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/Restrictions
Applicant’s election without traverse of Group I, drawn to a compound described by Formula I, Formula II, Formula III or Formula IV, including pharmaceutically acceptable salts, solvates, and/or prodrugs thereof; and 2-((3S,4R)-3-amino-4-fluoropyrrolidin-1-yl)-N-(benzo[d][1,3]dioxol-5-yl(5-chloro-8-hydroxyquinolin-7-yl)methyl)acetamide (G37) having the structure of:
PNG
media_image1.png
113
114
media_image1.png
Greyscale
as the elected compound species described by Formula I are maintained.
Please note the elected compound species described by Formula I
PNG
media_image2.png
49
60
media_image2.png
Greyscale
, wherein X1 is N; X2, X3, X4, X6 are independently CR1, wherein each R1 is H; X5 is CR1 is Cl; E is hydrogen; B is hydrogen; A is CO;
PNG
media_image2.png
49
60
media_image2.png
Greyscale
is
PNG
media_image3.png
140
117
media_image3.png
Greyscale
; and Z is
PNG
media_image1.png
113
114
media_image1.png
Greyscale
.
Claims 4, 7, 12, 15, 18 and 21-31 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim.
Expansion of Election of Species Requirement
As necessitated by amendments, a reasonable and comprehensive search of the elected compound species was conducted again by the Examiner and determined that the prior art at the time of the present invention was such that it did not anticipate or render obvious the elected compound species having the structure of:
PNG
media_image1.png
113
114
media_image1.png
Greyscale
. In light of this discovery, the search is expanded to the subject matter of the subgenus of the elected compound species, i.e., the compound having the structure of:
PNG
media_image4.png
116
186
media_image4.png
Greyscale
,
PNG
media_image5.png
186
164
media_image5.png
Greyscale
,
PNG
media_image6.png
282
359
media_image6.png
Greyscale
, such that it does not encompass the full scope of the claims.
Status of Claims
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on June 23, 2026, wherein claims 1 and 19 are amended; claims 2-3, 5-6, 8-11, 13-14, 16-17 and 20 are cancelled; claims 4, 7, 12, 15, 18 and 21-31 are unchanged; and claims 32 are newly added.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 4, 7, 12, 15, 18-19 and 21-32 are pending.
Claims 4, 7, 12, 15, 18 and 21-31 remain withdrawn.
Claims 1, 19 and 32 are under examination in accordance with the elected compound species along with the expanded compound species set forth in the Expansion of Election of Species Requirement section above.
Action Summary
All rejections pertaining to claims 2-3 are moot because the claims were cancelled in view of the amendments filed on June 23, 2026.
Applicant’s amendment to the claims overcomes each and every objection previously set
forth in the Non-Final Office Action mailed on March 24, 2026. Specifically, claim 3 is now cancelled in view of the amendments.
Acknowledgement is made of the receipt and entry of the amendment to the drawings filed on June 23, 2026, in which Fig. 2 to Fig. 4 are amended. Applicant’s amendments to Fig. 3 and Fig. 4 overcome each and every objection previously sets forth in the Non-Final Office Action mailed on March 24, 2026; However, amendments to Fig. 2 does not overcome the objection of record for the same reasons of record and for the reasons set forth herein.
Claims 1-3 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 are withdrawn in view of the claim amendments. Specifically, the claim amendments delete the previous recitation of “solvates and/or prodrugs thereof”.
Claims 1-3 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for Compound YUM70 having the structure of: for inhibiting GRP78, for inducing cytotoxic effect to pancreatic cancer cell lines PNC-1 and UM59, and for reducing the growth of pancreatic cancer cells MIA PaCa-2; and DX2-145 (i.e., Compound P6) and YUM513 (i.e., Compound P1) for degrading GRP78, does not reasonably provide enablement for the entire scope of each and every compound described by Formula I, Formula II, Formula III or Formula IV for inhibiting GRP78; for treating, ameliorating, and preventing the entire scope of various forms of cancer, viral infections, and inflammatory disease; for inducing ER stress-mediated apoptosis in the tumor cells implanted in mice without major toxicity to normal tissues; and for inducing ER stress and triggers UPR by inhibiting GRP78 are withdrawn in view of the claim amendments. Specifically, the claim amendments delete the previous recitation of “independently include any chemical moiety that permits the resulting compound capable of inhibiting GRP78”.
Claim 2-3 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 are withdrawn in view of the claim amendments. Specifically, these claims were cancelled.
Claim 1 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 are maintained, but revisited and modified in view of the claim amendments.
Claims 1-3 and 19 rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives are maintained, but revisited and modified in view of the claim amendments.
Claims 1-3 and 19 rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kang et al. (Bull. Korean Chem. Soc., 2010. Vol. 31, 5: 1407-1410) are withdrawn in view of the claim amendments. Specifically, Applicant deletes “C1-6 alkyl” from the scope of Z substituent.
Claims 1-3 and 19 rejected under 35 U.S.C. 102(a)(1) as being anticipated by Samanta et al. (Cancer Res. 2021. Vol. 81(7): 1883-1895. Published on April 1, 2021; cited in the IDS filed on February 19, 2025) are withdrawn in view of the claim amendments. Specifically, Applicant deletes “C1-6 alkyl” from the scope of Z substituent.
Priority
The instant application 18/273,942 filed on July 24, 2023 is a 371 of PCT/US2022/014893 filed
on February 2, 2022, which claims priority to, and the benefits of U.S. Provisional Application No.
63/144,658 filed on February 2, 2021.
Drawings
The drawings are objected to because of the following matters (newly reapplied as necessitates by amendments):
Fig 2:
PNG
media_image7.png
272
734
media_image7.png
Greyscale
. The lines in Fig. 2A and 2B are colored. Given that the drawings are black and white rather than colored drawings, it is not clear which shade of grey represents which group or concentration.
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.
Please note color photographs and color drawings are not accepted in utility applications unless
a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the
appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as
appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or
color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system,
and, unless already present, an amendment to include the following language as the first paragraph of
the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this
patent or patent application publication with color drawing(s) will be provided by the Office upon
request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and
white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Drawings and Specification
The amendment to the drawings and the specification filed on June 23, 2026 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows:
The amended drawings added new labeling to 50.0 μM, 25.0 μM, 12.5 μM, 6.25 μM, and 1% DMSO groups in Fig. 3, which are found on the bottom right of Fig. 3C; new labeling to control group in Fig. 4A and Fig. 4B; However, the originally filed disclosure does not permit one of ordinary skill in the art to determine which curve or line corresponds to which group or concentration. Therefore, the subsequent assignment of groups/concentrations to particular curve or line introduces substantive information that is not present in the application as originally filed, and that constitutes a new matter.
Additionally, applicant amends the brief description of the drawings disclosed on page 48, line 23-24 of the specification from the originally filed recitation of “[t]he Numbers in red are thermal shift at respective concentration” to the recitation of “[t]he numbers are thermal shift at respective concentration” in Figure 2. The deletion of “red” from Figure 2 broadens the statement from a particular subset of number to potentially all numbers appearing in the figure. Given that Figure 2 contains other numerical information besides the originally red thermal-shift values, the amended description now includes numbers that were not originally identified as thermal-shift values.
Applicant is required to cancel the new matter in the reply to this Office Action.
Response to Arguments
Applicant's arguments filed On June 23, 2026 with respect to the objection to the drawings have been fully considered but they are not persuasive.
In Summary, Applicant argues the amendments made to the specification and the drawings overcomes the rejection of record.
In response, applicant’s arguments are not found persuasive, because as noted in the objection of record, the lines displayed in Fig. 2A and 2B are not colored. Without proper labeling, and it is not clear which lines correspond to which group indicated in Fig. C. It is respectfully noted that color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted, and such petition has not been filed. Given these reasons above, the objection has been maintained but revisited and modified in view of the claim amendments.
Claim Objections
Claim 32 is objected to because of the following informalities (newly applied as necessitated by amendments):
Regarding claim 32, the underline “_” recites after the compound shown below:
PNG
media_image8.png
118
137
media_image8.png
Greyscale
, appears to be a typographical error. Said underline should be deleted.
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.
Claims 1, 19 and 32 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 (newly applied as necessitated by amendments).
Instant amended claim 1 recites “[a] compound described by Formula I:
PNG
media_image9.png
176
229
media_image9.png
Greyscale
”, which introduces a double bond between Y3 and Y4. However, the double bond between Y3 and Y4 is not supported by the application as originally filed. It is respectfully noted that the Formula I as originally filed depicts no double bond between Y3 and Y4 (e.g., see page 5, line 2, the Formula I are provided:
PNG
media_image10.png
120
166
media_image10.png
Greyscale
), and the definitions of Y3 and Y4 do not expressly or inherently require such bond.
This is a new matter rejection.
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 1 remain 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.
Regarding claim 1,
It is noted that the term “a” is an indefinite, singular article used exclusively with singular nouns; thus, when the phrase “[a] compound” is used in the context to include plural form of pharmaceutically acceptable salt can cause confusion as it is not clear if applicant is trying to claim a mixture composed more than one compound. The lack of clarity renders the claims indefinite since the resulting claims do not clearly set forth the metes and bounds of the patent protection desired.
Response to Arguments
Applicant's arguments filed on Jun 23, 2026 with respect to the rejection of claim 1-3 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 have been fully considered but they are not persuasive.
All rejections pertaining to claims 2-3 are moot because the claims were cancelled in view of the amendments filed on June 23, 2026.
In Summary, applicant argues the claim amendments overcome the rejection of record.
In response, applicant arguments are not found persuasive. It is respectfully noted that instant claim 1 still recites “[a] compound described by Formula I …, including pharmaceutically acceptable salts”. As noted in the rejection of record, when the phrase “[a] compound” is used in the context to include plural form of pharmaceutically acceptable salt (see the recitation of “including pharmaceutically acceptable salts”), it is not clear if applicant is trying to claim a mixture composed more than one compounds described by Formula I rather than “a” singular compound described by Formula I. Therefore, the rejection has been maintained for the same reasons of record and for the reasons set forth herein.
Claims 1 and 19 remain rejected and claim 32 is rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives (partially newly applied as necessitated by amendments). 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 Markush grouping of compounds is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
Instant claim 1 recites “[a] compound described by Formula I:
PNG
media_image11.png
168
226
media_image11.png
Greyscale
” composed of wide variety of X1-X6, Y2-Y6, A, B, E and Z instantly claimed that does not belong to the same art-recognized chemical class. For instance, naphthyl and hydroxyl do not belong to the same chemical class.
The compound described by instant Formula I only shares the structure feature of:
PNG
media_image12.png
75
101
media_image12.png
Greyscale
in common. According to Eickhoff et al. (US 9,096,608 B2; cited in the previous Office Action), Compound XXIX-6 having the same structure feature shown below:
PNG
media_image13.png
284
332
media_image13.png
Greyscale
is an inhibitors for a protein kinase CDK7 (see e.g., Col. 239, Compound (XXIX-6); Col. 119, line 1-4). Even though the compound XXIX-6 of Eickhoff et al. contains the same structure feature noted above (
PNG
media_image12.png
75
101
media_image12.png
Greyscale
), said compound is taught to have inhibiting effect against protein kinase CDK7 rather than inhibiting GRP78. Therefore, it is not apparent that this common structure alone contributes to the substantial feature essential for the compound to give the desired property of inhibiting GRP78.
In addition, instant claim 19 broadly recites a list of structurally distinct compounds that can be selected. The Markush grouping of these compounds are improper, because they do not share a single structural similarity and a common use that flows from the substantial structure feature they have in common. For instance, the compounds recites therein include a wide variety of compound species, such as
PNG
media_image14.png
189
269
media_image14.png
Greyscale
,
PNG
media_image15.png
110
167
media_image15.png
Greyscale
,
PNG
media_image16.png
213
309
media_image16.png
Greyscale
, and
PNG
media_image17.png
172
146
media_image17.png
Greyscale
, that do not share a substantial structure feature and a common use that flows from the substantial structure feature. It is noted that the structure feature they have in common is the structure shown as follows:
PNG
media_image18.png
84
182
media_image18.png
Greyscale
. According to Maloney et al. (US 2013/0096159 A1; cited in the previous Office Action), compound 23 having the structure of:
PNG
media_image19.png
141
236
media_image19.png
Greyscale
, wherein R1 is H; R2 is Cl; R3 is H; R= is Me is a compound of Formula (I) useful for inhibiting human 12-lipoxygenase (see e.g., Table 1; abstract). Even though the compound 23 of Maloney et al. shares the same common structure feature indicated as follows:
PNG
media_image20.png
146
234
media_image20.png
Greyscale
, it is recognized to have inhibiting effect for human 12-lipoxygenase rather than inhibiting GRP78. Therefore, it is not apparent that this common structure feature alone (
PNG
media_image18.png
84
182
media_image18.png
Greyscale
) constitutes to the substantial feature essential for the compound to give the desired property of inhibiting GRP78 as well as treating, ameliorating, and preventing the entire scope of various forms of cancer, viral infections, and inflammatory disease.
Same logic noted above is applicable to newly added claim 32, which also broadly recites a list of structurally distinct compounds that can be selected. The Markush grouping of these compounds are improper, because they do not share a single structural similarity and a common use that flows from the substantial structure feature they have in common. For instance, the compounds recites therein include a wide variety of compound species, such as
PNG
media_image21.png
123
191
media_image21.png
Greyscale
,
PNG
media_image22.png
113
196
media_image22.png
Greyscale
,
PNG
media_image23.png
190
422
media_image23.png
Greyscale
, and
PNG
media_image24.png
297
419
media_image24.png
Greyscale
, that do not share a substantial structure feature and a common use that flows from the substantial structure feature. As noted above, the compound 23 taught by Maloney et al. (US 2013/0096159 A1) shares the same common structure feature indicated as follows:
PNG
media_image20.png
146
234
media_image20.png
Greyscale
; However, said compound is taught by the prior art to have inhibiting effect for human 12-lipoxygenase rather than inhibiting GRP78. Therefore, it is not apparent that this common structure feature alone (
PNG
media_image18.png
84
182
media_image18.png
Greyscale
) constitutes to the substantial feature essential for the compound to give the desired property of inhibiting GRP78 as well as treating, ameliorating, and preventing the entire scope of various forms of cancer, viral infections, and inflammatory disease.
Each of these findings demonstrate that not all members recited in the Markush groupings noted above share a substantial structural feature and a common use that flows from the substantial structural feature.
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 claims(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 CFR 41.31(a)(1) (emphasis provided).
Response to Arguments
Applicant's arguments filed on June 23, 2026 with respect to the rejection of claims 1-3 and 19 on the judicially-created basis that it contains an improper Markush grouping of alternatives have been fully considered but they are not persuasive.
All rejections pertaining to claims 2-3 are moot because the claims were cancelled in view of the amendments filed on June 23, 2026.
In the present case, applicant newly added claim 32. Applicant also amends claim 1 by replacing the previous recitation of Formula I to Formula IV, with another formula:
PNG
media_image25.png
175
226
media_image25.png
Greyscale
as the new Formula I; and further replacing the previous recitation of “
PNG
media_image26.png
106
659
media_image26.png
Greyscale
” with the particular X1-X6, Y2-Y6, A, B, E, Z groups instantly claimed; and that changes the scope of the claims. Applicant further amends claim 19 from “compounds recited in Table I or II” to a list of compounds instantly claimed.
In Summary, Applicant argues the amendments now only recites Formula I in claim 1 and specific compounds in claim 19 that overcomes the rejection of record.
In response, Applicant’s arguments are not found persuasive. Even though the claim amendments now narrow the scope of Formula (I) recites in claim 1, the Markush grouping of these compound species of Formula (I) recites therein and the Markush grouping of the compound species recites in amended claim 19 and newly added claim 32, respectively, which includes compounds that are not encompassed by instant Formula (I), still do not share any substantial structural feature in common, i.e., a significant structural element is shared by all of the alternatives or all alternatives belong to a
recognized class of chemical compounds in the art to which the invention pertains.
Again, the grouping is improper if either (1) the members of the Markush grouping do not share
a “single structural similarity” or (2) the members do not share a common use. Applicant’s assertion that each of these Markush grouping of compounds species recited in the amended claims shares a substantial structural feature and a common use that flows from the substantial structure feature appears to be mere arguments without objective evidence. Applicant does not provide any sound technical and scientific reasonings to support the structurally distinct compounds, e.g.,
PNG
media_image14.png
189
269
media_image14.png
Greyscale
and
PNG
media_image17.png
172
146
media_image17.png
Greyscale
in claim 19 are, in fact, sharing a substantial structural in common. The compound species only share the circled structure:
PNG
media_image27.png
183
175
media_image27.png
Greyscale
in common, and that clearly does not constitute a significant portion of the compound as a whole. In other words, the structure they have in common does not occupy a large portion of their structures. Same analysis is applicable to the compound of instant Formula (I)
PNG
media_image28.png
205
267
media_image28.png
Greyscale
, the only thing they have in common is
PNG
media_image12.png
75
101
media_image12.png
Greyscale
, and that structure clearly do not occupy a large portion of their structures as well. Given that Applicant fails to provide any objective evidence demonstrating that this structure feature (i.e.,
PNG
media_image27.png
183
175
media_image27.png
Greyscale
or
PNG
media_image12.png
75
101
media_image12.png
Greyscale
of Formula (I)) alone constitutes a substantial structure essential for the compound to give the properties of inhibiting GRP78 as well as treating, ameliorating, and preventing the entire scope of various forms of cancer, viral infections, and inflammatory disease.
In view of the foregoing, applicant’s assertion that the Markush grouping of compound species
shares a substantial structure feature and a common use that flows from the substantial structure
feature does not have any factual support. If applicant contends the structure feature they have in common is substantial and has a common use that flows from the from the substantial structural feature, such evidence is respectfully requested.
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.
(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.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Baum et al. (Antimicrob Agents Chemother, 2007. Vol. 51(12): 4420-4426) (newly applied as necessitated by amendments).
Baum et al. teaches a compound 3 having the structure of:
PNG
media_image4.png
116
186
media_image4.png
Greyscale
(see e.g., Table 1, Compound 3).
The compound 3 of Baum et al. is a compound of instant Formula I:
PNG
media_image29.png
188
245
media_image29.png
Greyscale
, wherein X1 is N; X2, X3, X4, X5, X6 are each CR1 and R1 is independently H; E is hydrogen; B is hydrogen; A is CO; and Z is phenyl; and
PNG
media_image30.png
80
77
media_image30.png
Greyscale
is
PNG
media_image31.png
70
58
media_image31.png
Greyscale
. Therefore, the claimed invention is being anticipated by Baum et al.
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 1 is rejected under 35 U.S.C. 103 as being unpatentable over Ratan et al. (US 2016/0317526 A1) (newly applied as necessitated by amendments).
Ratan et al. teaches a compound (bd) having the structure of:
PNG
media_image32.png
162
242
media_image32.png
Greyscale
as an exemplary compound according to Formula (1) useful for inhibiting hypoxia inducible factor (HIF) prolyl-4-hydroxylases (PHDs) and/or ATF4 (see e.g., p. 12, left column, compound (bd); [0002]). Ratan et al. further teaches further teaches the chemical structure of Formula (1):
PNG
media_image33.png
136
292
media_image33.png
Greyscale
(see e.g., [0040]), wherein R2 in Formula (1) can be selected from any of the cyclic groups described above for R'; and the cyclic group may (optionally) be attached to the carbonyI carbon or nitrogen atom shown in Formula (1) via any of the linkers described above under R' (see e.g., [0046]). Ratan et al. further teaches linkers (R) can be, for
example, saturated and straight-chained (i.e., straight chained alkyl groups or alkylene linkers); and some examples of straight-chained alkyl groups (or alkylene linkers) include methyl (or methylene linker, i.e., -CH2-) (see e.g., [0024]). It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by selecting the Compound (bd) of Ratan et al., and then modifying said compound by removing the methylene linker between the carbonyI and phenyl ring, and then directly attached said phenyl to the carbonyI carbon. One would have been motivated to do so, because Ratan et al. teaches the cyclic group at the R2 position can be attached to the carbonyI carbon or via an alkylene linker such as -CH2-, and identifies Compound (bd) as of the compound of Formula (1) useful for inhibiting hypoxia inducible factor (HIF) prolyl-4-hydroxylases (PHDs) and/or ATF4. Thus, Ratan et al. itself would have suggested the removal of methylene linker presents in between the carbonyl carbon and R2, and directly attached said R2 to the carbonyl carbon while retaining the disclosed inhibiting effect of hypoxia inducible factor (HIF) prolyl-4-hydroxylases (PHDs) and/or ATF4. Accordingly, one of ordinary skill in the art seeking to arrive at additional analogs of Ratan’s Compound (bd) would have been motivated to remove methylene linker, and directly attach the phenyl ring to the carbonyl carbon because such modification was taught by Ratan et al. while seeking to preserve the biological activity of Compound (bd) as the lead compound, thereby arriving at the compound with a reasonable expectation of success. Please note the modified compound (bd) of Ratan et al. set forth above is a compound having the structure of:
PNG
media_image6.png
282
359
media_image6.png
Greyscale
, which reads on instant Formula I:
PNG
media_image34.png
92
136
media_image34.png
Greyscale
, wherein
PNG
media_image34.png
92
136
media_image34.png
Greyscale
is
PNG
media_image35.png
67
105
media_image35.png
Greyscale
; E is hydrogen; B is hydrogen; Y2, Y3, and Y6 are each independently CH; Y4 and Y5 are each independently CR2, R2 is -O-CH3 (reads on C1-alkoxy); A is CO; Z is phenyl.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Claims 19 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Ratan et al. (US 2016/0317526 A1), in view of Patani et al. (Chem. Rev., 1996. Vol. 96, 8: 3147-3176) (newly applied as necessitated by amendments).
Ratan et al. teaches a compound (bg) having the structure of:
PNG
media_image36.png
160
175
media_image36.png
Greyscale
as an exemplary compound according to Formula (1) useful for inhibiting hypoxia inducible factor (HIF) prolyl-4-hydroxylases (PHDs) and/or ATF4 (see e.g., p. 12, right column, compound (bg); [0002]). Ratan et al. further teaches the chemical structure of Formula (1):
PNG
media_image33.png
136
292
media_image33.png
Greyscale
(see e.g., [0040]), wherein R2 in Formula (1) is selected from acyclic hydrocarbon groups R5 containing up to twelve carbon atoms (see e.g., [0047]); the acyclic hydrocarbon group R5 (and hence, R2) can be any of the saturated or unsaturated, straight-chained or branched, and heteroatom-unsubstituted or heteroatom-substituted hydrocarbon groups described under R and having up to twelve carbon atoms (see e.g., [0047]).
Kang et al. does not teach the compound as claimed in claims 19 and 32.
Patani et al. teaches bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents (see e.g., “introduction” section on p. 3147). Patani et al. further teaches a group of bioisosteres elicit similar biological activity, and have been classified as either classical or nonclassical, wherein the classical bioisosteres are a series of replacements defined by Grimm’s Hydride Displacement Law and Erlenmeyer’s definition of isosteres (see e.g., p. 3148-3149). Patani et al. further teaches the use of the classical bioisosteres benzene and pyridine resulted in analogues with retention of biological activity within different series of pharmacological agents (see e.g., p. 3158, “E. Ring Equivalents” section). Patani et al. further teaches fluorine and hydroxyl, amino, or methyl Groups as replacements for hydrogen is a result of the direct adaptation of Grimm’s Hydride Displacement Law (see e.g., p. 3152, left column, 1 paragraph under “4. Fluorine and Hydroxyl, Amino, or Methyl Groups as Replacements for Hydrogen (Grimm’s Hydride Displacement Law” section); and as an extension to the above group defined by Grimm’s Hydride Displacement Law, the widespread use of the chlorine atom as a bioisostere has been observed in several different series of biologically active compounds, including the one shown below:
PNG
media_image37.png
289
379
media_image37.png
Greyscale
(see e.g., p. 3153, left column, 2nd paragraph).
Please note the difference between the Compound (bg) of Ratan et al. and the claimed compound is shown below (see shaded):
PNG
media_image38.png
275
551
media_image38.png
Greyscale
.
It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by selecting the Compound (bg) of Ratan et al., and then modifying said compound by replacing the hydrogens with chlorine as taught by Patani et al. One would have been motivated to modify Compound (bg) of Ratan et al. by replacing the corresponding hydrogens of 8-hydroxyquinolinyl and -CH3 with chlorine thereby arriving at the claimed invention, because Ratan et al. expressly teaches the hydrocarbon group presents at R2 can be heteroatom-substituted, and identifies Compound (bg) as of the compound of Formula (1) useful for inhibiting hypoxia inducible factor (HIF) prolyl-4-hydroxylases (PHDs) and/or ATF4. Thus, Ratan et al. itself would have suggested the replacement of one or more hydrogens in the hydrocarbon group with one of more heteroatoms. With respect to the hydrogen-to-chlorine substitution, Patani et al. teaches that replacement of hydrogen with chlorine constitutes a classical bioisosteric replacement and such bioisosteric substitution is employed in medicinal chemistry for the rational modification of lead compounds to obtained structurally related compounds having similar biological activity. Accordingly, one of ordinary skill in the art seeking to arrive at additional analogs of Ratan’s Compound (bg) would have been motivated to employ the known H/Cl bioisosteric replacement, because such modification was a recognized medicinal-chemistry approach for obtaining structurally related analogs while seeking to preserve the biological activity of Compound (bg) as the lead compound, thereby arriving at the compound with a reasonable expectation of success.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Response to Arguments
Applicant’s arguments filed on June 23, 2026 with respect to the rejection of claims 1-3 and 19 under 35 U.S.C. §102(a)(1) as being anticipated by Kang et al. (Bull. Korean Chem. Soc., 2010. Vol. 31, 5: 1407-1410), and the rejection of claims 1-3 and 19 were rejected under 35 U.S.C. §102(a)(1) as being anticipated by Samanta (Cancer Res. 2021. Vol. 81(7): 1883-1895. Published on April 1, 2021; cited in the IDS filed on February 19, 2025) have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. In the present case, applicant amends the scope of claims 1 and 19, and that necessitated the new ground of rejection.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Chihyi Lee whose telephone number is (571)270-0663. The examiner can normally be reached Monday - Friday 8:30 am - 5:00 pm EST.
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 at (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.
/CHIHYI LEE/Examiner, Art Unit 1628 /JEAN P CORNET/Primary Examiner, Art Unit 1628
Prosecution Insights