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).
Request for Continued Examination (RCE)
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 4/13/26 has been entered.
Status
Claims 1-13, 15-17 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Claim rejections not reiterated in this action are withdrawn.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 1-8, 10-11, 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fodor et al. (ACS Chem. Biol. 2018, 13, p. 647−656, SI 1-25).
Fodor teaches screening strategies identified a first and second small molecule allosteric combination, that has multiple targets (Abstract). Fodor modeled a first and second drug in a corresponding first and second binding site showing contact interactions in 3D (Figs. 1-8, SI 17). Fodor administered the combination and measured cell viability assays which showed an additive effect (p. 651-652, Fig 6). Thus, the claims are anticipated.
Regarding claim 2, Fodor teaches allosteric sites (abstract).
Regarding claim 3, Fodor teaches small molecules (abstract).
Regarding claim 4-5, Fodor teaches selecting hits, including small molecules, from screening data (abstract, Fig 3 compound library).
Regarding claim 6, Fodor teaches screening paradigm (p. 649, Fig 3).
Regarding claim 7, Fodor teaches docking (p. 649, Fig 3-4).
Regarding claim 8, Fodor teaches determining atomic displacement (p. 652-53).
Regarding claim 10-11, Fodor teaches normalized ranking (p. 649, Fig 3).
Regarding claim 16, Fodor teaches measuring cell viability assay (Fig. 6, 8).
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 Fodor et al. (ACS Chem. Biol. 2018, 13, p. 647−656, SI 1-25) 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).
Fodor 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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Sivakumar teaches the use of Autodock in docking the drugs molecules (p. 690-694).
One of ordinary skill in the art following the teaching of Fodor 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 Fodor et al. (ACS Chem. Biol. 2018, 13, p. 647−656, SI 1-25) 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, Fodor teaches ranking by screening paradigm (p. 648-649) 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 Fodor 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.
New Claim Rejections - 35 USC § 103 – Yang in view of Heudel and Tan
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) and Tan et al. (OncoTargets and Therapy 2019:12, p. 635-645).
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 ponatinib with vinorelbine.
Heudel teaches the successful treatment of breast cancer with viorelbine (Title, Abstract) and in combination with other chemotherapies (p. 3910-11).
Tan teaches the use of ponatinib for the treatment of cancers including breast cancer and in combination with other anti-cancer therapies (p. 640-642).
One of ordinary skill in the art following the teaching of Yang would reasonably consider the teaching of Heudel and Tan 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 vinorelbine and ponatinib 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.
New Double Patenting
Claims 1-13, 15 are 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 Fodor 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.
Response to remarks
Applicant argues regarding rejections that were withdrawn in favor of the above new grounds of rejection in view of the claim amendments, rendering the argument moot.
Applicant requests the double patenting rejections be held in abeyance. Thus, the rejections are maintained as amended above.
Conclusion
No claims allowed.
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
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