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 .
Claim Status
Claims 1-6, 8-9, 13-14, 20-21, 24, 28, 34-36, 73-77, 79-81, 90, 93, 97 and 103–105 are pending. Claims 8, 14, 20-21, 24, 28, 34-36, 73-77, 79-81, 90, 93, 97 and 103–105 are withdrawn. Claims 1-6, 9 and 13 are rejected.
Response to Arguments
Applicant traverses the 35 USC 103 obviousness rejections over Touaibia arguing that the instant claims are directed to a method which includes administering a combination of CAPE and a CAPE analog. The rejection of claims 1 and 9 in view of Touaibia is directed to a method of treatment comprising administering a single CAPE analog, As26, therefore a person of ordinary skill would not be motivated to combine two compounds via Touaibia’s disclosure. Applicant’s argument is unpersuasive because the instant claims as drafted are not directed to a method of administering a combination of CAPE and a CAPE analog. Claim 1 recites a method for treating comprising “administering to the patient a therapeutically effective amount of a compound selected from the group consisting of CAPE and a CAPE analog…” The claim employs Markush language which recites a list of alternatives, i.e., CAPE or a CAPE analog. MPEP 2173.05(h) teaches the following:
A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members. Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196.
If a claim is intended to encompass combinations or mixtures of the alternatives set forth in the Markush grouping, the claim may include qualifying language preceding the recited alternatives (such as "at least one member" selected from the group), or within the list of alternatives (such as "or mixtures thereof"). Id. at 1281.
Therefore, the disclosure of Touaibia et al. as previously cited sufficiently teaches the claimed method of treatment which only requires administration of Applicant’s elected species, CAPE analog As26. All previous rejections under 35 USC 103 are maintained.
The previously presented double patenting rejection has been converted to a nonprovisional double patenting rejection as U.S. Patent No. 12,605,352 has issued over Application. 17/604,508; however, the grounds of rejection remain the same.
Election/Restrictions
As per MPEP 803.02, the examiner will determine whether the entire scope of the claims is patentable. Applicant’s elected species combination of Panobinostat as a downregulating agent and As26 as the CAPE-related compound is not allowable. Therefore, examination has been limited to claims embracing the elected species which are claims 1-6, 9 and 13. Claims 1-6, 9 and 13 have been examined to the extent that they are readable on the elected embodiment. Subject matter not embraced by the elected embodiment is therefore withdrawn from further consideration.
Claims 8, 14, 20-21, 24, 28, 34-36, 73-77, 79-81, 90, 93, 97 and 103–105 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
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) 1 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2017/147718 A1 by Touaibia et al.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
The prior art discloses (title) “modulators of lipoxygenase and cyclooxygenase enzyme activity” including compound 152 which is identical to As26 of instant claim 9 (page 33, Table 9). Compound 152 is represented by the structure below:
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Regarding instant claims 1 and 9, Touaibia et al. teach a method of treating a lipoxygenase and/or a cyclooxygenase-mediated disease, including cancers such as breast cancer, by administering the prior art compound (paragraphs [0019]-[0020]).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art discloses methods of treating cancer by administering the compound 152 but is silent to the downregulation of cancer genes and the effect of CAPE analog wherein the compound reduces the number of cancer cells, tumor burden or tumor growth in the patient.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
Although the prior art does not explicitly recite the intended use and effects of the instant claims a compound and its properties are inseparable so the properties of the instant compound would be inherent in the prior art given that the compounds are identical. Accordingly, the instant method of treating cancer by administering a CAPE analog to downregulate a cancer gene or protein target expression is obvious in view of the method of Touaibia et al. which involves administering the instant compound to treat cancer. A person of ordinary skill performing the method of Touiabia et al. could expect to achieve the same reduction in cancer cells, tumor burden, etc. recited by administering compound 152 as taught in the prior art.
Claim(s) 2-4 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2017/147718 A1 by Touaibia et al. as applied to claims 1 and 9 above, and further in view of Qin, et al. (2019). Panobinostat (LBH589) inhibits Wnt/β-catenin signaling pathway via upregulating APCL expression in breast cancer. Cellular signalling, 59, 62-75.
Touaibia et al. disclose a method of treating lipoxygenase and/or cyclooxygenase-mediated diseases, including cancers such as breast cancer, by administering the prior art compound in combination with an additional therapeutic agent that is useful for treating the same condition (paragraph [00261]); however, the prior art but does not suggest HDAC inhibitors such as Panobinostat.
Qin et al. discuss the effects of administering Panobinostat to treat breast cancer and teach (abstract):
Breast cancer is the most common malignant disease among women worldwide and the novel therapeutic agents are urgently needed. Panobinostat (LBH589), a pan-HDACs inhibitor, has shown promising anti-tumor effect in recent years. However, the targets of this compound are largely unclear because of its low selectivity. In consideration of the transcription promoting activity of panobinostat, we speculated that specific tumor suppressor genes might be upregulated after panobinostat treatment. In this study, we verified the inhibition effect of panobinostat in different subtypes of breast cancer cells in vivo and in vitro. We found that panobinostat suppressed proliferation, migration as well as invasion, and induced apoptosis in both TNBC and non-TNBC cells. Consistently, panobinostat inhibited breast cancer growth and metastasis in mouse models…
Accordingly, a person of ordinary skill seeking to treat breast cancer in the method of Touaibia et al. would have been motivated to administer prior art compound 152 in combination with the HDAC inhibitor panobinostat in order to improve therapeutic outcomes.
Claim(s) 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2017/147718 A1 by Touaibia et al. as applied to claims 1 and 9 above, and further in view of Bernard, et al. (2008). Targeting cyclooxygenase-2 in hematological malignancies: rationale and promise. Current pharmaceutical design, 14(21), 2051–2060.
Touaibia et al. disclose a method of treating lipoxygenase and/or cyclooxygenase-mediated diseases including some cancers by administering the prior art compound but do not teach that the compound is useful for treating the blood cancers of the instant claims.
Bernard et al. discuss (title) “Targeting cyclooxygenase-2 in hematological malignancies: rationale and promise” and teach (abstract):
Malignancies of hematopoietic and non-hematopoietic origin often have increased expression of cyclooxygenase-2 (Cox-2), a key modulator of inflammation. For example, hematological malignancies such as chronic lymphocytic leukemia, chronic myeloid leukemia, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma and multiple myeloma often highly express Cox-2, which correlates with poor patient prognosis. Expression of Cox-2 enhances survival and proliferation of malignant cells, while negatively influencing anti-tumor immunity. Hematological malignancies expressing elevated levels of Cox-2 potentially avoid immune responses by producing factors that enhance angiogenesis and metastases. Cellular immune responses regulated by natural killer cells, cytotoxic T lymphocytes, and T regulatory cells are also influenced by Cox-2 expression. Therefore, Cox-2 selective inhibitors have promising therapeutic potential in patients suffering from certain hematological malignancies.
Accordingly, a person of ordinary skill seeking to treat additional cyclooxygenase mediated cancers in the method of Touaibia et al. would have been motivated to administer cyclooxygenase inhibitor compound 152 to improve therapeutic outcomes in subjects with blood cancers such as certain leukemias lymphomas or multiple myeloma.
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 1-6, 9 and 13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12,605,352 in view of Lemoine, Manuela et al. “The pan-deacetylase inhibitor panobinostat induces cell death and synergizes with everolimus in Hodgkin lymphoma cell lines.” Blood vol. 119,17 (2012): 4017-25.
Claim 1 of the patent discloses a method of inhibiting the growth of blood cancer cells by contacting the cells with As26 which identical to As26 of instant claim 9 (Col. 20); this method embraces the instant method of treating blood cancers by administering CAPE analog As26. Claims 2, 5, and 9 of the patent further teach that the blood cancer cells are multiple myeloma cells, lymphoma cells, or leukemia cells which corresponds to instant claims 1 and 5-6 (Col. 20).
Regarding instant claims 2-4 and 13, the patent’s claims are silent to contacting the blood cancer cells with a downregulating agent such as an HDAC inhibitor however MPEP 2144.06 suggests:
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)
Lemoine et al. teach the following regarding Panobinostat for treating lymphoma (abstract):
The pan-deacetylase inhibitor panobinostat (LBH589) recently has been shown to have significant clinical activity in patients with relapsed Hodgkin lymphoma, but its mechanism of action in Hodgkin lymphoma remains unknown. In this study, we demonstrate that panobinostat has potent antiproliferative activity against Hodgkin lymphoma-derived cell lines…
Accordingly, a person of ordinary skill seeking to inhibit the growth of lymphoma cells in the copending method would have been motivated to administer As26 in combination with the HDAC inhibitor panobinostat in order to improve therapeutic outcomes.
Conclusion
THIS ACTION IS MADE FINAL. 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.
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/A.A.C./Examiner, Art Unit 1626
/KAMAL A SAEED/Primary Examiner, Art Unit 1626
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