DETAILED ACTION
All rejections and objections not mentioned below have been withdrawn.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 05/13/2026 has been entered.
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 .
Priority
Acknowledgment is made of applicant’s claim for priority. The certified copy has been filed in parent Application No. 63/070,343, filed on 8/26/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/04/2023 , 09/27/2024 05/30/2025, 01/08/2026, 05/13/2026 are being considered by the examiner.
Claim Rejections - 35 USC § 103- Updated
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
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.
Claim(s) 157, 190, 213, 219, 221, 223, 285, 291, 310 is/are rejected under 35 U.S.C. 103 as being unpatentable over HOWERTON (HOWERTON et al., US 2020255436 A1, 2020-08-13, previously provided) in view of HOWERTON (HOWERTON et al., WO2019210266A1, 2019-10-31, previously provided) as evidenced by Stöppler (Stöppler et al ., Definition of Body surface area, 2025, previously provided) further in view of Atzrodt (Atzrodt et al., Deuterium- and Tritium-Labelled Compounds: Applications in the Life Sciences, Angew.Chem. Int. Ed. 2018, 57, 1758–1784) .
The reference HOWERTON 2020 teaches “In one embodiment, the present disclosure provides 3-(4-chloro-2-(morpholin-4-yl)thiazol-5-yl)-7-(1-ethyl-propyl)-2,5-dimethylpyrazolo(1,5-a)pyrimidine or 4-(4-chloro-5-(2,5-dimethyl-7-(pentan-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)thiazol-2-yl)morpholine, wherein the 7-(1-ethyl-propyl) moiety comprises at least one deuterium”[0018] and “The present disclosure provides forms of CRF antagonists and methods using such CRF antagonists for treating diseases. In some embodiments, such CRF antagonists are used to treat congenital adrenal hyperplasia (CAH)”[0003]. The reference HOWERTON 2020 teaches “In some embodiments, the methods described herein administer a compound of Formula I, II, III, and IV, or Compounds 1 or 2 , or a pharmaceutically acceptable salt or solvate thereof twice a day”[0181]. This helps to teach claims 157, 190.
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Wherein, 3-(4-chloro-2-(morpholin-4-yl)thiazol-5-yl)-7-(1-ethyl-propyl)-2,5-dimethylpyrazolo(1,5-a)pyrimidine is the structure below:
Wherein, R1=R2=CH2CH3, R3=methyl, R4=methyl, RA=H=RB.
The reference HOWERTON 2020 teaches “In one embodiment, the 7-(1-ethyl-propyl) moiety comprises 1 deuterium, 2 deuterium, 3 deuterium, 4 deuterium, 5 deuterium, 6 deuterium, 7 deuterium, 8 deuterium, 9 deuterium, 10 deuterium, or 11 deuterium”[0099]. This helps to teach claims 157, 190, 213, 219, 221, 223, 285, 291, 310.
The reference HOWERTON 2020 teaches “In one embodiment, one or both of the 2,5-dimethyl groups independent comprises 3 deuterium, or 6 deuterium” [0099]. This helps to teach claim 157, 190, 213, 219, 221, 223, 285, 291, 310.
The reference HOWERTON 2020 teaches “In some embodiments, the pharmaceutical composition comprises about 400 mg of a compound of Formula I, II, III, and IV, or Compounds 1 or 2, or a pharmaceutically acceptable salt or solvate thereof”[0160]. This helps to teach claim 190.
The reference HOWERTON 2020 teaches “Disclosed herein is a method of treating congenital adrenal hyperplasia (CAH) in a subject in need thereof, comprising administering a combination of a compound of Formula I, II, III, and IV, or Compounds 1 or 2 , or a pharmaceutically acceptable salt or solvate thereof; and a glucocorticoid. In some embodiments, the amount of glucocorticoid administered is reduced as compared to a method not comprising administering a compound of Formula I, II, III, and IV, or Compounds 1 or 2 , or a pharmaceutically acceptable salt or solvate thereof. In some embodiments, the methods described herein reduce the amount of a glucocorticoid administered from a supraphysiologic amount to a physiologic amount. In some embodiments, the methods described herein reduce the symptoms associated with high-dose glucocorticoid therapy. In some embodiments, the symptoms associated with high-dose glucocorticoid therapy are obesity, insulin resistance, metabolic abnormalities, hypertension, cardiovascular diseases, or osteoporosis”[0190-192]. This helps to teach claim 221, 223 and 285.The instant specification defines: “In some embodiments, the corticosteroid is a glucocorticoid” [0072].
The instant claims recite 11 mg/m2/day glucocorticoid HOWERTON does not use the same units so one must convert the units to compare the prior art. The average adult human body in m2 is approximately(Stöppler) 1.7 m2. This means that 1.7 m2 x 11 mg/m2/day =18.7 mg/ day. The reference HOWERTON 2020 teaches “In some embodiments, the glucocorticoid is administered at a dose between about 0.1 mg/day and about 25 mg/day” [0195] and “In some embodiments, a compound of Formula I, II, III, and IV, or Compounds 1 or 2 , or a pharmaceutically acceptable salt or solvate thereof, and the glucocorticoid are administered sequentially”[0179]. This helps to teach claim 285.
The reference HOWERTON 2020 teaches “ In some embodiments, the capsule has a dose strength of up to 200 mg”[0113] and “In some embodiments, the methods described herein administer a compound of Formula I, II, III, and IV, or Compounds 1 or 2 , or a pharmaceutically acceptable salt or solvate thereof once a day”[0181]. This helps to teach claim 285.
The reference HOWERTON 2020 teaches “In some embodiments, molded tablets are made by molding a mixture of the powdered a compound of Formula I, II, III, and IV, or Compounds 1 or 2 moistened with an inert liquid diluent”[0116] and “Glidants such as silicon dioxide”[0138]. This helps to teach claim 291 and 310.
The reference HOWERTON 2020 teaches “In one embodiment, the pharmaceutical composition is in an oral dosage form. In one embodiment, the oral dosage form is selected from the group consisting of a tablet, a capsule, a buccal tablet, a sub-lingual table, an orally-disintegrating tablet, a thin film, a liquid solution, a liquid suspension, a syrup, a powder, solid crystals, minitabs, coated pellets and sachets”[0023] and “In some embodiments, the capsule is formed using materials which include, but are not limited to, natural or synthetic gelatin, pectin, casein, collagen, protein, modified starch, polyvinylpyrrolidone, acrylic polymers, cellulose derivatives, or any combinations thereof. In some embodiments, the capsule is formed using preservatives, coloring and opacifying agents, flavorings and sweeteners, sugars, gastroresistant substances, or any combinations thereof”[0111]. This helps to teach claim 310.
The reference HOWERTON 2020 does not teach “wherein the amount of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, in the first administration is less than the amount of the compound of Formula (I), or a pharmaceutically acceptable salt thereof, in the second and any subsequent administrations” (claim 157, 190, 213, 219, 221, 223, 285, 291, 310). The exact formulas of claims 329, 330, 334. The reference HOWERTON 2020 does not teach reducing the symptoms of claim 213. The reference HOWERTON 2020 does not teach the specific biomarkers of claim 219.
The reference HOWERTON 2019 teaches the following compound ( reference claim 12). Wherein, “… structures depicted herein are also meant to include compounds which differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures except for the replacement of a hydrogen by a deuterium or tritium, or the replacement of a carbon by13 C- or14 C-enriched carbon are within the scope of this invention” [0088].
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The reference HOWERTON 2019 teaches (reference claim 13):
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The reference HOWERTON 2019 teaches “The pharmaceutical compositions can be administered on a regimen of one (1) to four (4) times per day, including once, twice, three times, and four times per day” [0230] and “In certain embodiments, the compound of Formula (I), or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof is administered in an amount of about 5 mg twice daily for a period of up to at least about 14 days. In certain embodiments, the compound of Formula (I), or an isotopic variant thereof…”[0234]. The reference also teaches “Dosages may be varied depending upon the requirements of the patient and the compound being employed. The dose administered to a patient, in the context of the present invention should be sufficient to effect a beneficial therapeutic response in the patient over time. The size of the dose also will be determined by the existence, nature, and extent of any adverse side-effects. Determination of the proper dosage for a particular situation is within the skill of the practitioner. Generally, treatment is initiated with smaller dosages which are less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under circumstances is reached. Dosage amounts and intervals can be adjusted individually to provide levels of the administered compound effective for the particular clinical indication being treated. This will provide a therapeutic regimen that is commensurate with the severity of the individual's disease state” [0135]. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955.). This helps to teach claim 157, 213, 219, 285 and 221.
The reference HOWERTON 2019 teaches “ Testicular adrenal rest tumor(s)” or“TART” and/or ovarian adrenal rest tumor(s) are a complication of congenital adrenal hyperplasia (CAH), which may develop from ectopic remnants of intra-testicular adrenal tissue stimulated by adrenocorticotropic hormone (ACTH) hypersecretion. TART lesions are typically located within the rete testis and are bilateral, synchronous, nodular and multiple. TART can lead to testicular structural damage, spermatogenesis disorders, infertility and mass-forming lesions” [0118]. This helps to teach claim 213.
The reference HOWERTON 2019 teaches “Compound 1, a potent and selective CRFi receptor antagonist, offers a novel nonsteroidal oral treatment approach for CAH. Compound 1 was well tolerated and efficacious in reducing excess ACTH, 170HP, and androstenedione in patients with classic CAH” [0338]. This helps to teach claim 219.
The reference Atzrodt teaches “The underlying principle of deuterated drugs being assessed as new drugs relies on the assumption that specific deuterium labelling may result in potential beneficiary properties. Such properties include reduced systemic clearance and higher systemic exposure, as well as reduced formation of toxic or reactive metabolites, while retaining the potency of the original drug (Scheme 6).[3] Consequently, potential drug benefits could include a reduced dosage or dosing regimen, a smaller potential for drug–drug interactions, and a lower incidence of side effects, overall resulting in an improved pharmacokinetic and safety profile and enhanced effectiveness”(page 1763). This helps to teach all claims.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified HOWERTON 2020 with HOWERTON 2019 and Atzrodt because both HOWERTON references discuss the same compounds (deuterated Tildacerfont) for the same purpose of treating congenital adrenal hyperplasia (CAH) and all three reference discuss deuterated drugs. One would be motivated to combine the references because one would want to use the specific embodiments of the compounds in HOWERTON 2020 for the more specific methods taught by HOWERTON 2019 for the benefits described by Atzrodt about deuterium compounds. One would be motivated to use the embodiments of HOWERTON 2020 over the generic compounds of HOWERTON 2019 for the methods of HOWERTON 2019 as these are more specific in some areas such as biomarker and dosing procedures. One would have a reasonable expectation of success because they use the same core compound. Thus one would have a reasonable expectation of success of combining the two methods since they read on very similar methods and one would be motivated to do so to treat CAH using combinations of those methods were one reads on more specifics than the other to acquire more details. While the exact formulas of claims 157 and 190 are not taught it is obvious to one of ordinary skill in the art to envision these deuteration locations in light of HOWERTON 2020 pointing out specific locations on the molecule and number of D atoms that could be added and because there is a limited number of locations those specific atoms could be located on the molecule. For example the first and second compounds of instant claims 157 and 190 are immediately obvious to one of ordinary skill in the art from the references because the reference HOWERTON 2020 teaches “In one embodiment, one or both of the 2,5-dimethyl groups independent comprises 3 deuterium, or 6 deuterium” [0099]. Since 2,5-dimethyl groups independent comprises 3 deuterium is specifically mentioned it would be obvious to achieve compound 1 of the instant invention. The second compound would also be obvious to one of ordinary skill in the art because the reference HOWERTON 2020 teaches “In one embodiment, the 7-(1-ethyl-propyl) moiety comprises 1 deuterium…”[0099] and since there are only 11 locations for 1 deuterium all location combinations would be immediately oblivious to one of ordinary skill in the art. One would be motivated to make these compounds because the compounds of the reference are taught to treat congenital adrenal hyperplasia (CAH), to achieve advantages of deuterated compound (e.g., a reduced dosage or dosing regimen, a smaller potential for drug–drug interactions, and a lower incidence of side effects, overall resulting in an improved pharmacokinetic and safety profile and enhanced effectiveness, etc.) and one would have a reasonable expectation of success because the compounds are specifically pointed out by the reference.
The specific combination of features claimed is disclosed within the broad generic ranges taught by the reference but such “picking and choosing” within several variables does not necessarily give rise to anticipation. Corning Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989).
However, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S,Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Since all limitations of the current claims have been found within the two HOWERTON references and the references have been found obvious to combine and the limitation found are doing no more than one would expect from such an arrangement, the combination is obvious.
Claim(s) 157, and 322 is/are rejected under 35 U.S.C. 103 as being unpatentable over HOWERTON (HOWERTON et al., US 2020255436 A1, 2020-08-13, previously provided) in view of HOWERTON (HOWERTON et al., WO2019210266A1, 2019-10-31, previously provided) and further in view of Al-kasmia (Al-kasmia et al., Mechanical microencapsulation: The best technique in taste masking for the manufacturing scale - Effect of polymer encapsulation on drug targeting. Journal of Controlled Release 260 (2017) 134–141, previously provided) further in view of Atzrodt (Atzrodt et al., Deuterium- and Tritium-Labelled Compounds: Applications in the Life Sciences, Angew.Chem. Int. Ed. 2018, 57, 1758–1784).
The references HOWERTON and Atzrodt have been discussed supra in the 103 rejection above (which is incorporated herein by reference). The reference HOWERTON 2020 also teaches “In some embodiments, the pharmaceutical composition is formulated as a capsule. In some embodiments, the pharmaceutical composition is formulated as a hard gel capsule. In some embodiments, the pharmaceutical composition is formulated as a soft gel capsule. In some embodiments, the capsule is formed using materials which include, but are not limited to, natural or synthetic gelatin, pectin, casein, collagen, protein, modified starch, polyvinylpyrrolidone, acrylic polymers, cellulose derivatives, or any combinations thereof”[0110-0111] and “In some embodiments, the tablet is coated with a coating material, e.g., a sealant. In some embodiments, the coating material is water soluble. In some embodiments, the coating material comprises a polymer, plasticizer, a pigment, or any combination thereof… In some embodiments, the coating material allows immediate disintegration for fast release of Compound 1. In some embodiments, the coating material is pigmented, clear, or white. In some embodiments, the coating is an enteric coating. ”[0121]. The reference also teaches “Poorly soluble drugs may be difficult to formulate using technologies such as high shear wet granulation. Optimum delivery of poorly soluble drugs may require complex technologies such as solid solutions or amorphous dispersions (for example hot melt extrusion or spray drying), nano-formulations or lipid-based formulations”[0100].
The references HOWERTON do not teach the specific polymer-drug ratios of claim 322.
The reference Al-kasmia teaches “Effect of polymer encapsulation on drug targeting” (title) and “Regarding spray drying, both drug and polymer are dissolved in solvent then sprayed into temperature controlled chamber, thus the solvent evaporates and polymer encapsulates the drug [30,31]. (Table 3) shows the drugs masked by microencapsulation technique in the last three years”(page 136). The reference Al-kasmia also teaches some of the most common polymer drug ratios (table 7) for different masking techniques including spray drying which is included under a mechanical technique (page 138). This ratios across all methods are between 1:2-1:4. Thus this appears to be a common selected range for drug to polymer. The reference also teaches " Drug taste masking is a crucial process for the preparation of pediatric and geriatric formulations as well as fast dissolving tablets. Taste masking techniques aim to prevent drug release in saliva and at the same time to obtain the desired release profile in gastrointestinal tract. Several taste masking methods are reported, however this review has focused on a group of promising methods; complexation, encapsulation, and hot melting. The effects of each method on the physicochemical properties of the drug are described in details. Furthermore, a scoring system was established to evaluate each process using recent published data of selected factors. These include, input, process, and output factors that are related to each taste masking method. Input factors include the attributes of the materials used for taste masking. Process factors include equipment type and process parameters. Finally, output factors, include taste masking quality and yield. As a result, Mechanical microencapsulation obtained the highest score (5/8) along with complexation with cyclodextrin suggesting that these methods are the most preferable for drug taste masking”(abstract). This helps to teach claim 322.
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It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified HOWERTON 2020, HOWERTON 2019 and Atzrodt with Al-kasmia because HOWERTON 2020 teaches polymers and spray drying for drug delivery and so does Al-kasmia. Thus it would have been obvious with a reasonable expectation of success to use the technique and the polymers suggested by HOWERTON with the general suggested ratios for the same technique as provided by Al-kasmia because it is a ratio that is meant for the spray drying technique. One would be motivated to do so to mask the taste of the drug.
Response to Arguments
Applicant's arguments filed 05/13/2026 have been fully considered but they are not persuasive.
The applicant argues that:
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This argument is not persuasive because the possible deuteration sites are specific embodiments of the HOWERTON 2020. For instance the reference HOWERTON 2020 teaches “In one embodiment, one or both of the 2,5-dimethyl groups independent comprises 3 deuterium, or 6 deuterium” [0099]. Since 2,5-dimethyl groups independent comprises 3 deuterium is specifically mentioned it would be obvious to achieve compound 1 of the instant invention. The reference HOWERTON 2020 also teaches “In one embodiment, the 7-(1-ethyl-propyl) moiety comprises 1 deuterium…”[0099] and since there are only 11 locations for 1 deuterium all location combinations would be immediately oblivious to one of ordinary skill in the art. Since there is a finite number of locations for these deuteriums and HOWERTON 2020 suggests using all compounds therein for treating congenital adrenal hyperplasia this argument is not persuasive. The why a POSITA would have been motivated to combine or modify the prior art elements to arrive at the claimed invention is to achieve advantages of deuterated compound (e.g., e.g., a reduced dosage or dosing regimen, a smaller potential for drug–drug interactions, and a lower incidence of side effects, overall resulting in an improved pharmacokinetic and safety profile and enhanced effectiveness, etc.).
The applicant argues that:
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Any of the positions suggested as embodiments could provide these isotope improvements since they are suggested deuterated versions of a known drug one would have a reasonable expectation of success. Obviousness does not require absolute predictability of success.” Id. at 903, 7 USPQ2d at 1681". A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). The prior art in addition does give reason to expect the modified compound would have the claimed properties because the reference suggest their use as an embodiment of the reference invention. Additionally site specific guidance is given, for example when 7-(1-ethyl-propyl) moiety comprises 1 deuterium all 11 positions would them be considered embodiments to one of ordinary skill in the art.
Additionally, as no experimental evidence of enablement is provided in the instant application the only evidence of enablement of the instance application is the prior art. If the applicant argument is considered persuasive (which at this point it has not) then the application will be rejected under 112(a) for lack of enablement as no evidence has been provided other than the prior art of similar compounds that these compounds would be useful in treating the diseases of the instant claims. Thus if the reasoning that the specific deuteration of the molecule would make the molecules activity so unpredictable that one would not consider its activity similar to the core compound than no evidence has been provided that these deuterated compounds would treat congenital adrenal hyperplasia.
The applicant argues that:
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This argument is not persuasive because it is obvious to
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Because HOWERTON 2019 teaches “Generally, treatment is initiated with smaller dosages which are less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under circumstances is reached”[0135]. This is standard procedure as taught by HOWERTON 2019. Obviousness does not require absolute predictability of success.” Id. at 903, 7 USPQ2d at 1681". Additionally, one could have a reasonable expectation of treatment with the compounds of HOWERTON 2020 and 2019 because they are suggested for treatment of the instant diseases and one would have routinely optimized the procedure by starting with lower dosages and then increasing the dosages for safe administration as this is a common practice.
It is obvious to track biomarkers as the reference HOWERTON 2019 teaches doing so “Compound 1, a potent and selective CRFi receptor antagonist, offers a novel nonsteroidal oral treatment approach for CAH. Compound 1 was well tolerated and efficacious in reducing excess ACTH, 170HP, and androstenedione in patients with classic CAH” [0338].
It is obvious to reduce the specific symptom of claim 213 because the reference HOWERTON 2020 teaches “Disclosed herein is a method of treating congenital adrenal hyperplasia (CAH) in a subject in need thereof, comprising administering a combination of a compound of Formula I, II, III, and IV, or Compounds 1 or 2 , or a pharmaceutically acceptable salt or solvate thereof; and a glucocorticoid. In some embodiments, the amount of glucocorticoid administered is reduced as compared to a method not comprising administering a compound of Formula I, II, III, and IV, or Compounds 1 or 2 , or a pharmaceutically acceptable salt or solvate thereof. In some embodiments, the methods described herein reduce the amount of a glucocorticoid administered from a supraphysiologic amount to a physiologic amount. In some embodiments, the methods described herein reduce the symptoms associated with high-dose glucocorticoid therapy. In some embodiments, the symptoms associated with high-dose glucocorticoid therapy are obesity, insulin resistance, metabolic abnormalities, hypertension, cardiovascular diseases, or osteoporosis”[0190-192]. This includes reduction in hypertension which is a symptom included in claim 213.
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).
The applicant argues that:
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One would be motivated to combine the references because one would want to use the specific embodiments of the compounds in HOWERTON 2020 for the more specific methods taught by HOWERTON 2019 for the benefits described by Atzrodt about deuterium compounds. One would be motivated to use the embodiments of HOWERTON 2020 over the generic compounds of HOWERTON 2019 for the methods of HOWERTON 2019 as these are more specific in some areas such as biomarker and dosing procedures. One would have a reasonable expectation of success because they use the same core compound. Thus one would have a reasonable expectation of success of combining the two methods since they read on very similar methods and one would be motivated to do so to treat CAH using combinations of those methods were one reads on more specifics than the other to acquire more details.
The applicant argues that:
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This argument is not persuasive because a generalized reference meant for the spray draying technique that HOWERTON 2020 also teaches would likely be common ratios for such a technique and thus are obvious to use.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
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).
Conclusion
Claims 157, 190, 213, 219, 221, 223, 285, 291, 310 and 322 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALISON AZAR SALAMATIAN whose telephone number is (703)756-4584. The examiner can normally be reached Mon-Thurs 7:30am-5pm EST Friday 7:30-4pm EST (every other Friday off).
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/A.A.H./ Examiner, Art Unit 1627
/Kortney L. Klinkel/ Supervisory Patent Examiner, Art Unit 1627
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