DETAILED ACTION
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.
Claims 1 – 2, 4 – 6, and 9 – 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US Patent Number US 8450479 B2 to Stevens et. al. (Stevens’479).
Regarding claims 1 – 2, 4 – 6, and 9 – 12, Stevens’479 teach that the present invention pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit cell proliferation, and in the treatment of proliferative disorders such as cancer. See column 1 lines 22 – 25. Specifically, Stevens’479 teach compound EE-001 of structure
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where X = O; R1 = -C(=O)NH2 where Rb = Rc = H; and R2 = R3 = H. See column 15 lines 7 – 16. See claims 1 and 6. See claim 2 limitation X is O. See claim 4 limitation R2 is H. See claim 5 limitation for a compound where R3 is H. Additionally, Stevens’479 teach compound EE-002 of structure
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where X = O; R1 = -C(=O)NH2 where Rb = Rc = H; R2 = CH3; and R3 = H. See column 15 lines 7 – 16. See claims 1 and 6. See claim 2 limitation X is O. See claim 5 limitation for a compound where R3 is H. Stevens’479 teach that compounds of the disclosure, which include EE-001 and EE-002, can be administered to a subject by any convenient route of administration, which includes orally or intravenously. See column 60 line 61 and column 61 line 2.
Moreover, Stevens’479 teach that the administration of compositions comprising compounds of the disclosure, which include EE-001 and EE-002, can be effected in one dose, continuously or intermittently (e.g., in divided doses at appropriate intervals) throughout the course of treatment. See column 65 lines 1 – 3. Additionally, Stevens’479 teach that there are methods of determining the most effective means and dosage of administration are well known to those of skill in the art and will vary with the formulation used for therapy, the purpose of the therapy, the target cell(s) being treated, and the subject being treated. See column 65 lines 3 – 8. Furthermore, Stevens’479 teach that single or multiple administrations can be carried out with the dose level and pattern being selected by the treating physician, veterinarian, or clinician. See column 65 lines 8 – 10. Stevens’479 teach that in general, a suitable dose of the compounds of the disclosure, which include EE-001 and EE-002, which is in the range of about 10 μg to about 250 mg (more typically about 100 μg to about 25 mg) per kilogram body weight of the subject per day. See column 65 lines 11 – 14.
Furthermore, Stevens’479 teach that 50% inhibition of control cell growth (GI50) was determined for each compound of the disclosure, which includes EE-001 and EE-002, against Glioma cell lines, SNB19 and U373, both MGMT transfected (i.e., SNB19M and U373M) and vector controls (i.e.,SNB19V and U373V); colorectal carcinoma cell lines, HCT116, HT29, and DLD1; melanoma cell line, SKMEL-28; breast cell line, MCF-7; and normal human fetal lung fibroblast cell line, MRC-5. See column 109 lines 25 – 30 and column 110 lines 15 – 17. See claim 10 limitation for a method of treating cancer. See claim 11 limitation for method where the cancer is colon cancer, melanoma, or breast cancer. Additionally, Stevens’479 teach that serial dilutions in tissue culture medium of a 100 mM stock of test compound in DMSO were prepared immediately before each assay to ten times the final concentrations required, and then 20 μL was added to each well (200 μL total media per well) to achieve final concentrations of 0.5 μM, 1 μM, 5 μM, 10 μM, 50 μM, 100 μM, 500 μM, and 1000 μM. See column 109 lines 47 – 53 and column 116 Table 6. See claim 9 limitation for a composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient. See claim 12 limitation for a method where the concentration of the compound touching the cell is 1 nM to 10 μM. Additionally, Stevens’479 teach that as shown by the data in Table 6 (above), compound EE-001 is more potent than TMZ in the glioma MGMT- and MGMT+ lines as well as other lines ( e.g., colon, melanoma); and compound EE-001 is a particularly efficacious compound, independent of the MGMT repair status of cell line. See column 125 lines 5 – 10.
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 13 – 14 are rejected under 35 U.S.C. 103 as being unpatentable over US Patent Number US 8450479 B2 to Stevens et. al. (Stevens’479).
The teachings of Stevens’479 as they relate to claims 1 and 10, from which claims 13 – 14 depend, are given previously in this office action and are fully incorporated here.
While, Stevens’479 fails to specifically teach a method where the compound is administered once a day, twice a day or thrice a day or a method where the compound is administered orally, intravenously, or intracranially, as taught above, Stevens’479 does teach that compounds of the disclosure, which include EE-001 and EE-002, can be administered to a subject by any convenient route of administration, which includes orally or intravenously. See column 60 line 61 and column 61 line 2. See claim 14 limitation for a method where the compounds id administered orally or intravenously.
Moreover, Stevens’479 does teach that the administration of compositions comprising compounds of the disclosure, which include EE-001 and EE-002, can be effected in one dose, continuously or intermittently (e.g., in divided doses at appropriate intervals) throughout the course of treatment. See column 65 lines 1 – 3. Additionally, Stevens’479 teach that there are methods of determining the most effective means and dosage of administration are well known to those of skill in the art and will vary with the formulation used for therapy, the purpose of the therapy, the target cell(s) being treated, and the subject being treated. See column 65 lines 3 – 8. Furthermore, Stevens’479 teach that single or multiple administrations can be carried out with the dose level and pattern being selected by the treating physician, veterinarian, or clinician. See column 65 lines 8 – 10. Stevens’479 teach that in general, a suitable dose of the compounds of the disclosure, which include EE-001 and EE-002, which is in the range of about 10 μg to about 250 mg (more typically about 100 μg to about 25 mg) per kilogram body weight of the subject per day. See column 65 lines 11 – 14.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to modify the method of Stevens’479 for a method of treating cancer comprising administering either compound EE-001 or EE-002 either orally or intravenously at a dosage interview of once daily, twice daily, or thrice daily. One of ordinary skill in the art would have been motivated to make this modification and have a reasonable expectation of success because the prior art taught teach that single or multiple administrations can be carried out with the dose level and pattern being selected by the treating physician, veterinarian, or clinician.
Claims 3, 7 – 8, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over US Patent Number US 8450479 B2 to Stevens et. al. (Stevens’479) as applied to claims 1 – 2, 4 – 6, and 9 – 14 above, and further in view of Meanwell ((2011), Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design, J Med Chem, 54, 2529 – 2591).
The teachings of Stevens’479 as they relate to claims 1, 6, and 10, from which claims 3, 7 – 8, and 15 depend, are given previously in this office action and are fully incorporated here.
However, Stevens’479 fails to teach a compound where R1 is -C(=O)-N[(C1-C6)alkyl]2 or -C(=O)-NH(C1-C6)alkyl. See claim 3. Moreover, Stevens’479 fails to teach a compound where Rb is -(C1-C6)alkyl, Rc is -(C1-C6)alkyl, and R2 is -(C1-C6)alkyl; or wherein Rb, Rc and R2 are CH3. See claim 7. Furthermore, Stevens’479 fails to teach a compound where the compound is:
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. See claim 8. Additionally, Stevens’479 fails to teach a method where the compound is 3-(but-2-yn-1-yl)-N,N-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide (TABZ), that is a compound of structure
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. See claim 15.
Nevertheless, Meanwell teaches that in the contemporary practice of medicinal chemistry, the development and application of bioisosteres have been adopted as a fundamental tactical approach useful to address a number of aspects associated with the design and development of drug candidates. See page 2529 column 1 paragraph 1. Additionally, Meanwell teaches that bioisosteres are typically less than exact structural mimetics and are often more alike in biological rather than physical properties. See page 2529 column 1 paragraph 1. Moreover, Meanwell teaches that H, F, OH, NH2, and CH3 are classical monovalent bioisosteres. See page 2530 column 1 Table 1. Thus Meanwell suggest the ability to substitute H for CH3 with a reasonable expectation that compounds with either H or CH3 would have similar biological properties.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filling date of the instant application to modify either compound EE-001 or EE-002 of Stevens’479 in view of Meanwell, that is to replace 1 and/or 2 H atom of the amide with a CH3 group to get compounds of the following structures
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. One of ordinary skill in the art would be motivated to make this modification and have a reasonable expectation of success because both H and CH3 are classical monovalent bioisosteres and would be reasonable expected to at least have the same biological properties.
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 – 8, 10 – 11, and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 6 of U.S. Patent No. US 12234240 B2 to Hergenrother et. al. (Hergenrother’240).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the invention of Hergenrother’240 and the instant application direct to compounds of Formula (I)
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. The genus of compounds recited by the reference claims of Hergenrother’240 overlaps with the subgenus of compounds recited in examined claims 1 – 8, and 15. In particular, Hergenrother’240 recites a compound of Formula (I)
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where R1-3, and X are defied. See reference claims 1 – 4. See examined claims 1 – 8, and 15.
With regard to examined claims 10 – 11, Hergenrother’240 recites a method for treating cancer in a subject, where the method comprises administering to the subject in need thereof a therapeutically effective amount of a compound of (reference) claim 1, or a pharmaceutically acceptable salt thereof. See reference claim 5. See examined claim 10. In particular, Hergenrother’240 recites a method for treating cancer where the cancer in glioblastoma. See reference claim 6. See examined claim 11.
Claims 9 – 10, and 12 – 14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, and 5 – 6 of U.S. Patent No. US 12234240 B2 to Hergenrother et. al. (Hergenrother’240) in view of US Patent Number US 8450479 B2 to Stevens et. al. (Stevens’479).
Hergenrother’240 recites a method for treating cancer in a subject, where the method comprises administering to the subject in need thereof a therapeutically effective amount of a compound of (reference) claim 1, or a pharmaceutically acceptable salt thereof. See reference claim 5. See examined claim 10.
However, Hergenrother’240 fails to recite a composition comprising a pharmaceutically acceptable excipient. See examined claim 9. Hergenrother’240 fails to recite a method where the dose of the compound is about 0.5 mg/kg to about 100 mg/kg of body weight per day; or wherein a dose of the compound administered is 5 mg/m2 to 1000 mg/m2 of body surface area; or wherein a unit dose of the compound administered is 5 mg to 1000 mg; or wherein a therapeutically effective concentration of the compound contacting the cancer is about 1 nM to about 10 μM. See examined claim 12. Moreover, Hergenrother’240 fails to recite a method where a dose of the compound is administered once per day, twice per day, or thrice per day. See examined claim 13. Furthermore, Hergenrother’240 fails to recite a method where the compound is administered orally, intravenously, or intracranially. See examined claim 14.
The teachings of Stevens’479 as they relate to the prior art rejections of examined claims 1 – 15, are given previously in this office action and are fully incorporated here.
Therefore, it would have been obvious before the effective filing date of the instant application to modify the invention of Hergenrother’240 for a method of treating cancer in view of Stevens’479 that is, to formulation the compound in a composition comprising pharmaceutically acceptable excipient a where the compound is further administered within the recited dosage ranges, dosage frequency, and administration routes. One of ordinary skill in the art would have been motivated to make this modification and have a reasonable expectation of success because the prior art taught teach that single or multiple administrations can be carried out with the dose level and pattern being selected by the treating physician, veterinarian, or clinician.
Conclusion
Claims 1 – 15 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAWANNA S WHITE whose telephone number is (703)756-4687. The examiner can normally be reached 7:00 am - 5:00 pm [EST] M - Th.
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/DAWANNA SHAR-DAY WHITE/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627
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