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, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03/27/2026 has been entered.
Response to Arguments
Applicant's arguments filed 03/27/2026 have been fully considered but they are not persuasive.
Applicant’s amendments to claim 1 are essentially a rewording of previous claims 1, and 6-7 previously presented.
On page 2, 2nd full paragraph Applicant asserts “Xie does not teach a nanoparticle comprising a distinct polymer coating layer surrounding a nanoparticle core.” This is incorrect see the abstract, and figure 21 for example. Applicant also asserts therein “Xie disclose a photosensitizer covalently conjugated to such a coating layer.” This is corrected and conceded in the obviousness rejection (other prior art references of the 103 rejection teach this this subject matter).
On page 2, 3rd full paragraph Applicant asserts “Chen does not disclose a nanoparticle comprising a scintillation core surrounded by a polymer coating.” This may be true but Chen et al. certainly disclose a nanoparticle comprising a scintillation core surrounded by a polymer coating (see [0073]). Applicant also asserts “nor does Chen teach covalent conjugation of a photosensitizer specifically to a coating layer distinct from the nanoparticle core.” The examiner concedes there is no covalent conjugation disclosed by the Chen et al. prior art (that is taught by the Lin, Ph.D. et al. prior art – see the comments and rejections below).
On page 2, last paragraph through page 3, line 5 Applicant addresses the Lin, Ph.D. et al. prior art. Applicant asserts therein Lin, Ph.D. et al. “does not disclose or suggest a core-shell nanoparticle having a polymer coating layer with a photosensitizer conjugated thereto.” This is incorrect and contradicted by [0206]-[0207] of the Lin, Ph.D. et al. prior art and included in the rejection below. For completeness the examiner includes [0206]-[0207] here:
Examples of photosensitizers conjugated to X-ray scintillating nanoparticles for use in X-ray induced PDT include, but are not limited to: photosensitizers coordinatively bonded to a particle surface, where the coordination methods include but are not limited to carboxylate or phosphate coordination (such as via the coordination of a carboxylate or phosphate group on the PS to open metal sites (e.g., Ln.sup.3+, Zn.sup.2+, Al.sup.3+, etc.) on nanoparticles); thiol coordination to nanoparticles, (via PSs containing thiols conjugating to nanoparticles through the coordination of thiol groups to Au (in gold nanoparticles) or, for example, Zn, Cd, in quantum dots); polymer conjugation and surface coating, for example, via covalently conjugating PSs to oligomers or polymers with functional groups (e.g., cyclodextrin, polyethylene glycol (PEG), poly (maleic acid) derivatives, etc.) and conjugating the scintillator particles through coordination of additional functional groups (e.g., carboxylates, thiols, hydroxyls, amines, etc.) to the metals on a particle surface, for example using photosensitizers such, but not limited to, any of those shown in FIGS. 27 and 28, covalently bonding to a MOF ligand, for example via amide conjugation, ester conjugation, thiourea conjugation, “click chemistry”, disulfide bond conjugation, etc.; surface modification of porous materials and entrapment, mesoporous silica coating and entrapment, and MOF coating and entrapment, for example with photosensitizers entrapped in the pores of the silica layer.
In a nutshell, Lin, Ph.D. et al. teach bonding a photosensitizer via polymer conjugation (i.e., covalent conjugation) to a polymer surface coating, wherein the polymer coating comprises an element from a polyethylene glycol (PEG) group.
Next on page 3, 1st full paragraph Applicant asserts “Even when combined, the cited references fail to teach or suggest the claimed invention. At most, the references collectively disclose scintillation nanoparticles (Xie), general attachment of photosensitizers to nanoparticles (Chen), and MOF-based systems incorporating photosensitizers into a framework (Lin, Ph.D.). However, none of these references teaches or suggests modifying a scintillation nanoparticle to include a polymer coating layer surrounding the core, with a photosensitizer covalently conjugated specifically to that coating layer, as required by the claims.” This assertion is shown to be unpersuasive, and incorrect in light of the above rebuttals.
Applicant appears to have missed the full weight of [0206]-[0207] of the Lin, Ph.D. et al. prior art. Applicant has the right to challenge the obviousness rejection and has done so, unsuccessfully. The teaching(s) of the Lin, Ph.D. et al. prior art appear clear to the examiner and make up for any of the alleged deficiencies of combination of the other pieces of prior art used in the rejections as shown above and in the rejections below.
Due to the RCE this action is made non-final.
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.
Claims 1-4, 11, 14, 16-19. 21-23, 25-26, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Xie et al. (U.S. Patent Application Publication 2017/0209575) in view of Chen et al. (U.S. Patent Application Publication 2007 /0218049) in view of Lin, Ph.D. et al. (U.S. Patent Application Publication 2017 /0231903).
Regarding Claims 1, 11, 16, 18-19, 25-26, and 30, Xie et al. disclose a nanoparticle
composition comprising and a PDT method comprising:
a scintillation nanoparticle core (see A) "Scintillation nanoparticles, as used herein, refer to nanoparticles that can absorb ionizing radiation such as X-rays, neutrons, alpha, beta, or gamma-rays" in [0040], and B) abstract, [0005], [0058], [0077], [0084], and claim 3 regarding the core) having:
a coating layer (comprising the first and second shells, see [0057]-[0062] and figure 21), and
a photosensitizer coupled to the coating layer ("the photosensitizer can be embedded in the mesoporous material," see abstract, [0008], [0037], [0056] for example),
wherein the scintillation nanoparticle emits electromagnetic radiation having a first wavelength when irradiated with electromagnetic radiation having a second wavelength (see [0008]), and
wherein the photo sensitizer absorbs electromagnetic radiation of said first wavelength (see [0008]).
Xie et al. further disclose 1) administering to the subject an effective amount of a composition comprising the nanoparticle composition (see [0071]); and administering to the subject electromagnetic radiation having a second wavelength (see [0008]).
Xie et al. also disclose cell targeting moiety in for the invention (see [0063 ]-[0067] and claims 26-27) but fail to explicitly recite:
1) the photosensitizer is conjugated to the coating layer,
2) the cell targeting moiety conjugated to the coating layer,
3) the coating layer a polymer layer that in turn comprises one or more polyethylene glycol (PEG) group, and
4) the photosensitizer from the PEG group is covalently conjugated to the photosensitizer.
Like Xie et al., Chen et al. disclose scintillation nanoparticle for treating cancer having a photosensitizer and a coating and teach providing:
conjugating the photosensitive material to the shells/coating of nanoparticles (see [0 102]), and
conjugating cell targeting to the coat/shell (see [0122])
as a known and workable means for providing the scintillating nanoparticle with cell targeting capabilities and photosensitive properties in order to treat tissue (e.g., cancer).
Like both Xie et al. and Chen et al., Lin, Ph.D. et al. disclose scintillation nanoparticles comprising gold, a coating and a photosensitizer used to treat cancer and teach providing “Examples of photosensitizers conjugated to X-ray scintillating nanoparticles for use in X-ray induced PDT include, but are not limited to: photosensitizers coordinatively bonded to a particle surface, where the coordination methods include but are not limited to carboxylate or phosphate coordination (such as via the coordination of a carboxylate or phosphate group on the PS to open metal sites (e.g., Ln.sup.3+, Zn.sup.2+, Al.sup.3+, etc.) on nanoparticles); thiol coordination to nanoparticles, (via PSs containing thiols conjugating to nanoparticles through the coordination of thiol groups to Au (in gold nanoparticles) or, for example, Zn, Cd, in quantum dots); polymer conjugation and surface coating, for example, via covalently conjugating PSs to oligomers or polymers with functional groups (e.g., cyclodextrin, polyethylene glycol (PEG), poly (maleic acid) derivatives, etc.) and conjugating the scintillator particles through coordination of additional functional groups (e.g., carboxylates, thiols, hydroxyls, amines, etc.) to the metals on a particle surface, for example using photosensitizers such, but not limited to, any of those shown in FIGS. 27 and 28, covalently bonding to a MOF ligand, for example via amide conjugation, ester conjugation, thiourea conjugation, “click chemistry”, disulfide bond conjugation, etc.; surface modification of porous materials and entrapment, mesoporous silica coating and entrapment, and MOF coating and entrapment, for example with photosensitizers entrapped in the pores of the silica layer” (see [0206]-[0207]) in order to provide a known and workable manner of coating a nanoparticle and/or nanoparticle core in order to treat cancer (see [0075], [0077], [0079]-[0080] for example).
In a nutshell, Lin, Ph.D. et al. teach bonding a photosensitizer via polymer conjugation (i.e., covalent conjugation) to a polymer surface coating, wherein the polymer coating comprises an element from a polyethylene glycol (PEG) group.
Therefore, at the time of the of invention it would have been obvious to one of ordinary skill in the art to modify the invention of Xie et al., as taught by Chen et al., to provide the system with conjugating the photosensitive material to the shells/coating of nanoparticles and conjugating cell targeting to the coat/shell in order to provide a known and workable means for providing the scintillating nanoparticle with cell targeting capabilities and photosensitive properties in order to treat tissue (e.g., cancer), and as further taught by Lin, Ph.D. et al., to provide a “photosensitizers coordinatively bonded to a particle surface, where the coordination methods include but are not limited to carboxylate or phosphate coordination (such as via the coordination of a carboxylate or phosphate group on the PS to open metal sites (e.g., Ln.sup.3+, Zn.sup.2+, Al.sup.3+, etc.) on nanoparticles); thiol coordination to nanoparticles, (via PSs containing thiols conjugating to nanoparticles through the coordination of thiol groups to Au (in gold nanoparticles) or, for example, Zn, Cd, in quantum dots); polymer conjugation and surface coating, for example, via covalently conjugating PSs to oligomers or polymers with functional groups (e.g., cyclodextrin, polyethylene glycol (PEG), poly (maleic acid) derivatives, etc.) and conjugating the scintillator particles through coordination of additional functional groups (e.g., carboxylates, thiols, hydroxyls, amines, etc.) to the metals on a particle surface, for example using photosensitizers such, but not limited to, any of those shown in FIGS. 27 and 28, covalently bonding to a MOF ligand, for example via amide conjugation, ester conjugation, thiourea conjugation, “click chemistry”, disulfide bond conjugation, etc.; surface modification of porous materials and entrapment, mesoporous silica coating and entrapment, and MOF coating and entrapment, for example with photosensitizers entrapped in the pores of the silica layer” (see [0207]) in order to provide a known and workable manner of coating a nanoparticle and/or nanoparticle core in order to treat cancer.
Regarding claims 2 and 21, Xie et al. disclose the claimed invention, see figure 9b and
[0037].
Regarding claims 3-4 and 22-23, Xie et al. disclose the claimed invention, see [0046],
[0062] and claim 13 for example.
Regarding claim 14, Xie et al. disclose the claimed invention, see [0069].
Regarding claim 17, Xie et al. disclose the claimed invention, see figure 9b and [0037].
Regarding claim 18, Xie et al. in view of Chen et al. in view of Lin, Ph.D. et al. disclose the claimed invention including the nanoparticle composition and the electromagnetic radiation provide the subject a combination therapy where the therapeutic results are synergistic compared to either electromagnetic radiation or photodynamic therapy alone, since the delivery of electromagnetic radiation alone - that is without the photodynamic effect the delivery of the photosensitive nanoparticles - yields nominal electromagnetic radiation influence not tuned to addressing the desired tissue effects, while delivering the photodynamic photosensitive nanoparticles alone - that is without the photosensitive activating electromagnetic radiation - yields delivering nanoparticles having photosensitive properties a that are never activated.
Claims 8 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Xie et al. (U.S. Patent Application Publication 2017 /0209575) in view of Chen et al. (U.S. Patent Application Publication 2007/0218049) in view of Lin, Ph.D. et al. (U.S. Patent Application Publication 2017 /0231903) as applied to claim 1 and 16 above, and further in view of Lin et al. (U.S. Patent Application Publication 2018/0153796).
Regarding claim 8 and 27, Xie et al. in view of Chen et al. in view of Lin, Ph.D. et al. disclose (or make obvious) the invention shown above, but fail to recite the photosensitizer is Chlorin e6 (Ce6).
Like Xie et al., Chen et al., and Lin, Ph.D. et al., Lin et al. disclose scintillation nanoparticles comprising gold, a coating and a photosensitizer used to treat cancer and teach providing the nanoparticle with "Exemplary photosensitizers for such combination therapy include, but are not limited to: upconversion nanoparticles, such as NaYF.sub.4 (for example, doped at a ratio of Y:Yb:Er=78%:20%:2%), combined with chlorin e6 or MC540" (see [0209]) in order to provide a known and workable photosensitizer for the treatment of cancer with scintillation nanoparticles.
Therefore, at the time of the of invention it would have been obvious to one of ordinary skill in the art to modify the invention of Xie et al. in view of Chen et al. in view of Lin, Ph.D. et al., as taught by Lin et al., to provide the nanoparticle with a photosensitizer in the form of Chlorin e6 (Ce6) in order to provide a known and workable photosensitizer for scintillation nanoparticles used to treat cancer.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AARON F ROANE whose telephone number is (571)272-4771. The examiner can normally be reached generally Mon-Fri 8am-9pm.
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/AARON F ROANE/Primary Examiner, Art Unit 3792