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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 9/21/26 has been entered.
Election/Restrictions
Applicant’s election without traverse of invention I in the reply filed on 7/8/25 is acknowledged.
Claims 8-17 and 19-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/8/25.
Claims 1-7 are examined on the merits.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(Withdrawn in view of amendment) Claim(s) 1, 4, 6 and 7 are rejected under 35 U.S.C. 102a1 as being anticipated by Anderson et al. (US PGPub 2019/0225968).
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.
(new rejection necessitated by amendments) Claim(s) 1, 4, 6 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Anderson et al. (US PGPub 2019/0225968) in view of MPEP 2144.06.
The claimed invention is drawn to a composition comprising a class B CpG conjugated to a nanoparticle and a class C CpG conjugated to a nanoparticle. The composition is also part of a pharmaceutical composition with a pharmaceutically acceptable carrier, excipient or diluent and it is in injectable formulation.
Wherein, class B CpG conjugated nanoparticle is free of class C CpG and class C CpG conjugated nanoparticle is free of class B CpG.
Anderson et al. compositions comprising CpG sequences formed into spherical nucleic acid (SNA) structures. [see paragraphs 27-29] More specifically, Anderson et al. teach at paragraph 29, “The SNAs of the invention include CpG oligonucleotides. In some embodiments those CpG oligonucleotides are sub-optimal or non- traditional CpG oligonucleotides. A “non-traditional” CpG oligonucleotide is an oligonucleotide containing an unmethylated CpG motif that while immunostimulatory in vitro does not produce a sufficient immune response in vivo to have a therapeutic benefit. In some embodiments a non-traditional CpG oligonucleotide has a length of less than 24 nucleotides. In other embodiments a non-traditional CpG oligonucleotide has one or more missing structural features from a traditional A-class, B-class, or C-class CpG oligonucleotide.” Therefore, Anderson et al. teach the SNAs can comprise either class A, B or C CpG oligonucleotides. In addition, these CpGs are TLR9 agonists. [see paragraph 2] In order to form the spherical nucleic acids, Anderson et al. teaches that gold nanoparticles can be used as the core of the SNA. [see paragraph 51] Anderson et al. also teach that oligo ethylene glycol and poly T sequences can be part of the oligonucleotide structure. [see paragraph 115] Anderson et al. also teach that their SNA can be delivered via injection. [see paragraph 88]
While Anderson et al. do not specifically state that the class B CpG conjugated nanoparticle is free of class C CpG and class C CpG conjugated nanoparticle is free of class B CpG, they do teach that their SNA (i.e., nanoparticles) can exclusively comprise a class B or class C CpG. MPEP 2144.06 provides guidance about Art Recognized Equivalence for the Same Purpose, more specifically, I. COMBINING EQUIVALENTS KNOWN FOR THE SAME PURPOSE. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)
It would have been obvious to one of ordinary skill in the art to modify the compositions taught by Anderson et al. in order to combine class B CpG conjugated nanoparticle that are free of class C CpG with class C CpG conjugated nanoparticle that are free of class B CpG. One would have been motivated to do so, given the suggestion by Anderson et al. that be used both Class B and C CpGs, which are both TLR9 agonists, can be conjugated to a nanoparticle. There would have been a further motivation in view of MPEP 2144.06, which states It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. Thus the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Response to arguments:
Applicant presents the following arguments in traversal of the rejection:
Anderson et al. fails to teach a composition comprising class B CpG conjugated nanoparticle is free of class C CpG and class C CpG conjugated nanoparticle is free of class B CpG and they fail to teach the specific combination of these CpG conjugated nanoparticles.
In response, while Anderson et al. teach spherical nucleic acids that comprise class A, B and C CpGs [see paragraph 33]; that mixtures class A, B and C CpGs are also contemplated [see paragraph 14]; and that lipid nanoparticles comprising a mixture of classes A, B and C are contemplated [see claims 18, 19 and 32, paragraphs 14 and 33]. It is acknowledged that Anderson et al. fail to teach specifically combining a SNA exclusively comprising a Class C CpG with a SNA exclusively comprising a Class B CpG. However, in view of the summarized teachings of Anderson et al. and the guidance from MPEP 2144.06, it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.
(New Rejection Necessitated by Amendments) Claim(s) 2, 4 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Anderson et al. in view of MPEP 2144.06 as applied to claims 1, 3, 6 and 7 above, and further in view of Lin et al. (PLoS ONE, 2013, Vol. 8, No. 5).
The claimed composition also comprises CpG is conjugated to different nanoparticles and each CpG has a spacer between the CpG and the nanoparticle. Examples of spacers are a polyT sequence and oligo ethylene glycol or both are used.
The teachings of Anderson et al. are summarized above. However, they do not teach the specific use of polyT or oligo ethylene glycol as spacers between the CpG and the nanoparticle.
Lin et al. teach the development gold nanoparticles which deliver CpG in order to stimulate an immune response. Examples of the gold nanoparticles + CpG are shown in figure 1:
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Therefore, Lin et al. teach the use of polyT linkers with or without oligoethylene glycol in order to conjugate a CpG to a gold nanoparticle.
It would have been obvious to one of ordinary skill in the art to modify the compositions taught by Anderson et al. in order to combine class B CpG conjugated nanoparticle that are free of class C CpG with class C CpG conjugated nanoparticle that are free of class B CpG, and to utilize polyT sequences and/or oligo ethylene glycol to link the class B and C CpGs to gold nanoparticles. One would have been motivated to do so, given the suggestion by Anderson et al. that be used both Class B and C CpGs, which are both TLR9 agonists, can be conjugated to a nanoparticle and CpGs of class A, B and/or C be immobilized on nanoparticles, including gold nanoparticles. There would have been a further motivation in view of MPEP 2144.06, which states it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. There would have been a reasonable expectation of success, given the knowledge that polyT and oligo ethylene glycol can be used to immobilize CpG to gold nanoparticles, as taught by Lin et al. Thus the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Response to arguments:
Applicant’s arguments have been considered, but they are not persuasive:
The deficiencies of Anderson et al. related to claims 1, 3, 6 and 7 are addressed above.
The combined teachings of Anderson et al., the guidance from MPEP 2144.06 and Lin et al. provide sufficient teachings, motivation and a reasonable expectation of success at generating a composition comprising class B CpG conjugated nanoparticle is free of class C CpG and class C CpG conjugated nanoparticle is free of class B CpG and they fail to teach the specific combination of these CpG conjugated nanoparticles and each CpG has a spacer (polyT sequence and oligo ethylene glycol or both are used) between the CpG and the nanoparticle.
With regard to the unexpected results, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., treating a tumor with the combined nanoparticle CpG composition presently claimed) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Furthermore, the claimed invention is not commensurate in scope with the unexpected results applicants are presenting. The instant invention of claims 1-7 is drawn to a composition comprising a nanoparticle CpG oligonucleotides and makes no mention of cancer or tumor or treatment.
With regard to applicants unexpected results, Figure 9A of the instant application provides tumor size as a result treatment by:
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However, when comparing the tumor size following treatment by BNP and BNP+CNP, tumor volume appears to be the same by approximately day 22 and by day 23 or day 24 BNP alone saw a slight increase in tumor size. In addition, the CNP alone also achieved a marked decrease of tumor volume compared to the PBS control. Therefore, these results do not support applicant’s purported unexpected results since the BNP alone performed the same as BNP+CNP for a majority of the experiment and CNP alone also decreased tumor volume. With the tumor volume decrease achieved by CNP alone and BNP alone being added together, the results of BNP+CNP is not interpreted to be synergistic, but rather additive. Therefore, the results are expected and applicant’s arguments are not convincing.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN P BLUMEL whose telephone number is (571)272-4960. The examiner can normally be reached M-F 8-5 EST.
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/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671
