DETAILED ACTION
Notice of 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
The amendments filed 6/30/2026 have been entered.
Response to Arguments
Applicant’s arguments, filed 6/30/2026, have been fully considered.
The rejection of claims under 35 U.S.C. 102(a)(1) as being anticipated by Nimmagadda et al (WO 2018/119313; of record) is WITHDRAWN in view of Applicant’s amendments to the claims.
Applicant traverses the rejection of claims under 35 U.S.C. 103(a) as being unpatentable over Nimmagadda et al (WO 2018/119313; of record) in view of Shetty et al (Bioorg Med Chem 20:5941-5947, 2012; of record). As argued by Applicant, “[t]o arrive at the claimed compound” starting with DK-A-222 as taught by Nimmagadda et al, “a POSA would have to had to take the additional and distinct step of replacing DK-A-222’s linker with the specific isothiocyanatobenzyl-derived (benzyl-thiourea) linker now recited in claim 1 and depicted in claim 42. The Office Action has not established why a POSA would have been motivated to make this change” (Applicant Arguments, Pages 9-10).
The argument is not found persuasive. As discussed in the basis of the rejection, Shetty et al teach “a bifunctional chelating agent containing isothiocyanate residue for one step F-18 labeling of peptides” (Title) as follows (Page 5942, Scheme 1):
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which “can be conjugated to a target molecule containing an amino functional group under weak basic conditions by way of thiourea bond formulation” (Abstract). As further taught by Shetty et al, “[t]he conjugated peptide was labeled with the [18F]AlF method with high radiochemical efficiency” and “[b]iodistribution and microPET imaging studies... showed significant uptakes of the labeled peptide” (Page 5944, Column 1), specifically disclosing an Al18F-NODA-peptide as follows (Page 5943, Scheme 2):
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Based on all of the foregoing, it would have been prima facie obvious to formulate Applicant’s instantly elected compound species. In particular, it would have been prima facie obvious to modify DK-A-222 and/or [64Cu]DK-A-222 (taught by Nimmagadda et al) such that the peptide is labeled with the [18F]AlF method to comprise Al18F-NODA-peptide (based on Nimmagadda et al and Shetty et al) to arrive at the instantly elected compound species with a reasonable expectation of success. The simple substitution of one known radiolabeled chelating agent useful in peptide-specific PET imaging agents for another is prima facie obvious.
However, as further argued by Applicant, “[w]hile Shetty ‘report[s] an iosthiocyanatobenzyl NODA (NODA-Bz-SCN, 5) derivative that can be conjugated to bio-molecules under mild conditions,’ Shetty says nothing about PD-L1 or about any reason why a POSA would have been motivated to employ Shetty’s aromatic thiourea conjugation over Nimmagadda’s existing linker for this agent” (Applicant Arguments, Page 10). Although Applicant acknowledges that “the Office Action has established that a POSA would have been aware of Shetty’s alternative linker chemistry”, Applicant argues that “knowledge is not enough” (Applicant Arguments, Page 11). In particular, Applicant points to Virtek Vision Int'l ULC V. Assembly Guidance Sys., Inc., 97 F.4th 882 (Fed. Cir. 2024) which states that “[i]n short, this case involves nothing other than an assertion that because two coordinate systems were disclosed in a prior art reference and were therefore 'known,' that satisfies the motivation to combine analysis. That is an error as a matter of law”. As further stated by the court, “[i]t does not suffice to simply be known. A reason for combining must exist”.
The argument is not found persuasive. Whereas the court in Virtek Vision Int'l ULC V. Assembly Guidance Sys., Inc. addressed the substitution of known alternatives, the instant rejection is based on the substitution of known equivalents. Specifically, Nimmagadda et al disclose PET imaging agents comprising a peptide, a reporting moiety (including, wherein the reporting moiety is “labeled with 18F using the AlF method, for example, based on the chelation of aluminum fluoride by... NODA” (Page 19, Lines 15-17)) and “a linker, wherein the linker... connects the peptide and the reporting moiety” (Page 2, Lines 19-21) (including, “[b]y way of non-limiting examples... linkers... disclosed in U.S. patent application publication numbers 2015/0246144” (Page 22, Line 19 to Page 23, Line 2) which discloses:
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(Page 20)). And Shetty et al similarly disclose PET imaging agents comprising a peptide, a reporting moiety (in particular, wherein the reporting moiety is NODA labeled with 18F using the AIF method), and a linker connecting the peptide and the reporting moiety (in particular, wherein the linker is an isothiocyanatobenzyl-derived (benzyl thiourea) linker).
As such, it would have been obvious to select the linker connecting a peptide with a reporting moiety of the PET imaging agent taught by Shetty et al as the linker connecting a peptide with a reporting moiety of the PET imaging agent taught by Nimmagadda et al (i.e., it would have been obvious to substitute one known linker useful in connecting a peptide with a reporting moiety of the PET imaging agent with another known linker useful in connecting a peptide with a reporting moiety of the PET imaging agent with a reasonable expectation of success). And, as noted by the court in In re Fout, 675 F.2d 297 (CCPA 1982), an express suggestion to substitute one equivalent component (e.g., an equivalent linker) for another is not necessary to render such substitution obvious.
In the instant case, (1) the prior art element performs the function specified in the claim; (2) the claimed component and its function was known in the art; (3) a person of ordinary skill in the art would have recognized the interchangeability of the elements and could have substituted one known element for another; and (4) the results of the substitution would have been predictable. As stated by the Court in KSR International Co., v. Teleflex Inc., 127 US 1727 (2007), “when a patent ‘simply arranges old elements with each performing the same function it had been known to perform’ and yields no more than one would expect from such an arrangement, the combination is obvious” (quoting Sakraida v. AG Pro, Inc., 425 US 273 (1976); see also: Merck v. Biocraft (874 F.2d 804, 807 (Fed. Cir. 1989), indicating that it is a matter of obviousness for one of ordinary skill in the art to select a particular component from among many disclosed by the prior art as long as it is taught that the selection will result in the disclosed effect, even when the possible selections number 1200 or in the thousands).
Applicant, however, next argues that “[e]ven assuming, arguendo, that the Office Action had established the requisite motivation, the Office Action has not satisfied the requirement that a POSA would have had a reasonable expectation of success in achieving the specifically claimed invention” (Applicant Arguments, Page 11). In particular, Applicant argues that “[q]antifying PD-L1 dynamics presents a challenge”, yet “[18F]DK222 exhibits high specificity to PD-L1” (Applicant Arguments, Page 11). Additionally, Applicant argues that, “at the low nM concentrations administered, [18F]DK222 does not interfere with anti-PD-L1 therapy” and “exhibits PK and biodistribution features distinct from that of reported PD-L1 imaging agents” (Applicant Arguments, Pages 11-12). As such, Applicant argues that “a POSA would [not] have had a reasonable expectation of success in modifying Nimmagadda’s disclosed compound in a manner that would have maintained high affinity and specificity for PD-L1, had low non-specific accumulation in normal tissues, exhibited suitable image contrast, and avoided interference with anti-PD-L1 therapy” (Applicant Arguments, Page 12).
The argument is not found persuasive. As taught by Nimmagadda et al, “[i]maging... and biodistribution... data show superior pharmacokinetics of [64Cu]DK222” (Page 8, Lines 21-34). Considering that each of the proposed modifications to [64Cu]DK222 are expressly envisioned by Nimmagadda et al (see Page 19, Lines 15-17 and Page 22, Line 19 to Page 23, Line 2) and are specifically utilized in another PET imaging agent (as taught by Shetty et al), it is maintained that a person of ordinary skill in the art would have reasonably expected the prima facie obvious compound based on [64Cu]DK222 to have maintained the desirable properties thereof with a reasonable expectation of success. Applicants are reminded that obviousness does not require absolute predictability, only a reasonable expectation of success of obtaining similar properties. In re O'Farrell, 853 F.2d 894 (Fed. Cir. 1988).
Lastly, Applicant traverses the rejection of claims on the grounds of obvious type non-statutory double patenting (Applicant Arguments, Pages 12-13). The arguments are not found persuasive for the reasons discussed above.
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.
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 1, 6 and 41-42 are rejected under 35 U.S.C. 103(a) as being unpatentable over Nimmagadda et al (WO 2018/119313; of record) in view of Shetty et al (Bioorg Med Chem 20:5941-5947, 2012; of record).
As amended, claims 1, 6 and 42 are drawn to an imaging agent comprising a compound of formula (I) which embraces Applicant’s elected compound species:
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.
Nimmagadda et al teach “an imaging agent comprising a conjugate of a peptide having binding specificity for programmed death ligand 1 (PD-L1) and a reporting moiety, and optionally a linker” (Page 2, Lines 18-20), specifically disclosing the imaging agents DK-A-222 (Figure 30) having the following structure:
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and [64Cu]DK-A-222 (Figure 31), which differ from Applicant’s instantly elected compound in comprising a different linker and a different radiometal.
Yet, as further taught by Nimmagadda et al, “[i]n some embodiments, the substrate is labeled with 18F using the AlF method, for example, based on the chelation of aluminum fluoride by... NODA” (Page 19, Lines 15-17)j and “[b]y way of non-limiting examples... linkers are disclosed in U.S. patent application publication numbers 2015/0246144... incorporated herein by reference in [its] entirety” (Page 22, Line 19 to Page 23, Line 2) which discloses:
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(Page 20)).
And Shetty et al teach “a bifunctional chelating agent containing isothiocyanate residue for one step F-18 labeling of peptides” (Title) as follows (Page 5942, Scheme 1):
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which “can be conjugated to a target molecule containing an amino functional group under weak basic conditions by way of thiourea bond formulation” (Abstract). As further taught by Shetty et al, “[t]he conjugated peptide was labeled with the [18F]AlF method with high radiochemical efficiency” and “[b]iodistribution and microPET imaging studies... showed significant uptakes of the labeled peptide” (Page 5944, Column 1), specifically disclosing an Al18F-NODA-peptide as follows (Page 5943, Scheme 2):
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Based on all of the foregoing, it would have been prima facie obvious to formulate Applicant’s instantly elected compound species. In particular, it would have been prima facie obvious to modify DK-A-222 and/or [64Cu]DK-A-222 (taught by Nimmagadda et al) such that the peptide is labeled with the [18F]AlF method to comprise Al18F-NODA-peptide (based on Nimmagadda et al and Shetty et al) to arrive at the instantly elected compound species with a reasonable expectation of success. The simple substitution of one known radiolabeled chelating agent useful in peptide-specific PET imaging agents for another is prima facie obvious.
As such, claims 1, 6 and 42 are rejected as prima facie obvious.
Claim 41 is drawn to a kit for detecting PD-L1, the kit comprising the imaging agent of any of claim 1 and the radiometal Al18F.
Nimmagadda et al teach “a kit for detecting Programmed Death Ligand 1 (PD-L1), the kit comprising an imaging agent” (Page 4, Lines 1-3), in particular “a presently disclosed imaging agent” (Page 29, Lines 32-33).
Accordingly, claim 41 is also rejected as prima facie obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 6 and 41-42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-44 of U.S. Patent No. 11/607,466 alone or in view of Shetty et al (Bioorg Med Chem 20:5941-5947, 2012; of record).
Although the claims at issue are not identical, they are not patentably distinct from each other. The ‘466 claims are drawn to compounds of DK-A-221-(L)n-Rpt (claim 1), including DK-A-222 (claim 7) and [64Cu]DK-A-222 (claim 8) and a kit thereof (claim 24), which reads on the instantly claimed compounds and wherein, in further view of Shetty et al, it would have been obvious to arrive at Applicant’s elected compound species for the same reasons as discussed above.
Conclusion
Any new ground(s) of rejection presented in this Office action are necessitated by Applicant’s amendments to the claims. 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 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CRAIG D RICCI whose telephone number is (571) 270-5864. The examiner can normally be reached on Monday through Thursday, and every other Friday, 7:30 am - 5:00 pm ET.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany Barham can be reached on (571) 272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CRAIG D RICCI/Primary Examiner, Art Unit 1611
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