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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/29/2026 has been entered.
Status of the Application
Claims 13-15, 21-24, 26-36, and 38-39 are pending.
Receipt and consideration of Applicants' amended claim set and remarks/arguments filed on 05/29/2026 are acknowledged. Claims 13, 15, 21, 32, and 36 are amended and new claims 38-39 are added. Claims under consideration in the instant office action are claims 13-15, 21-24, 26-36, and 38-39.
Applicants' arguments, filed 05/29/2026, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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 13-15, 27-32, and 35-36 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. claim 13). Regarding the amendment of claim 13, filed 05/29/2026, Koyama et al. teaches the administration of BPS in an amount of 120 μg/day, 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.
Claims 21-24, 26, 33-34, and 38-39 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 13-15, 27-32, and 35-36 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). Mak et al. teaches that “The wasting/cachexia syndrome in CKD patients consists of anorexia, increased energy expenditure, decreased protein stores characterized by a low serum albumin, and loss of body weight and loss of muscle mass.” (pg. 10, left and right column, bridging paragraph), and specifically a serum albumin level of < 3.2 g/dL (see Fig. 1).
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.
Even though the range for serum albumin levels and BMI as taught by Mak et al. is not the same as the claimed levels, Mak et al. does teach an overlapping range of serum creatinine levels and BMI, 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 albumin levels and BMI 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.
Response to Arguments
Applicant argues that “the clinical data derive from the CASSIOPEIR trial, a large-scale, randomized, double-blind, placebo-controlled study that enrolled 892 CKD patients and followed them for up to 4 years, administering the identical BPS sustained-release formulation at 240 μg/day-the same drug, formulation, and dosage described in Koyama.” The Examiner respectfully disagrees since Koyama et al. teaches the treatment regimen as noted by Applicant. 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. Applicant has not provided evidence of unexpected results over the teachings of the prior art.
Conclusion
Claims 13-15, 21-24, 26-36, and 38-39 are rejected.
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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/ANDREW P LEE/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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