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 .
Terminal Disclaimer
The terminal disclaimer filed on 8/7/2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US Patent 12067714 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Claim Objections
Claim 33 is objected to because of the following informalities:
The amendment to claim 33 defining the acronym has misspelled both perivascular and the acronym.
Appropriate correction is required.
Response to Arguments
Note: The previous grounds for rejection under USC 112(b) are withdrawn in light of the amendments to the claims.
Note: The previous grounds for claim objections are withdrawn in light of the amendments to the claims.
Applicant's arguments filed 8/7/2026 have been fully considered but they are not persuasive. The examiner thoroughly reviewed the applicant’s arguments but firmly believes that the cited reference reasonably and properly meets the claimed limitation as rejected.
Applicant’s argument: The applicant has argued the grounds for combining the Gillies and Antoniades references. “Applicants respectfully submit that it would not have been obvious to someone of ordinary skill in the art to combine Gillies and Antoniades, and neither would such a hypothetical combination yield the method as recited in claim 25. Gillies discloses calculating radiomic features from radiographic imaging of cancers for "diagnosis, a prognosis or recommended treatment" (see paragraph [0004] of Gillies). While the invention of Gillies relates to radiographic imaging, it does not refer to heart, cardiac or coronary imaging, let alone imaging specifically the perivascular region or tissue, and extracting radiomic features from said regions. Gillies relates only to the field of diagnosing and treating cancer through medical imaging. Whereas Antoniades specifically relates only to imaging perivascular tissue surrounding coronary arteries (see, page 1 line 8 of Antoniades). Therefore, for at least this reason alone, given these two fields of Gilles and Antoniades do not intersect, it would not be obvious for someone to combine the two disparate disclosures.”
Examiner’s response: The Examiner has reviewed the applicant’s argument regarding the combination of references, but respectfully disagrees with the assertion made. Specifically, the applicant has stated “While the invention of Gillies relates to radiographic imaging, it does not refer to heart, cardiac or coronary imaging, let alone imaging specifically the perivascular region or tissue, and extracting radiomic features from said regions. Gillies relates only to the field of diagnosing and treating cancer through medical imaging.” Respectfully, this assertion as to the nature of the Gillies reference is incorrect, and not supported through the disclosure of the Gillies reference. At paragraph 0004, Gillies discloses “An example method for analyzing quantitative information obtained from radiological images can include identifying a region of interest (ROI) or a volume of interest (VOI) in a radiological image, segmenting the ROI or the VOI from the radiological image and extracting a plurality of quantitative features that describe the ROI or the VOI from the radiological image. Herein, ROI or VOI may include a tumor region and/or its the surroundings. it may also be other organ systems, non cancerous. The method can also include creating a radiological image record including the quantitative features describing the ROI or the VOI from the radiological image, imaging parameters related to the radiological image and clinical parameters and storing the radiological image record in a data structure containing a plurality of radiological image records. In addition, the method can include receiving a request related to a patient's radiological image, where the request includes the patient's radiological image or information related to a patient's radiological image, analyzing the data structure to determine a statistical relationship between the request and the plurality of radiological image records and generating a patient report (e.g., a patient decision support report) with a diagnosis, a prognosis or a recommended treatment regimen for the patient's disease based on a result of analyzing the data structure. The statistical or numerical relationship between the request and plurality of radiological image records can be either determined at the time of the request or pre-determined and be embodied in a mathematical equation that is applied. In addition, the method can be used to develop, in a stand-alone platform, relationships between the image features and patient characteristics, including clinical responses to therapy or prognostic information.(sic)” Additionally at Paragraph 0049 Gillies discloses “Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure. As used in the specification, and in the appended claims, the singular forms “a,” “an,” “the” include plural referents unless the context clearly dictates otherwise. The term “comprising” and variations thereof as used herein is used synonymously with the term “including” and variations thereof and are open, non-limiting terms. The terms “optional” or “optionally” used herein mean that the subsequently described feature, event or circumstance may or may not occur, and that the description includes instances where said feature, event or circumstance occurs and instances where it does not. While implementations will be described for analyzing quantitative information obtained from radiological images of a patient with cancer, it will become evident to those skilled in the art that the implementations are not limited thereto, but are applicable for analyzing quantitative information obtained from radiological images of a patient with other diseases such as, inter alia, cardiovascular disease, autoimmune disease, trauma, neurodegenerative or psychiatric disorders, or infectious diseases. It should also be understood that the implementations are also applicable for analyzing quantitative information obtained from radiological images of a patient with no diseases such as in a screening setting, for example.(sic)” This disclosure is in direct contrast with the association made by the applicant regarding the disclosure of Gillies and the scope of consideration made in the Gillies disclosure. Specifically, the disclosure of Gillies clearly states that the disclosure can be used for more than cancer, and explicitly states it can be used in the analyzing of cardiovascular disease. Therefore, this disclosure within Gillies renders the argument of the applicant incorrect and allows for considerations for obviousness as it relates to heart-related diseases being fully supported. Therefore, the motivation for combining the references is maintained, and the grounds for rejection previously presented are further maintained.
Applicant’s argument: The applicant has argued that Antoniades does not teach the claimed limitations, specifically “Antoniades relates only to using "radiodensity values" for volumetric characterization (see page 7 lines 8 to 21). Antoniades simply suggests measuring the radiodensity of perivascular adipose tissue (PVAT) and comparing this measured radiodensity against a baseline radiodensity value. No radiomic signature is calculated in Antoniades, and certainly not one calculated after extracting a radiomic feature from the medical image as claimed. There is no suggestion in Antoniades that such a calculated radiomic signature would provide a medically useful characterisation of perivascular tissue that is indicative of vascular disease. Antoniades, instead, suggests comparing simple radiodensity values with baseline values.
The present method as recited in claim 1 extracts radiomic features and a radiomic signature from a perivascular region or volume of interest comprising perivascular tissue. There is no disclosure in Antoniades of "extracting a radiomic feature from the medical imaging data; and calculating a value of a radiomic signature of the perivascular region or volume of interest using the medical imaging data; wherein the radiomic signature is calculated on the basis of the radiomic feature extracted from the medical imaging data" as in claim 25.
Therefore, there is no teaching in Antoniades, that in combination with Gilles, would lead the skilled person to extract a radiomic features from a "perivascular region" and calculate a radiomic signature from the same region, as in the method of claim 25.” The applicant then further argues “Fundamentally, the link between radiomics of perivascular tissue and cardiac risk is new science revealed by the inventors of the present patent application, as they explain therein.
For example, as explained on page 23, lines 4-11, of the application as filed, the present method exploits the finding by the inventors that the coronary wall and the adjacent perivascular tissue interact in a bidirectional manner to cause changes in the perivascular tissue. It was previously unknown that vascular disease causes perivascular fibrosis and microvascular remodelling, and that this is manifested in changes in the perivascular tissue. This biology, which is specific to vascular disease, was previously unknown. The present application demonstrates for the first time that perivascular tissue changes, for example in tissue texture, are driven by vascular disease and that these changes can be sufficiently captured and quantified using a radiomic signature based on an extracted radiomic feature to provide a medically useful characterisation of the perivascular tissue that is strongly indicative of vascular disease and provides improved prognostic indications.
Neither Gilles nor Antoniades, either taken individually or in combination, discloses "extracting a radiomic feature from the medical imaging data; and calculating a value of a radiomic signature of the perivascular region or volume of interest using the medical imaging data; wherein the radiomic signature is calculated on the basis of the radiomic feature extracted from the medical imaging data" as recited in claim 25.”
Examiner’s response: First, to address the assertions made towards the use of Antoniades, this reference was never once stated in the office action to provide radiomic signatures. The applicant’s own claim states that the radiomic signature is based on radiomic features extracted from a medical image. The office action has stated that Antoniades recites the medical imaging of the perivascular region. The disclosure further shows the finding or analysis of radiomic features. This consideration of the radiomic features through medical imaging provides a strong basis for the motivation for combination in the obviousness consideration. The office action however does not state that Antoniades discloses a radiomic signature. Antoniades is stated to provide a medical image, with disclosure supporting the consideration of radiomic features. Gillies is cited to show the consideration of determining a radiomic signature from a medical image from the consideration of radiomic features. Thus, the clear motivation for USC 103 considerations. Specifically, this assertion is incorrect because it does not address the grounds of the office action, but rather argues a position that was never provided as grounds for rejection. The use of Antoniades and the associated grounds for rejection are therefore maintained. Finally, the applicant has stated that the claimed link is ‘new science’ and therefore is not disclosed in the provided arts. However, Gillies clearly states the ability to use imaging to determine heart disease concerns, while Antoniades clearly states the ability to provide imaging of an area related to heart disease. The above rebuttals to the provided arguments are sufficient to support a case for motivation in an obviousness rejection, and simply stating the discovery is new lacks validity over the teachings shown in the cited prior art. Therefore the grounds for rejection under USC 103 are respectfully maintained as previously presented.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 25-26, 29-39 are rejected under 35 U.S.C. 103 as being unpatentable over Gillies (US Pub 20160203599) in view of Antoniades (herein after Ant) (WO 2016/024128, see IDS [copy provided in parent application per note above]).
Re claim 25, Gillies discloses a method for characterizing an imaged region or volume of interest comprising imaged tissue of a subject, the method comprising:
(a) obtaining or having obtained medical imaging data (Par 52-53, 57, 63-65 – radiological image) of the imaged region (Par 52-53, 57, 63-65 -ROI) or volume of interest of the subject (Par 52-53, 57, 63-65 -VOI);
(b) extracting a radiomic feature from the medical imaging data (Par 50, 55, 65, 78-79, 107, 112 – radiomic feature); and
(c) calculating a value of a radiomic signature (Par 65, 107, 112, 137) of the imaged region or volume of interest using the medical imaging data (Par 65, 107, 112, 137);
wherein the radiomic signature (Par 65, 107, 112, 137) is calculated based on the radiomic feature extracted from the medical imaging data (Par 65, 107, 112, 137 – “best performing feature selected … and combined into a multivariate radiomic signature”); however, Gillies fails to explicitly disclose wherein the imaged region comprising imaged tissue comprises a perivascular region comprising perivascular tissue.
This design is however disclosed by Ant. Ant discloses wherein the imaged region comprising imaged tissue comprises a perivascular region (Page 1 lines 8-17; Page 5 line 29-Page 6 line 12 – PVAT imaging and calculations) comprising perivascular tissue (Page 1 lines 8-17; Page 5 line 29-Page 6 line 12 – PVAT imaging and calculations).
Therefore, it would have been obvious to one of ordinary skill in the art at the effective filing date of the invention to modify the disclosure of Gillies in order to incorporate the perivascular considerations of Ant based on the rationale of the use of a known technique to improve similar designs in the same way, in this instance as processing medical imaging to determine and establish diagnostic signatures, it would be obvious to apply this medical imaging of other areas within the body or to a specific area within the human body, thereby improving the models capacity to train of specific areas of the body, improving the efficiency and quality of the diagnostic model, and further increasing the likelihood of correct and accurate diagnostic procedures at the benefit to both the patient and service providers.
Re claim 26, the combined disclosure of Gillies and Ant as a whole discloses the method of claim 25, Ant further discloses wherein the subject is a human (Page 8 description of Fig 6; Page 23, lines 26-29), and the perivascular tissue is located adjacent to or surrounds a blood vessel (Page 1 lines 8-17; Page 5 line 29-Page 6 line 12) or artery in the subject (Page 1 lines 8-17; Page 5 line 29-Page 6 line 12).
Re claim 29, the combined disclosure of Gillies and Ant as a whole discloses the method of claim 25, Gillies further discloses wherein the value of the radiomic signature is used to aid in the diagnosis (Par 65, 107, 112, 137), and Ant further discloses wherein the diagnosis is related to detection of vascular disease (Page 5 line 29-Page 6 line 12; Page 21 lines 1-6; Page 22 lines 27-35).
Re claim 30, the combined disclosure of Gillies and Ant as a whole discloses the method of claim 29, Ant further discloses wherein the vascular disease is selected from the group consisting of atherosclerosis (Page 22 lines 27-35; Page 45 claim 39), vascular calcification (Page 8 lines 17-19; Page 24 lines 15-21; Page 45 claim 39), intima hyperplasia (Page 45 claim 39), vascular aneurysm (Page 10 description of Fig 11; Page 23 lines 16-24; Page 45 claim 39), and vascular inflammation (Page 2 line 31-Page 3 line 5; Page 37 lines 7-10).
Re claim 31, the combined disclosure of Gillies and Ant as a whole discloses the method of claim 25, Ant further discloses wherein the value of the radiomic signature is used to identify local vascular inflammation caused by unstable plaques (Page 1 lines 19-22; Page 8 line 29-Page 9 line 7; Page 9 line 23-Page 10 line 5; Page 23 lines 16-24).
Re claim 32, the combined disclosure of Gillies and Ant as a whole discloses the method of claim 25, Gillies further discloses wherein the value of the radiomic signature (Par 65, 107, 112, 137) is used on its own (Par 65, 107, 112, 137) or is combined with prognostic models (Par 61, 78, 131) or risk factors (Par 9, 22, 124, 137).
Re claim 33, the combined disclosure of Gillies and Ant as a whole discloses the method of claim 32, Gillies further discloses wherein the prognostic models are selected from the group consisting of the pervascular Fat Attenuation Index (FAIPVAT), a metric of the extent of vascular plaque disease and/or conventional demographic models (Par 14, 55, 60 119).
Re claim 34, the combined disclosure of Gillies and Ant as a whole discloses the method of claim 32, Ant further discloses wherein the risk factors are selected from the group consisting of the presence of coronary calcium (Page 3 lines 26-29; Page 22 lines 27-35), high-risk plaque features (Page 1 el 24-32; Fig 6; Page 8 line 29-Page 9 line 7), and/or epicardial adipose tissue (EAT) volume (Figure 13, 15; Page 11 lines 14-22; Page 12 lines 4-9).
Re claim 35, the combined disclosure of Gillies and Ant as a whole discloses the method of claim 32, Gillies further discloses wherein the value of the radiomic signature (Par 65, 107, 112, 137) is used alone (Par 65, 107, 112, 137) or is combined with high-risk plaque features to provide diagnostic (Par 65, 107, 112, 137) or prognostic information (Par 61, 78, 131) related to imaged tissue characterization (Par 107, 112, 137); and Ant further discloses wherein the imaged tissue characterization relates to perivascular tissue characterization (Page 5 line 29-Page 6 line 12; Page 21 lines 1-6; Page 22 lines 27-35).
Re claim 36, the combined disclosure of Gillies and Ant as a whole discloses the method of claim 25, Gillies further discloses wherein the value of the radiomic signature (Par 65, 107, 112, 137) is used on its own (Par 65, 107, 112, 137) or is combined with non-imaging patient risk factors and/or demographic features to provide diagnostic (Par 14, 55, 60 119 or prognostic information (Par 61, 78, 131) relating to tissue characterization (Par 107, 112, 137); and Ant further discloses wherein the imaged tissue characterization relates to perivascular tissue characterization (Page 5 line 29-Page 6 line 12; Page 21 lines 1-6; Page 22 lines 27-35).
Re claim 37, the combined disclosure of Gillies and Ant as a whole discloses the method of claim 25, Ant further discloses wherein the radiomic signature is used to predict future adverse cardiovascular events (Page 23 lines 1-8), evaluate cardiovascular health (Page 22 lines 27-35, Page 23 lines 1-8) and risk (Page 23 lines 1-14), or identify or diagnose coronary artery disease (Page 22 lines 27-35) or coronary heart disease (Page 22 lines 27-35; Page 45 claim 42).
Re claim 38, the combined disclosure of Gillies and Ant as a whole discloses the method of claim 26, Ant further discloses wherein the artery is a coronary artery (Page 19 lines 21-30), carotid artery (Page 23 lines 1-14), aorta (Page 19 lines 21-30), or any other artery in a human body (Page 23 lines 1-14 – peripheral arteries; Page 23 line 26-29).
Re claim 39, the combined disclosure of Gillies and Ant as a whole discloses the method of claim 25, Gillies further discloses wherein the radiomic signature (Par 107, 112, 137) is calculated based on two or more (Par 107, 112, 137) radiomic features (Par 50, 55, 65, 78-79, 107, 112 – radiomic feature) extracted from the medical imaging data (Par 107, 112, 137).
Allowable Subject Matter
Claims 27 and 28 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: The prior art of record fails to anticipate or render obvious the limitations of the above cited claims. Re claims 27 and 28 the prior art fails to explicitly disclose the signature characteristics and functionality.
Conclusion
THIS ACTION IS MADE FINAL. 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 MICHAEL R NEFF whose telephone number is (571)270-1848. The examiner can normally be reached Mon-Fri 5:30am-2:00pm.
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/MICHAEL R NEFF/Primary Examiner, Art Unit 2631
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