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 .
Information Disclosure Statement
The IDS filed 7/26/2022, 9/22/2022, 5/30/2023, 6/08/2023, 10/17/2023, 11/16/2023, 1/31/2024, 3/18/2024, 7/08/2024, 10/04/2024, 4/03/2025, 2/26/2026 have been considered by the Examiner.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Priority of US application 63/209164 filed 6/10/2021 has been considered in view of newly presented claim 21 filed 11/03/2023. Claim 21 recites step (d) of determining which molecular mechanism levels elevated and which molecular mechanism levels are decreased in the patient as compared to molecular mechanism data used to train the virtual tissue model, thereby determining per-patient molecular level signatures for the atherosclerotic plaque in the patient. A review of US application 63/209164 does not reveal support for the totality of claim 21, step (d). US application 63/209164 in Figure 5 shows a general plan to, “Identify individual signatures ranked by the cross product of dysregulation and significance.” However support for step (d) of determining which molecular mechanisms are elevated or decreased a compared to mechanism data used to train a virtual tissue model, is not found.
For the purposes of prior art, the filing date of the instant specification filed 11/3/2022 will be used.
Status of Claims
Claims 2-32 are under examination.
Claim 1 is cancelled.
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 2-32 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Step 1: Process, Machine, Manufacture or Composition
Claims 2-32 are drawn to a method, so a process.
Step 2A Prong One: Identification of an Abstract Idea
The claim(s) recite(s):
1. processing non-invasively obtained imaging dataset with a virtual tissue model to obtain quantitative plaque data, as in claim 21, step (b).
This step reads on a process achievable through math or mental steps. Information data obtained from an image can be analyzed with mathematics or mental algorithms to obtain data about lipid composites which may also be visualized. The virtual model reads on math or mental process steps carried out on a computer. The step is therefore an abstract idea.
2. processing the quantitative plaque data with a virtual expression model to quantify molecular mechanisms for the plaque in the patient, as in claim 21, step (c).
This step reads on an analysis that can be performed by the human mind comparing information from plaque data to a model of expression levels of molecular mechanisms. The step is therefore an abstract idea.
3. determining which molecular mechanism levels are elevated and which molecular mechanism levels are decreased in the patient as compared to molecular mechanism data used to train the virtual tissue model, thereby determining per-patient molecular level signatures for the atherosclerotic plaque in the patient.
This step reads on a process of comparing information that can be performed by the human mind or with math. Comparing molecular mechanism data to determine molecular signatures can be performed mentally. The step is therefore an abstract idea.
Claims 2-3 describe imagining techniques used to collect the non-invasively collected radiological imagine data set. The claims characterized the data and are therefore part of the abstract idea.
Claims 4-10, 12-20 and 22-32 further characterize the data and analysis steps and are therefore also abstract ideas.
Claim 11 recites correcting image data intensity correction using a three-dimensional point spread function. This step is drawn to math and is therefore an abstract idea.
Step 2A Prong Two: Consideration of Practical Application
The claims result in a step of determining elevated or decreased molecular mechanisms to thereby determine patient molecular level signatures for atherosclerotic plaque. The step is an analysis step that reads on an abstract idea and not a practical application.
The claims do not recite any additional elements that integrate the abstract idea into a practical application.
This judicial exception is not integrated into a practical application because the claims do not meet any of the following criteria:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
an additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
an additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
an additional element effects a transformation or reduction of a particular article to a different state or thing; and
an additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than
a drafting effort designed to monopolize the exception.
Step 2B: Consideration of Additional Elements and Significantly More
The claimed method also recites "additional elements" that are not limitations drawn to an abstract idea. The recited additional elements are drawn to:
1. receiving a non-invasively obtained imaging dataset for an atherosclerotic plaque in a patient, as in claim 21, step (a).
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because receiving imaging data of anatomy containing atherosclerotic plaque, obtained by medical imaging including at least CT, MIR or PET is routine conventional and well understood.
Other elements of the method suggest the implementation of a computer (i.e. “virtually,” and “processing”) which is a recitation of generic computer structure that serves to perform generic computer functions that are well-understood, routine, and conventional activities previously known to the pertinent industry. Viewed as a whole, these additional claim element(s) do not provide meaningful limitation(s) to transform the abstract idea recited in the instantly presented claims into a patent eligible application of the abstract idea such that the claim(s) amounts to significantly more than the abstract idea itself. Therefore, the claim(s) are rejected under 35 U.S.C. 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 112-2nd paragraph
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 7-8 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 pre-AIA the applicant regards as the invention.
Claim 7 recites “whose expression profiles are illustrated in Figure 5.”
Claim 8 recites “gene transcripts” listed in Table 4 or Table 5. MPEP 2173.05(s)
regarding Reference to Figures of Tables, states:
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993).
Incorporation of the gene transcripts listed in Figure 5 and Tables 4-5 are possible. Incorporation of Tables 4-5 is also possible. Therefore, applicants are required to do so or else cancel the reference to the drawing and tables in the claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 2-32 are rejected under 35 U.S.C. 103(a) as being unpatentable over Buckler et al.(US 2019/0180438) in view of Buckler et al. (herein “Buckler 2”)(Vascular Biology, vol. 42 (May 2021) pages 1738-1750; IDS filed 7/26/2022).
Buckler teach receiving radiological data which is non-invasive (par. 0131) as applied to atherosclerosis imagine data (par. 0080) and atherosclerotic plaques (par. 0160)(i.e. receiving a non-invasively obtained imaging dataset for an atherosclerotic plaque in a patient), as in claim 21, step (a).
Buckler et al. teach (par. 0166) converting radiological images of vessels with plaque into various shape descriptors and radiological imaging intensity values; Buckler teach modeling relative spatial positioning of vascular plaque components (“blobs”) within the vessel wall (i.e. processing non-invasively obtained imaging dataset with a virtual tissue model to obtain quantitative plaque data), as in claim 21, step (b).
Buckler et al. teach (par. 0131) quantifying gene expression profiling through radiological data; Buckler teach that clinically correlated data may be used to train machine learning algorithms to correlate biological analytes to pathologies with a known outcome. (i.e. processing quantitative plaque data with a virtual expression model to quantify molecular mechanisms for the plaque in the patient), as in claim 21, step (c).
Buckler et al. do not specifically teach determining molecular mechanism levels that are elevated and decreased in the patient as compared to molecular mechanism data used to train virtual tissue model, thereby determining per-patient molecular level signatures for the atherosclerotic plaque in the patient, as in claim 21, step (d).
“Buck’er 2” teach (Abstract and page 1739, col. 2, par. 2) determining per-patient molecular signatures of atherosclerotic lesions with models to interpret computed-tomography angiography (CTA) image (i..e. thereby determining per-patient molecular level signatures for the atherosclerotic plaque in the patient); Buckler et al. teach that the models are developed from atherosclerotic lesion images (CTAs) and gene expression as a basis of plaque biology (page 1740, col. 1, par. 1); the models use genes that were found to be highly dysregulated from differentially expressed probe sets (1741, col. 2, “Predictive Model”)(i.e. determining molecular mechanism levels that are elevated and decreased in the patient as compared to molecular mechanism data used to train virtual tissue model), as in claim 21, step (d).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the teaching of Buckler et al. for quantifying biological analytes using predicative models trained on radiological images of plaque with “Buckler 2” for determining dysregulated expression molecular signatures with predicative models trained on radiological images of plaque. “Buckler 2” provide motivation by teaching that the mathematical modeling arrives at accurate predictions of molecular signatures to give an elucidation of molecular signature of atherosclerotic lesions. One of skill in the art would have had a reasonable expectation of success at combining the teachings of Buckler et al. and “Buckler 2” because both teach predicative analysis of atherosclerotic plaque phenotyping from CTA images of plague morphology.
Regarding dependent claims 2-20 and 22-32
Buckler teach correlating imaging phenotypes with transcriptomic or metabolomic analytes (par. 0015); Buckler et al. teach (par. 0131) radiological image data which is non-invasive, as in claim 2.
Buckler teach (par. 0006) CT, CCTA, MRI, spectral CT, CTA, US, as in claim 3.
Buckler teach vessel geometry or anatomical structure and plaque morphology in the walls (i.e. plaque burden)(par. 0048); and ulceration, remodeling, stenosis, dilation and calcification (par. 0055); LRNC and IPH (par. 0065), as in claims 4-6.
“Buckler 2” teach (page 1743, Figure 3) gene transcript in instant Figure 5, as in claim 7.
Buckler et al. teach using radiological data to identify gene expression profiles which are biological analytes (par. 0131) and using biological analytes to determine clinical findings (i.e. provide patient-specific determination of mechanisms related to subject’s plaque pathophysiology or plaque instability), as in claim 9.
Buckler et al. teach determining plaque that is mostly matrix (par. 0049); and characteristic patterns of extracellular matrix fibers (pr. 0056)(i.e. extracellular matrix organization), as in claim 10.
Buckler et al. teach deblurring using patient-specific point spread determination algorithm to mitigate artifacts (par. 0112), as in claim 11.
“Buckler 2” teach (page 1743, col. 2, par. 1) models were built for dichotomized classification of transcript levels above or below median expression value. For example, dichotomized expression (higher vs. lower) of microRNA, as in claims 12 and 31-32.
Regarding claims 13-20 “Buckler 2” teach predicative models using the combination of expressions from the recited biomarkers in the models taught in “Results” pages 1742- col. 2 to page 1745).
“Buckler 2” teach (page 1740, col. 2, par. 1) using images from patients with high and low calcified carotid lesions (i.e. plaque morphology)(i.e. subjects without atherosclerosis and with a plaque), as in claims 22-23 and 25.
“Buckler 2” teach (page 1745, col. 2, par. 1) per-patient molecular level signatures for atherosclerotic plaque phenotyping based on molecular signature in atherosclerosis (page 11, par. 3), as in claim 24.
“Buckler 2” teach (page 1745, col. 2, par. 1) using supervised models to estimate gene expression based on plaque morphology, as in claim 26.
:”Buckler 2” teach (Abstract) predicting four hundred fourteen (414)coding and non-coding RNA using supervised models, as in claim 27.
“Buckler 2” teach (page 1741, col. 1, “Predictive Modeling”) analysis with genes of which 1783 were upregulated and 1604 downregulated, as in claim 28.
“Buckler 2” teach the models use genes that were found to be highly dysregulated (page 1741, col. 2, “Predictive Modeling”)(i.e. molecular mechanisms that are elevated or decreased), as in claims 29-30.
E-mail communication Authorization
Per updated USPTO Internet usage policies, Applicant and/or applicant’s representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting the following statement via EFS Web (using PTO/SB/439) or Central Fax (571-273-8300):
Recognizing that Internet communications are not secure, I hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. I understand that a copy of these communications will be made of record in the application file.
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Anna Skibinsky whose telephone number is (571) 272-4373. The examiner can normally be reached on 12 pm - 8:30 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Ram Shukla can be reached on (571) 272-7035. 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 http://pair-direct.uspto.gov. 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.
/Anna Skibinsky/
Primary Examiner, AU 1635
Prosecution Insights