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 Claims
Pursuant to the preliminary amendment, filed on January 7, 2025, claims 18-20 and 22 have been amended.
Claims 1-22 are pending.
Priority
This application, filed on July 7, 2022, is a National Stage entry from International Application No. PCT/CN2023/105915, filed on July 5, 2023, which claims priority under 35 U.S.C. 119 or 365 to the benefit of the Chinese Application No. CN202210794939. The certified copy of the foreign application has been received.
Information Disclosure Statement
The information disclosure statement (IDS), filed on January 7, 2025, has been acknowledged and considered.
Claim Objections
Claims 1, 3-7, and 9 are objected to for improper capitalization. Each claim includes a clause reciting, “The heteroatoms in the heteroaryl . . .” Generally, unless a claim is referring to a proper noun, only the first word of the claim should be capitalized.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 21 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
The claim does not fall within at least one of the four categories of patent eligible subject matter because claim 21 recites a “use” of a product. “Use” claims that do not purport to claim a process, machine, manufacture, or composition of matter fail to comply with 35 U.S.C. 101. In re Moreton, 288 F.2d 708, 709, 129 USPQ 227, 228 (CCPA 1961) (“one cannot claim a new use per se, because it is not among the categories of patentable inventions specified in 35 U.S.C. § 101”). In Ex parte Dunki, 153 USPQ 678 (Bd. App. 1967). See MPEP 2173.05(q).
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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.
Claim 20 is rejected under 35 U.S.C. 112(a) because the specification, while being enabling for the treatment of breast cancer, does not reasonably provide enablement for the prevention of all types of diseases associated with PI3K. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope of claims.
MPEP § 2164.01(a) explains how enablement for the claimed invention can be analyzed:
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is “reasonable” or is “undue.” . . . These factors include, but are not limited to:
(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.
The Wands factors are analyzed with respect to the claimed invention in turn below.
The breadth of the claim is broad in scope. The claim recites: “The compound according to claim 1, or a salt thereof, or a stereoisomer thereof, or a solvate thereof or a hydrate thereof, or a prodrug thereof, or a deuterated compound thereof for use in the manufacture of medicaments for the prevention and/or treatment of diseases associated with PI3K.” The intended use of prevention extends to all possible diseases associated with PI3K with a vast population of subjects. The claim therefore encompasses treating and/or preventing diseases associated with PI3K, which makes the claim extremely broad in nature.
The nature of the invention generally relates to the pharmaceutical art and more specifically to a composition including a compound according to Formula I. The instant specification states: “It has been demonstrated that PI3K is a promising drug target, and using selective PBK inhibitors as anti-tumor medicaments can increase treatment selectivity, and reduce the occurrence of adverse reactions and toxic side effects. The number and structure types of selective PI3K inhibitors currently reported are still quite limited, and their effectiveness needs to be further improved. Studying a PI3K inhibitor with excellent efficacy, as well as minimal adverse reactions and toxic side effects is of great significance for the clinical treatment of cancer.” (Spec. p.1). Thus, the nature of the invention is sophisticated.
The state of the prior art is discussed in the specification as noted above, as well as a review article, which states: “Over three decades of intensive basic research and drug development have resulted in slow yet undeniable progress in targeting the PI3K/mTOR pathway for the treatment of cancer, along with renewed optimism for future success. The rapalogs have generally failed to deliver on expectations that these drugs would be broadly impactful anti-cancer agents, yet the combination of everolimus with aromatase inhibitors is now an approved second-line therapy in hormone-dependent breast cancer. Although early trials with PI3K/mTOR pathway inhibitors were not as successful as hoped, the next wave of clinical trial approaches is likely to improve the clinical outcome in many oncology settings.” (Fruman et al., Cell 170, August 10, 2017; pp. 626-627). Fruman et al., also states: “Idelalisib, a selective PI3Kδ inhibitor, was approved in 2014 for relapsed chronic lymphocytic leukemia (CLL) and two subtypes of non-Hodgkins lymphoma (NHL) in combination with rituximab…Toxicities associated with idelalisib are considered mechanism based, given the similarity to the pathologies seen in mice genetically engineered to lack p110d activity.” (pp. 624-625, Lessons Learned from Clinical Experience with Idelalisib). Accordingly, the state of the prior art is ascending for therapies targeting PI3K for cancer treatment, but the therapies still have failed to be broadly impactful anti-cancer agents and still have serious adverse events and toxicities associated with them.
The level of one of ordinary skill may be found by inquiring into: (i) the type of problems encountered in the art; (ii) prior art solutions to those problems; (iii) the rapidity with which innovations are made; (iv) the sophistication of the technology; and (v) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of the factors may not be present in every case, and one or more of them may predominate. Ent. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983). Based on the typically high education level of workers in the pharmaceutical art and the high degree of sophistication required to solve problems encountered in the art, Examiner finds a person having ordinary skill in the art would have at least a college degree in chemistry, biology, biochemistry, pharmacology, or a related field, and several years of experience.
The level of predictability in the art is generally unpredictable. The relevant art requires each potential drug candidate to be assessed for physiological activity. In re Fisher, 427 F.2d 833, 166 USPQ 18, 24 (CCPA 1970). The more unpredictable an area is the more specific disclosure is necessary to satisfy the statutory requirement. MPEP § 2164.02(II) explains that a correlation between the claimed invention and the evidence provided in an application, along with a correlation between the evidence and the models recognized in the art, are required:
“Correlation” as used herein refers to the relationship between in vitro or in vivo animal model assays and a disclosed or a claimed method of use. An in vitro or in vivo animal model example in the specification, in effect, constitutes a “working example” if that example “correlates” with a disclosed or claimed method invention. If there is no correlation, then the examples do not constitute “working examples.” In this regard, the issue of “correlation” is also dependent on the state of the prior art. In other words, if the art is such that a particular model is recognized as correlating to a specific condition, then it should be accepted as correlating unless the examiner has evidence that the model does not correlate. Even with such evidence, the examiner must weigh the evidence for and against correlation and decide whether one skilled in the art would accept the model as reasonably correlating to the condition. In re Brane, 51 F.3d 1560, 1566, 34 USPQ2d 1436, 1441 (Fed. Cir. 1995) (reversing a USPTO decision based on finding that in vitro data did not support in vivo applications).
Further, treatments may be effective for some subjects and ineffective for other subjects. Thus, each candidate for pharmaceutical or veterinary medicine must be evaluated on its own even when a nexus to an existing drug or class of drugs has been established.
The amount of direction provided by the inventor includes background information as discussed in factor A). The specification does not define the diseases that are associated with PI3K or provide detailed guidance regarding treating and/or preventing the diseases associated with PI3K.
The existence of working examples relates to testing the pharmacokinetics of the compounds in rats and beagle dogs, inhibitory effects on the proliferation of MCF-10A and T47D cells, and pharmacodynamics of the compounds in a xenograft model with MDA-MB-453 cells (Spec., pp. 108-116). The present disclosure does not provide working examples for methods of treating and/or preventing all diseases associated with PI3K.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure is extensive, as it includes in vitro and in vivo screening for each specific disease or disorder encompassed by the claims. As claimed, the indefinite scope of such diseases is essentially unbound.
Scope of Enablement Conclusion
In view of the Wands factors discussed above, the disclosure of the instant application does not reasonably enable a person having ordinary skill in the art to use the full scope of the claimed invention. The breadth of the claims is broad in scope; the nature of the invention is sophisticated; the state of the prior art is ascending for therapies targeting PI3K for cancer treatment, but the therapies still have failed to be impactful anti-cancer agents and still have serious adverse events and toxicities associated with them; the level of skill in the art is high; the pharmaceutical art is unpredictable; the direction provided by the inventor is limited to pharmacodynamics studies in a mice xenograft model of breast cancer; and does not demonstrate treating all specific cancer types within the scope of, “…medicaments for the prevention and/or treatment of diseases associated with PI3K”; and the quantify of experimentation needed to practice the claimed invention is extensive. Thus, when the evidence is considered as a whole, undue experimentation would be required to practice the full scope of the claimed invention.
Examiner recommends amending the claim to delete the intended use phrases or to recite the specific diseases as well as deleting the term “preventing.”
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 19-21 are rejected under 35 U.S.C. 112(b), or 35 U.S.C. 112 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c),(d). In the present instance, claims 19 and 21 recite broad recitations “PI3K inhibitors” and “cancer,” respectively, and the claims also recites “preferably… [examples of the broad recitation],” which is the narrower statement of the broad limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 20-21 recite “diseases related to PI3K” and “diseases associated with PI3K,” respectively. The terms “associated” in claim 20 and “related” in claim 21, are relative terms that render the claims indefinite. The terms are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The relative terms render the diseases unclear, because it is difficult to discern if the relative terms are defining, for example, direct or indirect interaction or up-regulation or down-regulation activities of PI3K in the diseases “related” and/or “associated” with it.
Claim 21 recites “use” of a product. Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. Ex parte Erlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986). See MPEP 2173.05(q). Accordingly, the instant “use” claim is indefinite because it recites a use of a product without setting forth any active steps defining how the use is practiced, leaving the metes and bounds of the claim unclear.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 1-7, 19-20, and 22 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by WO2021202964 (IDS-January 7, 2025, Foreign Patent Document Cite No. 8) (“Anderson ‘964”).
Anderson ‘964 teaches compound (R)-N-[(1R)-1-(2-ethylsulfanyl-6-methyl-4-oxo-chromen-8-yl)ethyl]-2-methyl-propane-2-sulfinamide with the structure,
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171
268
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, a species of Formula I:
R1 is a methyl group and m is 1;
R2 is ethanethiol;
R3 is
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97
96
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, where R7 is tert-butyl;
Y1 and Y2 are C substituted with methyl, and NH, respectively; and
the core structure is a chromone (p. 246, Step 2).
This compound anticipates claims 1-4.
Anderson ‘964 also teaches additional compounds with the same chromone core structure, but with a substituted heterocycle, morphinyl, at the R2 position and a substituted aryl with a carboxylic acid at the R3 position, like compound
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127
238
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(p. 291, Table 7, #122). Similar substituted heterocycles at the R2 position, piperidyl, with trifluoromethyl and/or a halogen at the R1 position are also taught,
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201
324
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and
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131
215
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(p. 350, Table 23, #339-340; p. 343, Table 20, #317-318). These additional compounds anticipate claims 5-7.
Regarding claim 19, Anderson ‘964 teaches the compounds disclosed are allosteric chromenone inhibitors of phosphoinositide 3-kinas (PI3K) (Abstract). The intended use language “…for use in the manufacture of PI3K inhibitors…” does not provide further structure to the composition claimed and is not given much patentable weight (MPEP §2111.02).
Regarding claim 20, Anderson ‘964 teaches the compounds disclosed a pharmaceutically acceptable salt, prodrug, solvate, hydrate, isomer, or tautomer thereof, in the manufacture of a medicament for treating or preventing a disease or disorder disclosed herein. The intended use language “…for use in the manufacture of medicaments for the prevention and/or treatment of diseases associated with PI3K.” does not provide further structure to the composition claimed and is not given much patentable weight (MPEP §2111.02).
Regarding claim 22, Anderson ‘964 teaches pharmaceutical compositions where the compounds disclosed are the active ingredient and the compositions contains one or more pharmaceutically acceptable carrier or excipients (¶ [1052]). Suitable acceptable excipients include those selected from the group consisting of a solubility enhancing agent, chelating agent, preservative, tonicity agent, viscosity/suspending agent, buffer, and pH modifying agent, and a mixture thereof (¶[1055]).
Claims 1-8 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO2022235574 (IDS-January 7, 2025, Foreign Patent Document Cite No. 5; Effective Filing Date: May 3, 2021) (“Anderson ‘574”).
Anderson ‘574 teaches compound
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120
176
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, which is a species of Formula II-5:
R1 is a methyl group and m is 1;
R2 is a substituted aryl, where R2’ is a halogen and a is 1;
R3 is an aryl group substituted with a carboxylic acid, where Z1 is CH, and R61 is H;
Y1 and Y2 are C substituted with methyl, and NH, respectively; and
the core structure is a chromone (p. 299, claim 42).
Additional compounds with the same structure but a different R2’, such as a cyano group, and a methyl group (Id.). These compounds anticipate claim 8.
Claims 1 and 9-16 is rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO2023159155 (Effective Filing Date: February 18, 2022) (“Cee”).
Cee teaches compound 209,
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176
194
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, which is a species of Formulae I and III-1-8:
R1 is a methyl group and m is 1;
R2 is a phenyl group;
R3 is an aryl group substituted with a carboxylic acid and a halogen R6, where n is 1;
Y1 and Y2 are C substituted with methyl, and NH, respectively; and
the core structure is a quinazolinone (p. 289).
This compound anticipates claims 1 and 9-16.
Claims 1 and 17 is rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO2023060262 (IDS-January 7, 2025, Foreign Patent Document Cite No. 1; Effective Filing Date: October 7, 2021) (“Boezio”).
Boezio teaches compound I-271,
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230
250
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, which is a species of Formulae I and IV:
Z2 is N;
R62 is a carboxyl group;
(R2’)a where a is 0; and
the core structure is a 4H-Pyrido[1,2-a]pyrimidin-4-one (p. 217, Table 1).
This compound anticipates claims 1 and 17.
Claims 1 and 18 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO2022251482 (IDS-January 7, 2025, Foreign Patent Document Cite No. 6; Effective Filing Date: July 30, 2021) (“Anderson ‘482”).
Anderson ‘482 teaches compound
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156
261
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, which is a species of Formula I and the same compound instantly claimed (p. 506).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAHIL CHANDER AGGARWAL whose telephone number is (571)272-7755. The examiner can normally be reached 7am-5pm.
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/SAHIL CHANDER AGGARWAL/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
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