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 .
DETAILED ACTION
Applicant’s amendments and remarks filed on August 5, 2026 are acknowledged. Claims 2, 4, 6, and 8-11 have been canceled. Claims 1 and 7 were amended. Claims 1, 3, 5, 7, and 12-17 are pending. Claims 14-17 are withdrawn.
Claims 1, 3, 5, 7, 12, and 13 are examined on the merits herein.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 submission filed on August 5, 2026 has been entered.
Withdrawn Objections
In view of Applicant’s amendments and response, the objection to the drawings is withdrawn.
In view of Applicant’s amendments and response, the objection to claim 1 is withdrawn.
Withdrawn Rejections
In view of Applicant’s amendments and response, the 35 U.S.C. 112(a) written description rejection is withdrawn.
Drawings
The drawings were received on August 5, 2026. These drawings are found acceptable by the examiner.
New Grounds of Rejections Necessitated by Amendment
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, 3, 7, 12, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over List et al. (WO 2016/070045; reference previously cited by the Examiner) in view of Pourianazar et al. (Journal of Nanoparticle Research 2014) and Juliano et al. (US 2008/0199960).
Regarding claims 1, 3, 7, and 12, List et al. discloses compositions for targeted treatment of TLR9-expressing cancers. In particular, molecules containing TLR9 targeting ligands that target cytotoxic agents to TLR9-expressing malignant cells. The molecule can comprise a TLR9 targeting ligand and a cytotoxic agent that is joined to the targeting ligand by a bivalent linker [page 4, 3rd and 4th full paragraphs]. List et al. discloses that in some embodiments the TLR9 targeting ligand is an unmethylated CpG oligodeoxynucleotide, or an analogue or derivative thereof that binds TLR9 [page 4, fifth full paragraph].
Regarding claim 13, List et al. discloses a pharmaceutical composition comprising a molecule disclosed in a pharmaceutically acceptable carrier [page 2, last paragraph].
However, List et al. does not teach a cytotoxic nanoparticle. List et al. also does not teach that the cytotoxic nanoparticle comprises a cationic poly(amidoamine) (PAMAM) dendrimer having 3, 4 or 5 dendritic layers covalently conjugated to the unmethylated CpG oligodeoxynucleotide. List et al. does not teach that the cytotoxic nanoparticle has a mean diameter of 1.5 to 10 nm. List et al. also does not teach wherein the ligand is covalently conjugated to the PAMAM dendrimer via the bivalent linker.
Pourianazar et al. teaches that biodegradability, non-toxicity, non-immunogenicity, and multifunctionality of PAMAM dendrimer are the key factors which facilitate steady increase of its application in drug delivery, gene transfection, tumor therapy, and diagnostics applications with precision and selectivity [page 1, right column, first paragraph]. Pourianazar et al. teaches that a PAMAM dendrimer posseses three distinguishable architectural components: a core, interior layers (generations) consisting of repeating units radially attached to the core, and terminal functional groups (the exterior shell) [page 3, left column, second full paragraph]. Further, the size of PAMAM dendrimers ranges from 1 to 13 nm in diameter for generation 0 (G0) through generation 10 (G10) [page 3, right column, second paragraph] and an increase in the generation number has a direct relationship with in vitro toxicity [page 5, left column]. Pourianazar et al. also teaches that therapeutic agents can be either encapsulated within the dendritic structure or attached to the terminal functional groups of PAMAM dendrimers via electrostatic or covalent bonds (prodrug) to be delivered [page 19, left column, first full paragraph]. Pourianazar et al. also teaches that drug loading can be tuned by varying the generation number of the PAMAM dendrimer [page 21, right column, last paragraph bridging to page 22, left column].
Juliano et al. teaches that the dendrimeric structure can comprise at least two oligonucleotides covalently attached to each other through a linker (dendrimeric oligonucleotide structure) or is a cationic polymer such as PAMAM dendrimers [0034]. Juliano et al. also teaches that conjugate moieties can be attached to the oligomeric compound or to the dendrimeric structure directly or through a linking moiety (linker or tether). Further, linkers are bifunctional moieties that serve to covalently connect a conjugate moiety to a dendrimeric structure or to an oligomeric compound. The linker can have at least two functionalities, one for attaching to the dendrimeric structure or the oligomeric compound and the other for attaching to the conjugate moiety [0206].
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the molecule of List et al. by incorporating a cytotoxic nanoparticle wherein the cytotoxic nanoparticle comprises a cationic poly(amidoamine) (PAMAM) dendrimer having 3, 4 or 5 dendritic layers covalently conjugated to the unmethylated CpG oligodeoxynucleotide wherein the cytotoxic nanoparticle has a mean diameter of 1.5 to 10 nm and wherein the ligand is covalently conjugated to the PAMAM dendrimer via the bivalent linker because List et al. taught molecules containing TLR9 targeting ligands that target cytotoxic agents to TLR9-expressing malignant cells, Pourianazar et al. taught that the size of PAMAM dendrimers ranges from 1 to 13 nm in diameter for generation 0 (G0) through generation 10 (G10) and drug loading can be tuned by varying the generation number, Pourianazar et al. taught that an increase in the generation number has a direct relationship with in vitro toxicity, Pourianazar et al. taught that therapeutic agents can be attached to the terminal functional groups of PAMAM dendrimers via electrostatic or covalent bonds (prodrug) to be delivered, Juliano et al. taught that a dendrimeric structure can comprise at least two oligonucleotides covalently attached to each other through a linker (dendrimeric oligonucleotide structure) or is a cationic polymer such as PAMAM dendrimers, and Juliano et al. taught that linkers are bifunctional moieties that serve to covalently connect a conjugate moiety to a dendrimeric structure or to an oligomeric compound. One of ordinary skill in the art would have made such a modification because it would have amounted to combining known prior art elements to yield predictable results.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over List et al. (WO 2016/070045; reference previously cited by the Examiner) in view of Pourianazar et al. (Journal of Nanoparticle Research 2014) and Juliano et al. (US 2008/0199960) as applied to claims 1, 3, 7, 12, and 13 above, and further in view of Epstein et al. (WO 2006/052900; reference previously cited by the Examiner), and Cao et al. (Scientific Reports 2017; reference previously cited by the Examiner).
Regarding claim 5, the teachings of List et al., Pourianazar et al., and Juliano et al. are discussed above.
However, List et al., Pourianazar et al., and Juliano et al. do not teach that the bivalent linker is a C6 amino-SMCC linker.
Epstein et al. teaches a cancer therapeutic agent comprising a cancer targeting molecule linked to a CpG oligodeoxynucleotide. Epstein et al. also teaches methods of reducing the size of a tumor or inhibiting the growth of cancer cells in an individual or inhibiting the development of metastatic cancer [abstract]. Epstein et al. teaches that antibodies may be linked to CpG immunostimulatory oligonucleotides using crosslinkers such as maleimide crosslinkers (Table 1) which possess two different reactive groups that allow for conjugations with specific sites on antibodies, minimizing undesirable polymerization or self-conjugation [0067]. SMCC/Sulfo-SMCC is an example of a maleimide crosslinking reagent listed in Table 1 [0068].
Cao et al. teaches the synthesis of antisense oligonucleotides and thyroid hormone T3 conjugates for obesity treatment using the principle that antibody-drug conjugates deliver highly potent cytotoxic agents to cancer cells for cancer therapy [abstract]. Cao et al. teaches that phosphorothioate-modified ASOs with a 5’-thiol and C6 amino linker were synthesized and thyroid hormone T3 was reacted with sulfo-SMCC to generate maleimide-activated T3 [page 6, first full paragraph].
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the molecule of List et al., Pourianazar et al., and Juliano et al. wherein the bivalent linker comprises a C6 amino-SMCC linker because List et al., Pourianazar et al., and Juliano et al. taught a molecule comprising a TLR9 targeting ligand conjugated to a cytotoxic nanoparticle via a bivalent linker, Epstein et al. taught that maleimide crosslinking reagents such as SMCC/Sulfo-SMCC allows for conjugations with specific sites on antibodies while minimizing undesirable polymerization or self-conjugation, and Cao et al. taught ASO-T3 conjugates for targeted delivery of cytotoxic drugs to cancer cells. One of ordinary skill in the art would have made such a modification because it would have amounted to combining known prior art elements to yield predictable results.
Conclusion
No claims are allowed.
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/C.T./
Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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