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 .
Status of the Claims and Response to Restriction Requirement
Claims 1-2, 4 and 16-40 are pending as of the response filed 03/11/2026. Claims 3, 5-15 and 41-53 are cancelled. Applicant’s election of group I claims 1-2, 4 and 16-26 without traverse is acknowledged. Claims 27-40 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicant’s election of a species of compound, Compound 14A, shown below is acknowledged.
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Claims 1-2, 4, 16-18, 20-22 and 24-26 encompasses the elected species. Claims 19 and 23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Therefore, claims 1-2, 4, 16-18, 20-22 and 24-26 have been examined to the extent to which they are readable on the above identified elected species.
Because Applicant did not distinctly and specifically point out the supposed errors in the election of species requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The elected species was examined and was found to be free of prior art. Therefore, the examiner has extended the search to include the entire genus of compounds of the Formula as in claim 1. The compounds of the Formula as in claim 1 was found to be free of prior art.
Claim 1 is allowable. Claims 19, 23 and 27-40, previously withdrawn from consideration as a result of a restriction requirement, require all the limitations of an allowable claim. Pursuant to the procedures set forth in MPEP § 821.04(a), the restriction requirement between inventions of group I and II, as set forth in the Office action mailed on 01/12/2026, is hereby withdrawn and claims 19, 23 and 27-40 hereby rejoined and fully examined for patentability under 37 CFR 1.104. In view of the withdrawal of the restriction requirement, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
In view of the pending claims, the following objections and rejections are made.
Priority
This application claims priority to PRO 63/591,725 filed 10/19/2023, PRO filed 63/511,400 06/30/2023, PRO 63/496,280 filed 04/14/2023 and PRO 63/421,277 filed 11/01/2022.
Applicant’s claim for the benefit of a prior filed application under 35 U.S.C. 119(e) or under 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 earlier-filed nonprovisional application or provisional application for which benefit is claimed). 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 earliest prior-filed application, Application No. 63/421,277 filed 11/01/2022 fails to provide adequate support and 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. The ‘277 application does not disclose wherein the R1 of the compound of Formula as in claim 1 is
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. Accordingly, claims 1, 4, 16, 18, 20-22, 24 and 26 have an effective filing date of 04/14/2023, the subject matter of which is supported in PRO 63/496,280 filed 04/14/2023, while claims 2, 17 and 25 get the priority benefit of the earliest PRO 63/421,277 application filed 11/01/2022 and have an effective filing date of 11/01/2022.
Information Disclosure Statement
The information disclosure statements submitted on 03/11/2026 and 06/07/2024 (2) are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claim 21 is objected to because of the following informalities:
In claim 21, the limitation “wherein R2 is bound to the chromenone core of the carbon via a ring carbon of a cycloalkyl group, …” should be amended to read “wherein R₂ is bound to the carbon of the chromenone core [[of the carbon]] via a ring carbon of a cycloalkyl group, …” for clarity of claim language.
Appropriate correction is required.
Claim Rejections - 35 USC § 112 - Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(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 27-34 and 36-40 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 a method of inhibiting phosphoinositide 3-kinase (PI3K), comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof, does not reasonably provide enablement for a method of treating a disease or condition associated with modulation of phosphoinositide 3-kinase (PI2K) in a patient in need thereof OR a method of treating cancer or a disorder associated with modulation of phosphoinositide 3-kinase (PI2K) in a patient in need thereof, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof. 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. This is a scope of enablement rejection.
To be enabling, the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). The determination that "undue experimentation” would have been needed to practice the claimed invention in full scope is not a single, simple factual determination.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." In re Wands, 8 USPQe2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. Keeping that in mind, the Wands factors are relevant to the instant application for the following reasons:
The breadth of the claims/The nature of the invention
The claims recite a method of treating a disease or condition associated with modulation of phosphoinositide 3-kinase (PI2K) in a patient in need thereof OR a method of treating cancer or a disorder associated with modulation of phosphoinositide 3-kinase (PI2K) in a patient in need thereof, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof. The instant specification defines the term “modulation” to refer to “a biological activity of a compound or substrate that inhibits and/or activates PI3K” (Para. [75] of the instant specification). Therefore, the scope of the method claims is extensive, as they encompass not only diseases or conditions that respond to inhibition of PI3K but also activation of PI3K. Moreover, the claims broadly recite treating any type of cancer (as in instant claim 30).
The state of the prior art/The level of predictability in the art
Liang et al. (US 8,513,221 B2, 20 August 2013, hereinafter Liang, in the IDS); Lovly et al. (Tumor Heterogeneity and Therapeutic Resistance, 2016, hereinafter Lovly).
Liang is in the field of treating disorders related to abnormal PI3K activities that respond to PI3K modulation (Abstract; Col. 1, Lns. 15-22). Liang teaches the scope of diseases or disorders mediated by PI3K to include cancer, immune disorders, cardiovascular disease, viral infections, inflammation, metabolic/endocrine disorders and neurological disorders (Col. 25, Lns. 45). Liang teaches the diseases and conditions to include an exhaustive list including but not limited to, cancer, stroke, diabetes, hepatomegaly, cardiovascular disease, Alzheimer's disease, cystic fibrosis, viral disease, autoimmune diseases, atherosclerosis, restenosis, psoriasis, allergic disorders, inflammation, neurological disorders, a hormone-related dis ease, conditions associated with organ transplantation, immunodeficiency disorders, destructive bone disorders, proliferative disorders, infectious diseases, conditions associated with cell death, thrombin-induced platelet aggregation, chronic myelogenous leukemia (CML), liver disease, pathologic immune conditions involving T cell activation, and CNS disorders in a patient (Col. 25, Ln. 60 – Col. 26, Ln. 6). Therefore, the conditions that respond to a method of modulating the activity of a PI3K is vast.
Lovly teaches tumor heterogeneity encompasses more than just the clinical picture and can represent both intratumor and intertumor differences (Abstract). Lovly teaches tumor heterogeneity is not one distinct term but rather encompasses several facets – within a disease, within a patient and within a tumor itself - that render tumors unique (Pg. e585, first column, last paragraph; Pg. e591, second column, first full paragraph). Lovly teaches ongoing challenges include the accurate and timely assessment of genetic changes as well as the development of resistance and the resultant compensatory mechanisms (Abstract; Pg. e586, second column, second full paragraph). Lovly, highlights the complexity of tumor heterogeneity in clinical decision making (e589-e590, case studies) and emphasizes that the need to understand the underlying causes of this heterogeneity and development of resistance, to effect better treatment outcomes (Pg. e591, second column, first full paragraph; Pg. e590, first column, first paragraph).
Therefore, the state of the prior art indicates that the breadth of diseases or conditions associated with the modulation of PI3K activity is vast. Moreover, it is clear that there is significant variability found within and between tumors that is a major contributor to treatment failure and cancer recurrence in patients. Therefore, cancer therapy remains highly unpredictable.
Additionally, it is noted that the state of the art with regard to pharmacology is unpredictable. The field of pharmacology involves screening compounds both in vitro and in vivo to determine lead compounds that exhibit the desired pharmacological activity. According to MPEP 2164.03, “The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).”, with physiological activity being considered to be an unpredictable factor.
Therefore, in consideration of the high level of unpredictability in the field of cancer treatments and the vastness of the conditions responsive to the modulation of PI3K, it is unclear how the claimed method would achieve the intended result of treating any and all conditions associated with PI3K modulation by administering the compounds of the instant invention.
The level of one of ordinary skill in the art
The relative level of skill in the art is high, such as, a synthetic organic chemist, healthcare professionals such as, an oncologist or molecular biologist with advanced educational degrees (e.g., M.D. and/or Ph.D.). Additionally there is significant unpredictability in the art regarding the development of therapies, due to the heterogenous nature of cancers and relatively high failure rates in drug discovery and development.
The amount of direction provided by the inventor/The existence of working examples
Applicants have provided biochemical assays supporting the inhibition of PI3K using the tested compounds of the invention (Paras. [518]-[521] of the instant specification). The disclosed data represents PI3Kα inhibitory activity in mutant breast cancer cell lines (Paras. [523]-[531] of the instant specification). The instant specification does not show tests or biological data to establish the full scope of the recitation "modulation of PI3K" as in instant claims 27 and 36, wherein the term 'modulation' includes activation and/or inhibition. The instant specification does not provide any guidance on how the disclosed assays are correlated to the clinical efficacy of the treatment of all types of cancers or other diseases/disorders within the scope of instant claims that respond to PI3K modulation. Based on the provided biological activity for the compounds, only a method of inhibition of PI3K using the compounds of the invention is enabled. Thus, a PHOSITA would have to engage in tedious research and determine which diseases can be treated with the compounds of the instant invention, with no assurance of success.
Therefore, there is lack of direction or guidance regarding treatment of all types of diseases and/or conditions that would respond to the inhibition of PI3K, using the instantly claimed compounds.
The quantity of experimentation needed
Drug development is inherently a burdensome endeavor that generally requires an exorbitant amount of experimentation over many years of focused research. While the rigorous research invested in the claimed invention is evident, a PHOSITA would,
nevertheless, be tasked with an undue burden of experimentation in order to (a) perform assay experiments to test the genus of claimed compounds towards the desired activity of PI3K modulation (that encompasses both activation and inhibition), (b) ascertain which diseases, disorders or conditions known to respond to PI3K modulation would benefit from administering the genus of instantly claimed compounds.
Considering the state of the art as discussed in the references above, high degree of unpredictability in the field, and lack of sufficient guidance in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in scope with the claims.
Claim Rejections - 35 USC § 112
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.
Claim 20 is 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.
Regarding claim 20, the claim depends from claim 1 and recites “wherein R’ is -SO₂NR11R11, -SO₂N(R11)(R13), -C(O)NR11R12, or -C(O)-NHSO₂R16”. However, the variable R’ of claim 1 does not recite -SO₂N(R11)(R13) and -C(O)-NHSO₂R16 as options for R’. This broadens the scope of the claim, which is improper.
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.
Allowable Subject Matter
The compounds of the Formula as in claim 1 have been found to be free of prior art.
The following is a statement of reasons for the indication of allowable subject matter:
The instant application relates to a compound of general Formula as in instant claim 1 or a pharmaceutically acceptable salt thereof, pharmaceutical compositions and methods of treatment thereof.
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The closest prior art of record is Anderson et al. (WO 2021/202964 A1, 07 October 2021, hereinafter Anderson, in the IDS) and Jackson et al. (WO 2004/016607 A1, 26 February 2004, in the IDS).
Anderson teaches allosteric chromenone inhibitors of phosphoinositide-3-kinase (PI3K) for the treatment of diseases associated with PI3K modulation (Abstract). Anderson teaches compounds of Formula (I) or pharmaceutically acceptable salts thereof, or prodrugs, solvates, hydrates, isomers, or tautomers thereof, with variables as defined (Para. [15]).
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There is some overlap in scope of the compounds of Anderson when X is O; R7 is not H (as required by the instant claims). However, Anderson does not teach any species of compounds wherein X is O and -W(R1)(R2) of Anderson falls within the scope of instant variable R2. Anderson does not teach or suggest the compounds of the instant invention.
Jackson teaches inhibitors of PI3-kinase beta (Abstract). Jackson teaches compounds of formula (III) with variables as defined (Pg. 6, first full paragraph – Pg. 7, continued paragraph).
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Jackson teaches an exemplary compound, KN-313, 6-methyl-8-phenoxymethyl-2-(4-pyridinyl)-4H-benzopyran-1-one (Pg. 37, Example 2i), represented by the following structure.
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KN-313 of Jackson overlaps the scope of a compound of the Formula of instant claim 1, wherein,
R3 is -H;
R4 is -H;
R6 is -H;
R5 is C1-C6 alkyl (methyl);
R7 is C1-C6 alkyl (methyl);
R8 is -H;
R1 is
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, each R9 is -H, R’ is hydrogen.
KN-313 of Jackson differs in the R2 being a pyridine-4-yl group that is not encompassed by the instant claims.
There is no teaching or suggestion in the prior art to arrive at the compounds of the instant invention. Therefore, the instant compounds are novel and non-obvious over the compounds of the prior art.
Conclusion
Claims 1-2, 4, 16-19, 22-26 and 35 are allowed.
Claims 20, 27-34 and 36-40 are rejected.
Claim 21 is objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PADMAJA S RAO whose telephone number is (571)272-9918. The examiner can normally be reached 9:00-5:30pm EDT.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney L Klinkel can be reached on (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PADMAJA S RAO/Examiner, Art Unit 1627
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