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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/12/2026 has been entered.
Response to Amendment
The amendments received 08/12/2026 have been entered. Claims 2-18 are pending. Claims 12-14 and 17 are withdrawn. Any objection or rejection previously set forth in the Office Action mailed 05/15/2026 has been overcome and is withdrawn.
Examiner has considered Applicant’s arguments regarding the rejection under 35 U.S.C. 103 and finds them persuasive. The rejection is withdrawn.
New grounds of rejection are set forth herein.
Election/Restrictions
Examiner has expanded the search scope to encompass all of the claimed species and further to formula (I). The election of species requirement set forth on 11/14/2025 has been withdrawn and claims 12-14 and 17 are rejoined and examined herein.
Information Disclosure Statement
The Information Disclosure Statement filed on 08/12/2026 is in compliance with the provisions of 37 CFR 1.97 and has been considered in full. A signed copy of list of references cited from the IDS is included with this Office Action.
Claim Rejections – Improper Markush Grouping
Claims 2-18 are rejected on the judicially-created basis that they contain 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.
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:
The variable structure of formula (I) is defined as seen below:
PNG
media_image1.png
46
120
media_image1.png
Greyscale
The core structure of formula (I) lacks any structure shared by each species of formula (I). Ring A, for example, is selected from the below alternatives.
PNG
media_image2.png
188
592
media_image2.png
Greyscale
These rings vary in size, saturation, number and identity of heteroatoms, and the location of their substituents. Moreover, there is no identifiable function shared by each of the alternative ring structures. Even the linker, L, varies between species and is selected from C(O), C(S), or CH2, while virtually every species in claims 17 and 18 has the linker C(O). No examples or evidence are set forth in the instant disclosure to suggest that a compound with any combination of the above rings and linkers would share a common function.
Examiner additionally notes that a search of the full scope of formula (I) requires an incredibly broad, multi-query search that yields over 1 million hits in STN for the compounds alone.
Clearly no ‘‘single structural similarity’’ can be seen.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claim(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. § 134 and 37 CFR41.31 (a) (1) (emphasis provided).
Claim Rejections - 35 USC § 112(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.
Claim 2 is 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.
Claim 2 recites the limitation "the heart" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 17 and 18 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 17 sets forth the following compounds.
PNG
media_image3.png
257
629
media_image3.png
Greyscale
Compound 72 is not within the scope of claim 2 because methyl is not a substituent when R1 is aryl. Compounds 91, 92, and 96 are not substituted by aryl or heteroaryl in the R1 position. Compound 31 contains a fused ring formed by ring A, R1, and R2 that contains more than 10 atoms. Compound 40 is not within the scope of claim 2 because aryl is not a substituent when R1 is aryl. Claim 17 therefore fails to incorporate the limitations of the claim upon which it depends and does not properly depend on claim 2.
Claim 18 sets forth the following compounds.
PNG
media_image4.png
86
508
media_image4.png
Greyscale
Compound 121 is not within the scope of claim 2 because methyl is not a substituent when R1 is aryl. Compound 146 is not substituted by aryl or heteroaryl in the R1 position. Claim 18 therefore fails to incorporate the limitations of the claim upon which it depends and does not properly depend on claim 2. Correction is required.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
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.
Claim(s) 2-4, 6-8, 10, and 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kawamoto (US 2007299086 A1; 2007) in view of Cerrada et al. (Stem Cells and Development; 2013).
Kawamoto discloses HIF-1α prolyl hydroxylase inhibitors with the following structure (p. 30).
PNG
media_image5.png
124
613
media_image5.png
Greyscale
The compounds are within the scope of formula (I) wherein ring A is pyridinyl, R1 is phenyl substituted by cyano or chloro, L is C(O), R3 is C1 alkyl substituted by -C(O)2 RA wherein RA is H, and R4 is H. Kawamoto additionally discloses that HIF-1α under normal conditions is degraded by enzymes called hydroxylase inhibitors, a process which is stopped in hypoxic conditions (par. [0003]). In hypoxia, HIF-1α forms a transcription factor complex that activates several biological pathways including angiogenic, erythropoietic, glucose metabolism, and matrix alteration responses (par. [0003]). Kawamoto discloses that prolyl hydroxylase inhibitors are beneficial in that the pathways activated by HIF-1α would not require oxygen deficiency (par. 0004) and can be used to induce angiogenic responses (par. [0005]). Kawamoto teaches that the compounds can be used in methods of controlled peripheral vascular disease, coronary artery disease, heart failure, ischemia, and/or anemia (par. [0010]).
Kawamoto does not explicitly teach a method of increasing cell proliferation in the heart. These limitations are obvious in view of Cerrada et al.
Cerrada et al. discloses that HIF-1α expression in rats, following induction of myocardial infarction, improved cardiac function while inducing angiogenesis and promoting tissue regeneration, including cardiomyocyte proliferation (p. 504 last paragraph – 508 col. 2 par. 2). Cerrada et al. discloses that prolyl hydroxylase knockout in mice leads to HIF-dependent tissue protection, increased capillary density, and preserved cardiac structure and function in myocardial infarction. Cerrada et al. additionally suggests the development of additional prolyl hydroxylase inhibitors in the art for clinical use (p. 509, col. 2, par. 3).
It would be prima facie obvious for one of ordinary skill in the art to administer the compounds of Kawamoto to increase cell proliferation in the heart. One would have been motivated to do so, with reasonable expectation of success, as increased HIF-1α expression has been demonstrated to be cardioprotective in models of myocardial infarction while also promoting cardiomyocyte proliferation and tissue regeneration. Kawamoto suggests, especially in view of Cerrada et al., that increasing HIF-1α expression by administering prolyl hydroxylase inhibitors would be beneficial to achieve this effect by removing the need for hypoxia induction and/or oxygen deprivation.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MADELINE E BRAUN whose telephone number is (703)756-4533. The examiner can normally be reached M-F 8:30am-5:00pm ET.
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, Jeffrey Murray can be reached at (571) 272-9023. 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.
/MADELINE E BRAUN/Examiner, Art Unit 1624 08/28/2026
Prosecution Insights