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 .
Status of the Claims
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 05/09/2025 has been entered.
Claim 3 is cancelled.
Claim 13 is withdrawn.
Claims 1-2 and 4-12 are under current examination.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2 and 4-12 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (US 2017/0281797 A1, published October 5, 2017; of record), hereafter “Lee” in view of Vieira et al. (“Synthesis and characterization of gold nanostructured Chorin e6 for Photodynamic Therapy” Photodiagnosis and Photodynamic Therapy 2017, 18, 6-11; included on IDS submitted 07/08/2024), hereafter “Vieira”.
Regarding instant claim 1, Lee teaches a lactoferrin-conjugated nanoparticle complex comprising metal nanoparticles, glutathione, and lactoferrin (abstract, claim 1); the lactoferrin is taught to be bound to the metal nanoparticles (abstract). The nanoparticles are taught to be gold nanoparticles (claim 2, paragraph [0005]); further, the nanoparticles are taught to be glutathione coated (paragraphs [0005], [0066]). Lee teaches that the nanoparticle complex can be used for oral administration (paragraph [0073]). Lee further teaches that the nanoparticle complex can be used as an effective ingredient in a composition for photothermal/photodynamic therapy (paragraph [0082]). Photodynamic therapy comprises processes of treating a subject in a pathological state with a photosensitizer; compounds that can be used as photosensitizers include chlorin compounds (paragraph [0084]).
Regarding instant claim 4, Lee teaches that the lactoferrin may be surface-modified with a biocompatible polymer (paragraph [0011], claim 3).
Regarding instant claim 5, Lee teaches the biocompatible polymer may be selected from the group consisting of polyethylene glycol, polycaprolactone, polylactic acid, polyglycolic acid, polylactate-co-glycolic acid, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), poly(L-lactide-co-caprolactone), and poly(L-lactide-co-D-lactide) (paragraph [0012], claim 4).
Regarding instant claim 6, Lee teaches that the biocompatible polymer may be modified to have a thiol (-SH) group at one terminal thereof (paragraph [0012], claim 5); Lee further teaches that the lactoferrin may be bound to the metal nanoparticles by disulfide bonds (paragraphs [0013] and [0068], claim 6).
Regarding instant claim 7, Lee teaches that the nanoparticle complex has an average diameter of 4 to 20 nm (paragraph [0014]), claim 7). From MPEP 2144.05, “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”.
Regarding instant claim 9, Lee teaches a pharmaceutical composition comprising the nanoparticle complex (paragraphs [0015], [0075]), which can be administered orally (paragraph [0080]).
Regarding instant claim 10, Lee teaches the pharmaceutical composition can be used for treating brain tumors (paragraphs [0015], [0075]).
Regarding instant claim 11, Lee teaches the pharmaceutical composition can be used for a photothermal or photodynamic therapy (paragraph [0015], [0082]).
Regarding instant claim 12, Lee teaches that the pharmaceutical composition may be targeted to brain tissues (paragraph [0018]) and that the nanoparticle complex, an effective ingredient in the pharmaceutical composition (paragraph [0075]), is efficiently targeted to brain tumor tissues (abstract, paragraph [0021]).
Lee does not teach the limitation of instant claim 1 that a photosensitizer, wherein the photosensitizer is chlorin e6 (Ce6), is bonded to the gold nanoparticles or the limitation of instant claim 2 that the photosensitizer has a substituted thiourea group.
Vieira teaches chlorin e6 (Ce6) functionalized with thiourea and bonded to gold nanoparticles (AuNPs) via the sulphur end group (abstract; pg. 7, sections 2.3-2.4), which is interpreted to be disulfide-bonded to the gold nanoparticles. Vieira further teaches that such nanoparticles can be used in photodynamic therapy as an alternative treatment for cancer (abstract). Photodynamic therapy uses the interaction of radiation with a photosensitizer to produce a reactive oxygen species, leading to cell death; the photodynamic effect causes selective destruction of cancerous tissues and generates fewer side effects compared to conventional methods (pg. 6, “Introduction”, paragraph 4). Vieira further teaches that Ce6 absorbs in a range where the coefficient of biological tissue absorption is low, which is ideal for biological application (abstract), but the use of photosensitizers such as Ce6 are limited by their poor water solubility (pg. 7, column 1, paragraph 1). They further teach that gold nanoparticles have chemical inertness, low toxicity, and strong light absorption at a tunable plasmon resonance which allows for diversified applications; gold nanoparticles conjugated to photosensitizers enhance the PDT of cancer cells by the additional reactive oxygen species generation of the photosensitizer due to the highly localized plasmonic field of the gold nanoparticles (pg. 7, column 1, paragraph 3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to modify the nanoparticle complex of Lee with the bonded thiourea-functionalized chlorin e6 photosensitizer of Vieira.
One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in order to achieve a complex for selective cancer cell destruction with few side effects and enhanced chlorin photosensitizer photodynamic therapy effect, as taught by Vieira. There is a reasonable expectation of success as the gold nanoparticle complex of Lee can be used as an effective ingredient in a composition for photothermal/photodynamic therapy for selective toxicity to cancer cells with the use of a chlorin photosensitizer (paragraphs [0082]-[0084]). Binding the photosensitizer to the gold nanoparticle would predictably result in an enhanced PDT effect of the photosensitizer.
Regarding instant claim 8, MPEP 2144.05 II. A. teaches that generally, differences in concentration will not support patentability. “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.” and "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”.
Here, the prior art teaches the general conditions of lactoferrin bound to glutathione coated gold nanoparticles and chlorin e6 bound to gold nanoparticles, both for use in photodynamic therapy. Further, Lee teaches that the binding ratio of lactoferrin to polyethylene glycol and binding ratio of lactoferrin to which polyethylene glycol is bound and the gold nanoparticles to which glutathione is bound are not limited (paragraph [0072]), suggesting the weight ratios of components bound to gold nanoparticles are similarly not limited. Viera tested a range of concentrations of Ce6-AuNPs and mixtures of Ce6 + AuNPs and found all concentrations to have similar effects on cell viability (Fig. 5), further suggesting the concentration, and therefore mass, of Ce6 is not particularly limited. One of ordinary skill in the art could experiment with the general conditions described in the art to optimize the binding ratios lactoferrin and Ce6, and thus the weight ratio of components, and reach the ratio of the instant claims.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2 and 4-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 10,828,083 B2 in view of Lee et al. (US 2017/0281797 A1, published October 5, 2017; of record), hereafter “Lee” and Vieira et al. (“Synthesis and characterization of gold nanostructured Chorin e6 for Photodynamic Therapy” Photodiagnosis and Photodynamic Therapy 2017, 18, 6-11; included on IDS submitted 07/08/2024), hereafter “Vieira”.
Claims 1-12 are directed to an invention not patentably distinct from claims 1-3 of commonly assigned copending U.S. Patent No. 10,828,083 B2.
Both the instant claims and those of U.S. Patent No. 10,828,083 B2 recite a nanoparticle complex comprising gold nanoparticles, glutathione, and lactoferrin covalently linked/bonded to the gold nanoparticles for oral administration; the lactoferrin is bound/modified with polyethylene glycol. The nanoparticle complex of both sets of claims targets brain tissue and is used for photothermal or photodynamic treatment for treating brain tumors.
The claims of U.S. Patent No. 10,828,083 B2 do not recite that the gold nanoparticles are coated with glutathione or that the lactoferrin is surface-modified with a biocompatible polymer selected from the group consisting of polyethylene glycol, polycaprolactone, polylactic acid, polyglycolic acid, polylactate-co-glycolic acid, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), poly(L-lactide-co-caprolactone), and poly(L-lactide-co-D-lactide) or a biocompatible polymer that has a substituted thiol group, as required by the instant claims. The claims of U.S. Patent No. 10,828,083 B2 further do not recite the average diameter of the nanoparticle complex or a pharmaceutical composition comprising the nanoparticle complex.
Lee teaches a lactoferrin-conjugated nanoparticle complex comprising metal nanoparticles, glutathione, and lactoferrin (abstract, claim 1); the lactoferrin is taught to be bound to the metal nanoparticles (abstract). The nanoparticles are taught to be gold nanoparticles (claim 2, paragraph [0005]); further, the nanoparticles are taught to be glutathione coated (paragraphs [0005], [0066]). Lee teaches that the nanoparticle complex can be used for oral administration (paragraph [0073]). Lee further teaches a pharmaceutical composition comprising the nanoparticle complex (paragraphs [0015], [0075]), which can be administered orally (paragraph [0080]) which can be used for treating brain tumors (paragraphs [0015], [0075]), can be used for a photothermal or photodynamic therapy (paragraph [0015], [0082]), and may be targeted to brain tissues (paragraph [0018]); the nanoparticle complex, an effective ingredient in the pharmaceutical composition (paragraph [0075]), is efficiently targeted to brain tumor tissues (abstract, paragraph [0021]).
Lee further teaches that the lactoferrin may be surface-modified with a biocompatible polymer (paragraph [0011], claim 3) which may be selected from the group consisting of polyethylene glycol, polycaprolactone, polylactic acid, polyglycolic acid, polylactate-co-glycolic acid, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), poly(L-lactide-co-caprolactone), and poly(L-lactide-co-D-lactide) (paragraph [0012], claim 4); Lee further teaches that the biocompatible polymer may be modified to have a thiol (-SH) group at one terminal thereof (paragraph [0012], claim 5) and that the lactoferrin may be bound to the metal nanoparticles by disulfide bonds (paragraphs [0013] and [0068], claim 6). Lee teaches that the nanoparticle complex has an average diameter of 4 to 20 nm (paragraph [0014]), claim 7). From MPEP 2144.05, “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”.
It would have been prima facie obvious to one of ordinary skill in the art to modify the nanoparticle complex of U.S. Patent No. 10,828,083 B2 to have glutathione coating the gold nanoparticles, lactoferrin surface-modified with a biocompatible polymer bound to the nanoparticles by disulfide bonds and an average diameter of 4 to 20 nm, as taught by Lee; if would further have been prima facie obvious to formulate a pharmaceutical composition comprising the nanoparticle complex, as taught by Lee. One of ordinary skill would have been motivated to do so to develop a nanoparticle complex that is efficiently targeted to brain tumor tissues for the treatment of brain tumors with maintained stability, even in in vivo conditions (Lee, paragraphs [0021], [0066]) with enhanced bioavailability, particularly oral absorption rate (Lee, paragraph [0068]) and good transmission rate of the blood brain barrier (Lee, paragraph [0071]). Formulating a composition comprising the nanoparticle complex allows for its use in photothermal/photodynamic therapy (paragraph [0082]).
The claims of U.S. Patent No. 10,828,083 B2 do not recite that a photosensitizer of chlorin e6 is bonded to the gold nanoparticles or that the photosensitizer has a substituted thiourea group, as required by the instant claims.
Vieira teaches chlorin e6 (Ce6) functionalized with thiourea and bonded to gold nanoparticles (AuNPs) via the sulphur end group (abstract; pg. 7, sections 2.3-2.4), which is interpreted to be disulfide-bonded to the gold nanoparticles. Vieira further teaches that such nanoparticles can be used in photodynamic therapy as an alternative treatment for cancer (abstract). Photodynamic therapy uses the interaction of radiation with a photosensitizer to produce a reactive oxygen species, leading to cell death; the photodynamic effect causes selective destruction of cancerous tissues and generates fewer side effects compared to conventional methods (pg. 6, “Introduction”, paragraph 4). Vieira further teaches that Ce6 absorbs in a range where the coefficient of biological tissue absorption is low, which is ideal for biological application (abstract), but the use of photosensitizers such as Ce6 are limited by their poor water solubility (pg. 7, column 1, paragraph 1). They further teach that gold nanoparticles have chemical inertness, low toxicity, and strong light absorption at a tunable plasmon resonance which allows for diversified applications; gold nanoparticles conjugated to photosensitizers enhance the PDT of cancer cells by the additional reactive oxygen species generation of the photosensitizer due to the highly localized plasmonic field of the gold nanoparticles (pg. 7, column 1, paragraph 3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to modify the nanoparticle complex of U.S. Patent No. 10,828,083 B2 with the bonded thiourea-functionalized chlorin photosensitizer of Vieira. One of ordinary skill in the art would have been motivated to do so to produce a complex for selective cancer cell destruction with few side effects that exhibits an enhanced photodynamic therapy effect and additional reactive oxygen species generation, as taught by Vieira.
The claims of U.S. Patent No. 10,828,083 B2 do not recite a specific weight ratio of gold nanoparticle, photosensitizer, and lactoferrin. However, MPEP 2144.05 II. A. teaches that generally, differences in concentration will not support patentability. “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.” and "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”.
Here, the prior art teaches the general conditions of lactoferrin bound to glutathione coated gold nanoparticles and chlorin e6 bound to gold nanoparticles, both for use in photodynamic therapy. Further, Lee teaches that the binding ratio of lactoferrin to polyethylene glycol and binding ratio of lactoferrin to which polyethylene glycol is bound and the gold nanoparticles to which glutathione is bound are not limited (paragraph [0072]), suggesting the weight ratios of components bound to gold nanoparticles are similarly not limited. Viera tested a range of concentrations of Ce6-AuNPs and mixtures of Ce6 + AuNPs and found all concentrations to have similar effects on cell viability (Fig. 5), further suggesting the concentration, and therefore mass, of Ce6 is not particularly limited. One of ordinary skill in the art could experiment with the general conditions described in the art to optimize the binding ratios lactoferrin and Ce6 and thus the weight ratio of components and reach the ratio of the instant claims.
As the invention of the instant claims is obvious and substantially overlaps those of U.S. Patent No. 10,828,083 B2, the instant claims are rejected on the ground of nonstatutory double patenting.
The U.S. Patent and Trademark Office may not institute a derivation proceeding in the absence of a timely filed petition. The USPTO normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). Commonly assigned U.S. Patent No. 10,828,083 B2, discussed above, may form the basis for a rejection of the noted claims under 35 U.S.C. 102 or 103 if the commonly assigned case qualifies as prior art under 35 U.S.C. 102(a)(2) and the patentably indistinct inventions were not commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention.
In order for the examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(c)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 U.S.C. 102(c) and 37 CFR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement.
A showing that the inventions were commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention will preclude a rejection under 35 U.S.C. 102 or 103 based upon the commonly assigned case. Alternatively, applicant may take action to amend or cancel claims such that the applications, or the patent and the application, no longer contain claims directed to patentably indistinct inventions.
Response to Arguments
Applicants’ arguments filed 05/09/2025 have been fully considered, but they are not persuasive.
Regarding the claim rejections under 35 USC § 103, Applicant argues that Office Action’s position is that the claimed nanoparticle complex is a combination of known elements taught in Lee (AuNP + Lactoferrin) and Vieira (Ce6 + AuNP). Applicant argues (referring to the Declaration under 37 CFR. 1.132 filed 12/11/2024) that the claimed nanoparticle complex exhibits unexpected advantages. Particularly, Applicant argues that the claimed Ce6-AuNP-Lf exhibited PTT efficiency higher than that of AuNP, AuNPLf, or Ce6-AuNP and is superior in brain tumor targeting effect, which correlates its high PTT efficiency. Regarding the Examiners previous response that "it is unclear that the differences in maximum temperature and PTT efficiency observed for Ce6-AuNP-Lf represent a statistical and practically significant difference," Applicant submits that this is best addressed by a subject matter expert. Applicant argues that the evidence of unexpected results is now commensurate in scope with the amended claims.
These arguments are unpersuasive to overcome the claim rejections set forth above. First, the Examiner respectfully maintains the position of the Office Action mailed 02/25/2025 that, contrary to Applicant’s claims, the above rejection does not set forth a rationale of a combination of known elements; rather, the rejection sets forth a rationale that there is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference and there was a reasonable expectation of success in doing so (see MPEP 2143 I.G.). Particularly, one of ordinary skill in the art would be motivated to modify the nanoparticle complex of Lee with the bonded thiourea-functionalized chlorin e6 photosensitizer of Vieira to produce a complex for selective cancer cell destruction with few side effects and enhanced chlorin photosensitizer photodynamic therapy effect, as taught by Vieira. There is a reasonable expectation of success as the gold nanoparticle complex of Lee can be used as an effective ingredient in a composition for photothermal/photodynamic therapy for selective toxicity to cancer cells with the use of a chlorin photosensitizer (paragraphs [0082]-[0084]). Binding the photosensitizer to the gold nanoparticle would predictably result in an enhanced PDT effect of the photosensitizer.
The Examiner also respectfully notes that it is not necessary that the prior art achieve the same advantage or result discovery by Applicant. Per MPEP 2144 IV., “The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006)”. Further, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Regarding the argument that it is best for a subject matter expert to address the statistical and practically significant difference of the evidence of unexpected results, the Examiner respectfully notes that, per MPEP 716.02(b), Applicants have the burden of explaining proffered data: “"[A]ppellants have the burden of explaining the data in any declaration they proffer as evidence of non-obviousness." Ex parte Ishizaka, 24 USPQ2d 1621, 1624 (Bd. Pat. App. & Inter. 1992).” Absent any further explanation from the Applicant, the Examiner maintains the position regarding the Declaration under 37 CFR 1.132 set forth in the Office Action mailed 02/25/2025.
Particularly, the prior art of Lee teaches a lactoferrin-conjugated nanoparticle complex comprising gold nanoparticles, glutathione, and lactoferrin bound to the nanoparticles for oral administration which can be used as an effective ingredient in a composition for photothermal/photodynamic therapy, and that photosensitizers including chlorins can be used in such compositions. Lee further teaches that these nanoparticles are efficiently targeted to brain tumor tissues (see particularly paragraphs [0021] and [0121]-[0127] and Fig. 20) and have a photothermal therapeutic effect on brain tumor cells (see particularly paragraphs [0115]-[0117] and [0135]-[0142] and Fig. 27).
Per MPEP 716.02(b), “The evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992)“ and per 716.02(e), “An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979).” The Examiner respectfully maintains that the Declaration does not provide an explanation of how the instantly claimed nanoparticle complex have a achieved an effect that is “in fact unexpected an unobvious and of both statistical and practical significance” over the teachings of the prior art nor an explanation of how the brain tumor targeting effect correlates to the PTT efficiency. Further, the Declaration does not provide a comparison in brain tumor targeting effect of the instant invention to the Lf-AuNP complexes of Lee, and therefore no unexpected improvement can be concluded.
In view of the foregoing, and as further detailed in the above rejections, the Examiner maintains
that the instant claims are prima facie obvious over the teachings of the modified Lee.
With regards to the non-statutory double-patenting rejections, Applicants wish to address them after all other rejections are overcome.
The Examiner notes that a request to address the rejections once the claims are found allowable is not a proper response to a rejection (see MPEP 37 CFR 1.111(b) and 714.02). Thus, the double patenting rejections of record have been maintained as no action regarding these rejections has been taken by Applicants at this time and Applicants have not addressed the merits of the rejections.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JUDITH M KAMM whose telephone number is (703)756-4575. The examiner can normally be reached M-F 8:00 am-4:30 pm EST.
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/J.M.K./Examiner, Art Unit 1611
/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611