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 .
Preliminary Amendment
Preliminary Amendment dated 11/14/2022 has been formally entered and claims 1-7 and 9-21 submitted with Preliminary Amendment dated 11/14/2022 are being examined on the merits.
Specification
The disclosure is objected to because of the following informalities:
“…the method of the invention is demonstrated effective using cultured cells and tumor-mimicking 3D organoids…” in page 11 lines 16-17 needs to be corrected. A suggested correction is --the method of the invention is demonstrated in terms of effectiveness using cultured cells and tumor-mimicking 3D organoids—or -- the method of the invention is effectively demonstrated [[effective]] using cultured cells and tumor-mimicking 3D organoids --.
Appropriate correction is required.
Claim Objections
Following claims are objected to because of the following informalities:
Claim 13 include acronyms/abbreviations. At least first occurrence of each acronym/abbreviation should be spelled out in full.
Claim 20 "the magnetic particles " in line 2 should read -- the magnetic nanoparticle -- in order to maintain consistent terminology with its antecedent at line 2 of Claim 1.
Claim 3 line 1 “A method for killing tumor cells in a subject, comprising;” needs to be corrected to --A method for killing tumor cells in a subject, comprising[[;]]:--.
Appropriate correction is required.
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 2-3, 10, 11, 13-21 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.
Each of claims 2-3 recite “effective amount” which renders this claim unclear. More specifically, the term “effective” in claim 2-3 is a subjective relative term which renders the claim indefinite. The term “effective” is not defined by the claim, and thus one of ordinary skill in the art would not be reasonably apprised of the scope of the invention i.e. is it therapeutically effective, is it effective in terms of not causing any adverse effects, is it effective in terms of being under toxicity thresholds or effective in terms of magnetization capability or some other.
Claim 3 in line 3 recites “the solid tumor”. There is insufficient antecedent basis for this limitation in the claim.
Claim 14 in line 1, each of claim 17-18 in line 1 recites “the cells”. There is insufficient antecedent basis for this limitation in the claim.
Claim 16 in line 1 recites “the subject”. There is insufficient antecedent basis for this limitation in the claim.
Claim 20 in line 2 recites “the magnetic particles”. There is insufficient antecedent basis for this limitation in the claim.
Each of claim 10 in line 2 and claim 21 in line 2 recites “the magnetic nanoparticles”. There is insufficient antecedent basis for this limitation in the claim.
Claim 14 in line 2 recites “parallel magnetic field” which renders this claim unclear. More specifically, it is unclear as to whether claim 14 line 2 “parallel magnetic field” is the same as, different than or in addition to “parallel magnetic field” recited in claim 1 line 3.
Claim 13 in line 2 recites “about” which renders the claim unclear. The term " about" here in claim13 is a relative range term which renders the claim indefinite. The term " about" is not defined by the claim with respect to the boundary i.e. unclear as to whether the term “about” refers herein to a value of +/-0.25% of the defined measure; or the term “about” refers herein to a value of +/-0.10% of the defined measure or some other value or percentage. Additionally, the specification does not provide a standard for ascertaining the requisite degree/range, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Dependent claims 11, 15, 19 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 11, 15, 19 are also rejected under 35 U.S.C. 112(b) based on their direct/indirect dependency on their respective base claims.
Claim Interpretation
Claims terms where relevant are being interpreted in light of definitions enumerated in instant application specification page 5 lines 22-page 6 line 2, page 6.
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.
Claims 1-7, 9-19, 21 are rejected under 35 U.S.C. 103 as being unpatentable over Slade et al. (Pub. No.: US 20070197953 A1, hereinafter referred to as "Slade") in view of Wong et al. (Pub: Wong W, Gan WL, Teo YK, Lew WS. Interplay of cell death signaling pathways mediated by alternating magnetic field gradient. Cell Death Discov. 2018 Apr 27;4:49, hereinafter referred to as “Wong”).
As per independent Claim 1, Slade discloses a method for inducing cell death (Slade in at least abstract, fig. 4, [0001], [0013-0017], [0019], [0026-0027], [0029-0035], [0067], [0076-0082], [0084-0091], [0093], [0097-0098], [0104-0106], [0109-0112] for example discloses relevant subject-matter. More specifically, Slade in at least abstract, [0014-0017], [0089], [0091], [0097] for example discloses a method of inducing cell death. See at least Slade [0014] “magnetic particles are used in the manufacture of a medicament for administration to a patient to treat a disorder associated with a cellular or tissue structure, or the accumulation of an undesirable biological material, wherein the or each particle … localise at or within the structure or material, and wherein the treatment is … carried out by applying a magnetic field, to … disrupt the structure or material”; [0015] “a method for disrupting a material”; [0089]” magnetic particles may be used to target and disrupt any suitable material. Disruption may be carried out for a therapeutic … purpose and targeting may be carried out in vitro or in vivo… material is a biological material… a mammalian cellular or tissue structure…particles will localise at the surface of the cell membrane or may be internalised, prior to the application of the magnetic field. Once activated by the magnetic field, the particles disrupt internal or external cellular structures, resulting in cell death”; [0091] “material may also be a cell comprising an infectious agent”), comprising:
(a) contacting a cell with a magnetic nanoparticle (Slade in at least [0014-0016], [0089], [0093] for example discloses contacting a cell with a magnetic nanoparticle. See at least Slade [0014] “each particle is preferably adapted to localise at or within the structure or material”; [0016] “localising one or more magnetic particles at or within the material”; [0089] “particles will localise at the surface of the cell membrane or may be internalised, prior to the application of the magnetic field”;[0093] “particles may be administered to a patient in a variety of ways. … parenteral administration, i.e. subcutaneous, intramuscular or intravenous administration”);
(b) after a pre-determined period of time, subjecting the cell to a parallel magnetic field for a time sufficient to achieve cell death (Slade in at least fig. 4, [0014-0016], [0033-0035], [0089], [0104] for example discloses after a pre-determined period of time, subjecting the cell to a parallel magnetic field for a time sufficient to achieve cell death. See at least [0014] “treatment is intended to be carried out by applying a magnetic field, to …disrupt the structure or material”; [0016-0017] “(i) localising one or more magnetic particles at or within the material; and …. (ii) applying a magnetic field to the or each magnetic particle, to induce …disrupt the material”; [0089]” particles will localise at the surface of the cell membrane or may be internalised, prior to the application of the magnetic field. Once activated by the magnetic field, the particles disrupt internal or external cellular structures, resulting in cell death.” ).
Slade does not explicitly disclose magnetic field is a parallel magnetic field as interpreted in light of explicit and specific definition in instant application specification as-filed page 5 line 28- page 6 line 2
However, in an analogous cell death inducing field of endeavor, Wong discloses a method for inducing cell death (Wong in at least abstract, fig. 1, page 1-2, page 7 for example discloses relevant subject-matter. WONG in abstract, page 1-2, page 7 for example discloses method for inducing cell death. See at least Wong abstract “magneto-actuation of magnetic nanoparticles (MNPs) to induce different cell death … apoptosis and necrosis… MNPs were able to apply sufficient force on the cell to trigger the intracellular pathway for cell apoptosis, thus significantly reducing the cell viability”; page 1 “magnetic nanoparticles (MNPs) have rapidly gained traction in the biomedical fields … MNPs with engineered magnetic properties and high biocompatibility have been shown to be a promising candidate for cancer treatment”; page 2 “the force exerted by MNPs with different aspect ratios under both uniform and non-uniform magnetic fields. The magnetic field generates a magnetic torque on the MNPs, which in turns exerts a force onto … cells inducing apoptosis or necrosis.”), comprising
subjecting the magnetic nanoparticle associated cell to a parallel magnetic field for a time sufficient to achieve cell death (Wong in at least abstract, fig. 1, page 2, page 7 for example discloses subjecting the magnetic nanoparticle associated cell to a parallel magnetic field for a time sufficient to achieve cell death. See at least Wong page 2 “A pair of electromagnetic coils was employed to create a vertically oriented magnetic field with two configurations…”; page 7 “control the initiation of cell apoptosis or necrosis by magneto-actuation of MNPs. The force exerted by low aspect ratio MNPs on the cells is sufficient to induce cell apoptosis in a uniform magnetic field or FG. By introducing an AFG, the force exerted from oscillations of the MNPs is sufficient to physically rupture the cell membrane, leading to necrosis… this remote magneto-actuation approach is … inhibit cancer cell proliferation by the induction of apoptosis or necrosis” ).
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 magnetic field used in the method for inducing cell death as taught by Slade, such that the magnetic field is a parallel magnetic field, as taught by Wong. A person of ordinary skill would have been motivated to do so, with a reasonable expectation of success, for the advantage of deriving a non-invasive and highly effective treatment method that can inhibit cancer cell proliferation by the induction of apoptosis or necrosis via use of parallel magnetic field (Wong, page 7, fig. 1).
As per independent Claim 2, Slade discloses a method for inducing cell death in a subject (Slade in at least abstract, fig. 4, [0001], [0013-0017], [0019], [0026-0027], [0029-0035], [0067], [0076-0082], [0084-0091], [0093], [0097-0098], [0104-0106], [0109-0112] for example discloses relevant subject-matter. More specifically, Slade in at least abstract, [0014-0017], [0089], [0091], [0097-0098] for example discloses a method of inducing cell death. See at least Slade [0014] “magnetic particles are used in the manufacture of a medicament for administration to a patient to treat a disorder associated with a cellular or tissue structure, or the accumulation of an undesirable biological material, wherein the or each particle … localise at or within the structure or material, and wherein the treatment is … carried out by applying a magnetic field, to … disrupt the structure or material”; [0015] “a method for disrupting a material”; [0089]” magnetic particles may be used to target and disrupt any suitable material. Disruption may be carried out for a therapeutic … purpose and targeting may be carried out … in vivo… material is a biological material… a mammalian cellular or tissue structure…particles will localise at the surface of the cell membrane or may be internalised, prior to the application of the magnetic field. Once activated by the magnetic field, the particles disrupt internal or external cellular structures, resulting in cell death”; [0091] “material may also be a cell comprising an infectious agent”; [0098] “treatment of cancer is the potential ability to treat all malignant cells in a patient's body”), comprising:
(a) administering an effective amount of magnetic nanoparticles to a subject (Slade in at least [0014-0016], [0089], [0093] for example discloses administering an effective amount of magnetic nanoparticles to a subject . See at least Slade [0014] “each particle is preferably adapted to localise at or within the structure or material”; [0016] “localising one or more magnetic particles at or within the material”; [0089] “particles will localise at the surface of the cell membrane or may be internalised, prior to the application of the magnetic field”; [0093] “particles may be administered to a patient in a variety of ways. … parenteral administration, i.e. subcutaneous, intramuscular or intravenous administration”);
(b) after a pre-determined period of time, subjecting the subject to a localized parallel magnetic field for a time sufficient to achieve cell death (Slade in at least fig. 4, [0014-0016], [0033-0035], [0089], [0104] for example discloses after a pre-determined period of time, subjecting the subject to a localized magnetic field for a time sufficient to achieve cell death. See at least [0014] “treatment is intended to be carried out by applying a magnetic field, to …disrupt the structure or material”; [0016-0017] “(i) localising one or more magnetic particles at or within the material; and …. (ii) applying a magnetic field to the or each magnetic particle, to induce …disrupt the material”; [0089] “magnetic particles may be used to target and disrupt any suitable material. Disruption may be carried out for a therapeutic … purpose and targeting may be carried out … in vivo… material is a biological material, e.g. an aberrant …mammalian cellular or tissue structure…magnetic particles of the invention are particularly suitable for the treatment of a tumour which can be targeted …particles will localise at the surface of the cell membrane or may be internalised, prior to the application of the magnetic field. Once activated by the magnetic field, the particles disrupt internal or external cellular structures”).
Slade does not explicitly disclose magnetic field is a parallel magnetic field as interpreted in light of explicit and specific definition in instant application specification as-filed page 5 line 28- page 6 line 2
However, in an analogous cell death inducing field of endeavor, Wong discloses method for inducing cell death (Wong in at least abstract, fig. 1, page 1-2, page 7 for example discloses relevant subject-matter. WONG in abstract, page 1-2, page 7 for example discloses method for inducing cell death. See at least Wong abstract, page 1 “magneto-actuation of magnetic nanoparticles (MNPs) to induce different cell death … apoptosis and necrosis… MNPs were able to apply sufficient force on the cell to trigger the intracellular pathway for cell apoptosis, thus significantly reducing the cell viability”; page 1 “magnetic nanoparticles (MNPs) have rapidly gained traction in the biomedical fields … MNPs with engineered magnetic properties and high biocompatibility have been shown to be a promising candidate for cancer treatment”; page 2 “the force exerted by MNPs with different aspect ratios under both uniform and non-uniform magnetic fields. The magnetic field generates a magnetic torque on the MNPs, which in turns exerts a force onto … cells inducing apoptosis or necrosis.”), comprising
subjecting the magnetic nanoparticle associated cell to a parallel magnetic field for a time sufficient to achieve cell death (Wong in at least abstract, fig. 1, page 2, page 7 for example discloses subjecting the magnetic nanoparticle associated cell to a parallel magnetic field for a time sufficient to achieve cell death. See at least Wong page 2 “A pair of electromagnetic coils was employed to create a vertically oriented magnetic field with two configurations…”; page 7 “control the initiation of cell apoptosis or necrosis by magneto-actuation of MNPs. The force exerted by low aspect ratio MNPs on the cells is sufficient to induce cell apoptosis in a uniform magnetic field or FG. By introducing an AFG, the force exerted from oscillations of the MNPs is sufficient to physically rupture the cell membrane, leading to necrosis… this remote magneto-actuation approach is … inhibit cancer cell proliferation by the induction of apoptosis or necrosis” ).
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 magnetic field used in the method for inducing cell death as taught by Slade, such that the magnetic field is a parallel magnetic field, as taught by Wong. A person of ordinary skill would have been motivated to do so, with a reasonable expectation of success, for the advantage of deriving a non-invasive and highly effective treatment method that can inhibit cancer cell proliferation by the induction of apoptosis or necrosis via use of parallel magnetic field (Wong, page 7, fig. 1).
As per independent Claim 3, Slade discloses a method for killing tumor cells in a subject (Slade in at least abstract, fig. 4, [0001], [0013-0017], [0019], [0026-0027], [0029-0035], [0067], [0076-0082], [0084-0091], [0093], [0097-0098], [0104-0106], [0109-0112] for example discloses relevant subject-matter. More specifically, Slade in at least abstract, [0014-0017], [0089], [0090], [0097-0098] for example discloses method for killing tumor cells in a subject. See at least Slade [0014] “magnetic particles are used in the manufacture of a medicament for administration to a patient to treat a disorder associated with a cellular or tissue structure, or the accumulation of an undesirable biological material, wherein the or each particle … localise at or within the structure or material, and wherein the treatment is … carried out by applying a magnetic field, to … disrupt the structure or material”; [0015] “a method for disrupting a material”; [0089] “magnetic particles may be used to target and disrupt any suitable material. Disruption may be carried out for a therapeutic … purpose and targeting may be carried out … in vivo… material is a biological material, e.g. an aberrant …mammalian cellular or tissue structure…magnetic particles of the invention are particularly suitable for the treatment of a tumour which can be targeted …particles will localise at the surface of the cell membrane or may be internalised, prior to the application of the magnetic field. Once activated by the magnetic field, the particles disrupt internal or external cellular structures, resulting in cell death”; [0090] “Tumours which may be treated using the present invention will be apparent to the skilled person. The tumours may be solid or liquid tumours (e.g. leukaemia), and may be macro or micro tumours”;), comprising;
(a) administering an effective amount of magnetic nanoparticles to a subject (Slade in at least [0014-0016], [0089], [0093] for example discloses administering an effective amount of magnetic nanoparticles to a subject. See at least Slade [0014] “each particle is preferably adapted to localise at or within the structure or material”; [0016] “localising one or more magnetic particles at or within the material”; [0089] “particles will localise at the surface of the cell membrane or may be internalised, prior to the application of the magnetic field”; [0093] “particles may be administered to a patient in a variety of ways. … parenteral administration, i.e. subcutaneous, intramuscular or intravenous administration”);
(b) after a pre-determined period of time, subjecting the solid tumor to a localized parallel magnetic field for a time sufficient to achieve cell death and decrease the size of the tumor (Slade in at least fig. 4, [0014-0016], [0033-0035], [0089-0090], [0104] for example discloses after a pre-determined period of time, subjecting the solid tumor to a localized magnetic field for a time sufficient to achieve cell death and decrease the size of the tumor. See at least Slade [0016-0017] “(i) localising one or more magnetic particles at or within the material; and …. (ii) applying a magnetic field to the or each magnetic particle, to induce …disrupt the material”; [0089] “magnetic particles may be used to target and disrupt any suitable material. Disruption may be carried out for a therapeutic … purpose and targeting may be carried out … in vivo… material is a biological material, e.g. an aberrant …mammalian cellular or tissue structure…magnetic particles of the invention are particularly suitable for the treatment of a tumour which can be targeted …particles will localise at the surface of the cell membrane or may be internalised, prior to the application of the magnetic field. Once activated by the magnetic field, the particles disrupt internal or external cellular structures, resulting in cell death”; [0098] “treatment of cancer is the potential ability to treat all malignant cells in a patient's body… in the main tumour””).
Slade does not explicitly disclose magnetic field is a parallel magnetic field as interpreted in light of explicit and specific definition in instant application specification as-filed page 5 line 28- page 6 line 2
However, in an analogous tumor cell killing field of endeavor, Wong discloses method for killing tumor cells (Wong in at least abstract, fig. 1, page 2, page 7 for example discloses relevant subject-matter. WONG in abstract, page 1-2, page 7 for example discloses method for killing tumor cells. See at least Wong abstract “magneto-actuation of magnetic nanoparticles (MNPs) to induce different cell death … apoptosis and necrosis… MNPs were able to apply sufficient force on the cell to trigger the intracellular pathway for cell apoptosis, thus significantly reducing the cell viability”; page 1 “magnetic nanoparticles (MNPs) have rapidly gained traction in the biomedical fields … MNPs with engineered magnetic properties and high biocompatibility have been shown to be a promising candidate for cancer treatment”; page 2 “the force exerted by MNPs with different aspect ratios under both uniform and non-uniform magnetic fields. The magnetic field generates a magnetic torque on the MNPs, which in turns exerts a force onto … cells inducing apoptosis or necrosis.”), comprising
subjecting the magnetic nanoparticle associated cell to a parallel magnetic field for a time sufficient to achieve cell death (Wong in at least abstract, fig. 1, page 2, page 7 for example discloses subjecting the magnetic nanoparticle associated cell to a parallel magnetic field for a time sufficient to achieve cell death. See at least Wong page 2 “pair of electromagnetic coils was employed to create a vertically oriented magnetic field with two configurations…”; page 7 “control the initiation of cell apoptosis or necrosis by magneto-actuation of MNPs. The force exerted by low aspect ratio MNPs on the cells is sufficient to induce cell apoptosis in a uniform magnetic field or FG. By introducing an AFG, the force exerted from oscillations of the MNPs is sufficient to physically rupture the cell membrane, leading to necrosis… this remote magneto-actuation approach is … inhibit cancer cell proliferation by the induction of apoptosis or necrosis” ).
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 magnetic field used in the method for killing tumor cells in a subject as taught by Slade, such that the magnetic field is a parallel magnetic field, as taught by Wong. A person of ordinary skill would have been motivated to do so, with a reasonable expectation of success, for the advantage of deriving a non-invasive and highly effective treatment method that can inhibit cancer cell proliferation by the induction of apoptosis or necrosis via use of parallel magnetic field (Wong, page 7, fig. 1).
As per dependent Claim 4, the combination of Slade and Wong as a whole further discloses method wherein the magnetic nanoparticle is an iron oxide nanoparticle (Slade in at least [0067] discloses magnetic nanoparticle is an iron oxide nanoparticle which well-known subject-matter is also evidentiarily collaborated by Slade in [0005]. See at least Slade [0005] “nanoparticles are prepared from iron oxide, e.g. Fe.sub.2O.sub.3,”; [0067] “particles, made from…ferrous and ferric oxide (Fe.sub.2O.sub.3 and Fe.sub.3O.sub.4, ie: magnetite)).
As per dependent Claim 5, the combination of Slade and Wong as a whole further discloses method, wherein the magnetic nanoparticle is a dextran- or polyethylene glycol-coated magnetic nanoparticle (Slade in at least [0076] for example discloses the magnetic nanoparticle is a dextran- or polyethylene glycol-coated magnetic nanoparticle. See at least Slade [0076] “particles may be prepared with a coating of a bio-compatible material, which is biologically inert… polyethylene glycol… dextrin… and naturally occurring proteins such as albumin.”).
As per dependent Claim 6, the combination of Slade and Wong as a whole further discloses method wherein the magnetic nanoparticle further comprises a targeting agent for selective cell targeting (Slade in at least [0077-0082], [0089], [0098] for example discloses magnetic nanoparticle further comprises a targeting agent for selective cell targeting. See at least [0077] “particles may be localised at a target site using any convenient means, including the use of a targeting moiety. The targeting moiety may be any suitable molecule that permits selective targeting to the target site… include antibodies and receptor ligands, e.g. hormones”; [0089] “the magnetic particles of the invention are particularly suitable for the treatment of a tumour which can be targeted due to the expression of specific tumour-associated antigens”; [0098] “treatment of cancer is the potential ability to treat all malignant cells in a patient's body, not just those in the main tumour. This is a benefit of the antibody targeting technology, which targets cells having a particular characteristic in any tissue that is reached by the patient's circulatory system”).
As per dependent Claim 7, the combination of Slade and Wong as a whole further discloses method wherein the magnetic nanoparticle is a magnetic resonance imaging agent (Slade in at least Slade [0110-0111] for example discloses magnetic nanoparticle is a magnetic resonance imaging agent. See at least Slade [0110] “MRI type magnets can be used and in this case, it is feasible that an MR image could be obtained at various stages during the process, and also before and after the process, of the structure in the working volume”; [0111] “MRI system to image the patient after administration of the nanoparticles and before magnetic therapy, to ensure correct location of the nanoparticles, which will appear in a suitably constructed MR imaging sequence due to their strong magnetic properties”).
As per dependent Claim 9, the combination of Slade and Wong as a whole further discloses method wherein the magnetic nanoparticle is an aqueous colloid of superparamagnetic iron oxide coated with polyglucose sorbitol carboxymethylether (Slade disclosure in [0049], [0076], [0093] for example makes the magnetic nanoparticle is an aqueous colloid of superparamagnetic iron oxide coated with polyglucose sorbitol carboxymethylether as recited obvious. See at least Slade [0049] “the particle displays superparamagnetic behaviour”; [0076] “particles may be prepared with a coating of a bio-compatible material, which is biologically inert. Examples include polyethylene glycol… dextrin…Additional compounds include polyglutaric acid, carbohydrates and naturally occurring proteins such as albumin”; [0093] “particles are formulated in compositions for parenteral administration…compositions for parenteral administration which comprise the particles dispersed in a suitable carrier material, preferably an aqueous carrier material.”).
As per dependent Claim 10, the combination of Slade and Wong as a whole further discloses method wherein the magnetic nanoparticles are administered by local injection, subcutaneous injection, and intravenous injection (Slade in [0093] for example discloses magnetic nanoparticles are administered by local injection, subcutaneous injection, and intravenous injection. See at least Slade [0093] “particles may be administered to a patient in a variety of ways… parenteral administration, i.e. subcutaneous, intramuscular or intravenous administration”).
As per dependent Claim 11, the combination of Slade and Wong as a whole further discloses method wherein the magnetic nanoparticles are administered by injection into the solid tumor (Slade in at least [0078-0079], [0093] for example discloses the magnetic nanoparticles are administered by injection some of which ending up in the solid tumor. See at least Slade [0078-0079] “polymers achieve site-specific passive capture through the enhanced permeability and retention (EPR) effect…In addition to the tumour angiogenesis (hypervasculature) and irregular and incompleteness of vascular networks, the attendant lack of lymphatic drainage promotes accumulation of macromolecules that extravasate. This effect is observed in many solid tumours for macromolecular agents and lipids… Suitable polymers with which have been used to target tumours by the EPR effect, include polyethylene glycol, ethyleneglycol copolymers, dextrin, polymers and copolymers of hydroxyalkyl(meth)acrylamide, for instance, hydroxypropylmethacrylamide, and copolymers of styrene and maleic anhydride.”; [0093] “particles may be administered to a patient in a variety of ways… parenteral administration, i.e. subcutaneous, intramuscular or intravenous administration”).
As per dependent Claim 12, the combination of Slade and Wong as a whole further discloses method wherein the parallel magnetic field is provided by a first and a second permanent magnet(Slade in [0104] discloses magnetic field is provided by permanent magnet while Wong, fig. 1, page 2 discloses parallel magnetic field is provided by a first and a second magnet. Thus, combination of applied art as a whole discloses subject-matter as now explicitly, positively and specifically recited by the Applicants. See at least Slade [0104] “magnet assembly made from prismatic blocks of rare-earth permanent magnet material 15 having fixed magnetization … generates a fairly uniform magnetic field, directed as indicated by an arrow 13, across the bore 11 of a support structure 16 in which a patient 12 is inserted… Field strengths of up to 0.2 T are envisaged with a slew rate of up to or about 3 T/sec”; See at least Wong page 2 “pair of electromagnetic coils was employed to create a vertically oriented magnetic field with two configurations…”;).
As per dependent Claim 13, the combination of Slade and Wong as a whole further discloses method wherein the parallel magnetic field has a field strength up to about 3 T (Slade in at least [0104-0105] for example discloses wherein the magnetic field has a field strength up to about 3 T while Wong discloses use of parallel magnetic field. Thus, combination of applied art as a whole discloses subject-matter as now explicitly, positively and specifically recited by the Applicants. See at least Slade [0104] “magnet assembly made from prismatic blocks of rare-earth permanent magnet material 15 having fixed magnetization … generates a fairly uniform magnetic field, directed as indicated by an arrow 13, across the bore 11 of a support structure 16 in which a patient 12 is inserted… Field strengths of up to 0.2 T are envisaged with a slew rate of up to or about 3 T/sec”; [0105] “a set of coils 20, 21 …electromagnets … Magnetic field strengths up to about 0.5 T are possible with a slew rate in the range of 1-5 T/sec”).
As per dependent Claim 14, the combination of Slade and Wong as a whole further discloses method wherein the cells to be treated are positioned within parallel magnetic field provided by a first and a second permanent magnet (Slade in [0104] discloses cells to be treated are positioned within magnetic field provided by a first and a second magnet while Wong, fig. 1, page 2 discloses cells to be treated are positioned within parallel magnetic field provided by a first and a second magnet. Thus, combination of applied art as a whole discloses subject-matter as now explicitly, positively and specifically recited by the Applicants. See at least Slade [0104] “magnet assembly made from prismatic blocks of rare-earth permanent magnet material 15 having fixed magnetization … generates a fairly uniform magnetic field, directed as indicated by an arrow 13, across the bore 11 of a support structure 16 in which a patient 12 is inserted… Field strengths of up to 0.2 T are envisaged with a slew rate of up to or about 3 T/sec”; See at least Wong page 2 “pair of electromagnetic coils was employed to create a vertically oriented magnetic field with two configurations…”;).
As per dependent Claim 15, the combination of Slade and Wong as a whole further discloses method wherein the parallel magnetic field provided by a first and a second permanent magnet is positioned on opposite sides of the solid tumor(Slade in [0019], [0090], [0104] discloses magnetic field provided by a permanent magnet is positioned on opposite sides of the solid tumor while Wong, fig. 1, page 2 discloses parallel magnetic field provided by a first and a second t magnet is positioned on opposite sides of the target cells/tissue. Thus, combination of applied art as a whole discloses subject-matter as now explicitly, positively and specifically recited by the Applicants. See at least Slade See at least Slade [0019] “apparatus for disrupting a material, including a cellular or tissue structure, comprises a magnetic field generator for generating a magnetic field in a working volume; one or more magnetic particles localised at or in the material in the working volume”; [0089] “magnetic particles ….for the treatment of a tumour …particles will localise at the surface of the cell membrane or may be internalised, prior to the application of the magnetic field. Once activated by the magnetic field, the particles disrupt internal or external cellular structures, resulting in cell death”; [0090] “Tumours which may be treated …solid … tumours…and may be macro or micro tumours”;[0104] “magnet assembly made from prismatic blocks of rare-earth permanent magnet material 15 having fixed magnetization … generates a fairly uniform magnetic field, directed as indicated by an arrow 13, across the bore 11 of a support structure 16 in which a patient 12 is inserted… Field strengths of up to 0.2 T are envisaged with a slew rate of up to or about 3 T/sec”; See at least Wong page 2 “pair of electromagnetic coils was employed to create a vertically oriented magnetic field with two configurations…”).
As per dependent Claim 16, the combination of Slade and Wong as a whole further discloses method the subject's liver is shielded from the magnetic field (Slade in at least [0077-0079], [0081] [0089], [0097] and Wong in fig. 1 for example at least make obvious subject-matter as now explicitly, positively and specifically recited by the Applicants. See at least Slade [0089] “magnetic particles may be used to target and disrupt any suitable material. Disruption may be carried out for a therapeutic … purpose and targeting may be carried out in vitro… magnetic particles of the invention are particularly suitable for the treatment of a tumour which can be targeted due to the expression of specific tumour-associated antigens. The particles will localise at the surface of the cell membrane or may be internalised, prior to the application of the magnetic field. Once activated by the magnetic field, the particles disrupt internal or external cellular structures, resulting in cell death. The particles are then removed from the body by normal excretory mechanisms such as macrophage action.”).
As per dependent Claim 17, the combination of Slade and Wong as a whole further discloses method wherein the cells are cancer cells (Slade in at least [0098] “treatment of cancer is the potential ability to treat all malignant cells in a patient's body”).
As per dependent Claim 18, the combination of Slade and Wong as a whole further discloses method wherein the cells are non-cancer cells (Slade in at least [0091] “material may also be a cell comprising an infectious agent”).
As per dependent Claim 19, the combination of Slade and Wong as a whole further discloses method wherein the solid tumor is a cancerous solid tumor (Slade in at least [0090-0091] for example discloses solid tumor is a cancerous solid tumor . See at least Slade [0089] “magnetic particles ….for the treatment of a tumour …particles will localise at the surface of the cell membrane or may be internalised, prior to the application of the magnetic field. Once activated by the magnetic field, the particles disrupt internal or external cellular structures, resulting in cell death”; [0090] “Tumours which may be treated …solid … tumours…and may be macro or micro tumours”).
As per dependent Claim 21, the combination of Slade and Wong as a whole further discloses method wherein the parallel magnetic field induces intracellular self assembly of the magnetic nanoparticles resulting in cell death (Slade in at least abstract, [0013-0014], [0048], [0089], [0102] for example discloses the magnetic field induces intracellular self assembly of the magnetic nanoparticles resulting in cell death while Wong in at least fig. 1 discloses use of parallel magnetic field. Thus, combination of applied art as a whole discloses subject-matter as now explicitly, positively and specifically recited by the Applicants. See at least Slade abstract “Magnetic particles are used in therapeutic applications to disrupt a biological material…By applying a magnetic field, the magnetic particles are induced to rotate when localised at the target biological material, thereby disrupting the material.”; [0013] “exposing selected magnetic particles …. magnetic field, thereby causing them to rotate and align with the applied field”; [0048] “In the presence of an external magnetic field the nanoparticle's magnetization will try to align with the field”; [0089] “magnetic particles may be used to target and disrupt any suitable material… Once activated by the magnetic field, the particles disrupt internal or external cellular structures, resulting in cell death”; [0102] “When the field is on, particles will attempt to rotate to align with the field… rotating field will cause the particles to rotate to follow the field direction, thus maximising chances for cell damage”).
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Slade in view of Wong and further in view of Lunov et al. (Pub.: Lunov O, Uzhytchak M, Smolková B, Lunova M, Jirsa M, Dempsey NM, Dias AL, Bonfim M, Hof M, Jurkiewicz P, Petrenko Y, Kubinová Š, Dejneka A. Remote Actuation of Apoptosis in Liver Cancer Cells via Magneto-Mechanical Modulation of Iron Oxide Nanoparticles. Cancers (Basel). 2019 Nov 26;11(12):1873, hereinafter referred to as “Lunov”).
As per dependent Claim 20, the combination of Slade and Wong as a whole discloses method of claim 1 (see claim 1)
The combination of Slade and Wong as a whole does not explicitly disclose or require that the magnetic particles be endocytosed into the cell.
However, in an analogous cell death inducing field of endeavor, Lunov discloses a method for inducing cell death (Lunov in at least abstract, page 1-3, page 15 for example discloses relevant subject-matter. More specifically, Lunov in at least abstract, page 15 discloses method for inducing cell death. See at least Lunov page 15 “Initiated by PMF, lysosomal leakage results in mitochondrial damage, which in turn leads to apoptosis execution and subsequent cell death… PMF treatment of SPION-loaded cells represents a fast, feasible and noninvasive tool to remotely control apoptosis”) wherein the magnetic particles are endocytosed into the cell (Lunov in at least abstract, page 1-3, page 15 for example discloses the magnetic particles are endocytosed into the cell. See at least abstract “Lysosome-activated apoptosis represents an alternative method of overcoming tumor resistance … lysosomal permeabilization in cancer cells via mechanical actuation of magnetic nanomaterials… used a noninvasive tool… magnetic system, which enabled remote activation of apoptosis in liver cancer cells…SPIONs retained in lysosomal compartments can be effectively actuated with a …magnetic field (PMF), resulting in lysosomal membrane permeabilization (LMP) in cancer cells…PMF treatment of SPION-loaded lysosomes can be utilized as a noninvasive tool to remotely induce apoptosis.”, page 2 “external application of magnetic fields as a simple, noninvasive tool to remotely control cell behavior via SPION mediated magneto-mechanical actuation… mechanical forces transmitted by magnetic nanoparticles under alternating or dynamic magnetic field treatment are large enough to disrupt lysosomal membranes, resulting in lysosomal membrane permeabilization (LMP) and the subsequent initiation of apoptotic cell death … treatment requires loading of cells with appropriate magnetic nanoparticles and subsequent application of external … magnetic fields”).
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 method for inducing cell death of Slade, as modified with Wong, by further including a step wherein the magnetic particles are endocytosed into the cell as disclosed by Lunov. A person of ordinary skill would have been motivated to do so, with a reasonable expectation of success, for the advantage deriving a fast, feasible and noninvasive tool and method to remotely induce and control apoptosis (Lunov, abstract, page 15)
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure and/or the claims.
Prior US 20110054237; US 20090287036; US 20160310718; US 20090299127; US 20090082611; US 20120283503; US 20060142749 for disclosing therapeutic methods that use magnetic nanoparticles directed by external magnetic fields to therapeutically effect or disrupt cancer cells.
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/SUNITA REDDY/Primary Examiner, Art Unit 3791