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
Examiner acknowledges that, according to the Filing receipt received 04/04/2025, that the instant application 18/271,954 filed 07/12/2023 is a 371 of PCT/EP2022/050702 filed 01/13/2022 which claims benefit of Swiss applications CH00024/21 filed 01/13/2021, CH00026/21 filed 01/13/2021, CH00388/21 filed 04/14/2021, CH00387/21 filed 04/14/2021, CH00656/21 filed 06/04/2021, and CH00657/21 filed 06/04/2021.
However, the limitations of the instant claims are not adequately supported or enabled in the manner provided by 35 U.S.C. 112(a) or pre-AIA U.S.C. 112, first paragraph by the foreign priority documents. More specifically, the limitations of Formula Va (claim 29) are not taught or suggested in their entirety by CH00024/21 filed 01/13/2021 and CH00026/21 filed 01/13/2021. The earliest disclosure of Formula Va is in CH00388/21 filed 04/14/2021. Moreover, the final listed compound in claim 31 is not taught or suggested by any of the foreign priority documents. As such, claim 31 has been awarded the effective date of 01/13/2022, claim 29 has been awarded the effective filing date of 04/14/2021, and claims 1-28 and 30 are awarded the effective filing date of 01/13/2021.
Information Disclosure Statement
The Information Disclosure Statement filed on 11/07/2025 is in compliance with the provisions of 37 CFR 1.97 and has been considered in full. A signed copy of list of references cited from the IDS is included with this Office Action.
Specification
The disclosure is objected to because of the following informalities:
Page 35, "thatdemonstrates" should read "that demonstrates";
Page 181, “descrIbed” should read “described”;
Page 470, “measn” should read “means”;
Page 472, “atthis” should read “at this”;
Page 472, “(50μl, Sigma HT5011))” should read “(50μl, Sigma HT5011)”.
Appropriate correction is required.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
The abstract of the disclosure is objected to because "the of efficacy" should read "the efficacy of". A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claims 1, 6, 8, 9, 13, 16, 17, 21, 23, 25, and 27-30 are objected to because of the following informalities:
Claims 1, 8, 13, 16, 25: each instance of “one more” should read “one or more”;
Claim 6: “copy number a gene” should read “copy number of a gene”;
Claims 9, 17, 23: “degraders” should read “degrader”;
Claim 21: “Myc-driver” should read “Myc-driven”;
Claims 27-28: each instance of “one or more of C1-4 alkyl, halogen” should recite “or” before “halogen”;
Claim 29: the resolution of formula Va is too low to interpret the labels of the structure;
Claim 30: “501 to 573” should read “501-573” to be consistent with the other ranges in the claim.
Appropriate correction is required.
Drawings
The drawings are objected to because portions of Figures 4A, 4B, and 4C are on multiple pages and are not labeled with their figure number. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 5, 13-20, 26, and 28-30 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 5 recites “the tumor nucleic acid”. This limitation lacks antecedent basis.
Claims 13 and 16 recite “the one [or] more Myc transcription factor biomarkers”. This limitation lacks antecedent basis. Claims 14-15 and 17-20 do not clarify the limitation at issue and are also rejected.
Claim 26 recites “the Myc-driven cancer”. This limitation lacks antecedent basis, as claim 1 recites “a Myc-driven tumor”.
Claim 28 recites “Y is N or O”. However, Y cannot be N as its valence would not be satisfied without a third substituent or point of attachment.
Claim 28 recites “preferably methyl, ethyl, or halogen, preferably F”. The term “preferably” is indefinite as it is unclear whether the limitation following it is part of and/or required by the claimed invention. See MPEP 2173.05(c) and (d).
Claim 29 recites “the compound of formula 1”. This limitation lacks antecedent basis.
Claim 30 recites “any of Compounds 1-160, 201-440, and 501 to 573” but does not depict any of the compound structures. MPEP 2173.05(s), “Where possible, claims are to be complete in themselves.” The scope of claim 30 is unclear because the claim, which incorporates by reference structures depicted in the tables of the specification, is itself incomplete. Examiner recommends that Applicant amend claim 30 to depict the structures of compounds 1-160, 201-440, and 501-573.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-25 and 27-31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating a Myc-driven tumor selected from breast cancer, small cell lung carcinoma, non-small cell lung carcinoma, neuroendocrine cancer, acute myelogenous leukemia, lymphoma, and multiple myeloma, does not reasonably provide enablement for treating Myc-driven tumors/cancers generally. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, "The Federal Circuit has repeatedly held that "the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation." In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)" (emphasis added). The "make and use the full scope of the invention without undue experimentation" language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: "A lack of enablement for the full scope of a claim, however, is a legitimate rejection." The principle was explicitly affirmed most recently in Liebel-Flarsheim Co. v. Medrad, Inc., 481 F.3d 1371, 82 USPQ2d 1113; Auto. Tech. Int'l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008).
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. Some experimentation is not fatal; the issue is whether the amount of experimentation is "undue"; see In re Vaeck, 20 USPQ2d 1438, 1444.
The treatment of cancer generally cannot possibly be considered enabled.
By way of background, four cases are of particular relevance to the question of enablement of a method of treating cancers broadly or even generally:
In In re Buting, 57 CCPA 777, 418 F.2d 540, 163 USPQ 689, the claim was drawn to "The method of treating a malignant condition selected from the group consisting of leukemias, sarcomas, adenocarcinomas, lymphosarcomas, melanomas, myelomas, and ascitic tumors" using a small genus of compounds. The Court decided that human testing "limited to one compound and two types of cancer" was not "commensurate with the broad scope of utility asserted and claimed".
In Ex parte Jovanovics, 211 USPQ 907 the claims were drawn to "the treatment of certain specified cancers in humans" by the use of a genus of exactly two compounds, the N-formyl or N-desmethyl derivative of leurosine. Applicants submitted "affidavits, publications and data" for one of the compounds, and a dependent claim drawn to the use of that species was allowed. For the other, no data was presented, applicants said only that the other derivative would be expected to be less effective; claims to the genus were refused.
In Ex parte Busse, et al., 1 USPQ2d 1908, claims were drawn to "A therapeutic method for reducing metastasis and neoplastic growth in a mammal" using a single species. The decision notes that such utility "is no longer considered to be "incredible", but that "the utility in question is sufficiently unusual to justify the examiner's requirement for substantiating evidence. Note also that there is also a dependent claim 5 which specified "wherein metastasis and neoplastic growth is adenocarcinoma, squamous cell carcinoma, melanoma, cell small lung or glioma." The decision notes that "even within the specific group recited in claim 5 some of the individual terms used actually encompass a relatively broad class of specific types of cancer, which specific types are known to respond quite differently to various modes of therapy."
In Ex parte Stevens, 16 USPQ2d 1379 a claim to "A method for therapeutic or prophylactic treatment of cancer in mammalian hosts" was refused because there was "no actual evidence of the effectiveness of the claimed composition and process in achieving that utility."
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. Some experimentation is not fatal; the issue is whether the amount of experimentation is "undue"; see In re Vaeck, 20 USPQ2d 1438, 1444.
The analysis is as follows:
1) Breadth of claims.
"Cancer" is not a single disease, or cluster of closely related disorders. There are hundreds of cancers, which have in common only some loss of controlled cell growth. Cancers are highly heterogeneous at both the molecular and clinical level, something seen especially in, for example, the cancers of the breast, brain and salivary glands. They can occur in pretty much every part of the body. To be able to simply stop cancer cells generally from being able to proliferate. Many of these approaches --- and there have been others as well --- have produced anti-cancer drugs. However, despite high hopes for success, and a plausible theory why these should work for cancers generally, none of these approaches have ever produced a drug which come remotely near such a goal.
Specifically, the prior art knows that there never has been a compound capable of treating cancers generally. "The cancer therapy art remains highly unpredictable, and no example exists for efficacy of a single product against tumors generally." (<http://www.uspto.gov/web/offices/pac/dapp/1pecba.htm#7> ENABLEMENT DECISION TREE, Example F, situation 1). A similar statement appears at In re Application of Hozumi et al., 226 USPQ 353: "In spite of the vast expenditure of human and capital resources in recent years, no one drug has been found which is effective in treating all types of cancer. Cancer is not a simple disease, nor is it even a single disease, but a complex of a multitude of different entities, each behaving in a different way". There are compounds that treat a modest range of cancers, but no one has ever been able to figure out how to get a compound to be effective against cancer generally, or even a majority of cancers.
The attempts to find compounds to treat the various cancers arguably constitute the single most massive enterprise in all of pharmacology. This has not resulted in finding any treatment for tumors generally. Indeed, the existence of such a "silver bullet" is contrary to our present understanding in oncology. This is because it is now understood that there is no "master switch" for cancers generally; cancers arise from a bewildering variety of differing mechanisms. Even the most broadly effective antitumor agents are only effective against a small fraction of the vast number of different cancers known. This is true in part because cancers arise from a wide variety of sources, primarily a wide variety of failures of the body's cell growth regulatory mechanisms, but also such external factors such as viruses (an estimated at least 20% are of viral origin e.g. Human papillomavirus, EBV, Hepatitis B and C, HHV-8, HTLV-1 and other retroviruses, and quite possibly Merkel cell polyomavirus, and there is some evidence that CMV is a causative agent in glioblastoma), exposure to chemicals such as tobacco tars, excess alcohol consumption (which causes hepatic cirrhosis, an important cause of HCC), ionizing radiation, and unknown environment factors.
Accordingly, there is substantive "reason for one skilled in the art to question the objective truth of the statement of utility or its scope" (In re Langer, 183 USPQ 288, 297), specifically, the scope of covering cancer generally.
Similarly, In re Novak, 134 USPQ 335, 337-338, says "unless one with ordinary skill in the art would accept those allegations as obviously valid and correct, it is proper for the examiner to ask for evidence which substantiates them." There is no such evidence in this case. Likewise, In re Cortright, 49 USPQ2d 1464, states: "Moreover, we have not been shown that one of ordinary skill would necessarily conclude from the information expressly disclosed by the written description that the active ingredient" does what the specification surmises that it does. That is exactly the case here. Moreover, even if applicants' assertion that cancer in general could be treated with these compounds were plausible --- which it is not ---, that "plausible" would not suffice, as was stated in Rasmusson v. SmithKline Beecham Corp., 75 USPQ2d 1297, 1301: "If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to "inventions" consisting of little more than respectable guesses as to the likelihood of their success."
Different types of cancers affect different organs and have different methods of growth and harm to the body, and different vulnerabilities. The skill thus depends on the particular cancer involved. There are some cancers where the chemotherapy skill level is high and there are multiple successful chemotherapeutic treatments. The mechanism in these situations, however, is not necessarily the same as is alleged for these compounds.
One skilled in the art knows that chemotherapy of brain tumors is especially difficult. This is because 1) the blood-brain barrier, which is often intact in parts or all of a brain tumor, will block out many drugs, as it is the purpose of the blood-brain barrier to protect the brain from alien chemicals, and 2) CNS tumors are characterized by marked heterogeneity, which greatly decreases vulnerability to chemotherapy. As a result, many categories of CNS tumors simply have no chemotherapy available. These include, generally, hemangioblastomas, meningiomas, craniopharyngiomas, acoustic neuromas, pituitary adenomas, optic nerve gliomas, glomus jugulare tumors and chordomas, to name just some. With regard to gliomas, GBM is considered untreatable; no effective agents have emerged for the treatment of GBM, despite 20 years of enrolling patients in clinical trials. It is radiation and surgery which are used for low grade gliomas (e.g. pilocytic astrocytoma and diffuse astrocytomas), as no drug has been found effective. There is no drug treatment established as effective for optic nerve gliomas or gangliogliomas. Indeed, very few gliomas of any type are treated with pharmaceuticals; it is one of the categories of cancer that is the least responsive to drugs.
Lymphomas of the stomach are not commonly treated with anti-cancer agents per se, but instead, surgery or radiation and antibiotic therapy (e.g. amoxicillin, metronidazole, bismuth, and omeprazole) are the primary treatments.
Neuroendocrine tumors of the cervix generally do not respond to chemotherapy.
A number of sarcomas, including alveolar soft part sarcoma (ASPS), retroperitoneal sarcoma, most liposarcomas, and the assorted chondrosarcomas, are generally considered not to respond to chemotherapy; no chemotherapeutic agent has been established as effective.
It is important to note that tumors can need to be treated quite differently even though they are tumors of the same organ. For example, the drugs used most often to treat Wilms tumor, the most common malignant tumor of the kidneys in children, are actinomycin D and vincristine. Such drugs are never used with clear cell renal carcinoma, which is treated, although without much success, with immunotherapy using the cytokines interleukin-2 and interferon-alpha. However, such immunotherapy has never been established as effective in non-clear cell RCC forms such as papillary renal cell carcinoma. Despite strenuous efforts over a period of decades, no chemotherapeutic agent has ever been found effective against this cancer. Cancers of the stomach can be lymphomas, GISTs, carcinoid tumors, carcinomas, or soft tissue sarcomas, and for a single agent to be effective against all or even most of these categories would be contrary to what is known in oncology.
The scope of treating inflammation generally is extraordinarily broad. Inflammation is a process which can take place in virtually any part of the body. There is a vast range of forms that it can take, causes for the problem, and biochemical pathways that mediate the inflammatory reaction. It is one of the most pervasive of all body processes. Inflammation is a very general term which encompasses a huge variety of specific processes.
2) The nature of the invention and predictability in the art.
With specific reference to cancer, Ex parte Kranz, 19 USPQ2d 1216, 1219 notes the "general unpredictability of the field [of] …anti-cancer treatment." In re Application of Hozumi et al., 226 USPQ 353 notes the "fact that the art of cancer chemotherapy is highly unpredictable". More generally, the invention is directed toward medicine and is therefore physiological in nature. It is well established that "the scope of enablement varies inversely with the degree of unpredictability of the factors involved," and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
3) State of the Prior Art. The claimed compounds are GSPT1 negative modulators with structures such as Formula I, II, and Va. So far as the examiner is aware these compounds have not been successfully used as broad range anticancer agents.
4) Working Examples. Applicants have provided no working examples which are successfully used as broad range anticancer agents. Applicants have, however, demonstrated the cytotoxicity of Compound 8 in vivo against breast cancer and lung cancer xenograft models with high N-Myc (p. 485-487 of specification).
5) Skill of those in the art. Many, many mechanisms have been proposed over the decades as methods of treating the assorted cancers generally. Cytotoxic agents could be applied directly to the tumor cells, directly killing them. Immunotherapy involves stimulating the patient's immune system to attack cancer cells generally, either by immunization of the patient, in which case the patient's own immune system is trained to recognize tumor cells as targets, or by the administration of therapeutic antibodies as drugs, so the patient's immune system is recruited to destroy tumor cells by the therapeutic antibodies. Another approach would be to increase the amount or activity of the body's tumor suppressor genes, e.g. p53, PTEN, APC and CD95, which can for example activate DNA repair proteins, suppress the Akt/PKB signaling pathway, or initiate apoptosis of cancer cells. The angiogenesis inhibitor strategy was based on cutting off the blood supply that growing tumors need by shutting off the growth of new blood vessels by, for example, suppressing proliferation of endothelial cells or inducing apoptosis of endothelial cells. There is also the cancer stem cell paradigm, which hypothesizes that cancer could be treated generally, either by targeting the cancer stem cells themselves, or by targeting the epithelial-to-mesenchymal transition which supposedly generates the cancer stem cells. Yet another approach is to inhibit one or more of the assorted HSP90 proteins, which will supposedly disrupt the proper folding of signaling proteins that all cancers rely on. Inhibiting telomerase was said to be able to be able to simply stop cancer cells generally from being able to proliferate. Many of these approaches --- and there have been others as well --- have produced anti-cancer drugs. However, despite high hopes for success, and a plausible theory why these should work for cancers generally, none of these approaches have ever produced a drug which come remotely near such a goal.
Accordingly, there is substantive "reason for one skilled in the art to question the objective truth of the statement of utility or its scope" (In re Langer, 183 USPQ 288, 297), specifically, the scope of covering cancer generally. Moreover, even if applicants' assertion that cancer in general could be treated with these compounds were plausible --- which it is not ---, that "plausible" would not suffice, as was stated in Rasmusson v. SmithKline Beecham Corp., 75 USPQ2d 1297, 1301: "If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to "inventions" consisting of little more than respectable guesses as to the likelihood of their success."
6) Scope of the claims. The scope of the claims involves GSPT1 negative modulators generally, such as compounds of the following formulae:
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and their use as potential treatment to Myc-driven cancers, thus, the scope of claims is very broad.
7) The quantity of experimentation needed. Given the fact that, historically, the development of new cancer drugs has been difficult and time consuming, and especially in view of factors 1 and 4 and 6, the quantity of experimentation needed is expected to be great.
MPEP 2164.01(a) states, "A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)." That conclusion is clearly justified here.
Claims 1-26 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for GSPT1 negative modulators of Formula I, II, Va; compounds 1-160, 201-440, and 501-573; and the compounds of claim 31, does not reasonably provide enablement for GSPT1 negative modulators generally. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The instant invention is directed toward methods of treating Myc-driven cancers comprising determining the expression level of a Myc transcription factor and administering a therapeutically effective amount of a GSPT1 negative modulator.
The specification does not define that which is intended in the use of a “GSPT1 negative modulator” and potentially encompasses compounds that have yet to be discovered, as well as GSPT1 negative modulators known in the art that are not contemplated by the instant invention. Patent Protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable. The applicants are not entitled to preempt the efforts of others in future discoveries, wherein the claims are directed toward agents that have yet to be discovered. The applicants are only entitled to those GSPT1 negative modulators contemplated at the time of filing, which include compounds that have been demonstrated in the working examples to be effective against particular Myc-driven cancers.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-28 and 30-31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zou et al. (J Mol Med; 2020; IDS filed 11/07/2025) in view of Roberts et al. (WO 2015/123377 A1; 2015; IDS filed 11/07/2025), Xiao et al. (Biomedicine & Pharmacotherapy; 2015; IDS filed 11/07/2025), and Matyskiela et al. (Nature; 2016; IDS filed 11/07/2025).
Zou et al. discloses a protein homeostatic modulator BTX306 with the following structure (p. 1164, Fig. 1).
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Zou et al. additionally discloses a method of treating myeloma cells with BTX306 wherein BTX306 induced GSPT1 degradation and reduced GSPT1 and c-MYC levels more potently than other cereblon-targeting molecules such as thalidomide (Abstract; p. 1168 col. 1). Zou et al. further discloses a method of treating mice inoculated with myeloma cells and treating the mice with BTX306 via injection (p. 1163, cols. 1-2 bridging paragraph) which resulted in a dose-dependent reduction in myeloma tumor burden (p. 1166 col. 2 – p. 1167 col. 1). Zou et al. additionally discloses that the activity of BTX306 is cereblon-dependent1 (p. 1164). Zou et al. suggests that BTX306 provides an option for patients with high c-MYC expression due to translocations at 8q24 (p. 1171, col. 1).
Zou et al. does not disclose that the method of treatment includes determining that the myeloma is Myc-driven or determining the relative expression of Myc transcription factor biomarkers from a biological sample obtained from the patient. Zou et al. does not teach that the GSPT1 negative modulator is a compound of Formula I, II, Va, Compounds 1-160, 201-440, or 501-573. These limitations are obvious over Roberts et al., Chan et al., and Xiao et al.
Roberts et al. discloses methods of treating c-Myc-dependent cancers comprising obtaining or providing a sample from a patient with c-Myc-dependent cancer, wherein the sample comprises nucleic acid molecules; determining the copy number of at least one biomarker from Table 1; comparing said copy number to that of a control, wherein an increased copy number is more likely to be responsive to treatment (p. 4, first paragraph). Roberts et al. teaches that the skilled artisan would be apprised that a computer system could be used to collect data generated by the disclosed methods (p. 108-109, bridging paragraph). Roberts et al. additionally teaches that phosphorylation of 4EBP1 renders EIF4E available for translation and EIF4E has been implicated in the regulation of c-Myc (p. 136). Roberts et al. additionally teaches that c-Myc is upregulated in a majority of cancers and is a major therapeutic target, but is difficult to inhibit as it lacks a druggable pocket, thus leading to indirect c-Myc targeting through pathways such as cell division and initiation of protein translation (p. 1-2).
Xiao et al. discloses that down-regulation of GSPT1 results in decreased expression of c-Myc in colorectal cancer cells (Abstract; p. 143, col. 2).
Matyskiela et al. teaches a cereblon-dependent GSPT1 degrader CC-885 (p. 252, col. 2; p. 253, Figure 1).
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Matyskiela et al. teaches that CC-885 triggered depletion of GSPT1 in leukemia cells, but other cereblon-targeting molecules such as lenalidomide did not (p. 253, col. 1).
It would have been prima facie obvious for one of ordinary skill in the art to combine the method of Roberts et al. with that of Zou et al. in order to determine if a biological sample of c-Myc-driven cancer over-expresses a c-Myc biomarker. One would have been motivated to do so, with reasonable expectation of success, as BTX306 is a GSPT1 degrader that is particularly useful in reducing GSPT1 and c-Myc and has been suggested as a treatment for patients with high c-Myc expression. Moreover, as taught by Xiao et al., down-regulation of GSPT1 would be expected to reduce c-Myc expression, which is implicated in many cancers (Roberts et al.). One would therefore be motivated to target c-Myc through administration of a GSPT1 degrader in cancers with high expression of c-Myc.
One would have further found it prima facie obvious to further determine the level of phosphorylation of EIF4EBP1 in a biological sample of c-Myc-driven cancer. One would have been motivated to do so, with reasonable expectation of success, as phosphorylation of EIF4EBP1 would be expected to increase translation of c-Myc. One of ordinary skill in the art would therefore be apprised that a biological sample with a higher level of phosphorylation of EIF4EBP1 would have increased expression of c-Myc and would benefit from treatment with a GSPT1 degrader.
The following claimed GSPT1 degrader would be prima facie obvious over Matyskiela et al.
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The claimed compound and CC-885 differ in the point of attachment of the moiety circled above and are therefore position isomers. Since substitution in the 4-position is a position isomer of substitution in the 5-position, these compounds are considered equivalent. The MPEP 2144.09 states “Compounds which are… position isomers (compounds having the same radicals in physically different positions on the same nucleus) …are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).” Furthermore, since the compound of Matyskiela et al. is functionally equivalent to the claimed compound and the compound of Zou et al. as a GSPT1 degrader, it would therefore be prima facie obvious for one of ordinary skill in the art to substitute one for the other and expect similar results.
Claims 1-28 and 30-31 is/are rejected under 35 U.S.C. 103 as being obvious over Flohr et al. (WO 2021/069705 A1) in view of Roberts et al. (WO 2015/123377 A1; 2015; IDS filed 11/07/2025).
The applied reference (Flohr et al.) has a common assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
Flohr et al. discloses compounds 1-165 (p. 119-132) which are within the scope of Formula I and II, and are identical to those of claims 30 and 31. Flohr et al. discloses that the compounds are GSPT1 degraders which efficiently target c-Myc dependent cells over non c-Myc dependent cells and are for treating solid tumors (p. 2, p. 295). Flohr et al. discloses that cancers to be treated include glioma, thyroid cancer, lung cancer, colorectal cancer, head and neck cancer, stomach cancer, liver cancer, pancreatic cancer, renal cancer, urothelial cancer, prostate cancer, testis cancer, breast cancer, cervical cancer, endometrial cancer, ovarian cancer, melanoma and multiple myeloma (p. 11).
Flohr et al. does not disclose that the method of treatment includes determining that the myeloma is Myc-driven or determining the relative expression of Myc transcription factor biomarkers from a biological sample obtained from the patient. This is obvious over Roberts et al.
Roberts et al. teaches as above.
It would have been prima facie obvious for one of ordinary skill in the art to combine the method of Roberts et al. with that of Flohr et al. in order to determine if a biological sample of c-Myc-driven cancer over-expresses a c-Myc biomarker. One would have been motivated to do so, with reasonable expectation of success, as Flohr et al. discloses that the GSPT1 inhibitors are particularly effective against c-Myc dependent cells. One would therefore be motivated to target c-Myc through administration of a GSPT1 degrader in cancers with high expression of c-Myc.
One would have further found it prima facie obvious to further determine the level of phosphorylation of EIF4EBP1 in a biological sample of c-Myc-driven cancer. One would have been motivated to do so, with reasonable expectation of success, as phosphorylation of EIF4EBP1 would be expected to increase translation of c-Myc. One of ordinary skill in the art would therefore be apprised that a biological sample with a higher level of phosphorylation of EIF4EBP1 would have increased expression of c-Myc and would benefit from treatment with a GSPT1 degrader.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 19, and 43 of copending Application No. 18/485,766 in view of Roberts et al. (WO 2015/123377 A1; 2015; IDS filed 11/07/2025).
The claims of the ‘766 application are drawn to compounds of formula I which significantly overlap with instant claims 27-29. The claims of the ‘766 application are further directed to a method of treating a Myc-driven cancer.
Roberts et al. teaches as above.
For the same reasons as in the above 103 rejections, it would be prima facie obvious for one of ordinary skill in the art to determine the relative expression of Myc biomarkers in the patient prior to administering the compound of formula I.
This is a provisional nonstatutory double patenting rejection.
Claims 1-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 17, and 41 of copending Application No. 18/485,780 in view of Roberts et al. (WO 2015/123377 A1; 2015; IDS filed 11/07/2025).
The claims of the ‘780 application are drawn to compounds of formula I. The claims of the ‘780 application are further directed to a method of treating a Myc-driven cancer.
Roberts et al. teaches as above.
For the same reasons as in the above 103 rejections, it would be prima facie obvious for one of ordinary skill in the art to determine the relative expression of Myc biomarkers in the patient prior to administering the compound of formula I.
This is a provisional nonstatutory double patenting rejection.
Claims 1-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 and 17 of copending Application No. 18/640,909 in view of Roberts et al. (WO 2015/123377 A1; 2015; IDS filed 11/07/2025).
The claims of the ‘909 application are drawn to compounds of formula I. The claims of the ‘909 application are further directed to a method of treating cancer.
In looking to the specification to construe the scope of the claims, paragraph [0055] of the specification indicates that the claimed compounds can be used to treat cancers with increased expression of c-Myc, L-Myc, N-Myc, EIF4EBP1, and EIF4EBP2 as well as those with increased phosphorylation of EIF4EBP1 or EIF4EBP2.
Roberts et al. teaches as above.
For the same reasons as in the above 103 rejections, it would be prima facie obvious for one of ordinary skill in the art to determine the relative expression of Myc biomarkers in the patient prior to administering the compound of formula I.
This is a provisional nonstatutory double patenting rejection.
Claims 1-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 and 20 of copending Application No. 18/640,889 in view of Roberts et al. (WO 2015/123377 A1; 2015; IDS filed 11/07/2025).
The claims of the ‘889 application are drawn to compounds of formula X. The claims of the ‘889 application are further directed to a method of treating cancer.
In looking to the specification to construe the scope of the claims, paragraph [0064] of the specification indicates that the claimed compounds can be used to treat cancers with increased expression of c-Myc, L-Myc, N-Myc, EIF4EBP1, and EIF4EBP2 as well as those with increased phosphorylation of EIF4EBP1 or EIF4EBP2.
Roberts et al. teaches as above.
For the same reasons as in the above 103 rejections, it would be prima facie obvious for one of ordinary skill in the art to determine the relative expression of Myc biomarkers in the patient prior to administering the compound of formula X.
This is a provisional nonstatutory double patenting rejection.
Claims 1-28 and 30-31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17/716,169 in view of Roberts et al. (WO 2015/123377 A1; 2015; IDS filed 11/07/2025).
The claims of the ‘169 application are drawn to compounds of formula I which substantially overlap with the compounds of instant claims 27-28 and 30-31.
When making obviousness-type double patenting decisions, the Federal Circuit has stated, “[O]bviousness-type double patenting encompasses any use for a compound that is disclosed in the specification of an earlier patent claiming the compound and is later claimed as a method of using that compound”. Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381 (Fed. Cir. 2010).
In looking to the specification to construe the scope of the claims, page 2 of the specification indicates that the claimed compounds can be used to treat cancers with increased expression of c-Myc.
Roberts et al. teaches as above.
For the same reasons as in the above 103 rejections, it would be prima facie obvious for one of ordinary skill in the art to determine the relative expression of Myc biomarkers in the patient prior to administering the compound of formula I.
This is a provisional nonstatutory double patenting rejection.
Claims 1-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of U.S. Patent No. 11,912,682 B2 (IDS filed 11/07/2025) in view of Roberts et al. (WO 2015/123377 A1; 2015; IDS filed 11/07/2025).
The claims of the ‘682 patent are drawn to the following compound and a method of treating cancer selected from lung cancer, breast cancer, or neuroendocrine cancer.
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In looking to the specification to construe the scope of the claims, column 19 of the specification indicates that the claimed compound can be used to treat Myc-driven cancers.
Roberts et al. teaches as above.
For the same reasons as in the above 103 rejections, it would be prima facie obvious for one of ordinary skill in the art to determine the relative expression of Myc biomarkers in the patient prior to administering the compound.
Claims 1-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 16 of U.S. Patent No. 12,391,663 B2 (IDS filed 11/07/2025) in view of Roberts et al. (WO 2015/123377 A1; 2015; IDS filed 11/07/2025).
The claims of the ‘663 patent are drawn to compounds of formula I and a method of treating cancer selected from lung cancer, breast cancer, or neuroendocrine cancer. The compounds of formula I substantially overlap with those of instant claims 27-31.
In looking to the specification to construe the scope of the claims, column 19 of the specification indicates that the claimed compounds can be used to treat Myc-driven cancers.
Roberts et al. teaches as above.
For the same reasons as in the above 103 rejections, it would be prima facie obvious for one of ordinary skill in the art to determine the relative expression of Myc biomarkers in the patient prior to administering the compound.
Conclusion
No claims are allowed.
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