DETAILED ACTION
1. Claims 1-20 are currently pending and under examination in this office action.
Notice of Pre-AIA or AIA Status
2. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
3. The present application claims the benefit of priority from PCT/US2022/020489 filed on 3/16/2022 and provisional application 63/161,724 filed on 3/16/2021. The present claims were reviewed and determined to cover subject matter disclosed in the above applications. Therefore, priority and the effective filing date of 3/16/2021 is granted to the present application.
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.
4. Claims 1-14 and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Turtle (WO 2017/214207 A2, published 12/14/2017) in view of Langenhorst (Clinical Pharmacokinetics, 2019, 58:627-637, also cited in IDS from 6/27/2024).
Turtle discloses a method of treating a subject with B cell malignancies, including B cell leukemia, B cell lymphoma, and B cell acute lymphoblastic leukemia (B-ALL), using a preconditional treatment of fludarabine or other chemotherapeutic agent prior to administration of adoptive cell therapy, including administration of a CAR. (See Turtle, abstract). Turtle also discloses treating patients with a disease burden as characterized by the presence of extramedullary disease, CNS disease, and the presence of abnormal B cells in the bone marrow of the patient prior to the preconditioning treatment. (See Turtle, Examples 1, 3, and 4). Turtle further discloses the use of lymphoid cells (See Turtle, pg. 76 [0251]) that express T cell receptor or CAR that includes a target antigen of CD19, the intracellular signaling domain of CD3zeta and costimulatory domains of 4-1BB and CD28. (See Turtle, pg. 7 [0028-0029]).
Turtle does not disclose administration of a personalized amount of chemotherapeutic agent using the area under the curve (AUC) of at least about 10 mg.h/L of the chemotherapeutic agent. Turtle also does not disclose a method of determining the AUC by using body weight and renal function, where renal function is determined by estimated glomerular filtration rate (eGFR) calculated by a creatinine clearance test in the subject.
Langenhorst discloses a method for using the AUC of a subject as determined by their body weight and renal function. (See Langenhorst, pg. 627, abstract, results). The renal function is determined by the eGFR of the subject, calculated by creatinine clearance. (See Langenhorst, pg. 630, column 1, paragraph 4). Langenhorst discloses that the AUC varies for individuals’ subjects varies between 10-66 mg.h/L for the patient population tested. (See Langenhorst, pg. 632. Column 1, lines 3-6). Langenhorst further teaches a population PK model for dosage of fludarabine that uses the body weight and renal function of the subject as compared to the traditional method of body surface area, to better personalize the dosage of the chemotherapeutic agent. (See Langenhorst, pg. 628, Introduction). Finally, Langenhorst also discloses the calculation used in the present application to determine the dosage of the personalized amount of chemotherapeutic agent:
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(See Langenhorst, pg. 632, Table 2; also present specification pg. 13).
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date to apply the dosage method disclosed in Langenhorst with a reasonable amount of success to a preconditional treatment of a chemotherapeutic agent for treating cancer using an adoptive cell therapy. It would have been obvious to improve the traditional models of preconditioning therapy using a chemotherapeutic agent with an adoptive cell therapy by applying new dosing methods because the traditional method of dosing fludarabine leads to highly variable exposures in patients, limiting the dosage amount of a chemotherapeutic preconditioning agent would be less damaging to a patient about to undergo another therapy following the chemotherapeutic agent, and decreasing the damage from the chemotherapeutic agent would allow for a stronger response from the body to the adoptive cell therapy. Therefore, it would have been obvious to a person of ordinary skill in the art to improve the method of Turtle using the dosage method of Langenhorst to develop the safer cancer treatment claimed in the present invention.
5. Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Turtle (WO 2017/214207 A2, published 12/14/2017) in view of Langenhorst (Clinical Pharmacokinetics, 2019, 58:627-637, also cited in IDS from 6/27/2024) as applied to claims 1-14 and 16-20 above, and further in view of Larson (Leukemia & Lymphoma, 59(1):3-13).
Turtle and Langenhorst disclose the method of treating a subject for cancer using a personalized preconditional treatment of a chemotherapeutic agent, as determined by an AUC of > 10 mg.h/L prior to the administration of a cell comprising an antigen recognizing receptor in subject with a high disease burden including the presence of CNS disease as discussed above.
Turtle and Langenhorst does not disclose the CNS disease as being CNS3 or the diagnostic criteria used for determining CNS disease status.
Larson discloses the diagnostic criteria for CNS status as being 5 leukocytes/mL of CSF with leukemic blast cells present in a cytocentrifuged sample. (See Larson, pg. 4, paragraph 3, lines 1-4).
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date to use the diagnostic criteria for determining CNS 3 status in Larson to evaluating patients for disease burden prior to treatment with a personalized chemotherapeutic agent prior to the administration of adoptive cell therapy. It would have been obvious because as Larson states this is the traditional method for diagnosing CNS status in cancer patients. Therefore, it would have been obvious to a person of ordinary skill in the art to use the diagnostic criteria for CNS status for determining disease burden in a subject being treated with the cancer treatment of the claimed invention.
Conclusion
6. Claims 1-20 are rejected.
7. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LINDSAY DUNN whose telephone number is (571)272-5825. The examiner can normally be reached Monday-Friday 8-4:30.
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/LINDSAY DUNN/Examiner, Art Unit 1644
/Laura B Goddard/Primary Examiner, Art Unit 1642