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 .
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 30 March 2026 has been entered.
Applicant’s amendment of 30 March 2026, in which claim 72 has been amended, claims 73, 75-77 have been cancelled, and new claims 79, 80 have been added, is acknowledged.
Claims 72, 74, 78-80 are pending in the instant application.
Claims 72, 74, 78-80 are examined herein.
Response to arguments of 30 March 2026
In view of Applicant’s amendment of 30 March 2026, all the rejections to claims 73, 75-77 are herein withdrawn. Claims 73, 75-77 have been cancelled.
In view of Applicant’s amendment of 30 March 2026, the rejection of claims 72-78 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, written description/new matter, is herein withdrawn. Applicant has deleted from claim 72 the recitation “subject is not suffering from metabolic acidosis”.
Applicant’s arguments (Remarks of 30 March 2026, pages 5-12) against the rejection of claims 72-78 under 35 U.S.C. 103 over Loniewski, in view of Niwa, are acknowledged. On 30 March 2026, Applicant has amended claim 72 to recite that the method is to treat or prevent uremia.
Applicant argues (point 2(a), pages 6-8) that Loniewski relates to preventing progression of CDK with sodium bicarbonate, and that the effects of Polycitra are due to bicarbonate in the body upon administration of the citric acid preparation (page 6, last two paragraphs).
Applicant refers to Tables 1-1-1 and 1-2-1 of the application and argues (page 7, page 8, first paragraph) that the combination preparation of hydrates of sodium citrate and potassium citrate has been shown to be highly effective in excreting indoxyl sulfate from the body (decreased the amount of indoxyl sulfate in the blood and increased the amount of indoxyl sulfate in the urine), compared to sodium bicarbonate administration group and the control group.
In response, the examiner acknowledges the data presented by Applicant. However, Loniewski teaches (page 533, right column, first paragraph under Galenic forms, also Table 4) administration of Polycitra, which is an oral pharmaceutical composition comprising Na citrate and K citrate (and thus an alkalinizing agent of the instant claims), to patients suffering from CKD, which are the very patients in the instant claims.
Thus, Loniewski teaches administration of the same therapeutic agent, combination Na citrate and K citrate (Polycitra), to the same patient population, patients suffering from chronic kidney disease, as in the instant claims.
Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. See MPEP 2145.II. In this case, the closest prior art, Loniewski, teaches that a combination of sodium citrate and potassium citrate (Polycitra), is administered to CKD patients to treat treat/suppress progression of CKD in said patients. Since administration of a combination of sodium citrate and potassium citrate alkalinizing agents (as Polycitra) to patients suffering from CKD was known (Loniewski), determining the effect of the therapeutic agent/combination on the concentration of indoxyl sulfate in blood and urine of the CKD patients treated with said combination, and investigating the mechanism of action for said combination, will not render the method unobvious because the instantly claimed increase in excretion of indoxyl sulfate into urine and decrease in concentration of indoxyl sulfate in the blood of said patients would necessarily occur with the administration of sodium citrate and potassium citrate.
Applicant argues (point 2(b), pages 8-12) that the instant claims are directed to a patient with stage G2 to stage G3b chronic disease.
In response, Loniewski teaches (Table 2, reference by Phisitkul) administering oral sodium citrate at a dose equivalent to 1 mEq NaHCO3/kg b.w. daily, to patients with eGFR 20-60 ml/min per 1.73 m2, which are patients with stage G3a and stage G3b CKD, included in the patient population of instant claim 72, to treat CKD.
Applicant submits a reference by Shah (2009) and seems to argue (pages 8-9) a limitation no longer present in claim 72, namely patients not suffering from metabolic acidosis.
Applicant refers (page 9, last 2 lines, page 10) to a literature reference (Mahajane) cited by Loniewski and argues that Mahajane teaches that the concentration of creatinine in the blood of CKD patients continues to increase even with administration of sodium bicarbonate. Applicant argues (page 10, last paragraph) unexpected results of lowering the blood concentration of indoxyl sulfate and increasing its concentration in urine, with administration of citrate instead of bicarbonate.
In response, this argument seems to compare bicarbonate administration with citrate administration in CKD patients to treat CKD. Yet, the closest prior arty, Loniewski, teaches administration of citrate as Polycitra to CKD patients to treat CKD. As such, a comparison between bicarbonate and citrate is not relevant, as Loniewski already teaches administering the same therapeutic agent, citrate, to the same patient population, CKD patients, as in the instant claims, to treat said patients.
Applicant argues (page 11) that Niwa is silent about the fact that citric acid reduces the blood concentration of indoxyl sulfate in CKD patients. This argument is not persuasive. Niwa is used in the rejection for teaching that indoxyl sulfate is an uremic toxin that accelerates the progression of CKD. Thus, Niwa implicitly teaches that suppressing progression of chronic kidney disease ameliorates uremic symptoms/to treat or prevent uremia by reducing the accumulation of uremic toxin indoxyl sulfate in the serum of the CKD patient.
Applicant argues (page 11, last two paragraphs) non-obviousness because the patients do not suffer from metabolic acidosis. In response, this limitation has been deleted from the claims.
Applicant argues (page 11, last paragraph, page 12, first paragraph) that a person skilled in the art would have understood that in order to excrete uremic substances such as indoxyl sulfate into urine, it was necessary to improve renal function, that is, to increase the GFR value or eGFR value, which is an overall index thereof, or if the GFR value or eGFR value was the same between the different subject groups, the effect of reducing indoxyl sulfate in blood and the effect of increasing indoxyl sulfate in urine would be the same or similar between the different subject groups.
In response, in terms of increasing GFR or eGFR value, it is noted that chronic kidney disease (CKD) is characterized by a chronic reduction in the glomerular filtration rate (GFR); as such, a therapeutic agent that effectively suppresses the progression of CKD does not need to increase GFR- rather, keeping the GFR constant for a period of time is associated with suppressing the progression of CKD (since progression of the disease CKD is associated with worsening kidney function and decrease in GFR values).
Applicant argues that excretion effects for indoxyl sulfate with the combination preparation of hydrates of potassium citrate and sodium citrate administration are unexpected results because patients with similar eGFR levels should have similar excretion effects for indoxyl sulfate.
In response, the examiner acknowledges the data presented by Applicant, as well as the data in the Declaration submitted on 22 August 2023, which was thoroughly considered in the office action mailed on 12/21/2023, pointing to an unexpected mechanism for the combination of Na citrate and K citrate in a method of treating CKD patients.
However, Loniewski teaches administration of Polycitra, which is an oral pharmaceutical composition comprising Na citrate and K citrate (an alkalinizing agent of the instant claims), to patients suffering from CKD, which are the very patients in the instant claims.
Thus, Loniewski teaches administration of the same therapeutic agent, combination Na citrate and K citrate (Polycitra), to the same patient population, patients suffering from chronic kidney disease, as in the instant claims. Since administration of a combination of sodium citrate and potassium citrate alkalinizing agents (as Polycitra) to patients suffering from CKD was known (Loniewski), determining the effect of the therapeutic agent/combination on the concentration of indoxyl sulfate in blood and urine of the CKD patients treated with said combination, and investigating the mechanism of action for said combination, will not render the method unobvious because the instantly claimed increase in excretion of indoxyl sulfate into urine and decrease in concentration of indoxyl sulfate in the blood of said patients would necessarily occur with the administration of sodium citrate and potassium citrate.
For all the reasons above, the rejection of claims 72-78 under 35 U.S.C. 103 over Loniewski, in view of Niwa is herein maintained, and a modified rejection is made below, based on Applicant’s amendment of 30 March 2026.
Applicant argues (Remarks of 30 March 2026, pages 13-14) against the rejection of claims 72-78 on the ground of nonstatutory double patenting over claims of copending Application No. 17/284,862 (now US patent 12,324,793), in view of Niwa, on the grounds that the methods in the reference patent application are different from the instantly claimed method of decreasing uremic substances from blood. This argument is not persuasive, because claims of US patent 12,324,793 recite administration of the same therapeutic agents, a mixture of potassium citrate and Na citrate, in similar/overlapping daily dose, to the same patients, patients suffering from CKD, wherein the mammalian subject is not suffering from metabolic acidosis, as in the instant claims.
Administration of the same therapeutic agents to the same patient population is expected to have inherently the same effect on the concentration of uremic substances in the blood of the patients. The person of ordinary skill in the art would have been motivated to monitor the effectiveness of sodium citrate and potassium citrate in treating CKD in the method of claims of US patent 12,324,793 by measuring the concentration of uremic substance indoxyl sulfate in the blood of patients throughout treatment, because Niwa teaches that indoxyl sulfate is an uremic toxin which accumulates in the serum of chronic kidney disease (CKD) patients and accelerates the progression of CKD. Thus, the person of ordinary skill in the art would have monitored the effectiveness of sodium citrate and potassium citrate in treating CKD by measuring the concentration of uremic substance indoxyl sulfate in the blood of patients, with the expectation that treatment is correlated with a decrease in the concentration of uremic substance indoxyl sulfate in the blood of patients due to increased excretion of indoxyl sulfate from blood into urine of the patient. This rejection is herein maintained.
Determining the effect of the therapeutic agent/combination on the concentration of indoxyl sulfate in blood and urine of the CKD patients treated with said combination, and investigating the mechanism of action for said combination, will not render the method unobvious because the instantly claimed increase in excretion of indoxyl sulfate into urine and decrease in concentration of indoxyl sulfate in the blood of said patients would necessarily occur with the administration of sodium citrate and potassium citrate.
Applicant’s amendment of 30 March 2026 necessitated the following new and/or modified rejections.
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 74 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 74 depends on claim 72 and recites that each of potassium citrate monohydrate and sodium citrate dihydrate is administered at 0.5 to 1.5 g/day; yet, claim 72 does not recite potassium citrate monohydrate and sodium citrate dihydrate. As such, there is insufficient antecedent basis for the recitation potassium citrate monohydrate and sodium citrate dihydrate of claim 74, in claim 72.
Appropriate correction is required.
In the interest of compact prosecution, claim 74 is considered to be dependent on claim 78.
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.
Claims 72, 74, 78-80 are rejected under 35 U.S.C. 103 as being unpatentable over Loniewski et al. (Kidney International 2014, 85, 529-535, cited in PTO-892 of 25 June 2021), in view of Niwa, T. (Nagoya J. Med. Sci. 2010, 72, 1-11, cited in PTO-892 of 14 April 2022).
Loniewski teaches (page 533, right column, first paragraph under Galenic forms, also Table 4) administering alkalinizing agent Polycitra, which is an oral pharmaceutical composition which is a mixture of alkalinizing agents Na citrate 1mEq/ml and K citrate 1 mEq/ml, to CKD patients to suppress the progression of chronic kidney disease.
Thus, Loniewski teaches a method for suppressing the progression of chronic kidney disease (CKD) in a mammalian subject in need thereof, comprising administering to a mammalian subject in need thereof a pharmaceutical composition which is a mixture of alkalinizing agents Na citrate and K citrate.
Loniewski teaches (page 533, right column, last paragraph, page 534, right column, first paragraph, also Table 5) Na citrate and K citrate (Table 5) as alkalinizing agents.
Lonieski teaches (Abstract, also Table 1, reference by Phisitkul, delayed GFR decline) that alkalization attenuates kidney injury and slows glomerular filtration rate decline in CKD.
Loniewski teaches (Table 4) that Polycitra, which is an oral pharmaceutical composition which is a mixture of alkalinizing agents Na citrate 1mEq/ml and K citrate 1 mEq/ml, is an oral bicarbonate precursor, and a galenic form of NaHCO3 (page 533, right column, second paragraph).
Loniewski teaches (Table 2, reference by Phisitkul) administering oral sodium citrate at a dose equivalent to 1 mEq NaHCO3/kg b.w. daily, to patients with eGFR 20-60 ml/min per 1.73 m2, which are patients with stage G3a and stage G3b CKD, included in the patient population of instant claim 72, to treat CKD. The duration of treatment is 24 months, which is more than 6 weeks, as in instant claim 72, and is more than 24 weeks, as in instant claims 79.
Loniewski teaches (page 533, right column, first paragraph) administering alkalinizing agent NaHCO3 to patients with chronic kidney disease (CKD), to treat said patients/ to suppress the progression of chronic kidney disease in said patients. Loniewski teaches (page 533, right column, first paragraph) that in CKD patients, NaHCO3 was administered at a dose of 0.5 mEq., i.e. 42 mg/kg b.w. daily, where patients weighing 70 kg received approximately 3 g NaHCO3 divided in three doses. Thus, Loniewski teaches that alkalinizing agent NaHCO3 is effective to treat chronic kidney disease (CKD) in CKD patients, at a dose of NaHCO3 3 g/day.
Loniewski does not specifically teach a method of treating CKD in CKD patients by administering to the patients a mixture of potassium citrate monohydrate and sodium citrate dihydrate, as in instant claims 74, 78.
Loniewski does not specifically teach administering Polycitra to a subject who suffers from chronic kidney disease, to treat or suppress uremia, as in the instant claims.
Loniewski does not teach that Polycitra is administered at 1 to 6 g/day, or that each of potassium citrate and sodium citrate is administered at 0.5 to 1.5 g/day, as in instant claims 72, 74.
Loniewski does not teach continuous administration for 6 weeks, or for 24 weeks, as in instant claims 72, 79, 80.
Niwa teaches (Abstract) that indoxyl sulfate, an uremic toxin, is accumulated in the serum of chronic kidney disease (CKD) patients. Niwa teaches (page 1, Introduction) that uremic toxins such as indoxyl sulfate are involved in a variety of symptoms in patients with advanced CKD. Niwa teaches (page 2, first paragraph) that indoxyl sulfate is an uremic toxin that accelerates the progression of CKD. Thus, Niwa implicitly teaches that suppressing progression of chronic kidney disease ameliorates uremic symptoms/to treat or prevent uremia by reducing the accumulation of uremic toxin indoxyl sulfate in the serum of the CKD patient.
It would have been obvious for a person of ordinary skill in the art to use the teachings of Loniewski and Niwa to arrive at the instantly claimed invention.
The person of ordinary skill in the art would have been motivated to administer to a CKD patient a pharmaceutical composition comprising an effective amount of an alkalinizing agent which is a mixture of potassium citrate monohydrate and sodium citrate dihydrate, because Loniewski teaches that Polycitra, which is a composition comprising a mixture of alkalinizing agents Na citrate, K citrate (1:1 molar), and is an oral bicarbonate precursor and a galenic form of NaHCO3, is effective to suppress the progression of chronic kidney disease. Thus, the person of ordinary skill in the art would have administered to a patient suffering from chronic kidney disease a mixture of potassium citrate monohydrate and sodium citrate dihydrate, with the expectation that such a mixture of hydrates of two alkalinizing agents present in Polycitra, Na citrate and K citrate, effectively suppress progression of chronic kidney disease in said patient.
Since Loniewski teaches administration of NaHCO3 or of its galenic form a mixture of potassium citrate and sodium citrate (Polycitra), to patients suffering from chronic kidney disease (CKD), to suppress progression of CKD/treat CKD, the hydrates of the alkalinizing agents, upon administration, are expected to elicit the same effect on CKD and on uremic symptoms of CKD/uremia/ due to accumulation of uremic toxin indoxyl sulfate in blood.
Further, the person of ordinary skill in the art would have administered the mixture of potassium citrate monohydrate and sodium citrate dihydrate to a subject suffering from stage G2 to G3b chronic kidney disease, because Loniewski teaches administering sodium citrate to CKD stage G3a or CDK stage G3b patients to treat CKD. Further, Loniewski teaches that Polycitra (potassium citrate and sodium citrate mixture 1:1 molar) is a galenic form of NaHCO3, and Loniewski teaches administering NaHCO3 to CKD2 patients to treat CKD. Thus, the person of ordinary skill in the art would have administered to CKD2 patients Polycitra, or a mixture of potassium citrate monohydrate and sodium citrate dihydrate, with the expectation that Polycitra or a mixture of potassium citrate monohydrate and sodium citrate dihydrate, will act as bicarbonate precursors effective to suppress progression of chronic kidney disease in the subject suffering from stage G2 to G3b chronic kidney disease.
Furthermore, with respect to claims 72, 74, the person of ordinary skill in the art would have determined the therapeutically effective dose of sodium citrate and potassium citrate as Polycitra or the corresponding hydrates administered in the method, because Loniewski teaches that Polycitra (mixture of sodium citrate and potassium citrate 1:1 molar) is a galenic form of NaHCO3, and NaHCO3 is effective to treat CKD in CKD patients at an average dose of NaHCO3 of 3 g/day. Thus, the person of ordinary skill in the art would have calculated the dose of Polycitra (mixture of sodium citrate and potassium citrate 1:1 molar) or the corresponding dose of sodium citrate dihydrate and potassium citrate monohydrate, equivalent to a dose of NaHCO3 of 3 g/day, with the expectation of achieving therapeutic effect. Such a determination of effective dose of active ingredients in a method of treatment is routine and well within the skill of the artisan.
Further, the person of ordinary skill in the art would have been motivated to monitor the effectiveness of sodium citrate and potassium citrate in treating CKD by measuring the concentration of uremic substance indoxyl sulfate in the blood of patients throughout treatment, because Niwa teaches that indoxyl sulfate is an uremic toxin which accumulates in the serum of chronic kidney disease (CKD) patients and accelerates the progression of CKD. Thus, the person of ordinary skill in the art would have monitored the effectiveness of sodium citrate and potassium citrate in treating CKD by measuring the concentration of uremic substance indoxyl sulfate in the blood and urine of patients, with the expectation that treatment is correlated with a decrease in the concentration of uremic substance indoxyl sulfate in the blood of patients due to increased excretion of indoxyl sulfate from blood into urine of the patient.
Even though Loniewski does not specifically teach that suppressing progression of chronic kidney disease ameliorates uremia as uremic symptoms in the CKD patient, as in instant claims, such amelioration of uremic symptoms inherently occurs in the method of suppressing the progression of chronic kidney disease/treating CKD, as evidenced by Niwa. Niwa teaches (Abstract) that indoxyl sulfate, an uremic toxin, is accumulated in the serum of chronic kidney disease (CKD) patients. Niwa teaches (page 1, Introduction) that uremic toxins such as indoxyl sulfate are involved in a variety of symptoms in patients with advanced CKD. Niwa teaches (page 2, first paragraph) that indoxyl sulfate is an uremic toxin that accelerates the progression of CKD. Thus, Niwa implicitly teaches that suppressing progression of chronic kidney disease ameliorates uremic symptoms by reducing the accumulation of uremic toxin indoxyl sulfate in the serum of the CKD patient.
Since Loniewski teaches administration of the very same alkalinizing agent, namely a mixture of potassium citrate and sodium citrate (Polycitra), to the very same patient population, patients suffering from chronic kidney disease (CKD), to suppress progression of CKD/treat CKD, said alkalinizing agent, upon administration, will inherently elicit the same effect on uremic symptoms/uremia due to accumulation of uremic toxin indoxyl sulfate in blood.
Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. See MPEP 2145.II. In this case, since administration of a combination of sodium citrate and potassium citrate alkalinizing agents Polycitra to patients suffering from CKD was taught by Loniewski, determining the effect of the combination on the concentration of indoxyl sulfate in blood and urine of the CKD patients treated with said combination, and investigating the mechanism of action for said combination, will not render the method unobvious because the instantly claimed increase in excretion of indoxyl sulfate into urine and decrease in concentration of indoxyl sulfate in the blood of said patients would necessarily occur with the administration of sodium citrate and potassium citrate.
Further, determining the length of treatment in a method of treatment, in order to achieve therapeutic effect, is well within the skill of the artisan.
As such, claims 72, 74, 78-80 are rejected as prima facie obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 72, 74, 78-80 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of US patent 12,324,793 (Application No. 17/284,862, cited in PTO-892 of 23 March 2023), in view of Niwa, T. (Nagoya J. Med. Sci. 2010, 72, 1-11, cited in PTO-892 of 14 April 2022). Although the claims at issue are not identical, they are not patentably distinct from each other because a method of claims 1-8 of US patent 12,324,793 anticipates or renders obvious the instant claims.
Claims 1-8 of US patent 12,324,793 are drawn to a method for renal protection in a mammalian subject suffering from chronic kidney disease, comprising administering to a subject in need of the renal protection an effective amount of a pharmaceutical composition comprising a mixture of sodium citrate or a hydrate thereof and potassium citrate or a hydrate thereof, wherein the renal protection is, for example, (v) suppression of the decrease in osmotic pressure of urine, wherein the mammalian subject is not suffering from metabolic acidosis; claim 4 recites a dose of 1 to 1.5 g per day, which is encompassed by the dose in instant claims 72, 74; claim 5 recites that the mammalian subject suffering from chronic kidney disease is a patient with chronic kidney disease of stage G2 or more and G3b or less, which overlaps with the patient population in instant claim 72.
Thus, claims of 1-8 of US patent 12,324,793 recite administration of the same therapeutic agents, a mixture of potassium citrate and Na citrate, in similar/overlapping daily dose, to the same patients, patients suffering from CKD, wherein the mammalian subject is not suffering from metabolic acidosis, as in the instant claims.
Niwa is as above.
It would have been obvious for a person of ordinary skill in the art to use the teachings of claims 1-8 of US patent 12,324,793 and Niwa to arrive at the instantly claimed invention. The person of ordinary skill in the art would have been motivated to monitor the effectiveness of sodium citrate and potassium citrate in treating CKD in the method of claims of US patent 12,324,793 by measuring the concentration of uremic substance indoxyl sulfate in the blood of patients throughout treatment, because Niwa teaches that indoxyl sulfate is an uremic toxin which accumulates in the serum of chronic kidney disease (CKD) patients and accelerates the progression of CKD. Thus, the person of ordinary skill in the art would have monitored the effectiveness of sodium citrate and potassium citrate in treating CKD by measuring the concentration of uremic substance indoxyl sulfate in the blood of patients, with the expectation that treatment is correlated with a decrease in the concentration of uremic substance indoxyl sulfate in the blood of patients due to increased excretion of indoxyl sulfate from blood into urine of the patient.
Conclusion
Claims 72, 74, 78-80 are rejected.
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/IRINA NEAGU/Primary Examiner, Art Unit 1629
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