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, claims 1-15 in the reply filed on 10/1/2025 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Claims 16-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 1, 6-7, 9-10 and 12-15 is/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, 7216}, 5978-5994)
Regarding claim 1, Kang teaches a magnetic screen (nanocage), the magnetic barrier comprises magnetic particle units (iron oxide nanoparticles) (Pg. 5990, right column, Synthesis of Magnetic Nanocages, lines 1-2), a linker attached to the magnetic screen 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 stem cells 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).
Regarding claim 6, Kang teaches wherein the linker is “functionalized” with a flexible polymer linker wherein the linker is thiol-poly(ethylene glycol) (PEG) which forms a chemical bond with the magnetic screen and the substrate comprising gold nanoparticles (Pg. 5979, right column, last para., lines 1-2 and Scheme 2).
Regarding claim 7, the magnetic screen was synthesized as carboxylate- capped iron oxide nanoparticles (Pg. 5990, right column, Synthesis of Magnetic Nanocages, lines 1-2), the carboxylate 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).
Regarding claim 12, Kang teaches wherein the density of the gold nanoparticles on the substrate is 54 +12 particles/um2 (Pg. 5980, left column, second para., lines 5-7) and wherein the substrate is a 22mm? 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.
Regarding claim 13, Kang teaches wherein 83% of the gold nanoparticles substrate is coupled with the magnetic nanobarrier (Pg. 5980, right column, lines 8-9).
Regarding claim 14, claim 14 recites a method of producing the nanoscreen 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 ona 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 nanoscreen 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 nanoscreen via combining the magnetic nanoscreen 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 nanoscreen 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 nanoscreen 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).
Regarding claim 15, 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
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 2-5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kang in view of Akhtari (US 200880206146).
Refer above for the teachings of Kang.
Kang teaches a magnetic nanoscreen comprising iron oxide nanoparticles (Pg. 5990, right column, Synthesis of Magnetic Nanocages, lines 1-2) wherein the nanoscreen comprises a flexible linker attached to the magnetic nanoscreen 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 nanoscreen 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 fails to teach the magnetic screens include one or more of a first average diameter of 150 to 250 nm, a second average diameter of 450 to 580 nm, and a third average diameter of 650 to 900 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, about 400 nm to 600 nm, and about 600 nm to 800 nm (Para. [0024)). Akhtari also 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 nanoscreen 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.
Claim(s) 8-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kang.
Refer above for the teachings of Kang.
Kang teaches a flexible amine-poly(ethylene glycol)-thiol linker wherein an amino group at one end of the linker binds to a magnetic nanoscreen, 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 nanoscreen, 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) anda maleimide or alkenyl group at the other end (R2). Kang further 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 fails to 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 nanoscreen 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 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).
Therefore, it would have been obvious to one having ordinary skill in the art to rearrange the structural elements such that the linker having a magnetic nanoscreen 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 nanoscreen 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 nanoscreen connected to one side affect the ability of the nanoscreen 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, farther in proximity to the gold nanoparticles comprising bound ligands.
Conclusion
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/JYOTI NAGPAUL/Primary Examiner, Art Unit 1798