DETAILED ACTION
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 the Claims
Claims 1-2, 5-28, 30, 32 and 116 are pending and are rejected.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 7/9/2026 has been entered.
Information Disclosure Statement
The information disclosure statements submitted on 7/9/2026 and 9/9/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Declaration –37 CFR § 1.132
The declaration under 37 CFR 1.132 filed on 7/9/2026 is insufficient to overcome the rejection of claims 1-2, 5-28, 30, 32 and 116 based upon Ravert et al. US 10,947,197 B2 in view of Vanderheyden US 5,393,512, as evidenced by Anderson, as set forth in the last Office action because: Although the well-written declaration supports Applicant’s arguments, when reconsidered in view of the prior art, the arguments are ultimately not persuasive.
Applicant respectfully argues that a PHOSITA “could not base the level of ascorbate for an imaging agent with 18F, a positron-emitter, on the therapeutic agents of Vanderheyden with radioisotopes, which are beta-emitters.” Declaration ¶ 13. Although Applicant provides an excellent and very helpful explanation of the radioisotopic differences, such as half-lives and emission properties, between the compounds of Ravert and Vanderheyden, these differences do not amount to a teaching away, nor are they evidence that combining ascorbic acid and [18F]DCFPyL would give rise to any unpredictable or unexpected effects. Both Ravert and Vanderheyden teach ascorbic acid acts as a stabilizer, and Ravert uses ascorbic acid to stabilize [18F]DCFPyL. Therefore, a PHOSITA would have expected the claimed amounts of ascorbic acid (the same amounts taught by Vanderheyden) to stabilize [18F]DCFPyL.
Applicant respectfully argues that a PHOSITA would not have been motivated to combine the teachings of the cited references, because “the only rationale for combining all of these teachings is found with the disclosure of the instant application.” Remarks 7, declaration ¶ 14-15. This is not found persuasive, because “[t]he reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by application. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323, 76 USPQ2d 1662, 1685 (Fed. Cir. 2005) ("One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings."). See MPEP 2144(IV). In addition, “[t]he Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham” (MPEP 2143). Furthermore, “[o]ther rationales to support a conclusion of obviousness may be relied upon by Office personnel. Any rationale employed must provide a link between the factual findings and the legal conclusion of obviousness.” In this case, the rationale for modifying Ravert’s reference is based on the routine experimentation that a PHOSITA would employ, namely experimentation with the amount of ascorbic acid. Since Vanderheyden teaches an anticipatory range of ascorbic acid amounts, a prima facie case of obviousness exists. In fact, Vanderheyden’s disclosure of various ranges of ascorbic acid is evidence that a PHOSITA would routinely experiment with ascorbic acid amounts. See MPEP 2144.05 (“In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).)
Applicant respectfully argues that a PHOSITA “would have had no reasonable expectation of success from the combination of the teachings of Ravert and Vanderheyden.” Remarks 8, declaration ¶ 15. Applicant further argues “the selection of a suitable radiolysis stabilizer is highly context-dependent and unpredictable… Neither of the cited references provide sufficient information with respect to the amount of ascorbic acid that would be predictably successful” in the claimed solution. Remarks 8. Applicant also argues that the references do not teach the “amount of ascorbic acid that would be predictably successful” in the claimed composition. This is not persuasive, because Ravert explicitly selects ascorbic acid (in its buffered form, sodium ascorbate) as the preferred stabilizer for [18F]DCFPyL (e.g., at col. 29). Vanderheyden also selects ascorbic acid as a preferred stabilizer (e.g., at col. 11). Both references demonstrate that ascorbic acid is a preferred stabilizer for radiolabeled therapeutics, and Vanderheyden explicitly teaches a preferred range of ascorbic acid that falls within the claimed range. (“[M]ost preferably about 7-10 mg/ml stabilizing agent” (col.11:30-32).) Therefore, a PHOSITA would have expected that combining 7-10 mg/mL of ascorbic acid with a radiolabeled therapeutic such as [18F]DCFPyL would have had a stabilizing effect.
Applicant respectfully argues the “rejection cannot be maintained” because “the Examiner has put forth many conclusory statements and has cobbled together cherry-picked passages from the cited references.” Remarks 9. This is not persuasive, because patents “are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). Furthermore, discussing Ravert’s and Vanderheyden’s teachings is the first step in the obviousness analysis and is, therefore, a required step. The teachings are not conclusory statements, but rather facts with pinpoint citations.
Applicant respectfully argues “the rejections were made by using… impermissible hindsight reasoning.” Remarks 9, declaration ¶ 19. However, 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).
Therefore, the obviousness rejection is maintained.
Claim Rejections - 35 USC § 103
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.
Claims 1-2, 5-28, 30, 32 and 116 are rejected under 35 U.S.C. 103 as being unpatentable over Ravert et al. US 10,947,197 B2 in view of Vanderheyden US 5,393,512, as evidenced by Anderson, P. S. “Vitamin C. Ascorbic Acid versus Sodium Ascorbate.” Consult Dr A. 2020. https://www.consultdranderson.com/ascorbic-acid-versus-sodium-ascorbate/.
Contents of the Prior Art
Ravert purifies [18F]DCFPyL by HPLC with ethanol, wherein “sodium ascorbate was added to the HPLC collection reservoir and the saline solution used for eluting the product.” Col. 29 lines 43-56. The sodium ascorbate, a buffered form of ascorbic acid,1 is used to stabilize the product. See, e.g., col. 17 lines 43-46. Ravert reports an end-of-synthesis radiochemical purity (RCP) of 99.7%, with a radioactive concentration of 122 mCi/mL, and a 98.8%, 98.5% and 98.2% RCP at 3, 4 and 6 hours post EOS, respectively (col. 29, lines 51-56). The “reported results meet or exceed all previously stated acceptance specifications,” which includes a pH in the range of 4.5-8.5, with an average pH of 5. Table 1 and col. 28:42-50.
Differences Compared to the Claims and Obviousness Thereof
Ravert teaches the same components as the instant composition, but is silent regarding the amount of ascorbic acid (e.g., claims 1-2). However, Vanderheyden teaches “[a]scorbic acid is an especially preferred stabilizing agent” for “therapeutic radiolabeled compounds” (col. 11:15-20). “[P]atient preparations preferably comprise from about 1 mg/ml to about 15 mg/ml stabilizing agent, … and most preferably about 7-10 mg/ml stabilizing agent” (col.11:30-32). Since Vanderheyden’s amounts of ascorbic acid overlap with the claimed ranges and since a PHOSITA would have been motivated to modify the ascorbic acid/sodium ascorbate amount in Ravert’s composition, the PHOSITA would have found it obvious to arrive at the claimed invention after routine experimentation. See MPEP § 2144.05.
The pH of claims 5-7 read on Ravert’s reported average pH of 5 (Table 1).
The RCP of claims 8-11 (at least 96% at 10 hours post EOS) would have been inherent in
Ravert’s composition, since linear extrapolation suggests a 97% RCP at 10 hours.
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The radioactive concentration of 122 mCi/mL(col. 29, line 53) falls within the ranges of claims 12-14.
Ravert teaches “not more than 0.5% of the precursor or its byproducts remaining in the final product matrix”, which amounts to 0.5% or less of any impurities, including free 18F, as required by claims 15-19. Ravert would have also rendered obvious the impurity ranges of claims 27-28 and 30, since a PHOSITA would have found it desirable to minimize or eliminate all impurities to improve pharmaceutical properties. Furthermore, Ravert teaches the composition comprising an average of 0 ppm of acetonitrile which meets claim 32. See Table 1.
Regarding claims 20-24 and 26, Ravert teaches an extract comprising [18F]DCFPyL in 1 mL EtOH and 14 mL normal saline. Although ascorbic acid/sodium ascorbate was not added to this product, a PHOSITA would have found it obvious to stabilize the product using ascorbic acid/sodium ascorbate to improve RCP over time. This extract sample contains 5.3% w/v of EtOH ((1 mL *0.789 g/mL)*100%/(1 mL+14 mL)). According to Ravert’s Table 1, a PHOSITA would have found it obvious to arrive at the composition of claim 116, since Ravert teaches 5.3% w/v EtOH, 0% acetonitrile, an average pH of 5, and less than 0.5% of other impurities (as discussed for claims 15-19).
Regarding claim 25, since Ravert teaches a composition comprising about 5.3% w/v of ethanol and a composition comprising between 0-50 ppm of methanol (a homolog of ethanol with similar properties)2, a PHOSITA would have been motivated to optimize the amount of ethanol in the [18F]DCFPyL product as part of routine experimentation in seeking improved and optimized pharmaceutical properties; thereby rendering obvious the claimed range of less than 5% w/v of ethanol. (50 ppm is equivalent to 5% w/v/.)
Conclusion
All claims are drawn to the same invention claimed in the application prior to the entry of the submission under 37 CFR 1.114 and 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 extension fee 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.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMANDA L AGUIRRE whose telephone number is (571)272-5592. The examiner can normally be reached 10 am-6 pm MST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY H MURRAY can be reached on 571-272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMANDA L. AGUIRRE/ Primary Examiner, Art Unit 1626
1 As evidenced by Anderson (2020). (“In oral administration ASC is well absorbed but some report GI upset and will have less GI symptoms with a mineral “buffered” form of ASC. Commonly this is NaASC, Calcium ASC or mixtures that include one or both of these forms and any number of other mineral ascorbate forms.” Anderson 2.)
2 Ravert col. 14:11-18.
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