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 .
Claims 4, 7, 10, 12-13, 15-16, and 24-33 are cancelled.
Claims 1-3, 5-6, 8-9, 11, 14, 17-23, and 34-35 are pending.
Applicant's election with traverse of Group II, claims 11-14 and 17-23 in the reply filed on 01/23/2026 is re-acknowledged. The traversal is on the ground(s) that Groups I-III have unity of invention because they represent the third combination of categories enumerated by 37 CFR 1,475(c). This remains persuasive because the third combination of categories enumerated by 37 CFR 1,475(c) requires the groups to be a product, a process specially adapted for the manufacture of the product, and a use of the said product. Group I is not a process specially adapted for the manufacture of the product (the product allegedly being a disconnection agent of instant claim 35). The process to which Group I is directed is not a process for manufacture and not product is made. Instead, Group I is a screening assay process that identifies already existing compounds as having the desired properties in a specific (to the cell line used and at particular doses) context.
The requirement is still deemed proper and therefore remains FINAL.
Claims 1-3, 5-6, 8-9, and 34-35 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to one or more nonelected Groups/inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 01/23/2026.
Claims 11, 14, 17, and 22 are currently amended.
Claims 11, 14, and 17-23 are under examination on the merits.
Priority
This application is a 371 of PCT/GB2021/052449, filed 09/21/2021, which claims priority to United Kingdom 2014831.8, filed 09/21/2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Maintained-Notice
It appears Applicant’s claims are directed to the mechanism by which one or more prior art method(s) effect(s) treatment. The MPEP provides that:
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel." Id. See also MPEP 2112(I) with regard to inherency and product-by-process claims and MPEP § 2141.02 with regard to inherency and rejections under 35 U.S.C. 103,”
(see MPEP 2112(I)). Therefore, references teaching the active method steps using the same products with the same starting population will be deemed to anticipate and/or make obvious the claimed treatment method(s).
Withdrawn Objections/Rejections
The objections to the specification are withdrawn as overcome by the corrective amendments to the specification dated 07/20/2026. The rejections of the claims under 35 USC §112(a) for partial lack of enablement are withdrawn in light of Applicant’s amendments which narrow the claim scope to the scope deemed enabled (see the 07/20/2026 claim amendments). The rejections under 35 USC §102 are withdrawn in light of Applicant’s significant claim amendment dated 07/20/2026. The rejections under 35 USC §103 are withdrawn in light of Applicant’s significant claim amendment dated 07/20/2026 and are replaced with the rejections under 35 USC §103 as presented in this Office Action to account for the newly amended claim scope.
Maintained-Notice
Applicant is advised that claims using comprising language will not be examined as consisting of or a combination thereof (see for example, lines 15-20 of page 22 of the specification). The MPEP provides that the transitional phrases “comprising”, “consisting essentially of” and “consisting of” define the scope of a claim with respect to what unrecited additional components or steps, if any, are excluded from the scope of the claim (see MPEP §2111.03). Without a clear transitional term, the metes and bounds of the claims are indefinite and fail to provide the critical notice function to the artisan and public as to what is protected by the claim scope. Therefore, recitations of ‘comprising’ will be interpreted to comprise the following elements, but will be understood to potentially encompass more than what is explicitly recited. Recitations of ‘consisting of’ will be interpreted as closed and limited to the explicitly recited, so-modified elements.
A disconnection agent is understood to mean an agent that reduces the ability of cells to exchange, share, or transfer molecules with other cells, through connections, in particular through tumour microtubules. A disconnection agent may thus reduce the number of, inhibit the function of, or inhibit the formation of tumour microtubules between cells. An agent which has direct toxic effects (killing more than 10% of the cells at the concentration required to have demonstrated/observed disconnection effects) would not be a "disconnection agent" in accordance with the present invention, at least for the tumour type where toxicity was observed (see for example, lines 23-33 of page 22 through lines 1-6 of page 23 of the specification).
‘About’ means +/- 10% of the modified numerical value (see for example, page 22 of the specification).
Maintained with Amendments related to Claim Amendments-Claim Rejections - 35 USC § 112
35 USC § 112(a)
Written Description
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 11, 14, and 17-23 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. This is a written description rejection.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B. V. v. Dianwnd Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
The Application claims a broad genus of disconnection agents that are Protein Kinase C (PKC) stimulators, without disclosure of a conserved structure/representative number of species to adequately describe said genus and sub-genus. The Application discloses that PKC modulators are known in the art (see for example, lines 4-20 of page 5 of the specification) and provides a list of acknowledged modulators (see for example, lines 10-25 of page 8 and page 13 of the specification; noting that Applicant acknowledges that not all of these enumerated modulators would function as a disconnection agent in the claimed invention and further noting that among these ‘modulators’ there is no distinction for which compounds stimulate or inhibit PKC, let alone which would stimulate PKC and function in the claimed method as required), but also discloses that the effects of a given modulator are highly dependent upon the cell/cancer/tumor type contacted with said modulator (see for example, line 19 of page 10 through line 9 of page 11 of the specification) and does not provide evidence of predictable function of a representative number of species of disconnection agent (or PKC stimulators) that would function as claimed to disconnect junctions across the breadth of heterogenous cancers claimed (while killing less than 10% of the cells, see the claim interpretation section above). Therefore, in view of this disclosure, Applicant is claiming a broad genus of disconnection agents that are PKC stimulators and cancers to be treated with said agents. The specification does not provide adequate written description for the entire claimed genus of disconnection agents (or PKC modulators) as claimed or cancers to be treated therewith, because in the absence of empirical determination, one skilled in the art would be unable to immediately envision, recognize, or distinguish at least most of the members comprised within the genus claimed, specifically, which agents would be disconnection agents that stimulate PKC for treating cancer (where the agent would act as a disconnection agent) as claimed.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. Applicant has disclosed 5 species of PKC modulators which function as disconnection agents, but also discloses 5 species which do not function as disconnection agents as claimed (see for example, page 27 of the specification). The five evidenced disconnection agents were only shown to function as disconnection agents in 3 solid tumor cell lines (breast cancer, glioblastoma, and hepatocellular carcinoma) in vitro (see for example, Example 2 bridging pages 26-27 of the specification; Examples 3-4 using TPPB in solid brain tumor in vivo (see for example, pages 28-31); Example 5-6 TPPB and glioblastoma in vivo (see for example, pages 31-34)).
Furthermore, Applicant has not disclosed relevant, identifying characteristics of said disconnection agents (PKC stimulators) or of the cancers to be treated therewith that confer upon said agent the ability to function as claimed because the instant specification does not provide structural/sequential features that correlate with an anti-cancer, disconnection-function as claimed. Further, the cancers for which a given agent would predictably function as claimed are not described with regard to any unifying features correlating with a reasonable probability to be treated as claimed.
Absent a clear description of the at least minimal structural features correlating with an ability to function as claimed which are shared by members of a genus commonly sharing this function, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish which disconnection agents would possess the ability to function as claimed and which cancers would respond as claimed (be treated, with the disconnection agent acting as a disconnection agent) by the instantly recited method.
Furthermore, MSK (WO 1997030174 A1; citation 1 under the Foreign Patent Document section of the 03/17/2023 IDS) teaches that the agents themselves are dependent upon contact/incubation time, with regard to their effects on PKC (see for example, lines 5-25 of page 44, teaching that the effects of bryostatin-1 on PKC appear to be time and context-dependent; see further, page 70 at lines 15-20).
Accordingly, absent empirical determination, one skilled in the art would be unable to predict or envision which disconnection agents (PKC stimulators) comprised within the genus possesses the therapeutic, disconnection function, as claimed. The general knowledge and level of skill in the art does not adequately supplement the omitted description, because specific, not general guidance is needed. Since the disclosure fails to describe relevant, identifying structural characteristics, in the form of specified, evidenced, disconnection agents and specific cancers to be treated therewith having defined features, that correlate with the ability to function as claimed, and because the disclosed guidance and examples, discussed above, are not sufficient to describe the claimed genus of disconnection agents that are PKC stimulators or the recited genus of cancers, it is submitted that the written description requirement of 35 U.S.C. 112(a) has not been met.
Applicant is directed to MPEP § 2163 for guidelines on compliance with the written description requirement. Here, applicant has not described a reasonable number of members of the genus of disconnection agents that would function in the method(s) as claimed, but rather has presented the public with an idea of how to perform an assay that might identify some compounds/agents and cancers that fall within the scope of the claim. Of course, depending on what agents/cancers are used in the screening assay, it may well identify none. The Court of Appeals for the Federal Circuit addressed claims of this sort in great detail in University of Rochester v. G.D. Searle and Co. (69 USPQ 2nd 1886, CAFC 2004). In Rochester, the Federal Circuit upheld the district court's ruling that patent claims which recited administration of compounds not disclosed, but rather to be identified in a screening assay, were invalid on their face. The claims not only encompass agents which are not yet known to have this function, but also encompass agents/compounds which have not yet been invented.
In Ariad, the court further noted that the written description plays a particularly important role in the biological arts, where patentees might otherwise be tempted to claim a genus of compounds by its function or result:
“The written description requirement also ensures that when a patent claims a genus by its function or result, the specification recites sufficient materials to accomplish that function—a problem that is particularly acute in the biological arts. 5 See Guidelines for Examination of Patent Applications Under the 35 U.S.C. 112, 1, “Written Description” Requirement, 66 Fed. Reg. 1099, 1105-1106 (Jan. 5, 2001). This situation arose not only in Eli Lilly but again in University of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916 [69 USPQ2d 1886] (Fed. Cir. 2004). In Rochester, we held invalid claims directed to a method of selectively inhibiting the COX-2 enzyme by administering a non-steroidal compound that selectively inhibits the COX-2 enzyme. Id. at 918. We reasoned that because the specification did not describe any specific compound capable of performing the claimed method and the skilled artisan would not be able to identify any such compound based on the specification's function description, the specification did not provide an adequate written description of the claimed invention. Id. at 927-28. Such claims merely recite a description of the problem to be solved while claiming all solutions to it and, as in Eli Lilly and Ariad's claims, cover any compound later actually invented and determined to fall within the claim's functional boundaries—leaving it to the pharmaceutical industry to complete an unfinished invention.”
Ariad Pharmaceuticals., Inc. v. Eli Lilly & Co., 94 USPQ2d 1161, 1173 (Fed. Cir. 2010) (en banc). Emphasis added.
Therefore, claims 11-14 and 17-23 are deemed to fail to meet the written description requirement, as presently drafted. The disclosure fails to provide written description for the claimed genus of disconnection agents that are PKC stimulators. The genus of disconnection agents is not limited to a particular class (protein, antibody, aptamer, etc.). The genus of disconnection agents that are PKC stimulators, as recited, is not described by a representative number of species of a structure-function correlation. In light of the disclosure, only the use of a disconnection agent that is a PKC stimulator that is TPPB is deemed to be described as functioning as a disconnection agent that stimulates PKC and treats cancer.
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 (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 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.
Claim(s) 11, 17, and 20-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over MSK (WO 1997030174 A1; citation 1 under the Foreign Patent Document section of the 03/17/2023 IDS).
Regarding claim 11, as provided in the maintained notice section set forth above, the method claims will be Examined with respect to obviousness of the active methods steps and compositions used for the recited population/disease and not to discover of any mechanism by which the method functions. The active steps are administration of a PKC stimulator to a mammal with a tumour prior to or concomitant with administration of a toxic agent toxic to cells of the tumour. The population is a mammal with a tumour.
Regarding claim 11, MSK teaches that Protein kinase C (PKC) functions in processes relevant to carcinogenesis, tumor cell metastasis, and apoptosis.
MSK teaches a method for treating cancer in a subject (which is not defines, but where all examples use human cells and IRB approval and obtaining written consent are discussed, the subject is most reasonably understood to be a human mammal, the reference generally with pages 181-185 serving as exemplary; administration and proof of concept are shown, for example, in human gastric cancer cells and murine mammary carcinoma at exemplary, pages 194 and 195-197, reading on treatment of a subject that is a mammal) comprising administering to the subject an effective amount of at least one antitumor therapeutic agent, and at least one modulating agent, sequentially or concomitantly (see for example, page 15 at lines 5-8). The modulating agent includes, but is not limited to bryostatin-1 (see for example, page 16 at lines 5-15). The antitumor therapeutic agents is a chemotherapeutic agent. The chemotherapeutic agent includes but is not limited to mitomycin C, carboplatin, cisplatin, paclitaxel, etoposide, and doxorubicin (see for example, likes 15-20 of page 16). In an embodiment of the method of MSK, the cancer is a gastrointestinal cancer, breast cancer or an ovarian cancer, lymphoma, adenocarcinoma, glioblastoma, leukemia, esophageal carcinoma, head and neck cancer, prostate cancer, lung cancer, melanoma, cervical carcinoma, pancreatic cancer, sarcoma, hepatoma, or gallbladder cancer (see for example, lines 25-35 of page 16). Bryostatin-1 is taught to be a PKC stimulator upon short duration and PKC inhibition upon long duration (see for example, page 44 at lines 1-20). Where there is no apparent structural difference in the bryostatin-1 compound used by MSK and the bryostatin-1 compound listed as exemplary of a disconnection agent by Applicant (see for example lines 10-25 of page 8 of the instant specification), the compound is presumed to be a disconnection agent acting as a PKC stimulator as claimed absent an evidence, convincing showing to the contrary.
The difference between MSK’s disclosure and that of the instant claims is that MSK doesn’t teach bryostatin-1 as a disconnection agent that is a PKC stimulator in a manner consistent with anticipation, i.e. to arrive at the selection of bryostatin-1 as a PKC stimulator requires an understanding of the biphasic effect of bryostatin-1 on PKC (time-dependent activity as set forth above).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the combined references before the effective filing date of the claimed invention. The artisan would have been motivated to make and use the invention as claimed to treat cancer by administering a PKC modulator sequentially or concomitantly with a toxic agent (such as a chemotherapeutic of MSK). Where MSK discusses Bryostatin-1 as a PKC modulator for use in the method, there is a clear intent to encompass both inhibition and stimulation. The instant claims, failing to provide clear evidence as to the contact time of bryostatin-1 when administered so as to distinguish over the administration taught by MSK. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references prior to the effective filing date.
Regarding claim 17, as noted above, MSK teach that in an embodiment of the method, the cancer is glioblastoma (see for example, lines 25-35 of page 16).
Regarding claim 20, MSK teaches treatment pf human gastric cancer cells with safingol for only 1 hour prior to 24 hours of treatment with MMC (a chemotherapeutic drug) resulted in an increase in apoptosis (44%±4% of exposed cells) that was essentially equivalent to that which was observed with concomitant exposure of the cells to the two drugs for the entire 24 hour interval (see for example, pages 3, 21, and 23-24; noting that MSK additionally teaches administration of PKC modulator (such as safingol) 30 minutes, 1 hr, 3hrs, 6hrs, 18hrs, and 24hrs prior to exposure with an toxic agent (such as the chemotherapeutic agent MMC) at exemplary page 96).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the combined references before the effective filing date of the claimed invention. The artisan would have been motivated to make and use the invention as claimed to treat cancer by administering a PKC modulator sequentially or concomitantly with a toxic agent (such as a chemotherapeutic of MSK; note that where safingol and bryostatin-1 are disclosed as equivalent PKC modulators for treating cancer, the artisan would have found it obvious to swap safingol for bryostatin-1 to develop an optimized treatment method). The artisan would have found it obvious to adopt this administration schedule/dosing regimen for any of the disclosed PKC modulators of MSK, including brystatin-1. Doses and dosage regimens are result effective variables.
It is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and therefore obvious).
As the enumerated dosage regimens were known to the ordinary artisan, it would have been obvious to optimize the dosage regimens, including the particular dosing regimen/timing of dosing recited in the claims to treat cancer by administering a PKC modulator (stimulator) and toxic agent in order to achieve therapeutic effects.
It is not inventive to discover the optimum or workable ranges by routine experimentation, In re Aller, 220 F.2d 454, 456 (CCPA; see also In re Peterson, 315, F.3D, 1325 (Fed. Cir. 2003).
Only if the results of optimizing a variable are unexpectedly good can a patent be obtained for the claimed critical ranges, In re Geisler, 116 F.3d 1465, 1469, (Fed. Cir. 1997) quoiting in re Antoine, 559 F.2d 618, 620 (CCPA 1977). Discovery for an optimum value or a result effective variable in a known process is ordinarily with the skill of the art, In re Boesch 617 F,2d 272, 276 (CCPA 1980). The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references prior to the effective filing date.
Regarding claim 21, MSK teaches a method for treating cancer in a subject comprising administering to the subject an effective amount of at least one antitumor therapeutic agent, and at least one modulating agent, sequentially (wherein the tumor bearing subject is administered at least one PKC-modulating (stimulator) agent and subsequently administered at least one antitumor therapeutic agent) or concomitantly, wherein at least one of the antitumor therapeutic agents is a radiotherapeutic agent (understood to encompass/read upon radiation therapy by art-known means; this appears to be consistent with the instant claim scope in light of lines 5-20 of page 23 of the instant specification which appears to equate a radiotherapeutic agent with radiation) (see for example, claims 15, 19, and 31 at pages 205 and 207).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the combined references before the effective filing date of the claimed invention. The artisan would have been motivated to make and use the invention as claimed with the toxic agent being a radiotherapy to treat cancer. The artisan would have found it obvious to adopt this administration schedule/dosing regimen for any of the disclosed PKC modulators of MSK, including brystatin-1. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references prior to the effective filing date.
Regarding claim 22, MSK teaches a method for treating cancer in a subject comprising administering to the subject an effective amount of at least one antitumor therapeutic agent, and at least one modulating agent, sequentially (wherein the tumor bearing subject is administered at least one PKC-modulating agent (stimulator) and subsequently administered at least one antitumor therapeutic agent) or concomitantly, wherein at least one of the antitumor therapeutic agents is a chemotherapeutic agent (see for example, claims 15, 19, and 30 at pages 205 and 207).
Claim(s) 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over MSK, as applied to claims 11, 17, and 20-22 above, in view of Yi et al (J Mol Neurosci. 2012 Sep;48(1):234-44. doi: 10.1007/s12031-012-9816-3. Epub 2012 Jun 15).
Regarding claim 14, MSK teaches as set forth above.
MSK does not clearly teach that TPPB is a PKC stimulator.
However, Yi et al teach that bryostatin-1 and TPPB individually and selectively activated PKC-δ and PKC-ε (see for example, the abstract).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the combined references before the effective filing date of the claimed invention. The artisan would have been motivated to make and use the invention as claimed to treat cancer by administering a PKC modulator sequentially or concomitantly with a toxic agent (such as a chemotherapeutic of MSK). Where bryostatin-1 is taught to be a therapeutic PKC modulator and where TPPB is taught to also stimulate PKC, it would have been prima facie obvious to swap one known PKC stimulator with another, such as by swapping bryostatin-1 for TPPB because both are individually known in the art to stimulate PKC (see MPEP sections 2143(I)(B) and 2144.06 (II)). Where there is no apparent structural difference in the TPPB compound used by Yi et al and the TPPB compound listed as exemplary of a disconnection agent by Applicant (see for example lines 10-25 of page 8 of the instant specification), the compound is presumed to be a disconnection agent acting as a PKC stimulator as claimed absent an evidence, convincing showing to the contrary. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references prior to the effective filing date.
Claim(s) 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over MSK, as applied to claims 11, 17, and 20-22 above, as evidenced by Serwer et al (J Vis Exp. 2010 Aug 16;(42):1992. doi: 10.3791/1992).
Regarding claim 18, MSK teaches as set forth above and further teaches intravenous and/or intraperitoneal administration of safingol (see for example, pages 55-57 and 61), infusion of UCN-01 (see for example, pages 61 and 63 (also teachings that administration (route and dosing) would be selected based upon prior art teachings)), intravenous and/or intraperitoneal administration of a 20-mer that inhibits PKCα (see for example, page 75), and intravenous administration of flavopiridol (see for example, pages 126 and 165) (where safingol, UCN-01, the 20-mer that inhibits PKCα, and flavopiridol are taught to be PKC inhibitors and other PKC modulators, including bryostatin-1, are taught to be ripe for clinical trials where doing and route would depend upon the prior art safety and efficacy data (see for example, page 63)). Intravenous, infusion, and intraperitoneal administration are widely known in the art to be means for systemic administration (as evidenced by Serwer et al at exemplary page 1 of 6).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the combined references before the effective filing date of the claimed invention. The artisan would have been motivated to make and use the invention as claimed to treat cancer by administering a PKC modulator systemically. Where MSK discusses bryostatin-1 as a PKC modulator for use in the method, there is a clear intent to encompass both inhibition and stimulation. Where MSK at length discusses intravenous or intraperitoneal (systemic) administration of PKC modulators, the artisan would have found it obvious to try administering a PCK modulator, such as bryostatin-1 (which is a PKC stimulator) systemically. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references prior to the effective filing date.
Claim(s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over MSK, as applied to claims 11, 17, and 20-22 above, in view of Jonathan et al (Blood 2015; 126 (23): 1552. doi: https://doi.org/10.1182/blood.V126.23.1552.1552).
Regarding claim 19, MSK anticipates instant claim 11 (noting that the cancers MSK teaches that the method may be practiced in are breast cancer, pancreatic cancer, lung cancer, liver cancer (hepatoma), stomach cancer (gastric cancer), or ovarian cancer (see for example, lines 10-25 of page 6 and claims 15 and 32-34 at pages 205 and 207)), as discussed above.
MSK does not teach administration local to the tumor.
However, Jonathan et al teach that intratumoral (held to read on the recitation of administration local to the tumor) administration of immunotherapeutic agents has several advantages including 1) higher concentrations of agents in close proximity to target antigens and tumor-infiltrating lymphocytes 2) lower doses overall with less systemic exposure and toxicity 3) potentially a novel mechanism of action such as depletion of intratumoral Tregs 4) potential for an abscopal effect, essentially acting as an in-situ cancer vaccine (see for example, paragraph 1 of the abstract at page 1).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the combined references. The artisan would have been motivated to use the invention as claimed to achieve the noted anti-cancer effects taught by MSK while, at least reducing any potential off-target effects and/or toxicities and potentially recognizing one or more of the additionally enumerated benefits associated with intratumoral administration.
The MPEP provides that:
“The Supreme Court in KSR reaffirmed the familiar framework for determining obviousness as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), but stated that the Federal Circuit had erred by applying the teaching-suggestion-motivation (TSM) test in an overly rigid and formalistic way. KSR, 550 U.S. at 404, 82 USPQ2d at 1391. Specifically, the Supreme Court stated that the Federal Circuit had erred in four ways: (1) “by holding that courts and patent examiners should look only to the problem the patentee was trying to solve ” (Id. at 420, 82 USPQ2d at 1397); (2) by assuming “that a person of ordinary skill attempting to solve a problem will be led only to those elements of prior art designed to solve the same problem” (Id.); (3) by concluding “that a patent claim cannot be proved obvious merely by showing that the combination of elements was ‘obvious to try’” (Id. at 421, USPQ2d at 1397); and (4) by overemphasizing “the risk of courts and patent examiners falling prey to hindsight bias” and as a result applying “[r]igid preventative rules that deny factfinders recourse to common sense” (Id.). See also Novartis Pharms. Corp. v. West-Ward Pharms. Int'l Ltd., 923 F.3d 1051, 1059, 2019 USPQ2d 171676 (Fed. Cir. 2019); Apple Inc. v. Samsung Elecs. Co., 839 F.3d 1034, 1047-48, 120 USPQ2d 1400, 1410 (Fed. Cir. 2016); and Aventis Pharma S.A. v. Hospira, Inc., 675 F.3d 1324, 1332, 102 USPQ2d 1445, 1449 (Fed. Cir. 2012)… Importantly, the Supreme Court reaffirmed principles based on its precedent that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.”Id. at 415-16, 82 USPQ2d at 1395. The Supreme Court stated that there are “[t]hree cases decided after Graham [that] illustrate this doctrine.” Id. at 416, 82 USPQ2d at 1395. (1) “In United States v. Adams, . . . [t]he Court recognized that when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result.” Id. (2) “In Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., . . . [t]he two [pre-existing elements] in combination did no more than they would in separate, sequential operation.” Id. at 416-17, 82 USPQ2d at 1395. (3) “[I]n Sakraida v. AG Pro, Inc., the Court derived . . . the conclusion that when a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” Id. at 417, 82 USPQ2d at 1395-96 (Internal quotations omitted.). The principles underlining these cases are instructive when the question is whether a patent application claiming the combination of elements of prior art would have been obvious. The Supreme Court further stated that:
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability. For the same reason, if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond his or her skill. Id. at 417, 82 USPQ2d at 1396.
When considering obviousness of a combination of known elements, the operative question is thus “whether the improvement is more than the predictable use of prior art elements according to their established functions.” Id,”
(see MPEP §2141(I)). It would have been obvious for the artisan to try locally administering the disconnection agent (PKC modulator such as bryostatin-1, which is a PKC stimulator), such as the modulators of MSK, by known means such as by intertumoral administration as taught by Jonathan et al. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Claim(s) 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over MSK, as applied to claims 11, 17, and 20-22 above, in view of Hardman et al (Nat Commun 11, 1879 (2020). https://doi.org/10.1038/s41467-020-15742-7).
Regarding claim 23, MSK teaches as set forth above.
MSK does not teach that the treatment/toxic agent is an immunotherapy.
However, Hardman et al teach that targeted biologics and cell therapies for the treatment of cancer, including monoclonal antibodies (mAbs), antibody-drug conjugates (ADC’s), bi- and tri-specific antibodies (biAbs, triAbs), chimeric antigen receptor (CAR) T and NK cell therapies, and neoantigen-directed cell therapies, are revolutionizing oncology. By targeting tumor-specific cell surface antigens and neoantigens, these therapies offer distinct advantages over traditional treatment options as they avoid the systemic toxicity associated with cytotoxic chemotherapies while efficiently and selectively clearing malignant cells. However, durability of patient-response to said treatments is observed to diminish across a variety of settings due top variable and decreased antigen density. Protein kinase C (PKC) modulators offer a potentially general solution to this antigen density and persistence problem. Among the most studied PKC modulators, plant-derived phorbol esters (PEs) have long been known to influence antigen expression in a variety of cell lines. Additionally, bryostatin 1, a marine macrolide and potent PKC modulator, also alters expression of surface antigens in tumor cell lines, making them more immunogenic and thus more susceptible to immune or other antigen-targeted clearance strategies. Indeed, several pre-clinical and clinical studies have reported that bryostatin 1 (where bryostatin-1 and its synthesized analogues are understood to activate PKC, see for example, the results section at pages 3-8) can alter the immunophenotype and increase the immunogenicity of cancer cells in acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin’s lymphoma (NHL). These and related studies indicate that PKC modulators can enhance expression and persistence of certain antigens, potentially enhancing a variety of (neo)antigen-targeted therapies (see for example, column 1 of page 2). Hardman et al designed and prepared a set of structurally diverse analogs and evaluated how variations in their structures influence their binding to PKC, their in vitro translocation of a PKC fusion protein, and their enhancement of CD22 antigen density in in vitro models of ALL and AIDS-related NHL (see for example, column 2 of page 8). Hardman et al teach that these synthetic studies have enabled access to a class of promising leads for enhancing antigen-targeted immunotherapy, including enhanced CD22-targeted CAR T therapy (see for example, column 1 of page 9).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the combined references. The artisan would have been motivated to use the invention as claimed to enhance antigen-targeted immunotherapy, as discussed above. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Claim(s) 11, 14, 17, and 21-23 is/are alternatively rejected under 35 U.S.C. 103 as being unpatentable over Phipps et al (US 20050020482 A1) in view of Baskar et al (Int J Med Sci. 2012;9(3):193-9. doi: 10.7150/ijms.3635) and Yi et al (J Mol Neurosci. 2012 Sep;48(1):234-44. doi: 10.1007/s12031-012-9816-3. Epub 2012 Jun 15).
Regarding claims 11-14, Phipps et al teach a method of treating a cancer/tumour (noting that Phipps limits its discussion and teachings to treatment of neuroblastoma and certain breast cancers (see the disclosure generally with paragraphs 0012 (column 1, page 2), 0035 (column 1, page 3), 0039 (column 3, page 3), column 0047 (column 1, page 4), and tables 1-3 and claim 11 (pages 6-7)) where the teachings of Phipps are being understood as limited to neuroblastoma and breast cancer) in a patient, comprising the steps of: (a) providing the cell with a protein kinase A (PKA) activator; and (b) providing the cell with modulator for specifically inhibiting or activating one or more PKC isoforms (see for example, claim 17).
Phipps et al do not teach additionally, subsequent of concomitant treatment with a toxic agent (understood to comprise, for example, a chemotherapeutic agent or radiotherapy).
However, Baskar et al teach that cancer treatment modalities include radiation therapy, surgery, chemotherapy, immunotherapy and hormonal therapy (see for example, the abstract at page 193).
Phipps et al and Baskar et al do not teach that TPPB is a PKC stimulator (modulator)
However, Yi et al teach that TPPB selectively activated PKC-δ and PKC-ε (see for example, the abstract).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the combined references before the effective filing date of the claimed invention. The artisan would have been motivated to make and use the invention as claimed to treat cancer by administering a PKC activator/stimulator sequentially or concomitantly with a toxic agent (such as a chemotherapeutic of Baskar et al). Where TPPB is taught to stimulate PKC so as to be a PKC modulator within the genus taught by Phipps et al (noting that Phipps does not disclose examples of said modulators of PKC leading the artisan to look to the art for functional equivalents), it would have been prima facie obvious to use TPPB as an art-known PKC stimulator as the PKC modulator in the method of Phipps et al (see MPEP sections 2143(I)(B) and 2144.06 (II)). Where there is no apparent structural difference in the TPPB compound used by Yi et al and the TPPB compound listed as exemplary of a disconnection agent by Applicant (see for example lines 10-25 of page 8 of the instant specification), the compound is presumed to be a disconnection agent acting as a PKC stimulator as claimed absent an evidence, convincing showing to the contrary. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references prior to the effective filing date.
Regarding claim 17, as discussed above, Phipps et al teach treatment of neuroblastoma (see for example, paragraph 0039 where Phipps et al state that exemplary of cancer tumours, they studied neuroblastoma cells).
Regarding claim 21, as discussed above, Baskar et al teach the use of radiation therapy (held to read on radiotherapy) as a known toxic agent for treating cancer (see for example, the abstract at page 193).
Regarding claim 22, as discussed above, Baskar et al teach the use of chemotherapy (held to read on a chemotherapeutic agent) as a known toxic agent for treating cancer (see for example, the abstract at page 193).
Regarding claim 23, as discussed above, Baskar et al teach the use of immunotherapy (held to read on an immunotherapeutic agent) as a known toxic agent for treating cancer (see for example, the abstract at page 193).
Claim(s) 18 is/are alternatively rejected under 35 U.S.C. 103 as being unpatentable over Phipps et al, Baskar et al, and Yi et al, as applied to claims 11, 14, 17, and 21-23 above, in view of Moffitt (Systemic Therapy, obtained from: https://web.archive.org/web/20190121051708/https://www.moffitt.org/treatments/systemic-therapy/; available as of 01/21/2019 as evidenced by Wayback Machine).
Regarding claim 18, the combined references teach as set forth above.
The combined references do not explicitly teach systemic administration of the PKC stimulator that is a disconnection agent.
However, Moffitt teaches that systemic therapy refers to any type of cancer treatment that targets the entire body. For example, chemotherapy – the most common form of systemic cancer treatment – circulates throughout the bloodstream to destroy cancerous cells in multiple locations. Chemo medications can be administered through several different methods (e.g., as a pill, injection or intravenous infusion), but once the medications enter the bloodstream, they disperse and destroy abnormal cells in various locations. As a result, chemotherapy is often used to treat cancers that have spread beyond their original point of development (see for example, the first paragraph).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the combined references before the effective filing date of the claimed invention. The artisan would have been motivated to make and use the invention as claimed to treat cancer by administering a PKC activator/stimulator sequentially or concomitantly with a toxic agent (such as a chemotherapeutic of Baskar et al), systemically in order to treat all cancer in the body, including metastatic lesions which may yet be undetected to decrease the likelihood of leaving any cancer untreated or of recurrence from seeded cancer. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references prior to the effective filing date.
Claim(s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Phipps et al, Baskar et al, and Yi et al, as applied to claims 11, 14, 17, and 21-23 above, in view of Jonathan et al (Blood 2015; 126 (23): 1552. doi: https://doi.org/10.1182/blood.V126.23.1552.1552).
Regarding claim 19, the combined references teach as set forth above.
The combined references do not explicitly teach local administration of the disconnection agent.
However, Jonathan et al teach that intratumoral (held to read on the recitation of administration local to the tumor) administration of immunotherapeutic agents has several advantages including 1) higher concentrations of agents in close proximity to target antigens and tumor-infiltrating lymphocytes 2) lower doses overall with less systemic exposure and toxicity 3) potentially a novel mechanism of action such as depletion of intratumoral Tregs 4) potential for an abscopal effect, essentially acting as an in-situ cancer vaccine (see for example, paragraph 1 of the abstract at page 1).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the combined references. The artisan would have been motivated to use the invention as claimed to achieve the noted anti-cancer effects taught by Phipps et al and Baskar et al while, at least reducing any potential off-target effects and/or toxicities and potentially recognizing one or more of the additionally enumerated benefits associated with intratumoral administration.
The MPEP provides that:
“The Supreme Court in KSR reaffirmed the familiar framework for determining obviousness as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), but stated that the Federal Circuit had erred by applying the teaching-suggestion-motivation (TSM) test in an overly rigid and formalistic way. KSR, 550 U.S. at 404, 82 USPQ2d at 1391. Specifically, the Supreme Court stated that the Federal Circuit had erred in four ways: (1) “by holding that courts and patent examiners should look only to the problem the patentee was trying to solve ” (Id. at 420, 82 USPQ2d at 1397); (2) by assuming “that a person of ordinary skill attempting to solve a problem will be led only to those elements of prior art designed to solve the same problem” (Id.); (3) by concluding “that a patent claim cannot be proved obvious merely by showing that the combination of elements was ‘obvious to try’” (Id. at 421, USPQ2d at 1397); and (4) by overemphasizing “the risk of courts and patent examiners falling prey to hindsight bias” and as a result applying “[r]igid preventative rules that deny factfinders recourse to common sense” (Id.). See also Novartis Pharms. Corp. v. West-Ward Pharms. Int'l Ltd., 923 F.3d 1051, 1059, 2019 USPQ2d 171676 (Fed. Cir. 2019); Apple Inc. v. Samsung Elecs. Co., 839 F.3d 1034, 1047-48, 120 USPQ2d 1400, 1410 (Fed. Cir. 2016); and Aventis Pharma S.A. v. Hospira, Inc., 675 F.3d 1324, 1332, 102 USPQ2d 1445, 1449 (Fed. Cir. 2012)… Importantly, the Supreme Court reaffirmed principles based on its precedent that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.”Id. at 415-16, 82 USPQ2d at 1395. The Supreme Court stated that there are “[t]hree cases decided after Graham [that] illustrate this doctrine.” Id. at 416, 82 USPQ2d at 1395. (1) “In United States v. Adams, . . . [t]he Court recognized that when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result.” Id. (2) “In Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., . . . [t]he two [pre-existing elements] in combination did no more than they would in separate, sequential operation.” Id. at 416-17, 82 USPQ2d at 1395. (3) “[I]n Sakraida v. AG Pro, Inc., the Court derived . . . the conclusion that when a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” Id. at 417, 82 USPQ2d at 1395-96 (Internal quotations omitted.). The principles underlining these cases are instructive when the question is whether a patent application claiming the combination of elements of prior art would have been obvious. The Supreme Court further stated that:
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability. For the same reason, if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond his or her skill. Id. at 417, 82 USPQ2d at 1396.
When considering obviousness of a combination of known elements, the operative question is thus “whether the improvement is more than the predictable use of prior art elements according to their established functions.” Id,”
(see MPEP §2141(I)). It would have been obvious for the artisan to try locally administering the disconnection agent (PKC modulator such as bryostatin-1, which is a PKC stimulator), such as the modulators of MSK, by known means such as by intertumoral administration as taught by Jonathan et al. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Applicant’s Arguments and Responses:
A. Applicant request withdrawal of the rejections for lack of written description arguing that disclosure of methods of testing/screening disconnection agents for their PKC stimulating/ cancer therapeutic properties is sufficient to demonstrate possession (see pages 9-10 of the 07/20/2026 remarks).
Response: This is unpersuasive because, as noted in the rejection for lack of written description set forth above, an invitation to screen (or that the artisan could screen) is insufficient to meet the requirements of 35 USC §112(a) (see for example, page 10 discussing MPEP § 2163 and University of Rochester v. G.D. Searle and Co. (69 USPQ 2nd 1886, CAFC 2004)). Therefore, the rejection for lack of written description as presented in this Office Action is maintained at this time.
B. Applicant argues for withdrawal of the rejections under 35 USC §103 for obviousness.
Response: The rejections Applicant argues against have been withdrawn and replaced with the substantially redrafted rejections presented in this Office Action. While few of Applicant’s concerns remain applicable upon this substantial re-drafting of the rejections to account for Applicant’s newly amended claim scope, a few points stand out for clarification to guide future remarks. First, the MPEP provides that:
“A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v.Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)… Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971),”
(see MPEP section 2123(I-II)). “[T]he prior art' s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).' “Even if a reference discloses an inoperative device, it is prior art for all that it teaches.” Beckman Instrumentsv.LKB Produkter AB, 892 F.2d 1547, 1551, 13 USPQ2d 1301, 1304 (Fed. Cir. 1989). Therefore, “a non-enabling reference may qualify as prior art for the purpose of determining obviousness under 35 USC §130” Symbol Techs. Inc. v. Opticon Inc., 935 F.2d 1569, 1578, 19 USPQ2d 1241, 1247 (Fed. Cir. 1991). Second, the prior art is presumed enabled (see MPEP §2121(I)), Therefore, the prior art is presumed to function absent a convincing showing to the contrary. Additionally, as set forth above, a discovery as to how a compound accomplishes its function, while of academic interest, does not make patentable an otherwise obvious method of administering the compound to the same population for treatment of the same disease absent something like an evidenced, convincing showing of surprising results or criticality.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US 20180221479 A1 (disclosing an agent for use in the treatment of glioma in a subject, wherein said agent is capable of interfering with tumor microtube (TM)-mediated (a) invasion and/or (b) proliferation and/or (c) intracellular communication and/or (d) resistance to radiotherapy and/or chemotherapy of glioma cells);
Roehlecke et al ( Cancers. 2020; 12(4):857. https://doi.org/10.3390/cancers12040857);
Morley et al (Cell Tissue Res 340, 229–242 (2010). https://doi.org/10.1007/s00441-010-0938-z);
Potthoff et al (Cancers 2019, 11, 858; Cancers 2019, 11, 858);
Nihei et al (BMC Cell Biology 2010, 11:3);
Kreitzburg et al (Cancer Drug Resist 2018;1:181-97; http://dx.doi.org/10.20517/cdr.2018.06)
Newton et al (Trends in Pharmacological Sciences, May 2017, Vol. 38, No. 5; http://dx.doi.org/10.1016/j.tips.2017.02.002)
McIlwain et al (xPharm: The Comprehensive Pharmacology Reference, Elsevier, 2008,
Pages 1-5, ISBN 9780080552323, https://doi.org/10.1016/B978-008055232-3.63983-2);
Kraft et al (Cancer Res. 1992 Apr 15;52(8):2143-7. PMID: 1559218.);
Dickson et al (Clin Cancer Res. 2011 April 15; 17(8): 2484–2492. doi:10.1158/1078-
0432.CCR-10-2323; a phase I clinical trial of safingol in combination with cisplatin in
advanced solid tumors);
Haimovitz-Friedman et al (Cancer Research 54, 2591-2597, May 15, 1994;
disclosing that PKC mediates protection of cells against radiation-induced apoptosis);
The sources cited on the 11/13/2025 IDS;
The sources cited on the 03/17/2023 IDS; and
The sources cited on the 08/31/2023 IDS
are deemed relevant to claimed subject matter.
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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supervisor, Gregory Emch can be reached on (571) 272-8149. The fax phone number for the
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/Ashley Gao/
Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
