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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/04/2026 has been entered.
Response to Arguments
Applicant's arguments filed 01/12/2026 have been fully considered but they are not persuasive. Applicants argument with respect to the 103 rejection of claim 1 over Jou et al. (US 20120129869 A1) in view of Guo et al. EML4-ALK induces epithelial-mesenchymal transition consistent with cancer stem cell properties in H1299 non-small cell lung cancer cells, Biochem and Biophysicial Research comm, February 2015, Pages 389-404 and Mondal et al. Matrix metalloproteinase-9 (MMP-9) and its inhibitors in cancer: A minireview, Euro Journal Med Chem, March 2020, Pages 1-7 is rendered moot on the basis of unexpected results over ALK inhibitors. Applicant argues synergistic effects of ALK inhibitors with MMP inhibitor of marimastat, and emphasizes examples 5-8 of the specification to further convey synergistic effects.
It is noted Claim 1 of claimed invention states any ALK inhibitor of EML4-ALK fusion protein in combination with marimastat. Thus applicant is stating the list of ALK inhibitor of EML4-ALK fusion protein in claim 6 are all synergistic with MMP inhibitor marimastat. The list of ALK inhibitors are of different structures, thus one skilled in the art would test multiple ALK inhibitor of EML4-ALK fusion protein with marimastat to test the synergistic effects. Applicant has not provided such examples outside of crizotinib and alectinib, thus the teachings of any ALK inhibitor of EML4-ALK fusion protein in combination with marimastat, as stated in claim 1, having unexpected synergistic results is not commensurate to the scope of the specifications as per MPEP 716.02(d) for unexpected results: Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). For the reasons above the 103 rejection is maintained.
Applicant has canceled claims 3, 8-9, 13, 18-19, 23, 25, 27, 29 and added claims 31-32. Claims 1, 4-6, 10-11, 14-16, 20-22, 24, 26, 28 and 30-32 is now evaluated on its merits
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, 4-6, 10-11, 14-16, 20-22, 24 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Jou et al. (US 20120129869 A1) in view of Guo et al. EML4-ALK induces epithelial-mesenchymal transition consistent with cancer stem cell properties in H1299 non-small cell lung cancer cells, Biochem and Biophysicial Research comm, February 2015, Pages 389-404 and Mondal et al. Matrix metalloproteinase-9 (MMP-9) and its inhibitors in cancer: A minireview, Euro Journal Med Chem, March 2020, Pages 1-7.
Regarding claims 1, 4-6, 10-11, 14-16, 20-22, 24 and 28, Jou teaches a method of diagnosing and treating lung cancer comprising steps of detecting ALK mutations from lung adenocarcinoma patients (relevant to claims 10 and 20) and detecting the tumorigenic activities and treating the ALK mutation lung adenocarcinoma by administration of an ALK inhibitor (claim 16). Jou teaches the ALK mutations from lung adenocarcinoma patients are expressed in H1299 cells lines which are EML4-ALK NSCLC cell lines (relevant to claims 21-22) (Fig. 4) are treated with an ALK inhibitors selected from WHI-P154, TAE684 and Crizotinib (relevant to claims 6, 16, 24 and 28).
In reference to claims 4-5 and 14-15, applicant’s specification page 11 paragraph 00058, EML4-ALK is known in the art with the absence of an inhibitor to be “of oncogenic RTK fusion protein in the tumor cells dramatically suppress signaling through the transmembrane RTKs by sequestration of downstream effectors for the transmembrane RTKs”. Thus, the teaching of Jou on treating cancer tumor cells associated ALK fusion protein which comprises inhibiting EML4-ALK read to the limitations of claims 4-5 and 14-15 and will inherently “ sequester GRB2 or SOS from the above EML4-ALK downstream effector for the transmembrane RTKs as per MPEP 2112.01 (II): "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
Jou does not teach the combination of a MMP inhibitor to treat EML4-ALK NSCLC.
Gou teaches the properties of EML4-ALK H1299 non-small lung cancer cells, in which MMP-2 and MMP-9, two crucial proteins involved in cancer cell metastasis, were significantly increased in cells of EML4-ALK expression compared with control cells. Additionally, EML4-ALK in H1299 cells attributed to increased expression of MMP2 and MMP9, modulating invasive migration during EMT (abstract, Page 400 2nd column 1st para.)
Mondal teaches MMP-9 is an important therapeutic approach for combating various diseases including lung cancer (abstract, fig. 5). Inhibitors of MMP-9 can be used as anticancer agents and inhibitors of MMP-9 includes Batimastat, Marimastat, Tanomastat, Rebimastat, Priomastat and Doxycycline (relevant to claim 1).
Therefore, it would have been obvious to someone of ordinary skill in the art at the time of filling to have developed a method for treating EML4-ALK NSCLC by administrating a pharmaceutical composition comprising a ALK inhibitor of EML4-ALK NSCLC cell lines and MMP inhibitor of Marimastat. One would have been motivated to do so from the teaching of Gou on the properties of EML4-ALK NSCLC increasing the expression of MMP-9 and the teachings of Mondal on the known inhibitor of MMP-9 of Marimastat, in combination with the teaching of Jou on the treatment of EML4-ALK NSCLC. There is a reasonable expectation of treating EML4-ALK NSCLC as well as increasing the efficacy of the therapeutic by administration of the ALK inhibitors taught by Jou in combination with the MMP-9 inhibitors taught by Mondal.
In regards to claims 11, It would also have been obvious to incorporate a pharmaceutical acceptable carrier for it is known in the art and routine experimentation to include pharmaceutical excipients for delivery of therapeutics to a patient.
Allowable Subject Matter
Claims 26 and 30-32 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
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MIKHAIL O'DONNEL. ROBINSON
Examiner
Art Unit 1627
/MIKHAIL O'DONNEL ROBINSON/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627