DETAILED ACTION
This Office Action is in response to Applicant’s Amendment filed on 09/01/2025.
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 .
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-4 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement for the following reasons:
Please note, USPTO personnel are to give claims their broadest reasonable interpretation in light of the supporting disclosure. In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997). Limitations appearing in the specification but not recited in the claim should not be read into the claim. E-Pass Techs., Inc. v. 3Com Corp., 343 F.3d 1364, 1369, 67 USPQ2d 1947, 1950 (Fed. Cir. 2003) (claims must be interpreted "in view of the specification" without importing limitations from the specification into the claims unnecessarily). In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550-551 (CCPA 1969). See also In re Zletz, 893 F.2d 319, 321-22, 13 USPQ2d 1320, 1322 (Fed. Cir. 1989) ("During patent examination the pending claims must be interpreted as broadly as their terms reasonably allow.... The reason is simply that during patent prosecution when claims can be amended, ambiguities should be recognized, scope and breadth of language explored, and clarification imposed.... An essential purpose of patent examination is to fashion claims that are precise, clear, correct, and unambiguous. Only in this way can uncertainties of claim scope be removed, as much as possible, during the administrative process.").
Consequently, when claim 1 is broadly yet reasonably interpreted, the limitation “the amount of the iron oxide represents the amount prior to administration into the cartilage injury site” encompasses the interpretation the amount of the iron oxide represents the amount prior to uptake by cell i.e. in a preparation/incubation medium prior to administration into the cartilage injury site. Using this broad yet reasonable interpretation, claim 1 is rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Still more particularly, claim 1 subject-matter “the amount of the iron oxide represents the amount prior to administration into the cartilage injury site” was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. The specification as-filed at least [0006-0007], [0010-0012] and [0026] explicitly and specifically discuss and pertain to iron/iron oxide concentration as pertaining to that within the cell with no discussion of amount of the iron oxide represents the amount prior to administration for example see [0006] “a magnetized cell … contains iron oxide, the magnetized cell containing iron, derived from the iron oxide, in an amount of not less than 35 pg/cell”; [0007] “the magnetized cell containing iron, derived from the iron oxide, in an amount of not less than 35 pg/cell”; [0010] “A magnetized cell …contains iron oxide, the magnetized cell containing iron, derived from the iron oxide, in an amount of not less than 35 pg/cell… animal cell containing iron oxide … is herein referred to as a “magnetized cell”.” [0011] “magnetized cell contains iron, derived from iron oxide, in an amount of not less than 35 pg/cell. … Specifically, only under a condition that a magnetized cell contains iron oxide containing iron in an amount of not less than 35 pg per cell, … a magnetic field having a magnetic flux density of 0.1 T makes it possible to guide a magnetized cell without the need to generate any excessively intense magnetic field” [0012] “magnetized cell can contain iron, derived from iron oxide, in an amount of preferably not less than 35 pg/cell” and [0026] “the magnetized cell containing iron oxide, the magnetized cell containing iron, derived from the iron oxide, in an amount of not less than 35 pg/cell”. Thus, claim 1 is rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not sufficiently described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Dependent claims 2-4 when analyzed as a whole are held to be patent ineligible under 35 U.S.C. 112(a) because the additional recited limitations fail to cure the 35 U.S.C. 112 (a) issue in base claim 9. Consequently, dependent claims 2-4 are also rejected under 35 U.S.C. 112(a) based in their direct/indirect dependency on base claim 1.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-4 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 1 recites “wherein the amount of the iron oxide represents the amount prior to administration” which renders this claim unclear. More specifically, it is unclear as to “the amount prior to administration” is referring to [a] iron oxide prior to uptake by cell i.e. in a preparation/incubation medium or [b] after uptake i.e. within the cells. If [a] “the amount prior to administration” is referring to iron oxide prior to uptake by cell i.e. in a preparation/incubation medium, it is unclear as to what structure, process, composition is used to derive a 100% uptake of extracellular iron/iron oxide amount into cell to generate the magnetized cell containing iron, derived from the iron oxide, in an amount of 35 or more picograms (pg)/cell.
Claim 1 recites “the magnetized cell containing iron, derived from the iron oxide, in an amount of 35 or more picograms (pg)/cell…wherein the amount of the iron oxide represents the amount prior to administration into the cartilage injury site” which renders this claim unclear. Here, the claim is being interpreted as if reciting --the magnetized cell containing iron, derived from the iron oxide, in an amount of 35 or more picograms (pg)/cell…wherein the amount of the iron oxide within magnetized cell represents the amount prior to administration into the cartilage injury site--. Under this interpretation, Claim 1 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential elements, such omission amounting to a gap between the elements. See MPEP § 2172.01. The omitted elements are: the guiding magnetic field parameter that the magnetized cell containing iron, derived from the iron oxide, in an amount of 35 or more picograms (pg)/cell is specifically and explicitly designed to therapeutically work with as disclosed in instant application specification as-filed at least [0011] (“magnetized cell contains iron, derived from iron oxide, in an amount of not less than 35 pg/cell. Conventionally, there has been no detailed knowledge of what magnetized cell can be guided to a desired position by application of a magnetic field. The inventors of the present invention have found the following. Specifically, only under a condition that a magnetized cell contains iron oxide containing iron in an amount of not less than 35 pg per cell, for example, a magnetic field having a magnetic flux density of 0.1 T makes it possible to guide a magnetized cell without the need to generate any excessively intense magnetic field”) and also detailed in [0026].
Dependent claims 2-4 when analyzed as a whole are held to be patent ineligible under 35 U.S.C. 112(b) because the additional recited limitations fail to cure the 35 U.S.C. 112 (b) issue in their respective base claims. Consequently, dependent claims 2-4 are also rejected under 35 U.S.C. 112(b) based in their direct/indirect dependency on their respective base claims.
Claim Interpretation
The magnetized cell iron amount concentrations/amount as recited in claims are being interpreted in light of instant application specification at least para. [0010-0013] with the upper range being 500 pg/cell.
The magnetic field magnetic flux density range as recited in claim 3 is being interpreted in light of instant application specification para. [0030] with upper range being 1 Tesla.
The iron concentrations/amount in claims are being interpreted in light of instant application specification as-filed at least [0006-0007], [0010-0013], [0026].
Please note that USPTO personnel are to give claims their broadest reasonable interpretation in light of the supporting disclosure. In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997). Limitations appearing in the specification but not recited in the claim should not be read into the claim. E-Pass Techs., Inc. v. 3Com Corp., 343 F.3d 1364, 1369, 67 USPQ2d 1947, 1950 (Fed. Cir. 2003) (claims must be interpreted "in view of the specification" without importing limitations from the specification into the claims unnecessarily). In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550-551 (CCPA 1969). See also In re Zletz, 893 F.2d 319, 321-22, 13 USPQ2d 1320, 1322 (Fed. Cir. 1989) ("During patent examination the pending claims must be interpreted as broadly as their terms reasonably allow.... The reason is simply that during patent prosecution when claims can be amended, ambiguities should be recognized, scope and breadth of language explored, and clarification imposed.... An essential purpose of patent examination is to fashion claims that are precise, clear, correct, and unambiguous. Only in this way can uncertainties of claim scope be removed, as much as possible, during the administrative process.").
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 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 of this title, 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.
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 1-4 are rejected under 35 U.S.C. 103 as being unpatentable over Kamei et al. (Pub.: Kamei N, Adachi N, Ochi M. Magnetic cell delivery for the regeneration of musculoskeletal and neural tissues. Regen Ther. 2018 Nov 2;9:116-119. doi: 10.1016/j.reth.2018.10.001. PMID: 30525082; PMCID: PMC6222975, hereinafter referred to as "Kamei") in view of Yang et al. (Pub. No.: US 20110054236 A1, hereinafter referred to as “Yang”) as evidenced by English Translation of JP 2007151605 A (hereinafter referred to as NPL-Ochi) .
As per independent Claim 1, Kamei discloses a magnetized cell comprising iron oxide (Kamei in at least abstract, section 1-2, 3.1-3.3, 4 for example discloses relevant subject-matter. More specifically, Kamei in at least fig. 1, abstract, section 1 page 116, page 118 section 5 for example discloses magnetized cell comprising iron oxide. See at least Kamei abstract “Magnetic targeting is a cell delivery system using the magnetic labeling of cells and the magnetic field… It enhances the accumulation and adhesion of locally injected cells, resulting in the improvement of tissue regeneration.”; section 1 page 116 “a delivery system of magnetically labeled cells, termed magnetic targeting… magnetically labeled cells were locally injected into the body and controlled using an external magnetic field …Magnetic targeting has been applied for the transplantation of bone marrow mesenchymal stem cells … pluripotent stem cells, and for the regeneration of bone, cartilage, skeletal muscles, and the spinal cord. It enhances the accumulation and adhesion of locally injected cells, resulting in the improvement of tissue regeneration.”; section 1 page 116 “magnetically labeled cells were locally injected into the body and controlled using an external magnetic field”; page 118 section 5 “Magnetic targeting can be utilized for the transplantation of various types of cells and the treatment for various kinds of musculoskeletal … disorders”),
the magnetized cell containing iron, derived from the iron oxide, in an amount of 35 or more picograms (pg)/cell (The instant application specification in at least [0012] states “magnetized cell can contain iron, derived from iron oxide, in an amount of preferably not less than 35 pg/cell, more preferably not less than 40 pg/cell, and even more preferably not less than 45 pg/cell” (emphasis added) disclosing recited iron amount contained per magnetized cell as just one option/preference and in [0013] states “amount of the iron contained in the magnetized cell … has an upper limit that is not particularly limited, provided that the upper limit does not impair a function of the magnetized cell and prevents any adverse health event from occurring in an animal into which the magnetized cell has been introduced…the amount of the iron contained in the magnetized cell … can be, for example, not more than 1 pg/cell, not more than 500 pg/cell, not more than 250 pg/cell, not more than 200 pg/cell, not more than 150 pg/cell, or not more than 125 pg/cell” (emphasis added) disclosing recited iron amount contained per magnetized cell as just one option/preference. Thus, this limitation is being broadly yet reasonably interpreted in light of the instant application specification as being met by an iron amount contained per magnetized cell that does not impair a function of the magnetized cell and prevents any adverse health event from occurring in an animal into which the magnetized cell has been introduced. Kamei in at least abstract, section 2 for example discloses the magnetized cell containing iron, derived from the iron oxide, in a therapeutically efficacious or effective amount per cell i.e. that does not impair a function of the magnetized cell and prevents any adverse health event from occurring in an animal into which the magnetized cell has been introduced as recited. See at least Kamei abstract “Magnetic targeting is a cell delivery system using the magnetic labeling of cells and the magnetic field… developed for …Cell transplantation with both minimal invasiveness and high efficacy on tissue repair … Magnetic targeting has been applied for the transplantation of bone marrow mesenchymal stem cells … pluripotent stem cells, and for the regeneration of bone, cartilage, skeletal muscles, and the spinal cord. It enhances the accumulation and adhesion of locally injected cells, resulting in the improvement of tissue regeneration. It is a promising technique for minimally invasive and effective cell transplantation therapy”; section 1 page 116 “magnetically labeled cells were locally injected into the body and controlled using an external magnetic field”; section 2 “Ferucarbotran was used for the magnetic labeling of bone marrow MSCs”),
wherein the magnetized cell is a mesenchymal stem cell(Kamei in at least section 2 for example discloses the magnetized cell is a mesenchymal stem cell . See Kamei section 2 “Ferucarbotran was used for the magnetic labeling of bone marrow MSCs”),
wherein the magnetized cell is configured for injection directly into a cartilage injury site (Kamei in at least fig.1, section 3.1, section 4 for example discloses the magnetized cell is configured for injection directly into a cartilage injury site . See at least Kamei section 3.1 “Magnetic targeting of bone marrow MSCs enhanced the infiltration of MSCs into the artificial bone and bone formation … enhancement of bone formation in a non-healing femoral fracture rat model using the magnetic targeting of bone marrow MSCs. Magnetically labelled … bone marrow MSCs were injected into the bone fracture site in the presence … a magnetic field…magnetic targeting was found to enhance the proliferation and survivability of the transplanted MSCs”; section 4 “magnetic targeting of autologous bone marrow MSCs in 5 patients with a focal articular cartilage defect… magnetically labeled autologous bone marrow MSCs were injected into the knee joint… the cartilage defect areas were almost completely filled with cartilage-like tissue.”).
wherein the amount of the iron oxide represents the amount prior to administration into the cartilage injury site ( Here, the limitation is being broadly yet reasonably interpreted as if reciting wherein the amount of the iron oxide represents the amount within the magnetized cell prior to administration into the cartilage injury site. The instant application specification in at least [0012] states “magnetized cell can contain iron, derived from iron oxide, in an amount of preferably not less than 35 pg/cell, more preferably not less than 40 pg/cell, and even more preferably not less than 45 pg/cell” (emphasis added) disclosing recited iron amount contained per magnetized cell as just one option/preference and in [0013] states “amount of the iron contained in the magnetized cell … has an upper limit that is not particularly limited, provided that the upper limit does not impair a function of the magnetized cell and prevents any adverse health event from occurring in an animal into which the magnetized cell has been introduced…the amount of the iron contained in the magnetized cell … can be, for example, not more than 1 pg/cell, not more than 500 pg/cell, not more than 250 pg/cell, not more than 200 pg/cell, not more than 150 pg/cell, or not more than 125 pg/cell” (emphasis added) disclosing recited iron amount contained per magnetized cell as just one option/preference. Thus, this limitation is being broadly yet reasonably interpreted in light of the instant application specification as being met by an iron amount contained per magnetized cell that does not impair a function of the magnetized cell and prevents any adverse health event from occurring in an animal into which the magnetized cell has been introduced. Kamei in at least abstract, section 2 for example discloses the magnetized cell containing iron, derived from the iron oxide, in a therapeutically efficacious or effective amount per cell, i.e. that does not impair a function of the magnetized cell and prevents any adverse health event from occurring in an animal into which the magnetized cell has been introduced, wherein the therapeutically effective amount of the iron oxide represents the amount within the magnetized cell prior to administration into the cartilage injury site (See at least Kamei abstract “Magnetic targeting has been applied for the transplantation of bone marrow mesenchymal stem cells … pluripotent stem cells, and for the regeneration of bone, cartilage, skeletal muscles, and the spinal cord. It enhances the accumulation and adhesion of locally injected cells, resulting in the improvement of tissue regeneration) as recited. See at least Kamei abstract “Magnetic targeting is a cell delivery system using the magnetic labeling of cells and the magnetic field… developed for …Cell transplantation with both minimal invasiveness and high efficacy on tissue repair … Magnetic targeting has been applied for the transplantation of bone marrow mesenchymal stem cells … pluripotent stem cells, and for the regeneration of bone, cartilage, skeletal muscles, and the spinal cord. It enhances the accumulation and adhesion of locally injected cells, resulting in the improvement of tissue regeneration. It is a promising technique for minimally invasive and effective cell transplantation therapy”; section 1 page 116 “magnetically labeled cells were locally injected into the body and controlled using an external magnetic field”; section 2 “Ferucarbotran was used for the magnetic labeling of bone marrow MSCs”).
Kamei does not explicitly disclose does not explicitly disclose or require the magnetized cell containing iron be in an amount of 35 or more picograms (pg)/cell with the amount of the iron oxide representing the amount prior to use.
However, in an analogous system for guiding a magnetized cell field of endeavor, Yang discloses a magnetized cell containing iron, derived from the iron oxide, in an amount of 35 or more picograms (pg)/cell with the amount of the iron oxide representing the amount prior to therapeutic use (Yang in at least [0196-0199] for example discloses magnetized cell containing iron, derived from the iron oxide, in an amount of 58+/-17 pg Fe/cell which is in an amount of 35 or more picograms (pg)/cell with the amount of the iron oxide representing the amount within the magnetized cell prior to therapeutic use such as targeted drug delivery. See at least Yang [0196] “ability of a nanocarrier to internalize into cells can augment its drug delivery performance”; [0197] “after nanoparticle incubation with … cells … enhanced cellular uptake of GPEI … the extent of cellular uptake was 138-fold higher (p=0.013, FIG. 15) for GPEI (58+/-17 pg Fe/cell) …Despite the significantly enhanced cellular uptake, … nanoparticle surface did not increase cell toxicity”; [0198-0199] “Magnetic Targeting of GPEI … feasibility of delivering GPEI to tumors …via magnetic targeting”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the iron amount contained per magnetized cell used in the magnetized cell comprising iron oxide system as taught by Kamei, such that iron amount contained per magnetized cell is 35 or more picograms (pg)/cell, as taught by Yang. A person of ordinary skill would have been motivated to do so, with a reasonable expectation of success, for the advantage of maximizing therapeutic efficacy while ensuring nanocarriers internalized by cells are not at cytotoxic levels (Yang, [0197]).
As per dependent Claim 2, the combination of Kamei and Yang as a whole further discloses magnetized cell wherein the iron derived from the iron oxide is contained in an amount of 125 or less pg/cell (The instant application specification in at least [0012] states “magnetized cell can contain iron, derived from iron oxide, in an amount of preferably not less than 35 pg/cell, more preferably not less than 40 pg/cell, and even more preferably not less than 45 pg/cell” (emphasis added) disclosing recited iron amount contained per magnetized cell as just one option/preference and in [0013] states “amount of the iron contained in the magnetized cell … has an upper limit that is not particularly limited, provided that the upper limit does not impair a function of the magnetized cell and prevents any adverse health event from occurring in an animal into which the magnetized cell has been introduced…the amount of the iron contained in the magnetized cell … can be, for example, not more than 1 pg/cell, not more than 500 pg/cell, not more than 250 pg/cell, not more than 200 pg/cell, not more than 150 pg/cell, or not more than 125 pg/cell” (emphasis added) disclosing recited iron amount contained per magnetized cell as just one option/preference. Thus, this limitation is being broadly yet reasonably interpreted in light of the instant application specification as being met by an iron amount contained per magnetized cell that does not impair a function of the magnetized cell and prevents any adverse health event from occurring in an animal into which the magnetized cell has been introduced. Consequently, Yang’s disclosure in at least [0197] for example of a magnetized cell containing iron, derived from the iron oxide, in a therapeutically efficacious or effective amount per cell such as amount of 58+/-17 pg Fe/cell reads on the subject-matter as now recited. See MPEP 2144.05. See at least Yang [0197] “after nanoparticle incubation with … cells … enhanced cellular uptake of GPEI … the extent of cellular uptake was 138-fold higher (p=0.013, FIG. 15) for GPEI (58+/-17 pg Fe/cell) …Despite the significantly enhanced cellular uptake, … nanoparticle surface did not increase cell toxicity”).
As per dependent Claim 3, the combination of Kamei and Yang as a whole further discloses a method (Kamei in at least abstract, section 1 page 116 for example discloses method for guiding a magnetized cell.), comprising:
directly injecting a magnetized cell of Claim 1 into a cartilage injury site of an animal (Kamei in at least fig.1, section 3.1, section 4 for example discloses directly injecting a magnetized cell of Claim 1(also cross reference claim 1 analysis and mapping of claim 1 limitations to combination of applied art as a whole above) into a cartilage injury site of an animal. See at least Kamei section 3.1 “Magnetic targeting of bone marrow MSCs enhanced the infiltration of MSCs into the artificial bone and bone formation … enhancement of bone formation in a non-healing femoral fracture rat model using the magnetic targeting of bone marrow MSCs. Magnetically labelled … bone marrow MSCs were injected into the bone fracture site in the presence … a magnetic field…magnetic targeting was found to enhance the proliferation and survivability of the transplanted MSCs”; section 4 “magnetic targeting of autologous bone marrow MSCs in 5 patients with a focal articular cartilage defect… magnetically labeled autologous bone marrow MSCs were injected into the knee joint… the cartilage defect areas were almost completely filled with cartilage-like tissue.”);
applying a magnetic field to the magnetized cell within the cartilage injury site, wherein the magnetic field has a magnetic flux density of not less than 0.1 or more Tesla (T), wherein the magnetic field is applied in a manner as to guide the magnetized cell to a desired position within the cartilage injury site (Kamei in at least fig.1, abstract, section 1, section 3.1, section 3.2, section 3.3 for example discloses applying a magnetic field to the magnetized cell within the cartilage injury site as shown in fig. 1, wherein the magnetic field has a magnetic flux density of not less than 0.1 or more Tesla (T), wherein the magnetic field is applied in a manner as to guide the magnetized cell to a desired position within the cartilage injury site. See at least abstract “Magnetic targeting is a cell delivery system using the magnetic labeling of cells and the magnetic field… Magnetic targeting has been applied for the transplantation of bone marrow mesenchymal stem cells… for the regeneration of bone, cartilage, skeletal muscles, and the spinal cord. It enhances the accumulation and adhesion of locally injected cells, resulting in the improvement of tissue regeneration”; section 1 “a delivery system of magnetically labeled cells, termed magnetic targeting… magnetically labeled cells were locally injected into the body and controlled using an external magnetic field …Magnetic targeting has been applied for the transplantation of bone marrow mesenchymal stem cells … pluripotent stem cells, and for the regeneration of bone, cartilage, skeletal muscles, and the spinal cord. It enhances the accumulation and adhesion of locally injected cells, resulting in the improvement of tissue regeneration”; section 3.1 “Magnetic targeting of bone marrow MSCs enhanced the infiltration of MSCs into the artificial bone and bone formation … enhancement of bone formation in a non-healing femoral fracture rat model using the magnetic targeting of bone marrow MSCs. Magnetically labelled … bone marrow MSCs were injected into the bone fracture site in the presence … a magnetic field…magnetic targeting was found to enhance the proliferation and survivability of the transplanted MSCs”; section 3.2 “magnetic targeting of bone marrow MSCs in a mini-pig patella cartilage defect model using a bulk superconducting magnet system. … adhesion rate of the MSCs transplanted to the cartilage defect site was increased by the magnetic targeting… the adhesion rate of the transplanted MSCs was similar in four different magnetic flux densities and exposure times (0.6 T)… magnetic targeting promoted the accumulation of transplanted MSCs into the cartilage defect site and cartilage repair,”, section 3.3 “magnetic targeting of bone marrow MSCs, the optimum strength and time of exposure to the magnetic field for cell retention at the transplantation site and muscle repair were investigated using human bone marrow MSCs… optimum magnetic field conditions were examined using a combination of one of three magnetic flux densities …0.6 T”).
As per dependent Claim 4, the combination of Kamei and Yang as a whole as evidenced by NPL-Ochi further discloses method wherein, in the step of applying the magnetic field, a solenoid coil is used to generate the magnetic field (Applicants in at least [0003] admit recited subject-matter as prior art and disclose Japanese Patent Application Publication Tokukai No. 2007-151605 as evidence that the recited a solenoid coil is used to generate the magnetic field is well-known prior art as also evidenced by NPL-Ochi see at least [0006-0009], [0036] page fig. 1, 7-9. See NPL-Ochi at least [0006] “the magnetic induction device of the present invention is characterized in that it has a solenoid coil”; [0036] “a magnetic composite consisting of cells having the effect of promoting cell division and minute magnetic bodies is injected into the synovial fluid in the joint of the knee 6 of a patient 5. The leg 7 of the patient 5 is inserted into the through hole 13 of the casing 11 … a magnetic field is generated by adjusting … the solenoid coil so as to guide the magnetic composite to … the area affected by osteochondritis… magnetic composite may be injected into synovial fluid in the joint while a coil current is applied to the solenoid coil to generate a magnetic field”).
Response to Amendment
According to the Amendment, filed 09/01/2025, the status of the claims is as follows:
Claim 1 is currently amended; and
Claims 2-4 are previously presented.
By the current amendment, as a result, claims 1-4 are now pending in this application and are being examined on the merits.
Response to Arguments
Issues Raised and Arguments/Remarks to Rejections Based On Prior Art presented on Pages 3-4 of Applicant’s Amendment dated 09/01/2025 where Applicant’s’ remarks inter alia that:
35 U.S.C. § 103 Rejection of the Amended Independent Claim 1-4
[A] Claims 1-4 were rejected under 35 U.S.C. §103 as being obvious in light of Kamei in combination with Yang and NPL-Ochi. The Applicant respectfully disagrees.
[B] However, for purposes of expediting prosecution, Claim 1 is now further amended to additionally recite, "...wherein the amount of the iron oxide represents the amount prior to administration into the cartilage injury site..." Support for this amendment is located throughout application (see, e.g., paragraphs 10, 17-21, 25, 28-31, 35, 57-58, and 63-67).
[C] Indeed, Yang does disclose cells with an iron content of "58 ± 17 pg Fe/cell"(1[0197]). However, according to Yang, iron-containing magnetic cells are not injected into the body. In contrast, the present invention relates to the injection of cells already contain iron; thus, the underlying purpose is fundamentally different.
[D] Neither Yang nor Kamei, alone in combination, teach all of the limitations recited in amended Claim 1.
Applicant’s arguments [A-D] above, with respect to the above claim limitation in amended independent Claim 1 have been fully considered but were not found persuasive for the following reasons:
With respect Applicant’s arguments [B] above, with respect to the recitation “wherein the amount of the iron oxide represents the amount prior to administration into the cartilage injury site”, Examiner notes that the combination of prior art, Kamei and Yang, as a whole discloses this limitation as now explicitly, positively and specifically recited by the Applicants. First, here, the limitation is being broadly yet reasonably interpreted as if reciting wherein the amount of the iron oxide represents the amount within the magnetized cell prior to administration into the cartilage injury site. Additionally, more specifically, Kamei in abstract, section 2 for example discloses the magnetized cell containing iron, derived from the iron oxide, in a therapeutically efficacious or effective amount per cell ( i.e. that does not impair a function of the magnetized cell and prevents any adverse health event from occurring in an animal into which the magnetized cell has been introduced), wherein the therapeutically effective amount of the iron oxide represents the amount within the magnetized cell prior to administration into the cartilage injury site (See at least Kamei abstract “Magnetic targeting has been applied for the transplantation of bone marrow mesenchymal stem cells … pluripotent stem cells, and for the regeneration of bone, cartilage, skeletal muscles, and the spinal cord. It enhances the accumulation and adhesion of locally injected cells, resulting in the improvement of tissue regeneration) as recited. Also see Kamei abstract “Magnetic targeting is a cell delivery system using the magnetic labeling of cells and the magnetic field… developed for …Cell transplantation with both minimal invasiveness and high efficacy on tissue repair … Magnetic targeting has been applied for the transplantation of bone marrow mesenchymal stem cells … pluripotent stem cells, and for the regeneration of bone, cartilage, skeletal muscles, and the spinal cord. It enhances the accumulation and adhesion of locally injected cells, resulting in the improvement of tissue regeneration. It is a promising technique for minimally invasive and effective cell transplantation therapy”; section 1 page 116 “magnetically labeled cells were locally injected into the body and controlled using an external magnetic field”; section 2 “Ferucarbotran was used for the magnetic labeling of bone marrow MSCs”. Further, Yang in at least [0196-0199] for example discloses magnetized cell containing iron, derived from the iron oxide, in an amount of 58+/-17 pg Fe/cell which is in an amount of 35 or more picograms (pg)/cell with the amount of the iron oxide representing the amount within the magnetized cell prior to therapeutic use such as targeted drug delivery. See at least Yang [0196] “ability of a nanocarrier to internalize into cells can augment its drug delivery performance”; [0197] “after nanoparticle incubation with … cells … enhanced cellular uptake of GPEI … the extent of cellular uptake was 138-fold higher (p=0.013, FIG. 15) for GPEI (58+/-17 pg Fe/cell) …Despite the significantly enhanced cellular uptake, … nanoparticle surface did not increase cell toxicity”; [0198-0199] “Magnetic Targeting of GPEI … feasibility of delivering GPEI to tumors …via magnetic targeting”. Thus, the combination of prior art, Kamei and Yang, as a whole discloses the limitation “wherein the amount of the iron oxide represents the amount prior to administration into the cartilage injury site” as now explicitly, positively and specifically recited by the Applicants.
With respect to Applicant’s arguments [C] above, in response to applicant's arguments against the references individually as done here, Examiner notes that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). As noted by Applicants, indeed, Yang was brought in for disclosing the specific iron concentration i.e. the magnetized cell containing iron be in an amount of 35 or more picograms (pg)/cell. As detailed above Kamei was applied as disclosing direct injection of the magnetized cell into a cartilage injury site. Thus, Examination asserts that the combination of prior art, Kamei and Yang, as a whole was detailed as disclosing all the limitations as now explicitly, positively and specifically recited by the Applicants and not that all the limitations are individually disclosed by the prior art as incorrectly argued by the Applicants. Lastly, in response to Applicant’s argument “according to Yang, iron-containing magnetic cells are not injected into the body”, Examiner notes that Yang in [0198-0199] detail “Magnetic Targeting of GPEI with Intravenous Administration” i.e. iron-containing magnetic cells are not injected intravenously into the body.
Examiner suggest amending the claims to explicitly, positively and specifically include such features which the Applicant consider are critical, patentably novel, non-obvious and distinguish over prior art.
For the above reasons, the 35 U.S.C. § 103 rejection of claims 1 is being maintained at this time as claim 1 as now explicitly, positively and specifically recited is rejectable over the combination of Kamei and Yang as a whole . Please also cross-reference detailed claim 1 interpretation, claim limitation mapping to prior art disclosed features and method steps and detailed explanations above.
Conclusion
Applicant’s’ amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee 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 date of this final action.
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/SUNITA REDDY/Primary Examiner, Art Unit 3791