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 .
Priority
This application, filed November 5, 2022, is a national stage application of PCT/EP2021/061775, filed May 5, 2021, which claims priority to foreign priority applications EP21156317.6, filed February 10, 2021, and EP20173755.8, filed May 8, 2020.
Status of the Application
Applicant’s communication, received October 21, 2025, wherein claims 1, 2, 4-13, and 15-22 are amended and new claim 23 is added, is acknowledged.
Claims 1-23 are pending in this application.
Claims 16-21 were withdrawn with the Office action mailed July 24, 2025.
Claims 1-15 and 22-23 are examined on the merits herein.
Withdrawn Objections
Applicant’s amendment, received October 21, 2025, with respect to the objection to claims 12 and 13 for minor informalities, has been fully considered and found to be persuasive to remove the objection because the minor informalities in claims 12 and 13 have been corrected. Therefore the objection is withdrawn.
Withdrawn Rejections
Applicant’s amendment, received October 21, 2025, with respect to the rejection of claims 1-15 and 22 under 35 USC § 112(a) for lacking enablement of solvates of the claimed compounds has been fully considered and found to be persuasive to remove the rejection because the present claims are amended to remove solvates from the claims. Therefore the rejection is withdrawn.
Applicant’s amendment, received October 21, 2025, with respect to the rejection of claims 1-4 and 6 under 35 USC § 102 as anticipated by the compound with CAS RN 1368158-46-6 has been fully considered and found to be persuasive to remove the rejection because the present claims are amended to require R1 is selected from the groups shown in the claims, which does not include methyl as included in the compound with CAS RN 1368158-46-6. Therefore the rejection is withdrawn.
Applicant’s amendment, received October 21, 2025, with respect to the rejection of claims 1-4 and 6-7 under 35 USC § 102 as anticipated by the compound with CAS RN 1784000-41-4 has been fully considered and found to be persuasive to remove the rejection because the present claims are amended to require R1 is selected from the groups shown in the claims, which does not include methyl as included in the compound with CAS RN 1784000-41-4. Therefore the rejection is withdrawn.
Applicant’s amendment, received October 21, 2025, with respect to the rejection of claims 1-4 and 6-7 under 35 USC § 102 as anticipated by the compound with CAS RN 2114798-08-0 has been fully considered and found to be persuasive to remove the rejection because the present claims are amended to require R1 is selected from the groups shown in the claims, which does not include methyl as included in the compound with CAS RN 2114798-08-0. Therefore the rejection is withdrawn.
Applicant’s amendment, received October 21, 2025, with respect to the rejection of claims 1-6 under 35 USC § 102 as anticipated by the compound with CAS RN 2105452-38-6 has been fully considered and found to be persuasive to remove the rejection because the present claims are amended to require R1 is selected from the groups shown in the claims, which does not include methyl as included in the compound with CAS RN 2105452-38-6. Therefore the rejection is withdrawn.
Applicant’s amendment, received October 21, 2025, with respect to the rejection of claims 1-6 and 11 under 35 USC § 102 as anticipated by the compound with CAS RN 663196-68-7 has been fully considered and found to be persuasive to remove the rejection because the present claims are amended to require R1 is selected from the groups shown in the claims, which does not include methyl as included in the compound with CAS RN 663196-68-7. Therefore the rejection is withdrawn.
Applicant’s amendment, received October 21, 2025, with respect to the rejection of claims 1-6 under 35 USC § 102 as anticipated by the compound with CAS RN 896594-87-9 has been fully considered and found to be persuasive to remove the rejection because the present claims are amended to require R2 is selected from a group of functional groups recited in the claims, which does not include fluorine as included in the compound with CAS RN 896594-87-9. Therefore the rejection is withdrawn.
Applicant’s amendment, received October 21, 2025, with respect to the rejection of claims 1-4, 6, and 15 under 35 USC § 102 as anticipated by McBride has been fully considered and found to be persuasive to remove the rejection because the present claims are amended to require R2 is selected from a group of functional groups recited in the claims, which does not include fluorine as included in the compounds taught by McBride. Therefore the rejection is withdrawn.
Applicant’s amendment, received October 21, 2025, with respect to the rejection of claims 1-4, 6, and 15 under 35 USC § 102 as anticipated by Cheruvallath has been fully considered and found to be persuasive to remove the rejection because the present claims are amended to require R2 is selected from the groups shown in the claims, which does not include fluorine as included in the compounds taught by Cheruvallath. Therefore the rejection is withdrawn.
The following are new rejections, necessitated by Applicant’s amendment received October 21, 2025, wherein claims 1, 2, 4-13, and 15-22 are amended and new claim 23 is added.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 1-4 are rejected under 35 U.S.C. 103 as being unpatentable over Park (Publication no. KR 20140107026 A; cited in PTO-892) in view of Ji (Ji, J.; et al. Dyes and Pigments 2019, vol. 171, 107670; cited in PTO-892) and Luo (Luo, Q.-L.; et al. Journal of Organic Chemistry 2012, vol. 77, pp. 8332-8337; cited in PTO-892).
Park was published in a language other than English. Both the original document and an English language machine translation document are included with this Office action and cited in the PTO-892. Citations below refer to either the original document or English translation, as indicated.
Park teaches compounds that may be used organic layers in organic electronic devices with light-emitting properties (English translation, document p. 4, [0003], lines 1-3).
Park teaches compounds of their invention may be prepared by the following synthetic scheme (original document, p. 42, [0097]).
PNG
media_image1.png
233
512
media_image1.png
Greyscale
Park teaches exemplary Sub compounds that may be used in their method of synthesis, including Sub 1(1) and Sub 1(8) (original document, p. 43, [0111]). These compounds satisfy all limitations of claims 1-4, except for the requirements of variable group R2 recited in claims 1 -4. These compounds have R2 as Br, which is not permitted by the present claims.
PNG
media_image2.png
131
88
media_image2.png
Greyscale
PNG
media_image3.png
133
81
media_image3.png
Greyscale
Park teaches that group L (as shown in their synthetic scheme) may be, for example, a C6 aryl group (English translation, document p. 18, [0058]), and further teaches an example wherein a compound derived from Sub 1(1) has L as phenyl (original document, p. 47, starting material in scheme shown in [0129]).
Park does not teach a compound that satisfies all limitations of claim 1, specifically with respect to variable group R2.
Ji teaches the conversion of an aryl bromide structurally related to Sub 1-4 taught by Park to a boronic acid (p. 2, Scheme 1; shown below) and subsequent cross-coupling with an aryl bromide to form compound DCzCl (p. 2, Scheme 1; shown below).
PNG
media_image4.png
274
598
media_image4.png
Greyscale
Luo teaches examples in which aryl iodides are used in Suzuki-Miyaura cross-coupling reactions with boronic acids (p. 8332, title). Specifically, Luo teaches the reaction scheme in Table 2, in which an aryl iodide may react with aryl boronic acids to yield the expected product (compound 7) (p. 8334, Table 2, entries 1-7).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to prepare a compound according to Park, such as a compound beginning from Sub 1(1) or Sub 1(8), by proceeding through a boronic acid intermediate, wherein variable group R2 is B(OH)2, instead of the boronic ester intermediate denoted as Sub 1-5 in the synthesis of Park. One of ordinary skill in the art would have been motivated to perform the synthesis of Park proceeding through a boronic acid intermediate, wherein variable group R2 is B(OH)2, instead of the boronic ester intermediate because Park teaches their synthesis as proceeding by conversion of an aryl bromide to a boronic ester intermediate before cross-coupling with an aryl iodide, Ji teaches conversion of aryl bromides to boronic acids, and Luo teaches effective coupling of boronic acids with aryl iodides.
In this instance, the rationale “simple substitution of one known element for another to obtain predictable results” would apply. Because Park teaches the synthesis above that proceeds through a boronic ester intermediate, and because Ji and Luo demonstrate conversion of aryl bromides to boronic acids and cross-coupling of boronic acids with aryl iodides, one of ordinary skill in the art would have recognized that the synthetic route disclosed by Park may reasonably proceed through the boronic acid intermediate instead of the boronic ester intermediate, and thus when considering this alternative synthetic route, would have contemplated the intermediate derived from Sub 1(1) or Sub 1(8) with presently defined R2 as B(OH)2.
Therefore the invention taken as a whole is 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 § 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.
Claims 1-15 and 23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of co-pending U.S. patent application 18/559048 (reference application, herein referred to as ‘048). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘048 anticipate the claimed invention.
The present application and ‘048 are each assigned to Merck Patent GmbH and Cancer Research Technology Ltd. and include Timo Heinrich, Sarah Schlesinger, Jakub Gunera, Lisa Koetzner, Emma Carswell, and Andreas Blum as inventors.
The amended claims received November 4, 2023 are cited in this provisional non-statutory double patenting rejection.
The compounds of claim 1 ‘048 cited below are representative compounds recited in ‘048 that anticipate the present claims. These compound do not represent all compounds in ‘048 that anticipate the present claims.
Claim 1 of ‘048 recites several compounds that anticipate the present claims. As one example, claim 1 of ‘048 recites compound C110 (structure shown below), which anticipates claims 1, 3, 6-7, and 23 is the same compound as compound 366 as recited in present claim 14.
PNG
media_image5.png
184
186
media_image5.png
Greyscale
As a second example, claim 1 of ‘048 recites compound C227 (structure shown below), which anticipates claims 1, 3, 6, 8-10, and 23.
PNG
media_image6.png
184
187
media_image6.png
Greyscale
As a third example, claim 1 of ‘048 recites compound C6 (structure shown below), which anticipates claims 1-4, 6, 11, and 23.
PNG
media_image7.png
217
159
media_image7.png
Greyscale
As a fourth example, claim 1 of ‘048 recites compound C11 (structure shown below), which anticipates claims 1-4, 6, 11-13, and 23.
PNG
media_image8.png
139
124
media_image8.png
Greyscale
As a fifth example, claim 1 of ‘048 recites compound C155 (structure shown below), which anticipates claims 1-5, 8-10, and 12-13.
PNG
media_image9.png
168
121
media_image9.png
Greyscale
Claim 3 of ‘048 claims the compound according to claim 1, or any pharmaceutically acceptable salt thereof, wherein the compound is suitable as a medicament. This claim, together with the compounds of claim 1 of ‘048 recited above, anticipates present claim 15.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not been patented.
Response to Applicant’s arguments: Regarding the previous provisional non-statutory double patenting rejection over co-pending U.S. patent application 18/559048, Applicant argues that the scope of claim 1 includes numerous possible substituents, and a person having ordinary skill in the art would not have arrived at the scope of claim 1 from the individual compounds claimed in the 18/559,048 application.
This argument has been fully considered but is not found persuasive. Because the claims of ‘048 anticipate the present claims, the rejection is maintained. To anticipate a claim, a compound must only satisfy all limitations of that claim, it need not inform on the full scope of that claim.
Therefore, the provisional nonstatutory double patenting rejection over the claims of 18/559048 is maintained.
However, because ‘048 is later filed than the present application, this provisional nonstatutory double patenting rejection would be withdrawn when there are no other rejections remaining and ‘048, provided a notice of allowance has not been issued in ‘048.
Allowable Subject Matter
Claim 22 is allowed.
In addition, claims 5-15 and 23 are provisionally rejected as unpatentable over claims 1 and 3 of copending U.S. patent application 18/559048, but if all outstanding rejections were overcome, the provisional rejection over ‘048 would be withdrawn and these claims would also be allowed.
The closest prior art to the presently compounds of claims 5-15 and 22-23 is considered McBride (McBride, C.; et al. Bioorganic and Medicinal Chemistry Letters 2016, vol. 26, pp. 2779-2783; cited in restriction requirement mailed May 9, 2025) and Cheruvallath (U.S. pre-grant publication no. US 20150225405 A1; cited in IDS received June 30, 2025).
McBride teaches compounds that are inhibitors of methionine aminopeptidase-2 (MetAP2) (p. 2781, Table 1). As one example, McBride teaches compound 7, wherein R1 is F and R2 is H (p. 2781, Table 1; structure shown below). This compound has the core structure of formula I-A as shown in claim 1, Z1, Z2, and Z3 as CRZ1, CRZ2, and CRZ3 with RZ1, RZ2, and RZ3 each as H, R2 as F, Ring A as formula A-7 with RA1 as H and RA2 as H, and R1 as a 6-membered heterocycle with nitrogen as the ring heteroatom.
PNG
media_image10.png
160
171
media_image10.png
Greyscale
However, compound 7 of McBride differs from the presently claimed compounds of formula I-A of claim 1 because presently defined R1 may not be unsubstituted pyridyl and presently defined R2 may not be halogen, such as fluorine. In addition, McBride does not teach or suggest modifying these groups in such a way to satisfy the requirements of independent claim 1.
Cheruvallath teaches compounds that are inhibitors of methionine aminopeptidase-2 (MetAP2) (p. 2781, Table 1). As one example, Cheruvallath teaches the compound of Example 3 (p. 29, [0311]), which is the same compound as compound 7 taught by McBride. As another example, Cheruvallath teaches the compound of Example 2 (p. 29, [0309]; structure shown below). This compound has Z1, Z2, and Z3 as CRZ1, CRZ2, and CRZ3, RZ1 and RZ3 as H, RZ2 as halogen, ring A as A-7, RA1 and RA2 as H, and R1 as benzyl, and R2 as F. This compound satisfies the limitations of claim 1 except for having RZ2 as F and R2 as F.
PNG
media_image11.png
163
187
media_image11.png
Greyscale
Although Cheruvallath provides motivation to substitute the pyridyl group of Example 2 for, as one example, a benzyl group, neither McBride nor Cheruvallath teach or suggest compounds with variable groups R1 and/or R2 required by the present claims.
Accordingly, one of ordinary skill in the art would not have reasonably modified the compounds disclosed by McBride or Cheruvallath to satisfy the limitations of claims
5-15 and 22-23.
Rejoinder
Claims 16-21 were withdrawn in this application in response to a restriction/election requirement. These claims will be considered for rejoinder when no outstanding rejections remain in this application.
In the event of rejoinder, the requirement for restriction between the product claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112.
In this instance, claims 16 and 17 lack enablement for preventing a medical condition or disease. In addition, claim 16, while being enabling for inhibiting the YAP-TEAD and/or TA'Z-TEAD interaction by administering the compound according to claim 1 to a subject, lacks enablement for treating diseases or conditions affected by inhibiting YAP-TEAD and/or TAZ-TEAD interaction by administering the compound of claim 1, because one of ordinary skill in the art would not have recognized the full scope of diseases that may be affected by inhibiting the YAP-TEAD and/or TAZ-TEAD interaction.
In addition, please amend claims 16 and 17 to specify the compounds are administered to a subject in need of said treatment.
Conclusion
Claims 1-15 and 23 are rejected.
Claim 22 is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. 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 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 BENJAMIN BRANDSEN whose telephone number is (703)756-4780. The examiner can normally be reached Monday - Friday from 9:00 am to 5:00 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, Scarlett Goon can be reached at (571)270-5241. 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.
/B.M.B./ Examiner, Art Unit 1693
/ANDREA OLSON/ Primary Examiner, Art Unit 1693