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
Claims 1-2, 4-8, 10-12, 14, 16, 18, 20, 22, 24, 26, 28, 30-31 are currently pending.
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.
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.
Claims 1-2 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Burrows (WO2020046966, published 5/03/2020 claiming priority though 62/723,368 to 8/27/2018).
Burrows teaches in Claims 1 and 49-50 on Page 123 and 133 treating a KRAS mutant cancer comprising administering an MAPK inhibitor and a second therapeutic agent, a CDK4/6 inhibitor, voruciclib, the same compound as instant Formula Ib.
Claims 1-2 and 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Blake (Sci. Signal. 12, eaav7259 (2019) 1-15).
Blake teaches “There has been a renewed interest in developing selective CDK9 inhibitors for cancer treatment (50–53), due in large part to their inhibition of MCL-1 and MYC transcription…destabilization of MYC protein is a third antitumor activity of CDK9 inhibitors. This supports their clinical evaluation in…KRAS-mutant PDAC”, a pancreatic cancer (Page 11, Last Para). Blake cites reference 50 in the above quote, titled “Voruciclib, a clinical stage oral CDK9 inhibitor, represses MCL-1 and sensitizes high-risk Diffuse Large B-cell Lymphoma to BCL2 inhibition”, naming voruciclib as a CDK9 inhibitor which is promising for KRAS-mutant PDAC. If one of ordinary skill in the art is able to "at once envisage" the specific compound within the generic chemical formula, the compound is anticipated. In other words, a reference can anticipate a claim even if it “d[oes] not expressly spell out” all the limitations arranged or combined as in the claim, if a person of skill in the art, reading the reference, would “at once envisage” the claimed arrangement or combination. In re Petering, 301 F.2d 676, 133 USPQ 275 (CCPA 1962). Flo Healthcare Solutions, LLC v. Kappos, 697 F.3d 1367, 1375. Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 114 U.S.P.Q.2d 1250. See MPEP 2131.02 III. Voruciclib is immediately envisageable as a CDK9i and thus treatment of a KRAS mutant cancer with the species is anticipated.
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 1-2 and 4-8 are rejected under 35 U.S.C. 103 as being unpatentable over Burrows (WO2020046966, published 5/03/2020 claiming priority though 62/723,368 to 8/27/2018).
Burrows teaches in Claims 1 and 49-50 on Page 123 and 133 treating a KRAS mutant cancer comprising administering an MAPK inhibitor and a second therapeutic agent, a CDK4/6 inhibitor, voruciclib, the same compound as instant Formula Ib. The MAPK pathway inhibitor includes Ras inhibitors like MRTX849 and AMG510 (Para 164-165). Figure 1 depicts particular KRAS-mutant NSCLC variants to be treated, including G12C, G12D, Q61H, and G12V (Abstract). Other KRAS-mutant cancers taught to be treated include breast, pancreatic, and AML cancer (Para 82). One of skill in the art seeking to treat KRAS mutant cancer would elect to treat the particular embodiments explicitly contemplated by Burrows and expect success in these variants as suggested by burrows before the effective filing date of the instant application.
Claims 1-2 and 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over Blake (Sci. Signal. 12, eaav7259 (2019) 1-15).
Blake teaches “There has been a renewed interest in developing selective CDK9 inhibitors for cancer treatment (50–53), due in large part to their inhibition of MCL-1 and MYC transcription…destabilization of MYC protein is a third antitumor activity of CDK9 inhibitors. This supports their clinical evaluation in…KRAS-mutant PDAC”, a pancreatic cancer (Page 11, Last Para). Blake cites reference 50 in the above quote, titled “Voruciclib, a clinical stage oral CDK9 inhibitor, represses MCL-1 and sensitizes high-risk Diffuse Large B-cell Lymphoma to BCL2 inhibition”, naming voruciclib as a CDK9 inhibitor which is promising for KRAS-mutant PDAC. If one of ordinary skill in the art is able to "at once envisage" the specific compound within the generic chemical formula, the compound is anticipated. In other words, a reference can anticipate a claim even if it “d[oes] not expressly spell out” all the limitations arranged or combined as in the claim, if a person of skill in the art, reading the reference, would “at once envisage” the claimed arrangement or combination. In re Petering, 301 F.2d 676, 133 USPQ 275 (CCPA 1962). Flo Healthcare Solutions, LLC v. Kappos, 697 F.3d 1367, 1375. Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 114 U.S.P.Q.2d 1250. See MPEP 2131.02 III. Voruciclib is immediately envisageable as a CDK9i and thus treatment of a KRAS mutant cancer with the species is anticipated. Also, named in the reference is DLBCL, the KRAS-mutant variant of which would be expected to be treated with voruciclib, a CDK9i, before the effective filing date of the instant application because Blake teaches DLBCL as a KRAS cancer to be treated with the envisaged compound.
Claims 1-2, 4-8, 10-14, 16, 18, 20, 22, 24, 26, 28, and 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over Burrows as applied to Claims 1-2 and 4-8 in view of Duncan (WO2020210760, published 10/15/2020 claiming priority to 4/11/2019 through 62/832,637).
The teachings of Burrows are set forth above and incorporated by reference herein.
Burrow does not teach crystal polymorphs or cocrystals or dosing regimens of voruciclib.
Duncan teaches crystal forms of voruciclib including free base, HCl, malonate, dibenzoyl-tartrate, phosphate, oxalate, and napadisylate (Para 16-50). XRPD patterns are given in Para 4-8.
Duncan teaches dosing amounts of the compound and its cocrystals up to 1000mg and discrete amounts encompassed thereby once per day (Para 406 and 437-442). Dosing every other day or once a week is taught. Continuous dosing for 14 days is taught; dosing for 6, 7, 10, 14, and 28 days is also described (Para 434-436). “The specific dose will vary depending on the particular compounds chosen, the dosing regimen to be followed, whether the compound is administered in combination with other compounds, timing of administration, the tissue to which it is administered, and the physical delivery system in which the compound is carried” and “weight, age and gender of the subject” (Para 365). Therefore, a practitioner of ordinary skill would find it obvious to continually administer the claimed compound for 14 days and pause administration for the next 14 depending on toxicity levels of the drug or polymorph or cocrystal and certain patient factors when treating a KRAS-mutant cancer, the mutation possibly being present in a multitude of cancer types. Further, differences in concentration or temperature [or schedules] will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature [or schedule] is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See MPEP 2144.05 II (A). Regarding criticality, see MPEP 716.02(d) (II). One of ordinary skill in the art would expect success in treating KRAS-mutant cancers with voruciclib according to the dosing schedules taught by Duncan before the effective filing date because Duncan allows great variation in regimens depending on the patient, disease, and voruciclib form. The resultant crystals would be expected to have peaks associated with the obvious cocrystal polymorphs upon formation as claimed.
Claims 1-2, 7-8, 10-14, 16, 18, 20, 22, 24, 26, 28, and 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over Blake as applied to Claims 1-2 and 7-8 in view of Duncan (WO2020210760, published 10/15/2020 claiming priority to 4/11/2019 through 62/832,637).
The teachings of Blake are set forth above and incorporated by reference herein.
Blake does not teach crystal polymorphs or cocrystals or dosing regimens of voruciclib.
Duncan teaches crystal forms of voruciclib including free base, HCl, malonate, dibenzoyl-tartrate, phosphate, oxalate, and napadisylate (Para 16-50). XRPD patterns are given in Para 4-8.
Duncan teaches dosing amounts of the compound and its cocrystals up to 1000mg and discrete amounts encompassed thereby once per day (Para 406 and 437-442). Dosing every other day or once a week is taught. Continuous dosing for 14 days is taught; dosing for 6, 7, 10, 14, and 28 days is also described (Para 434-436). “The specific dose will vary depending on the particular compounds chosen, the dosing regimen to be followed, whether the compound is administered in combination with other compounds, timing of administration, the tissue to which it is administered, and the physical delivery system in which the compound is carried” and “weight, age and gender of the subject” (Para 365). Therefore, a practitioner of ordinary skill would find it obvious to continually administer the claimed compound for 14 days and pause administration for the next 14 depending on toxicity levels of the drug or polymorph or cocrystal and certain patient factors when treating a KRAS-mutant cancer, the mutation possibly being present in a multitude of cancer types. Further, differences in concentration or temperature [or schedules] will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature [or schedule] is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See MPEP 2144.05 II (A). Regarding criticality, see MPEP 716.02(d) (II). One of ordinary skill in the art would expect success in treating KRAS-mutant cancers with voruciclib according to the dosing schedules taught by Duncan before the effective filing date because Duncan allows great variation in regimens depending on the patient, disease, and voruciclib form. The resultant crystals would be expected to have peaks associated with the obvious cocrystal polymorphs upon formation as claimed.
Claims 1-2, 4-8, 10-14, 16, 18, 20, 22, 24, 26, 28, and 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over Burrows as applied to Claims 1-2 and 4-8 view of Haudenschild (WO2019209825, published 10/31/2019), Thakral (Mol. Pharmaceutics 2016, 13, 4141−4151), and Sivakumar (WO2007148158, published 12/27/2007).
Burrows does not teach crystal polymorphs or cocrystals or dosing regimens of voruciclib.
Haudenschild teaches salts of voruciclib including oxalates, malonates, and phosphates for administration (Para 50).
Thakral teaches with respect to drug salt formation that “the napadisylate salt is a hemisalt, two drug molecules are associated with one napadisylate molecule”, making for more economical drug delivery in that only one-half equivalent of each coformer is necessary to form a crystal with a molecule of voruciclib (Page 4145).
Sivakumar teaches crystal forms of voruciclib with coformers like HCl, phosphate and oxalate for administration to treat cancers (Abstract, Page 10). 5-500mg of the API or its salt crystal can be administered to a patient daily. “Actual dosage levels of the active ingredients in the pharmaceutical compositions of this invention may be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration without being toxic to the patient.” A multitude of factors are considered including “activity of the particular compound of the present invention employed, or the salt thereof, the route of administration, the time of administration, the rate of excretion of the particular compound being employed, the duration of the treatment, other drugs, compounds and /or materials used in combination with the particular compounds employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated” (Page 31). Further, differences in concentration or temperature [or schedules] will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature [or schedule] is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See MPEP 2144.05 II (A). Regarding criticality, see MPEP 716.02(d) (II).
One of ordinary skill in the art would expect success in treating KRAS-mutant cancers with voruciclib in the forms taught by Haudenschild and Sivakumar according to the dosing schedules taught by Sivakumar because Haudenschild and Sivakumar teach acceptable salts for administration to a patient and Sivakumar allows great variation in regimens depending on the patient, disease, and voruciclib form. Therefore, one of skill in the art would find it obvious to use the dosing forms to better deliver the API to a patient to treat the claimed disease before the effective filing date of the instant application. The resultant crystals would be expected to have peaks associated with the obvious cocrystal polymorphs upon formation as claimed.
Claims 1-2, 7-8, 10-14, 16, 18, 20, 22, 24, 26, 28, and 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over Blake as applied to Claims 1-2 and 4-8 view of Haudenschild (WO2019209825, published 10/31/2019), Thakral (Mol. Pharmaceutics 2016, 13, 4141−4151), and Sivakumar (WO2007148158, published 12/27/2007).
Blake does not teach crystal polymorphs or cocrystals or dosing regimens of voruciclib.
Haudenschild teaches salts of voruciclib including oxalates, malonates, and phosphates for administration (Para 50).
Thakral teaches with respect to drug salt formation that “the napadisylate salt is a hemisalt, two drug molecules are associated with one napadisylate molecule”, making for more economical drug delivery in that only one-half equivalent of each coformer is necessary to form a crystal with a molecule of voruciclib (Page 4145).
Sivakumar teaches crystal forms of voruciclib with coformers like HCl, phosphate and oxalate for administration to treat cancers (Abstract, Page 10). 5-500mg of the API or its salt crystal can be administered to a patient daily. “Actual dosage levels of the active ingredients in the pharmaceutical compositions of this invention may be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration without being toxic to the patient.” A multitude of factors are considered including “activity of the particular compound of the present invention employed, or the salt thereof, the route of administration, the time of administration, the rate of excretion of the particular compound being employed, the duration of the treatment, other drugs, compounds and /or materials used in combination with the particular compounds employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated” (Page 31). Further, differences in concentration or temperature [or schedules] will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature [or schedule] is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See MPEP 2144.05 II (A). Regarding criticality, see MPEP 716.02(d) (II).
One of ordinary skill in the art would expect success in treating KRAS-mutant cancers with voruciclib in the forms taught by Haudenschild and Sivakumar according to the dosing schedules taught by Sivakumar because Haudenschild and Sivakumar teach acceptable salts for administration to a patient and Sivakumar allows great variation in regimens depending on the patient, disease, and voruciclib form. Therefore, one of skill in the art would find it obvious to use the dosing forms to better deliver the API to a patient to treat the claimed disease before the effective filing date of the instant application. The resultant crystals would be expected to have peaks associated with the obvious cocrystal polymorphs upon formation as claimed.
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.
PROVISIONAL:
Claims 1-2, 6-7, 11-12, 24, 26, 28, and 30-31 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1, 5, 19-22, 25, 27-28, 30-33, 42, 44-46, 48, 50, and 53 of copending Application No. 18554497 (hereinafter referred to as Gold).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to a method of treating KRAS-mutant cancer with crystal forms of malonate-voruciclib with the same effective amounts and treatment cycles; e.g., 14 days on, 14 days off.
Regarding the claims directed to compositions of matter, In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010). See MPEP 804 (II) (B) (1). Gold teaches the following use: “A method of treating a hyperproliferative disease or disorder in a subject, the method comprising administering to the subject a therapeutically effective amount of voruciclib, wherein the hyperproliferative disease or disorder is a KRAS mutant cancer… The method of clause 5, wherein the KRAS mutant cancer is characterized by a mutation selected from G12A, G12C, G12D, G12S, G12V, G13C, G13D, and Q61H” (Spec: Para 145-146).
Since both applications teach methods of treating KRAS-mutant cancers with voruciclib, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of Gold.
This is a provisional nonstatutory double patenting rejection.
Claims 1-2, 4-8, 10-14, 16, 18, 20, 22, 24, 26, 28, and 30-31 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1, 5, 19-22, 25, 27-28, 30-33, 42, 44-46, 48, 50, and 53 of copending Application No. 18554497 (hereinafter referred to as Gold) in view of Burrows (WO2020046966, published 5/03/2020 claiming priority though 62/723,368 to 8/27/2018), Duncan (WO2020210760, published 10/15/2020 claiming priority to 4/11/2019 through 62/832,637), Haudenschild (WO2019209825, published 10/31/2019), Thakral (Mol. Pharmaceutics 2016, 13, 4141−4151), and Sivakumar (WO2007148158, published 12/27/2007).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to a method of treating KRAS-mutant cancer with crystal forms of malonate-voruciclib with the same effective amounts and treatment cycles; e.g., 14 days on, 14 days off.
Regarding the claims directed to compositions of matter, In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010). See MPEP 804 (II) (B) (1). Gold teaches the following use: “A method of treating a hyperproliferative disease or disorder in a subject, the method comprising administering to the subject a therapeutically effective amount of voruciclib, wherein the hyperproliferative disease or disorder is a KRAS mutant cancer… The method of clause 5, wherein the KRAS mutant cancer is characterized by a mutation selected from G12A, G12C, G12D, G12S, G12V, G13C, G13D, and Q61H” (Spec: Para 145-146).
Gold fails to teach dependent limitations like crystal forms, particular additional agents, and cancer variants.
Burrows teaches in Claims 1 and 49-50 on Page 123 and 133 treating a KRAS mutant cancer comprising administering an MAPK inhibitor and a second therapeutic agent, a CDK4/6 inhibitor, voruciclib, the same compound as instant Formula Ib. The MAPK pathway inhibitor includes Ras inhibitors like MRTX849 and AMG510 (Para 164-165). Figure 1 depicts particular KRAS-mutant NSCLC variants to be treated, including G12C, G12D, Q61H, and G12V (Abstract). Other KRAS-mutant cancers taught to be treated include breast, pancreatic, and AML cancer (Para 82).
Duncan teaches crystal forms of voruciclib including free base, HCl, malonate, dibenzoyl-tartrate, phosphate, oxalate, and napadisylate (Para 16-50). XRPD patterns are given in Para 4-8.
Duncan teaches dosing amounts of the compound and its cocrystals up to 1000mg and discrete amounts encompassed thereby once per day (Para 406 and 437-442). Dosing every other day or once a week is taught. Continuous dosing for 14 days is taught; dosing for 6, 7, 10, 14, and 28 days is also described (Para 434-436). “The specific dose will vary depending on the particular compounds chosen, the dosing regimen to be followed, whether the compound is administered in combination with other compounds, timing of administration, the tissue to which it is administered, and the physical delivery system in which the compound is carried” and “weight, age and gender of the subject” (Para 365). Therefore, a practitioner of ordinary skill would find it obvious to continually administer the claimed compound for 14 days and pause administration for the next 14 depending on toxicity levels of the drug or polymorph or cocrystal and certain patient factors when treating a KRAS-mutant cancer, the mutation possibly being present in a multitude of cancer types. Further, differences in concentration or temperature [or schedules] will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature [or schedule] is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See MPEP 2144.05 II (A). Regarding criticality, see MPEP 716.02(d) (II). One of ordinary skill in the art would expect success in treating KRAS-mutant cancers with voruciclib according to the dosing schedules taught by Duncan before the effective filing date because Duncan allows great variation in regimens depending on the patient, disease, and voruciclib form.
Haudenschild teaches salts of voruciclib including oxalates, malonates, and phosphates for administration (Para 50).
Thakral teaches with respect to drug salt formation that “the napadisylate salt is a hemisalt, two drug molecules are associated with one napadisylate molecule”, making for more economical drug delivery in that only one-half equivalent of each coformer is necessary to form a crystal with a molecule of voruciclib (Page 4145).
Sivakumar teaches crystal forms of voruciclib with coformers like HCl, phosphate and oxalate for administration to treat cancers (Abstract, Page 10). 5-500mg of the API or its salt crystal can be administered to a patient daily. “Actual dosage levels of the active ingredients in the pharmaceutical compositions of this invention may be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration without being toxic to the patient.” A multitude of factors are considered including “activity of the particular compound of the present invention employed, or the salt thereof, the route of administration, the time of administration, the rate of excretion of the particular compound being employed, the duration of the treatment, other drugs, compounds and /or materials used in combination with the particular compounds employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated” (Page 31). Further, differences in concentration or temperature [or schedules] will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature [or schedule] is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." See MPEP 2144.05 II (A). Regarding criticality, see MPEP 716.02(d) (II).
One of skill in the art seeking to treat KRAS mutant cancers would select those varieties identified by Burrows to treat with the Gold method and compound because both Gold and Burrows identify the claimed API as an effective pharmaceutical agent for the claimed cancers and variants. One would expect success in forming and using the crystals using coformers described in the foregoing references because voruciclib is taught to be formulated for dosing as a cocrystal and a large degree of flexibility in dosing is extended to the medical practitioner administering the API due to complex patient and disease factors. The resultant crystals would be expected to have peaks associated with the obvious cocrystal polymorphs upon formation as claimed.
Since both applications teach methods of treating KRAS-mutant cancers with voruciclib, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of Gold.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowable.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Richard G. Peckham whose telephone number is (703)756-4621. The examiner can normally be reached 8:30am - 4:30pm EST.
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/RICHARD GRANT PECKHAM/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627