DETAILED ACTION
Claims 1-28 are currently pending and are examined on the merits herein.
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 .
Application Priority
This application filed 09/19/2024 is a 371 of PCT/US2023/016029 filed on 03/23/2023 which has PRO 63/323,053 filed on 03/23/2022.
Information Disclosure Statement
The information disclosure statement(s) (IDS) filed on 1/31/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS is being considered by the Examiner.
The following rejections are made:
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, 11, 16-17 and 27 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Arora et al. (Plasma and brain pharmacokinetics of letrozole and drug interaction studies with temozolomide in NOD-scid gamma mice and sprague dawley rats. Cancer Chemother Pharmacol. 2019 Jan;83(1):81-89. doi: 10.1007/s00280-018-3705-6. Epub 2018 Oct 24. PMID: 30357450).
Arora et al. teaches an aromatase inhibitor, letrozole, being investigated in experimental animal models as a novel treatment for high-grade gliomas (HGGs) and the potential PK interactions between letrozole and temozolomide (TMZ) in Sprague-Dawley rats. Exemplified are single dose administration of letrozole (4 mg/kg) with or without TMZ (20 mg/kg) via the intraperitoneal route. The combination of TMZ and letrozole may not have safety concerns, as no overt toxicity (body weight, lack of diet, neuromuscular toxicity and overall appearance) were observed in a sub-chronic 20 day toxicity study.
Claim Rejections - 35 USC § 103
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 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 3, 5-10, 15, 18, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Arora et al. (Plasma and brain pharmacokinetics of letrozole and drug interaction studies with temozolomide in NOD-scid gamma mice and sprague dawley rats. Cancer Chemother Pharmacol. 2019 Jan;83(1):81-89. doi: 10.1007/s00280-018-3705-6. Epub 2018 Oct 24. PMID: 30357450), as applied to claims 1-2, 4, 11, 16-17 and 27, in view of Ansel et al. (Pharmaceutical Dosage Forms and Drug Delivery Systems. 1995).
Arora et al. teaches an aromatase inhibitor, letrozole, being investigated in experimental animal models as a novel treatment for high-grade gliomas (HGGs) and the potential PK interactions between letrozole and temozolomide (TMZ) in Sprague-Dawley rats. Exemplified are single dose administration of letrozole (4 mg/kg) with or without TMZ (20 mg/kg) via the intraperitoneal route. The combination of TMZ and letrozole may not have safety concerns, as no overt toxicity (body weight, lack of diet, neuromuscular toxicity and overall appearance) were observed in a sub-chronic 20 day toxicity study.
While Arora teaches intraperitoneal animal studies, and that the standard of care for HGGs includes maximal safe tumor resection upon diagnosis, followed by adjuvant radiation and chemotherapy with TMZ, the reference fails to specify treatment of humans, the form of administration , and the specific dose and concentrations of the actives.
Ansel et al. teaches "absorption by the parenteral route is not only faster than after oral administration, but the blood levels of drug that result are far more predictable, because little is lost after subcutaneous or intramuscular injection, and virtually none by intravenous injection; this also generally permits the administration of smaller doses." Additionally, absorption of drugs after oral administration may occur at various body sites between the mouth and rectum. In general, the higher up a drug is absorbed along the length of the alimentary tract, the more rapid will be its action, a desirable feature in most instances. The oral cavity is used on certain occasions as the absorption site of certain drugs. Physically, the oral absorption of drugs is managed by allowing the drug substance to be dissolved with the oral cavity with infrequent or no swallowing until the taste of the drug has dissipated. Drugs capable of being absorbed in the mouth present themselves to the absorbing surface in a much more concentrated from than when swallowed, since drugs become progressively more diluted with gastrointestinal secretions and contents as they pass along the alimentary tract. Ansel et al. teaches compared with alternate routes, the oral route is considered the most natural, uncomplicated, convenient, and safe means of administering drugs.
It would have been obvious to one of ordinary skill in the art the time of the invention to interchange an administration mode from intraperitoneal to oral or parenteral. The motivation comes from the teaching of Ansel that compared with alternate routes, the oral route is considered the most natural, uncomplicated, convenient, and safe means of administering drugs and the parenteral route is faster and the blood levels of drug that result are far more predictable. Hence, a skilled artisan would have had reasonable expectation of successfully achieving similar efficacy and results.
With respect to human subject limitation of claim 3, the Examiner states the normal protocol before a drug is used in the clinic is that it must progress through a series of in vitro trials, first through animal studies then human. Hence, a skilled artisan would expect if the in vitro trials are efficacious then to move on to in vivo trials.
With respect to the dose amounts and concentrations of claims 7-9, it would have been obvious to one having ordinary skill in the art at the time the invention was made to modify the dosage, since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USP 233.
Claims 12-15, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Arora et al. (Plasma and brain pharmacokinetics of letrozole and drug interaction studies with temozolomide in NOD-scid gamma mice and sprague dawley rats. Cancer Chemother Pharmacol. 2019 Jan;83(1):81-89. doi: 10.1007/s00280-018-3705-6. Epub 2018 Oct 24. PMID: 30357450) in view of Ansel et al. (Pharmaceutical Dosage Forms and Drug Delivery Systems. 1995), as applied to claims 1-11, 15-18 and 27-28 in view of Rutledge et al. (Bevacizumab and Temozolomide Plus Radiation Regimen for (Glioblastoma Multiforme. Hosp Pharm. 2015 Sep;50(8):672-7. doi: 10.1310/hpj5008-672. Epub 2015 Sep 16. PMID: 26823616; PMCID: PMC4686471).
Arora et al. and Ansel are as discussed above.
Arora et al. and Ansel do not teach treatment with cancer chemotherapy and radiation therapy.
Rutledge et al. teaches concomitant temozolomide and radiation followed by maintenance temozolomide is recommended for adjuvant treatment of newly diagnosed glioblastoma multiforme (GBM). Bevacizumab is recommended in recurrent disease, as monotherapy or in combination with temozolomide. The studies reviewed utilized bevacizumab and temozolomide plus radiation as initial therapy in patients with newly diagnosed GBM.
It would have been obvious to one of ordinary skill in the art at the time of filing to incorporate the teachings of Rutledge et al. The motivation to incorporate radiation and bevacizumab is because Rutledge et al. teaches concomitant temozolomide and radiation followed by maintenance temozolomide is recommended for adjuvant treatment of newly diagnosed glioblastoma multiforme (GBM). Bevacizumab is recommended in recurrent disease, as monotherapy or in combination with temozolomide. The studies reviewed utilized bevacizumab and temozolomide plus radiation as initial therapy in patients with newly diagnosed GBM. A skilled artisan would have reasonable expectation of successfully treating glioblastoma.
Conclusion
No claims allowed.
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/LAYLA SOROUSH/ Primary Examiner, Art Unit 1622
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