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 .
Summary
Receipt of Applicants Remarks and Restriction/Elections filed on 02/13/2026 is acknowledged. Claims 1-14 are pending. Claims 7-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention. Claims 2, 3 and 5 are cancelled.
Claims 1, 4 and 6 are pending and under examination.
Maintained Rejections
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) 1, 4 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over KR 101927196 B1 (hereinafter the reference is referred as KR ‘196) in view of Jeon (Magnetically actuated microrobots as a platform for stem cell transplantation).
KR ‘196 is directed to provide a magnetic drive articular cartilage regeneration system for efficiently and non-surgically regenerating articular cartilage. However, these problems are exemplary and do not limit the scope of the present invention (¶ 0004).
Regarding claim 1, KR ‘196 discloses preparation of amine-functionalized Fe₃O₄ magnetic nanoparticles (MNPs) coated with polyethylenimine (PEI), a cationic polymer with amine groups, for attachment to a biocompatible PLGA micro-scaffold (¶ 0044), and the PEI-coated MNPs are coupled to the scaffold surface via EDC/NHS amino bond formation (¶ 0046). Moreover, KR ’196 further confirms that mesenchymal stem cells loaded onto the MNP-bearing scaffold exhibit normal proliferation (Example 4, Fig. 5) and successful chondrocyte differentiation (Example 5, Fig. 7), establishing that the coating material promotes attachment, proliferation, and differentiation of stem cells as claimed. Additionally, KR ’196 explicitly discloses two modes of associating the magnetic material with stem cells: (i) surface attachment of MNPs to the scaffold to which cells adhere, and (ii) direct internalization of the magnetic body into cartilage-producing cells via endocytosis when cells are cultured in a medium containing the magnetic bodies (¶ 0020, ¶0030). This directly corresponds to the claimed “internalizing or attaching the coated magnetic material into stem cells.” Even assuming a distinction exists between the micro-scaffold structure of KR ‘196 and the claimed microrobot, it would have been obvious to a person having skill in the art (PHOSITA) that the magnetically-driven micro-scaffold cell complex of KR ’196 constitutes a microrobot for cell therapy delivery, as both structures are defined by their function, namely, magnetic field-driven movement carrying stem cells to an affected site (¶ 0030, ¶ 0035). Both the micro-scaffold cell complex of KR’196 and the claimed microrobot are defined by the same operative features: a magnetic material associated with stem cells and driven by an external magnetic field to navigate to a target site and because the structural and functional elements are coextensive, no patentable distinction exists between the two constructs and the limitation is met.
KR ’196 explicitly teaches that the cartilage therapeutic agent may be prepared as either a single cell (configuration A) for cartilage regeneration, or as a spheroid cell structure (configuration B) (¶ 0030). The single cell configuration in which a magnetic body is internalized into or attached to a single cartilage regeneration cell directly anticipates or renders obvious the limitation of claim 2. Thus the limitation that a single stem cell and the coated magnetic material become one microrobot configuration is taught.
KR ’196 further teaches that to improve treatment efficiency, a spheroid-shaped cell structure for cartilage regeneration may be prepared by three-dimensional culture of cartilage regeneration cells together with magnetic bodies on a microstructure (¶ 0030). Moreover, KR ’196 further discloses that three-dimensional culture can be formed by culturing cells in a container having conical grooves rather than a normal plate culture container (¶ 0019). This teaching maps directly onto the spheroid culture limitation of claim 3.
Regarding claim 4, KR ’196 teaches 3D spheroid culture using conical groove culture containers (¶ 0019) but does not expressly recite hanging-drop or U-shaped 96-well plate methods. Furthermore, KR ’196 teaches bone marrow-derived, cord blood-derived, and adipose-derived stem cells (¶ 0016, ¶ 0023) but does not expressly disclose inferior turbinate-derived stem cells.
Regarding claim 6, KR ’196 confirms chondrocyte differentiation of mesenchymal stem cells loaded onto the MNP-bearing scaffold (Example 5), establishing that the coating and fabrication method preserves differentiation capacity. To the extent any specific differentiation lineage requires further support, the art broadly recognizes inferior turbinate-derived stem cells as multipotent mesenchymal stem cells capable of the recited differentiation outcomes. The claim recites that the inferior turbinate-derived stem cells are differentiated into one of chondrocytes, bone cells, adipocytes, mucosal differentiation, and nerve cells. It is noted that the multipotent differentiation capacity of inferior turbinate-derived mesenchymal stem cells into these specific lineages was well-established in the art prior to the effective filing date and is expressly recited in the background of the present application itself (Specification ¶ 0003), and constitutes an admission by applicant that this property of inferior turbinate-derived mesenchymal stem cells was known in the art prior to the effective filing date. Accordingly, applicant may not rely on the multipotent differentiation capacity of inferior turbinate-derived stem cells as a point of distinction over the prior art. See MPEP § 2129.
Jeon teaches magnetic microrobots developed for three-dimensional culture and the precise delivery of stem cells in vitro, ex vivo, and in vivo. Hippocampal neural stem cells attached to the microrobots proliferated and differentiated into astrocytes, oligodendrocytes, and neurons. Microrobots carrying mesenchymal stem cells derived from human nose were manipulated inside the intraperitoneal cavity of a nude mouse (Abstract)
Regarding claim 4, Jeon teaches formation of stem cell spheroids for microrobot fabrication using methods well-known in the art for generating 3D cell aggregates. Hanging-drop culture (page 4) and U-shaped 96-well plate methods were standard (page 8-9), well-established techniques in the stem cell and tissue engineering art for generating spheroids (page 2) prior to the effective filing date. It would have been obvious to a PHOSITA to apply these routine spheroid formation techniques in the fabrication method of Park KR ’196, with a reasonable expectation that stem cells cultured by these methods would form spheroids equivalent to those disclosed in Park KR ’196, given that all such methods share the common goal of promoting 3D cell aggregation and that the choice among them represents nothing more than routine optimization. Furthermore, Jeon explicitly teaches that human nasal inferior turbinate-derived stem cells (hNTSCs) are internalized with magnetic nanoparticles to form a magnetically-steerable microrobot for cell therapy delivery (page 4-11). It would have been obvious to a PHOSITA to substitute inferior turbinate-derived stem cells, as taught by Jeon, into the fabrication method of KR ’196. Both references operate in the same field of magnetically-guided stem cell therapy delivery, and Jeon confirms that hNTSCs are compatible with magnetic nanoparticle internalization without loss of viability or differentiation capacity. The substitution represents a routine selection among known mesenchymal stem cell sources with a reasonable expectation of success.
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to arrive at the claimed method of culturing a plurality of stem cells in a spheroid, internalizing or attaching of the coated magnetic material into the stem cells in cultured in the spheroid shape as taught by KR ‘196. Moreover, KR ‘196 discloses a complete fabrication methodology: amine-functionalized Fe₃O₄ MNPs coated with PEI, a cationic polymer, are coupled to a biocompatible PLGA micro-scaffold; mesenchymal stem cells are then loaded onto the scaffold and confirmed to attach, proliferate, and differentiate into chondrocytes (¶ 0044–¶ 0054), Examples 4–5. Critically, KR ’196 also teaches that the magnetic body may alternatively be internalized directly into cartilage-producing cells via endocytosis, yielding either a single-cell or spheroid-shaped therapeutic agent steerable by an external magnetic field (¶ 0020, ¶ 0030). Jeon operates in the same technological space but extends the platform specifically to human nasal inferior turbinate-derived stem cells (hNTSCs) as the cell therapy vehicle (page 4), confirming that magnetic nanoparticle internalization into hNTSCs preserves cell viability, proliferation, and multipotent differentiation capacity including neuronal lineages. Jeon further discloses intranasal administration of the resulting cell-magnetic material composite for brain-targeted delivery via the peri-olfactory pathway (page 1). Taken together, KR ‘196 in view of Jeon establish that every element of the claimed fabrication method: (a) coating magnetic material with a biocompatible cationic polymer to promote stem cell attachment, proliferation, and differentiation; (b) internalizing or attaching the coated magnetic material to stem cells including in spheroid form; (c) and using inferior turbinate-derived stem cells capable of multipotent differentiation, was individually known and demonstrated in the art prior to the effective filing date. However, prior art differ from claimed method in two aspect: (i) the use of inferior turbinate-derived stem cells rather than bone marrow or adipose-derived mesenchymal stem cells; and (ii) the recitation of hanging-drop or U-shaped 96-well plate culture methods for spheroid formation (claim 4). Jeon supplies the inferior turbinate-derived stem cell teaching. The spheroid culture methods of claim 4 represent well-known routine techniques in the art, the selection of which constitutes no more than ordinary skill. Thus, no structural or functional distinction separates the claimed microrobot from the magnetically-driven cell-MNP composite of KR ‘196, as each operative element of the claimed fabrication method is disclosed or rendered obvious by the combined teachings of the references.
Moreover, a PHOSITA would have working familiarity with magnetic nanoparticle synthesis and surface functionalization, stem cell culture techniques including 3D spheroid formation, and targeted cell delivery systems. Such a person would be familiar with both the scaffold-based and direct-internalization approaches disclosed in the prior art and would understand the functional equivalence of different mesenchymal stem cell sources for purposes of magnetic microrobot fabrication. One would have been motivated to combine KR ‘196 and Jeon with clear and articulate reason to do so with a reasonable expectation of success for the following reasons:
First, both references address the identical technical problem: fabricating a magnetically-steerable stem cell delivery vehicle capable of precise, minimally-invasive navigation to a diseased target site. A PHOSITA seeking to optimize the stem cell source used in the fabrication method of KR ’196 would naturally look to contemporaneous literature in the same field, where Jeon directly teaches that inferior turbinate-derived stem cells are not only compatible with magnetic nanoparticle internalization but offer particular clinical advantages, including reduced immunogenicity due to shared genetic origin with the patient and established multipotent differentiation capacity. This constitutes a recognized benefit that would motivate a PHOSITA to make the substitution.
Second, substituting one known mesenchymal stem cell source for another, the combination is prima facie obvious. KR ’196 itself acknowledges that the stem cell source is not limited to bone marrow- or adipose-derived cells, noting that “cells and embryo-derived stem cells may also be used.” (¶ 0016). This open-ended disclosure signals to a PHOSITA that the stem cell source is a variable parameter subject to routine optimization, and Jeon provides specific, affirmative guidance that inferior turbinate-derived stem cells (page 4) perform well in precisely this application.
Third, there is no credible technical barrier to the combination. Jeon confirms that hNTSCs tolerate magnetic nanoparticle internalization without adverse effects on viability, morphology, or differentiation capacity (page 4). A PHOSITA would therefore have had a reasonable expectation that substituting hNTSCs into the fabrication method of KR ’196 would yield a functional microrobot with preserved therapeutic properties, consistent with the results already demonstrated in Jeon.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Taken in combination, KR ‘196 and Jeon establish that each element of the claimed fabrication method was individually known and demonstrated in the art prior to the effective filing date, and a PHOSITA would have had both the motivation to combine these teachings and a reasonable expectation of success in doing so.
Response to Arguments
Applicant’s arguments filed 06/23/2026 with respect to the rejection of claims 1–6 (now 1, 4, and 6) under 35 U.S.C. § 103 over KR 101927196 B1 (“KR ’196”) in view of Jeon have been fully considered but are not persuasive.
Applicant argues that neither KR ’196 nor Jeon teaches or suggests a microrobot in which a spheroid-shaped stem cell aggregate and a coated magnetic material together configure the microrobot, asserting instead that the cited references rely on a separate scaffold/carrier structure on or within which stem cells are cultured or supported.
This argument mischaracterizes the scope of KR ’196. KR ’196 discloses two distinct configurations for its magnetically-driven cell therapy construct:
1. A scaffold-based configuration, in which PEI-coated Fe₃O₄ magnetic nanoparticles are covalently coupled to a biocompatible PLGA micro-scaffold via EDC/NHS chemistry, and stem cells are loaded onto the scaffold (¶¶ 0044–0046). This configuration was relied upon, in part, in the prior rejection of original claim 1.
2. A direct-internalization configuration, in which the magnetic body is internalized directly into the therapeutic cells via endocytosis — with no scaffold, carrier, or intervening structure of any kind — and which may be prepared either as a single cell (Configuration A) or, when the cells are three-dimensionally cultured together with the magnetic bodies in a conical-groove culture container, as a spheroid-shaped cell structure (Configuration B) (¶¶ 0019–0020, 0030). This is the embodiment relied upon in the prior rejection of original claim 3, and it was cited precisely because it does not depend on the PLGA scaffold at all.
Because the PEI coating taught at ¶ 0044 is disclosed generically as a property of the magnetic nanoparticles themselves — not as a feature exclusive to the scaffold-attachment configuration — KR ‘196’s direct-internalization/spheroid configuration already discloses a coated magnetic material internalized directly into a plurality of stem cells cultured in spheroid shape, with the spheroid-cell/magnetic-particle composite itself constituting the therapeutic microrobot construct, without any separate carrier. This directly corresponds to the amended claim 1 limitation that the plurality of stem cells cultured in the spheroid shape and the coated magnetic material “together configure the microrobot.” Jeon, as before, supplies the motivation and teaching to use inferior turbinate-derived stem cells specifically as the cell source in this same type of magnetically-internalized, spheroid-form microrobot construct.
Applicant’s characterization of the rejection as requiring “impermissible hindsight reconstruction” is likewise not persuasive, as no feature of amended claim 1 has been drawn from outside the four corners of KR ’196 and Jeon; the amendment merely consolidates into independent claim 1 limitations that were already separately mapped to these same two references under original claims 1, 3, and 5 in the prior Office Action. The combination of references, and the motivation to combine, are unchanged from the prior Office Action and are restated above as applied to the claims in their amended form.
A PHOSITA would have had working familiarity with magnetic nanoparticle synthesis and surface functionalization, stem cell culture techniques including 3D spheroid formation, and targeted cell delivery systems, and would have been motivated to combine KR '196 and Jeon because: (1) both references address the identical technical problem of fabricating a magnetically-steerable stem cell delivery vehicle for precise, minimally-invasive navigation to a diseased target site; (2) KR '196 itself discloses that its stem cell source is not limited to any particular tissue origin, signaling that the stem cell source is a variable subject to routine optimization, and Jeon provides specific, affirmative guidance that inferior turbinate-derived stem cells perform well in this exact application, including reduced immunogenicity and established multipotent capacity; and (3) Jeon confirms no technical barrier exists to the substitution, as hNTSCs tolerate magnetic nanoparticle internalization without adverse effect on viability, morphology, or differentiation capacity, consistent with results already demonstrated in KR '196's own internalization-based configuration. The amended claims are rejected on the same combination of references (KR '196 in view of Jeon) already of record and previously applied, individually, to the corresponding limitations under original claims 1, 3, and 5, and thus the rejections are maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDRE MACH whose telephone number is (571)272-2755. The examiner can normally be reached 0800 - 1700 M-F.
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/ANDRE MACH/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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