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 .
Withdrawn Objections/Rejections
The objection to the specification is withdrawn because the substitute specification has removed the browser-executable code at paragraph [0337].
The objection to claim 5 is withdrawn in view of the cancellation of the claim.
The objections to claims 1, 45, and 68 are withdrawn as the amended claims have addressed the informalities.
The rejections of claims 2 and 5 are withdrawn in view of the cancellation of the claims.
The rejections of claims 61, 64, 68, and 72-74 under 35 USC § 112(b) are withdrawn in view of the claim amendments.
Claim Status
Applicants' amendments and arguments filed 03/23/2026 have been fully considered.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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.
Claims 2, 5-9, 11-12, 14-42, 44, 46-52, 54-55, 57-59, 62-63, 65-67, 69-71, 75-83, 85-86, 88-93, and 95-108 are cancelled.
Claim 109 is newly added.
Claims 56 and 60 are withdrawn as being directed to a nonelected species, and claim 94 is withdrawn as being drawn to a nonelected invention.
Claims 1, 3-4, 10, 13, 43, 45, 53, 61, 64, 68, 72-74, 84, 87, and 109 are under current examination. The claims were read in view of the species elections of a GSK3 inhibitor of AZD1080, components of the lipid bilayer of DSPC, cholesterol, and PE-PEG2000, and an additional therapeutic agent of doxorubicin in the reply filed 07/14/2025.
Objections Maintained
Claim 53 is objected to because of the following informalities: it is believed that “DPSC” in lines 2 and 3, respectively, should read “DSPC” as presented in claim 45, as an abbreviation for distearoylphosphatidylcholine, and later in claim 53.
Appropriate correction is required.
Rejections Maintained, Slightly Modified to Address Claim Amendments and Newly Added Claim 109
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, 3-4, 10, 13, 43, 45, 53, 61, 64, 68, 72-74, 84, 87, and 109 are rejected under 35 U.S.C. 103 as being unpatentable over Nel et al. (WO 2017/120537 A1, published July 13, 2017; included on IDS submitted 06/09/2025), hereafter “Nel” in view of O’Flaherty et al. (WO 2018/083483 A1, published May 11, 2018; of record), hereafter “O’Flaherty”.
Regarding instant claim 1, Nel teaches a nanoparticle drug carrier, referred to as a silicasome, comprising a silica nanoparticle having a surface and defining a plurality of pores (one or more cavities disposed within the nanoparticle) that are suitable to receive molecules therein; a lipid bilayer coating the surface; a cargo-trapping agent within pores comprising said plurality of pores; a cargo comprising a drug where said cargo is associated with said cargo-trapping agent in said pores, wherein the lipid bilayer stably seals (fully encapsulates) the plurality of pores (see abstract, claim 1, and paragraphs [0209] and [0219]). The nanoparticles are shown to have an outside surface and the drug is loaded into the pores via remote loading by incubating with a drug solution (see Figure 1 and description at paragraph [0228]; paragraphs [0012] and [0264]); it is therefore interpreted that the pores are in “fluid communication” with the outside surface of the nanoparticle. The cargo comprises one or more drugs selected from the group including a protein kinase inhibitor (claim 25).
Regarding instant claims 10 and 13, Nel teaches that the silica nanoparticle is a mesoporous silica nanoparticle (claim 16), a porous inorganic nanoparticle.
Regarding claims 43, 45, and 53, Nel teaches that the lipid bilayer comprises a phospholipid, cholesterol (CHOL), and an mPEG phospholipid (claim 2); per the instant specification PE-PEG2000 is an mPEG phospholipid (paragraph [0228]). Nel teaches that the phospholipid comprises a saturated fatty acid selected from the group including DSPC (claim 4). Nel exemplifies a lipid composition of DSPC/cholesterol/PE-PEG2000 (paragraph [0433]).
Regarding instant claim 61, as noted above, Nel teaches a cargo comprising a drug that is associated with a cargo-trapping agent in the pores of the nanoparticle (claim 1). In certain embodiments, the trapping agent comprises a protonating agent (paragraph [0263]).
Regarding instant claims 64 and 68, Nel teaches that the cargo comprises one or more drugs selected from the group including an antitumor anthracycline antibiotic and a protein kinase inhibitor (claim 25, paragraph [0055]). The antitumor anthracycline antibiotic is selected from the group including doxorubicin (paragraph [0058], claim 26).
Regarding instant claims 72-73, Nel teaches that the lipid bilayer comprises a hydrophobic drug selected from the group including paclitaxel (paragraphs [0078]-[0080] and [0322], claims 39-41).
Regarding instant claim 74, Nel teaches that the drug carrier is conjugated to a moiety selected from the group consisting of a targeting moiety, a fusogenic peptide, and a transport peptide (claim 27).
Regarding instant claim 84, Nel teaches that the silicasomes can significantly reduce the toxicity of the drugs administered thereby (paragraph [0365]; see also paragraphs [0268]-[0269]), and that anti-cancer drugs show reduced toxicity as compared to free drug (claim 47); further, reduced leakage and slower drug release from the lipid bilayer-coated nanoparticles reduces the rate of toxicity compared to a liposomal carrier (paragraph [0010]). It is interpreted that drugs delivered by the silicasomes of Nel have reduced drug toxicity compared to their free counterparts.
Regarding instant claim 87, Nel teaches a pharmaceutical formulation comprising a plurality of nanoparticle drug carriers and a pharmaceutically acceptable carrier (claim 49).
Regarding instant claim 109, as noted above, Nel teaches a cargo comprising a drug that is associated with a cargo-trapping agent in the pores of the nanoparticle (claim 1). In certain embodiments, the trapping agent comprises a protonating agent (paragraph [0263]).
While Nel teaches that the drug cargo in the pores of the nanoparticle can be a protein kinase inhibitor, Nel does not teach the inclusion of a weak basic, amphipathic GSK3 inhibitor (instant claim 1) of AZD1080 (instant claims 3-4).
O’Flaherty teaches a GSK3 (glycogen synthase kinase 3) inhibitor for use in treating cancer, wherein the GSK3 inhibitor is to be administered in combination with a chemotherapy agent (abstract, claim 1). The GSK3 inhibitor is selected from the group including AZD-1080 (claim 2), and the chemotherapy agent is selected from one or more including doxorubicin and paclitaxel (pg. 3, paragraph 3). The GSK3 inhibitor and chemotherapy agent may be supplied in an encapsulated formulation such as a nanoparticle in which both the inhibitor and the chemotherapy agent are encapsulated (pg. 4, paragraph 1). The cancer may be characterized by GSK3 dependency and may be one or more of non-small cell lung carcinoma, pancreatic cancer, prostate cancer, colon cancer, leukemia, ovarian cancer, liver cancer, or glioblastoma (pg. 5, paragraphs 1-2). GSK3 is implicated in a diverse range of disease states including cancer (pg. 1, paragraph 2), and GSK3 inhibitors modulate its activity such that the net enzyme activity is decreased (pg. 2, paragraph 3); GSK3 inhibitors act to destabilize mitotic microtubules and enhance the effect of chemotherapy agents, providing treatment that may be more effective than conventional monotherapy (pg. 3, paragraph 2).
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 drug carrier of Nel to include the GSK3 inhibitor AZD-1080, as suggested by O’Flaherty. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in order to achieve a drug carrier capable of treating cancers characterized by GSK3 dependency such as non-small cell lung carcinoma, pancreatic cancer, etc. and which acts on the mitotic apparatus to provide a treatment that is more effective than conventional monotherapy, as suggested by O’Flaherty; O’Flaherty further suggests encapsulation of a GSK3 inhibitor in combination with a chemotherapy agent such as doxorubicin to achieve these effects upon administration. There is a reasonable expectation of success as the nanoparticle drug carrier of Nel is used in treating cancers including lung and pancreatic cancers (claims 56, 60-61) and can include encapsulated drug cargos of a protein kinase inhibitor and the antitumor agent doxorubicin.
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, 3-4, 10, 13, 43, 45, 53, 61, 64, 68, 72-74, 84, 87, and 109 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 134-136, 142-144, 146-151, and 153 of copending Application No. 18/935,112 in view of O’Flaherty et al. (WO 2018/083483 A1, published May 11, 2018; of record), hereafter “O’Flaherty” and Nel et al. (WO 2017/120537 A1, published July 13, 2017; included on IDS submitted 06/09/2025), hereafter “Nel”.
Both the instant claims and those of copending Application No. 18/935,112 are directed to drug delivery vehicles comprising a porous silica nanoparticle (interpreted as having pores in fluid communication with an outside surface), a lipid bilayer on the surface of the nanoparticle which fully encapsulates (coats) the nanoparticle, a protonating cargo-trapping agent, and a cargo comprising at least one of two different drugs; at least one of the drugs is trapped in the pores of the nanoparticle. The drugs of both sets of claims are recited to comprise a protein kinase inhibitor and doxorubicin. Both sets of claims recite that the lipid bilayer can comprises a phospholipid, cholesterol, and a mPEG phospholipid. Both sets of claims recite that the lipid bilayer comprises a hydrophobic drug of paclitaxel. Both sets of claims recite a nanoparticle drug carrier conjugated to a targeting moiety, a fusogenic peptide, or a transport peptide.
The claims of copending Application No. 18/935,112 do not recite that the protein kinase inhibitor is a GSK3 inhibitor which comprises AZD1080, as required by the instant claims.
O’Flaherty teaches a GSK3 (glycogen synthase kinase 3) inhibitor for use in treating cancer, wherein the GSK3 inhibitor is to be administered in combination with a chemotherapy agent (abstract, claim 1). The GSK3 inhibitor is selected from the group including AZD-1080 (claim 2), and the chemotherapy agent is selected from one or more including doxorubicin and paclitaxel (pg. 3, paragraph 3). The GSK3 inhibitor and chemotherapy agent may be supplied in an encapsulated formulation such as a nanoparticle in which both are encapsulated (pg. 4, paragraph 1). The cancer may be characterized by GSK3 dependency and may be one or more of non-small cell lung carcinoma, pancreatic cancer, prostate cancer, colon cancer, leukemia, ovarian cancer, liver cancer, or glioblastoma (pg. 5, paragraphs 1-2). GSK3 in implicated in a diverse range of disease states including cancer (pg. 1, paragraph 2), and GSK3 inhibitors modulate its activity such that the net enzyme activity is decreased (pg. 2, paragraph 3); GSK3 inhibitors act to destabilize mitotic microtubules and enhance the effect of chemotherapy agents, providing treatment that may be more effective than conventional monotherapy (pg. 3, paragraph 2).
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 drug carrier of copending Application No. 18/935,112 to include the GSK3 inhibitor AZD-1080, as suggested by O’Flaherty. One of ordinary skill would have been motivated to do so in order to achieve a drug carrier capable of treating cancers characterized by GSK3 dependency such as non-small cell lung carcinoma, pancreatic cancer, etc. and which acts on the mitotic apparatus and to provide a treatment that is more effective than conventional monotherapy, as suggested by O’Flaherty; O’Flaherty further suggests encapsulation of a GSK3 inhibitor in combination with a chemotherapy agent such as doxorubicin to achieve these effects upon administration.
The claims of copending Application No. 18/935,112 do not recite that the lipid bilayer comprises the elected species of DSPC, cholesterol, and PE-PEG2000, that the drug delivery vehicle shows reduced drug toxicity, or a composition comprising the drug delivery vehicle and a pharmaceutically acceptable carrier.
Nel teaches a nanoparticle drug carrier, referred to as a silicasome, comprising a mesoporous silica nanoparticle having a surface and defining a plurality of pores (one or more cavities disposed within the nanoparticle) that are suitable to receive molecules therein; a lipid bilayer coating the surface; a cargo-trapping agent within pores comprising said plurality of pores; a cargo comprising a drug where said cargo is associated with said cargo-trapping agent in said pores, wherein the lipid bilayer stably seals the plurality of pores (see abstract, claims 1 and 16, and paragraphs [0209] and [0219]). The cargo comprises one or more drugs selected from the group including a protein kinase inhibitor and an antitumor anthracycline antibiotic of doxorubicin (claims 25-26). Nel teaches that the lipid bilayer comprises a phospholipid, cholesterol (CHOL), and an mPEG phospholipid (claim 2); per the instant specification PE-PEG2000 is an mPEG phospholipid (paragraph [0228]). Nel teaches that the phospholipid comprises a saturated fatty acid selected from the group including DSPC (claim 4). Nel exemplifies a lipid composition of DSPC/cholesterol/PE-PEG2000 (paragraph [0433]). Nel teaches that the silicasomes can significantly reduce the toxicity of the drugs administered thereby (paragraph [0365]); further, reduced leakage and slower drug release from the lipid bilayer-coated nanoparticles reduces the rate of toxicity compared to a liposomal carrier (paragraph [0010]. Nel teaches a pharmaceutical formulation comprising a plurality of nanoparticle drug carriers and a pharmaceutically acceptable carrier (claim 49).
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 drug carrier of copending Application No. 18/935,112 with the DSPC/cholesterol/PE-PEG2000 lipid bilayer and reduced toxicity taught by Nel. One of ordinary skill would have been motivated to do so in order to use a combination of lipids known to be used to stably seal mesoporous silica nanoparticles with protein kinase inhibitors and anti-cancer agents within the pores to achieve a drug carrier capable of treating various cancers (see Nel claims 56 and 61) and to reduce leakage and resulting toxicity of such drugs, as suggested by Nel.
It would further have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to incorporate the nanoparticle drug carrier of copending Application No. 18/935,112 into a pharmaceutical formulation comprising the drug carrier and a pharmaceutically acceptable carrier, as suggested by Nel. One of ordinary skill in the art would have been motivated to do so to achieve a formulation that can be formulated for administration via a desired route and which can be used in cancer treatment methods, as suggested by Nel (see claims 49, and 53-61).
Given the subject matter of the instant claims is obvious and substantially overlaps the subject matter of copending Application No. 18/935,112, the instant claims are rejected on the ground of nonstatutory double patenting. This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-4, 10, 13, 43, 45, 53, 61, 64, 68, 72-74, 84, 87, and 109 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 8-10, 13, 15, and 17 of U.S. Patent No. 12,171,884 B2 in view of in view of O’Flaherty et al. (WO 2018/083483 A1, published May 11, 2018; of record), hereafter “O’Flaherty” and Nel et al. (WO 2017/120537 A1, published July 13, 2017; included on IDS submitted 06/09/2025), hereafter “Nel”.
The claims of U.S. Patent No. 12,171,884 B2 are drawn to a method of making a drug nanocarrier. Similar to the drug delivery vehicle of the instant claims, the drug nanocarrier made by the method of U.S. Patent No. 12,171,884 B2 comprises a porous silica nanoparticle (interpreted as having pores in fluid communication with an outside surface), a phospholipid bilayer comprising cholesterol on the surface of the nanoparticle which encapsulates the nanoparticle, a protonating cargo-trapping agent, and a cargo in the plurality of pores; the cargo can comprise a protein kinase inhibitor and doxorubicin.
The claims of U.S. Patent No. 12,171,884 B2 do not recite that the protein kinase inhibitor is a GSK3 inhibitor which comprises AZD1080, as required by the instant claims.
O’Flaherty teaches a GSK3 (glycogen synthase kinase 3) inhibitor for use in treating cancer, wherein the GSK3 inhibitor is to be administered in combination with a chemotherapy agent (abstract, claim 1). The GSK3 inhibitor is selected from the group including AZD-1080 (claim 2), and the chemotherapy agent is selected from one or more including doxorubicin and paclitaxel (pg. 3, paragraph 3). The GSK3 inhibitor and chemotherapy agent may be supplied in an encapsulated formulation such as a nanoparticle in which both are encapsulated (pg. 4, paragraph 1). The cancer may be characterized by GSK3 dependency and may be one or more of non-small cell lung carcinoma, pancreatic cancer, prostate cancer, colon cancer, leukemia, ovarian cancer, liver cancer, or glioblastoma (pg. 5, paragraphs 1-2). GSK3 in implicated in a diverse range of disease states including cancer (pg. 1, paragraph 2), and GSK3 inhibitors modulate its activity such that the net enzyme activity is decreased (pg. 2, paragraph 3); GSK3 inhibitors act to destabilize mitotic microtubules and enhance the effect of chemotherapy agents, providing treatment that may be more effective than conventional monotherapy (pg. 3, paragraph 2).
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 drug nanocarrier made by the method of U.S. Patent No. 12,171,884 B2 to include the GSK3 inhibitor AZD-1080, as suggested by O’Flaherty. One of ordinary skill would have been motivated to do so in order to achieve a drug carrier capable of treating cancers characterized by GSK3 dependency such as non-small cell lung carcinoma, pancreatic cancer, etc. and which acts on the mitotic apparatus and to provide a treatment that is more effective than conventional monotherapy, as suggested by O’Flaherty; O’Flaherty further suggests encapsulation of a GSK3 inhibitor in combination with a chemotherapy agent such as doxorubicin to achieve these effects upon administration.
The claims of U.S. Patent No. 12,171,884 B2 do not recite that the lipid bilayer comprises the elected species of DSPC, cholesterol, and PE-PEG2000, that the drug delivery vehicle shows reduced drug toxicity, or a composition comprising the drug delivery vehicle and a pharmaceutically acceptable carrier. The claims of U.S. Patent No. 12,171,884 B2 do not recite that the lipid bilayer comprises a hydrophobic drug of paclitaxel or that the drug carrier is conjugated to a targeting moiety, a fusogenic peptide, or a transport peptide.
Nel teaches a nanoparticle drug carrier, referred to as a silicasome, comprising a mesoporous silica nanoparticle having a surface and defining a plurality of pores (one or more cavities disposed within the nanoparticle) that are suitable to receive molecules therein; a lipid bilayer coating the surface; a cargo-trapping agent within pores comprising said plurality of pores; a cargo comprising a drug where said cargo is associated with said cargo-trapping agent in said pores, wherein the lipid bilayer stably seals the plurality of pores (see abstract, claims 1 and 16, and paragraphs [0209] and [0219]). The cargo comprises one or more drugs selected from the group including a protein kinase inhibitor and an antitumor anthracycline antibiotic of doxorubicin (claims 25-26). Nel teaches that the lipid bilayer comprises a phospholipid, cholesterol (CHOL), and an mPEG phospholipid (claim 2); per the instant specification PE-PEG2000 is an mPEG phospholipid (paragraph [0228]). Nel teaches that the phospholipid comprises a saturated fatty acid selected from the group including DSPC (claim 4). Nel exemplifies a lipid composition of DSPC/cholesterol/PE-PEG2000 (paragraph [0433]). Nel teaches that the silicasomes can significantly reduce the toxicity of the drugs administered thereby (paragraph [0365]); further, reduced leakage and slower drug release from the lipid bilayer-coated nanoparticles reduces the rate of toxicity compared to a liposomal carrier (paragraph [0010]. Nel teaches a pharmaceutical formulation comprising a plurality of nanoparticle drug carriers and a pharmaceutically acceptable carrier (claim 49). Nel teaches that the lipid bilayer comprises a hydrophobic drug selected from the group including paclitaxel (paragraphs [0078]-[0080] and [0322], claims 39-41) and that the drug carrier is conjugated to a moiety selected from the group consisting of a targeting moiety, a fusogenic peptide, and a transport peptide (claim 27).
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 drug nanocarrier made by the method of U.S. Patent No. 12,171,884 B2 with the DSPC/cholesterol/PE-PEG2000 lipid bilayer and reduced toxicity taught by Nel. One of ordinary skill would have been motivated to do so in order to use a combination of lipids known to be used to stably seal mesoporous silica nanoparticles with protein kinase inhibitors and anti-cancer agents within the pores to achieve a drug carrier capable of treating various cancers (see Nel claims 56 and 61) and to reduce leakage and resulting toxicity of such drugs, as suggested by Nel.
It would further have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to incorporate the drug nanocarrier made by the method of U.S. Patent No. 12,171,884 B2 into a pharmaceutical formulation comprising the drug carrier and a pharmaceutically acceptable carrier, as suggested by Nel. One of ordinary skill in the art would have been motivated to do so to achieve a formulation that can be formulated for administration via a desired route and which can be used in cancer treatment methods, as suggested by Nel (see claims 49, and 53-61).
It would further 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 lipid bilayer of the drug nanocarrier made by the method of U.S. Patent No. 12,171,884 B2 to comprise the hydrophobic drug of paclitaxel and to conjugate the nanocarrier to a targeting moiety, a fusogenic peptide, or a transport peptide, as suggested by Nel. One of ordinary skill in the art would have been motivated to do so to achieve a drug carrier that can co-deliver a multi-drug regimen of drugs with varying lipophilicity which is capable of treating various cancers (see Nel, paragraphs [0321]-[0322]; claims 56 and 61) and which can bind to a cancer marker and facilitate specific delivery to specific cells (see Nel, claims 104-105; paragraph [0324]).
Given the subject matter of the instant claims is obvious and substantially overlaps the subject matter of U.S. Patent No. 12,171,884 B2, the instant claims are rejected on the ground of nonstatutory double patenting.
Response to Arguments
Applicant’s arguments filed 03/23/2026 have been fully considered, but they are not persuasive.
Regarding the claim rejections under 35 U.S.C. 103, Applicant argues that the prior art of O'Flaherty shows efficacy only of a combination of a GSK3 inhibitor (administered by oral gavage) and a chemotherapeutic agent (administered intraperitoneally) in an animal model, and lack of efficacy of the GSK3 inhibitor when administered alone (e.g., Figure 3A, 3B(ii)). Applicant argues that, in contrast, the claimed drug delivery vehicle demonstrates significant effectiveness in tumor models compared to the free GSK3 inhibitor (e.g., Figure 5A-C, for example) and compared to efficacy of the drug delivery vehicle itself (Figures 8A-C), and that a GSK3 inhibitor administered using the claimed drug delivery vehicle is as efficacious, or more efficacious, against tumors as checkpoint inhibitor therapy (see Figures 5A-C and 8A-C; see also paragraph [0311 ]). Applicant argues that such efficacy is unexpected.
These arguments are unpersuasive. Here, Applicant argues against the prior art of O'Flaherty 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). Further, the test for obviousness is not that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). Further, the teachings of the prior art are not limited to disclosed examples; per MPEP 2123 I., “A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). See also Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005)”.
Here, as detailed above, the prior art of Nel teaches nanoparticles consistent with those instantly claimed, and the inclusion of a cargo of the genus of kinase inhibitors. Nel teaches the benefits of such nanoparticles including significantly reducing the toxicity of the drugs administered thereby (paragraph [0365]; see also paragraphs [0268]-[0269]) and reduced leakage and slower drug release from the lipid bilayer-coated nanoparticles (paragraph [0010]). Nel further teaches that the nanoparticle drug carrier is used in treating cancers including lung and pancreatic cancers (claims 56, 60-61) and can further include antitumor agents. O’Flaherty provides motivation to the skilled artisan to particularly select the kinase inhibitor species of the GSK3 inhibitor AZD-1080 to achieve a drug carrier capable of treating cancers characterized by GSK3 dependency such as non-small cell lung carcinoma, pancreatic cancer, etc. and which acts on the mitotic apparatus to provide a treatment that is more effective than conventional monotherapy. 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).
The fact that O’Flaherty suggests administration of a GSK3 inhibitor in combination with an anticancer agent is more effective than the GSK3 inhibitor alone does not negate the conclusions one of ordinary skill in the art would draw in considering the prior art as a whole, as Nel similarly teaches encapsulation of a kinase inhibitor and a chemotherapy agent for the treatment of cancers. Further, the Examiner notes that the instant claims recite the open “comprising” language, and dependent claims 64 and 68 recite the inclusion of an additional therapeutic agent including chemotherapeutics.
Regarding the allegation that the instantly claimed drug delivery vehicle shows unexpected activity of a weak basic, amphiphilic GSK3 inhibitor in the delivery vehicle instantly claimed, the Examiner notes that evidence of unexpected results must be commensurate in scope with the claimed invention (see MPEP 716.02(d)). Instant independent claim 1 is broad, drawn to a drug delivery vehicle comprising any nanoparticles comprising one or more cavities disposed within and any lipid bilayer disposed on the surface. The evidence cited to by Applicant demonstrates a narrow embodiment of MSNPs and a single lipid combination (see instant specification paragraph [0315] describing the loading of GSK3 inhibitors), and is not commensurate in scope with the claimed invention.
In view of the forgoing, and as further detailed in the above rejections, the Examiner maintains that the instant claims are rendered prima facie obvious by the teachings of the modified Nel.
Regarding the nonstatutory double patenting rejections, Applicant argues, as previously, that porous nanoparticles comprising a GSK3 inhibitor are not only more potent against cancer than the GSK3 inhibitor administered alone, but such nanoparticles are as efficacious as checkpoint inhibitor therapy, if not more efficacious, which is unexpected over the teaching of the prior art.
The previous arguments are addressed above, and for these reasons, the Examiner respectfully maintains that the instant claims are rendered prima facie obvious over the claims of copending Application No. 18/935,112 and U.S. Patent No. 12,171,884 B2 in view of the teachings of the cited prior art. Thus, the nonstatutory double patenting rejections have been maintained.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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
/TREVOR LOVE/Primary Examiner, Art Unit 1611