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 .
Claim Objections
Claims 1 and 2 are objected to because of the following informalities:
Regarding claim 1, “R1”, “R2”, and “R3” should read “R1”, “R2”, and “R3.” The “, ,” should read “,” (after the -C(O)-Het 1 structure).
Regarding claim 2, the “, ,” should read “,” (after the -C(O)-Het 1 structure). “preferablythe” should read “preferably the” (last line).
Claim Rejections - 35 USC § 112 Indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 1, 2, 4, 5, 7, 8, 10, 12, 15, and 18, the term or phrases "preferably", “more preferably”, and “most preferably” render the claims indefinite because it is unclear whether the limitations following the term or phrases are mandatory limitations or merely an optional choice. The meters and bounds of the claim cannot be determined with reasonable certainty.
Regarding claim 12, the recitation of “NxS4-x (N4, N2S2, N3S)” is improper and confusing for multiple reasons. First, the variable “x” is undefined within the body of the claim, leaving the boundaries and mathematical constraints of the formula “NxS4-x“ impermissibly vague. Second, the use of parentheses introduces ambiguity, as it is unclear whether the expressions inside the parentheses are intended to be exemplary, restrictive, or synonymous with the preceding formula. Third, the specific chemical formulas listed within the parentheses appear as an improper recitation of preferred embodiments. Including preferred or exemplary embodiments within a claim limitation fails to define the exact metes and bounds of the claim, thereby rendering the claim indefinite.
The dependent claims fall therewith.
Clarification and/or amendment is required.
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 1-18 are rejected under 35 U.S.C. 103 as being unpatentable over Haberkorn et al. (WO 2019 154886; cited on PTO-892) in view of Vodela et al. (Chinese Chemical Letters, 2013; cited on PTO-892).
Regarding claims 1-4, 9-12, and 14, Haberkorn discloses a fibroblast activation protein (FAP) inhibitor compound such as FAPI-04
PNG
media_image1.png
275
945
media_image1.png
Greyscale
(page 55, Table 5). The FAPI-4 of Haberkorn and the 3BP-3412 compound of instant claim 14 share an identical backbone comprising DOTA (1,4,7,10-tetraazacyclododecane-N,N',N,N'-tetraacetic acid) chelator, piperazine linker, and quinoline core, except the right-hand terminal moiety. The FAPI-4 of Haberkorn contains a cyano group (-CN) attached to the pyrrolidine ring whereas the 3BP-3412 compound of instant claim 14 contains benzoxazole-2-carbonyl group attached to the pyrrolidine ring. Regarding claim 5, Haberkorn discloses that the DOTA-linker moiety (R6 or R7 of Haberkorn, R8-L of instant claim) can attached to the 7-quinolyl position (R7 of instant claim) (claim 3). Regarding claims 6-8, Haberkorn discloses that R6 or R7 can be R8-L, wherein L (linker) can comprise aryl (Lin1 of instant claims) and sulfonyl (Lin 2 of instant claims) (claim 1; page 15, lines 7-23). The linking positions can be at the 1,4-positions and the L can comprise the Lin2-Lin1 structure
PNG
media_image2.png
302
399
media_image2.png
Greyscale
of instant claim 8. Regarding claim 13, Haberkorn discloses that R8 can be a radioisotope or a radioactive drug (a biologic active compound modified by a radioisotope) (claim 9; page 19, lines 19-20). A radioisotope can be a cytotoxic agent (page 65, ¶ 2 of instant specification as filed). Regarding claims 15-17, Haberkorn discloses that the compound can be used for the diagnosis or treatment of a disease characterized by overexpression of FAP (abstract). Haberkorn discloses that the compound can comprise diagnostic or therapeutic radionuclides (claim 9; page 85, lines 13-14). Accordingly, Haberkorn discloses the same intended use of the compound as recited in instant claims 16 and 17. Regarding claim 18, Haberkorn discloses that a pharmaceutical composition can comprise the compound and a pharmaceutically acceptable excipient (claim 13).
Haberkorn does not disclose the -C(O)-Het 1 moiety
PNG
media_image3.png
404
206
media_image3.png
Greyscale
at R3 position.
Vodela discloses the structure of bezoxazol-2-carboxylic acid (1) and synthesis of its derivatives such as bezoxazol-2-carbonyl chloride (2) and Benzoxazole-2-carboxylic acid methyl ester (3)
PNG
media_image4.png
257
1121
media_image4.png
Greyscale
(page 626, Scheme 1). Vodela discloses the substituted benzoxazoles can possess pharmaceutical activities such as antitumor and potential activity with lower toxicities in the chemotherapeutic approach (page 625, column 1, ¶¶ 1-2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the compound of Haberkorn by replacing the cyano group (-CN) with benzoxazol-2-carbonyl group to prepare more effective pharmaceutical agent. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Vodela teaches benzoxazol-2-carbonyl group can be attached to another functional group. Further, a person of ordinary skill in the art would have been motivated to utilize more stable heteroaryl ketone structure such as benzoxazol-2-carbonyl instead of cyano group at the terminal in order to enhance metabolic longevity and binding affinity. Additionally, synthesizing and evaluating both the R- and S-enantiomeric configurations (wedge and dash) to screen for optimal steric fit is a standard, routine optimization protocol in medicinal chemistry. Selecting the wedge orientation can be a mere choice of design modification resulting from routine screening. Therefore, the compound (3BP-3412) of instant claim14 is an obvious combination of the established core skeleton of Haberkorn with the terminal structure of Vodela, realized via conventional coupling method and routine stereochemical screening.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JONG HWAN BAEK whose telephone number is (571)272-0670. The examiner can normally be reached Mon - Thu, 9 am - 3 pm ET.
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 G 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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JONG HWAN BAEK/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
Prosecution Insights