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 .
Applicant’s preliminary amendments filed 9/25/2024 have been entered.
Claims 1, 4, 9, 10, 13, 54, and 55 are pending.
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 1, 4, , 9, 10, 13, 54, and 55 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO2013/184621 (‘621) in view of US2010/0197753 (‘753) and Sarker et al., Clin Cancer Res, 2009;15(15):4799-4805. The references are of record in the parent application 16/659,943.
‘621 teaches a combination which comprises (a) a phosphatidylinositol 3-kinase inhibitor selected from the group consisting of a compound of formula (I) or a compound of formula (II), or pharmaceutically acceptable salt thereof, (b) a 17a-Hydroxylase/ Ci7,2O-lyase inhibitor (CYP17 inhibitor) or pharmaceutically acceptable salt thereof, for simultaneous, separate or sequential use for the treatment of a tumor disease (see page 1, Field of the invention Section). ‘621 also teaches the activation of PI3K, and its downstream effectors, has been clearly validated as an essential step for the initiation and maintenance of the tumorigenic phenotype. Prostate cancers are associated with frequent genetic alterations of the PI3K and/or androgen receptor pathways. Aberrant PI3K signaling is common in prostate cancer with approximately 40% of primary and 70% of metastatic tumors carrying genomic alterations of the PI3K signaling pathway, mostly through loss of PTEN. (Sarker et al, Clinical Cancer Research, August 1, 2009, 15:4799- 4805). In preclinical studies, PTEN loss promotes resistance to castration, and PI3K pathway activation in prostate cancer is associated with adverse pathologic and clinical features, and resistance to radiation and chemotherapy. (see page 1, second paragraph). ‘621 teaches one of the CYP17 inhibitor is 1-(2-Chloro-pyridin-4-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one (aka CFG920) (see page 2, last paragraph and page 3, 4th paragraph). ‘621 teaches such combination as useful in treating prostate cancer (see for example, page 4, third paragraph; page 27, second and third paragraphs). Various pharmaceutical acceptable carriers can be used to formulate composition containing the actives (see page 21, last three paragraphs; also page 22, 4th paragraph).
‘621 does not expressly teach the compound (II) or its hydrochloride salt in combination with CFG920.
‘753 teaches the compound of formula II and its HCl salt, as AKT inhibitor, as useful in treating prostate cancer (see [0002], claims 17 and 26).
Sarker et al. teaches the activation of PI3 and the downstream AKT would mediate the phosphorylation and activation of mTOR complex 1 (mTORC1), a serine/threonine kinase that plays critical roles in the regulation of protein translation and synthesis, angiogenesis, and cell cycle progression (see page 4799, Col. 2). Sarker et al. teaches Simultaneous targeting of AKT-1 and AKT-2 was shown to be superior to the inhibition of a single isozyme for induction of caspase-3 activity in tumor cells, suggesting that pan-AKT inhibitors such as the ATP-competitive inhibitor GSK690693 (GlaxoSmithKline) are therefore likely to be more promising, although toxicity may be a potential issue. Several other small-molecule AKT inhibitors are now in early clinical trials, including a potent highly selective pan-AKT allosteric inhibitor MK2206 (Merck,Inc) that is currently in Phase I trials, both as a single agent and also in combination with other agents including docetaxel (see page 4803, col. 2, first paragraph).
It would have been obvious to one of ordinary skill in the art to incorporate CFG920 and the compound of formula (II) or its HCl salt into a single composition and method of treating prostate cancer.
One of ordinary skill in the art would have been motivated to incorporate CFG920 and the compound of formula (II) or its HCl salt into a single composition and method of treating prostate cancer. Since it is known that the PI3/AKT/mTor pathway is involved in prostate cancer proliferation, cell growth, and developments, employing AKT inhibitors would be reasonably expected to be useful in treating prostate cancer. It is also known that CFG920 combines with PI3 inhibitors (one of the PI3/AKT/mTor pathway inhibitors) as effective in treating prostate cancer. Therefore, it flows logically to combine both CFG920 and any known PI3/AKT/mTor pathway inhibitors such as the herein claimed compound of formula (II) in a single composition and/or method useful for treating the very same disorder (prostate cancer) (see In re Kerkhoven 205 USPQ 1069 (CCPA 1980)). Employing the two agents either in sequential or together at the same time would be seen as obvious for being within the purview of skilled artisan.
As for the PTEN-deficient prostate cancer, the examiner notes that it is known that aberrant PI3K signaling is common in prostate cancer with approximately 40% of primary and 70% of metastatic tumors carrying genomic alterations of the PI3K signaling pathway, mostly through loss of PTEN. (Sarker et al, Clinical Cancer Research, August 1, 2009, 15:4799- 4805). Accordingly, it is clear that PTEN loss or deficiency plays a significant role in prostate cancer development. Therefore, employing the herein claimed combination to treat PTEN-deficient prostate cancer would be reasonably expected to be effective.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAN MING R HUI whose telephone number is (571)272-0626. The examiner can normally be reached Mon - Fri 9:30-5:30.
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/SAN MING R HUI/Primary Examiner, Art Unit 1627
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