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 .
Election/Restrictions
Applicant’s election without traverse of a polymer (claims 73-90) in the reply filed on 8/27/2026 is acknowledged.
Claim 91 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected a process of making the polymer, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/27/2026.
Note that Requirements for election of species are lifted by Examiner.
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.
Claims 73-75, 78, 81, 85, 87 and 90 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lidický et al. ("Anti-Lymphoma Efficacy Comparison of Anti-CD20 Monoclonal Antibody-Targeted and Non-Targeted Star-Shaped Polymer-Prodrug Conjugates" Molecules 2015, 20, 19849–19864).
Lidický teaches star-shaped polymer-doxorubicin conjugates (see Abstract and Figures 1 and 2) with a PAMAM dendrimer core (meeting the limitations of claim 85) with amine functional
groups (component O) and nine (defined by an integer, “n”), N-(2-hydroxypropyl)methacrylamide (HPMA) -based polymer arms (component A) attached to the anticancer drug doxorubicin (component D2):
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Note that claimed A1 and A2 arm can be the same or different (see instant claim 1) and the drug molecule is amphiphilic.
Lidicky discloses a reactive group (Hydrazide) density within the range of 4.4 to 5.2% mol (meeting the corresponding limitations of claims 73, 75 and 81) and the polymer art has a number average molecular weight Mn =27000/1.8=15000 (see Table 2, Entry 1 at page 19853), meeting the corresponding limitations of claims 74 and 87.
Regarding claims 78, D2 is linked to methacrylamide residue (see Figure 1 at page 19852).
Claims 73-77, 81-82, 84 and 90 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lynn et al (Impact of Polymer-TLR-7/8 Agonist (Adjuvant) Morphology on the Potency and Mechanism of CD8 T Cell Induction, Biomacromolecules 2019, 20, 854−870).
Lynn discloses Multiblock copolymer PPG-b-P[(HPMA)-co-(PGMA)-co (AEMA)] (PP4) synthesized by copolymerizing HPMA, PGMA and Boc-AEMA at the presence of azobis(isobutyronitrile) (AIBN) as an initiator and PPG-(CTP)3 as a trifunctional macro-RAFT agent (see page 858, left column, meeting the limitations of claim 84).
In reference to claims 73, 75 and 81, Lynn teaches that “importantly, by keeping the TLR-7/8a density below 7 mol %, the hydrophobic TLR-7/8a had minimal impact on the hydrodynamic characteristics of the polymer-TLR-7/8a conjugates.” (see page 860, right column).
Regarding claim 74, Lynn teaches that the polymer art has a number average molecular weight Mn =42600/1.19=35800 (see entry PP3 at Table S1, see Supplementary tables).
In reference to claims 75-77, Lynn teaches An imidazoquinoline based agonist, which is approximately 40-fold more potent than the structurally related and commercially available analog, R848 (see page 860, left column).
Regarding claim 78, Lynn teaches the claimed methacrylamide based formula (see Figure 1, for example PC7-PC9 at page 857).
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.
Claims 86, 88-89 and 90 are rejected under 35 U.S.C. 103 as being unpatentable over Lidicky as applied to claims 73-75, 81 and 90 above, and further in view of over Pourianazar et al (Bioapplications of poly(amidoamine) (PAMAM) dendrimers in nanomedicine, J. Nanopart Res. (2014) 16:2342).
Lidicky fails to teach 5th generation PAMAM.
Pourianazar teaches a Poly(amidoamine) (PAMAM) dendrimers core comprising poly(N,N-dimethylaminoethyl methacrylate) arms used for controlled, pH-dependent release of chlorambucil (see page 2342, left column).
In reference to claim 86, Pourianazar teaches that 5th generation PAMAM can be used (see Table 1 at page 2342).
Regarding claims 88-90, Pourianazar discloses enzyme-mediated drug release, thereby decreasing the cytotoxicity of the conjugate). In addition, the reference teaches preparation of starlike carriers of the anticancer drug doxorubicin by the conjugation of poly(N-(2 hydroxypropyl)methacrylamide) macromonomers to PAMAM dendrimers, followed by attachment of the drug to the polymer arms by a biodegradable peptide spacer(see page 2342, left column).
Note that Pourianazar fails to teach 5th generation PAMAM in formula recited in instant claim 73.
However, the reference discloses that regulation of surface charge density of the dendrimer (determined by generation number) is very important for drug delivery (see page 2341, left column).
Therefore, it would have been obvious to a person of ordinary skills in the art before the effective filing date of the invention to use 5th generation PAMAM, when high surface charge density of the dendrimer is required.
Claim 79 is rejected under 35 U.S.C. 103 as being unpatentable over Lidicky as applied to claims 73-75, 81 and 90 above, and further in view of over Feng et al (Anticancer nanoparticulate polymer-drug conjugate, Bioengineering & Translational Medicine 2016; 1: 277-296).
Lidicky fails to teach formula of claim 73.
Feng discloses a star polymer comprising the following arm link (see Figure 2 at page 280):
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In addition, Feng teaches widely used short peptide linker is citrulline-valine, which can be cleaved by specific lysosomal proteases but impart greater stability (see page 283, chapter 2.3.3 | Enzyme sensitive linker).
The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945) , 325 U.S. at 335, 65 USPQ at 301, see also In re Leshin, 227 F.2d 197, 125 USPQ 416 (CCPA 1960), Ryco, Inc. v. Ag-Bag Corp., 857 F.2d 1418, 8 USPQ2d 1323 (Fed. Cir. 1988) and MPEP 2144.07.
Therefore, it would have been obvious to a person of ordinary skills in the art before the effective filing date of the invention to use valine-based linker in Lidicky’s star polymer, since it is enzymatically cleavable and suitable for drug delivery purposes.
Allowable Subject Matter
Claims 80 and 83 objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Search for prior art does not result in a reference covering the subject matter of the claims above.
The closest prior art found is represented by Lidicky (see rejection above).
Lidický teaches star-shaped polymer-doxorubicin conjugates (see abstract and Figures 1 and 2) with a PAMAM dendrimer core (meeting the limitations of claim 85)with amine functional groups (component O) and nine (an integer, n), N-(2-hydroxypropyl)methacrylamide (HPMA) -based polymer arms (component A) attached to the anticancer drug doxorubicin (component D2).
However, the reference fails to teach polymer structures recited in claims 80 and 83.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GREGORY LISTVOYB whose telephone number is (571)272-6105. The examiner can normally be reached 9am-5pm EST M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heidi Riviere Kelley can be reached at (571) 270-1831. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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GL
/GREGORY LISTVOYB/Primary Examiner, Art Unit 1765
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