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 1, claims 1-15, drawn to a nanobarrier for regulating macrophage adhesion and polarization comprising: magnetic barriers each comprising an aggregate of one or more magnetic particle units; a linker connected to one side of each of the magnetic barriers; and a substrate connected to the magnetic barriers via the linkers, wherein the substrate comprises ligands to which macrophages adhere in the reply filed on August 6, 2025 is acknowledged.
Claims 16-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Status of the Claims
Claims 1-15 are examined on the merits.
Priority
Applicant claims foreign priority to Korean patent application KR10-2021-0157180 filed on November 16, 2021. Receipt is acknowledged of certified copies of papers received in the original language as required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on October 11, 2022 and April 21, 2023 are in compliance with the provisions of 37 CFR 1.97 and have been considered by the examiner.
Claim Rejections - 35 USC § 112
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 7, 10 – 12, and 15 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.
Claim 7, which depends from claim 1, recites the limitation "the first bonding portion" in line 3 and “the second binding portion” in line 6. There is insufficient antecedent basis for this limitation in the claim as there is no previous mention of a first or second binding portion in claim 7 or in claim 1 thus rendering the scope of the claim indefinite. Appropriate correction is required.
Claim 10, which depends from claim 1, recites the limitation “the ligands provided on the substrate”. There is insufficient antecedent basis for this limitation in the claim as there is no previous mention of ligands provided on the substrate, only that “the substrate comprises ligands”. Appropriate correction is required. Depended Claims 11 and 12 are also included in the basis of this rejection because they do not provide sufficient antecedent basis for the ligands provided on the substrate.
Claim 11, which depends from claim 10 and claim 1, recites the limitation "the thiol groups" in lines 3 and 7. There is insufficient antecedent basis for this limitation in the claim as there in no previous mention of thiol groups. Appropriate correction is required.
Claim 11, which depends from claim 10 and claim 1, recites the limitation “the other portion of the thiol groups”. There is insufficient antecedent basis for this limitation in the claim as there is no previous mention of an "other portion" of thiol groups. Appropriate correction is required.
Claim 11 recites the limitations “bonding with a portion of the thiol groups provided on the substrate” and “bonding with the other portion of the thiol groups provided on the substrate”. It is unclear whether the limitations “the portion” and “the other portion” of the thiol groups is intended to refer to different molecules binding to portions of the same thiol group or to different populations of thiol groups to which different molecules are bound thus rendering the scope of the instant claim indefinite. Appropriate correction is required.
Claim 15, which depends from claims 14 and 1, recites the limitation “ligands provided on at least one surface of the glass substrate”. There is insufficient antecedent basis for this limitation in the claim as there is no previous mention of ligands provided on the substrate, only that “the substrate comprises ligands” in claim 1 and “a substrate on which…ligands are present” in claim 14. Appropriate correction is required.
Claim 15, which depends from claim recites the limitation a substrate comprising a glass substrate wherein “thiol groups and ligands provided on at least one surface of the glass substrate” in lines 3-4 and also the limitation “the ligands are bound to the gold nanoparticles bound to the thiol groups” in lines 9-10. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). Note the explanation given by the Board of Patent Appeals and Interferences in Ex parte Wu, 10 USPQ2d 2031, 2033 (Bd. Pat. App. & Inter. 1989), as to where broad language is followed by "such as" and then narrow language. The Board stated that this can render a claim indefinite by raising a question or doubt as to whether the feature introduced by such language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Note also, for example, the decisions of Ex parte Steigewald, 131 USPQ 74 (Bd. App. 1961); Ex parte Hall, 83 USPQ 38 (Bd. App. 1948); and Ex parte Hasche, 86 USPQ 481 (Bd. App. 1949). In the present instance, claim 15 recites the broad recitation “ligands provided on at least one surface of the glass substrate” , and the claim also recites “the ligands are bound to the gold nanoparticles” which is the narrower statement of the range/limitation.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 6-7, 9-10, and 12-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kang et al. (2018, Magnetic manipulation of reversible nanocaging controls in vivo adhesion and polarization of macrophages. Acs Nano, 12(6), 5978-5994, hereafter “Kang”).
With regard to claim 1, Kang teaches a magnetic “nanocage”, which is considered to read on a magnetic barrier, wherein the magnetic barrier comprises iron oxide nanoparticles, which is considered to read on a magnetic particle unit (Pg. 5990, right column, Synthesis of Magnetic Nanocages, lines 1-2), a flexible linker attached to the magnetic barrier and to an RGD ligand-bearing gold nanoparticle present on a substrate, and wherein macrophages are able to bind to the RGD ligand (Abstract), which is considered to read on a substrate comprising ligands to which macrophages adhere. Additionally, Kang teaches wherein the displacement of the magnetic barrier using a magnetic field promotes adhesion and M2 polarization of macrophages while inhibiting M1 polarization (Abstract).
With regard to claim 6, Kang teaches wherein the magnetic barrier is “functionalized” with a flexible polymer linker wherein the linker is thiol-poly(ethylene glycol) which forms a chemical bond with the magnetic barrier and the substrate comprising gold nanoparticles (Pg. 5979, right column, last para., lines 1-2 and Scheme 2).
With regard to claim 7, Kang teaches wherein the magnetic barrier was synthesized as citrate-capped iron oxide nanoparticles (Pg. 5990, right column, Synthesis of Magnetic Nanocages, lines 1-2), which is considered to read on a magnetic barrier including a carboxylate group, and wherein the citrate group on the magnetic nanoparticle reacts with the amino group present on an amine-poly(ethylene glycol)-thiol linker (Pg. 5990, right column, Functionalization of NMC with a Long and Flexible Linker Molecule, lines 6-7). Additionally, Kang teaches a maleimide poly(ethylene glycol) which is capable of binding to thiol groups on a substrate (Pg. 5991, left column, lines 7-8 and Scheme 2).
With regard to claim 9, although Kang is silent to the specific length of the linker, Kang teaches a linker comprising a structure similar to the instantly claimed linker of claim 8 and as disclosed as Formula 1 on Pg. 5 of the instant specification wherein, in the instantly claimed linker, n is 30 to 5,000. The linker as taught by Kang comprises an amino group which binds to a magnetic barrier and a thiol group at the opposite end which is able to bind to a substrate and wherein n is 113. This is considered to read on a linker which has a length of 10 nm to 1 µm. Since the average bond length of an ethylene glycol unit is about 0.28 nm, the length of 113 units is about 30 nm.
With regard to claim 10, Kang teaches wherein the RGD ligands are bound to gold nanoparticles which are bound to the substrate (Scheme 1 and Pg. 5990, right column, GNP-Grafted Substrate, Pg. 5991, left column, Heterodimeric Substrate, lines 1-2).
With regard to claim 12, Kang teaches wherein the density of the gold nanoparticles on the substrate is 54 ± 12 particles/µm2 (Pg. 5980, left column, second para., lines 5-7) and wherein the substrate is a 22mm2 glass coverslip (Pg. 5990, right column, GNP-Grafted Substrate). Thus, Kang teaches wherein the gold nanoparticles cover 0.2-0.3% of the area of the substrate.
With regard to claim 13, Kang teaches wherein 83% of the gold nanoparticles substrate is coupled with the magnetic nanobarrier (Pg. 5980, right column, lines 8-9).
With regard to claim 14, claim 14 recites a method of producing the nanobarrier comprising forming aggregates of one or more magnetic particle units, forming a carboxylate group on the surface of the aggregates to form magnetic barriers, binding each of the magnetic barriers to one end of each linker by stirring the magnetic barriers and the linkers, chemically binding the other end of each linker to thiol groups on a substrate on which thiol groups and ligands are present, and deactivating thiol groups on the substrate which remain unbound to the linkers. This is interpreted as product-by-process. MPEP 2113(I) states:
"[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).”
Kang teaches wherein the magnetic nanobarrier is prepared by synthesizing citrate-capped iron oxide nanoparticles, which is considered to read on a magnetic barrier comprising a carboxylate group (Pg. 5990, Synthesis of Magnetic Nanocages), binding of one end of a linker of the magnetic nanobarrier via combining the magnetic nanobarrier and the linker and stirring them (Pg. 5990, Functionalization of MNC with a Long and Flexible Linker Molecule), and binding of the other end of the linker to a substrate comprising gold nanoparticles and RGD ligands (Scheme 2) wherein the binding occurs via a thiol group on the linker. Absent evidence to the contrary, there appears to be no structural difference between the nanobarrier comprising magnetic nanoparticles comprising a carboxylate group which binds one end of a linker and wherein the other end of the linker is bound via a thiol group on the linker to a substrate comprising ligands as taught by Kang and the instantly claimed nanobarrier wherein magnetic particles comprising carboxylate groups bind to one end of a linker and wherein the other end of the linker is bound to a substrate comprising ligands via a thiol groups on the substrate. Kang also teaches a substrate comprising thiol groups and ligands (Pg. 5990 and 5991, GNP-Grafted Substrate and Heterodimeric Substrate, lines 1-2) wherein unbound thiol groups on the substrate can be deactivated to reduce non-specific adhesion (Scheme 2 and Pg. 5991, left column, first para., lines 6-7).
With regard to claim 15, claim 15 depends from claim 14 and is also interpreted as product-by-process as detailed above in claim 14. Kang teaches wherein the gold nanoparticle grafted substrate comprises a glass coverslip which is thiolized, incubated with gold nanoparticles to generate a gold nanoparticle-grafted substrate (Pg. 5990 and 5991, GNP-Grafted Substrate), and then coated with RGD ligands (Pg. 5991, Heterodimeric Substrate, lines 1-2 and Scheme 2).
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 2-5, are rejected under 35 U.S.C. 103 as being unpatentable over Kang (as above in 102 rejections) and Akhtari et al. (US 20080206146 A1, hereafter “Akharti”).
With regard to claim 2, as detailed above in the 102 rejections, Kang teaches a magnetic nanobarrier comprising iron oxide nanoparticles (Pg. 5990, right column, Synthesis of Magnetic Nanocages, lines 1-2) wherein the nanobarrier comprises a flexible linker attached to the magnetic nanobarrier and to a RGD ligand-bearing gold nanoparticle present on a substrate, and wherein macrophages are able to bind to the RGD ligand (Abstract). Kang teaches wherein the magnetic nanobarrier is spherical and has a diameter of ranging from 27 – 44 nm (Pg. 5979, right column, Results and Discussion, lines 13-15). Additionally, Kang teaches wherein the displacement of the magnetic barrier using a magnetic field promotes adhesion and M2 polarization of macrophages while inhibiting M1 polarization (Abstract).
Kang does not teach wherein the magnetic barriers include one or more of a first average diameter of 150 to 250 nm, a second average diameter of 450 to 530 nm, and a third average diameter of 650 to 750 nm.
Akhtari teaches functionalized magnetic nanoparticles for use in binding to tissue (Abstract) which can be made of iron oxide (Para. [0026], line 3) and wherein the diameter of the magnetic nanoparticles can vary widely, including diameters of about 100 nm to about 200 nm (which is considered to read on a first average diameter of 150 nm to 250 nm), about 400 nm to 600 nm (which is considered to read on a second average diameter of 450 nm to 530 nm), and about 600 nm to 800 nm (which is considered to read on a third average diameter of 650 nm to 750 nm) (Para. [0024]). Additionally Akhtari teaches that wherein compounds can be attached to the functionalized magnetic nanoparticle via a poly(ethylene glycol) linker (Para. [0075, lines 6-7). Thus, the teachings of Akhtari provide support for magnetic nanoparticles of different diameters which can have linkers attached and which can be used in biological methods.
Therefore it would have been obvious to one having ordinary skill in the art, before the effective filing date of the instant invention, to substitute the spherical iron oxide magnetic nanobarrier having a diameter between 27 – 44 nm comprising a linker as taught by Kang with the magnetic iron oxide containing nanoparticle having various diameters, including about 100 nm to about 200 nm, about 400 nm to 600 nm, and about 600 nm to 800 nm comprising a linker as taught by Akhtari with the predictable result of generating a magnetic barrier wherein the magnetic nanoparticles have different diameters. A skilled artisan would have had a reasonable expectation of success as both Kang and Akhtari teach iron oxide containing magnetic nanoparticles which can comprise linkers and which can be used in biological methods.
With regard to claim 3, as detailed above, the combined teachings of Kang and Akhtari teach wherein a nanobarrier comprising magnetic particle units, a linker connected to one side of the magnetic barrier, a substrate connected to the magnetic barrier via the linkers, and wherein the substrate comprises ligands and wherein the average diameter of the magnetic barrier can be varied to include diameters of 150 nm to 250 nm, 450 nm to 530 nm, and 650 nm to 750 nm. Kang teaches wherein the “nanoscale displacement” of the magnetic barrier and its proximity to ligands on a gold nanoparticle can be reversibly changed via use of a magnetic field (Abstract and Scheme 1). This is considered to reasonably read of separation of the magnetic barrier and ligand by a nanogap wherein the distance can be reversibly changed by application of a magnetic field. One having ordinary skill in the art would have recognized that a nanoscale displacement of the magnetic barrier via use of a magnetic field as taught by Kang could be applied to a magnetic barriers with variable diameters as taught by Akharti with the result of creating a magnetic barrier with various diameters which could be reversibly displaced using a magnetic field. A skilled artisan would have had a reasonable expectation of success as both Kang and Akharti teach iron oxide containing magnetic nanoparticles which can comprise linkers and which can be used in biological methods.
With regard to claim 4, as detailed above in the 102 rejections, Kang teaches a magnetic nanobarrier wherein the nanobarrier comprises a flexible linker attached to the magnetic nanobarrier and to an RGD ligand-bearing gold nanoparticle present on a substrate, and wherein macrophages are able to bind to the RGD ligand (Abstract). Kang teaches wherein the magnetic nanobarrier is spherical and has a diameter of ranging from 27 – 44 nm (Pg. 5979, right column, Results and Discussion, lines 13-15). Additionally, Kang teaches wherein the displacement of the magnetic barrier using a magnetic field promotes adhesion and M2 polarization of macrophages while inhibiting M1 polarization (Abstract). Specifically, Kang teaches that when a magnetic field is applied to the magnetic nanobarrier such that the flexible linker is lengthened and moved away from the RGD ligand (i.e., “uncaged”), macrophage adhesion and M2 polarization is promoted (Abstract and Scheme 1) via the ability of macrophages to bind to the “uncaged” RGD ligand (Pg. 5979, right column, first full para., lines 6-10).
Kang does not teach a magnetic nanobarrier wherein the average diameter of the magnetic nanobarrier is 150 to 250 nm.
As detailed above in claim 2, Akhtari teaches a magnetic nanoparticle having a diameter of about 100 nm to 200 nm (Para. [0024], line 11), which is considered to reasonably read on a magnetic nanobarrier having an average diameter of 150 to 250 nm, and which can comprise a linker (Para. [0075, lines 6-7).
Therefore, it would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to substitute the magnetic barrier comprising an average diameter of about 100 nm to 200 nm as taught by Akhtari for the magnetic barrier having a diameter ranging from 27 – 44 nm as taught by Kang with the predictable result of generating a magnetic barrier having an average diameter of about 150 to 250 nm for use in Kang’s method of promoting macrophage adhesion and M2 polarization by applying a magnetic field to the magnetic nanobarrier such that the linker is lengthened and moved away from an RGD ligand. A skilled artisan would have had an reasonable expectation of success as both Kang and Akhtari teach magnetic nanoparticles which comprise iron oxide and linkers and which can be used in biological methods.
With regard to claim 5, as detailed above in the 102 rejections, Kang teaches a magnetic nanobarrier wherein the nanobarrier comprises a flexible linker attached to the magnetic nanobarrier and to an RGD ligand-bearing gold nanoparticle present on a substrate, and wherein macrophages are able to bind to the RGD ligand (Abstract). Kang teaches wherein the magnetic nanobarrier is spherical and has a diameter of ranging from 27 – 44 nm (Pg. 5979, right column, Results and Discussion, lines 13-15). Additionally, Kang teaches wherein the displacement of the magnetic barrier using a magnetic field promotes adhesion and M2 polarization of macrophages while inhibiting M1 polarization (Abstract). Specifically, Kang teaches that when a magnetic field is applied to the magnetic nanobarrier such that the flexible linker is lengthened and moved away from the RGD ligand (i.e., “uncaged”), macrophage adhesion and M2 polarization is promoted (Abstract and Scheme 1) via the ability of macrophages to bind to the “uncaged” RGD ligand (Pg. 5979, right column, first full para., lines 6-10). Further, Kang teaches that when the linker is shortened the magnetic nanobarrier blocks the RGD ligand, thus preventing macrophage binding which inhibits adhesion and M2 polarization while promoting M1 polarization (Scheme 1).
Kang does not teach wherein the diameter of the magnetic nanoparticles is 650 nm to 750 nm nor does Kang specifically teach application of a magnetic field in order to shorten the flexible linker. However, Kang does teach that blocking of the RGD ligand by shortening of the linker promotes M1 polarization.
Akhtari teaches functionalized magnetic nanoparticles made of iron oxide (Para. [0026], line 3) wherein the magnetic nanoparticles have a diameter about 600 nm to 800 nm, which is considered to read on a third average diameter of 650 nm to 750 nm, (Para. [0024], line 13) and can comprise a linker (Para. [0075, lines 6-7).
Therefore it would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to substitute the magnetic barrier comprising an average diameter of about 600 nm to 800 nm as taught by Akhtari for the magnetic barrier having a diameter ranging from 27 – 44 nm as taught by Kang with the predictable result of generating a magnetic barrier having an average diameter of about 650 to 750 nm for use in Kang’s method of regulating macrophage adhesion and polarization via use of “caging” of an RGD ligand, wherein the nanobarrier blocks the RGD ligand and prevents macrophage binding (thus promoting M1 polarization) and which can be reversed using a magnetic field to lengthen the linker and allow for macrophage binding (thus promoting M2 polarization). One having ordinary skill in the art would have been motivated to combine the nanoparticle having a diameter of 650 nm to 750 nm as taught by Akhtari with the method of regulating macrophage adhesion and polarization wherein blocking of the RGD ligand promotes M1 proliferation as taught by Kang because they would have recognized that using a magnetic nanobarrier with a larger diameter would lead to a nanobarrier having greater blocking ability of the RGD ligand thus preventing macrophage binding and promoting M1 proliferation. Although Kang does not directly teach use of a magnetic field to shorten the linker in order to prevent binding of macrophages to the RGD ligand, Kang does teach that lengthening the linker using a magnetic field “uncages”, or unblocks, the RGD ligand and allows for macrophage binding and M2 polarization and that removal of the magnetic field causes shortening of the linker and reverses M2 polarization (Scheme 1). Therefore, a skilled artisan would have recognized that application of a magnetic field such that the linker is shortened would block the RGD ligand, inhibiting macrophage adhesion and promoting M1 proliferation. A skilled artisan would have a had a reasonable expectation of success as both Kang and Akhtari teach magnetic nanoparticles which comprise iron oxide and linkers and which can be used in biological methods and Kang teaches that linker length, which can be controlled via application of a magnetic field, can regulate macrophage polarization.
Claims 8 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Kang (as above in 102 rejections).
With regard to claim 8, Kang teaches a flexible amine-poly(ethylene glycol)-thiol linker wherein an amino group at one end of the linker binds to a magnetic nanobarrier, a thiol group at the opposite end binds to a gold nanoparticle grafted thiolized substrate, and wherein n is 113 (Scheme 2). Kang also teaches wherein a maleimide poly(ethylene glycol) is used as a blocking agent which binds to a thiolized substrate comprising gold nanoparticles (Pg. 5991, left column, lines 7-8 and Scheme 2). Therefore, a skilled artisan could have derived a linker comprising an amino group at one end, which Kang teaches will bind to a magnetic nanobarrier, and a maleimide group at the opposite end, which Kang teaches will bind to a thiolized substrate, to arrive at the instantly claimed structure of a linker wherein n is 30 to 5,000 and comprising an amino or thiol group at one end (R1) and a maleimide or alkenyl group at the other end (R2).
With regard to claim 11, Kang teaches wherein the gold nanoparticles are grafted to a substrate via thiol groups on the substrate (Pg. 5990, right column, GNP-Grafted Substrate and Scheme 2) and wherein the RGD ligands are bound to the gold nanoparticles (Pg. 5991, left column, Heterodimeric Substrate, lines 1-2). Additionally, Kang teaches wherein the linkers are connected to the gold nanoparticles bound to the substrate via thiol groups (Pg. 5991, left column, Heterodimeric Substrate, lines 1-4 and Scheme 2).
Kang does not teach wherein the gold nanoparticles comprising bound ligands and the linker connected to one side of the magnetic nanobarrier are bound to thiol groups on the same substrate.
However, the difference between the instant invention and the disclosure of Kang is in the arrangement of the structural elements of the inventions. Specifically, in the instant application, the linker having a magnetic nanobarrier attached to one side is attached to the substrate instead of to the gold nanoparticle comprising bound RGD ligands as taught in Kang. Therefore, the instantly claimed invention is interpreted as rearrangement of parts. MPEP 2144.04(IV)(C) provides support for an obviousness rejection due to rearrangement of parts.
In re Japikse, 181 F.2d 1019, 86 USPQ 70 (CCPA 1950) (Claims to a hydraulic power press which read on the prior art except with regard to the position of the starting switch were held unpatentable because shifting the position of the starting switch would not have modified the operation of the device.); In re Kuhle, 526 F.2d 553, 188 USPQ 7 (CCPA 1975) (the particular placement of a contact in a conductivity measuring device was held to be an obvious matter of design choice).
In the instant case, rearrangement of the structural elements such that the linker having a magnetic nanobarrier connected to one side is attached to the substrate instead of to the gold particle comprising bound ligands would not affect the ability of the nanobarrier to physically block binding of macrophages to the ligands on the gold nanoparticles, thus inhibiting macrophage adhesion and promoting M1 polarization, when the linker was compressed e.g., closer in proximity to the gold nanoparticles comprising bound ligands. Nor would binding of the linker having a magnetic nanobarrier connected to one side affect the ability of the nanobarrier to allow binding of macrophages to the ligands on the gold nanoparticles, thus promoting macrophage adhesion and promoting M2 polarization, when the linker was elevated, e.g. farther in proximity to the gold nanoparticles comprising bound ligands.
Claim 11 is rejected under 35 U.S.C. 103 as being obvious over Kang (as above in 102 rejections) and Kang et al. (US 2021/0269773 A1, hereafter “US ‘773” for clarity). Kang et al. (US 2021/0269773 A1) is an intervening reference between Applicant’s US application filed 10/11/2022 and foreign application KR 10-2021-0157180 filed 11/16/2021.
The applied reference has a common applicant and joint inventors with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
With regard to claim 11, Kang teaches wherein the gold nanoparticles are grafted to a substrate via thiol groups on the substrate (Pg. 5990, right column, GNP-Grafted Substrate and Scheme 2) and wherein the RGD ligands are bound to the gold nanoparticles (Pg. 5991, left column, Heterodimeric Substrate, lines 1-2). Additionally, Kang teaches wherein the linkers are connected to the gold nanoparticles bound to the substrate via thiol groups (Pg. 5991, left column, Heterodimeric Substrate, lines 1-4 and Scheme 2).
Kang does not teach wherein the gold nanoparticles comprising bound ligands and the linker connected to one side of the magnetic nanobarrier are bound to thiol groups on the same substrate.
US ‘773 teaches that macrophage adhesion can be regulated by controlling the density of a nanoligand (Abstract) wherein the nanoligand is RGD (Para. [0007], line 8) and wherein macrophage adhesion and M2 polarization is promoted by spatially orienting the RDG ligands such that ligand density is increased (Para. [0035], lines 24-30 and FIG. 1). Therefore, one having ordinary skill in the art would have been motivated to make the structural alteration such that the linker connected to a magnetic nanobarrier is bound to the substrate instead of to the gold nanoparticle in order to allow for increased binding sites for RDG ligands on the gold nanoparticle which would increase the density of RDG ligands which is associated with increased macrophage adhesion and M2 polarization as taught by US ‘773. A skilled artisan would have had a reasonable expectation of success as both Kang and US ‘773 teach regulation of macrophage adhesion and polarization by binding to RDG ligands.
Overcoming Rejection by Declaration under 37 CFR 1.130
Kang et al. (US 2021/0269773 A1) appears to be Applicant’s own work. Applicant may rely on the exception under 35 U.S.C. 102(b)(1)(A) to overcome this rejection under 35 U.S.C. 102(a)(1) by a
(1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Overcoming Rejection by Translation
Applicant is advised of possible benefits under 35 U.S.C. 119(a)-(d) and (f), wherein an application for patent filed in the United States may be entitled to claim priority to an application filed in a foreign country.
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a) -(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action, 37 CFR 41.154(b) and 41.202(e).
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Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
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 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 17/963,578 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-15 of the instant application, drawn to a “nanobarrier”, contain structural elements which are anticipated by the disclosed structural elements of the “nanoscreen” recited in claims 1-15 of reference application ‘578. While the intended use of the instant application (regulating macrophage adhesion and polarization) differs from that of reference application ‘578 (regulating stem cell adhesion and differentiation), the intended use of the instant application and reference application ‘578 do not impart structural differences and therefore are not considered to be limiting. See MPEP 2111.02(II). Since the instant application claims are anticipated by the reference application claims, said claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
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/ERIN V PAULUS/Examiner, Art Unit 1631
/ARTHUR S LEONARD/ Examiner, Art Unit 1631