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 .
Summary
Claims 1-9 and 11-34 are pending in this office action. Claim 10 is cancelled. All pending claims are under examination in this application.
Priority
The current application filed on April 3, 2023 claims domestic priority to a provisional patent application 63/326,541 filed on April 1, 2022.
Claim Objections
Claims 1-9, 11-22, and 31 are objected to because of the following informalities:
Claim 1: Please insert an “and” after the second semi-colon.
Dependent claims 2-9 and 11-22 are included here because they depend from claim 1 and fail to cure the defect.
Claims 33-34: These new claims were presented within the Request for Continued Examination submitted on January 26, 2026. In the most recent claim set, submitted on August 13, 2026 these claims were not presented or cancelled by the Applicant. The Applicant is requested to elaborate on the status of these claims.
Appropriate correction is required.
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 non-obviousness.
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 1-9 and 11-34 are rejected under 35 U.S.C. 103 as being unpatentable over Khan et al. (US2017/0079916A1) in view of Shalek et al. (WO2019/018441A1), Wu et al. (Chemical Communications, 2005), Guc et al. (Drug Development and Industrial Pharmacy, 2010), Mehta et al. (Molecular Pharmaceutics, 2018), Lallana et al. (Pharmaceutical Research, 2012), Nigavekar et al. (Pharmaceutical Research, 2004), Peng et al. (Macromolecules, 2009), Niu et al. (Chinese Chemical Letters, 2014), Carlmark et al. (Chemical Society Reviews, 2013), Gillies et al. (JACS, 2002), and Pittelkow et al. (Synthesis, 2002).
[The Examiner is going to introduce each reference and then combine them in the rejection of the instant claims.]
1. Khan et al.
Khan et al. is considered to be the closest prior art to the present invention and teaches compositions and methods for modified dendrimer nanoparticle delivery (see title). In addition, Khan et al. disclose compositions and methods for modified dendrimer nanoparticle (“MDNP”) delivery of therapeutic, prophylactic and/or diagnostic agent such as large repRNA molecules to the cells of a subject have been developed. MDNPs efficiently drive proliferation of antigen-specific T cells against intracellular antigen, and potentiate antigen-specific antibody responses. MDNPs can be multiplexed to deliver two or more different repRNAs to modify expression kinetics of encoded antigens and to simultaneous deliver repRNAs and mRNAs including the same UTR elements that promote expression of encoded antigens (see abstract).
2. Shalek et al.
Shalek et al. teach the cell atlas of healthy and diseased barrier tissues (see title). Furthermore, Shalek et al. disclose a cell atlas of barrier tissues from healthy and diseased subject. The atlas was obtained by single cell sequencing of approximately 18,036 cells in a surgical data set and 18,704 cells from scrapings. The present invention discloses novel markers for cell types. Moreover, genes associated with disease, including type 2 inflammation are identified. The invention provides for diagnostic assays based on gene markers and cell composition, as well as therapeutic targets for controlling differentiation, proliferation, maintenance and/or function of the cell types disclosed herein. In addition, novel cell types and methods of quantitating, detecting and isolating the cell types are disclosed (see abstract).
3. Wu et al.
Wu et al. teach multivalent, bifunctional dendrimers prepared by click chemistry (see title). Furthermore, Wu et al. disclose unsymmetrical dendrimers, containing both mannose binding units and coumarin fluorescent units, have been prepared using click chemistry and shown to be highly efficient, dual-purpose recognition/detection agents for the inhibition of hemagglutination (see abstract).
4. Guc et al.
Guc et al. teach fatty acid based hyperbranched polymeric nanoparticles for hydrophobic drug delivery (see title). Also, Guc et al. disclose the following abstract:
Background: In recent years nano-sized dendrimer/hyperbranched polymers gained importance in drug delivery applications.
Objective: In this study, a novel fatty acid-based hyperbranched resin (HBR) was synthesized and used for tamoxifen (TAM) and idarubicin (IDA) delivery. Methods: The core of the HBR was dipentaerythritol, and the branching was provided by dimethylolpropionic acid. The molecule was terminated by ricinoleic acid. Chemical and structural characterization of the resin was carried out and then drug-loading experiments were performed.
Conclusion: The loading efficiencies were found to be 73.3%
for TAM and 74% for IDA. The Fourier transform infrared spectroscopy analysis showed that TAM physically bounded onto the resin whereas IDA interacted chemically. Cont rolled release in phosphate buffer was improved by Pseudomonas sp. lipase and sodium dodecyl sulfate. The release rates decreased with the increase of loading concentrations. The cytotoxicity analyses were carried out on MCF-7 breast cancer
cells for both drug-free and drug-loaded HBR. Drug-free particles did not have significant toxicity. Drug loaded nanoparticles caused higher levels of cell death than pure drugs (see abstract).
5. Mehta et al.
Mehta et al. teach reducing dendrimer generation and PEG chain length increases drug release and promotes anticancer activity of PEGylated polylysine dendrimers conjugated with doxorubicin via a cathepsin-cleavable peptide linker (see title). Additionally, Mehta et al. disclose PEGylation typically improves the systemic exposure and tumor biodistribution of polymeric drug delivery systems but may also restrict enzyme access to peptide-based drug linkers. The impact of dendrimer generation (G4 vs G5) and PEG length (570 vs 1100 Da) on the pharmacokinetics, tumor biodistribution, drug release kinetics, and anticancer activity of a series of PEGylated polylysine dendrimers conjugated with doxorubicin via a cathepsin-B cleavable valine-citrulline linker was therefore investigated in rodents. Although the smallest G4 PEG570 dendrimer showed the most efficient cathepsin-mediated doxorubicin release, systemic exposure and tumor uptake were limited. The largest G5 PEG1100 dendrimer showed good tumor uptake and retention but restricted drug liberation and therefore limited anticancer activity. Superior anticancer activity was achieved using an intermediate sized dendrimer that showed better drug release kinetics, systemic exposure, tumor uptake, and retention. The data suggest that balancing PEG molecular weight and dendrimer size is critical when designing chemotherapeutic dendrimers (see abstract).
6. Lallana et al.
Lallana et al. teach click chemistry with polymers, dendrimers, and hydrogels
for drug delivery (see title). Furthermore, Lallana et al. disclose that during the last decades, great efforts have been devoted to design polymers for reducing the toxicity, increasing the absorption, and improving the release profile of drugs. Advantage has been also taken from the inherent multivalency of polymers and dendrimers for the incorporation of diverse functional molecules of interest in targeting and diagnosis. In
addition, polymeric hydrogels with the ability to encapsulate drugs and cells have been developed for drug delivery and tissue engineering applications. In the long road to this successful story, pharmaceutical sciences have been accompanied by parallel
advances in synthetic methodologies allowing the preparation of precise polymeric materials with enhanced properties. In this context, the introduction of the click concept by Sharpless and coworkers in 2001 focusing the attention on modularity and
orthogonality has greatly benefited polymer synthesis, an area where reaction efficiency and product purity are significantly challenged. The purpose of this Expert Review is to discuss the impact of click chemistry in the preparation and functionalization of polymers, dendrimers, and hydrogels of interest in drug delivery (see abstract).
7. Nigavekar et al.
Nigavekar et al. teach 3H dendrimer nanoparticle organ/tumor distribution (see title). In addition, Nigavekar et al. disclose the following abstract:
Purpose. To determine the in vivo biodistribution for differently charged poly(amidoamine) (PAMAM) dendrimers in B16 melanoma and DU145 human prostate cancer mouse tumor model systems.
Methods. Neutral (NSD) and positive surface charged (PSD) generation
5 (d _5 nm) PAMAM dendrimers were synthesized by using 3H-labeled acetic anhydride and tested in vivo. Dendrimer derivatives were injected intravenously, and their biodistribution was determined via liquid scintillation counting of tritium in tissue and excretory samples. Mice were also monitored for acute toxicity.
Results. Both PSD and NSD localized to major organs and tumor. Dendrimers cleared rapidly from blood, with deposition peaking at 1 h for most organs and stabilizing from 24 h to 7 days post injection. Maximal excretion occurred via urine within 24 h post injection. Neither dendrimer showed acute toxicity.
Conclusions. Changes in the net surface charge of polycationic PAMAMs modify their biodistribution. PSD deposition into tissues is higher than NSD, although the biodistribution trend is similar. Highest levels were found in lungs, liver, and kidney, followed by those in tumor, heart, pancreas, and spleen, while lowest levels were found in brain. These nanoparticles could have future utility as systemic biomedical delivery devices (see abstract).
8. Peng et al.
Peng et al. teach dendron-like polypeptide/linear poly(ethylene oxide) biohybrids with both asymmetrical and symmetrical topologies synthesized via the combination of click chemistry and ring-opening polymerization (see title). Furthermore, Peng et al. disclose that dendron-like poly(γ-benzyl-L-glutamate)/linear poly(ethylene oxide) block copolymers with both asymmetrical and symmetrical topologies (i.e., ABn type Dm-PBLG-b-PEO and BnABn type Dm-PBLG-b-PEOb-Dm-PBLG; n ) 2m, m ) 0, 1, 2, and 3; Dm are the propargyl focal point poly(amido amine) type dendrons having 2m terminal primary amine groups) were synthesized via the combination of ring-opening polymerization (ROP) of γ-benzyl-L-glutamate N-carboxyanhydride (BLG-NCA) and click chemistry according to the “arm-first” and “core-first” strategies. In the arm-first method, the propargyl focal point dendrons Dm having 2m terminal primary amine groups were first used for initiating the ROP of BLG-NCA, generating “clickable” dendron-like Dm-PBLG homopolymers having 2m branches, which were then click conjugated with azide-terminated PEO (PEO-N3) to produce asymmetrical Dm-PBLG-b-PEO. In the core-first strategy, the propargyl focal point Dm was first click conjugated with PEO-N3 to generate primary amine-terminated PEO dendrons, which were further
used as the macroinitiators for the ROP of BLG-NCA to produce the targeted copolymers with both asymmetrical and symmetrical topologies. Their molecular structures and physical properties were characterized in detail by FT-IR, NMR, gel permeation chromatography, differential scanning calorimetry, and wide-angle X-ray diffraction. Both spherical and wormlike micelles self-assembled from these Dm-PBLG-b-PEO copolymers in aqueous solution, and mainly the PBLG composition controlled the morphology of nanostructures (see abstract).
9. Niu et al.
Niu et al. teach synthesis of ester-capped carbosilane dendrimers via a hybrid divergent–convergent method (see title). In addition, Niu et al. disclose that a series of novel ester-capped carbosilane dendrimers (G0-COOCH3–G2-COOCH3) were designed and successfully synthesized via a hybrid divergent–convergent method through a facile hydrosilylation reaction. The structures of these dendrimers were confirmed by FTIR, 1H NMR, and HRMS analyses (see abstract).
10. Carlmark et al.
Carlmark et al. teach dendritic architectures based on bis-MPA: functional
polymeric scaffolds for application-driven research (see title). Additionally, Carlmark et al. disclose that dendritic polymers are highly branched, globular architectures with multiple representations of functional groups. These nanoscale organic frameworks continue to fascinate researchers worldwide and are today under intensive investigation in application-driven research. A large number of potential application areas have been suggested for dendritic polymers, including theranostics, biosensors, optics, adhesives and coatings. The transition from potential to real applications is strongly dictated by their commercial accessibility, scaffolding ability as well as biocompatibility. A dendritic family that fulfills these requirements is based on the 2,2-bismethylolpropionic acid (bis-MPA) monomer. This critical review is the first of its kind to cover most of the research activities generated on aliphatic polyester dendritic architectures based on bis-MPA. It is apparent that these scaffolds will continue to be in the forefront of cutting-edge research as their structural variations are endless including dendrons, dendrimers, hyperbranched polymers, dendritic linear hybrids and their hybridization with inorganic surfaces (see abstract).
11. Gillies et al.
Gillies et al. teach designing macromolecules for therapeutic applications:
polyester dendrimers-poly(ethylene oxide) “bow-tie” hybrids with tunable molecular weight and architecture (see title). Also, Gillies et al. disclose that the design and preparation of new polyester dendrimer, poly(ethylene oxide) hybrid systems
for drug delivery and related therapeutic applications, are described. These systems consist of two covalently attached polyester dendrons, where one dendron provides multiple functional handles for the attachment of therapeutically active moieties, while the other is used for attachment of solubilizing poly(ethylene oxide) chains. By varying the generation of the dendrons and the mass of the poly(ethylene oxide) chains, the molecular weight, architecture, and drug loading can be readily controlled. The “bow-tie” shaped dendritic scaffold was synthesized using both convergent and divergent methods, with orthogonal protecting groups on the periphery of the two dendrons. Poly(ethylene oxide) was then attached to the periphery of one dendron using an efficient coupling procedure. A small library of eight carriers with molecular weights ranging from about 20 kDa to 160 kDa were prepared and characterized by various techniques, confirming their well-defined structures (see abstract).
12. Pittelkow et al.
Pittelkow et al. teach selective synthesis of carbamate protected polyamines using alkyl phenyl carbonates (see title). Furthermore, Pittelkow et al. disclose utilising alkyl phenyl carbonates, an economical, practical and versatile method for selective Boc, Cbz and Alloc protection of polyamines has been developed. This method allows Boc, Cbz and Alloc protection of primary amines in the presence of secondary amines by reaction of the polyamines with the alkyl phenyl carbonates. Also, this method allows mono carbamate protection of simple symmetrical aliphatic a,w-alkanediamines in high yields with respect to the diamine. Finally, the method allows selective carbamate protection of a primary amine located on a primary carbon in the presence of a primary amine located on a secondary or a tertiary carbon in excellent yields (see abstract).
Combination of Khan et al., Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Peng et al., Niu et al., and Carlmark et al.
Regarding instant claim 1, Khan et al., Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Peng et al., Niu et al., and Carlmark et al. teach a nanoparticle composition for delivery of a nucleic acid agent, comprising: a nucleic acid agent and a carrier. The necessary citations within Khan et al., Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Peng et al., Niu et al., and Carlmark et al. that correspond to instant claim 1 are compiled within Table I.
Table I
Instant Claim 1
Khan et al., Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Peng et al., Niu et al., and Carlmark et al. Citations
A nanoparticle composition for delivery of a nucleic acid agent, comprising:
Khan et al. disclose compositions and methods for modified dendrimer nanoparticle (“MDNP”) delivery of therapeutic, prophylactic and/or diagnostic agent such as large repRNA molecules (nucleic acids) to the cells of a subject have been developed (see title, abstract, and paragraph [0017] within Khan et al.)
Shalek et al. disclose delivery is by encapsulation of the programmable nucleic acid modifying agents in a lipid particle such as a lipid nanoparticle (LNP) (see paragraph [0498] within Shalek et al.). Although Shalek et al. does not disclose MDNPs, the reference does mesh very well with the nanoparticles of Khan et al., which therefore makes it analogous art.
a nucleic acid agent and a carrier, wherein the carrier comprises: a dendritic polymer skeleton, wherein the dendritic polymer skeleton further comprises:
Khan et al. disclose the use of a nucleic acid and a carrier dendritic skeleton (see title, abstract, and Figure 2A within Khan et al.).
Wu et al. disclose the use of the starting material PE-G1-Acetylene-OH en route to the desired dendritic polymer skeleton (see scheme 1, structure 2; within Wu et al.). Wu et al. additionally disclose that the key chemical transformation which allows simple and facile preparation of these dual-purpose, multifunctional materials is the copper(I)-catalyzed azide–alkyne cycloaddition, a premier ‘‘click’’ reaction (see page 5775, left column, paragraph 1 within Wu et al.).
Click chemistry is fundamental to dendrimer formation of the present application and is discussed within Wu et al., Lallana et al., Peng et al., and Carlmark et al.
The exact molecular structure of the desired dendrimer is not disclosed in the literature. However, the functional groups and polymeric groups are known, as well as the chemical transformations to incorporate the desired substituents. [Any alkyl or amine group could be installed]. The structure would thus be obvious to a skilled artisan (POSITA; person of ordinary skill in the art) based on routine synthetic organic chemistry.
one or more amines;
Carlmark et al. disclose the use of amine functional substituents to yield a carbamate (see scheme 4 within Carlmark et al.). Furthermore, Carlmark et al. disclose …dendritic structures can be divergently grown from any type of hydroxyl or amine group (see page 5866, left column, paragraph 2 within Carlmark et al.).
Peng et al. disclose the synthesis of terminal primary amines (see abstract within Peng et al.).
Niu et al. disclose the synthesis of terminal tertiary amines (see scheme 1, within Niu et al.).
Khan et al. disclose the use of primary amine surface groups (see paragraph [0075] within Khan et al.).
A skilled artisan (POSITA) could install most amines [primary, secondary, or tertiary; one or more] under routine experimental conditions.
one or more hydrophobic units comprising ricinoleic acid,
Guc et al. disclose a nano-sized dendrimer/ hyperbranched polymer (see abstract within Guc et al. Moreover, fatty acid-based drug carriers are expected to depict least toxicity, and they are mostly preferred for hydrophobic
drug delivery. These carriers have low viscosity,
low melting point, and relatively high flexibility. Therefore, they can be easily used for implantation and injection delivery. Ricinoleic acid is a type of fatty acid that is found in castor oil at high percentage (85-90%). Its double bond is at the ninth carbon, and it has a hydroxyl group at the 12th carbon. It is the only commercially available fatty acid with two functional groups, one is
acid and the other is alcohol (see page 1139, right column, 2nd paragraph; also see Figure 1 within Guc et al.).
Wu et al., Lallana et al., Peng et al., and Carlmark et al. all disclose “click chemistry” with the functional groups, azide and acetylene.
Wu et al. uses the starting material PE-G1-Acetylene-OH which incorporates the hydrophobic branched alkyl group H2C-CH(CH3)-CH2 (see scheme 1, structure 2; within Wu et al.).
A skilled artisan (POSITA) could install most alkyl groups or hydrophobic groups under routine experimental conditions.
a first moiety covalently connected to the dendritic skeleton, wherein the first moiety is selected from a group consisting of a PEG moiety and a PEG moiety alternative, wherein the first moiety comprises a weight of 100 Daltons to 750 Daltons.
PEG groups have been used by many authors within dendrimers including Lallana et al. (see page 903, page 905-906, pages 908, 909, 911, 913-917 within Lallana et al.), Peng et al. (see page 104 within Peng et al.), and Carlmark et al. (see pages 5866, 5868-5869, 5871, 5873-5875 within Carlmark et al.).
As cited within Applicant’s Remarks many of the PEG groups have a molecular weight greater than 1000 Daltons.
However, Mehta et al. disclose the use of a PEG chain length (570 Da) for enhanced bioactivity (see title, abstract, and page 4574, right column “In summary”; all within Mehta et al.). Therefore, illustrating the importance of using PEG moieties less than 750 Daltons.
The combination of the Khan et al., Shalek et al., Wu et al., Mehta et al., Lallana et al., Peng et al., Niu et al., and Carlmark et al. references make instant claim 1 obvious to a skilled artisan (POSITA).
[The remainder of the instant claims are either directly or indirectly dependent on instant claim 1, which is taught in full by the combination of Khan et al., Shalek et al., Wu et al., Mehta et al., Lallana et al., Peng et al., Niu et al., and Carlmark et al.]
Regarding instant claims 2-3 and 25-26, Khan et al., Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Peng et al., Niu et al., and Carlmark et al. teach wherein the nucleic acid agent is composed at least in part of at least one type of ribonucleic acid or deoxyribonucleic acid. Khan et al. disclose the nucleic acids included in the nanoparticles (miRNA, siRNA, dsRNA, and cDNA) (see paragraphs [0019], [0053], and [0127] within Khan et al.)
Regarding instant claims 4 and 5, Khan et al., Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Peng et al., Niu et al., and Carlmark et al. teach wherein the amine comprises a secondary or tertiary amine. Please see the citations and discussion within Table I (especially regarding the amine subunit).
The chemical transformations to incorporate a secondary or tertiary amine are well-known in medicinal chemistry. Almost any commercially available or synthetically designed amine group could be installed. The overall reaction scheme would thus be obvious to a skilled artisan (POSITA). This would not require inventive skill.
Regarding instant claims 6-9, Khan et al., Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Peng et al., Niu et al., and Carlmark et al. teach wherein the hydrophobic unit comprises an alkyl chain of 1 to 28 carbon atoms or an alkenyl chain comprising 2 to 28 carbon atoms. Please see the citations and discussion within Table I (especially regarding the hydrophobic subunit). Additionally, Niu et al. disclose the intermediates G0, G1, and G2 which all have a terminal alkene comprising three carbon atoms.
The chemical transformations to incorporate an alkyl or alkenyl chain are well-known in medicinal chemistry. Almost any commercially available or synthetically designed alkyl or alkenyl group could be installed. The overall reaction scheme would thus be obvious to a skilled artisan (POSITA). This would not require inventive skill.
Regarding instant claims 11 and 24, Khan et al., Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Peng et al., Niu et al., and Carlmark et al. teach wherein the first moiety comprises a length of 1 monomer to 15 monomer units. Please see the citations and discussion within Table I (especially regarding the PEG subunit) for the necessary rejection citations.
Regarding instant claims 13-16, Khan et al., Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Peng et al., Niu et al., and Carlmark et al. teach further comprising a polymer-lipid conjugate such as a PEG-lipid conjugate. Khan et al. disclose that the MDNPs include hydrophililic-hydrophobic polymers such as PEG-lipid conjugates which are biocompatible, non-immunogenic and are non-toxic (see paragraph [0096] within Khan et al.). Furthermore, Khan et al. disclose that an exemplary lipid-anchored mPEG (methoxy terminated) is a 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (see paragraph [0098] within Khan et al.). Finally, Shalek et al. disclose two examples where the PEG-lipid is 10 mol percent and 1.5 mol percent, respectively (see paragraph [0580] within Shalek et al.). These percentages supplied by Shalek et al. are standard within the art. Thus, a skilled artisan (POSITA) would integrate this limitation.
Regarding instant claims 17-20, Khan et al., Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Peng et al., Niu et al., and Carlmark et al. teach further comprising an amphipathic lipid such as a phospholipid. Khan et al. disclose that one type of hydrophobic component which is well adapted to association within a hydrophobic or lipidic bilayer is a phospholipid such as…1,2-dioleolylglyceryl phosphatidylethanolamine (DOPE) (see paragraph [0098] within Khan et al.). Additionally, Shalek et al. disclose that phospholipids are defined as helper lipids (see paragraph [0525] within Shalek et al.) and can range from 20 to 80 mol percent (see paragraph [0527] within Shalek et al.). This percentage range supplied by Shalek et al. are standard within the art. Thus, a skilled artisan (POSITA) would integrate this limitation.
Regarding instant claims 21 and 22, Khan et al., Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Peng et al., Niu et al., and Carlmark et al. teach , further comprising cholesterol or a derivative thereof. Khan et al. disclose that one type of hydrophobic component which is well adapted toto association within a hydrophobic or lipidic bilayer is …cholesterol (see paragraph [0098] within Khan et al.). Additionally, Shalek et al. disclose that steroids such as cholesterol are defined as helper lipids (see paragraph [0525] within Shalek et al.) and can range from 20 to 80 mol percent (see paragraph [0527] within Shalek et al.). This percentage range supplied by Shalek et al. are standard within the art. Thus, a skilled artisan (POSITA) would integrate this limitation.
Regarding instant claim 23, Khan et al., Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Peng et al., Niu et al., and Carlmark et al. teach a method of managing disease, the method comprising: administering a therapeutically effective amount of a nanoparticle composition to a subject, wherein the nanoparticle composition comprises: a nucleic acid agent and a nucleic acid carrier, wherein the carrier comprises: a dendritic-polymer skeleton; an amine; and a hydrophobic unit, wherein: the dendritic-polymer skeleton comprises a PEG moiety; and the amine connects the hydrophobic unit to the dendritic-polymer skeleton. Please see the citations and discussion within Table I for synthesizing the MDNP composition. Khan et al. disclose the administration of their MDNPs (see paragraphs [0208-0218] within Khan et al.). Therefore, a skilled artisan (POSITA) would ascertain this instant method claim.
Regarding instant claim 27, Khan et al., Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Peng et al., Niu et al., and Carlmark et al. teach wherein the nucleic acid agent is present in a concentration in the range of about 0.01 mg to about 10 mg of nucleic acid agent per kg body weight of the subject. Khan et al. disclose that generally dosage levels of between 0.001 and 100 mg/kg of body weight daily are administered to subjects such as mammals, most preferably, humans. Generally, for intravenous injection or infusion, dosage may be lower. Preferably, the compositions are formulated to achieve a modified prokaryotic cell serum level of between about 1 and about 1000 M (see paragraph [0307] within Khan et al.).
Combination of Khan et al., Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Nigavekar et al., Peng et al., Niu et al., and Carlmark et al.
Regarding instant claim 12, Khan et al., Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Nigavekar et al., Peng et al., Niu et al., and Carlmark et al. teach wherein the carrier further comprises a functional group suitable for tracking the carrier. Nigavekar et al. disclose the synthesis of tritium-labeled dendrimers using 3H labeled acetic anhydride (see page 479, left column, Results and Figure 1 within Nigavekar et al.). In addition, radioactive labeling of dendrimers by 3H-containing acetic anhydride allowed proper and accurate quantification of the modified dendrimer derivatives for the true in vivo biodistribution as a function of time (see page 479, left column, Results within Nigavekar et al.). Therefore, allowing Nigavekar et al. to successfully track the material.
Combination of Khan et al., Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Peng et al., Niu et al., Carlmark et al., Gillies et al., and Pittelkow et al.
Regarding instant claims 28-34, Khan et al., Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Peng et al., Niu et al., Carlmark et al., Gillies et al., and Pittelkow et al. teach the dendritic polymer skeleton:
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with the correct substituents as defined within the instant claim limitations. “Click-chemistry” involves the reaction of an azide and an acetylene (see Table I within Carlmark et al.). Both the azide and acetylene reactants would be afforded synthetically from the Gillies et al. and Pittelkow et al. disclosures. As a synthetic example, the Examiner will focus on the acetylene portion. Starting from commercially available acetylene:
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A skilled artisan (POSITA) can convert this to the 4-nitrophenyl carbamate intermediate, and then form the desired amide (see Scheme 4 within Gillies et al.). The amide in question could be any commercially available or synthetic amine (see Schemes 1-3 and Table I within Pittelkow et al.). In a similar fashion, the azide portion could be synthesized to afford the desired reactant for “click-chemistry.” None of the synthetic steps are challenging and would be routine for a skilled artisan (POSITA). The review by Carlmark et al. gives routine experimental examples of “click-chemistry” (see pages 5862-5863, II. Accelerated approaches of homofunctional dendrimers, within Carlmark et al.). The dendrimer skeleton structure within instant claim 30 would be realized through the chemistry outlined above and use of commercially available PEG-azides (see PTO-892 NPL W).
In the context of instant method claims 23-27, the desired purpose defines an effect that arises from, and is implicit in the method step(s). Thus, where the purpose is limited to stating a technical effect that inevitably occurs during the performance of the claimed method step(s), and is therefore inherent in that/those step(s), that technical effect is not limiting to the subject-matter of the claim. Thus, the present method claim, defining the application/use of the composition according to claims 1-22 and defining its purpose as "use", is anticipated by any document of the state of the art describing a method of application/use although not mentioning this specific use.
Analogous Art
The Khan et al., Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Nigavekar et al., Peng et al., Niu et al., Carlmark et al., Gillies et al., and Pittelkow et al. references are all applicable to the endeavor of the instant application. Therefore, these teachings make the references relevant to instant claims 1-9 and 11-34.
Obviousness
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the MDNP delivery of a nucleic acid disclosed by Khan et al. using the teachings of Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Nigavekar et al., Peng et al., Niu et al., Carlmark et al., Gillies et al., and Pittelkow et al. to incorporate the necessary claim limitations. Starting with Khan et al., the skilled person only had to try the necessary claim limitations disclosed by Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Nigavekar et al., Peng et al., Niu et al., Carlmark et al., Gillies et al., and Pittelkow et al. The combination of Khan et al., Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Nigavekar et al., Peng et al., Niu et al., Carlmark et al., Gillies et al., and Pittelkow et al. would allow one to arrive at the present application without employing inventive skill. This combination of the MDNP delivery of a nucleic acid taught by Khan et al. along with the use of the necessary claim limitations taught by Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Nigavekar et al., Peng et al., Niu et al., Carlmark et al., Gillies et al., and Pittelkow et al. would allow a research and development scientist (POSITA) to develop the invention taught in the instant application. It would have only required routine experimentation to modify the MDNP delivery of a nucleic acid disclosed by Khan et al. with the use of the necessary claim limitations taught by Shalek et al., Wu et al., Guc et al., Mehta et al., Lallana et al., Nigavekar et al., Peng et al., Niu et al., Carlmark et al., Gillies et al., and Pittelkow et al. This combined modification would have led to an enhanced MDNP delivery of a nucleic acid that would be beneficial for patients.
Response to Arguments
Applicant's arguments filed August 13, 2026 have been fully considered but they are not persuasive.
The claim objection was determined to be an artifact that does not require further corrective action. Therefore, the claim objection is withdrawn from the Non-Final office action dated February 13, 2026.
The new instant claims did necessitate a new ground of rejection.
Applicant Argument: The Applicant argues that the art of record does not address the claim limitation, “one or more hydrophobic units comprising ricinoleic acid;”
Examiner’s Rebuttal: The argument is now moot. The Examiner has added the Guc et al. reference to address this new limitation in full.
Thus, the 35 U.S.C. §103 rejection for instant claims 1-9 and 11-34 is maintained.
Conclusion
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.
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/JOHN W LIPPERT III/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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