DETAILED ACTION
This office action is in response to the Applicant’s filing dated December 16th, 2025.
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 18-23 and 25-30 are pending in the instant application. Acknowledgement is made of Applicant’s remarks and amendments filed on December 16th, 2025. Claims 20-22, 26-27 and 29-30 remain withdrawn. Claims 18-19, 23, 25 and 28 are presently under examination as they relate to the elected species.
Priority
This application is a 371 of PCT/US2021/063552 filed on December 15th, 2021; and has a PRO 63/166,484 filed on March 26th, 2021 and 63/126,100 filed on December 16th, 2020.
Objections and/or Rejections and Response to Arguments
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated (Maintained Objections and/or Rejections) or newly applied (New Objections and/or Rejections, Necessitated by Amendment or New Objections and/or Rejections, NOT Necessitated by Amendment). They constitute the complete set presently being applied to the instant application.
Maintained Objections and/or Rejections
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 18-19, 23, 25 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Cook et al. (US 2022/0290140 A1), cited in a previous Office Action; in view of Brockschnieder et al. (The Journal of Nuclear Medicine, (2012), 53(11), 1794-1801), cited in a previous Office Action.
Regarding claims 18-19, 23, 25 and 28, Cook teaches Compound 6 shown below:
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Compound 6 of Cook is a compound of Formula IIb wherein Rb1, Rb2 and Rb3 are H; wherein L is -NH-C(O)-; wherein n is 0 and wherein z is 18F (page 7, paragraph [0091]; page 8, paragraph [0097-0103]; page 9, right column, last compound). Compound 6 differs from the instantly elected compound by the absence of an N atom in the terminal [18F]fluorophenyl ring, and the attachment point of the terminal [18F]fluorophenyl ring to the core scaffold. Cook further teaches Compound 6 is a radiolabeled tetrazine radioligand suitable for in vivo diagnostic imaging (page 7, paragraph [0081]), and as being administered to a subject and imaged as a PET radiotracer (page 14, paragraph [0125]). Cook teaches a pharmaceutical composition comprising Compound 6 and sterile water as a pharmaceutically acceptable carrier (page 2, paragraph [0018]).
Cook does not teach a tetrazine radioligand with a terminal 2-[18F]fluoropyridine ring.
Brockshnieder teaches Compound 5 shown below (page 1797, Figure 1):
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Compound 5 is a structurally similar compound containing a terminal 2-[18F]fluoropyridine ring bound in the same position as the instantly elected compound. Brockschnieder reports that Compound 5 is one of the top performing radiotracer compounds, exhibiting favorable pharmacokinetic properties, including a brain uptake of 5.37% ID/g and Brain washout ratio of 4.2, illustrating Compound 5 as an effective PET radiotracer (page 1796, right column, third and fourth paragraphs; page 1797, Table 1).
It would have been prima facie obvious to a person of ordinary skill in the art to select Compound 6 of Cook as a lead compound, and modify the terminal [18F]fluorophenyl ring to a [18F]fluoropyridyl ring, in view of Brockschnieder’s teaching that a terminal 2-[18F]fluoropyridine ring at this position in structurally similar compounds yields effective PET tracers with favorable demonstrated pharmacokinetics. The structural modification of replacing a phenyl ring with pyridine ring represents a routine isosteric substitution; one of ordinary skill in the art would have a reasonable expectation of success in retaining radiolabeling capability, while potentially improving radiotracer performance.
“[T]he rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395.
Taken together, all this would result in the compound and composition of instant claims 18-19, 23, 25 and 28 with a reasonable expectation of success.
Applicant argues:
Cook lacks any teaching of a terminal [18F]fluoropyridyl group; and Brockschnieder lacks any teaching of tetrazine containing compounds or pre-targeted imaging.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
A prima facie case of obviousness does not require that the primary reference expressly disclose the claimed modification, nor that each reference address the exact same application. Under KSR, 550 U.S. at 416, 82 USPQ2d at 1395 and MPEP §2143, the references may be combined for what they collectively teach to one of ordinary skill in the art.
As explained above, Cook teaches structurally analogous [18F]-labeled aromatic substituents suitable for PET imaging, and Brockschnieder teaches that [18F]fluoropyridyl substitution at the same terminal position yields effective PET radiotracers with favorable pharmacokinetics, thereby providing both motivation and a reasonable expectation of success for the claimed modification.
Therefore, the rejection is maintained for the reasons of record.
Applicant argues:
Brockschnieder identifies BAY 1008472 as a preferred clinical candidate, not Compound 5.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
While Brockschnieder identifies BAY 1008472 as a preferred clinical candidate, Brockschnieder expressly reports Compound 5 as one of the top performing radiotracers with favorable pharmacokinetic properties as discussed in the above rejection. The reference therefore provides a clear teaching, without discrediting or criticizing or otherwise discouraging, that the [18F]fluoropyridyl substitution at the relevant position is viable and effective. "[A] reference does not teach away if it merely expresses a general preference for an alternative invention but does not criticize, discredit or otherwise discourage investigation into the invention claimed." In re DePuy Spine, Inc. v. Medtronic Sofamor Danek, Inc., 567 F.3d 1314, 1327 (Fed. Cir. 2009).
Conclusion
Claims 18-19, 23, 25 and 28 are rejected.
No claim is allowed.
THIS ACTION IS MADE FINAL. 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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/C.L.J./Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691