DETAILED ACTION
This Office action details a first action on the merits for the above referenced application No. Claims 1-20 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 .
Priority
This application is a 35 USC 111(a) filing that claims benefit as a continuation in part of US application No. 16/482,492 filed on 31 Jul. 2019 (US 11,696,960 B2) and is a 35 USC 371 National Stage filing of PCT/CA2018/050125 filed on 5 Feb. 2018, and claims benefit under 35 USC 119(e) to US provisional application No. 62/455,132 filed on 6 Feb. 2017.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 31 Oct. 2023 has been considered by the examiner.
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 1-20 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. In claims 1 and 11, the recitation of “Y1, Y2, Y3, and Y4 are independently H; a substituent selected from” is indefinite because it is not clear if the section starting further defines Y1, Y2, Y3, and Y4 as alternatives to the H. The Examiner suggest possibly replacing the semi-colon with a comma and adding or to recite “H, or”
In claims 7 and 17, the recitation of a molecular weight (MW) of less that 100 is indefinite because the recitation does not include any units such as Da or kDa.
The dependent clams fall therewith.
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.
Claim(s) 20 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by Kool et al. (Org. Lett.; published 21 Feb. 2014; see IDS filed on 31 Oct. 2023) or, in the alternative, under 35 U.S.C. 103 as obvious over Kool et al. (Org. Lett.; published 21 Feb. 2014; see IDS filed on 31 Oct. 2023), in view of Chen et al. (US 2010/0291547 A1; published 18 Nov. 2010; see attached 892).
Regarding claim 20, Kool et al. disclose the substrate 11
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(OCPC) (see table 1). This reads on a compound of formula I
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wherein X=C, Y1=Y2=Y3=Y4=Z=H. Regarding the recitation of “together with instructions for use”, in instructions for use amount to non-limiting non-functional printed matter. Non-functional printed matter does not distinguish claimed product from otherwise identical prior art. In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004).
Although Kool et al. disclose a compound of instant formula I, Kool et al. does not teach a kit.
Chen et al. teach kit for detecting analyte and compound therein that binds to an analyte and instructions for detecting an analyte ([0060]-[0063]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the composition of Kool et al. (composition comprising OCPC) so that the OCPC is part of a kit and together with instructions for use as taught by Chen et al. because it the kit and instructions would have been expected to enable facile detection of aldehyde containing compounds.
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) 11-12, 14-18, and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Singh et al. (J. Cereb. Blood Flow; published 2013; see IDS filed on 31 Oct. 2023), in view of Kool et al. (Org. Lett.; published 21 Feb. 2014; see IDS filed on 31 Oct. 2023) and Chen et al. (US 2010/0291547 A1; published 18 Nov. 2010; see attached 892).
Singh et al. teach phenelzine mitochondrial function preservation and neuroprotection after traumatic brain injury related to scavenging of the lipid peroxidation derived aldehyde (see title). Singh et al. teach that PZ is a scavenger of the lipid peroxidation (LP)-derived aldehyde (4-NE) due to its hydrazone functionality which can covalently react with 4-HNE. Western blot analysis demonstrated a PZ decrease in 4-HNE in mitochondrial proteins. PZ’s neuroprotective effect is due to mitochondrial protection by scavenging of LP-derived 4-HNE (see abstract). Singh et al. teach that the 4-HNE is a major mediator of oxidative damage induced mitochondrial failure. It was demonstrated by other that hydrazine containing compounds including PZ can covalently scavenge 4-HNE and other LP derived aldehydic products (pg. 593). Singh et al. teach the covalent reaction of 4-NE with hydrazine moiety of phenelzine (PZ)
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(Fig. 1). Sprague-Dawley rates were subjected to unilateral cortical contusion using a pneumatic impact device (concussion) (pg. 594). PZ sulfate was dissolved in 0.9% saline and administered as a single dose (pg. 595). Multiple aldehydic end-products of LP are generated during oxidative damage depending on the particular polysaturated fatty acid that is involved. These aldehydic products include MDA, 2-propanal, and 4-HNE (pg. 596). Singh et al. teach formaldehyde induced toxicity (pg. 597). A single subcutaneous dose of PZ at 15 min significantly reduced degree of post-TBI respiratory compromise (pg. 597).
Singh et al. do not teach claimed method comprising administering a compound of formula (I) to a subject and detecting the product of the compound of formula I and the freely diffusing small molecule aldehyde using fluorescence and wherein the detecting is indicative of the presence or severity of the concussion. Singh et al. do not further teach the malondialdehyde reaction products such as
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,
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, or
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Kool et al. teach as discussed above. Kool et al. teach fast alpha nucleophiles: structures that undergo rapid hydrazone/oxime formation at neutral pH (see title). Kool et al. identified especially reactive carbonyl compounds with acid/base groups near the reactive center that formed products rapidly even without an added catalyst at biological pH (pg. 1454). Kool et al. teach the reactivity of varied hydrazines including 10
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and 11
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(OCPC) with 2-formylpyridine (table 1). Kool et al. teach that OCPH reacts significantly more rapidly: 13-fold more rapid than the slowest hydrazine (pg. 1455). OCPH reacts more rapidly with all new aldehyde and ketone substrates (pg. 1455). The high reactivity is the ability to donate a proton intramolecularly at the transition state of the reaction (pg. 1456). The identification of rapid-reacting hydrazines has special significance because aldehyde reactive groups can be generated in a wide range of biomolecules. One can envision hydrazine reagents carrying useful labels for rapid conjugation to biomolecules (pg. 1456).
Chen et al. teach as discussed above. Chen et al. teach fluorogenic hydrazine substituted compounds (see title). Chen et al. teach dyes containing a nucleophilic appendage capable of binding and detecting analytes in vivo (see abstract). Chen et al. teach hydrazinyl-substituted compounds capable of binding aldehyde and ketone containing analytes in solution indicating the presence of the analyte ([0008]). Chen et al. teach kit for detecting analyte and compound therein that binds to an analyte ([0060]-[0063]). Chen et al. teach that once a hydrazine reacts with an aldehyde or ketone a Schiff base is formed. The resultant compound is highly fluorescent ([0079]-[0080], [0185]). Chen et al. teach MDA ([0181]-[0185]) and acetaldehyde (Fig. 1). The sample is immobilized on a silicon chip, microwell plate or glass slide (test strip) (0318). Chen et al. teach aldehyde reactivity (example 13).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the method of Singh et al. (method of labeling 4-HNE, malondialdehyde and 2-propanal with phenelzine, wherein the method comprises administering phenelzine to a subject having a concussion resulting from a blow or impact) by substituting the phenelzine with the OCPC optionally further comprising 4-OMe to arrive at 4-MeO-OCPC and then detect the product of the OCPC or 4-MeO-OCPC with freely diffusing small molecule aldehydes such as acetaldehyde, MDA, 2-propanal or 4-HE, optionally wherein product with MDA or acetaldehyde is
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, or
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using fluorescence detection such that the detection of the freely diffusing small molecule aldehyde is indicative of the presence of a concussion as taught by Kool et al. and Caravan et al. because the OCPC or 4-MeO-OCPC hydrazines would have been expected to enable fast reaction kinetics with freely diffusing aldehydes at physiological pH because the fluorescence detecting would have been expected to enable quantitative assessment or therapeutic monitoring of a concussion. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Singh et al. by further forming a kit comprising the OCPC or 4-MeO-OCPC together with instructions for use as taught by Chen et al. because that kit would have been expected to enable facile detection of aldehyde containing compounds of interest.
Claim(s) 1-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Singh et al. (J. Cereb. Blood Flow; published 2013; see IDS filed on 31 Oct. 2023), in view of Kool et al. (Org. Lett.; published 21 Feb. 2014; see IDS filed on 31 Oct. 2023) and Chen et al. (US 2010/0291547 A1; published 18 Nov. 2010; see attached 892), in further view of Caravan et al. (WO 2015/085005 A1; published 11 Jun. 2015; see IDS filed on 31 Oct. 2023) and Zhou et al. (Nucl. Med. Biol.; published 2012; see attached 892).
Singh et al. teach as discussed above.
Singh et al. do not further teach a compound of formula I-A1 or IA3. Singh et al. do not further teach detecting the product of the compound of formula I and the freely diffusing small molecule aldehyde using MRI or PET.
Kool et al. teach as discussed above.
Chen et al. teach as discussed above.
Caravan et al. teach molecular imaging probes (see title). Caravan et al. teach that certain compounds containing an imaging group and a functional group that can react with an aldehyde group on collagen or elastin can be used as an imaging probe (e.g. MRI, PET) for the diagnosis of disorders (see pg. 1). Caravan et al. teach hydrazine compounds of formula 1 (pg. 1). Caravan et al. teach PET and MRI (pg. 2). Caravan et al. teach brain tissue (pg. 2). Caravan et al. teach PET and MRI labels including 18F and Gd (pg. 30). Caravan et al. teach imaging experiments (examples 6-14).
Zhou et al. teach highly efficient click labeling using 2-[18F]fluoroethyl azide and synthesis of 18F-N-hydroxysuccinamide ester conjugation agent (see title). The triazole group is stable to acid and base hydrolysis, as well as reductive and oxidation conditions due to its aromatic. The triazole is stable and possesses polarity and size similar to that of an amide bond thereby improving water solubility and allowing the synthesis of a wide range of compounds with biological potential (see pg. 1175). Zhang et al. teach the click labeling of an aldehyde
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(pg. 1179). The method can be used to label small molecules in high yield and with easy purification, but also the [18F] labeled click-NHS ester can be used for conjugation chemistry with primary amines (pg. 180)
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Singh et al. by further substituting the -OMe on the obvious 4-OMe-OCPC with propargyloxy or 18F-fluoropropargyloxy to arrive at formula I-A1 or formula I-A3 as taught by Zhou et al. and Caravan et al. because those propargyloxy substituents would have been expected to advantageously enable fast and stable click reaction with an azide such as 2-[18F]fluoroethyl azide whereby enabling 18F labeling and/or bioconjugation such as immobilization.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify the method of Singh et al. so that the method detects the product of formula I and the freely diffusing small molecule aldehyde using MRI or PET imaging optionally wherein the aldehyde binding compound additionally comprises the 18F label for use in PET imaging wherein the detection is indicative of the presence or severity of the concussion as taught by Caravan et al. and Zhou et al. because those methods of detection would have been expected to provide sensitive detection of labeled aldehydes inside and outside the body.
Claim(s) 10 and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shuhendler et al. (WO 2018/141069 A1; published 9 Aug. 2018; see attached 892), in view of Zhou et al. (Nucl. Med. Biol.; published 2012; see attached 892) and Majo et al. (Bioorg. Med. Chem. Lett.; published 2013; see attached 892).
Shuhendler et al. teach compounds and methods for detection and binding of aldehydes (see title). Shuhendler et al. teach detecting an aldehyde containing compound in a subject comprising administering an aldehyde-binding compound of formula I to a subject or sample and detecting the product by MRI, CEST-MRI or PET or may involve fluorescence or electrochemical detection method and can be used to detect brain injury such as concussion (abstract, [0058]). The aldehyde may be acetone or MDA ([00105]) and the detect product may be
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. Shuhendler et al. teach the compound
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(Fig. 1). In the compound of formula I-A the compound may Y2 may be an aryl or propargyl ([00112]).
Shuhendler et al. teach a claimed method wherein the compound of formula I comprises a compound of formula I-A1, I-A2, or I-A3.
Zhou et al. teach as discussed above.
Majo et al. teach the synthesis and in vitro evaluation of [18F]BMS-754807 (see title). Majo et al. teach a metabolically stable fluorine in the 2-substituted pyridine ring which is amenable for radiofluorination using nucleophilic displacement with [18F]fluoride and low lipophilicity (pg. 4192). Majo et al. teach radiosynthesis of [18F]BMS-754807 (see scheme 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the methods of Shuhendler et al. (methods for the detection of freely diffusing small molecule aldehyde in a subject having a concussion said method comprising administering an aldehyde compound of formula I to the subject and detecting the product of the compound of formula I and the freely diffusing small molecule aldehyde using MRI, CEST-MRI, PET, fluorescence or electrochemical detection optionally wherein the compound comprises a radiolabel for PET imaging) so that the Y2 of formula I comprises a ([18F]fluoro)progargyloxy to arrive at a compound of instant formula I-A1 or I-A3 or so that the Y2 of formula I comprises a 6-[18F]fluoropyridyl amine to arrive at a compound of instant formula I-A2 as taught by Zhou et al. and Majo et al. because those propargyloxy substituents would have been expected to advantageously enable fast and stable click reaction with an azide such as 2-[18F]fluoroethyl azide whereby enabling 18F labeling and/or bioconjugation such as immobilization and because the 6-fluoropyridyl amine would have been expected to enable a metabolically stable 18F-labeled substrate prepared by nucleophilic displacement reaction..
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 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,696,960 B2, in view of Zhou et al. (Nucl. Med. Biol.; published 2012; see attached 892) and Chen et al. (US 2010/0291547 A1; published 18 Nov. 2010; see attached 892).
Claims 1-11 of U.S. Patent No. 11,696,960 B2 claim a method of detecting a freely diffusing small molecule aldehyde in a subject comprising administering an aldehyde-binding compound of formula I to the subject and detecting the product of the compound of formula I
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wherein Y4 may be a substituent selected from propargyloxy and the freely diffusing small molecule aldehyde using MRI, CEST-MRI, and PET optionally wherein the compound of formula I is a compound of formula IA
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and the freely diffusing aldehyde is an acetone or MDA optionally where the product detected is
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and optionally wherein a brain injury is a concussion.
Claims 1-11 of U.S. Patent No. 11,696,960 B2 do not claim a method wherein the compound comprises a propargyloxy or the compound is a compound of formula I-A1 or formula I-A3. Claims 1-11 of U.S. Patent No. 11,696,960 B2 do not claim a method of detecting wherein the method comprises fluorescence detection.
Zhou et al. teach as discussed above.
Chen 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 further modify claims 1-11 of U.S. Patent No. 11,696,960 B2 so that the compound of formula I comprises a propargyloxy substituent optionally to arrive at a compound of instant formula I-AI or I-A3 as taught by Zhou et al. because those propargyloxy substituted compounds would have been expected to advantageously enable fast and stable click reaction with an azide such as 2-[18F]fluoroethyl azide whereby enabling 18F labeling and/or bioconjugation such as immobilization.
Conclusion
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/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
/SEAN R. DONOHUE/
Examiner, Art Unit 1618