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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114 was filed in this application after a decision by the Patent Trial and Appeal Board, but before the filing of a Notice of Appeal to the Court of Appeals for the Federal Circuit or the commencement of a civil action. Since this application is eligible for continued examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on 03/02/2026 has been entered.
Status of the Claims
This action is in response to papers filed 03/02/2026 in which claims 4 and 18-20 were canceled; claims 1-3, 5-12, and 14-16 were withdrawn; and claims 13 and 17 were amended. All the amendments have been thoroughly reviewed and entered.
Claims 13, 17, and 21 are under examination.
Withdrawn Rejection
The Examiner has re-weighted all the evidence of record. Any rejection and/or objection not specifically addressed below is hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
New Rejections
Necessitated by Applicant’s Claim Amendments
Claim Rejections - 35 USC § 103
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.
Claims 13, 17 and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fan et al (Angew. Chem. Int. Ed., 2016, 55, pages 5477-5482; cited in IDS filed 10/07/2019) in view of Rana et al (Dalton Transactions, 2016, 45: 17401-17408), Koyakutty et al (19 July 2012; US 2012/0184495 A1) and Lange et al (20 August 2009; US 2009/0209508 A1).
Regarding claims 13 and 17, Fan teaches a photosensitizer- MnO2 nanosystem for highly efficient photodynamic therapy, wherein the MnO2 nanosheet absorb photosensitizer chlorin e6 (Ce6), protect it from self-destruction upon light irradiation and efficiently deliver it into cells (Abstract; page 5477, right column; page 5480; page 5481, left column). Fan teaches the Ce6- MnO2 nanosheet is used for treating cancer (Abstract; page 5477, right column; page 5480; page 5481, left column). Fan teaches MnO2 nanosheets can strongly adsorb small organic molecules, such as photosensitizers, via electrostatic interaction and Mn-N coordinate bonds, which can facilitate their endocytosis for intracellular photodynamic therapy (PDT) (page 5477, right column). Fan further teaches MnO2 nanosheets have an intense and broad optical absorption spectrum (~200-600 nm), making them an efficient broad-spectrum fluorescence quencher for the design of fluorescence turn-on probes for monitoring delivery efficiency (page 5477, right column). Fan further teaches MnO2 nanosheets can react with intracellular glutathione (GSH), resulting in the disintegration of the nanosheets and, hence, complete release of photosensitizers for PDT (page 5477, right column). Fan teaches the MnO2 nanosheets were mixed with the photosensitizer such that the photosensitizer is loaded directly on the surface of the MnO2 nanosheets (page 5478, left column, last paragraph to top of right column).
However, Fan does not teach the folic acid being covalently bonded to a surface of the metallic nanosheet; and zinc-phthalocyanine (ZnPc) as the photosensitizer of claims 13 and 17.
Regarding the folic acid being covalently bonded to a surface of the metallic nanosheet of claims 13 and 17, Rana teaches a magnetic nanoparticles (iron oxide nanoparticles) having folic acid conjugated (covalent bonded) on a surface of the iron oxide nanoparticles via EDC-NHS coupling reaction (Abstract; pages 17401-17407). Rana teaches the folic acid conjugated nanoparticles provides higher cellular internalization capability in cancer cells over-expressing folate receptors (Abstract; pages 17401-17407).
It would have been obvious to one of ordinary skill in the art to covalent bond folic acid on a surface of the MnO2 nanosheet of Fan, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Rana provided the guidance to do so by teaching that folic acid can be advantageously loaded on the surface of a metal nanoparticle by conjugating (covalent bonding) folic acid via EDC-NHS coupling reaction and such folic acid conjugated nanoparticles provides higher cellular internalization capability in cancer cells over-expressing folate receptors. Thus, an ordinary artisan interested in providing higher cellular internalization capability in cancer cells over-expressing folate receptors would have looked to conjugating (covalent bonding) folic acid on a surface of the metallic nanosheet of Fan via EDC-NHS coupling reaction with a reasonable predictability that the resultant photosensitizer-MnO2-folic acid nanosheet that would specifically target the folate receptor on the tumor/cancer cells, thereby providing the desired cancer treatment, and achieve Applicant’s claimed methods with reasonable expectation of success.
Regarding the zinc-phthalocyanine (ZnPc) of claims 13 and 17, Koyakutty teaches a photosensitizer-containing metal nanoparticle used for killing cancer cells by photodynamic treatment, wherein the suitable photosensitizers include chlorin e6 (Ce6) and metal phthalocyanine (Abstract; [0001], [0004]-[0008], [00013], [0015], [0018]-[0023], [0027], [0046], [0051], [0059] and [0088]; claims 18, 19, 21 and 24). Lange teaches chlorin e6 (Ce6) and zinc phthalocyanine are known photosensitizers conventional used in photochemotherapeutic treatment of cancer (Abstract; [0005]-[0006], [0018], [0020], [0025], [0079]-[0080], [0117]-[0121]; Table 3).
It would have been obvious to one of ordinary skill in the art to incorporate or substitute zinc phthalocyanine as the photosensitizer in the MnO2 nanosheet of Fan, and produce the claimed invention. One of ordinary skill in the art would have motivated to so because Koyakutty and Lange provided the guidance to do so by teaching that not only chlorin e6 (Ce6) of Fan is suitable as photosensitizers in photodynamic therapy of treating cancer, but zinc phthalocyanine is also a photosensitizer conventionally known in the art to be suitable as photosensitizers in photodynamic therapy of treating cancer, as well as, Fan establishes that MnO2 nanosheets can strongly absorbed photosensitizers by electrostatic interactions and Mn-N coordinate bonds, providing a photosensitizer-MnO2 nanosheet that have enhanced photodynamic therapy efficient (Fan: page 5477, right column). Thus, it would have been merely simple substitution of one known photosensitizer for another to achieve the desired photosensitizer-MnO2 nanosheet with enhanced photodynamic therapy efficient in the treatment of cancer. As such, [t]he selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945). "Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.).
As such, based on the guidance from Rana, Koyakutty and Lange, an ordinary artisan seeking to maximize cancer treatment would have looked to covalently bonding folic acid on a surface of the metallic nanosheet (MnO2 nanosheet) via EDC-NHS coupling reaction, as well as, as mixing the MnO2 nanosheet with photosensitizer such as zinc phthalocyanine so as to form a resultant zinc phthalocyanine-MnO2-FA nanosystem that have specific target to the folate receptor on the tumor/cancer cells, as well as, enhanced photodynamic therapy efficient in the treatment of cancer, and achieve Applicant’s claimed invention with reasonable expectation of success.
Regarding claim 21, Lange teaches zinc phthalocyanine has an irradiated wavelength between 580-630 nm ([0117]-[0121]; Table 3).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 13, 17 and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fan et al (Angew. Chem. Int. Ed., 2016, 55, pages 5477-5482; cited in IDS filed 10/07/2019) in view of Hao et al (Nanotechnology, 2015, 27: 1-14; cited in IDS filed 10/07/2019), Koyakutty et al (19 July 2012; US 2012/0184495 A1) and Lange et al (20 August 2009; US 2009/0209508 A1).
Regarding claims 13 and 17, Fan teaches a photosensitizer- MnO2 nanosystem for highly efficient photodynamic therapy, wherein the MnO2 nanosheet absorb photosensitizer chlorin e6 (Ce6), protect it from self-destruction upon light irradiation and efficiently deliver it into cells (Abstract; page 5477, right column; page 5480; page 5481, left column). Fan teaches the Ce6- MnO2 nanosheet is used for treating cancer (Abstract; page 5477, right column; page 5480; page 5481, left column). Fan teaches MnO2 nanosheets can strongly adsorb small organic molecules, such as photosensitizers, via electrostatic interaction and Mn-N coordinate bonds, which can facilitate their endocytosis for intracellular photodynamic therapy (PDT) (page 5477, right column). Fan further teaches MnO2 nanosheets have an intense and broad optical absorption spectrum (~200-600 nm), making them an efficient broad-spectrum fluorescence quencher for the design of fluorescence turn-on probes for monitoring delivery efficiency (page 5477, right column). Fan further teaches MnO2 nanosheets can react with intracellular glutathione (GSH), resulting in the disintegration of the nanosheets and, hence, complete release of photosensitizers for PDT (page 5477, right column). Fan teaches the MnO2 nanosheets were mixed with the photosensitizer such that the photosensitizer is loaded directly on the surface of the MnO2 nanosheets (page 5478, left column, last paragraph to top of right column).
However, Fan does not teach the folic acid being covalently bonded to a surface of the metallic nanosheet; and zinc-phthalocyanine (ZnPc) as the photosensitizer of claims 13 and 17.
Regarding the folic acid being covalently bonded to a surface of the metallic nanosheet of claims 13 and 17, Hao teaches folic acid conjugated to a surface of MnO2 nanosheet via EDC and PEGlyation (Abstract; pages 2-5 and 7-13). Hao teaches the folic acid conjugated on MnO2 nanosheet specifically target the folate receptor on the tumor/cancer cells, thereby leading to enhanced anti-tumor efficiency (Abstract; pages 2-5 and 7-13).
It would have been obvious to one of ordinary skill in the art to covalent bond folic acid on a surface of the MnO2 nanosheet of Fan, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Hao provided the guidance to do so by teaching that folic acid can be advantageously loaded on the surface of by conjugating (covalent bonding) folic acid via EDC and PEGlyation, and such folic acid conjugated MnO2 nanosheet specifically target the folate receptor on the tumor/cancer cells, thereby leading to enhanced anti-tumor efficiency. Thus, an ordinary artisan interested in providing enhanced anti-tumor efficiency in cancer cells over-expressing folate receptors would have looked to conjugating (covalent bonding) folic acid on a surface of the metallic nanosheet of Fan via EDC and PEGlyation with a reasonable predictability that the resultant photosensitizer-MnO2-folic acid nanosheet that would specifically target the folate receptor on the tumor/cancer cells, thereby providing the desired cancer treatment, and achieve Applicant’s claimed methods with reasonable expectation of success.
Regarding the zinc-phthalocyanine (ZnPc) of claims 13 and 17, Koyakutty teaches a photosensitizer-containing metal nanoparticle used for killing cancer cells by photodynamic treatment, wherein the suitable photosensitizers include chlorin e6 (Ce6) and metal phthalocyanine (Abstract; [0001], [0004]-[0008], [00013], [0015], [0018]-[0023], [0027], [0046], [0051], [0059] and [0088]; claims 18, 19, 21 and 24). Lange teaches chlorin e6 (Ce6) and zinc phthalocyanine are known photosensitizers conventional used in photochemotherapeutic treatment of cancer (Abstract; [0005]-[0006], [0018], [0020], [0025], [0079]-[0080], [0117]-[0121]; Table 3).
It would have been obvious to one of ordinary skill in the art to incorporate or substitute zinc phthalocyanine as the photosensitizer in the MnO2 nanosheet of Fan, and produce the claimed invention. One of ordinary skill in the art would have motivated to so because Koyakutty and Lange provided the guidance to do so by teaching that not only chlorin e6 (Ce6) of Fan is suitable as photosensitizers in photodynamic therapy of treating cancer, but zinc phthalocyanine is also a photosensitizer conventionally known in the art to be suitable as photosensitizers in photodynamic therapy of treating cancer, as well as, Fan establishes that MnO2 nanosheets can strongly absorbed photosensitizers by electrostatic interactions and Mn-N coordinate bonds, providing a photosensitizer-MnO2 nanosheet that have enhanced photodynamic therapy efficient (Fan: page 5477, right column). Thus, it would have been merely simple substitution of one known photosensitizer for another to achieve the desired photosensitizer-MnO2 nanosheet with enhanced photodynamic therapy efficient in the treatment of cancer. As such, [t]he selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945). "Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." 325 U.S. at 335, 65 USPQ at 301.).
As such, based on the guidance from Hao, Koyakutty and Lange, an ordinary artisan seeking to maximize cancer treatment would have looked to covalently bonding folic acid on a surface of the metallic nanosheet (MnO2 nanosheet) via EDC and PEGlyation, as well as, as mixing the MnO2 nanosheet with photosensitizer such as zinc phthalocyanine so as to form a resultant zinc phthalocyanine-MnO2-FA nanosystem that have specific target to the folate receptor on the tumor/cancer cells, as well as, enhanced photodynamic therapy efficient in the treatment of cancer, and achieve Applicant’s claimed invention with reasonable expectation of success.
Regarding claim 21, Lange teaches zinc phthalocyanine has an irradiated wavelength between 580-630 nm ([0117]-[0121]; Table 3).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 03/02/2026 have been fully considered but they are not persuasive because Applicant’s arguments on pages 6-9 of the Remarks 03/02/2026 are solely directed to the Hu reference, which is a reference not used in the pending 103 rejections, and thereby are moot in view of the new 103 rejections as set forth in this office action.
Conclusion
No claim is allowed.
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/DOAN T PHAN/ Primary Examiner, Art Unit 1613