DETAILED ACTION
This Office action details a final action on the merits for the above referenced application No. Claims 1-4, 7-8, 10-14, 16-17, and 19-21 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 .
Status of Claims
Claims 1, 7, 10-11, 14, 17, and 19-20 are amended. Claims 5-6, 9, 15, and 18 are cancelled. Claim 21 is new.
Response to Amendment
The amendments filed on 9 Jun. 2026 have been entered.
Response to Arguments
In view of Applicants arguments, the rejection of claims 1-20 under 35 USC 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter is withdrawn.
In view of Applicants amendments, the rejection of claim 20 under 35 USC 102(a)(1) as being anticipated by Kool et al. (Org. Lett.; published 21 Feb. 2014) is withdrawn.
In view of the approved terminal disclaimer, the rejection of claims 1-20 on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of US patent No. 11,696,960 B2, in view of Zhou et al. (Nucl. Med. Biol.; published 2012) and Chen et al. (US 2010/0291547 A1; published 18 Nov. 2010) is withdrawn.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) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kool et al. (Org. Lett.; published 21 Feb. 2014), in view of Chen et al. (US 2010/0291547 A1; published 18 Nov. 2010) for the reasons cited in the Office action filed on 12 Mar. 2026.
Applicants Arguments
Applicants assert that the rejection to claim 20 is believed to be traversed with the amendments to claim 11 (from which claim 20 depends) to specify Y2 definitions that no longer include H in Formula I-A and so the kit in claimed in amended claim 20 would not contain an aldehyde binding compound as taught by Kool in table 1 as OCPC.
Applicant's arguments filed 9 Jun. 2026 have been fully considered but they are not persuasive. Kool provides for the OCPH compound that forms hydrazones rapidly with aryl and alkyl aldehydes and with aryl and alkyl ketones as well. At pg. 1454, Kool teaches biological and biological chemistry applications. At table 1, Kool teaches substituent modifications including an -OMe substituent modification para to the hydrazine moiety (substrate 8) enabling fast reaction kinetics. Accordingly, a person of ordinary skill in the art would have understood that the OCPH compound is capable of being modified to include an -OMe labeling group with a reasonable expectation of success. It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the OCPH compound in Kool by incorporating an -OMe substituent at the instant Y2 position as taught by Kool because that OMe modified OCPH derivative would have been expected to provide an equivalent hydrazine capable of forming hydrazones rapidly with aryl and alkyl aldehydes. Chen teaches and motivates kits for detection of analytes wherein the kit comprises a hydrazine capable to aldehydes together with instructions for use. A recognized advantage is the strongest reason to combine. It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify further modify Kool et al. so that the obvious OMe modified OCPH derivative expected to exhibit fast reaction kinetics with a range of aldehydes is part of a kit together with instructions for use as taught by Kool et al. and Chen et al. because that kit would have been expected to enable rapid detection of aryl and alkyl aldehydes.
Claim(s) 11-12, 14, 16, 17, and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Singh et al. (J. Cereb. Blood Flow; published 2013), in view of Kool et al. (Org. Lett.; published 21 Feb. 2014), and Chen et al. (US 2010/0291547 A1; published 18 Nov. 2010) for the reasons cited in the Office action filed on 12 Mar. 2026.
Claim(s) 1-4, 7-8, 10-14, 16-17, and 19-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Singh et al. (J. Cereb. Blood Flow; published 2013), in view of Kool et al. (Org. Lett.; published 21 Feb. 2014), and Chen et al. (US 2010/0291547 A1; published 18 Nov. 2010), in further view of Caravan et al. (WO 2015/085005 A1; published 11 Jun. 2015) and Zhou et al. (Nucl. Med. Biol.; published 2012) for the reasons cited in the Office action filed on 12 Mar. 2026.
Applicants Arguments
Applicants assert that the amendment of formula I in claim 11 to be formula I-A renders the teachings of the primary citation of Kool as inapplicable. The secondary and tertiary references combined in this rejection of claim 11 do not provide teachings that would encompass the remaining structures of Formula I-A in the context of amended claim 11. The mention in Kool of a molecule in table 1 as a substrate 11 (OCPC) is no longer applicable to the claim set given the refinements to the definition of Y2 that do not include the option of H.
Applicant's arguments filed 9 Jun. 2026 have been fully considered but they are not persuasive. Kool is not deficient for the reasons discussed above. Singh provides a method of detecting freely diffusing small molecule aldehydes in a sample from a subject having a concussion or suspected of having a concussion wherein the method comprises combining a phenelzine as an aldehyde binding compound with a sample. Singh teaches that multiple aldehydic end-products of LP are generated during oxidative damage depending upon the particular polyunsaturated fatty acid that is involved. The aldehydic products include neurotoxic MDA, 2-propanol and 4-HNE. Chen teaches and motivates the fluorescence detection of MDA, 2-propanol and 4-HNE using a hydrazine compound capable reacting capable of reacting the aldehyde or ketone functionality. According to Chen, once a hydrazone reacts with an aldehyde or a ketone a shift base is formed. The resultant compound is highly fluorescent. 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 so that the method detects by fluorescence imaging an expected fast hydrazone formation of the obvious OMe modified OCPC with neurotoxic aldehydes because it would have been expected to enable a method for detection and monitoring of brain injury following a suspected concussion.
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), in view of Zhou et al. (Nucl. Med. Biol.; published 2012), and Majo et al. (Bioorg. Med. Chem. Lett.; published 2013) for the reasons cited in the Office action filed on 12 Mar. 2026.
Applicants Arguments
Applicants assert that the application of Shuhendler et al. is believed to be overcome in that the present application is a CIP that claims benefit of PCT/CA2018/050125.
Applicant's arguments filed 9 Jun. 2026 have been fully considered but they are not persuasive. The instant application is a continuation in part PCT/CA2018/050125 and the response filed on 9 Jun. 2026 does not point to sections of the priority documents supporting the compounds recited in claim 10 and 19. Accordingly, Shuhendler is prior art to claim 10 and 19 since those claims claim material not supported in cited priority documents.
New Grounds of Rejection
Claim Rejections - 35 USC § 103
Claim(s) 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kool et al. (Org. Lett.; published 21 Feb. 2014), in view of Chen et al. (US 2010/0291547 A1; published 18 Nov. 2010) and Zhou et al. (Nucl. Med. Biol.; published 2012).
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).
Kool et al. do not teach a kit comprising an aldehyde binding compound according to formula I-A1, formula I-A2, formula I-A3, or formula I-A4 as defined in claim 19 together with instructions for use.
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). Chen et al. teach kit for detecting analyte and compound therein that binds to an analyte and instructions for detecting an analyte ([0060]-[0063]).
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 Kool et al. by substituting the 4-OMe of the obvious 4-OMe modified OCPC derivative with a propargyloxy or 18F-fluoropropargyloxy to arrive at formula I-A1 or formula I-A3 and by further forming a kit with one of those compounds together with instructions as taught by Chen et al. and Zhou et al. because the compounds of formula I-A1 or formula I-A3 would have been expected to enable fast and stable click reactions such as bioconjugation reactions and because the kit would have been expected to advantageously enable facile distribution and use.
Claim(s) 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shudendler et al. (WO 2018/141069 A1; published 9 Aug. 2018), in view of Zhou et al. (Nucl. Med. Biol.; published 2012).
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 kit for detecting or monitoring these conditions wherein the kit comprises an aldehyde binding compound of formula I together with instructions for use ([0074]).
Shuhendler et al. do not teach a kit comprising an aldehyde binding compound according to formula I-A1, formula I-A2, formula I-A3, or formula I-A4 as defined in claim 19 together with instructions for use.
Zhou 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 Shuhendler et al. by substituting the 4-OMe of the 4-OMe modified OCPC derivative in Fig. 1 with a propargyloxy or 18F-fluoropropargyloxy to arrive at formula I-A1 or formula I-A3 and by further forming a kit with one of those compounds together with instructions as taught by Shuhendler et al. and Zhou et al. because the compounds of formula I-A1 or formula I-A3 would have been expected to enable fast and stable click reactions such as bioconjugation reactions and because the kit would have been expected to advantageously enable facile distribution and use.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN R DONOHUE whose telephone number is (571)270-7441. The examiner can normally be reached on Monday - Friday, 8:00 - 5:00 EST.
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/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
/SEAN R. DONOHUE/
Examiner, Art Unit 1618
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