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 .
Receipt is acknowledged of Amendments, Remarks and a Declaration filed on 02/17/26, and an IDS filed on 01/21/26 and an IDS filed on 12/18/25. Claim 1 has been amended, no claims have been canceled and new claims 20-22 have been added. Accordingly, claims 1-4, 16 and 20-22 are pending and under examination on the merits.
Rejections and/or objections not reiterated from the previous Office Action are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Claim interpretation:
Indicating that the citrate is the active ingredient does not materially affect the scope of the claimed method.
The term “decreasing” is a relative term and encompasses any degree of decrease, including 0.1%.
Neutral fat is defined as triglyceride in the Specification.
Applicant claims a method of decreasing triglyceride level in the blood and improving insulin resistance, the method comprising administering 1 to 10 g per day of citrate as an active ingredient to a subject having metabolic syndrome or letting a subject having metabolic syndrome ingest 1 to 10 g per day of citrate as an active ingredient, wherein the citrate is sodium citrate and/or potassium citrate and the neutral fat level of the subject is 150 mg/dL or more. Claims 2-3 recite a mixture of citrates being sodium and potassium citrates.
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 1-4, 16 and 20-22 are rejected under 35 U.S.C. 103 as being unpatentable over Werner (WO 2017032665) in view of Grundy (Hypertiglyceridemia, insulin resistance, and the metabolic syndrome) and Abe et al (US 2021/0121426 A1) as evidenced by WO 2009084732.
Werner teaches applications of mixtures of three or more citrate salts, comprising magnesium citrate, the mixture of two, three or more citrate salts additionally comprising calcium citrate and/or zinc citrate, in particular to stimulate or boost the carbohydrate metabolism, preferably the glucose metabolism, in particular to stimulate or boost the cellular energy metabolism (See abstract).
Werner teaches a composition for use in a therapeutic method, wherein the composition contains a mixture of three or more citrate salts comprising magnesium citrate as the active ingredient, the mixture of three or more citrate salts additionally, consists of calcium citrate, sodium citrate, potassium citrate, etc. The said therapeutic method is for treating an/or preventing one or more or all metabolic disorders including metabolic syndrome (See Page 1, 2nd para, Page 5, lines 21-27 and claims 3 and 6, Page 14, 5th full para and paragraph bridging pages 14 and 15).
Another embodiment relates to a mixture of or comprising magnesium citrate, potassium citrate and sodium citrate for use in a therapeutic method for stimulating or enhancing the carbohydrate metabolism, preferably the glucose metabolism, in particular for stimulating or enhancing the cellular energy metabolism (See page 9, lines 1-6).
Werner also discloses a composition for use in a therapeutic method, wherein the composition is selected from the group consisting of granules, preferably for direct ingestion, for dissolution or for stirring in meals (food), tablets, etc, (See Page 19, lines 19-22).
In one embodiment a composition for use in a therapeutic method is disclosed, the composition also comprising one or more other ingredients selected from the group consisting of edible fatty acids, acidulants, preferably citric acid: flavors, further citrate salts, preferably sodium citrate, potassium citrate, magnesium carbonate, sodium bicarbonate; vitamins, etc (See Page 18, last para).
It is disclosed that “the term metabolic syndrome refers to the combination of disrupted carbohydrate metabolism manifested by insulin resistance or increased blood glucose levels, hypertension, dyslipoproteinemia, i.e. increase of VLDL with simultaneous lowering of HDL lipoproteins, and abdominal obesity. The defect most likely underlying the metabolic syndrome is peripheral insulin resistance and the associated chronic hyperinsulinemia. The metabolic syndrome is considered a precursor of type 2 diabetes” (See Page 15, 3rd full para).
Werner discloses that in a preferred embodiment, the daily dose of magnesium citrate in the said method is 15 to 1000 mg (See Page 18, 4th para). Furthermore, the said composition for use in a therapeutic method may comprise a total amount of citrate salts in the range of 4 to 70% by weight of the total weight of the composition (See Page 19, 2nd and 3rd para).
Furthermore, Werner exemplifies a granulated formulation that comprises more than 3 g of citrate, in combination, and almost 3 g from sodium and potassium citrate (See page 24, Table 2).
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It is disclosed that an acidification of the body can be prevented or reduced with the citrate salts due to a reduction of the production of lactate by stimulating the oxidative carbohydrate metabolism and by the influence of the citrate anion on the pH value in the organism (See Page 22, 6th para).
Werner does not expressly disclose that the said method of administering the said composition would result in a decrease in triglyceride levels in blood. However, Grundy and Abe remedy this deficiency.
Grundy teaches that the metabolic syndrome consists of a cluster of metabolic disorders, many of which promote the development of atherosclerosis and increase the risk of cardiovascular disease events. Insulin resistance may lie at the heart of the metabolic syndrome. Elevated serum triglycerides commonly associate with insulin resistance and represent a valuable clinical marker of the metabolic syndrome (See Abstract).
Grundy teaches that hypertriglyceridemia commonly occurs along with other components of the metabolic syndrome. An elevated triglyceride is frequently the most available laboratory marker to uncover the coexistence of multiple risk factors, including nonlipid risk factors, such as hypertension, elevated plasma glucose, and a prothrombotic state. Hypertriglyceridemic patients thus must be carefully evaluated for the other metabolic risk factors that occur with the metabolic syndrome. Any patient whose triglyceride concentrations exceed 150 mg/dL is suspect for the metabolic syndrome (See Page 25F, 2nd col. 2nd full para).
It is disclosed that in summary, when patients have elevated secretion of nonesterified fatty acids, whether due to excess adipose tissue (obesity), abnormal fat distribution (abdominal obesity), or a primary insulin resistance in adipose tissue, they will have an elevated level of nonesterified fatty acids in the plasma. Excess nonesterified fatty acids overload a variety of different tissues in the body with lipid and apparently alter cellular processes, predisposing patients to the metabolic syndrome (See page 26F, 2nd col. 2nd full para).
It is disclosed that many patients with the metabolic syndrome have combined hyperlipidemia (an increase in both cholesterol and triglycerides in serum) (See page 28F, 1st col. 1st full para).
Abe discloses a food composition comprising an alkalinizing agent, particularly an alkali metal salt of citric acid. Ingestion of the food composition maintains kidney function (abstract). In an embodiment, the food composition comprises an alkalinizing agent and exhibits an effect of decreasing the concentration of uremic substance in blood (reading on improving metabolism) (para.0428). The alkalinizing agent is a mixture of potassium citrate and sodium citrate (para.0437). Abe discloses a method for decreasing a concentration of uremic substance in blood and promoting excretion of uremic substance into urine (reading on improving metabolism) comprising ingesting the food composition discussed above (para.0455-0456).
It is disclosed that the said pharmaceutical composition is administered to a patient receiving treatment according to a CKD medical guide, including blood glucose level control and lipid management (para. 0322).
In another embodiment, Abe discloses a pharmaceutical composition, such as a tablet, produced by mixing an alkalinizing agent (e.g., a mixture of potassium citrate and sodium citrate) with excipients, such as citric acid (para.0259, 0265).
Abe discloses a tablet in which one tablet comprises 231.5 mg of potassium citrate and 195.0 mg of sodium citrate hydrate orally administered 3 times a day, 2 tablets at one time; and in a case where the alkalinizing agent is sodium bicarbonate: oral administration of 3 to 5 g a day, (para. 0268 and 0270-0271).
As Evidenced by:
WO ‘732 teaches an acidosis-ameliorating agent such as a preparation containing potassium citrate and sodium citrate (Uralyt-U®, Uralyt Tablets (registered trade names)) is used as a prophylactic or therapeutic agent for anemia which is an adverse side effect produced in the interferon/ribavirin combination therapy (See abstract).
WO ‘732 teaches that when URALIT® u (registered trademark) or URALIT tablet (registered trademark) is administered orally, the total amount of the active ingredients citrate strength rum and citrate sodium is: -12 g / day, preferably 3-12 g / day, divided into 3 or 4 doses per day, but the total dose may be administered once or in several doses as needed Good. (See 3rd page, last para).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Grundy and Abe with that of Werner to arrive at the instant invention. It would have been obvious to do so because Werner also discloses administration of a mixture of citrates including sodium and potassium citrates with citric acid and sodium bicarbonates to treat metabolic syndrome in a subject. The said treatment is said to improve metabolism and reduce lipid/fat levels in the subject’s blood and improve insulin resistance. Werner discloses that the said formulations reduce acidification in a subject. Grundy teach that high levels of triglyceride, especially of those exceeding 150 mg/dL is an important marker of a subject suffering from metabolic syndrome. Abe teaches administration of a food composition comprising sodium citrate, potassium citrate and citric acid to a subject in need of decreasing the concentration of uremic substance in blood because the said composition acts as an alkalinizing agent. Thus, one of ordinary skill in the art having possession of the said references would have recognized that hypertriglyceridemia as disclosed by Grundy is a common occurrence in subjects with metabolic syndrome and that a composition comprising one or more citrates would be effective in treating metabolic syndrome symptoms in a subject. Additionally, one of ordinary skill in the art would have recognized that a subject with metabolic syndrome has acidic body fluids and that alkalizing agents including citrates and sodium bicarbonates would be effective. As such one of ordinary skill in the art would have been motivated to have implemented the citrate and/or alkalizing agents of Werner and Abe for all subjects needing a treatment for metabolic syndrome would have also recognized that the triglyceride levels have reduced.
In other words, one of ordinary skill in the art is given sufficient teachings and motivation to deduce that the compositions taught by the references would have results in a reduced level of lipids and triglycerides in blood, improve insulin resistance and improve the subject’s acidified body fluids.
Regarding the daily dose, Werner and Abe provide guidance on lower daily doses of about 1 to about 3 gram per day. with regard to the concentration/amount ranges, the courts have held 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); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969); Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed.Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997).
Additionally, as evidenced by WO ‘732, doses of up to 12 g per day are disclosed and known (Also see Frang below).
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Frang (A Comparative Study of Three Different Citrate Combinations of Litholytic Action; published 1978).
Frang discloses the administration of Uralyt-U, Magurlit, or Eisenberg solution to patients whose body fluids are acidified (abstract; pg. 196, para.7-8; pg. 197, para.4). Magurlit is composed of citric acid, sodium citrate, potassium citrate, magnesium citrate, and vitamin B6 (pg.195, para.4 to pg. 196, para. 1). The three drugs act by shifting the reaction of the urine to alkalinity. The shift of urinary PH to alkalinity modifies the solubility of the urate calculi by interfering with crystallization and enabling existing calculi to be dissolved (reading on improving metabolism) (pg.196, para.2). the dosage of Uralyt-U is disclosed as about 6 to 8 g daily (See Page 197, last para). On a comparative study, Magurlit and Uralyt-U both have been found hygienic and easy to handle by the patients. The required pH range can be attained within a short time and maintained with similar doses. Side effects, if any, were transitory (pg. 199, para.2).
Response to Arguments
Applicant's arguments filed 02/17/26 have been fully considered but they are not persuasive.
Applicant argues that the references do not teach the claimed embodiment because they are directed to a different patient population than which is claimed, i.e. a subject having a neutral fat level of 150 mg/dL. Applicant argues that the subjects in Abe requiring the excretion of uremic substances outside the body are mainly chronic kidney disease patients with a triglyceride level of 129 mg/dL (See Remarks, pages 7-8).
The above argument is not found persuasive. Werner teaches treating subjects with metabolic syndrome by administering to them a citrate composition. Grundy teach that metabolic syndrome constitutes of conditions including increased triglyceride levels, levels of 150 mg/dL or more and hyperglycemia (i.e. increased insulin resistance). Werner also discloses that the said compositions are effective in treating subjects that have acidic body fluids and that the said alkalizing agents are effective in treating such subjects by alkalizing their body. Additionally, Abe teaches that citrates are alkalizing agents that help reduce the acidity in a subject and treat their symptoms, such as high uremic substances and treating kidney disease.
Applicant also argues that “Werner does not explicitly indicate the quantity of granule or drinking powder which a subject would receive per day. However, even if receiving one granulate composition or one drinking powder composition, the quantity of citrate would be below the 3 g lower bound of new claim 22. Therefore, at least new claim 22 is patentable over the cited art” (See Remarks, page 8).
This argument is also not found persuasive. Werner exemplifies a granulated formulation that comprises more than 3 g of citrate, in combination, and almost 3 g from sodium and potassium citrate. Furthermore, even if the other citrate salts are not considered from this formulation, potassium and sodium citrates provide 2574 g of citrate which is an obvious variation of 3 grams, as held by courts, such as In re Aller, stated above. Additionally, the rejection shows, as the Specification and arguments have also put on the record, that the combination of potassium citrate and sodium citrate is a commercially available composition (Uralyte-U®) that is known to be administered at doses of up to 12 g daily, see WO ‘732 or Frang.
Next Applicant argues that based on the teachings of Grundy, Wu et al, Yang, etc, not all patients with metabolic syndrome have a triglyceride level of 150 mg/dL or more as claimed. Applicant argues that because of this, one of ordinary skill in the art would not have had an expectation of success with Werner’s teachings in decreasing triglyceride levels in the blood (See Remarks, pages 7-9).
The above argument is not persuasive. Werner clearly discloses treating subjects with metabolic syndrome with a mixture of citrate salts, and that the term metabolic syndrome refers to the combination of disrupted carbohydrate metabolism manifested by insulin resistance or increased blood glucose levels, hypertension, dyslipoproteinemia, i.e. increase of VLDL with simultaneous lowering of HDL lipoproteins, and abdominal obesity”. Additionally, Grundy discloses that “Any patient whose triglyceride concentrations exceed 150 mg/dL is suspect for the metabolic syndrome”, and that high triglyceride levels are a common symptom of metabolic syndrome and an important marker in diagnosing metabolic syndrome. Furthermore, according to the Specification, “Metabolic syndrome is a pathological condition that exhibits two symptoms out of following i) to iii): i) abnormal serum lipid, ii) high blood pressure value, and iii) hyperglycemia, in addition to visceral fat accumulation”.
Thus, based on the teachings of Werner, one of ordinary skill in the art is more than motivated to treat a subject with metabolic syndrome with a composition comprising one or more citrates and bicarbonates. The subjects with metabolic syndrome, according to Grundy and Applicant, are those with an elevated triglyceride levels of 150 mg/dL or more. Thus, by following Werner’s teachings, one would necessarily decrease the triglyceride levels.
Regarding the evidences Applicant points to, including Wu et al, it is noted that according to Wu et al, none of the symptoms of metabolic syndrome are present in 100% of the patients. See reproduced Table 3 below:
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As can be seen, high serum triglyceride levels in both men and women have the highest prevalence of all abnormalities. Thus, an argument that increased blood triglyceride level of in a subject with metabolic syndrome would not have been reasonably expected is unconvincing.
Applicant’s next argument is against the teachings of Abe. Applicant recites “As to Abe, Applicant again respectfully submits that this reference discloses a different patient population than the claimed subject. The claims recite patients with metabolic syndrome who have blood triglyceride level of 150 mg/dL or more. On the other hand, Abe is a method for promoting excretion of uremic substance outside the body in patients with chronic kidney disease in stage G2 to G3b. As noted in the Declaration under 37 CFR 1.132 by co-inventor Satomi YAMASAKI filed on July 24, 2025, in Abe, the median of triglyceride level in blood prior to drug administration among the patients with chronic kidney disease in stage G2 to G3b was 129 mg/dL, and only 36% of the patients had triglyceride levels of 150 mg/dL or more. This means that 64% of patients had normal blood triglyceride levels (less than 150 mg/dL). Therefore, in Abe, there was little need to lower triglyceride levels in these patients” (See Remarks, page 9).
While the interpretation of the references is correct, the argument is not sufficient to obviate the rejection or place the claims in condition for allowance.
As stated above, Werner clearly teaches that the citrates are effective in treating metabolic syndrome and Grundy teach that metabolic syndrome constitutes an elevated level of triglycerides. Thus, one of ordinary skill in the art following Werner’s teachings and methods and administering citrate to a subject with metabolic syndrome would necessarily decrease the triglyceride levels. That is Werner provides the motivation to one of ordinary skill in the art to administer a composition comprising citrates to a subject with metabolic syndrome, whom also has a triglyceride level of 150 mg/dL or more.
That is, even if Werner did not recognize that the citrate composition can decrease triglyceride levels, it is held that "The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
As to the disclosure of Abe, it is disclosed that a mixture of potassium citrate and sodium citrate is an effective alkalinizing agent and employed in a method for decreasing a concentration of uremic substance in blood and urine and to control blood glucose level and lipid management. That is Abe discloses a method of alkalizing body fluids (as in insta claim 4) and treating elevated levels of lipid and blood glucose (as in instant claim 1).
In response to the argument that the median triglyceride level in Abe is 129 mg/dL and that “only 36% of the patients had triglyceride levels of 150 mg/dL or more”, it is noted that there is no requirement that 100% of patients show triglyceride levels of 150 mg/dL or more for one of ordinary skill in the art to consider a treatment.
Additionally, Abe is one reference in a combination of references wherein the rejection is based on the recited combined teachings and the common elements are that alkalinizing agents including citrates (and sodium bicarbonate) are effective in treating metabolic syndrome including high blood pressure, hyperglycemia and hyperlipidemia. It is disclosed in both Werner and Abe references as well as the Specification that the said conditions are related and one may lead to another and that the treatments of these conditions overlap. Thus, one of ordinary skill in the art would have been motivated to implement the disclosed combination of citrates as a lipid lowering/triglyceride lowering agent in a subject with a reasonable expectation of success. Additionally, the instant Specification also states that said combination is effective in reducing both glucose levels, acid levels and neutral fat (e.g. triglyceride) levels. That is one of ordinary skill in the art having possession of the references would have readily recognized that the same compounds can be effective in multiple metabolism functions of the body. It is also noted that claim 4 is directed to treating a patient having acidified body fluids and claim 1 is to a subject having metabolic syndrome.
Applicant noted that a response to Yamasaki Declaration file don July 24, 2025 was missing in the Office action and the Response filed on 11/21/25. The response is now recited above.
Applicant points to the Declaration of Masuzaki, and argue that “the Examiner seems to consider that the purpose of the Declaration by Dr. Masuzaki was to demonstrate that Kanda demonstrates a benefit from administering citrate. However, the opposite is true. In fact, the Declaration demonstrates that, in view of Kanda, reduction of triglycerides in response to administering citrate would not have been expected.” (See Remarks, page 10).
The above argument is not persuasive either. Firstly, since the data in Kanda reference is not reliable, According to Dr. Masuzaki’s recent Declaration, Kanda reference and its data cannot be considered. Additionally, Dr. Masuzaki states in the Declaration, that when he saw the data (In Kanda’s test), they did not appear to be correct. He states “Then, I had a question because the triglyceride levels measured in Kanda et al. were low (actual data: control group had 6.6 ± 5.1 mg/dl, while Ulalyt®-treated group had 6.0 ± 2.9 mg/dl: mean ± standard deviation). I wondered why this may be, and therefore, we decided to repeat the test under the same conditions as those disclosed in Kanda et al” (See Declaration, page 5, 1st para).
That is, the same test under the same conditions were repeated which may have resulted in different values. Thus, as stated in the response to the Declaration (and reproduced below), the same composition is administered to the same population by the same method. Therefore, whether the reduction in triglyceride was expected or not, the claimed method does not comprise any inventive step.
Applicant further argues that “Next, Applicant herein amends the claims to recite that the method is a method of decreasing triglyceride level in the blood and improving insulin resistance. It is noted that the cited art does not disclose an "improvement of insulin resistance." This is supported at least by paragraph [0014] of the specification as filed. The improvement of insulin resistance is supported by the significant reduction of HOMA-IR level in Table 2 of the specification as filed. Although Werner measured blood glucose and insulin concentrations in healthy people before and after administration of the active drug, no significant difference was observed. See Figure 2” (See Remarks, page 10).
This argument is similarly found unconvincing. Firstly, and contrary to Applicant’s interpretation, the references indeed teach improving insulin resistance. Werner teaches that “The term metabolic syndrome refers to the combination of disrupted carbohydrate metabolism manifested by insulin resistance or increased blood glucose levels, hypertension, dyslipoproteinemia, i. Increase of VLDL with simultaneous lowering of HDL lipoproteins, and abdominal obesity. The defect most likely underlying the metabolic syndrome is peripheral insulin resistance and the associated chronic hyperinsulinemia. The metabolic syndrome is considered a precursor of type 2 diabetes”.
And Grundy teaches that “in summary, when patients have elevated secretion of nonesterified fatty acids, whether due to excess adipose tissue (obesity), abnormal fat distribution (abdominal obesity), or a primary insulin resistance in adipose tissue, they will have an elevated level of nonesterified fatty acids in the plasma”.
As to above argument related to Fig. 2 of Werner, it is stated that “As seen in Figure 2, after four weeks of supplementation with the composition as defined in Example 1 (verum), the basal and postprandial levels of glucose were decreased. Of the postprandial increase in insulin in serum supplemented with verum was also lower than placebo” (See page 33).
Applicants comments regarding Grundy’s disclosure about weight loss or other treatments having side effects, are not relevant to its teachings that metabolic syndrome is a combination of conditions including elevated triglyceride levels.
Response to the Declaration under Rule 132
Dr. Satomi Yamasaki provided a Declaration under Rule 132 that is dated 02/17/26. The Declaration meets the formal requirements. In this Declaration, Dr. Yamasaki provides an explanation, in his opinion for the data provided in Kanda reference, argued in the previous Declaration. Dr. Yamasaki states that “The discrepancy in triglyceride levels of the control group between the two datasets (6.6 mg/dl in Kanda et al. VS. 64.9 mg/dl in the present application) suggests to me that prolonged sample storage in the test of Kanda could have caused triglycerides in the samples to degrade, resulting in lower triglyceride values. Therefore, there may have been flaws in the test of Kanda” (See page 2, 3rd para). This appears to be an opinion of Dr. Yamasaki for a test after the test was performed and data published. However, since it is not possible to determine the validity of the documented data, this reference is not relied upon.
Dr. Hiroaki Masuzaki provided a Declaration under Rule 132 that is dated 07/24/25. The Declaration meets the formal requirements. In the most relevant part, the Declaration details the unexpected results of the claimed method.
A Declaration is due full consideration and weight for all that it discloses. Declarations are reviewed for the following considerations: 1) whether the Declaration presents a nexus such as a side-by-side or single-variable comparison (In re Huang, 40 USPQ2d 1685, 1689 (Fed. Cir. 1996)), 2) whether the Declaration presents a comparison to the closest art, 3) whether the Declaration is commensurate in scope with the scope of the claims (In re Kulling, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)), 4) whether the Declaration shows a difference in kind rather than merely a difference in degree (In re Waymouth, 182 USPQ 290, 293 (C.C.P.A. 1974)), and 5) whether the prima facie case is sufficiently strong that allegedly superior results are insufficient to overcome the case for obviousness (Pfizer Inc. v. Apotex, Inc., 82 USPQ2d 1321, 1339 (Fed. Cir. 2007)).
The relevant criterion here are Nos. 3, 4 and 5, whether the Declaration presents a comparison to the closest art, whether the Declaration is commensurate in scope with the scope of the claims, whether the Declaration shows a difference in kind rather than merely a difference in degree and whether the prima facie case is sufficiently strong that allegedly superior results are insufficient to overcome the case for obviousness. The examiner has carefully reviewed the Declaration, including the data presented in the Declaration.
Regarding criterion No. 3, whether the Declaration is commensurate in scope with the scope of the claims, it is not. Claims are drawn to a method of decreasing triglyceride level in a subject by administering an effective amount of a composition comprising citrate. There is no definition of an effective amount. Thus, the claims encompass any amount of citrate. The Declaration compares the claimed method to the method of Kanda et al, administering a 0.8% Ulalyt® solution comprising 370 mg of potassium and 312 mg of sodium citrate hydrate.
Regarding criterion No. 4, whether the Declaration shows a difference in kind rather than merely a difference in degree, it does not. The Declaration states, as disclosed in the Specification, that the same formulation as disclosed in Kanda et al was administered to the same population, i.e. subjects with metabolic syndrome. In Kanda et al, the triglyceride levels were not affected by the solution, while in the tested group in the Specification the levels decreased. This is however, a difference in degree as it was the same composition, the same population and same method step.
Furthermore, the Table of Kanda et al, reproduced and relied upon by the Declarant shows that the Ulalyt® had a small effect on insulin, but no other body or blood chemistry is different between the Ulalyt® and casein and potassium recipients.
That is, data from Kanada et al does not support any benefit from the citrate containing compositions.
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Dr. Masuzaki also points to the data provided in the Specification at Table 2 as evidence of superior results. Table 2 is shown below.
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The table shows that the level of triglyceride in the subjects taking 13LK, i.e. test group was 36±36 and was 18±17 in the 13LK+0.8% K/Na Cit group, i.e. treated group. However, taking the standard deviation into calculation, the difference triglyceride levels in the treated group could be from 1 mg/dL to 35 mg/dL, (18-17=1 and 18+17=35). Additionally, the test group may have had triglyceride levels from 0 mg/dL to 72 mg/dL (36-36=0 and 36+36=42).
Regarding criterion No. 5, whether the prima facie case is sufficiently strong that allegedly superior results are insufficient to overcome the case for obviousness, it is. The prior art references, especially Werner clearly teach that a composition comprising one or more citrate is effective in treating metabolic syndrome, which includes elevated levels of triglyceride, as shown by Grundy.
Thus, the Declaration is insufficient to overcome the rejection or place the claims in condition for allowance.
In conclusion,
From the combined teaching of the cited references, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Claims 1-4, 16 and 20-22 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.
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/Mina Haghighatian/
Mina Haghighatian
Primary Examiner
Art Unit 1616
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