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 § 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 – 10 are rejected under 35 U.S.C. 103 as being unpatentable over US Patent No. US 9018251 B2 to Harn et. al. (herein after Harn’251) in view of Huntoon et. al. ((2020), Meningioma: A Review of Clinicopathological and Molecular Aspects, Frontiers in Oncology, 10, 1 – 14).
Regarding claims 1 – 10, Harn’251 teach a method for reducing temozolomide-resistance of brain cancer cells in a subject comprising administering to the subject an effective amount of an active ingredient (Z)-butylidenephthalide of the structure
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(column 2 lines 27 – 31) wherein the compound is of instant formula (I); instant p = 0; instant R2 is propyl (claims 1, and 3 – 4). Furthermore, Harn’251 teach that the most common brain tumors can be divided into gliomas and non-gliomas; and that non-gliomas include meningiomas (claim 1) (column 3 lines 66 – 67 and column 4 lines 2 – 3). Additionally, Harn’251 teach that compositions comprising (Z)-butylidenephthalide can be administrated by any suitable approach which includes oral, subcutaneous, nasal or intravenous (claim 6) (column 4 lines 52 – 55).
Furthermore, Harn’251 teach in example 7 that as the dosage of (Z)-butylidenephthalide increased from 0 – 400 µM, (Z)-butylidenephthalide was able to inhibit the growth (claim 5) of cancer cell lines DBTRG, 8401, 8901, and G5T/VGH (column 11 lines 38 – 43). Moreover, Harn’251 teach that in Balb/c nude mice with GBM22-TMZ tumors, a glioma cancer cell line resistant to temozolomide, when compared to the solvent of monotherapy mice that received the combination of (Z)-butylidenephthalide and temozolomide, a methylating agent (claims 8 – 10) (column 1 line 58), had a relative tumor size of 1.5 (fold) (column 14 Table 7 and Figure 11A). Additionally, Harn’251 teach that in example 10, (Z)-butylidenephthalide and polylactic acid-co-glycolic acid were mixed to form round wafers (claim 7) that (column 15 lines 5 – 18), that was administered to mice with GBM22-TMZ tumors in example 11 for survival analysis (column 16 lines 5 – 51). Thus Harn’251 teach the effectiveness of (Z)-butylidenephthalide especially in combination with another anticancer agent for the treatment of brain tumors, specifically malignant gliomas.
Even though, Harn’251 failed to exemplify a method for treating meningiomas (claim 1) wherein the meningiomas are at least one of benign meningiomas, atypical meningiomas, and malignant meningiomas (claim 2); as stated above, Harn’251 does teach that there are a subset of brain tumors that are non-gliomas and are meningiomas.
Nevertheless, Huntoon et. al. teach that meningiomas (claim 1) represent 37.6% of all primary brain tumors in adults, making them the most common type of intracranial tumor with an incidence of 8.83 per 100,000 in the most recent Central Brain Tumor Registry of the United States (page 1 paragraph 1). Additionally, Huntoon et. al. teach that meningiomas are generally slow growing lesions with a linear growth rate of 2–4 mm/year for asymptomatic meningiomas (claim 2) (page 2 column 1 paragraph 2). Moreover, Huntoon et. al. teach that the estimated 10-year survival (overall 61.7%) for malignant meningiomas (claim 2) is very much dependent on age; 10-year relative survival is estimated to be around 76.8% for 20–44 year olds, while it is only 39.5% for patients age 75 years and older (page 2 column 1 paragraph 3).
Furthermore, Huntoon et. al. teach that malignant meningioma of the spine has a higher 10-year relative survival of 73.4% when compared to the survival rate of 55.7% for intracranial tumors (page 2 column 1 paragraph 3). Additionally, Huntoon et. al. teach that in terms of recurrence differences with grade, the five-year progression free survival (PFS) for a WHO grade I tumors is ~90% after gross total resection (GTR), Grade II are ~ 60%–90%, whereas grade III PFS after GTR is 28% (page 2 column 1 paragraph 3). Huntoon et. al. teach that these recurrences translate into meningioma-specific mortality in these patients, with 10-year overall survival rates of 53% for grade II patients and 0% for grade III patients, despite aggressive therapeutic efforts (page 2 column 1 paragraph 3).
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 Harn’251 for the application of (Z)-butylidenephthalide in view of Huntoon et. al. that is in the treatment of meningiomas especially malignant meningiomas. One of ordinary skill in the art would have been motivated to make this modification to improve the survival rate of a patient especially if the patient has a malignant meningiomas. One of ordinary skill in the art would have had a reasonable expectation of success because (Z)-butylidenephthalide with a methylating agent was effective in reducing the tumor size for glioma a more aggressive brain tumor.
Claims 11 - 20 are rejected under 35 U.S.C. 103 as being unpatentable over US Patent No. US 9018251 B2 to Harn et. al. (herein after Harn’251) in view of Huntoon et. al. ((2020), Meningioma: A Review of Clinicopathological and Molecular Aspects, Frontiers in Oncology, 10, 1 – 14).
Regarding claims 11 – 20, Harn’251 teach a method for reducing temozolomide-resistance of brain cancer cells in a subject comprising administering to the subject an effective amount of an active ingredient (Z)-butylidenephthalide of the structure
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(column 2 lines 27 – 31) wherein the compound is of instant formula (I); instant p = 0; instant R2 is propyl (claims 11, and 13 – 14). Furthermore, Harn’251 teach that the most common brain tumors can be divided into gliomas and non-gliomas; and that non-gliomas include meningiomas (claim 11) (column 3 lines 66 – 67 and column 4 lines 2 – 3). Additionally, Harn’251 teach that compositions comprising (Z)-butylidenephthalide can be administrated by any suitable approach which includes oral, subcutaneous, nasal or intravenous (claim 6) (column 4 lines 52 – 55).
Furthermore, Harn’251 teach in example 7 that as the dosage of (Z)-butylidenephthalide increased from 0 – 400 µM, (Z)-butylidenephthalide was able to inhibit the growth (claim 15) of cancer cell lines DBTRG, 8401, 8901, and G5T/VGH (column 11 lines 38 – 43). Moreover, Harn’251 teach that in Balb/c nude mice with GBM22-TMZ tumors, a glioma cancer cell line resistant to temozolomide, when compared to the solvent of monotherapy mice that received the combination of (Z)-butylidenephthalide and temozolomide, a methylating agent (claims 18 – 20) (column 1 line 58), had a relative tumor size of 1.5 (fold) (column 14 Table 7 and Figure 11A). Additionally, Harn’251 teach that in example 10, (Z)-butylidenephthalide and polylactic acid-co-glycolic acid were mixed to form round wafers (claim 17) that (column 15 lines 5 – 18), that was administered to mice with GBM22-TMZ tumors in example 11 for survival analysis (column 16 lines 5 – 51). Furthermore, Harn’251 teach that in example 11, mice that received (Z)-butylidenephthalide and temozolomide had a 100 % survival rate even at 30 days (column 16 Table 8). the Thus Harn’251 teach the effectiveness of (Z)-butylidenephthalide especially in combination with another anticancer agent for the treatment of brain tumors, specifically malignant gliomas.
However, Harn’251 fail to teach a method for reducing meningiomas recurrence rate (claim 11) wherein the meningiomas are at least one of benign meningiomas, atypical meningiomas, and malignant meningiomas (claim 12).
Nevertheless, Huntoon et. al. teach that meningiomas (claim 11) represent 37.6% of all primary brain tumors in adults, making them the most common type of intracranial tumor with an incidence of 8.83 per 100,000 in the most recent Central Brain Tumor Registry of the United States (page 1 paragraph 1). Additionally, Huntoon et. al. teach that meningiomas are generally slow growing lesions with a linear growth rate of 2–4 mm/year for asymptomatic meningiomas (claim 12) (page 2 column 1 paragraph 2). Moreover, Huntoon et. al. teach that the estimated 10-year survival (overall 61.7%) for malignant meningiomas (claim 12) is very much dependent on age; 10-year relative survival is estimated to be around 76.8% for 20–44 year olds, while it is only 39.5% for patients age 75 years and older (page 2 column 1 paragraph 3).
Furthermore, Huntoon et. al. teach that malignant meningioma of the spine has a higher 10-year relative survival of 73.4% when compared to the survival rate of 55.7% for intracranial tumors (page 2 column 1 paragraph 3). Additionally, Huntoon et. al. teach that in terms of recurrence differences (claim 11) with grade, the five-year progression free survival (PFS) for a WHO grade I tumors is ~90% after gross total resection (GTR), Grade II are ~ 60%–90%, whereas grade III PFS after GTR is 28% (page 2 column 1 paragraph 3). Huntoon et. al. teach that these recurrences translate into meningioma-specific mortality in these patients, with 10-year overall survival rates of 53% for grade II patients and 0% for grade III patients, despite aggressive therapeutic efforts (page 2 column 1 paragraph 3).
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 Harn’251 for the application of (Z)-butylidenephthalide in view of Huntoon et. al. that is for a method of reducing meningioma recurrence rate especially malignant meningiomas. One of ordinary skill in the art would have been motivated to make this modification to improve the survival rate of a patient especially if the patient has a malignant meningiomas. One of ordinary skill in the art would have had a reasonable expectation of success because (Z)-butylidenephthalide with a methylating agent was effective in prolonging mice survival at 30 days in comparison to the monotherapy.
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, 3 – 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, and 6 – 7 of U.S. Patent No. US 9018251 B2 to Harn et. al. (herein after Harn’251) in view of Huntoon et. al. ((2020), Meningioma: A Review of Clinicopathological and Molecular Aspects, Frontiers in Oncology, 10, 1 – 14).
Harn’251 recite a method for treating a glioma in a subject, comprising: administering to the subject (1) an effective amount of the (Z)-butylidenephthalide isomer of formula (I) substantially free from the (E)-butylidenephthalide isomer of formula (I), wherein the (Z)-butylidenephthalide isomer of formula (I) is in the form of the (Z)-butylidenephthalide isomer, a pharmaceutically acceptable salt of the (Z)-butylidenephthalide isomer, a pharmaceutically acceptable ester of the (Z)-butylidenephthalide isomer, or a combination thereof:
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(instant claims 1, and 3 – 4 ) and (2) an effective amount of temozolomide (instant claims 8 – 10), wherein (1) and (2) together provide a combination index less than 1 (reference claim 1). Harn’251 recite the method as claimed in (reference) claim 1, wherein the (Z)butylidenephthalide isomer of formula (I) and temozolomide are administered together, separately, or successively (reference claim 6; instant claims 8 – 10). Moreover, Harn’251 recite the method as claimed in (reference) claim 1, wherein the (Z)butylidenephthalide isomer of formula (I) is administered orally or administered by subcutaneous or intravenous injection (instant claim 6) and temozolomide is administered orally (reference claim 7).
However, Harn’251 fails to recite a method for treating meningiomas (claim 1) wherein the meningiomas are at least one of benign meningiomas, atypical meningiomas, and malignant meningiomas (claim 2).
Nevertheless, Huntoon et. al. teach that meningiomas (instant claim 1) represent 37.6% of all primary brain tumors in adults, making them the most common type of intracranial tumor with an incidence of 8.83 per 100,000 in the most recent Central Brain Tumor Registry of the United States (page 1 paragraph 1). Additionally, Huntoon et. al. teach that meningiomas are generally slow growing lesions with a linear growth rate of 2–4 mm/year for asymptomatic meningiomas (instant claim 2) (page 2 column 1 paragraph 2). Moreover, Huntoon et. al. teach that the estimated 10-year survival (overall 61.7%) for malignant meningiomas (instant claim 2) is very much dependent on age; 10-year relative survival is estimated to be around 76.8% for 20–44 year olds, while it is only 39.5% for patients age 75 years and older (page 2 column 1 paragraph 3).
Furthermore, Huntoon et. al. teach that malignant meningioma of the spine has a higher 10-year relative survival of 73.4% when compared to the survival rate of 55.7% for intracranial tumors (page 2 column 1 paragraph 3). Additionally, Huntoon et. al. teach that in terms of recurrence differences with grade, the five-year progression free survival (PFS) for a WHO grade I tumors is ~90% after gross total resection (GTR), Grade II are ~ 60%–90%, whereas grade III PFS after GTR is 28% (page 2 column 1 paragraph 3). Huntoon et. al. teach that these recurrences translate into meningioma-specific mortality in these patients, with 10-year overall survival rates of 53% for grade II patients and 0% for grade III patients, despite aggressive therapeutic efforts (page 2 column 1 paragraph 3).
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 Harn’251 for the application of (Z)-butylidenephthalide in view of Huntoon et. al. that is in the treatment of meningiomas especially malignant meningiomas. One of ordinary skill in the art would have been motivated to make this modification to improve the survival rate of a patient especially if the patient has a malignant meningiomas. One of ordinary skill in the art would have had a reasonable expectation of success because (Z)-butylidenephthalide with a methylating agent was effective in reducing the tumor size for glioma a more aggressive brain tumor.
Conclusion
Claims 1 – 20 are rejected.
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/DAWANNA SHAR-DAY WHITE/Examiner, Art Unit 1627