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 .
Applicant’s Response
In Applicant’s Response dated 2/3/26, the Applicant amended claims 1, 3, 4, 6-10, 12-14, 16-20, canceled Claim 2, 5, 11, 15, added Claims 22-28, and argued Claims previously rejected in the Office Action dated 8/6/26.
In light of the Applicant’s amendments and remarks, the 35 USC 101 and 102 rejections have been withdrawn.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
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.
Claims 1, 3, 4, 6, 8-10, 13-14, 16-22, 25 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Albertson et al., United States Patent Publication 20200352998 (hereinafter “Albertson”), in view of Forbes et al., United States Patent Publication 2017/0333490 (hereinafter “Forbes”).
Claim 1:
Albertson discloses:
A method of assaying the response of a lymphoma in a subject to a therapy comprising chimeric antigen receptor (CAR) T-cell infusion (see abstract). Albertson teaches assessing a change in a factor indicative of tumor burden prior to administration of a cell therapy in a subject that is associated with, comprising:
measuring tumor volume (MTV) by functional imaging that measures glucose uptake in the subject prior to administration of the therapy comprising CAR T-cell infusion to create a baseline MTV (see paragraph [0060] and [0708]). Albertson teaches measuring tumor burden prior to giving therapy. Albertson recites quantifying a fold change in one or more factors indicative of disease burden at two time points prior to treatment with the therapy, wherein the fold change indicates the risk, probability, or likelihood of the subject developing a toxicity following administration of and/or associated with the therapy;
wherein a low baseline MTV indicates that the subject will have an efficacious response to the therapy comprising CAR T-cell infusion relative to a control (see paragraphs [0060], [0076]-[0078], [0083]). Albertson teaches based on the comparison of two points prior to administering therapy, a decision is then made whether the therapy was toxic or if it will succeed based on the high or low initial measurements;
wherein a high baseline MTV indicates that the subject will have a decreased, less efficacious, and/or less durable response to the therapy comprising CAR T-cell infusion (see paragraphs [0060], [0076]-[0078], [0083]). Albertson teaches based on the comparison of two points prior to administering therapy, a decision is then made whether the therapy was toxic or if it will succeed based on the high or low initial measurements.
Albertson fails to expressly disclose tumor volume measured by functional imaging that measure glucose uptake.
Forbes discloses:
measuring total metabolic tumor volume by functional imaging that measures glucose uptake in the subject (see paragraph [0159]). Forbes teaches tumor volume will be measured at the beginning and end of each experiment with 18F-FDG small-animal PET.
Accordingly, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method disclosed by Albertson to include total metabolic tumor volume is measured by 18 fluorodeoxyglucose (18F-FDG) PET for purpose of accurately and efficiently measuring tumor growth using a specific radiotracer, as taught by Forbes.
Claim 3:
Albertson discloses:
measuring MTV 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 19, 20, 21, 22, 23, 24, 25 or more additional times after administration of therapy comprising CAR T-cell infusion (see paragraphs [0005], [0076], [0083]). Albertson teaches measuring the tumor burden and the folds up to 7 days/7 times after administration of the therapy.
Claim 4:
Albertson discloses:
wherein MTV is measured manually (see paragraph [0708]). Albertson teaches the metabolic tumor volume is measure manually by the user manually operating the PET scan.
Claim 6:
Albertson fails to expressly disclose tumor volume measured by functional imaging that measure glucose uptake.
Forbes discloses:
wherein MTV is measured by position emission tomography (PET) (see paragraph [0159]). Forbes teaches tumor volume will be measured at the beginning and end of each experiment with 18F-FDG small-animal PET.
Accordingly, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method disclosed by Albertson to include total metabolic tumor volume is measured by 18 fluorodeoxyglucose (18F-FDG) PET for purpose of accurately and efficiently measuring tumor growth using a specific radiotracer, as taught by Forbes.
Claim 8:
Albertson discloses:
wherein the therapy comprising and a CAR T-cell infusion comprises an immunodepleting therapy comprising and an autologous CAR T-cell infusion (see paragraphs [0062], [0072] and [0310]). Albertson teaches immune therapies such as immunodepleting and CAR T cell infusion.
Claim 9:
Albertson discloses:
wherein the CAR T cell infusion comprises an anti-CD19 CAR T cell infusion (see paragraphs [0033] and [0054]). Albertson teaches CAR T cell infusion including antigen CD19.
Claim 10:
Albertson discloses:
Claim 1 teaches the limitations of Claim 10 (see the rejection of Claim 1) including:
(ii) administering to the subject with a low baseline MTV therapy comprising CAR T-cell infusion or administering to a subject with a high baseline MTV a therapy selected from a chemotherapeutic agent, a higher dose of the therapy comprising CAR T-cell infusion, or multiple rounds of the therapy comprising CAR T-cell infusion (see paragraph [0062]-[0063]). Albertson teaches based on the evaluating and monitoring compared to the baseline, tailoring a therapy for the patient such as targeted therapy or administering an agent;
Claim 13:
Albertson discloses:
wherein measuring MTV 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 19, 20, 21, 22, 23, 24, 25 or more additional times after administration of the therapy CAR T-cell infusion (see paragraphs [0005], [0076], [0083]). Albertson teaches measuring the tumor burden and the folds up to 7 days/7 times after administration of the therapy.
Claims 14, 16:
These claims are interpreted and rejected for the same reasons as the method of claims 4 and 6.
Claim 17:
Albertson discloses:
wherein the therapy comprises CAR T-cell infusion comprises an immunodepleting therapy and a CAR T cell infusion (see paragraphs [0062], [0072] and [0310]). Albertson teaches immune therapies such as immunodepleting and CAR T cell infusion.
Claim 18:
Albertson discloses:
wherein the CAR T cell infusion comprises an anti-CD19 CAR T cell infusion (see paragraphs [0033] and [0054]). Albertson teaches CAR T cell infusion including antigen CD19.
Claim 19:
Albertson fails to expressly disclose tumor volume measured by 18 fluorodeoxyglucose (18F-FDG) PET.
Forbes discloses:
wherein the MTV is measured by 18 fluorodeoxyglucose (18F-FDG) PET (see paragraph [0159]). Forbes teaches tumor volume will be measured at the beginning and end of each experiment with 18F-FDG small-animal PET.
Accordingly, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method disclosed by Albertson to include total metabolic tumor volume is measured by 18 fluorodeoxyglucose (18F-FDG) PET for purpose of accurately and efficiently measuring tumor growth using a specific radiotracer, as taught by Forbes.
Claim 20:
Albertson fails to expressly disclose tumor volume measured by 18 fluorodeoxyglucose (18F-FDG) PET.
Forbes discloses:
wherein the MTV is measured by 18 fluorodeoxyglucose (18F-FDG) PET (see paragraph [0159]). Forbes teaches tumor volume will be measured at the beginning and end of each experiment with 18F-FDG small-animal PET.
Accordingly, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method disclosed by Albertson to include total metabolic tumor volume is measured by 18 fluorodeoxyglucose (18F-FDG) PET for purpose of accurately and efficiently measuring tumor growth using a specific radiotracer, as taught by Forbes.
Claim 21:
Albertson discloses:
wherein the lymphoma comprises Large B-cell lymphoma (LBCL) (see paragraph [0027]). Albertson teaches LBCL lymphoma.
Claim 22:
Albertson discloses:
wherein the lymphoma is refractory or relapsed (see paragraph [0706]). Albertson teaches Therapeutic CAR+ T cell compositions containing autologous T cells expressing a chimeric antigen-receptor (CAR) specific for CD19 were administered to adult human subjects with relapsed or refractory (R/R) aggressive non-Hodgkin's lymphoma (NHL) .
Claims 25, 26:
These claims are interpreted and rejected for the same reasons as the method of claims 21 and 22.
Claims 7, 12, 23 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Albertson, in view of Forbes, in further view of Ilyas et al., “Defining the optimal method for measuring baseline metabolic tumor volume in diffuse large B cell lymphoma” (hereinafter “Ilyas”).
Claim 7:
Albertson and Forbes fails to expressly disclose the MTV being greater than 130 ml.
Ilyas discloses:
wherein the high baseline MTV comprises MTV greater than 130 mL (see page 6, Discussions). Ilyas teaches a high MTV ranging from 220-600 ml.
Accordingly, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method disclosed by Albertson and Forbes to include a high baseline for MTV for purpose of efficiently separating patients into groups with high and low MTVs, as taught by Ilyas.
Claim 12:
Albertson and Forbes fails to expressly disclose the MTV being greater than 130 ml.
Ilyas discloses:
wherein the high baseline MTV comprises MTV greater than 130 mL (see page 6, Discussions). Ilyas teaches a high MTV ranging from 220-600 ml.
Accordingly, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method disclosed by Albertson and Forbes to include a high baseline for MTV for purpose of efficiently separating patients into groups with high and low MTVs, as taught by Ilyas.
Claim 23:
Albertson and Forbes fails to expressly disclose the MTV being greater than 147.5 ml.
Ilyas discloses:
wherein the high baseline MTV comprises an MTV of greater than 147.5 mL (see page 6, Discussions). Ilyas teaches a high MTV ranging from 220-600 ml.
Accordingly, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method disclosed by Albertson and Forbes to include a high baseline for MTV for purpose of efficiently separating patients into groups with high and low MTVs, as taught by Ilyas.
Claim 27:
Albertson and Forbes fails to expressly disclose the MTV being greater than 147.5 ml.
Ilyas discloses:
wherein the high baseline MTV comprises an MTV of greater than 147.5 mL (see page 6, Discussions). Ilyas teaches a high MTV ranging from 220-600 ml.
Accordingly, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method disclosed by Albertson and Forbes to include a high baseline for MTV for purpose of efficiently separating patients into groups with high and low MTVs, as taught by Ilyas.
Claims 24 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Albertson, in view of Forbes, in further view of Wiezorek, US Patent Publication 20190151361.
Claim 24:
Albertson and Forbes fails to expressly disclose axicabtagene ciloleucel (axi-cel).
Wiezorek discloses:
wherein the anti-CD19 CAR T cell infusion comprises axicabtagene ciloleucel (axi-cel) (see paragraph [0007]). Wiezorek teaches administering to the patient in need thereof axicabtagene ciloleucel suspension by intravenous infusion.
Accordingly, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method disclosed by Albertson and Forbes to include the anti-CD19 CAR T cell infusion comprises axicabtagene ciloleucel (axi-cel) for purpose of efficiently administer therapy that allow T cells to target and kill cancer cells that express the particular tumor antigen, as taught by Wiezorek.
Claim 28:
Albertson and Forbes fails to expressly disclose axicabtagene ciloleucel (axi-cel).
Wiezorek discloses:
wherein the anti-CD19 CAR T cell infusion comprises axicabtagene ciloleucel (axi-cel) (see paragraph [0007]). Wiezorek teaches administering to the patient in need thereof axicabtagene ciloleucel suspension by intravenous infusion.
Accordingly, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method disclosed by Albertson and Forbes to include the anti-CD19 CAR T cell infusion comprises axicabtagene ciloleucel (axi-cel) for purpose of efficiently administer therapy that allow T cells to target and kill cancer cells that express the particular tumor antigen, as taught by Wiezorek.
Response to Arguments
Applicant's arguments filed 2/3/26 have been fully considered but they are not persuasive.
Claims Rejections – 35 USC 101
Applicant argues Applicant notes that the amended independent claim 1 now recites an active step of measuring total metabolic tumor volume (MTV) which is accomplished by functional imaging that measures glucose uptake in the subject, with choice and urgency of treatment of the subject being dictated by the level of MTV in the subject according to the inventive model disclosed in the present application.
The Examiner agrees and the rejection has been withdrawn.
Claims Rejections – 35 USC 102
Applicant argues Applicant respectfully notes that this teaching is the subject-matter of previously pending (now canceled herein) claims 5 and 15, claims which were not encompassed by this 35 USC 102(a)(2) rejection. This subject-matter has been incorporated into independent claims 1 and 10, respectively.
The Examiner agrees and the 35 USC 102 rejections have been withdrawn.
Applicant argues the purpose of using tumor volume in Forbes is to experimentally determine the then unknown anti-tumor effect of NIPP1/EXH2 depletion by bacterial shRNA delivery. This is very different from categorizing subject having lymphoma into different therapy regimens based on a single initial baseline MTV value.
The Examiner disagrees.
Although Forbes may be different in the invention, the claims provide very broad limitations that does not further define the two methods of therapy regimens based on a value. Therefore the combination of Albertson and Forbes teaches the limitations of the independent claims.
Applicant argues This finding was a significant advance in the state of lymphoma treatment art at the time of filing the present application. At most, the Examiner has identified the various parts of the claimed invention, but has not provided any scientifically credible evidence as to an apparent reason for one of ordinary skill in
the art to measure a single baseline MTV value by which to guide treatment of a subject having a lymphoma.
The Examiner disagrees.
The claims very broadly claim measure MTV by imaging and administering therapy based on measurements. The Examiner suggest further defining how the imaging is performed or how measurements are calculated based on the imaging to differentiate the claims from the prior art.
Applicant argues Therefore, Applicant respectfully asserts that a difference in MTV values of 25 ml, as taught by Lee, represents fundamentally different risk
profiles which are related to the individual nature of different cancers, and one's definition of "near" has a considerable impact on a given patient's outlook.
The Examiner agrees.
Lee is no longer used in this rejection.
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 TIONNA M BURKE whose telephone number is (571)270-7259. The examiner can normally be reached M-F 8a-4p.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Stephen Hong can be reached at (571)272-4124. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TIONNA M BURKE/Examiner, Art Unit 2178 5/28/26
/STEPHEN S HONG/Supervisory Patent Examiner, Art Unit 2178
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