DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant's reply filed on 1/27/2026 is acknowledged. Claims 1, 4, 7, 10-12, 15-16 and 18-23 are pending. Claims 2, 3, 5, 6, 8, 9, 13, 14 and 17 are canceled. Claims 22 and 23 are withdrawn. Claim 1 is amended.
3. Claims 1, 4, 7, 10-12, 15-16 and 18-21 are under examination.
Rejections Withdrawn
4. The following rejections are withdrawn in view of applicant’s amendments:
The rejection of claims 1, 5 and 10 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph.
The rejection of claim 6 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph.
Rejections Maintained
Claim Rejections - 35 USC § 103
5. 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.
6. Claims 1, 4, 7, 10-12, 15-16 and 18-21 remain rejected under 35 U.S.C. 103 as being unpatentable over Rob et al. (J Clin Oncol, 2014, 32(15_suppl), abstract, PTO 892 dated 8/4/2023), in view of NCT00799110 (version 15, pub. date 1/21/2016), WO2013/004708A1 (Bartunkova et al., pub. date 1/10/2013, PTO 892 dated 8/4/2023), and Wu et al. (Cancer Immunol Immunother, 2010, 59:279-291).
Regarding claims 1, 15, 16, 20 and 21, Rob et al discloses a method of treating ovarian cancer in human patients, the method comprising administering to the human patients DCVAC/OvCa and chemotherapy, wherein the DCVAC/OvCa is autologous dendritic cells differentiated from PBMC and presenting tumor antigens derived from killed ovarian cancer (OC) cell lines (SK-OV-3, OV90) (whole tumor cells), wherein the chemotherapy comprises carboplatin and paclitaxel (which does not comprise cyclophosphamide), wherein the DCVAC/OvCa is added to the 1st line standard chemotherapy of carboplatin and paclitaxel in women with newly diagnosed epithelial ovarian carcinoma (see abstract). Regarding the limitation “stage II-IV”, Rob et al. teaches that the newly diagnosed ovarian cancer is an advanced stage cancer (Title). An advanced stage cancer is known in the art as stage II and higher.
Regarding claim 10, ovarian cancer cell lines are allogeneic to the patients (abstract).
Regarding claim 1, Rob et al. does not teach that the killed ovarian cancer cells were ovarian cancer cells killed by high hydrostatic pressure, and from 5-30 doses of DCVA/OvCa are administered.
Regarding claims 1, 4 and 18, Rob et al. does not teach that DCVAC/OvCa is administered within two months, one month or 2 weeks after the last dose of the chemotherapy.
Regarding claim 7, Rob et al. does not teach that DCVAC/OvCa is administered in combination of a maintenance therapy.
Regarding claim 11, Rob et al. teaches that autologous dendritic cells were differentiated from PBMC. However, Rob et al. does not teach that the dendritic cells are obtained from monocytes cultivated in the presence of cytokines prior to chemotherapy.
Regarding claim 12, Rob et al. does not teach administering DC/VAC/OvCa once every three weeks.
Regarding claim 19, Rob et al. does not teach administering 8 to 15 doses DC vaccine to patients.
NCT00799110 (version 15) teaches a method of treating patients having ovarian cancer, the method comprising administering to the patient dendritic cell/tumor fusion vaccine (dendritic cells mixed with tumor cells) (page 5, under Study Description and page 7, under Arms). NCT00799110 (version 15) discloses eligibility criteria prior to first vaccination: at maximum of twelve weeks after the last dose of chemotherapy, patients must fulfill the following criteria: 1) complete clinical response after first-line chemotherapy for newly-diagnosed of patient, or after second-line chemotherapy for relapsed patient who requires secondary cytoreduction, 2) asymptomatic, low volume disease not requiring further chemotherapy prior to initiating vaccination (page 9, under eligibility criteria), 3) resolution of all chemotherapy related grade III-IV toxicity, and 4) laboratories: Laboratories: WBC > 2.0 X 103/uL, Platelets > 50,000/uL, Bilirubin < 2.0 mg/dL Creatinine <2.0mg/dL, AST/ALT < 2.5 x ULN (page 9). NCT00799110 teaches that the DC vaccine is administered together with GM-CSF and imiquimod (page 7, under Arms). Imiquimod and GM-CSF meets the limitation of a maintenance therapy recited in claim 7). NCT00799110 (version 15) teach administering DC/tumor fusion vaccine once every three weeks (page 7, Under Arms). NCT00799110 (version 15) teaches that the dendritic cells are prepared from patient’s monocytes obtained by leukapheresis (page 5). The patients included stage III or IV ovarian cancer (under Eligibility).
WO2013/004708A1 teaches that combination of tumor cells killed by the high hydrostatic pressure and dendritic cells results in the phagocytosis and efficient presentation of tumor antigens and the induction of strong anti-tumor immune response (page 3, para 1), wherein the tumor cells may be primary ovarian cancer cells or ovarian cancer cell line (page 5, para 1). WO2013/004708A1 teaches that the degree of the anti-tumor immune response obtained by the combination of tumor cells treated by high hydrostatic pressure and dendritic cells is about 10-fold higher than the immune response induced by immunogenic tumor cells alone (page 4, para 2).
WO2013/004708A1 teaches that before the chemotherapy started, immature dendritic cells were generated from monocytes obtained during leukapheresis( page 21, para 3). WO2013/004708A1 teaches that dendritic cells are obtained by cultivating monocytes in the presence of GM-CSF and interleukin 4 or interleukin 13 (page 9). WO2013/004708A1 teaches that administration of this form of cancer immunotherapy is preferably repeated in regular intervals of 2-6 weeks in order to continuously boost the immune response (page 5, para 3), for example up to 12 doses in 4-6 weeks intervals (Example 8).
Wu et al. teaches that the window period of days 12-14 after paclitaxel and carboplatin chemotherapy in advanced ovarian cancer patients provides the best opportunity for immunotherapy (abstract and page 289, last para).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have obtained DC by cultivating monocytes in the presence of GM-CSF and interleukin 4 or 13, and treat ovarian patients with DC vaccine comprising DC loaded with ovarian cancer cells or ovarian cancer cell lines killed by high hydrostatic pressure in view of WO2013/004708A1. One of ordinary skill in the art would have been motivated to do so because WO2013/004708A1 teaches that before the chemotherapy started, immature dendritic cells were generated from monocytes obtained during leukapheresis ( page 21, para 3), and DC were obtained by cultivating monocytes in the presence of GM-CSF and interleukin 4 or 13, and combination of tumor cells killed by the high hydrostatic pressure and dendritic cells results in the phagocytosis and efficient presentation of tumor antigens and the induction of strong anti-tumor immune response (page 3, para 1). One of ordinary skill in the art would have had a reasonable expectation of success because WO2013/004708A1 has shown that the degree of the anti-tumor immune response obtained by the combination of tumor cells treated by high hydrostatic pressure and dendritic cells is about 10-fold higher than the immune response induced by immunogenic tumor cells alone (page 4, para 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered the first dose of the vaccine in the window period of days 12-14 after completion of paclitaxel and carboplatin chemotherapy in view of Wu. One of ordinary skill in the art would have been motivated to do so because Wu et al. teaches that the window period of days 12-14 after paclitaxel and carboplatin chemotherapy in advanced ovarian cancer patients provides the best opportunity for immunotherapy (abstract and page 289, last para). One of ordinary skill in the art would have had a reasonable expectation of success because NCT00799110 (version 15) teaches/suggests that the vaccine should be given to the patients who had complete clinical response after chemotherapy and no more than 12 weeks after completion of chemotherapy and Wu et al. teaches that the window period of days 12-14 after paclitaxel and carboplatin chemotherapy in advanced ovarian cancer patients provides the best opportunity for immunotherapy (abstract and page 289, last para).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered DC vaccines at 2-6 week intervals for one year or 12 doses in view of WO2013/004708A1. One of ordinary skill in the art would have been motivated to do so because WO2013/004708A1 teaches that administration of this form of cancer immunotherapy is preferably repeated in regular intervals of 2-6 weeks in order to continuously boost the immune response (page 5, para 3), for example up to 12 doses in 4-6 weeks intervals (Example 8). One of ordinary skill in the art would have had a reasonable expectation of success because WO2013/004708A1 provides working example on treating patients with DC vaccine for 12 doses in 4-6 weeks intervals (Example 8).
Applicant’s Arguments
The response states that the outstanding Office Action on page 15 acknowledges that applicant has shown surprising results for a DC vaccine comprising tumor cells killed by high hydrostatic pressure added to a first line chemotherapy consisting of paclitaxel and carboplatin, and particularly notes that the chemotherapy as cited in the previously pending claims was not limited to a first-line chemotherapy. The present claims have been amended to require that the chemotherapy is a first-line chemotherapy as indicated in the Office Action. The response states that the results presented in the present application as filed support the full scope of the present claims as amended, since the surprising results as described in the present specification are fairly representative of treatments of Stage II-IV ovarian cancer in a patient comprising administering to the patient a first-line chemotherapy with administration of a dendritic cell vaccine as presently claimed.
Response to Arguments
Applicant’s arguments of surprising results have been carefully considered and are not found persuasive because the showing of unexpected results is not commensurate in scope with claimed invention.
MPEP 716.02(d) states “Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support."
In the instant case, applicant has only shown surprising results for a DC vaccine comprising tumor cells killed by high hydrostatic pressure added to a first line chemotherapy consisting of paclitaxel and carboplatin. However, the claims encompass a first line chemotherapy comprising any chemotherapeutic agents. Different chemotherapy agents target cancer in different ways, mainly by targeting different parts of the cancer cell life cycle or different cellular processes. For example, mitotic inhibitors prevent cell division by targeting mitosis, topoisomerase inhibitors block enzymes need for replication, and alkylating agents damage cancer cell DNA so cells can’t divide. This is why oncologists carefully choose and often combine multiple drugs to get the best results. Applicant has not provided evidence of unexpected results for the full scope of the invention.
Conclusion
7. No claims are allowed.
THIS ACTION IS MADE FINAL. 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.
8. Any inquiry concerning this communication or earlier communications from the examiner should be directed to HONG SANG whose telephone number is (571)272-8145. The examiner can normally be reached Monday-Friday 8am-5pm.
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/HONG SANG/Primary Examiner, Art Unit 1643