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
The instant application, filed 09/28/2022, is a 371 filing of PCT/CN2021/084008, filed 03/30/2021, which claims foreign priority to CN202010245573.6, filed 03/31/2020. Receipt of certified documents as required by 37 CFR § 1.55 is acknowledged.
Amendments and Claim Status
The amendment to the claims filed on 08/28/2025 is acknowledged and entered.
Claims 1, 12, 13, and 42 are amended;
Claims 3, 4, 6, 10, 11, 14-18, 20-41, 43-52, 56- 61, 63, 65- 74, 78-83, and 85 are cancelled;
Claims 86 and 87 are added;
Claims 2, 5, 7-9, 42, 53-55, 62, 64, 75-77 and 84 remain withdrawn pursuant to 37 CFR § 1.142(b), as being drawn to a nonelected invention;
Claims 1, 3, 12, 13, 19, 86, and 87 read on an elected invention and species and are being examined on the merits as such;
Claims 1, 2, 5, 7-9, 12, 13, 19, 42, 53-55, 62, 64, 75- 77, 84, 86, and 87 are pending.
Response to arguments
Applicant arguments, filed 08/25/2025, with respect to the rejections under 102 (a) (1), and 103, and the data submitted in the declaration under 37 CFR §1.132, filed 09/04/2025, have been fully considered.
With respect to the rejection of claims 1, 3, 12, and 13 under 35 U.S.C. § 102 (a) (1) as being anticipated by Fong et al. (J Biol Chem Vol 285, Iss 41, pg 31427-31434, published August 2, 2010), hereinafter Fong, Applicant has amended the claim to strike the claim language “from the group consisting of: a Notch signaling pathway inhibitor, an HH signaling pathway inhibitor, a Porcupine inhibitor, an RXRa inhibitor, Niclosamide, a CKla inhibitor, and a Frizzled receptor inhibitor,” and added the claim language, “wherein the second therapeutic agent is a Notch signaling pathway inhibitor, and the Notch signaling pathway inhibitor is MK0752, R04929097, and/or PF-03084014” removing the disclosure by Fong from consideration as a prior art rejection under this statue. As such, the rejection is hereby withdrawn.
With respect to the rejection of claims 1, 3, 12, 13 and 19 under 35 U.S.C. § 103 as being unpatentable over Fong (see earlier citation), the claim amendments made by Applicant have necessitated the inclusion of new references. The arguments made by applicant are herein addressed as follows.
Applicant alleges that the instant specification, filed 09/28/2022, and the Declaration under 37 CFR §1.132, filed 09/04/2025 provides evidence of unexpected results necessitating secondary consideration, and sufficient to overcome the prima facie case of obviousness set forth in the office action filed on 05/28/2025.
The burden of demonstrating the need for secondary considerations such as unexpected results belongs to Applicant. The following factors are considered in determining whether the burden to establish unexpected results, worthy of secondary consideration has been met:
(1) Evidence must show unexpected results, see MPEP §716.02 (a);
(2) Results are of statistical and practical significance, see MPEP §716.02 (b) (I);
(3) Applicant explains evidence presented, see MPEP §716.02 (b) (II);
(4) Evidence is appropriately comparative, see MPEP §716.02 (b) (III);
(5) Evidence is weighed against prima facie case of obviousness, see MPEP §716.02 (c) (I);
(6) Results are commensurate in scope within the instant claims, see MPEP §716.02 (d);
In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986)
In re Waymouth, 499 F.2d 1273, 1276, 182 USPQ 290, 293 (CCPA 1974)
In re Wagner, 371 F.2d 877, 884, 152 USPQ 552, 560 (CCPA 1967)
Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992)
UCB, Inc. v. Actavis Labs, UT, Inc., 65 F.4th 679, 693, 2023 USPQ2d 448 (Fed. Cir. 2023)
Upon consideration of Applicant arguments, presented in the instant specification, and aforementioned declaration, as well as the amendments filed on 08/28/2025, the Examiner has determined that Applicant has not met their burden for the reasons and stated hereinafter.
Firstly, Applicant has not met their burden because according to MPEP § 716.02 (a), in order to overcome a prima facie case of obviousness Applicant must submit evidence which shows results which are greater than expected. According to MPEP § 716.02 (a) (III),
III. PRESENCE OF AN UNEXPECTED PROPERTY IS EVIDENCE OF NONOBVIOUS
Presence of a property not possessed by the prior art is evidence of nonobviousness. In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (rejection of claims to compound structurally similar to the prior art compound was reversed because claimed compound unexpectedly possessed anti-inflammatory properties not possessed by the prior art compound); Ex parte Thumm, 132 USPQ 66 (Bd. App. 1961) (Appellant showed that the claimed range of ethylene diamine was effective for the purpose of producing "‘regenerated cellulose consisting substantially entirely of skin’" whereas the prior art warned "this compound has ‘practically no effect.’ "). The submission of evidence that a new product possesses unexpected properties does not necessarily require a conclusion that the claimed invention is nonobvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979).
According to Applicant arguments, filed on 08/28/2025, in reference to the evidence presented—more specifically, examples 9-11 on pages 47 and 48 of the instant specification, filed on 09/28/2022 and Figures 13-15 of the instant drawings, filed on 09/28/2020—Applicant argues that the results presented are synergistic. The Examiner disagrees with the assessment for the following reasons: Applicant relies on a limited data set for their determination of synergy. The practical significance of the data is not demonstrated by the comparative examples, nor by the arguments of Applicant’s counsel. According to MPEP § 716.02 (b) (I),
I. BURDEN ON APPLICANT TO ESTABLISH RESULTS ARE UNEXPECTED AND SIGNIFICANT
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) (Mere conclusions in appellants’ brief that the claimed polymer had an unexpectedly increased impact strength “are not entitled to the weight of conclusions accompanying the evidence, either in the specification or in a declaration.”); Ex parte C, 27 USPQ2d 1492 (Bd. Pat. App. & Inter. 1992) (Applicant alleged unexpected results with regard to the claimed soybean plant, however there was no basis for judging the practical significance of data with regard to maturity date, flowering date, flower color, or height of the plant.). See also In re Nolan, 553 F.2d 1261, 1267, 193 USPQ 641, 645 (CCPA 1977) and In re Eli Lilly, 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) as discussed in MPEP § 716.02(c).
According to examples 9-11 of the instant specification filed on 09/28/2020 (see Figure 1, below), Applicant relies on a measure of cell viability to calculate the combination drug index (CDI), wherein a value < 1 demonstrates synergy. However, in the absence of dose response curves for combination matrices, these values don’t demonstrate robust synergy, only a possible interaction at one arbitrary concentration. That is, a single measurement of CDI lacks context. Synergistic interactions between components could be absent at other ratios or doses.
Figure 1. Reproduced Figures 13-15 according to the instant drawings/specification
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Fig 1. a) MK0752 and sodium ascorbate; b) RO492097 and sodium ascorbate; c) PF-03084014 and sodium ascorbate
Furthermore, the single fixed drug concentrations used concentrations used are arbitrary. There is no evidence that these concentrations are representative for optimized for therapeutic relevance or even comparable potency. The apparent synergy may simply result from non-physiologic or cytotoxic levels rather than mechanistic interaction. Finally, the graphs show only cell viability without pathway specific assays confirming notch inhibition or oxidative stress effects. The data is phenotypic, and not mechanistic, so they do not prove that there is an interaction between ascorbate and Notch pathway signaling inhibitor, as claimed.
Additionally, Applicant has failed to meet their burden because according to MPEP § 716.02 (b) (II), Applicant must offer an explanation of all submitted data, and explain why the results are unexpected.
II. APPLICANTS HAVE BURDEN OF EXPLAINING PROFFERED DATA
“[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).
Applicants have provided data within the Declaration under 37 CFR §1.132, filed which Applicants allege to contain unexpected results. The Examiner disagrees that these results are sufficient to meet Applicant’s burden because Applicants have not explained why the results are unexpected. It is presumed that said results (reproduced in Figure 2, below) are intended to be compared with that of the instant specification (see Figure 1, above), wherein the synergy is alleged.
Figure 2. Reproduced Figures A-C of the Declaration under 37 CFR §1.132, filed 09/04/2025
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Fig 2. a) Ozaliplatin and Ascorbic acid; b) Hereceptin and Ascorbic acid; c) DS8201 and Ascorbic acid
The examiner disagrees that these results demonstrate the synergistic capability of the instantly claimed composition. Firstly, Applicants have not provided conclusive explanation as to which altered parameter within the comparative experiments led to the presented results. According to the produced figures of the declaration under 37 CFR §1.132, filed 09/04/2025, the therapeutic agents have been combined with ascorbic acid, which will undoubtedly have a lower pH than examples 9-11, which were combined therapeutic agents with sodium ascorbate. Furthermore, it is not absolutely certain that the same cell lines were tested, as Applicant not addressed or explained these results in their remarks whatsoever. The figures indicate an MC cell line while the instantly claimed species are tested in HOF and 143B cell lines. According to the analysis above, not only are the results not directly comparative, whatsoever, the results are not unexpected in any way. It is widely known that low pH can alter the local microenvironment of cells, resulting in detectable differences and different pH values. Also, it is widely known that a single therapeutic regimen may not be applicable to different cell types. Finally, there is very little clarity about which un-recited components are included within each composition.
Furthermore, applicant has failed to meet their burden MPEP § 716.02 (b) (III) states that Applicant must identify the property directly attributable to the presented results by way of comparison to the closest prior art.
III. DIRECT AND INDIRECT COMPARATIVE TESTS ARE PROBATIVE OF NONOBVIOUSNESS
Evidence of unexpected properties may be in the form of a direct or indirect comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims. See In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980) and MPEP § 716.02(d) - § 716.02(e). See In re Blondel, 499 F.2d 1311, 1317, 182 USPQ 294, 298 (CCPA 1974) and In re Fouche, 439 F.2d 1237, 1241-42, 169 USPQ 429, 433 (CCPA 1971) for examples of cases where indirect comparative testing was found sufficient to rebut a prima facie case of obviousness.
“In order to establish that the claimed intermediate is a ‘contributing cause’ of the unexpectedly superior activity or property of an end product, an applicant must identify the cause of the unexpectedly superior activity or property (compared to the prior art) in the end product and establish a nexus for that cause between the intermediate and the end product.” Id. At 479.
As discussed earlier, a difference in composition components (ascorbic acid/sodium ascorbate) resulting in a different pH, different cell types tested, or even the inclusion of an un-recited component may directly contribute to the alleged unexpected results, more than any combination of the components of the composition, altogether. This simply means that there are at least 4 variables which could contribute to the alleged unexpected result. Thus the instantly claimed is not comparative to the closest prior art, nor are the results presented unexpected in any way.
Furthermore, according to MPEP § 716.02 (c), Applicant has the burden of weighing the strength of the alleged unexpected results against the strength of the prima facie case of obviousness set forth by the Examiner,
I. EVIDENCE OF UNEXPECTED AND EXPECTED PROPERTIES MUST BE WEIGHED
Where the unexpected properties of a claimed invention are not shown to have a significance equal to or greater than the expected properties, the evidence of unexpected properties may not be sufficient to rebut the evidence of obviousness. In re Nolan, 553 F.2d 1261, 1267, 193 USPQ 641, 645 (CCPA 1977) The court held the evidence of nonobviousness was not sufficient to rebut the evidence of obviousness.); See MPEP § 716.01(d) for guidance on weighing evidence submitted to traverse a rejection.
Applicant has not submitted any newly presented arguments which discuss the results presented in the instant specification or declaration under 37 CFR §1.132, in light of the teachings of the prior art detailed in the prima facie case of obviousness set forth in the office action, filed on 05/28/2025. There have been no arguments presented addressing the prior art teachings in comparison to the results presented in the instant specification for the declaration—namely the claimed usage of DAPT or compound E in combination with ascorbic acid.
Finally, according to MPEP § 716.02 (d), Applicant has failed to demonstrate that the results are commensurate in scope with the instant claims. According to MPEP § 716.02 (d),
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.
As highlighted earlier, the compositions have only been tested in a narrow range concentration range. Independent claim 1 recites no specific critical concentrations of ascorbic acid/ascorbate or second therapeutic agent, thus, it is deemed very broad. The dependent claims 12 and 13, in contrast, recite a vast range of ratio of ascorbic acid/ascorbate to second therapeutic agent. The results presented in the both the instant specification, filed 09/28/2020, (see Figure 1) as well as the declaration under 37 CFR §1.132, filed 09/04/2025, (see Figure 2) test simply a single data point within the vast range claimed. Thus, no trend in the data can be reasonably be established which correlates to the scope of the instant claims. In contrast, the data only suggest a single concentration for each agent, under one condition (0.5mM sodium ascorbate/ascorbic acid) in absence of a dose range, and in vivo validation. Therefore, the very limited in vitro viability data cannot support the entire claimed genus, which covers all effective amounts at all possible Notch pathway inhibitor combinations in all therapeutic contexts. Furthermore, the independent claim 1 contains the open claim language “comprising,” which according to MPEP § 2111.03, may include an un-recited additional variable capable of contribute to the alleged “unexpectedness” of the results. Therefore, the data is not commensurate in scope with the instant claims at least because of the use of the language “comprising.”
Thus, applicant has failed to meet the burden to: (1) demonstrate that any asserted unexpected results are significant and unexpected; (2) adequately explain the results presented; (3) weigh against the strength of the prima facie case of obviousness; (4) demonstrate the results are commensurate in scope with the instant claims. Applicant has failed to establish that the results presented are directly attributable to the instantly claimed composition and not on a parameter such as any un-recited variable, which may be the greatest contributing factor; or a critical concentration within a claimed range would be considered a routine optimization and would therefore, be obvious.
According to MPEP § 716.02 (e), Applicant may rebut a case of prima facie case of obviousness by direct comparison of their claimed composition with the closest prior art. According to MPEP § 716.02 (e),
An affidavit or declaration under 37 CFR § 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979). “A comparison of the claimed invention with the disclosure of each cited reference to determine the number of claim limitations in common with each reference, bearing in mind the relative importance of particular limitations, will usually yield the closest single prior art reference.” In re Merchant, 575 F.2d 865, 868, 197 USPQ 785, 787 (CCPA 1978) (emphasis in original). Where the comparison is not identical with the reference disclosure, deviations therefrom should be explained, In re Finley, 174 F.2d 130, 81 USPQ 383 (CCPA 1949), and if not explained should be noted and evaluated, and if significant, explanation should be required. In re Armstrong, 280 F.2d 132, 126 USPQ 281 (CCPA 1960) (deviations from example were inconsequential).
However, Applicant is entitled to submit a comparison of the results with prior art that is closer than that applied by the Examiner. According to MPEP § 716.02 (e) (I),
I. THE CLAIMED INVENTION MAY BE COMPARED WITH PRIOR ART THAT IS CLOSER THAN THAT APPLIED BY THE EXAMINER
Applicants may compare the claimed invention with prior art that is more closely related to the invention than the prior art relied upon by the examiner. In re Holladay, 584 F.2d 384, 199 USPQ 516 (CCPA 1978); Ex parte Humber, 217 USPQ 265 (Bd. App. 1961) (Claims to a 13-chloro substituted compound were rejected as obvious over nonchlorinated analogs of the claimed compound. Evidence showing unexpected results for the claimed compound as compared with the 9-, 12-, and 14- chloro derivatives of the compound rebutted the prima facie case of obviousness because the compounds compared against were closer to the claimed invention than the prior art relied upon.)
However, no such comparison with the prior art of record, or with any other prior art that is closer than that applied by the Examiner has been set forth. For the reasons outlined above, the comparisons set forth in the instant specification are not direct and do not isolate variables. As such, the rejection is maintained.
Applicants are reminded that “attorney argument [is] not the kind of factual evidence that is required to rebut a prima facie case of obviousness.” In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997). The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965).
Claim Rejections – 35 U.S.C. § 103
The text of those sections of title 35, U.S. Code not included in this action can be found in the prior Office action.
Claims 1, 3, 12, 13, 19, 86, and 87 are rejected under 35 U.S.C. § 103 as being unpatentable over Fong (see earlier citation) in view of Hu and Fu (Am J Cancer Res. Issue 2, Volume 3, pages 340–356, published April 28, 2012), and Shenoy et al. (Perspective Volume 34, Issue 5, pages 700-706, published November 12, 2018), hereinafter Shenoy.
The instant claims are drawn to a pharmaceutical combination comprising ascorbic acid/ascorbate and a Notch signaling pathway inhibitor selected from MK0752, RO4929097, and PF-03084014. The claims further comprise a kit containing the pharmaceutical combination.
Fong teaches how breast cancer-derived factors impact bone health, particularly focusing on osteoblast differentiation and promoting osteoclastogenesis (Title, Abstract). The study revealed that conditioned media from breast cancer cells inhibited osteoblast differentiation, even in the presence of ascorbic acid, which typically promotes this process. This inhibition was associated with the activation of the Notch signaling pathway via g-secretase. By introducing g-secretase, DAPT or Compound E, the suppression of osteoblast different creation was reversed, allowing ascorbic acid to effectively promote bone formation (page 31431, Figure 4). The findings by Fong suggest that g-secretase plays a crucial role in mediating the negative effects of breast cancer derived factors on bone-forming cells, and that its inhibition can restore the beneficial actions of ascorbic acid (pages 31431 and 31433). Fong teaches a concentration of ascorbic acid of 50 µg/mL (page 31428), effectively 2.84 x 10-4 M. The Notch signaling pathway g-secretase inhibitors, DAPT or Compound E, are both taught at a concentration of 100nM (Figure 4 and 5 legends), effectively 1.0 x 10-7 M. Therefore, the mass ratio of the Notch signaling pathway inhibitor to ascorbic acid is taught by Fong to be 1:2840.
Further regarding claim 1, Fong fails to teach wherein the second therapeutic agent is MK0752, R04929097, or PF-03084014 and wherein the composition may comprise ascorbate.
The deficiencies of Fong are remedied by Hu and Fu who teach that compounds, DAPT, MK0752, RO4929097, PF-03084014, inhibit the Notch signaling pathways through the inhibition of γ-secretase (see Table 2, Figure 2 and figure legend). Additionally, Hu and Fu highlight the use of several vitamins in cancer treatments such as vitamin D3 (Tables 2 and 3, pages 349-50) as well as vitamin A (page 351).
According to the teachings of Hu and Fu, DAPT, MK0752, RO4929097, and PF-03084014, are all known to be γ-secretase inhibitors, capable of inhibiting Notch signaling pathways, i.e. substitutable equivalents. According to MPEP 2144.06 (II), art-recognized equivalents substituted for the same purpose are rendered obvious. The courts have stated:
In order to rely on equivalence as a rationale supporting an obviousness rejection, the equivalency must be recognized in the prior art, and cannot be based on applicant’s disclosure or the mere fact that the components at issue are functional or mechanical equivalents. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958) (The mere fact that components are claimed as members of a Markush group cannot be relied upon to establish the equivalency of these components. However, an applicant’s expressed recognition of an art-recognized or obvious equivalent may be used to refute an argument that such equivalency does not exist.); Smith v. Hayashi, 209 USPQ 754 (Bd. of Pat. Inter. 1980) (The mere fact that phthalocyanine and selenium function as equivalent photoconductors in the claimed environment was not sufficient to establish that one would have been obvious over the other. However, there was evidence that both phthalocyanine and selenium were known photoconductors in the art of electrophotography. "This, in our view, presents strong evidence of obviousness in substituting one for the other in an electrophotographic environment as a photoconductor." 209 USPQ at 759.). An express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).
As such, a person of ordinary skill in the art prior to the effective filing date of the instant claims would have found it obvious to substitute DAPT according to the teachings of Fong with MK0752, RO4929097, and PF-03084014 according to the teachings of Hu and Fu, and a pharmaceutical combination with vitamin C, as they are all known to be γ-secretase inhibitors, commonly capable of inhibiting Notch signaling pathways.
Fong also fails to teach ascorbate, namely sodium ascorbate.
These deficiencies of Fong are remedied by Shenoy who teaches the use of ascorbic acid/ascorbate in cancer treatment (Title). Within the disclosure, Vitamin C is referred to as (ascorbic acid, ascorbate)—showing that these two are both substitutable equivalents and comprise Vitamin C, both acting as anticancer agents.
According to MPEP 2144.06 (II), art-recognized equivalents substituted for the same purpose are rendered obvious. Therefore, a person of ordinary skill in the art prior to the effective filing date of the instant claims would have found it obvious to use ascorbate to treat cancer, following the teachings of Shenoy, who identifies ascorbic acid/ascorbate as vitamin C, and capable of treating cancer. Furthermore, the species sodium ascorbate is merely a commonly known salt of vitamin C. As such, a person of ordinary skill in the art have found it obvious to use sodium ascorbate in their composition.
Regarding claim 19, directed to a kit comprising the pharmaceutical combination of claim 1, the courts have determined that the combinations of elements known to be suitable for an intended purpose are deemed obvious.
The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945) (Claims to a printing ink comprising a solvent having the vapor pressure characteristics of butyl carbitol so that the ink would not dry at room temperature but would dry quickly upon heating were held invalid over a reference teaching a printing ink made with a different solvent that was nonvolatile at room temperature but highly volatile when heated in view of an article which taught the desired boiling point and vapor pressure characteristics of a solvent for printing inks and a catalog teaching the boiling point and vapor pressure characteristics of butyl carbitol.) See also In re Leshin, 277 F.2d 197, 125 USPQ 416 (CCPA 1960) (selection of a known plastic to make a container of a type made of plastics prior to the invention was held to be obvious); Ryco, Inc. v. Ag-Bag Corp., 857 F.2d 1418, 8 USPQ2d 1323 (Fed. Cir. 1988) (Claimed agricultural bagging machine, which differed from a prior art machine only in that the brake means were hydraulically operated rather than mechanically operated, was held to be obvious over the prior art machine in view of references which disclosed hydraulic brakes for performing the same function, albeit in a different environment) see MPEP § 2144.07
According to Fong, ascorbic acid is known to promote osteoblast differentiation (the formation of new bone cells), and Notch pathway signaling inhibitors, or g-secretase inhibitors are known to counteract cancer induced suppression of this process. When Notch signaling is shut down by g-secretase inhibitors, the full effect of ascorbic acid in osteoblast differentiation is restored, and the cancer-induced blockage of this process is relieved (Abstract). Therefore, osteoblasts can develop normally again, effectively allowing for bone formation, restoring ascorbic acid’s full effect. The combination as demonstrated in the disclosure by Fong would help reverse cancer-induced bone damage (pages 31431 and 31433).
A person of ordinary skill in the art, prior to the effective filing date of the instant application following the teachings of Fong would be motivated to combine ascorbic acid and Notch pathway signaling in a kit in order to promote bone formation in patients having cancer. The combination of ascorbic acid and a g-secretase inhibitor in a kit would be an obvious solution to cancer-induced bone degradation, especially in cases where breast cancer metastasizes to bone. A skilled artisan would predict the effect of the combination would promote bone growth, as well as counteract bone degradation.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new grounds 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sophia P. Hirakis whose telephone number is +1 (571) 272-0118. The examiner can normally be reached within the hours of 5:00 am to 5:00pm EST, Monday through Friday.
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/SOPHIA P HIRAKIS/Examiner, Art Unit 1623
/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623