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 November 18, 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.
Drawings
The drawings were received on November 18, 2025. These drawings are acceptable.
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.
Claim(s) 1, 7 – 10 and 16 were rejected under 35 U.S.C. 103 as being unpatentable over Goodman et al. (US 5,817,776; cited on IDS filed February 1, 2023) in view of Park et al. (Annu Rev Pharmacol Toxicol, 2001; cited on IDS filed February 1, 2023) and Biffinger et al. (ChemBioChem, 2004). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed August 18, 2025 and those set forth herein.
Applicants traverse this rejection on the grounds of a post-filing date article (complete citation at the bottom on p 6 of the Remarks and cited on February 1, 2023 Office Action) in The Journal of Medicinal Chemistry that is “a pear-review [sic]” and does not publish what is considered obvious to the skilled artisans.
This arguments in unpersuasive. There is no evidence of record that either a pear- or peer-review process for a submission to a journal evaluates the subject matter of the paper by standards required for patentability including 35 USC §§ 101, 102, 103 and 112 amongst other requirements that are required to grant a patent. Without such evidence, the fact that claimed subject matter was published in a journal does not patentably distinguish the claims over the prior art.
Applicants also argue that the cyclopentane derivatives in US’776 have a single 18F fluorine at a different position and does not provide a synthetic method for di-fluoro substituted amino acid derivatives as claimed. Direction or synthetic methods to such di-fluoro substituted amino acid derivatives as claimed are also not provided by either of Park or Biffinger. Regarding the arguments about fluorine being a bioisostere for hydrogen, Applicants state that the replacement is made due to the size similarities between hydrogen and fluorine but fluorine has a higher electronegativity than hydrogen. This might induce altered biological responses due to its electronegativity, which is more similar to a hydroxyl group oxygen than a hydrogen. Prior to testing, it was unpredictable whether the di-fluoro substituted amino acid derivatives as claimed would have desirable pharmacokinetic and tumor infiltrating properties. After citing the first few sentences of Biffinger, Applicants state that while fluorine substitution of such groups might be interesting experimental research, it does not suggest the desirable properties of the claimed difluorinated compounds. Without being able to reasonable predict the effect of hydrogen substitution with a fluorine, the claims would not have been obvious.
These arguments are unpersuasive. The determination of obviousness takes into account the explicit, implicit and inherent teachings of the prior art and the knowledge of one of ordinary skill in the art. A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton (MPEP 2141(II)(C). One of ordinary skill in the art is aware of various synthetic methods and failure of the applied prior art to explicitly disclose synthetic methodology for di-fluoro substituted amino acid derivatives as claimed does not render the instant claims patentable. Arguments without factual support are mere allegations and are not found persuasive. Bioisosteres are not identical in all aspects but are sufficiently similar that properties of the new molecules will be broadly similar biological properties but not identical and that fluorine introduction could, for example, increase the lipophilicity, with two fluorines being more lipophilic than a single fluorine compound and would contain 18F at both positions as this is a naturally occurring isotope, while reasonably being expected to maintain the binding ability disclosed by Goodman et al. Only a reasonable and not an absolute expectation of success is required for a prima facie case of obviousness and one of ordinary skill in the art need not have to predict the exact properties of the difluoro compounds in order for such compounds to be rendered obvious. There are no claim limitations related to pharmacokinetic and tumor infiltrating properties. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Applicants have not established evidence of record as to any unexpected results for the claimed compounds compared to those of Goodman et al. that could demonstrate secondary considerations of non-obviousness.
Claim(s) 17 and 18 were rejected under 35 U.S.C. 103 as being unpatentable over Goodman et al., Park et al. and Biffinger et al. further in view of Klunk et al. (US 2008/0219931). This rejection is MAINTAINED for the reasons of record set forth in the Office Action mailed August 18, 2025 and those set forth herein.
Applicants argue that ‘931 provides some examples for intravenous injection but does not provide for the desirable properties of the claimed compounds or provide a synthetic method for preparing di-fluoro substituted amino acid derivatives as claimed.
These arguments are unpersuasive. Goodman et al., Park et al. and Biffinger et al. are not deficient as alleged by Applicants as discussed in greater detail above. Therefore, Klunk et al. need not explicitly teach such elements.
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
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