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 .
Receipt is acknowledged of IDS filed on 05/14/2026 and 12/18/2025.
Claim 4 is pending.
Claim 4 is amended.
Claims 1-3 and 5 are cancelled.
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn. The following rejections or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 4 is rejected under 35 U.S.C. 103 as being unpatentable over CESATI (WO 2014/026079) in view of ENGELL (US 2015/0139902 A1) and RADIOLOGY KEY (Quality Control of Pet Radiopharmaceuticals. 2017.).
Regarding claim 4, CESATI teaches a method of imaging a subject using a radiopharmaceutical composition (abstract). The method is for imaging an area of interest in a subject, which reads on imaging a subject in need thereof (abstract).
The method comprising intravenously injection the imaging agent (page 112, paragraph 4). The composition comprising: the radiopharmaceutical with the structure of:
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, where F is 18F (page 59), which reads on 18F flurpiridaz, ascorbic acid, ethanol (page 122, paragraph 3) and cyclodextrins, which are used as solubilizing aids (Page 127, paragraph 1). Pharmaceutically acceptable excipients/carriers are added, such as pyrogen-free water, isotonic saline or phosphate buffer (page 127, paragraph 3).
Ethanol is used as a preservative (page 129, paragraph 5). Ascorbic acid is used as a stabilizing agent (page 121, paragraph 5). PET images were taken after injection (Page 310, paragraph 1).
The reference does not specifically teach the amounts of ascorbic acid and ethanol as claimed by the Applicant. The amounts of ascorbic acid and ethanol is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of the ordinary skill to determine the optimal amounts of ascorbic acid and ethanol in order to best achieve desired results, such as having the optimal amount of ascorbic acid for stabilization and having the optimal amount of ethanol as a preservative, both of which would increase the shelf life of the composition. Thus, absent of some demonstration of unexpected results from the claimed parameters, this optimization of the amounts of ascorbic acid and ethanol would have been obvious at the time of Applicant’s invention.
Additional disclosures: CESATI further teaches that the radioactive concentration can be lowered so that it is usable and appropriate for administration to a subject (page 117, paragraph 3 and page 126, paragraph 1). The radioisotope, and in turn the radioactive concentration, is what allows the imaging to take place (page 71, paragraph 4).
CESATI does not teach a pH of 4.5-9.5 or the radiochemical purity or the radioactive concentration as claimed by Applicant.
ENGELL teaches a radiopharmaceutical for mammalian administration (page 4, paragraph 0058). The pH of the composition should be between 6.5 to 9.5 so that it is biocompatible with the patient (page 4, paragraph 0058).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate a pH of between 6.5 to 9.5. The person of ordinary skill in the art would have been motivated to make those modifications, because it makes the composition biocompatible with the patient, and reasonably would have expected success because the references are in the same field of endeavor, such as radiopharmaceutical administered to patients. Furthermore, CESATI teaches the composition, in one embodiment can be between a pH of 5.5 to 6 (page 116, paragraph 4).
RADIOLOGY KEY teaches that a high radiochemical purity for PET imaging radiopharmaceuticals because the control of radiochemical impurities is important to avoid the patient unnecessary radiation exposure because the radiochemical impurities could have a different biodistribution and not specific uptake which may affect and invalidate the clinical outcome of PET imaging studies (page 1, paragraph 4).
The reference does not specifically teach the radiochemical purity as claimed by the Applicant. The radiochemical purity is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of the ordinary skill to determine the optimal radiochemical purity in order to best achieve desired results, such as having a high radiochemical purity, and in turn that radiochemical purity persisting over a prolonged period of time (aka shelf life), so that the radiopharmaceutical remains stable until injection so that the patient does not receive unnecessary radiation exposure which can invalidate the outcome of the PET imaging. Thus, absent of some demonstration of unexpected results from the claimed parameters, this optimization of radiochemical purity would have been obvious at the time of Applicant’s invention. Furthermore, CESATI teaches the radiochemical purity can be greater than 99% (page 108, paragraph 3).
The reference does not specifically teach the radioactive concentration as claimed by the Applicant. The radioactive concentration is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of the ordinary skill to determine the optimal radioactive concentration in order to best achieve desired results, such as having a high enough concentration so that a clear image can be obtained, but a low enough concentration so that the composition is appropriate for administration to the patient. It is known in the art that too high of a radioactive concentration can cause harm to the patient when administered. Thus, absent of some demonstration of unexpected results from the claimed parameters, this optimization of the radioactive concentration would have been obvious at the time of Applicant’s invention.
Response to Arguments
Applicant argues, Applicant assert that mere optimization of any simple result effective variable, as described in the cited art, could not lead a person of skill in the art to arrive at the claimed method using the claimed stable radiopharmaceutical. Further, there is nothing in the cited art establishing to a person of skill in the art that would suggest that e.g., the claimed amount of ascorbic acid is a result effective variable that affects stability, and the specific radioactive concentration as claimed, as also explained in the Grigg Declaration (Grigg Declaration [4,5]).
The examiner does not find the argument persuasive because as discussed above, CESATI teaches that the ascorbic acid is used as a stabilizing agent (page 121, paragraph 5) and can be optimized to achieve stability. Furthermore, as discussed above, it would have been customary for an artisan of the ordinary skill to determine the optimal radioactive concentration in order to best achieve desired results, such as having a high enough concentration so that a clear image can be obtained, but a low enough concentration so that the composition is appropriate for administration to the patient.
Applicant argues, the instantly claimed method is surprising and unexpectedly possible in part due to the claimed administration of the stable radiopharmaceutical composition that includes the specifically recited amounts of ascorbic acid, together with cyclodextrin, that provides (a) surprising stability over 8 to 10 hours while b) surprising capable of introducing increased radioactivity concentration (RAC) of the radioactive agent in the formulation, allowing significant increase in the available doses of the radiopharmaceutical produced. Grigg Declaration at paragraph 3.
The examiner does not find the argument persuasive because in order to overcome a prima facie case of obviousness, it is incumbent upon the Applicant to provide comparative test evidence that demonstrates unexpected superiority of the claimed compositions versus the closest prior art compositions, and not simply an advantage predictable from the prior art. See In re Chapman, 148 USPQ 711, 715 (CCPA, 1966). Moreover, such proffered comparisons must be commensurate in scope with the breadth of the claims. See In re Clemens, 206 USPQ 289, 296 (CCPA, 1980) and In re Coleman, 205 USPQ 1172, 1175 (CCPA 1980). In the instant case, the examples given showing unexpected and significant results rely on a limitation not recited in the instant claims. The table provided that shows the superior RCP is based on using a specific species of cyclodextrin, hydroxypropyl-β-cycloodextrin, with a concentration of 40-47 mg/mL. The affidavit states “the claimed formulation having a critical amount of 30 to 50 mg/mL of ascorbic acid and 40 to 47 mg/mL hydroxypropyl-β-cycloodextrin compared to a formulation having 50 mg/mL ascorbic acid alone”. This statement and the table show that the hydroxypropyl-β-cyclodextrin and the concertation is critical to the unexpected results. Both of these limitations are not recited in instant claim 4, so the evidence is not commensurate in scope with the claims.
For a complete discussion of unexpected results, Applicants are referred to MPEP 716.02 et seq.
The affidavit under 37 CFR 1.132 filed 07/29/2026 is insufficient to overcome the rejection of claim 4 based upon the above references as set forth in the last Office action because:
In order to overcome a prima facie case of obviousness, it is incumbent upon the Applicant to provide comparative test evidence that demonstrates unexpected superiority of the claimed compositions versus the closest prior art compositions, and not simply an advantage predictable from the prior art. See In re Chapman, 148 USPQ 711, 715 (CCPA, 1966). Moreover, such proffered comparisons must be commensurate in scope with the breadth of the claims. See In re Clemens, 206 USPQ 289, 296 (CCPA, 1980) and In re Coleman, 205 USPQ 1172, 1175 (CCPA 1980). In the instant case, the examples given showing unexpected and significant results rely on a limitation not recited in the instant claims. The table provided that shows the superior RCP is based on using a specific species of cyclodextrin, hydroxypropyl-β-cycloodextrin, with a concentration of 40-47 mg/mL. The affidavit states “the claimed formulation having a critical amount of 30 to 50 mg/mL of ascorbic acid and 40 to 47 mg/mL hydroxypropyl-β-cycloodextrin compared to a formulation having 50 mg/mL ascorbic acid alone”. This statement and the table show that the hydroxypropyl-β-cyclodextrin and the concertation is critical to the unexpected results. Both of these limitations are not recited in instant claim 4, so the evidence is not commensurate in scope with the claims.
For a complete discussion of unexpected results, Applicants are referred to MPEP 716.02 et seq.
Conclusion
No claims are allowable.
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 SAMANTHA L. MEJIAS whose telephone number is (703)756-5666. The examiner can normally be reached M-F.
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/S.L.M./Examiner, Art Unit 1618 /JAKE M VU/Primary Examiner, Art Unit 1618
