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 .
This Office Action is responsive to the Amendment filed 26 November 2025. Claims 1-5 and 7-20 are currently under consideration. The Office acknowledges the amendments to claims 1, 7-9, 12, 13, 15-17, and 20, as well as the cancellation of claim 6.
Claim Objections
Claim 16 is objected to because of the following informalities: in lines 1-2, “the medical imaging technique” should apparently read --the at least one medical imaging technique--. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-5 and 7-12 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.
Claim 1 recites the limitations "the second pulse dose" in line 5, “the duration” in line 5, and “the observation period” in lines 5-6. There is insufficient antecedent basis for these limitations in the claim.
Claim 1 also recites the limitations "a second pulse dose" in line 7, “an observation period” in line 8, and “a duration” in line 8. It is not clear if these are intended to refer to the previously recited second pulse dose, duration, and observation, or to separate elements.
Claims 2-5 and 7-12 are rejected by virtue of their dependence upon claim 1.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
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.
Claims 1-5 and 7-20 are rejected under 35 U.S.C. 103 as being unpatentable over Parry et al. (U.S. Pub. No. 2019/0022411 A1; hereinafter known as “Parry”), in view of He et al. (U.S. Pub. No. 2021/0027878 A1; hereinafter known as “He”).
Regarding claim 1, Parry discloses a method of adaptive treatment of a subject with a tumor (Abstract; [0207]) comprising: administering a first pulse dose of radiation to the tumor within the subject and administering a second pulse dose of radiation to the tumor, wherein the second pulse dose is administered after an observation period, the observation period having a duration of at least 7 days ([0121]; [0214]; e.g., weekly doses depending on treatment needs); and concurrently treating the subject with an immunotherapy ([0204]; [0209]; [0216]). Parry fails to disclose, in response to administering the first pulse dose, determining at least one of a level of radiation for the second pulse dose, the duration of the observation period, and a target field for the second pulse dose using a machine learning model. He discloses a similar method (Abstract) for adaptive fractionated treatment ([0004]-[0005]; [0010]; [0026]; [0044]) comprising, using a machine learning model after administering a first pulse dose, determining at least one of a level of radiation for a second pulse dose, a duration of an observation period, and a target field for the second pulse dose in order to quickly and efficiently adapt treatment ([0014]-[0015]; [0027]; [0043]-[0045]). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Parry by, in response to administering the first pulse dose, using a machine learning mode to determine at least one of a level of radiation for the second pulse dose, the duration of the observation period, and a target field for the second pulse dose, as taught by He, in order to quickly and efficiently adapt treatment.
Regarding claims 2 and 3, the combination of Parry and He discloses the invention as claimed, see rejection supra, and Parry further discloses that the first and second pulse doses of radiation are ablative, wherein the first and second pulse doses are part of a radiotherapy, the radiotherapy comprising SABR ([0178]).
Regarding claims 4 and 5, the combination of Parry and He discloses the invention as claimed, see rejection supra, and Parry further discloses that concurrently treating the subject with the immunotherapy comprises administering an immune stimulant with at least one dose of radiation, wherein the immune stimulant comprises at least one of a checkpoint inhibitor, an immune stimulating cytokine, a tumor derived immune stimulant, or an agent associated with the cGAS STING pathway ([0204]; [0233]-[0235]).
Regarding claim 7, the combination of Parry and He discloses the invention as claimed, see rejection supra, and He further discloses training the machine learning model to analyze radiomic features and biologic features ([0027]-[0028]; [0042]-[0043]; [0062]).
Regarding claim 8, the combination of Parry and He discloses the invention as claimed, see rejection supra, and He further discloses that the biologic features comprise at least one of target tissue vascularity, normal tissue vascularity, target tissue oxygenation status, normal tissue oxygenation status, target tissue cytokine profile, normal tissue cytokine profile, target tissue gene expression, normal tissue gene expression, circulating tumor DNA indicative of tumor response to therapy, levels of circulating tumor cells, target tissue receptor expression, normal tissue receptor expression, target tissue white blood cell infiltration, normal tissue white blood cell infiltration, tumor markers, tumor burden, systemic immune status, changes in subject health, or changes in patient weight ([0004]; [0027]; [0043]-[0044]).
Regarding claim 9, the combination of Parry and He discloses the invention as claimed, see rejection supra, and He further discloses that the radiomic features comprise at least one of anatomical imaging characteristics, functional imaging characteristics, or metabolic imaging characteristics ([0005]; [0010]; [0026]-[0027]; [0043]-[0044]; [0062]-[0063]).
Regarding claim 10, the combination of Parry and He discloses the invention as claimed, see rejection supra, and Parry further discloses that the tumor is one of a benign tumor and a malignant tumor ([0009]; [0132]).
Regarding claims 11 and 12, the combination of Parry and He discloses the invention as claimed, see rejection supra, and Parry further discloses that the first pulse dose is at least 6 Gy and the second pulse dose is between 15 Gy and 50 Gy ([0124]; [0213]-[0214]).
Regarding claim 13, Parry discloses a method of adaptive treatment of a subject with a tumor (Abstract; [0207]) comprising: administering a first pulse dose of radiation to the tumor within the subject ([0121]; [0214]; e.g., weekly doses depending on treatment needs); concurrently treating the subject with an immunotherapy ([0204]; [0209]; [0216]); measuring biologic features of at least one of the subject or the tumor ([0033]-[0054]); applying at least one medical imaging technique to at least one of the subject or the tumor ([0033]; [0140]; [0203]); and administering a second pulse dose, wherein the second pulse dose is administered at least 7 days after the first pulse dose ([0121]; [0214]; e.g., weekly doses depending on treatment needs). Parry fails to disclose analyzing results of the at least one medical imaging technique and the biologic features with a machine learning model and determining, based on the analysis with the machine learning model, at least one of a level of radiation for the second pulse dose, a duration between the first dose and the second pulse dose, or a target field for the second pulse dose. He discloses a similar method (Abstract) for adaptive fractionated treatment ([0004]-[0005]; [0010]; [0026]; [0044]) comprising using a machine learning model to analyze results of at least one medical imaging technique and measured biologic features and to determine at least one of a level of radiation for a second pulse dose, a duration of an observation period, or a target field for the second pulse dose, in order to quickly and efficiently adapt treatment ([0014]-[0015]; [0027]; [0043]-[0045]). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Parry by using a machine learning model to analyze the results of the at least one medical imaging technique and the measured biologic features and to determine at least one of a level of radiation for the second pulse dose, a duration of an observation period, or a target field for the second pulse dose, as taught by He, in order to quickly and efficiently adapt treatment.
Regarding claim 14, the combination of Parry and He discloses the invention as claimed, see rejection supra, and Parry further discloses that the first and second pulse doses of radiation are ablative ([0178]).
Regarding claim 15, the combination of Parry and He discloses the invention as claimed, see rejection supra, and further discloses that the biologic features comprise at least one of target tissue vascularity, normal tissue vascularity, target tissue oxygenation status, normal tissue oxygenation status, target tissue cytokine profile, normal tissue cytokine profile, target tissue gene expression, normal tissue gene expression, circulating tumor DNA indicative of tumor response to therapy, levels of circulating tumor cells, target tissue receptor expression, normal tissue receptor expression, target tissue white blood cell infiltration, normal tissue white blood cell infiltration, tumor markers, tumor burden, systemic immune status, changes in subject health, or changes in patient weight (Parry: [0033]-[0054]; He: [0004], [0027], [0043]-[0044]).
Regarding claim 16, the combination of Parry and He discloses the invention as claimed, see rejection supra, and further discloses that the medical imaging technique comprises at least one of anatomical imaging, functional imaging, or metabolic imaging (Parry: [0033], [0140], [0203]; He: [0005], [0010], [0026]-[0027], [0043]-[0044], [0062]-[0063]).
Regarding claims 17 and 18, the combination of Parry and He discloses the invention as claimed, see rejection supra, and Parry further discloses that concurrently treating the subject with the immunotherapy comprises administering an immune stimulant with at least one of the first pulse dose of radiation or the second pulse dose of radiation, wherein the immune stimulant comprises at least one of a checkpoint inhibitor, an immune stimulating cytokine, a tumor derived immune stimulant, or an agent associated with the cGAS STING pathway ([0204]; [0233]-[0235]).
Regarding claim 19, the combination of Parry and He discloses the invention as claimed, see rejection supra, and Parry further discloses that the first and second pulse doses of radiation are part of a radiotherapy, the radiotherapy comprising SABR ([0178]).
Regarding claim 20, Parry discloses a method of adaptive treatment of a subject with a tumor (Abstract; [0207]) comprising: administering a first pulse dose of radiation to the tumor within the subject ([0121]; [0214]; e.g., weekly doses depending on treatment needs); measuring biologic features of at least one of the subject or the tumor ([0033]-[0054]); applying at least one medical imaging technique to at least one of the subject or the tumor ([0033]; [0140]; [0203]); and administering a second pulse dose, wherein the second pulse dose is administered at least 7 days after the first pulse dose ([0121]; [0214]; e.g., weekly doses depending on treatment needs). Parry fails to disclose analyzing results of the at least one medical imaging technique and the biologic features with a machine learning model and determining, based on the analysis with the machine learning model, at least one of a level of radiation for the second pulse dose, a duration between the first dose and the second pulse dose, or a target field for the second pulse dose. He discloses a similar method (Abstract) for adaptive fractionated treatment ([0004]-[0005]; [0010]; [0026]; [0044]) comprising using a machine learning model to analyze results of at least one medical imaging technique and measured biologic features and to determine at least one of a level of radiation for a second pulse dose, a duration of an observation period, or a target field for the second pulse dose, in order to quickly and efficiently adapt treatment ([0014]-[0015]; [0027]; [0043]-[0045]). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Parry by using a machine learning model to analyze the results of the at least one medical imaging technique and the measured biologic features and to determine at least one of a level of radiation for the second pulse dose, a duration of an observation period, or a target field for the second pulse dose, as taught by He, in order to quickly and efficiently adapt treatment.
Response to Arguments
Applicant’s arguments with respect to the claim objections and the rejections under 35 U.S.C. 112(b) have been fully considered and are persuasive in light of the amendments. The objections and rejections have been withdrawn.
Applicant's arguments regarding the rejections based upon the combination of Parry and He have been fully considered but they are not persuasive. Applicant argues that He fails to disclose that the ART recommendation includes a level of radiation for the second pulse dose, the duration of the observation period, or a target field for the second pulse dose. The examiner disagrees. He describes generating an initial radiation therapy treatment plan, which can be a fractionated treatment plan. This treatment plan includes a prescribed dosage, which is delivered over a certain number of fractions that may be spaced apart by days or weeks. He teaches that changes may occur during this extended time frame, wherein the changes may not be accurately accounted for in the treatment plan. He teaches updating the treatment prescription to meet these sorts of changes by using a neural network. This updating may be performed between successive fractions of the applied therapy. Accordingly, He clearly teaches at least determining a level of radiation for the second pulse dose as part of updating the treatment prescription (i.e., the first pulse dose is administered and ART is performed, using the neural network, to adjust the treatment plan between the first and second fractions; then, the second pulse dose is administered based upon the updated treatment plan).
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 THADDEUS B COX whose telephone number is (571)270-5132. The examiner can normally be reached M-F 9am-6pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jason M. Sims can be reached at (571)272-7540. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/THADDEUS B COX/Primary Examiner, Art Unit 3791