DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submissions filed on 10/30/2025 and 1/30/2026 have been entered.
Response to Amendments
Applicant's amendments filed 10/30/2025 to claim 1 have been entered. Claims 2, 4, 5, 6, and 8-71 are canceled. Applicant’s supplemental remarks dated 1/30/2026 are acknowledged, and supersede the remarks dated 10/30/2025. Claims 1, 3, 7, and 72 remain pending, and are being considered on their merits. No claims are withdrawn from consideration at this time. References not included with this Office action can be found in a prior action. Any rejections of record not particularly addressed below are withdrawn in light of the claim amendments and/or applicant’s comments.
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.
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.
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.
Claims 1, 3, 7, and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (WO 2017/066530; of record) in view of Hattori et al. (International Journal of Molecular Sciences (April 2019), 20, 2057), Passweg et al. (Leukemia (2004), 18, 1835-1838), and Vu et al. (Biol Blood Marrow Transplant (2015), 21, 1425-1430).
Applicant’s definition on page 16 of the specification is acknowledged. “CYNK cells” are read in light of the specification as CD34+-derived natural killer cells.
Zhang teaches a method of treating cancer, the method comprising administering natural killer (NK) cells to a subject. ([00477-00478]), reading on claim 1. In a separate embodiment, Zhang teaches producing natural killer cells from CD34+ hematopoietic stem or progenitor cells (Example 1), reading on claim 1. Zhang teaches that the hematopoietic stem or progenitor cells are placental cells (claim 27), reading on claims 2 and 3. Zhang teaches that the NK cells are positive for CDCR4 and GZMB (Example 3, the table below [00501]; claim 220, respectively), reading in-part on claims 1 and 7. Zhang teaches treating multiple myeloma and acute myelogenous leukemia (AML) ([0062]), reading on claim 1.
Regarding claim 1, it would have been obvious to a person of ordinary skill in the art before the invention was filed to combine the CD34+-derived natural killer cells of Zhang with the methods of treating cancer of Zhang. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Zhang expressly considers the combination The skilled artisan would have been motivated to do so because the combination would be predictably advantageous as a source of natural killers cells from a renewable source (e.g. CD34+ stem cells) to then treat subjects for cancer in need thereof.
Regarding claims 1 and 7, where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." See M.P.E.P. § 2112. In this case, Zhang teaches the same cells as claimed, i.e. CD34+-derived natural killer cells, and so any combination of cell marker expression must necessarily be inherent to said cells. Therefore, Zhang reads on cell marker expression profile of claims 1 and 7 in the absent of any persuasive showing to the contrary.
Regarding claim 1, Zhang does not teach wherein providing an effective treatment comprises reducing the rate of minimal residual disease (MRD) relative to placebo. Regarding claim 1, Zhang does not teach wherein the subject is MRD positive. Regarding claim 1, Zhang does not teach wherein the subject has a morphologic leukemia free state (MLFS). Regarding claim 72, Zhang does not teach wherein reducing the rate of MRD is a conversion to MRD negativity or a reduction in MRD positivity.
Hattori teaches that relapse is the most common cause of death in acute myeloid leukemia patients receiving allogeneic hematopoietic stem cell transplantation therapy (HSCT) (Abstract; see Fig. 1 with active disease being a higher leukemia burden than the MRD detection limit), reading in-part on claims 1 and 72. Hattori teaches that previous studies have shown an association between clinical outcomes and NK cell recovery after HSCT therapy, likely because NK cells play an essential role in graft-versus-leukemia (GVL) effects and to prevent further infection after HSCT therapy (paragraph spanning p 2-3), reading on claim 1 and 72.
Passweg teaches methods of administering NK cells after stem cell transplantation (Abstract). Passweg teaches that administration of NK cells to subjects with high-risk myeloid malignancies increased donor chimerism (e.g. engraftment of the donor stem cells) in two subjects and stable chimerism in a single subject (Abstract; see pages 1835-1836 for detailed methods and Table 1), reading on claim 1. Passweg teaches that four of the five treated patients achieved continuous remission (paragraph spanning both columns on p1836), reading on claims 1 and 72.
Vu teaches MLFS as meeting all of the criteria of complete remission without recovery of both neutrophil and platelet counts (Abstract), reading in-part on claim 72.
Regarding claim 1, it would have been obvious to a person of ordinary skill in the art before the invention was filed to further treat the subjects of Zhang envisioned to have acute myeloid leukemia with the CD34+-derived natural killer cells of Zhang such as to achieve continuous remission and thus reduce the minimal residual disease in the subjects in view of Hattori and Passweg. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Hattori teaches a predictable relationship between leukemia burden, minimal residual disease, remission, and the active disease state, because Passweg teaches detailed methods of administering natural killer cells to acute myeloid leukemia subjects and further measurement of the disease state in the subjects. The skilled artisan would have been motivated to do so because Hattori teaches there is a clear need in this art to improve upon methods of treating acute myeloid leukemia such that the subjects disease state is in remission (e.g. below the MRD), and Passweg teaches a treatment regimen with natural killer cells that would be advantageous to induce continuous remission of acute myeloid leukemia in patents thereof.
Regarding claim 72, it would have been obvious to a person of ordinary skill in the art before the invention was filed to further treat the subjects of Zhang envisioned to have acute myeloid leukemia with the CD34+-derived natural killer cells of Zhang such as to achieve MLFS in view of Vu, Hattori, and Passweg. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Hattori teaches a predictable relationship between leukemia burden, minimal residual disease, remission, and the active disease state, because Passweg teaches detailed methods of administering natural killer cells to acute myeloid leukemia subjects and further measurement of the disease state in the subjects, and because Vu teaches that complete remission is the more stringent measurement of patient recovery than MLFS. The skilled artisan would have been motivated to do so because Hattori teaches there is a clear need in this art to improve upon methods of treating acute myeloid leukemia such that the subjects disease state is in remission (e.g. more stringent than MLFS), and Passweg teaches a treatment regimen with natural killer cells that would be advantageous to induce continuous remission of acute myeloid leukemia in patents thereof.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Response to Arguments
Applicant's arguments on pages 4-7 of the reply have been fully considered, but not found persuasive of error for the reasons given below. Pages 4-6 are considered a summary by Applicant of the rejections of record, and the specific arguments start on page 7 of the reply.
On page 7 of the reply, Applicant alleges that the instant amendments to claim 1 have overcome the obviousness rejection of record over Zhang in view of Hattori, Passweg, and Vu set forth above. Applicant’s arguments appear to be alleging that Zhang is deficient by not teaching the cell marker expression profile of claims 1 (and also relevant for claim 7). This is not found persuasive because where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977) (emphasis added). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." See M.P.E.P. § 2112. In this case, Zhang teaches the same cells as claimed, i.e. CD34+-derived natural killer cells, and so any combination of cell marker expression must necessarily be inherent to said cells unless Applicant presents persuasive evidence to the contrary that Zhang’s cells cannot meet the cell marker expression profiles of claims 1 and 7. Also see M.P.E.P. § 2121, in that the prior art is presumed operable in the absence of any persuasive showing to the contrary.
Conclusion
No claims are allowed. No claims are free of the art.
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/Sean C. Barron/Primary Examiner, Art Unit 1653