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 reply to the previous Office action, dated April 2, 2026, has been received. By way of this reply, Applicant has amended claim 1 and cancelled claims 22, 23, and 32.
Claims 1-2, 5-17, 19, and 30-31 are pending. Claims 8, 10 and 14 remain withdrawn from consideration, pursuant to the Restriction Requirement mailed April 11, 2024.
Claims 1-2, 5-7, 9, 11-13, 15-17, 19, and 30-31 are therefore under examination before the Office.
The rejections of record can be found in the previous Office action, dated October 2, 2025.
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.
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 1-2, 5-6, 9, 12-13, and 15-17 are rejected under 35 U.S.C. 103 as being unpatentable over Callan (WO2012143739A1) in view of Zheng (Nanomedicine (Lond). 2018 Feb; 13(3):297-311) and Zhang (Cancer Sci. 2018 May;109(5):1330-1345).
Applicant argues that the combination of sonodynamic therapy and a PD-L1 inhibitor produces unexpected results in view of the cited references with regards to treatment of metastatic pancreatic cancer, as the combination of these treatment is significantly enhanced over either treatment alone. Applicant also argues that pancreatic cancers are typically not sensitive to anti-PD-L1 treatments, making the benefit of the combination treatment even more unexpected. Applicant further argues that the teachings of Zheng are limited to ex vivo experiments in the context of B-cell lymphoma and with an anti-PD-1 antibody, and therefore does not permit one of ordinary skill in the art to visualize the use of an anti-PD-L1 antibody in combination with sonodynamic therapy.
Applicant's arguments have been considered but are not found to be persuasive.
"Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof." In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967). MPEP 716.02(c)(II).
The abscopal effect from the use of sonodynamic therapy was well known in the art, according to the teachings of Zhang (see Figure 6 and page 1337: "Therefore, a total of 10 mice showed abscopal responses in response to SDT, and 2 mice showed complete abscopal responses, indicating that the combination of HPD with ultrasound can successfully elicit antitumor immunity."). Zhang also teaches combinations of sonodynamic therapy and an immune checkpoint inhibitor (Zhang at 1344, left column, second paragraph: "In summary, we propose that SDT can induce vaccine-like immune responses that could be combined with immune adjuvants and immune checkpoint inhibitors to design a highly effective cancer immunotherapy. Moreover, we examined the antitumor effects of SDT in both subcutaneous tumor and artificially engineered metastatic tumor models.").
Callan teaches a microbubble-sonosensitizer complex, wherein said sonosensitizer is Rose Bengal (page 3, first paragraph, page 7, fifth paragraph, and claim 11). Callan further teaches that the above complex is useful for treating pancreatic cancer and metastases (claim 16 and page 10, first and second paragraphs). Callan further teaches that the microbubble-sonosensitizer complex may be co-administered with chemotherapeutic agents or anti-tumor antibodies (page 13, second and third paragraphs).
Callan also teaches liver cancer and lymphoma may be treated with sonodynamic therapy (claim 16 and page 10, first and second paragraphs). This indicates that the therapy of Callan is useful in other tumor types besides pancreatic cancer.
Contrary to Applicant's assertion, Zheng does teach in vivo applications of rituximab-conjugated and doxorubicin-loaded microbubbles with ultrasonication (page 301, first paragraph: "In our previous study, it was proved that RDMs induced high cytotoxicity and apoptotic effects on human B-cell lymphoma cells in vitro. To further evaluate the antitumor activity of RDMs with US irradiation for B-cell lymphoma treatment, antitumor growth ability was observed in vivo in this study."). The experiments demonstrating enhanced PD-L1 expression were also carried out on tumor tissue harvested from animals (page 301, third and fourth paragraph). Zheng is explicit in stating: "In this study, we showed that PD-L1 expression in SU-DHL-4 cells could be induced after treatment with DOX-based therapy." (page 306, fourth paragraph). Zheng also notes the immunosuppressive tumor microenvironment as an obstacle that is overcome (page 308, "Summary Points").
Given that combinations of sonodynamic therapy and immune checkpoint inhibition were known to produce a synergistic effect, as evidenced by Zheng and Zhang, Applicant's results cannot be said to be unexpected.
This rejection is therefore maintained.
Claims 7, 11 and 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over Callan, Zheng, and Zhang as applied to claim 1 above, and further in view of Callan 2017 (WO2017089800A1).
Applicant argues that the teachings of Callan 2017 do not remedy the alleged deficiencies of Callan, Zheng, and Zhang. This is not found persuasive, for reasons described supra.
This rejection is therefore maintained.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Callan, Zheng, and Zhang as applied to claim 1 above, and further in view of Rastelli (US20170266280A1).
Applicant argues that the teachings of Rastelli do not remedy the alleged deficiencies of Callan, Zheng, and Zhang. This is not found persuasive, for reasons described supra.
This rejection is therefore maintained.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 5-7, 9, 11-13, 15-17, 19, and 30-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over the following claims of the indicated patents and patent applications in view of Callan, Zheng, Zhang, Callan 2017, and Rastelli:
Patent/application Conflicting claims
U.S. patent 11,382,987 1-5, 7-11
U.S. patent 11,878,059 1-2, 13-14, 16-17, 20
Application 17/734,484 2-4, 6-7, 11, 14-15, 23, 35-38, 41, 43, 46
Application 17/915,251 1, 6-10, 16-17
Applicant argues that the combination of sonodynamic therapy and a PD-L1 inhibitor produces unexpected results in view of the cited references with regards to treatment of metastatic pancreatic cancer, as the combination of these treatment is significantly enhanced over either treatment alone. Applicant also argues that pancreatic cancers are typically not sensitive to anti-PD-L1 treatments, making the benefit of the combination treatment even more unexpected. Applicant further argues that the teachings of Zheng are limited to ex vivo experiments in the context of B-cell lymphoma and with an anti-PD-1 antibody, and therefore does not permit one of ordinary skill in the art to visualize the use of an anti-PD-L1 antibody in combination with sonodynamic therapy. This is not found persuasive, for reasons described supra.
The above rejections are therefore maintained.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Singer (US20170173079A1) teaches that PV-10 (an aqueous composition of 10% Rose Bengal formulated for intralesional injection, see para. 0005 and 0041) may enhance tumor-specific immune responses in combination with the blockade of immune checkpoint molecules such as CTLA-4, PD-1, PD-L1 and PD-L2 (para. 0107). Singer also teaches that this treatment is useful for pancreatic cancer (para. 0083).
Liu (PLoS One. 2018 Apr 25;13(4):e0196033) teaches that combinations of PV-10 (i.e., Rose Bengal, see abstract) and an anti-PD-L1 antibody delays growth of treated and untreated bystander tumors in melanoma (page 8, third paragraph and Figure 6).
No claim is 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER JOHANSEN whose telephone number is (571)272-0280. The examiner can normally be reached Monday-Friday, 7:00 to 3:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PETER JOHANSEN/Examiner, Art Unit 1644
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