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 .
Election/Restriction
Applicant's election without traverse of Group I invention and species, crystalline form II of compound A, in the reply filed on 06/04/2026, is acknowledged.
Claims 11 ,13 and 17 read on elected invention and species.
Claims 18-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected inventions.
Claims 12, 14-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim.
Claim Status
Claims 11-21 are pending.
Claims 12, 14-16 and 18-21 are withdrawn.
Claims 11 ,13 and 17 are currently under examination in this office action.
Priority
This instant application 18/691,908, filed on 03/14/2024, is a national stage of PCT/CN2022/119269 filed on 09/16/2022, which claims the benefit of priority to CHINA Patent Application No. 202111103170.9, filed on 09/18/2021.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). No English translation copy is included in the certified copy of CHINA Application No. 202111103170.9 filed on 03/14/2024 in Chinese. Applicant’s right of foreign priority is not perfected due to lack of English translation thereof.
Information Disclosure Statement
The information disclosure statement 03/14/2024 is in compliance with the provisions of 37 CFR1.97. Accordingly, the reference listed in IDS are being considered by the examiner. Reference written in foreign language is considered to the degree of English abstract or patent family of foreign patent by Examiner.
Drawings
The drawings are objected to because the title and values of characteristic XRPD peaks are not shown in Figures, the text in the Figures are blurry/not legible, e.g. Figures 5-8 and 20 referring to instant elected crystalline form II. Instant claims are drawn to various crystalline forms with XRPD peak values that are similar. Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d).
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
Example 1 at page 16 of instant disclosure contains structure/ text that are not legible in PGPub US20240376086A1.
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Rejections - 35 USC § 112
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.
Claims 11, 13 and 17 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
Claim 11 recites multiple crystalline forms of compound A, monohydrate or anhydrate characterized by three XRPD peaks for each crystalline form. Crystalline Form II and III recite XRPD peaks that are very close or similar, e.g. 8.6±0.2º , 12.5±0.2º. It is well recognized in the art that X-ray diffraction patterns may have different appearance due to artifacts and small differences in X-ray diffraction may be due to solvent, thus must be carefully evaluated for true new polymorphs. It’s not clear the recited three XRPD peaks are significant to characterize/differentiate different crystalline forms. It’s not clear if the claimed crystalline form comprise other different crystalline forms.
Claim 13 recites crystalline Form II has an XRPD pattern comprising characteristic peaks at diffraction angles (2θ) of about 6.7±0.2°, 8.6±0.2°, 12.5±0.2°, 13.5±0.2°, 13.8±0.2°, 21.9±0.2° and 24.9±0.2°; and preferably comprising characteristic peaks at diffraction angles (2θ) of about 6.2±0.2°, 6.7±0.2°, 8.6±0.2°, 11.1±0.2°, 12.5±0.2°, 13.5±0.2°, 13.8±0.2°, 15.2±0.2°, 17.3±0.2°, 18.2±0.2°, 18.6±0.2°, 21.0±0.2°, 21.9±0.2°, 24.3±0.2°, 24.9±0.2° and 25.9±0.2°. The recitation of peaks “about 6.7±0.2°, 8.6±0.2°, 12.5±0.2°, 13.5±0.2°, 13.8±0.2°, 21.9±0.2° and 24.9±0.2°” refers to wide limitation, and “preferably.. about 6.2±0.2°...” refers to narrow range of limitation. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
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 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.
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 11, 13 and 17 are rejected under 35 U.S.C. § 103 as unpatentable over Zhao et al. (US20190276440A1, family member of WO2019001572A1 in Applicant’s IDS dated 03/14/2024), in view of Hilfiker et al. (Polymorphism in the Pharmaceutical Industry, January 2006).
Zhao teaches compound of Formula I or salt, polymorph, solvate, etc. thereof as Rho- associated protein kinase (ROCK) inhibitor, a pharmaceutical composition comprising aforementioned compound, preparation thereof, and use of aforementioned compounds in preventing or treating a disease mediated by Rho - associated protein kinase (ROCK) (e.g. pulmonary fibrosis, vascular disease, neurological disease, cancer, etc. )(See abstract, [0004]- [0021], Table 1 starting [0398], Examples 1-34, claims 1-15). Zhao teaches pharmaceutical composition comprising compound of Formula I and one or more pharmaceutically acceptable carriers (See [0208], claim 11).
Zhao explicitly teaches TDI01470 which is instant claimed compound A (See [0836]-[0850], Example 34 on page 355; Table 1 on page 548; claim 10),
PNG
media_image1.png
63
362
media_image1.png
Greyscale
PNG
media_image2.png
116
381
media_image2.png
Greyscale
Zhao teaches preparation of TDI01470 characterized by 1HNMR and compound of Formula I might be crystalline forms or polymorphs of the compound of the present invention, either as a single polymorph, or as a mixture of more than one polymorph (See [0051]).
Zhao is silent about specific crystalline form of instant claimed compound A (i.e.TDI01470) and XRPD pattern thereof. The peaks in X-ray diffraction spectrum are the physical properties of the crystalline form once the crystal form is obtained and could be easily measured by a person skilled in the art through a normal measurement method .
It’s common practice in the pharmaceutical industry to explore different crystalline forms of compounds for purpose of solubility, stability, and bioavailability etc. as taught by Hilfiker. Hilfiker reviews polymorphisms/crystalline forms of small molecular drug in pharmaceutical industry. Hilfiker teaches crystalline form of solvate/hydrate (See Ch 2.8, page 37). Hilfiker teaches polymorph/solvate screening / characterization (XRPD, DSC, etc.) (See Ch 3.).
It would have been obvious for one of ordinary skilled in the art before the effective filing date of instant invention to explore different crystalline form of compound A (i.e.TDI01470), based on the collective teachings of Zhao and general knowledge of pharmaceutical composition comprising crystalline pharmaceutical active compound as illustrated in Hilfiker and arrive at instantly claimed crystalline form of compound A with reasonable expectation of success. A skilled artisan would have known the general knowledge and technique of preparing different crystalline form and measurement of XRPD pattern and other spectrum analysis, etc. as routine experimentation. The skilled artisan would be motivated to explore the crystalline forms for compound A and reasonably expect crystalline form might provide improved solubility/ bioavailability.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art together with optimization based on general knowledge of crystalline pharmaceuticals. As stated in MPEP 2144.05, " It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions". Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
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.
Claim 11, 13 and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of US patent No. 11,390,609. Although the claims at issue are not identical, they are not patentably distinct from each other.
Reference claims are directed to compound of Formula XVII , or pharmaceutical acceptable salt, ester, stereoisomer, polymorph, solvate, N-oxide, or isotopically labeled compound thereof.
Reference claim 6 specifically discloses instant claimed compound A.
PNG
media_image3.png
148
440
media_image3.png
Greyscale
It’s common practice in the pharmaceutical industry to explore different crystalline forms of compounds for purpose of solubility, stability, and bioavailability etc. It would have been obvious for one of ordinary skilled in the art to explore different crystalline form of compound A based on the reference claims and general knowledge of pharmaceutical composition comprising crystalline pharmaceutical active compounds. The limitation of XRPD peaks are the physical properties of the crystalline form once the crystal form is obtained and could be easily measured by a person skilled in the art through a normal measurement method .
As stated in MPEP 2144.05, " It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions".
Claim 11, 13 and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 29-46 of copending Application No. 18/023,394 (reference application). Notice of Allowance of 18/023,394 is mailed on 04/24/2026. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Reference claims are directed to crystalline form I, II, III, IV of compound A monohydrochloride characterized by XRPD peaks, and composition comprising the crystalline forms of compound A. monohydrochloride.
PNG
media_image4.png
140
346
media_image4.png
Greyscale
Reference claims 30-32 recite XRPD peaks that are similar to instant claimed crystalline form II of compound A, for example, 8.3±0.2º, 12.6±0.2º , 18.5±0.2º, 21.7±0.2°, etc.
It’s common practice in the pharmaceutical industry to explore different crystalline forms of compounds for purpose of solubility, stability, and bioavailability etc. It would have been obvious for one of ordinary skilled in the art to explore different crystalline form of compound A based on the reference claims and general knowledge of pharmaceutical composition comprising crystalline pharmaceutical.
As stated in MPEP 2144.05, " It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions".
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIYUAN MOU whose telephone number is (571)270-1791. The examiner can normally be reached Mon-Fri 9:00-5:30.
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, Amy L Clark can be reached on (571)272-1310. 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.
/L.M./Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628
Prosecution Insights