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 .
Priority
This application has PRO 63/289,176 (12/14/2021).
Status
Claims 1-17 are pending.
Claim rejections not reiterated in this action are withdrawn.
New Claim Rejections - 35 USC § 102
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.
Claims 1-11, 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wong et al. (BMC Medical Genomics 2015, 8(Suppl 4):S4, pages 1-23 and S1-32).
Wong teaches the technique of determining a drug combination, “cocktail”, that have multiple targets (Abstract). Wong docked a first and second drug in a corresponding first and second binding site showing contact interactions in 3D showing high “Libdock” scores corresponding (p. 9, 14-19, S10, S29-32). Wong administered the combination and measured cell viability assays which showed an additive effect (p. 19, S27-28 “combination drug always get a better efficiency than only single”). Thus, the claims are anticipated.
Regarding claim 2, Wong teaches active sites (p. 9).
Regarding claim 3, Wong teaches small molecules (p. S10-S13).
Regarding claim 4-5, Wong teaches selecting hits, including small molecules, from data sets and databases (p. S10-S13: NCI Drugs).
Regarding claim 6, Wong teaches scoring and ranking, at least via Libdock (p. S10-S13).
Regarding claim 7, Wong teaches docking and pose (p. 14).
Regarding claim 8, Wong teaches determining atomic displacement (S29-32).
Regarding claim 9, Wong teaches docking using an equivalent docking program Libdock (p. 14, S29-32).
Regarding claim 10, Wong teaches normalized ranking (p. 10-12, S20).
Regarding claim 11, Wong teaches ranking based on docking score (p. 9-12).
Regarding claim 16, Wong teaches measuring cell viability assay ((p. 19, S27-28 “combination drug always get a better efficiency than only single”).
New 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.
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.
Claims 1-11, 16 are rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (BMC Medical Genomics 2015, 8(Suppl 4):S4, pages 1-23 and S1-32) in view of Sivakumar et al. (“Prospects of multitarget drug designing strategies by linking molecular docking and molecular dynamics to explore the protein–ligand recognition process.” Drug Dev Res. 2020;81:685–699.) in view of Yang et al. (US20190183860, published 2019-06-20).
Wong teaches every element of the claims as detailed in the 35 USC 102 rejection supra and incorporated herein.
Sivakumar teaches a method of using docking and molecular dynamics to search for effective drugs and drug cocktails based on interactions with pharmacophores/target-sites as depicted Figure 1 shown below:
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One of ordinary skill in the art following the teaching of Wong in view of Sivakumar would have considered applying the same technique to a drug combination to achieve greater therapeutic effect.
One of ordinary skill in the art would have also considered Yang in the same field of endeavor of cancer therapeutics which teaches treating breast cancer by administering tioconazole with a second chemotherapeutic agent, including vinorelbine (Claims 1, 3, 4; [0007]-[0008]); tioconazole has sensitizes / synergizes when combined with a second chemotherapeutic drug ([0110]-[0113]); and teaches in silico screening of FDA-approved drugs using a docking, MD simulations, and Autodock which were also ranked by binding-interaction energy ([0054]-[0055]).
With each of the claims, the level of skill in the art is very high such that one of ordinary skill in the art would consider routine the combination of elements from the teaching of the art in the same field of endeavor. One of ordinary skill in the art would have recognized that the results of the combination would be predictable due to the well-known nature and optimizations routinely performed in the art. Thus, one of ordinary skill in the art would have arrived at the invention as claimed with a reasonable expectation of success.
Claims 12 is rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (BMC Medical Genomics 2015, 8(Suppl 4):S4, pages 1-23 and S1-32) in view of Sivakumar et al. (“Prospects of multitarget drug designing strategies by linking molecular docking and molecular dynamics to explore the protein–ligand recognition process.” Drug Dev Res. 2020;81:685–699.) and Yang et al. (US20190183860, published 2019-06-20) as applied to claims 1-11, 16 above and further in view of Belew et al. (J. Chem. Inf. Model. 2016, 56, 1597−1607).
Regarding claim 12, Wong teaches ranking by docking score and Sivakumar teaches determining from energies of atomic contacts (Figs. 1, p. 689), but does not specifically teach “logarithm of odds scoring”.
Belew teaches analysis of ligand docking and classification / scoring of actives (Title, Abstract) through use of numerical calculations including “log odds” (p. 1601).
One of ordinary skill in the art following the teaching of Wong and Sivakumar would have considered using known numerical calculations shown to be useful in scoring interactions among ligand-drug targets as taught by Belew. One of ordinary skill in the art would have considered using such a known technique to improve scoring and arrive at the claimed invention with a reasonable expectation of success based on Belew’s teaching in the same field of endeavor.
Claim Rejections - 35 USC § 103 – Yang in view of Heudel
Claims 13-15, 17 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (US20190183860, published 2019-06-20) in view of Heudel et al. (Anticancer Research July 2020, 40 (7) 3905-3913, Published July 3, 2020).
Regarding claims 13-15, Yang teaches treating breast cancer by administering tioconazole with a second chemotherapeutic agent, including vinorelbine (Claims 1, 3, 4; [0007]-[0008]). Yang teaches tioconazole sensitizes / synergizes when combined with a second chemotherapeutic drug ([0110]-[0113]) Yang also teaches in silico screening of FDA-approved drugs using a docking, MD simulations, and Autodock which were also ranked by binding-interaction energy ([0054]-[0055]).
Yang does not teach the specific embodiment of a combination of tioconazole with vinorelbine.
Heudel teaches the successful treatment of breast cancer with viorelbine (Title, Abstract) and in combination with other chemotherapies (p. 3910-11).
One of ordinary skill in the art following the teaching of Yang would reasonably consider the teaching of Heudel in the same field of endeavor and know that combinations of such anticancer compounds are effective. One of ordinary skill in the art would consider routine and well within their technical grasp the process of combining anti-cancer therapies as suggested by the prior art. In addition, those of ordinary skill in the art would first look to successful therapies already known in the art. “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, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 126 USPQ 186 (CCPA 1960) (the “joint use [of magnesium oxide and calcium carbide] is not patentable” where the prior art teaches “that both magnesium oxide and calcium carbide, individually, promote the formation of a nodular structure in cast iron, and it would be natural to suppose that, in combination, they would produce the same effect and would supplement each other”); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious).
See also Merck & Co., Inc. v. Biocraft Labs, Inc., 874 F.2d 804, 808 (Fed. Cir. 1989) (“Given the prior art teaching that both amiloride and hydrochlorothiazide are natriuretic, it is to be expected that their coadministration would induce more sodium excretion than would either diuretic alone”); In re Diamond, 360 F.2d 214, 217 (CCPA 1966) (where the evidence showed that synergy was expected because combined drugs targeted different cellular mechanisms, and no evidence to the contrary was produced, “[w]e are not convinced of [the] non-obviousness of the combination of two drugs, A5MP and a glucocorticoid . . . particularly since Appeal the record supports the [PTO’s] contention that the drugs selected are two of the commonly used drugs in the treatment of such collagen diseases”).
In this case, the prior art teaches the tioconazole and vinorelbine are individually effective for treating breast cancer and also suggests their combination with another chemotherapeutic. Therefore, the combination of the two compounds for the very same purpose is prima facie obvious. “[T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 205 USPQ 1069, 1072 (CCPA 1980).
Because combining the two anticancer therapies is taught by the prior art and such combinations have been shown to be successful, one of ordinary skill in the art would have a reasonable expectation of success in arriving at the combination as in the claimed invention.
Regarding new claim 17, as with claim 13 Yang and Heudel combined teach the method and further Yang teaches the activity is measured by a method of in silico drug screening ([0054]-[0055]) which one of ordinary skill in the art would have considered and arrived at the claimed invention with a reasonable expectation of success.
Response to remarks - 35 USC § 103 – Yang in view of Heudel
Applicant argues that the claimed invention has “unexpected beneficial features” from the combination shown in Examples of the Specification, including synergistic effects and lower toxicity.
Applicant’s argument is not persuasive as the alleged unexpected result is not commensurate in scope with the claims in view of the vast scope of combinations that are within “the drug combination obtained from the method of claim 1” which is practically unlimited in scope and covers as yet unknown combinations. In addition, the examples Applicant refers to are primarily only tioconazole with vinorelbine, TAT-N-term-9,-7, which is very limited in scope. Furthermore, Yang teaches tioconazole sensitizes / synergizes when combined with a second chemotherapeutic drug ([0110]-[0113]) which is what one of ordinary skill in the art would expect and thus would not be considered an unexpected result. Regarding lower toxicity, Applicant bears the burden of explaining how this result was unexpected and of statistical and practical significance. MPEP 716.02(b). In this case, Applicant has not met that burden.
New 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 1-15 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 10583123 (sharing the same disclosure as Yang et al. US20190183860 in the above rejections) in view of Wong et al. (BMC Medical Genomics 2015, 8(Suppl 4):S4, pages 1-23 and S1-32), Sivakumar et al. (“Prospects of multitarget drug designing strategies by linking molecular docking and molecular dynamics to explore the protein–ligand recognition process.” Drug Dev Res. 2020;81:685–699.), Belew et al. (J. Chem. Inf. Model. 2016, 56, 1597−1607), and Heudel et al. (Anticancer Research July 2020, 40 (7) 3905-3913, Published July 3, 2020). Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims a method of treating cancer with a combination of tioconazole with a second chemotherapeutic and as with the above prior art rejections renders the instant claims obvious.
Conclusion
No claims allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT H HAVLIN whose telephone number is (571)272-9066. The examiner can normally be reached 9am - 6pm.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626