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 .
Applicants' arguments, filed July 3, 2025, have been fully considered but they are not deemed to be fully persuasive. The following rejections and/or objections constitute the complete set presently being applied to the instant application.
Information Disclosure Statement
The information disclosure statement filed July 3, 2025 fails to comply with the provisions of 37 CFR 1.98(a)(4) because it lacks the appropriate size fee assertion. It has been placed in the application file, but the information referred to therein has not been considered as to the merits.
Note that there were two identical copies of the document present in the file wrapper and both copies were annotated by the Examiner as it was not clear if the same documents were submitted twice, although only a single fee was paid, or if the duplication occurred after filing by Applicants.
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.
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 and 2 were rejected under 35 U.S.C. 103 as being obvious over Cheng et al. (US 2017/0360759) in view of Donnelly et al. (WO 2015/066456). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed April 3, 2025 and those set forth herein.
Applicants traverse this rejection on the grounds that Donnelly is the closest prior art for assessment of obviousness as it is concerned with the same technical problem of imaging of LPA1 receptors in mammals. In vivo imaging results are reported in Example 10 of Donnelly et al. and a skilled person starting from Donnelly looking to provide further improved compounds would have started from the compound in this example referred to as [11C]-MNT-136088 [structure on the left shown below for reference]. Any of the compounds in Cheng could be labeled with 11C to render them suitable for PET imaging and there are a number of other fluorine containing compounds which could be labelled with 18F, some of which have lower IC50 values such as compound 98. The selection of compound 192 for 18F labelling can only be made with hindsight knowledge of the present invention.
These arguments are unpersuasive. Even if the instant claims were drawn to a method and not just the compounds themselves, the compounds of Donnelly et al. are not the closest prior art due to the numerous structural differences between the compounds. Compound 192 of the primary reference Cheng et al. only differs in the isotope of fluorine present in the structure and therefore is the closest prior art rather than a compound that bears little structural similarity to the claimed compound (both structures shown below for ease of comparison). The rejection is not based on Donnelly as the primary reference and therefore what one of ordinary skill in the art may or may not have done starting with Donnelly et al. is not germane to the rejection of record. 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). The fact that it would have been equally obvious to radiolabel other compounds containing fluorine disclosed by Cheng et al. with 18F to prepare other compounds for imaging purposes does not make the preparation of the 18F-labelled version of compound 192 of Cheng et al. any less obvious. The IC50 value for compound 192 is 36 nM while that of the immediately preceding compound on p 161 is 553 nM so compound 192 is not even close to the weakest inhibitor prepared by Cheng et al. One of ordinary skill would use not only IC50 values but also other properties such as selectivity when determining the best compound to use for a particular application.
Applicants also argue direct attention to two references submitted herewith [As discussed above, due to the lack of an IDS size fee assertion statement, those references have not been considered. Therefore only the material set forth in the remarks will be addressed.] The remarks state that it was unexpected that the claimed compound would be superior to the first generation compound of example 1 of Donnelly and a table with various parameters for the two compounds such as KD and protein binding is shown. The 11C labeled compound failed to meet its clinical goal and the presently claimed compound was found to be surprisingly superior to [11C]-MNT-136088. This compound was found to be very protein bound, a low overall PET signal within lung tissue and an unexpected decrease in radioligand in vivo stability. The claimed compound was found to be free from protein binding within human plasma samples, leading to an increase in the PET signal within lung tissues and more metabolic stability in in vivo rat and cynomolgus monkey studies. There was also an unexpected increase in isolated yield and chemical purity for the claimed compound compared to [11C]-MNT-136088. Nothing in Donnelly et al. or Cheng et al, alone or in combination, to have led a skilled person to the particularly claimed compound if looking for an improved radioligand for imaging LPA1 receptors.
These arguments are unpersuasive. Arguments without factual support are mere allegations and are not found persuasive. Even if submitted in evidentiary form, given the large differences in structure between the claimed compound and [11C]-MNT-136088 and the differences between radiolabeling using 11C and 18F, one of ordinary skill in the art would expect large difference in behavior between the claimed compound and [11C]-MNT-136088. The standard for obviousness is a reasonable expectation of success in preparing the claimed compound and not meeting clinical efficacy goals. Conclusions as to the surprising or unexpected properties are alleged but no reasoning such as what the expected results would be are set forth even in non-evidentiary form. While there is no per se rule that the only way to establish unexpected results is by a comparison with the closest prior art, in order to be particularly probative, evidence of unexpected results must establish that there is a difference between the results obtained and those of the closest prior art and that is compound 192 of Cheng et al. and not the very different compound of Donnelly et al. Rather the comparison with much more probative value would be between compound 192 as synthesized by Cheng et al. and the 18F labeled compound of the instant claims. There is no suggestion in the discussion of alleged unexpected results that the differences in behavior between these two compounds (e.g., protein binding) arise from the replacement of the F in compound 192 of Cheng et al. with 18F and not from the numerous other structural differences between the claimed compound and [11C]-MNT-136088. It does not appear that any evidence is of record relating to such a comparison of radiolabeled and non-radiolabeled compounds. Therefore the rejection is maintained for the reasons of record.
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 § 2146 et seq. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Applicants make no mention of the nonstatutory double patenting rejections in their arguments. Applicant's failure to argue the rejection on the grounds of non-statutory double patenting over US Patent Nos. RE49,253, 10,071,078 and 10,576,062 is noncompliant with the regulations under 37 C.F.R. 1.111. The instant rejection is not a provisional rejection as the claims of US Patent Nos. RE49,253, 10,071,078 and 10,576,062 have been issued. In the interest of compact prosecution, the Examiner has examined the instant application. However, in order for the response to the instant Office Action to be fully responsive and in compliance with the regulations under 37 C.F.R. 1.111, the Applicant should either file a terminal disclosure or traverse the rejection based on US Patent Nos. RE49,253, 10,071,078 and 10,576,062. Because applicant did not distinctly and specifically point out the supposed errors in the instant non-statutory double patenting rejection based on US Patent Nos. RE49,253, 10,071,078 and 10,576,062 and no Terminal Disclaimers have been filed, the rejection is maintained for the reasons of record set forth in the Office Action mailed April 3, 2025.
Claims 1 and 2 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 7, 9, 10, 12 – 15 and 17 - 15 of U.S. Patent No. RE49,253 in view of Donnelly et al. (WO 2015/066456). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed April 3, 2025 and those set forth herein.
Claims 1 and 2 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 7, 9 and 12 - 16 of U.S. Patent No. 10,071,078 in view of Donnelly et al. (WO 2015/066456). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed April 3, 2025 and those set forth herein.
Claims 1 and 2 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 12 and 15 - 18 of U.S. Patent No. 10,576,062 in view of Donnelly et al. (WO 2015/066456). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed April 3, 2025 and those set forth herein.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nissa M Westerberg whose telephone number is (571)270-3532. The examiner can normally be reached M - F 8 am - 4 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached at 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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/Nissa M Westerberg/Primary Examiner, Art Unit 1618