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 January 6, 2026 are acknowledged. Claims 2, 4, 6, and 11 have been canceled. Claim 1 was amended. Claims 1, 3, 5, 7-10, and 12-17 are pending. Claims 14-17 are withdrawn.
Claims 1, 3, 5, 7-10, 12, and 13 are examined on the merits herein.
Withdrawn Objections
In view of Applicant’s amendments and response, the objection to the drawings in reference to paragraphs [0015] and [0100] is withdrawn.
In view of Applicant’s amendments and response, the objection to the specification is withdrawn.
Drawings
The drawings were received on January 6, 2026.
The drawings are objected to because Figures 1A, 1B, and 6B are blurry and hard to decipher. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Response to Arguments
Applicant's arguments filed January 6, 2026 have been fully considered but they are not persuasive.
Applicant has submitted replacement sheets for Figure 1 (now Figures 1A and 1B) and Figure 6B (now Figures 6B, 6C, 6D, and 6E) in an attempt to overcome the drawing objections for previous Figures 1 and 6B; however, Figures 1A and 1B (previous Figure 1) and Figure 6B (previous image on top left of Figure 6B) are still blurry and hard to decipher.
Therefore, the Examiner is maintaining the objection to the drawings.
Specification
The substitute specification filed on January 6, 2026 has been entered.
Claim Objections
Claim 1 is objected to because of the following informality:
Claim 1 recites in part “comprises a cationic a poly(amidoamine) (PAMAM) dendrimer dendritic polymer” and should recite “comprises a cationic poly(amidoamine) (PAMAM) dendrimer”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3, 5, 7-10, 12, and 13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1, 3, 5, 7-10, 12, and 13 are drawn to a genus of toll like receptor 9 (TLR9) targeting ligands wherein the TLR9 targeting ligand is a CpG oligodeoxynucleotide and to a genus of cytotoxic nanoparticles wherein the cytotoxic nanoparticle comprises a cationic PAMAM dendrimer defined by function of being non-toxic outside the cell but cytotoxic once internalized.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof.
The specification asserts that the cationic structure of the nanoparticle/polymer can be cytotoxic once internalized by a cell, but non-toxic outside the cell [0007]. Specifically, cytotoxicity can be modulated by adjusting the sizes, branching, functional groups, cationic components, or a combination thereof. For example, a dendritic polymer can be adjusted to have different sizes such as two or more concentric dendritic layers (generations). In further examples, a 3 or 5 layer PAMAM or PEI dendrimer can be suitable [0103]. The specification further asserts in Example 1 that CpG, a cognate danger-associated molecular pattern (DAMP) recognized by TLR9, was used as a target for internalization of an amphipatic lytic peptide capable of lysis only when internalized [0144].
The specification asserts that the TLR9 targeting ligand (TTL) can be a CpG oligodeoxynucleotide such as an unmethylated CpG oligodeoxynucleotide, or an analogue or derivative thereof [0088]. Furthermore, the specification envisions that the TTL comprises an antibody which refers to natural or synthetic antibodies and encompasses polyclonal antibodies, monoclonal antibodies, and immunoglobulin molecules [0090]. However, the specification only describes that the TLR9 targeting ligand comprises the CpG sequence (SEQ ID NO: 1) [0008]. Example 5 asserts that Figures 30 to 43 show in vivo effects of CpG-dendrimers [0159]; however, it is unclear from the figures and the description of drawings section what the figures are showing (e.g., Figure 30) because no further explanation is provided with respect to in vivo treatment using CpG dendrimer conjugates.
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of unmethylated CpG oligodeoxynucleotide as the TLR9 targeting ligand. The results are not necessarily predictive of other CpG oligodeoxynucleotides or PAMAM dendrimers falling within the broadly claimed genus. Thus, it is impossible for one to extrapolate from the limited examples described herein those CpG oligodeoxynucleotides and PAMAM dendrimers that would necessarily meet the structural/functional characteristics of the rejected claims.
Fox et al. (Advances in Colloid and Interface Science 2018; reference previously cited by the Examiner) discloses that application of PAMAM dendrimers has been hindered by uncertainties in their cytotoxicity which is influenced by dendrimer generation, surface chemistry, dosage, and cell specificity [abstract]. Furthermore, a limited understanding of the cytotoxicity of nanomaterials and nanoparticles remains, particularly with how they impart interactions with cell membranes [page 2, left column, first paragraph].
Chis et al. (Molecules 2020; reference previously cited by the Examiner) discloses that molecular cytotoxicity constitutes a limiting characteristic, especially for cationic and higher-generation dendrimers [abstract]. Chis et al. discloses in Figure 2 (reproduced below) the types of dendrimers and how surface charge affects their in vitro and in vivo cytotoxicity, biopermeability, and immunogenicity [page 4].
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Thus, the prior art does not appear to offset the deficiencies of the instant specification in that it does not describe a genus of TLR9 targeting ligands and cytotoxic nanoparticles that are non-toxic outside the cell but cytotoxic once internalized.
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 1, 3, 5, 7-10, 12, and 13.
Response to Arguments
Applicant's arguments filed January 6, 2026 have been fully considered but they are not persuasive.
Applicant asserts that amending claim 1 to specify that the TLR9 targeting ligand is a CpG oligonucleotide and that the cytotoxic nanoparticle is a PAMAM cationic dendritic polymer having 3, 4, or 5 dendritic layers, a mean diameter of 1.5 to 10 nm overcomes the 35 U.S.C. 112(a) written description rejection.
Contrary to Applicant’s assertions, amended claim 1 is still drawn to a genus of TLR9 targeting ligands wherein the TLR9 targeting ligand is a CpG oligodeoxynucleotide and to a genus of cytotoxic nanoparticles wherein the cytotoxic nanoparticle comprises a cationic PAMAM dendrimer defined solely by function of being non-toxic outside the cell but cytotoxic once internalized.
The claim as currently written encompasses an unmethylated CpG oligodeoxynucleotide, or an analogue or derivative thereof. As discussed in the original 35 U.S.C. 112(a) written description rejection, the specification only describes that the TLR9 targeting ligand comprises the CpG sequence (SEQ ID NO: 1) [0008]. Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of unmethylated CpG oligodeoxynucleotide as the TLR9 targeting ligand. Further, specifying that the cytotoxic nanoparticle comprises a cationic PAMAM dendrimer does not mean that it meets the functional limitation of being non-toxic outside the cell but cytotoxic once internalized. Therefore, it is impossible for one to extrapolate from the limited examples described herein those CpG oligodeoxynucleotides and PAMAM dendrimers that would necessarily meet the structural/functional characteristics of the rejected claims. Further, as disclosed in the instant specification, the amphipatic lytic peptide is capable of lysis only when internalized.
Conclusion
No claims are 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.
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/C.T./
Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637