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 .
Election/Restrictions
Applicant’s election without traverse of the invention of Group I (claims 1, 7-9, 11-16, 18-20, 26-27), a species of LSD1 inhibitor that is ORY-1001, a species of PLK1 inhibitor that is onvansertib, and a species of cancer that is lung cancer in the reply filed on 08/10/2026 is acknowledged.
Claims 38, 45, 49, and 71 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/10/2026.
Priority
Examiner acknowledges that, according to the Filing receipt received 03/10/2025, that the instant application is a 371 of PCT/US2022/079939 filed 11/16/2022 which claims benefit of U.S. provisional applications 63/280,565 filed 11/17/2021 and 63/310,431 filed 02/15/2022. All of the instant claims have been awarded the effective filing date of 11/17/2021.
Information Disclosure Statement
The Information Disclosure Statement filed on 06/18/2024 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.
Examiner notes that non-patent literature document #27 (Lynch et al.) was only considered to the extent of the first page of the document (p. 1239) as pages 1240-1249 were not provided in the copy placed in the file wrapper.
Specification
The disclosure is objected to because of the following informalities: p. 25, paragraph [0085], “admiration” should read “administration”; p. 36, paragraph [0124], "ovansertib" should read "onvansertib".
Appropriate correction is required.
Claim Objections
Claims 1 and 12 are objected to because of the following informalities:
Claim 1: “administrating” should read “administering”;
Claim 12: should “give times” read “five times”?
Appropriate correction is required.
Drawings
The drawings are objected to because Figures 1A-1E and 2A-2E are of low resolution such that their labels and/or legends cannot be interpreted by Examiner. 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 13-15 and 18 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 13 recites “wherein the LSD1 inhibitor, the PLK1 inhibitor, or both are administered in a cycle of at least 7 days”. This limitation is unclear as one cannot ascertain whether “a cycle” refers to the period of time in which the LSD1 inhibitor and/or PLK1 inhibitor is administered, or the number of times the LSD1 inhibitor and/or PLK1 inhibitor is administered within a given period of time.
Claims 14 and 15 recite the limitation “the cycle”. This limitation lacks antecedent basis.
Claim 18 recites “wherein the subject undergoes at least two cycles of the administration of the LSD1 inhibitor and the PLK1 inhibitor”. This limitation is unclear as one cannot ascertain whether the term “cycles” refers to the period of time in which the LSD1 inhibitor and/or PLK1 inhibitor is administered, or the number of times the LSD1 inhibitor and/or PLK1 inhibitor is administered within a given period of time.
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, 7-9, 11-16, 18-20, and 26-27 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 therapeutically treating a cancer selected from lung cancer or prostate cancer comprising administering a therapeutically effective amount of an LSD1 inhibitor and onvansertib, does not reasonably provide enablement for treating a cancer generally, comprising administering an LSD1 inhibitor and a PLK1 inhibitor generally, wherein treating includes prophylaxis. 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.
The instant invention is directed toward a method of treating cancer generally. The specification additionally defines “treating” to include prophylactic and therapeutic treatment (p. 6, par. [0028]). It is presumed prevention of the claimed diseases would require a method of identifying those individuals who will develop the claimed diseases before they exhibit symptoms. There is no evidence of record that would guide the skilled clinician to identify those who have the potential of becoming afflicted.
"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 state of the art is that no general procedure is art-recognized for determining which patients generally will suffer from cancer before the fact. The claimed compounds are PLK1 and LSD1 inhibitors. 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 or prophylactic agents. Applicants have, however, demonstrated the combination of onvansertib (PLK1 inhibitor) with ORY-1001 or IMG-7289 (LSD1 inhibitors) against small-cell lung cancer and prostate cancer cells, as well as prostate cancer xenograft models (specification, p. 36-38). No other PLK1 inhibitors were tested.
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 a combination treatment of compounds that are LSD1 inhibitors and PLK1 inhibitors, and their use as potential treatment to cancers generally, administered at an unspecified dose. Thus, the scope of claims is very broad.
7) The quantity of experimentation needed. Given the fact that, historically, the development of new cancers 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.
Claim 20 is 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 enantiomers, diastereomers, tautomers, isotopic variants, and pharmaceutically acceptable salts of a compound of claim 1, does not reasonably provide enablement for derivatives, solvates, hydrates, and/or prodrugs of the claimed LSD1 inhibitors. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the application coupled with information known in the art without undue experimentation. (United States v. Teletronics Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is needed is not based on a single factor, but rather a conclusion reached by weighing many factors (See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988).
These factors include the following:
1) Amount of guidance provided by applicant. The instant specification provides no species of derivatives, solvates, hydrates, or prodrugs of the claimed LSD1 inhibitors. The terms “derivatives”, “solvates”, “hydrates”, and “prodrugs” are incredibly broad.
As was stated in Morton International Inc. v. Cardinal Chemical Co., 28 USPQ2d 1190 “The specification purports to teach, with over fifty examples, the preparation of the claimed compounds with the required connectivity. However...there is no evidence that such compounds exist...the examples of the '881 patent do not produce the postulated compounds...there is...no evidence that such compounds even exist.” The same circumstance appears to be true here. Hence, Applicants must show that solvates, hydrates, or prodrugs of these compounds can be made, or limit the claims accordingly.
2) The nature of the invention and predictability in the art. The invention is directed toward bicyclic quinone compounds. Regarding predictability in the art, chemistry is generally regarded as unpredictable, particularly the formation of solvates and hydrates. Moreover, the terms “prodrug” and “derivative” provide no particular guidance as to what structures are encompassed by the instant claims. Additionally see In Re Marzocchi and Horton, 169 USPQ at 367 paragraph 3:
“Most non-chemists would probably be horrified if they were to learn how
many attempted syntheses fail, and how inefficient research chemists are.
The ratio of successful to unsuccessful chemical experiments in a normal
research laboratory is far below unity, and synthetic research chemists, in
the same way as most scientists, spend most of their time working out
what went wrong, and why. Despite the many pitfalls lurking in organic
synthesis, most organic chemistry textbooks and research articles do give
the impression that organic reactions just proceed smoothly and that the
total synthesis of complex natural products, for instance, is maybe a labor-
intensive but otherwise undemanding task. In fact, most syntheses of
structurally complex natural products are the result of several years of
hard work by a team of chemists, with almost every step requiring careful
optimization. The final synthesis usually looks quite different from that
originally planned, because of unexpected difficulties encountered in the initially chosen synthetic sequence. Only the seasoned practitioner who
has experienced for himself the many failures and frustrations which the
development (sometimes even the repetition) of a synthesis usually
implies will be able to appraise such work ......Chemists tend not to publish
negative results, because these are, as opposed to positive results, never
definite (and far too copious)...” Dorwald F. A. Side Reactions in Organic
Synthesis, 2005, Wiley: VCH, Weinheim pg. IX of Preface.
The scope of any compounds, compositions, or pharmaceutically acceptable salts where the variables were not those mentioned above are not adequately enabled or defined. Applicants provide no guidance as how these compounds are made.
3) Number of working examples. The compounds claimed as LSD1 inhibitors are known in the art, thus Applicant has provided sufficient guidance to make and use; however, this disclosure is not sufficient to allow extrapolation of the limited examples to enable the scope of the derivatives, solvates, hydrates, or prodrugs thereof instantly claimed. Applicant has provided no working examples of any derivatives, solvates, hydrates, or prodrugs.
Within the specification, “specific operative embodiments or examples of the invention must be set forth, Examples and description should be of sufficient scope as to justify the scope of the claims, Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula.” See MPEP 608.01(p).
4) Scope of the claims. The scope of the claims is all of the LSD1 inhibitors listed in claim 20, as well as derivatives of tranylcypromine and hydrates, solvates, or prodrugs of every listed compound.
Therefore, the claims are incredibly broad.
5) Level of skill in the art. The artisan using Applicant’s invention would be an individual with an M.D. or chemist with a Ph.D. degree and having several years of bench experience.
6) Undue experimentation. 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)."
The conclusion is clearly justified here that Applicant is not enabled for making these compounds or compositions.
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, 7, 9, 12-16, 18-20, and 26-27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Demario et al. (WO 2017157825 A1; 2017) in view of Valsasina et al. (US 8927530 B2; 2015; IDS filed 06/18/2024) and Dalvi et al. (Molecular Cancer Research; 2019; IDS filed 06/18/2024).
Demario et al. teaches a therapeutic combination comprising an LSD1 inhibitor or a pharmaceutically acceptable salt thereof and an anti-mitotic agent or a pharmaceutically acceptable salt thereof (p. 39, lines 27-29). Demario et al. teaches a particular embodiment wherein the LSD1 inhibitor is (trans)-N1-((1R,2S)-2-phenylcyclopropyl)cyclohexane-1,4-diamine, or ORY-1001 (p. 6, lines 1-5; p. 42, lines 30-32). Demario et al. teaches a method of treating a neoplastic disease that is lung cancer comprising administering an effective amount of the therapeutic combination to a human or animal (p. 49, lines 24-28; p. 51, line 3). Demario et al. additionally teaches an embodiment wherein the combination is administered as an oral solution (p. 49, lines 33-34). Demario et al. discloses a dosing schedule of five days on/two days off for three weeks (p. 45-46).
Demario et al. does not disclose combining ORY-1001 with onvansertib. Demario et al. does not disclose a dose of onvansertib. Demario et al. does not disclose that the subject has elevated LSD1 gene amplification, high LSD1 expression, or LSD1 overexpression. These limitations are obvious in view of Valsasina et al. and Dalvi et al.
Valsasina et al. discloses a combination for treatment of proliferative disorders, preferably cancer, wherein the combination comprises a compound of formula (I) and one or more antineoplastic agents (col. 2, lines 8-13) wherein the compound of formula (I) has the following structure (col. 2).
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1
Valsasina et al. additionally teaches that the course of therapy for the compound of formula (I) (onvansertib, see footnote) is from about 5 to about 500 mg per dose, administered from 1 to 5 times daily (col. 5, lines 11-13). Valsasina et al. discloses that the cancers to be treated include lung cancer (col. 6, lines 42-46).
Dalvi et al. discloses that lysine-specific demethylase 1 (LSD1) is a histone modifier which is highly overexpressed in lung adenocarcinoma (Abstract) and is linked to poor prognosis (p. 1326, col. 2). Dalvi et al. teaches that inhibition of LSD1 reduces cell proliferation, downregulates cell growth regulatory pathways, and downregulates the polo-like kinase 1 (PLK1) mitotic pathway (p. 1326-1327, bridging paragraph; p. 1328-1329, bridging paragraph) which leads to mitotic arrest (p. 1331, col. 2). Dalvi et al. further teaches that overexpression of PLK1 overcomes the effects of LSD1 inhibition (p. 1331, col. 1).
It would be prima facie obvious for one of ordinary skill in the art to combine ORY-1001, an LSD1 inhibitor, with onvansertib, a PLK1 inhibitor, in a method of treating lung cancer. One would have been motivated to do so, with reasonable expectation of success, as Demario et al. suggests combining ORY-1001 with mitotic inhibitors for the treatment of lung cancers. One of ordinary skill in the art would expect, based on the disclosure of Dalvi et al., that the combination of ORY-1001 with a PLK1 inhibitor such as onvansertib would enhance inhibition of the PLK1 mitotic pathway, thereby improving the antiproliferative effect of the LSD1 inhibitor.
Moreover, it would have been prima facie obvious for one of ordinary skill in the art to arrive at the claimed dose range of onvansertib and dose schedules. One would have been motivated to do so, with reasonable expectation of success, as the doses and schedules of Demario et al. and Valsasina et al. substantially overlap with those of the instant invention. Absent evidence of criticality, it would be within the desire of one of ordinary skill in the art to adjust the doses, frequency of administration, and cycles of dosing in order to arrive at an optimal administrative schedule for the treatment of lung cancer. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Conclusion
No claims are allowed.
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/MADELINE E BRAUN/Examiner, Art Unit 1624 09/04/2026
1 Onvansertib, see structure on p. 16 of the instant specification and definition of onvansertib in par. [0062] of the instant specification.
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