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 .
Non-Final Rejection
. The Status of Claims:
Claims 1-20 are pending.
Claims 1-19 are rejected.
Claim 20 is objected.
DETAILED ACTION
1. Claims 1-20 are under consideration in this Office Action.
Priority
2. It is noted that this application is a CIP of 18569568 12/12/2023, which is a 371 of PCT/KR2022/008444 06/15/2022, which has a foreign priority document, KOREA, REPUBLIC OF KR10-2021-0077709 06/15/2021.
Drawings
3. The drawings field on 8/28/24 are accepted by the examiner.
IDS
4. The IDS filed on 8/28/24,12/02/24,12/23/24, 5/7/25, 7/11/25, 6/22/26 have
been reviewed by the examiner.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Objections
Claim 20 is objected to as being dependent upon a rejected base claim.
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.
Claims 1-5, 10-11 are 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.
In claim 1, the phrase “a hyperuricemia-related disease in a subject” is recited.
This expression can be confusing because the claim does not explain what kinds of diseases are related to the hyperuricemia. The examiner recommends to put the specific names of diseases related to the hyperuricemia.
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 1-11 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for treating a hyperuricemia-related disease , does not reasonably provide enablement for preventing a hyperuricemia-related disease. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. Applicants are not enabled for preventing any of these diseases. The only established prophylactics are vaccines not the 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazol-4-carboxylic acid compound such as present here. In addition, it is presumed that “prevention” would requires a method of identifying those individuals who will develop the claimed disease before they exhibit symptoms. There is no evidence of record that would guide the skilled clinician to identify those who have the potential of becoming afflicted.
“The factors to be considered [in making an enablement rejection] have been summarized as the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art, and the breadth of the claims”, In re Rainer, 146 USPQ 218 (1965); In re Colianni, 195 USPQ 150, Ex parte Formal, 230 USPQ 546. 1) As discussed above, preventing the disease requires identifying those patients who will acquire the disease before the hyperuricemia-related disease occurs. This would require extensive and potentially opened ended clinical research on healthy subjects. 2) The passages spanning lines 3-13 on page 12 and lines16-19 on page 14 mention the diseases Applicant intend to treat. 3) There is no working example of such a preventive procedure in man or animal in the specification. 4) The claims rejected are drawn to clinical preventative medicine for the hyperuricemia-related disease and are therefore physiological in nature. 5) The state of the art is that no general procedure is art-recognized for determining which patients generally will become a hyperuricemia-related disease before the fact. 6) The artisan using Applicants invention would be a Board Certified physician in the preventative diseases with an MD degree and several years of experience. Despite intensive efforts, pharmaceutical science has been unable to find a way of getting a compound to be effective for the prevention of a hyperuricemia-related disease generally. Under such circumstances, it is proper for the PTO to require evidence that such an unprecedented feat has actually been accomplished, In re Ferens, 163 USPQ 609. No such evidence has been presented in this case. The failure of skilled scientists to achieve a goal is substantial evidence that achieving such a goal is beyond the skill of practitioners in that art, Genentech vs. Novo Nordisk, 42 USPQ2nd 1001, 1006. This establishes that it is not reasonable to any agent to be able to prevent a hyperuricemia-related disease generally. That is, the skill is so low that no compound effective generally against any hyperuricemia-related disease has ever been found let alone one that can prevent such conditions. 7) It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved", and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). 8) The claims broadly read on all patients, not just those undergoing therapy for the claimed disease and on the 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazol-4-carboxylic acid compound.
The Examiner suggests deletion of the word “preventing” and the phrase "reducing the risk".
Double Patenting
Claims 12-19 of this application is patentably indistinct from claims 29-35 and 37 of Application No.18/569,568. Pursuant to 37 CFR 1.78(f), when two or more applications filed by the same applicant or assignee contain patentably indistinct claims, elimination of such claims from all but one application may be required in the absence of good and sufficient reason for their retention during pendency in more than one application. Applicant is required to either cancel the patentably indistinct claims from all but one application or maintain a clear line of demarcation between the applications. See MPEP § 822.
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 12-19 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 29-35 and 37 of copending Application No.18/569,568 (reference application). This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
Claim Rejections - 35 USC § 103
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.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
6. Claims 1-11 are rejected under 35 U.S.C. 103 as being unpatentable over Song et al (US 2012/0184582 Al) in view of Yun et al (WO 2012/138147 A2) and Pillinger et al ( Seminars in Arthritis and Rheumatism 50, 2020, S24-S30) and Wikipedia (Glomerular filtration rate, November, 2020, p. 1-16).
.
Determination of the scope and content of the prior art
Song et al discloses an oral administration pharmaceutical composition as in claim 30 (see page 8 ,a paragraph#0140) comprising 1-(3-cyano-l-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid( compound 1) or a pharmaceutically acceptable salt thereof and a method for treating hyperuriemia, gout, heart failure, cardiovascular disease, hypertension, diabetes, complications of diabetes, kidney disease, inflammation, articular disease and inflammatory bowel disease (see page 1 , a paragraph#0014) by the composition comprises 1-(3-cyano-l-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid( compound 1) as in claim 1 (partially) (see page 33, claim 1; page 36, claim 9; page 38, claims 13-15).
Also, it teaches that the incidence rate of gout is 0.5% in a patient group with a blood uric acid level of 7.0 mg/dl or more, and the incidence rate of gout is 5.5% in a patient group with a uric acid level of 9.0 mg/dl or more (G. Nuki, Medicine, 2006, 34, 417.about.423). Considering the incidence rate as described above, blood uric acid level is found to be an important causative factor for gout (see page 1, a paragraph#0006).
Furthermore, it shows that the compound 1 with 10 mg/kg can reduce a plasma uric acid level in the range of less than 1 mg/dl (Fig. 1 ) as in claims 4-5 (partially) and also the compound 1 with 10 mg/kg can inhibit a plasma uric acid in the range of more than 60% (% inhibition) (Fig. 2 ).
The current invention, however, differs from the prior art in that the claimed dosage of 50 to 200 mg/day and the subject having an estimated glomerular filtration rate (eGFR) of less than 90 mL/min/1.73m2 and a therapeutic agent for suppressing gout flare are unspecified in the prior art.
Yun et al discloses a composition comprising 1-(3-cyano-l-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid for the treatment of diseases associated with xanthine oxidase selected from the group consisting of hyperuricemia, gout, heart ,cardiovascular disease, hypertension, diabetes, kidney disease as in claims 6-10 (partially) inflammation and articular disease, and inflammatory bowel disease(see page 20 .claim 1 ; page 21, claim 11).
In addition, it describes that the dosage needed for the treatment of an adult is typically from about 1 to 1,000 mg per day, depending on the intensity and frequency of the administration. When administered to an adult via an intramuscular or intravenous route, a total dosage from about 1 to 500 mg per day will be sufficient when separately administered in a single dosage as in claims 1, 4, (partially) (see page 6 , aparagraph#50).
Also, Pillinger et al teaches that gout is a disease in which the metabolic condition hyperuricemia leads to the formation of monosodium urate crystals, which provoke acute and chronic inflammatory responses through activation of the innate immune system (see abstract ).
Acute flares can be treated by using NSAIDS such as celecoxib, naproxen, and etc,(see page and colchicine as in claim 11 (partially) (see page S25, a left col., the first and third paragraphs).
In addition, Wikipedia teach that an estimated glomerular filtration rate (eGFR) is a blood test calculation that measures how well your kidneys filter waste, acting as a key indicator of kidney function and stage of disease. A result below 60 mL/min/1.73
for three months indicates chronic kidney disease (CKD), while a normal level is generally 90 or higher.
The severity of chronic kidney disease (CKD) is described by six stages; the most severe three are defined by the MDRD-eGFR value, and first three also depend on whether there is other evidence of kidney disease (e.g., proteinuria):
0) Normal kidney function – GFR above 90 mL/min/1.73 m2 and no proteinuria
1) CKD1 – GFR above 90 mL/min/1.73 m2 with evidence of kidney damage
2) CKD2 (mild) – GFR of 60 to 89 mL/min/1.73 m2 with evidence of kidney damage as in claims 1-3 (partially)
3) CKD3 (moderate) – GFR of 30 to 59 mL/min/1.73 m2
4) CKD4 (severe) – GFR of 15 to 29 mL/min/1.73 m2
5) CKD5 kidney failure – GFR less than 15 mL/min/1.73 m2 Some people add CKD5D for those stage 5 patients requiring dialysis; many patients in CKD5 are not yet on dialysis (see page 12, a section of chronic kidney disease stages).
Ascertainment of the difference between the prior art and the claims
The difference between the instant application and the applied Song et al art is that the Song et al does not expressly teach the claimed dosage of 50 to 200 mg/day and the subject having an estimated glomerular filtration rate (eGFR) of less than 90 mL/min/1.73m2 and a therapeutic agent for suppressing gout flare are unspecified in the prior art. The deficiencies of the Song et al are partially cured by the Yun et al and Pillinger et al and Wikipedia.
The difference between the instant application and the applied Yun et al art is that the Yun et al does not expressly teach the claimed subject having an estimated glomerular filtration rate (eGFR) of less than 90 mL/min/1.73m2 and a therapeutic agent for suppressing gout flare. The deficiencies of the Yun et al are partially cured by the Pillinger et al and Wikipedia.
The difference between the instant application and the applied Pillinger et al art is that the Pillinger et al does not expressly teach the claimed composition comprising 1-(3-cyano-l-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid with the dosage of 50 to 200 mg/day and the subject having an estimated glomerular filtration rate (eGFR) of less than 90 mL/min/1.73m2 . The deficiencies of the Pillinger et al are partially cured by the Song et al and Yun et al and Wikipedia.
The difference between the instant application and the applied Wikipedial art is that the Wikipedia does not expressly teach the claimed composition comprising 1-(3-cyano-l-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid with the dosage of 50 to 200 mg/day and and a therapeutic agent for suppressing gout flare. The deficiencies of the Wikipedia Pillinger et al are partially cured by the Song et al and Yun et al and Wikipedia.
Resolving the level of ordinary skill in the pertinent art.
Regarding the Claim 1 with respect to the lack of disclosing the claimed dosage of 50 to 200 mg/day, the secondary Yun et al does teach generally that the dosage needed for the treatment of an adult is typically from about 1 to 1,000 mg per day or from about 1 to 500 mg per day(see page 6 , a paragraph#50); the claimed dosage of 50 to 200 mg/day is within the dosage range of Yun et al. Thus, the prior art is relevant to the claimed invention.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Song et al expressly discloses the oral administration pharmaceutical composition (see page 8 ,a paragraph#0140) comprising 1-(3-cyano-l-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid( compound 1) or a pharmaceutically acceptable salt thereof and the method for treating hyperuriemia, gout, heart failure, cardiovascular disease, hypertension, diabetes, complications of diabetes, kidney disease, inflammation, articular disease by using the comprising 1-(3-cyano-l-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid.
Similarly, Yun et al does teach the composition comprising 1-(3-cyano-l-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid with the dosage of from about 1 to 500 mg per day for the treatment of diseases associated with xanthine oxidase selected from the group consisting of hyperuricemia, gout, heart ,cardiovascular disease, hypertension, diabetes, kidney disease , inflammation and articular disease.
Furthermore, Pillinger et al does describe that gout flare associated with the metabolic condition hyperuricemia can be treated by using NSAIDS such as celecoxib, naproxen, and etc,(see page and colchicine (see page S25, a left col., the first and third paragraphs).
In addition, Wikipedia does give a guidance that
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an estimated glomerular filtration rate (eGFR) indicates that a value between 60 and 89 mL/min/1.73 is for kidney damage while a normal level is generally 90 or higher.
Song et al and Yun et al are closely related to the treatment of hyperuricemia by using the same composition containing 1-(3-cyano-l-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid, whereas Pillinger et al teaches the additional therapeutic agent for gout flare.
So, if the skilled artisan in the art had desired to develop the method of treating hyperuricemia for a patient with an (eGFR) of less than 90 mL/min/1.73m2 by using a composition containing 1-(3-cyano-l-isopropyl-indol-5-yl)pyrazole-4-carboxylic acid with the specific dosage range for enhancing the overall treatment, it would have been obvious to the skilled artisan in the art before the effective filing date of the claimed invention to be motivated to incorporate the teaching of Yun’s specific dosage range and Wikipedia’s guidance about the value of eGFR in combination with Pillinger’s additional therapeutic agent into the Song’s et al method. This is because the skilled artisan in the art would expect such combined composition for the method to be successful and feasible as guidance shown in the prior art.
Conclusion
Claims 1-19 are rejected.
Claim 20 is objected.
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/TAYLOR V OH/Primary Examiner, Art Unit 1625 6/27/2026
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