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 .
Information Disclosure Statement
The information disclosure statement(s) (IDS) filed 02/17/2026 has/have been considered by the Examiner.
Status of the Claims
Claims 1-2 and 4-19 are currently pending. Claims 1-2 and 4-19 are currently rejected.
Response to Arguments
Applicant's arguments filed 04/20/2026 have been fully considered but they are not persuasive.
In response to applicant's arguments against the references individually, 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 previously noted regarding Schmidt, Applicant argues that Schmidt does not teach releasing the chemotherapeutic and that one of ordinary skill in the art would not have been motivated to modify Schmidt with the teaching of Aznar that uses an alternating electric field to deliver the chemotherapeutic from the nanoparticle. However, as noted in the 103 rejection of claim 1 below, since Schmidt [0050] notes that the electric field activity is what synchronizes mitosis, and the synchronization makes the cells more uniformly susceptible to the chemotherapeutic, it would make sense to deliver the therapeutic while the synchronization effect is active in order to take maximum advantage of the synchronization effect. Additionally, triggering delivery of the therapeutic from the nanoparticle with an alternating electric field allows a clinician to better control the timing, and thus targeting, of the drug delivery. Since there would be benefits to the modification of Schmidt, one of ordinary skill in the art would have been motivated to modify the method of Schmidt. Although the chemotherapeutic may not be constantly available in the modified method, the chemotherapeutic would be more precisely delivered (both temporally and spatially) to the target cells at their most susceptible, thereby improving the effect of the method of Schmidt while decreasing risk to non-targeted tissues.
Applicant argues that the drug release mechanism of Kolosnjaj-Tabi is incompatible with the alternating electric field of the claimed method. However, Kolosnjaj-Tabi is not relied on for teaching an alternating electric field, or an alternating electric field used to release a therapeutic. Examiner relies on Kolosnjaj-Tabi only for teaching that applying an electric field to a chitosan hydrogel (a chitosan-based drug carrier) causes changes in the polarity, ionic strength, and pH which cause the chitosan hydrogel to release a therapeutic (see repeated rejection of claim 1 below).
Applicant asserts that one or ordinary skill in the art “would expect an alternating electric field to impede, rather than facilitate, controlled drug release from the polymer”. However, this argument made by Applicant is mere supposition and is not supported by any cited reference. Although Applicant does make reference to Kolosnjaj-Tabi using a direct current, and this causing the chitosan hydrogel to swell, there is no discussion in Kolosnjaj-Tabi that supports the assumption of an alternating electric current causing alternating swelling and shrinking. Applicant further states that the “sustained, unidirectional electrochemical reduction is opposite of the claimed alternating electric field”. Although the electric field applied in Kolosnjaj-Tabi may not be alternating, it is at least halfway aligned with the claimed alternating electric field, not diametrically opposed to the alternating electric field, and further supports that an electric field interacts with ionic bonds, as noted in the rejection of claim 1 below, thus providing a PHOSITA with a reasonable expectation of success of disrupting ionic bonds, as previously explained. Furthermore, Kolosnjaj-Tabi states that “changes in polarity, ionic strength and pH alter the net osmotic pressure within polymers (cause electro-osmosis), which results in bending, swelling, shrinking or erosion of the polymer and a consequent release of the active ingredient” (section 2.2.1, pg. 59 bottom of first column to top of second column). Thus, Kolosnjaj-Tabi states that shrinking as well as swelling may result in the release of the therapeutic, so even if a PHOSITA were to have the expectation of alternate shrinking as swelling as asserted by Applicant, Kolosnjaj-Tabi still provides a reasonable expectation of such a situation leading to release of the therapeutic.
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.
Claim(s) 1, 2, 4-7, 9-12, and 16-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schmidt et al (US 20200330758 A1; hereafter Schmidt) in view of Aznar et al (Aznar et al “Gated materials for on-command release of guest molecules” Chemical Reviews, vol 116, no 2, Jan 2016, pages 561-718; hereafter Aznar), Yuntao (Wang, Yuntao, et al., “Nanogels fabricated from bovine serum albumin and chitosan via self-assembly for delivery of anticancer drug,” Colloids and Surfaces B: Biointerface, Vol. 146, pages 107-113 (2016); hereafter Yuntao) and Kolosnjaj-Tabi et al (Kolosnjaj-Tabi et al “Electric field-responsive nanoparticles and electric fields: physical, chemical, biological mechanisms and therapeutic prospects”. Advanced Drug Delivery Reviews, vol 138, 7 November 2018, pg. 56-67; hereafter Kolosnajaj-Tabi). Examiner notes that Schmidt, Aznar, and Kolosnjaj-Tabi were included in Applicant’s IDS of 09/23/2022 and Yuntao was included in Applicant’s IDS of 10/04/2023.
Regarding claim 1, Schmidt discloses a method of delivering a therapeutic to a target site of a subject ([0007] a method of treating a cancerous tumor includes administering a chemotherapeutic agent to the subject) comprising:
administering a nanoparticle ([0026] chemotherapeutic agent may include nanoparticles) to a target site of a subject ([0123] chemotherapeutic agent including nanoparticles is released at the target site, a cancerous tumor), wherein the nanoparticle comprises a therapeutic agent ([0026] chemotherapeutic agent may include nanoparticles, [0123] nanoparticles include effective amount of chemotherapeutic agent); and
applying an alternating electric field, at a frequency ([0010] method includes generating an electric field with a frequency between 100 kHz and 300 kHz) for a period of time ([0007] electric field is generated, applied to site, and removed from site during the method), to the target site of the subject ([0007] electric field applied at site of tumor).
Schmidt is silent to the application of the alternating electric field releasing the therapeutic from the nanoparticles. Examiner notes that Schmidt does have support for administering the therapeutic while the electric field is active ([0051] nanoparticles may be administered in combination with electrical stimulation therapy; [0057] chemotherapeutic agent is administered to the cancerous cell population before the electric field is released).
Aznar, disclosing using an electric field to cause drug release form nanoparticles, teaches wherein an alternating electric field releases the therapeutic (IBU, ibuprofen) from the nanoparticle (MSNs, mesoporous silica nanoparticles) at the target site of the subject (pg. 593 col 2 para 4, application of alternating electric field facilitated drug release from nanoparticles).
It would have been obvious to one of ordinary skill in the art prior to the filing date of the claimed invention to link the electric field to delivery of the therapeutic because doing so would allow the release of the drug during the forced mitotic synchronization caused by the alternating electric field. Since Schmidt [0050] notes that the electric field activity is what synchronizes mitosis, and the synchronization makes the cells more uniformly susceptible to the chemotherapeutic, it would make sense to deliver the therapeutic while the synchronization effect is active in order to take maximum advantage of the synchronization effect. Additionally, triggering delivery of the therapeutic from the nanoparticle with an alternating electric field allows a clinician to better control the timing, and thus targeting, of the drug delivery.
Schmidt and Aznar are silent to the nanoparticle being a cationic-anionic polymer nanoparticle.
Yuntao, directed to nanogels for drug delivery, teaches wherein the nanoparticle is a cationic-anionic polymer nanoparticle (Abstract, bovine serum albumin (BSA) and chitosan (CS) form a BSA-CS nanogel through self-assembly; pg. 108 col. 1 para. 2, biodegradable and biocompatible NPs based on chitosan (CS) and BSA were fabricated by the self-assembly technique; pg. 111 col 1 para 1 CS, is positively charged and BSA is negatively charged).
Kolosnjaj-Tabi, directed to electric field-responsive nanoparticles, teaches that an applied electric field induces changes in polarity, ionic strength, and pH which may result in drug release, and that chitosan hydrogels exposed to electric fields generally collapse (see section 2.2.1, pg. 59 bottom of first column to top of second column).
It would have been obvious to one of ordinary skill in the art prior to the filing date of the claimed invention to use the nanoparticles based on BSA and CS as taught by Yuntao as the nanoparticles disclosed by Schmidt modified by Aznar since the nanoparticle of Yuntao was also investigated as a drug delivery system for treating cancer (Yuntao pg. 108 col 1 para 2). One would have been modified to make the modification because Yuntao (pg. 108 col 1 para 2) notes that the nanoparticles based on CS and BSA are biodegradable, biocompatible, and can be formed through a simple, green, low-cost process, all of which are desirable characteristics for a nanoparticle drug delivery system. Additionally, it would have been obvious to replace the type of nanoparticle of Aznar with the cationic-anionic nanoparticle taught by Yuntao because Kolosnjaj-Tabi notes not only that electric fields influence ionic relationships, but specifically notes that applied electric fields are known to cause chitosan hydrogels to collapse. Since Yuntao teaches a nanoparticle partially composed of chitosan, it would further have been obvious to one of ordinary skill in the art to combine the teachings of Yuntao and Aznar in light of the teachings of Kolosnjaj-Tabi with a reasonable expectation of success.
Regarding claim 2, Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi discloses the method of claim 1. Schmidt is silent to the form of the therapeutic agent.
Kolosnjaj-Tabi further teaches wherein the therapeutic agent is a nucleic acid, carbohydrate, lipid, peptide (pg. 57 col. 2 section 2 “Therapeutic electroresponsive systems” para. 1, electric field responsive systems enable a controlled release of polypeptides), antibody (pg. 59, Table 1, “Nanoparticles made of intrinsically conducting polymers releasing their cargo when low voltage electric fields are applied”, note that anti-iNOS antibodies were successfully delivered when an electric field was applied), or antibody fragment.
It would have been obvious to one of ordinary skill in the art prior to the filing date of the claimed invention to further modify the method of Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi as applied to claim 1 above to deliver a peptide or antibody as taught by Kolosnjaj-Tabi since Kolosnjaj-Tabi notes that both antibodies and peptides can be delivered via electric-field responsive systems. One would have been motivated to make the modification because peptides and antibodies are common genres of drug, and being able to incorporate either into a method may increase the versatility of the method. Furthermore, as noted in Table 1 of Kolosnjaj-Tabi, antibodies can be used to detect certain molecules, and this could be applied to identification of molecules common in cancer cells, such as enzymes used in mitosis, by a person of ordinary skill in the art
Regarding claim 4, Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi discloses method of claim 1, including wherein the nanoparticle is a self-assembling (Yuntao: Abstract, bovine serum albumin (BSA) and chitosan (CS) form a BSA-CS nanogel through self-assembly; pg. 113 col. 1 para. 4, nanogel based on BSA and CS was prepared by a simple green self-assembly technique) cationic-anionic polymer nanoparticle (Yuntao: pg. 111 col 1 para 1, CS is positively charged and BSA is negatively charged).
Regarding claim 5, Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi discloses the method of claim 1 including wherein the cationic-anionic polymer comprises chitosan (Yuntao pg. 111 col 1 para 1, CS is positively charged) or polyethylenimine (PEI) as a cationic portion.
Regarding claim 6, Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi discloses the method of claim 1 including wherein the cationic-anionic polymer comprises bovine serum bovine serum albumin (BSA) (Yuntao pg. 111 col 1 para 1, BSA is negatively charged) as an anionic portion.
Regarding claim 7, Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi discloses the method of claim 1. Schmidt further discloses wherein the therapeutic is an anti-cancer therapeutic ([0123] chemotherapeutic agent including nanoparticles is released at the target site, a cancerous tumor), an anti-viral therapeutic, an anti-bacterial therapeutic, an anti- fungal therapeutic, a pro-inflammatory therapeutic, or an anti-inflammatory therapeutic.
Regarding claim 9, Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi discloses the method of claim 1, and discloses wherein the nanoparticle (Schmidt [0026] chemotherapeutic agent may include nanoparticles) enters the target site (Schmidt [0123] chemotherapeutic agent including nanoparticles is released at the target site, a cancerous tumor).
Regarding claim 10, Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi as applied to claim 1 above discloses the method of claim 1, and discloses wherein the subject has cancer (Schmidt [0123] chemotherapeutic agent including nanoparticles is released at the target site, a cancerous tumor), an infection, an inflammatory disorder, or is immune suppressed.
Regarding claim 11, Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi discloses the method of claim 1. Schmidt further discloses wherein the target site comprises a cell ([0007] electric field applied at target site of cancerous tumor, cancerous tumor can include a cancerous cell population).
Regarding claim 12, Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi as applied to claim 11 above discloses the method of claim 11, and wherein the cell is a cancer cell (Schmidt [0007] tumor includes cancerous cell population, see 103 rejection of claim 11), a pathogen-infected cell, a mutant cell, or an immune cell.
Regarding claim 16, Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi discloses the method of claim 1, as applied above. Schmidt further discloses wherein the frequency of the alternating electric field is between 100 and 1,000 kHz ([0010] electric fields are applied at frequencies selected from a range of between 100 kHz and 300 kHz).
Regarding claim 17, Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi as applied to claim 1 above discloses the method of claim 1. Schmidt further discloses wherein the nanoparticle is administered prior to, during or after exposing the target site to the alternating electric field ([0007] method may include administering chemotherapeutic agent after one or more electric fields have been removed).
Regarding claim 18, Schmidt discloses a method of increasing target site specific release of a therapeutic agent in a subject ([0007] a method of treating a cancerous tumor includes administering a chemotherapeutic agent to the subject) comprising:
administering a nanoparticle ([0026] chemotherapeutic agent may include nanoparticles) to a target site of a subject ([0123] chemotherapeutic agent including nanoparticles is released at the target site, a cancerous tumor), wherein the nanoparticle comprises a therapeutic agent ([0026] chemotherapeutic agent may include nanoparticles, [0123] nanoparticles include effective amount of chemotherapeutic agent); and
applying an alternating electric field, at a frequency ([0010] method includes generating an electric field with a frequency between 100 kHz and 300 kHz) for a period of time ([0007] electric field is generated, applied to site, and removed from site during the method), to the target site of the subject ([0007] electric field applied at site of tumor),
Schmidt is silent to the application of the alternating electric field releasing the therapeutic from the nanoparticles.
Aznar, disclosing using an electric field to cause drug release form nanoparticles, teaches wherein an alternating electric field releases the therapeutic agent (IBU, ibuprofen) from the nanoparticle (MSNs, mesoporous silica nanoparticles) at the target site of the subject (pg. 593 col 2 para 4, application of alternating electric field facilitated drug release from nanoparticles), thereby increasing the target site specific release of the therapeutic agent.
It would have been obvious to one of ordinary skill in the art prior to the filing date of the claimed invention to link the electric field to delivery of the therapeutic because doing so would allow the release of the drug during the forced mitotic synchronization caused by the alternating electric field. Since Schmidt [0050] notes that the electric field activity is what synchronizes mitosis, and the synchronization is what makes the cells more susceptible to the chemotherapeutic, it would make sense to deliver the therapeutic while the synchronization effect is active in order to take maximum advantage of the synchronization effect.
Schmidt and Aznar are silent to the nanoparticle being a cationic-anionic polymer nanoparticle.
Yuntao, directed to nanogels for drug delivery, teaches wherein the nanoparticle is a cationic-anionic polymer nanoparticle (Abstract, bovine serum albumin (BSA) and chitosan (CS) form a BSA-CS nanogel through self-assembly; pg. 108 col. 1 para. 2, biodegradable and biocompatible NPs based on chitosan (CS) and BSA were fabricated by the self-assembly technique; pg. 111 col 1 para 1 CS, is positively charged and BSA is negatively charged).
Kolosnjaj-Tabi, directed to electric field-responsive nanoparticles, teaches that an applied electric field induces changes in polarity, ionic strength, and pH which may result in drug release, and that chitosan hydrogels exposed to electric fields generally collapse (see section 2.2.1, pg. 59 bottom of first column to top of second column).
It would have been obvious to one of ordinary skill in the art prior to the filing date of the claimed invention to use the nanoparticles based on BSA and CS as taught by Yuntao as the nanoparticles disclosed by Schmidt modified by Aznar since the nanoparticle of Yuntao was also investigated as a drug delivery system for treating cancer (Yuntao pg. 108 col 1 para 2). One would have been modified to make the modification because Yuntao (pg. 108 col 1 para 2) notes that the nanoparticles based on CS and BSA are biodegradable, biocompatible, and can be formed through a simple, green, low-cost process, all of which are desirable characteristics for a nanoparticle drug delivery system. Additionally, it would have been obvious to replace the type of nanoparticle of Aznar with the cationic-anionic nanoparticle taught by Yuntao because Kolosnjaj-Tabi notes not only that electric fields influence ionic relationships, but specifically notes that applied electric fields are known to cause chitosan hydrogels to collapse. Since Yuntao teaches a nanoparticle partially composed of chitosan, it would further have been obvious to one of ordinary skill in the art to combine the teachings of Yuntao and Aznar in light of the teachings of Kolosnjaj-Tabi with a reasonable expectation of success.
Regarding claim 19, Schmidt discloses a method of treating a subject in need thereof ([0007] a method of treating a cancerous tumor includes administering a chemotherapeutic agent to the subject) comprising:
administering a nanoparticle ([0026] chemotherapeutic agent may include nanoparticles) to a target site of a subject in need thereof ([0123] chemotherapeutic agent including nanoparticles is released at the target site, a cancerous tumor), wherein the nanoparticle comprises a therapeutic agent ([0026] chemotherapeutic agent may include nanoparticles, [0123] nanoparticles include effective amount of chemotherapeutic agent); and
applying an alternating electric field, at a frequency ([0010] method includes generating an electric field with a frequency between 100 kHz and 300 kHz) for a period of time ([0007] electric field is generated, applied to site, and removed from site during the method), to the target site of the subject in need thereof ([0007] electric field applied at site of tumor),
wherein the therapeutic agent kills a cancer or pathogen-infected cell, reduces inflammation, increases a humoral immune response, and/or increases a cell- mediated immune response ([0058] Administration of the chemotherapeutic agent can cause a disruption of mitosis within the cancerous cell population 514 and eventually lead to cell death within the cancerous cell population 516.).
Schmidt is silent to the application of the alternating electric field releasing the therapeutic from the nanoparticles.
Aznar, disclosing using an electric field to cause drug release form nanoparticles, teaches wherein an alternating electric field releases the therapeutic agent (IBU, ibuprofen) from the nanoparticle (MSNs, mesoporous silica nanoparticles) at the target site of the subject in need thereof (pg. 593 col 2 para 4, application of alternating electric field facilitated drug release from nanoparticles).
It would have been obvious to one of ordinary skill in the art prior to the filing date of the claimed invention to link the electric field to delivery of the therapeutic because doing so would allow the release of the drug during the forced mitotic synchronization caused by the alternating electric field. Since Schmidt [0050] notes that the electric field activity is what synchronizes mitosis, and the synchronization is what makes the cells more susceptible to the chemotherapeutic, it would make sense to deliver the therapeutic while the synchronization effect is active in order to take maximum advantage of the synchronization effect.
Schmidt and Aznar are silent to the nanoparticle being a cationic-anionic polymer nanoparticle.
Yuntao, directed to nanogels for drug delivery, teaches wherein the nanoparticle is a cationic-anionic polymer nanoparticle (Abstract, bovine serum albumin (BSA) and chitosan (CS) form a BSA-CS nanogel through self-assembly; pg. 108 col. 1 para. 2, biodegradable and biocompatible NPs based on chitosan (CS) and BSA were fabricated by the self-assembly technique; pg. 111 col 1 para 1 CS, is positively charged and BSA is negatively charged).
Kolosnjaj-Tabi, directed to electric field-responsive nanoparticles, teaches that an applied electric field induces changes in polarity, ionic strength, and pH which may result in drug release, and that chitosan hydrogels exposed to electric fields generally collapse (see section 2.2.1, pg. 59 bottom of first column to top of second column).
It would have been obvious to one of ordinary skill in the art prior to the filing date of the claimed invention to use the nanoparticles based on BSA and CS as taught by Yuntao as the nanoparticles disclosed by Schmidt modified by Aznar since the nanoparticle of Yuntao was also investigated as a drug delivery system for treating cancer (Yuntao pg. 108 col 1 para 2). One would have been modified to make the modification because Yuntao (pg. 108 col 1 para 2) notes that the nanoparticles based on CS and BSA are biodegradable, biocompatible, and can be formed through a simple, green, low-cost process, all of which are desirable characteristics for a nanoparticle drug delivery system. Additionally, it would have been obvious to replace the type of nanoparticle of Aznar with the cationic-anionic nanoparticle taught by Yuntao because Kolosnjaj-Tabi notes not only that electric fields influence ionic relationships, but specifically notes that applied electric fields are known to cause chitosan hydrogels to collapse. Since Yuntao teaches a nanoparticle partially composed of chitosan, it would further have been obvious to one of ordinary skill in the art to combine the teachings of Yuntao and Aznar in light of the teachings of Kolosnjaj-Tabi with a reasonable expectation of success.
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi, as applied to claim 7 above, and further in view of Khizroev et al (US 20150283368 A1; hereafter Khizroev).
Regarding claim 8, Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi discloses the method of claim 7, as described above, but is silent to which anti-cancer therapeutic used.
Khizroev, disclosing controlled drug release from magneto-electric nanoparticles with ionic bonds, teaches wherein the anti-cancer therapeutic is Gemcitabine (GEM) ([0061] gemcitabine, an anticancer drug, may be used with the nanotechnology).
It would have been obvious to one of ordinary skill in the art prior to the filing date of the claimed invention to use the nanoparticles of Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi to deliver gemcitabine as taught by Khizroev. One would have been motivated to do so because Schmidt [0017] calls for a chemotherapeutic agent to be used and gemcitabine, as noted in Khizroev [0061], is an anticancer drug.
Claim(s) 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi as applied to claims 1 and 12 above, and further in view of Mirkin et al (US 9376690 B2; hereafter Mirkin).
Alternatively, regarding claim 2, Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi discloses the method of claim 1. Schmidt is silent to the form of the therapeutic agent.
Mirkin, disclosing targeted delivery of a therapeutic using nanoparticles, further teaches wherein the therapeutic agent is a nucleic acid, carbohydrate, lipid, peptide (col. 33 ln. 40-47, therapeutic agent may be a peptide), antibody, or antibody fragment.
It would have been obvious to one of ordinary skill in the art prior to the filing date of the claimed invention to modify the method of Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi to specifically delivery a peptide as taught by Mirkin since Mirkin also deals with treating cancer (col. 82. ln. 16-18) and suggests that a therapeutic agent delivered via a nanoparticle may be a peptide (col. 33 ln. 40-47). One would have been motivated to make the modification because peptides may be therapeutic agents that can improve a patient’s outlook.
Regarding claim 13, Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi as applied to claim 12 discloses the method of claim 12, but is silent to the specific type of cancer cell.
Mirkin, disclosing targeted delivery of a therapeutic using nanoparticles, teaches wherein the cancer cell is a pancreatic cancer cell, glioblastoma cell, colon cancer cell, skin cancer cell, or lung metastatic carcinoma cell (col 82 ln 20-29 cancer cells may be pancreatic cancer cells, among others).
It would have been obvious to one of ordinary skill in the art prior to the filing date of the claimed invention to use the method of Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi to treat pancreatic cancer cells or other specific cell types as taught by Mirkin. One would be motivated to make this modification because treating the pancreatic cancer cells with the method of Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi may help to put the cancer patient in remission.
Regarding claim 14, Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi as applied to claim 12 discloses the method of claim 12, but is silent to the nanoparticle entering the cell.
Mirkin teaches wherein the nanoparticle enters the cancer cell or pathogen-infected cell (col 5 ln 17-18, nanoconjugate comprises a nanoparticle; col 20 ln 4-13, nanoconjugate enters cell).
It would have been obvious to one of ordinary skill in the art prior to the filing date of the claimed invention to modify the method of Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi to include the nanoparticle entering the target cancer cell as taught by Mirkin. One would have been motivated to make this modification because the nanoparticle entering the target cell during drug delivery, as opposed to only being nearby the cell, would better achieve targeted drug delivery since the drug would be delivered directly into the cancer cell itself.
Regarding claim 15, Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi as applied to claim 1 discloses the method of claim 1, but is silent to the nanoparticle being 20-500 nm.
Mirkin teaches wherein the nanoparticle is 20-500 nm (col 29 ln 23-30, nanoparticle may be from about 40-80 nm).
It would have been obvious to one of ordinary skill in the art prior to the filing date of the claimed invention to modify the nanoparticle of Schmidt modified by Aznar, Yuntao, and Kolosnjaj-Tabi to have a diameter of 40-80 nm as taught by Mirkin because, as Mirkin notes, the size of the nanoparticles may advantageously optimize certain physical characteristics (col 29 ln 23-30). Mirkin (col 20 ln 4-13) also notes that the nanoparticles enter the cell. One would have been motivated to make the modification because smaller molecules more easily enter cells. It would be advantageous to have a small diameter nanoparticle as taught by Mirkin which could enter the cell and therefore more directly delivery the therapeutic of Schmidt modified by Aznar, Yuntao, and Kolosnjaj.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Mohapatra A, et al., “Electric Stimulus Response of Chitosan Microbeads Embedded with Magnetic Nanoparticles for Controlled Drug Delivery”. IEEE Healthcare Innovation Conference (HIC). (2014). (submitted as NPL entry 26 of IDS 02/17/2026)
Results show that alternating electric field application at 500Hz caused chitosan microbeads to release dye and showed “significant rupturing and shrinking of microbeads subjected to electrical stimulus”.
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.
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/I.S.N./Examiner, Art Unit 3783
/JASON E FLICK/Primary Examiner, Art Unit 3783 06/12/2026
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