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, 15-17, 20, 23-37 are pending.
Claims 1, 15-17, 20, 23-28 are rejected.
Claims 29-37 are allowable.
DETAILED ACTION
1. Claims 1, 15-17, 20, 23-37 are under consideration in this Office Action.
Priority
2. It is noted that this application 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 12/12/2023 are accepted by the examiner.
IDS
4. The IDS filed on 12/27/23,12/02/24,12/23/24, 5/07/25, 7/11/25 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 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 1 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.
In claim 1, the phrase “A pharmaceutical composition for treating or inhibiting a hyperuricemia-related disease of a subject” is recited.
This expression can be confusing because this is a hybrid claim of combining a composition and a method claim. The examiner recommends to separate it into two different claims.
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 15-17, 20, 23-28 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for treating a hyperuricemia , does not reasonably provide enablement for preventing a hyperuricemia disease or the intent of preventing such as inhibiting a hyperuricemia. 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” or the intent of prevention such as the inbibition of the claimed disease 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 or the intent of preventing such as inhibiting requires identifying those patients who will acquire the disease before the hyperuricemia 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 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 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 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 generally. That is, the skill is so low that no compound effective generally against any hyperuricemia disorders 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” or “inhibiting” and the phrase "reducing the risk".
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1,15-17, 20, 23-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1,13-17, 20, 23-24 of copending Application No.18/569,571 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because of some difference between the scope of the claimed invention and that of the claims of the copending application in the followings:
The claims 1 and 13 of copending Application No. 18/569,571 describe the followings:
1. (Currently Amended) A pharmaceutical composition for treating or preventing inhibiting a hyperuricemia-related disease of a subject, comprising 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazol-4-carboxylic acid or a pharmaceutically acceptable salt thereof, wherein the 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazol-4-carboxylic acid or a pharmaceutically acceptable salt thereof in the pharmaceutical composition is orally administered at a dosage of 50 to 200 mg/day,
wherein when the pharmaceutical composition is administered daily for 12 weeks to a hyperuricemia patient group having a blood uric acid concentration of 8 to 12 mg/dL, it is possible to lower the blood uric acid concentration to less than 6.0 mg/dL in 55% or more of the patient group.
13. (Currently Amended) A method of treating or inhibiting a hyperuricemiarelated disease in a subject in need thereof, comprising orally administering to the subject a pharmaceutical composition comprising 1-(3-cyano-l-isopropyl-indol-5-yl)pyrazol-4-carboxylic acid or a pharmaceutically acceptable salt thereof at a dosage of 50 to 200 mg/day, wherein when the pharmaceutical composition is administered daily for 12 weeks to the subject the blood uric acid concentration in the subject is reduced to less than 6.0 mg/dL.
, whereas the instant claims 1 and 15 do disclose the following composition as shown below:
1. 1. (Currently Amended) A pharmaceutical composition for treating or preventing inhibitinga hyperuricemia-related disease ofa subject, comprising 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazol- 4-carboxylic acid or a pharmaceutically acceptable salt thereof, wherein the 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazol-4-carboxylic acid or a pharmaceutically acceptable salt thereof in the pharmaceutical composition is orally administered to the subject at a dosage of 50 to 200 mg/day, wherein the subject has an estimated glomerular filtration rate (eGFR) of less than 90 mL/min/1.73m2.
15. (Currently Amended) A method of treating or preventing-inhibitinga hyperuricemia- related disease in a subject in need thereof, comprising orally administering to the subject a pharmaceutical composition comprising 1-(3-cyano-1-isopropyl-indol-5-yl)pyrazol-4-carboxylic acid or a pharmaceutically acceptable salt thereof at a dosage of 50 to 200 mg/day, wherein the subject has an estimated glomerular filtration rate (eGFR) of less than 90 mL/min/1.73m2.
However, the instant claims differ from the co-pending Application No.18/569,571 in that the scope of the claimed invention with respect to a patient having an estimated glomerular filtration rate (eGFR) of less than 90 mL/min/1.73m2 and the limitations of being administered daily for 12 weeks; a hyperuricemia patient group having a blood uric acid concentration of 8 to 12 mg/dL and lowering the blood uric acid concentration to less than 6.0 mg/dL in 55% or more of the patient group are absent unlike the claims of co-pending Application No..
Even so, the specification does disclose estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73m2 or more (see page 15 , line 19). From this, it seems reasonable that the limitation of estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73m2 or more can be incorporated into the claim 1, while the limitations of being administered daily for 12 weeks; a hyperuricemia patient group having a blood uric acid concentration of 8 to 12 mg/dL and lowering the blood uric acid concentration to less than 6.0 mg/dL in 55% or more of the patient group can be removed in order to emphasize the particular aspect of the claimed invention. Moreover, such modification of limitations in the current claims can be anticipated; there is very little difference as to the patentable distinction.
So, it would have been obvious to the skilled artisan to be motivated to add that limitation to the claim and remove some of the limitations from the claim in order to get narrower the scope of the claimed invention. This is because the skilled artisan in the art would expect such a manipulation to be feasible and successful as guidance shown in the application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims 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, 15-17, 20, 23-28 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 claims 1,15 (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 17 and 20 (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 23-26 (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 1,15, 17 (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 claims 27-28 (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, 15-16 (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
PNG
media_image1.png
1
1
media_image1.png
Greyscale
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, 15-17, 20, 23-28 are rejected.
Claims 29-37 are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAYLOR V OH whose telephone number is (571)272-0689. The examiner can normally be reached 8:00-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at 571-272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TAYLOR V OH/Primary Examiner, Art Unit 1625 3/7/2026