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 . Claims 1-20 filed June 06, 2024 are currently pending.
Election/Restrictions
Applicant’s election without traverse of Group (III) in the reply filed on 07/13/2026 is acknowledged.
Claims 1-12 and 16-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 07/13/2026.
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Secondly, Applicant’s election without traverse of compound 37, as shown above, in the reply filed on 07/13/2026 is acknowledged.
Priority
Acknowledgement is made of the national stage entry of PCT/CN2022/103988 filed 07/05/2022 which claims foreign priority to Application 2021107571615 filed 07/05/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/28/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112-Paragraph B
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 13-15 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.
The term “a related disease” in claims 13-15 is a relative term which renders the claim indefinite. The term “a related disease” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
One interpretation is that the phrase “a related disease” embraces the phenotype of fibrosis in any organ. This genus includes cystic fibrosis and cardiac fibrosis. An alternative interpretation of the phrase “a related disease” embraces fibrotic tumors. As recited in MPEP 2173.05 (a) Claim language may not be "ambiguous, vague, incoherent, opaque, or otherwise unclear in describing and defining the claimed invention." Packard, 751 F.3d at 1311. Applicants need not confine themselves to the terminology used in the prior art, but are required to make clear and precise the terms that are used to define the invention whereby the metes and bounds of the claimed invention can be ascertained. In the instant case, Applicant has failed to do so regarding the claimed genus.
Claim Rejections – Improper Markush
Claims 13-15 are rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The instant claims do not share a common core chemical structure or single structural similarity. The claims are drawn to the treatment or prevention of fibrosis or a related disease thereof comprising administering an effective amount of a compound of formula (I), pharmaceutically acceptable salt, solvate, isomer, crystal form or prodrug thereof as shown below:
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Wherein Ring A, Ring B, Ring C, R6 and R7 may be any of a very large number of patentably distinct functional groups falling within patent classes C07D and A61K. The claims in their current form do not present any common chemical structure that can be attributed to the asserted utility of the compounds.
A Markush claim contains an "improper Markush grouping" if: (1) The species of the Markush group do not share a single structural similarity," or (2) the species do not share a common use. Members of a Markush group share a "single structural similarity" when they belong to the same recognized physical or chemical class or to the same recognized physical or chemical class or to the same art-recognized class. Members of a Markush group share a common use when they are disclosed in the specification or known in the art to be functionally equivalent (see Federal Register, Vol. 76, No. 27, Wednesday, February 9, 2011, p. 7166, left and middle columns, bridging paragraph).
The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons: Claims 13-15 recite chemical species alternatives of Formula (I) which are in different recognized physical classes, and the Markush list embraces different chemical compounds that do not share any single structural similarity between the species.
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The claims recite the Markush grouping of Ring A of Formula (I), wherein
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There is no 'single structural similarity' of Rings A, B, C and R7 in the compounds of Formula (1) as claimed in claims 13-15 of the instant application as Rings A, B, C and R7 may be defined by any of a very large number of patentably distinct functional groups falling within patent classes C07D and A61K.
For example, when Ring A is 5-10 membered heteroaryl (oxazole), Ring B is cycloalkyl (cyclopropyl) and Ring C is 5-10 membered heteroaryl (pyridine), the invention is classified as A61K subclass 31/422. Alternatively, when Ring A is phenyl ring, Ring B is piperidine and Ring C is phenyl, the invention is classified as A61K subclass 31/445. In the third alternative, when Ring A is quinoline, Ring B is cyclohexyl and Ring C is thiazole, the invention is classified in A61K subclass 31/47. The claims in their current form do not present any common chemical structure that can be attributed to the asserted utility of the compounds.
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The examiner suggests that this rejection may be overcome by amending the claims to the directed compounds that share the following single structural similarity: Ring A is C6-10 aryl, R7 is pyrazole or C1-6 cycloalkyl, Ring B is piperidine or piperazine, Ring C is C6-10 aryl. The formula above are classified in class A61K 31/445 and many of the 20 working examples in the specification correspond to this generic chemical structure.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 13-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Maruyama (US2005/0014942 published 01/20/2005).
Maruyama teaches treating pulmonary fibrosis in a subject in need comprising administering a therapeutically effective amount of a TGFb inhibitor of Formula (I) (abstract, [0001]-[0005], [0126], claims 1-2, 14-17). Embraced with Formula (I) is example 20 or ([0280], [0459] Table 6).
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Example 20 reads on the structural limitations of Formula (I) as follows: R7 is a C6 aryl, Ring A is 5-10 membered heteroaryl, RA is RA1 which is optionally substituted C1-C6 alkyl, L1 is C(O) and n1 is 1, Ring B is piperazine (4-12 member heterocycloalkyl), Ring C is 5-10 membered heteroaryl (pyridine), L2 is C(O) and n2 is 1, R6 is NR4R5 wherein R4 and R5 come together to form a 4-10 membered heterocycloalkyl. Maruyama teaches that said compound is efficacious at inhibiting collagen production, thereby treating pulmonary fibrosis. This is the same mechanism of action embraced within Table 3 of the instant specification to enable the presently claimed compounds to treat pulmonary fibrosis ([0126], [0458]-[0463] Tables 1-2, claims 1-2, 14-17).
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.
Claim(s) 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Maruyama (US2005/0014942 published 01/20/2005).
Maruyama (US2005/0014942 published 01/20/2005) teaches treating pulmonary fibrosis in a subject in need comprising administering a therapeutically effective amount of a TGFb inhibitor of Formula (I) (abstract, [0001]-[0005], [0126], claims 1-2, 14-17). Embraced with Formula (I) is example 20 or ([0280], [0459] Table 6).
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Example 20 reads on the structural limitations of Formula (I) as follows: R7 is a C6 aryl, Ring A is 5-10 membered heteroaryl, RA is RA1 which is optionally substituted C1-C6 alkyl, L1 is C(O) and n1 is 1, Ring B is piperazine (4-12 member heterocycloalkyl), Ring C is 5-10 membered heteroaryl (pyridine), L2 is C(O) and n2 is 1, R6 is NR4R5 wherein R4 and R5 come together to form a 4-10 membered heterocycloalkyl. Maruyama teaches that said compound is efficacious at inhibiting collagen production, thereby treating pulmonary fibrosis. This is the same mechanism of action embraced within Table 3 of the instant specification to enable the presently claimed compounds to treat pulmonary fibrosis ([0126], [0458]-[0463] Tables 1-2, claims 1-2, 14-17).
Therefore, one of ordinary skill in the art prior to the time of the invention would have found it prima facie obvious to administer the TGFb inhibitor 4-{1,5-dimethyl-2-phenyl-1H-indol-3-yl)carbonyl]-1-{5-thiomorpholin-4-yl)carbonyl]pyridine-2-yl}piperazine hydrochloride of Maruyama to treat pulmonary fibrosis in a subject in need, arriving at the presently claimed methodology.
Applicant is reminded that “[I]t is well settled that it is a matter of obviousness for one of ordinary skill in the art to select a particular component from among many disclosed by the prior art as long as it is taught that the selection will result in the disclosed effect, even when the possible selections number 1200 or in the thousands. Merck & Co., Inc. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989); In re Corkill, 771 F.2d 1496, 1500 (Fed. Cir. 1985).” Applicant is also reminded of MPEP 2144.07 wherein the selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945)
In the instant case, Maruyama teaches that 4-{1,5-dimethyl-2-phenyl-1H-indol-3-yl)carbonyl]-1-{5-thiomorpholin-4-yl)carbonyl]pyridine-2-yl}piperazine hydrochloride is one of 152 exemplified TGFb inhibiting compounds efficacious at treating pulmonary fibrosis in a subject in need (abstract, claims 1-2, 14-17). Consistent with this reasoning, it would have been obvious to have selected 4-{1,5-dimethyl-2-phenyl-1H-indol-3-yl)carbonyl]-1-{5-thiomorpholin-4-yl)carbonyl]pyridine-2-yl}piperazine hydrochloride of Maruyama and administer said TGF-b inhibitor to treat pulmonary fibrosis in a subject in need from within the prior art above, arriving at the claimed methodology yielding no more than one would expect from such an arrangement.
Conclusion
In view of the rejections set forth above, no claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GEORGE W KOSTURKO whose telephone number is (571)270-5903. The examiner can normally be reached M-F 9:00-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, CLINTON A BROOKS can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621
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