DETAILED ACTION
The present application is a domestic application filed 10 October 2023, which claims priority to US Provisional Application No. 63/414,955, filed 11 October 2022. Claims 1-17 are pending in the current application and are examined on the merits herein.
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-6 and 9-17 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Ohta et al. (US Patent No. 7,973,145, cited in IDS submitted 10 October 2023) as evidenced by Ruike et al. (Xenobiotica, 2019, vol. 49, no. 3, pp. 346-362, cited in PTO-892).
Ohta et al. disclose sulfoquinovosylacyl propanediol (SQAP) of formula (I) for treating tumors:
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, wherein R1 is an acyl residue of a fatty acid with 1-26 carbon atoms, Y is a number of 1, 2 or 3, M represents a hydrogen ion or a metal ion having a positive charge (abstract; claim 1 and 3). Exemplified salt forms include calcium and sodium (claims 4-6). Ohta et al. teach SQAP functions as a radiosensitizer, an antineoplastic agent or antitumor agent (claims 8 and 9). As a radiosensitizer, it may be combined with other radiosensitizers, antitumor agent, or other substance having pharmacological activity (col. 20:1-9). The composition may be administered to treat a human, a dog or a cat (col.22:9-16). Cancers that can be treated include prostate cancer (i.e. a solid tumor), as well as melanoma and lymphoma (col.19:52-65). Ohta et al. exemplify where R1 is a stearoyl group (example 1). The compound is administered at a dose of 0.001 to 100 mg/kg body weight via oral administration, 0.001 to 50 mg/kg body weight via injection, from 0.001 to 100 mg/kg body weight via transdermal administration, 0.001 to 50 mg/kg body weight via rectal administration, or about 0.001 to 3 wt.% solution via ocular instillation (col.20:54-61). Ohta et al. disclose an example of administering 2 mg/kg of the drug (example V-1; and other examples). They were also administered radiation treatment at a dose of 2 Gy on Day 1 and Day 4. Radiation is given over a period of one week to 6 months (col.21:1-17). Ohta et al. compare the properties of AQAP with 2mg/kg mitomycin C, wherein the mitomycin C serves as a positive control group (example VII-2)
Thus, Ohta et al. disclose a method of treating cancer, comprising administering the compound of formula (I) in combination with radiation treatment, and wherein the compound can be administered with an additional radiosensitizer or antitumor agent.
As evidenced by Ruike et al., 2 mg of [glucose-U-14C]-SQAP resulted in 4400 (ng eq•h/g or mL), (Table 1). Taking the MW of the compound to be 567.319 (p.353, LC/MS (MS/MS) measurement of plasma and tumor), the 4400 (ng eq•h/g or mL) of compound found in the plasma is equivalent to about 7.826 µM. This was determined by converting 4400 ng/mL to g/mL, which is 4.4400x10-6 g/mL. This is then multiplied by 1000 to give 4.4400x10-3 g/L. This is then divided by the molar mass of the SQAP to give 7.8263x10-6 mol/L. This is then multiplied by 1x106 to give 7.826 µmol/L or 7.826 µM. Thus, a 2 mg dose results in a blood concentration of SPAQ of 7.826 µM, which is less than 60 µM as recited in claim 10, and more than 1 µM as recited in present claim 12.
Thus, the disclosure of Ohta et al. as evidenced by Ruike et al. anticipates claims 1-6 and 9-17 of the present application
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.
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.
Claim(s) 1-17 are rejected under 35 U.S.C. 103 as being unpatentable over Ohta et al. (cited above) as evidenced by Ruike et al. (cited above) in view of Kawakubo et al. (Bioscience, Biotechnology, and Biochemistry, 2021, vol. 85, no. 1, pp. 85-91, cited in PTO-892) and further in view of Deb et al. (The Journal of Urology, 2011, vol. 186, pp. 2426-2433, cited in PTO-892).
Ohta et al. teach as discussed above.
Ohta et al. do not expressly disclose administering mitomycin C (present claims 7 and 8).
Kawakubo et al. teach
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, which reads on the compound of formula (I), wherein R1 is a stearoyl group, herein after referred to as SQAP (p.86, fig. 1). They report SQAP is a radiosensitizing agent that makes tumor cells more sensitive to radiation therapy (abstract). They found SQAP induced the degradation of hypoxia-inducible factor-1α and then decreased the expression of histone deacetylase (HDAC1). Kawakubo et al. note HDAC inhibitors, such as sodium butyrate and trichostatin A (TSA), enhance the sensitivity of cancer cells to ionizing radiation (p.86, third para). HDAC inhibitors are useful in anticancer therapy because of their ability to inhibit angiogenesis, and HDACs have been shown to be upregulated in response to hypoxia (p.86, fourth para).
Deb et al. teach mitomycin C is a known DNA damaging agent, and valproic acid is a known histone deacetylate (HDAC) inhibitor (abstract). Deb et al. found the combination of mitomycin C with valproic acid appeared to synergistically treat human bladder cancer compared to each drug alone (abstract). The HDAC inhibitor potentiated the induction of cell death by mitomycin C in multiple bladder cancer cells (abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer SQAP in combination with mitomycin C to treat cancer.
According to MPEP 2144.06: “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).
Combining known therapies into a single therapy is a commonly applied method for identifying improved therapeutic outcomes with minimal adverse effect for the patient because each monotherapy is already known to be effective. Here, SPAQ functions as a radiosensitizing agent that can be used to treat a variety of cancers including in combination with radiation treatment, while mitomycin C was a known DNA damaging agent (see p.75 Cocco, Discussion). Thus, the skilled artisan would have been motivated to combine the two drugs wherein they each produce different effects for the treatment of cancer. And, Ohta et al. teach SPAQ may be combined with additional radiosensitizing agents or antitumor agent.
The ordinary artisan would have been motivated to select mitomycin C because Deb et al. found its anticancer effects were potentiated when combined with an HDAC inhibitor. While SPAQ does not inhibit histone deacetylase, it does suppress expression of the enzyme, and increases acetylation of histone cells. Thus, SPAQ has a similar effect as an HDAC inhibitor. Accordingly, it would have been obvious to combine SPAQ with mitomycin C to treat cancer with a reasonable expectation of success in treating cancer.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
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 1-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 12,440,505 in view of Kawakubo et al. (cited above) and further in view of Deb et al. (cited above).
The reference Patent is drawn towards administered the same SPAQ compound to treat cancer, including melanoma, adenocarcinoma, or squamous cell carcinoma at a dose of 0.5 mg/kg or more. Radiation is applied at a dose of 10 Gy or more after administering the SPAQ.
The reference Patent do not expressly disclose administering mitomycin C (present claims 7 and 8).
Kawabuko et al. and Deb et al. teach as discussed above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer SQAP in combination with mitomycin C to treat cancer.
According to MPEP 2144.06: “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).
Combining known therapies into a single therapy is a commonly applied method for identifying improved therapeutic outcomes with minimal adverse effect for the patient because each monotherapy is already known to be effective. Here, SPAQ functions as a radiosensitizing agent that can be used to treat a variety of cancers including in combination with radiation treatment, while mitomycin C was a known DNA damaging agent (see p.75 Cocco, Discussion). Thus, the skilled artisan would have been motivated to combine the two drugs wherein they each produce different effects for the treatment of cancer.
The ordinary artisan would have been motivated to select mitomycin C because Deb et al. found its anticancer effects were potentiated when combined with an HDAC inhibitor. While SPAQ does not inhibit histone deacetylase, it does suppress expression of the enzyme, and increases acetylation of histone cells. Thus, SPAQ has a similar effect as an HDAC inhibitor. Accordingly, it would have been obvious to combine SPAQ with mitomycin C to treat cancer with a reasonable expectation of success in treating cancer.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Conclusion
In view of the rejections to the pending claims set forth above, no claim is allowed.
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/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699