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 .
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.
Current Status of 17/735,271
This Office Action is responsive to the amended claims received 15 December 2025.
Claims 1-23 are currently pending.
Priority
Applicant has not claimed the benefit of any prior-filed patent applications.
Response to Amendments
The objections to the drawings, present in the previous office action, are hereby withdrawn due to the replacement drawing sheets.
The objections to the specification, present in the previous office action, are hereby withdrawn due to Applicant’s amendments.
The objections to the claims, present in the previous office action, are hereby withdrawn due to Applicant’s amendments.
The 35 U.S.C. 112 rejections to the claims, present in the previous office action, are hereby partially withdrawn due to Applicant’s amendments.
The 35 U.S.C. 102(a)(1) and/or 35 U.S.C. 102(a)(2) rejections to the claims, present in the previous office action, are hereby withdrawn due to Applicant’s submission of an affidavit under 37 CFR 130(a). New rejections are presented herein, as necessitated by Applicant’s submission.
The 35 U.S.C. 103 rejections to the claims, present in the previous office action, are hereby withdrawn due to Applicant’s submission of an affidavit under 37 CFR 130(a). New rejections are presented herein, as necessitated by Applicant’s submission.
Response to Arguments
Applicant argues that actual reduction to practice is not necessary to satisfy the written description requirement. Applicant argues that a single combination of drugs, within the scope of instant claim 1, is “more than adequate to satisfy the written description requirement”, and points to the combination of sorafenib and ifenprodil, which is disclosed in the instant specification. Applicant argues that the limitations of the instant claims would be clear to one of ordinary skill in the art. Applicant argues that the additive effects of NMDAR inhibitors and kinase inhibitors are clearly shown in the instant application.
The Examiner has not argued that actual reduction to practice is necessary. Applicant appears to generally be arguing against the hypothetical argument that “the combination of an NMDAR inhibitor and a kinase inhibitor, wherein the specification gives sorafenib + ifenprodil as an exemplary embodiment, does not meet the written description requirement”. This is not what the Examiner is arguing. The Examiner is arguing that the combination of an NMDAR inhibitor and a kinase inhibitor, wherein that combination of genera is better than either of those genera alone, does not meet the written description requirement. If Applicant would like to remove the language in the instant claims that requires the combination of an unspecified NMDAR inhibitor and an unspecified kinase inhibitor to be better than each of them individually, the 35 USC 112(a) rejections below will most likely be withdrawn. If Applicant feels that the possible species of the instant claims would be clear to one of ordinary skill in the art, Applicant may consider submission of an affidavit or declaration from one with relevant experience as to why this is the case. If Applicant’s argument is that all combinations of NMDAR inhibitors and kinase inhibitors would meet the requirements of claim 1, then there would be no change in the scope of the claim if the “better than each type of inhibitor in isolation” language is removed. The Examiner does not agree that all combinations of NMDAR inhibitors and kinase inhibitors would meet the limitations of instant claim 1.
Applicant argues that the functional language in the instant claims is not indefinite. Applicant argues that the declaration included in their last correspondence removes the XU reference as prior art.
Because there is no way for one of ordinary skill in the art to determine whether an arbitrary combination of an NMDAR inhibitor and a kinase inhibitor fall within the scope of instant claims 1-2 and 13-14, based upon their own knowledge and the instant application, those claims are found to be indefinite by the Examiner. The instant examples do not provide enough guidance for one of ordinary skill in the art to make the determination described immediately above. The Examiner does not rely upon XU herein.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Each of these claims recites a composition of an NMDAR inhibitor and a kinase inhibitor or the use of the same composition, wherein the composition is capable of treating cancer to a greater degree than: an NMDAR inhibitor alone, a kinase inhibitor alone, or the addition of the anti-cancer effects produced by an NMDAR inhibitor alone and a kinase inhibitor alone. Applicant provides written description for a synergistic effect of some combinations of NMDARs and kinase inhibitors, such as in Example 2 of the specification. There are at least 1600 possible combinations of one NMDAR inhibitor and one kinase inhibitor in the specification, based upon the compounds present therein. The specification does not provide data or even a list showing which of these combinations fall under the synergistic combination limitations within the instant claims. Additionally, under the broadest reasonable interpretation of the instant claims, any combination of an NMDAR inhibitor and a kinase inhibitor that perform the necessary function would fall within the scope of the claims, this would include at least many thousands of inhibitory molecule combinations that have not yet been discovered. Those undiscovered inhibitor combinations are, of course, not provided by the specification.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-23 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1-2 and 13-14 each recite a composition of an NMDAR inhibitor and a kinase inhibitor or the use of the same composition, wherein the composition is capable of treating cancer to a greater degree than: an NMDAR inhibitor alone, a kinase inhibitor alone, or the addition of the anti-cancer effects produced by an NMDAR inhibitor alone and a kinase inhibitor alone. Each of these claims recites a functional characteristic without any indication of how this characteristic is provided. The functional characteristic does not follow from any structure recited by the claims. For instance, if the claims recited a particular NMDAR inhibitor and a particular kinase inhibitor, it would be understood that the function follows from the structures of those compounds. Therefore, these claims and all claims dependent thereupon (claims 1-23) are rendered indefinite, because it is not clear what structure produces the claimed function.
Claim Rejections - 35 USC § 102
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 1-3, 6-9, 11-14, and 18-23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
GYNTHER (Cited by Applicant in IDS of 10 January 2024; Gynther, M.; Silvestri, I.P.; Hansen, J.C.; et al. “Augmentation of Anticancer Drug Efficacy in Murine Hepatocellular Carcinoma Cells by a Peripherally Acting Competitive N-Methyl-D-aspartate (NMDA) Receptor Antagonist” J. Med. Chem. 2017, 60, 9885−9904).
GYNTHER generally teaches that they have produced a novel NMDA antagonist “1l”, and administered this compound in combination with sorafenib for the treatment of hepatocellular carcinoma (HCC) using a cell line (abstract). Figure 8 of GYNTHER shows that administration of a combination of 1l and sorafenib produces a synergistic anti-proliferative effect in the HCC cell line. Figure 8 also shows a synergistic anti-proliferative effect is produced when administering the combination of D-AP5 (at 100 µM) and sorafenib (at 1-10 µM). GYNTHER teaches that the data therein represents a promising strategy to reverse multi-drug resistance (MDR) in solid tumors including HCC (conclusion). One of ordinary skill in the art would understand that this strategy of GYNTHER is being pursued for later use in human patients.
The “D-AP5” compound of GYNTHER reads on the compound referred to in the instant claims as AP5; it simply has the enantiomer specified. AP5 is defined within the instant claims as an NMDAR inhibitor, and sorafenib is defined in the instant claims as a kinase inhibitor. The instant specification states that sorafenib is an FLT4/FGFR inhibitor (Pg. 22). The instant specification states that aberrant Wnt/Beta-catenin signaling is common in HCC (Pg. 39). The instant specification teaches that Lgr5 is overexpressed and involved in cancer stemness in HCC cells (Pg. 79).
Regarding claims 20-21 and 23: The outcomes within instant claims 20-21 and 23 are solely the result of administering the combination therein to a patient having a cancer of the type specified. There are no positive steps recited therein that would alter these outcomes unrelated to administering the combination of instant claim 13 to a patient having the specified cancer type. Therefore, because the method of administering the combination of instant claim 13 to a patient having HCC has been found to be obvious, these direct outcomes are also rendered obvious.
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 1-3, 6-9, 11-16, and 18-23 are rejected under 35 U.S.C. 103 as being unpatentable over:
GYNTHER (Cited by Applicant in IDS of 10 January 2024; Gynther, M.; Silvestri, I.P.; Hansen, J.C.; et al. “Augmentation of Anticancer Drug Efficacy in Murine Hepatocellular Carcinoma Cells by a Peripherally Acting Competitive N-Methyl-D-aspartate (NMDA) Receptor Antagonist” J. Med. Chem. 2017, 60, 9885−9904).
Teachings of GYNTHER are described in the 35 USC 102 rejections above.
Regarding claims 15-16: It would have been obvious to one of ordinary skill in the art, before the instant effective filing date, to administer the combination of D-AP5 and sorafenib of GYNTHER once per day. The artisan would have expected success in this combination, because administering any drug or drug cocktail once daily is a common starting point for administration.
Claims 1-3 and 6-23 are rejected under 35 U.S.C. 103 as being unpatentable over:
GYNTHER (Cited by Applicant in IDS of 10 January 2024; Gynther, M.; Silvestri, I.P.; Hansen, J.C.; et al. “Augmentation of Anticancer Drug Efficacy in Murine Hepatocellular Carcinoma Cells by a Peripherally Acting Competitive N-Methyl-D-aspartate (NMDA) Receptor Antagonist” J. Med. Chem. 2017, 60, 9885−9904)
in view of:
NEXAVAR (NEXAVAR FDA Label, Revised April 2020).
Teachings of GYNTHER are described in the rejections above. GYNTHER does not teach a dosage of sorafenib, nor does it teach radiation therapy or surgery for the treatment of HCC.
Regarding claim 10: NEXAVAR teaches the standard dosage of sorafenib to be two 200 mg tablets taken twice daily (800 mg total per day) for HCC (Dosage and Administration section). It would have been obvious to one of ordinary skill in the art, before the instant effective filing date, to administer sorafenib within the combination taught by GYNTHER at the dosage taught within the NEXAVAR (the FDA Label). The artisan would have expected success in this combination, because FDA label dosages, as in NEXAVAR, have been shown to be reasonably safe and efficacious.
Regarding claim 17: NEXAVAR teaches that the drug therein (NEXAVAR/sorafenib) is used to treat HCC “that can no longer be treated with radioactive iodine” (top of 28th page). Logically, this teaches a method of first treating HCC with radioactive iodine (a form of radiation therapy), and then treating the HCC with sorafenib. It would have been obvious to one of ordinary skill in the art, before the instant effective filing date, to administer sorafenib within the combination taught by GYNTHER after radioactive iodine therapy, as taught by NEXAVAR. The artisan would have expected success in this combination, because FDA labels, as in NEXAVAR, teach methods of treating diseases that have been extensively tested for efficacy.
Conclusion
No claims are currently allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN D MCANANY whose telephone number is (571)270-0850. The examiner can normally be reached 8:30 AM - 5:30 PM.
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/JDMc/Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625