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 .
Receipt is acknowledged of Applicant’s Amendment filed on 07/25/2025.
Claims 1, 7, 9, 10, 16, 19 have been amended.
Claims 1-17, 19-20, 25-26, 28, 30, 32, 37-38, 42 are pending in the instant application.
Claims 3-6, 9-10, 13-17, 28, 30, 38, 42 are withdrawn from further consideration.
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn. The following rejections or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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, 7-8, 11-12, 19-20, 25-26, 32, 37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending Application No. 18/572,423 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the co-application recites a method of treatment of a subject having been diagnosed with cancer (e.g. prostate cancer, ovarian cancer, a malignant brain tumor (e.g., brain or spinal), melanoma), the method comprising administering (e.g., via IV administration) to the subject a composition comprising ultrasmall nanoparticles in concert with administering one or more of (i) to (iv) as follows: (i) cellular therapy; (ii) one or more immune checkpoint blockade antibodies (ICB); (iii) one or more pharmacologic inhibitors; and (iv) external beam radiation or molecular radiotherapy (e.g., peptide radioligands (e.g., radiolabeled PSMA-targeting ligands)) (see claim 1), comprising administering external beam radiation or radiotherapy, wherein the nanoparticles in combination with radiation enhance efficacy of checkpoint blockade (see claim 2), wherein each of the nanoparticles has a hydrodynamic diameter no greater than 20 nm (see claim 36), wherein each of the nanoparticles comprises a silica core (see claim 38), wherein each of the nanoparticles comprises a polyethylene glycol (PEG) shell (see claim 40),wherein the silica composition controlled for ferroptosis comprises nanoparticles made using a ratio of phosphonate-silane to tetramethyl orthosilicate (TMOS) in a reaction feed from 0% to 20% (see claim 49).
The difference between instant application and the patented claims is that the patent claims include additional limitations. Thus, the invention of the patent is in effect a “species” of the “generic” invention of the application claims. It has been held that the generic invention is “anticipated” by the “species”, and, therefore, the application claims are not patentably distinct from the claims of the patent and are rejected on the ground of nonstatutory obviousness-type double patenting. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 7-8, 11-12, 19-20, 25-26, 32, 37 are rejected on the ground of nonstatutory double patenting as being unpatentable over U.S. Patent No. 9,999,694 in view of MENON et al (Cytotoxic Effects of Phosphonate-Functionalized Mesoporous Silica Nanoparticles. ACS Appl. Mater. Interfaces 2016, 8, 2416−2422).
The patent recites a method for detecting tumor cells in a human subject, comprising steps of: (a) administering to the human subject a plurality of multimodal silica-based nanoparticles in a dose ranging from about 0.01 nanomole/kg body weight to about 1 nanomole/kg body weight, each of the nanoparticles comprising: a silica-based core; a fluorescent compound within the core; and a silica shell surrounding at least a portion of the core, wherein each nanoparticle is coated with an organic polymer, wherein a plurality of discrete ligands no greater than 25 in number are attached to each polymer-coated nanoparticle for binding to a tumor marker, and wherein each of the polymer-coated nanoparticles with the ligands attached thereto has a hydrodynamic diameter within a range from 1 nm to 15 nm; (b) directing excitation light into the human subject to excite the fluorescent compound; and (c) imaging the nanoparticles, the nanoparticles being excreted by renal clearance, by the human subject, within a range from 90% of initial dose (ID) to 100% ID in 24 hours after administration.
The patent does not teach using phosphonate.
MENON teaches the prior art had known of treating cancer, such as breast adenocarcinoma (see abstract and reference #49 on pg. 2422), using phosphonate functionalized silica nanoparticles (see title).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate functionalizing phosphonate onto the silica core/nanoparticle. The person of ordinary skill in the art would have been motivated to make those modifications, because it would allow additive affect in treating cancer, and reasonably would have expected success because the references dealt in the same filed of endeavor, such as cancer treatment.
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.
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.
Claim(s) 1-2, 7-8, 11-12, 19-20, 25-26, 32, 37 is/are rejected under 35 U.S.C. 103 as being unpatentable over KIM et al (Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth. Nature Nanotechnology volume 11, pages977–985 (2016) as evidenced by MA et al (Control of Ultrasmall Sub-10 nm Ligand-Functionalized Fluorescent Core−Shell Silica Nanoparticle Growth in Water. Chem. Mater. 2015, 27, 4119−4133) in view of MENON et al (Cytotoxic Effects of Phosphonate-Functionalized Mesoporous Silica Nanoparticles. ACS Appl. Mater. Interfaces 2016, 8, 2416−2422).
KIM teaches a method of treating cancer (see title and abstract), such as pancreatic carcinoma, lung carcinoma and renal carcinoma (see pg. 980, 1st col), comprised of: administering (see pg. 981, 1st col) ultrasmall nanoparticle (see title and abstract) composition comprised of: polyethylene glycol-coated silica nanoparticle (see abstract), which reads on a core and a shell, functionalized with targeting peptides (see abstract), wherein the size in less than 10 nm in diameter of core-shell SNP (see abstract), such a 6nm (see pg. 977, 1st), and appears to be the same method of making the nanoparticle as disclosed by Applicant. Additional disclosures include: radiolabels (see pg. 977, 1st col), which reads on radiotherapy; fluorescent dye (see pg. 977, 1st col+); hydrodynamic radius was determined by fluorescence correlation spectroscopy (“FCS”; see additional page 986, 1st col), which disclosed reference #10 and is the MA et al reference (see pg. 984, under reference #10) discussed below; multidosing delivery scheme (see pg. 980, 2nd col), which reads on multiple doses; ferroptosis (see abstract).
MA is the reference disclosed in KIM discussing about particle size, wherein MA teaches control of ultrasmall sub-10 nm PEGylated nanoparticle (see title and abstract), wherein hydrodynamic sizes range from 4.3-7.8 nm (see pg. 4123, Figure 2) and the thickness of the PEG layer is about 1.5nm (see pg. 4131, 1st col), which reads on a hydrodynamic diameter no greater than 20nm. Thus, it would have been inherent or obvious that KIM has these hydrodynamic diameter ranges. Additional disclosures include: hydrodynamic particle sizes and size distributions are measured by dynamic light scattering (“DLS”; see pg. 4122, 2nd col) and hydrodynamic diameter is also measured by fluorescence correlation spectroscopy (“FCS” see pg. 4123; 4131, 1st col).
KIM as evidence by MA does not teach using phosphonate.
MENON teaches the prior art had known of treating cancer, such as breast adenocarcinoma (see abstract and reference #49 on pg. 2422), using phosphonate functionalized silica nanoparticles (see title).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate functionalizing phosphonate onto the silica core/nanoparticle. The person of ordinary skill in the art would have been motivated to make those modifications, because it would allow additive affect in treating cancer, and reasonably would have expected success because the references dealt in the same filed of endeavor, such as cancer treatment.
Note, the prior art’s nanoparticle composition would have the same chemical/physical properties, such as non-toxic to normal tissue, internalized within one or more cell types of the microenvironment, activation of the microenvironment of the tumor comprises a change in at least one M1 macrophage polarization marker, and the activation of the microenvironment comprises changing a population and/or level of activation of one or more cell types within the microenvironment, as claimed by Applicant, because the prior art’s nanoparticle composition has the same hydrodynamic diameter and ingredients as claimed by Applicant, unless proven otherwise.
The references do not specifically teach the concentration amount of nanoparticle within the microenvironment of the tumor as claimed by Applicant. The concentration amount of a nanoparticle composition used in treating cancer is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal concentration amount in order to best achieve the desired results, such as treating the cancer. Thus, absent some demonstration of unexpected results from the claimed parameters, this optimization of concentration amount within the microenvironment of the tumor would have been obvious at the time of Applicant's invention.
Response to Arguments
Applicant argues that the claims of the Reference Application and paent are silent on a nanoparticle comprising a core and a shell, wherein the nanoparticle core comprises phosphonate.
The Examiner finds this argument unpersuasive, because as discussed in the rejection, the co-application teaches these limitations.
Applicant argues that Kim does not describe or suggest a method of treating cancer by administering a nanoparticle, wherein the nanoparticle core comprises phosphonate, as required by amended claim 1. Ma does not cure the deficiencies of Kim. According to the Examiner, Ma describes control of ultrasmall, less than 10 nm PEGylated nanoparticles. However, Ma does not describe or suggest a nanoparticle wherein the nanoparticle core comprises phosphonate, as recited by the amended claims. Thus, for at least these reasons, Applicants submit that the applied references, either alone or in combination, fail to provide a skilled person with a reasonable expectation of achieving Applicant's claimed invention with predictable results.
The Examiner finds this argument unpersuasive, because as discussed in the rejection, the secondary reference MENON teaches using phosphonate.
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.
Telephonic Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAKE MINH VU whose telephone number is (571)272-8148. The examiner can normally be reached Mon-Fri 9:00am-5:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached at (571) 272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAKE M VU/Primary Examiner, Art Unit 1618
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