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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/27/2025 has been entered.
This Official Action considers the response filed 10/27/2025. The amendments and arguments therein are sufficient to overcome the rejection under 35 U.S.C. 102(a)(1) as being anticipated by Njar et al (US20180147216).
It is noted that applicant has previously asserts that Njar et al do not teach a “direct androgen receptor antagonist”. Applicants specification does not provide a specific definition of a “direct androgen receptor antagonist”, however applicant asserts in paragraph in pargraph 52 of the corresponding publication 20220186227:
“[0052] A number of AR antagonists (sometimes also referred to as antiandrogens) that directly target the AR rather than the ligand androgen are known in the art. These include nonsteroidal androgen receptor antagonists, e.g., diarylthiohydantoin derivatives apalutamide (Erleada, ARN-509), proxalutamide, enzalutamide (Xtandi), and RD-162, as well as the related flutamide, nilutamide, bicalutamide, and topilutamide; AZD3514 (Omlin et al., Invest New Drugs. 2015 June; 33(3):679-90); darolutamide (ODM-201, BAY-1841788) (Shore, Expert Opin Pharmacother. 2017 June; 18(9):945-952); and diarylhydantoins, e.g., 4-(hydroxymethyl)diarylhydantoin (see, e.g., Nique et al., J Med Chem. 2012 Oct. 11; 55(19):8225-35; Nique et al., J Med Chem. 2012 Oct. 11; 55(19):8236-47; EP2444085B1). Steroidal androgen receptor antagonists include 17α-Hydroxyprogesterone derivatives (e.g., cyproterone acetate, megestrol acetate, chlormadinone acetate, osaterone acetate); 19-Norprogesterone derivatives (e.g., nomegestrol acetate); 19-Nortestosterone derivatives (e.g., dienogest, oxendolone); 17α-Spirolactone derivatives (e.g., spironolactone, drospirenone); some progestins (e.g., some listed above as well as medrogestone, promegestone and trimegestone) that have direct androgen receptor antagonistic activity; and N-Terminal domain antiandrogens (e.g., bisphenol A, EPI-001, ralaniten, JN compounds). Others can include EZN-4176, AZD-5312, apatorsen, galeterone, ODM-2014, TRC-253, and BMS-641988."
It is established on this record that galeterone is a “direct AR antagonist” (see paragraph 121 of Njar et al). See also Bastos et al (Drug Design, Development and Therapy Vol.10:2289-2297, 2016), for example, where galeterone is asserted to be an AR antagonist.
Applicant has amended claim 1 to require the tumor be a solid tumor with a KRAS G12, G13, or Q61. It is noted that PDAC is a solid tumor.
Applicant arguments against the prior art are based on the assertion that Njar et al is drawn toward treating cancers in patients resistant to an antagonist of AR and points to paragraph 143 to support this position. This assertion is incorrect and the teachings of Njar et al, while including embodiments of such a patient group, are clearly not limited in such a way. Applicant is directed to all of paragraphs 136-145 which provide for a much broader base of patients than asserted by applicant.
Applicant asserts the prior art does not provide a motivation to treat cancers with KRAS mutations while the prior art applied is directed to treating cancers such as PDAC via AR inhibitors including the same inhibitors recited in the instant claims and where it is also asserted by the prior art that more that 90% of PDACs contain KRAS mutations which would include those specifically recited in the claims.
Applicants assertion of unexpected properties is limited to two inhibitors recited in one dependent claim and where the advantage asserted is unclear since applicant does not provide any evidence or explanation of why the results are unexpected or advantageous.
A revised rejection under 35 U.S.C. 103 as being unpatentable over Njar et al (US20180147216) in view of Erlander et al (US20150139946) and Lennerz et al (The Oncologist Vol.20:e8-e9, 2015).
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.
Claim(s)s 1-4, 13-16, and 30-36 is/are rejected under 35 U.S.C. 103 as being unpatentable over Njar et al (US20180147216) in view of Erlander et al (US20150139946) and Lennerz et al (The Oncologist Vol.20:e8-e9, 2015).
Njar et al have disclosed treating a subject with androgen receptor inhibitors (ARDAs), which include “direct androgen receptor antagonists”, where the subject has a KRAS driven cancer and the inhibitors include inhibitors such as galeterone (steroidal) (see paragraphs 121-122, for example), flutamide (non-steroidal and recited in the instant claim 30), bicalutamide (non-steroidal and recited in the instant claim 30), nilutamide (non-steroidal and recited in the instant claim 30), ARN-509 ( (apalutamide=ARN-509) non-steroidal and recited in the instant claim 30), enzalutamide (non-steroidal and recited in the instant claim 30) (see paragraph 94, for example). It has been taught that 90% of PDAC contain a KRAS mutations and that KRAS mutations are the KEY driver of pancreatic cancer (see paragraph 96). It has also been taught (at paragraphs 126-131to determine the type of cancer a subject is suffering from as well as other indicators and markers. While the entire reference is relevant and relied on, applicant is directed to paragraphs 5, 6, 17, 19, 44, 70, 82, 87, 88, 90, 94-96, 101-103, 121, 122, 127, 170 and 198, for example. Njar et al have therefore taught to monitor disease/cancer markers of at least PDAC, to treat PDAC via androgen receptor antagonists, that KRAS mutations are indicated in over 90% of PDACs and that KRAS mutations are key drivers in pancreatic cancer. The actual KRAS mutation is not relevant to the teachings of Njar as far as obviousness is concerned since the assertions and teachings of Njar et al would direct one in the art to treat all PDAC including any particular KRAS mutation. The instant specification provides no teachings that the specified mutations play any particular role to determine a more effective treatment with any particular AR inhibitor, for example.
Njar et al do not specifically teach the inhibitors recited in claim 31 or the determination of the specific KRAS mutations recited.
Njar et al teachings above show reasons and motivation to target AR in the treatment of KRAS related cancer. One in the art would select various AR inhibitors in such treatments since AR inhibitors were well known in the art and since one in the art may choose various combinations of AR inhibitors and further select various AR inhibitors in situations such as patients becoming insensitive to inhibitors previously utilized, for example. See paragraph 52 of applicant pregrant publication cited above, for example.
Erlander et al have taught to determine and monitor gene mutations associated with a cancer, including pancreatic cancer, over time including KRAS G12 and G13 mutations. It has been taught that such monitoring is beneficial in determining treatment options and monitoring cancer progression.
Lennerz et al have taught that over 90% of PDACs contain KRAS mutations and assert that tumor specific allelic ratios of somatically mutated genes should be an integral component of a comprehensive molecular diagnostic report for personalized cancer care.
It would have been obvious to utilize the methods of Erlander and the teachings of Lennerz et al to monitor KRAS mutations in at least pancreatic cancers to monitor cancer progression and determine treatment options in the methods of treatment taught by Njar et al since Njar et al have taught the association of KRAS mutations as key drivers in pancreatic cancers to be treated via androgen inhibitors.
The invention as a whole would therefore have been prima facie obvious to one in the art at the time the application was effectively filed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN MCGARRY whose telephone number is (571)272-0761. The examiner can normally be reached M-Th/F 9:00-7:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ram Shukla can be reached at 571 272 1600. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SEAN MCGARRY/Primary Examiner, Art Unit 1635
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