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 .
Formal Matters
Applicant’s claim amendments and arguments in the reply filed on 19 November 2025 are acknowledged and have been fully considered. Claims 1-4 and 6-18 are pending. Claims 1-4, 6-9, and 16-18 are under consideration in the instant office action. Claims 10-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claims. Claim 5 is canceled. Applicant’s claim amendments and arguments necessitated a new ground of rejections under 35 USC 103 as set forth below. Accordingly, this office action is made final.
Withdrawn Objections/Rejections
Rejections and/or objections not reiterated from the previous office actions are hereby withdrawn as are those rejections and/or objections expressly stated to be withdrawn.
Moot Arguments
Applicant’s arguments with respect to claim(s) 1-4, 6-9, and 16-18 have been considered but are moot because the new ground of rejection as set forth below.
New Ground of rejections-Necessitated by Amendments
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.
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 nonobviousness.
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 1-4, 6-8, and 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Cheng et al. (Adv. Sci. 2020, 7, 1903301, First Published on February 05, 2020, previously cited) in view of Fang et al. (Nano Letters, 14(4), 2181-21-88, 2014, newly cited) and as evidenced by Cespedes et al. (The FEBS Journal 288 (2021) 1070–1090).
Note: Cespedes et al. is incorporated in the rejection to prove that biological cell membranes are formed by lipid bilayers. Cespedes et al. disclose that from the structural point of view, biological membranes are formed by lipid bilayers (LBs) arranged as asymmetric, semipermeable, and dynamic structures. These features of the LB are defined in part by its comprising phospholipids, which interact with the environment through their hydrophilic, polar headgroups while maintaining a hydrophobic core of acyl chains. The high heterogeneity of phospholipid species leads to their asymmetric distribution both laterally and between the inner and outer leaflet of the bilayer. This spatial and compositional asymmetry helps define the physical and mechanical properties of the membrane and correlates with the specific functions of a given organelle and cell type (see page 1071).
Applicant Claims
Applicant claims a dendritic cell-mimicked nanostructure comprising a nanoparticle core; and a shell including a cell membrane of lipid molecules derived from dendritic cells, wherein the shell includes a double layer of lipid molecules, wherein the dendritic cell-mimicked nanostructure is fabricated by fusing liposomes prepared by sonicating the cell membrane of lipid molecules derived from dendritic cells and the nanoparticle core, wherein the dendritic cell-mimicked nanostructure has a nanoparticle-to-cell membrane surface area ratio (XDM) in the range of 0.9 to 1.3. and wherein XDM represents the ratio of the surface area of the cell membrane to that of the nanoparticle core. Dependent claims thereof recite other features.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
Cheng et al. teach that ovarian cancer is the most lethal gynecological malignancy with high recurrence rates and low survival rates, remaining a disease of high unmet need. Cancer immunotherapy, which harnesses the potential of the immune system to attack tumors, has emerged as one of the most promising treatment options in recent years. As an important form of immunotherapy, dendritic cell (DC)–based vaccines have demonstrated the ability to induce an immune response, while clinical efficacy of DC vaccines remains unsubstantiated as long-term benefit is only reported in a restricted proportion of patients. Here, a biomimetic nanovaccine derived from DCs is developed through cell membrane coating nanotechnology. This nanovaccine, denoted “mini DC,” inherits the ability of antigen presentation and T cells’ stimulation from DCs and is shown to elicit enhanced activation of T cells both in vitro and in vivo. In a mouse model of ovarian cancer, mini DCs exhibit superior therapeutic and prophylactic efficacy against cancer including delayed tumor growth and reduced tumor metastasis compared with DC vaccine. These findings suggest that mini DCs may serve as a facile and potent vaccine to boost anti-cancer immunotherapy (see abstract). More recently, cell membrane coating nanotechnology has gained much attention as it offers a feasible way to modify nanoparticles with natural cell membranes. Through a simple process of extrusion, cell membranes can be readily fused onto synthetic polymeric cores. These nanoparticles obtain some unique properties of donor cells, enabling them to exert donor cells’ function without limitations of cellular structure, size, and viability. One of the most promising examples is the nanoparticles coated with erythrocyte membranes (RBC-NPs), acting as decoys to absorb pathological pore- forming toxins and detain auto-antibodies (see introduction page 2). Inspired by the aforementioned biomimetic method, we have developed dendritic cell–like nanoparticles (denoted “mini DC”) through coating cell membranes extracted from ovarian cancer cell lysate-primed DCs onto interleukin-2 (IL-2)-loaded biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles using an extrusion approach. By presenting DCs’ functional plasma membrane proteins (such as MHC, CD86, and CD40) on its surface, mini DC is expected to mimic DCs’ antigen presentation ability and releases IL-2 in a paracrine manner, thus activating T cells and provoking robust anti- tumor immune response without being affected by immuno- suppressive TAM and physiological barrier during migration and antigen presentation (Figure 1). Furthermore, the feasible storage condition and long shelf-life offer better clinical maneuverability compared with DC vaccines. Here we demonstrate that the administration of nanoparticulated mini DC can induce systemic immune responses through its specific interaction with T cells and efficiently inhibit growth and metastasis of ovarian cancer, suggesting its potential as a robust and safe strategy for cancer immunotherapy (see introduction page 2).
To fabricate mini DC, bone marrow–derived dendritic cells (BMDCs) were pulsed with homogenized ID8 murine ovarian tumor cell lysate after HOCl oxidation as reported in previous studies. Trypan blue staining showed that HOCl-oxidized tumor cells had a cell viability of 0%, and homogenization could effectively enhance the uptake of tumor cell lysate by BMDC (Figure S1, Supporting Information). Then the membranes of primed BMDC were isolated and extruded with PLGA polymeric cores, which were synthesized using a double emulsion method (Figure 2A). As one of important cytokines involving in the expansion and differentiation of T cells, IL-2 was loaded into the PLGA nanoparticle (PLGA-NP) during the synthesis process. Transmission electron microscopy (TEM) imaging after uranyl acetate negative staining showed that PLGA-NP was fully encapsulated into DCs’ membrane and the resulting nanoparticles, mini DC, possessed a core–shell structure with a diameter of about 160–170 nm (Figure 2B; Figure S2, Supporting Information). Dynamic light scattering also revealed that mini DC gained an increase of approximately 20 nm, which is consistent with the thickness of double layers of cell membrane, in hydrodynamic diameter compared with the bare PLGA-NP (Figure 2C; Figure S3A, Supporting Information). The examiner notes that the gain of 20 nm is equivalent to the thickness of the coating or shell. The surface zeta potential of mini DC decreased from -14 to -22 mV, similar to that of DCs’ membrane-derived vesicle (BMDC vesicle), also indicating that the PLGA-NP had been wrapped in natural BMDC membranes successfully (Figure 2D; Figure S3B, Supporting Information) (see results and discussion section 2.1 on page 2).
With regard to the limitations of claims 7 and 18 in addition to the teachings of Cheng et al., the claims are written in product-by-process format. "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted) (Claim was directed to a novolac color developer. The process of making the developer was allowed. The difference between the inventive process and the prior art was the addition of metal oxide and carboxylic acid as separate ingredients instead of adding the more expensive pre-reacted metal carboxylate. The product-by-process claim was rejected because the end product, in both the prior art and the allowed process, ends up containing metal carboxylate. The fact that the metal carboxylate is not directly added, but is instead produced in-situ does not change the end product.). Furthermore, "[b]ecause validity is determined based on the requirements of patentability, a patent is invalid if a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes." Amgen Inc. v. F. Hoffmann-La Roche Ltd., 580 F.3d 1340, 1370 n. 14, 92 USPQ2d 1289, 1312, n. 14 (Fed. Cir. 2009). See also Biogen MA Inc. v. EMD Serono, Inc., 976 F.3d 1326, 1334, 2020 USPQ2d 11129 (Fed. Cir. 2020) ("Biogen is certainly correct that the scope of composition and method of treatment claims is generally subject to distinctly different analyses. But where, as here, the novelty of the method of administration rests wholly on the novelty of the composition administered, which in turn rests on the novelty of the source limitation, the Amgen analysis will necessarily result in the same conclusion on anticipation for both forms of claims."); United Therapeutics Corp. v Liquidia Techs., Inc., 74 F.4th 1360, 1373, 2023 USPQ2d 862 (Fed. Cir. 2023) (the court held that product-by-process claims were properly rejected as "anticipated by a disclosure of the same product irrespective of the processes by which they are made."); and Purdue Pharma v. Epic Pharma, 811 F.3d 1345, 117 USPQ2d 1733 (Fed. Cir. 2016). However, in the context of an infringement analysis, a product-by-process claim is only infringed by a product made by the process recited in the claim. Id. at 1370 ("a product in the prior art made by a different process can anticipate a product-by-process claim, but an accused product made by a different process cannot infringe a product-by-process claim").
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.012)
Cheng et al. do not specifically teach wherein the dendritic cell-mimicked nanostructure has a nanoparticle-to-cell membrane surface area ratio (XDM) in the range of 0.9 to 1.3. This deficiency is cured by the teachings of Fang et al.
Fang et al. teach a biomimetic nanostructure comprising a nanoparticle core (PLGA which is polymeric nanoparticle) a shell including a cell membrane of lipid molecules (plasma membrane derived forming a double layer lipid bilayer shell 7-10 nm thick, right side out orientation) derived from source cells. The shell is fabricated by preparing membrane vesicles (via hypotonic lysis plus mechanical disruption/sonication/extrusion of cell membranes into liposomes /vesicles) and fusing them with the nanoparticle core (co extrusion or sonication fusion). This produces core shell structures with consistent membrane coating (see page 2182).
Regarding the XDM ratio (nanoparticle to membrane surface area ratio of cell membrane to NP core) of 0.9-1.3, noting the claim wording appears to define XDM as membrane to core surface area, Fang et al. teach In order to optimize the membrane coating, CCNPs were synthesized at membrane-to-core weight ratios ranging from 0.125 to 4 mg of membrane protein per 1 mg of PLGA particles (Figure 4a). At lower membrane-to-core ratios, a significant increase in the hydrodynamic diameter was observed when the particles were transferred to 1× PBS. This suggested incomplete coverage, which exposes the surfaces of the cores to charge screening, (24) resulting in low stability in ionic buffers. This effect was even more pronounced after 15 days of storage, as samples with membrane coverage lower than 0.25 mg of protein per 1 mg of PLGA aggregated significantly. The lowest membrane-to-core ratio at which the particles maintained size stability over time was around 1 mg of protein per 1 mg of PLGA. At this ratio, there was minimal size increase throughout the 15 days of observation (Figure 4b). To further test for the long-term storage capacity of the CCNPs, the particles were lyophilized in 5 wt % sucrose solution (Supporting Information Figure S1). Upon reconstitution in water, the particles exhibited a hydrodynamic size consistent with that prior to freeze-drying (see page 2183-2184).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the instant invention to modify the teachings of Cheng et al. by preparing wherein the dendritic cell-mimicked nanostructure has a nanoparticle-to-cell membrane surface area ratio (XDM) in the range of 0.9 to 1.3 because Fang et al. teach a biomimetic nanostructure comprising a nanoparticle core (PLGA which is polymeric nanoparticle) a shell including a cell membrane of lipid molecules (plasma membrane derived forming a double layer lipid bilayer shell 7-10 nm thick, right side out orientation) derived from source cells. The shell is fabricated by preparing membrane vesicles (via hypotonic lysis plus mechanical disruption/sonication/extrusion of cell membranes into liposomes /vesicles) and fusing them with the nanoparticle core (co extrusion or sonication fusion). This produces core shell structures with consistent membrane coating (see page 2182). Regarding the XDM ratio (nanoparticle to membrane surface area ratio of cell membrane to NP core) of 0.9-1.3. One of ordinary skill in the art would have been motivated to do so because noting the claim wording appears to define XDM as membrane to core surface area, Fang et al. teach in order to optimize the membrane coating, CCNPs were synthesized at membrane-to-core weight ratios ranging from 0.125 to 4 mg of membrane protein per 1 mg of PLGA particles (Figure 4a). At lower membrane-to-core ratios, a significant increase in the hydrodynamic diameter was observed when the particles were transferred to 1× PBS. This suggested incomplete coverage, which exposes the surfaces of the cores to charge screening, (24) resulting in low stability in ionic buffers. This effect was even more pronounced after 15 days of storage, as samples with membrane coverage lower than 0.25 mg of protein per 1 mg of PLGA aggregated significantly. The lowest membrane-to-core ratio at which the particles maintained size stability over time was around 1 mg of protein per 1 mg of PLGA. At this ratio, there was minimal size increase throughout the 15 days of observation (Figure 4b). To further test for the long-term storage capacity of the CCNPs, the particles were lyophilized in 5 wt % sucrose solution (Supporting Information Figure S1). Upon reconstitution in water, the particles exhibited a hydrodynamic size consistent with that prior to freeze-drying (see page 2183-2184). In the case where the claimed ratio "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). Furthermore, differences in measurable parameters will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233,235 (CCPA 1955). One of ordinary skill in the art would have had a reasonable chance of success in combining the teachings of Cheng et al. and Fang et al. because both references teach cell membrane mimicking nanostructures containing nanoparticles.
In light of the forgoing discussion, one of ordinary skill in the art would have concluded that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cheng et al. (Adv. Sci. 2020, 7, 1903301, First Published on February 05, 2020, previously cited) in view of Fang et al. (Nano Letters, 14(4), 2181-21-88, 2014, newly cited) and as evidenced by Cespedes et al. (The FEBS Journal 288 (2021) 1070–1090) as applied to claims 1-4, 6-8, and 16-18 above, and further in view of Liu et al. (NATURE COMMUNICATIONS, 2019 Jul 19;10(1):3199, IDS reference, previously cited).
Note: Cespedes et al. is incorporated in the rejection to prove that biological cell membranes are formed by lipid bilayers. Cespedes et al. disclose that from the structural point of view, biological membranes are formed by lipid bilayers (LBs) arranged as asymmetric, semipermeable, and dynamic structures. These features of the LB are defined in part by its comprising phospholipids, which interact with the environment through their hydrophilic, polar headgroups while maintaining a hydrophobic core of acyl chains. The high heterogeneity of phospholipid species leads to their asymmetric distribution both laterally and between the inner and outer leaflet of the bilayer. This spatial and compositional asymmetry helps define the physical and mechanical properties of the membrane and correlates with the specific functions of a given organelle and cell type (see page 1071).
Applicant Claims
Applicant claims a dendritic cell-mimicked nanostructure comprising a nanoparticle core; and a shell including a cell membrane of lipid molecules derived from dendritic cells, wherein the shell includes a double layer of lipid molecules. Dependent claims thereof recite other features.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
The teachings of Cheng et al. and Fang et al. are described above in detail and are incorporated by reference herein.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.012)
Cheng et al. and Fang et al. do not specifically teach wherein the surface zeta potential of the nanostructure is - 35 to - 25 mV as recited in claim 9. This deficiency is cured by the teachings of Liu et al.
Liu et al. teach most cancer vaccines are unsuccessful in eliciting clinically relevant effects. Without using exogenous antigens and adoptive cells, we show a concept of utilizing biologically reprogrammed cytomembranes of the fused cells (FCs) derived from dendritic cells (DCs) and cancer cells as tumor vaccines. The fusion of immunologically interrelated two types of cells results in strong expression of the whole tumor antigen complexes and the immunological co-stimulatory molecules on cytomembranes (FMs), allowing the nanoparticle-supported FM (NP@FM) to function like antigen presenting cells (APCs) for T cell immunoactivation. Moreover, tumor-antigen bearing NP@FM can be bio-recognized by DCs to induce DC- mediated T cell immunoactivation. The combination of these two immunoactivation path- ways offers powerful antitumor immunoresponse. Through mimicking both APCs and cancer cells, this cytomembrane vaccine strategy can develop various vaccines toward multiple tumor types and provide chances for accommodating diverse functions originating from the supporters (see abstract). Liu et al. teach in Fig. 2 (g) Zeta potentials of MOF, MOF@CM, MOF@DM and MOF@FM. Measurements were taken from distinct samples (n = 3). Source data are provided as a Source Data file
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The examiner notes that the surface zeta potential of the cell membrane coated nanoparticles range -34 and -25 mV as shown above. Liu et al. teach on page 3 that PCN-224 MOF, a fluorescent NP, was used here for imaging purpose. MOF@FM was prepared by cloaking MOF with FMs under ultrasound in ice bath. The nanoscale morphology of MOFs and MOF@FMs was clearly observable by scanning electron microscopy (SEM) (Fig. 2e). Transmission electron microscopy (TEM) reflects the core-shell structure of MOF@FM with a uniform cell membrane shell at about 10 nm in thickness (Fig. 2f). The uncloaked MOFs had a mean hydrodynamic diameter (Dh) at about 145.6 nm with a narrow size distribution (Supplementary Fig. 3) and a positive charge potential (ζ) at 24.5 mV (Fig. 2g). Coating FM to MOF surface led to a subtle increase of Dh and a charge reversal of ζ potential. These findings manifest the successful coating of FM on MOF supporter. As the controls, the 4T1 cell membrane coated MOF@CM and the DC membrane coated MOF@DM were prepared in the same manner. Both of them showed similar Dh and ζ with MOF@FM. Of note, Dh of MOF@FM in the medium containing 10% serum remained steady over 7 days, as contrary to the marked increase of Dh observed for uncoated MOFs (Supplementary Fig. 4).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the instant invention to prepare nanostructures with surface zeta potential of the nanostructure being - 35 to - 25 mV because Liu et al. teach most cancer vaccines are unsuccessful in eliciting clinically relevant effects. Without using exogenous antigens and adoptive cells, we show a concept of utilizing biologically reprogrammed cytomembranes of the fused cells (FCs) derived from dendritic cells (DCs) and cancer cells as tumor vaccines. The fusion of immunologically interrelated two types of cells results in strong expression of the whole tumor antigen complexes and the immunological co-stimulatory molecules on cytomembranes (FMs), allowing the nanoparticle-supported FM (NP@FM) to function like antigen presenting cells (APCs) for T cell immune activation. Moreover, tumor-antigen bearing NP@FM can be bio-recognized by DCs to induce DC- mediated T cell immune activation. The combination of these two immune activation path- ways offers powerful antitumor immune response. Through mimicking both APCs and cancer cells, this cytomembrane vaccine strategy can develop various vaccines toward multiple tumor types and provide chances for accommodating diverse functions originating from the supporters (see abstract). Liu et al. teach in Fig. 2 (g) Zeta potentials of MOF, MOF@CM, MOF@DM and MOF@FM. Measurements were taken from distinct samples (n = 3). Source data are provided as a Source Data file
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The examiner notes that the surface zeta potential of the cell membrane coated nanoparticles range -34 and -25 mV as shown above. Liu et al. teach on page 3 that PCN-224 MOF, a fluorescent NP, was used here for imaging purpose. MOF@FM was prepared by cloaking MOF with FMs under ultrasound in ice bath. The nanoscale morphology of MOFs and MOF@FMs was clearly observable by scanning electron microscopy (SEM) (Fig. 2e). Transmission electron microscopy (TEM) reflects the core-shell structure of MOF@FM with a uniform cell membrane shell at about 10 nm in thickness (Fig. 2f). The uncloaked MOFs had a mean hydrodynamic diameter (Dh) at about 145.6 nm with a narrow size distribution (Supplementary Fig. 3) and a positive charge potential (ζ) at 24.5 mV (Fig. 2g). One of ordinary skill in the art would have been motivated to do so because Liu et al. teach that coating FM to MOF surface led to a subtle increase of Dh and a charge reversal of ζ potential. These findings manifest the successful coating of FM on MOF supporter. As the controls, the 4T1 cell membrane coated MOF@CM and the DC membrane coated MOF@DM were prepared in the same manner. Both of them showed similar Dh and ζ with MOF@FM. Of note, Dh of MOF@FM in the medium containing 10% serum remained steady over 7 days, as contrary to the marked increase of Dh observed for uncoated MOFs (Supplementary Fig. 4). In the case where the claimed particle sizes, surface zeta potentials, etc. "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). Furthermore, differences in measurable parameters will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233,235 (CCPA 1955). One of ordinary skill in the art would have had a reasonable chance of success in combining the teachings of Cheng et al., Fang et al., and Liu et al. because all of the references teach cell membrane mimicking nanostructures containing nanoparticles.
In light of the forgoing discussion, one of ordinary skill in the art would have concluded that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments to the extent thy apply to the current rejection
Applicant argues as shown in additional Fig. 1, T-cell activation increases sharply when XDM exceeds 0.5, reaching maximum activity around XDM ≈ 1. In contrast, when XDM approaches 2, the activation decreases again. This trend is illustrated as a line graph in Additional Fig. 2. As shown in Additional Fig. 2, T-cell activation reaches its highest level at XDM= 1, and activation levels of ≥ 60% of the maximum are observed at XDM = 0.9 (within the 0.5-1 range) and XDM = 1.3 (within the 1-2 range). These values define a critical XDM range (0.9-1.3) that is fully supported by the detailed description of the present invention. The significant enhancement of T-cell activation within this critical XDM range is a non-obvious technical effect that could not have been predicted by a person skilled in the art based on the prior art.
The above assertions are not found persuasive because Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (Claims were directed to a process for removing corrosion at "elevated temperatures" using a certain ion exchange resin (with the exception of claim 8 which recited a temperature in excess of 100°C). Appellant demonstrated unexpected results via comparative tests with the prior art ion exchange resin at 110°C and 130°C. The court affirmed the rejection of claims 1-7 and 9-10 because the term "elevated temperatures" encompassed temperatures as low as 60°C where the prior art ion exchange resin was known to perform well. The rejection of claim 8, directed to a temperature in excess of 100°C, was reversed.). See also In re Peterson, 315 F.3d 1325, 1329-31, 65 USPQ2d 1379, 1382-85 (Fed. Cir. 2003) (data showing improved alloy strength with the addition of 2% rhenium did not evidence unexpected results for the entire claimed range of about 1-3% rhenium); In re Grasselli, 713 F.2d 731, 741, 218 USPQ 769, 777 (Fed. Cir. 1983) (Claims were directed to certain catalysts containing an alkali metal. Evidence presented to rebut an obviousness rejection compared catalysts containing sodium with the prior art. The court held this evidence insufficient to rebut the prima facie case because experiments limited to sodium were not commensurate in scope with the claims.). The examples are drawn to a specific nanoparticle with a specific liposome making the membrane at specific amounts for the nanoparticle and the liposome based membrane resulting in the XDM values as recited in claim 1. Claim 1 is applicable to any dendritic cell derived membrane and any type of nanoparticle at any amount. The data is not commensurate in scope with the claims.
Conclusions
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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/TIGABU KASSA/
Primary Examiner, Art Unit 1619
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