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
Pursuant to the amendment dated 12/29/2025, claim 3 has been cancelled. Claims 1, 2, and 4-20 are pending. Claims 18-20 stand withdrawn without traverse.
Claims 1, 2, and 4-17 are under current examination.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63109298, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The following limitations are not supported:
The full scope of the phrase “nucleic acid molecule” is broader than the “oligonucleotide” discussed in the provisional application;
The limitation that a chelator is present and covalently bound to the radiolabel and the therapeutic nanoparticle;
the polymer coating;
the full scope of modified or locked nucleic acid molecule; and
the full scope of the radiolabels listed in instant claim 6.
As none of the claims are fully supported in the provisional application, all claims are afforded a filing date of the international application, PCT/US2021/057912, specifically 11/03/2021.
Claim Rejections - 35 USC § 112
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.
Claims 1, 2, and 4-17 are 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.
The phrase “wherein the chelator and the nucleic acid molecule are each independently attached to different functional groups on the surface of the therapeutic nanoparticle” could be interpreted to require the chelator to be attached to one category of functional group and the nucleic acid molecule to be attached to a different category of functional group, or it could be interpreted to require that each functional group is only bound to a chelating agent or to a nucleic acid molecule; i.e. under this interpretation, the claim permits both the chelator and the nucleic acid molecule to be bound to the same category of functional group, so long as no single functional group is bound to both the chelator and the nucleic acid molecule at once. As the scope of the claim differs depending upon the interpretation, and the interpretation is ambiguous, the claim is indefinite under 35 USC §112(b).
Claims depending from rejected claims have also been rejected because they incorporate all of the limitations of the claims from which they depend, but fail to resolve the indefiniteness concerns outlined above.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 4 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 4 fails to include all the limitations of the claim upon which it depends. Claim 1, from which claim 4 depends, limits the chelator to only NODAGA; however, claim 4 allows the chelator to be selected from multiple chelators that are not NODAGA. As such, claim 4 permits the chelator to be substances that have been excluded from claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
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, 4-6, 12-17 are rejected under 35 U.S.C. 103 as being unpatentable over Moore et al. (US 2022/0031873; available as prior art under 35 USC 102(a)(2), filed 07/23/2021 and claiming priority to US provisional application no. 63058225, filed 07/29/02020) in view of Chan et al. (US 2017/0051044; publication date: 02/23/2017; of record).
With respect to claim 1, Moore discloses a multi-modal contrast agent for medical imaging comprising a nanoparticle having a magnetic core with a chelating compound coupled to the magnetic core that chelates (i.e. is covalently bound to) either copper-64 or technetium-99m, wherein the magnetic core has a diameter of 1-50 nm (0014-0016; please note the range disclosed by Moore for diameter overlaps with the range recited in the instant claims, see MPEP 2144.05). The magnetic core is coated with dextran (0018) that has been modified for coupling the chelating agents by reaction with epichlorohydrin that is aminated (i.e. pendant amine groups to covalently couple ligands; 0024, 0028). Moore discloses further that the nanoparticle may optionally include an adjunct agent coupled to the magnetic core such as an oligonucleotide (i.e. 0094) and that the nanoparticle surface is configured to couple or conjugate ligands via functional groups selected from the group consisting of inter alia sulfhydryl groups (0084), thus Moore discloses coupling, i.e. conjugating, a nucleic acid molecule to the surface of the nanoparticle. Moreover, the at least one functional group is configured to couple, i.e., conjugate, detectable agents to the at least one magnetic core and is selected from the group consisting of an amine (e.g., amino), a thiol (also referred to as a sulfanyl group or a sulfhydryl group), a hydroxyl, a carboxyl, a phosphate, an aldehyde, an azide, a vinyl (e.g., vinyl sulfone), an alkyne/dibenzocyclooctyne (DBCO), a lysine, a maleimide, biotin, and combinations thereof, as non-limiting examples (0084). Thus, Moore teaches different functional groups that can be used to conjugate compounds to the particle.
Although Moore does not describe a single example magnetic particle containing a chelated radiolabel and an oligonucleotide, it would have been prima facie obvious to synthesize a magnetic nanoparticle having both pendant moieties because such was contemplated by Moore. Moore renders obvious a therapeutic nanoparticle comprising: a radiolabel; a chelator that is covalently linked to the therapeutic nanoparticle and to the radiolabel; and a nucleic acid molecule that is covalently linked to the therapeutic nanoparticle, wherein the therapeutic nanoparticle has a diameter between about 10 to about 30 nm, and wherein the therapeutic nanoparticle is magnetic.
Moore does not disclose using NODAGA as the chelator as required by instant claim 1.
Chan discloses that NODAGA as well as NOTA and DOTA was known for chelating copper isotopes and also discloses that zirconium-89 was known for PET imaging (0307).
It would have been prima facie obvious to replace the DOTA or NOTA chelating agents with NODAGA because these substances were known to serve the same purpose as of the instant effective filing date (see MPEP 2144.06).
With regard to claim 4, the chelators may be inter alia, p-SCN-Bn-DOTA or NOTA (0091, 0124).
With regard to claim 5, as noted above the radiolabel may be copper-64.
With regard to claim 6, Moore does not disclose the specific radioisotopes recited in instant claim 6; however, as noted above Chan also discloses that zirconium-89 was known for PET imaging. It would have been prima facie obvious to replace the copper-64 radioisotope chelate for PET with a zircomium-89 complex because these substances were known to serve the same purpose as of the instant effective filing date (see MPEP 2144.06).
With regard to claim 12, the core comprises iron oxide (Moore, claim 2).
With regard to claims 13 and 14, as noted above, the coating comprises the polymer dextran.
With regard to claims 15-17, the particle may be included in a pharmaceutical composition containing a pharmaceutically acceptable carrier e.g. the diluents water or saline, and be formulated for injection (i.e. injectable).
Claims 2 and 7-11 are rejected under 35 U.S.C. 103 as being unpatentable over Moore et al. (US 2022/0031873; available as prior art under 35 USC 102(a)(2), filed 07/23/2021 and claiming priority to US provisional application no. 63058225, filed 07/29/02020) and Chan et al. (US 2017/0051044; publication date: 02/23/2017; of record) as applied to claims 1, 4-6, and 12-17 above, and further in view of Medarova et al. (US 2018/0055781; publication date: 03/01/2018).
The relevant disclosure of Moore is set forth above. Moore renders obvious a therapeutic nanoparticle comprising: a radiolabel; a chelator that is covalently linked to the therapeutic nanoparticle and to the radiolabel; and a nucleic acid molecule that is covalently linked to the therapeutic nanoparticle, wherein the therapeutic nanoparticle has a diameter between about 10 to about 30 nm, and wherein the therapeutic nanoparticle is magnetic. As noted above, Moore discloses that amine or sulfhydryl groups are functional groups that can be used to conjugate substances to the dextran surface of the coated nanoparticle.
Moore does not disclose that the amine linkage to the chelator is via a secondary amine as required by instant claim 2, nor does Moore disclose the more specific features of the nucleic acid molecule as claimed in instant claims 7-11.
Medarova discloses that imaging labels (specifically a fluorophore) can be linked to dextran coated magnetic nanoparticles through a chemical moiety that contains a secondary amine (0008).
Medarova also discloses that antagomirs such as one targeting miR-10b can be attached to magnetic nanoparticles that have been coated with dextran (abstract). More specifically a knock-down LNA (locked nucleic acid; 0021) targeting human anti-miR-10b (0038) is covalently linked via a disulfide bond (Medarova claim 37) to a dextran coated magnetic nanoparticle and the nanoparticles are effectively distributed through the breast tumor tissue and can and the MN-anti-miR10b builds up in tissue after a second treatment (0172). The locked nucleic acid (LNA) has a modified sugar (0088) and is therefore considered a modified nucleotide.
With regard to claim 2, it would have been prima facie obvious to conjugate the chelator bound to a radiolabel via a secondary amine because one having ordinary skill would have recognized this to be a suitable linker, falling within the small genus of “amine” disclosed by Moore, see MPEP 2144.07.
With regard to claims 7-11, it would have been prima facie obvious to conjugate Moore’s nanoparticle with the modified, locked nucleic acid molecule anti-miR10b, an antagomir, via a disulfide linkage. The skilled artisan would have been motivated to do so in order to create a particle that could be used to both treat and provide multimodal imaging of a tumor, with targeted delivery of therapy (i.e. the antagomir targeting miR-10b). The skilled artisan would have had reasonable expectation of success because (1) Moore teaches suitable conjugating groups for disulfide linkages, i.e. coatings having pendant sulfhydryl groups for conjugating ligands and (2) because Medarova shows effective distribution and accumulation of a closely related magnetic nanoparticle (dextran coated nanoparticles having pendant antagomir and fluorophore).
Claims 1, 2, and 4-17 are rejected under 35 U.S.C. 103 as being unpatentable over view of Medarova et al. (US 2018/0055781; publication date: 03/01/2018; of record) in view of Tassa et al. (Accounts of Chemical Research 44(10), p 842-852; publication year: 2011; of record), and further in view of Zhang (Website: NCBI Bookshelf 64Cu-DTPA-CLIO-VT680; last updated online 2011; of record), Udupa et al. (US 2019/0259159; publication date: 08/22/2019; of record), and Chan et al. (US 2017/0051044; publication date: 02/23/2017; of record).
With respect to claim 1, Medarova discloses a therapeutic magnetic nanoparticle having an epichlorohydrin crosslinked dextran coating (0020, 0026), and a nucleic acid molecule that is 10 – 30 nm in diameter (0006). The nucleic acid molecule is covalently linked to the nanoparticle (0007). The nanoparticle can be used in imaging and treatment of cancer (abstract, 0011). As discussed in more detail in the context of instant claims 2 and 11, Medarova teaches conjugation via different functional groups (see 0025: linking a fluorophore imaging agent via secondary amine; claim 37: linking via disulfide).
Medarova does not disclose a radiolabel or a chelator that is covalently linked to the therapeutic nanoparticle and to the radiolabel.
Tassa discloses that superparamagnetic epichlorohydrin crosslinked dextran coated iron oxide magnetic nanoparticle (CLIO) are a versatile platform for targeted molecular imaging, diagnostics, and therapy. Tassa discloses that, in addition to fluorescent labels (page 844, right col), CLIO nanoparticles can be labeled with ligands for MRI and PET (sections 6.2 and 6.3, on pages 848-9). Tassa describes a study in which experiments established a 64Cu-CLIO-VT680 (having both a radiolabel, copper-64, and a fluorophore covalently linked to a CLIO particle) or 18F-CLIO nanoparticles can provide sensitive, multichannel assessments of different biological signals in vivo (page 849, left col). Tassa discloses further that imaging ligands can be combined with therapeutic ligands (specifically photodynamic therapy ligands; section 6.4, page 849).
Zhang discloses the structure of 64Cu-CLIO-VT680, which is a triple labeled reporter CLIO nanoparticle. Specifically, in addition to the magnetic core that can function as an MRI signal, the particle is labeled with 64Cu chelated by DTPA as well as a fluorescent label.
Udupa discloses inter alia “positron emission tomography/magnetic resonance imaging (PET/MRI), improves the sensitivity for detection of pathology at the molecular, subcellular, or cellular level well before gross anatomic changes manifest, and simultaneously improves the specificity of diagnosis to distinguish whether macroscopic abnormalities are benign or malignant in nature. As such, it changes management in up to 40% of patients with cancer prior to implementation of treatment, often due to improved detection of regional lymph node metastases and distant metastases in the body, and improves the diagnostic performance of post-treatment assessment compared to structural imaging with CT or MRI alone. Importantly, PET provides image data that are quantifiable prior to and following treatment, allowing for individualized regional and global disease assessment of patients with cancer and other non-neoplastic disease conditions.” (0008)
In view of Tassa and Zhang, one having ordinary skill would have understood that epichlorohydrin crosslinked dextran coated magnetic iron oxide nanoparticles can be labeled with a variety of imaging or therapeutic ligands to provide imaging options chosen from PET, SPECT, MRI, CT, and fluorescence and can be simultaneously labeled with therapeutic conjugates. In view of Udupa, one would have understood that PET/MRI is more sensitive than either technique alone for detecting/diagnosing cancers and improves diagnostic performance of post-treatment assessment.
It would have been prima facie obvious to add a radiolabel like the DTPA chelated 64Cu described by Tassa and Zhang to Medarova’s therapeutic nanoparticle bound to a nucleic acid molecule. The artisan of ordinary skill would have been motivated to do so to take advantage of PET/MRI’s enhanced diagnostic and disease monitoring sensitivity for improved patient outcomes. The skilled artisan would have had reasonable expectation of success because the chemistry to link multiple ligands to an epichlorohydrin crosslinked dextran coated nanoparticle was established as of the instant effective filing date and because the benefit of PET/MRI was also known.
The relevant disclosures Medarova, Tassa, Zhang, and Udupa are set forth above. None of these references disclose the chelators required by instant claims 1 or 4, nor do they disclose using the specific radioisotopes recited in instant claim 6.
Chan discloses that NODAGA as well as NOTA and DOTA was known for chelating copper isotopes and also discloses that zirconium-89 was known for PET imaging (0307).
With regard to claim 1, it would have been prima facie obvious to replace the DTPA chelating agent described by Tassa/Zhang with NODAGA because these substances were known to serve the same purpose as of the instant effective filing date (see MPEP 2144.06).
With regard to claim 2, Medarova discloses the ligands can be linked by a secondary amine (0025).
With regard to claim 5, as noted above Tassa/Zhang disclose copper-64.
With regard to claim 6, it would have been prima facie obvious to replace the copper-64 radioisotope chelate for PET with a zircomium-89 complex because these substances were known to serve the same purpose as of the instant effective filing date (see MPEP 2144.06).
With regard to claims 7-11, Medarova specifies that antagomirs such as one targeting miR-10b can be attached to magnetic nanoparticles that have been coated with dextran (abstract). More specifically a knock-down LNA (locked nucleic acid; 0021) targeting human anti-miR-10b (0038) is covalently linked via a disulfide bond (Medarova claim 37) to a dextran coated magnetic nanoparticle and the nanoparticles are effectively distributed through the breast tumor tissue and can and the MN-anti-miR10b builds up in tissue after a second treatment (0172). The locked nucleic acid (LNA) has a modified sugar (0088) and is therefore considered a modified nucleotide.
With regard to claim 12, Medarova discloses iron oxide cores (0071).
With regard to claims 13 and 14, as noted above, the particles are coated with the polymer, dextran.
With regard to claims 15-17, Medarova discloses pharmaceutical compositions having diluents formulated for various routes of injection (0111).
Response to Arguments
Applicant's arguments filed 12/29/2025 have been fully considered but they are not persuasive.
On page 6, Applicant argues that Chan’s disclosure of NODAGA is in a laundry list and in the context of protein-based constructs not nanoparticles and therefore cannot provide the motivation to modify the nanoparticle art without impermissible hindsight. Applicant argues further that Chan does not involve therapeutic nanoparticles, radiolabels, chelators, or therapeutic nucleic acid molecules and does not disclose or suggest attaching different payloads to different functional groups, and that the primary nanoparticle references do not mention NODAGA at all and teach other chelators (e.g. DOTA, NOTA and DTPA). Applicant concludes on pages 6-7 that none of the cited references either alone or in combination provide any reason or motivation to formulate a therapeutic nanoparticle comprising a chelator consisting of NODAGA and that motivation could only result from hindsight reasoning.
With regard to the argument that there is no motivation to select NODAGA from among a laundry list of chelating agents, Applicant is reminded that it is prima facie obvious to combine or substitute substances known to serve the same purpose (see MPEP 2144.06: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Similarly, it is obvious to substitute equivalents that had been recognized in the art to serve the same purpose. The Examiner also directs Applicant’s attention to Merck &Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Circ. 1989), which states with regards to its more than 1200 combinations: that the prior art “discloses a multitude of effective combinations does not render any particular formulation less obvious. This is especially true because the claimed composition is used for the identical purpose taught by the prior art.” Furthermore, it is noted that Applicants do not identify any secondary consideration demonstrating criticality or anything unexpected about the combination of two known prior art pharmaceutical agents. For the foregoing reasons, selection of any known chelating agent would have been prima facie obvious to the artisan of ordinary skill.
With regard to the argument that Chan does not disclose nanoparticles and the references cited for their teachings regarding nanoparticles do not disclose NODAGA, In response to applicant's arguments against the references 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).
Insomuch as Applicant may be arguing that Chan is non-analogous art, the examiner respectfully disagrees. Chan is in the art of biomedicine, and more specifically radiographic imaging agents bound by chelators to targeting moieties. The examiner considers Chan to be sufficiently related to the instant invention and to the cited prior art to be properly combined under 35 USC 103.
Finally, in response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
On pages 7-8, Applicant argues that the cited prior art does not disclose or suggest the limitation now recited in amended claim 1 requiring the chelator and the nucleic acid molecule to each independently be attached to different functional groups.
The examiner respectfully disagrees. As detailed in the rejection above, the rejection over Moore and Chan as well as the rejection over Medarova, Tassa, Zhang, Udupa, and Chan both render obvious linking a radiolabel via a chelator with an amine bond and linking a nucleic acid via a disulfide bond. Moreover, Moore generally teaches selected from the group consisting of an amine (e.g., amino), a thiol (also referred to as a sulfanyl group or a sulfhydryl group), a hydroxyl, a carboxyl, a phosphate, an aldehyde, an azide, a vinyl (e.g., vinyl sulfone), an alkyne/dibenzocyclooctyne (DBCO), a lysine, a maleimide, biotin, and combinations thereof could be used as conjugation sites and Medarova teaches both secondary amine linkages and disulfide linkages, as claimed.
Although not relevant to the current grounds of rejection, the examiner also points out that claim 1 as it is currently worded does not clearly require the chelator and the nucleic acid molecule to be attached to different categories of functional groups because the claim could equally well be interpreted to simply require the chelator and the nucleic acid molecule to be bound to distinct pendant moieties that are the same type of functional group e.g. each bound to separate secondary amine groups.
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 4-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 1-28 of U.S. Patent No. 10,463,627; and
claims 1-13 of U.S. Patent No. 9,763,891
in view of Tassa et al. (Accounts of Chemical Research 44(10), p 842-852; publication year: 2011; of record), and further in view of Zhang (Website: NCBI Bookshelf 64Cu-DTPA-CLIO-VT680; last updated online 2011; of record), and Udupa et al. (US 2019/0259159; publication date: 08/22/2019; of record) Chan et al. (US 2017/0051044; publication date: 02/23/2017; of record).
.
Inter alia, the clams of the ‘627 and ‘891 patents embrace a magnetic therapeutic nanoparticle coated with dextran and linked to a nucleic acid molecule by a disulfide bond. The nucleic acid molecule may be a modified, locked nucleotide according to the ‘627 patent’s SEQ ID NO: 18, which is an antagomir of miR10b (see col 30, lines 32-37 of the specification in which SEQ ID NO: 18 is identified).
The claims of the ‘627 and ‘891 patents are silent with respect to a radiolabel covalently bound to the nanoparticle via a chelator, and do not specify the size of the nanoparticles.
Tassa discloses that superparamagnetic epichlorohydrin crosslinked dextran coated iron oxide (CLIO) are a versatile platform for targeted molecular imaging, diagnostics, and therapy. Tassa discloses that, in addition to fluorescent labels (page 844, right col), CLIO nanoparticles can be labeled with ligands for MRI and PET (sections 6.2 and 6.3, on pages 848-9). Tassa describes a study in which experiments established a 64Cu-CLIO-VT680 (having both a radiolabel, copper-64, and a fluorophore covalently linked to a CLIO particle) or 18F-CLIO nanoparticles can provide sensitive, multichannel assessments of different biological signals in vivo (page 849, left col). Tassa discloses further that imaging ligands can be combined with therapeutic ligands (specifically photodynamic therapy ligands; section 6.4, page 849).
Zhang discloses the structure of 64Cu-CLIO-VT680, which is a triple labeled reporter CLIO nanoparticle. Specifically, in addition to the magnetic core that can function as an MRI signal, the particle is labeled with 64Cu chelated by DTPA as well as a fluorescent label.
Udupa discloses inter alia “positron emission tomography/magnetic resonance imaging (PET/MRI), improves the sensitivity for detection of pathology at the molecular, subcellular, or cellular level well before gross anatomic changes manifest, and simultaneously improves the specificity of diagnosis to distinguish whether macroscopic abnormalities are benign or malignant in nature. As such, it changes management in up to 40% of patients with cancer prior to implementation of treatment, often due to improved detection of regional lymph node metastases and distant metastases in the body, and improves the diagnostic performance of post-treatment assessment compared to structural imaging with CT or MRI alone. Importantly, PET provides image data that are quantifiable prior to and following treatment, allowing for individualized regional and global disease assessment of patients with cancer and other non-neoplastic disease conditions.” (0008)
In view of Tassa and Zhang, one having ordinary skill would have understood that epichlorohydrin crosslinked dextran coated magnetic iron oxide nanoparticles can be labeled with a variety of imaging or therapeutic ligands to provide imaging options chosen from PET, SPECT, MRI, CT, and fluorescence and can be simultaneously labeled with therapeutic conjugates. In view of Udupa, one would have understood that PET/MRI is more sensitive than either technique alone for detecting/diagnosing cancers and improves diagnostic performance of post-treatment assessment.
It would have been prima facie obvious to add a radiolabel like the DTPA chelated 64Cu described by Tassa and Zhang to the ‘627 or ‘891 therapeutic nanoparticle bound to a nucleic acid molecule. The artisan of ordinary skill would have been motivated to do so to take advantage of PET/MRI’s enhanced diagnostic and disease monitoring sensitivity for improved patient outcomes. The skilled artisan would have had reasonable expectation of success because the chemistry to link multiple ligands to an epichlorohydrin crosslinked dextran coated nanoparticle was established as of the instant effective filing date and because the benefit of PET/MRI was also known.
With regard to the range in particle size required by the instant claims, Tassa discloses further that CLIO (i.e. dextran coated magnetic nanoparticles) have sizes of about 20-45 nm.
It would have been prima facie obvious for the dextran coated magnetic particles of the ‘627 and ‘891 patents to have an iron oxide core because Tassa describes this substance as highly suitable for this purpose (see MPEP 2144.07).
The relevant limitations of the ‘627 and ‘891 patents are set forth above. The claims are silent with respect to the specific chelators required by instant claims 3 or 4, nor do they mention using the specific radioisotopes recited in instant claim 6.
Chan discloses that NODAGA as well as NOTA and DOTA was known for chelating copper isotopes and also discloses that zirconium-89 was known for PET imaging (0307).
With regard to claim 3, it would have been prima facie obvious to replace the DTPA chelating agent described by Tassa/Zhang with NODAGA because these substances were known to serve the same purpose as of the instant effective filing date (see MPEP 2144.06).
With regard to claim 6, it would have been prima facie obvious to replace the copper-64 radioisotope chelate for PET with a zircomium-89 complex because these substances were known to serve the same purpose as of the instant effective filing date (see MPEP 2144.06).
Claims 1, 2, and 4-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,086,093 in view of Tassa et al. (Accounts of Chemical Research 44(10), p 842-852; publication year: 2011; of record), and further in view of Zhang (Website: NCBI Bookshelf 64Cu-DTPA-CLIO-VT680; last updated online 2011; of record), Udupa et al. (US 2019/0259159; publication date: 08/22/2019; of record) Chan et al. (US 2017/0051044; publication date: 02/23/2017; of record) and Medarova et al. (US 2018/0055781; publication date: 03/01/2018; of record).
.
Inter alia, the clams of the ‘093 patent embrace an iron oxide (i.e. magnetic) therapeutic nanoparticle coated with dextran and linked to a nucleic acid molecule; the nucleic acid molecule may be modified. The nucleic acid molecule targets a miRNA such as miR-10b, and is linked by thiol crosslinking (i.e. a disulfide bond). The particle size ranges from 20-30 nm.
The claims of the ‘093 patent are silent with respect to a radiolabel covalently bound to the nanoparticle via a chelator, and do not specify the size of the nanoparticles.
Tassa discloses that superparamagnetic epichlorohydrin crosslinked dextran coated iron oxide (CLIO) are a versatile platform for targeted molecular imaging, diagnostics, and therapy. Tassa discloses that, in addition to fluorescent labels (page 844, right col), CLIO nanoparticles can be labeled with ligands for MRI and PET (sections 6.2 and 6.3, on pages 848-9). Tassa describes a study in which experiments established a 64Cu-CLIO-VT680 (having both a radiolabel, copper-64, and a fluorophore covalently linked to a CLIO particle) or 18F-CLIO nanoparticles can provide sensitive, multichannel assessments of different biological signals in vivo (page 849, left col). Tassa discloses further that imaging ligands can be combined with therapeutic ligands (specifically photodynamic therapy ligands; section 6.4, page 849).
Zhang discloses the structure of 64Cu-CLIO-VT680, which is a triple labeled reporter CLIO nanoparticle. Specifically, in addition to the magnetic core that can function as an MRI signal, the particle is labeled with 64Cu chelated by DTPA as well as a fluorescent label.
Udupa discloses inter alia “positron emission tomography/magnetic resonance imaging (PET/MRI), improves the sensitivity for detection of pathology at the molecular, subcellular, or cellular level well before gross anatomic changes manifest, and simultaneously improves the specificity of diagnosis to distinguish whether macroscopic abnormalities are benign or malignant in nature. As such, it changes management in up to 40% of patients with cancer prior to implementation of treatment, often due to improved detection of regional lymph node metastases and distant metastases in the body, and improves the diagnostic performance of post-treatment assessment compared to structural imaging with CT or MRI alone. Importantly, PET provides image data that are quantifiable prior to and following treatment, allowing for individualized regional and global disease assessment of patients with cancer and other non-neoplastic disease conditions.” (0008)
In view of Tassa and Zhang, one having ordinary skill would have understood that epichlorohydrin crosslinked dextran coated magnetic iron oxide nanoparticles can be labeled with a variety of imaging or therapeutic ligands to provide imaging options chosen from PET, SPECT, MRI, CT, and fluorescence and can be simultaneously labeled with therapeutic conjugates. In view of Udupa, one would have understood that PET/MRI is more sensitive than either technique alone for detecting/diagnosing cancers and improves diagnostic performance of post-treatment assessment.
It would have been prima facie obvious to add a radiolabel like the DTPA chelated 64Cu described by Tassa and Zhang to the ‘093 therapeutic nanoparticle bound to a nucleic acid molecule. The artisan of ordinary skill would have been motivated to do so to take advantage of PET/MRI’s enhanced diagnostic and disease monitoring sensitivity for improved patient outcomes. The skilled artisan would have had reasonable expectation of success because the chemistry to link multiple ligands to an epichlorohydrin crosslinked dextran coated nanoparticle was established as of the instant effective filing date and because the benefit of PET/MRI was also known.
The relevant limitations of the ‘093 patent are set forth above. The claims are silent with respect to the specific chelators required by instant claims 1 or 4, nor do they mention using the specific radioisotopes recited in instant claim 6.
Chan discloses that NODAGA as well as NOTA and DOTA was known for chelating copper isotopes and also discloses that zirconium-89 was known for PET imaging (0307).
With regard to claim 1, it would have been prima facie obvious to replace the DTPA chelating agent described by Tassa/Zhang with NODAGA because these substances were known to serve the same purpose as of the instant effective filing date (see MPEP 2144.06).
With regard to claim 6, it would have been prima facie obvious to replace the copper-64 radioisotope chelate for PET with a zircomium-89 complex because these substances were known to serve the same purpose as of the instant effective filing date (see MPEP 2144.06).
The relevant limitations of the ‘093 patent are set forth above. The claims are silent with respect to the nucleic acid molecule being a locked nucleotide as required by claim 8, or the particles being in a pharmaceutical composition as required by claims 15-17.
Medarova discloses therapeutic magnetic particles having pendant nucleic acid molecules and indicates that a locked nucleic acid is suitable for closely related nanoparticles. The nanoparticles may be functionalized with secondary amines for further linkage to other ligands.
It would have been prima facie obvious to use a locked nucleotide for the nucleic acid molecule of the ‘093 patent because one having ordinary skill in the art would have recognized this as a known suitable option as of the instant effective filing date (see MPEP 2144.07).
Medarova discloses further that the nanoparticles can be formulated for delivery in a pharmaceutical composition having a carrier or diluent and be formulated for injection (0111).
It would have been prima facie obvious to bind the chelated radionuclide to the nanoparticle by a secondary amine because one having ordinary skill would have recognized this type of linkage to be suitable. See MPEP 2144.07.
It would have been prima facie obvious to formulate the nanoparticles of the ‘093 patent according to the teachings of Medarova because this would merely have been combining prior art elements according to known techniques to yield predictable results (see MPEP 2143(I(A)).
Claims 1, 4-6, and 12-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6-11, 13, 14, 17, 19, 21, 24, 25, 27, 30, and 31 of copending Application No. 17/782,369 in view of Tassa et al. (Accounts of Chemical Research 44(10), p 842-852; publication year: 2011; of record), and further in view of Zhang (Website: NCBI Bookshelf 64Cu-DTPA-CLIO-VT680; last updated online 2011; of record), and Udupa et al. (US 2019/0259159; publication date: 08/22/2019; of record) and of Chan et al. (US 2017/0051044; publication date: 02/23/2017; of record).
Inter alia, the claims of the ‘369 application embrace a therapeutic magnetic iron oxide nanoparticle having size between 10 nm – 50 nm covalently liked to a oligonucleotide. The nanoparticles coated with dextran that is functionalized with amine groups and are in a pharmaceutical composition, which contains a diluent or carrier. The claims embrace a method of administering the nanoparticle.
The claims of the ‘369 application are silent with respect to a radiolabel covalently bound to the nanoparticle via a chelator, and do not specify the size of the nanoparticles.
Tassa discloses that superparamagnetic epichlorohydrin crosslinked dextran coated iron oxide (CLIO) are a versatile platform for targeted molecular imaging, diagnostics, and therapy. Tassa discloses that, in addition to fluorescent labels (page 844, right col), CLIO nanoparticles can be labeled with ligands for MRI and PET (sections 6.2 and 6.3, on pages 848-9). Tassa describes a study in which experiments established a 64Cu-CLIO-VT680 (having both a radiolabel, copper-64, and a fluorophore covalently linked to a CLIO particle) or 18F-CLIO nanoparticles can provide sensitive, multichannel assessments of different biological signals in vivo (page 849, left col). Tassa discloses further that imaging ligands can be combined with therapeutic ligands (specifically photodynamic therapy ligands; section 6.4, page 849).
Zhang discloses the structure of 64Cu-CLIO-VT680, which is a triple labeled reporter CLIO nanoparticle. Specifically, in addition to the magnetic core that can function as an MRI signal, the particle is labeled with 64Cu chelated by DTPA as well as a fluorescent label.
Udupa discloses inter alia “positron emission tomography/magnetic resonance imaging (PET/MRI), improves the sensitivity for detection of pathology at the molecular, subcellular, or cellular level well before gross anatomic changes manifest, and simultaneously improves the specificity of diagnosis to distinguish whether macroscopic abnormalities are benign or malignant in nature. As such, it changes management in up to 40% of patients with cancer prior to implementation of treatment, often due to improved detection of regional lymph node metastases and distant metastases in the body, and improves the diagnostic performance of post-treatment assessment compared to structural imaging with CT or MRI alone. Importantly, PET provides image data that are quantifiable prior to and following treatment, allowing for individualized regional and global disease assessment of patients with cancer and other non-neoplastic disease conditions.” (0008)
In view of Tassa and Zhang, one having ordinary skill would have understood that epichlorohydrin crosslinked dextran coated magnetic iron oxide nanoparticles can be labeled with a variety of imaging or therapeutic ligands to provide imaging options chosen from PET, SPECT, MRI, CT, and fluorescence and can be simultaneously labeled with therapeutic conjugates. In view of Udupa, one would have understood that PET/MRI is more sensitive than either technique alone for detecting/diagnosing cancers and improves diagnostic performance of post-treatment assessment.
It would have been prima facie obvious to add a radiolabel like the DTPA chelated 64Cu described by Tassa and Zhang to the ‘369 therapeutic nanoparticle bound to a nucleic acid molecule. The artisan of ordinary skill would have been motivated to do so to take advantage of PET/MRI’s enhanced diagnostic and disease monitoring sensitivity for improved patient outcomes. The skilled artisan would have had reasonable expectation of success because the chemistry to link multiple ligands to an epichlorohydrin crosslinked dextran coated nanoparticle was established as of the instant effective filing date and because the benefit of PET/MRI was also known.
The relevant limitations of the ‘369 application are set forth above. The claims are silent with respect to the specific chelators required by instant claims 3 or 4, nor do they mention using the specific radioisotopes recited in instant claim 6.
Chan discloses that NODAGA as well as NOTA and DOTA was known for chelating copper isotopes and also discloses that zirconium-89 was known for PET imaging (0307).
With regard to claim 3, it would have been prima facie obvious to replace the DTPA chelating agent described by Tassa/Zhang with NODAGA because these substances were known to serve the same purpose as of the instant effective filing date (see MPEP 2144.06).
With regard to claim 6, it would have been prima facie obvious to replace the copper-64 radioisotope chelate for PET with a zircomium-89 complex because these substances were known to serve the same purpose as of the instant effective filing date (see MPEP 2144.06).
This is a provisional nonstatutory double patenting rejection.
Claims 2, 7-11, and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6-11, 13, 14, 17, 19, 21, 24, 25, 27, 30, and 31 of copending Application No. 17/782,369 and Tassa et al. (Accounts of Chemical Research 44(10), p 842-852; publication year: 2011; of record), Zhang (Website: NCBI Bookshelf 64Cu-DTPA-CLIO-VT680; last updated online 2011; of record), Udupa et al. (US 2019/0259159; publication date: 08/22/2019; of record), and Chan et al. (US 2017/0051044; publication date: 02/23/2017; of record) as applied to claims 1, 4-6, and 12-16 above, and further in view of Medarova et al. (US 2018/0055781; publication date: 03/01/2018; of record).
The relevant limitations of the ‘369 application are set forth above. The claims are silent with respect to the chelating agent being bound by to the particle via a secondary amine as required by claim 2, the nucleic acid molecule being a locked nucleotide as required by claim 8, or the particles being in the particular pharmaceutical compositions required by claim 17.
Medarova discloses therapeutic magnetic particles having pendant nucleic acid molecules and indicates that a modified, locked nucleic acid is suitable for closely related nanoparticles. The nucleic acid molecule can be an antagomir targeting miR-10b for treatment of breast cancer. The nanoparticles may be functionalized with secondary amines for further linkage to other ligands.
It would have been prima facie obvious to use a modified locked nucleotide for the nucleic acid molecule of the ‘369 application because one having ordinary skill in the art would have recognized this as a known suitable option as of the instant effective filing date (see MPEP 2144.07). One having ordinary skill in the art would have been motivated to link an antagomir targeting miR-10b to treat breast cancer, and would have had reasonable expectation of success because Medarova teaches very similar particles can reach the tumor site in an animal model.
It would have been prima facie obvious to bind the chelated radionuclide to the nanoparticle by a secondary amine because one having ordinary skill would have recognized this type of linkage to be suitable. See MPEP 2144.07.
Medarova discloses further that the nanoparticles can be formulated for delivery in a pharmaceutical composition having a carrier or diluent and be formulated for injection (0111).
It would have been prima facie obvious to formulate the nanoparticles of the ‘369 application according to the teachings of Medarova because this would merely have been combining prior art elements according to known techniques to yield predictable results (see MPEP 2143(I(A)).
This is a provisional nonstatutory double patenting rejection.
Claims 1, 4-7, and 9-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of copending Application No. 18/339,621 in view of Tassa et al. (Accounts of Chemical Research 44(10), p 842-852; publication year: 2011; of record), and further in view of Zhang (Website: NCBI Bookshelf 64Cu-DTPA-CLIO-VT680; last updated online 2011; of record), and Udupa et al. (US 2019/0259159; publication date: 08/22/2019; of record) and further in view of Chan et al. (US 2017/0051044; publication date: 02/23/2017; of record).
Inter alia, the claims of the ‘621 application embrace a therapeutic magnetic iron oxide nanoparticle having size between 10 nm – 50 nm covalently liked via thiol crosslinking (i.e. disulfide bonds) to a oligonucleotide. The nucleotide may be a modified nucleotide and targets inter alia miR-10b (i.e. the ‘621 claims embrace an antagomir). The claims embrace a method of administering the nanoparticle.
The claims of the ‘621 application are silent with respect to a radiolabel covalently bound to the nanoparticle via a chelator, and do not specify the size of the nanoparticles.
Tassa discloses that superparamagnetic epichlorohydrin crosslinked dextran coated iron oxide (CLIO) are a versatile platform for targeted molecular imaging, diagnostics, and therapy. Tassa discloses that, in addition to fluorescent labels (page 844, right col), CLIO nanoparticles can be labeled with ligands for MRI and PET (sections 6.2 and 6.3, on pages 848-9). Tassa describes a study in which experiments established a 64Cu-CLIO-VT680 (having both a radiolabel, copper-64, and a fluorophore covalently linked to a CLIO particle) or 18F-CLIO nanoparticles can provide sensitive, multichannel assessments of different biological signals in vivo (page 849, left col). Tassa discloses further that imaging ligands can be combined with therapeutic ligands (specifically photodynamic therapy ligands; section 6.4, page 849).
Zhang discloses the structure of 64Cu-CLIO-VT680, which is a triple labeled reporter CLIO nanoparticle. Specifically, in addition to the magnetic core that can function as an MRI signal, the particle is labeled with 64Cu chelated by DTPA as well as a fluorescent label.
Udupa discloses inter alia “positron emission tomography/magnetic resonance imaging (PET/MRI), improves the sensitivity for detection of pathology at the molecular, subcellular, or cellular level well before gross anatomic changes manifest, and simultaneously improves the specificity of diagnosis to distinguish whether macroscopic abnormalities are benign or malignant in nature. As such, it changes management in up to 40% of patients with cancer prior to implementation of treatment, often due to improved detection of regional lymph node metastases and distant metastases in the body, and improves the diagnostic performance of post-treatment assessment compared to structural imaging with CT or MRI alone. Importantly, PET provides image data that are quantifiable prior to and following treatment, allowing for individualized regional and global disease assessment of patients with cancer and other non-neoplastic disease conditions.” (0008)
In view of Tassa and Zhang, one having ordinary skill would have understood that epichlorohydrin crosslinked dextran coated magnetic iron oxide nanoparticles can be labeled with a variety of imaging or therapeutic ligands to provide imaging options chosen from PET, SPECT, MRI, CT, and fluorescence and can be simultaneously labeled with therapeutic conjugates. In view of Udupa, one would have understood that PET/MRI is more sensitive than either technique alone for detecting/diagnosing cancers and improves diagnostic performance of post-treatment assessment.
It would have been prima facie obvious to add a radiolabel like the DTPA chelated 64Cu described by Tassa and Zhang to the ‘621 therapeutic nanoparticle bound to a nucleic acid molecule. The artisan of ordinary skill would have been motivated to do so to take advantage of PET/MRI’s enhanced diagnostic and disease monitoring sensitivity for improved patient outcomes. The skilled artisan would have had reasonable expectation of success because the chemistry to link multiple ligands to an epichlorohydrin crosslinked dextran coated nanoparticle was established as of the instant effective filing date and because the benefit of PET/MRI was also known.
The relevant limitations of the ‘621 application are set forth above. The claims are silent with respect to the specific chelators required by instant claims 1 or 4, nor do they mention using the specific radioisotopes recited in instant claim 6.
Chan discloses that NODAGA as well as NOTA and DOTA was known for chelating copper isotopes and also discloses that zirconium-89 was known for PET imaging (0307).
With regard to claim 1, it would have been prima facie obvious to replace the DTPA chelating agent described by Tassa/Zhang with NODAGA because these substances were known to serve the same purpose as of the instant effective filing date (see MPEP 2144.06).
With regard to claim 6, it would have been prima facie obvious to replace the copper-64 radioisotope chelate for PET with a zircomium-89 complex because these substances were known to serve the same purpose as of the instant effective filing date (see MPEP 2144.06).
This is a provisional nonstatutory double patenting rejection.
Claims 2, 8, and 15-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of copending Application No. 18/339,621 and Tassa et al. (Accounts of Chemical Research 44(10), p 842-852; publication year: 2011; of record), Zhang (Website: NCBI Bookshelf 64Cu-DTPA-CLIO-VT680; last updated online 2011; of record), Udupa et al. (US 2019/0259159; publication date: 08/22/2019; of record) and Chan et al. (US 2017/0051044; publication date: 02/23/2017; of record) as applied to claims 1, 4-7 and 9-14 above, and further in view of Medarova et al. (US 2018/0055781; publication date: 03/01/2018; of record).
The relevant limitations of the ‘621 application are set forth above. The claims are silent with respect to the chelating agent being bound by to the particle via a secondary amine as required by claim 2, the nucleic acid molecule being a locked nucleotide as required by claim 8, or the particles being in a pharmaceutical composition as required by claims 15-17.
Medarova discloses therapeutic magnetic particles having pendant nucleic acid molecules and indicates that a modified, locked nucleic acid is suitable for closely related nanoparticles. The nucleic acid molecule can be an antagomir targeting miR-10b for treatment of breast cancer. The nanoparticles may be functionalized with secondary amines for further linkage to other ligands.
It would have been prima facie obvious to use a modified locked nucleotide for the nucleic acid molecule of the ‘621 application because one having ordinary skill in the art would have recognized this as a known suitable option as of the instant effective filing date (see MPEP 2144.07). One having ordinary skill in the art would have been motivated to link an antagomir targeting miR-10b to treat breast cancer, and would have had reasonable expectation of success because Medarova teaches very similar particles can reach the tumor site in an animal model.
It would have been prima facie obvious to bind the chelated radionuclide to the nanoparticle by a secondary amine because one having ordinary skill would have recognized this type of linkage to be suitable. See MPEP 2144.07.
Medarova discloses further that the nanoparticles can be formulated for delivery in a pharmaceutical composition having a carrier or diluent and be formulated for injection (0111).
It would have been prima facie obvious to formulate the nanoparticles of the ‘621 application according to the teachings of Medarova because this would merely have been combining prior art elements according to known techniques to yield predictable results (see MPEP 2143(I(A)).
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 12/29/2025 have been fully considered but they are not persuasive. On pages 9-10, Applicant asserts that the cited patents and copending applications do not teach or suggest all of the limitations of amended claim 1 and therefore cannot properly form the basis of the obviousness-type double patenting rejections.
In response to applicant's arguments against the references 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).
Applicant is also referred to MPEP 804:
The doctrine of double patenting seeks to prevent the unjustified extension of patent exclusivity beyond the term of a patent. The public policy behind this doctrine is that:
The public should . . . be able to act on the assumption that upon the expiration of the patent it will be free to use not only the invention claimed in the patent but also modifications or variants which would have been obvious to those of ordinary skill in the art at the time the invention was made, taking into account the skill in the art and prior art other than the invention claimed in the issued patent. (Emphasis added.)
Therefore, the examiner should take into account what was understood in the art at the time the instant invention was filed.
Conclusion
No claims are allowed.
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.
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/KATHERINE PEEBLES/ Primary Examiner, Art Unit 1617