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 .
Election/Restrictions
Applicant’s election without traverse of Group I (drawn to a compound/pharmaceutical
composition), in the reply filed on 04/03/2026 is acknowledged.
Claims 58-78 are pending of which claims 71 and 76-77 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected INVENTION, there being no allowable generic or linking claim. The restriction requirement is still deemed proper and is made Final.
Pending claims 58-70 and 72-75 have been examined on the merits.
Please note, for clarity of the record, Applicant’s election of the following:
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During the course of examination, prior art was identified that relates to the elected or non-elected subject matter.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 61, 65-66 and 74 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 74 recites “the cancer has normal or high levels of one or more genes or gene products,” including BRCA1 and/or BRCA2. Although, the specification mentions “normal or high levels” of DDR biomarkers, however, the specification fails to provide representative species, working examples demonstrating possession of a defined subpopulation characterized by elevated or intact DDR activity. The specification fails to describe how “normal” versus “high” DDR gene expression is quantitatively determined, nor does it prove guidance for how patients within these categories are triaged or selected for treatment with an MDM2 antagonist alone or in combination. In particular, the specification does not define, quantify, or otherwise describe what constitutes “normal or high” expression levels for any DDR gene, including BRCA1/1, nor does it provide reference standards, control comparisons, ranges, or representative assays that would allow a person of ordinary skill in the art (POSITA) to identify such patients. Therefore, absence of such guidance, a POSITA cannot reasonably conclude that the Applicant was in possession to claimed invention at the time of filing. The specification’s failures to disclose any specific polymer meeting the claimed limitations further supports the conclusion that the specification lacks adequate written description of the claimed subject matter.
Claim 61 recites “the one or more genes or gene products comprise MSH2, MSH3, MSH6” and “the one or more genes or gene products comprise FANCA, FANCB, FANCC, FANCD1, FANCD2, etc.,” Claim 65 recites “increased expression, relative to a control, of one, two, three, four, five or more of the interferon signature genes, optionally wherein the interferon signature genes are CXCLl0, CXCLl 1, etc.” Claim 66 recites “increased expression of one, two, three, four, five or more of IRF7, STATI, IRF3, etc. Although the specification includes these genes in broad list of potential biomarkers associated with MDM2- antagonist, however, the specification does not provide specific experimental data, examples or a defined expression “signature” demonstrating that each gene or numerous combinations thereof, actually correlates with sensitivity, resistance or any other clinically relevant outcomes in the context of the claimed subject matter of MDM2 antagonist treatment. Thus, merely listing genes names without describing the specific expression patterns and functional relationship, is insufficient to show that Applicant has possession of the claimed subjection at the time of filing.
The specification’s failures to disclose any specific regarding the claimed limitations further supports the conclusion that the specification lacks adequate written description of the claimed subject matter.
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 62-65, 67-70, 74, 75 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 67 and 70, recite wherein the MDM2 antagonist is selected from a group of compounds identified by names or internal designations (e.g., SJ-0211, ADO-21, CTX-50-CTX-1, PM-2) without providing chemical structure or sufficient identifying information in the specification. For instance, the specification (page 45) discloses “SJ-0211 is an antagonist of MDM2 is being developed by University of Tennessee, University of Kentucky and St Jude Children’s Research Hospital for treatment of Retinotherapy. The structure is a Nutlin-3 analogue.” However, the Examiner cannot determine the chemical structure of SJ-0211 or CTX-50-CTX-l, as an example. It is not clear what compound is being referred to by the Applicant. Therefore, the claim recites MDM2 antagonist that is indefinite, because the specification does not clearly point out the chemical structure of the MDM2 antagonists. In addition, the claim recites multiple conjunctions ("and" and "or") that renders the claim indefinite, because it can lead to various interpretations. For instance, the recitation of “K-178, MMRi-64 and
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, or a tautomer or a solvate or a pharmaceutically acceptable salt thereof” can be interpretated that the MDM2 antagonist is (a) K-178, the combination of (MMRi-64 and
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), or a tautomer or a solvate or a pharmaceutically acceptable salt thereof; or (b) the combination of (K-178, MMRi-64 and
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), or a tautomer or a solvate or a pharmaceutically acceptable salt thereof. The lack of clarity renders the claim indefinite as one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Regarding claim 75, the phrase “e.g.,” in the recitation of “e.g. ASTX660 or a tautomer or a solvate or a pharmaceutically acceptable salt thereof” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Lack antecedent basis
Claim 65 recites the limitation “the interferon signature genes” in the fifth line of the claim. It is unclear which the interferon signature genes is referred to by “the interferon signature genes.” There is insufficient antecedent basis for this limitation in the claim.
Claim 68 recites the limitation “the biomarker profile” in the thirteenth line of the claim. It is unclear which the biomarker profile is referred to by “the biomarker profile.” There is insufficient antecedent basis for this limitation in the claim.
Claim 69 recites the limitation “the biomarker profile” in the second line of the claim. It is unclear which the biomarker profile is referred to by “the biomarker profile.” There is insufficient antecedent basis for this limitation in the claim.
Indefinite
Claim 63 recites “the determined expression profile” and “the cancer expression profile”, which are not clearly defined in the instant claim. The claim does not specify which genes, gene products, or biomarkers are included in the expression profile, nor does it provide threshold for the claim profile. While the claim recites “DNA, ctDNA” these techniques, merely describe methods of detection and do not clarify the scope or content of the “expression profile” being determined, which renders the claims indefinite.
Claim 64 recites “at least a proportion of the cancer cells.” The phrase “proportion” is vague and does not provide a clear a reference and causes ambiguity, which renders the claims indefinite.
Claim 74 recites “normal or high levels” of one or more genes or gene products. However, the claim fails to define what constitutes “normal” or “high” levels, including a reference to subpopulation, or control for comparison, which renders the claims indefinite.
Furthermore, the claim also recites “no detectable loss of function mutation in any DDR pathway gene” which is dependent on the sensitivity and type of detection method employed, which is not specified. Furthermore, the term of “any” is very broad and does not identify which genes must be evaluated, which renders the claims indefinite.
In addition, claim 63 also recites “an agent to induce sensitivity to an MDM2 antagonist” the claim does not provide criteria for determining whether a given agent “induces sensitivity”, nor does it specify the degree of sensitivity required, thus the scope remains unclear.
Claims 68 recites “determining whether the tested expression or activity level indicates that the cancer should be treated” and classifies patients as “responder,” “non=responders,” or “strong responders.” However, the claims and specification do not provide standardized metrics for determining degree of responsiveness or treatment suitability. It is unclear what level of expression or activity corresponds to each classification, which renders the claims indefinite.
For Example
Claim 67 and 70 recite at line 3, “for example (2S,3S)-3-(4-chlorophenyl)-3-[(1 R)-1-(4-chlorophenyl )-7-fl uoro-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-lH-isoindol-2-yl]-2-methylpropanoic acid, therefore it is unclear if the parenthetical is a required limitation of the claim or not. It is suggested to remove the phrase “for example.” Furthermore, the phrase “for example” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Appropriate correction is required.
Claim 74 recites at line 7, “for example to lower the levels of” and at line 16 bridged line 17 “for example by lowering the levels of” thus, the phrase “for example” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Appropriate correction is required.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office
action.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 58-65, 67-70 and 72-73 is rejected under 35 U.S.C. 103 as being unpatentable over Chessari et al. WO2017/055860 (cited in the IDS filed on 04/29/2024), Li et al., Front Pharmacol. 2020 May 7;11:631, Brown et al., Cancer Discov. 2017 Jan;7(1):20-37, Liptay et al., Front Oncol. 2020 May 5;10:670; Zhang et al., Biomark Res. 2020 Jun 29;8:23.
Regarding claims 58, 67 and 70, Chessari (page 104-105; page 108; page 1-2) teaches a method for treating cancer, e.g., breast cancer, by administering a therapeutic amount of at least one compound of formula (I) to a patient. Chassari (page 83, 119-120, 259) discloses a compound of Example 124, (2S,3S)-3-(4-chlorophenyl)-3-[(1 R)-1-(4-chlorophenyl )-7-fl uoro-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-lH-isoindol-2-yl]-2-methylpropanoic acid, useful for disrupting MDM2-p53 interaction. Chessari (page 1 and 2) teaches that binding of MDM2 to p53 inhibits transcriptional activity and promotes its ubiquination, thereby functionally inactivating p53, which is a frequent causal event in the development and progression of cancer. Chessari (page 1) also teaches activation of p53 plays an important role in DNA damage response (DDR) pathway and in the regulation of programmed cell death. Therefore, according to Chessari (page 2) “The therapeutic rationale for MDM2-p53 inhibition is that a potent inhibitor of the protein-protein interaction will liberate p53 from the repressive control of MDM2, and activate p53 mediated cell death in the tumor.”
Chessari does not explicitly disclose selecting cancers that deficient in DNA damage or harbor mutations in specific DDR.
Liptay (page 1 bridged page 2) teaches that certain breast and ovarian cancers habor mutations in homologous recombination repair (HR) genes such as BRCA1 and BRCA2, resulting in defects in DDR response pathways. Liptay (page 2) teaches that cancer cell deficient in DDR pathways, such as homologous recombination (HR) due to BRCA1/2 mutations, accumulate DNA damage and are more susceptible to therapeutic intervention. Liptay (page 1-22) also teaches that selectively inhibiting these alternative pathways gives an opportunity to induce synthetic lethality in these tumor cells, leading to cells death; because the tumor cells that lack proper DNA repair cannot and die. In addition, Brown (page 20) teaches genetic instability or germline mutation in DDR pathway including but not limited to BRCA1/2 as the hallmark of cancer. Therefore, a person of ordinary skill in the art (POSITA) would reasonably understand that genomic instability is directly associated with mutation leading to a decreased protein function, level, and expression and thereby reduced function of DDR pathway. expression of key DDR genes. It is important to note that the specification (page 88), defines “depleted” as the following:
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Therefore, it would have been obvious to a person of ordinary skill in the art (POSITA) would have recognized that p53 is a central mediator of cellular response to DNA damage, including cell cycle arrest and apoptosis, and that MDM2 negatively regulates p53, as thought by Chessari. Therefore, it would have been obvious to a POSITA to use an MDM2 antagonist to stabilize and activate p53 in DDR-deficient cancer cells, e.g., breast and ovarian cancer, thereby enhancing DNA damage-induced cell cycle arrest and apoptosis, as MDM2 negatively regulates p53 activity. Furthermore, a POSITA would have been motivated to modify Chessari’s teachings in view of Liptay and administer an MDM2 antagonist to a patient having a DDR-deficient cancer in order to inhibit the MDM2-p53 interaction, thereby stabilizing and activating p53. Thus, a POSITA would expect that activation of p53 would reasonably be expected to enhance cell cycle arrest and or apoptosis, providing a therapeutic benefit; as such view is supported by Li (page 3):
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Li (page 10, Table 1) mentions that HDM201, an MDM2 antagonist, is in phase 1 clinical trials for the treatment of triple negative breast cancer. Triple negative breast cancer is known to be associated with deficiencies in DDR pathways, including dysfunction of BRCA1.
Regarding claim 59-60, and as applied to claim 58 above, Li (page 2) teaches the following regarding p53 and DDR pathway:
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Furthermore, Brown (page 21, Table 1; page 22, Figure 1) teaches the DDR comprises multiple interconnected repair pathways, as supported Li, including HR, NHEJ, BER, and identify key genes involves in these pathways including BRCA1/2, ATM, POLE:
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Therefore, given the combined teachings Brown, Li, Chessari, and Liptay teach defects in these pathways are common in cancer and result in genomic instability and increased reliance on remaining cellular mechanism. Thus, a POSITA would have recognized that mutations or loss function in in such DDR genes broadly impair genome stability and increase cellular stress. Thus, a POSITA would reasonably modify Chessari’s teachings in view of Brown, Li, and Liptay and would obviously apply MDM2 antagonist to cancer with defects in any of the identified DDR pathways or genes, with a reasonable expectation that activation of p53 would enhance DNA damage-induced cellular response, including arrest and apoptosis.
Regarding claim 62, and as applied to claim 58 above, Brown (page 32) teaches that high levels of microsatellite instability (MSI) is associated with mismatch repair–deficiency and genomic instability in cancer, and serve as a DDR defect biomarker when selecting ideal patient for treatment. This is supported by Zhang (page 2-4) identifying both MSI and Tumor mutation burden (TMB) as biomerkers, particularly MSI, as biomarkers associated with DDR defect.
Thus, it would have been obvious to a POSITA to assess MSI and/or TMB to identify DDR deficient-tumor before selecting an ideal candidate for treatment with an MDM2 antagonist to enhance p53 activity.
Regarding claim 63, 69, Chessari (page 110) teaches the following:
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Regarding claim 64, Chessari (page 107) teaches the following:
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Regarding claim 65, Chessari (page 2) teaches loss of p14ARF by a homozygous mutation in the CDKN2A (INK4A) gene will lead to elevated levels in MDM2 and, therefore, loss of p53 function and cell cycle control. Please note the homozygous mutation of CDKN2A that leads to loss of p14ARF protein taught by Chessari et al. is a mutation of CDKN2A with low protein expression of CDKN2A (p14ARF), and that is CDKN2A depleted.
Regarding claim 68-69 and 72, as applied to claim 1 above, Chessari (page 109 and 110) teaches administering MDM2 antagonist and that prior to treatment, a patient may be screen by analyzing a biological sample to detect genetic abnormalities or altered expression biomarkers, including markers associated with MDM2/p53 pathway; in order to determine whether such patient is likely to respond to treatment.
Li (page 10, Table 1) also teaches HDM201, an MDM2 antagonist, is in phase 1 clinical trials for the treatment of triple negative breast cancer. Triple negative breast cancer is known to be associated with deficiencies in DDR pathways, including dysfunction of BRCA1, a key genetic biomarker for assessing hereditary risk. This is supported by Brown (page 21, Table 1; page 22, Figure 2) who teaches that DDR pathway genes, including down signaling BRAC1, are well-established cancer biomarkers, and that assessment of their expression or activity is known in the art as a guide for therapeutic treatment regimen.
Diagnostic methods include (Chessari, page 110):
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Therefore, it would have been obvious to a POSITA to assess expression or activity of DDR pathways genes and complementary down signaling including BRCA1, e.g., in a biological sample from cancer patient as part of the pre-treatment screening to determine responsiveness to MDM2 antagonist therapy, because analysis of cancer biomarkers, including DDR related biomarkers, is well-established approach for patient stratification and treatment selection in the art.
Regarding claim 73, Chessari (page 121 and 125) teaches the MDM2 antagonist can be used in combination with PARP inhibitor. This is also supported by Brown (page 22-23) by disclosing the same concept and further added that PARP inhibition is undeniably an effective treatment for BRCA1/2 -mutated cancers, with response rates in the region of 50% for platinum-sensitive ovarian cancers.
Claims 75 is rejected under 35 U.S.C. 103 as being unpatentable over Chessari, Brown, Li, Zhang, Liptay in further view of Chessari et al. WO 2015/092420 (“Chessari ‘420”)
Regarding claim 75, and as applied to claim 1 above, Chessari ‘420 (abstract; page 115-116; page ) teaches a the use of compound 1-{6-[(4-fluorophenyl)methyl]-5-(hydroxymethyl)-3,3-dimethyl-1H,2H,3H- pyrrolo[3,2-b]pyridin-1-yl}-2-[(2R,5R)-5-methyl-2-{[(3R)-3-methylmorpholin-4-yl]methyl}piperazin-1-yl]ethan-1-one (ASTX660) as prophylaxis or treatment of cancer including but not limited to breast cancer. Chessari ‘420 (page 166; page 6, line 6-8; page 72, line 7-10) teaches that the compound can also be used in combination with other therapeutic agents (e.g. anticancer agents). Given the combined teachings of Cherissa, Li, and Brown on the use of MDM2 antagonist against breast cancer, and Chessari also teaches ASTX660 for the same utility, thus it would have been obvious to a POSITA to combine mdm2 antagonist with ASTX660 to seek additive or synergistic effects. This is because combining different classes of inhibitors against related target is well known in the art to enhance treatment efficacy.
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.
Claim 58, 63-65, 67-70, 73, 75 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 48, 50, 52, 55, 59, 61-65, 67-72, 74, and 76 and 75 of copending Application No. 17575843.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference application is also drawn to administering a therapeutically effective amount of the elected MDM2 antagonist for the treatment of cancer with decreased expression of CDKN2A as the gene in one or more DNA damage repair pathway, assessing said expression in a sample from the cancer patient prior to the administration step, and further combine the elected MDM2 antagonist with ASTX600 or optionally PARP inhibitor, as the additional therapeutic agent.
Claim 48, 50, 52, 61-65, 68-72, 74, and 76 of co-pending application is drawn to a method of treating cancer in a patient, comprising a treatment step that comprises administering to the patient a therapeutically effective amount of an MDM2 antagonist, wherein the cancer is depleted of CDKN2A or show shows increased expression of one or more of: CXCLl0, CXCLl, etc., wherein step of detecting the expression or activity level of the biomarkers in a sample of cancer cells from said human patient, optionally wherein the detection is carried out using an in vitro detection assay (see claim 63, 65, 68-69).
Claim 55 and 67 of co-pending application drawn to MDM2 antagonist is a compound of formula (1), is, for example, (2S,3S)-3-(4-chlorophenyl)-3-[(1 R)-1-(4-chlorophenyl )-7-fl uoro-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-lH-isoindol-2-yl]-2-methylpropanoic acid (see claim 58, 67 and 70).
Claim 59 and 67 of co-pending application is drawn to wherein the addition compound is ASTX600 (see claim 75).
Claim 63 of co-pending application is drawn to testing a sample of patient tissue to determine the cancer expression profile prior to treatment (see claim 63).
Claims 64 of co-pending application is drawn to wherein the cancer is P53
wild-type (see claim 64)
Therefore, this is a provisional nonstatutory double patenting rejection.
Claim 42, 44-49 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 63-65, 67-70 and 75 of copending Application No. 18042167.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference application is also drawn to administering a therapeutically effective amount of the elected MDM2 antagonist for the treatment of cancer with SKP2 depleted as the gene in one or more DNA damage repair pathway, assessing said expression in a sample from the cancer patient prior to the administration step, and further combine the elected MDM2 antagonist with ASTX600.
Claim 42, 44, 47-48 of co-pending application is drawn to a method of treating cancer in a patient, comprising a treatment step that comprises administering to the patient a therapeutically effective amount of an MDM2 antagonist, wherein the cancer is depleted of SKP2; wherein step of detecting the expression or activity level of the biomarkers in a sample of cancer cells from said human patient, optionally wherein the detection is carried out using an in vitro detection assay (see claim 63, 65, 68-69).
Claim 46, 49 of co-pending application drawn to MDM2 antagonist is a compound of formula (1), is, for example, (2S,3S)-3-(4-chlorophenyl)-3-[(1 R)-1-(4-chlorophenyl )-7-fl uoro-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-lH-isoindol-2-yl]-2-methylpropanoic acid; or is selected from the group consisting of Compound 1, idasanutlin (RG-7388), HDM-201, (see claim 67 and 70).
Claim 55 and 58 of co-pending application is drawn to wherein the addition compound is ASTX600 (see claim 75).
Claim 44 of co-pending application is drawn to testing a sample of patient tissue to determine the cancer expression profile prior to treatment (see claim 63).
Claims 45 of co-pending application is drawn to wherein the cancer is p53
wild-type (see claim 64)
Therefore, this is a provisional nonstatutory double patenting rejection.
Subject Matter Free of the Art of Record
The subject matter of claim 66 and 74 are free of the art of record. The closest prior art is the Chessari et al. WO2017/055860 in view of Brown et al., Cancer Discov. 2017 Jan;7(1):20-37. While Chessari teaches method of treating cancer in a patient with MDM2 antagonist, however there is no motivation for an ordinary skill in the art to modify the teaching of Chessari to arrive at the method claim. These claims are not allowable until the 112 rejection and 103 rejection are overcome.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PIERRE PAUL ELENISTE whose telephone number is (571)270-0589. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm (EST).
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/P.P.E./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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