DETAILED ACTION
This Office action details a non-final action on the merits for the above referenced application No. Claims 21, 23-30, and 33-35 are pending in this application.
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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 17 Feb. 2025 has been entered.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 17 Feb. 2026 has been considered by the examiner.
Response to Amendment
The amendments filed on 17 Feb. 2026 have been entered.
The declaration under 37 CFR 1.132 filed 17 Feb. 2026 is insufficient to overcome the rejection of claims as set forth in the last Office action because of the reasons set forth below.
Dr. Wlostowska declares that in the case of ischemic disease, damaged heart cells clearly do not have increased levels of cardiolipin but rather the opposite or cardiolipin in damaged cells has a different structure incapable of accumulating the cardiotracer. Damaged heart cells are poorly visible or completely invisible on PET imaging which distinguishes them from healthy cells and allows for diseased areas in the heart to be located using scans performed with the cardiotracer. Rodriguez does not indicate that the compounds as claimed would be useful as cardiotracers for examining the cardiovascular system of a mammal as recited in claim 21 because cardiotracers useful in these methods would require high selective accumulation in the heart muscle compared to other organs. Based on Herrnstadt, skilled artisans would understand that only mutated cytochromes selectively accumulate lipophilic cations and would not expect those compounds to accumulate in the heart not expected to have mutated cytochromes. Rodriguez points out that in some cells the compounds is no absolutely dependent on cardiolipin. In vitro experiments in Rodriguez and Herndstadt give the skilled artisan no reason to expect that it would be possible to differentiate between living and dead hear muscle cells and examine the cardiovascular system as claimed. In a phase 2 clinical study, [18F]SYN2 accumulated in healthy heart tissue of a patient but not unhealthy tissue. In a phase 1 clinical study, [18F]SYN2 was rapidly taken up by the myocardial wall of the patient and the left ventricle wall of the patients heart was clearly visualized 3 min after injection. The difference in PET-CT imaging when using the [18F]SYN2 cardiotracer between a patient with ischemia and a healthy patient is clearly visible. Imaging from phase 1 clinical trials of [18F]SYN2 show that the heart is clearly against the background of other organs. A skilled artisan would understand based on Herndstadt that damaged mitochondria are different enough from healthy mitochondria to be selectively captured by acridine derivatives and destroyed, leaving healthy mitochondria untouched. Cardiolipin is found in many organs and is not specific to the heart. A person of ordinary skill in the art would know that there is no correlation between myocardial damage and the mutated cytochrome C oxidase discussed in Herndstadt. Reading Jacobson a skilled artisan would have no reason to use the compounds as claimed in PET cardiological diagnostic method for examining cardiovascular system of mammal as claimed. As shown in Fig. 6 of Krajewski, [18F]SYN2 accumulates more in the heart than lungs, liver and blood. The Fig. 6 shows significantly higher cardiotracer uptake by heart compared to nearby organs. The [18F]SYN2 allowed for clear visualization of the heart in microPET imaging. Fig. 7 of Krajewski shows that the ratio of radioactivity accumulation of [18F]SYN2 in the heart to liver was the most statistically significant after 2 h of administration. [18F]SYN2 can be synthesized in a one-step process. The phase I study confirmed the safety profile of [18F]SYN2. Neither Madar nor Jacobson describe the compounds as claimed as being useful in examining the cardiovascular system of a mammal and therefore they do not fill the gaps left by Rodriguez and Herrnstadt.
The Dr. Wlostowska filed 17 Feb. 2026 has been fully considered but it is not persuasive. Claims 25-30 are directed to a pharmaceutical composition comprising a compound of formula I and pharmaceutical carrier or diluent. While claim 25 has been amended to recite a cardiotracer compound, this recitation amounts to an intended use or purpose. A recitation of intended use must result in a structural different between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art is capable of intended use, the it meets the claim. In this case, the obvious [18F]NAO, [18F]HAO, [18F]MAO and their 18F-labeled homologue derivatives made obvious by Rodriguez and Herrnstadt comprise all structural limitations of a cardiotracer compound as described in the specification. Accordingly, the obvious [18F]NAO, [18F]HAO, [18F]MAO and 18F-labeled their homologue derivatives are capable of being cardiotracer tracer compounds in addition to being compounds for the sensitive PET detection of CL and mitochondria. Rodriguez and Herrnstadt provide more than adequate reason and motivation to modify NAO, HAO, MAO and their homologue derivatives to arrive at [18F]NAO, [18F]HAO, [18F]MAO and their 18F-labeled their homologue derivatives for the reasons cited herein and in the Office action filed on 14 Aug. 2025. The showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. See In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). The results described in the instant specification only refer to [18F]SYN2; however, the claims as amended require a formula I that encompasses thousands of compounds. It is not possible to extend the results obtained for [18F]SYN2 to the thousands of claimed compounds. Clearly, the data provided in the affidavit is not commensurate in scope with the instant claims. Expected beneficial results are evidence of obviousness. See In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967). Rodriguez teaches that NAO, HAO, and MAO are mitochondria probes that bind to CL. The HAO allowed clear and specific targeting to mitochondria. Herrnstadt provides direct teaching, suggestion and motivation to 18F-label NAO at the termina end of the nonyl alkyl chain. Yuan (cited herein) teaches that myocardium is mitochondria rich. Probes that target the mitochondria can be used for imaging the mitochondria rich myocardium and perfusion deficits implying regions of restricted blood flow and tracer distribution/binding. Yuan provides an example of imaging using an mitochondria targeted 18F-labeled cardiotracer compound. A person of ordinary skill in the art would have expected the obvious [18F]NAO, [18F]HAO, [18F]MAO and 18F-labeled their homologue derivatives to be cardiotracers for performing cardiological diagnostic PET and examination of the cardiovascular system.
Response to Arguments
The rejection of claims 21, 23, and 33-35 under 35 USC 103 as being unpatentable over Rodriguez et al. (Mitochondrion; published 2008), in view of Herrnstadt et al. (US 2003/0087858 A1) and Madar et al. (US 2004/0033197 A1; published 19 Feb. 2004) is withdrawn.
The rejection of claims 21, 23-30, and 33-35 under 35 USC 103 as being unpatentable over Rodriguez et al. (Mitochondrion; published 2008), in view of Herrnstadt et al. (US 2003/0087858 A1) and Madar et al. (US 2004/0033197 A1; published 19 Feb. 2004), in further view of Jacobson et al. (Nucl. Med. Biol.; published 2013) is withdrawn.
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.
Claim(s) 25-30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rodriguez et al. (Mitochondrion; published 2008), in view of Herrnstadt et al. (US 2003/0087858 A1; published 8 May 2003) and Madar et al. (US 2004/0033197 A1; published 19 Feb. 2004) for the reasons cited in the Office action filed on 14 Aug. 2025.
Applicants Arguments
Applicants assert that one of ordinary skill would not know that the compounds of the clams are effective selective cardiotracers. Cardiolipin is not selective to heart muscle but to mitochondria. Rodriguez contains no teaching that the compounds as claimed would be useful as cardiotracers for examining the cardiovascular system of a mammal. Cardiotracers useful for these methods require high selective binding to cardiolipin in the heart compared to other organs and Rodriguez contains no teaching that the compounds as claimed would have any selectivity for the heart. Rodriguez contains no teaching that the compounds recited in claim 21 have any selectivity for binding to cardiolipin or any other molecule in the heart. Herrnstadt teaches that NAO binds to cardiolipin and accumulates in dysfunctional mitochondria. A skilled artisan would not expect acridine derivatives to have an affinity for non-mutated cardiac muscles. The mutated cytochrome C oxidase genes described in Herrnstadt are not representative of myocardial cells or heart tissue. Skilled artisans would know that there is no correlation between myocardial damage and the mutated cytochrome C oxidase genes in Herrnstadt. Herrnstadt contains no teaching that the claimed compounds would accumulate in myocardial tissue of the heart. Madar does not cure the deficiencies of Rodriguez or Herrnstadt. The data provided in the Dr. Wlostowska declaration represents an unexpected result in the selectivity of that compound for the heart. Applicants refer to the Dr. Wlostowska declaration. A skilled artisan would not expect there to be a greater ratio of damaged mitochondria in the heart versus other organs and Herrnstadt gives no indication that those compounds would be useful for imaging the heart. Madar fails to describe the compounds as claimed as being useful in examining the cardiovascular system of a mammal. The reference fails to provide any reason to further test a myocardial perfusion a myocardium of the mammal to quantify a regional blood flow as in the method of claim 23.
Applicant's arguments filed 17 Feb. 2026 have been fully considered but they are not persuasive. The Dr. Wlostowska declaration has been found ineffective for the reasons discussed above. Claims 25-30 as amended are directed to a pharmaceutical composition comprising a structure according to formula I. While claim 25 has been amended to recite a cardiotracer compound, this recitation amounts to an intended use. As discussed herein, the [18F]NAO, [18F]HAO, [18F]MAO and their 18F-labeled homologue derivatives made obvious by Rodriguez and Herrnstadt comprise all structural limitations of a cardiotracer compound as described in the specification. Rodriguez teaches NAO, HAO, and MAO as mitochondria probes that bind to CL. The HAO allowed very clear and specific targeting to mitochondria. At [0111], Herrnstadt teaches that in in vivo diagnosis NAO is labeled with 18F as an imaging ligand. At Fig. 4, Herrnstadt teaches modifying NAO at the terminal end of its nonyl alkyl substituent. It would have been obvious to a person of ordinary skill in the art before the effective filing date the pharmaceutical compositions containing NAO, HAO, and MAO in Rodriguez by incorporating 18F at the terminal end of N-alkyl substituent to form [18F]NAO, [18F]HAO, and [18F]MAO because the incorporating of 18F would have been expected to advantageously enable sensitive in vitro and in vivo PET imaging of CL and related disorders, mitochondria, and mitochondria rich tissue.
New Grounds of Rejection
Claim Objections
Claim 21 is objected to because of the following informalities: in claim 21, the recitation of “diagnostic diagnostic” should be “diagnostic”. Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 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.
Note that this rejection relies on intervening prior art since a certified translation of the foreign priority document has not been made of record. This rejection and any rejection under 35 USC 103 deemed necessary may be overcome by filing a certified translation of the foreign priority document and if the foreign priority document contains written description of the claimed invention.
Claim(s) 21, 25-28, 30, and 34-35 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Inkster et al. (J Nucl. Med.; published May 2019; see attached 892).
Regarding claims 25-28, and 30, Inkster et al. disclose AO-DEG-[18F] formulated in 10% EtOH in saline. (This reads on a pharmaceutical composition comprising a pharmaceutically acceptable carrier that is a sterile solution and a compound of formula I wherein R3 and R4 combine to form an acridinium ring; 5R1=H and 2R1=NMe2 (at least 1 R1 is other than H); and R2=DEG (a chain aliphatic substituent having 4 carbons, an atom of 18F replacing a H at one of the carbons and a -CH2- fragment as a terminal member of a chain and the chain contains a bivalent link that is -O-) and X- =-OTs (monobasic aryl sulfonic acid).) Regarding claims 21 and 34-35, Inkster et al. teach that rats were injected with AO-DEG-18F and scanned for 60 min using PET. The AO-DEG-18F showed modest uptake in the rat heart with high accumulation in the liver and gut. (Reads on a PET cardiological diagnostic method comprising (a) administering the cardiotracer of formula I wherein R2 has a total of 4 carbon atoms to a mammal, (b) performing cardiological diagnostic PET scan on the mammal, and (c) examining the cardiovascular system of the mammal.)
Claim Rejections - 35 USC § 103
Claim(s) 21, 23-30, and 33-35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rodriguez et al. (Mitochondrion; published 2008), in view of Herrnstadt et al. (US 2003/0087858 A1; published 8 May 2003) and Yuan et al. (Chem Commun.; published 2013; see attached 892), in further view of Mou et al. (Molecules; published 30 Mar. 2017; see attached 892).
Rodriguez et al. teach targeting of mitochondria by 10-N-alkyl acridine orange analogues: role of alkyl chain length in determining cellular uptake and localization (see title). Rodriguez et al. teach that cardiolipin CL has an important role in pathologies such as heart ischemia and Barth syndrome (see pg. 237). The fluorescent dye 10-N-nonyl-acridine orange (NAO) has been used as a highly specific probe for CL. The high binding affinity of NAO to CL has been used to determine a number of properties of CL, e.g. to image CL (see pg. 238). Rodriguez et al. teach synthesizing 3 analogues of NAO bearing C-1 (MAO), C-6-(HAO), and C-16-alkyl chains (HDAO) (Table 1; instant X=Br-) in the 10-position.
These compounds read in part on compounds of the instant formula n=9; R1= H and -NMe2 (substituted amino having 2 Hs replaced with C1 alkyl, at least 2 R1 is other than H); R2=C1, C6, and C9-aliphatic chains, R3 and R4 combine to an acridinium ring, and X=Br- (anion of monobasic inorganic acid).
A variety of derivatives have been made for different applications. All acridine orange compounds show some selectivity for mitochondria and CL (see pg. 238). MAO and NAO have similar uptake in MCF-7c3 cells (human breast cancer cells). HAO showed the highest uptake. HAO and NAO enter the cells quicky, reaching maximum values by 30 min (see pg. 241). MAO, HAO, and NAO showed excellent specificity for mitochondria (pg. 242). The data show that a long chain alkyl chain is not essential for cellular binding. HAO appears to be a superior acridine orange derivative for imaging mitochondria, because it is useful at very low concentrations with minimal perturbation of cells (pg.245).
Rodriguez et al. do not teach the instant cardiological diagnostic method comprising administering to a mammal the instant cardiotracer compound of comprising a structure according to formula I having an R2 atom of 18F replaces a hydrogen at the terminal carbon atom to form a CH2 fragment at the end of the chain and wherein the method comprises performing cardiological diagnostic PET scan on the mammal, and examining the cardiovascular system of the mammal optionally wherein the method further comprises testing a myocardial perfusion of a myocardium of the mammal to quantify regional blood flow and optionally further comprising quantifying a coronary reserve of the mamma optionally wherein the mammal is human. Rodriguez et al. do further claim the instant pharmaceutical composition comprising a pharmaceutically acceptable carrier and the instant structure according to formula I.
Herrnstadt et al. teach diagnostic and therapeutic compositions for Alzheimer’s disease (see title). Herrnstadt et al. teach that mitochondria carrying mutated cytochrome c oxidase genes have increased levels of cardiolipin and other negatively charged phospholipids as well as increased mitochondrial membrane potential. As a result, the mitochondria selectively accumulate acridine orange and lipophilic cations such as rhodamine 123 and JC-derivatives. In in vivo diagnosis a targeting molecule such as acridine orange is labeled with 18F as an imaging ligand. This labeled targeting molecule is introduced into the bloodstream of a patient ([0101]-[0102], [0110]-[0111]). Herrnstadt et al. teach acridine orange derivatives (see Fig. 4). Hernstadt et al. teach human disease ([0003])
Yuan et al. teach fluorescent and radiolabeled triphenylphosphonium probes for imaging mitochondria (see title). Yuan et al. teach that diverse types of lipophilic cations have been used for mitochondrial targeting and imaging mitochondria. The TPP group has been used to obtain [18F] probes to image myocardial perfusion (see pg. 10361). The TPP fluorochromes behave like many other lipophilic cations with uptake by the functional myocardium and not by perfusion deficit (pg. 10361). Yuan et al. teach imaging myocardial perfusion deficit after injection of [18F]-labelled TPP fluorochrome (Fig. 3; connotes pharmaceutically acceptable carrier formulated as a sterile solution). A perfusion deficit was observed in the lateral wall of the heart. Mitochondrial targeted probes can be either of the mitochondrial membrane potential dependent type or mitochondrial binding, potential independent type. Examples of the potential independent probes include BODIPY based OBEP and nonyl acridine orange (NOA) which binds to a cardiolipin. Substantial corrections for mitochondrial binding are essential when determining mitochondrial membrane potential (pg. 10363).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify Rodriguez et al. (NAO and its homologue derivatives such as MOA, HAO that that show some selectivity to CL and show excellent specificity to mitochondria and their use for detection of mitochondria) by incorporating 18F at the terminal carbon of their N-alkyl substituents to arrive at [18F]NAO, [18F]HAO, [18F]MAO or a C2 [18F]EAO homologue derivative and then administer that compound with a pharmaceutically acceptable carrier that is sterile solution that enables injection to a mammal such as a human and perform cardiac diagnostic PET on the subject and examine the cardiovascular system of the subject as taught Herrnstadt et al., and Yuan et al. because those compounds and cardiological diagnostic method would have been expected to advantageously enable imaging the mitochondrial rich myocardium and perfusion deficits independent of mitochondrial membrane potential. Homologues are prima facie obvious due to a general expectation of similar properties. See In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).
Mou et al. teach research progress on 18F labeled agents for imaging of myocardial perfusion with PET (see title). Mou et al. teach that PET technology leads to absolute quantification of regional myocardial blood flow and coronary flow reserve (see pg. 1). Mou et al. teach 18F-labeled ammonium lipophilic cations including a BODIPY based OBEP derivative and phosphonium lipophilic cations (pg. 2-3). Mou et a. teach human subjects (pg. 3). Mou et al. teach 5% ethanol solution (pg. 10).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Rodriguez et al. so the at the method further comprises quantifying coronary reserve as taught by Mou et al. because it would have been expected to advantageously enable the absolute quantification of coronary reserve by PET in a living subject.
Note that this rejection relies on intervening prior art since a certified translation of the foreign priority document has not been made of record. This rejection may be overcome by filing a certified translation of the foreign priority document and if the foreign priority document contains written description of the claimed invention.
Claim(s) 21, 23-30, and 33-35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Inkster et al. (J. Nucl. Med.; published May 2019; see attached 892), in view of Rodriguez et al. (Mitochondrion; published 2008) and Mou et al. (Molecules; published 30 Mar. 2017; see attached 892).
Inkster et al. teach as discussed above. In addition, Inkster et al. teach the synthesis of 18F-labeled acridinium cations as a new class of potential myocardial perfusion agents (see title). Inkster et al. teach that fluorescence DLC dyes based on AO have proven to be useful for staining mitochondria in vitro. Inkster et al. teach determining 18F-labeled acridinium cations could be useful for myocardial perfusion imaging. AO-DEG-18F show modest uptake in the rat heart. Inkster et al. plan to use this approach to generate a library of 18F-labeled acridinium cations to determine if acridine orange can serve as a basis for an 18F-labeled MPI agent (see abstract).
Inkster et al. do not teach a pharmaceutical composition comprising [18F]NAO, [18F]HAO, [18F]MAO or a C2 [18F]EAO homologue derivative or exemplify a method further comprising testing a myocardial perfusion of a myocardium of a mammal to quantify a regional blood flow or quantifying a coronary reserve of the mammal or a human subject.
Rodriguez et al. teach as discussed above.
Mou et al. teach as discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the composition of Inkster et al. so that the bivalent link between chain carbons is absent as taught by Rodriguez et al. because those 18F-labeled acridinium cations would have been expected for show enhance mitochondria uptake. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Inkster et al. so that the cardiological diagnostic method further comprises testing myocardial perfusion of a mammal optionally human to quantify regional blood flow and optionally further comprises quantifying coronary reserve of the mammal as taught by Mou et al. because it would have been expected to advantageously enable absolute in vivo quantification of a human subject using high resolution PET technology.
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 21, 23-30, and 33-35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of copending Application No. 19/312,604, in view of Rodriguez et al. (Mitochondrion; published 2008), and Yuan et al. (Chem Commun.; published 2013; see attached 892). This is a provisional nonstatutory double patenting rejection.
Claims 1-17 of copending Application No. 19/312,604 a PET diagnostic method and compound I
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wherein X- is a pharmaceutically acceptable counterion such as mono-basic inorganic acid; n is an integer of 9; R3 and R4 combine to form a butadienyl-1,3 substituent whose terminal atoms are linked to adjacent non-nodal carbon atoms to for an aromatic C ring with the A and B ring systems; and wherein R1 may H, or amino group having 2 hydrogen atoms replaced with C1-C6 alkyl; and wherein R2 is a carbon aliphatic chain having 1-16 carbon atoms, 18F fluorine radioisotope replacing a H on one of the carbon atoms and a CH2 fragment as a terminal member of a chain wherein the chain connects to H and wherein the method administers the compound to a subject and performs a PET scan on the subject and further comprises testing myocardial perfusion of a myocardium of the subject to quantify blood flow or further comprises quantifying coronary reserve and pharmaceutical composition further comprising a pharmaceutically acceptable carrier or diluent and optionally formulated as a sterile solution
Claims 1-17 of copending Application No. 19/312,604 do not claim a compound of instant formula I wherein at least 1 R1 is other than H, R3 and R4 combine to form an acridinium ring.
Rodriguez et al. teach as discussed above.
Yuan et al. teach as discussed above.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify claims 1-17 of copending Application No. 19/312,604 so that 2R1’s=-NMe2 and R3 and R4 combine to form an acridinium ring as taught by Rodriguez et al. and Yuan et al. because those compounds would have been expected to form quaternary ammonium cation capable of in vivo and in vitro PET detection of CL, mitochondria and/or mitochondria rich myocardium whereby enabling a cardiotracer and myocardial perfusion imaging.
Technical Background Material
Zhou et al. (Bioconjugate Chem.; published 2011; see attached 892) is being made of record; however, it is not being used in a rejection because it is cumulative. Zhou et al. teach a 64Cu-labeled acridinium cation as a PET tracer for targeting tumor mitochondria (see abstract).
Conclusion
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/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
/SEAN R. DONOHUE/
Examiner, Art Unit 1618