DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s Response to Election/Restriction Filed and Arguments/Remarks, filed 26 September 2025, have been entered. Claims 1-21 are currently pending. Claims 1 and 12 are independent claims. Applicant’s election of the following species:
Compounds that modulate PI5P4Kbeta: a. PI5P4Kbeta inhibitors: viii. IMPDH inhibitors: 1. mycophenolic acid (MPA),
without traverse in a reply filed 26 September 2025 is acknowledged. Note that species election was previously made between a) Pl5P4Kbeta inhibitors and b) Pl5P4Kbeta agonists.
Claims 4, 8-11, and 17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a species, there being no allowable generic or linking claim.
Claims 1-3, 5-7, 12-16, and 18-21 are currently pending in the application and under examination to which the following grounds of rejection are applicable. An action on the merits follows.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US2021/020405, filed 02 March 2021, which claims priority to U.S. Provisional Application No. 62/984,026, filed 02 March 2020.
Thus, the earliest possible priority for the instant application is 02 March 2020.
Information Disclosure Statement
The information disclosure statements filed 23 May 2023 and 01 March 2024 have been considered by the Examiner.
Specification
The disclosure is objected to because of the following informalities: the Brief Description of the Drawings does not include a description of each panel. Specifically, the descriptions of Figure 6 does not include individual descriptions of panels A and B and Figure 13 does not include individual descriptions of panels A, B, and C. See MPEP 608.01(f), which states, “When there are drawings, there shall be a brief description of the several views of the drawings and the detailed description of the invention shall refer to the different views by specifying the numbers of the figures, and to the different parts by use of reference letters or numerals”. Further, MPEP 608.01(f) instructs Examiners such that “If the drawings show Figures 1A, 1B, and 1C and the brief description of the refers only to Figure 1, the examiner should object to the brief description, and require applicant to provide a brief description of Figures 1A, 1B, and 1C.” Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 5-7, 12-16, and 18-21 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.
Independent claim 1 recites, “when the subject suffers from” in line 5 and in line 7, which is indefinite because it is unclear if the administration is being limited in time such that the administration is occurring only when the subject is suffering, or if the administration is meant to occur anytime that the patient is presenting with the claimed metabolic disorder. As such, the metes and bounds of the claim cannot be determined.
Independent claim 1 and independent claim 12 each recite, “an effective amount” of a compound that modulates PI5P4Kβ kinase activity [lines 3-4 of claim 1] or of a PI5P4Kβ inhibitor [claim 12 lines 2-3]. The term “effective” in claims 1 and 12 is a relative term which renders the claim indefinite. The term “effective” is 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 specification teaches “the term ‘effective amount’ refers to an amount sufficient to achieve beneficial or desired results” [page 9 lines 23-24]. However, this definition is itself indefinite in reciting “sufficient to achieve beneficial or desired results” as such beneficial or desired results are not taught by the specification nor the claims. As such, the metes and bounds of the claim cannot be determined.
Claims 2-3, 5-7, 13-16, and 18-21 are included in this rejection due to their dependence on independent claims 1 or 12.
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.
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, 5-7, 12-16, and 18-21 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The broadest independent claim, claim 1, is drawn to a method for treating a metabolic disorder associated with abnormal bodyweight in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound that modulates phosphatidylinositol 5-phosphate 4-kinase beta (PI5P4Kβ) kinase activity, wherein a PI5P4Kβ inhibitor is administered when the subject suffers from a metabolic disorder associated with an underweight bodyweight; and wherein a PI5P4Kβ agonist is administered when the subject suffers from a metabolic disorder associated with an overweight or obese bodyweight. Claims 2-3 and 5-7 depend on independent claim 1. Independent claim 12 is drawn to a method for treating cachexia in a subject in need thereof, the method comprising administering to the subject an effective amount of a PI5P4Kβ inhibitor. Claims 13-16 and 18-21 are dependent on independent claim 12.
Applicant has elected an PI5P4Kβ inhibitor as the PI5P4Kβ modulator, and the IMPDH inhibitor mycophenolic acid (MPA) as the PI5P4Kβ inhibitor.
The working examples of the specification disclose a Pip4k2bF205L/F205L knock-in mutant mouse, wherein the F205L mutant decreases the GTP sensing activity of PI5P4Kβ, and wherein the homozygous PIP4k2bF205L/F205L mice demonstrate increased bodyweight and increased fat deposits in the liver on a high fat diet [page 3 line 26– page 4 line 2, page 4 lines 7-15, page 5 lines 2-5, Figure 1, 3D]. The specification does not provide any bodyweight data for any conditions other than the data for the Pip4k2bF205L/F205L knock-in mutant mouse on a normal diet (indicating no significant difference in body weight) or a high fat diet (indicating a small significant increase in bodyweight) [Figures 1 and 3].
The specification also teaches administration of the IMPDH inhibitor MPA to MEF cells, wherein MEFs treated with MPA demonstrate suppressed lysosomal acidification under serum-starved conditions in cells expression WT PI5P4Kβ [page 5 lines 10-14, Figure 5]. The specification does not any data for any treatments with MPA other than assessment of lysosomal acidification upon treatment of MEF cells with MPA in culture. The specification does not provide any data resulting from administration of MPA to any subject. Specifically, the specification does not teach any data regarding bodyweight effects upon treatment with the IMPDH inhibitor MPA.
The claims as written read broadly on the administration of any PI5P4Kβ inhibitor (e.g., the elected IMPDH inhibitor MAP) when the subject suffers from a metabolic disorder associated with an underweight bodyweight. Independent claim 12 specifically recites administration of the elected inhibitor to a subject for treating cachexia. While the specification provides broad generalized descriptions of administration of a PI5P4Kβ inhibitor (including the elected IMPDH inhibitor MAP) [e.g., page 14 lines 6-15], the working examples do not exemplify the administration of any inhibitor/drug to any subject suffering from any metabolic disorder associated with any underweight bodyweight, including a lack of data for administration of any inhibitor/drug to any subject for treating cachexia. The specification does not provide an enabling disclosure for treating a metabolic disorder associated with abnormal bodyweight in a subject in need thereof, wherein a PI5P4Kβ inhibitor (e.g., the elected IMPDH inhibitor MAP) is administered when the subject suffers from a metabolic disorder associated with an underweight bodyweight (e.g., cachexia).
At the time of filing, the art teaches the administration of the elected IMPDH inhibitor MAP for treating disorders associated with increased bodyweight (e.g., obesity), such that IMPDH inhibitors are used for the negative regulation of adipogenesis, including down-regulating the differentiation potential and/or proliferation of preadipocytes and/or the accumulation of lipids in adipocytes [Whitehead (US20060106097A1, published 18 May 2006), 0001, 0015, 0133]. Whitehead teaches that MPA treatment blocks lipid accumulation and adipocyte differentiation [0041, 0044, 0789-0790, 0792, Figure 9, 12]. Whitehead further teaches the administration of IMPDH agonists for the treatment of metabolic disorders associated with decreased bodyweight, such as cachexia [0016, 0025].
Further, Sumita teaches that PI5P4Kβ knockout mice have reduced body weight and resistance to obesity induced by high-fat diets [Sumita et al. 2016, Molecular Cell, 61, 187-198, IDS, column 18 ¶ 2]. Maes teaches that some patients treated with MMF (a pro-drug for MPA) as an immunosuppressant following renal transplantation present with a significant decrease in body weight [Maes et al. 2003, Transplantation, 75(5), 665-672, column 6 ¶ 2].
Thus, at the time of filing, the ordinarily skilled artisan would have expected administration of MPA to result in loss of body weight, and not an increase of body weight. As taught by Whitehead, an ordinarily skilled artisan would therefore have used MPA as a treatment for conditions associated with an overweight or obese body weight rather than as a treatment for conditions associated with an underweight bodyweight. Therefore, the ordinarily skilled artisan would have considered treatment of conditions associated with an underweight bodyweight by administration of the IMPDH inhibitor MPA as highly unpredictable.
Applicant’s disclosure does not overcome this art recognized unpredictability as the disclosure does not provide sufficient guidance for treating a subject having a condition associated with an underweight bodyweight using the elected PI5P4Kβ inhibitor (e.g., the IMPDH inhibitor MPA), nor any other inhibitor.
Therefore, in view of the state of the art at the time of filing for using IMPDH inhibitors (e.g., MPA) to treat obesity; the art teachings that PI5P4Kβ knockout mice have reduced body weight and resistance to obesity induced by high-fat diets; the art teachings that some human patients taking MPA experience weight loss side effects; the art recognized unpredictability for treating a condition associated with an underweight bodyweight by administration of MPA; the lack of teachings in the working examples demonstrating the effects of MPA (nor any other drug) on bodyweight; the limitation of the working examples with regards to bodyweight to the comparison of wild-type mice vs mice having a single point mutation of PI5P4Kβ; and the breadth of the claims; it would have required undue experimentation to practice the methods of treating a metabolic disorder associated with abnormal bodyweight in a subject in need thereof comprising administering to the subject an effective amount of a compound that modulates PI5P4Kβ kinase activity, wherein a PI5P4Kβ inhibitor is administered when the subject suffers from a metabolic disorder associated with an underweight bodyweight without undue experimentation.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Dr. KATIE L PENNINGTON whose telephone number is (703)756-4622. The examiner can normally be reached M-Th 8:30 am - 5:30 pm, Friday 8:30 am - 12:30 pm CT.
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DR. KATIE L. PENNINGTON
Examiner
Art Unit 1634
/KATIE L PENNINGTON/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634