DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined
under the first inventor to file provisions of the AIA .
2. 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.
Election/Restrictions
3. This is an acknowledgment of Applicant’s election of species of Compound 3-13 without traverse, in the reply filed on 4/22/2026.
PNG
media_image1.png
176
212
media_image1.png
Greyscale
4. Applicant’s elected species reads on claims 1-2, 4-5 and 7-14 (Applicants did not make the required selection, and it was determined by the Examiner).
5. Claims 3 and 6 are withdrawn from further consideration pursuant to 37 CFR1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 4/22/2026.
6. A search of Applicants’ elected species of Compound 3-13 did not retrieve any reference.
7. Extended search of claim 8 did not retrieve any prior art references.
8. Markush search was extended to the entire scope of claim 1 Formula (1) (wherein X is CH₂ or O; Y, Z¹, Z² and Z³ is N or CH; n is 0, 1, 2 or 3; R1 is H, heterocycloalkyl, C₃-C₇cycloalkyl, or C₁-C₆alkyl; R2 is H, N or amino; R3 is heteroaryl, R4 and R5 are H, C, X, OH, C₁-C₃alkyl, or C₁-C₃alkoxy) retrieved only the current application and another patent application filed two weeks prior from the Applicant.
9. The elected species and the Markush search read on claims 1-14.
Current Status of 18/601,428
10. This Office Action is responsive to the amended claims of 1/28/2025.
11. Claims 1-14 have been examined on the merits.
Priority
12. The effective filing date is April 18, 2023.
Information Disclosure Statement
13. The information disclosure statements (IDS) submitted on 01/28/2025, are in
compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure
statement is being considered by the examiner.
Claim Objections
14. Claim 1, 2, 6 and 8 are objected to because of the following informalities:
(1). Claim 1 -
a). A comma is missing between heterocycloalkyl and C₃-C₇cycloalkyl in the sentence “R¹ is H, heterocycloalkyl C₃-C₇cycloalkyl, or C₁-C₆alkyl wherein a nitrogen on the heterocycloalkyl is optionally substituted with C₁-C₃alkyl,…”
b). The R⁷ and R⁸ cited in the last paragraph of claim 1 (page 3) should be R8 and R9, respectively, since they are attached to two separated Ns as indicated for R2 (NR6R7 and NR8R9), and can’t form a ring with the attached nitrogen.
Please also make corrections in the Specification.
c). An action word is missing between bonded and “a 4-6 membered …” in the last paragraph of claim 1.
(2). Claim 2 – A comma is missing between heterocycloalkyl and C₃-C₇cycloalkyl in the sentence “wherein R¹ is H, heterocycloalkyl C3-C₇cycloalkyl, or C₁-C₆ alkyl wherein a nitrogen on heterocycloalkyl is optionally substituted with methyl or ethyl,”
(3). Claim 6, line 3 – R9 and R9 should be R8 and R9, respectively.
(4). Claim 8 –
a). Page 4: The first three entries are identical.
b). The third entry on page 5: “dihydrobrobide” should read “dihydrobromide”.
c). The last entry on page 11: “ … methanonell” should read “… methanone”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
15. Claims 1-14 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
In the instant claims, prodrug is cited, however prodrug forms are not known and thus the skill in the art as to what constitutes a prodrug form is beyond that of the artisan. The artisan understands that prodrug forms are generally determined a posteriori, and it is only through trial and error that prodrugs are identified. The artisan understands the concept of prodrugs, however the artisan does not per se understand what specifically describes a specific prodrug form. The art acknowledges there is no specific definition for prodrug (e.g. page 1, H.-K. HAN. AAPS Pharmsci. (2000) 2(1), article 6, pages 1-11), but that in general, the 'prodrug' is an inactivated form of the drug that activates in vivo to the active form. While some prodrugs are simply esters or salts, other prodrug forms are not chemically or structurally related to their active form, one example being glucose as the prodrug form of hydrogen peroxide (Table 1, page 5), as is hypoxanthine, thus posing a problem as to understanding what is the exact prodrug form of a compound, as hydrogen peroxide has two prodrug forms in the limited set of compounds exemplified in Han.
ETTMAYER (Ettmayer P. et al. J. Med. Chem. (2004) 47(10), pages 2393-2404), prodrugs are often accidental discoveries and TESTA (Testa B. Biochem. Pharm. (2004) 68, pages 2097-2106) teaches that, “A number of challenges await medicinal chemists and biochemists carrying out prodrug research, such as the additional work involved in synthesis, physicochemical profiling, pharmacokinetic profiling and toxicological assessment. Two of these challenges are introduced here, namely biological variability and toxicity potential. The challenge of biological variety results principally but not only from the huge number and evolutionary diversity of enzymes involved in xenobiotic metabolism. Inter- and intra-species differences in the nature of these enzymes, as well as many other differences such as the nature and level of transporters, may render prodrug optimization difficult to predict and achieve.” (page 2098).
The specification and claims provides the ROCK2 protein kinase inhibitors, as does the prior art, however the specification briefly mentions prodrugs and is absent any examples of prodrugs that are contemplated. Additionally, the compound must function as a prodrug and that the active drug form must function as claimed, however the specification fails to provide any exemplary prodrug forms. Methods of making compounds, in general, are known to the artisan, however the methods of making any specific prodrug are complex and poorly understood, requiring an undue amount of experimentation to determine if a compound is actually a prodrug, and the instant specification fails to provide guidance to overcome the complexity and difficulties known to the artisan, as discussed above.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
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.
16. Claims 1-7 and 9-14 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.
Claims 1-2 - In the sentence “R¹ is H, heterocycloalkyl C₃-C₇cycloalkyl, or C₁-C₆alkyl wherein a nitrogen on the heterocycloalkyl is optionally substituted with …”, it is unclear if the N is on the ring, as it states- that is “attached” or whether it is in the ring, e.g. pyridine, thereby rendering the claims indefinite.
Additionally, in the last paragraph of claim 1 shown below, “Partially saturated monocyclic group” highlight in yellow lacks the antecedent base since the base is a 4-6 membered saturated monocyclic group.
PNG
media_image2.png
187
1002
media_image2.png
Greyscale
In Claims 9-14, the phrases “Use of” and “The use of …” are used to describe the compound for treatment of diseases. e
MPEP 2173.05(q): Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. For example, a claim which read: "[a] process for using monoclonal antibodies of claim 4 to isolate and purify human fibroblast interferon" was held to be indefinite because it merely recites a use without any active, positive steps delimiting how this use is actually practiced. Ex parte Erlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
17. Claims 9-14 are rejected under 35 U.S.C. 101 because:
The claimed invention is directed to non-statutory subject matter. The claim(s) do not fall within at least one of the four categories of patent eligible subject matter.
MPEP 2173.05(q): "Use" claims that do not purport to claim a process, machine, manufacture, or composition of matter fail to comply with 35 U.S.C. 101. In re Moreton, 288 F.2d 708, 709, 129 USPQ 227, 228 (CCPA 1961)("one cannot claim a new use per se, because it is not among the categories of patentable inventions specified in 35 U.S.C. § 101 ").
Double Patenting
18. 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, 3, 4, 7 and 9-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 3, 4 and 6-10 of copending Application No. 18/601,424 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Both reference application ’424 and the current application are directed to Rock2 protein kinase inhibitors and their uses thereof. The Markush structures of the instant claim 1 and application ’424 claim 1 are almost identical in spite of the different markings of some substitutions as shown below:
Formula (1) of instant claim 1 :
PNG
media_image3.png
170
343
media_image3.png
Greyscale
Formula (1) of reference claim 1:
PNG
media_image4.png
133
257
media_image4.png
Greyscale
The limitations of the substitutions (Rs, Zs, Ys, Xs and ns) on both structures are almost same, thereby rendering the two Markush structures and thus two claim 1s overlap substantially, if not identical. So, instant claim 1 is obvious over claim 1 of application ’424.
Similarly, instant claims 3, 4, 7 and 9-13 are obvious over claims 2, 3, 4 and 6-10 of application ’424, respectively, since they are almost identical each other and the intended use doesn’t limit the compound or composition.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
19. No claims are presently allowable as written.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BIN TAO whose telephone number is (571)272-0398. The examiner can normally be reached Monday-Friday 8-5PM.
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, Andrew Kosar can be reached at 571-272-0913. 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.T./
Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
Prosecution Insights