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 .
Priority
The present application claims the benefit of U.S. Provisional Application No. 63/072,414, filed on August 31, 2020.
Requirement for Election/Restriction -Status of the Claims
In response to the restriction requirement, the applicant hereby elects, without traverse, the Group I invention (claims 1-33) for prosecution. In addition, the applicant hereby elects, without traverse, the species of administration of antiprogestin frequency ranging from once daily to once monthly, where the antiprogestin is administered in an amount ranging from about 0.5 mg to about 1000 mg, and wherein the subject has not been diagnosed with high-grade serous ovarian cancer, or breast cancer. Claims 1-33 are generic. Claims 19 and 20 have been amended. No new matter has been introduced.
The election of the group is:
Group I Claims 1-33 are drawn to a method to prevent a high-grade serous ovarian cancer by administering a therapeutically effective amount of antiprogestin;
Group II Claims 34-66 are drawn to a method of preventing breast cancer by administering a therapeutically effective amount of antiprogestin.
The election of the species is:
the dosing regimen - Applicants are required to elect a single dosing regimen. A complete reply will define the dosage amount, the pharmaceutical form and route of administration, and the duration and interval of administration
Amount ranging from about 0.5 mg to about 1000 mg once daily to once monthly.
the patient population having the “high grade serous ovarian cancer” - Applicants are required to elect a single stage and rating of the “high grade serous ovarian cancer” patient. For example, certain claims are using language that appears to be characterizing the grade and stage of cancer, such as, claims 2 and 3 that are directed to the number of occurrences being prevented. Claim 7 has the requirement that the patients all meet the condition of having the cancer be undetectable by ultrasound and a CA-125 blood test when the antiprogestin administration begins. Claim 10 has a biomarker for the patient undergoing the preventative treatment. Other claims have further requirements.
Subject has not been diagnosed with high-grade serous ovarian cancer.
the patient population having breast cancer – Applicants are required to elect a stage and rating of the breast cancer in the patient. For example, certain claims are using language that appears patients having been not diagnosed with breast cancer (Claim 39), asmetastasized or non-metastasized as in Claim 37, diagnosed or undetectable by biopsy as in Claims 34, 39 and 40. Other claims have further requirements.
Subject has not been diagnosed with high-grade breast cancer.
Therefore, for the reasons above and those made of record of the Office Action dated September 5, 2025 the requirement remains proper and is hereby made FINAL.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 2/24/2023 (11 references) and 12/12/2024 (4 reference). The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of the Claims
Claims: 34-66 are canceled.
Claims 1-33 are pending and are the subject of the Office Action below.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-12, 20-24, 25-29 and 33 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Goyeneche, et. al., Antiprogestins in gynecological diseases, Reproduction, (2015), 149, R15–R33.
By way of background, antiprogestins constitute a group of compounds, developed since the early 1980s, that bind progesterone receptors with different affinities. The first clinical uses for antiprogestins were in reproductive medicine, e.g., menstrual regulation, emergency contraception and termination of early pregnancies. The initial uses belied the capacity for these compounds to interfere with cell growth. Ovarian cancer is the second most common gynecologic cancer among women and the second leading cause of death from gynecologic malignancy worldwide.
Goyeneche teaches:
“Within the context of gynecological diseases, antiprogestins can block the growth of and kill gynecological-related cancer cells, such as those originating in the breast, ovary, endometrium, and cervix. They can also interrupt the excessive growth of cells giving rise to benign gynecological diseases such as endometriosis and leiomyomata (uterine fibroids).”
Goyeneche, Abstract, page R15 (emphasis added).
Claim 1 is drawn to a method to prevent an occurrence of a high-grade serous ovarian cancer in a subject, the method comprising the step of administering a therapeutically effective amount of an antiprogestin to the subject.
The method is anticipated by Goyeneche of using an antiprogestin to block the growth of and kill gynecological-related cancer cells, such as those originating in the breast, ovary anticipates the method of the instant claim of administering an antiprogestin in order to prevent an occurrence of a high-grade serous ovarian cancer.
Claims 2 and 3 are drawn to methods according to claim 1, where the occurrence being prevented is the first (as in claim 2) and second (as in claim 3).
The method is anticipated by Goyeneche of using an antiprogestin within the context of gynecological diseases, antiprogestins that can kill gynecological-related cancer cells, such as those originating in the breast, ovary, endometrium, and cervix anticipates the method of the instant claims because the teaching of Goyeneche anticipates the effectiveness of antiprogestin to kill cancer cells.
Claim 4 is drawn to the method according to claim 1 where the high-grade serous ovarian cancer is selected from the group consisting of non-metastasized high-grade serous ovarian cancer and metastasized high-grade serous ovarian cancer.
As described in the rejection above, the method taught by Goyeneche of using an antiprogestin within the context of gynecological diseases, antiprogestins that can kill gynecological-related cancer cells, such as those originating in the breast, ovary, endometrium, and cervix anticipates the method of the instant claim because the teaching of Goyeneche anticipates the effectiveness of antiprogestin to kill cancer cells; that would include non-metastasized or metastasized high-grade serous ovarian cancer.
By way of definition, the National Ovarian Cancer Coalition website https://ovarian.org/about-ovarian-cancer/ovarian-cancer-diagnosis/) describes a variety of tests used to diagnose ovarian cancer, included in the following figure:
PNG
media_image1.png
509
762
media_image1.png
Greyscale
Claim 5 -8 further limit claim 1 where the subject has not been diagnosed with
high-grade serous ovarian cancer (as in claim 5), where the high-grade serous ovarian cancer is
undetectable by biopsy in the subject when the antiprogestin administration begins (as in claim 6), where the high-grade serous ovarian cancer is undetectable by transvaginal ultrasound and a CA-125 blood test in the subject when the antiprogestin administration begins (as in claim 7) and where the antiprogestin is administered to the subject to minimize the probability that the subject develops high grade serous ovarian cancer (as in claim 8).
As described in the rejection to claim 1 above where Goyeneche anticipates the method of using antiprogestin to block the growth of gynecological-related cancer cells including ovarian cancer; a patient not diagnosed with ovarian cancer would benefit from such treatment. The instant claims are only describing an undetected ovarian “cancer” utilizing the tests normally used to diagnose ovarian cancer and administering antiprogestin to block the growth of cancer cells as anticipated by Goyeneche.
Claim 9 further limits claim 1where administering the antiprogestin extends
overall survival time of the subject.
Goyeneche describes in the Introduction, that antiprogestins represent a family of compounds developed with the purpose of antagonizing the effect of progesterone on progesterone receptors (PR). Further, when describing the heterogeneous nature of ovarian cancer from not only a histological standpoint, but also genetically they discuss the survivability of patients. For example,
“For instance, the value of patient stratification by disease subtype has been recently evidenced in a study by the Ovarian Tumor Tissue Analysis (OTTA) consortium including almost 3000 women worldwide with invasive epithelial ovarian cancer (Sieh et al. 2013). The study provided a significant positive association between expression of PR and survival advantage in patients with high-grade serous and endometrial ovarian cancers, but not in patients with mucinous, clear cell, or low grade serous ovarian carcinomas.”
Goyeneche, column 2, paragraph 1, R18 (emphasis added).
Goyeneche anticipates the method administering antiprogestin with an antagonizing the effect of progesterone, on progesterone receptors (PR) that is a characteristic of high-grade serous ovarian cancer and a survival advantage of the instant claim.
Claim 10 further limits claim 1 where an absence of high-grade serous ovarian
cancer is monitored by measuring one or more biomarkers.
The figure shown by the National Ovarian Cancer Coalition website illustrated above details the use of a blood test of the CA-125 protein which is a marker for ovarian cancer found in the blood. Elevated levels of this marker are found in elevated levels in individuals with ovarian cancer.
Claim 11 further limits claim 1 where the subject is a human female.
Goyeneche anticipates the method administering antiprogestin for gynecological-related cancer cells, such as those originating in the breast, ovary, endometrium, and cervix. Treating ovarian cancer is a condition that is only found in females.
Claim 12 further limits claim 1 where the subject is a human female and the female is a pre-menopausal female or a post-menopausal female.
Goyeneche anticipates the method administering antiprogestin for gynecological-related cancer cells, such as those originating in the breast, ovary, endometrium, and cervix. All human females that have had a menstrual cycle fall into the category of pre-menopausal or post-menopausal.
Claims 20-24 further limit claim 1 where the antiprogestin is a small molecule inhibitor for a progesterone receptor (as in claim 20), where the antiprogestin is a selective progesterone receptor modulator (as in claim 21), where the selective progesterone receptor modulator is a Type II selective progesterone receptor modulator (as in claim 22), where the antiprogestin is (8S, l lR, 13S, 14S, l 7S)-l l-[ 4-(dimethylamino)phenyl]-17-hydroxy-13-methyl-17-prop-l-ynyl-1,2,6,7,8, 11, 12, 14, 15, 16-decahydrocyclopenta[a]phenanthren-3-one (as in claim 23) or where the antiprogestin is [(8S, l lR, 13S, 14S, 17R)-17-acetyl-l l-[4-(dimethylamino)phenyl]-13-methyl-3-oxol, 2,6,7,8, 11, 12, 14, 15, 16-decahydrocyclopenta[a]phenanthren-17-yl] acetate (as in claim 24).
According to page 9 of the applicant’s specification, the antiprogestin compound in claim 23 is commonly referred to as mifepristone and the antiprogestin compound in claim 24 is commonly referred to as ulipristal acetate.
“We observed that when used at concentrations likely achievable in the clinic (i.e., pharmacological), mifepristone, ulipristal, and ORG-31710 all had cytostatic effects, with cells returning to the cell cycle upon drug removal; however, if used at suprapharmacological doses, the antiprogestins, instead, killed the cells (Goyeneche et al. 2007, 2012).”
Goyeneche, column 1, paragraph 1, R18 (emphasis added).
Therefore, Goyeneche anticipates the use of both of the compounds referred to as mifepristone and ulipristal of the instant claims to treat ovarian cancer. Both molecules are small molecules and act as type II selective progesterone inhibitors.
Claims 25-29 further limit claim 1 where the antiprogestin is administered to the
subject in a frequency ranging from once daily to once monthly (as in claim 25), where the antiprogestin is administered in an amount ranging from about 0.5 mg to about 1000 mg (as in claim 26), where the antiprogestin is administered as a low-dose (as in claim 27), where the antiprogestin is administered as a high-dose (as in claim 28) and where the antiprogestin is administered to the subject short-term (as in claim 29).
According to page 16 of the applicant’s specification, Low dose refers to embodiments when the weight of the antiprogestin in unit dosage form is less than or equal to 5 mg, such as 4 mg, 3 mg, 2 mg, and 1 mg; high dose refers to embodiments when the weight of the antiprogestin in unit dosage form is greater than 10 mg, such as 25 mg, 50 mg, 75 mg, 100 mg, 200 mg, and 300 mg; the treatment period is short-term such as less than or equal to 3 years.
Goyeneche details the dosage concentration of the antoprogestin, mifepristone used to treat ovarian cancer. For example:
“Using various ovarian cancer cell lines of different genetic backgrounds, our laboratory additionally found that mifepristone blocked cell growth in vitro and demonstrated its efficacy in vivo at doses of 0.5 or 1 mg/day in mice carrying ovarian cancer xenografts (Goyeneche et al. 2007).”
Goyeneche, column 1, paragraph 1, R18 (emphasis added). And,
“In 2000, in a phase II clinical trial, 34 patients with recurrent ovarian cancer no longer responsive to cisplatin–paclitaxel chemotherapy were treated daily with 200 mg oral mifepristone in courses of 28 days.”
Goyeneche, column 1, paragraph 1, R18 (emphasis added).
Goyeneche anticipates the method of the instant claims using a low dose of <5.0 mg (0.5 or 1.0 mg/day) and the high dose of >10 mg/day (200 mg/day) and the short term less than or equal to 3 years (28 days) of the instant claims.
Claim 33 further limits claim 1 where the administered progestin obviates a
need for a subsequent targeted therapy, chemotherapy and/or hormone therapy.
Goyeneche details a phase II clinical trial with the use of antiprogestin in patients that are no longer responsive to chemotherapy.
“In 2000, in a phase II clinical trial, 34 patients with recurrent ovarian cancer no longer responsive to cisplatin–paclitaxel
chemotherapy were treated daily with 200 mg oral
mifepristone in courses of 28 days. Nine patients had a
response to mifepristone showing a decrease in tumor
size by at least 50%, or a 50% decline in antigen CA-125
used to assess disease recurrence (Rocereto et al. 2000).”
Goyeneche, column 1, paragraph 2, R18 (emphasis added)
Goyeneche anticipates the method of the instant claim by administering mifepristone to patients that have become unresponsive to chemotherapy. The use of mifepristone to patients with ovarian cancer for which chemotherapy is no longer effective and yet observes a 50% decrease in tumor size or a 50% decline in the blood marker CA-125.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claims 13-18 are rejected under 35 U.S.C. 103 as being unpatentable over Goyeneche, et. al., Antiprogestins in gynecological diseases, Reproduction, (2015), 149, R15–R33 in view of Hartmann, et.al., The Role of Risk-Reducing Surgery in Hereditary Breast and Ovarian Cancer, N Engl J Med 2016; 374, pages 454-68 and in further view of Clarke, et.al., Monoclonal Antibodies to Human Progesterone Receptor: Characterization by Biochemical and Immunohistochemical Techniques, Endocrinology, 1987, Vol. 121, No. 3, pages 1123-1132.
Claims 13-18 further limit claim 1 and are drawn to ovarian cancer as a condition that has risk factors associated to a genetically inherited component that contributes to the likelihood that an individual may develop the disease. Specifically, the genes of BRCA 1 and BRCA 2 are purported to be contributing factors to the inherited nature of the disease including the presence or absence of the genes and the whether a first-degree family member (i.e. mother, sister or daughter) has been diagnosed with the disease or is not diagnosed with breast cancer.
Applicants purports in the instant claims, the subject is a human female and the human female subject has a first-degree relative diagnosed with ovarian cancer, a mother diagnosed with ovarian cancer, a sister diagnosed with ovarian cancer, or a daughter diagnosed with ovarian cancer (as in claim 13), the subject has a genetic status that is ovarian cancer-predictive (as in claim 14), the subject has a risk status that is ovarian cancer-predictive (as in claim 15), the subject is positive for a BRCAl or 2 mutation (as in claim 16), the subject does not have a BRCAl or 2 mutation (as in claim 17) and the subject does not have breast cancer (as in claim 18).
As described in the rejection to claims 1-12, 20-24, 25-29 and 33 above, Goyeneche describes the use of antiprogestins to effectively prevent or treat an occurrence of a high-grade serous ovarian cancer ovarian cancer. Goyeneche does not describe the relationship of the disease as it relates to the familial inheritance pattern or the genetic contribution of the genes of BRCA 1 and BRCA 2 of the instant claims.
Hartmann teach that the genes BRCA 1 and BRCA 2 and the familial connection to the disease to first-degree relatives. For example,
“Hereditary breast and ovarian cancer is a syndrome that involves an increased predisposition to breast cancer, ovarian cancer, or both and an autosomal dominant pattern of transmission. The numbers of breast-cancer diagnoses, the ages of patients at diagnosis, and the occurrence of ovarian cancer in addition to breast cancer vary among families with hereditary breast and ovarian cancer syndrome. The likelihood of detecting an underlying disease-causing mutation is highest in the most severely affected families, especially those with ovarian cancer. Disease-causing mutations in BRCA1 and BRCA2, the genes most often associated with hereditary breast and ovarian cancer syndrome, are identified in only a minority of families with suspected hereditary breast and ovarian cancer syndrome.”
Hartmann, page 454, paragraph 1 (emphasis added),
And
“In contrast, breast cancers in BRCA2 carriers mirror those seen in the general population (77% are ER-positive and only 16% are triple-negative breast cancers).4 Ovarian cancer typically occurs earlier and with greater frequency among BRCA1 carriers than among BRCA2 carriers (Fig. 1), and serous ovarian cancers predominate in both types of carriers.4”
Hartmann, page 454, paragraph 1 (emphasis added)
“The likelihood that breast or ovarian cancer will develop in a mutation carrier is influenced by multiple factors. Even among families with mutations in the same gene, there is considerable variability in the risk of cancer.5 The observed risk of breast or ovarian cancer is higher among carriers with a positive family history than among those with no family history, presumably because of an underlying polygenic predisposition, multifactorial predisposition, or both. Defining genetic and nongenetic modifiers of risk is the subject of ongoing research.6,7”
Hartmann, page 455, paragraph 2 (emphasis added).
Goyeneche discloses that the use of antiprogestins are effective to prevent or treat an occurrence of a high-grade serous ovarian cancer ovarian cancer. Hartmann teaches the risk factors associated with both ovarian and breast cancer are influenced by disease-causing mutations in BRCA1 and BRCA2; the genes most often associated with hereditary breast and ovarian cancer syndrome. He details that Even though mutations of the genes play some role in the development of the disease; among families with mutations in the same gene, there is considerable variability in the risk of cancer. Specifically, that breast cancers in BRCA2 carriers mirror those seen in the general population indicating that the mutation in BRCA2 gene does not indicate any greater risk of breast cancer than would be found in the general population without the mutation. Further, that risk of breast or ovarian cancer is higher among carriers with a positive family history than among those with no family history.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Goyeneche for preventing or treating serous ovarian cancer with the conditions and limitations of the disease as detailed by Hartmann to obtain the invention of the instant claims.
Claims 30-32 further limit the method of claim 1 where the antiprogestin is administeredto the subject long-term (as in claim 30), where the antiprogestin is administered to the subject for a duration ranging from about 6 months to about 10 years (as in claim 31) and where the antiprogestin is administered to the subject for a duration ranging from about 6 months to about 20 years (as in claim 32).
Goyeneche discloses that the use of antiprogestins are effective to prevent or treat an occurrence of a high-grade serous ovarian cancer ovarian cancer in the low dose of dose of 0.5 or 1 mg/day and the high dose of 200 mg/day and the short term duration of less than 3 years as described in rejection to claims 25-29 above. Goyeneche does not detail a long-term dosage regimen lasting greater than 6 months as defined on page 16 of the applicant’s specification in the instant claims.
It would have been prima facie obvious to one of ordinary skill in the art to utilize the amount of an antiprogestin and the treatment regimen taught by Goyeneche as a starting point for optimizing the amount and treatment regimen of antiprogestin utilized to ovarian cancer since Goyenenche teaches antiprogestin is useful for treating both ovarian and breast cancer and because dosage and treatment regimen are result-effective variables, i.e. a variable that achieves a recognized result. Therefore, the determination of the optimum or workable dosages would have been well within the practice of routine experimentation by the skilled artisan. Furthermore, absent any evidence demonstrating a patentable difference between the compositions and the criticality of the claimed dosage range, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II)(A) and In re Aller, 220 F. 2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). ("[W]here the general conditions of claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Accordingly, the instant claims are rejected.
Claim 19 further limits claim 1 here the antiprogestin is an antibody to a progesterone receptor or to progesterone.
As described in the rejection to claims 1-12, 20-24, 25-29 and 33 above, Goyeneche describes the use of antiprogestins to effectively prevent or treat an occurrence of a high-grade serous ovarian cancer ovarian cancer and Hartmann teaches the risk factors associated with both ovarian and breast cancer are influenced by disease-causing mutations in BRCA1 and BRCA2 and hereditary risks. They don’t teach an antibody to a progesterone receptor or to progesterone.
Clarke teaches,
“The preparation of polyclonal antisera and, more recently, monoclonal antibodies against the avian and mammalian progesterone receptors (PR) has been documented (2-10). Antibodies directed against human PR have been described only recently (11), possibly due to the lack of a reproducible source of the human receptor.”
Clarke, page 1123, paragraph 1 (emphasis added).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Goyeneche for preventing or treating serous ovarian cancer with the conditions and limitations of the disease as detailed by Hartmann and the use of an antibody for progesterone receptors (PR) as taught by Clarke.
Accordingly, the instant claim is rejected.
Conclusion
Claims 1-33 are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL RANDALL GAUGER whose telephone number is (571)272-1325. The examiner can normally be reached M-F 7:30-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffery Lundgren can be reached at (571)272-5541. 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.
/P.R.G./
Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629