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 Application
Claims 13-16, 21-24, and 26-37 are pending.
Receipt and consideration of Applicants' amended claim set and remarks/arguments filed on 09/08/2025 are acknowledged. Claim 15 is amended and new claims 27-37 is added. Claims under consideration in the instant office action are claims 13-16, 21-24, and 26-37.
Applicants' arguments, filed 09/08/2025, have been fully considered but they are not deemed to be persuasive. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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.
Claims 13-16, 27-32, and 35-37 are rejected under 35 U.S.C. 103 as being unpatentable over Koyama et al. (Orally active prostacyclin analogue beraprost sodium in patients with chronic kidney disease: a randomized, double-blind, placebo-controlled, phase II dose finding trial, BMC Nephrology, 2015, 16(165), pp. 1-15, as disclosed in IDS) in view of Salle (EP 1 479 383).
Koyama et al. teaches “Beraprost sodium (BPS) is an orally active prostacyclin (PGI2)
analogue demonstrating prevention of the progression of chronic kidney disease (CKD) in various animal models by maintaining renal blood flow and attenuating renal ischemic condition. This multicenter, randomized, double-blind, placebo-controlled, phase II trial was designed to determine the recommended dose of the sustained-release form of BPS (TRK-100STP 120 μg/day or 240 μg/day) in Japanese patients with CKD.” (see abstract). Koyama et al. teaches “An increasing number of patients with end-stage renal disease (ESRD) require dialysis or transplantation. Although diabetic nephropathy is a major reason for eventual ESRD, primary glomerular diseases and nephrosclerosis still comprise significant proportions of chronic kidney disease (CKD) patients, especially in Asian countries.” (pg. 1, left column, first paragraph). Koyama et al. teaches Inclusion criteria wherein female subjects were selected with serum creatinine levels of 1.30 – 4.00 mg/dL and male subjects with serum creatinine levels of 1.50 – 4.50 mg/dL (see Fig. 2). Koyama et al. teaches “Ratio of eGFR (the final evaluation point/W0) was assessed by ANCOVA with the SCr (R20) as covariate.” (pg. 7, right column, third paragraph). Koyama et al. teaches that “TRK-100STP may be a useful for treatment of CKD patients in combination with ACEIs or ARBs.” (pg. 12, left and right column, bridging paragraph). As a consequence it would follow that one of ordinary skill in the art would administer BPS and angiotensin-converting enzyme inhibitors (ACEI) simultaneously for the treatment of CKD.
Koyama et al. does not teach wherein the serum creatinine level of 2.0 mg/dl or more and less than 3.0 mg/dl. Koyama et al. does not teach a sustained-release formulation comprising beraprost sodium.
Salle is drawn towards oral sustained-release compositions comprising beraprost sodium (see abstract). Salle teaches sustained-release compositions that provides stable release and absorption following a meal (paragraph 0007).
It would have been obvious to one of ordinary skill in the art to select a patient wherein the serum creatinine level of 2.0 mg/dl or more and less than 3.0 mg/dl, as suggested by Koyama et al., and produce the instant invention.
Even though the range for serum creatinine levels as taught by Koyama et al. is not the same as the claimed levels, Koyama et al. does teach an overlapping range of serum creatinine levels, and it has been held that in the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See MPEP § 2144.05(I). Furthermore, the determination of serum creatinine levels is well within the purview of those skilled in the art through routine experimentation, and it has been held that “it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP § 2144.05(II). It would have been obvious to one of ordinary skill in the art to optimize the serum creatinine levels in order to determine the appropriate patient population.
The amounts of active agents to be used, the pharmaceutical forms, e.g., tablets, etc; mode of administration, flavors, surfactant are all deemed obvious since they are all within the knowledge of the skilled pharmacologist and represent conventional formulations and modes of administration.
Furthermore, no unobviousness is seen in the ratio claimed because once the usefulness of a compound is known to treat a condition, it is within the skill of the artisan to determine the optimum ratio.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to formulate an oral sustained-release composition comprising beraprost sodium, as suggested by Salle, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since Salle teaches sustained-release compositions that provides stable release and absorption following a meal (paragraph 0007), with a reasonable expectation of success absent evidence of criticality of the particular steps.
With regards to the limitation claimed in instant claims 15 and 25, which claims a range of eGFR values, Koyama et al. does not specifically teach the exact amounts claimed in instant claims 15 and 25. However, it would be within the skill of an ordinary artisan to be able to modify the criteria for eGFR values in order to obtain the desired patient population. It is noted that "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
When the composition recitations are met, the desired properties are met, as any component that materially affects the composition and its properties would have to be present in the claim to be commensurate in scope (i.e. claims 16, 27). Additionally, when the composition is delivered in the same manner as claimed, the effects of the composition would be the same such as the therapeutic profile, as they are a direct result of the components of the composition and the mode of administration which are met by the art, whereby the resulting properties and effects would intrinsically be met. 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. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01.
Response to Arguments
Applicant argues that “in the present application, it is important to be able to prevent dialysis shift or renal death only in a limited subset of patients when administered at 240 μg, and this cannot be inferred from Koyama.” The Examiner respectfully disagrees since although Koyama does not explicitly recite the intended purpose of preventing dialysis shift or renal death, Koyoma does disclose preventing the progression of CKD by administering 240 μg of beraprost sodium , which would include dialysis shift or renal death (see abstract). Koyama et al. teaches Inclusion criteria wherein female subjects were selected with serum creatinine levels of 1.30 – 4.00 mg/dL and male subjects with serum creatinine levels of 1.50 – 4.50 mg/dL (see Fig. 2). Koyama et al. teaches “Ratio of eGFR (the final evaluation point/W0) was assessed by ANCOVA with the SCr (R20) as covariate.” (pg. 7, right column, third paragraph). Koyoma thus reads on the active steps of the claimed invention for an overlapping patient population, and renders the claimed invention obvious.
Claims 21-24, 26, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Koyama et al. (Orally active prostacyclin analogue beraprost sodium in patients with chronic kidney disease: a randomized, double-blind, placebo-controlled, phase II dose finding trial, BMC Nephrology, 2015, 16(165), pp. 1-15, as disclosed in IDS) and Salle (EP 1 479 383) as applied to claims 13-16, 27-32, and 35-37 above and further in view of Mak et al. (Wasting in chronic kidney disease, J. Cachexia, Sarcopenia Muscle, 2011, 2, pp. 9-25).
The teachings of Koyama et al. and Salle are presented above.
Koyama et al. and Salle do not teach the subject with a nutritional disorder.
Mak et al. is drawn towards wasting in CKD, which is prevalent among CKD patients (see abstract). Mak et al. teaches “In the context of CKD, the term protein–energy wasting (PEW) has been proposed by The International Society of Renal Nutrition and Metabolism (ISRNM) to describe a “state of decreased body stores of protein and energy fuels (body protein and fat masses).” (pg. 10, right column, second paragraph). Mak et al. teaches “The proposed criteria for a diagnosis of PEW fall into four distinct categories: (1) biochemical indicators, (2) low body weight, reduced body fat or weight loss, (3) decreased muscle mass, and (4) low protein or energy intake (Table 1).” (pg. 11, left column, first paragraph). Mak et al. teaches a criteria of BMI < 20 kg/m2 (pg. 11, left column, first paragraph).
It would have been obvious to one of ordinary skill in the art to treat a subject with a nutritional disorder, as suggested by Mak et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since cachexia is prevalent among CKD patients as taught by Mak et al., with a reasonable expectation of success absent evidence of criticality of the particular steps.
Conclusion
Claims 13-16, 21-24, and 26-37 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREW P LEE whose telephone number is (571)270-1016. The examiner can normally be reached Monday-Friday 9am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Renee Claytor can be reached at (571)272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ANDREW P LEE/Examiner, Art Unit 1691
/SAVITHA M RAO/Primary Examiner, Art Unit 1691
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