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 with traverse of Group II (claims 1, 3-5, drawn to a method for treating cancer comprising administering to a subject in need thereof an effective amount of (one or more agents that upregulate interferon production; and one or more nuclear export inhibitors thereby treating the subject's cancer; species: melanoma) in the reply filed on 8/6/2026 is acknowledged. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 2, 6-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Information Disclosure Statement
3. The information disclosure statement (IDS) submitted on 1/29/2024 is in compliance with the provisions of 37 CFR 1.97 and has been considered by the examiner.
Applicant is reminded of their duty to disclose to the Office all information known to the person to be material to patentability as defined in 37 CFR 1.56. As stated therein, “[e]ach individual associated with the filing and prosecution of a patent application has a duty of candor and good faith in dealing with the Office, which includes a duty to disclose to the Office all information known to that individual to be material to patentability as defined in this section”.
Claim Rejections - 35 USC § 112(a), lack of written description
4. 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.
4a. Claims 1, 3-5, 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
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, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, 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 Applicants were in possession of the claimed genus.
Independent claim 1 is drawn to “a method for treating cancer comprising administering to a subject in need thereof an effective amount of one or more agents that upregulate interferon production; and one or more nuclear export inhibitors thereby treating the subject's cancer”.
Dependent claim 3 further limits claim 1 to “wherein the one or more nuclear export inhibitors comprise a leptomycin, a ratjadone, an anguinomycin, callystatin, valtrate, oridonin, acetoxychavicol acetate, curcumin, gonionthalamin, piperlongumine, plumbagin, CBS-9106, KPT-185, KPT-249, KPT- 251, KPT-276, KPT-301, KPT-330, KPT-335 or KPT-8602”.
Dependent claim 4 further limits claim 1 to “wherein the one or more agents that upregulate interferon production comprise amidobenzimidazoles, flavone acetic acid analogues or cyclic dinucleotides”.
Independent claim 1 requires administration of “one or more nuclear export inhibitors” and “one or more agents that upregulate interferon production”. The claims, however, do not require that the agents recited in claim 1 possess any particular conserved structure, or other distinguishing feature.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, and any combination thereof. In this case, the only factor present in the claim that is sufficiently disclosed is a recitation of a desired activity, “one or more nuclear export inhibitors” and “one or more agents that upregulate interferon production”. The specification does not identify any particular portion of the structure, nor does it provide a disclosure of structure/function correlation. The distinguishing characteristics of the claimed genus for the “one or more nuclear export inhibitors” and “one or more agents that upregulate interferon production” are not described. Accordingly, the specification does not provide adequate written description of the claimed genus of “one or more nuclear export inhibitors” and “one or more agents that upregulate interferon production” to be administered in the claimed method.
To satisfy the written-description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. Vas-Cath, 935 F.3d at 1563; see also Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 [41 USPQ2d 1961] (Fed. Cir. 1997) (patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention”); In re Gosteli, 872 F.2d 1008, 1012 [10 USPQ2d 1614] (Fed. Cir. 1989) (“the description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed”). Thus, an Applicant complies with the written-description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572.
See University of Rochester v. G.D. Searle & Co., 68 USPQ2d 1424 (DC WNY 2003) and University of Rochester v. G.D. Searle & Co. et al. CAFC [(03-1304) 13 February 2004]. In University of Rochester v. G.D. Searle & Co. a patent directed to method for inhibiting prostaglandin synthesis in human host using an unspecified compound, in order to relieve pain without side effect of stomach irritation, did not satisfy written description requirement of 35 U.S.C. §112, since the patent described the compound's desired function of reducing activity of the enzyme PGHS-2 without adversely affecting PGHS-1 enzyme activity, but did not identify said compound, since invention consists of performing “assays” to screen compounds in order to discover those with desired effect. The patent did not name even one compound that assays would identify as suitable for practice of invention, or provide information such that one skilled in art could identify suitable compound. And since specification did not indicate that compounds are available in public depository, the claimed treatment method cannot be practiced without compound. Thus, the inventors cannot be said to have “possessed” claimed invention without knowing of a compound or method certain to produce compound. Thus said patent constituted an invitation to experiment to first identify, then characterize, and then use a therapeutic a class of compound defined only by their desired properties.
Therefore, the full breadth of the claims fails to meet the written description provision of 35 U.S.C. §112, first paragraph. In the instant case, for example, Applicants have failed to describe which “one or more nuclear export inhibitors” and “one or more agents that upregulate interferon production” has the desirable property of treating cancer in a subject in need thereof. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision.
To demonstrate possession of a method of treatment one must provide substantially more than the description of a compound or collection of related compounds having an in vitro activity, in combination with a hypothesis that the administration of a compound having that activity to an individual suffering from a particular disease or disorder might produce a beneficial effect. What is required is an established nexus between the administration of such a compound to an individual and a beneficial result consequent thereto. Such a nexus can be established by the presentation of evidence demonstrating clinical efficacy of the claimed method in the treatment of a particular disease or disorder, demonstrating efficacy of that method in the treatment of an art accepted animal model of a disease or disorder wherein that model is known to be reasonably predictive of the efficacy of a treatment protocol in the treatment of that disease or disorder, or providing evidence of an in vitro activity for the recited compound in combination with a showing that other compounds possessing that activity (mode of action) have been shown to have clinical efficacy in the treatment of the recited disease or disorder. The instant specification fails to show possession of the claimed method as of the effective filing date of the instant application because it provides none of these.
As stated in M.P.E.P. § 2163(II)(A)(3), a specification may describe an actual reduction to practice by showing that the inventor constructed an embodiment or performed a process that met all the limitations of the claim and determined that the invention would work for its intended purpose. Cooper v. Goldfarb, 154 F.3d 1321, 1327, 47 USPQ2d 1896, 1901 (Fed. Cir. 1998). See also UMC Elecs. Co. v. United States, 816 F.2d 647, 652, 2 USPQ2d 1465, 1468 (Fed. Cir. 1987) (“[T]here cannot be a reduction to practice of the invention ... without a physical embodiment which includes all limitations of the claim.”); Estee Lauder Inc. v. L’Oreal, S.A., 129 F.3d 588, 593, 44 USPQ2d 1610, 1614 (Fed. Cir. 1997) (“[A] reduction to practice does not occur until the inventor has determined that the invention will work for its intended purpose.”); Mahurkar v. C.R. Bard, Inc., 79 F.3d 1572, 1578, 38 USPQ2d 1288, 1291 (Fed. Cir. 1996) (determining that the invention will work for its intended purpose may require testing depending on the character of the invention and the problem it solves).
Whereas a reduction to practice of an uncomplicated invention such as a simple mechanical or electrical device can be achieved by merely providing a diagram of the device wherein one skilled in the relevant art can predict the likely operability of the device by reviewing the diagram, the operability of the claimed invention cannot be predicted by merely reviewing diagrams or illustrations. To demonstrate the reduction to practice of a method of treating a subject afflicted with a particular disease or disorder such as in the instant application treatment of “all cancers” requires either a working embodiment, a demonstration of operability in the treatment of an art accepted animal model of the condition to be treated, wherein that animal model has been shown to be reliably predictive of efficacy in the treatment of the condition, or a demonstration that the therapeutic agent employed therein possesses an activity in which the majority of compounds possessing that activity have been shown to be effective in the treatment of that condition in the absence of further inventive contribution. In the instant case, Applicant has provided none of these. Consequently, Applicant has failed to demonstrate possession of the claimed method as of the earliest effective filing date of the instant application.
With respect to the demonstration of a reduction to practice of a generic invention, MPEP 2163(II)(A)(3)(ii) states that 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, above). 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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
The above position is further supported by In re Clarke, 148 USPQ 665, (CCPA 1966), which held that;
“It appears to be well settled that a single species can rarely, if ever, afford support for a generic claim. In re Soll, 25 C.C.P.A. (Patents) 1309, 97 F.2d 623, 38 USPQ 189; In re Wahlforss et al., 28 C.C.P.A. (Patents) 867, 117 F.21 270, 48 USPQ 397. The decisions do not however fix any definite number of species which will establish completion of a generic invention and it seems evident therefrom that such number will vary, depending on the circumstances of particular cases. Thus, in the case of a small genus such as halogens, consisting of four species, a reduction to practice of three, or perhaps even two, might serve to complete the generic invention, while in the case of a genus comprising hundreds of species, a considerably large number of reductions to practice would probably be necessary.”
In the instant case, Applicant has failed to demonstrate a reduction to practice of a method of treating every and all cancers by administering “one or more nuclear export inhibitors” and “one or more agents that upregulate interferon production” as recited in claim 1.
Claim Rejections - 35 USC § 112(a), enablement
4b. Claims 1, and 3-5 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 1, for example, is drawn very broadly to a method of treatment of all cancers in a subject by administering “one or more nuclear export inhibitors” and “one or more agents that upregulate interferon production”. However, the specification fails to provide any guidance for such a method by administering “one or more nuclear export inhibitors” and “one or more agents that upregulate interferon production”.
The specification on pages 20-22, [0040], discloses:
“In one aspect, the methods of the present invention are used to treat cancers of the head and neck, which include, but are not limited to, tumors of the nasal cavity, paranasal sinuses, nasopharynx, oral cavity, oropharynx, larynx, hypopharynx, salivary glands, and paragangliomas. In another aspect, the method of the present invention includes the treatment of cancers of the liver and biliary tree, particularly hepatocellular carcinoma. In another aspect, the method of the present invention includes the treatment of intestinal cancers, particularly colorectal cancer. In another aspect, the method of the present invention includes the treatment of ovarian cancer. In another aspect, the method of the present invention includes the treatment of gastric or pancreatic cancer. In another aspect, the method of the present invention includes the treatment of prostate cancer. In another aspect, the method of the present invention includes the treatment of melanoma. In another aspect, the method of the present invention includes the treatment of small cell and non-small cell lung cancer. In another aspect, the method of the present invention includes the treatment of breast cancer. In another aspect, the method of the present invention includes the treatment of sarcomas, including fibrosarcoma, malignant fibrous histiocytoma, embryonal rhabdomysocarcoman, leiomyosarcoma, neuro-fibrosarcoma, osteosarcoma, synovial sarcoma, liposarcoma, and alveolar soft part sarcoma. In another aspect, the method of the present invention includes the treatment of neoplasms of the central nervous systems, particularly brain cancer. In another aspect, the method of the present invention includes the treatment of lymphomas which include non-Hodgkin's lymphoma, Hodgkin's lymphoma, lymphoplasmacytoid lymphoma, follicular lymphoma, mucosa-associated lymphoid tissue lymphoma, mantle cell lymphoma, B-lineage large cell lymphoma, Burkitt's lymphoma, and T-cell anaplastic large cell lymphoma. In another aspect, the method of the present invention includes the treatment of leukemias which include acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndromes (MDS). In another aspect, the method of the present invention includes the treatment of multiple myeloma. In other aspects, the method of this invention is used in the prevention or treatment of autoinflammatory diseases driven by IFNs.”
Furthermore, on pages 43-44, [0078], the specification discloses:
“ Example 8: Combined Treatment with IFN and NEI Regresses Tumors
The inflammatory cell death induced by the combination of IFN and NEIs was dependent on ZBPl. Therefore, the efficacy of IFN and NEIs in treating melanoma was evaluated. Wild-type mice treated with KPT-330 8 days after B16 melanoma cell implantation showed reduced melanoma growth. However, mice treated with the combination of IFN-α (FIG. 3A), IFN-β (FIG. 3B), or IFN-γ (FIG. 3C), and KPT-330 had a significantly improved regression of their tumors. To determine whether the tumor regression was dependent on ZBP11/1, the combination of IFN-y and KPT-330 was administered to wild-type and mice. IFN-y and KPT-330 failed to regress melanoma in ZBP11/1 mice. Altogether, these data indicate that IFN and KPT-330 combination therapy is a superior treatment combination and that ZBP1 suppresses tumorigenesis in the absence of ADAR1.”
However, other than this disclosure in the instant specification, there is no guidance for a method of treating every and all cancers by administering . There is absolutely no disclosure in the instant specification with respect to the administration of the claimed IL-1 receptor antagonist for the treatment of every and all cancers. The specification clearly fails to supply the guidance that would be needed by a routine practitioner to treat cancer.
The instant specification is attempting to link cancer treatment by administering an IL-1 receptor antagonist. However, Applicants have failed to demonstrate, using a conventional cancer model for mice, that administering an IL-1 receptor antagonist can treat cancer in this mouse model in which the mice develop cancer.
The instant specification has failed to demonstrate the nexus between treatment of cancer and administration of IL-1 receptor antagonist. The instant specification has also failed to disclose the duration and quantity of administration of the IL-1 receptor antagonist, in this case, anakinra, to a subject depending on the severity of the cancer for treatment, which are important parameters. In the absence of this guidance, a practitioner would have to resort to a substantial amount of undue experimentation involving the variation in the amount and duration of administration of the IL-1 receptor antagonist in the method of the instant invention.
In Genentech v. Novo Nordisk, 108 F.3d 1361, 42 U.S.P.Q.2d 1001, the CAFC stated that “Genentech's arguments, focused almost exclusively on the level of skill in the art, ignoring the essence of the enablement requirement. 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. See Brenner v. Manson, 383 U.S. 519, 536, 86 S.Ct. 1033, 1042-43, 16 L.Ed.2d 69, 148 USPQ 689, 696 (1966) (stating, in context of the utility requirement, that "a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.") Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.”
Therefore, this requirement has not been met in the instant specification with respect to providing guidance for the treatment of every and all cancers by administering the claimed “one or more nuclear export inhibitors” and “one or more agents that upregulate interferon production”.
The instant situation is directly analogous to that which was addressed in In re Colianni, 195 U.S.P.Q. 150, C.A.F.C., which held that a "disclosure that calls for application of 'sufficient'ultrasonic energy to practice claimed method of fusing bones but does not disclose what'sufficient' dosage of ultrasonic energy might be or how those skilled in the art might select appropriate intensity, frequency, and duration, and contains no specific examples or embodimentby way of illustration of how claimed method is to be practiced does not meet requirements of 35 U.S.C. § 112 first paragraph".
In view of this unpredictability in the treatment of every and all cancers by administering the claimed “one or more nuclear export inhibitors” and “one or more agents that upregulate interferon production”., there cannot be said to be any reasonable expectation of success at the in vivo application of the claimed method. Therefore, it would require undue experimentation for the ordinary artisan to determine how to use the claimed method.
Furthermore, there is no data presented to demonstrate the treatment of cancer by administering the claimed “one or more nuclear export inhibitors” and “one or more agents that upregulate interferon production”.
The CAFC decision (Genentech Inc. v. Novo Nordisk, 42 USPQ2d 1001, 1997) expressly states that:
"When there is no disclosure of any specific starting material or of any of the conditions underwhich a process can be carried out, undue experimentation is required; there is a failure to meetthe enablement requirement that cannot be rectified by asserting that all the disclosure related to the process is within the skill of the art. It is the specification, not the knowledge of one skilled inthe art, which must supply the novel aspects of an invention in order to constitute adequateenablement".
The factors listed below have been considered in the analysis of enablement [see MPEP §2164.01(a) and In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)]:
(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.
Given the breadth of claims 1, 3-5, in light of the predictability of the art as determined by the number of working examples, the level of skill of the artisan, and the guidance provided in the instant specification and the prior art of record, it would require undue experimentation for one of skill in the art to practice the claimed invention.
In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) states, “The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.” “The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling” (MPEP 2164.03). The MPEP further states that physiological activity can be considered inherently unpredictable. Given the inherent unpredictability of physiological activity, which would include biological processes, i.e., methods of treatment, a certain amount of enablement beyond mere assertion must be required.
Further, in Rasmusson v. SmithKline Beecham Corp., 75 USPQ2d 1297-1303 (CAFC 2005), the court states "[W]here there is "no indication that one skilled in [the] art would accept without question statements [as to the effects of the claimed drug products] and no evidence has been presented to demonstrate that the claimed products do have those effects," an applicant has failed to demonstrate sufficient utility and therefore cannot establish enablement" and "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. When one of the guesses later proved true, the "inventor" would be rewarded the spoils instead of the party who demonstrated that the method actually worked. That scenario is not consistent with the statutory requirement that the inventor enable an invention rather than merely proposing an unproved hypothesis."
Therefore, when an application is drawn to a method of treatment it is reasonable that actual evidence be submitted for one of skill in the art to accept that the method would produce the desirable effects.
In the context of determining whether sufficient "utility as a drug, medicant, and the like in human therapy" has been alleged, "it is proper for the examiner to ask for substantiating evidence unless one with ordinary skill in the art would accept the allegations as obviously correct." In re Jolles, 628 F.2d 1322, 1332 ([CCPA] 1980), citing In re Novak, 306 F.2d 924 ([CCPA] 1962); see Application of Irons, 340 F.2d 974, 977- 78 ([CCPA] 1965) .... However, where there is "no indication that one skilled in [the] art would accept without question statements [as to the effects of the claimed drug products] and no evidence has been presented to demonstrate that the claimed products do have those effects," an applicant has failed to demonstrate sufficient utility and therefore cannot establish enablement. Novak, 306 F.2d at 928.
Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 132375 USPQ2d 1297 (Fed. Cir. 2005) (bracketed material in original).
With these teachings in mind, an enabling disclosure in the form of a nexus between treatment of every and all cancers by administering the claimed “one or more nuclear export inhibitors” and “one or more agents that upregulate interferon production” is required.
Furthermore, the term “cancer” encompasses treatment of all cancers including melanoma, brain cancers, liver cancers, esophageal cancers, leukemias, etc., and the Examiner presumes the conditions contemplated encompass all these conditions. The instant specification does not adequately teach how to effectively treat all these other conditions to reach a therapeutic endpoint by administering the pharmaceutical compositions as recited in claims 10 and 25. Art recognized methods for treatment of malignancies are set forth in the Merck Manual (pages 986-995). The Merck Manual indicates that absent any data, it would require undue experimentation to practice the claimed method of treatment of all malignancies.
In the instant case, the method of treating leukemia, is very different from a method of treating melanoma or a brain cancer. The treatment of malignancies has been the subject of intense study for the past several decades. Many promising treatments and therapies have been identified via in vitro experiments, and have not lived up to expectations when tested in vivo. In fact, the number of such treatments, which have failed to live up to their promise exceeds those, which have been performed as hoped by orders of magnitude. The claims encompass malignancies of bone, brain, etc. The disclosure fails to teach one of ordinary skill in the art a method of treatment of all types of malignancies whether adenomas, glioblastomas, neuroblastomas etc. The effectivity of the claimed method against one type of tumor malignancy may be different from another specific type of malignancy depending on the type of cells involved and the developmental stage of the malignancy. With respect to the disparate tissues, the skilled artisan would have to undergo undue experimentation to determine if there is a therapeutically effective amount of the claimed products to be utilized for treating the various types of malignancies because with respect to dosage, experiments in vitro where a single cell type is present cannot be correlated to in vivo conditions where several different cell types are present. It would not be reasonable to expect the claimed products to work on the various types of aforementioned malignancies because it is well known that results obtained on a tissue such as skin are generally not reasonably predictive of results to be expected for neural and other tissues. It would be difficult to achieve treatment of malignancies in nerve or bone tissue as opposed to treatment of leukemia, which is certainly not representative of the various types of malignancies. Thus, it would require undue experimentation on the part of the skilled artisan to use the claimed method for treated as recited, in the absence of sufficient information to predict the results with an adequate degree of certainty. In view of this unpredictability in the treatment of different malignancies, there cannot be said to be any reasonable expectation of success at the in vivo application of a potential therapy, especially in view of the fact that the current specification as filed presents no working examples pertaining to the method of treatment of various malignancies in vivo. Therefore, a method for treating all cancers as recited in the claims has not been enabled by the specification.
Claim Rejections - 35 U.S.C. § 112(b)
5. 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.
5a. Claims 1, 3-5 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 pre-AIA the applicant regards as the invention.
Claim 1 is vague and indefinite for several reasons.
Claim 1 is vague and indefinite because it is a method claim but fails to recite steps in the method.
Claim 1 is vague and indefinite because it fails to recite the “cancers” claimed
Claim 1 is vague and indefinite because it is a method claim but fails to recite which ““one or more nuclear export inhibitors” and “one or more agents that upregulate interferon production” are encompassed by the claim. Therefore, the metes and bounds of the claim are unclear.
Claims 3-5 are rejected as vague and indefinite insofar as they depend on the above rejected claim 1 for their limitations.
Claim rejections-35 U.S.C. 103
6. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
6a. Claims 1, 35 are rejected under 35 U.S.C. 103 as being unpatentable over US 2017/0196836 A1 (hereinafter ‘836) in view of Xi et al. (2020).
‘836 discloses a method for treating cancer comprising administering to a subject in need thereof an effective amount of one or more nuclear export inhibitors, leptomycin A or leptomycin B, thereby treating the subject's cancer, wherein the cancer is selected from a lung, a pancreatic, a leukemia, a glioma, a cervical, an ovarian, an osteosarcoma, multiple myeloma, or a renal cell cancer, (See claims 1, 4; claim 12; claims 10-11). The reference is silent with respect to administering an effective amount of one or more agents that upregulate interferon production in combination with the leptomycin.
Xi et al teaches a method of treating cancer by administering an effective amount of a stimulator of interferon genes (STING) receptor agonist, amidobenzimidazoles (compound 24b) (Table 4, page 267) which plays a vital role in innate immune sensing of exogenous or endogenous DNA, which then induces type I interferons for significant tumor inhibition (abstract; page 261, Figure 1; page 271, column 1, last 3 lines, column 2).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the instant invention was conceived, to modify the method of treating cancer by administering leptomycin as taught by ‘836 such that it includes administering in combination with leptomycin, the agent that upregulates interferon production, amidobenzimidazoles, as taught by Xi to obtain the known functions and advantages of both leptomycin and amidobenzimidazoles, to increase the clinical efficacy of the claimed invention. One would have been motivated to administer the amidobenzimidazoles with the leptomycin because Xi et al teaches that treatment of cancer, by administration of amidobenzimidazoles, significantly inhibited tumors. To combine two compositions each of which is taught by the prior art to be useful for the same purpose in order to form a third composition that is to be used for the very same purpose would have been obvious to one of ordinary skill in the art at the time the invention was made. The combination would have been obvious to the skilled artisan and the results achieved would have been expected (In re Kerkhoven, 205 USPQ 1069).
Therefore, in the absence of evidence to the contrary, the combined teachings of ‘836 and Xi et al renders obvious claims 1, and 3-5.
Conclusion
No claim is allowed.
Claims 1-5 are rejected.
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/PREMA M MERTZ/ Primary Examiner, Art Unit 1674
