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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 07/24/25 has been entered.
Receipt is acknowledged of Amendments, Remarks and a Declaration filed on 07/24/25 and an IDS filed on 07/10/25. Claim 1 has been amended, no new claims have been added and no claims have been canceled. Accordingly, claims 1-4 and 16 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Rejections and/or objections not reiterated from the previous Office Action are hereby withdrawn.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.
NOTE: In the Declaration filed on 07/24/25, Applicant points to the IDS filed on 02/22/21 listing the reference, Kanda et al (Role of visceral adiposity and aciduria in animal protein + low potassium-induced obese rats, Part 2) as related to “0.8% Ulalyt®”.
Applicants provided only the English translation of the abstract. Examiner was not able to obtain a translation of the full text. Accordingly, the rejections below and the arguments solely rely on the English abstract and Applicant’s interpretation of this reference.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-4 and 16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
To be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In Genentech Inc. v. Novo Nordisk 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997); In re Wright 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993). See also Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1212, 18 USPQ2d 1016, 1026 (Fed. Cir. 1991); In re Fisher 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) and In re Wands 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue”. See In re Wands, 858 F.2d 731, 737, 8 USPQ 2d 1400, 1404 (Fed. Cir. 1998). The court set forth the eight factors to consider when assessing if a disclosure would require undue experimentation. Citing Ex parte Forman, 230 USPQ 546, the court recited eight factors.
These factors include, but are not limited to:
1) The breadth of the claims,
2) The nature of the invention,
3) The state of the prior art,
4) The level of one of ordinary skill,
5) The level of predictability in the art,
6) The amount of direction provided by the inventor,
7) The existence of working examples,
8) The quantity of experimentation needed to male or use the invention based on the content of the disclosure.
(1 and 2) The breadth of the claims and the nature of the invention: The claims are broad. The claims are drawn to a method of decreasing triglyceride level in the blood comprising administering an effective amount of a composition comprising citrate to a subject having metabolic syndrome.
(3 and 5) The state of the prior art and the level of predictability in the art: The art teaches methods of treating metabolic syndrome in a subject by oral administration of a composition comprising an alkalizing agent including one or more citrates. However, according to Applicant’s Declaration, in Kanda et al’s reference it is disclosed that the composition comprising sodium citrate and potassium citrate (Ulalyt®) administered to animal models with metabolic syndrome did not affect their triglyceride levels in blood (See Declaration, page 4). Therefore, the prior art contradicts the claimed method and lead to unpredictability of the claimed method.
(6 and 7) The amount of direction provided by the inventors and the existence of working examples: Applicants have provided in the specification disclosure regarding treating metabolic syndrome and a subject having neutral fat levels of about 150 mg/dL or more with a composition comprising al alkalizing agent including a citrate or sodium bicarbonate.
(8) The quantity of experimentation needed to make or use the invention bases on the content of the disclosure: The quantity of experimentation needed to make and use the invention based on the contents of the disclosure and the unpredictability asserted by Kanda et al’s reference as declared by the Applicant, is very high and not enabled by the specification.
Conclusion
In view of the unpredictability in the art, it would require undue experimentation on the part of the person of skill in the art to practice the full scope of the invention.
Claims 1-4 and 16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. The Specification does not provide support for the claims because the claims are broadly directed to a method of decreasing triglyceride level by administering a composition comprising an effective amount of citrate. This claim encompasses any amount of a citrate. The Specification has not shown or provided support that any amount of citrate can achieve the claimed method. The Specification states “As a medicine containing such an active ingredient, a tablet containing 231.5 mg of potassium citrate and 195.0 mg of sodium citrate hydrate in one tablet can be also used as the metabolism improving agent of the present invention” (See [0031] of published Spec). And that “For example, when using a mixture of potassium citrate and sodium citrate hydrate as the alkalizing agent, potassium citrate and sodium citrate hydrate may be contained in the food to take potassium citrate and sodium citrate hydrate in a total of 1 to 10 g (e.g., 1 to 6 g), and preferably 1 to 3 g per day. When the food provided by the present invention is a tablet supplement, for example, 300 mg to 600 mg tablets may be produced to contain 70 to 80% by weight of an alkalizing agent (e.g., potassium citrate and sodium citrate hydrate) per tablet” (See [0041]).
Claims 1-4 and 16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claim 1 recites a method of decreasing triglyceride level in the blood comprising administering an effective amount of a composition comprising citrate. However, there is no definition or recitation of an effective amount of citrate. Thus, the specification fails to comply with the written description requirement.
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%.
Applicant claims a method of decreasing triglyceride level in the blood comprising administering an effective amount of a composition comprising citrate as an active ingredient to a subject having metabolic syndrome or letting a subject having metabolic syndrome ingest an effective amount of a composition comprising 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 and 16 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).
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).
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).
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. 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 and improve the subject’s acidified body fluids.
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). 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 07/24/25 have been fully considered but they are not persuasive.
Applicant’s amendments to the claims have necessitated modified grounds of rejections. Applicant’s arguments so far as they pertain to the maintained references and rejections are discussed below.
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 metabolic syndrome and 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 4-5).
The above argument is not found persuasive because the rejection has been modified to meet the claimed amendments and is now relying on the teachings of Werner in view of Grundy and Abe. 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. 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.
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” (See [0034]).
Additionally, Grundy teach that high triglyceride levels are a common symptom of metabolic syndrome and an important marker in diagnosing metabolic syndrome.
Werner et al specifically teach treating a subject having metabolic syndrome. For example, it is stated that “A further embodiment relates to a mixture of three or more citrate salts for use as described herein, wherein the therapeutic method comprises the treatment and/or prevention of a metabolic disorder, wherein the metabolic disorder comprises at least one selected from the group consisting of diabetes mellitus, obesity and metabolic syndrome” (See page 14).
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.
Applicant’s next argument is that “Werner discloses a method for stimulating the metabolism of carbohydrates, particularly glucose, using a mixture of citric acid comprising magnesium citrate, and also describes potassium citrate and sodium citrate as examples of such mixture of citric acid. However, Werner does not mention that a mixture of citric acid can lower triglycerides. Furthermore, the fact that glucose and triglycerides are metabolized through different pathways is well known in the field of medical physiology. For instance, Werner states that “Different forms of metabolism exist, the carbohydrate, the protein, the fat and the mineral substance metabolism, which are named after the substances processed therein” (See Remarks, page 6).
The above argument is not persuasive either. While Werner does not expressly teach that the citrate combination as claimed is effective in decreasing triglyceride levels in a subject, they do state that such combination is effective in treating metabolic diseases including metabolic syndrome. That is, Werner expressly discloses a method of treating subjects having a metabolic syndrome by administration of the said compositions comprising one or more citrates including sodium citrate and potassium citrate. As stated above, it is well known in the art and expressly taught by Grundy, elevated levels of triglyceride is a common symptom of metabolic syndrome. Thus, by following the teachings of Werner and treating a subject having metabolic syndrome with a composition comprising one or more citrates, the levels of triglyceride would necessarily decrease.
More importantly, 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 also argues that “Next, the Examiner states that Werner explicitly discloses the treatment method for patients with metabolic syndrome (“Werner et al. expressly disclose treating subjects having a metabolic syndrome.”). However, as discussed above, Werner merely administers citrate salts to “healthy people.”” (See Remarks, pages 8-9).
The above argument is neither correct nor persuasive. The term “healthy” is disclosed in the Werner document 3 times, one in relations to the test subjects and it compares blood glucose levels before and after intervention. On the other hand, there is multiple recitation of the said compositions being administered to subjects for treatment of metabolic disorders including metabolic syndrome.
The below recitation is from Werner reference:
A further embodiment relates to a mixture of three or more citrate salts for use as described herein, wherein the therapeutic method comprises the treatment and/or prevention of a metabolic disorder, wherein the metabolic disorder comprises at least one selected from the group consisting of diabetes mellitus, obesity and metabolic syndrome. (See pages 1, 14 and 15). In fact, not only Werner teaches this, but Werner claims a method of treating metabolic syndrome by a composition comprising citrates (See claim 3).
Applicant argues that Abe and Werner do not disclose that citrate salts decrease triglycerides (See Remarks, page 9).
While this 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 is 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).
Applicant also points to the Declaration of Masuzaki demonstrating that it was well-known that Ulalyt® does not decrease blood triglyceride levels in metabolic syndrome model animals (See Remarks, page 9).
This argument is addressed below.
Response to the Declaration under Rule 132
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. Additionally, as stated above, this results in an enablement rejection because Kanda et al clearly shows that this method did not result in a decrease in triglyceride levels.
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 and 16 are rejected.
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/Mina Haghighatian/
Mina Haghighatian
Primary Examiner
Art Unit 1616