
Applicants traverse this rejection on the grounds that the combination of steps that occurs at about the same time is important because it provides a less invasive way to measure TMEM activity based on simultaneous tests. Clinical practice requires a formalin-fixed paraffin embedded (PFFE) tissue sample which requires extensive tissue collection from a core biopsy. The claimed invention uses FNA (fine needle aspiration) to measure MenaINV as a minimally invasive method. The claimed invention solves the problem of the presence of TMEM sites not informing about the activity of the sites. None of the cited references teach or suggest the combination claimed. The rejection is based on improper hindsight reconstruction as the cited references do not individually or collectively provide the specific guidance or motivation to arrive at the claimed method. The five references used underscores the lack of clear teaching or suggestion in the prior art and the courts have cautioned against such hindsight analysis.
These arguments are unpersuasive. The clinical standard of care can be used to establish obviousness but other methods that are known in the art but not routinely practiced in a clinical setting can also form part of an obviousness rejection. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). No information gleaned only from applicant’s disclosure has been identified and while motivation to combine the various references is not explicitly disclosed in the applied prior art, rationale has been set forth by Examiner as to why the proposed modifications would have been obvious but no arguments about that reasoning were set forth. In response to applicant's argument that the examiner has combined an excessive number of references, reliance on a large number of references in a rejection does not, without more, weigh against the obviousness of the claimed invention. See In re Gorman, 933 F.2d 982, 18 USPQ2d 1885 (Fed. Cir. 1991). The importance of TMEM sites for metastatic potential, determination of the presence of MenaINV and vascular permeability at such sites is known in the art such as indicated by the applied prior art. The evidence of record does not establish the criticality of the claimed MRI acquisition parameters or unexpected results that are reasonably commensurate in scope with the claims. Therefore the rejection is maintained for the reasons of record.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 2 and 12 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 1 - 27 of U.S. Patent No. 8,642,277 in view of Harney et al. (Cancer Discov, 2015) in view of Bhujwalla et al. (Neoplasia, 2001), Radjenovic et al. (Br J Radiology, 2008), Li et al. (Br J Radiol, 2003) and Roussos et al. (Clin Exp Metastasis, 2011). This rejection is MAINTAINED for the reasons of record set forth in the Office action mailed June 9, 2025 and those set forth herein.
As to the amended claims, Li et al. discloses T1 weighted 3D images that are acquired at different times at varying flip angles and the sequences with the highest flip angle was repeated (¶ bridging cols 1 and 2 on p 40), with time being the 4th dimension in the claimed method step so such data acquisition reads on the 4D rapid T1-w acquisition of the amended claims. Rapid intravenous injection of Gd-DTPA was immediately followed by another dynamic data acquisition with a temporal resolution of 5.1 sec with data from the first minute of acquisition being used for analysis based the first pass pharmacokinetic model (¶ bridging cols 1 and 2 on p 40). The approach taken uses decomposition tissue residue functions measured during the first passage of CA (contrast agent) bolus on T1W images intro intravascular and extravascular components (p 40, col 1, ¶ 2) so the data analysis will result in score as required by amended step (a)(ii) is rendered obvious as intravascular and extravascular components determines leakage from the vascular system into extravascular tissue. Data collected in close temporal proximity can provide improved information about vascular leakage as once leaked from the vascular system, the Gd-DTPA has less time to diffuse in the extravascular space, potentially leading to a lower MRI signal. Roussos et al. discloses the positive correlation between TMEM sites and metastasis and the measurement of MenaINV expression in fine needle aspirate biopsy samples. While this reference does not disclose vascular permeability measurements using MRI and Gd-DTPA in conjunction with such sample collection and therefore cannot disclose the relative timing of the two steps, given the potential for a tumor to change over time, one of ordinary skill in the art would be motivated to carry out these two tests in as close temporal proximity as practical. This could permit the patient to have both tests done on the same date and overall location such as a hospital to minimize burdens on the patient while also maximizing the overlap of the information provided by each test result. As discussed by Harney et al., transient vascular permeability is part of TMEM sites that are known in the art to be associated with tumor cell intravasation and information about not only the number of sites but that are also exhibiting vascular permeability, reflected in the results from the MRI measurements with Gd-DTPA so an indication of the activity levels of such sites would be reasonably be expected by one of ordinary skill in the art to provide information as to at least the metastatic risk of the tumor being investigated.
Applicants traverse by highlighting that the same combination of references is used in the nonstatutory double patenting rejection as under § 103 above and the same arguments apply to this rejection.
Those arguments were unpersuasive for the reasons discussed above and the instant claims are not patentably distinguished over the claims of US’277 in view Harney et al., Bhujwalla et al., Radjenovic et al., Li et al. and Roussos et al.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nissa M Westerberg whose telephone number is (571)270-3532. The examiner can normally be reached M - F 8 am - 4 pm.
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/Nissa M Westerberg/Primary Examiner, Art Unit 1618