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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted: one on 03/16/2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of the Claims
Claims 1-3, 8-14, and 19-20 are pending in this application. Claims 4-7 and 15-18 have been cancelled by applicant.
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 1-3, 8-14, and 19-20 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.
Claim 1 reads “a method of reducing prostate specific antigen (PSA) doubling time”. The instant specification ([0003]) says that “PSA is used to measure the activity of prostate tissue”, and that “shorter PSA doubling times indicate faster tumor growth”. Therefore, it is unclear whether applicant intends to claim a method that will reduce PSA doubling time, and thus facilitate tumor growth? Or “a method of reducing PSA levels” (?) or “a method of increasing prostate specific antigen (PSA) doubling time” (?) or “a method of reducing the speed with which PSA levels double” (?) – for the purposes of applying art, it will be assumed that Applicant intended to claim a method which will benefit (and not further harm) subjects in need, and that the claims were meant to be directed toward “a method of increasing prostate specific antigen (PSA) doubling time” (via reducing PSA levels).
Claims 2-3, 8-14, and 19-20 are rejected for depending upon the limitations of claim 1.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-3, 8, 10-14, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Hunt et al. (US 10,047,082 B2 – Pub. Date: August 14th, 2018 – cited in IDS – previously cited) (“Hunt”); further in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”).
Regarding claim 1, De Santis teaches corticosteroids have been used in combination with chemotherapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC) for more than three decades, and that more recently, they have been used in combination with hormonal agents, such as enzalutamide (abstract; and page 156, col. 1, para. 2; and page 161, col. 1). De Santis teaches that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels in retrospective and prospective clinical studies of men with mCRPC.
While De Santis doesn’t specifically teach: (i) selective glucocorticoid receptor modulator (SGRM), exicorilant; (ii) wherein the subject has a 24 h UFC greater than 17.5 µg/ 24 h; the teachings of Serritella, Hunt, and Sullivan are relied upon for these disclosures.
Serritella teaches androgen receptors (AR) and glucocorticoid receptors (GR) are in the same nuclear hormone receptor family and share target DNA sequence binding homology. Serritella teaches that GR expression significantly increases after AR signal inhibition (ARSI), and that subsequent to ARSI, GR activation promotes prostate cancer cell survival and proliferation. Serritella also teaches that in preclinical models, GR antagonism with mifepristone (a nonselective steroidal AR and GR antagonist) or other more selective GR modulators delay CRPC progression when administered in combination with ARSI. Serritella teaches that GR expression may represent a therapeutic target for progressive castration-resistant prostate cancer (CRPC) (page 1549, col. 2, para. 3). Serritella teaches clinical trials of enzalutamide (an AR inhibitor) and mifepristone (an AR/GR inhibitor) was safe and well tolerated in subjects with CRPC, however, it didn’t meet its primary endpoint. Serritella suggests that selective GR antagonists combined with AR antagonists should be explored further (abstract – conclusions).
Hunt teaches selective glucocorticoid receptor modulators (SGRM) of Formula I below (left), and specifically discloses exicorilant below (right) (Example 2C, col. 42, line 60). Hunt discloses their compounds as suitable for use in the treatment of cancers, including prostate cancer (col 23, lines 47-48). Hunt also teaches their compounds as viable for the treatment of Cushing’s disease (col 23, line 30).
PNG
media_image1.png
317
505
media_image1.png
Greyscale
(Formula I)
PNG
media_image2.png
462
493
media_image2.png
Greyscale
(2C)
Sullivan teaches monitoring of cortisol in urine can help diagnose Cushing’s or Addison’s disease, which result from having too high or too low levels of cortisol, respectively, for prolonged periods of time (page 2). Sullivan discloses high cortisol levels may arise from long term use of glucocorticoids, increasing the risk of Cushing’s disease (page 3). Sullivan teaches normal urinary free cortisol values for healthy adults ranges between 30-145 nmol/ L over 24 hours (cortisol MW is 362.46 g/mol – therefore, this value equates to 10.8 µg/L to 52.6 µg/L over 24 hours).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a combination treatment of corticosteroids (specifically a selective GR antagonist, as taught by Serritella, such as Hunt’s SGRM, exicorilant) and enzalutamide to reduce PSA levels (increase PSA doubling time – see 112(b)) in a subject with mCRPC, and having a UFC greater than 17.5 µg/24 h, as taught by De Santis and Serritella in view of Hunt, further in view of Sullivan. One of ordinary skill would have been motivated to do so because De Santis teaches corticosteroids have been used in combination with enzalutamide for the treatment of mCRPC, and that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels; Serritella teaches that AR inhibition results in GR activation, which promotes prostate cancer cell survival and proliferation in CRPC, and suggests that selective GR antagonists combined with AR antagonists should be explored further for CRPC therapy; further because Hunt discloses their SGRM, exicorilant, suitable for administration for treating cancers, including prostate cancer, as well as Cushing’s disease (which is associated with elevated cortisol levels – as taught by Sullivan); and Sullivan teaches that long-term glucocorticoid treatment can result in high levels of cortisol, which can result in Cushing’s disease. Thus, by administering Hunt’s SGRM, which modulates cortisol levels and is effective in treating Cushing’s disease as well as prostate cancer, one can treat the mCRPC and as well as the symptoms associated with Cushing’s, thus optimizing patient outcome. One of ordinary skill would have had a reasonable expectation of success because De Santis and Serritella disclose enzalutamide (an AR inhibitor) is safe as part of a combination therapy with a GR for treating CRPC; Hunt discloses exicorilant and pharmaceutical compositions thereof, useful for treating prostate cancer and Cushing’s; and Sullivan teaches how the test UFC (see pages 6-7) and what the expected cortisol values are for a healthy individual.
Regarding claims 2-3, De Santis and Serritella disclose castration resistant, and metastatic castration resistant prostate cancers (abstract).
Regarding claim 8, Serritella discloses that their treated subjects received combination treatment of enzalutamide and mifepristone, with doses administered once per day (page 1550, line bridging col. 1-2). Hunt teaches their compounds may be administered once a day (col. 22, para. 1, last 3 lines).
Regarding claims 10-11 and 19-20, Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Regarding claims 12-14 and 19-20, Serritella discloses their GR inhibitor in combination therapy with enzalutamide was administered at 300 mg/ day (page 1550, col. 1-2). Hunt teaches exicorilant, and discloses their doses may range from 1 mg to about 1000 mg, or about 50 mg to 250 mg.
Regarding the claimed ranges for UFC of 17.5 µg/ 24 h, as well as those for enzalutamide and exicorilant administration, as recited in claims 1-3, 8-14, and 19-20, Applicant is advised that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01). The courts have also found that where 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. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05-II.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Hunt et al. (US 10,047,082 B2 – Pub. Date: August 14th, 2018 – cited in IDS – previously cited) (“Hunt”); further in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”); as applied to claims 1-3, 8, 10-14, and 19-20; further in view of Glazier et al. (Retrieved from thecalifornian.com [Retrieved on 11/23/2025] <URL: https://www.thecalifornian.com/story/life/2017/08/24/ask-drs-when-and-how-take-medication-food/598150001/> - previously cited) (“Glazier”).
The teachings of De Santis, Serritella, Hunt, and Sullivan are disclosed above and incorporated herein.
Serritella discloses nausea in some cases after oral administration of their enzalutamide and mifepristone combination therapy (Phase II, Table 2, page 1554).
Hunt discloses their compounds may be administered orally and are suitable for ingestion (col. 18, lines 40-45).
While De Santis and Serritella in view of Hunt, further in view of Sullivan do not specifically teach administration of the GRM with food, the teachings of Glazier are relied upon for these disclosures.
Glazier teaches there are multiple reasons why one might take a medication with food, including that some medications may cause stomach upset, such as nausea, if they are not taken with food. Glazier specifically mentions that corticosteroids should be taken with food (para. 3).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer De Santis and Serritella in view of Hunt, further in view of Sullivan’s treatment with food as part of De Santis and Serritella’s AR/GR inhibitor combination therapy in view of Glazier. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Serritella teaches some of their subjects reported nausea in phase II clinical trials of their combination therapy; Hunt discloses their compounds are suitable for oral ingestion; and Glazier warns that some medications, particularly glucocorticoids, may cause stomach upset and nausea, and that subjects taking these treatments might benefit from doing so with food.
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 conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 8, 10-14, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-13 of U.S. Patent No. 10,980,797 B2 (US ‘797); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”).
Regarding instant claims 1-3, 8, 10-14, and 19-20, US ‘797 claims a method of reducing tumor load in a patient comprising administration of an SGRA (specifically exicorilant) (US ‘797’s claims 1 and 7). US ‘797 specifically claims treatment of prostate cancer (US ‘797’s claim 9).
While US ‘797 does not specifically teach: (i) reducing PSA levels; (ii) wherein the subject has UFC levels greater than 17.5 µg/24h; (iii)coadministration of an AR inhibitor, such as enzalutamide, at doses of about 150-200 mg/day (claims 1, 10-11, and 19-20); (ii) wherein the cancer is CRPC or metastatic CRPC (claims 1); (iii) administration of the GR inhibitor once a day (claim 8); (iv) administration of GRM (exicorilant) at doses of 100-350 mg/day (claims 12-14 and 19-20); the teachings of De Santis, Serritella, and Sullivan are relied upon for these disclosures.
De Santis teaches corticosteroids have been used in combination with chemotherapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC) for more than three decades, and that more recently, they have been used in combination with hormonal agents, such as enzalutamide (abstract; and page 156, col. 1, para. 2; and page 161, col. 1). De Santis teaches that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels in retrospective and prospective clinical studies of men with mCRPC.
Serritella teaches that GR expression significantly increases after AR signal inhibition (ARSI), and that subsequent to ARSI, GR activation promotes prostate cancer cell survival and proliferation. Serritella teaches that GR expression may represent a therapeutic target for progressive castration-resistant prostate cancer (CRPC) (page 1549, col. 2, para. 3). Serritella teaches clinical trials of enzalutamide (an AR inhibitor) and mifepristone (an AR/GR inhibitor) was safe and well tolerated in subjects with CRPC, however, it didn’t meet its primary endpoint. Serritella suggests that selective GR antagonists combined with AR antagonists should be explored further (abstract – conclusions). Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Sullivan teaches monitoring of cortisol in urine can help diagnose Cushing’s or Addison’s disease, which result from having too high or too low levels of cortisol, respectively, for prolonged periods of time (page 2). Sullivan discloses high cortisol levels may arise from long term use of glucocorticoids, increasing the risk of Cushing’s disease (page 3). Sullivan teaches normal urinary free cortisol values for healthy adults ranges between 30-145 nmol/ L over 24 hours (cortisol MW is 362.46 g/mol – therefore, this value equates to 10.8 µg/L to 52.6 µg/L over 24 hours).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a combination treatment of corticosteroids (specifically a selective GR antagonist, as taught by Serritella, such as US 797’s SGRM, exicorilant) and enzalutamide to reduce PSA levels (increase PSA doubling time – see 112(b)) in a subject with mCRPC, and having a UFC greater than 17.5 µg/24 h, as taught by US ‘797 in view of De Santis and Serritella, further in view of Sullivan. One of ordinary skill would have been motivated to do so because US ‘797 discloses exicorilant as an SGRA, as part of a method for treating prostate cancer; De Santis teaches corticosteroids have been used in combination with enzalutamide have been used for the treatment of mCRPC, and that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels; Serritella teaches that AR inhibition results in GR activation, which promotes prostate cancer cell survival and proliferation in CRPC, and suggests that selective GR antagonists combined with AR antagonists should be explored further for CRPC therapy; and Sullivan teaches that long-term glucocorticoid treatment can result in high levels of cortisol, which can result in Cushing’s disease. One of ordinary skill would have had a reasonable expectation of success because US ‘797 discloses exicorilant; De Santis and Serritella disclose enzalutamide (an AR inhibitor) is safe as part of a combination therapy with a GR for treating CRPC; and Sullivan teaches how the test UFC (see pages 6-7) and what the expected cortisol values are for a healthy individual.
Regarding instant claims 2-3, Serritella discloses castration resistant, and metastatic castration resistant prostate cancers (abstract).
Regarding claim 8, Serritella discloses that their treated subjects received combination treatment of enzalutamide and mifepristone, with doses administered once per day (page 1550, line bridging col. 1-2).
Regarding claims 10-11 and 19-20, Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Regarding claims 12-14 and 19-20, Serritella discloses their GR inhibitor in combination therapy with enzalutamide was administered at 300 mg/ day (page 1550, col. 1-2).
Regarding the claimed ranges for enzalutamide and exicorilant administration, as recited in claims 10-14 and 19-20, Applicant is reminded that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that where 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.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Claim 9 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-13 of U.S. Patent No. 10,980,797 B2 (US ‘797); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”); as applied to claims 1-3, 8, 10-14, and 19-20; further in view of Glazier et al. (Retrieved from thecalifornian.com [Retrieved on 11/23/2025] <URL: https://www.thecalifornian.com/story/life/2017/08/24/ask-drs-when-and-how-take-medication-food/598150001/>) (“Glazier”).
The teachings of US ‘797, De Santis, Serritella, and Sullivan are disclosed above and incorporated herein.
Serritella discloses nausea in some cases after oral administration of their enzalutamide and mifepristone combination therapy (Phase II, Table 2, page 1554).
While US ‘797 in view of De Santis, Serritella, and Sullivan do not specifically teach administration of the GRM with food, the teachings of Glazier are relied upon for these disclosures.
Glazier teaches there are multiple reasons why one might take a medication with food, including that some medications may cause stomach upset, such as nausea, if they are not taken with food. Glazier specifically mentions that corticosteroids should be taken with food (para. 3).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer US ‘797’s GRM with food as part of De Santis and Serritella’s AR/GR inhibitor combination therapy in view of Glazier. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘797 discloses their GRM compounds; Serritella teaches some of their subjects reported nausea in phase II clinical trials of their combination therapy for CRPC; and Glazier warns that some medications, particularly glucocorticoids, may cause stomach upset and nausea, and that subjects taking these treatments might benefit from doing so with food.
Claims 1-3, 8, 10-14, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-11 of U.S. Patent No. 12,171,760 B2 (US ‘760); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”).
Regarding instant claims 1-3, 8, 10-14, and 19-20, US ‘760 claims a method of reducing tumor load in a patient comprising administration of 50-500 mg/ day of the SGRA below (reading on exicorilant and on instant claims 1, 12-14 and 19-20) (US ‘760’s claim 1). US ‘760 specifically claims treatment of prostate cancer (US ‘760’s claim 5).
PNG
media_image3.png
183
201
media_image3.png
Greyscale
US ‘760’s compound differs from exicorilant in that they have a pyrazole where exicorilant has a triazole. However, Applicant is advised that similar properties may normally be presumed when compounds are very close in structure. Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. See MPEP 2144.08(d).
While US ‘760 does not specifically teach: (i) reducing PSA levels; (ii) wherein the subject has UFC levels greater than 17.5 µg/24h; (iii)coadministration of an AR inhibitor, such as enzalutamide, at doses of about 150-200 mg/day (claims 1, 10-11, and 19-20); (ii) wherein the cancer is CRPC or metastatic CRPC (claims 1); (iii) administration of the GR inhibitor once a day (claim 8); (iv) administration of GRM (exicorilant) at doses of 100-350 mg/day (claims 12-14 and 19-20); the teachings of De Santis, Serritella, and Sullivan are relied upon for these disclosures.
De Santis teaches corticosteroids have been used in combination with chemotherapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC) for more than three decades, and that more recently, they have been used in combination with hormonal agents, such as enzalutamide (abstract; and page 156, col. 1, para. 2; and page 161, col. 1). De Santis teaches that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels in retrospective and prospective clinical studies of men with mCRPC.
Serritella teaches that GR expression significantly increases after AR signal inhibition (ARSI), and that subsequent to ARSI, GR activation promotes prostate cancer cell survival and proliferation. Serritella teaches that GR expression may represent a therapeutic target for progressive castration-resistant prostate cancer (CRPC) (page 1549, col. 2, para. 3). Serritella teaches clinical trials of enzalutamide (an AR inhibitor) and mifepristone (an AR/GR inhibitor) was safe and well tolerated in subjects with CRPC, however, it didn’t meet its primary endpoint. Serritella suggests that selective GR antagonists combined with AR antagonists should be explored further (abstract – conclusions). Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Sullivan teaches monitoring of cortisol in urine can help diagnose Cushing’s or Addison’s disease, which result from having too high or too low levels of cortisol, respectively, for prolonged periods of time (page 2). Sullivan discloses high cortisol levels may arise from long term use of glucocorticoids, increasing the risk of Cushing’s disease (page 3). Sullivan teaches normal urinary free cortisol values for healthy adults ranges between 30-145 nmol/ L over 24 hours (cortisol MW is 362.46 g/mol – therefore, this value equates to 10.8 µg/L to 52.6 µg/L over 24 hours).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a combination treatment of corticosteroids (specifically a selective GR antagonist, as taught by Serritella, such as US 760’s SGRM, exicorilant derivative) and enzalutamide to reduce PSA levels (increase PSA doubling time – see 112(b)) in a subject with mCRPC, and having a UFC greater than 17.5 µg/24 h, as taught by US ‘760 in view of De Santis and Serritella, further in view of Sullivan. One of ordinary skill would have been motivated to do so because US ‘760 discloses exicorilant as an SGRA, as part of a method for treating prostate cancer; De Santis teaches corticosteroids have been used in combination with enzalutamide have been used for the treatment of mCRPC, and that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels; Serritella teaches that AR inhibition results in GR activation, which promotes prostate cancer cell survival and proliferation in CRPC, and suggests that selective GR antagonists combined with AR antagonists should be explored further for CRPC therapy; and Sullivan teaches that long-term glucocorticoid treatment can result in high levels of cortisol, which can result in Cushing’s disease. One of ordinary skill would have had a reasonable expectation of success because US ‘760 discloses exicorilant; De Santis and Serritella disclose enzalutamide (an AR inhibitor) is safe as part of a combination therapy with a GR for treating CRPC; and Sullivan teaches how the test UFC (see pages 6-7) and what the expected cortisol values are for a healthy individual.
Regarding instant claims 2-3, Serritella discloses castration resistant, and metastatic castration resistant prostate cancers (abstract).
Regarding claim 8, Serritella discloses that their treated subjects received combination treatment of enzalutamide and mifepristone, with doses administered once per day (page 1550, line bridging col. 1-2).
Regarding claims 10-11 and 19-20, Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Regarding the claimed ranges for enzalutamide and exicorilant administration, as recited in claims 10-14 and 19-20, Applicant is reminded that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that where 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.
Claim 9 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-11 of U.S. Patent No. 12,171,760 B2 (US ‘760); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”); as applied to claims 1-3, 8, 10-14, and 19-20; further in view of Glazier et al. (Retrieved from thecalifornian.com [Retrieved on 11/23/2025] <URL: https://www.thecalifornian.com/story/life/2017/08/24/ask-drs-when-and-how-take-medication-food/598150001/>) (“Glazier”).
The teachings of US ‘760 De Santis, Serritella, and Sullivan are disclosed above and incorporated herein.
Serritella discloses nausea in some cases after oral administration of their enzalutamide and mifepristone combination therapy (Phase II, Table 2, page 1554).
While US ‘760 in view of De Santis, Serritella, and Sullivan does not specifically teach administration of the GRM with food, the teachings of Glazier are relied upon for these disclosures.
Glazier teaches there are multiple reasons why one might take a medication with food, including that some medications may cause stomach upset, such as nausea, if they are not taken with food. Glazier specifically mentions that corticosteroids should be taken with food (para. 3).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer US ‘760’s GRM with food as part of De Santis and Serritella’s AR/GR inhibitor combination therapy in view of Glazier. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘760 discloses their GRM compounds; Serritella teaches some of their subjects reported nausea in phase II clinical trials of their combination therapy for CRPC; and Glazier warns that some medications, particularly glucocorticoids, may cause stomach upset and nausea, and that subjects taking these treatments might benefit from doing so with food.
Claims 1-3, 8, 10-14, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-20 of U.S. Patent No. 12,097,192 B2 (US ‘192); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”).
Regarding instant claims 1-3, 8, 10-14, and 19-20, US ‘192 claims a method of treating hypercortisolemia or comorbidity thereof comprising administration of and SGRM, like exicorilant (reading on instant claims 1, 5-7) (US ‘192’s claim 1).
While US ‘192 does not specifically teach: (i) coadministration of an AR inhibitor, such as enzalutamide, at doses of about 150-200 mg/day (claims 1, 10-11, and 19-20); (ii) treatment of CRPC or metastatic CRPC with their compounds (claims 1-3); (iii) administration of the GR inhibitor once a day (claim 8); (iv) administration of GRM (exicorilant) at doses of 100-350 mg/day (claims 12-14 and 19-20); the teachings of De Santis, Serritella, and Sullivan are relied upon for these disclosures.
De Santis teaches corticosteroids have been used in combination with chemotherapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC) for more than three decades, and that more recently, they have been used in combination with hormonal agents, such as enzalutamide (abstract; and page 156, col. 1, para. 2; and page 161, col. 1). De Santis teaches that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels in retrospective and prospective clinical studies of men with mCRPC.
Serritella teaches that GR expression significantly increases after AR signal inhibition (ARSI), and that subsequent to ARSI, GR activation promotes prostate cancer cell survival and proliferation. Serritella teaches that GR expression may represent a therapeutic target for progressive castration-resistant prostate cancer (CRPC) (page 1549, col. 2, para. 3). Serritella teaches clinical trials of enzalutamide (an AR inhibitor) and mifepristone (an AR/GR inhibitor) was safe and well tolerated in subjects with CRPC, however, it didn’t meet its primary endpoint. Serritella suggests that selective GR antagonists combined with AR antagonists should be explored further (abstract – conclusions). Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Sullivan teaches monitoring of cortisol in urine can help diagnose Cushing’s or Addison’s disease, which result from having too high or too low levels of cortisol, respectively, for prolonged periods of time (page 2). Sullivan discloses high cortisol levels may arise from long term use of glucocorticoids, increasing the risk of Cushing’s disease (page 3). Sullivan teaches normal urinary free cortisol values for healthy adults ranges between 30-145 nmol/ L over 24 hours (cortisol MW is 362.46 g/mol – therefore, this value equates to 10.8 µg/L to 52.6 µg/L over 24 hours).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a combination treatment of corticosteroids (specifically a selective GR antagonist, as taught by Serritella, such as US 192’s SGRM, exicorilant derivative) and enzalutamide to reduce PSA levels (increase PSA doubling time – see 112(b)) in a subject with mCRPC, and having a UFC greater than 17.5 µg/24 h, as taught by US ‘192 in view of De Santis and Serritella, further in view of Sullivan. One of ordinary skill would have been motivated to do so because US ‘192 discloses exicorilant as an SGRA, as part of a method for treating prostate cancer; De Santis teaches corticosteroids have been used in combination with enzalutamide have been used for the treatment of mCRPC, and that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels; Serritella teaches that AR inhibition results in GR activation, which promotes prostate cancer cell survival and proliferation in CRPC, and suggests that selective GR antagonists combined with AR antagonists should be explored further for CRPC therapy; and Sullivan teaches that long-term glucocorticoid treatment can result in high levels of cortisol, which can result in Cushing’s disease. One of ordinary skill would have had a reasonable expectation of success because US ‘192 discloses exicorilant; De Santis and Serritella disclose enzalutamide (an AR inhibitor) is safe as part of a combination therapy with a GR for treating CRPC; and Sullivan teaches how the test UFC (see pages 6-7) and what the expected cortisol values are for a healthy individual.
Regarding instant claims 2-3, Serritella discloses castration resistant, and metastatic castration resistant prostate cancers (abstract).
Regarding claim 8, Serritella discloses that their treated subjects received combination treatment of enzalutamide and mifepristone, with doses administered once per day (page 1550, line bridging col. 1-2).
Regarding claims 10-11 and 19-20, Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Regarding claims 12-14 and 19-20, Serritella discloses their GR inhibitor in combination therapy with enzalutamide was administered at 300 mg/ day (page 1550, col. 1-2).
Regarding the claimed ranges for enzalutamide and exicorilant administration, as recited in claims 10-14 and 19-20, Applicant is advised that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that where 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.
Claim 9 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-20 of U.S. Patent No. 12,097,192 B2 (US ‘192); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”); as applied to claims 1-3, 8, 10-14, and 19-20; further in view of Glazier et al. (Retrieved from thecalifornian.com [Retrieved on 11/23/2025] <URL: https://www.thecalifornian.com/story/life/2017/08/24/ask-drs-when-and-how-take-medication-food/598150001/>) (“Glazier”).
The teachings of US ‘192 De Santis, Serritella, and Sullivan are disclosed above and incorporated herein.
Serritella discloses nausea in some cases after oral administration of their enzalutamide and mifepristone combination therapy (Phase II, Table 2, page 1554).
While US ‘192 in view of De Santis, Serritella, and Sullivan does not specifically teach administration of the GRM with food, the teachings of Glazier are relied upon for these disclosures.
Glazier teaches there are multiple reasons why one might take a medication with food, including that some medications may cause stomach upset, such as nausea, if they are not taken with food. Glazier specifically mentions that corticosteroids should be taken with food (para. 3).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer US ‘192’s GRM with food as part of De Santis and Serritella’s AR/GR inhibitor combination therapy in view of Glazier. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘192 discloses their GRM compounds; Serritella teaches some of their subjects reported nausea in phase II clinical trials of their combination therapy for CRPC; and Glazier warns that some medications, particularly glucocorticoids, may cause stomach upset and nausea, and that subjects taking these treatments might benefit from doing so with food.
Claims 1-3, 8, 10-14, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-20 of U.S. Patent No. 11,684,612 B2 (US ‘612); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”).
Regarding instant claims 1-3, 8, 10-14, and 19-20, US ‘612 claims a method of treating hypercortisolemia or comorbidity thereof comprising administration of and SGRM, like exicorilant (reading on instant claims 1, 5-7) (US ‘612’s claim 1). US ‘612 claims administration of about 50 – 500 mg of exicorilant (reading on instant claims 12-14 and 19-20) (US ‘612’s claim 18).
While US ‘612 does not specifically teach: (i) coadministration of an AR inhibitor, such as enzalutamide, at doses of about 150-200 mg/day (claims 1, 4, 10-11, and 19-20); (ii) treatment of CRPC or metastatic CRPC with their compounds (claims 1-3); (iii) administration of the GR inhibitor once a day (claim 8); the teachings of De Santis, Serritella, Sullivan are relied upon for these disclosures.
De Santis teaches corticosteroids have been used in combination with chemotherapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC) for more than three decades, and that more recently, they have been used in combination with hormonal agents, such as enzalutamide (abstract; and page 156, col. 1, para. 2; and page 161, col. 1). De Santis teaches that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels in retrospective and prospective clinical studies of men with mCRPC.
Serritella teaches that GR expression significantly increases after AR signal inhibition (ARSI), and that subsequent to ARSI, GR activation promotes prostate cancer cell survival and proliferation. Serritella teaches that GR expression may represent a therapeutic target for progressive castration-resistant prostate cancer (CRPC) (page 1549, col. 2, para. 3). Serritella teaches clinical trials of enzalutamide (an AR inhibitor) and mifepristone (an AR/GR inhibitor) was safe and well tolerated in subjects with CRPC, however, it didn’t meet its primary endpoint. Serritella suggests that selective GR antagonists combined with AR antagonists should be explored further (abstract – conclusions). Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Sullivan teaches monitoring of cortisol in urine can help diagnose Cushing’s or Addison’s disease, which result from having too high or too low levels of cortisol, respectively, for prolonged periods of time (page 2). Sullivan discloses high cortisol levels may arise from long term use of glucocorticoids, increasing the risk of Cushing’s disease (page 3). Sullivan teaches normal urinary free cortisol values for healthy adults ranges between 30-145 nmol/ L over 24 hours (cortisol MW is 362.46 g/mol – therefore, this value equates to 10.8 µg/L to 52.6 µg/L over 24 hours).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a combination treatment of corticosteroids (specifically a selective GR antagonist, as taught by Serritella, such as US 612’s SGRM, exicorilant derivative) and enzalutamide to reduce PSA levels (increase PSA doubling time – see 112(b)) in a subject with mCRPC, and having a UFC greater than 17.5 µg/24 h, as taught by US ‘612 in view of De Santis and Serritella, further in view of Sullivan. One of ordinary skill would have been motivated to do so because US ‘612 discloses exicorilant as an SGRA, as part of a method for treating prostate cancer; De Santis teaches corticosteroids have been used in combination with enzalutamide have been used for the treatment of mCRPC, and that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels; Serritella teaches that AR inhibition results in GR activation, which promotes prostate cancer cell survival and proliferation in CRPC, and suggests that selective GR antagonists combined with AR antagonists should be explored further for CRPC therapy; and Sullivan teaches that long-term glucocorticoid treatment can result in high levels of cortisol, which can result in Cushing’s disease. One of ordinary skill would have had a reasonable expectation of success because US ‘612 discloses exicorilant; De Santis and Serritella disclose enzalutamide (an AR inhibitor) is safe as part of a combination therapy with a GR for treating CRPC; and Sullivan teaches how the test UFC (see pages 6-7) and what the expected cortisol values are for a healthy individual.
Regarding instant claims 2-3, Serritella discloses castration resistant, and metastatic castration resistant prostate cancers (abstract).
Regarding claim 8, Serritella discloses that their treated subjects received combination treatment of enzalutamide and mifepristone, with doses administered once per day (page 1550, line bridging col. 1-2).
Regarding claims 10-11 and 19-20, Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Regarding the claimed ranges for enzalutamide and exicorilant administration, as recited in claims 10-14 and 19-20, Applicant is advised that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that where 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.
Claim 9 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-20 of U.S. Patent No. 11,684,612 B2 (US ‘612); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”); as applied to claims 1-3, 8, 10-14, and 19-20; further in view of Glazier et al. (Retrieved from thecalifornian.com [Retrieved on 11/23/2025] <URL: https://www.thecalifornian.com/story/life/2017/08/24/ask-drs-when-and-how-take-medication-food/598150001/>) (“Glazier”).
The teachings of US ‘612 De Santis, Serritella, and Sullivan are disclosed above and incorporated herein.
Serritella discloses nausea in some cases after oral administration of their enzalutamide and mifepristone combination therapy (Phase II, Table 2, page 1554).
While US ‘612 in view of De Santis, Serritella, and Sullivan does not specifically teach administration of the GRM with food, the teachings of Glazier are relied upon for these disclosures.
Glazier teaches there are multiple reasons why one might take a medication with food, including that some medications may cause stomach upset, such as nausea, if they are not taken with food. Glazier specifically mentions that corticosteroids should be taken with food (para. 3).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer US ‘612’s GRM with food as part of De Santis and Serritella’s AR/GR inhibitor combination therapy in view of Glazier. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘612 discloses their GRM compounds; Serritella teaches some of their subjects reported nausea in phase II clinical trials of their combination therapy for CRPC; and Glazier warns that some medications, particularly glucocorticoids, may cause stomach upset and nausea, and that subjects taking these treatments might benefit from doing so with food.
Claims 1-3, 8, 10-14, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-22 of U.S. Patent No. 11,590,113 B2 (US ‘113); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”).
Regarding instant claims 1-3, 8, 10-14, and 19-20, US ‘113 claims a method of treating hypercortisolemia or comorbidity thereof comprising administration of and SGRM, like exicorilant (reading on instant claims 1, 5-7) (US ‘113’s claim 1).
While US ‘113 does not specifically teach: (i) coadministration of an AR inhibitor, such as enzalutamide, at doses of about 150-200 mg/day (claims 1, 4, 10-11, and 19-20); (ii) treatment of CRPC or metastatic CRPC with their compounds (claims 1-3); (iii) administration of the GR inhibitor once a day (claim 8); (iv) administration of GRM (exicorilant) at doses of 100-350 mg/day (claims 12-14 and 19-20); the teachings of De Santis, Serritella, and Sullivan are relied upon for these disclosures.
De Santis teaches corticosteroids have been used in combination with chemotherapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC) for more than three decades, and that more recently, they have been used in combination with hormonal agents, such as enzalutamide (abstract; and page 156, col. 1, para. 2; and page 161, col. 1). De Santis teaches that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels in retrospective and prospective clinical studies of men with mCRPC.
Serritella teaches that GR expression significantly increases after AR signal inhibition (ARSI), and that subsequent to ARSI, GR activation promotes prostate cancer cell survival and proliferation. Serritella teaches that GR expression may represent a therapeutic target for progressive castration-resistant prostate cancer (CRPC) (page 1549, col. 2, para. 3). Serritella teaches clinical trials of enzalutamide (an AR inhibitor) and mifepristone (an AR/GR inhibitor) was safe and well tolerated in subjects with CRPC, however, it didn’t meet its primary endpoint. Serritella suggests that selective GR antagonists combined with AR antagonists should be explored further (abstract – conclusions). Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Sullivan teaches monitoring of cortisol in urine can help diagnose Cushing’s or Addison’s disease, which result from having too high or too low levels of cortisol, respectively, for prolonged periods of time (page 2). Sullivan discloses high cortisol levels may arise from long term use of glucocorticoids, increasing the risk of Cushing’s disease (page 3). Sullivan teaches normal urinary free cortisol values for healthy adults ranges between 30-145 nmol/ L over 24 hours (cortisol MW is 362.46 g/mol – therefore, this value equates to 10.8 µg/L to 52.6 µg/L over 24 hours).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a combination treatment of corticosteroids (specifically a selective GR antagonist, as taught by Serritella, such as US 113’s SGRM, exicorilant derivative) and enzalutamide to reduce PSA levels (increase PSA doubling time – see 112(b)) in a subject with mCRPC, and having a UFC greater than 17.5 µg/24 h, as taught by US ‘113 in view of De Santis and Serritella, further in view of Sullivan. One of ordinary skill would have been motivated to do so because US ‘113 discloses exicorilant as an SGRA, as part of a method for treating prostate cancer; De Santis teaches corticosteroids have been used in combination with enzalutamide have been used for the treatment of mCRPC, and that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels; Serritella teaches that AR inhibition results in GR activation, which promotes prostate cancer cell survival and proliferation in CRPC, and suggests that selective GR antagonists combined with AR antagonists should be explored further for CRPC therapy; and Sullivan teaches that long-term glucocorticoid treatment can result in high levels of cortisol, which can result in Cushing’s disease. One of ordinary skill would have had a reasonable expectation of success because US ‘113 discloses exicorilant; De Santis and Serritella disclose enzalutamide (an AR inhibitor) is safe as part of a combination therapy with a GR for treating CRPC; and Sullivan teaches how the test UFC (see pages 6-7) and what the expected cortisol values are for a healthy individual.
Regarding instant claims 2-3, Serritella discloses castration resistant, and metastatic castration resistant prostate cancers (abstract).
Regarding claim 8, Serritella discloses that their treated subjects received combination treatment of enzalutamide and mifepristone, with doses administered once per day (page 1550, line bridging col. 1-2).
Regarding claims 10-11 and 19-20, Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Regarding claims 12-14 and 19-20, Serritella discloses their GR inhibitor in combination therapy with enzalutamide was administered at 300 mg/ day (page 1550, col. 1-2).
Regarding the claimed ranges for enzalutamide and exicorilant administration, as recited in claims 10-14 and 19-20, Applicant is advised that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that where 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.
Claim 9 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-22 of U.S. Patent No. 11,590,113 B2 (US ‘113); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”); as applied to claims 1-3, 8, 10-14, and 19-20; further in view of Glazier et al. (Retrieved from thecalifornian.com [Retrieved on 11/23/2025] <URL: https://www.thecalifornian.com/story/life/2017/08/24/ask-drs-when-and-how-take-medication-food/598150001/>) (“Glazier”).
The teachings of US ‘113, De Santis, Serritella, and Sullivan are disclosed above and incorporated herein.
Serritella discloses nausea in some cases after oral administration of their enzalutamide and mifepristone combination therapy (Phase II, Table 2, page 1554).
While US ‘113 in view of De Santis, Serritella, and Sullivan does not specifically teach administration of the GRM with food, the teachings of Glazier are relied upon for these disclosures.
Glazier teaches there are multiple reasons why one might take a medication with food, including that some medications may cause stomach upset, such as nausea, if they are not taken with food. Glazier specifically mentions that corticosteroids should be taken with food (para. 3).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer US ‘113’s GRM with food as part of De Santis and Serritella’s AR/GR inhibitor combination therapy in view of Glazier. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘113 discloses their GRM compounds; Serritella teaches some of their subjects reported nausea in phase II clinical trials of their combination therapy for CRPC; and Glazier warns that some medications, particularly glucocorticoids, may cause stomach upset and nausea, and that subjects taking these treatments might benefit from doing so with food.
Claims 1-3, 8, 10-14, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-14 of U.S. Patent No. 12,109,272 B2 (US ‘272); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”).
Regarding instant claims 1-3, 8, 10-14, and 19-20, US ‘272 claims a method of treating cancer in a patient comprising administration of 150 mg/ day of the SGRA below (reading on exicorilant and on instant claims 1, 12-14 and 19-20) (US ‘272’s claims 1 and 14).
PNG
media_image3.png
183
201
media_image3.png
Greyscale
US ‘272’s compound differs from exicorilant in that they have a pyrazole where exicorilant has a triazole, and in the olefin in the tricyclic core. However, Applicant is advised that similar properties may normally be presumed when compounds are very close in structure. Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. See MPEP 2144.08(d).
While US ‘272 does not specifically teach: (i) coadministration of an AR inhibitor, such as enzalutamide, at doses of about 150-200 mg/day (claims 1, 4, 10-11, and 19-20); (ii) wherein the cancer is CRPC or metastatic CRPC (claims 2-3); (iii) administration of the GR inhibitor once a day (claim 8); the teachings of De Santis, Serritella, and Sullivan are relied upon for these disclosures.
De Santis teaches corticosteroids have been used in combination with chemotherapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC) for more than three decades, and that more recently, they have been used in combination with hormonal agents, such as enzalutamide (abstract; and page 156, col. 1, para. 2; and page 161, col. 1). De Santis teaches that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels in retrospective and prospective clinical studies of men with mCRPC.
Serritella teaches that GR expression significantly increases after AR signal inhibition (ARSI), and that subsequent to ARSI, GR activation promotes prostate cancer cell survival and proliferation. Serritella teaches that GR expression may represent a therapeutic target for progressive castration-resistant prostate cancer (CRPC) (page 1549, col. 2, para. 3). Serritella teaches clinical trials of enzalutamide (an AR inhibitor) and mifepristone (an AR/GR inhibitor) was safe and well tolerated in subjects with CRPC, however, it didn’t meet its primary endpoint. Serritella suggests that selective GR antagonists combined with AR antagonists should be explored further (abstract – conclusions). Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Sullivan teaches monitoring of cortisol in urine can help diagnose Cushing’s or Addison’s disease, which result from having too high or too low levels of cortisol, respectively, for prolonged periods of time (page 2). Sullivan discloses high cortisol levels may arise from long term use of glucocorticoids, increasing the risk of Cushing’s disease (page 3). Sullivan teaches normal urinary free cortisol values for healthy adults ranges between 30-145 nmol/ L over 24 hours (cortisol MW is 362.46 g/mol – therefore, this value equates to 10.8 µg/L to 52.6 µg/L over 24 hours).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a combination treatment of corticosteroids (specifically a selective GR antagonist, as taught by Serritella, such as US 272’s SGRM, exicorilant derivative) and enzalutamide to reduce PSA levels (increase PSA doubling time – see 112(b)) in a subject with mCRPC, and having a UFC greater than 17.5 µg/24 h, as taught by US ‘272 in view of De Santis and Serritella, further in view of Sullivan. One of ordinary skill would have been motivated to do so because US ‘272 discloses exicorilant as an SGRA, as part of a method for treating prostate cancer; De Santis teaches corticosteroids have been used in combination with enzalutamide have been used for the treatment of mCRPC, and that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels; Serritella teaches that AR inhibition results in GR activation, which promotes prostate cancer cell survival and proliferation in CRPC, and suggests that selective GR antagonists combined with AR antagonists should be explored further for CRPC therapy; and Sullivan teaches that long-term glucocorticoid treatment can result in high levels of cortisol, which can result in Cushing’s disease. One of ordinary skill would have had a reasonable expectation of success because US ‘272 discloses exicorilant; De Santis and Serritella disclose enzalutamide (an AR inhibitor) is safe as part of a combination therapy with a GR for treating CRPC; and Sullivan teaches how the test UFC (see pages 6-7) and what the expected cortisol values are for a healthy individual.
Regarding instant claims 2-3, Serritella discloses castration resistant, and metastatic castration resistant prostate cancers (abstract).
Regarding claim 8, Serritella discloses that their treated subjects received combination treatment of enzalutamide and mifepristone, with doses administered once per day (page 1550, line bridging col. 1-2).
Regarding claims 10-11 and 19-20, Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Regarding the claimed ranges for enzalutamide and exicorilant administration, as recited in claims 10-14 and 19-20, Applicant is advised that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that where 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.
.
Claim 9 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-14 of U.S. Patent No. 12,109,272 B2 (US ‘272); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”); as applied to claims 1-3, 8, 10-14, and 19-20; further in view of Glazier et al. (Retrieved from thecalifornian.com [Retrieved on 11/23/2025] <URL: https://www.thecalifornian.com/story/life/2017/08/24/ask-drs-when-and-how-take-medication-food/598150001/>) (“Glazier”).
The teachings of US ‘272, De Santis, Serritella, and Sullivan are disclosed above and incorporated herein.
Serritella discloses nausea in some cases after oral administration of their enzalutamide and mifepristone combination therapy (Phase II, Table 2, page 1554).
While US ‘272 in view of De Santis, Serritella, and Sullivan does not specifically teach administration of the GRM with food, the teachings of Glazier are relied upon for these disclosures.
Glazier teaches there are multiple reasons why one might take a medication with food, including that some medications may cause stomach upset, such as nausea, if they are not taken with food. Glazier specifically mentions that corticosteroids should be taken with food (para. 3).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer US ‘272’s GRM with food as part of De Santis and Serritella’s AR/GR inhibitor combination therapy in view of Glazier. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘272 discloses their GRM compounds; Serritella teaches some of their subjects reported nausea in phase II clinical trials of their combination therapy for CRPC; and Glazier warns that some medications, particularly glucocorticoids, may cause stomach upset and nausea, and that subjects taking these treatments might benefit from doing so with food.
Claims 1-3, 8, 10-14, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-41 of U.S. Patent No. 12,152,028 B2 (US ‘028); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”).
Regarding instant claims 1-3, 8, 10-14, and 19-20, US ‘028 claims a method of making the compound below and a method of treating a condition through antagonizing a glucocorticoid receptor (the SGRA below reads on exicorilant and on instant claim 1) (US ‘028’s claims 1 and 39).
PNG
media_image4.png
202
226
media_image4.png
Greyscale
US ‘028 differs from exicorilant because of the olefin in the tricyclic core. Applicant is reminded that similar properties may normally be presumed when compounds are very close in structure. (“When chemical compounds have very close structural similarities and similar utilities, without more a prima facie case may be made.”). Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious.
While US ‘028 does not specifically teach: (i) coadministration of an AR inhibitor, such as enzalutamide, at doses of about 150-200 mg/day (claims 1, 4, 10-11, and 19-20); (ii) wherein the cancer is CRPC or metastatic CRPC (claims 2-3); (iii) administration of the GR inhibitor once a day (claim 8); (iv) administration of GRM (exicorilant) at doses of 100-350 mg/day (claims 12-14 and 19-20); the teachings of Serritella are relied upon for these disclosures.
De Santis teaches corticosteroids have been used in combination with chemotherapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC) for more than three decades, and that more recently, they have been used in combination with hormonal agents, such as enzalutamide (abstract; and page 156, col. 1, para. 2; and page 161, col. 1). De Santis teaches that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels in retrospective and prospective clinical studies of men with mCRPC.
Serritella teaches that GR expression significantly increases after AR signal inhibition (ARSI), and that subsequent to ARSI, GR activation promotes prostate cancer cell survival and proliferation. Serritella teaches that GR expression may represent a therapeutic target for progressive castration-resistant prostate cancer (CRPC) (page 1549, col. 2, para. 3). Serritella teaches clinical trials of enzalutamide (an AR inhibitor) and mifepristone (an AR/GR inhibitor) was safe and well tolerated in subjects with CRPC, however, it didn’t meet its primary endpoint. Serritella suggests that selective GR antagonists combined with AR antagonists should be explored further (abstract – conclusions). Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Sullivan teaches monitoring of cortisol in urine can help diagnose Cushing’s or Addison’s disease, which result from having too high or too low levels of cortisol, respectively, for prolonged periods of time (page 2). Sullivan discloses high cortisol levels may arise from long term use of glucocorticoids, increasing the risk of Cushing’s disease (page 3). Sullivan teaches normal urinary free cortisol values for healthy adults ranges between 30-145 nmol/ L over 24 hours (cortisol MW is 362.46 g/mol – therefore, this value equates to 10.8 µg/L to 52.6 µg/L over 24 hours).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a combination treatment of corticosteroids (specifically a selective GR antagonist, as taught by Serritella, such as US 028’s SGRM, exicorilant derivative) and enzalutamide to reduce PSA levels (increase PSA doubling time – see 112(b)) in a subject with mCRPC, and having a UFC greater than 17.5 µg/24 h, as taught by US ‘028 in view of De Santis and Serritella, further in view of Sullivan. One of ordinary skill would have been motivated to do so because US ‘028 discloses exicorilant as an SGRA, as part of a method for treating prostate cancer; De Santis teaches corticosteroids have been used in combination with enzalutamide have been used for the treatment of mCRPC, and that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels; Serritella teaches that AR inhibition results in GR activation, which promotes prostate cancer cell survival and proliferation in CRPC, and suggests that selective GR antagonists combined with AR antagonists should be explored further for CRPC therapy; and Sullivan teaches that long-term glucocorticoid treatment can result in high levels of cortisol, which can result in Cushing’s disease. One of ordinary skill would have had a reasonable expectation of success because US ‘028 discloses exicorilant; De Santis and Serritella disclose enzalutamide (an AR inhibitor) is safe as part of a combination therapy with a GR for treating CRPC; and Sullivan teaches how the test UFC (see pages 6-7) and what the expected cortisol values are for a healthy individual.
Regarding instant claims 2-3, Serritella discloses castration resistant, and metastatic castration resistant prostate cancers (abstract).
Regarding claim 8, Serritella discloses that their treated subjects received combination treatment of enzalutamide and mifepristone, with doses administered once per day (page 1550, line bridging col. 1-2).
Regarding claims 10-11 and 19-20, Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Regarding claims 12-14 and 19-20, Serritella discloses their GR inhibitor in combination therapy with enzalutamide was administered at 300 mg/ day (page 1550, col. 1-2).
Regarding the claimed ranges for enzalutamide and exicorilant administration, as recited in claims 10-14 and 19-20, Applicant is advised that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that where 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.
Claim 9 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-41 of U.S. Patent No. 12,152,028 B2 (US ‘028); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”); as applied to claims 1-3, 8, 10-14, and 19-20; further in view of Glazier et al. (Retrieved from thecalifornian.com [Retrieved on 11/23/2025] <URL: https://www.thecalifornian.com/story/life/2017/08/24/ask-drs-when-and-how-take-medication-food/598150001/>) (“Glazier”).
The teachings of US ‘028, De Santis, Serritella, and Sullivan are disclosed above and incorporated herein.
Serritella discloses nausea in some cases after oral administration of their enzalutamide and mifepristone combination therapy (Phase II, Table 2, page 1554).
While US ‘028 in view of De Santis, Serritella, and Sullivan does not specifically teach administration of the GRM with food, the teachings of Glazier are relied upon for these disclosures.
Glazier teaches there are multiple reasons why one might take a medication with food, including that some medications may cause stomach upset, such as nausea, if they are not taken with food. Glazier specifically mentions that corticosteroids should be taken with food (para. 3).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer US ‘028’s GRM with food as part of De Santis and Serritella’s AR/GR inhibitor combination therapy in view of Glazier. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘028 discloses their GRM compounds; Serritella teaches some of their subjects reported nausea in phase II clinical trials of their combination therapy for CRPC; and Glazier warns that some medications, particularly glucocorticoids, may cause stomach upset and nausea, and that subjects taking these treatments might benefit from doing so with food.
Claims 1-3, 8, 10-14, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-30 of U.S. Patent No. 10,946,005 B2 (US ‘005); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”).
Regarding instant claims 1-8, 10-14, and 19-20, US ‘005 claims a method of reducing the size of a tumor in a patient comprising administration of 50 - 500 mg/ day of the SGRA below (reading on exicorilant and on instant claims 1, 5-7, 12-14 and 19-20) (US ‘005’s claims 1 and 9).
PNG
media_image3.png
183
201
media_image3.png
Greyscale
US ‘005’s compound differs from exicorilant in that they have a pyrazole where exicorilant has a triazole, and in the olefin in the tricyclic core. However, Applicant is advised that similar properties may normally be presumed when compounds are very close in structure. Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. See MPEP 2144.08(d).
While US ‘005 does not specifically teach: (i) coadministration of an AR inhibitor, such as enzalutamide, at doses of about 150-200 mg/day (claims 1, 4, 10-11, and 19-20); (ii) wherein the cancer is CRPC or metastatic CRPC (claims 2-3); (iii) administration of the GR inhibitor once a day (claim 8); the teachings of De Santis, Serritella, Sullivan are relied upon for these disclosures.
De Santis teaches corticosteroids have been used in combination with chemotherapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC) for more than three decades, and that more recently, they have been used in combination with hormonal agents, such as enzalutamide (abstract; and page 156, col. 1, para. 2; and page 161, col. 1). De Santis teaches that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels in retrospective and prospective clinical studies of men with mCRPC.
Serritella teaches that GR expression significantly increases after AR signal inhibition (ARSI), and that subsequent to ARSI, GR activation promotes prostate cancer cell survival and proliferation. Serritella teaches that GR expression may represent a therapeutic target for progressive castration-resistant prostate cancer (CRPC) (page 1549, col. 2, para. 3). Serritella teaches clinical trials of enzalutamide (an AR inhibitor) and mifepristone (an AR/GR inhibitor) was safe and well tolerated in subjects with CRPC, however, it didn’t meet its primary endpoint. Serritella suggests that selective GR antagonists combined with AR antagonists should be explored further (abstract – conclusions). Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Sullivan teaches monitoring of cortisol in urine can help diagnose Cushing’s or Addison’s disease, which result from having too high or too low levels of cortisol, respectively, for prolonged periods of time (page 2). Sullivan discloses high cortisol levels may arise from long term use of glucocorticoids, increasing the risk of Cushing’s disease (page 3). Sullivan teaches normal urinary free cortisol values for healthy adults ranges between 30-145 nmol/ L over 24 hours (cortisol MW is 362.46 g/mol – therefore, this value equates to 10.8 µg/L to 52.6 µg/L over 24 hours).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a combination treatment of corticosteroids (specifically a selective GR antagonist, as taught by Serritella, such as US 005’s SGRM, exicorilant derivative) and enzalutamide to reduce PSA levels (increase PSA doubling time – see 112(b)) in a subject with mCRPC, and having a UFC greater than 17.5 µg/24 h, as taught by US ‘005 in view of De Santis and Serritella, further in view of Sullivan. One of ordinary skill would have been motivated to do so because US ‘005 discloses exicorilant as an SGRA, as part of a method for treating prostate cancer; De Santis teaches corticosteroids have been used in combination with enzalutamide have been used for the treatment of mCRPC, and that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels; Serritella teaches that AR inhibition results in GR activation, which promotes prostate cancer cell survival and proliferation in CRPC, and suggests that selective GR antagonists combined with AR antagonists should be explored further for CRPC therapy; and Sullivan teaches that long-term glucocorticoid treatment can result in high levels of cortisol, which can result in Cushing’s disease. One of ordinary skill would have had a reasonable expectation of success because US ‘005 discloses exicorilant; De Santis and Serritella disclose enzalutamide (an AR inhibitor) is safe as part of a combination therapy with a GR for treating CRPC; and Sullivan teaches how the test UFC (see pages 6-7) and what the expected cortisol values are for a healthy individual.
Regarding instant claims 2-3, Serritella discloses castration resistant, and metastatic castration resistant prostate cancers (abstract).
Regarding instant claim 4, Serritella discloses enzalutamide as an AR inhibitor (abstract).
Regarding claim 8, Serritella discloses that their treated subjects received combination treatment of enzalutamide and mifepristone, with doses administered once per day (page 1550, line bridging col. 1-2).
Regarding claims 10-11 and 19-20, Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Regarding the claimed ranges for enzalutamide and exicorilant administration, as recited in claims 10-14 and 19-20, Applicant is advised that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that where 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.
Claim 9 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-30 of U.S. Patent No. 10,946,005 B2 (US ‘005); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”); as applied to claims 1-3, 8, 10-14, and 19-20; further in view of Glazier et al. (Retrieved from thecalifornian.com [Retrieved on 11/23/2025] <URL: https://www.thecalifornian.com/story/life/2017/08/24/ask-drs-when-and-how-take-medication-food/598150001/>) (“Glazier”).
The teachings of US ‘005, De Santis, Serritella, and Sullivan are disclosed above and incorporated herein.
Serritella discloses nausea in some cases after oral administration of their enzalutamide and mifepristone combination therapy (Phase II, Table 2, page 1554).
While US ‘005 in view of De Santis, Serritella, and Sullivan does not specifically teach administration of the GRM with food, the teachings of Glazier are relied upon for these disclosures.
Glazier teaches there are multiple reasons why one might take a medication with food, including that some medications may cause stomach upset, such as nausea, if they are not taken with food. Glazier specifically mentions that corticosteroids should be taken with food (para. 3).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer US ‘005’s GRM with food as part of De Santis and Serritella’s AR/GR inhibitor combination therapy in view of Glazier. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘005 discloses their GRM compounds; Serritella teaches some of their subjects reported nausea in phase II clinical trials of their combination therapy for CRPC; and Glazier warns that some medications, particularly glucocorticoids, may cause stomach upset and nausea, and that subjects taking these treatments might benefit from doing so with food.
Claims 1-3, 8, 10-14, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-20 of U.S. Patent No. 12,005,055 B2 (US ‘055); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”).
Regarding instant claims 1-3, 8, 10-14, and 19-20, US ‘055 claims a method of reducing the size of a pituitary tumor in a patient comprising administration of 20 - 800 mg/ day of the SGRA below (reading on exicorilant and on instant claims 1, 5-7, 12-14 and 19-20) (US ‘055’s claims 1 and 9).
PNG
media_image3.png
183
201
media_image3.png
Greyscale
US ‘055’s compound differs from exicorilant in that they have a pyrazole where exicorilant has a triazole, and in the olefin in the tricyclic core. However, Applicant is advised that similar properties may normally be presumed when compounds are very close in structure. Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. See MPEP 2144.08(d).
While US ‘055 does not specifically teach: (i) coadministration of an AR inhibitor, such as enzalutamide, at doses of about 150-200 mg/day (claims 1, 4, 10-11, and 19-20); (ii) wherein the cancer is CRPC or metastatic CRPC (claims 2-3); (iii) administration of the GR inhibitor once a day (claim 8); the teachings of De Santis, Serritella, and Sullivan are relied upon for these disclosures.
De Santis teaches corticosteroids have been used in combination with chemotherapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC) for more than three decades, and that more recently, they have been used in combination with hormonal agents, such as enzalutamide (abstract; and page 156, col. 1, para. 2; and page 161, col. 1). De Santis teaches that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels in retrospective and prospective clinical studies of men with mCRPC.
Serritella teaches that GR expression significantly increases after AR signal inhibition (ARSI), and that subsequent to ARSI, GR activation promotes prostate cancer cell survival and proliferation. Serritella teaches that GR expression may represent a therapeutic target for progressive castration-resistant prostate cancer (CRPC) (page 1549, col. 2, para. 3). Serritella teaches clinical trials of enzalutamide (an AR inhibitor) and mifepristone (an AR/GR inhibitor) was safe and well tolerated in subjects with CRPC, however, it didn’t meet its primary endpoint. Serritella suggests that selective GR antagonists combined with AR antagonists should be explored further (abstract – conclusions). Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Sullivan teaches monitoring of cortisol in urine can help diagnose Cushing’s or Addison’s disease, which result from having too high or too low levels of cortisol, respectively, for prolonged periods of time (page 2). Sullivan discloses high cortisol levels may arise from long term use of glucocorticoids, increasing the risk of Cushing’s disease (page 3). Sullivan teaches normal urinary free cortisol values for healthy adults ranges between 30-145 nmol/ L over 24 hours (cortisol MW is 362.46 g/mol – therefore, this value equates to 10.8 µg/L to 52.6 µg/L over 24 hours).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a combination treatment of corticosteroids (specifically a selective GR antagonist, as taught by Serritella, such as US 055’s SGRM, exicorilant derivative) and enzalutamide to reduce PSA levels (increase PSA doubling time – see 112(b)) in a subject with mCRPC, and having a UFC greater than 17.5 µg/24 h, as taught by US ‘055 in view of De Santis and Serritella, further in view of Sullivan. One of ordinary skill would have been motivated to do so because US ‘055 discloses exicorilant as an SGRA, as part of a method for treating prostate cancer; De Santis teaches corticosteroids have been used in combination with enzalutamide have been used for the treatment of mCRPC, and that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels; Serritella teaches that AR inhibition results in GR activation, which promotes prostate cancer cell survival and proliferation in CRPC, and suggests that selective GR antagonists combined with AR antagonists should be explored further for CRPC therapy; and Sullivan teaches that long-term glucocorticoid treatment can result in high levels of cortisol, which can result in Cushing’s disease. One of ordinary skill would have had a reasonable expectation of success because US ‘055 discloses exicorilant; De Santis and Serritella disclose enzalutamide (an AR inhibitor) is safe as part of a combination therapy with a GR for treating CRPC; and Sullivan teaches how the test UFC (see pages 6-7) and what the expected cortisol values are for a healthy individual.
Regarding instant claims 2-3, Serritella discloses castration resistant, and metastatic castration resistant prostate cancers (abstract).
Regarding claim 8, Serritella discloses that their treated subjects received combination treatment of enzalutamide and mifepristone, with doses administered once per day (page 1550, line bridging col. 1-2).
Regarding claims 10-11 and 19-20, Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Regarding the claimed ranges for enzalutamide and exicorilant administration, as recited in claims 10-14 and 19-20, Applicant is advised that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that where 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.
Claim 9 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-20 of U.S. Patent No. 12,005,055 B2 (US ‘055); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”); as applied to claims 1-3, 8, 10-14, and 19-20; further in view of Glazier et al. (Retrieved from thecalifornian.com [Retrieved on 11/23/2025] <URL: https://www.thecalifornian.com/story/life/2017/08/24/ask-drs-when-and-how-take-medication-food/598150001/>) (“Glazier”).
The teachings of US ‘055, De Santis, Serritella, and Sullivan are disclosed above and incorporated herein.
Serritella discloses nausea in some cases after oral administration of their enzalutamide and mifepristone combination therapy (Phase II, Table 2, page 1554).
While US ‘055 in view of De Santis, Serritella, and Sullivan does not specifically teach administration of the GRM with food, the teachings of Glazier are relied upon for these disclosures.
Glazier teaches there are multiple reasons why one might take a medication with food, including that some medications may cause stomach upset, such as nausea, if they are not taken with food. Glazier specifically mentions that corticosteroids should be taken with food (para. 3).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer US ‘055’s GRM with food as part of De Santis and Serritella’s AR/GR inhibitor combination therapy in view of Glazier. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘055 discloses their GRM compounds; Serritella teaches some of their subjects reported nausea in phase II clinical trials of their combination therapy for CRPC; and Glazier warns that some medications, particularly glucocorticoids, may cause stomach upset and nausea, and that subjects taking these treatments might benefit from doing so with food.
Claims 1-3, 8, 10-14, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-18 of U.S. Patent No. 12,336,985 B2 (US ‘985); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”).
Regarding instant claims 1-3, 8, 10-14, and 19-20, US ‘985 claims a method of reducing the size of a pituitary tumor in a patient comprising administration of 50 - 200 mg/ day of the SGRA below (reading on exicorilant and on instant claims 1, 5-7, 12-14 and 19-20) (US ‘985’s claims 1 and 9).
PNG
media_image3.png
183
201
media_image3.png
Greyscale
US ‘985’s compound differs from exicorilant in that they have a pyrazole where exicorilant has a triazole, and in the olefin in the tricyclic core. However, Applicant is advised that similar properties may normally be presumed when compounds are very close in structure. Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. See MPEP 2144.08(d).
While US ‘985 does not specifically teach: (i) coadministration of an AR inhibitor, such as enzalutamide, at doses of about 150-200 mg/day (claims 1, 4, 10-11, and 19-20); (ii) wherein the cancer is CRPC or metastatic CRPC (claims 2-3); (iii) administration of the GR inhibitor once a day (claim 8); the teachings of De Santis, Serritella, Sullivan are relied upon for these disclosures.
De Santis teaches corticosteroids have been used in combination with chemotherapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC) for more than three decades, and that more recently, they have been used in combination with hormonal agents, such as enzalutamide (abstract; and page 156, col. 1, para. 2; and page 161, col. 1). De Santis teaches that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels in retrospective and prospective clinical studies of men with mCRPC.
Serritella teaches that GR expression significantly increases after AR signal inhibition (ARSI), and that subsequent to ARSI, GR activation promotes prostate cancer cell survival and proliferation. Serritella teaches that GR expression may represent a therapeutic target for progressive castration-resistant prostate cancer (CRPC) (page 1549, col. 2, para. 3). Serritella teaches clinical trials of enzalutamide (an AR inhibitor) and mifepristone (an AR/GR inhibitor) was safe and well tolerated in subjects with CRPC, however, it didn’t meet its primary endpoint. Serritella suggests that selective GR antagonists combined with AR antagonists should be explored further (abstract – conclusions). Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Sullivan teaches monitoring of cortisol in urine can help diagnose Cushing’s or Addison’s disease, which result from having too high or too low levels of cortisol, respectively, for prolonged periods of time (page 2). Sullivan discloses high cortisol levels may arise from long term use of glucocorticoids, increasing the risk of Cushing’s disease (page 3). Sullivan teaches normal urinary free cortisol values for healthy adults ranges between 30-145 nmol/ L over 24 hours (cortisol MW is 362.46 g/mol – therefore, this value equates to 10.8 µg/L to 52.6 µg/L over 24 hours).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a combination treatment of corticosteroids (specifically a selective GR antagonist, as taught by Serritella, such as US ‘985’s SGRM, exicorilant derivative) and enzalutamide to reduce PSA levels (increase PSA doubling time – see 112(b)) in a subject with mCRPC, and having a UFC greater than 17.5 µg/24 h, as taught by US ‘985 in view of De Santis and Serritella, further in view of Sullivan. One of ordinary skill would have been motivated to do so because US ‘985 discloses exicorilant as an SGRA, as part of a method for treating prostate cancer; De Santis teaches corticosteroids have been used in combination with enzalutamide have been used for the treatment of mCRPC, and that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels; Serritella teaches that AR inhibition results in GR activation, which promotes prostate cancer cell survival and proliferation in CRPC, and suggests that selective GR antagonists combined with AR antagonists should be explored further for CRPC therapy; and Sullivan teaches that long-term glucocorticoid treatment can result in high levels of cortisol, which can result in Cushing’s disease. One of ordinary skill would have had a reasonable expectation of success because US ‘985 discloses exicorilant; De Santis and Serritella disclose enzalutamide (an AR inhibitor) is safe as part of a combination therapy with a GR for treating CRPC; and Sullivan teaches how the test UFC (see pages 6-7) and what the expected cortisol values are for a healthy individual.
Regarding instant claims 2-3, Serritella discloses castration resistant, and metastatic castration resistant prostate cancers (abstract).
Regarding claim 8, Serritella discloses that their treated subjects received combination treatment of enzalutamide and mifepristone, with doses administered once per day (page 1550, line bridging col. 1-2).
Regarding claims 10-11 and 19-20, Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Regarding the claimed ranges for enzalutamide and exicorilant administration, as recited in claims 10-14 and 19-20, Applicant is advised that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that where 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.
Claim 9 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-18 of U.S. Patent No. 12,336,985 B2 (US ‘985); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”); as applied to claims 1-3, 8, 10-14, and 19-20; further in view of Glazier et al. (Retrieved from thecalifornian.com [Retrieved on 11/23/2025] <URL: https://www.thecalifornian.com/story/life/2017/08/24/ask-drs-when-and-how-take-medication-food/598150001/>) (“Glazier”).
The teachings of US ‘985, De Santis, Serritella, and Sullivan are disclosed above and incorporated herein.
Serritella discloses nausea in some cases after oral administration of their enzalutamide and mifepristone combination therapy (Phase II, Table 2, page 1554).
While US ‘985 in view of De Santis, Serritella, and Sullivan does not specifically teach administration of the GRM with food, the teachings of Glazier are relied upon for these disclosures.
Glazier teaches there are multiple reasons why one might take a medication with food, including that some medications may cause stomach upset, such as nausea, if they are not taken with food. Glazier specifically mentions that corticosteroids should be taken with food (para. 3).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer US ‘985’s GRM with food as part of De Santis and Serritella’s AR/GR inhibitor combination therapy in view of Glazier. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘985 discloses their GRM compounds; Serritella teaches some of their subjects reported nausea in phase II clinical trials of their combination therapy for CRPC; and Glazier warns that some medications, particularly glucocorticoids, may cause stomach upset and nausea, and that subjects taking these treatments might benefit from doing so with food.
Claims 1-3, 8, 10-14, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-22 of U.S. Patent No. 11,058,670 B2 (US ‘670); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”).
Regarding instant claims 1-3, 8, 10-14, and 19-20, US ‘670 claims a method of treating hypercortisolemia comprising administration of 10 - 500 mg/ day of the SGRA below (reading on exicorilant and on instant claims 1, 5-7, 12-14 and 19-20) (US ‘670’s claims 1 and 21).
PNG
media_image3.png
183
201
media_image3.png
Greyscale
US ‘670’s compound differs from exicorilant in that they have a pyrazole where exicorilant has a triazole, and in the olefin in the tricyclic core. However, Applicant is advised that similar properties may normally be presumed when compounds are very close in structure. Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. See MPEP 2144.08(d).
While US ‘670 does not specifically teach: (i) coadministration of an AR inhibitor, such as enzalutamide, at doses of about 150-200 mg/day (claims 1, 4, 10-11, and 19-20); (ii) wherein the cancer is CRPC or metastatic CRPC (claims 2-3); (iii) administration of the GR inhibitor once a day (claim 8); the teachings of De Santis, Serritella, and Sullivan are relied upon for these disclosures.
De Santis teaches corticosteroids have been used in combination with chemotherapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC) for more than three decades, and that more recently, they have been used in combination with hormonal agents, such as enzalutamide (abstract; and page 156, col. 1, para. 2; and page 161, col. 1). De Santis teaches that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels in retrospective and prospective clinical studies of men with mCRPC.
Serritella teaches that GR expression significantly increases after AR signal inhibition (ARSI), and that subsequent to ARSI, GR activation promotes prostate cancer cell survival and proliferation. Serritella teaches that GR expression may represent a therapeutic target for progressive castration-resistant prostate cancer (CRPC) (page 1549, col. 2, para. 3). Serritella teaches clinical trials of enzalutamide (an AR inhibitor) and mifepristone (an AR/GR inhibitor) was safe and well tolerated in subjects with CRPC, however, it didn’t meet its primary endpoint. Serritella suggests that selective GR antagonists combined with AR antagonists should be explored further (abstract – conclusions). Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Sullivan teaches monitoring of cortisol in urine can help diagnose Cushing’s or Addison’s disease, which result from having too high or too low levels of cortisol, respectively, for prolonged periods of time (page 2). Sullivan discloses high cortisol levels may arise from long term use of glucocorticoids, increasing the risk of Cushing’s disease (page 3). Sullivan teaches normal urinary free cortisol values for healthy adults ranges between 30-145 nmol/ L over 24 hours (cortisol MW is 362.46 g/mol – therefore, this value equates to 10.8 µg/L to 52.6 µg/L over 24 hours).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a combination treatment of corticosteroids (specifically a selective GR antagonist, as taught by Serritella, such as US ‘670’s SGRM, exicorilant derivative) and enzalutamide to reduce PSA levels (increase PSA doubling time – see 112(b)) in a subject with mCRPC, and having a UFC greater than 17.5 µg/24 h, as taught by US ‘670 in view of De Santis and Serritella, further in view of Sullivan. One of ordinary skill would have been motivated to do so because US ‘670 discloses exicorilant as an SGRA, as part of a method for treating prostate cancer; De Santis teaches corticosteroids have been used in combination with enzalutamide have been used for the treatment of mCRPC, and that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels; Serritella teaches that AR inhibition results in GR activation, which promotes prostate cancer cell survival and proliferation in CRPC, and suggests that selective GR antagonists combined with AR antagonists should be explored further for CRPC therapy; and Sullivan teaches that long-term glucocorticoid treatment can result in high levels of cortisol, which can result in Cushing’s disease. One of ordinary skill would have had a reasonable expectation of success because US ‘670 discloses exicorilant; De Santis and Serritella disclose enzalutamide (an AR inhibitor) is safe as part of a combination therapy with a GR for treating CRPC; and Sullivan teaches how the test UFC (see pages 6-7) and what the expected cortisol values are for a healthy individual.
Regarding instant claims 2-3, Serritella discloses castration resistant, and metastatic castration resistant prostate cancers (abstract).
Regarding claim 8, Serritella discloses that their treated subjects received combination treatment of enzalutamide and mifepristone, with doses administered once per day (page 1550, line bridging col. 1-2).
Regarding claims 10-11 and 19-20, Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Regarding the claimed ranges for enzalutamide and exicorilant administration, as recited in claims 10-14 and 19-20, Applicant is advised that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that where 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.
Claim 9 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-22 of U.S. Patent No. 11,058,670 B2 (US ‘670); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”); as applied to claims 1-3, 8, 10-14, and 19-20; further in view of Glazier et al. (Retrieved from thecalifornian.com [Retrieved on 11/23/2025] <URL: https://www.thecalifornian.com/story/life/2017/08/24/ask-drs-when-and-how-take-medication-food/598150001/>) (“Glazier”).
The teachings of US ‘670, De Santis, Serritella, and Sullivan are disclosed above and incorporated herein.
Serritella discloses nausea in some cases after oral administration of their enzalutamide and mifepristone combination therapy (Phase II, Table 2, page 1554).
While US ‘670 in view of De Santis, Serritella, and Sullivan does not specifically teach administration of the GRM with food, the teachings of Glazier are relied upon for these disclosures.
Glazier teaches there are multiple reasons why one might take a medication with food, including that some medications may cause stomach upset, such as nausea, if they are not taken with food. Glazier specifically mentions that corticosteroids should be taken with food (para. 3).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer US ‘670’s GRM with food as part of De Santis and Serritella’s AR/GR inhibitor combination therapy in view of Glazier. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘670 discloses their GRM compounds; Serritella teaches some of their subjects reported nausea in phase II clinical trials of their combination therapy for CRPC; and Glazier warns that some medications, particularly glucocorticoids, may cause stomach upset and nausea, and that subjects taking these treatments might benefit from doing so with food.
Claims 1-3, 8, 10-14, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-24 of U.S. Patent No. 11,234,971 B2 (US ‘971); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”).
Regarding instant claims 1-3, 8, 10-14, and 19-20, US ‘971 claims a method of treating cancer in a patient comprising administration of the SGRA below (reading on exicorilant and on instant claim 1) (US ‘971’s claim 1).
PNG
media_image3.png
183
201
media_image3.png
Greyscale
US ‘971’s compound differs from exicorilant in that they have a pyrazole where exicorilant has a triazole, and in the olefin in the tricyclic core. However, Applicant is advised that similar properties may normally be presumed when compounds are very close in structure. Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. See MPEP 2144.08(d).
While US ‘971 does not specifically teach: (i) coadministration of an AR inhibitor, such as enzalutamide, at doses of about 150-200 mg/day (claims 1, 4, 10-11, and 19-20); (ii) wherein the cancer is CRPC or metastatic CRPC (claims 2-3); (iii) administration of the GR inhibitor once a day (claim 8); (iv) administration of GRM (exicorilant) at doses of 100-350 mg/day (claims 12-14 and 19-20); the teachings of De Santis, Serritella, and Sullivan are relied upon for these disclosures.
De Santis teaches corticosteroids have been used in combination with chemotherapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC) for more than three decades, and that more recently, they have been used in combination with hormonal agents, such as enzalutamide (abstract; and page 156, col. 1, para. 2; and page 161, col. 1). De Santis teaches that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels in retrospective and prospective clinical studies of men with mCRPC.
Serritella teaches that GR expression significantly increases after AR signal inhibition (ARSI), and that subsequent to ARSI, GR activation promotes prostate cancer cell survival and proliferation. Serritella teaches that GR expression may represent a therapeutic target for progressive castration-resistant prostate cancer (CRPC) (page 1549, col. 2, para. 3). Serritella teaches clinical trials of enzalutamide (an AR inhibitor) and mifepristone (an AR/GR inhibitor) was safe and well tolerated in subjects with CRPC, however, it didn’t meet its primary endpoint. Serritella suggests that selective GR antagonists combined with AR antagonists should be explored further (abstract – conclusions). Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Sullivan teaches monitoring of cortisol in urine can help diagnose Cushing’s or Addison’s disease, which result from having too high or too low levels of cortisol, respectively, for prolonged periods of time (page 2). Sullivan discloses high cortisol levels may arise from long term use of glucocorticoids, increasing the risk of Cushing’s disease (page 3). Sullivan teaches normal urinary free cortisol values for healthy adults ranges between 30-145 nmol/ L over 24 hours (cortisol MW is 362.46 g/mol – therefore, this value equates to 10.8 µg/L to 52.6 µg/L over 24 hours).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a combination treatment of corticosteroids (specifically a selective GR antagonist, as taught by Serritella, such as US ‘971’s SGRM, exicorilant derivative) and enzalutamide to reduce PSA levels (increase PSA doubling time – see 112(b)) in a subject with mCRPC, and having a UFC greater than 17.5 µg/24 h, as taught by US ‘971 in view of De Santis and Serritella, further in view of Sullivan. One of ordinary skill would have been motivated to do so because US ‘971 discloses exicorilant as an SGRA, as part of a method for treating prostate cancer; De Santis teaches corticosteroids have been used in combination with enzalutamide have been used for the treatment of mCRPC, and that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels; Serritella teaches that AR inhibition results in GR activation, which promotes prostate cancer cell survival and proliferation in CRPC, and suggests that selective GR antagonists combined with AR antagonists should be explored further for CRPC therapy; and Sullivan teaches that long-term glucocorticoid treatment can result in high levels of cortisol, which can result in Cushing’s disease. One of ordinary skill would have had a reasonable expectation of success because US ‘971 discloses exicorilant; De Santis and Serritella disclose enzalutamide (an AR inhibitor) is safe as part of a combination therapy with a GR for treating CRPC; and Sullivan teaches how the test UFC (see pages 6-7) and what the expected cortisol values are for a healthy individual.
Regarding instant claims 2-3, Serritella discloses castration resistant, and metastatic castration resistant prostate cancers (abstract).
Regarding claim 8, Serritella discloses that their treated subjects received combination treatment of enzalutamide and mifepristone, with doses administered once per day (page 1550, line bridging col. 1-2).
Regarding claims 10-11 and 19-20, Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Regarding claims 12-14 and 19-20, Serritella discloses their GR inhibitor in combination therapy with enzalutamide was administered at 300 mg/ day (page 1550, col. 1-2).
Regarding the claimed ranges for enzalutamide and exicorilant administration, as recited in claims 10-14 and 19-20, Applicant is advised that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that where 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.
Claim 9 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-24 of U.S. Patent No. 11,234,971 B2 (US ‘971); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”); as applied to claims 1-3, 8, 10-14, and 19-20; further in view of Glazier et al. (Retrieved from thecalifornian.com [Retrieved on 11/23/2025] <URL: https://www.thecalifornian.com/story/life/2017/08/24/ask-drs-when-and-how-take-medication-food/598150001/>) (“Glazier”).
The teachings of US ‘971, De Santis, Serritella, and Sullivan are disclosed above and incorporated herein.
Serritella discloses nausea in some cases after oral administration of their enzalutamide and mifepristone combination therapy (Phase II, Table 2, page 1554).
While US ‘971 in view of De Santis, Serritella, and Sullivan does not specifically teach administration of the GRM with food, the teachings of Glazier are relied upon for these disclosures.
Glazier teaches there are multiple reasons why one might take a medication with food, including that some medications may cause stomach upset, such as nausea, if they are not taken with food. Glazier specifically mentions that corticosteroids should be taken with food (para. 3).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer US ‘971’s GRM with food as part of De Santis and Serritella’s AR/GR inhibitor combination therapy in view of Glazier. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘971 discloses their GRM compounds; Serritella teaches some of their subjects reported nausea in phase II clinical trials of their combination therapy for CRPC; and Glazier warns that some medications, particularly glucocorticoids, may cause stomach upset and nausea, and that subjects taking these treatments might benefit from doing so with food.
Claims 1-3, 8, 10-14, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-19 of U.S. Patent No. 1,389,432 B2 (US ‘432); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”).
Regarding instant claims 1-3, 8, 10-14, and 19-20, US ‘432 claims a method of treating cancer in a patient comprising administration of the SGRA below (reading on exicorilant and on instant claims 1, 5-7) (US ‘432’s claim 1).
PNG
media_image3.png
183
201
media_image3.png
Greyscale
US ‘432’s compound differs from exicorilant in that they have a pyrazole where exicorilant has a triazole, and in the olefin in the tricyclic core. However, Applicant is advised that similar properties may normally be presumed when compounds are very close in structure. Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. See MPEP 2144.08(d).
While US ‘432 does not specifically teach: (i) coadministration of an AR inhibitor, such as enzalutamide, at doses of about 150-200 mg/day (claims 1, 4, 10-11, and 19-20); (ii) wherein the cancer is CRPC or metastatic CRPC (claims 2-3); (iii) administration of the GR inhibitor once a day (claim 8); (iv) administration of GRM (exicorilant) at doses of 100-350 mg/day (claims 12-14 and 19-20); the teachings of De Santis, Serritella, and Sullivan are relied upon for these disclosures.
De Santis teaches corticosteroids have been used in combination with chemotherapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC) for more than three decades, and that more recently, they have been used in combination with hormonal agents, such as enzalutamide (abstract; and page 156, col. 1, para. 2; and page 161, col. 1). De Santis teaches that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels in retrospective and prospective clinical studies of men with mCRPC.
Serritella teaches that GR expression significantly increases after AR signal inhibition (ARSI), and that subsequent to ARSI, GR activation promotes prostate cancer cell survival and proliferation. Serritella teaches that GR expression may represent a therapeutic target for progressive castration-resistant prostate cancer (CRPC) (page 1549, col. 2, para. 3). Serritella teaches clinical trials of enzalutamide (an AR inhibitor) and mifepristone (an AR/GR inhibitor) was safe and well tolerated in subjects with CRPC, however, it didn’t meet its primary endpoint. Serritella suggests that selective GR antagonists combined with AR antagonists should be explored further (abstract – conclusions). Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Sullivan teaches monitoring of cortisol in urine can help diagnose Cushing’s or Addison’s disease, which result from having too high or too low levels of cortisol, respectively, for prolonged periods of time (page 2). Sullivan discloses high cortisol levels may arise from long term use of glucocorticoids, increasing the risk of Cushing’s disease (page 3). Sullivan teaches normal urinary free cortisol values for healthy adults ranges between 30-145 nmol/ L over 24 hours (cortisol MW is 362.46 g/mol – therefore, this value equates to 10.8 µg/L to 52.6 µg/L over 24 hours).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a combination treatment of corticosteroids (specifically a selective GR antagonist, as taught by Serritella, such as US ‘432’s SGRM, exicorilant derivative) and enzalutamide to reduce PSA levels (increase PSA doubling time – see 112(b)) in a subject with mCRPC, and having a UFC greater than 17.5 µg/24 h, as taught by US ‘432 in view of De Santis and Serritella, further in view of Sullivan. One of ordinary skill would have been motivated to do so because US ‘432 discloses exicorilant as an SGRA, as part of a method for treating prostate cancer; De Santis teaches corticosteroids have been used in combination with enzalutamide have been used for the treatment of mCRPC, and that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels; Serritella teaches that AR inhibition results in GR activation, which promotes prostate cancer cell survival and proliferation in CRPC, and suggests that selective GR antagonists combined with AR antagonists should be explored further for CRPC therapy; and Sullivan teaches that long-term glucocorticoid treatment can result in high levels of cortisol, which can result in Cushing’s disease. One of ordinary skill would have had a reasonable expectation of success because US ‘432 discloses exicorilant; De Santis and Serritella disclose enzalutamide (an AR inhibitor) is safe as part of a combination therapy with a GR for treating CRPC; and Sullivan teaches how the test UFC (see pages 6-7) and what the expected cortisol values are for a healthy individual.
Regarding instant claims 2-3, Serritella discloses castration resistant, and metastatic castration resistant prostate cancers (abstract).
Regarding claim 8, Serritella discloses that their treated subjects received combination treatment of enzalutamide and mifepristone, with doses administered once per day (page 1550, line bridging col. 1-2).
Regarding claims 10-11 and 19-20, Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Regarding claims 12-14 and 19-20, Serritella discloses their GR inhibitor in combination therapy with enzalutamide was administered at 300 mg/ day (page 1550, col. 1-2).
Regarding the claimed ranges for enzalutamide and exicorilant administration, as recited in claims 10-14 and 19-20, Applicant is advised that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that where 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.
Claim 9 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-19 of U.S. Patent No. 1,389,432 B2 (US ‘432); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”); as applied to claims 1-3, 8, 10-14, and 19-20; further in view of Glazier et al. (Retrieved from thecalifornian.com [Retrieved on 11/23/2025] <URL: https://www.thecalifornian.com/story/life/2017/08/24/ask-drs-when-and-how-take-medication-food/598150001/>) (“Glazier”).
The teachings of US ‘432, De Santis, Serritella, and Sullivan are disclosed above and incorporated herein.
Serritella discloses nausea in some cases after oral administration of their enzalutamide and mifepristone combination therapy (Phase II, Table 2, page 1554).
While US ‘432 in view of De Santis, Serritella, and Sullivan does not specifically teach administration of the GRM with food, the teachings of Glazier are relied upon for these disclosures.
Glazier teaches there are multiple reasons why one might take a medication with food, including that some medications may cause stomach upset, such as nausea, if they are not taken with food. Glazier specifically mentions that corticosteroids should be taken with food (para. 3).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer US ‘432’s GRM with food as part of De Santis and Serritella’s AR/GR inhibitor combination therapy in view of Glazier. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘432 discloses their GRM compounds; Serritella teaches some of their subjects reported nausea in phase II clinical trials of their combination therapy for CRPC; and Glazier warns that some medications, particularly glucocorticoids, may cause stomach upset and nausea, and that subjects taking these treatments might benefit from doing so with food.
Claims 1-3, 8, 10-14, and 19-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, and 16-21 of copending Application No. 17/793,271 (Copending ‘271); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”).
Regarding instant claims 1-3, 8, 10-14, and 19-20, Copending ‘271 claims a method of improving an immune function in a cancer patient having a solid tumor comprising administration of an SGRM below (reading on exicorilant) (Copending ‘271’s claims 1, 8, and 12-13).
PNG
media_image5.png
148
177
media_image5.png
Greyscale
Copending ‘271’s compound differs from exicorilant in that they have a pyrazole where exicorilant has a triazole, and in the olefin in the tricyclic core. However, Applicant is advised that similar properties may normally be presumed when compounds are very close in structure. Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. See MPEP 2144.08(d).
While Copending ‘271 does not specifically teach: (i) coadministration of an AR inhibitor, such as enzalutamide, at doses of about 150-200 mg/day (claims 1, 10-11, and 19-20); (ii) wherein the cancer is CRPC or metastatic CRPC (claims 2-3); (iii) administration of the GR inhibitor once a day (claim 8); (iv) administration of GRM (exicorilant) at doses of 100-350 mg/day (claims 12-14 and 19-20); the teachings of De Santis, Serritella, and Sullivan are relied upon for these disclosures.
De Santis teaches corticosteroids have been used in combination with chemotherapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC) for more than three decades, and that more recently, they have been used in combination with hormonal agents, such as enzalutamide (abstract; and page 156, col. 1, para. 2; and page 161, col. 1). De Santis teaches that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels in retrospective and prospective clinical studies of men with mCRPC.
Serritella teaches that GR expression significantly increases after AR signal inhibition (ARSI), and that subsequent to ARSI, GR activation promotes prostate cancer cell survival and proliferation. Serritella teaches that GR expression may represent a therapeutic target for progressive castration-resistant prostate cancer (CRPC) (page 1549, col. 2, para. 3). Serritella teaches clinical trials of enzalutamide (an AR inhibitor) and mifepristone (an AR/GR inhibitor) was safe and well tolerated in subjects with CRPC, however, it didn’t meet its primary endpoint. Serritella suggests that selective GR antagonists combined with AR antagonists should be explored further (abstract – conclusions). Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Sullivan teaches monitoring of cortisol in urine can help diagnose Cushing’s or Addison’s disease, which result from having too high or too low levels of cortisol, respectively, for prolonged periods of time (page 2). Sullivan discloses high cortisol levels may arise from long term use of glucocorticoids, increasing the risk of Cushing’s disease (page 3). Sullivan teaches normal urinary free cortisol values for healthy adults ranges between 30-145 nmol/ L over 24 hours (cortisol MW is 362.46 g/mol – therefore, this value equates to 10.8 µg/L to 52.6 µg/L over 24 hours).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a combination treatment of corticosteroids (specifically a selective GR antagonist, as taught by Serritella, such as Copending ‘271’s SGRM, exicorilant derivative) and enzalutamide to reduce PSA levels (increase PSA doubling time – see 112(b)) in a subject with mCRPC, and having a UFC greater than 17.5 µg/24 h, as taught by Copending ‘271 in view of De Santis and Serritella, further in view of Sullivan. One of ordinary skill would have been motivated to do so because Copending ‘271 discloses exicorilant as an SGRA, as part of a method for treating prostate cancer; De Santis teaches corticosteroids have been used in combination with enzalutamide have been used for the treatment of mCRPC, and that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels; Serritella teaches that AR inhibition results in GR activation, which promotes prostate cancer cell survival and proliferation in CRPC, and suggests that selective GR antagonists combined with AR antagonists should be explored further for CRPC therapy; and Sullivan teaches that long-term glucocorticoid treatment can result in high levels of cortisol, which can result in Cushing’s disease. One of ordinary skill would have had a reasonable expectation of success because Copending ‘271 discloses exicorilant; De Santis and Serritella disclose enzalutamide (an AR inhibitor) is safe as part of a combination therapy with a GR for treating CRPC; and Sullivan teaches how the test UFC (see pages 6-7) and what the expected cortisol values are for a healthy individual.
Regarding instant claims 2-3, Serritella discloses castration resistant, and metastatic castration resistant prostate cancers (abstract).
Regarding claim 8, Serritella discloses that their treated subjects received combination treatment of enzalutamide and mifepristone, with doses administered once per day (page 1550, line bridging col. 1-2).
Regarding claims 10-11 and 19-20, Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Regarding claims 12-14 and 19-20, Serritella discloses their GR inhibitor in combination therapy with enzalutamide was administered at 300 mg/ day (page 1550, col. 1-2).
Regarding the claimed ranges for enzalutamide and exicorilant administration, as recited in claims 10-14 and 19-20, Applicant is advised that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that where 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.
This is a provisional nonstatutory double patenting rejection.
Claim 9 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7-22 of copending Application No. 17/793,271 (Copending ‘271); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”); as applied to claims 1-3, 8, 10-14, and 19-20; further in view of Glazier et al. (Retrieved from thecalifornian.com [Retrieved on 11/23/2025] <URL: https://www.thecalifornian.com/story/life/2017/08/24/ask-drs-when-and-how-take-medication-food/598150001/>) (“Glazier”).
The teachings of Copending ‘271, De Santis, Serritella, and Sullivan are disclosed above and incorporated herein.
Serritella discloses nausea in some cases after oral administration of their enzalutamide and mifepristone combination therapy (Phase II, Table 2, page 1554).
While Copending ‘271 in view of De Santis, Serritella, and Sullivan does not specifically teach administration of the GRM with food, the teachings of Glazier are relied upon for these disclosures.
Glazier teaches there are multiple reasons why one might take a medication with food, including that some medications may cause stomach upset, such as nausea, if they are not taken with food. Glazier specifically mentions that corticosteroids should be taken with food (para. 3).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer Copending ‘271’s GRM with food as part of De Santis and Serritella’s AR/GR inhibitor combination therapy in view of Glazier. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Copending ‘271 discloses their GRM compounds; Serritella teaches some of their subjects reported nausea in phase II clinical trials of their combination therapy for CRPC; and Glazier warns that some medications, particularly glucocorticoids, may cause stomach upset and nausea, and that subjects taking these treatments might benefit from doing so with food.
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 8, 10-14, and 19-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of copending Application No. 18/460,226 (Copending ‘226); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”).
Regarding instant claims 1-3, 8, 10-14, and 19-20, Copending ‘226 claims a method of improving an immune function in a cancer patient having a solid tumor comprising administration of an SGRM of Formula I below, specifically mentioning instant exicorilant (Copending ‘226’s claims 1 and 4).
While Copending ‘226 does not specifically teach: (i) coadministration of an AR inhibitor, such as enzalutamide, at doses of about 150-200 mg/day (claims 1, 4, 10-11, and 19-20); (ii) wherein the cancer is CRPC or metastatic CRPC (claims 2-3); (iii) administration of the GR inhibitor once a day (claim 8); (iv) administration of GRM (exicorilant) at doses of 100-350 mg/day (claims 12-14 and 19-20); the teachings of De Santis, Serritella, and Sullivan are relied upon for these disclosures.
De Santis teaches corticosteroids have been used in combination with chemotherapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC) for more than three decades, and that more recently, they have been used in combination with hormonal agents, such as enzalutamide (abstract; and page 156, col. 1, para. 2; and page 161, col. 1). De Santis teaches that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels in retrospective and prospective clinical studies of men with mCRPC.
Serritella teaches that GR expression significantly increases after AR signal inhibition (ARSI), and that subsequent to ARSI, GR activation promotes prostate cancer cell survival and proliferation. Serritella teaches that GR expression may represent a therapeutic target for progressive castration-resistant prostate cancer (CRPC) (page 1549, col. 2, para. 3). Serritella teaches clinical trials of enzalutamide (an AR inhibitor) and mifepristone (an AR/GR inhibitor) was safe and well tolerated in subjects with CRPC, however, it didn’t meet its primary endpoint. Serritella suggests that selective GR antagonists combined with AR antagonists should be explored further (abstract – conclusions). Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Sullivan teaches monitoring of cortisol in urine can help diagnose Cushing’s or Addison’s disease, which result from having too high or too low levels of cortisol, respectively, for prolonged periods of time (page 2). Sullivan discloses high cortisol levels may arise from long term use of glucocorticoids, increasing the risk of Cushing’s disease (page 3). Sullivan teaches normal urinary free cortisol values for healthy adults ranges between 30-145 nmol/ L over 24 hours (cortisol MW is 362.46 g/mol – therefore, this value equates to 10.8 µg/L to 52.6 µg/L over 24 hours).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a combination treatment of corticosteroids (specifically a selective GR antagonist, as taught by Serritella, such as Copending ‘226’s SGRM, exicorilant) and enzalutamide to reduce PSA levels (increase PSA doubling time – see 112(b)) in a subject with mCRPC, and having a UFC greater than 17.5 µg/24 h, as taught by Copending ‘226 in view of De Santis and Serritella, further in view of Sullivan. One of ordinary skill would have been motivated to do so because Copending ‘226 discloses exicorilant as an SGRA, as part of a method for treating prostate cancer; De Santis teaches corticosteroids have been used in combination with enzalutamide have been used for the treatment of mCRPC, and that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels; Serritella teaches that AR inhibition results in GR activation, which promotes prostate cancer cell survival and proliferation in CRPC, and suggests that selective GR antagonists combined with AR antagonists should be explored further for CRPC therapy; and Sullivan teaches that long-term glucocorticoid treatment can result in high levels of cortisol, which can result in Cushing’s disease. One of ordinary skill would have had a reasonable expectation of success because Copending ‘226 discloses exicorilant; De Santis and Serritella disclose enzalutamide (an AR inhibitor) is safe as part of a combination therapy with a GR for treating CRPC; and Sullivan teaches how the test UFC (see pages 6-7) and what the expected cortisol values are for a healthy individual.
Regarding instant claims 2-3, Serritella discloses castration resistant, and metastatic castration resistant prostate cancers (abstract).
Regarding claim 8, Serritella discloses that their treated subjects received combination treatment of enzalutamide and mifepristone, with doses administered once per day (page 1550, line bridging col. 1-2).
Regarding claims 10-11 and 19-20, Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Regarding claims 12-14 and 19-20, Serritella discloses their GR inhibitor in combination therapy with enzalutamide was administered at 300 mg/ day (page 1550, col. 1-2).
Regarding the claimed ranges for enzalutamide and exicorilant administration, as recited in claims 10-14 and 19-20, Applicant is advised that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that where 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.
This is a provisional nonstatutory double patenting rejection.
Claim 9 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of copending Application No. 18/460,226 (Copending ‘226); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”); as applied to claims 1-3, 8, 10-14, and 19-20; further in view of Glazier et al. (Retrieved from thecalifornian.com [Retrieved on 11/23/2025] <URL: https://www.thecalifornian.com/story/life/2017/08/24/ask-drs-when-and-how-take-medication-food/598150001/>) (“Glazier”).
The teachings of Copending ‘226, De Santis, Serritella, and Sullivan are disclosed above and incorporated herein.
Serritella discloses nausea in some cases after oral administration of their enzalutamide and mifepristone combination therapy (Phase II, Table 2, page 1554).
While Copending ‘226 in view of De Santis, Serritella, and Sullivan does not specifically teach administration of the GRM with food, the teachings of Glazier are relied upon for these disclosures.
Glazier teaches there are multiple reasons why one might take a medication with food, including that some medications may cause stomach upset, such as nausea, if they are not taken with food. Glazier specifically mentions that corticosteroids should be taken with food (para. 3).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer Copending ‘226’s GRM with food as part of De Santis and Serritella’s AR/GR inhibitor combination therapy in view of Glazier. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Copending ‘226 discloses their GRM compounds; Serritella teaches some of their subjects reported nausea in phase II clinical trials of their combination therapy for CRPC; and Glazier warns that some medications, particularly glucocorticoids, may cause stomach upset and nausea, and that subjects taking these treatments might benefit from doing so with food.
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 8, 10-14, and 19-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of copending Application No. 18/522,749 (Copending ‘749); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”).
Regarding instant claims 1-3, 8, 10-14, and 19-20, Copending ‘749 claims a method of Cushing’s in a patient comprising administration of 50 - 800 mg/ day of the SGRA below (reading on exicorilant and on instant claims 1, 5-7, 12-14 and 19-20) (Copending ‘749’s claims 1 and 3).
PNG
media_image3.png
183
201
media_image3.png
Greyscale
Copending ‘749’s compound differs from exicorilant in that they have a pyrazole where exicorilant has a triazole, and in the olefin in the tricyclic core. However, Applicant is advised that similar properties may normally be presumed when compounds are very close in structure. Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. See MPEP 2144.08(d).
While Copending ‘749 does not specifically teach: (i) coadministration of an AR inhibitor, such as enzalutamide, at doses of about 150-200 mg/day (claims 1, 4, 10-11, and 19-20); (ii) wherein the cancer is CRPC or metastatic CRPC (claims 2-3); (iii) administration of the GR inhibitor once a day (claim 8); the teachings of De Santis, Serritella, and Sullivan are relied upon for these disclosures.
De Santis teaches corticosteroids have been used in combination with chemotherapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC) for more than three decades, and that more recently, they have been used in combination with hormonal agents, such as enzalutamide (abstract; and page 156, col. 1, para. 2; and page 161, col. 1). De Santis teaches that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels in retrospective and prospective clinical studies of men with mCRPC.
Serritella teaches that GR expression significantly increases after AR signal inhibition (ARSI), and that subsequent to ARSI, GR activation promotes prostate cancer cell survival and proliferation. Serritella teaches that GR expression may represent a therapeutic target for progressive castration-resistant prostate cancer (CRPC) (page 1549, col. 2, para. 3). Serritella teaches clinical trials of enzalutamide (an AR inhibitor) and mifepristone (an AR/GR inhibitor) was safe and well tolerated in subjects with CRPC, however, it didn’t meet its primary endpoint. Serritella suggests that selective GR antagonists combined with AR antagonists should be explored further (abstract – conclusions). Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Sullivan teaches monitoring of cortisol in urine can help diagnose Cushing’s or Addison’s disease, which result from having too high or too low levels of cortisol, respectively, for prolonged periods of time (page 2). Sullivan discloses high cortisol levels may arise from long term use of glucocorticoids, increasing the risk of Cushing’s disease (page 3). Sullivan teaches normal urinary free cortisol values for healthy adults ranges between 30-145 nmol/ L over 24 hours (cortisol MW is 362.46 g/mol – therefore, this value equates to 10.8 µg/L to 52.6 µg/L over 24 hours).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a combination treatment of corticosteroids (specifically a selective GR antagonist, as taught by Serritella, such as Copending ‘749’s SGRM, exicorilant derivative) and enzalutamide to reduce PSA levels (increase PSA doubling time – see 112(b)) in a subject with mCRPC, and having a UFC greater than 17.5 µg/24 h, as taught by Copending ‘749 in view of De Santis and Serritella, further in view of Sullivan. One of ordinary skill would have been motivated to do so because Copending ‘749 discloses exicorilant as an SGRA, as part of a method for treating prostate cancer; De Santis teaches corticosteroids have been used in combination with enzalutamide have been used for the treatment of mCRPC, and that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels; Serritella teaches that AR inhibition results in GR activation, which promotes prostate cancer cell survival and proliferation in CRPC, and suggests that selective GR antagonists combined with AR antagonists should be explored further for CRPC therapy; and Sullivan teaches that long-term glucocorticoid treatment can result in high levels of cortisol, which can result in Cushing’s disease. One of ordinary skill would have had a reasonable expectation of success because Copending ‘749 discloses exicorilant; De Santis and Serritella disclose enzalutamide (an AR inhibitor) is safe as part of a combination therapy with a GR for treating CRPC; and Sullivan teaches how the test UFC (see pages 6-7) and what the expected cortisol values are for a healthy individual.
Regarding instant claims 2-3, Serritella discloses castration resistant, and metastatic castration resistant prostate cancers (abstract).
Regarding claim 8, Serritella discloses that their treated subjects received combination treatment of enzalutamide and mifepristone, with doses administered once per day (page 1550, line bridging col. 1-2).
Regarding claims 10-11 and 19-20, Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Regarding the claimed ranges for enzalutamide and exicorilant administration, as recited in claims 10-14 and 19-20, Applicant is advised that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that where 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.
This is a provisional nonstatutory double patenting rejection.
Claim 9 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of copending Application No. 18/522,749 (Copending ‘749); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”); as applied to claims 1-3, 8, 10-14, and 19-20; further in view of Glazier et al. (Retrieved from thecalifornian.com [Retrieved on 11/23/2025] <URL: https://www.thecalifornian.com/story/life/2017/08/24/ask-drs-when-and-how-take-medication-food/598150001/>) (“Glazier”).
The teachings of Copending ‘749, De Santis, Serritella, and Sullivan are disclosed above and incorporated herein.
Serritella discloses nausea in some cases after oral administration of their enzalutamide and mifepristone combination therapy (Phase II, Table 2, page 1554).
While Copending ‘749 in view of De Santis, Serritella, and Sullivan does not specifically teach administration of the GRM with food, the teachings of Glazier are relied upon for these disclosures.
Glazier teaches there are multiple reasons why one might take a medication with food, including that some medications may cause stomach upset, such as nausea, if they are not taken with food. Glazier specifically mentions that corticosteroids should be taken with food (para. 3).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer Copending ‘749’s GRM with food as part of De Santis and Serritella’s AR/GR inhibitor combination therapy in view of Glazier. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Copending ‘749 discloses their GRM compounds; Serritella teaches some of their subjects reported nausea in phase II clinical trials of their combination therapy for CRPC; and Glazier warns that some medications, particularly glucocorticoids, may cause stomach upset and nausea, and that subjects taking these treatments might benefit from doing so with food.
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 8, 10-14, and 19-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of copending Application No. 18/670,160 (Copending ‘160); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”).
Regarding instant claims 1-3, 8, 10-14, and 19-20, Copending ‘160 claims a method of reducing the size of an adrenal gland tumor in a patient comprising administration of the SGRM of Formula I below, wherein J can be triazole (reading on exicorilant) (Copending ‘160’s claims 1-2).
PNG
media_image6.png
96
257
media_image6.png
Greyscale
PNG
media_image7.png
180
211
media_image7.png
Greyscale
Copending ‘160’s compound differs from exicorilant in that they have a pyrazole where exicorilant has a triazole, and in the olefin in the tricyclic core. However, Applicant is advised that similar properties may normally be presumed when compounds are very close in structure. Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. See MPEP 2144.08(d).
While Copending ‘160 does not specifically teach: (i) coadministration of an AR inhibitor, such as enzalutamide, at doses of about 150-200 mg/day (claims 1, 4, 10-11, and 19-20); (ii) wherein the cancer is CRPC or metastatic CRPC (claims 2-3); (iii) administration of the GR inhibitor once a day (claim 8); (iv) administration of GRM (exicorilant) at doses of 100-350 mg/day (claims 12-14 and 19-20); the teachings of De Santis, Serritella, and Sullivan are relied upon for these disclosures.
De Santis teaches corticosteroids have been used in combination with chemotherapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC) for more than three decades, and that more recently, they have been used in combination with hormonal agents, such as enzalutamide (abstract; and page 156, col. 1, para. 2; and page 161, col. 1). De Santis teaches that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels in retrospective and prospective clinical studies of men with mCRPC.
Serritella teaches that GR expression significantly increases after AR signal inhibition (ARSI), and that subsequent to ARSI, GR activation promotes prostate cancer cell survival and proliferation. Serritella teaches that GR expression may represent a therapeutic target for progressive castration-resistant prostate cancer (CRPC) (page 1549, col. 2, para. 3). Serritella teaches clinical trials of enzalutamide (an AR inhibitor) and mifepristone (an AR/GR inhibitor) was safe and well tolerated in subjects with CRPC, however, it didn’t meet its primary endpoint. Serritella suggests that selective GR antagonists combined with AR antagonists should be explored further (abstract – conclusions). Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Sullivan teaches monitoring of cortisol in urine can help diagnose Cushing’s or Addison’s disease, which result from having too high or too low levels of cortisol, respectively, for prolonged periods of time (page 2). Sullivan discloses high cortisol levels may arise from long term use of glucocorticoids, increasing the risk of Cushing’s disease (page 3). Sullivan teaches normal urinary free cortisol values for healthy adults ranges between 30-145 nmol/ L over 24 hours (cortisol MW is 362.46 g/mol – therefore, this value equates to 10.8 µg/L to 52.6 µg/L over 24 hours).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a combination treatment of corticosteroids (specifically a selective GR antagonist, as taught by Serritella, such as Copending ‘160’s SGRM, exicorilant derivative) and enzalutamide to reduce PSA levels (increase PSA doubling time – see 112(b)) in a subject with mCRPC, and having a UFC greater than 17.5 µg/24 h, as taught by Copending ‘160 in view of De Santis and Serritella, further in view of Sullivan. One of ordinary skill would have been motivated to do so because Copending ‘160 discloses exicorilant as an SGRA, as part of a method for treating prostate cancer; De Santis teaches corticosteroids have been used in combination with enzalutamide have been used for the treatment of mCRPC, and that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels; Serritella teaches that AR inhibition results in GR activation, which promotes prostate cancer cell survival and proliferation in CRPC, and suggests that selective GR antagonists combined with AR antagonists should be explored further for CRPC therapy; and Sullivan teaches that long-term glucocorticoid treatment can result in high levels of cortisol, which can result in Cushing’s disease. One of ordinary skill would have had a reasonable expectation of success because Copending ‘160 discloses exicorilant; De Santis and Serritella disclose enzalutamide (an AR inhibitor) is safe as part of a combination therapy with a GR for treating CRPC; and Sullivan teaches how the test UFC (see pages 6-7) and what the expected cortisol values are for a healthy individual.
Regarding instant claims 2-3, Serritella discloses castration resistant, and metastatic castration resistant prostate cancers (abstract).
Regarding claim 8, Serritella discloses that their treated subjects received combination treatment of enzalutamide and mifepristone, with doses administered once per day (page 1550, line bridging col. 1-2).
Regarding claims 10-11 and 19-20, Serritella discloses that their patients who received enzalutamide monotherapy received 160 mg/ day, while those receiving combination therapy with mifepristone received 40 mg/ day (page 1550, col. 1-2).
Regarding claims 12-14 and 19-20, Serritella discloses their GR inhibitor in combination therapy with enzalutamide was administered at 300 mg/ day (page 1550, col. 1-2).
Regarding the claimed ranges for enzalutamide and exicorilant administration, as recited in claims 10-14 and 19-20, Applicant is advised that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that where 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.
This is a provisional nonstatutory double patenting rejection.
Claim 9 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of copending Application No. 18/670,160 (Copending ‘160); in view of De Santis et al. (Urology, 2016, 96, 156-164) (“De Santis”); and Serritella et al. (Clin. Cancer Res., 2022; 28: 1549–1559 – Pub. Date: April 15th, 2022 – cited in IDS – previously cited) (“Serritella”); in view of Sullivan et al. (Retrieved from medicalnewstoday.com [Retrieved on 11/23/2025]<URL: https://www.medicalnewstoday.com/articles/324573#what-can-affect-the-results> - previously cited) (“Sullivan”); as applied to claims 1-3, 8, 10-14, and 19-20; further in view of Glazier et al. (Retrieved from thecalifornian.com [Retrieved on 11/23/2025] <URL: https://www.thecalifornian.com/story/life/2017/08/24/ask-drs-when-and-how-take-medication-food/598150001/>) (“Glazier”).
The teachings of Copending ‘749, De Santis, Serritella, and Sullivan are disclosed above and incorporated herein.
Serritella discloses nausea in some cases after oral administration of their enzalutamide and mifepristone combination therapy (Phase II, Table 2, page 1554).
While Copending ‘749 in view of De Santis, Serritella, and Sullivan does not specifically teach administration of the GRM with food, the teachings of Glazier are relied upon for these disclosures.
Glazier teaches there are multiple reasons why one might take a medication with food, including that some medications may cause stomach upset, such as nausea, if they are not taken with food. Glazier specifically mentions that corticosteroids should be taken with food (para. 3).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer Copending ‘749’s GRM with food as part of De Santis and Serritella’s AR/GR inhibitor combination therapy in view of Glazier. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Copending ‘749 discloses their GRM compounds; Serritella teaches some of their subjects reported nausea in phase II clinical trials of their combination therapy for CRPC; and Glazier warns that some medications, particularly glucocorticoids, may cause stomach upset and nausea, and that subjects taking these treatments might benefit from doing so with food.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Claims
Claim amendments are acknowledged and have been entered. No new matter has been introduced.
Claim Rejections - 35 USC § 103
Applicant’s arguments, starting on page 4, filed 03/12/2026, with respect to the rejection(s) of the claim(s) under 35 USC § 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of De Santis, Serritella, Hunt, and Sullivan.
Applicant states their methods amount to “improvements in PSA trajectories after treatment with exicorilant and exzalutamide were predominantly observed in patients with baseline UFC levels greater than 17.5 µg/24 h”. Applicant cited para. [0008] of the spec. (shown below for convenience), and states it was unexpected that patients with UFC levels greater than 17.5 µg/24 h suffering from prostate cancer benefited more from the claimed treatment.
PNG
media_image8.png
163
621
media_image8.png
Greyscale
Applicant states no reference cited or combination thereof teaches or suggests this effect with a reasonable expectation of success.
Applicant argues that Serritella and Hunt fail to identify the UFC greater than 17.5 µg/24h, and administering of an effective amount of enzalutamide and exicorilant effective to reduce PSA doubling time, and that the disclosures of Serritella would teach away from combining exicorilant with enzalutamide. Applicant states that Glazier and Sullivan do not cure these deficiencies, as they don’t identify a group of prostate cancer patients with UFC levels > 17.5 µg/24h.
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).
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, De Santis teaches corticosteroids have been used in combination with chemotherapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC) for more than three decades, and that more recently, they have been used in combination with hormonal agents, such as enzalutamide (abstract; and page 156, col. 1, para. 2; and page 161, col. 1). De Santis teaches that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels in retrospective and prospective clinical studies of men with mCRPC.
Serritella teaches androgen receptors (AR) and glucocorticoid receptors (GR) are in the same nuclear hormone receptor family and share target DNA sequence binding homology. Serritella teaches that GR expression significantly increases after AR signal inhibition (ARSI), and that subsequent to ARSI, GR activation promotes prostate cancer cell survival and proliferation. Serritella also teaches that in preclinical models, GR antagonism with mifepristone (a nonselective steroidal AR and GR antagonist) or other more selective GR modulators delay CRPC progression when administered in combination with ARSI. Serritella teaches that GR expression may represent a therapeutic target for progressive castration-resistant prostate cancer (CRPC) (page 1549, col. 2, para. 3). Serritella teaches clinical trials of enzalutamide (an AR inhibitor) and mifepristone (an AR/GR inhibitor) was safe and well tolerated in subjects with CRPC, however, it didn’t meet its primary endpoint. Serritella suggests that selective GR antagonists combined with AR antagonists should be explored further (abstract – conclusions).
Hunt teaches selective glucocorticoid receptor modulators (SGRM) of Formula I below (left), and specifically discloses exicorilant below (right) (Example 2C, col. 42, line 60). Hunt discloses their compounds as suitable for use in the treatment of cancers, including prostate cancer (col 23, lines 47-48). Hunt also teaches their compounds as viable for the treatment of Cushing’s disease (col 23, line 30).
PNG
media_image1.png
317
505
media_image1.png
Greyscale
(Formula I)
PNG
media_image2.png
462
493
media_image2.png
Greyscale
(2C)
Sullivan teaches monitoring of cortisol in urine can help diagnose Cushing’s or Addison’s disease, which result from having too high or too low levels of cortisol, respectively, for prolonged periods of time (page 2). Sullivan discloses high cortisol levels may arise from long term use of glucocorticoids, increasing the risk of Cushing’s disease (page 3). Sullivan teaches normal urinary free cortisol values for healthy adults ranges between 30-145 nmol/ L over 24 hours (cortisol MW is 362.46 g/mol – therefore, this value equates to 10.8 µg/L to 52.6 µg/L over 24 hours).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a combination treatment of corticosteroids (specifically a selective GR antagonist, as taught by Serritella, such as Hunt’s SGRM, exicorilant) and enzalutamide to reduce PSA levels (increase PSA doubling time – see 112(b)) in a subject with mCRPC, and having a UFC greater than 17.5 µg/24 h, as taught by De Santis and Serritella in view of Hunt, further in view of Sullivan. One of ordinary skill would have been motivated to do so because De Santis teaches corticosteroids have been used in combination with enzalutamide for the treatment of mCRPC, and that corticosteroids have been shown to decrease prostate-specific antigen (PSA) levels; Serritella teaches that AR inhibition results in GR activation, which promotes prostate cancer cell survival and proliferation in CRPC, and suggests that selective GR antagonists combined with AR antagonists should be explored further for CRPC therapy; further because Hunt discloses their SGRM, exicorilant, suitable for administration for treating cancers, including prostate cancer, as well as Cushing’s disease (which is associated with elevated cortisol levels – as taught by Sullivan); and Sullivan teaches that long-term glucocorticoid treatment can result in high levels of cortisol, which can result in Cushing’s disease. Thus, by administering Hunt’s SGRM, which modulates cortisol levels and effective in treating Cushing’s disease as well as prostate cancer) – one can treat the mCRPC and benefit symptoms associated with Cushing’s, thus optimizing patient outcome. One of ordinary skill would have had a reasonable expectation of success because De Santis and Serritella disclose enzalutamide (an AR inhibitor) is safe as part of a combination therapy with a GR for treating CRPC; Hunt discloses exicorilant and pharmaceutical compositions thereof, useful for treating prostate cancer and Cushing’s; and Sullivan teaches how the test UFC (see pages 6-7) and what the expected cortisol values are for a healthy individual.
Therefore, the result applicant relies upon are not unexpected in view of the disclosures above.
Double Patenting
Applicant’s arguments, starting on page 4, filed 03/12/2026, with respect to the rejection(s) of the claim(s) under non-statutory double patenting (NSDP) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of the cited patents, in view of De Santis, Serritella, and Sullivan (in all cases except the provisional NSDP rejection over copending Application No. 19/226,690 (Copending ‘690), which has been withdrawn).
The arguments below apply to all NSDP rejections (provisional and not provisional) made in this final action.
Applicant argues US ‘797; US ‘760; US ‘192; US ‘612; US ‘113; US ‘272; US ‘028; US ‘188; US ‘005; US ‘055; US ‘985; US ‘670; US ‘971; US ‘432; Copending ‘271; Copending ‘226; Copending ‘749; and Copending ‘160; lack identification of patients suffering from prostate cancer with UFC 17.5 µg/24 h, and the claimed method of reducing PSA doubling time in patients suffering from prostate cancer. Applicant argues that Serritella, Glazier, and Sullivan do not remedy these deficiencies.
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 there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). Please see rejections made in this final office action and arguments provided in the response to the traversal to the 103 rejections, presented above.
Conclusion
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 nonprovisional extension fee (37 CFR 1.17(a)) 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
Examiner interviews are available via telephone 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, Kortney L. Klinkel can be reached at (571) 270-5239. 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.
/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
Prosecution Insights