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 .
Priority
This application is a national stage application under 35 U.S.C. § 371 of International Application No. PCT/US2020/060549, filed 11/13/2020, which claims the priority benefit of PRO Application No. 62/935,448, filed 11/14/2019.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 05/12/2022, 06/01/2022,
10/20/2023, 12/01/2023, 10/31/2024, and 11/12/2024 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
The listing of references in the specification (Specification pgs. 30-38) is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Status of the Application
Claims 14, 23, 26, 28-29, 48, 50-61, and 64-65 are pending. Claim 57 has been amended. Claims 14, 23, 26, 28-29, and 48 have been withdrawn. Claims 1-13, 15-22, 24-35, 27, 30-47, 49, and 62-63 have been cancelled. Claims 50-61 and 64-65 are currently under examination.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (Specification, pg. 30). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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.
(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 50-54, and 56-59, are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Rathinavelu (Anti-cancer effects of F16: A novel vascular endothelial growth factor receptor-specific inhibitor).
Rathinavelu teaches the anti-angiogenic drug l,3-dioxo-2,3-dihydro-lH-isoindol-4-yl) amide, named F16 used for treating solid tumors by inhibiting angiogenesis through direct binding with VEGFR-2 and it's use in combination with cytotoxic agents including Taxol, a known chemotherapeutic compound (introduction, page 2, 2nd col. Para 1-2). Rathinavelu et al. also teach the compound of Fl6, administered as a 100 mg/kg dose in combination cancer
therapy with the chemotherapeutic compound Taxol in a 10 mg/kg dose to inhibit tumor growth
(fig. 7, page 9). The teachings of Rathinavelu anticipate the limitations of a pharmaceutical
composition for treatment of delaying progression of brain cancer, delaying intracranial
progression of glioblastoma multiforme (GBM), and a brain tumor comprising a
therapeutically effective dosage of F16, isoindole (1,3-dioxy-2, 3-dihydro-lH-isoindol-4-yl)-
amide) and further comprising a pharmaceutical carrier. Claims 51-56 are dependent on claim
50, claims 58-61 are dependent on claim 57, claim 63 is dependent on claim 62, and wherein all
claims are drawn to compositions having an intended use rather than method of using type
claims. See MPEP 2111.02 (II) and MPEP 2131.03 Anticipation of Ranges.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 50-61 and 64-65 are rejected under 35 U.S.C. 103 as being unpatentable over Rathinavelu (Anti-cancer effects of F16: A novel vascular endothelial growth factor receptor-specific inhibitor) in view of Lee (Combined inhibition of vascular endothelial growth factor receptor signaling with temozolomide enhances cytotoxicity against human glioblastoma cells via downregulation of Neuropilin-1).
The instant claims are directed to a pharmaceutical composition comprising F16, isoindole (1,3-dioxy-2, 3-dihydro-1H-isoindol-4-yl)-amide) in a pharmaceutical carrier further comprising the chemotherapeutic agent of temozolomide (TMZ).
Rathinavelu et al. teach the compound of Fl6, administered as a 100 mg/kg dose in combination cancer therapy with the chemotherapeutic compound Taxol in a 10 mg/kg dose to inhibit tumor growth (fig. 7, page 9). Rathinavelu also teaches that compound Fl6 exerts inhibitory effects on angiogenesis and anti-angiogenic therapy and has added value to traditional chemotherapy for solid tumors due to the suppression of tumor invasion and metastasis by inhibiting VEGF-driven migration of endothelial cells (pg. 9, col. 1). Rathinavelu discloses the role VEGFR-2 and PAK have on human gliomas and discloses Fl6 influences a decline in p-FAK level associated with the rapid dissolution of cell (cytoskeletal) integrity, disintegration of cell adhesion molecules and initiation of cell migration and related events such as metastasis in cancer cells (page 10, col. 2).
However, Rathinavelu et al. fails to disclose temozolomide as the additional chemotherapeutic administered in a 50 mg/kg per body weight dose.
Lee et al. teach synergistic action of temozolomide (TMZ) and anti-VEGF therapy in GBM cells in four human GBM cell lines: TMZ-sensitive U251-MG and U373-MG cells, and TMZ-resistant CRT-MG and LN215- MG cells, and that treatment of TMZ along with a sublethal dosage range of SU1498, a chemical inhibitor of the VEGF receptor signaling, induced significant cell death in both TMZ-sensitive and TMZ-resistant GBM cells without changing the status of the MGMT promoter methylation (Abstract). Lee discloses “TMZ can be orally administered with excellent bioavailability and efficiently crosses the blood–brain barrier. Due to its favorable pharmacokinetic properties, TMZ is used as an effective chemotherapeutic agent against primary brain tumors including GBM. In the present study, we investigated the synergistic action and its molecular mechanism of TMZ and VEGF antagonists in human GBM cells to test the potential use of VEGF antagonists as adjuvant options for overcoming the resistance to TMZ treatment” (Introduction, pg. 29-30).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the instant application, to combine the use of a TMZ and VEGF inhibitor in a composition for the treatment of GBM as disclosed by Lee wherein a skilled artisan would select the VEGFR inhibitor compound of F16 disclosed by Rathinavelu because F16 demonstrated synergistic effects when combined with TMZ, specifically the desirable property of overcoming the resistance in TMZ treatment.
Regarding the limitations “composition” “pharmaceutical”– it is noted that these claims merely recite properties of the anticipated compounds. “Products of an identical chemical composition cannot have mutually exclusive properties.” Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F. 2d 705, 709, 15 USPQd 1655, 1658 (Fed. Cir. 1990). Since the prior art teaches a product of identical chemical composition to that claimed, and the application discloses that all of the claimed compositions have the claimed properties, these limitations are also anticipated. Since the prior art teaches the identical chemical structure, the properties applicant claims are necessarily present. In re Spada, 911 F. 2d 705, 709, 15 USPQd 1655, 1658 (Fed. Cir. 1990). Since the prior art teaches a product of identical chemical composition to that claimed, and the prior art discloses that all of the claimed compositions have the claimed properties and no additional components are claimed (such as an excipient, adjuvant, carrier, etc.), these limitations are also anticipated. Therefore, the claims are anticipated by the aforementioned compounds, capable of being used with the claimed intended uses of ‘composition’ and ‘pharmaceutical’ as described herein.
MPEP 2111.02(II) provides the following instruction for interpreting the preamble of a claim: “During examination, statements in the preamble reciting the purpose or intended use of the claimed invention must be evaluated to determine whether the recited purpose or intended use results in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art. If so, the recitation serves to limit the claim.” If a prior art structure is capable of performing the intended use as recited in the preamble, then it meets the claim. See, e.g., In re Schreiber, 128 F.3d 1473, 1477, 44 USPQ2d 1429, 1431 (Fed. Cir. 1997). Since the compositions taught by the prior art do not have any structural difference from the claimed compositions and the prior art compositions are capable of the intended uses, those limitations are also anticipated, as discussed herein. As such, the claims are directed to the same invention.
A person of ordinary skill in the art would have been motivated to administer the compound of F16 to a subject in need thereof for its effects on cancer angiogenesis, VEGF and the favorable results of a combination therapy with a chemotherapy agent based on the disclosures of Rathinavelu, specifically Rathinavelu's teachings of VEGF receptors as targets in the treatment of glioblastomas would have further reinforced the motivation, especially in light of Lee’s disclosures of a combination therapy with TMZ and other standard treatments of glioblastoma including VEGF inhibitors. A person of ordinary skill would have had a reasonable expectation of success in treating glioblastoma from the cumulative effects of combining two compounds known in the prior art which are used for the same purpose. Therefore the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made based on the current record. See also MPEP 2144.06, MPEP 2112.01(I and II) and 2111.02(II).
Conclusion
All claims are rejected, no claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNESTO VALLE JR whose telephone number is (703)756-5356. The examiner can normally be reached 0730-1700 M-F EST, 1st Friday off.
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/E.V./Examiner, Art Unit 1623
/SAMANTHA L SHTERENGARTS/Primary Examiner, Art Unit 1623