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 . 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.
Claim Objections
Claim 94 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 92. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112 –
Indefiniteness and Lack of Antecedent Basis
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 92 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 92, line three bridging to line four, recites “reacting… with a therapeutic radioisotope and/or a therapeutic radioisotope”. The second recitation of therapeutic radioisotope is redundant and requires clarification. In the interest of compact prosecution, the second therapeutic radioisotope is interpreted as “a precursor of a therapeutic radioisotope”, however, correction of the claim scope is required.
Claim 92 recites the limitation "the precursor" in lines four and five. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 102 - Anticipation
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 6, 8, 13, 26, 31, 37-39, 92, 94-95, 97, 107-108 and 132 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al (ACSNano, 9(8), 7950-7959, 2015).
Chen taught zirconium-89 (89Zr) labeling of mesoporous silica nanoparticles (MSN) [abstract; see also Figure 1c], whereby numerous de-protonated silanol groups (-Si—0-) inside the meso-channels or on the surface of MSN functioned as inherent hard oxygen donors for stable radio-labeling of Zr [page 7951, right column and 1st full paragraph]. Chen’s labelled particles are reproduced below:
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Zr4+ is a hard Lewis acid, and thus prefers hard Lewis bases, as donor groups. It has been known for many decades that, during the hydrolysis and condensation of tetra- ethyl orthosilicate (TEOS), abundant silanol groups (-Si—OH) form on the surface of amorphous silica particles. Chen demonstrated that it is the deprotonated silanol groups (—Si—0-) that function as the hard Lewis bases for the successful Zr labeling of amorphous silica nanoparticles [page 7951, 2nd to last paragraph], with dominant in vivo liver uptake [page 7953, right column, 1st full paragraph; see also the abstract Figure, and Figure 5f. See the below reproduction:
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.
For 89Zr production, natural yttrium-89 (89Y) was irradiated with a proton beam to create 89Zr, via the 89Y(p,n)89Zr reaction, using a cyclotron. Afterwards, MSN were synthesized, and for 89Zr labeling, the MSN were mixed with 89Zr-oxalate, to produce 89Zr-MSN. Then, 89Zr-MSN were loaded with anticancer drugs (e.g., doxorubicin), and imaged with in vivo PET [page 7957, each of the sections under Materials and Methods].
Chen reads on claims 1, 6, 8, 13, 26, 31, 37-39, 92, 94-95, 97, 107-108 and 132.
Claim Rejections - 35 USC § 103 - Obviousness
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.
Claim(s) 1, 6, 8, 13, 26, 31, 35, 37-39, 92, 94-95, 97, 107-108 and 132 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (ACSNano, 9(8), 7950-7959, 2015).
Chen et al is believed to be anticipatory as described above, but if en arguendo it is not, in the interest of completeness of prosecution, purely arguendo, and for the purposes of this ground of rejection only, Chen will be interpreted as if it is not anticipatory.
In that case, claims 1, 6, 8, 13, 26, 31, 37-39, 92, 94-95, 97, 107-108 and 132 are rendered prima facie obvious over the teachings of Chen, because it is prima facie obvious to combine prior art elements according to known methods, in order to yield predictable results. In the instant case, all the claimed elements (e.g., radioisotopic particles, methods of preparing and methods of using, thereof) were known in the prior art (e.g., Chen) and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would yield nothing more than predictable results (e.g., zirconium-89-labeled mesoporous silica nanoparticles) to one of ordinary skill in the art. MPEP 2143.A.
Chen reads on claims 1, 6, 8, 13, 26, 31, 37-39, 92, 94-95, 97, 107-108 and 132.
Regarding claim 35, Chen was not explicit a teaching of 90Y, however Chen disclosed a belief that the use of intrinsic deprotonated silanol groups from MSN (or other mesoporous silica-coated nanoparticles) for radio-labeling may be applicable to other oxophilic radio-metals, such as yttrium-90 (90Y) [page 7956, last paragraph].
As such, it would have been prima facie obvious to one of ordinary skill in the art to include 90Y within the teachings of Chen. The ordinarily skilled artisan would have been motivated by Chen’s guidance that the use of intrinsic deprotonated silanol groups from MSN for radiolabeling is applicable to 90Y [Chen at the last paragraph of page 7956].
Claim(s) 44 is rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (ACSNano, 9(8), 7950-7959, 2015), in view of Erbe et al (Journal of Biomedical Materials Research, 27, 1301-1308, 1993).
The 35 U.S.C. 103 rejection over Chen was previously described.
Chen was silent yttrium aluminum silicon oxide, as recited in claim 44.
Erbe taught microspheres made from Y2O3-Al2O3-SiO2 as durable and effective in vivo radiation delivery vehicles, without harmful side effects [Abstract and Introduction].
Since Chen taught silica nanoparticles for the in vivo delivery of radioactivity (e.g., 89Zr-MSN), it would have been prima facie obvious to one ordinary skill in the art to include, within the teachings of Chen, Y2O3-Al2O3-SiO2, as taught by Erbe. The ordinarily skilled artisan would have been so motivated, because yttrium aluminum silicon oxide particles are durable and effective in vivo radiation delivery vehicles, without harmful side effects, as taught by Erbe at the Abstract and Introduction.
Claim(s) 112 is rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (ACSNano, 9(8), 7950-7959, 2015), in view of Xie et al (International Journal of Pharmaceutics, 474, 2014, 223-231).
The 35 U.S.C. 103 rejection over Chen was previously described.
Although Chen taught dominant liver uptake by MSNs loaded with anticancer agents (e.g., doxorubicin), Chen was not specific treating liver cancer.
Xie taught doxorubicin-loaded mesoporous silica nanoparticles (DOX–MSN), prepared, and used for imaging and targeting therapy of hepatocellular carcinoma. In vitro studies showed that the nanoparticles were easily endocytosed by liver cancer cells, and were well-accumulated in the liver by passive targeting. In vivo studies proved the ability of DOX–MSN to inhibit the tumor growth, and prolong the survival time, of mice bearing hepatocellular carcinoma in situ, giving better results than free DOX, when the mice were administered either normal saline, free DOX or MSN-DOX by tail vein injection [page 221, section 2.10]. More importantly, histological examination showed no histopathological abnormalities of normal liver cells and heart cells, after the administration of DOX–MSN, while the treatment with free DOX caused damage to those cells. In conclusion, DOX–MSN exhibited enhanced antitumor efficacy, as well as reduced side effects, for liver cancer therapy [abstract; see also Figures 7-9].
Since Chen taught dominant liver uptake by MSNs loaded with doxorubicin, it would have been prima facie obvious to one of ordinary skill in the art to include, within the teachings of Chen, treating liver cancer, as taught by Xie. The ordinarily skilled artisan would have been so motivated, because DOX–MSN inhibits the tumor growth, and prolongs the survival time, of mice bearing hepatocellular carcinoma in situ, with enhanced antitumor efficacy, as well as reduced side effects, for liver cancer therapy, as taught by Xie et al [abstract; see also Figures 7-9].
Nonstatutory Double Patenting
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, 6, 8, 13, 26, 31, 35, 37, -39, 44, 92, 94-95, 97, 107-108, 112 and 132 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,904,029.
Claims 1, 6, 8, 13, 26, 31, 35, 37, -39, 44, 92, 94-95, 97, 107-108, 112 and 132 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12,440,587.
Although the claims at issue are not identical, they are not patentably distinct from each other because the species (imageable microspheres) recited in the claims of the issued patents fall within the genus (particles functionalized with therapeutic radioisotopes and methods of making and use thereof) recited in the claims of the instant application, and thus read on the instant claims.
Conclusion
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/CELESTE A RONEY/Primary Examiner, Art Unit 1612