DETAILED ACTION
This Office action details a final action on the merits for the above referenced application No. Claims 1-2, 6-11, and 17-26 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 13 Feb. 2026 has been entered.
Status of Claims
Claims 1, 17, 19, and 22 are amended. Claims 3-5, and 12-16 are cancelled. Claims 17-18, 20-21, and 23-25 are withdrawn.
Response to Amendment
The amendments filed on 13 Feb. 2026 have been entered.
Response to Arguments
In view of Applicants amendments, the objection to claim 1 because of minor informalities is withdrawn.
In view of Applicants amendments, the rejection of claims 11, 19, and 22 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35 USC 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter is withdrawn.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of claim 22 under 35 USC 112(d) as being of improper dependent for failing to further limit the subject matter is withdrawn.
In view of Applicants amendments, the rejection of claims 1-2 and 26 under 35 USC 102(a)(1) as being anticipated by Hoigebazar et al. (Bioorg. Med. Chem.; published 2011) is withdrawn.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) 1-2, 6, and 8-9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wiebe et al. (US 2006/0270610 A1; published 30 Nov. 2006), in view of Hoigebazar et al. (Bioorg. Med. Chem.; published 2011) for the reasons cited in the Office action filed on 13 Aug. 2025.
Applicants Arguments
Applicants assert that the Hoigebazar fails to teach or suggest the radiolabeled compound of independent claim 1. Hoigebazar provides no guidance that would have led a skilled artisan to produce a nitroimidazole with a sugar moiety. Hoigebazar describes the synthesis of two nitroimidazole derivatives both lacking a sugar moiety. Wiebe provides no teaching or suggestion to modify the position of the halogen of its disclosed compounds in order to include a linker that would be connected to a different radiolabel. The compounds of Wiebe have an R that is OH, etc, and Wiebe’s compounds lack an ether, amide, carboxylic acid or amide linker to a radiolabel. There would have been no reason to combine the compounds of Hoigebazar with those of Wiebe. Wiebe confirms that its compounds already have suitable properties for their intended purposes and provides no reason to make further modifications. Neither Wiebe nor Hoigebazar teach the chemistry necessary to combine the various components in order to achieve a compound within the scope of the present claims. Applicants assert conclusory statements and impermissible hindsight.
Applicant's arguments filed 13 Feb. 2026 have been fully considered but they are not persuasive. Wiebe teaches for example the IAZA
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and the [18F]1-α-D-FAZA
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that provides for strong tumor target to background contrast. The [18F]1-α-D-FAZA read on compounds of instant formula (II) wherein
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(BA) is a 2-nitroimidazole and the radiolabeled compound further comprises sugar substituted moiety, n=1, and X=18F radiohalogen.
At table 1-4, Wiebe teaches a wide range of IAZA and [18F]1-α-D-FAZA derivatives containing modifications at the 18F of the above compound. In addition, at pg, 15, Wiebe teaches the precursor compound
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having TsO leaving group, which is amenable to substitution with a labeling group.
Regarding radiolabels, at [0153], Wiebe merely teaches the inclusion of appropriate radionuclides. Radionuclides 125I and 131I are given only as examples. In the IAZA, the iodo group, which is leaving group, is placed at a primary carbon. Like Wiebe, Hoigebazar teaches the IAZA and FAZA compounds to detect hypoxia in tumors. However, Hoigebazar teaches and motivates DOTA-nitroimidazole derivatives. In other words, Hoigebazar was motivated to replace the 18F or 123I labels used on 2-nitroimidazole derivatives with DOTA chelator capable of complexing a wide range of diagnostic and therapeutic radiometals to at least detect hypoxia in tumors. For example, Hoigebazar teaches the 68Ga is promising since it can be obtained from a commercially available generator. 68Ga has cost and convenience benefits. A person of ordinary skill in the art would have known how to replace the TsO leaving group in the above compound with an amine and then react that amine with a DOTA chelator as taught by Hoigebazar. Hoigebazar teaches that the promising in vivo and in vitro results suggest that the 68Ga-labeled DOTA-nitroimidazole derivative offers the possibility of fast and efficient means of detecting tumor hypoxia. 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 for example the compounds of Wiebe such as [18F]1-α-D-FAZA or the above precursor compound by incorporating a DOTA chelator such that the instant R1 is an amide and the X radiolabel is 68Ga because those compounds would have been expected to enable cost effective and fast and efficient means of detecting tumor hypoxia. 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).
Claim(s) 1-2, and 6-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wiebe et al. (US 2006/0270610 A1; published 30 Nov. 2006), in view of Hoigebazar et al. (Bioorg. Med. Chem.; published 2011), in further view of Stasiuk et al. (Chem. Commun.; published 2013) for the reasons cited in the Office action filed on 13 Aug. 2025.
Applicants Arguments
Applicants assert that Stasiuk provides no teaching or suggestion that would have led a skilled artisan to combine Stasiuk’s DOTA linker and radiolabel with Wiebe’s radiolabeled compound or to further combine that modified compound with an into Hoigebazar’s compound in order to produce a compound without scope of the present claims.
Applicant's arguments filed 13 Feb. 2026 have been fully considered but they are not persuasive. Wiebe and Hoigebazar are not deficient for the reasons discussed above. Stasiuk teaches and motivates combining the 177Lu radiometal with a DOTA chelator since the 177Lu labeled DOTA would have been expected to enable radiotherapy. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Wiebe and Hoigebazar so that the radiometal is 177Lu because that radiometal would have been expected to enable radiotherapy of hypoxic tumors.
Claim(s) 1-2, 6-9, 19, 22, and 26, and is/are rejected under 35 U.S.C. 103 as being unpatentable over Kumar et al. (WO 2011/160216 A1; published 29 Dec. 2011), in view of Hoigebazar et al. (Bioorg. Med. Chem.; published 2011) and Das et al. (Bioorg. Med. Chem.; published 2004) for the reasons cited in the Office action filed on 13 Aug. 2025.
Applicants Arguments
Applicants assert that Kumar fails to teach or suggest a compound having the recited linker group. Hoigebazar and Das do not teach or suggest modifications suitable for remedying the deficiencies of Kumar to arrive at a compound of present independent claim 1. Each of the compounds disclosed in Kumar contain a nitroimidazole bound to a sugar but there is not teaching or suggestion that led a skilled artisan to the structure of the compounds of the present claims. Kumar provides no reason or motivation to substitute the L groups with radiolabels containing a linker. Kumar fails to teach or suggest any chemistry that would be suitable for modifying the compounds of Kumar to arrive at the claimed invention.
Applicant's arguments filed 13 Feb. 2026 have been fully considered but they are not persuasive. The teachings of Kumar are similar to the teachings of Wiebe and as discussed above Hoigebazar provides more than adequate reason and motivation to modify 2-nitroimidazole derivatives attached to a sugar moiety by incorporating a radiometal DOTA label such as 68Ga-DOTA to image hypoxic tumors cost effectively and with convenience benefits. The teachings of Das are similar to the teachings of Stasiuk who provides more than adequate reason and motivation to use the 177Lu-DOTA label for radiotherapy. Das teaches and motivates the 177Lu-DOTA label for radiotherapy of hypoxic tumors
Kumar teaches compounds for imaging hypoxic tumors and at [00124], Kumar teaches the compound
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. A recognized advantage is the strongest reason to combine. When there is recognized advantage, it cannot be considered hindsight analysis. It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the compound of Kumar by substituting the 18F label with a DOTA chelator attached by amide conjugation and labeled with 68Ga or 177Lu as taught by Hoigebazar and Das because the 68Ga-DOTA label would have been expected to advantageously enable cost effective and convenient imaging of hypoxic tumors and because the 177Lu-DOTA label would have been expected to advantageously enable radiotherapy of tumors.
Claim(s) 1-2, 6-11, 19, 22, and 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kumar et al. (WO 2011/160216 A1; published 29 Dec. 2011), in view of Hoigebazar et al. (Bioorg. Med. Chem.; published 2011) and Das et al. (Bioorg. Med. Chem.; published 2004), in further view of Wiebe et al. (US 2006/0270610 A1; published 30 Nov. 2006) for the reasons cited in the Office action filed on 13 Aug. 2025.
Applicants Arguments
Applicants assert that Wiebe in no wat remedies the deficient guidance of Kumar, Hoigebazar, and Das with regard to the structure of a radiolabeled compound so as to arrive at a radiolabeled compound of present claim 1 and its dependent claims. Wiebe does not provide any additional guidance relative to Kumar, Hoigebazar, and Das regarding modifications that would have led a skilled artisan to remove the radiolabel of its compounds so as to replace it with a different radiolabel-containing groups such as the recited in present independent claim 1.
Applicant's arguments filed 13 Feb. 2026 have been fully considered but they are not persuasive. Kumar, Hoigebazar and Das are not deficient for the reasons discussed above. In addition, Wiebe was found to be not deficient for the reasons discussed above. In this case, Wiebe was relied on for teaching and motivating chemosensitization and radiosensitization of hypoxic tumors.
Claim Objections
Claim 1 is objected to because of the following informalities: “
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(BA)” should be “BA”. Appropriate correction is required.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached on (571)272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
/SEAN R. DONOHUE/
Examiner, Art Unit 1618