DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I and species of an amphiphilic polymer is present, the amphiphilic polymer does not contain a polyethylene glycol (PEG) lipid, and the amphiphilic polymer having a structure of
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(n is 22) in the reply filed on June 15, 2026 and a telephone call with Tanyu Wang on July 15, 2026 is acknowledged.
Drawings
The drawings are objected to because at least one drawing submitted in file is in color without granted petition to accept color drawings.
Appropriate correction is required.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Specification
The disclosure is objected to because of the following informalities:
On pages 3, 4, 19, 20, 55, 56, 65, and 66, Formulas I and II contain “R’’’” but the specification does not define the variables that “R’’’” may represent. Instead, the specification defines the variables for “R’’”, which is not shown in Formulas I and II. It is suggested that Formulas I and II be amended to replace “R’’’” with “R’’” to obviate this objection.
Claim Rejections - 35 USC § 112 Indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3 and 10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 3, Formula I contains “R’’’” but the claim does not define the variables that “R’’’” may represent. Instead, the claim defines the variables for “R’’”, which is not shown in Formula I. It is suggested that Formula I be amended to replace “R’’’” with “R’’” to obviate this rejection.
Regarding claim 10, the claim recites the limitation “the IONRs.” The claim lacks an antecedent basis for this limitation, as “IONRs” is not previously recited in the claims. Note that “coated IONRs” is previously recited in the claims. It is suggested that claim 10 be amended to “the coated IONRs” to obviate this rejection.
Clarification and/or amendment is required.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-2, and 5-7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mohapatra et al. (Nanoscale, 2015; cited on IDS filed July 10, 2024; Supplementary information cited on PTO-892).
Note: In conducting a search on applicant’s elected species, prior art was found that reads on applicant’s broader claim(s). Thus, this prior art has been cited herein for purposes of compact prosecution.
This is not indicative that a search of the entire scope of the instant claims has been conducted.
Regarding claim 1, Mohapatra discloses iron oxide nanorods (IONRs) encapsulated (coated) with polyethyleneimine as efficient magnetic resonance imaging (MRI) contrast agents (abstract). Mohapatra discloses that the iron oxide magnetization (magnetic moment) can be different depending on size and shape, and that the IONRs can have a magnetic moment of at least about 40 emu/g at room temperature at 10 kOe (1 T magnetizing field strength), similar to saturation magnetization at 40 kOe (page 9179, column 2, ¶1; page 9180, Fig, 5 (c)).
Regarding claim 2, Mohapatra discloses that the IONRs can have a length of 30–70 nm and a diameter of 4–12 nm (abstract).
Regarding claim 5, the IONRs can be Fe3O4 nanorods (abstract).
Regarding claim 6, Mohapatra discloses that the hydrodynamic diameter can be different depending on the size and shape, and that the hydrodynamic size of the coated IONRs can be between 71-105 nm (Supplementary information Fig. S6 and Table S2).
Regarding claim 7, Mohapatra discloses that the coated IONRs can be dispersed in deionized water as colloidal suspension and that the coated IONRs can be very stable as water colloids for about a month without aggregation or precipitation (page 9175, column 2, ¶ 3; page 9179, column 1, ¶1; page 9179, Fig. 4 (b) and (c)). It can be expected that the coated IONRs can be disperse in an aqueous medium for at least 30 mins at room temperature.
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 1-3, and 5-8 are rejected under 35 U.S.C. 103 as being unpatentable over Mohapatra et al. (Nanoscale, 2015; cited on IDS filed July 10, 2024; Supplementary information cited on PTO-892) in view of Mao et al. (US 10,393,736, 2019; cited on IDS filed July 10, 2024).
As discussed above, regarding claim 1, Mohapatra discloses iron oxide nanorods (IONRs) encapsulated (coated) with polyethyleneimine as efficient magnetic resonance imaging (MRI) contrast agents (abstract). Mohapatra discloses that the iron oxide magnetization (magnetic moment) can be different depending on size and shape, and that the IONRs can have a magnetic moment of at least about 40 emu/g at room temperature at 10 kOe (1 T magnetizing field strength), similar to saturation magnetization at 40 kOe (page 9179, column 2, ¶1; page 9180, Fig, 5 (c)). Regarding claim 2, Mohapatra discloses that the IONRs can have a length of 30–70 nm and a diameter of 4–12 nm (abstract). Regarding claim 5, the IONRs can be Fe3O4 nanorods (abstract). Regarding claim 6, Mohapatra discloses that the hydrodynamic diameter can be different depending on the size and shape, and that the hydrodynamic size of the coated IONRs can be between 71-105 nm (Supplementary information Fig. S6 and Table S2). Regarding claim 7, Mohapatra discloses that the coated IONRs can be dispersed in deionized water as colloidal suspension and that the coated IONRs can be very stable as water colloids for about a month without aggregation or precipitation (page 9175, column 2, ¶ 3; page 9179, column 1, ¶1; page 9179, Fig. 4 (b) and (c)). It can be expected that the coated IONRs can be disperse in an aqueous medium for at least 30 mins at room temperature.
Mohapatra does not disclose that the coating comprises one or more amphiphilic polymer such as
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(n is 22) (instant claims 1 and 3). Mohapatra does not disclose a pharmaceutical composition (instant claim 8).
Mao discloses iron oxide nanoparticles (IONPs) coated with amphiphilic diblcok polymer, PEG-b-AGE (allyl glycidyl ether) copolymer (column 11, ¶ 4). Mao discloses that the polymer can minimize non-specific adsorption (anti-fouling property) (column 1, ¶¶ 5-7) and that the polymer can have a structure of
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(n can be 22 and R can be methyl or siloxane connecting point to the surface of the particle) (claims 2 and 9). The polymers of Mao and instant claims share a common structure except for the length of the alkyl linkers. The polymer of Mao contains a single propyl chain on either side of the sulfur atom, whereas the polymer of instant claims contains three repeating propyl units each, which merely increase the length of the linker portion. Regarding claim 8, Mao discloses pharmaceutical compositions comprising the particles and a pharmaceutically acceptable excipient (column 26, ¶ 4).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify IONRs of Mohapatra by replacing polyethyleneimine with the amphiphilic polymer of Mao in order to prepare coated IONRs with better fouling resistance. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Mao teaches that the amphiphilic polymer such as PEG-b-AGE can be used for coating IONPs. Further, a person of ordinary skill in the art would have been motivated to utilize an amphiphilic polymer for coating nanoparticles in order to prepare more stable, non-toxic, and versatile nanoparticles. Regarding the difference in the length of the alkyl linker, a person of ordinary skill in the art would have been motivated to adjust the length of linker as a routine design choice in order to optimize the stability, flexibility, and hydrophobicity of the linker portion. Compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties (MPEP 2144.09). Additionally, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare pharmaceutical compositions comprising the coated IONRs of Mohapatra and a pharmaceutically acceptable excipient taught by Mao to prepare more stable, effective pharmaceutical compositions for pharmaceutical applications. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Mao teaches pharmaceutical compositions comprising the particles and a pharmaceutically acceptable excipient. Accordingly, applying the teachings of Mao to the coated IONRs of Mohapatra constitutes no more than the predictable use of prior art elements according to their established functions and therefore renders instant claims obvious.
Claims 9 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Mohapatra and Mao as applied to claims 1-3 and 5-8 above, and further in view of Liu et al. (Lab on a Chip, 2020; cited on PTO-892).
Mohapatra is discussed above.
In addition to the teachings of Mao discussed above, Mao discloses a kit comprising the coated IONPs (column 28, ¶¶ 4-5).
Neither Mohapatra nor Mao discloses that a device comprises one or more deified regions(s) or well(s) and that each defined region or well contains one or more of the coated IONRs.
Liu discloses acoustofluidic multi-well plates for controllable enrichment of nanoscale object such as magnetic nanoparticles (abstract; page 3404, column 2, ¶ 2). Liu discloses that the nanoparticles in each well of the plate can be enriched, and that this simple, compatible plate system can be a versatile tool for many applications such as biomedical sensing (abstract).
It would have been obvious to a person of ordinary skill in the art before the effective
filing date of the claimed invention to utilize the multi-well plate of Liu as a device for the kit of Mohapatra and Mao in order to accurately controlled the coated IONRs in each well. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Liu teaches that the multi-well plate system can be used for controlled enrichment of nanoparticles. Further, a person of ordinary skill in the art would have been motivated to utilize the multi-well plate system for high-throughput screening applications. Accordingly, applying the teachings of Liu to the kit comprising coated IONRs of Mohapatra and Mao constitutes no more than the predictable use of prior art elements according to their established functions, thus rendering instant claims obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3 and 5-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. US 9,737,492 (cited on PTO-892) in view of Mohapatra et al. (Nanoscale, 2015; cited on IDS filed July 10, 2024; Supplementary information cited on PTO-892), Mao et al. (US 10,393,736, 2019; cited on IDS filed July 10, 2024), and Liu et al. (Lab on a Chip, 2020; cited on PTO-892).
Regarding claim 1, claim 1 of the ‘492 recites a pharmaceutical composition comprising a particle and an inner coating comprising an amphiphilic polymer. Claim 2 of the ‘492 recites that the particle can an iron oxide nanoparticle. Claims of the ‘492 do not recite that the iron oxide core has a magnetic moment of at least 10 emu/g, induced using 1 T magnetizing field strength, at room temperature. As discussed above, Mohapatra discloses that the iron oxide magnetization (magnetic moment) can be different depending on size and shape, and that the IONRs can have a magnetic moment of at least about 40 emu/g at room temperature at 10 kOe (1 T magnetizing field strength), similar to saturation magnetization at 40 kOe (page 9179, column 2, ¶1; page 9180, Fig, 5 (c)). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of the ‘492 by configuring the IONRs to have a magnetic moment of at least about 40 emu/g at room temperature at 10 kOe. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Mohapatra teaches that the IONRs can exhibit such a magnetic moment. Further, a person of ordinary skill in the art would have been motivated to optimize the magnetic moment according to the specific requirements of the applications by adjusting the size and shape of the IONRs, as taught by Mohapatra.
Regarding claim 2, claims of the ‘492 do not recite that the iron oxide core has a length in a range from about 20 nm to about 250 nm and a diameter in a range from about 2 nm to about 50 nm. As discussed above, Mohapatra discloses that the IONRs can have a length of 30–70 nm and a diameter of 4–12 nm (abstract). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of the ‘492 by configuring the iron oxide core to have a length of 30–70 nm and a diameter of 4–12 nm. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Mohapatra teaches that the IONRs can have such length and diameter. Further, a person of ordinary skill in the art would have been motivated to optimize the length and diameter of the iron oxide core according to the specific requirements of the applications. The size of iron oxide core is a clearly result-effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal size of the iron oxide core for achieving the desired characteristics of the IONRs.
Regarding claim 3, claims of the ‘492 do not recite the coating comprise one or more amphiphilic polymer such as
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(n is 22). As discussed above, Mao discloses iron oxide nanoparticles (IONPs) coated with amphiphilic diblcok polymer, PEG-b-AGE (allyl glycidyl ether) copolymer (column 11, ¶ 4). Mao discloses that the polymer can minimize non-specific adsorption (anti-fouling property) (column 1, ¶¶ 5-7) and that the polymer can have a structure of
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(n can be 22 and R can be methyl or siloxane connecting point to the surface of the particle) (claims 2 and 9). The polymers of Mao and instant claims share a common structure except for the length of the alkyl linkers. The polymer of Mao contains a single propyl chain on either side of the sulfur atom, whereas the polymer of instant claims contains three repeating propyl units each, which merely increase the length of the linker portion. Regarding claim 8, Mao discloses pharmaceutical compositions comprising the particles and a pharmaceutically acceptable excipient (column 26, ¶ 4). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the amphiphilic polymer of Mao as a coating material of the coated IONRs of the ‘492 in order to prepare coated IONRs with better fouling resistance. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Mao teaches that the amphiphilic polymer such as PEG-b-AGE can be used for coating IONPs. Further, a person of ordinary skill in the art would have been motivated to utilize an amphiphilic polymer for coating nanoparticles in order to prepare more stable, non-toxic, and versatile nanoparticles. Regarding the difference in the length of the alkyl linker, a person of ordinary skill in the art would have been motivated to adjust the length of linker as a routine design choice in order to optimize the stability, flexibility, and hydrophobicity of the linker portion. Compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties (MPEP 2144.09).
Regarding claim 5, claims of the ‘492 do not recite that the iron oxide core comprises Fe3O4 magnetite or a combination of Fe3O4 magnetite and FeO(OH) goethite. As discussed above, Mohapatra discloses that the IONRs can be Fe3O4 nanorods (abstract). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use Fe3O4 as the iron oxide core of the ‘492. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Mohapatra teaches that the Fe3O4 nanorods can be used as iron oxide core. Further, a person of ordinary skill in the art would have been motivated to utilize Fe3O4 as an iron oxide in order to achieve strong ferrimagnetism which allows for easy magnetic separation.
Regarding claim 6, claims of the ‘492 do not recite specific ranges in a hydrodynamic length or a zeta potential. As discussed above, Mohapatra discloses that the hydrodynamic diameter can be different depending on the size and shape, and that the hydrodynamic size of the coated IONRs can be between 71-105 nm (Supplementary information Fig. S6 and Table S2). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of the ‘492 by configuring the IONRs to have a hydrodynamic size between 71-105 nm. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Mohapatra teaches that the coated IONRs can have such a hydrodynamic length. Further, a person of ordinary skill in the art would have been motivated to optimize the hydrodynamic size of the coated IONRs according to the specific requirements of the applications. The hydrodynamic size of the coated IONRs is a clearly result-effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal hydrodynamic size of the coated IONRs for achieving the desired characteristics of the coated IONRs.
Regarding claim 7, claims of the ‘492 do not recite a dispersion time or a separation efficiency. As discussed above, Mohapatra discloses that the coated IONRs can be dispersed in deionized water as colloidal suspension and that the coated IONRs can be very stable as water colloids for about a month without aggregation or precipitation (page 9175, column 2, ¶ 3; page 9179, column 1, ¶1; page 9179, Fig. 4 (b) and (c)). It can be expected that the coated IONRs can be disperse in an aqueous medium for at least 30 mins at room temperature. It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of the ‘492 by configuring the IONRs to be disperse in an aqueous medium for at least 30 mins at room temperature, as taught by Mohapatra. Further, a person of ordinary skill in the art would have been motivated to optimize the dispersion time of the coated IONRs in an aqueous medium according to the specific requirements of the applications. Optimization of such a result-effective parameter is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success.
Regarding claim 8, claims of the ‘492 do not recite a pharmaceutically acceptable carrier and/or excipient. As discussed above, Mao discloses pharmaceutical compositions comprising the particles and a pharmaceutically acceptable excipient (column 26, ¶ 4). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use a pharmaceutically acceptable excipient for pharmaceutical composition of the ‘492 to prepare more stable, effective pharmaceutical compositions. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Mohapatra teaches that a pharmaceutically acceptable excipient can be included in the pharmaceutical composition.
Regarding claims 9-10, claims of the ‘492 do not recite a kit comprising a device and the coated IONRs, wherein the device comprises one or more defined region(s) or well(s); and a device comprising one or more defined region(s) or well(s) and the coated IONRs, wherein each defined region or well contains one or more of the IONRs. As discussed above, Mao discloses a kit comprising the coated IONPs (column 28, ¶¶ 4-5). As discussed above, Liu discloses acoustofluidic multi-well plates for controllable enrichment of nanoscale object such as magnetic nanoparticles (abstract; page 3404, column 2, ¶ 2). Liu discloses that the nanoparticles in each well of the plate can be enriched and this simple, compatible plate system can be a versatile tool for many applications such as biomedical sensing (abstract). It would have been obvious to a person of ordinary skill in the art before the effective
filing date of the claimed invention to use the multi-well plate of Liu as a device for the kit of Mao comprising the coated IONRs of the ‘492 in order to accurately controlled the coated IONRs in each well in the device of the kit for biomedical applications. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Mao teaches a kit comprising the coated IONRs and Liu teaches that the multi-well plate system can be used for controlled enrichment of nanoparticles. Further, a person of ordinary skill in the art would have been motivated to utilize the multi-well plate system for high-throughput screening applications.
Claims 1-3 and 5-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. US 10,537,531 (cited on PTO-892) in view of Mohapatra et al. (Nanoscale, 2015; cited on IDS filed July 10, 2024; Supplementary information cited on PTO-892), Mao et al. (US 10,393,736, 2019; cited on IDS filed July 10, 2024), and Liu et al. (Lab on a Chip, 2020; cited on PTO-892).
Regarding claim 1, claim 1 of the ‘531 recites a coated nanoparticles comprising an iron oxide particle and an inner coating comprising an amphiphilic polymer. Claims of the ‘492 do not recite that the iron oxide core has a magnetic moment of at least 10 emu/g, induced using 1 T magnetizing field strength, at room temperature. As discussed above, Mohapatra discloses that the iron oxide magnetization (magnetic moment) can be different depending on size and shape, and that the IONRs can have a magnetic moment of at least about 40 emu/g at room temperature at 10 kOe (1 T magnetizing field strength), similar to saturation magnetization at 40 kOe (page 9179, column 2, ¶1; page 9180, Fig, 5 (c)). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of the ‘531 by configuring the IONRs to have a magnetic moment of at least about 40 emu/g at room temperature at 10 kOe. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Mohapatra teaches that the IONRs can exhibit such a magnetic moment. Further, a person of ordinary skill in the art would have been motivated to optimize the magnetic moment according to the specific requirements of the applications by adjusting the size and shape of the IONRs, as taught by Mohapatra.
Regarding claim 2, claims of the ‘531 do not recite that the iron oxide core has a length in a range from about 20 nm to about 250 nm and a diameter in a range from about 2 nm to about 50 nm. As discussed above, Mohapatra discloses that the IONRs can have a length of 30–70 nm and a diameter of 4–12 nm (abstract). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of the ‘531 by configuring the iron oxide core to have a length of 30–70 nm and a diameter of 4–12 nm. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Mohapatra teaches that the IONRs can have such length and diameter. Further, a person of ordinary skill in the art would have been motivated to optimize the length and diameter according to the specific requirements of the applications. The size of iron oxide core is a clearly result-effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal size of the iron oxide core for achieving the desired characteristics of the IONRs.
Regarding claim 3, claims of the ‘531 do not recite the coating comprise one or more amphiphilic polymer such as
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(n is 22). As discussed above, Mao discloses iron oxide nanoparticles (IONPs) coated with amphiphilic diblcok polymer, PEG-b-AGE (allyl glycidyl ether) copolymer (column 11, ¶ 4). Mao discloses that the polymer can minimize non-specific adsorption (anti-fouling property) (column 1, ¶¶ 5-7) and that the polymer can have a structure of
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(n can be 22 and R can be methyl or siloxane connecting point to the surface of the particle) (claims 2 and 9). The polymers of Mao and instant claims share a common structure except for the length of the alkyl linkers. The polymer of Mao contains a single propyl chain on either side of the sulfur atom, whereas the polymer of instant claims contains three repeating propyl units each, which merely increase the length of the linker portion. Regarding claim 8, Mao discloses pharmaceutical compositions comprising the particles and a pharmaceutically acceptable excipient (column 26, ¶ 4). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the amphiphilic polymer of Mao as a coating material of the coated IONRs of the ‘531 in order to prepare coated IONRs with better fouling resistance. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Mao teaches that the amphiphilic polymer such as PEG-b-AGE can be used for coating IONPs. Further, a person of ordinary skill in the art would have been motivated to utilize an amphiphilic polymer for coating nanoparticles in order to prepare more stable, non-toxic, and versatile nanoparticles. Regarding the difference in the length of the alkyl linker, a person of ordinary skill in the art would have been motivated to adjust the length of linker as a routine design choice in order to optimize the stability, flexibility, and hydrophobicity of the linker portion. Compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties (MPEP 2144.09).
Regarding claim 5, claims of the ‘531 do not recite that the iron oxide core comprises Fe3O4 magnetite or a combination of Fe3O4 magnetite and FeO(OH) goethite. As discussed above, Mohapatra discloses that the IONRs can be Fe3O4 nanorods (abstract). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use Fe3O4 as the iron oxide core of the ‘531. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Mohapatra teaches that the Fe3O4 nanorods can be used as iron oxide core. Further, a person of ordinary skill in the art would have been motivated to utilize Fe3O4 as an iron oxide in order to achieve strong ferrimagnetism which allows for easy magnetic separation.
Regarding claim 6, claims of the ‘531 do not recite specific ranges in a hydrodynamic length or a zeta potential. As discussed above, Mohapatra discloses that the hydrodynamic diameter can be different depending on the size and shape, and that the hydrodynamic size of the coated IONRs can be between 71-105 nm (Supplementary information Fig. S6 and Table S2). It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of the ‘531 by configuring the IONRs to have a hydrodynamic size between 71-105 nm. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Mohapatra teaches that the coated IONRs can have such a hydrodynamic length. Further, a person of ordinary skill in the art would have been motivated to optimize the hydrodynamic size of the coated IONRs according to the specific requirements of the applications. The hydrodynamic size of the coated IONRs is a clearly result-effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal hydrodynamic size of the coated IONRs for achieving the desired characteristics of the coated IONRs.
Regarding claim 7, claims of the ‘531 do not recite a dispersion time or a separation efficiency. As discussed above, Mohapatra discloses that the coated IONRs can be dispersed in deionized water as colloidal suspension and that the coated IONRs can be very stable as water colloids for about a month without aggregation or precipitation (page 9175, column 2, ¶ 3; page 9179, column 1, ¶1; page 9179, Fig. 4 (b) and (c)). It can be expected that the coated IONRs can be disperse in an aqueous medium for at least 30 mins at room temperature. It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of the ‘531 by configuring the IONRs to be disperse in an aqueous medium for at least 30 mins at room temperature, as taught by Mohapatra. Further, a person of ordinary skill in the art would have been motivated to optimize the dispersion time of the coated IONRs in an aqueous medium according to the specific requirements of the applications. Optimization of such a result-effective parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success.
Regarding claim 8, claims of the ‘531 do not recite a pharmaceutical composition. As discussed above, Mao discloses pharmaceutical compositions comprising the particles and a pharmaceutically acceptable excipient (column 26, ¶ 4). it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare pharmaceutical compositions comprising the coated IONRs of the ‘531 and a pharmaceutically acceptable excipient taught by Mao to prepare more stable, effective pharmaceutical compositions for pharmaceutical applications. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Mao teaches pharmaceutical compositions comprising the particles and a pharmaceutically acceptable excipient.
Regarding claims 9-10, claims of the ‘531 do not recite a kit comprising a device and the coated IONRs, wherein the device comprises one or more defined region(s) or well(s); and a device comprising one or more defined region(s) or well(s) and the coated IONRs, wherein each defined region or well contains one or more of the IONRs. As discussed above, Mao discloses a kit comprising the coated IONPs (column 28, ¶¶ 4-5). As discussed above, Liu discloses acoustofluidic multi-well plates for controllable enrichment of nanoscale object such as magnetic nanoparticles (abstract; page 3404, column 2, ¶ 2). Liu discloses that the nanoparticles in each well of the plate can be enriched and this simple, compatible plate system can be a versatile tool for many applications such as biomedical sensing (abstract). It would have been obvious to a person of ordinary skill in the art before the effective
filing date of the claimed invention to utilize the multi-well plate of Liu as a device for the kit of Mao comprising the coated IONRs of the ‘531 in order to accurately controlled the coated IONRs in each well in the device of the kit for biomedical applications. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Mao teaches a kit comprising the coated IONRs and Liu teaches that the multi-well plate system can be used for controlled enrichment of nanoparticles. Further, a person of ordinary skill in the art would have been motivated to utilize the multi-well plate system for high-throughput screening applications.
Claims 1-3 nad 5-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims of copending Application No. 19/481,185 in view of Mao et al. (US 10,393,736, 2019; cited on IDS filed July 10, 2024).
Regarding claim 1, claim 1 of the ‘185 recited coated IONRs comprising an iron oxide core and a coating, wherein the iron oxide core has a magnetic moment of at least 10 emu/g, induced using 1 T magnetizing field strength, at room temperature.
Regarding claim 2, claim 2 of the ‘185 recites that the iron oxide core can have a length in a range from about 20 nm to about 250 nm and a diameter in a range from about 2 nm to about 50 nm.
Regarding claim 3, claims of the ‘185 do not recite the coating comprise one or more amphiphilic polymer such as
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(n is 22). As discussed above, Mao discloses IONPs coated with amphiphilic diblcok polymer, PEG-b-AGE (allyl glycidyl ether) copolymer (column 11, ¶ 4). Mao discloses that the polymer can minimize non-specific adsorption (anti-fouling property) (column 1, ¶¶ 5-7) and that the polymer can have a structure of
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(n can be 22 and R can be methyl or siloxane connecting point to the surface of the particle) (claims 2 and 9). The polymers of Mao and instant claims share a common structure except for the length of the alkyl linkers. The polymer of Mao contains a single propyl chain on either side of the sulfur atom, whereas the polymer of instant claims contains three repeating propyl units each, which merely increase the length of the linker portion. It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the amphiphilic polymer of Mao as a coating material of the coated IONRs of the ‘185 in order to prepare the coated IONRs with better fouling resistance. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Mao teaches that the amphiphilic polymer such as PEG-b-AGE can be used for coating IONPs. Further, a person of ordinary skill in the art would have been motivated to utilize an amphiphilic polymer for coating nanoparticles in order to prepare more stable, non-toxic, and versatile nanoparticles. Regarding the difference in the length of the alkyl linker, a person of ordinary skill in the art would have been motivated to adjust the length of linker as a routine design choice in order to optimize the stability, flexibility, and hydrophobicity of the linker portion. Compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties (MPEP 2144.09).
Regarding claim 5, claim 7 of the ‘185 recites that the iron oxide core can comprise Fe304 magnetite.
Regarding claim 6, claim 2 of the ‘185 recites that the coated IONRs can have a hydrodynamic length in a range from about 50 nm to about 300 nm.
Regarding claim 7, claim 10 of the ‘185 recites that the coated IONRs can be dispersed in an aqueous medium for at least 30 mins at room temperature.
Regarding claim 8, claim 14 of the ‘185 recites a pharmaceutical composition comprising the coated IONRs and a pharmaceutically acceptable carrier and/or excipient.
Regarding claim 9, claim 15 of the ‘185 recites a kit comprising a device and the coated IONRs, wherein the device comprises one or more defined region(s) or well(s).
Regarding claim 10, claim 16 of the ‘185 recites a device comprising one or more defined region(s) or well(s) and the coated IONRs, wherein each defined region or well contains the IONRs.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/JONG HWAN BAEK/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
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