DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The instant application, filed 03/18/2022, is a Continuation-in-Part of PCT/CN2020/117586, filed 09/25/2020, which claims foreign priority to CN201910915840.3, filed 09/26/2019. Receipt is acknowledged of certified copies of papers required by 37 CFR § 1.55.
Continued Examination Under 37 CFR § 1.114
A request for continued examination under 37 CFR § 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR § 1.114, and the fee set forth in 37 CFR § 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR § 1.114. Applicant's submission filed on 02/25/2025 has been entered.
Amendments and Claim Status
The amendment filed on 02/25/2026 is acknowledged and entered.
Claims 2 and 20 are amended;
Claim 1 and 21 are cancelled;
Claims 2-20 and 22 are pending and are under prosecution.
Response to arguments
Applicant’s arguments filed 02/25/26 with respect to the claim objections and claim rejections under 35 U.S.C. §§ 112(a) and 112 (b) have been fully considered.
With respect to the objection to claims 14, and 18 for depending on a rejected claim, the amendment to claim 2 is insufficient to overcome the objection. As such, the objection is maintained.
With respect to the rejection of claims 2-12, 15-17, 19-22 under U.S.C. § 112(a) for failing to comply with the written description requirement, the cancellation of claim 21 is sufficient to render the rejection against said claims moot. However, the claim amendments to claim 2 and Applicant’s arguments have been fully considered but are not persuasive for the reasons set forth below. The arguments made by Applicant are herein addressed as follows.
The following section of the MPEP is relied upon for the response to Applicant’s arguments. According to MPEP § 2163.02, the standard for determining compliance with the written description requirement is as follows,
Whenever the issue arises, the fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, inventor was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991). An applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the inventor was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"
Applicant asserts that the amended claims are reasonable generalization of the example compounds with respect to ring A, R2 and m in claim 2. Applicant further contends that the definitions of Z2, Z3, Z5, and Z6 is supported by compounds T-4 and T-3.
With regard to the amendment of ring A, applicant is only in possession of compounds wherein A is (iso)oxazolyl. With regard to the amendment of R2 and m, the amendment is consistent with the compounds which are supported by the instant specification. As such, substituents have been removed as R2 and m from the grounds for rejection. With regard to the substituents Z2, Z3, Z5, and Z6, it is unclear which compound within the specification (pages 41 to 53) are named compounds T-4 and T-3. There are no such labels which demonstrate exemplifications of Z2, Z3, Z5, and Z6 is instantly claimed. Neither a two-dimensional structure, nor a page number directing the examiner to the compounds has been provided. As such, the definitions of Z2, Z3, Z5, and Z6 continue to be unsupported by the instant specification.
Applicant is reminded that written description requires possession, not merely feasibility. While the level of skill in the art is relevant, it cannot substitute for written description the demonstrate possession of the claimed compounds. The written description requirement is satisfied only when the specification reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date. The specification does not describe the claimed compounds with sufficient specificity to distinguish them from the universe of possible conjugates and substitutions that can be theoretically made.
Genentech, 108 F.3d at 1366, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p]atent 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”.
Accordingly, applicant has not demonstrated the possession of the claimed compounds as required under 35 U.S.C. § 112 (a). The rejection is therefore maintained. Applicant is invited to amend the claims to correspond to subject matter that is adequately supported by the specification, or to provide persuasive evidence demonstrating possession of the claimed compounds as of the effective filing date.
The written description requirement demands more than a wish or plan for obtaining the invention—it requires evidence that Applicant was in possession of the invention as claimed. Accordingly, the breadth of the amended claims remains unsupported by the specification, and the grounds of the rejection are maintained.
With respect to the rejection of claims 20 and 21 under U.S.C. § 112(a) for failing to provide enablement for the treatment of a disease mediated by multiple mutants kinases, the cancellation of claim 21 is sufficient to render the rejection against said claim moot. However, Applicant’s arguments have been fully considered but are not persuasive for the reasons set forth below. The arguments made by Applicant are herein addressed as follows.
Although the originally recited wild-type and mutant kinases have been narrowed in scope, the claim remains unsupported in the broad scope of treating any and all diseases mediated by the recited kinase targets, across the breadth of diseases instantly claimed. The claim still lacks enablement, because the specification does not provide sufficient representative guidance, working examples, or data to show that the disclosed compounds can be used, without undue experimentation, to treat the full scope of diseases now claimed as being mediated by the recited kinase targets. The specification does not reasonably provide sufficient correlation between target inhibition and therapeutic efficacy across the full claimed disease scope.
Accordingly, the disclosure does not demonstrate that the claimed compounds are enabled for treating the full range of diseases and tumor contexts now encompassed by the instant claims without undue experimentation. As such, the rejection is maintained.
With respect to the rejection of claim 22 under U.S.C. § 112(a) for failing to provide enablement for the treatment of the long list of diseases claimed, Applicant’s arguments have been fully considered but are not persuasive for the reasons set forth below. The arguments made by Applicant are herein addressed as follows.
Applicant argues that one skilled in the art guided by structural biology and mechanistic knowledge of kinase inhibition would reasonably expect an inhibitor proven effective against certain mutants would be effective against the disease is mediated by these mutants. Applicant thus extrapolates that a therapeutic strategy shown to be effective in a specific disease model would reasonably be expected to be effective against all cancers harboring a similar driver without undue experimentation.
Applicant’s argument is unpersuasive because, as previously stated in the teachings of McKean, tumor microenvironments are incredibly complex, leading to treatment failures despite respective prescreening with biomarkers (p.e275). According to McKean, there is a necessity for therapies that are targeted in order to overcome failures that occurred as a result of complex and differentiated tumor microenvironments according to their disease classifications.
A single class of compounds cannot be expected to be a “one-size-fits-all” therapy for diseases of different nature simply because they have a proposed common mechanism. That is, put simply, that treatments in different certain microenvironments will have varied success levels in different disease contexts. For example, the inhibition of a certain protein in a particular disease context may be advantageous for therapeutic outcomes. In a separate disease context, inhibition of the same protein may cause other downstream effects that allow the disease to further progress. It is known within the art that therapeutic outcomes are highly context dependent. And for that reason, Applicant’s arguments are found unpersuasive. As such, the original rejection is maintained.
With respect to the rejection of claim 21 under U.S.C. § 112(a) for being indefinite, the cancellation of claim 21 is sufficient to render the rejection against said claim moot. As such, the rejection is withdrawn.
Claim Objections
Claims 14 and 18 are objected to for depending on a rejected claim (claim 2)
Claim Rejections - 35 U.S.C. § 112 (a)
The text of those sections of title 35, U.S. Code not included in this action can be found in the prior Office action.
Claims 2-13, 15-17, 19, 20, and 22 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 claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. § 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The compounds as claimed include the following substituents:
Ring A is oxazolyl or isoxazol
Z2 is CRZ2 or N
Z3 is C or N
Z5 is N, NRZ5, or CRZ5
Z6 is NRZ6, or CRZ6
Rn1 and Rn2 are independently selected from H, D, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 alkynyl
35 U.S.C. § 112(a) and the first paragraph of pre-AIA 35 U.S.C. § 112 require that the "specification shall contain a written description of the invention ...." This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc); Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1560, 19 USPQ2d 1111,1114 (Fed. Cir. 1991); see also Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ2d 1886, 1890-93 (Fed. Cir. 2004) (discussing the history and purpose of the written description requirement); In re Curtis, 354 F.3d 1347, 1357, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) ("conclusive evidence of a claim’s enablement is not equally conclusive of that claim’s satisfactory written description"). The written description requirement has several policy objectives. "[T]he ‘essential goal’ of the description of the invention requirement is to clearly convey the information that an applicant has invented the subject matter which is claimed." In re Barker, 559 F.2d 588, 592 n.4, 194 USPQ 470, 473 n.4 (CCPA 1977). Another objective is to convey to the public what the applicant claims as the invention. See Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997), cert, denied, 523 U.S. 1089 (1998). "The ‘written description’ requirement implements the principle that a patent must describe the technology that is sought to be patented; the requirement serves both to satisfy the inventor’s obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed." Capon v. Eshhar, 418 F.3d 1349, 1357, 76 USPQ2d 1078, 1084 (Fed. Cir. 2005). Further, the written description requirement promotes the progress of the useful arts by ensuring that patentees adequately describe their inventions in their patent specifications in exchange for the right to exclude others from practicing the invention for the duration of the patent’s term.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaffv. Wells Bees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); EliLilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm.,927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991). An application specification may show actual reduction to practice by describing testing of the claimed invention.
In the present case, the important factors leading to a conclusion of inadequate written description is the breadth of the claims, the lack of sufficient working examples of the invention as claimed, and the lack of predictability in the art.
In the instant specification, there is no disclosure of the following claimed substituents:
Ring A as oxazolyl
Z2 as CRZ2
Z3 as N
Z5 as NRZ5, or CRZ5
Z6 as CRZ6
Rn1 and Rn2 as C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 alkynyl
The instant specification (pages 41 to 53) teaches compounds which are characterized as having only the following substituents:
Ring A is isoxazol
Z2 is N
Z3 is C
Z5 is N
Z6 is NRZ6
Rn1 and Rn2 are H and D
Therefore, the compounds described in the instant specification detail only a limited number of the substituents claimed (total claimed substituents 1-16 as detailed above). All working examples presented in the instant specification are related to the compounds containing a fraction of the total claimed substituents (substituents 37-55 as detailed above).
There are no working examples in the instant specification for the wide range of substituents claimed (substituents 18-36 as detailed above), and thus the instant specification does not provide any evidence that Applicant was in possession of the entire broad scope of claimed invention prior to the effective filing of the instant application.
Vas-Cath Inc. Mahurkar, 19 USPQ2d 1111, makes clear the "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116).
Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that: ...To fulfill the written description requirement, a 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." Lockwood v. American Airlines, Inc., 107 F. 3d 1565, 1572, 41 USPQ2d 1961, 1966(1997); In re Gostoli, 872 F.2d 1008, 1012,10 USPQ2d 1614, 1618 (Fed Cir. 1989) ("[T]he 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, 41 USPQ2d at 1966.
It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession. For example, disclosure of only a method of making the invention and the function may not be sufficient to support a product claim other than a product-by-process claim. See, e.g., Fiers v. Revel, 984 F.2d at 1169, 25 USPQ2d at 1605; Amgen, 927 F.2d at 1206, 18 USPQ2d at 1021.
Thus, since Applicant has not described in adequate detail synthesis of compounds containing the claimed substituents as detailed above, or provided evidence that said compounds have been characterized, an ordinary skilled artisan could not completely envisage Applicants’ invention. Moreover, it is clear that the written description requirement has not been met since Applicant has not provided any evidence that Applicant was in possession of the compounds as detailed above prior to the effective filing of the instant application. Thus, the cited claims of the instant application are not supported by the instant specification and thus a rejection under 35 U.S.C. § 112 (a) for failing to comply with the written description requirement is proper.
14. Claims 20 and 22 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 the inhibition of wild-type and V804M mutant RET kinases, wild-type and V804M, V804L, and G810R mutant KIF5B-RET kinases (and the likely intended F691L and D835Y mutants of FLT3-ITD kinase) and treating B-cell lymphoma, it does not reasonably provide enablement for the treatment of any diseases mediated by wild-type and mutant kinases including the cancers listed in claim 22 (non-small cell lung cancer, papillary thyroid cancer, glioblastoma multiforme, acute myeloid leukemia, colorectal cancer, large cell neuroendocrine cancer, prostate cancer, colon cancer, acute lymphoblastic leukemia, sarcoma, pediatric glioma, intrahepatic bile duct carcinoma, pilocytic astrocytoma, low-grade glioma, lung adenocarcinoma, salivary gland carcinoma, secretory breast cancer, fibrosarcoma, kidney cancer, breast cancer, myelodysplastic syndrome, gastrointestinal stromal tumor, melanoma, seminoma, or intracranial germ cell tumor). The specification does not provide sufficient information to support the claimed invention as it pertains to the inclusion of a wide number of diseases mediated by specific kinases whether they be wild-type or mutant forms.
The instant specification fails to provide information that would allow the skilled artisan to fully practice the instant invention without undue experimentation. Attention is directed to In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention: The instant claims are drawn to a method of treating a disease comprising administering a compound of Formula (II). The claim encompasses treating diseases mediated by wild-type and mutant protein kinases RET, KIF5B-RET, and FLT3-ITD kinases wherein the mutant, RET and KIF5B-RET kinases are selected from V804L, V804M, and G810R, and the mutant FLT3-ITD kinases are selected from F691L and D835Y. The diseases encompassed by the instant claims include it does not reasonably provide enablement for the treatment of non-small cell lung cancer, papillary thyroid cancer, glioblastoma multiforme, acute myeloid leukemia, colorectal cancer, large cell neuroendocrine cancer, prostate cancer, colon cancer, acute lymphoblastic leukemia, sarcoma, pediatric glioma, intrahepatic bile duct carcinoma, pilocytic astrocytoma, low-grade glioma, lung adenocarcinoma, salivary gland carcinoma, secretory breast cancer, B-cell lymphoma, fibrosarcoma, kidney cancer, breast cancer, myelodysplastic syndrome, gastrointestinal stromal tumor, melanoma, seminoma, or intracranial germ cell tumor.
Breadth of the claims: The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims. The rejected claims are extremely broad. Applicant claims that the claimed compounds can be used to treat any disease mediated by a large range of mutant or wild-type kinases. Thus the cited claims are deemed very broad since these claims read on treating any disease mediated by numerous wild-type and mutant protein kinases, and as a result numerous distinct diseases, including non-small cell lung cancer, papillary thyroid cancer, glioblastoma multiforme, acute myeloid leukemia, colorectal cancer, large cell neuroendocrine cancer, prostate cancer, colon cancer, acute lymphoblastic leukemia, sarcoma, pediatric glioma, intrahepatic bile duct carcinoma, pilocytic astrocytoma, low-grade glioma, lung adenocarcinoma, salivary gland carcinoma, secretory breast cancer, B-cell lymphoma, fibrosarcoma, kidney cancer, breast cancer, myelodysplastic syndrome, gastrointestinal stromal tumor, melanoma, seminoma, or intracranial germ cell tumor.
State of the Prior Art: Regarding the variability of protein kinases in disease, Benn and Dawson (Front. Aging Neurosc, volume 12, published September 1, 2020), maintain that aberrant regulation of protein kinase activity has been linked to a diverse of disease states including cancer, inflammation, metabolic, autoimmune, neurological disorders (page 2). Figure 1 of the cited manuscript details the four different types of protein kinases Type I, Type II, Type III, and Type IV, which differ with respect to their allosteric activation and interaction with binding residues. In terms of small molecule inhibitors, Benn and Dawson summarize the efforts of developing competitive and noncompetitive inhibitors across different protein kinases, demonstrating that there is no “one-size-fits-all” protein kinase inhibitor (page 3). A small sample of the large number of protein kinases, their varied function, disease-specific rationale, and inhibitors are summarized in Table 1 of the disclosure by Benn and Dawson.
Regarding protein kinase targeted cancer therapies, Bhullar et al. (Molecular Cancer volume 17, Article number: 48, published February 19, 2018), hereinafter Bhullar teaches that the human genome encodes 538 protein kinases (abstract). Figures 1 and 5 of the disclosure by Bhullar exemplify the various chemical scaffolds and molecular species used to target different types of protein kinases. Furthermore, Bhullar teaches that there are five distinct types of kinase inhibitors termed types I, II, III, IV, and V kinase inhibitors. The type I kinase inhibitor binds to the active confirmation of the kinase the ATP pocket; the type II inhibitor binds to an inactive confirmation of the kinase (page 6); the type III inhibitor is an allosteric inhibitor; the type IV inhibitor undergoes a reversible interaction in the kinase substrate-binding site; and the type V inhibitor undergoes him an irreversible covalent bond with the kinase active site and target a catalytic nucleophile cysteine within the active site of the enzyme (page 7). Bhullar further discloses a wide range of protein kinase mutations leading to distinct cancers (page 4). The disclosure by Bhullar demonstrates that targeting protein kinases for cancers is not a straightforward process, but one that depends on the mechanism of action of the specific protein kinase, as well as the mutation which implicates the protein kinase in the cancer type.
Presently, there are no art-recognized methods that could be used to commonly identify subjects who would have predictably developed non-small cell lung cancer, papillary thyroid cancer, glioblastoma multiforme, acute myeloid leukemia, colorectal cancer, large cell neuroendocrine cancer, prostate cancer, colon cancer, acute lymphoblastic leukemia, sarcoma, pediatric glioma, intrahepatic bile duct carcinoma, pilocytic astrocytoma, low-grade glioma, lung adenocarcinoma, salivary gland carcinoma, secretory breast cancer, fibrosarcoma, kidney cancer, breast cancer, myelodysplastic syndrome, gastrointestinal stromal tumor, melanoma, seminoma, or intracranial germ cell tumors.
Regarding common disease mechanisms and biomarkers, McKean et al. (Biomarkers in precision cancer immunotherapy: Promise and challenges. American Society of Clinical Oncology – Educational Book (2020), 40, p.e275-e291), hereinafter McKean, teach that although ongoing studies and trials investigate the use of multiple biomarkers predictive of patient response or harm, none of these are comprehensive in predicting potential benefit (of treatment). This unmet need for validated biomarkers is largely secondary to a prohibitive complexity within tumor parenchyma and microenvironment, dynamic clonal and proteomic changes to therapy, heterogenous host immune defects, and varied standardization among sample preparation and reporting (abstract). McKean also teach that treatment failures occur even in ICI patient cohorts, despite respective prescreening with biomarkers such as PD-L1 tumor proportion scores (p.e275). Regarding gene expression profiles specifically, McKean teaches that an important concept within gene expression profiles is that the predictive utility of such algorithms may be dependent on individual therapy plans. Data suggest that signaling and transcriptomic patterns may correlate only with response to therapy of directly related targets (p.e280). Unrelated immune pathways may require separate and individualized gene expression assays for different therapies (p.e280).
The practice of Applicant's invention would require a common disease mechanism for the development of the range of the aforementioned diseases linked to a large range of protein kinases both wild-type and mutant, which has not been established by the state of the art at the present time. Therefore, the selection of a particular therapy for any specific type of cancer prevention is unpredictable, and requires individualized assays that are fully described to achieve correlation. For these reasons the state of the art fails to support the treatment of all diseases/disorders encompassed by the claims comprising the administration of the claimed compounds.
Predictability/Unpredictability in the Art: It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. In the instant case, the instant claimed invention is highly unpredictable since one skilled in the art would recognize that the recitation includes treating any disease mediated by protein kinases. Thus, the skilled artisan would view that successfully targeting the large number of diseases mediated by protein kinases encompassed by the claims comprising the administration of the compounds, is highly unpredictable, as there are a large number of protein kinase inhibitors, as demonstrated in the teachings of Bhullar, above.
Moreover, one of skill in the art would recognize that it is highly unpredictable in regard to therapeutic effects, side effects and toxicity generated by administering a singular class of compounds for treating all the disorders and diseases encompassed by the claims.
Guidance of the Specification/Working Examples: Applicant has only provided working examples demonstrating that compounds of claim 1 may inhibit wild-type and V840M mutant RET kinase (Table 1, pages 91 and 92 of the instant specification), wild-type and V804L and G810R KIF5B-RET (Table 2, pages 93 and 94 of the instant specification) and the treatment of B-cell lymphoma KIF5B-RET tumors (Tables 7 and 8, Figures 2 and 3, pages 95, 98-99 of the instant specification), KIF5B-RETG810R tumors (Table 9, Figure 4, pages 95, 99 of the instant specification). Only the aforementioned proteins, and mutants are enabled with evidence and working examples presented in the instant specification. Thus Applicant has only provided evidence that the claimed compounds are useful in the treatment of B-cell lymphoma and the inhibition of the various kinases as detailed above. Thus, the specification fails to provide sufficient evidence in support of the broad treatment of diseases comprising the administration of all compounds to all the mutant forms of protein kinases RET, KIF5B-RET, and FLT3-ITD as recited in the instant claims. Applicant has only provided working examples suggesting that compounds of claim 1 may treat B-cell lymphoma KIF5B-RET and KIF5B-RETG801R tumors (Tables 7 and 8, Figures 2 and 3, pages 95, 98-99 of the instant specification). Thus, the specification fails to provide sufficient evidence in support of the broad treatment of non-small cell lung cancer, papillary thyroid cancer, glioblastoma multiforme, acute myeloid leukemia, colorectal cancer, large cell neuroendocrine cancer, prostate cancer, colon cancer, acute lymphoblastic leukemia, sarcoma, pediatric glioma, intrahepatic bile duct carcinoma, pilocytic astrocytoma, low-grade glioma, lung adenocarcinoma, salivary gland carcinoma, secretory breast cancer, fibrosarcoma, kidney cancer, breast cancer, myelodysplastic syndrome, gastrointestinal stromal tumor, melanoma, seminoma, or intracranial germ cell tumors as recited in the instant claim.
The Quantitation of Experimentation Required: In order to practice Applicant’s invention, it would be necessary for one to design and conduct an exhaustive amount of complex experiments to demonstrate that the desired disease mediated by wild-type and mutant protein kinases such as RET, KIF5B-RET, and FLT3-ITD kinases can be treated by the administration of the compounds claimed. Therefore, in order to practice the claimed invention, the amount of experimentation required would be considered undue and burdensome.
In conclusion, Genentech, 108 F.3d at 1366, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p]atent 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”. A method for treating a disease mediated by the large range of wild-type and mutant protein kinases comprising administering a compound of Formula (II) to a subject is not enabled by the instant specification.
Claim Rejections - 35 U.S.C. § 112 (b)
The text of those sections of title 35, U.S. Code not included in this action can be found in the prior Office action.
Claims 20 and 22 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.
Claims 20 and 22 of the instant application claim a method of treating a disease mediated by one or more wild -type or mutant kinases, comprising administering to a subject in need thereof the compound or pharmaceutically acceptable salt thereof of Formula (II).
It is unclear what is meant by “a disease mediated by one or more wild -type or mutant kinases” refers to and how to determine if a disease is mediated by the wild-type or mutant kinases. The term “disease mediated” in claims 20 and 22 is a relative term which renders the claim indefinite. The term “disease mediated” is not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The specification does not define how to determine if a disease is mediated by the specific wild-type or mutant kinases. Thus it is unclear what would be considered mediated by the specific wild-type or mutant kinases by a person of ordinary skill in the art. There are a large number of diseases that could be considered mediated by the specific wild-type or mutant kinases. Moreover, there are diseases that could result from dysfunction of cellular pathways which implicate the specific wild-type or mutant kinases that do not directly have the specific wild-type or mutant kinases at the center of the disease morphology. The claims, as written, do not distinctly claim the disease to which the specific wild-type or mutant kinases is related, or how the relation is made—whether it be a disease, condition, or disorder directly implicating the specific wild-type or mutant kinase dysfunction or a disease which develop as a result of diseases, conditions, or disorders that implicate the specific wild-type or mutant kinase dysfunction. Thus an ordinary skilled artisan cannot ascertain the metes and bounds of the claimed invention and thus the claims are properly rejected as being indefinite.
Correspondence
Claims 14 and 18 are objected to.
Claims 2-13, 15-17, 19, 20, and 22 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sophia P. Hirakis whose telephone number is +1 (571) 272-0118. The examiner can normally be reached within the hours of 5:00 am to 5:00pm EST, Monday through Friday.
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/SOPHIA P HIRAKIS/Examiner, Art Unit 1623
/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623