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 .
Information Disclosure Statement
Three information disclosure statement (IDS) submitted: one on April 19th, 2023; one on August 30th, 2024; and one on November 19th, 2024. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
The disclosure is objected to because of the following informalities:
Some of the schemes are not clearly legible. Particularly Reaction Formulae 1, 2, 6, 7, 8, 10 (pages 23, 24, 30, 32, 33, and 38, respectively).
Appropriate correction is required.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-7 and 9-12), drawn to the compounds of Formula 1 and pharmaceutical compositions thereof, in the reply filed on November 4th, 2025 is acknowledged.
Upon election of Group I, Applicant was further required to elect a single compound of Formula 1 with all variables defined. Applicant elected the compound below:
PNG
media_image1.png
130
355
media_image1.png
Greyscale
The elected compound was found to be free of the prior art, therefore the search was expanded to encompass the compounds of Formula 1 when R1 is -S-R2, and R2 is phenyl substituted with any C3 to C12 heterocycloalkyl, heteroaryl, or halide.
Claims 8 and 13-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on November 4th, 2025
Status of the Claims
Claims 1-16 are pending in this application. Claims 1-7 and 9-12 are under examination herein. Claims 8 and 13-16 have been withdrawn from consideration.
Claim Objections
Claims 3 and 4 are objected to because of the following informalities:
The claims refer to different compounds by the same name, namely compounds are labeled 1-10, which have different structures.
PNG
media_image2.png
153
442
media_image2.png
Greyscale
PNG
media_image3.png
143
422
media_image3.png
Greyscale
Appropriate correction is required.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 5-7, and 9-12 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Cummins et al. (WO 2008/036747 A2) (“Cummins”).
Regarding claims 1-2, 5-7, and 9-12, Cummins discloses the compounds of Formula I below (page 7, line 20 and claims 1-21), which anticipate the instant claims when R2 is -NHCO2Me; and R1 is -SR3, wherein R3 is phenyl or
PNG
media_image4.png
152
246
media_image4.png
Greyscale
, wherein R4 is a halogen. Cummins also discloses the preferred embodiment II shown below (anticipating the instant compounds when R2 is unsubstituted aryl) (page 9, line 16).
PNG
media_image5.png
196
412
media_image5.png
Greyscale
(I)
PNG
media_image6.png
183
697
media_image6.png
Greyscale
(II)
Regarding claims 6-7, claim read “the thiobenzimidazole derivative OR the pharmaceutically acceptable salt thereof”. Cummins discloses the thiobenzimidazole derivatives, and thus anticipates the instant claims.
Regarding claims 9-12, Cummins discloses pharmaceutical compositions comprising their compounds above and an acceptable carrier (Cummins’ claim 15).
Further regarding claims 5 and 9-12, Applicant is advised that recitation of the intended use of the claimed invention, such as the use of Cummins’ compounds for inhibition of tubulin and treatment of cancers in the instant application, must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Note: MPEP 2111.02.
In the present case, Cummins’ discloses administration of their compounds and pharmaceutical compositions orally or via IV to warm blooded vertebrates, including humans (Cummins’ claims 1-10). Furthermore, Cummins teaches their methods can be used to potentiate an immune response to cancers that are tumorigenic, including lymphomas, melanomas, etc. (page 11, lines 3-16). Therefore, the compounds and compositions as disclosed are capable of performing the claimed intended use.
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.
Claims 3-4 are rejected under 35 U.S.C. 103 as being unpatentable over Cummins et al. (WO 2008/036747 A2) (“Cummins”); as applied to claims 1-2, 5-7, and 9-12; in view of Morita et al. (Obtained From gousei.f.u-tokyo.ac.jp [Retrieved on September 11th, 2025] <URL: https://gousei.f.u-tokyo.ac.jp/seminar/index.html#2012> - Published May 2012) (“Morita”).
The teachings of Cummins are disclosed in the 102-section above and incorporated herein.
While Cummins doesn’t specifically teach the claimed compounds with one or more fluoro-substituents on the group corresponding to instant R2; the teachings of Morita are relied upon for these disclosures.
Morita teaches fluorine as an isostere of hydrogen and discloses fluorine incorporation into drugs or lead compounds can productively modulate a range of properties of interest, like metabolic stability pKa, and lipophilicity etc. (page 7).
Therefore, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by Cummins’ disclosed formula in view of Morita; In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). See MPEP 2144.08. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of compounds disclosed by Cummins, who teaches halide substitution of the phenyl corresponding to instant R2; further in view of Morita’s disclosure that H and F are bioisosteres and the benefits of fluoride incorporation into lead compounds and drugs to improve metabolic stability pKa, and lipophilicity etc. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, particularly the ones shown below:
PNG
media_image7.png
131
343
media_image7.png
Greyscale
PNG
media_image8.png
150
346
media_image8.png
Greyscale
PNG
media_image9.png
93
292
media_image9.png
Greyscale
Claims 1-7 and 9-12 are rejected under 35 U.S.C. 103 as being unpatentable over Zetter et al. (WO 2017/095950 A2 – cited in IDS – previously cited) (“Zetter”).
Applicant is reminded that a recitation of the intended use of the claimed invention, such as the use of the instant compounds for inhibition of tubulin and treatment of cancers in the instant application, must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Regarding claims 1-7, Zetter discloses the compounds of Formula I [0085] and II below [0094], which render the instant compounds obvious when R1 is alkyl (particularly -Me [0086]); and RA is substituted aryl (particularly substituted or unsubstituted phenyl [0089]).
PNG
media_image10.png
190
381
media_image10.png
Greyscale
PNG
media_image11.png
167
360
media_image11.png
Greyscale
(II)
Zetter discloses the preferred embodiments below (pages 54, 61). While preferred embodiment I-10 shows the group corresponding to Zetter’s R1 as an oxetane, Zetter teaches their R1 can be preferably methyl (as in their example 8, shown below). Furthermore, while Zetter’s example 8 shows an oxygen instead of a sulfur in the position corresponding to their R2 in formula I, Zetter teaches their R2 can be -SRA, as in compound I-10). Therefore, Zetter’s Formulae I and II correspond to a small genus of compounds, which encompasses the instantly claimed invention.
PNG
media_image12.png
197
440
media_image12.png
Greyscale
(I-10)
PNG
media_image13.png
160
445
media_image13.png
Greyscale
(ex. 8)
Therefore, regarding instant claims 1-7, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by Zetter’s disclosed formulae and preferred embodiments. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of compounds disclosed by Zetter. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, particularly the compound shown below:
PNG
media_image14.png
122
408
media_image14.png
Greyscale
PNG
media_image15.png
122
360
media_image15.png
Greyscale
Applicant is advised that a novel useful compound that is isomeric with the prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. In re Norris, 179 F.2d. 970, 84 USPQ 458 (CCPA 1970). Therefore, it would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results. In re Finely, 81 USPQ 383 (CCPA 1949); 84 USPQ 458 (CCPA 1950).
Further regarding claim 5, Zetter discloses their compounds inhibit tubulin polymerization [0080] and Figure 2.
Further regarding claims 6-7, Zetter discloses their compounds and pharmacutically acceptable salts thereof, as discussed above. Zetter also teaches “pharmaceutically acceptable salts” include hydrochloric acid salts and benzenesulfonate, etc. [0052].
Regarding claims 9-12, Zetter discloses pharmaceutical compositions comprising their compounds and an acceptable excipient [0097]. Zetter also discloses their compounds as part of methods of treating cancers in subjects in need thereof comprising administration of said compounds. Therefore, the compounds and compositions as disclosed are capable of performing the claimed intended use.
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 1-7 and 9-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of copending Application No. 18/851,728 (Copending ‘728). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claims 1-7 and 9-12, Copending ‘728 claims a method of preparing the compounds of Formula 1 below, which anticipate the instant compounds and the instantly elected species when: A is phenyl (aryl group) and R is C1-10 heterocyclic or halogen (Copending ‘728’s claim 1). Copending ‘728 also claims methods of making HCl and other salts (Copending ‘728’s claim 14).
PNG
media_image16.png
80
206
media_image16.png
Greyscale
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-7 and 9-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of copending Application No. 18/851,918 (Copending ‘918). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claims 1-7 and 9-12, Copending ‘918 claims the thiobenzimidazole derivatives of Formula 1 below, which anticipate the instant compounds and the instantly elected species when: X is C and R1-3 are selected from is C1-10 heterocyclic or halogen (Copending ‘918’s claim 1). Copending ‘918 also claims methods of making HCl and other salts (anticipating instant claims 6-7) (Copending ‘918’s claims 6-7). Copending ‘918 also claims pharmaceutical compositions for treating cancers (anticipating instant claims 9-12) (Copending ‘918’s claims 8-11).
PNG
media_image17.png
90
238
media_image17.png
Greyscale
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
Examiner interviews are available via telephone 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, Kortney L. Klinkel can be reached at (571) 270-5239. 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.
/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627