DETAILED ACTION
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 .
Claims 1-21 are pending and will be examined on the merits.
Objections/Rejections Withdrawn
Claim Objections
The objections to claims 5-6 and 8-21 have been withdrawn in view of claim amendments.
All 35 USC 102 and 103 rejections have been withdrawn in view of claim amendments.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 5-6, 8 and 18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 6, 8 and 18
Regarding claims 6, 8 and 18, each instance of the phrase "preferably" each independently renders its respective claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Note: for examination, limitations indicated as “preferable” will not be considered as a required limitation of the respective claims.
Claim 5
Regarding claim 5, the limitations “including doxorubicin, daunorubicin, epirubicin and idarubicin" enclosed within parentheses as well as “including paclitaxel, docetaxel” also enclosed within parentheses each independently renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Note: for examination, the limitations enclosed in parentheses discussed above will not be considered as a required limitation of the respective claims.
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.
Claim(s) 1-6 and 8-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over De Jong (De Jong, et al., WO 2020/037433A1; Published 2/27/2020; Priority to 8/24/2018 via US 62/722,687, of record) in view of Van (Van, et al., FASEB 2012 26(8):3097)
De Jong teaches an immunomodulator for enhancing an innate immune response comprising: a TLR agonist covalently or non-covalently linked to glycogen-based polysaccharide nanoparticles having a molecular weight of 106 to 107 Da comprising alpha-D glucose chains having an average length of 11-12, with 1[Wingdings font/0xE0]4 linkage and branching point occurring at 1[Wingdings font/0xE0]6 and with a branching degree between 6% and 13% (De Jong, p 4, lines 6-10). De Jong teaches that the immunomodulatory compound of De Jong (which is identical to the instant claimed immunomodulatory compound) is administered to subjects in therapeutically effective amounts in cancer immunotherapy (tumor cells will inherently be contacted by the immunomodulatory compound of De Jong) (De Jong, claims 14 & 17). Regarding claims 2-3, De Jong teaches that the immunomodulatory compounds of De Jong induce CXCL10, IFN-b and ISG-15 very strongly (De Jong, Fig. 4). Regarding instant claim 4, as evidenced by the instant Specification, performing the contacting of a cancer cell with the immunomodulator of De Jong would inherently result in an increase of sensitivity to chemotherapeutics, wherein EC50 is lowered by greater than 10% (Specification, ¶ 0004). (Specification, ¶ 0004). Regarding instant claims 8-9, De Jong teaches that the TLR agonist present on the nanoparticles of De Jong is poly IC (De Jong, Claim 2). Regarding instant claim 10, De Jong teaches that the TLR agonist of De Jong is covalently linked to the nanoparticles of De Jong through a linking group (De Jong, Claim 8). Regarding instant claim 11, De Jong teaches that the nanoparticles of De Jong are cationic and the TLR agonist is linked to the particles though non-covalent electrostatic interactions (De Jong, Claim 9). Regarding instant claim 12, De Jong teaches that the TLR agonist of De Jong comprises between about 60-600% TLR agonist by weight relative to the nanoparticles of De Jong (De Jong, claim 5). Regarding instant claim 14, De Jong teaches that the nanoparticles of De Jong have a polydispersity index of less than 0.3 as measured by DLS and an average diameter between 10 and 150 nm (De Jong, Claim 6). Regarding instant claim 17, De Jong teaches that the nanoparticles of De Jong are covalently linked to an aptamer, small molecules, receptor ligands or antibodies for directing the nanoparticles to specific cells (De Jong, p 21, lines 12-16).
De Jong does not teach that the TLR agonist nanoparticles of De Jong are administered in a method of treating ovarian cancer in a patient, said method comprising administering the TLR agonist nanoparticles of De Jong to said patient in combination with the platinum chemotherapeutic carboplatin, wherein the TLR agonist nanoparticles of De Jong sensitize the cancer cells to the carboplatin. De Jong does not teach that that the TLR agonist is present in a weight ratio of 2:1 relative compared to the nanoparticles.
Van teaches on the subject of dsRNA TLR3 agonists inducing apoptosis in ovarian cancer cells and enhancing the potency of chemotherapeutics (Van, Abstract). Van teaches that combined administration of carboplatin with dsRNA TLR3 agonists led to synergistic reduction in cell viability in chemotherapy resistant cells, compared to additive reduction in cell viability observed upon combined administration car carboplatin and paclitaxel (Van, Abstract).
It would be prima facie obvious to one of ordinary skill in the art to combine the administration of TLR3 agonizing dsRNA (poly IC is a TLR3 agonizing dsRNA) nanoparticles of De Jong with administration of the carboplatin of Van in view of the teachings of Van to form a method of treating ovarian cancer in a patient, said method comprising administering the TLR agonist nanoparticles of De Jong to said patient in combination with the platinum chemotherapeutic carboplatin, wherein the TLR agonist nanoparticles of De Jong sensitize the cancer cells to the carboplatin of Van. One of ordinary skill in the art would have a reasonable expectation of success developing such a method because Van teaches that TLR3 agonizing dsRNA enhances the efficacy of carboplatin in a synergistic fashion. Regarding claims 15 and 18 specifically, the TLR3 agonists and carboplatin of Van were administered concurrently.
It would be prima face obvious to one of ordinary skill in the art to start with the 60-600% wt/wt ratio of TLR agonist to nanoparticle taught by De Jong and arrive at a weight ratio of 2:1 via routine experimentation. One of ordinary skill in the art would be motivated to do this in order to balance the ratio of active agent to carrier particle in the TLR agonist nanoparticles of De Jong. One of ordinary skill in the art would have a reasonable expectation of success starting with the 60-600% wt/wt ratio of TLR agonist to nanoparticle taught by De Jong and arrive at a weight ratio of 2:1 via routine experimentation because routine experimentation is within the purview of one of ordinary skill in the art. Additionally, In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) (Claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms" considered prima facie obvious in view of prior art reference teaching that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." (See MPEP 2144.05).
Response to Arguments
Applicant's arguments filed 6/17/2026 have been fully considered but they are not persuasive.
Applicant’s arguments with respect to the De Jong reference are twofold and will be addressed here. First, Applicant argues that De Jong focuses on treatment/protection from viral infections and does not disclose a method of treating cancer. This is not true. Use of the TLR agonizing nanoparticles of De Jong for cancer immunotherapy is a claimed embodiment of the De Jong document (De Jong, claim 17). Applicant also argues that the that the claims as amended now require administration of a chemotherapeutic agent (either a standard small molecule or a checkpoint inhibitor) in combination with the TLR agnonizing nanoparticles with the TLR agonizing nanoparticles sensitizing the cancer to the chemotherapeutic agent and the De Jong reference does not teach the administration of such additional chemotherapeutic agents. In response, this has been addressed by the inclusion of the Van reference (provides sufficient teaching, suggestion and motivation to combine with TLR agonizing nanoparticles with platinum chemotherapeutics and expect the TLR agonizing nanoparticles to sensitize cancer cells to the platinum chemotherapeutic and 2) the Boes reference, which provides sufficient teaching, suggestion and motivation to combine with TLR agonizing nanoparticles with PDL1 checkpoint inhibitor chemotherapeutic and expect the TLR agonizing nanoparticles to sensitize cancer cells to the PDL1 checkpoint inhibitor via upregulating PDL1 expression on the cancer cells.
Claim(s) 1-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over De Jong (De Jong, et al., WO 2020/037433A1; Published 2/27/2020; Priority to 8/24/2018 via US 62/722,687, of record ) and Van (Van, et al., FASEB 2012 26(8):3097) as applied to claims 1-6 and 8-21 above and in further view of Boes (Boes, et al., Cancer Lett 2015 361:49).
The combined teachings of De Jong and Van are discussed above.
The combined teachings of De Jong do not teach a method of treating a cancer that is neuroblastoma, said method comprising administering the TLR3 agonizing nanoparticles of De Jong in combination with a chemotherapeutic that is a PD-L1 checkpoint agonist, wherein the TLR3 agonizing nanoparticles induce PD-L1 expression and wherein the TLR3 agonizing nanoparticles of De Jong sensitize the cancer cells to the PD-L1 checkpoint inhibitor chemotherapeutic.
Boes teaches on the subject of TLR3 and PD-L1 in human neuroblastoma cells (Boes, Abstract). Boes teaches that TLR3 triggers strong upregulation of PD-L1 on neuroblastoma cells (Boes Abstract). Boex teaches a combined treatment comprising PD-L1 blockade in combination with TLR ligands for the treatment of neuroblastoma (Boes, Abstract).
It would be prima facie obvious to one of ordinary skill in the art to combine the administration of the TLR3 agonizing nanoparticles of De Jong with the PD-L1 checkpoint blockade of Boes in view of Boes to form a method of treating neuroblastoma, said method comprising the administration of the TLR3 agonizing nanoparticles of De Jong with the PD-L1 checkpoint inhibitor of Boes, wherein the TLR3 agonizing nanoparticles sensitize the tumor cells to the PD-L1 checkpoint inhibitor via inducing PD-L1 expression. One of ordinary skill in the art would be motivated to do this in order to better treat neuroblastoma. One of ordinary skill in the art would have a reasonable expectation of success forming such a method because Van teaches TLR3 agonists (such as the poly IC of De Jong) induce PD-L1 expression on neuroblastoma cells and Van also directly teaches combined administration of TLR3 agonists combined with PD-L1 checkpoint inhibitors for treatment of neuroblastoma.
Conclusion
Claims 1-21 are rejected.
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 Sydney Van Druff whose telephone number is (571)272-2085. The examiner can normally be reached 10 am - 6 pm.
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/SYDNEY VAN DRUFF/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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