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
Claims 1-25 are pending. Claims 1-25 are rejected.
Information Disclosure Statements
The Information Disclosure Statements (IDS’s) submitted on 4/12/2024 and 4/25/2025 were considered by the Examiner.
Claim Objections
Claim 6 is objected to because of the following informalities: Line 1, “Claim 5” should recite “claim 5”. Appropriate correction is required.
Claim 8 is objected to because of the following informalities: Line 1, “Claim 7” should recite “claim 7”. Appropriate correction is required.
Claim 9 is objected to because of the following informalities: Line 1, “Claim 8” should recite “claim 8”. Appropriate correction is required.
Claim 10 is objected to because of the following informalities: Line 1, “Claim 9” should recite “claim 9”. Appropriate correction is required.
Claim 14 is objected to because of the following informalities: Line 1, “Claim 13” should recite “claim 13”. Appropriate correction is required.
Claim 15 is objected to because of the following informalities: Line 1, “Claim 13” should recite “claim 13”. Appropriate correction is required.
Claim 18 is objected to because of the following informalities: Line 1, “Claim 17” should recite “claim 17”. Appropriate correction is required.
Claim 21 is objected to because of the following informalities: Line 1, “Claim 8” should recite “claim 8”. Appropriate correction is required.
Drawings
The drawings are objected to because Fig. 4 is blurry. 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.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 25 is 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.
Claim 25 recites the limitation "the pediatric subject" in line 1. There is insufficient antecedent basis for this limitation in the claim. Examiner recommends amending claims to clearly indicate where “the pediatric subject” is properly introduced.
Claim 25 recites the limitation "TZD therapy" in line 2. There is insufficient antecedent basis for this limitation in the claim. Examiner recommends amending claims to clearly indicate where “TZD therapy” is properly introduced.
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.
Claim(s) 1, 5, 7, 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, 25 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Agrawal et al. (Scientific Reports, 2016, 6:24392, p. 1-9).
Regarding instant claims 1, 7, 8, 11, 13-15, Agrawal teaches that pioglitazone (a PPARy agonist and thiazolidinedione) can be used to treat nephrotic syndrome and enhances the beneficial effects of glucocorticoids (see title). “Glucocorticoids are the primary therapy for nephrotic syndrome (NS), but have serious side effects and are ineffective in ~20-50% of patients. Thiazolidinediones have recently been suggested to be renoprotective, and to modulate podocyte glucocorticoid-mediated nuclear receptor signaling” (see abstract). Specifically, regarding instant claim 9, Agrawal teaches the GC used in Animal Study Design was methylprednisolone (see Methods: Animal Study Design p. 7). Specifically, regarding instant claim 12, Agrawal discloses Pio [pioglitazone] with low dose GC in Figure 4B:
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.
Regarding instant claim 5, Agrawal explains the following: “While a single case report certainly cannot imply cause and effect, the addition of pioglitazone to the treatment regimen of the child [with glucocorticoids] with refractory NS was associated with clinically important improvements in his condition” (see p. 7, 3rd para.). Regarding instant claim 25, which has been rejected under 112(b) supra for being indefinite, a child would be expected to be within the range of 1-17 years at initiation of TZD therapy, as this is the encompassing range of childhood.
Regarding instant claim 16, Agrawal teaches administering 10 mg/kg of Pio, which would equate to 30 mg (within the instantly claimed range) for a 3 kg child.
Regarding claim 17, Agrawal teaches pioglitazone was found to significantly reduce puromycin aminonucleoside-induced proteinuria, a type of proteinuria (see abstract).
Regarding claim 18, Agrawal discloses the following table:
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, wherein all the levels treated with “Pio” were lower on Day 11 than the “PAN”. Additionally, “Pio +high dose GC” is almost to control levels at Day 11. Eleven days is within 5-7 months, as instantly claimed and claim 1 uses the transitional phrase “comprising” which does not limit the inclusion of other treatments.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 6 and 19-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agrawal et al. (Scientific Reports, 2016, 6:24392, p. 1-9).
**The 102 rejection of claims 1, 5, 7, 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, 25 over Agrawal supra is incorporated herein by reference.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Agrawal teaches the treatment of a child with Pio + GC. Additionally, Agrawal fails to specifically disclose the following:
Wherein administering the PPARy agonist increases the level of serum albumin in the subject;
Wherein administering the PPARy agonist produces an immunosuppressive medication/glucocorticoid sparing effect;
Wherein NS is treated without any consequential adverse effects.
Regarding albumin levels, Agrawal teaches that after the treatment (Pio + GC), the need for albumin infusions was eliminated (see p. 6, third para.).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Agrawal fails to disclose the age of the child. Additional dependent limitations will be addressed below.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
Regarding instant claim 6, it would have been obvious to a PHOSITA to explore the age range of 1-12 with a reasonable expectation of success because a “child” was successfully treated. The total age range of being a child is 1-17, with 1-12 falling within that range. “In the case where the claimed ranges ’overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists.” MPEP 2144.05(I). As a result of routine optimization, a PHOSITA would have been motivated to treat a pediatric subject that has an age from 1-12 years, as needed.
Regarding instant claim 19, it would have been obvious to a PHOSITA that serum albumin was increased in the subject post PPARy agonist. Additionally, claim 1, from which claim 19 depends uses the transitional phrase “comprising” which does not eliminate the administration of another agent (including GC). If the need for albumin infusions was eliminated by the prior art treatment, a skilled artisan would have been motivated to investigate the successful replenishment of serum albumin in the subject.
Regarding instant claims 20-21, it would have been obvious to a PHOSITA that there was an immunosuppressive medication/glucocorticoid sparing effect because treatment was effect with Pio + lower than standard therapy GC (see Table 1 supra). The effectiveness of treatment while being able to lower GC (immunosuppressive medication) would imply to a skilled artisan that the GC was being spared in the subject. Additionally, regarding instant claim 22, Agrawal does not teach consequential adverse effects of the treatment of claim 1. Therefore, a skilled artisan would have a reasonable expectation of success that such a treatment would result without any consequential adverse effects.
Claim(s) 2-3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agrawal et al. (Scientific Reports, 2016, 6:24392, p. 1-9), in view of Dakshayani et al. (Turk Pediatri Ars, 2018; 53: 24-30—disclosed on 4/12/2024 IDS).
**The 102 rejection of claims 1, 5, 7, 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, 25 over Agrawal supra is incorporated herein by reference.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Agrawal fails to disclose treatment of nephrotic syndrome that is steroid-dependent nephrotic syndrome (SDNS) or frequent relapsing nephrotic syndrome (FRNS).
Dakshayani discloses steroid-dependent nephrotic syndrome and frequent relapsing nephrotic syndrome (NS is steroid-dependent; NS with frequent relapses—see p. 24, 1st column, 1st para.) “The majority of children have steroid-sensitive nephrotic syndrome (SSNS). Although SSNS has a favorable long-term outcome, about half of all patients with SSNS become frequent relapsers and or steroid dependent and may experience several adverse effects secondary to the disease or its treatment” (p. 24, 1st column).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
There is not a single embodiment in the art of treating SDNS or FRNS with a PPARy agonist.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
Regarding instant claims 2-3, it would have been obvious to a PHOSITA to explore treatment of both SDNS and/or FRNS with a PPARy agonist as both types of nephrotic syndrome are common and disruptive to patients. A skilled artisan would have been motivated to explore a successful nephrotic syndrome treatment on both the specific types: SDNS and FRNS, with a reasonable expectation of success in treatment efficacy.
Claim(s) 4 and 23-24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agrawal et al. (Scientific Reports, 2016, 6:24392, p. 1-9), in view of Troost et al. (Clinical Kidney Journal, 2020, vol. 13, no. 4, 597-606—disclosed on 4/12/2024 IDS).
**The 102 rejection of claims 1, 5, 7, 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, 25 over Agrawal supra is incorporated herein by reference.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Agrawal fails to disclose treatment of nephrotic syndrome wherein the subject has focal segmental glomerulosclerosis. Agrawal also fails to disclose wherein administering the PPARy agonist produces an improvement in PROs in the subject or an improvement in edema.
Troost teaches: “Focal segmental glomerulosclerosis (FSGS) is a common cause of nephrotic syndrome, frequently chronic and progressive in nature, and accounts for ~12% of children and 3% of adults with incident end-stage kidney disease in the USA” (see p. 599, left column).
Troost discloses an improvement in PROs including physical, mental, social and global health with NS treatment (see p. 599, 2nd column, 3rd para. Table 2). Troost additionally teaches the following regarding edema: “children with edema had significantly worse mobility, fatigue, pain interference and anxiety when compared to children with no edema” (see p. 603, 2nd column, 4th para.).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
There is not a single embodiment in the art of treating nephrotic syndrome with a PPARy agonist, wherein the subject has focal segmental glomerulosclerosis. Additional dependent limitations will be addressed below.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
Regarding instant claim 4, it would have been obvious to a PHOSITA to explore successfully demonstrated nephrotic syndrome treatment to a subject who has focal segmental glomerulosclerosis because focal segmental glomerulosclerosis is a known common cause of NS. A skilled artisan would have been motivated to explore treatment of NS for a patient who already has the cause of focal segmental glomerulosclerosis with a reasonable expectation of success in treatment efficacy.
Regarding instant claims 23-24, it would have been obvious to a PHOSITA to improve both PROs and edema in patients suffering from nephrotic syndrome, as these are both indicators of treatment success. A skilled artisan would have been motivated to improving patient health and comfort and reduce swelling to increase patient quality of life.
Claim(s) 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agrawal et al. (Scientific Reports, 2016, 6:24392, p. 1-9), in view of Kim J.S. et al. (Kidney International, Vol. 68, 2005, 1275-1281—disclosed on 4/12/2024 IDS).
**The 102 rejection of claims 1, 5, 7, 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, 25 over Agrawal supra is incorporated herein by reference.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Agrawal does not disclose when the glucocorticoid is prednisone.
Kim teaches treatment of nephrotic syndrome with prednisone (see p. 1276, left column, 4th para.).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
There is not a single embodiment in the art of a PPARy agonist used with prednisone for nephrotic syndrome.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
Regarding instant claim 10, it would have been obvious to a PHOSITA to explore the use of prednisone, as this had been previously demonstrated for use with nephrotic syndrome. Prednisone is a known glucocorticoid by which a skilled artisan would have been motivated to explore its utility with a PPARy agonist, specifically for the treatment of nephrotic syndrome, with a reasonable expectation of success.
Conclusion
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/MEGHAN C HEASLEY/Examiner, Art Unit 1626