DETAILED ACTION
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 .
Status of the Application
This Office Action is in response to Applicant's arguments filed on February 18, 2026. Claim(s) 42-53 and 57 are pending and examined herein.
Response to Arguments
In view of applicant’s amendments, the 112(a), first paragraph rejection over claims 42-59 is hereby withdrawn.
Applicant’s amendments and arguments with respect to the 103 rejection of claims 42-53 and 57-59 as being unpatentable over Ibanez (SUN-0102, Date of Presentation, June 14, 2014, Endocrine Society’s 96th Annual Meeting and Expo, June 21-24, 2014-Chicago, IDS dated 08/02/2023, NPL reference #17) as evidenced by Applicant’s specification and as evidenced by Ibanez (Nature Reviews Endocrinology, 2014, IDS dated 08/02/2023, NPL reference #11) of record (referred to as “Ibanez Nature”) in view of Beeley (US PG-PUB 2004/0266678) have been fully considered.
Applicant argues:
Claim 42, and claims 43-53 and 57, which depend therefrom, recites, inter alia, a method for treating low ovulation rate associated with liver steatosis comprising administering spironolactone, pioglitazone and metformin to a patient.
The Examiner cites Ibanez Endocrine for its alleged teaching of a pioglitazone, spironolactone and metformin (PioSpiMet) combination and its use for treating adolescent girls with hyperinsulinemic androgen excess and without risk of pregnancy. In no instance does this reference teach or suggest administering PioSpiMet for treating low ovulation rate associated with liver steatosis. The Examiner appears to rely on Ibanez Endocrine, at least in part, because this reference discloses that menstrual irregularity may be caused by hyperinsulinemic androgen excess; however, "menstrual irregularity" and "low ovulation rate" are not necessarily correlated, and the Examiner has not provided a rationale as to why one of ordinary skill in the art would have any reasonable expectation that Ibanez Endocrine's disclosure of PioSpiMet to treat menstrual irregularity associated with hyperinsulinemic androgen excess would be effective for treating low ovulation rate associated with liver steatosis. These are two separate indications, and without improper hindsight analysis of Applicant's own disclosure, it would not be obvious to one of ordinary skill in the art that a treatment of one cause of menstrual irregularity would also be effective to treat low ovulation rate associated with liver steatosis.
The Examiner appears to cite Ibanez Nature primarily for the notion that PCOS and hyperinsulinemic androgen excess are synonymous. The Examiner concedes that Ibanez Nature does not teach treatment of low ovulation. Accordingly, Ibanez Nature fails to cure the deficiencies of Ibanez Endocrine. Namely, neither Ibanez Endocrine nor Ibanez Nature alone, or in combination, teach or suggest administering a combination of spironolactone, pioglitazone and metformin for treating low ovulation rate associated with liver steatosis.
Regarding the arguments above, examiner respectfully notes that Ibanez teaches PioSpiMet had a normalizing effect on hepatic adiposity (a.k.a. hepatic steatosis). Thus, one of ordinary skill in the art would find it obvious that if hepatic adiposity is normalized with the therapeutic regimen, then the patient population with liver steatosis suffering with low ovulation will also benefit from the therapy.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Applicant further argues:
The Examiner thus turns to Beeley in an attempt to find a teaching related to administering a combination of spironolactone, pioglitazone and metformin for treating low ovulation rate associated with liver steatosis. Beeley is insufficient in this regard for several reasons. First, the Examiner points to claim 42 of Beeley and alleges that this reference teaches restoring ovulation in a subject suffering from PCOS. However, the Examiner has failed to establish how such a teaching would lead one of ordinary skill in the art to treatment of low ovulation rate associated with liver steatosis. In fact, Beeley is completely silent with respect to liver steatosis as it relates to low ovulation rate, and the Ibanez references do not make up this deficiency.
Second, Beeley is directed to treatment of PCOS or symptoms thereof, and, in all instances, the methods disclosed in Beeley require administration of GLP-1 or exendin (see e.g., claim 42). In some instances, Beeley teaches that an anti-androgenic drug or an insulin- sensitizing agent can be combined with the GLP-1 or exendin (see paragraphs [0517-518]), but there is no teaching in Beeley to use a combination therapy that includes both an anti-androgenic drug and an insulin-sensitizing agent, as presently claimed. Even assuming arguendo that Beeley does suggest combining an anti-androgenic drug and an insulin-sensitizing agent, the suggested combination would still necessarily include GLP-1 or exendin.
Finally, the two Ibanez references and Beeley cannot be combined with any reasonable expectation of successfully arriving at a method for treating low ovulation rate associated with liver steatosis in a patient selected from an adolescent girl and a woman of childbearing age, said method comprising administering spironolactone, pioglitazone and metformin to the patient. To combine Beeley with either one, or both, of the Ibanez references would require removal of a required element of Beeley (i.e., GLP-1 or exendin) and combining both an anti-androgenic drug and an insulin-sensitizing agent, which is not taught by Beeley. Further, none of the references teach or suggest treating low ovulation rate associated with liver steatosis. Instead, the cited references relate to treatment of PCOS and menstrual irregularities, none of which have a direct correlation with low ovulation rate associated with liver steatosis. Therefore, one of ordinary skill in the art would not have been motivated to combine Beeley and the Ibanez references to arrive at the claimed invention in the manner suggested by the Examiner.
Examiner respectfully notes that applicant inaccurately conveys the purpose of citing the Beeley reference. Said reference was employed merely to address the limitation that menstrual irregularity is a result of low ovulation. Ibanez teaches menstrual irregularity, but not specifically as a result of low ovulation. Thus, Beeley teaches that PCOS symptoms may include irregular ovulation, among others. It was never the intention of the examiner, as clearly set forth on the record, to attempt to teach administering a combination of spironolactone, pioglitazone and metformin for treating low ovulation rate associated with liver steatosis based on the teachings of Beeley. The only teaching that was relied upon with the Beeley reference was that PCOS symptoms may include irregular ovulation.
Based on the foregoing reasons, said rejection is hereby maintained.
Applicant’s cancelation of claims 54-56 as being unpatentable over Ibanez (SUN-0102, Date of Presentation, June 14, 2014, Endocrine Society’s 96th Annual Meeting and Expo, June 21-24, 2014-Chicago, IDS dated 08/02/2023, NPL reference #17) of record as evidenced by Applicant’s specification and as evidenced by Ibanez (Nature Reviews Endocrinology, 2014, IDS dated 08/02/2023, NPL reference #11) of record (referred to as “Ibanez Nature”) in view of Beeley (US PG-PUB 2004/0266678) as applied to claims 42-53 and 57-59 in the 103 rejection above in further view of De Zegher (US PG-PUB 2004/0157809) of record (IDS dated 08/02/2023, US Patent, reference #12) renders the rejection moot.
Any rejection from the previous Office action not set forth on record below is hereby withdrawn.
The maintained/modified rejections are made in the Final Office action below as necessitated by amendment.
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 of this title, 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 42-53 and 57 are rejected under 35 U.S.C. 103 as being unpatentable over Ibanez (SUN-0102, Date of Presentation, June 14, 2014, Endocrine Society’s 96th Annual Meeting and Expo, June 21-24, 2014-Chicago, IDS dated 08/02/2023, NPL reference #17) as evidenced by Applicant’s specification and as evidenced by Ibanez (Nature Reviews Endocrinology, 2014, IDS dated 08/02/2023, NPL reference #11) of record (referred to as “Ibanez Nature”) in view of Beeley (US PG-PUB 2004/0266678).
Ibanez teaches hyperinsulinemic androgen excess is the most common cause of hirsutism, acne, seborrhea and menstrual irregularity in adolescent girls. The ovarian androgen excess originates most often from an absolute or relative excess of fat in adipose tissue and from the ensuing elevations in insulinemia and gonadotropin secretion.
Ibanez teaches the effects of a novel low-dose insulin-sensitizing combination of pioglitazone (Pio, only 7.5 mg/d), spironolactone (Spi, 50 mg/d) and metformin (Met, 850 mg/d) in adolescents with hyperinsulinemic androgen excess and without need for contraception. Over 6 months, PioSpiMet had more normalizing effects than estro-progestogen contraceptive (OC), in particular on hirsutism score, on visceral and hepatic adiposity (a.k.a hepatic steatosis), on carotid intima-media thickness and on circulating C-Reactive Protein, LDL-cholesterol and GGT.
Ibanez teaches none of the girls dropped out of the study; there were no particular side-effects in either study subpopulation.
Ibanez teaches the preliminary evidence over 6 months suggests that PioSpiMet confers more benefit than OC the adolescent girls with hyperinsulinemic androgen excess and without risk of pregnancy (full abstract).
As evidenced by Applicant in the specification, “hyperinsulinaemic androgen excess, a symptom that leads to the diagnosis of polycystic ovary syndrome (PCOS), is the most common cause of hirsutism, acne, seborrhoea and menstrual irregularity in adolescent girls.’ The term ‘hyperinsulinaemic androgen excess’ can be used in place of the term ‘polycystic ovary syndrome’” (page 1, “Background of the Invention”).
Further evidenced by Ibanez (Nature), the authors state that instead of using the term PCOS, the term hyperinsulinaemic androgen excess is preferred (page 499, column 1, lines 5-7).
Ibanez teaches menstrual irregularity, but does not specifically teach the irregularity as a result of low ovulation.
Beeley teaches a method of restoring ovulation in a subject suffering from PCOS (claim 42), comprising an ovulation inducing drug, an anti-androgenic drug selected from spironolactone (claim 48), and an insulin sensitizing agent selected from metformin, pioglitazone, among a few others (claim 49).
Beeley teaches PCOS may include one or more symptoms selected from hyperlipidemia, anovulation, irregular ovulation, hyperandrogenism, hirsutism, acne, among others (claim 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have employed PioSpiMet as a method of treating menstrual irregularities as taught by Ibanez and envisioned that the menstrual irregularities arise from anovulation or irregular ovulation. Beeley teaches those that suffer from PCOS exhibit anovulation and irregular ovulation.
Ibanez does not teach the single or sequential administration of the drug combination as required by the limitations of claims 53, 58, and 59.
Beeley teaches the active ingredients of the compositions may be administered sequentially or concurrently (claim 51; [0520]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have known that the time spacing of drug delivery is considered a parameter within the purview of the skilled artisan to optimize, in the absence of secondary considerations (i.e., unexpected results).
Therefore, based on the foregoing reasons, the instant claims are deemed unpatentable over the cited art.
Conclusion
Claims 42-53 and 57 are not allowed.
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 extension fee 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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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sahar Javanmard whose telephone number is (571)270-3280. The examiner can normally be reached on Monday-Friday, 9:00-5:00 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Alstrum-Acevedo can be reached on 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/SAHAR JAVANMARD/Primary Examiner, Art Unit 1622
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