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 .
DETAILED ACTION
Preliminary amendment filed on 05/12/2023 is acknowledged. Claims 5-10 were canceled, claims 2-4 were amended, and claims 11-19 were newly added. Claims 1-4 and 11-19 are pending in the instant application and are examined on the merits herein.
Priority
This application is a National Stage Application of PCT/CN2021/098230, filed on 06/04/2021 and claims foreign priority to CHINA 202011617321.8 filed on 12/30/2020.
Information Disclosure Statement
The information disclosure statement (IDS) dated 05/12/2023 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, the IDS document has been placed in the application file and the information therein has been considered as to the merits.
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.
Claims 1, 3, 4, and 11-16 are rejected under 35 U.S.C. 103 as being unpatentable over Amtmann et al. (WO 2018/069525 Al, published 04/19/2018, see PTO-892).
Amtmann is drawn to a class of dithiocarbamate-metal complexes and their uses in medicine. Amtmann teaches combinations and pharmaceutical compositions, comprising a dithiocarbamate with a source of a heavy metal. The compounds and combination are particularly useful in the treatment of tumor diseases and other disorders (abstract). Amtmann teaches a combination of dithiocarbamate, a cyclodextrin and a heavy metal source (claim 7). The heavy metal is preferably from auranofin, aurothiomalate, Au-dithiocarbamate, and aurothioglucose (page 13). The combination, or compounds, according to the invention is for use in medicine, and preferably for the treatment of a proliferative disease such as a tumor disease, infectious diseases, cardiovascular disorders, rheumatic arthritis, or persisting HIV infection (page 16). The tumor disease may be lung cancer, most preferably is SCLC, colon carcinoma, ovary cancer, liver cancer, pancreatic cancer, melanoma, glioma, T-cell lymphoma, leukemia, and Burkitt lymphoma (claim 16). Amtmann teaches that for the treatment of tumor disease, the heavy metal source may be administered to the subject separately from the dithiocarbamate (claim 17). Amtmann exemplified a complex using diethyldithiocarbamate, DKFZ-00608 (page 31).
Regarding claim 16, it is noted that the prior art does not teach that the composition can be used in the manner instantly claimed, as a TrxR inhibitor. However, the cited recitations are considered an “intended use” of the claimed composition. The “intended use” of the claimed composition does not patentably distinguish the composition, per se, since such disclosed use is inherent in the reference composition. In order to be limiting, the intended use must create a structural difference between the claimed composition and the prior art composition. In the instant case, the intended use does not create a structural difference, thus the intended use is not limiting.
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Figure 1. (a) Amtmann’s structure I. (b) DKFZ-00608 (page 31)
Amtmann does not exemplify the combination of auranofin and a mercapto compound.
It would have been prima facie obvious before the effective filing date to select auranofin and a thiolate compound such as diethyldithiocarbamate as a composition to be used to treat cell proliferative disorders such as tumors as taught by Amtmann to arrive at the claimed invention. It would have been prima facie obvious for a person of ordinary skill in the art to select both auranofin and diethyldithiocarbamate because Amtmann teaches that auranofin is a preferred source of the heavy metal and teaches a gold complex compound using diethyldithiocarbamate (DKFZ-00608). One of ordinary skill in the art would have a reasonable expectation of success because Amtmann exemplifies a gold complex compound using diethyldithiocarbamate (DKFZ-00608) and teaches that auranofin is a preferred source of heavy metal.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Amtmann et al. (WO 2018/069525 Al, published 04/19/2018, see PTO-892) as applied to claim 1 above, and further in view of Che et al. (US 9,238,659 B2, published 01/19/2016, see PTO-892).
Claim 1 is rejected as discussed above.
Amtmann does not teach the specific use of sodium diethyldithiocarbamate.
Che is drawn to a method of treating cancer by administration of binuclear gold (I) compounds in patients in need thereof (abstract). Che teaches that the cancer may be cancer of the breast, liver, neuroblastoma, head, neck, eye, mouth, throat, esophagus, chest, bone, lung, kidney, colon, rectum or other gastrointestinal tract organs, stomach, spleen, skeletal muscle, subcutaneous tissue, prostate, breast, ovaries, testicles or other reproductive organs, skin, thyroid, blood, lymph nodes, kidney, liver, pancreas, and brain or central nervous system (column 8, lines 50-60). Che teaches a structural formula I where the L-L ligands may be a dithiol. The dithiol ligand could be diethyldithiocarbamate when R11 and R12 are both -C2H5 (column 4, lines 5-50). Che exemplifies the use of sodium diethylcarbamoditioate in the synthesis (Figure 2, see below).
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Figure 2. Che structural formula I where the L-L ligands could be a dithiol.
It would have been prima facie obvious to combine Amtmann and Che before the effective filing date of the claimed invention by selecting sodium diethyldithiocarbamate as the diethyldithiocarbamate compound used in the compound taught by Amtmann to arrive at the claimed invention. It would have been prima facie obvious for a person of ordinary skill in the art to select sodium diethyldithiocarbamate as the diethyldithiocarbamate compound because Che exemplified the use of sodium diethyldithiocarbamate in a binuclear gold (I) compound. One of ordinary skill in the art would have a reasonable expectation of success because both Che and Amtmann use diethyldithiocarbamate as a ligand in a binuclear gold (I) compound and Che shows that that sodium diethyldithiocarbamate may be used.
Claims 1, 16, 17 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Gunkel et al. (EP 3693740 A1, published 12/08/2020, see PTO-892).
Gunkel is drawn to dithiocarbamate complexes with increased tumor spheroid activity for the treatment of tumor diseases. The dithiocarbamate compounds of the invention were identified as competitive TrxR1 binders (abstract). Gunkel teaches that the composition comprising cyclodextrin, a dithiocarbamate and a heavy metal for the formation of the dithiocarbamate/heavy metal composition resulted in a product with excellent and synergistic anti-tumor activity (paragraph 0043). The preferred metal source of the invention may be auranofin (paragraph 0066). Gunkel teaches that DKFZ-608, is a homoleptic dithiocarbamate gold complex that reversibly binds TrxR1 in competition with the TrxR1 substrate thioredoxin -1 (Trx1). Consequently, cells expressing low levels of TRX1, like SCLC, are hypersensitive to DKFZ-608, while cells, which express higher levels of TRX1, are resistant. In an SCLC animal model, DKFZ-608 eradicates residual tumor cells surviving first line therapy and completely prevents tumor recurrence (paragraph 0015). Gunkel teaches a method of treatment of a disease by administering the disclosed dithiocarbamate compound or the pharmaceutical composition compromising the same (paragraph 0096). The disease may be a proliferative disease (paragraph 0097) or a tumor disease (paragraph 0099). The tumors diseases may be selected from lung cancer, colon carcinoma, ovary cancer, liver cancer, mamma carcinoma, pancreatic cancer, melanoma, glioma, T-cell lymphoma, leukemia, and Burkitt lymphoma (paragraph 0107). Gunkel shows a dose dependent inhibition of TrxR1 using DKFZ-608 in cells (Figure 4, paragraph 120)
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Figure 3. Structure of DKFZ-608 (paragraph 0061)
Gunkel does not exemplify the composition comprising auranofin and a mercapto compound.
It would have been prima facie obvious before the effective filing date by selecting a composition comprising a dithiocarbamate and a heavy metal such as gold sourced from auranofin as taught by Gunkel to arrive at the claimed invention. It would have been prima facie obvious for a person of ordinary skill in the art to select the use auranofin as the heavy metal source because Gunkel teaches that auranofin is a preferred source. One of ordinary skill in the art would have a reasonable expectation of success because Gunkel teaches that auranofin may be used as the heavy metal source and exemplified the composition comprising DKFZ-608 which is a complex of diethyldithiocarbamate and a gold source.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Gunkel et al. (EP 3693740 A1, published 12/08/2020, see PTO-892) as applied to claim 17 above, and further in view of Che et al. (US 9,238,659 B2, published 01/19/2016, see PTO-892).
Claim 17 is rejected as discussed above.
Gunkel does not teach the specific use of sodium diethyldithiocarbamate.
The teachings of Che are discussed above.
It would have been prima facie obvious to combine Gunkel and Che before the effective filing date of the claimed invention by selecting sodium diethyldithiocarbamate as the diethyldithiocarbamate compound used in the compound taught by Gunkel to arrive at the claimed invention. It would have been prima facie obvious for a person of ordinary skill in the art to select sodium diethyldithiocarbamate as the thiolate compound because Che exemplified the use of sodium diethyldithiocarbamate in a binuclear gold (I) compound. One of ordinary skill in the art would have a reasonable expectation of success because both Gunkel and Che use diethyldithiocarbamate as a ligand in a binuclear gold (I) compound and Che shows that that sodium diethyldithiocarbamate may be used.
Conclusion
No claims allowed.
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/SAMANTHA LYNN SCHACHERMEYER/Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693