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 filed on 08/22/2022, is a US National phase filing of PCT Application No. PCT/US2021/017661 filed on 02/11/2021 which claims the benefit of priority of United States Provisional Application No. 62/980,718, filed 02/24/2020, and 63/028,976, filed 05/22/2020.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 08/19/2025, complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits, except where noted.
Election/Restriction
Applicant’s response filed on 08/18/2025 to Restriction/Election Requirement filed on 06/25/2025, is acknowledged. Applicant elected without traverse “the invention drawn to a method of reducing the likelihood of, inhibiting or reversing one or more symptoms of chemo brain in a patient or subject secondary to anticancer therapy with a chemotherapy agent using a PKC inhibitor”, pending claims 1-18, 20-25. Pursuant to the Election of Species Requirement, Applicant respectively elected with traverse Chelerythrine as the species of the PKC inhibitors; paclitaxel as the species of the anticancer agents; breast cancer as the species of cancer; and administering PKC inhibitor in combination with lithium as the species of the methods.
DETAILED ACTION
Applicant amendment and arguments filed on 02/02/2026 have been received and have been fully considered.
Claims 1-46 were cancelled, and claims 47-58 were newly added. Claims 47-58 are pending.
Withdrawn claim objection
Objection to claims 1 and 24 is withdrawn in view of Applicant’s amendment filed on 02/02/2026, that canceled claims 1-46.
Rejections 35 U.S.C. 112(b)
Rejection to claim 20 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for reciting the term “especially”, is withdrawn in view of Applicant’s amendment filed on 02/02/2026, that canceled claims 1-46.
Rejection Maintained/Modified/added
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 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 47-58 are rejected under 35 U.S.C. 103 as being unpatentable over N. David (US PG-PUB 2017/0281649 A1, 10/05/2017, “David” cited in the IDS dated 08/19/2025) in view of Lin, W., et al. (Sci Rep 7, 2022 (2017), “Lin” cited in the PTO-892 dated 11/19/2025), Xie JD, et al. (J Biol Chem. 2016 Sep 9;291(37):19364-73, “Xie” cited in the PTO-892 dated 11/19/2025), Gao M, et al. (Neuroscience 2013 Dec 19;254:301-11, “Gao” cited in the PTO-892 dated 11/19/2025), H. Wang et al. (Psychopharmacology, (2001) 158:80–86, “Wang” cited in the PTO-892), and R. Tallarida (Genes & Cancer/vol. 2 no. 11 (2011), “Tallarida” cited in the PTO-892).
David teaches a method for treating a senescent cell-associated condition comprising administering to a subject in need thereof a therapeutically-effective amount of a compound selected from Obatoclax, Antimycin A, Chelerythrine, etc. wherein the senescent cell-associated condition is a chemotherapy-induced side effect, wherein chemotherapy-induced side effects include impaired cognitive function, wherein chemotherapeutic agents include anthracyclines, doxorubicin, daunorubicin, paclitaxel, gemcitabine, pomalidomide, and lenalidomide. David teaches that the method comprises administering compound e.g., Chelerythrine during an off-chemotherapy time interval or after the chemotherapy treatment regimen has been completed. [[0033], [0035]]. David teaches that in some embodiment the cancer is breast cancer. [0031].
David teaches in Example 5, Efficacy of a Test Compound in Treating Chemotherapy-Induced Side Effects, wherein, paclitaxel is administered for three days followed by test compound for three days, wherein the test compound was able to inhibit the paclitaxel adverse effect. [1009].
David’s method only differs from instant claim 1 method to the extent that one of ordinary skill in the art would need to specifically pick Chelerythrine from the list of compounds and paclitaxel from the list of chemotherapeutic agents. Also, David does not teach the combination with lithium salt.
With regard to specifically picking Chelerythrine and paclitaxel from David’s list, Lin teaches a method of treating breast cancer by administering PKC inhibitor, chelerythrine and chemotherapy agent, paclitaxel. Lin teaches the effect of chelerythrine in combination with paclitaxel is examined on the proliferation of breast cancer cells. Lin teaches that treatment with dual drug combination significantly decreased cell proliferation when compared to either drug given individually in all cell lines. Furthermore, dual treatment with both chelerythrine and paclitaxel had either additive effect or synergistic effect as manifested by combination index (CI) values at ED50 ranging from 0.75190 to 1.13763, wherein chelerythrine enhances the anti-proliferative effect of paclitaxel on breast cancer cells. [Pg. 5, last line, Pg. 6, last para.]. chelerythrine significantly inhibited in vivo xenograft formation and increased the cytotoxic effect of chemotherapy agent paclitaxel against breast cancer cells. [Pg. 7, last, para.].
Xie teaches the effect of chelerythrine on paclitaxel-induced neuropathy. Xie teaches that presynaptic NMDARs in the brain can enhance spontaneous neurotransmitter release and can be tonically activated by ambient glutamate, and at the spinal cord level, NMDARs are expressed at the nerves and neurons. [Pg. 19364, col. 2, last para.]. presynaptic NMDARs also regulate evoked neurotransmitter release in the cortex and cerebellum. [Pg. 19368, col. 2, 1st para.]. Xie teaches that paclitaxel treatment induces tonic activation of presynaptic NMDAR activity in the spinal cord through protein kinase C (PKC). [19365, col. 1, 2nd para.]. Paclitaxel increases PKC activity and PKC inhibition attenuates paclitaxel-induced neuropathic [Pg. 19366, col. 1, last para.]. chelerythrine inhibits PKC activity in spinal cord and normalized the baseline frequency of miniature excitatory postsynaptic currents for paclitaxel-treated rats. Xie teaches that the study results indicates that PKC plays a critical role in the paclitaxel induced increase in presynaptic NMDAR activity in the spinal cord. [Pg. 19366, col. 2, 1st para.].
With regard to combining lithium salt with Chelerythrine, Gao teaches prevention of paclitaxel-induced adverse effect by administration of lithium salt. Gao teaches that lithium chloride prevents increased production of pro-inflammatory cytokines including interleukin-1b, suppresses glial glutamate transporter activities, and inhibits glycogen synthase kinase 3beta (GSK3β) activity in the spinal dorsal horn. [Abstract]. Gao teaches that lithium chloride inhibits GSK3β activities in the brain and spinal cord. [302, Col. 2, 1st para.]. Inhibition of GSK3b with lithium suppresses demyelination, microglia activation, and leukocyte infiltration in the spinal cord. Goa teaches that GSK3β is hyperactive in an Alzheimer’s disease mice model, and inhibition of GSK3β activities reduces b-amyloid deposits and ameliorates cognitive deficits. [Pg. 308, col. 1, 2nd para.]. Gao teaches that lithium chloride administered before the first dose of paclitaxel, and daily after paclitaxel treatment. [Pg. 303, col. 1, last para.].
Wang teaches that lithium is an effective PKC inhibitor. [wang whole document].
Tallarida teaches that two or more drugs that individually produce overtly similar effects will display greatly enhanced effects when given in combination. Synergistic effect of combination is when the combined effect is greater than that predicted by their individual potencies. A synergistic interaction allows the use of lower doses of the combination constituents. Drug combinations are quite common in the treatment of cancers. [Abstract].
Tallarida teaches that “The assessment of drug combinations for determining synergy is a quantitative pursuit. This determination requires a quantitative approach that begins with the individual dose effect curves from which the combined additive effect is calculated. If the combined effect observed is significantly greater than the expected (additive) effect, there is synergism. This analysis follows from the individual drug’s dose-effect relations and the concept of dose equivalence. When synergism is detected, it is almost always dependent on the dose ratio of the combination that is tested and, thus, this information allows a determination of dose combinations that are optimal.” [page 1008, col. 1, 1st para.].
With regard to specifically pick Chelerythrine and paclitaxel from David’s list, in view of the foregoing discussion, it would have been prima facie obvious to one of ordinary skill in the art to select chelerythrine for inhibiting one or more symptoms of chemobrain in a patient or a subject treated with paclitaxel such as paclitaxel-induced adverse effects in the central nervous system. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because David teaches a method for treating impaired cognitive function induced by chemotherapy by administering to a subject in need thereof a compound that inhibit the adverse effect of the chemotherapy, and teaches chelerythrine as one of the compounds and paclitaxel as one of the chemotherapeutic agents; Lin teaches a method of treating breast cancer by administering chelerythrine and paclitaxel, wherein dual treatment with chelerythrine and paclitaxel had additive effect or synergistic effect and that chelerythrine enhances the anti-proliferative effect of paclitaxel on breast cancer cells; and Xie teaches that paclitaxel increases PKC activity and PKC inhibition attenuates paclitaxel-induced neuropathic, and chelerythrine inhibits PKC activity in spinal cord and normalized the baseline frequency of miniature excitatory postsynaptic currents for subject treated with paclitaxel. Moreover, Xie teaches that presynaptic NMDARs in the brain can enhance spontaneous neurotransmitter release, regulate evoked neurotransmitter release in the cortex and cerebellum, and Xie’s results showed that PKC plays a critical role in the paclitaxel induced increase in presynaptic NMDAR activity in the spinal cord. As the connection between NMDAR and cognitive ability is known in the art, Xie teaching would motivate skilled artisan to pick chelerythrine and paclitaxel from David list for inhibiting one or more symptoms of chemobrain induced by paclitaxel.
With regard to combining lithium salt with Chelerythrine, it would have been prima facie obvious to one of ordinary skill in the art to include lithium chloride in the method taught by David, Lin and Xie and administer lithium chloride with chelerythrine to the subject before or after paclitaxel administration for inhibiting paclitaxel-induced adverse effects in the central nervous system. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because Gao teaches that lithium chloride inhibits and prevent paclitaxel-induced adverse effects, specifically lithium chloride inhibits GSK3β activities in the brain and spinal cord, reduces b-amyloid deposits and ameliorates cognitive deficits. The effectiveness of lithium chloride in inhibiting GSK3β and prevent paclitaxel-induced adverse effect would motivate skilled artisan looking to inhibit paclitaxel-induced chemobrain to administer lithium with chelerythrine in David, Lin, and Xie method.
With regard to claim 1 synergistic effect of chelerythrine and lithium, one of ordinary skill in the art would presume that combining chelerythrine and lithium would produce enhanced effect because chelerythrine is a PKC inhibitor and lithium is a PKC inhibitor as taught by Wang, and Tallarida teaches that two or more drugs that individually produce overtly similar effects will display greatly enhanced effects when given in combination. Combining drugs in cancer therapy to produce an enhancement effect is well-known in the art as taught by Tallarida. Please note that, while Tallarida teaches that determining synergy requires a quantitative approach that begins with the individual dose effect curves, dose-effect relations, calculations, analysis and interpretation of the result, e.g., additive/synergism, and optimization strategy for determining the dose combination, the instant specification only recites “the use of at least one PKC inhibitor alone in combination with a lithium salt have shown unexpected activity, including as synergistic agents in the treatment and/or prevention of chemobrain.” [Page 2]. “The co-administration of an effective amount of a PKC inhibitor and a lithium salt produces a favorable therapeutic or prophylactic synergistic effect on chemobrain.” [page 20].
Therefore, the cited prior arts meet each and every limitation of claims 47-51, 54-55 and 56-58.
Regarding claim 52, Xie teaches that chelerythrine is administered before paclitaxel. [Pg. 19367, Fig. 5].
Regarding claim 53, one of ordinary skill in the art would have been motivated to administer lithium chloride before, concurrently with, or after chelerythrine administration because Gao teaches that lithium chloride is administered before the first dose of paclitaxel, and daily after paclitaxel treatment, [Pg. 303, col. 1, last para.], and the obviousness of administering chelerythrine during or after paclitaxel administration is established above, see page 7. David teaches that the method comprises administering chelerythrine during an off-chemotherapy time interval or after the chemotherapy treatment regimen has been completed. [0033]. Moreover, David teaches that the chemotherapy treatment regimens can comprise a finite number of cycles of on-drug therapy followed by off-drug therapy, or comprise a finite timeframe in which the chemotherapy is administered, and the protocols can be determined by clinical trials, drug labels, clinical staff in conjunction with the subject to be treated, and regimen can vary depending on the subject's response to the cancer therapy. [0033]. Furthermore, it has been held that the selection of optimal parameters, such as amounts of active agents or dosing regimen, to achieve a beneficial effect, is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980) and MPEP 2144.05. As such, an artisan having ordinary skill in the art would have been motivated to modify the administration regain amounts to achieve before, after or concurrent administration of lithium chloride and chelerythrine to inhibit paclitaxel-induced adverse effects in the central nervous system.
Response to Arguments
Applicant argues:
David, cited against the previously pending claims, is directed to an extremely lengthy and somewhat obtuse disclosure which appears to represent the results of the screening of a large number of compounds from one or more library of compounds. David discloses the treatment of senescent associated disease states and conditions with numerous compounds set forth in the application which are used to selectively destroy, kill, remove, or facilitate destruction of senescent cells in a patient or subject. The application is almost 1100 pages long and sets forth more than 3,000 specific compounds of unrelated chemical structure to treat a large number of disease states and conditions associated with senescent cells. The Examiner cites example 5 of the David specification as evidencing that an undisclosed compound as set forth in David can be used to treat paclitaxel-induced side effects of a patient. Applicant respectfully submits that David does not specifically teach the use of chelerythine to treat chemobrain caused by paclitaxel administration during breast cancer therapy. Instead, David teaches that one or more of literally thousands of disclosed compounds may be used to treat any number of disease states and conditions and that one of those compounds may be chelerythine and one of those disease states and conditions may be impaired cognitive function. David does not teach the use of chelerythine administration to treat cognitive impairment in patients administered paclitaxel. In point of fact, Example 5 of David does not in any way disclose chelerythrine for treating chemobrain according to the present invention. In particular, chemobrain and chelerythrine are not identified in Example 5. Instead, Example 5 of David provides an example of an approach for finding a compound disclosed in David which might have some impact on a paclitaxel induced side effect, but the David disclosure provides no teaching or insight as to how to affect such therapy. Applicant respectfully submits that the Examiner is relying on David for suggesting that chelerythrine can be used to treat chemobrain in patients administered paclitaxel, but there is no teaching to that effect in David. The skilled practitioner could not identify chelerythrine with treating chemobrain from the disclosure of David. Instead, the David teachings are an extremely broad generalized approach for finding an invention which is otherwise not specifically identified in David. The skilled practitioner would have to engage in hindsight reconstruction of the David disclosure by relying on the teachings of the present invention to even know that chelerythrine might be used to treat chemobrain caused by paclitaxel administration. Turning to Lin, Applicant respectfully submits that Lin does nothing to obviate the deficiencies of David in failing to teach the present invention. The Examiner relies on the teachings of Lin to evidence that chelerythrine and paclitaxel may be used effectively to treat breast cancer. The Examiner argues that the dual drug combination significantly decreased cancer cell proliferation in cancer breast cells. Lin is absolutely silent on the impact of chelerythrine on paclitaxel induced chemobrain and the skilled practitioner would not be able to make such an assessment from the disclosure of Lin. Xie is deficient as being silent on the use of chelerythrine for treating chemobrain induced by the administration of paclitaxel.
Examiner response:
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
One of ordinary skill in the art would have been motivated to select chelerythrine for inhibiting one or more symptoms of chemobrain in a patient or a subject treated with paclitaxel such as paclitaxel-induced adverse effects in the central nervous system with reasonable expectation of success because David teaches a method for treating impaired cognitive function induced by chemotherapy by administering to a subject in need thereof a compound that inhibit the adverse effect of the chemotherapy, and teaches chelerythrine as one of the compounds and paclitaxel as one of the chemotherapeutic agents; Lin teaches a method of treating breast cancer by administering chelerythrine and paclitaxel, wherein dual treatment with chelerythrine and paclitaxel had additive effect or synergistic effect and that chelerythrine enhances the anti-proliferative effect of paclitaxel on breast cancer cells; and Xie teaches that paclitaxel increases PKC activity and PKC inhibition attenuates paclitaxel-induced neuropathic, and chelerythrine inhibits PKC activity in spinal cord and normalized the baseline frequency of miniature excitatory postsynaptic currents for subject treated with paclitaxel. Moreover, Xie teaches that presynaptic NMDARs in the brain can enhance spontaneous neurotransmitter release, regulate evoked neurotransmitter release in the cortex and cerebellum, and Xie’s results showed that PKC plays a critical role in the paclitaxel induced increase in presynaptic NMDAR activity in the spinal cord. As the connection between NMDAR and cognitive ability is known in the art, Xie teaching would motivate skilled artisan to pick chelerythrine and paclitaxel from David list for inhibiting one or more symptoms of chemobrain induced by paclitaxel. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Applicant argues:
Combining the teachings of Lin and David arguably teaches away from the present invention inasmuch as Lin teaches that chelerythrine enhanced the cytotoxic activity of paclitaxel, suggesting that chelerythrine may increase the induction of chemobrain by paclitaxel, not inhibit chemobrain. Accordingly, Applicant respectfully submits that the teachings of Lin work at cross purposes to any construction to be gleaned from the disclosure of David that chelerythrine is a preferred compound for inhibiting paclitaxel-induced chemobrain. That teaching simply does not exist in the disclosures of Lin and David.
Examiner response:
In response to applicant's argument that Lin teaches away from using chelerythrine and paclitaxel for treating symptoms of chemobrain, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
In the instant case, David teaches a method for treating symptoms of chemobrain induced by chemotherapy by administering to a subject in need thereof a therapeutically-effective amount of an active compound. David lists Chelerythrine as one of the compounds and paclitaxel as one of the chemotherapies. One of ordinary skill in the art having access to David and looking to treat the symptoms of chemotherapy would have a reasonable expectation of success to pick Chelerythrine and paclitaxel from David’s teachings because Lin teaches the compatibility and the effectiveness of the combination of Chelerythrine and paclitaxel in treating cancer. The protective effect of Chelerythrine against the adverse effects of paclitaxel is taught by David and Lin does not teach away from using the two agents. Nevertheless, Lin would provide motivation to select Chelerythrine from David’s list to not only inhibit and reverse the symptoms of chemobrain but to provide more effective cancer treatment by increasing the cytotoxicity of paclitaxel while protecting against chemobrain. There is no teaching in Lin that chelerythrine may increase the induction of chemobrain by paclitaxel. Thus, Applicant's arguments are not persuasive.
Applicant argues:
Administration of effective amounts of chelerythrine combination with lithium exhibit synergistic activity in the inhibition and treatment of chemobrain induced by paclitaxel administered chemotherapy. The present invention is not taught or suggested by any one or more of the David, Lin, Xie and Gao references cited against the present invention. In particular, the teachings of the prior art are deficient in failing to teach that chelerythrine and/or lithium is effective in the treatment of chemobrain. Noteworthy is that David, Lin and Xie completely fail to mention lithium and none of these references clearly evidence that chelerythrine can be used to treat chemobrain induced in a patient being treated with paclitaxel for cancer. Gao, also cited, teaches that lithium can be used in the treatment of neuropathy, but does not teach or suggest lithium treatment alone or in combination with chelerythrine to treat chemobrain, or that a combination of effective amounts of lithium and chelerythrine can be used to synergistically inhibit or reduce the symptoms of paclitaxel induced chemobrain. In point of fact, Gao does not even mention chelerythrine alone or in combination with lithium or that such a combination could be used to treat paclitaxel- induced chemobrain synergistically.
Examiner response:
Applicant's arguments have been fully considered but they are not persuasive. Applicant’s argument against Geo is not persuasive when the teachings of Geo is combined with David, Lin and Xie. One of ordinary skill in the art would have been motivated to include lithium chloride in the method taught by David, Lin and Xie and combine lithium chloride with chelerythrine to inhibit paclitaxel-induced chemobrain with reasonable expectation of success because Gao teaches that lithium chloride inhibits and prevent paclitaxel-induced adverse effects, specifically lithium chloride inhibits GSK3β activities in the brain and spinal cord, reduces b-amyloid deposits and ameliorates cognitive deficits. The effectiveness of lithium chloride in inhibiting GSK3β and prevent paclitaxel-induced adverse effect would motivate skilled artisan looking to inhibit paclitaxel-induced chemobrain to administer combination of lithium and chelerythrine. One of ordinary skill in the art would presume that combining chelerythrine and lithium would produce enhanced effect because chelerythrine is a PKC inhibitor and lithium is a PKC inhibitor as taught by Wang, and Tallarida teaches that two or more drugs that individually produce overtly similar effects will display greatly enhanced effects when given in combination. Combining drugs in cancer therapy to produce an enhancement effect is well-known in the art as taught by Tallarida.
It appears that Applicant is asserting that combining chelerythrine and lithium produces unexpected synergy. As provided in MPEP 716 (b), the evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992). "[A]ppellants have the burden of explaining the data in any declaration they proffer as evidence of non-obviousness." Ex parte Ishizaka, 24 USPQ2d 1621, 1624 (Bd. Pat. App. & Inter. 1992). As provided in MPEP 2145, If a prima facie case of obviousness is established, the burden shifts to the applicant to come forward with arguments and/or evidence to rebut the prima facie case. See, e.g., In re Dillon, 919 F.2d 688, 692, 16 USPQ2d 1897, 1901 (Fed. Cir. 1990) (en banc). Rebuttal evidence and arguments can be presented in the specification, In re Soni, 54 F.3d 746, 750, 34 USPQ2d 1684, 1687 (Fed. Cir. 1995), by counsel, In re Chu, 66 F.3d 292, 299, 36 USPQ2d 1089, 1094-95 (Fed. Cir. 1995), or by way of an affidavit or declaration under 37 CFR 1.132, e.g., Soni, 54 F.3d at 750, 34 USPQ2d at 1687; In re Piasecki, 745 F.2d 1468, 1474, 223 USPQ 785, 789-90 (Fed. Cir. 1984). However, arguments of counsel cannot take the place of factually supported objective evidence. See, e.g., In re Huang, 100 F.3d 135, 139-40, 40 USPQ2d 1685, 1689 (Fed. Cir. 1996); In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984).
In the instant prosecution history of this application, Applicant does not provide factual evidence that the combination of lithium and chelerythrine resulted in synergism. The instant specification does not provide evidence of synergism. Tallarida teaches that determining synergy requires a quantitative approach that begins with the individual dose effect curves, dose-effect relations, calculations, analysis and interpretation of the result, whether the combination produces additive effect or synergism. The instant specification only recites “the use of at least one PKC inhibitor alone in combination with a lithium salt have shown unexpected activity, including as synergistic agents in the treatment and/or prevention of chemobrain.” [Page 2]. “The co-administration of an effective amount of a PKC inhibitor and a lithium salt produces a favorable therapeutic or prophylactic synergistic effect on chemobrain.” [page 20]. The instant specification does not provide evidence to support the synergism between lithium and chelerythrine. There is no description of the dose-effect relationship, there is no calculation of the drug doses, there is no comparison between each drug alone and the combination, and there is no optimization strategy for determining the dose combination.
Conclusion
Claims 47-58 are rejected. No claim is allowed.
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.
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/M.M.A./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/
Supervisory Patent Examiner, Art Unit 1622
Prosecution Insights