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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous office action has been withdrawn pursuant to 37 CFR 1.114.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 submission filed 12 March 2026 has been entered.
The Request for Continued Examination filed has been considered. The following information has been made of record in the RCE filed for the instant application:
1. Claims 2-3, 8-9 and 15-20 have been canceled. The said claims were canceled in the amendment filed 23 May 2025.
2. No new Claims have been added.
3. Claim 1 has been amended. Claim 1 was amended in the amendment filed 23 May 2025.
4. Declaration under 37 CFR 1.132 by Dr. Gregory L. Beatty.
Claims 1, 4-7 and 10-14 are pending in the case.
Claim Rejections - 35 USC § 103
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.
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, 4-7, and 10-14 are rejected under 35 U.S.C. 103 as being unpatentable over Bose et al (US 2017/0100425 A1; of record) in view of Thompson et al (US 2017/0298139; of record) and further in view of Bejerano et al (US 2017/0369570; of record).
Bose et al teaches a method of treating cancer in a subject comprising administering soluble -glucan and a CD40 agonist (Abstract; paras 0032, 0035; active agents recited in claims 1 and 14). One of the cancers that can be treated is pancreatic cancer (part of the limitations of claims 1 and 14 regarding the cancer being pancreatic). Bose uses BxPC3 pancreatic cancer cell lines that have been shown to contain several immunosuppressive cytokines. This means that the pancreatic cancer is poorly immunogenic (paras 0031, 0071, 0109 and 0112-112; poorly immunogenic pancreatic cancer as in claims 1 and 14). The combination of both components or either component can be formulated into a pharmaceutical composition (paras 0035, 0039; limitation of claims 4-5). The soluble -glucan can be derived from yeast, wherein the yeast is Saccharomyces cervisiae and the -glucan may be (1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-(1,3)-D-glucopyranose (paras 0002 and 0026; as in claims 1, 6-7 and 14). The CD40 agonist administered in the method is an agonistic CD40 antibody, is non-complement activating, and is an IgG2 antibody (para 0032; as in claims 10-11). The method of Bose also stimulates the subject’s immune system (abstract; para 0032; as in claim 14). The active agents acted synergistically to minimize growth of tumor (para 0121).
Bose does not expressly teach a method of treating or a method of stimulating immune system in a subject having poorly immunogenic pancreatic ductal adenocarcinoma as in claims 1 and 14 and does not teach the limitations of claims 12 and 13.
Thompson teaches that Dacetuzumab is an agonistic CD40 antibody that is useful in immunotherapy against cancer (paras 0172, 0210, 0211; the antibody recited in claim 12).
Bejerano et al teaches administering an anti--glucan antibody component to increase the efficacy of an antibody and -1,6-glucan combination in cancer immunotherapy (para 0090; component recited in claim 13). This renders obvious the administration of an anti--glucan antibody component in the method of claim 1.
MPEP 2141 states, "The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. The Court quoting In re Kahn, 441 F.3d 977, 988, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006), stated that "[R]ejections on obviousness cannot be sustained by mere conclusatory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.'" KSR, 550 U.S. at, 82 USPQ2d at 1396. Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) " Obvious to try " choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
According to the rationale discussed in KSR above, the rationale in (G) is seen to be applicable here since based on the prior art teachings, an agonistic CD40 antibody and -glucan combination including (1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-(1,3)-D-glucopyranose as the active agent is known in the art for use in a method of treating cancer in a subject (Bose et al), and Dacetuzumab is an anti-CD40 antibody for use in cancer immunotherapy (Thompson). Thus, it is obvious to arrive at the claimed method in view of the combined teachings of the prior art.
Thus, the claimed invention as a whole would have been obvious over the combined teachings of the prior art to one of ordinary skill in the art before the effective filing date of the instant invention. The artisan would have a reasonable expectation of success in treating pancreatic ductal adenocarcinoma in a subject as in claim 1, and in stimulating a subject’s immune system against pancreatic ductal adenocarcinoma as in claim 14 in view of the combined teachings of the prior art. In view of Thompson one of ordinary skill in the art would also use the other agonistic CD40 antibody components recited in claim 12.
Method improvement is the motivation. The artisan would also be motivated to use the combination in the claimed method of treatment since Bose teaches that animal models have demonstrated that administration of soluble -glucan in combination with an antibody result in significantly reduced tumor growth and improved overall survival compared to either agent alone in treating pancreatic cancer (Bose-para 0002). The artisan would also be motivated to further administer anti--glucan antibody component in the claimed method as in claims 12-13 in view of Thompson and Bejerano since Bejerano teaches that it increases the efficacy of the active agents taught by Bose, and Bose teaches that animal models have demonstrated that administration of soluble -glucan in combination with an antibody result in significantly reduced tumor growth and improved overall survival compared to either agent alone (Bose-para 0002). The combination will be more efficacious in the treatment of a pancreatic cancer like pancreatic ductal adenocarcinoma.
Response to Applicant’s Remarks
Applicant has traversed the rejection of the pending claims under 35 USC 103 of record arguing that:
The present application provides experimental data showing a remarkable synergism for the specific combination of (1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-(1,3)-D-glucopyranose (Imprime) as the b-glucan and the agonistic CD40 AbFGK45 in a mouse model of pancreatic cancer. The effect of the combination on antitumor immune response is also shown in Example 2 and Examples 4-5 in the specification.
Bose generally describes methods of treating cancer involving administering a soluble b-glucan and an antibody. While an immunosuppressive pancreatic cancer cell line (BxPC3) is used to generate the immunosuppressive tumor-conditioned medium in the study of Bose, the study does not actually demonstrate the treatment of said BxPC3 cells, much less the treatment of pancreatic ductal adenocarcinoma as in the instant claims. Moreover, Bose discloses that different b-glucans act in different ways. On the contrary, the present application describes an unexpected and remarkable synergistic effect that is seen with the specific b-glucan, namely
(1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-(1,3)-D-glucopyranose and an agonistic CD40 antibody combination therapy against poorly immunogenic pancreatic cancer, pancreatic ductal adenocarcinoma (see page 15 of specification).
Neither Thomson or Bejerano teach or suggest (1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-(1,3)-D-glucopyranose and pancreatic ductal adenocarcinoma as recited in the instant claims. Thomson teaches various methods for treating cancer involving CD40 antibodies but provides no teachings of soluble b-glucan or the specific b-glucan for use in combination with CD40 antibodies, much less that such a combination would result in the unexpected increase in efficacy in treating pancreatic ductal adenocarcinoma. Bejerano teaches various b-1,6-glucan drug conjugates but fails to teach that a combination of (1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-(1,3)-D-glucopyranose and an agonistic CD40 antibody would result in the unexpected increase in efficacy in treating pancreatic ductal adenocarcinoma.
The Declaration of Dr. Beatty provides objective indicia of non-obviousness and efficacy (Fig. 1, 5), novel mechanism (Figs 2-4, 6-7), clinical activity (Figs 8-9 and unexpected safety (Fig. 10). Pages 2-3 of Declaration.
The disclosure of Bose, Thompson and Bejerano do not disclose, teach or suggest these unexpected and remarkable synergistic effects as shown in the Declaration. For these reasons, withdrawal of the rejection is requested. (Pages 2-7 of Remarks).
Applicant’s arguments and the Declaration of Dr. Beatty have been considered but are not found to be persuasive.
Bose teaches treatment of pancreatic cancer (claim 3 of Bose). The active agents that are used in the method of Bose are (1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-(1,3)-D-glucopyranose, which is a soluble -glucan derived from yeast, wherein the yeast is Saccharomyces cervisiae. This is used in combination with a CD40 agonistic antibody. The soluble b-glucan used is IMPRIME, which is the same soluble b-glucan also used in the cited examples. The active agents also acted synergistically to minimize growth of tumor. Bose teaches the method of treatment of pancreatic cancer using the claimed active agent combination and also teaches synergism. Even though Bose does not expressly teach treatment of pancreatic ductal adenocarcinoma, there is a reasonable expectation that pancreatic ductal adenocarcinoma can also be treated using the soluble b-glucan and CD40 agonistic antibody combination. Bose may disclose that different b-glucans act in different ways. But it teaches the claimed soluble b-glucan and CD40 agonistic antibody combination in its method. Therefore, the (1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-(1,3)-D-glucopyranose taught by Bose should act in the same way as in the instant case. Therefore, the artisan would have observed the synergism using the combination of (1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-(1,3)-D-glucopyranose and CD 40 agonistic antibody that applicant claims. Bose also indicates synergism between the b-glucan and antibody combination in the methods as in claims 1 and 14.
Thomson or Bejerano need not necessarily teach or suggest (1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-(1,3)-D-glucopyranose because Bose teaches it. It has been acknowledged in the rejection that treatment of pancreatic ductal adenocarcinoma is not taught in the prior art. However, form the teachings of Bose one of ordinary skill in the art would have a reasonable expectation of success in treating pancreatic ductal adenocarcinoma using the claimed combination. Thomson is cited for teaching that Dacetuzumab is an agonistic CD40 antibody that is useful in immunotherapy against cancer, including pancreatic cancer (para 0443).
Bejerano teaches various b-1,6-glucan drug conjugates but fails to teach that a combination of (1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-(1,3)-D-glucopyranose and an agonistic CD40 antibody would result in the unexpected increase in efficacy in treating pancreatic ductal adenocarcinoma.
Bejerano et al is cited for teaching administration of an antibody component to increase the efficacy of an antibody and -1,6-glucan combination in cancer immunotherapy. Bejerano teaches that the b-glucan can be from Saccharomyces cervisiae and the cancer treated can be pancreatic cancer (paras 0044 and 0079).
Paragraph 5, and 8-10 of the Declaration points to superior efficacy, novel mechanism, clinical activity and unexpected safety. The mechanism of action of the instant active agent combination is not of patentable importance as long as the combined teachings of the prior art render obvious the claimed method of treatment. The prior art teaches the use of the claimed active agents for treating pancreatic cancer. Therefore, the safety seen by the applicant should be seen in the method of the prior art. As far as efficacy goes (para 11 in Declaration), Bose indicates that the active agent combination act synergistically. This shows efficacy of the combination. There is a reasonable expectation of efficacy of the instant active agents in a method of treating pancreatic ductal adenocarcinoma.
The combined teachings of the prior art do render the instant claims obvious. The rejection is maintained.
Conclusion
Pending claims 1, 4-7, and 10-14 are rejected
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
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.
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/GANAPATHY KRISHNAN/Primary Examiner, Art Unit 1693