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 14 August 2026 are acknowledged and have been fully considered. Claims 1-24 are pending. Claims 1-6 are under consideration in the instant office action. Claims 7-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant’s claim amendments and arguments necessitated a new ground of rejections. 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Withdrawn Objections/Rejections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withdrawn as are those rejections and/or objections expressly stated to be withdrawn.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) 1-6 have been considered but are moot because the new ground of rejection set forth below.
New 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.
Claims 1 and 4–5 are rejected under 35 U.S.C. § 103 as being unpatentable over Sikima et al. (US 2009/0269284 A1, previously cited) in view of Ding et al., (Chem. Mater. 2012, 24, 4572–4580, newly cited), Jang, (J. Korean Chem. Soc. 2012, 56, 478–483, newly cited), and Baig et al. (US 2010/0150848 A1, newly cited).
Applicants’ claims
Applicants claim a magnetoelectric nanoparticle composition comprising the components as recited. Dependent claims thereof recite additional features.
Determination of the Scope and Content of the Prior Art
(MPEP 2141.01)
Sikima teaches magnetic core–shell nanoparticles for biomedical use comprising a CoFe₂O₄ core and a silica (SiO₂ / SiOₓ) shell, with surface groups for covalent conjugation of functional moieties. Core: CoFe₂O₄ nanoparticles of about 7 nm (std. dev. ≤10%), tunable 7–20 nm by surfactant concentration and seed-mediated growth, paragraphs [0015], [0051], [0114], [0116], [0156], [0158]; Fig. 2a. Overall nanoparticle diameter: approximately 5–50 nm paragraph[0051]. Shell: silica formed by base-catalyzed hydrolysis of TEOS in a water-in-oil reverse microemulsion (Igepal CO-520 / cyclohexane / NH₄OH), paragraphs [0115], [0157]. Exemplified shell about 10 nm, “tunable from 10 to 50 nm by varying the TEOS concentration.” Paragraphs [0116], [0158]; Fig. 2c, Fig. 5. Surface: hydroxyls on the silica shell converted with APTES or MPTMS (silanization) to amine or thiol for covalent attachment of T₁ agents, peptides, PEG spacers, and targeting ligands (antibodies, peptides, sugars, etc.) paragraphs [0086]–[0089], [0115], [0117], [0160]–[0161]. Examiner notes EDC/sulfo-NHS coupling. Applications include localization to diseased/cancer cells and delivery of biomolecules paragraphs [0086]–[0087].Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP 2141.02)
Sikima therefore teaches every structural element of claim 1 except (i) a silica shell as thin as about 0.5–2.5 nm and (ii) express recitation of fused silica. Sikima exemplifies a silica shell of about 10 nm (range 10–50 nm) and does not use the words “fused silica.” Ding and Jang supply ultrathin silica shells of about 1.0 ± 0.5 nm (within about 0.5–2.5 nm) on closely related ferrite cores by the same TEOS reverse-microemulsion method. Baig supplies fused silica as a known grade of amorphous SiO₂.
Ding teaches reverse-microemulsion silica-coating regulations for magnetic ferrite nanoparticles (Fe₃O₄) to obtain single-core @SiO₂ particles with controlled shell thickness, including ultrathin shells. Abstract; pp. 4572–4573. “The small aqueous domain is suitable to coat ultrathin silica shell, while the large aqueous domain is indispensable for coating thicker shells.” Abstract; p. 4573. Matching the number of magnetic cores to the aqueous domain avoids core-free silica and permits different core sizes (Abstract). Shell thickness is a result-effective variable of TEOS amount, ammonia, water-to-surfactant ratio, and core concentration—the same levers Sikima already uses. pp. 4574–4578.
Jang teaches Fe₃O₄/SiO₂ core/shell nanoparticles with an ultrathin silica layer of 1.0 ± 0.5 nm, “fine controlled by changing concentration of Fe₃O₄,” using reverse microemulsion / TEOS chemistry. Abstract; pp. 478–479, 483. Jang states that prior reverse-microemulsion silica shells were typically 10–70 nm, and that raising magnetic-core concentration is more effective than W/S-ratio control for reaching ~1 nm. Abstract; p. 479. Jang expressly says the approach “could be available to apply on preparation of other core/shell nanoparticles with ultrathin silica layer.” Abstract; p. 483.
Baig teaches that fused silica is high-purity amorphous silicon dioxide (also called fused quartz, vitreous silica, silica glass). ¶ [0051]. Fused silica has low BET surface area, low porosity, and a low number of surface hydroxyl groups, and is less reactive than precipitated silica, so it adsorbs less of other components and improves availability/stability of those components. ¶ [0058].Differences (MPEP 2141.02)
Finding of Prima Facie Obviousness Rational and Motivation
(MPEP 2142-2143)
It would have been prima facie obvious before the effective filing date to modify Sikima’s CoFe₂O₄@SiO₂ particles by reducing silica-shell thickness into the about 0.5–2.5 nm range, and to select fused silica as the silica grade. One of ordinary skill in the art would have been motivated to do so because Sikima already teaches that shell thickness is controlled by TEOS amount paragraphs [0115]–[0116], [0157]–[0158]. Ding teaches that the same reverse-microemulsion process produces an ultrathin silica shell when the aqueous domain is small and core number is matched to that domain. Jang demonstrates an actual 1.0 ± 0.5 nm silica shell on a ferrite core and states the method applies to other core/shell nanoparticles. One of ordinary skill in the art would thin Sikima’s shell to retain more of the CoFe₂O₄ magnetic moment (Ding and Jang both discuss magnetic-property dependence on shell thickness), improve colloidal stability of small cores, and leave surface silanols available for conjugation—all goals already present in Sikima paragraphs [0051], [0116]. One of ordinary skill additionally would have been motivated to do so because Sikima’s shell is amorphous SiO₂ from TEOS. Baig teaches fused silica as high-purity amorphous SiO₂ that is less reactive and improves availability of co-formulated or surface-bound species paragraphs [0051], [0058]. Selecting a known material for its known properties is obvious. Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327 (1945). One of ordinary skill in the art would have had a reasonable chance of success because Sikima, Ding, and Jang use Igepal/TEOS/ammonia reverse microemulsion on ferrite nanocrystals. CoFe₂O₄ and Fe₃O₄ are both spinel ferrites coated by the identical sol-gel chemistry. Jang’s 1.0 ± 0.5 nm result is inside the claimed 0.5–2.5 nm range. Regarding the diameter recitations of claims 4–5 Sikima’s core is about 7 nm (tunable 7–20 nm) and overall particles about 5–50 nm paragraphs [0051], [0116]. With an ultrathin 0.5–2.5 nm shell, overall diameter is about 8–12 nm for a 7 nm core—inside both 1–18 nm and 4–8 nm when smaller cores within Sikima’s 7 nm / “approximately 5 nm” teaching are used. Where claimed sizes “overlap or lie inside ranges disclosed by the prior art,” a prima facie case exists. In re Wertheim, 541 F.2d 257 (CCPA 1976); In re Woodruff, 919 F.2d 1575 (Fed. Cir. 1990). Optimizing a result-effective size parameter is routine. In re Aller, 220 F.2d 454 (CCPA 1955). Sikima covalently attaches peptides, Gd-chelates, PEG, and targeting ligands to the silanized silica shell paragraphs [0086]–[0089], [0160]. “Therapeutic agents” in claim 1 are not limited to chemotherapeutics (that is claim 2). Sikima’s conjugated functional moieties meet the limitation. Accordingly, claims 1 and 4–5 would have been obvious.
In light of the forgoing discussion, the Examiner concludes 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) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sikima et al. (US 2009/0269284 A1, previously cited) in view of Ding et al., (Chem. Mater. 2012, 24, 4572–4580, newly cited), Jang, (J. Korean Chem. Soc. 2012, 56, 478–483, newly cited), and Baig et al. (US 2010/0150848 A1, newly cited) as applied to claims 1 and 4-5 above, and further in view of Nasiri et al. (Journal of the Chinese Chemical Society 65(2), 231-242, 2018, abstract only provided, previously provided).
Applicants’ claims
Applicants claim a magnetoelectric nanoparticle composition comprising the components as recited. Claim 3 recites the composition of claim 1, further comprising a polyethylene glycol (PEG)-linked folate or folic acid molecule covalently conjugated to the fused silica shell.
Determination of the Scope and Content of the Prior Art
(MPEP 2141.01)
The teachings of Sikima, Ding, Jang, and Baig are described above in detail and are incorporated herein by reference.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP 2141.02)
Sikima, Ding, Jang, and Baig do not specifically teach wherein the composition further comprising a polyethylene glycol (PEG)-linked folate or folic acid molecule covalently conjugated to the fused silica shell. It should be noticed that Sikima teach attaching PEG linkers to the silica coating surface to be able to couple active agents and targeting moieties. This deficiency is cured by the teachings of Nasir et al.
Nasir et al. teach a stable and biocompatible targeting complex CFNs@PEG-FA is developed. The initially synthesized cobalt ferrite nanoparticles (CFNs) were treated with poly(ethylene glycol) (PEG) in order to improve biocompatibility of the CFNs. Citric acid (CA) was used as the coupling agent, which made PEG to bond with the CFNs. CFNs@PEG were conjugated with folic acid (FA) to synthesize CFNs@PEG-FA, which was capable of targeting the FA receptor positive (FAR+) cancer cells. Synthesized nanoparticles were physically and chemically analyzed using EDX, FT-IR, XRD, TGA, FESEM, TEM, DLS, and VSM. The biocompatibility of CFNs@PEG-FA was assessed in vitro on HSF 1184 (human skin fibroblast cells) and HeLa (human cervical cancer cell, FAR+) using MTT assay and AO/EB staining florescence method. High level of CFNs@PEG-FA binding to HeLa was confirmed through quantitative and qualitative in vitro targeting studies. Results show that CFNs@PEG-FA can be a potential biomaterial for use in biomedical trials, especially magnetic hyperthermia. The findings through this in vitro study are to be compared in future with those of in vivo studies.
Finding of Prima Facie Obviousness Rational 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 Sikima, Ding, Jang, and Baig by incorporating a polyethylene glycol (PEG)-linked folate or folic acid molecule covalently conjugated to the fused silica shell because Nasir et al. teach a stable and biocompatible targeting complex CFNs@PEG-FA is developed. The initially synthesized cobalt ferrite nanoparticles (CFNs) were treated with poly(ethylene glycol) (PEG) in order to improve biocompatibility of the CFNs. Citric acid (CA) was used as the coupling agent, which made PEG to bond with the CFNs. CFNs@PEG were conjugated with folic acid (FA) to synthesize CFNs@PEG-FA, which was capable of targeting the FA receptor positive (FAR+) cancer cells. Synthesized nanoparticles were physically and chemically analyzed using EDX, FT-IR, XRD, TGA, FESEM, TEM, DLS, and VSM. The biocompatibility of CFNs@PEG-FA was assessed in vitro on HSF 1184 (human skin fibroblast cells) and HeLa (human cervical cancer cell, FAR+) using MTT assay and AO/EB staining florescence method. High level of CFNs@PEG-FA binding to HeLa was confirmed through quantitative and qualitative in vitro targeting studies. One of ordinary skill in the art would have been motivated to do so because Nasir et al. teach that results show that CFNs@PEG-FA can be a potential biomaterial for use in biomedical trials, especially magnetic hyperthermia. The findings through this in vitro study are to be compared in future with those of in vivo studies. One of ordinary skill in the art would have had a reasonable chance of success in combining the teachings of Sikima, Ding, Jang, Baig, and Nasir et al. because all of the references are drawn to the delivery of biomaterials for biomedical applications.
In light of the forgoing discussion, the Examiner concludes 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) 2 and 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sikima et al. (US 2009/0269284 A1, previously cited) in view of Ding et al., (Chem. Mater. 2012, 24, 4572–4580, newly cited), Jang, (J. Korean Chem. Soc. 2012, 56, 478–483, newly cited), and Baig et al. (US 2010/0150848 A1, newly cited) as applied to claims 1 and 4-5 above, and further in view of Mohapatra et al. (J. Mater. Chem., 2011, 21, 9185-9193, previously cited).
Applicants’ claims
Applicants claim a magnetoelectric nanoparticle composition comprising the components as recited. Claim 2 recites the composition of claim 1, wherein the one or more therapeutic agents comprise one or more chemotherapeutic drugs comprising doxorubicin or diphyllin. Claim 6 recites the composition of claim 1, wherein the one or more therapeutic agents are covalently conjugated to the fused silica shell through silanization with a succinic acid anhydride moiety on the fused silica shell.
Determination of the Scope and Content of the Prior Art
(MPEP 2141.01)
The teachings of Sikima, Ding, Jang, Baig, are described above in detail and are incorporated herein by reference.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP 2141.02)
Sikima, Ding, Jang, and Baig do not specifically teach wherein the one or more therapeutic agents are covalently conjugated to the fused silica shell through silanization with a succinic acid anhydride moiety on the fused silica shell and the therapeutic agent is doxorubicin. These deficiencies are cured by the teachings of Mohapatra et al.
Mohapatra et al. teach a multifunctional folic acid decorated superparamagnetic mesoporous CoFe2O4 based nanocarrier with the particle size of 35–40 nm was synthesized by a simple method. The particles show excellent aqueous dispersion stability in physiological pH without any deterioration in hydrodynamic size and zetapotential. The cytotoxicity and internalization efficiency of these nanocarriers have been evaluated on folate receptor overexpressed HeLa cells (see page 9185). Amine functionalized superparamagnetic CoFe2O4 nano particles were prepared by thermal decomposition of CoCl2.6H2O and FeCl3 in ethylene glycol in presence of sodium acetate and ethanol amine. Briefly, anhydrous FeCl3 (0.683 g, 4.2 mmol) and CoCl2.6H2O (0.576 g, 2.1 mmol) were taken in 30 mL ethylene glycol and 0.5 gm of sodium acetate was added to it. The reddish black color solution thus obtained was stirred for 30 min at 80 C followed by addition of 15 mL of ethanol amine. The entire solution was allowed to reflux for 6h during which fine black colloidal particles appeared in the reaction mixture. Then it was cooled down to room temperature. The CoFe2O4 particles were recovered using a magnetic separator (DynaMag2, Invitrogen) washed with millipore water (5 5 mL) and dried in hot air oven at 80 ºC for 2h (see Preparation of CoFe2O4-NH2 nanoparticles page 9186). 100 mg of amine functionalized CoFe2O4 nanoparticles were dispersed in 5mL of water. To a stirred solution of EDC (18 mg, 0.09 mmol)in5mLofH2O,NHS(41mg,0.35mmol)wasadded. To the resulting solution, alkaline solution of folic acid (13 mg, 0.031 mmol) in 5 mL of H2O was added followed by addition of 100 mg amine functionalized CoFe2O4 nanoparticles dispersed in 5mLH2O.Theentiresolutionwasstirredinthe darkfor12hand the particles were separated magnetically, washed thoroughly with (3 5mL) millipore H2O and dispersed in 5 mL H2O (CoFe2O4-FA). To this dispersion RITC (100 mg in 1mL DMSO/ H2O) was added. The resulting suspension was sonicated for 1 h in the dark. Particles were recovered by magnetic separation and washed thoroughly with millipore water (CoFe2O4-FA-RITC) (see Synthesis of folate decorated fluorescent magnetic carriers page 9186). Fluorescent molecule RITC and antitumor agents such as methotrexate and doxorubicin were successfully attached to the surface amine groups following simple organic coupling reactions thus endowing the nanoparticle with therapeutic and optical properties. These drug loaded nanoagents exhibit elevated cytotoxicity and induce apoptosis in HeLa cells. To load DOX, the amine functionalized magnetic nanoparticles (CoFe2O4-FA) were converted to acid terminated particles through ring opening reaction with succinic anhydride in the presence of DMAP. For this purpose, 10 ml aqueous dispersion (0.1 mg mL1) of nanoparticles were washed thoroughly with millipore water and then dispersed in 5 mL of methanol. In a 100 mL round bottom flask, succinic anhydride (0.05g, 0.5 mmol) and DMAP (0.06g, 0.5 mmol) were taken in 15mL methanol followed by addition of CoFe2O4nanoparticles. The total mixture was refluxed for 24 h at 80 C (CoFe2O4-FA COOH). The particles were recovered, washed thoroughly with methanol (5 5 mL), dried at 80 C. 5 mL of aqueous solution containing NHS (41 mg, 0.358 mMol) and EDC (18 mg, 0.0938 mmol) was taken in a 50 ml of round bottom flask and was kept in the dark for 2 h. After that the aqueous solution of DOX (74 mg in 12 mL water, molar ratio FA:DOXz1:5) was added to the above solution followed by addition of CoFe2O4 FA-COOH nanoparticles. The resulting suspension was stirred at room temperature for overnight and the particles (CoFe2O4 FA-DOX) were isolated magnetically. In order to study release behavior, 5 ml suspension of CoFe2O4-FA-DOX particles (0.1 mg mL1) was suspended in a solution containing 0.1mg ml 1 protease from bovine pancreas and 5 ml of PBS (0.1 mg ml 1). The solution pH was adjusted to 3, 5 and 7.4 using 0.1 M HCl and NaOH. Subsequent to incubation for 5, 10, 20, 25h, at 37 C, the nanoparticles were isolated magnetically and the recovered DOX in the supernatant was quantified spectro photometrically in UV spectrophotometer (lmax ¼ 255 nm).
Finding of Prima Facie Obviousness Rational 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 Sikima, Ding, Jang, and Baig by incorporating wherein the one or more therapeutic agents are covalently conjugated to the fused silica shell through silanization with a succinic acid anhydride moiety on the fused silica shell and the therapeutic agent is doxorubicin because first Sikima et al. teach the silanization processes while preparing the silica coating with the formation of available functional groups for further coupling with therapeutic agents on the surface of the silica coating. Furthermore, Mohapatra et al. teach a multifunctional folic acid decorated superparamagnetic mesoporous CoFe2O4 based nanocarrier with the particle size of 35–40 nm was synthesized by a simple method. The particles show excellent aqueous dispersion stability in physiological pH without any deterioration in hydrodynamic size and zetapotential. The cytotoxicity and internalization efficiency of these nanocarriers have been evaluated on folate receptor overexpressed HeLa cells (see page 9185). One of ordinary skill in the art would have been motivated to link the active doxorubicin via a succinic anhydride linker because Mohapatra et al. teach that amine functionalized superparamagnetic CoFe2O4 nano particles were prepared by thermal decomposition of CoCl2.6H2O and FeCl3 in ethylene glycol in presence of sodium acetate and ethanol amine. Briefly, anhydrous FeCl3 (0.683 g, 4.2 mmol) and CoCl2.6H2O (0.576 g, 2.1 mmol) were taken in 30 mL ethylene glycol and 0.5 gm of sodium acetate was added to it. The reddish black color solution thus obtained was stirred for 30 min at 80 C followed by addition of 15 mL of ethanol amine. The entire solution was allowed to reflux for 6h during which fine black colloidal particles appeared in the reaction mixture. Then it was cooled down to room temperature. The CoFe2O4 particles were recovered using a magnetic separator (DynaMag2, Invitrogen) washed with millipore water (5 5 mL) and dried in hot air oven at 80 ºC for 2h (see Preparation of CoFe2O4-NH2 nanoparticles page 9186). 100 mg of amine functionalized CoFe2O4 nanoparticles were dispersed in 5mL of water. To a stirred solution of EDC (18 mg, 0.09 mmol)in5mLofH2O,NHS(41mg,0.35mmol)wasadded. To the resulting solution, alkaline solution of folic acid (13 mg, 0.031 mmol) in 5 mL of H2O was added followed by addition of 100 mg amine functionalized CoFe2O4 nanoparticles dispersed in 5mLH2O.Theentiresolutionwasstirredinthe darkfor12hand the particles were separated magnetically, washed thoroughly with (3 5mL) millipore H2O and dispersed in 5 mL H2O (CoFe2O4-FA). To this dispersion RITC (100 mg in 1mL DMSO/ H2O) was added. The resulting suspension was sonicated for 1 h in the dark. Particles were recovered by magnetic separation and washed thoroughly with millipore water (CoFe2O4-FA-RITC) (see Synthesis of folate decorated fluorescent magnetic carriers page 9186). Fluorescent molecule RITC and antitumor agents such as methotrexate and doxorubicin were successfully attached to the surface amine groups following simple organic coupling reactions thus endowing the nanoparticle with therapeutic and optical properties. These drug loaded nanoagents exhibit elevated cytotoxicity and induce apoptosis in HeLa cells. To load DOX, the amine functionalized magnetic nanoparticles (CoFe2O4-FA) were converted to acid terminated particles through ring opening reaction with succinic anhydride in the presence of DMAP. For this purpose, 10 ml aqueous dispersion (0.1 mg mL1) of nanoparticles were washed thoroughly with millipore water and then dispersed in 5 mL of methanol. In a 100 mL round bottom flask, succinic anhydride (0.05g, 0.5 mmol) and DMAP (0.06g, 0.5 mmol) were taken in 15mL methanol followed by addition of CoFe2O4nanoparticles. The total mixture was refluxed for 24 h at 80 C (CoFe2O4-FA COOH). The particles were recovered, washed thoroughly with methanol (5 5 mL), dried at 80 C. 5 mL of aqueous solution containing NHS (41 mg, 0.358 mMol) and EDC (18 mg, 0.0938 mmol) was taken in a 50 ml of round bottom flask and was kept in the dark for 2 h. After that the aqueous solution of DOX (74 mg in 12 mL water, molar ratio FA:DOXz1:5) was added to the above solution followed by addition of CoFe2O4 FA-COOH nanoparticles. The resulting suspension was stirred at room temperature for overnight and the particles (CoFe2O4 FA-DOX) were isolated magnetically. In order to study release behavior, 5 ml suspension of CoFe2O4-FA-DOX particles (0.1 mg mL1) was suspended in a solution containing 0.1mg ml 1 protease from bovine pancreas and 5 ml of PBS (0.1 mg ml 1). The solution pH was adjusted to 3, 5 and 7.4 using 0.1 M HCl and NaOH. Subsequent to incubation for 5, 10, 20, 25h, at 37 C, the nanoparticles were isolated magnetically and the recovered DOX in the supernatant was quantified spectro photometrically in UV spectrophotometer (lmax ¼ 255 nm). One of ordinary skill in the art would have had a reasonable chance of success in combining the teachings of Sikima, Ding, Jang, Baig, and Mohapatra et al. because all of the references are drawn to the delivery of biomaterials for biomedical applications.
In light of the forgoing discussion, the Examiner concludes 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.
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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/TIGABU KASSA/Primary Examiner, Art Unit 1619