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:
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as the elected compound species described by Formula I in the reply filed on January 16, 2026 is acknowledged.
Please note the elected compound species described by Formula I
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, 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;
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is
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; and Z is
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.
Claims 4, 7, 12, 15, 18 and 21-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on January 16, 2026.
Expansion of Election of Species Requirement
A reasonable and comprehensive search of the elected compound species conducted by the Examiner 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:
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. 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:
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, 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 January 16, 2026, wherein claims 1-4, 7, 12, 15, 18-19, and 21-31 are unchanged; and claims 5-6, 8-11, 13-14 and 20 are cancelled.
Claims 1-4, 7, 12, 15, 18-19, and 21-31 are pending.
Claims 4, 7, 12, 15, 18 and 21-31 are withdrawn.
Claims 1-3 and 19 are under examination in accordance with the elected compound species.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 02/19/2025 and 07/10/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
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.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/144,568, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Specifically, the disclosure of the prior-filed application is drawn to a game call tether system rather than the compound described in the present application; and therefore, claims 1-3 and 19 under examination are not entitled to the benefit of the prior-filed application and will receive an effective filing date of February 2, 2022, which is the filing date of 371 of PCT/US2022/014893.
Claim Interpretation
The limitation of “capable of inhibiting GRP78” in claim 1, and the limitation of “serving as an effective therapeutic agent for treating, ameliorating, and preventing various forms of cancer, viral infections, and inflammatory diseases; inducing ER stress-mediated apoptosis in the tumor cells implanted in mice without major toxicity to normal tissues; and inducing ER stress and triggers UPR by inhibiting GRP78” in claim 2, are reasonably construed to be an intended use of the compound(s) instantly claimed. Since the claim is interpretated to be a product, the intended use of the compound does not further limit the chemical structural of compound; and therefore, if the prior art(s) meet the structural limitation of the claimed compound, it is capable of performing the intended use.
Claim Objections
Claim 3 is objected to because of the following informalities:
Regarding claim 3, the recitation of “
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” at R2 is missing a comma in between these two alternatives.
Appropriate correction is required.
Drawings
The drawings are objected to because of the following matters:
Fig 2: the numerical numbers in the x-axis and y-axis of these line graphs shown below are blurry and unreadable:
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. It is noted that these lines are labelled with the same pattern and color, thus, these lines cannot be distinguished from one another. It is noted that the specification indicates “numbers in red are thermal shift at respective concentrations”; However, the drawings are in black and white rather than colored drawings.
Fig. 3: the chemical structure recites therein are blurry and unreadable, for instance,
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. It is noted that the specification indicates “[t]wo bands indicated by the red box are submitted separately to the UM Proteomics Core facility for proteomics analysis. I”; However, the drawings are in black and white rather than colored drawings. In addition, the name recites in x-axis and y-axis of Fig. 3, I are blurry and unreadable shown below:
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Fig 4: the figure labeled control and YUM 70 using the same color and pattern, thus, it is not clear which line represents which group shown below:
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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).
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 1-3 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.
Instant claim 1 recites “[a] compound described by Formula I:
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(Formula I), Formula II
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(Formula II), Formula III
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(Formula III), or Formula IV:
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(Formula IV), including pharmaceutically acceptable salts… solvates, and/or prodrugs thereof; wherein X1…. Z (if present) independently include any chemical moiety that permits the resulting compound capable of inhibiting GRP78”. There is insufficient written basis for the solvates and prodrugs of the compound described by Formula I-IV in the specification.
Regarding the requirement for adequate written description of chemical entities, Applicant's attention is directed to the MPEP §2163. In particular, Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089, 118 S. Ct. 1548 (1998), holds that an adequate written description requires a precise definition, such as by structure, formula, chemical name, or physical properties, "not a mere wish or plain for obtaining the claimed chemical invention." Eli Lilly, 119 F.3d at 1566. The Federal Circuit has adopted the standard set forth in the Patent and Trademark Office ("PTO") Guidelines for Examination of Patent Applications under the 35 U.S.C. 112.I "Written Description" Requirement ("Guidelines"), 66 Fed. Reg. 1099 (Jan. 5,2001), which state that the written description requirement can be met by "showing that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics," including, inter alia, "functional characteristics when coupled with a known or disclosed correlation between function and structure ..." Enzo Biochem, Inc. v. Gen-Probe Inc., 296 F.3d 316, 1324-25 (Fed. Cir. 2002) (quoting Guidelines, 66 Fed. Reg. at 1106 (emphasis added)). The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus.
In the present case, Applicant has failed to provide any structural characteristics, chemical formula, name(s) or physical properties of the solvates and prodrugs of the compound described by Formula I-IV in the specification, aside from a broad recitation that such are contemplated for use in the invention. The disclosure does not describe any species of prodrugs and solvates. Therefore, it is not apparent that Applicant was actually in possession of, and intended to be used within the context of the present invention, any specific species of solvates and prodrugs of the compound described by Formula I-IV at the time the application was filed based on the limited disclosure provided.
Claims 1-3 are 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:
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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. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Attention is directed to in re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and, (8) the quantity of experimentation necessary. All of the Wand’s factors have been considered and discussed below:
(1, 5) The breadth of the claims and the Nature of the Invention: As stated in MPEP 2164.05(a), “[t]he initial inquiry” for determining whether the Specification is enabling “is into the nature of the invention, i.e., the subject matter to which the claimed invention pertains.”
Instant claims 1 recites “[a] compound described by Formula I:
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(Formula I), Formula II
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(Formula II), Formula III
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(Formula III), or Formula IV:
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(Formula IV), including pharmaceutically acceptable salts… solvates, and/or prodrugs thereof; wherein X1….Z (if present) independently include any chemical moiety that permits the resulting compound capable of inhibiting GRP78”.
Instant claim 2 recites “[t]he compound of claim 1, wherein A, B, E, X1, X2, X3, X4, X5, X6, Y2, Y3, Y4, Y5, Y6 and Z independently include any chemical moiety that permits the resulting compound capable of one or more of: serving as an effective therapeutic agent for treating, ameliorating, and preventing various forms of cancer, viral infections, and inflammatory diseases; inducing ER stress-mediated apoptosis in the tumor cells implanted in mice without major toxicity to normal tissues; and inducing ER stress and triggers UPR by inhibiting GRP78”.
The breadth of the claims covers the entire scope of compounds described by Formula I, Formula II, Formula III and Formula IV, including pharmaceutically acceptable salts, solvates, and/or prodrugs, for inhibiting GRP78; for treating, ameliorating, and preventing the entire scope of various forms of cancer, viral infections, and inflammatory diseases; 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.
(2, 3, 4) The state of the prior art, the level of skill in the art, and the predictability or lack
thereof in the art: As stated in MPEP 2164.05(a), “[t]the state of the prior art is what one skilled in the
art would have known, at the time the application was filed, about the subject matter to which the
claimed invention pertains” and, as stated in MPEP 2164.05(b), “[t]he relative skill of those in the art
refers to the skill of those in the art in relation to the subject matter to which the claimed invention
pertains at the time the application was filed.”
As discussed above, the claimed invention pertains the entire scope of compound described by Formula I, Formula II, Formula III and Formula IV for inhibiting GRP78; for treating, ameliorating, and preventing the entire scope of various forms of cancer, viral infections, and inflammatory diseases; 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.
To the extent that the effective filing date of the instant application is February 2, 2022 (see priority section above), at the time the application was filed, one of ordinary skill in the art would have known having the compound having the structure of:
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is capable of inhibiting GRP78 to induce ER stress-mediated apoptosis in pancreatic cancer; and showed in vivo efficacy in a pancreatic cancer xenograft model with no toxicity to normal tissues (see e.g., abstract; title; Figure 1); However, one of ordinary skill in the art would have also known that compound with the similar structure feature, such as compound having the structure of:
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, are not recognized as being capable of inhibiting GRP78, but was identified through virtual screening to be used for the molecular docking studies in order to provide valuable information for the design of Human FIH-1 Inhibitor, according to Zhang et al. (Bull. Korean Chem. Soc., 2010. Vol. 31, 5: 1407)(see e.g., Figure 3; Table 1, Compd 33; p. 1407, right column, line 2-6).
According to Zou et al. (Cell Stress Chaperones, 2023. Vol. 28(4): 409-422), studies have shown that Epigallocatechin gallate (EGCG) can directly interact with the ATP-binding-domain of GRP78
and block its interaction with procaspase-3, thus inhibiting its protective function; however, low dose
EGCG (10 μM) alone did not affect the survival of liver cancer cell colonies (see e.g., p. 415, right column, “ECGC sensitizes liver cancer cells to lysionotin” to p. 416, left column, line 13). In other words, the cited reference demonstrates the unpredictability surrounding the use of compound capable of inhibiting GRP78 for treating and ameliorating the entire scope of various forms of cancer, for instance, liver cancer.
According to Sun et al. (Aquaculture, 2023. Vol. 576: 739757), the inhibition of GRP78 can further induced the ER stress and inflammation induced by thapsigargin (see e.g., abstract); and therefore, the cited reference demonstrates the unpredictability surrounding the use of compound capable of inhibiting GRP78 for treating, ameliorating, and preventing the entire scope of inflammatory diseases.
According to CDC (“Hepatitis C Prevention and Control”. Published online on January 31, 2025), Hepatitis C is a disease of the liver caused by infection with the hepatitis C virus; and there is currently no vaccine to prevent hepatitis C (see e.g., “Key points” and “Overview”). Therefore, the cited reference demonstrates the unpredictability surrounding the prevention of the entire scope of viral infections, such as hepatitis C.
According to Cleveland Clinic (“Eye Cancer” [Online]), there is no way to prevent eye cancer (see e.g., “How can I prevent eye cancer?” section). Thus, the cited reference demonstrates that the state of the art with respect to preventing the entire scope of various forms of cancer is still underdeveloped.
In view of the foregoing, the relative skill of those in the art would not have known which compounds described by Formula I to Formula IV, including pharmaceutically acceptable salts, solvates, and/or prodrugs thereof include any chemical moieties can successfully be used across the entire scope of inhibiting CGRP78; treating, ameliorating, and preventing the entire scope of various forms of cancer, viral infections, and inflammatory diseases; inducing ER stress-mediated apoptosis in the tumor cells implanted in mice without major toxicity to normal tissues; and inducing ER stress and triggers UPR by inhibiting GRP78.
While applicant’s claimed compound YUM70 having the structure of:
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may play a role in inhibiting GRP78, inducing cytotoxic effect to pancreatic cancer cell lines PNC-1 and UM59, and reducing the growth of pancreatic cancer cells MIA PaCa-2; and applicant’s claimed compound DX2-145 (i.e., Compound P6) and YUM513 (i.e., Compound P1) for degrading GRP78, it is uncertain whether each and every compound species described by Formula I, Formula II, Formula III or Formula IV can be used 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 without undue experimentation.
(6, 7, 8) The amount of guidance given, the presence of working example and the quantitation
of experimentation required:
In view of all of the foregoing, at the time the invention was made, it would have required undue experimentation to practice the entire scope of the claimed invention. Although the instant specification tested the compound YUM70 having the structure of:
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(see e.g., Table 1) against a panel of pancreatic cell lines, including PANC-1 and UM59 (Example I); tested its binding to GRP78 (see e.g., Table II), and its ER stress-mediated apoptosis effect against pancreatic cancer cells MIA PaCA-2 in xenograft model, its biological activities against other cancer cell lines, viral infections, and inflammatory diseases has not been disclosed. The working examples does not test whether the compound trigger UPR. It is further noted the instant specification only further describes DX2-145 (i.e., Compound P6) and YUM513 (i.e., Compound P1) can degrading GRP78 at a concentration-dependent manner in MIA PaCa-2 cells (see e.g., Example II). Its biological activities against other cancer cell lines, viral infections, and inflammatory diseases has not been disclosed; and its effect on ER-stress and UPR have not been disclosed in mice.
Based on the amount of guidance given, the quantity of experimentation necessary to carry out the claimed invention is high, because one of the relative skill in the art could not reasonably predict which compound described by Formula I, Formula II, Formula III and Formula IV, including pharmaceutically acceptable salts, solvates, and/or prodrugs thereof can successfully be adapted for inhibiting GRP678; for treating, ameliorating, and preventing various forms of cancer, viral infections, and inflammatory disease; for inducing ER-stress mediated apoptosis in each and every tumor cells implanted in mice without major toxicity to normal tissues; and for inducing ER stress and triggers UPR by inhibiting GRP78 based on the limited disclosure provided. It would require undue experimentation as it is highly unpredictable that each and every compound species of Formula I-Formula IV would, in fact, be usable across the entire scope of cancers, viral infections, and inflammatory diseases.
Accordingly, the intended use of the claimed compound of Formula I to Formula IV, including pharmaceutically acceptable salts, solvates, and/or prodrugs thereof, that covers inhibiting GRP678; for treating, ameliorating, and preventing various forms of cancer, viral infections, and inflammatory disease; for inducing ER-stress mediated apoptosis in each and every tumor cells implanted in mice without major toxicity to normal tissues; and for inducing ER stress and triggers UPR by inhibiting GRP78 is not enabled by the instant specification. To overcome this rejection, Applicant should narrow the scope of the claims such that they bear a reasonable correlation with the disclosure.
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 1-3 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.
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, solvate and/or prodrug can cause confusion as it is not clear if applicant is trying to claim a mixture composed more than one compound. The lack of clarify renders the claims indefinite since the resulting claims do not clearly set forth the metes and bounds of the patent protection desired.
the recitation of “(e.g., e.g., 2,2,2-trifluoroacetate (TFA) salts and other salts) (e.g., physiologically tolerated acid addition salts)” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. Description of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, example and preference may lead to confusion over the intended scope of a claim.
The phrase “(if present)” in the recitation of “X1, X2, X3, X4, X5, X6, Y2, Y3, Y4, Y5, Y6, A, B, E, M, J, L, and Z (if present)” is a conditional limitation that renders the claim indefinite, because to the extent that X1, X2, X3, X4, X5, X6, Y2, Y3, Y4, Y5, Y6, A, B, E, M, J, L, and Z is not present, then a compound cannot be form. For instance, a compound of Formula I:
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having X1, X2, X3, X4, X5, X6, Y2, Y3, Y4, Y5 and Y6, cannot be form when one of them are not present. The lack of clarify renders the claims indefinite since the resulting claims do not clearly set forth the metes and bounds of the patent protection desired.
the recitation of “and/or” in the phrase of “pharmaceutically acceptable salts…solvates, and/or prodrugs thereof;” renders the claim indefinite, because it is not clear whether these limitations has to be selected individually, in combination, or all of them must be present together. The claim language can be interoperated in various ways, for instance, it is unclear if Applicant is intending to claim (i) a compound described by the claimed formulae including pharmaceutically acceptable salts or (solvate and prodrug); (ii) a compound described by the claimed formulae including (pharmaceutically acceptable salts and solvate) or prodrug; or (ii) compound described by the claimed formulae including pharmaceutically acceptable salts and solvate and prodrug.
The recitation of Formula I “
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” renders the claim indefinite, because there is no connection between Y3 and Y4 indicated as follows (see shaded):
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; therefore, it is not clear if Y3 and Y4 are connected or separated. The lack of clarify renders the claims indefinite since the resulting claims do not clearly set forth the metes and bounds of the patent protection desired.
In order to advance prosecution, the Examiner is examining claim 1 in light of the elected compound species to the extent that there is a double bond connecting Y3 and Y4 together.
Regarding claim 2, the recitation of “the tumor cells” lacks antecedent basis, because tumor cells are not mentioned prior to said recitation. It is not clear what tumor cells are being referred to therein.
Regarding claim 3,
the recitation of “Y5 is a bond, in which case one of Y3, Y4, or Y6 is NR2, O, or S, while the other two may be CR2 or N” renders the claim indefinite, because the Y5 recites therein is found in the Formula I, II, III or IV sets forth in claim 1, which it depends upon, indicated as follows:
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. To the extent that Y5 is a bond, it is not clear how a bond without any atom can form a double bond with Y6 and a single bond with Y4 as it violates octet rule in chemistry. The lack of clarify renders the claims indefinite since the resulting claims do not clearly set forth the metes and bounds of the patent protection desired.
the recitation of “Y2, Y3, Y4, Y5, Y6 are each independently selected from CH, CR2 and N… R2 is independently selected from the group consisting of…
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,
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” renders the claim indefinite. To the extent that the claim is drawn to the elected compound species G37 as the compound species described by Formula I and reads upon claim 3 as indicated in the reply filed on January 16, 2026, it is not clear how a single R2 being
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can be fused with
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to from the elected structure:
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, because the claim limitation does not set forth multiple R2 in CR2 at Y2, Y3, Y4, Y5 and Y6 are joined together. The lack of clarify renders the claims indefinite since the resulting claims do not clearly set forth the metes and bounds of the patent protection desired.
In order to advance prosecution, the Examiner is examining claim 3 in light of the elected compound species to the extent that
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is
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.
Claims 1-3 and 19 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.
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:
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(Formula I), Formula II
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(Formula II), Formula III
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(Formula III), or Formula IV:
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(Formula IV), including pharmaceutically acceptable salts… solvates, and/or prodrugs thereof; wherein X1….Z (if present) independently include any chemical moiety that permits the resulting compound capable of inhibiting GRP78”. The Markush grouping of the compounds described by Formula I-IV are improper, because the alternated compound species embraced by the Markush grouping do not share a substantial structure feature, and do not share a common use that flows from the substantial structure feature. It is noted that the claimed limitation includes any chemical moieties at X1, X2, X3, X4, X5, X6, Y2, Y3, Y4, Y5, Y6, A, B, E, M, J, L, and Z, which includes a wide variety of chemical structures that does not belong to the same art-recognized chemical class. For instance, naphthyl and hydroxyl do not belong to the same chemical class; and halogen and C1-6 alkoxy also do not belong to the same chemical class; however, the present claims has grouped these structures together for X1, X2, X3, X4, X5, X6, Y2, Y3, Y4, Y5, Y6, A, B, E, M, J, L, and Z to from the compound alternatives.
Furthermore, the compound described by Formula I-IV only shares the structure feature of:
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in common. According to Eickhoff et al. (US 9,096,608 B2), Compound XXIX-6 having the same structure feature shown below:
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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 (
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), 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 is drawn to “[a] compound selected from one of the compounds recited in Tables I or II”. It is further noted the Markush grouping of 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 recited in Table I or II includes a wide variety of compound species, such as compound G57 having the structure of:
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and compound G95 having the structure of:
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in in Table 1; compound P2 having the structure of:
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and compound P62 having the structure of:
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in Table II. Its is noted that these compounds recited in Table I and Table II 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:
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. According to Maloney et al. (US 2013/0096159 A1), compound 23 having the structure of:
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, 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:
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, 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 (
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) 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 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).
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.
Claims 1-3 and 19 are 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).
Kang et al. teaches compound 33 having the structure of:
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is one of the hit compounds selected from the virtual screening to be used for the molecular docking studies in order to provide valuable information for the design of Human FIH-1 Inhibitors (see e.g., Figure 3; Table 1, Compd 33; p. 1407, right column, line 2-6).
In the present case, Kang et al. is silent regarding “include any chemical moiety that permits the resulting compound capable of inhibiting GRP78” in claim 1, and “the resulting compound capable of one or more of: serving as an effective therapeutic agent for treating, ameliorating, and preventing various forms of cancer, viral infections, and inflammatory diseases; inducing ER stress-mediated apoptosis in the tumor cells implanted in mice without major toxicity to normal tissues; and inducing ER stress and triggers UPR by inhibiting GRP78” in claim 2; However, each of these limitations will inevitably flow from the compound 33 of Kang et al. because it is a compound recited in Table 1 as claimed in claim 19. According to MPEP 2112.01, II, “’[p]roducts of identical chemical composition cannot have mutually exclusive properties.’ In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”. In other words, the compound 33 of Kang et al. will necessarily have the claimed properties and capable of performing the intended use even though the prior art was not aware of it.
Please note the compound 33 of Kang et al. is a compound of Formula I
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in claim 3, 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;
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is
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; A is CO; and Z is n-propyl (i.e., C3 alkyl).
Therefore, the claimed invention is being anticipated by Kang et al.
Claims 1-3 and 19 are 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).
Samanta et al. teaches hydroxyquinoline analog YUM70 having the structure of:
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inhibits GRP78 to induce ER stress-mediated apoptosis in pancreatic cancer (see e.g., Figure 1; title). Samanta et al. further teaches the YUM70 inhibits pancreatic cancer cell growth in vitro and showed in vivo efficacy in a pancreatic cancer xenograft model with no toxicity to normal tissues (see e.g., abstract).
Therefore, the YUM70 taught by Samanta et al. anticipates the claimed invention.
Conclusion
No claims are allowed.
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/CHIHYI LEE/Examiner, Art Unit 1628
/JEAN P CORNET/Primary Examiner, Art Unit 1628