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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 2/26/2026 has been entered.
Claims 1, 3-13, 17, 18, 26, 30-34 are pending and under consideration.
The rejection of claims 1, 6-12, 17, 18, 26, 30, 31, 33, and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Au et al (ACS Central Science, Published 12/26/2018, Vol, 5, pp. 122-144, reference of the IDS submitted 7/21/2022) in view of Davis et al (Seminars in Immunology, 2017, Vol. 31, pp. 64-75) and Smits et al (Expert Opinion on Biological Therapy, 2016, Vol. 16, 1105-1112) is withdrawn in light of applicant’s arguments pointing out that Smits teaches against the combination of CD16 and 4-1BB targeting agents and applicant’s unexpected results regarding nanoparticles combining both of CD16 targeting agents and 4-1BB targeting agents. It is noted that the specification teaches the requirement for targeting the nanoparticles (page 33).
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, 3-13, 17, 18, 26, 30-34 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.
The instant claims are reliant on a generic “nanoparticle” comprising a first two targeting agents binding 4-1BB and either CD16 or CD27, and a second targeting agent that binds a target on a cancer cell surface. The specification teaches unexpected results in that “nanoparticles” containing both CD16 and 4-1BB activating agents result in significantly higher NK cell cytotoxicity than the nanoparticles containing only CD16 and only 4-1BB activating agents (page 34, lines 23-30).
When given the broadest reasonably interpretation “nanoparticles” comprise a genus of particles with different shapes and surface chemistries. Nanoparticles comprising the targeting agents encompass a genus of structures which serve to link or anchor the targeting agents to the surface of the nanoparticle. The specification states:
Types of particles of this invention include, but are not limited to, polymer nanoparticles such as PLGA-based, PLA-based, polysaccharide-based (dextran, cyclodextrin, chitosan, heparin), dendrimer, hydrogel; lipid-based nanoparticles such as lipid nanoparticles, lipid hybrid nanoparticles, liposomes, micelles; inorganics-based nanoparticles such as superparamagnetic iron oxide nanoparticles, metal nanoparticles, platin nanoparticles, calcium phosphate nanoparticles, quantum dots; carbon-based nanoparticles such as fullerenes, carbon nanotubes; and protein-based complexes with nanoscales. Types of microparticles of this invention include but are not limited to particles with sizes at micrometer scale that are polymer microparticles including but not limited to, PLGA-based, PLA-based, polysaccharide-based (dextran, cyclodextrin, chitosan, heparin), dendrimer, hydrogel; lipid-based microparticles such as lipid microparticles, micelles; inorganics-based microparticles such as superparamagnetic iron oxide microparticles, platin microparticles and the like as are known in the art. These particles may be generated and/or have materials be absorbed, encapsulated, or chemically bound through known mechanisms in the art, such as those described in Au et al. 2019 ACS Cent. Sci. 5(1):122-144 and Au et al. 2018 ACS Nano 12(2):1544-1563.
The specification states:
Design of multivalent EGFR-targeted nanoengagers for NK cell-mediated chemoimmunotherapy: Multivalent non-targeted and EGFR-targeted α-CD16- and α-4-1BB-functionalized drug-free and EPI-encapsulated PEG-PLGA NPs (EPI NPs) were engineered via a two-step fabrication method (FIGS. 1B, 1C, 2, and 3; Table 1). The core azide-functionalized drug-free and EPI-encapsulated NPs were first prepared via the nanoprecipitation method (Au et al. 2019 ACS Cent. Sci. 5(1):122-144). Dibenzocyclooctyne (DBCO)-functionalized α-CD16, α-4-1BB, and α-EGFR were then quantitatively conjugated to the azide-functionalized NPs via copper-free azide-cyclooctyne cycloaddition (Au et al. 2018 ACS Nano 12(2):1544-1563). A 1:1 α-CD16 to α-4-1BB molar ratio and a 1:1:1 α-CD16 to α-4-1BB to α-EGFR molar ratio were used for the fabrication of bivalent and trivalent NPs. The EPI NPs were encapsulated with approximately 2.7 wt/wt % of EPI (FIG. 1D).
The specification teaches spatiotemporal co-activation of CD16 and 4-1BB co-stimulatory molecules on NK cells by the nanoparticles prepared by the above method (Figures 7 and 8). The specification provides no evidence that generic nanoparticles, such as those contemplated in the specification, having the targeting agents linked or associated with the nanoparticles by any means at any density, would provide the spatiotemporal co-activation of CD16 and 4-1BB co-stimulatory molecules on NK cells responsible for the superior result.
Section 2163 of the M.P.E.P. states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a “representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention.
In the instant case, the trivalent nanoparticles prepared by the methods of Au et al exhibited the increased cytotoxicity attributed to “increased cooperative binding” and more effective clustering to the CD16 and 4-1BB co-stimulatory molecules (page 34, lines 25-27). The functionalized nanoparticles produced by the methods of Au et al do not describe a genus of generic nanoparticles, because the genus is highly variant encompassing different shaped particles in a range of “nano” sizes” having different surface chemistry, having different means for linking the activating agents to the surface and different densities of the activating agents. One of skill in the art could not envisage any other nanoparticle bearing the activating CD16 and 4-1BB agents which would result in increase cooperative binding of the activating agents and more effective clustering of the CD16 and 4-1BB co-stimulatory molecules. One of skill in the art would reasonably conclude that applicant was not in possession of the genus of generic nanoparticles comprising the targeting agent of 4-1BB, the targeting agent of CD16 or CD27 and a targeting agent that binds to a cancer cell at the time of filing.
All other rejections are withdrawn in light of applicant’s arguments.
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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643